Ruben I Kuzniecky, M.D.

Volume of the human septal forebrain region is a predictor of source memory accuracy
Butler, Tracy; Blackmon, Karen; Zaborszky, Laszlo; Wang, Xiuyuan; Dubois, Jonathan; Carlson, Chad; Barr, William B; French, Jacqueline; Devinsky, Orrin; Kuzniecky, Ruben; Halgren, Eric; Thesen, Thomas
2012 Jan;18(1):157-161, Journal of the International Neuropsychological Society
Septal nuclei, components of basal forebrain, are strongly and reciprocally connected with hippocampus, and have been shown in animals to play a critical role in memory. In humans, the septal forebrain has received little attention. To examine the role of human septal forebrain in memory, we acquired high-resolution magnetic resonance imaging scans from 25 healthy subjects and calculated septal forebrain volume using recently developed probabilistic cytoarchitectonic maps. We indexed memory with the California Verbal Learning Test-II. Linear regression showed that bilateral septal forebrain volume was a significant positive predictor of recognition memory accuracy. More specifically, larger septal forebrain volume was associated with the ability to recall item source/context accuracy. Results indicate specific involvement of septal forebrain in human source memory, and recall the need for additional research into the role of septal nuclei in memory and other impairments associated with human diseases. (JINS, 2012, 18, 157-161)
— id: 147692, year: 2012, vol: 18, page: 157, stat: Journal Article,

Structural evidence for involvement of a left amygdala-orbitofrontal network in subclinical anxiety
Blackmon K; Barr WB; Carlson C; Devinsky O; Dubois J; Pogash D; Quinn BT; Kuzniecky R; Halgren E; Thesen T
2011 Dec 30;194(3):296-303, Psychiatry research
Functional neuroimaging implicates hyperactivity of amygdala-orbitofrontal circuitry as a common neurobiological mechanism underlying the development of anxiety. Less is known about anxiety-related structural differences in this network. In this study, a sample of healthy adults with no history of anxiety disorders completed a 3T MRI scan and self-report mood inventories. Post-processing quantitative MRI image analysis included segmentation and volume estimation of subcortical structures, which were regressed on anxiety inventory scores, with depression scores used to establish discriminant validity. We then used a quantitative vertex-based post-processing method to correlate (1) anxiety scores and (2) left amygdala volumes with cortical thickness across the whole cortical mantle. Left amygdala volumes predicted anxiety, with decreased amygdala volume associated with higher anxiety on both state and trait anxiety measures. A negative correlation between left amygdala volume and cortical thickness overlapped with a positive correlation between anxiety and cortical thickness in left lateral orbitofrontal cortex. These results suggest a structural anxiety network that corresponds with a large body of evidence from functional neuroimaging. Such findings raise the possibility that structural abnormalities may result in a greater vulnerability to anxiety or conversely that elevated anxiety symptoms may result in focal structural changes
— id: 139495, year: 2011, vol: 194, page: 296, stat: Journal Article,

Structural evidence for involvement of a left amygdala-orbitofrontal network in subclinical anxiety
Blackmon, Karen; Barr, William B.; Carlson, Chad; Devinsky, Orrin; DuBois, Jonathan; Pogash, Daniel; Quinn, Brian T.; Kuzniecky, Ruben; Halgren, Eric; Thesen, Thomas (thomas.thesen@med.nyu.edu)
2011 DEC 30 ;194(3):296-303, Psychiatry Research Neuroimaging
Functional neuroimaging implicates hyperactivity of amygdala-orbitofrontal circuitry as a common neurobiological mechanism underlying the development of anxiety. Less is known about anxiety-related structural differences in this network. In this study, a sample of healthy adults with no history of anxiety disorders completed a 3T MRI scan and self-report mood inventories. Post-processing quantitative MRI image analysis included segmentation and volume estimation of subcortical structures, which were regressed on anxiety inventory scores, with depression scores used to establish discriminant validity. We then used a quantitative vertex-based post-processing method to correlate (1) anxiety scores and (2) left amygdala volumes with cortical thickness across the whole cortical mantle. Left amygdala volumes predicted anxiety, with decreased amygdala volume associated with higher anxiety on both state and trait anxiety measures. A negative correlation between left amygdala volume and cortical thickness overlapped with a positive correlation between anxiety and cortical thickness in left lateral orbitofrontal cortex. These results suggest a structural anxiety network that corresponds with a large body of evidence from functional neuroimaging. Such findings raise the possibility that structural abnormalities may result in a greater vulnerability to anxiety or conversely that elevated anxiety symptoms may result in focal structural changes. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 Thesen, Thomas; NYU, Dept Neurol, Comprehens Epilepsy Ctr, 223 E 34th St, New York, NY 10016 USA
— id: 150857, year: 2011, vol: 194, page: 296, stat: Journal Article,

Individual differences in verbal abilities associated with regional blurring of the left gray and white matter boundary
Blackmon, Karen; Halgren, Eric; Barr, William B; Carlson, Chad; Devinsky, Orrin; Dubois, Jonathan; Quinn, Brian T; French, Jacqueline; Kuzniecky, Ruben; Thesen, Thomas
2011 Oct 26;31(43):15257-15263, Journal of neuroscience
Blurring of the cortical gray and white matter border on MRI is associated with normal aging, pathological aging, and the presence of focal cortical dysplasia. However, it remains unclear whether normal variations in signal intensity contrast at the gray and white matter junction reflect the functional integrity of subjacent tissue. This study explores the relationship between verbal abilities and gray and white matter contrast (GWC) in healthy human adults. Participants were scanned at 3 T MRI and administered standardized measures of verbal expression and verbal working memory. GWC was estimated by calculating the non-normalized T1 image intensity contrast above and below the cortical gray/white matter interface. Spherical averaging and whole-brain correlational analyses were performed. Sulcal regions exhibited higher contrast compared to gyral regions. We found a strongly lateralized and regionally specific profile with reduced verbal expression abilities associated with blurring in left hemisphere inferior frontal cortex and temporal pole. Reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomical substrates of cognition in healthy and diseased populations
— id: 139752, year: 2011, vol: 31, page: 15257, stat: Journal Article,

Cortical thickness abnormalities associated with depressive symptoms in temporal lobe epilepsy
Butler T; Blackmon K; McDonald CR; Carlson C; Barr WB; Devinsky O; Kuzniecky R; Dubois J; French J; Halgren E; Thesen T
2011 Jan;23(1):64-67, Epilepsy & behavior
Depression in patients with temporal lobe epilepsy (TLE) is highly prevalent and carries significant morbidity and mortality. Its neural basis is poorly understood. We used quantitative, surface-based MRI analysis to correlate brain morphometry with severity of depressive symptoms in 38 patients with TLE and 45 controls. Increasing severity of depressive symptoms was associated with orbitofrontal cortex (OFC) thinning in controls, but with OFC thickening in TLE patients. These results demonstrate distinct neuroanatomical substrates for depression with and without TLE, and suggest a unique role for OFC, a limbic region for emotional processing strongly interconnected with medial temporal structures, in TLE-related depressive symptoms
— id: 141935, year: 2011, vol: 23, page: 64, stat: Journal Article,

Imaging Inflammation in a Patient with Epilepsy Due to Focal Cortical Dysplasia
Butler T; Ichise M; Teich AF; Gerard E; Osborne J; French J; Devinsky O; Kuzniecky R; Gilliam F; Pervez F; Provenzano F; Goldsmith S; Vallabhajosula S; Stern E; Silbersweig D
2011 Jan 11;:?-?, Journal of neuroimaging
BACKGROUND AND PURPOSE: Evidence from animal models and examination of human epilepsy surgery specimens indicates that inflammation plays an important role in epilepsy. Positron emission tomography (PET) using [C11]PK11195, a marker of activated microglia, provides a means to visualize neuroinflammation in vivo in humans. We hypothesize that in patients with active epilepsy, [C11]PK11195 PET (PK-PET) may be able to identify areas of focally increased inflammation corresponding to the seizure onset zone. METHODS: A young woman with intractable epilepsy underwent PK-PET as part of an approved research study. PK-PET results were compared with results from other clinical studies. RESULTS: PK-PET revealed an area of focally increased radiotracer uptake in the right frontal lobe corresponding to this patient's seizure focus as identified by ictal and interictal 18F-fluorodeoxyglucose (FDG)-PET and EEG. Routine brain magnetic resonance imaging (MRI) was initially considered normal, though high-resolution studies showed possible subtle dysplasia of the right frontal lobe. The patient underwent a right frontal lobe resection, and pathological evaluation showed focal cortical dysplasia with activated microglia. CONCLUSIONS: PK-PET can identify neuroinflammation associated with subtle focal cortical dysplasia, and may therefore have a clinical role in guiding epilepsy surgery for patients with difficult-to-localize seizure foci. J Neuroimaging 2011;XX:1-3
— id: 120738, year: 2011, vol: , page: ?, stat: Journal Article,

Abnormalities of cortical thickness in postictal psychosis
Dubois, J M; Devinsky, O; Carlson, C; Kuzniecky, R; Quinn, B T; Alper, K; Butler, T; Starner, K; Halgren, E; Thesen, T
2011 Jun;21(2):132-136, Epilepsy & behavior
Postictal psychosis (PIP), the occurrence of psychotic episodes following a seizure, is a common and serious comorbidity in patients with epilepsy. Yet, the anatomical correlates remain poorly defined. Here, we used quantitative MRI morphometry to identify structural abnormalities in the cortex of patients with PIP relative to patients with epilepsy without PIP and age- and gender-matched normal healthy controls. Comparison of patients with epilepsy and PIP with patients with epilepsy without PIP revealed increased cortical thickness in the right lateral prefrontal cortex, right anterior cingulate cortex, and right middle temporal gyrus. The PIP group was distinguished from the EC and NC groups by thicker cortex in the right rostral anterior cingulate cortex and thinner cortex in the right angular gyrus and the left middle temporal region. Findings indicate that PIP is associated with thickening of the right anterior cingulate cortex, which may serve as a marker for patients at risk for developing PIP
— id: 134446, year: 2011, vol: 21, page: 132, stat: Journal Article,

Hemispheric asymmetries of cortical volume in the human brain
Goldberg E; Roediger D; Kucukboyaci NE; Carlson C; Devinsky O; Kuzniecky R; Halgren E; Thesen T
2011 Nov 19;:?-?, Cortex
Hemispheric asymmetry represents a cardinal feature of cerebral organization, but the nature of structural and functional differences between the hemispheres is far from fully understood. Using Magnetic Resonance Imaging morphometry, we identified several volumetric differences between the two hemispheres of the human brain. Heteromodal inferoparietal and lateral prefrontal cortices are more extensive in the right than left hemisphere, as is visual cortex. Heteromodal mesial and orbital prefrontal and cingulate cortices are more extensive in the left than right hemisphere, as are somatosensory, parts of motor, and auditory cortices. Thus, heteromodal association cortices are more extensively represented on the lateral aspect of the right than in the left hemisphere, and modality-specific cortices are more extensively represented on the lateral aspect of the left than in the right hemisphere. On the mesial aspect heteromodal association cortices are more extensively represented in the left than right hemisphere
— id: 149915, year: 2011, vol: , page: ?, stat: Journal Article,

Cardiovascular and neuroendocrine features of Panayiotopoulos syndrome in three siblings
Gonzalez-Duarte, Alejandra; Norcliffe-Kaufmann, Lucy; Martinez, Jose; Rodriguez, Alcibiades J; Kuzniecky, Ruben; Axelrod, Felicia; Kaufmann, Horacio
2011 Jul;21(3):296-300, Epilepsy & behavior
OBJECTIVE: Panayiotopoulos syndrome is a benign idiopathic childhood epilepsy characterized by altered autonomic activity at seizure onset. METHODS: Three siblings with Panayiotopoulos syndrome underwent 24-hour EEG recording and head-up tilt testing with continuous blood pressure and RR interval monitoring. Plasma catecholamines and vasopressin were measured while supine, upright, and during a typical seizure. RESULTS: Patient 1, a 12-year-old girl, had a history of involuntary lacrimation, abdominal pain, and recurrent episodes of loss of muscle tone and unresponsiveness followed by somnolence. Her EEG revealed bilateral frontotemporal spikes. Patient 2, a 10-year-old boy, had episodic headaches with pinpoint pupils, skin flushing of the face, trunk, and extremities, purple discoloration of hands and feet, diaphoresis, nausea, and vomiting. Tilt testing triggered a typical seizure after 9minutes; there was a small increase in blood pressure (+5/4mm Hg, systolic/diastolic) and pronounced increases in heart rate (+59bpm) and norepinephrine (+242pg/mL), epinephrine (+175pg/mL), and vasopressin (+22.1pg/mL) plasma concentrations. Serum glucose was elevated (206mg/dL). His EEG revealed right temporal and parietal spikes. Patient 3, an 8-year-old boy, had a history of restless legs at night, enuresis, night terrors, visual hallucinations, cyclic abdominal pain, and nausea. His EEG showed bitemporal spikes. CONCLUSION: Hypertension, tachycardia, and the release of vasopressin suggest activation of the central autonomic network during seizures in familial Panayiotopoulos syndrome. These autonomic and neuroendocrine features may be useful in the diagnosis and may have therapeutic implications
— id: 136485, year: 2011, vol: 21, page: 296, stat: Journal Article,

Bottom-of-sulcus dysplasia: imaging features
Hofman, Paul A M; Fitt, Gregory J; Harvey, A Simon; Kuzniecky, Ruben I; Jackson, Graeme
2011 Apr;196(4):881-885, American journal of roentgenology
OBJECTIVE: Dysplasia at the bottom of a sulcus is a subtle but distinct malformation of cortical development relevant to epilepsy. The purpose of this study was to review the imaging features important to the clinical diagnosis of this lesion. MATERIALS AND METHODS: All cases recognized as typical bottom-of-sulcus dysplasia in our comprehensive epilepsy program over the period 2002-2007 were included in the study. RESULTS: In the 20 cases recognized, three major features were identified: cortical thickening at the bottom of a sulcus; a funnel-shaped extension of the lesion toward the ventricular surface, commonly with abnormal signal intensity; and an abnormal gyral pattern related to the bottom-of-sulcus dysplasia, sometimes with a puckered appearance. The pathologic features of the resected lesions were typical of focal cortical dysplasia. CONCLUSION: Bottom-of-sulcus dysplasia is a distinctive malformation of cortical development that can be diagnosed on the basis of imaging characteristics. Reliable identification of this type of malformation of cortical development is difficult but clinically important because the lesion appears to be highly epileptogenic and because the prognosis for seizure control is excellent after focal resection
— id: 134147, year: 2011, vol: 196, page: 881, stat: Journal Article,

A Novel Portable Seizure Detection Alarm System: Preliminary Results
Kramer U; Kipervasser S; Shlitner A; Kuzniecky R
2011 Feb;28(1):36-38, Journal of clinical neurophysiology
The unpredictable and random occurrence of seizures is of the most distressful issue affecting patients and their families. Unattended seizures can have serious consequences including injury or death. The objective of this study is to develop a small, portable, wearable device capable of detecting seizures and alerting patients and families on recognition of specific seizures' motor activity. Ictal data were prospectively obtained in consecutive patients admitted to two video-EEG units. This study included patients with a history of motor seizures, clonic or tonic, or tonic-clonic seizures or patients with complex partial seizures with frequent secondary generalization. A 'Motion Sensor' unit mounted on a bracelet was attached to one wrist. The 'Sensor' contains a three-axis accelerometer and a transmitter. The three-axis movements' data were transmitted to a portable computer. Algorithm specially developed for this purpose analyzed the recorded data. Seizures' alerts were compared with the video-EEG data. Ictal data were acquired in 15 of the 31 recruited patients. The algorithm correctly identified 20 of 22 (91%) captured seizures and generated an alarm within a median period of 17 seconds. All events lasting >30 seconds (i.e., 19 events) were identified. The system failed to identify 2 of 22 seizures (9%). There were eight false alarms during 1,692 hours of monitoring. Preliminary data suggest that this motion detection device/alarm system can identify most motor seizures with high sensitivity and with a low false alarm rate
— id: 120739, year: 2011, vol: 28, page: 36, stat: Journal Article,

An implantable triple-function device for local drug delivery, cerebrospinal fluid removal and EEG recording in the cranial subdural/subarachnoid space of primates
Ludvig N; Medveczky G; Rizzolo R; Tang HM; Baptiste SL; Doyle WK; Devinsky O; Carlson C; French JA; Kral JG; Charchaflieh J; Kuzniecky RI
2011 Oct 17;203(2):275-283, Journal of neuroscience methods
Transmeningeal pharmacotherapy for cerebral cortical disorders requires drug delivery through the subdural/subarachnoid space, ideally with a feedback controlled mechanism. We have developed a device suitable for this function. The first novel component of the apparatus is a silicone rubber strip equipped with (a) fluid-exchange ports for both drug delivery and local cerebrospinal fluid (CSF) removal, and (b) EEG recording electrode contacts. This strip can be positioned between the dura and pia maters. The second novel component is an implantable dual minipump that directs fluid movement to and from the silicone strip and is accessible for refilling and emptying the drug and CSF reservoirs, respectively. This minipump is regulated by a battery-powered microcontroller integrating a bi-directional radiofrequency (RF) communication module. The entire apparatus was implanted in 5 macaque monkeys, with the subdural strip positioned over the frontal cortex and the minipump assembly secured to the cranium under a protective cap. The system was successfully tested for up to 8months for (1) transmeningeal drug delivery using acetylcholine (ACh) and muscimol as test compounds, (2) RF-transmission of neocortical EEG data to assess the efficacy of drug delivery, and (3) local CSF removal for subsequent diagnostic analyses. The device can be used for (a) monitoring neocortical electrophysiology and neurochemistry in freely behaving nonhuman primates for more than 6months, (b) determining the neurobiological impact of subdural/subarachnoid drug delivery interfaces, (c) obtaining novel neuropharmacological data on the effects of central nervous system (CNS) drugs, and (d) performing translational studies to develop subdural pharmacotherapy devices
— id: 139939, year: 2011, vol: 203, page: 275, stat: Journal Article,

Transmeningeal muscimol can prevent focal EEG seizures in the rat neocortex without stopping multineuronal activity in the treated area
Ludvig, Nandor; Tang, Hai M; Artan, N Sertac; Mirowski, Piotr; Medveczky, Geza; Baptiste, Shirn L; Darisi, Sindhu; Kuzniecky, Ruben I; Devinsky, Orrin; French, Jacqueline A
2011 Apr 18;1385:182-191, Brain research
Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity. Rats were chronically implanted with a modified epidural cup over the right frontal cortex, with microelectrodes positioned underneath the cup. In each postsurgical experimental day, either saline or 0.005-, 0.05-, 0.5- or 5.0-mM muscimol was delivered through the cup, followed by a 20-min monitoring of the multineuronal activity and the subsequent delivery of Ach in the same way. Saline and muscimol pretreatment in the concentration range of 0.005-0.05mM did not prevent EEG seizures. In contrast, 0.5-mM muscimol reduced the average EEG Seizure Duration Ratio value from 0.30+/-0.04 to 0. At this muscimol concentration, the average baseline multineuronal firing rate of 10.9+/-4.4spikes/s did not change significantly throughout the 20-min pretreatment. Muscimol at 5.0mM also prevented seizures, but decreased significantly the baseline multineuronal firing rate of 7.0+/-1.8 to 3.7+/-0.9spikes/s in the last 10min of pretreatment. These data indicate that transmeningeal muscimol in a submillimolar concentration range can prevent focal neocortical seizures without stopping multineuronal activity in the treated area, and thus this treatment is unlikely to interrupt local physiological functions
— id: 129321, year: 2011, vol: 1385, page: 182, stat: Journal Article,

Periodic transmeningeal muscimol maintains its antiepileptic efficacy over three weeks without inducing tolerance, in rats
Tang, Hai M; French, Jacqueline A; Kuzniecky, Ruben I; Devinsky, Orrin; Ludvig, Nandor
2011 Apr 25;494(2):135-138, Neuroscience letters
Periodic transmeningeal administration of muscimol into the neocortical epileptogenic zone via a subdurally implanted device has been proposed for the treatment of intractable focal neocortical epilepsy. It is unknown whether such muscimol applications induce tolerance. The purpose of this study was to determine whether daily transmeningeal (epidural) muscimol applications into the rat parietal cortex induce tolerance to the antiepileptic effect of this drug. Rats were chronically implanted with an epidural cup and adjacent epidural EEG electrodes over the right parietal cortex. After recovery 1.0mM muscimol was delivered into the implanted cortical area through the cup while the animal behaved freely, once per day for 4 consecutive days in each week, with each delivery followed within 3min by the delivery of a seizure-inducing concentration of acetylcholine (Ach) into the same area. The study lasted for 3 weeks. In each week, one day was used to test the epileptogenicity of the examined cortical site by replacing muscimol with saline prior to Ach delivery. The duration of Ach-induced EEG seizures was measured in each experimental session to assess the antiepileptic efficacy of muscimol, while the rat's behavior was also monitored. The daily epidural muscimol pretreatments prevented Ach-induced EEG and behavioral seizures in all rats. This antiepileptic action did not diminish over time and was maintained throughout the 3-week test period. When muscimol was replaced with saline, the subsequent Ach administrations induced EEG and behavioral seizures. These results suggest that periodic transmeningeal administrations of a relatively low concentration of muscimol into the neocortex over three weeks do not induce tolerance to the localized antiepileptic effects of this drug
— id: 130302, year: 2011, vol: 494, page: 135, stat: Journal Article,

Detection of epileptogenic cortical malformations with surface-based MRI morphometry
Thesen, Thomas; Quinn, Brian T; Carlson, Chad; Devinsky, Orrin; DuBois, Jonathan; McDonald, Carrie R; French, Jacqueline; Leventer, Richard; Felsovalyi, Olga; Wang, Xiuyuan; Halgren, Eric; Kuzniecky, Ruben
2011 ;6(2):e16430-e16430, PLoS ONE
Magnetic resonance imaging has revolutionized the detection of structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we use an automated, surface-based method for quantifying morphometric features related to epileptogenic cortical malformations to detect abnormal cortical thickness and blurred gray-white matter boundaries. Using MRI morphometry at 3T with surface-based spherical averaging techniques that precisely align anatomical structures between individual brains, we compared single patients with known lesions to a large normal control group to detect clusters of abnormal cortical thickness, gray-white matter contrast, local gyrification, sulcal depth, jacobian distance and curvature. To assess the effects of threshold and smoothing on detection sensitivity and specificity, we systematically varied these parameters with different thresholds and smoothing levels. To test the effectiveness of the technique to detect lesions of epileptogenic character, we compared the detected structural abnormalities to expert-tracings, intracranial EEG, pathology and surgical outcome in a homogeneous patient sample. With optimal parameters and by combining thickness and GWC, the surface-based detection method identified 92% of cortical lesions (sensitivity) with few false positives (96% specificity), successfully discriminating patients from controls 94% of the time. The detected structural abnormalities were related to the seizure onset zones, abnormal histology and positive outcome in all surgical patients. However, the method failed to adequately describe lesion extent in most cases. Automated surface-based MRI morphometry, if used with optimized parameters, may be a valuable additional clinical tool to improve the detection of subtle or previously occult malformations and therefore could improve identification of patients with intractable focal epilepsy who may benefit from surgery
— id: 134079, year: 2011, vol: 6, page: e16430, stat: Journal Article,

Comparison of the antiepileptic properties of transmeningeally delivered muscimol, lidocaine, midazolam, pentobarbital and GABA, in rats
Baptiste, Shirn L; Tang, Hai M; Kuzniecky, Ruben I; Devinsky, Orrin; French, Jacqueline A; Ludvig, Nandor
2010 Jan 29;469(3):421-424, Neuroscience letters
This study compared the potencies of epidurally delivered muscimol, lidocaine, midazolam, pentobarbital and gamma-aminobutyric acid (GABA) to prevent focal neocortical seizures induced by locally applied acetylcholine (Ach), in rats (n=5). An epidural cup was chronically implanted over the right somatosensory cortex in each animal, with epidural EEG electrodes placed posterior to the edge of the cup. After recovery, either artificial cerebrospinal fluid (ACSF; control solution) or one of the five drugs was delivered into epidural cup, followed by Ach administration into the cup to induce seizures. EEG seizure duration ratio was calculated for each drug delivery/seizure induction session to determine the potency of ACSF and the drugs to prevent the focal Ach-seizures. The concentration of all examined drug solutions was 1.0mM. ACSF, lidocaine, midazolam, pentobarbital and GABA all failed to prevent the Ach-induced neocortical EEG seizures, yielding EEG seizure duration ratios ranging from 0.41 to 0.80. In contrast, muscimol pretreatment fully prevented the development of ictal EEG in all animals. These results suggest that when used at low concentration muscimol was the best of the five drugs for transmeningeal pharmacotherapy trials for focal neocortical epilepsy
— id: 106495, year: 2010, vol: 469, page: 421, stat: Journal Article,

Phonetically irregular word pronunciation and cortical thickness in the adult brain
Blackmon, Karen; Barr, William B; Kuzniecky, Ruben; Dubois, Jonathan; Carlson, Chad; Quinn, Brian T; Blumberg, Mark; Halgren, Eric; Hagler, Donald J; Mikhly, Mark; Devinsky, Orrin; McDonald, Carrie R; Dale, Anders M; Thesen, Thomas
2010 Jul 15;51(4):1453-1458, Neuroimage
Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high-resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTAR), is associated with regional variations in cortical structure. A sample of 60 right-handed, neurologically intact individuals were administered the WTAR and underwent 3T volumetric MRI. Using quantitative, surface-based image analysis, cortical thickness was estimated at each vertex on the cortical mantle and correlated with WTAR scores while controlling for age. Higher scores on the WTAR were associated with thicker cortex in bilateral anterior superior temporal gyrus, bilateral angular gyrus/posterior superior temporal gyrus, and left hemisphere intraparietal sulcus. Higher scores were also associated with thinner cortex in left hemisphere posterior fusiform gyrus and central sulcus, bilateral inferior frontal gyrus, and right hemisphere lingual gyrus and supramarginal gyrus. These results suggest that the ability to correctly pronounce phonetically irregular words is associated with structural variations in cortical areas that are commonly activated in functional neuroimaging studies of word reading, including areas associated with grapheme-to-phonemic conversion
— id: 109791, year: 2010, vol: 51, page: 1453, stat: Journal Article,

Response to Comment on "The Human K-Complex Represents an Isolated Cortical Down-State"
Cash, Sydney S.; Halgren, Eric; Dehghani, Nima; Rossetti, Andrea O.; Thesen, Thomas; Wang, ChunMao; Devinsky, Orrin; Kuzniecky, Ruben; Doyle, Werner; Madsen, Joseph R.; Eross, Lorand; Halasz, Peter; Karmos, George; Csercsa, Richard; Wittner, Lucia; Ulbert, Istvan
2010 OCT 1 ;330(6000):-, Science
— id: 113748, year: 2010, vol: 330, page: , stat: Journal Article,

Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex
Keller, Corey J; Truccolo, Wilson; Gale, John T; Eskandar, Emad; Thesen, Thomas; Carlson, Chad; Devinsky, Orrin; Kuzniecky, Ruben; Doyle, Werner K; Madsen, Joseph R; Schomer, Donald L; Mehta, Ashesh D; Brown, Emery N; Hochberg, Leigh R; Ulbert, Istvan; Halgren, Eric; Cash, Sydney S
2010 Jun;133(Pt 6):1668-1681, Brain
Epileptic cortex is characterized by paroxysmal electrical discharges. Analysis of these interictal discharges typically manifests as spike-wave complexes on electroencephalography, and plays a critical role in diagnosing and treating epilepsy. Despite their fundamental importance, little is known about the neurophysiological mechanisms generating these events in human focal epilepsy. Using three different systems of microelectrodes, we recorded local field potentials and single-unit action potentials during interictal discharges in patients with medically intractable focal epilepsy undergoing diagnostic workup for localization of seizure foci. We studied 336 single units in 20 patients. Ten different cortical areas and the hippocampus, including regions both inside and outside the seizure focus, were sampled. In three of these patients, high density microelectrode arrays simultaneously recorded between 43 and 166 single units from a small (4 mm x 4 mm) patch of cortex. We examined how the firing rates of individual neurons changed during interictal discharges by determining whether the firing rate during the event was the same, above or below a median baseline firing rate estimated from interictal discharge-free periods (Kruskal-Wallis one-way analysis, P<0.05). Only 48% of the recorded units showed such a modulation in firing rate within 500 ms of the discharge. Units modulated during the discharge exhibited significantly higher baseline firing and bursting rates than unmodulated units. As expected, many units (27% of the modulated population) showed an increase in firing rate during the fast segment of the discharge (+ or - 35 ms from the peak of the discharge), while 50% showed a decrease during the slow wave. Notably, in direct contrast to predictions based on models of a pure paroxysmal depolarizing shift, 7.7% of modulated units recorded in or near the seizure focus showed a decrease in activity well ahead (0-300 ms) of the discharge onset, while 12.2% of units increased in activity in this period. No such pre-discharge changes were seen in regions well outside the seizure focus. In many recordings there was also a decrease in broadband field potential activity during this same pre-discharge period. The different patterns of interictal discharge-modulated firing were classified into more than 15 different categories. This heterogeneity in single unit activity was present within small cortical regions as well as inside and outside the seizure onset zone, suggesting that interictal epileptiform activity in patients with epilepsy is not a simple paroxysm of hypersynchronous excitatory activity, but rather represents an interplay of multiple distinct neuronal types within complex neuronal networks
— id: 114446, year: 2010, vol: 133, page: 1668, stat: Journal Article,

Multimodal imaging of repetition priming: Using fMRI, MEG, and intracranial EEG to reveal spatiotemporal profiles of word processing
McDonald, Carrie R; Thesen, Thomas; Carlson, Chad; Blumberg, Mark; Girard, Holly M; Trongnetrpunya, Amy; Sherfey, Jason S; Devinsky, Orrin; Kuzniecky, Rubin; Dolye, Werner K; Cash, Sydney S; Leonard, Matthew K; Hagler, Donald J Jr; Dale, Anders M; Halgren, Eric
2010 Nov 1;53(2):707-717, Neuroimage
Repetition priming is a core feature of memory processing whose anatomical correlates remain poorly understood. In this study, we use advanced multimodal imaging (functional magnetic resonance imaging (fMRI) and magnetoencephalography; MEG) to investigate the spatiotemporal profile of repetition priming. We use intracranial electroencephalography (iEEG) to validate our fMRI/MEG measurements. Twelve controls completed a semantic judgment task with fMRI and MEG that included words presented once (new, 'N') and words that repeated (old, 'O'). Six patients with epilepsy completed the same task during iEEG recordings. Blood-oxygen level dependent (BOLD) responses for N vs. O words were examined across the cortical surface and within regions of interest. MEG waveforms for N vs. O words were estimated using a noise-normalized minimum norm solution, and used to interpret the timecourse of fMRI. Spatial concordance was observed between fMRI and MEG repetition effects from 350 to 450 ms within bilateral occipitotemporal and medial temporal, left prefrontal, and left posterior temporal cortex. Additionally, MEG revealed widespread sources within left temporoparietal regions, whereas fMRI revealed bilateral reductions in occipitotemporal and left superior frontal, and increases in inferior parietal, precuneus, and dorsolateral prefrontal activity. BOLD suppression in left posterior temporal, left inferior prefrontal, and right occipitotemporal cortex correlated with MEG repetition-related reductions. IEEG responses from all three regions supported the timecourse of MEG and localization of fMRI. Furthermore, iEEG decreases to repeated words were associated with decreased gamma power in several regions, providing evidence that gamma oscillations are tightly coupled to cognitive phenomena and reflect regional activations seen in the BOLD signal
— id: 134081, year: 2010, vol: 53, page: 707, stat: Journal Article,

DISRUPTIONS OF THE DEFAULT MODE NETWORK IN PATIENTS WITH PRIMARY GENERALIZED EPILEPSY
McGill, M.; Milhalm, M.; Carlson, C.; DuBois, J.; Quinn, B.; Wang, H.; Kuzniecky, R.; Devinsky, O.; French, J.; Halgren, E.; Castellano, X.; Thesen, T.
2010 JUN ;51(8):90-90, Epilepsia
— id: 112189, year: 2010, vol: 51, page: 90, stat: Journal Article,

Diagnostic validity of a neuropsychological test battery for Hispanic patients with epilepsy
Barr, William B; Bender, Heidi A; Morrison, Chris; Cruz-Laureano, Daniel; Vazquez, Blanca; Kuzniecky, Ruben
2009 Nov;16(3):479-483, Epilepsy & behavior
The Neuropsychological Screening Battery for Hispanics (NeSBHIS) was developed to address the growing need for linguistically appropriate Spanish-language assessment measures. Despite the potential benefits to clinical practice, no prior study has assessed its diagnostic validity in populations with epilepsy. One hundred and fifteen patients with confirmed epilepsy were evaluated via the NeSBHIS; these data were standardized according to age- and education-based norms. Performance decrements were observed in more than 40% of participants on measures of processing speed and naming. Deficits in verbal and visual recall were also exhibited by 29 and 26% of the sample, respectively. No significant differences in test performance emerged between patients with VEEG evidence of left (N=48) versus right (N=24) temporal lobe epilepsy. Although the NeSBHIS is sensitive to the cognitive impairments commonly observed in populations with epilepsy, there are limitations to its ability to identify lateralized neuropsychological impairment in patients with temporal lobe epilepsy
— id: 105248, year: 2009, vol: 16, page: 479, stat: Journal Article,

INTRA-OPERATIVE NEUROMOLECULAR IMAGING (NMI) IN NEOCORTEX OF EPILEPSY PATIENTS: COMPARISON WITH RESECTED EPILEPTOGENIC TISSUE
Broderick, PA; Doyle, WK; Pacia, SV; Kuzniecky, RI; Devinsky, O; Kolodny, EH
2009 NOV ;50(1):47-48, Epilepsia
— id: 106071, year: 2009, vol: 50, page: 47, stat: Journal Article,

QUANTITATIVE MAGNETIC RESONANCE IMAGING FINDINGS IN IDIOPATHIC GENERALIZED EPILEPSY
Carlson, C; DuBois, J; Marcuse, L; Kuzniecky, R; Devinsky, O; Boo, C; Mikhly, M; Blumberg, M; Thesen, T
2009 ;50:442-442, Epilepsia
— id: 106075, year: 2009, vol: 50, page: 442, stat: Journal Article,

The human K-complex represents an isolated cortical down-state
Cash, Sydney S; Halgren, Eric; Dehghani, Nima; Rossetti, Andrea O; Thesen, Thomas; Wang, Chunmao; Devinsky, Orrin; Kuzniecky, Ruben; Doyle, Werner; Madsen, Joseph R; Bromfield, Edward; Eross, Lorand; Halasz, Peter; Karmos, George; Csercsa, Richard; Wittner, Lucia; Ulbert, Istvan
2009 May 22;324(5930):1084-1087, Science
The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K-complex (KC), which occurs in slow-wave sleep. Here, we show that KCs are generated in widespread cortical areas by outward dendritic currents in the middle and upper cortical layers, accompanied by decreased broadband EEG power and decreased neuronal firing, which demonstrate a steep decline in network activity. Thus, KCs are isolated 'down-states,' a fundamental cortico-thalamic processing mode already characterized in animals. This correspondence is compatible with proposed contributions of the KC to sleep preservation and memory consolidation
— id: 114449, year: 2009, vol: 324, page: 1084, stat: Journal Article,

STRUCTURAL BRAIN ABNORMALITIES IN POSTICTAL PSYCHOSIS
DuBois, J; Carlson, C; Kuzniecky, R; Devinsky, O; Alper, K; Blumberg, M; Mikhly, M; Starner, K; Thesen, T
2009 ;50:447-447, Epilepsia
— id: 106076, year: 2009, vol: 50, page: 447, stat: Journal Article,

Guidelines for imaging infants and children with recent-onset epilepsy
Gaillard, William D; Chiron, Catherine; Cross, J Helen; Harvey, A Simon; Kuzniecky, Ruben; Hertz-Pannier, Lucie; Vezina, L Gilbert
2009 Sep;50(9):2147-2153, Epilepsia
The International League Against Epilepsy (ILAE) Subcommittee for Pediatric Neuroimaging examined the usefulness of, and indications for, neuroimaging in the evaluation of children with newly diagnosed epilepsy. The retrospective and prospective published series with n > or = 30 utilizing computed tomography (CT) and magnetic resonance imaging (MRI) (1.5 T) that evaluated children with new-onset seizure(s) were reviewed. Nearly 50% of individual imaging studies in children with localization-related new-onset seizure(s) were reported to be abnormal; 15-20% of imaging studies provided useful information on etiology or and seizure focus, and 2-4% provided information that potentially altered immediate medical management. A significant imaging abnormality in the absence of a history of a localization-related seizure, abnormal neurologic examination, or focal electroencephalography (EEG) is rare. Imaging studies in childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and benign childhood epilepsy with centrotemporal spikes (BECTS) do not identify significant structural abnormalities. Imaging provides important contributions to establishing etiology, providing prognostic information, and directing treatment in children with recently diagnosed epilepsy. Imaging is recommended when localization-related epilepsy is known or suspected, when the epilepsy classification is in doubt, or when an epilepsy syndrome with remote symptomatic cause is suspected. When available, MRI is preferred to CT because of its superior resolution, versatility, and lack of radiation
— id: 114451, year: 2009, vol: 50, page: 2147, stat: Journal Article,

Intracranial microprobe for evaluating neuro-hemodynamic coupling in unanesthetized human neocortex
Keller, Corey J; Cash, Sydney S; Narayanan, Suresh; Wang, Chunmao; Kuzniecky, Ruben; Carlson, Chad; Devinsky, Orrin; Thesen, Thomas; Doyle, Werner; Sassaroli, Angelo; Boas, David A; Ulbert, Istvan; Halgren, Eric
2009 May 15;179(2):208-218, Journal of neuroscience methods
Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a 'laminar optode,' a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans
— id: 114450, year: 2009, vol: 179, page: 208, stat: Journal Article,

Effect of epilepsy magnetic source imaging on intracranial electrode placement
Knowlton, Robert C; Razdan, Shantanu N; Limdi, Nita; Elgavish, Rotem A; Killen, Jeff; Blount, Jeffrey; Burneo, Jorge G; Ver Hoef, Lawrence; Paige, Lebron; Faught, Edward; Kankirawatana, Pongkiat; Bartolucci, Al; Riley, Kristen; Kuzniecky, Ruben
2009 Jun;65(6):716-723, Annals of neurology
OBJECTIVE: Intracranial electroencephalography (ICEEG) with chronically implanted electrodes is a costly invasive diagnostic procedure that remains necessary for a large proportion of patients who undergo evaluation for epilepsy surgery. This study was designed to evaluate whether magnetic source imaging (MSI), a noninvasive test based on magnetoencephalography source localization, can supplement ICEEG by affecting electrode placement to improve sampling of the seizure onset zone(s). METHODS: Of 298 consecutive epilepsy surgery candidates (between 2001 and 2006), 160 patients were prospectively enrolled by insufficient localization from seizure monitoring and magnetic resonance imaging results. Before presenting MSI results, decisions were made whether to proceed with ICEEG, and if so, where to place electrodes such that the hypothetical seizure-onset zone would be sampled. MSI results were then provided with allowance of changes to the original plan. RESULTS: MSI indicated additional electrode coverage in 18 of 77 (23%) ICEEG cases. In 39% (95% confidence interval, 16.4-61.4), seizure-onset ICEEG patterns involved the additional electrodes indicated by MSI. Sixty-two patients underwent surgical resection based on ICEEG recording of seizures. Highly localized MSI was significantly associated with seizure-free outcome (mean, 3.4 years; minimum, >1 year) for the entire surgical population (n = 62). INTERPRETATION: MSI spike localization increases the chance that the seizure-onset zone is sampled when patients undergo ICEEG for presurgical epilepsy evaluations. The clinical impact of this effect, improving diagnostic yield of ICEEG, should be considered in surgery candidates who do not have satisfactory indication of epilepsy localization from seizure semiology, electroencephalogram, and magnetic resonance imaging
— id: 114448, year: 2009, vol: 65, page: 716, stat: Journal Article,

Epilepsy: Is localization-related epilepsy a progressive disorder? Maybe..
Kuzniecky, Ruben; Thesen, Thomas; Devinsky, Orrin
2009 Jul;5(7):356-357, Nature reviews. Neurology
— id: 101386, year: 2009, vol: 5, page: 356, stat: Journal Article,

Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: Therapeutic implications
Ludvig, Nandor; Baptiste, Shirn L; Tang, Hai M; Medveczky, Geza; von Gizycki, Hans; Charchaflieh, Jean; Devinsky, Orrin; Kuzniecky, Ruben I
2009 Apr;50(4):678-693, Epilepsia
Summary Purpose: To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)-induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity. Methods: Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or muscimol (0.25-12.5 mm) was delivered locally as a 'pretreatment,' followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and muscimol (2.5 mm) exposures were measured. In a last group of four rats, muscimol (0.8-2.5 mm) was delivered epidurally during the ongoing, Ach-induced EEG seizure. Results: In contrast to ACSF pretreatments, epidural muscimol pretreatment in rats completely prevented the seizures at and above 2.5 mm. In the monkeys, subarachnoid muscimol pretreatments at 2.5 mm completely prevented the focal-seizure-inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 mm epidural muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1-3 min. Conclusions: The results of this study suggest that muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy
— id: 95775, year: 2009, vol: 50, page: 678, stat: Journal Article,

Distributed source modeling of language with magnetoencephalography: Application to patients with intractable epilepsy
McDonald, Carrie R; Thesen, Thomas; Hagler, Donald J Jr; Carlson, Chad; Devinksy, Orrin; Kuzniecky, Rubin; Barr, William; Gharapetian, Lusineh; Trongnetrpunya, Amy; Dale, Anders M; Halgren, Eric
2009 Oct;50(10):2256-2266, Epilepsia
Purpose: To examine distributed patterns of language processing in healthy controls and patients with epilepsy using magnetoencephalography (MEG), and to evaluate the concordance between laterality of distributed MEG sources and language laterality as determined by the intracarotid amobarbital procedure (IAP). Methods: MEG was performed in 10 healthy controls using an anatomically constrained, noise-normalized distributed source solution (dynamic statistical parametric map, dSPM). Distributed source modeling of language was then applied to eight patients with intractable epilepsy. Average source strengths within temporoparietal and frontal lobe regions of interest (ROIs) were calculated, and the laterality of activity within ROIs during discrete time windows was compared to results from the IAP. Results: In healthy controls, dSPM revealed activity in visual cortex bilaterally from approximately 80 to 120 ms in response to novel words and sensory control stimuli (i.e., false fonts). Activity then spread to fusiform cortex approximately 160-200 ms, and was dominated by left hemisphere activity in response to novel words. From approximately 240 to 450 ms, novel words produced activity that was left-lateralized in frontal and temporal lobe regions, including anterior and inferior temporal, temporal pole, and pars opercularis, as well as bilaterally in posterior superior temporal cortex. Analysis of patient data with dSPM demonstrated that from 350 to 450 ms, laterality of temporoparietal sources agreed with the IAP 75% of the time, whereas laterality of frontal MEG sources agreed with the IAP in all eight patients. Discussion: Our results reveal that dSPM can unveil the timing and spatial extent of language processes in patients with epilepsy and may enhance knowledge of language lateralization and localization for use in preoperative planning
— id: 101387, year: 2009, vol: 50, page: 2256, stat: Journal Article,

Classification of patterns of EEG synchronization for seizure prediction
Mirowski, Piotr; Madhavan, Deepak; Lecun, Yann; Kuzniecky, Ruben
2009 Nov;120(11):1927-1940, Clinical neurophysiology
OBJECTIVE: Research in seizure prediction from intracranial EEG has highlighted the usefulness of bivariate measures of brainwave synchronization. Spatio-temporal bivariate features are very high-dimensional and cannot be analyzed with conventional statistical methods. Hence, we propose state-of-the-art machine learning methods that handle high-dimensional inputs. METHODS: We computed bivariate features of EEG synchronization (cross-correlation, nonlinear interdependence, dynamical entrainment or wavelet synchrony) on the 21-patient Freiburg dataset. Features from all channel pairs and frequencies were aggregated over consecutive time points, to form patterns. Patient-specific machine learning-based classifiers (support vector machines, logistic regression or convolutional neural networks) were trained to discriminate interictal from preictal patterns of features. In this explorative study, we evaluated out-of-sample seizure prediction performance, and compared each combination of feature type and classifier. RESULTS: Among the evaluated methods, convolutional networks combined with wavelet coherence successfully predicted all out-of-sample seizures, without false alarms, on 15 patients, yielding 71% sensitivity and 0 false positives. CONCLUSIONS: Our best machine learning technique applied to spatio-temporal patterns of EEG synchronization outperformed previous seizure prediction methods on the Freiburg dataset. SIGNIFICANCE: By learning spatio-temporal dynamics of EEG synchronization, pattern recognition could capture patient-specific seizure precursors. Further investigation on additional datasets should include the seizure prediction horizon
— id: 114447, year: 2009, vol: 120, page: 1927, stat: Journal Article,

Postictal psychosis in partial epilepsy: a case-control study
Alper, Kenneth; Kuzniecky, Ruben; Carlson, Chad; Barr, William B; Vorkas, Charles K; Patel, Jignasa G; Carrelli, Angela L; Starner, Karen; Flom, Peter L; Devinsky, Orrin
2008 May;63(5):602-610, Annals of neurology
OBJECTIVE: Divergent findings among prior studies on correlates of risk for postictal psychosis (PIP) suggest the value of a controlled study involving a relatively large number of patients. METHODS: The study population consisted of a consecutive series of 59 patients with partial epilepsy and a history of PIP, and 94 control patients with partial epilepsy and no history of PIP evaluated as inpatients with video-electroencephalography. The groups did not differ significantly regarding demographic features. Exact tests yielded a subset of variables and a tentative interpretation that were evaluated further utilizing principal components analysis and logistic regression. RESULTS: PIP was associated with extratemporal versus temporal (p = 0.036) or undetermined (p = 0.001) localization of seizure onset, bilateral interictal epileptiform activity (p = 0.017), secondary generalization (p = 0.049), and history of encephalitis (p = 0.018). Interictal slow activity was more frequently absent in control patients (p = 0.045). PIP was associated with family histories of psychiatric disorders (p = 0.007) and epilepsy (p = 0.042), which themselves were significantly intercorrelated (r = 0.225; p = 0.006). Age of onset or duration of epilepsy and lateralized electroencephalographic or magnetic resonance imaging asymmetries did not differ significantly between control and PIP groups. The analysis indicated four underlying domains of risk for PIP: ambiguous/extratemporal localization, family neuropsychiatric history, abnormal interictal electroencephalographic activity, and encephalitis. Each unit increase on a simple additive scale composed of 9 dichotomous independent variables multiplied the odds ratio for PIP by 1.71 (95% confidence interval, 1.36-2.15; p < 0.0001). INTERPRETATION: PIP in partial epilepsy is associated with relatively broadly and bilaterally distributed epileptogenic networks, genetic determinants of psychiatric disorders and seizures, and encephalitis
— id: 79550, year: 2008, vol: 63, page: 602, stat: Journal Article,

EPIDURAL AND SUBDURAL MUSCIMOL DELIVERIES IN RATS AND MONKEYS, RESPECTIVELY, PREVENT FOCAL SEIZURES AT CONCENTRATIONS THAT CAUSE NO BEHAVIORAL SIDE-EFFECTS
Baptiste, SL; Tang, HM; Devinsky, O; Kuzniecky, RI; Charchaflieh, J; von Gizycki, H; Ludvig, N
2008 DEC ;49(12):375-376, Epilepsia
— id: 91398, year: 2008, vol: 49, page: 375, stat: Journal Article,

Kaplan-Meier analysis on seizure outcome after epilepsy surgery: do gender and race influence it?
Burneo, Jorge G; Villanueva, Vicente; Knowlton, Robert C; Faught, R Edward; Kuzniecky, Ruben I
2008 Jun;17(4):314-319, Seizure
OBJECTIVE: To evaluate seizure outcome following epilepsy surgery for patients with temporal lobe epilepsy and evaluate is gender and race/ethnicity influence it. METHODS: Data were obtained from the discharge database of the University of Alabama at Birmingham, Epilepsy Center, between 1985 and 2001. The sample consisted of all patients with a primary diagnosis of medically intractable temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy. Seizure recurrence was tabulated at 7 days, 2 months, 6 months, 1, 2, 3, 4, 5, and 6 years following surgery. Logistic regression analysis was used to model the presence of seizure recurrence after anterior temporal lobectomy for all patients. Kaplan-Meier analysis was done to obtain estimates and 95% CIs of seizure freedom from baseline. Baseline variables--age at surgery, age at seizure onset, sex, side of resection, immediate postoperative seizures, and pathology results--were assessed as potential predictors of each outcome by comparing the survival curves within each variable with a log rank test. RESULTS: Three hundred sixty-eight patients underwent surgical treatment for TLE, mean age of 30.2 years. Thirty-five patients were African American, 43% were men. Immediate postoperative seizures were seen in 23 patients, while seizure recurrence occurred in 27.3% patients within a year after surgery, and in 33.6% within 6 years. Logistic regression results showed no differences between African Americans and whites, between males and females. The occurrence of immediate postoperative seizures was a strong predictor of late seizure recurrence only at 1 year after surgery. CONCLUSIONS: The occurrence of seizures in the immediate postoperative period is a strong predictor of later seizure recurrence. Sex and race/ethnicity do not appear to be predictors of long-term outcome following surgery for temporal lobe epilepsy
— id: 95777, year: 2008, vol: 17, page: 314, stat: Journal Article,

Epilepsy
Gazzola, Deana M; Kuzniecky, Ruben I
2008 Winter;5(1):34-36, Reviews in Neurological Diseases
— id: 95776, year: 2008, vol: 5, page: 34, stat: Journal Article,

Temporal lobe epilepsy does not impair visual perception
Grant, Arthur C; Donnelly, Kiely M; Chubb, Charlie; Barr, William B; Kuzniecky, Ruben; Devinsky, Orrin
2008 Apr;49(4):710-713, Epilepsia
Temporal lobe epilepsy (TLE) can impair interictal cognitive function. In the perceptual domain, previous psychophysical studies demonstrated specific deficits in auditory and tactile perception in patients with TLE. This study compared performance of 25 TLE subjects and 27 controls on two low-level, visual tasks: luminance discrimination and frequency discrimination. Both tasks were performed under a relatively easy and a relatively difficult condition, by adjusting the stimulus duration. TLE subjects performed as well as controls on both tasks at both stimulus durations. These results imply that interictal occipital lobe function, as reflected in performance on low-level visual tasks, is not impaired in TLE, consistent with functional imaging data. Furthermore, since TLE subjects performed normally while taking therapeutic doses of multiple AEDs, the data suggest that these AEDs do not impair visual perception
— id: 95086, year: 2008, vol: 49, page: 710, stat: Journal Article,

EFFECT OF MAGNETIC SOURCE IMAGING ON INTRACRANIAL EEG RECORDING IN EPILEPSY SURGERY
Knowlton, R; Razdan, S; Riley, K; Blount, J; Limdi, NA; Elgavish, R; Kankirawatana, P; Burneo, JG; Paige, AL; Hoef, LV; Faught, E; Howell, J; Kuzniecky, RI
2008 ;49(4):303-303, Epilepsia
— id: 104850, year: 2008, vol: 49, page: 303, stat: Journal Article,

Functional imaging: II. Prediction of epilepsy surgery outcome
Knowlton, Robert C; Elgavish, Rotem A; Bartolucci, Al; Ojha, Buddhiwardhan; Limdi, Nita; Blount, Jeffrey; Burneo, Jorge G; Ver Hoef, Lawrence; Paige, Lebron; Faught, Edward; Kankirawatana, Pongkiat; Riley, Kristen; Kuzniecky, Ruben
2008 Jul;64(1):35-41, Annals of neurology
OBJECTIVE: To gain information on the value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and ictal single photon emission computed tomography (SPECT) to predict seizure-free outcome following epilepsy surgery in patients who require intracranial electroencephalography (ICEEG). METHODS: This work was part of a prospective observation study of epilepsy surgery candidates not sufficiently localized with scalp EEG and MRI. Of 160 patients enrolled 62 completed ICEEG and subsequent surgical resection. Sixty-one percent resulted in an Engel I seizure-free outcome at a minimum of one-year follow-up (mean = 3.4 years). Sensitivity, specificity, and predictive values were computed for each modality. Multivariate logistical regression was used to identify prediction of surgical outcome by imaging test. RESULTS: MSI sensitivity for a conclusively localized study was 55% with a positive predictive value of 78%. Eliminating non-diagnostic MSI cases (no spikes captured during recording) yielded a corrected negative predictive value of 64%. With available comparison subgroups FDG-PET and ictal SPECT values were similar to MSI. The OR (adjusted for epilepsy and MRI classification) for MSI prediction of seizure-free outcome was 4.4 (p =0.01). In cases with both PET and MSI, the adjusted OR for PET was 7.1 (p <0.01) and for MSI was 6.4 (p = 0.01). In the cases with all three tests (n = 27), ictal SPECT had the highest OR of 9.1 (p = 0.05). INTERPRETATION: MSI, FDG-PET, and ictal SPECT each have clinical value in predicting seizure-free surgical outcome in epilepsy surgery candidates who typically require ICEEG
— id: 114452, year: 2008, vol: 64, page: 35, stat: Journal Article,

Functional imaging: I. Relative predictive value of intracranial electroencephalography
Knowlton, Robert C; Elgavish, Rotem A; Limdi, Nita; Bartolucci, Al; Ojha, Buddhiwardhan; Blount, Jeffrey; Burneo, Jorge G; Ver Hoef, Lawrence; Paige, Lebron; Faught, Edward; Kankirawatana, Pongkiat; Riley, Kristen; Kuzniecky, Ruben
2008 Jul;64(1):25-34, Annals of neurology
OBJECTIVE: To gain information on the predictive and prognostic value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET), and ictal single-photon emission computed tomography (SPECT) as compared with intracranial electroencephalography (ICEEG) localization in epilepsy surgery. METHODS: This work was part of a cohort study of epilepsy surgery candidates not sufficiently localized with noninvasive studies. Of 160 patients enrolled over 4 years, 77 completed ICEEG seizure monitoring. Sensitivity, specificity, and predictive values relative to ICEEG were computed for each modality. RESULTS: Seizures were not captured in five patients. Of the 72 diagnostic ICEEG studies, seizure localization results were 74% localized, 10% multifocal, and 17% nonlocalized. Sixty-one percent were localized to neocortical regions. Depending on patient subgroup pairs, sensitivity ranged from 58 to 64% (MSI), 22 to 40% (PET), and 39 to 48% (SPECT); specificity ranges were 79 to 88% (MSI), 53 to 63% (PET), and 44 to 50% (SPECT). Gains in diagnostic yield were seen only with the combination of MSI and PET or MSI and ictal SPECT. Localization concordance with ICEEG was greatest with MSI, but a significant difference was demonstrated only between MSI and PET. Moderate redundancy was seen between PET and ictal SPECT (kappa = 0.452; p = 0.011). INTERPRETATION: Conclusively positive MSI has a high predictive value for seizures localized with ICEEG. Diagnostic gain may be achieved with addition of either PET or ictal SPECT to MSI. Diagnostic values for imaging tests are lower than 'true values' because of the limitations of ICEEG as a gold standard
— id: 114453, year: 2008, vol: 64, page: 25, stat: Journal Article,

Levetiracetam has no acute effects on brain gamma-aminobutyric acid levels
Kuzniecky, R; Pan, J; Burns, A; Devinsky, O; Hetherington, H
2008 Feb;12(2):242-244, Epilepsy & behavior
OBJECTIVE: The mechanism of action of levetiracetam (LEV), an antiepileptic drug, is related to a novel binding site, SV2, but LEV acts on GABA-A receptors. The objective of the study described here was to determine if LEV modulates brain GABA in vivo. METHODS: Concentrations of cerebral GABA and serum LEV were obtained in seven healthy individuals using 1H magnetic resonance spectroscopy at baseline and 3 and 6 hours following oral administration of 1 g of LEV. RESULTS: Brain cerebral GABA acutely concentrations did not change from baseline. CONCLUSION: The results indicate that LEV does not increase human cerebral GABA concentrations acutely in healthy individuals
— id: 76394, year: 2008, vol: 12, page: 242, stat: Journal Article,

Malformations of cortical development
Kuzniecky, Ruben I; Jackson, Graeme D
Epilepsy : a comprehensive textbook Philadelphia PA : Wolters Kluwer/Lippincott Williams & Wilkins, 2008,
— id: 5443, year: 2008, vol: ?, page: ?, stat: Chapter,

Structural neuroimaging
Kuzniecky, Ruben I; Jackson, Graeme D
Epilepsy : a comprehensive textbook Philadelphia PA : Wolters Kluwer/Lippincott Williams & Wilkins, 2008,
— id: 5449, year: 2008, vol: ?, page: ?, stat: Chapter,

Histological evidence for drug diffusion across the cerebral meninges into the underlying neocortex in rats
Ludvig, Nandor; Sheffield, Lynette G; Tang, Hai M; Baptiste, Shirn L; Devinsky, Orrin; Kuzniecky, Ruben I
2008 Jan 10;1188:228-232, Brain research
Transmeningeal pharmacotherapy has been proposed to treat neurological disorders with localized pathology, such as intractable focal epilepsy. As a step toward understanding the diffusion and intracortical spread of transmeningeally delivered drugs, the present study used histological methods to determine the extent to which a marker compound, N-methyl-D-aspartate (NMDA), can diffuse into the neocortex through the meninges. Rats were implanted with bilateral parietal cortical epidural cups filled with 50 mM NMDA on the right side and artificial cerebrospinal fluid (ACSF) in the contralateral side. After 24 h, the histological effects of these treatments were evaluated using cresyl violet (Nissl) staining. The epidural NMDA exposure caused neuronal loss that in most animals extended from the pial surface through layer V. The area indicated by this neuronal loss was localized to the neocortical region underlying the epidural cup. These results suggest that NMDA-like, water soluble, small molecules can diffuse through the subdural/subarachnoid space into the underlying neocortex and spread in a limited fashion, close to the meningeal penetration site
— id: 79135, year: 2008, vol: 1188, page: 228, stat: Journal Article,

Effects of subdural application of lidocaine in patients with focal epilepsy
Madhavan, Deepak; Mirowski, Piotr; Ludvig, Nandor; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Kuzniecky, Ruben
2008 Feb;78(2-3):235-239, Epilepsy research
Antiepileptic drug (AED) delivery directly into the neocortex has recently been shown to be able to both prevent and terminate focal seizures in rats. The present clinical experiment aimed to test the local effects of lidocaine delivered onto the pia mater adjacent to epileptogenic zones in human patients. Administration of lidocaine resulted in a marked diminishment of spike counts on all patients, with a decremental effect of lidocaine on the faster frequency elements of individual spikes and overall testing epochs. The direct cortical application of lidocaine appears to affect local epileptogenic activity in human patients with intractable focal epilepsy
— id: 78353, year: 2008, vol: 78, page: 235, stat: Journal Article,

Rey Osterrieth complex figure test spatial and figural scoring: relations to seizure focus and hippocampal pathology in patients with temporal lobe epilepsy
McConley, Regina; Martin, Roy; Palmer, Cheryl Ann; Kuzniecky, Ruben; Knowlton, Robert; Faught, Edward
2008 Jul;13(1):174-177, Epilepsy & behavior
The purpose of the study was to compare figural and spatial memory in patients with left (LTLE, n=56) and right (RTLE, n=48) temporal lobe epilepsy using J.I. Breier and colleagues' (J Int Neuropsychol Soc 1996;2:535-40) figural/spatial scoring method for the Rey Osterrieth Complex Figure Test (RCFT). The study also examined the association between figural and spatial components of the RCFT, temporal lobe laterality, and hippocampal structure (MRI hippocampal volumes and neuropathology ratings). Neither immediate or delayed trial figural and spatial memory scores were associated with seizure laterality or hippocampal pathology ratings. Immediate and delayed recall scores were not associated with right hippocampal volume. However, modestly positive correlations were found between left hippocampal volume and RCFT delayed recall scores. Similar to recent work (A.C. Kneebone et al., J Int Neuropsychol Soc 2007;13:664-71), stronger associations were related to left temporal lobe function. This study provides further evidence for the lack of sensitivity of the RCFT as a surrogate measure of right temporal lobe memory function
— id: 79400, year: 2008, vol: 13, page: 174, stat: Journal Article,

Distributed Source Modeling of Language with Magnetoencephalography: Application to Patients with Left Temporal Lobe Epilepsy
McDonald, CR; Thesen, T; Hagler, DJ; Carlson, C; Devinksy, O; Kuzniecky, R; Barr, W; Patel, RH; Gharapetian, L; Dale, AM; Halgren, E
2008 DEC ;64(6):S150-S150, Annals of neurology
— id: 98111, year: 2008, vol: 64, page: S150, stat: Journal Article,

SEIZURE PREDICTION USING MACHINE LEARNING ON BIVARIATE FEATURES FROM EEG
Mirowski, P; Madhavan, D; LeCun, Y; Kuzniecky, RI
2008 DEC ;49(12):21-22, Epilepsia
— id: 91391, year: 2008, vol: 49, page: 21, stat: Journal Article,

The interactions between sleep and epilepsy
Rodriguez, Alcibiades J; Kuzniecky, Ruben I
2008 Winter;5(1):1-7, Reviews in Neurological Diseases
The interactions between sleep and epilepsy have been recognized for centuries. The electroencephalogram and more recently the polysomnogram have helped us understand these interactions. Certain epilepsy syndromes are more common during sleep, and frequently a sleep disorder is misdiagnosed as epilepsy. Management of epilepsy includes improvements in sleep quality and quantity, and aggressive treatment of epilepsy has a positive impact on sleep disorders
— id: 79303, year: 2008, vol: 5, page: 1, stat: Journal Article,

Voltage-gated potassium channel antibody-mediated syndromes: a spectrum of clinical manifestations
Rueff, Laura; Graber, Jerome J; Bernbaum, Melissa; Kuzniecky, Ruben I
2008 Spring;5(2):65-72, Reviews in Neurological Diseases
Immune-related neurologic disorders have long been recognized. A number of specific targets have been identified, including neurons, Purkinje cells, and pre- and postsynaptic receptors. Over the past decade, antibodies against voltage-gated potassium channels (VGKCs) have been reported in a number of neurologic syndromes, such as neuromyotonia, limbic encephalitis, and Morvan's syndrome. Recent advances have supported the pathologic mechanism of VGKC in these disorders, their response to therapy, and the possible mechanisms of peripheral, central, and autonomic dysfunctions seen in these disorders. We present a patient with 1 of these syndromes and review the literature of these disorders
— id: 86655, year: 2008, vol: 5, page: 65, stat: Journal Article,

EVIDENCE FOR INCREASED NEURONAL ELECTROPHYSIOLOGICAL ACTIVITY BEFORE EEG SEIZURE ONSET IN THE RAT NEOCORTICAL SEIZURE FOCUS
Tang, HM; Mirowski, P; Baptiste, SL; Devinsky, O; Kuzniecky, RI; Ludvig, N
2008 DEC ;49(12):382-382, Epilepsia
— id: 91399, year: 2008, vol: 49, page: 382, stat: Journal Article,

Advances in epilepsy. Highlights from the 60th annual meeting of the American Epilepsy Society, December 1-5, 2006, San Diego, CA
Arnedo, Vanessa; Kuzniecky, Ruben
2007 Fall;4(4):217-221, Reviews in Neurological Diseases
— id: 76088, year: 2007, vol: 4, page: 217, stat: Journal Article,

Sex as a prognostic factor for surgical outcome in mesial temporal lobe epilepsy - Reply
Burneo, JG; Kuzniecky, RI
2007 FEB ;64(2):288-289, Archives of neurology
— id: 98057, year: 2007, vol: 64, page: 288, stat: Journal Article,

Temporal lobe epilepsy does not impair visual perception
Donnelly, K; Barr, W; Kuzniecky, R; Devinsky, O; Grant, AC
2007 OCT ;48(4):237-237, Epilepsia
— id: 104241, year: 2007, vol: 48, page: 237, stat: Journal Article,

Hippocampal 1H-MRSI correlates with severity of depression symptoms in temporal lobe epilepsy
Gilliam, F G; Maton, B M; Martin, R C; Sawrie, S M; Faught, R E; Hugg, J W; Viikinsalo, M; Kuzniecky, R I
2007 Jan 30;68(5):364-368, Neurology
OBJECTIVE: To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. METHODS: We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/N-acetylaspartate ratio maps derived from a previously validated (1)H magnetic resonance spectroscopic imaging ((1)H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. RESULTS: The extent of hippocampal (1)H-MRSI abnormalities correlated with severity of depression (Spearman rho = 0.65, p value < 0.001), but other clinical factors did not. CONCLUSION: The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability
— id: 104806, year: 2007, vol: 68, page: 364, stat: Journal Article,

A subcortical network of dysfunction in TLE measured by magnetic resonance spectroscopy
Hetherington, H P; Kuzniecky, R I; Vives, K; Devinsky, O; Pacia, S; Luciano, D; Vasquez, B; Haut, S; Spencer, D D; Pan, J W
2007 Dec 11;69(24):2256-2265, Neurology
OBJECTIVE: The goal of this work was to evaluate the relationship between neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe epilepsy (TLE) patients using (1)H magnetic resonance spectroscopic imaging. METHODS: (1)H spectroscopic images from the hippocampus and thalamus of controls and patients with TLE were acquired at 4 T. The spectroscopic imaging data were reconstructed using an automated voxel-shifting method based on anatomic landmarks providing four, six, and three loci for the hippocampus, thalamus, and putamen, respectively. For correlation analysis, the hippocampal and striatal loci were averaged to provide single estimates of the entire structure, whereas the thalamus was divided into two regions, an anterior and posterior measure, using the average of three loci each. RESULTS: The ratio of N-acetyl aspartate to creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the ipsilateral hippocampus was significantly correlated with the ipsilateral and contralateral anterior and posterior thalami, putamen, and contralateral hippocampus. In control subjects, the hippocampi were only correlated with each other. CONCLUSIONS: The data demonstrate that there is significant neuronal injury/loss in both the ipsilateral and contralateral thalami in temporal lobe epilepsy patients, with greater impairment in the anterior portions of the ipsilateral thalamus. The degree of injury/loss in the ipsilateral and contralateral thalamus and putamen is directly correlated with that of the ipsilateral hippocampus. This is consistent with the hypothesis that the impairment and damage associated with recurrent seizures as measured by N-acetyl aspartate originating in the hippocampus results in injury and impairment in other subcortical structures
— id: 104805, year: 2007, vol: 69, page: 2256, stat: Journal Article,

Predicting surgical outcome following temporal lobectomy using a neural network
Hetherington, HP; Kuzniecky, RI; Spencer, DD; Vives, K; Pan, JW
2007 ;48(24):166-166, Epilepsia
— id: 104851, year: 2007, vol: 48, page: 166, stat: Journal Article,

Transmeningeal delivery of GABA to control neocortical seizures in rats
John, Jenine E; Baptiste, Shirn L; Sheffield, Lynette G; von Gizycki, Hans; Kuzniecky, Ruben I; Devinsky, Orrin; Ludvig, Nandor
2007 Jun;75(1):10-17, Epilepsy research
Transmeningeal drug delivery, using an implanted hybrid neuroprosthesis, has been proposed as a novel therapy for intractable focal epilepsy. As part of a systematic effort to identify the optimal compounds and protocols for such a therapy, this study aimed to determine whether transmeningeal gamma-aminobutyric acid (GABA) delivery can terminate and/or prevent neocortical seizures in rats. Rats were chronically implanted with an epidural cup and an adjacent EEG electrode in the right parietal cortex. While the rat was behaving freely, a seizure-inducing concentration of acetylcholine (Ach) was applied into the cup. In a seizure termination study, either artificial cerebrospinal fluid (ACSF) or GABA (0.25, 2.5, 25 or 50mM) was delivered into the exposed neocortical area during an ongoing seizure. In a seizure prevention study, either ACSF or 50mM GABA was delivered into the epidural cup before the application of Ach. Epidural delivery of 50mM GABA completely terminated ongoing Ach-induced EEG seizures and convulsions within 17-437s after its delivery. ACSF and lower concentrations of GABA did not produce this effect, but 25mM GABA reduced seizure severity. However, the used GABA concentration could not prevent the development, or affect the severity, of Ach-induced EEG seizures and convulsions. This study indicates that transmeningeal GABA delivery can be used for terminating neocortical seizures, but to achieve seizure prevention via this route either a more efficient GABA delivery method needs to be developed or other neurotransmitters/pharmaceuticals should be employed for this purpose.
— id: 72893, year: 2007, vol: 75, page: 10, stat: Journal Article,

Surgery Insight: surgical management of epilepsy
Kuzniecky, Ruben; Devinsky, Orrin
2007 Dec;3(12):673-681, Nature clinical practice. Neurology
Epilepsy surgery has been shown to be an effective treatment for patients with intractable epilepsy. The only randomized controlled trial conducted in this setting to date found a dramatic advantage for surgery over medical treatment in temporal lobe epilepsy. In carefully selected patients, epilepsy surgery can control seizures, improve quality of life and reduce costs of medical care. Advances in diagnostic techniques are likely to improve patient selection, facilitate localization of epileptic foci and functional areas, and enable better prediction of outcomes
— id: 75674, year: 2007, vol: 3, page: 673, stat: Journal Article,

Neocortical multi-neuron recording as a potential tool for predicting focal seizures
Ludvig, N; Tang, HM; Baptiste, SL; Kuzniecky, RI; Devinsky, O
2007 OCT ;48(1):388-388, Epilepsia
— id: 87156, year: 2007, vol: 48, page: 388, stat: Journal Article,

Characterization of epileptogenic networks in tuberous sclerosis using independent component analysis
Madhavan, D; Mirowski, P; Weiner, HL; Devinsky, O; Kuzniecky, R
2007 MAR 20 ;68(12):A71-A72, Neurology
— id: 104244, year: 2007, vol: 68, page: A71, stat: Journal Article,

Effects of the subdural application of lidocaine on EEG spiking in patients with focal epilepsy
Madhavan, D; Mirowski, PW; Ludvig, N; Carlson, C; Devinsky, O; Doyle, W; Kuzniecky, R
2007 OCT ;48(4):307-308, Epilepsia
— id: 104242, year: 2007, vol: 48, page: 307, stat: Journal Article,

Temporal lobe surgery in patients with normal MRI
Madhavan, Deepak; Kuzniecky, Ruben
2007 Apr;20(2):203-207, Current opinion in neurology
PURPOSE OF REVIEW: The surgical approach to nonlesional temporal lobe epilepsy presents a significant challenge due to uncertainties regarding the extent of resection necessary to result in a seizure-free state. To outline an optimum surgical strategy, an understanding of the clinical and diagnostic presentation of mesial and lateral temporal epilepsy is required in order to properly characterize the location of the ictal onset zone. This review focuses on several methods used to identify this ictal onset zone, with emphasis on the impact each modality has on surgical outcome. RECENT FINDINGS: Factors predicting an excellent surgical outcome include the presence of a discrete zone of low voltage fast activity and prolonged propagation time on the electroencephalogram, and the absence of metabolic dysfunction in the contralateral temporal lobe. Identifying epileptogenic regions in the temporal lobe using magnetic source imaging is a recent technique that has also yielded promising surgical outcomes. Recent prospective studies have shown that a temporal neocortical resection is very effective in providing a seizure free outcome given strict localization of the ictal onset zone to the lateral temporal region, highlighting the need for accurate characterization of mesial versus lateral nonlesional epilepsy. SUMMARY: With accurate identification of the ictal onset zone with intracranial electroencephalography, a tailored temporal resection can yield excellent surgical results
— id: 72412, year: 2007, vol: 20, page: 203, stat: Journal Article,

Local epileptogenic networks in tuberous sclerosis complex: a case review
Madhavan, Deepak; Weiner, Howard L; Carlson, Chad; Devinsky, Orrin; Kuzniecky, Ruben
2007 Aug;11(1):140-146, Epilepsy & behavior
OBJECTIVE: Cortical tubers are a pathognomonic finding in some patients with tuberous sclerosis complex (TSC), and are believed to be epileptogenic foci. Surgery is an effective option in selected patients with TSC who are refractory to medical therapy. This article describes three patients with TSC who underwent three-stage epilepsy surgery at our center, with the intention of examining local electrophysiological changes after each stage of the procedure. METHODS: Magnetic resonance images were obtained after initial implantation of electrodes and after resection and electrode reimplantation. These images were co-registered and overlaid. The intracranial grids were overlaid in a similar procedure and manually traced, and then added to the volumetric image. Mean spike counts were obtained for each patient and expressed in spikes per minute. Statistical analysis was performed on spike counts prior to and after resection. RESULTS: All three patients displayed intense spiking in the regions around the dominant epileptogenic tuber. On tuber removal, spike counts diminished significantly. In each case, new areas of spiking emerged in regions remote from the tuber periphery after tuber resection, with the emergence of secondary ictal onset zones in the resection margin. CONCLUSION: This retrospective study highlights some common electrophysiological features among the patients examined. The observed epileptogenic activity and regions of ictal onset suggest that it may be the region of brain tissue surrounding the tuber that is responsible for the majority of epileptogenic activity in these patients
— id: 73894, year: 2007, vol: 11, page: 140, stat: Journal Article,

Scale for distinguishing sleep disorders from seizures
Rodriguez, Alcibiades J; Kuzniecky, Ruben I
2007 Aug;64(8):1206-1206, Archives of neurology
— id: 73403, year: 2007, vol: 64, page: 1206, stat: Journal Article,

Communication between Broca's and Wernicke's areas detected with intracranial electrophysiology in awake humans
Sahin NT; Pinker S; Cash S; Thesen T; Wang C; Devinsky O; Kuzniecky R; Doyle W; Halgren E
2007 ;36(S1):S74-S74, Neuroimage
— id: 74452, year: 2007, vol: 36, page: S74, stat: Journal Article,

Cortical abnormalities in epilepsy revealed by local EEG synchrony
Schevon, C A; Cappell, J; Emerson, R; Isler, J; Grieve, P; Goodman, R; McKhann, G Jr; Weiner, H; Doyle, W; Kuzniecky, R; Devinsky, O; Gilliam, F
2007 Mar;35(1):140-148, Neuroimage
Abnormally strong functional linkage between cortical areas has been postulated to play a role in the pathogenesis of partial epilepsy. We explore the possibility that such linkages may be manifest in the interictal EEG apart from epileptiform disturbances or visually evident focal abnormalities. We analyzed samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in nine patients with medically intractable partial epilepsy, measuring interelectrode synchrony using the mean phase coherence algorithm. This analysis revealed areas of elevated local synchrony, or 'hypersynchrony' which had persistent spatiotemporal characteristics that were unique to each patient. Measuring local synchrony in a subdural grid results in a map of the cortical surface that provides information not visually apparent on either EEG or structural imaging. We explore the relationship of hypersynchronous areas to the clinical evidence of seizure localization in each case, and speculate that local hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a valuable aid to clinical ICEEG interpretation
— id: 139498, year: 2007, vol: 35, page: 140, stat: Journal Article,

Pediatric language mapping: sensitivity of neurostimulation and Wada testing in epilepsy surgery
Schevon, Catherine A; Carlson, Chad; Zaroff, Charles M; Weiner, Howard J; Doyle, Werner K; Miles, Daniel; Lajoie, Josiane; Kuzniecky, Ruben; Pacia, Steven; Vazquez, Blanca; Luciano, Daniel; Najjar, Souhel; Devinsky, Orrin
2007 Mar;48(3):539-545, Epilepsia
PURPOSE: Functional mapping of eloquent cortex with electrical neurostimulation is used both intra- and extraoperatively to tailor resections. In pediatric patients, however, functional mapping studies frequently fail to localize language. Wada testing has also been reported to be less sensitive in children. METHODS: Thirty children (4.7 - 14.9 years) and 18 adult controls (18-59 years) who underwent extraoperative language mapping via implanted subdural electrodes at the NYU Comprehensive Epilepsy Center were included in the study. Ten children and 14 adults underwent preoperative Wada testing. Success of the procedures was defined as the identification of at least one language site by neurostimulation mapping and determination of hemispheric language dominance on the Wada test. RESULTS: In children younger than 10.2 years, cortical stimulation identified language cortex at a lower rate than was seen in children older than 10.2 years and in adults (p<0.05). This threshold, demonstrated by survival and chi2 analysis, was sharply defined in our data set. Additionally, Wada testing was more likely to be successful than was extraoperative mapping in this younger age group (p<0.05). CONCLUSIONS: Analysis of our series demonstrates that language cortex is less likely to be identified in children younger than 10 years, suggesting that alternatives to the current methods of cortical electrical stimulation, particularly the use of preoperative language lateralization, may be required in this age group
— id: 71610, year: 2007, vol: 48, page: 539, stat: Journal Article,

Histological evidence for transmeningeal drug diffusion in the rat cerebral cortex: A study on the neuropathological effects of epidurally delivered NMDA
Sheffield, LG; Baptiste, SL; Tang, HM; Kuzniecky, RI; Devinsky, O; Ludvig, N
2007 OCT ;48(1):310-310, Epilepsia
— id: 87155, year: 2007, vol: 48, page: 310, stat: Journal Article,

Non-invasive mapping of language and memory cortex with fMRI and MEG
Thesen T; McDonald CR; Carlson CE; Kuzniecky RI; Huang MX; Ahmadi; Hagler DJ; Stout JD; Nearing KI; Dale AM; Barr WB; Devinsky O; Halgren E
2007 ;:256-256 #G144, Annual meeting abstract program (Cognitive Neuroscience Society)
— id: 74457, year: 2007, vol: , page: 256, stat: Journal Article,

Comparing fMRI and MEG in the study of language processing
Thesen, T; Carlson, CE; McDonald, CM; Kuzniecky, RI; Hagler, DJ; Stout, JD; Nearing, KI; Dale, AM; Barr, WB; Devinsky, O; Halgren, E
2007 OCT ;48(3):221-222, Epilepsia
— id: 98145, year: 2007, vol: 48, page: 221, stat: Journal Article,

Magnetic source imaging for pre-surgical lateralization of refractory epilepsy
Carlson, C; Schevon, C; Stout, J; Nadkami, S; Doyle, W; Weiner, H; Pacia, S; Devinsky, O; Kuzniecky, R
2006 MAR ;47(1):4-5, Epilepsia
— id: 104248, year: 2006, vol: 47, page: 4, stat: Journal Article,

Inter- and intra-modality reliability of magnetoencephalographic somatosensory localization utilizing pneumatic digit and median nerve stimulation
Carlson, C; Stout, J; Schevon, C; Kuzniecky, R; Devinsky, O; Pacia, S
2006 MAR 14 ;66(5):A180-A180, Neurology
— id: 104257, year: 2006, vol: 66, page: A180, stat: Journal Article,

Multi-staged epilepsy surgery in multifocal tuberous sclerosis complex
Carlson, C; Weiner, H; Ridgway, E; Zaroff, C; Miles, D; LaJoie, J; Kuzniecky, R; Devinsky, O
2006 MAR 14 ;66(5):A322-A322, Neurology
— id: 104258, year: 2006, vol: 66, page: A322, stat: Journal Article,

Interictal perceptual disturbances in temporal lobe epilepsy
Grant, AC; Donnelly, KM; Barr, WB; Kuzniecky, R; Devinsky, O
2006 MAR ;47(1):97-97, Epilepsia
— id: 104250, year: 2006, vol: 47, page: 97, stat: Journal Article,

Epidural delivery of the combination of GABA and adenosine terminates locally induced neocortical seizures in rats
John, JE; Baptiste, SL; Medveczky, G; von Gizycki, H; Kuzniecky, RI; Devinsky, O; Ludvig, N
2006 SEP ;47(3):219-219, Epilepsia
— id: 69539, year: 2006, vol: 47, page: 219, stat: Journal Article,

Magnetic source imaging versus intracranial electroencephalogram in epilepsy surgery: a prospective study
Knowlton, Robert C; Elgavish, Rotem; Howell, Jennifer; Blount, Jeffery; Burneo, Jorge G; Faught, Edward; Kankirawatana, Pongkiat; Riley, Kristen; Morawetz, Richard; Worthington, Julie; Kuzniecky, Ruben I
2006 May;59(5):835-842, Annals of neurology
OBJECTIVE: Noninvasive brain imaging tests can potentially supplement or even replace the use of intracranial electroencephalogram (ICEEG), an invasive, costly procedure used in presurgical epilepsy evaluation. This study prospectively examined the agreement between magnetic source imaging (MSI) and ICEEG localization in epilepsy surgery candidates. METHODS: Patients completing video monitoring with scalp EEG who had intractable partial epilepsy based on ictal electro-clinico-anatomical features were screened. Forty-nine enrolled patients (mean age, 27 years; range, 1-61 years) completed MSI and ICEEG studies. Decisions about ICEEG and surgery were made at a consensus conference where MSI could only influence ICEEG coverage by indicating supplemental coverage to that already planned by an original hypothesis. RESULTS: The positive predictive value of MSI for seizure localization was 82 to 90%, depending on whether computed against ICEEG alone or in combination with surgical outcome. The kappa score of agreement for MSI with ICEEG was 0.2744 (p < 0.01) INTERPRETATION: MSI yields localizing information with a high positive predictive value in epilepsy surgery candidates who typically require ICEEG. This finding suggests that enough clinical validity exists for MSI to potentially replace ICEEG for seizure localization
— id: 74092, year: 2006, vol: 59, page: 835, stat: Journal Article,

Postictal psychosis: A case control study
Kuzniecky, R; Vorkas, CK; Alper, K; Carlson, C; Barr, W; Devinsky, O
2006 SEP ;47(3):279-279, Epilepsia
— id: 69541, year: 2006, vol: 47, page: 279, stat: Journal Article,

Malformations of cortical development and epilepsy, part 1: diagnosis and classification scheme
Kuzniecky, Ruben I
2006 Fall;3(4):151-162, Reviews in Neurological Diseases
Malformations of cortical development (MCDs) are a common cause of epilepsy, although seizures are not always the most prominent neurologic manifestation of these disorders. In localization-related epilepsy, certain features should create a strong suspicion that an MCD is the underlying cause; these include developmental delay and static focal neurologic deficits, a family history of developmental delay or epilepsy, frequent seizures from onset, and episodes of focal status epilepticus. MCDs can be classified according to a number of different criteria emphasizing clinical phenotype, imaging findings, pathology, or genetic defects. The overall classification of MCDs is based on the 3 fundamental events of cortical formation: 1) proliferation of neurons and glia in the ventricular and subventricular zones; 2) multidirectional migration of immature but postmitotic neurons to the developing cerebral cortex; and 3) cortical organization. Among the most common and distinct syndromes and entities affecting patients with MCDs and epilepsy are focal cortical dysplasia, hemimegalencephaly, tuberous sclerosis, classical lissencephaly, periventricular nodular heterotopia, focal subcortical heterotopia, polymicrogyria, and schizencephaly, all of which are discussed herein
— id: 74091, year: 2006, vol: 3, page: 151, stat: Journal Article,

News and views from the literature: epilepsy: improved diagnosis and unconventional treatments
Kuzniecky, Ruben I
2006 Fall;3(4):205-207, Reviews in Neurological Diseases
— id: 74090, year: 2006, vol: 3, page: 205, stat: Journal Article,

Anterior hippocampal dysfunction predicts post-surgical seizure outcomes in medial temporal lobe epilepsy: An MR spectroscopic study
Lee, G; Pan, J; Spencer, D; Kuzniecky, R; Hetherington, H
2006 SEP ;47(3):74-74, Epilepsia
— id: 69537, year: 2006, vol: 47, page: 74, stat: Journal Article,

Epidural pentobarbital delivery can prevent locally induced neocortical seizures in rats: the prospect of transmeningeal pharmacotherapy for intractable focal epilepsy
Ludvig, Nandor; Kuzniecky, Ruben I; Baptiste, Shirn L; John, Jenine E; von Gizycki, Hans; Doyle, Werner K; Devinsky, Orrin
2006 Nov;47(11):1792-1802, Epilepsia
PURPOSE: To determine whether epidural pentobarbital (PB) delivery can prevent and/or terminate neocortical seizures induced by locally administered acetylcholine (Ach) in freely moving rats. METHODS: Rats were implanted permanently with an epidural cup placed over the right parietal cortex with intact dura mater. Epidural screw-electrodes, secured to the cup, recorded local neocortical EEG activity. In the seizure-termination study, Ach was delivered into the epidural cup, and after the development of electrographic and behavioral seizures, the Ach solution was replaced with either PB or artificial cerebrospinal fluid (aCSF; control solution). In the seizure-prevention study, the epidural Ach delivery was preceded by a 10-min exposure of the delivery site to PB or aCSF. Raw EEG recordings, EEG power spectra, and behavioral events were analyzed. RESULTS: Ach-induced EEG seizures associated with convulsions, which were unaffected by epidural aCSF applications, were terminated by epidurally delivered PB within 2-2.5 min. Epidural deliveries of PB before Ach applications completely prevented the development of electrographic and behavioral seizures, whereas similar deliveries of aCSF exerted no influence on the seizure-generating potential of Ach. CONCLUSIONS: This study showed for the first time that epidural AED delivery can prevent, as well as terminate, locally induced neocortical seizures. The findings support the viability of transmeningeal pharmacotherapy for the treatment of intractable neocortical epilepsy
— id: 69701, year: 2006, vol: 47, page: 1792, stat: Journal Article,

Pediatric language mapping: Effectiveness of neurostimulation and Wada testing
Schevon, C; Carlson, C; Zaroff, C; Weiner, H; Kuzniecky, R; Devinsky, O
2006 MAR 14 ;66(5):A68-A68, Neurology
— id: 104256, year: 2006, vol: 66, page: A68, stat: Journal Article,

Synchrony changes between hippocampal and neocortical EEG signals precede seizure activity induced by intrahippocampal NMDA application in freely behaving rats
von Gizycki, H; Baptiste, SL; Medveczky, G; Kuzniecky, RI; Devinsky, O; Ludvig, N
2006 SEP ;47(3):47-47, Epilepsia
— id: 69536, year: 2006, vol: 47, page: 47, stat: Journal Article,

Pediatric language mapping: Sensitivity of neurostimulation and Wada testing in epilepsy surgery
Weiner, HL; Schevon, C; Carlson, C; Doyle, W; Miles, D; LaJoie, J; Kuzniecky, R; Devinsky, O
2006 AUG ;59(2):480-481, Neurosurgery
— id: 104252, year: 2006, vol: 59, page: 480, stat: Journal Article,

A developmental and genetic classification for malformations of cortical development
Barkovich, A J; Kuzniecky, R I; Jackson, G D; Guerrini, R; Dobyns, W B
2005 Dec 27;65(12):1873-1887, Neurology
Increasing recognition of malformations of cortical development and continuing improvements in imaging techniques, molecular biologic techniques, and knowledge of mechanisms of brain development have resulted in continual improvement of the understanding of these disorders. The authors propose a revised classification based on the stage of development (cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected. The categories are based on known developmental steps, known pathologic features, known genetics (when possible), and, when necessary, neuroimaging features. In those cases in which the precise developmental and genetic features are uncertain, classification is based on known relationships among the genetics, pathologic features, and neuroimaging features. The major change since the prior classification has been a shift to using genotype, rather than phenotype, as the basis for classifying disorders wherever the genotype-phenotype relationship is adequately understood. Other substantial changes include more detailed classification of congenital microcephalies, particularly those in which the genes have been mapped or identified, and revised classification of congenital muscular dystrophies and polymicrogyrias. Information on genetic testing is also included. This classification allows a better conceptual understanding of the disorders, and the use of neuroimaging characteristics allows it to be applied to all patients without necessitating brain biopsy, as in pathology-based classifications
— id: 104807, year: 2005, vol: 65, page: 1873, stat: Journal Article,

Multimodality imaging in the presurgical evaluation of extratemporal lobe epilepsies
Burneo, JG; Howell, J; Faught, D; Morawetz, R; Kuzniecky, RI; Knowlton, RC
2005 ;46(12):40-40, Epilepsia
— id: 104852, year: 2005, vol: 46, page: 40, stat: Journal Article,

Racial profile, short- and long-term outcome, and predictors of seizure freedom in a large series of patients undergoing surgical treatment for intractable temporal lobe epilepsy
Burneo, JG; Villanueva, V; Martin, R; Knowlton, RC; Faught, E; Kuzniecky, RI
2005 ;46(1):236-237, Epilepsia
— id: 104853, year: 2005, vol: 46, page: 236, stat: Journal Article,

Ictal SPECT compared to MEG in the presurgical evaluation of epilepsy
Knowlton, RC; Buddhiwarhdan, O; Howell, J; Blount, J; Morawetz, R; Faught, RE; Kuzniecky, RI
2005 ;46(3):77-77, Epilepsia
— id: 104854, year: 2005, vol: 46, page: 77, stat: Journal Article,

Report from the 2004 AES Annual Meeting. Highlights from the 58th Annual Meeting of the American Epilepsy Society, December 3-7, 2004, New Orleans, LA
Kuzniecky, Ruben I
2005 Spring;2(2):88-90, Reviews in Neurological Diseases
— id: 104352, year: 2005, vol: 2, page: 88, stat: Journal Article,

Spatio-temporal stages in word processing: Intracranial-recorded potentials and current source density in the human frontal, temporal and occipital cortices
Wang, CM; Ulbert, I; Doyle, WK; Devinsky, O; Kuzniecky, R; Halgren, A
2005 NOV ;46(10):323-323, Epilepsia
— id: 98090, year: 2005, vol: 46, page: 323, stat: Journal Article,

Self-report of cognitive abilities in temporal lobe epilepsy: cognitive, psychosocial, and emotional factors
Banos, James H; LaGory, Jason; Sawrie, Stephen; Faught, Edward; Knowlton, Robert; Prasad, Avinash; Kuzniecky, Ruben; Martin, Roy C
2004 Aug;5(4):575-579, Epilepsy & behavior
Self-report of cognitive functioning using the Multiple Abilities Self-Report Questionnaire (MASQ) was examined in 57 left (LTLE) and 36 right (RTLE) temporal lobe epilepsy patients. The MASQ is a 38-item self-report measure assessing five domains of self-perceived cognitive functioning: Language, Visual-Perceptual Abilities, Verbal Memory, Visual-Spatial Memory, and Attention/Concentration. Overall, LTLE patients self-reported more cognitive difficulties across all domains. Language was the only domain to emerge as a robust indicator of seizure lateralization (LTLE patients reporting more problems). Neuropsychological test performance did not emerge as a significant predictor for any domain, whereas measures of psychosocial and emotional functioning accounted for a significant but modest amount of variance in all of them. The results suggest caution in using such self-report measures as an ecological extension of objective testing, but suggest a role in assessing self-appraisal of deficits
— id: 74093, year: 2004, vol: 5, page: 575, stat: Journal Article,

Confirmatory factor analysis of the california verbal learning test in patients with epilepsy: relationship to clinical and neuropathological markers of temporal lobe epilepsy
Banos, James H; Roth, David L; Palmer, Cheryl; Morawetz, Richard; Knowlton, Robert; Faught, Edward; Kuzniecky, Ruben; Bilir, Erhan; Martin, Roy C
2004 Jan;18(1):60-68, Neuropsychology
Latent constructs involved in California Verbal Learning Test (D. C. Delis, J. H. Kramer, E. Kaplan, & B. A. Ober, 1987) performance were examined using confirmatory factor analysis in 388 epilepsy surgery candidates. Eight factor models were compared. A single-factor model was examined, along with 7 models accommodating constructs of auditory attention, inaccurate recall, and delayed recall in different combinations. The retained model consisted of 3 correlated factors: Auditory Attention. Verbal Learning, and Inaccurate Recall. Validity of this factor structure was examined in a subsample of patients with left and right temporal lobe epilepsy. All 3 factors were related to seizure focus and magnetic resonance imaging hippocampal volume. Only Verbal Learning was related to hippocampal neuropathology, supporting the distinction between learning and attention in the factor structure
— id: 74094, year: 2004, vol: 18, page: 60, stat: Journal Article,

Race and temporal lobe surgery outcome
Burneo, IG; Knowlton, RC; Prasad, A; Mattin, RC; Faught, E; Kuzniecky, RI
2004 ;45(2-3):159-159, Epilepsia
— id: 104855, year: 2004, vol: 45, page: 159, stat: Journal Article,

"Racial and ethnic differences in the use of surgical treatment among patients with mesial temporal sclerosis in Alabama, 1988 through 2003"
Burneo, JG; Black, L; Faught, E; Knowlton, RC; Kuzniecky, RI
2004 ;62(7):A92-A92, Neurology
— id: 104856, year: 2004, vol: 62, page: A92, stat: Journal Article,

Eclampsia, hippocampal sclerosis, and temporal lobe epilepsy: accident or association?
Lawn, N; Laich, E; Ho, S; Martin, R; Faught, E; Knowlton, R; Morawetz, R; Kuzniecky, R
2004 Apr 27;62(8):1352-1356, Neurology
BACKGROUND: Up to 30% of patients with temporal lobe epilepsy (TLE) have no identifiable risk factors. OBJECTIVE: S: To report nine patients with TLE who had a history of eclampsia as the only risk factor for epilepsy and to investigate whether this possible association existed in a larger cohort of women with surgically treated TLE. METHODS: The clinical data, video-EEG, neuroimaging, and neuropathology of 195 consecutive women undergoing anterior temporal lobectomy (ATL) were reviewed. Risk factors for TLE, age at epilepsy onset, and occurrence of pregnancy were identified in each patient. RESULTS: Twenty-six women had no identifiable risk factors or seizures following a pregnancy. Nine of the 26 women had a history of eclampsia. The median age at the time of eclampsia was 16 years, and the latent period between the occurrence of eclampsia and onset of epilepsy ranged from 1 month to 2 years. The clinical, EEG, MRI, and neuropathologic findings were typical of hippocampal sclerosis (HS) and other than age at onset were no different from those of noneclampsia ATL patients. At mean follow-up of 57 months, seven patients were seizure-free and the other two markedly improved. CONCLUSION: Eclampsia may be a risk factor for TLE and HS
— id: 133562, year: 2004, vol: 62, page: 1352, stat: Journal Article,

Evolving antiepileptic drug treatment in juvenile myoclonic epilepsy - In reply
Prasad, A; Kuzniecky, RI; Knowlton, RC; Welty, TE; Martin, RC; Mendez, M; Faught, RE
2004 ;61(8):1328-1329, Archives of neurology
— id: 104857, year: 2004, vol: 61, page: 1328, stat: Journal Article,

Newer antiepilepsy drug outcomes in juvenile myoclonic epilepsy patients
Welty, TE; Kuzniecky, RI; Faught, E
2004 ;45(8):145-146, Epilepsia
— id: 104858, year: 2004, vol: 45, page: 145, stat: Journal Article,

Hypothalamic hamartoma and seizures: a treatable epileptic encephalopathy
Berkovic, Samuel F; Arzimanoglou, Alexis; Kuzniecky, Ruben; Harvey, A Simon; Palmini, Andre; Andermann, Frederick
2003 Jul;44(7):969-973, Epilepsia
Hypothalamic hamartomas may be associated with gelastic seizures, focal seizures, and a generalized epileptic encephalopathy, with severe seizures and cognitive and behavior decline. Despite earlier views to the contrary, good evidence now exists that all these clinical features are caused, directly or indirectly, by the hamartoma. Resection of these lesions was long regarded as too hazardous and unlikely to benefit seizure control. It is now clear that hypothalamic hamartomas can be effectively treated with a variety of surgical approaches with sustained seizure control and often seizure freedom. Qualitative observations suggest that behavior and cognition also improve with treatment, but quantitative validation is required. The specific approach should be tailored according to the surgical anatomy of the lesion and the experience of the surgeon. Choices include a transcallosal approach (good for intraventricular lesions), a pterional approach (useful for interpeduncular lesions), a transventricular endoscopic approach, or destruction of the lesion with radiofrequency probes or gamma knife radiosurgery. The previously dismal outlook for children with severe seizures associated with this lesion has now dramatically changed. These insights may have implications for other epileptic encephalopathies of childhood
— id: 74095, year: 2003, vol: 44, page: 969, stat: Journal Article,

Temporal lobectomy in congenital porencephaly associated with hippocampal sclerosis
Burneo, Jorge G; Faught, Edward; Knowlton, Robert C; Martin, Roy C; Bebin, Martina; Morawetz, Richard; Kuzniecky, Ruben
2003 Jun;60(6):830-834, Archives of neurology
BACKGROUND: Clinical and neuroimaging features of patients with epilepsy and coexisting extratemporal porencephaly and hippocampal sclerosis have been previously described. OBJECTIVE: To present the clinical characteristics and surgical outcome of 6 patients with intractable epilepsy and coexisting extratemporal porencephaly and hippocampal sclerosis.Patients and METHODS: Twenty-four patients with porencephaly and epilepsy were studied. Of these, 6 had an epileptogenic focus in the temporal region. All patients underwent video electroencephalogram monitoring, magnetic resonance imaging studies, and neuropsychological evaluation. Of the subset of patients with temporal lobe epilepsy, 1 patient underwent intracranial electroencephalogram monitoring. Temporal lobe resection was performed in 5 patients. Outcomes were evaluated using the Engel classification. RESULTS: Freedom from seizures was achieved in all patients. Pathologic analysis of the resected tissue confirmed the presurgical diagnosis of mesial temporal sclerosis. CONCLUSION: Patients with extratemporal porencephaly and intractable seizures should be evaluated early and be considered for temporal lobectomy if clinical, magnetic resonance imaging, and electroencephalogram findings support the diagnosis of temporal lobe onset seizures
— id: 74096, year: 2003, vol: 60, page: 830, stat: Journal Article,

Frequency of epilepsy in patients with psychogenic seizures monitored by video-EEG
Martin, R; Burneo, J G; Prasad, A; Powell, T; Faught, E; Knowlton, R; Mendez, M; Kuzniecky, R
2003 Dec 23;61(12):1791-1792, Neurology
This study examined the frequency of epilepsy in a consecutive series of patients who received a definitive diagnosis of psychogenic nonepileptic seizures (PNES) after completing inpatient video-EEG (VEEG) monitoring. Of the 1,590 patients receiving definitive diagnosis, 514 (32.3%) were diagnosed with PNES. Twenty-nine (5.3%) of these patients were found to have both PNES and epilepsy. When strict diagnostic criteria are applied, there is little overlap between epileptic seizures and PNES among patients referred for VEEG monitoring
— id: 139940, year: 2003, vol: 61, page: 1791, stat: Journal Article,

Weight loss associated with vagus nerve stimulation
Burneo, J G; Faught, E; Knowlton, R; Morawetz, R; Kuzniecky, R
2002 Aug 13;59(3):463-464, Neurology
— id: 139941, year: 2002, vol: 59, page: 463, stat: Journal Article,

Modulation of cerebral GABA by topiramate, lamotrigine, and gabapentin in healthy adults
Kuzniecky, Ruben; Ho, S; Pan, J; Martin, R; Gilliam, F; Faught, E; Hetherington, H
2002 Feb 12;58(3):368-372, Neurology
BACKGROUND: Anticonvulsant drugs have multiple mechanisms of action. Recent in vivo MRS studies suggest that cerebral gamma-aminobutyric acid (GABA) increases occur with the administration of certain anticonvulsants in humans. OBJECTIVE: To investigate the effect of topiramate, gabapentin, and lamotrigine on cerebral GABA concentrations in healthy volunteers and correlate the GABA concentrations with serum drug levels. METHODS: Seventeen healthy adults were randomly assigned to receive topiramate, gabapentin, and lamotrigine and underwent GABA measurements using a 4.1-T magnet from a 13.5-mL volume over the occipital region. GABA concentrations and serum levels were measured at 3 and 6 hours following administration of an acute single dose of one of the drugs. Thereafter, drugs were titrated over 4 weeks to target doses, with GABA measurements performed at 2 and 4 weeks. RESULTS: Cerebral GABA concentrations rose 70% in the acute phase compared with baseline for topiramate. GABA rose 48% at 6 hours with gabapentin but not with lamotrigine. With long-term dosing and once target doses were achieved at 4 weeks, significant elevations in GABA were observed compared with baseline for all three drugs (topiramate 46%, gabapentin 25%, lamotrigine 25%). CONCLUSION: This study demonstrates that single doses of topiramate and gabapentin increase cerebral GABA concentrations acutely (hours) in healthy individuals, but all drugs at clinically utilized doses increase cerebral GABA at 4 weeks. These results suggest that the mechanisms of action of anticonvulsant drugs are more complex and are likely to be multiple in nature
— id: 74099, year: 2002, vol: 58, page: 368, stat: Journal Article,

Risk to verbal memory following anterior temporal lobectomy in patients with severe left-sided hippocampal sclerosis
Martin, Roy C; Kretzmer, Tracy; Palmer, Cheryl; Sawrie, Stephen; Knowlton, Robert; Faught, Edward; Morawetz, Richard; Kuzniecky, Ruben
2002 Dec;59(12):1895-1901, Archives of neurology
BACKGROUND: Previous investigations indicate low risk for memory loss following anterior temporal lobectomy (ATL) in patients with severe hippocampal sclerosis (HS) compared with patients with mild HS. However, these conclusions have been established primarily with group-level analyses. OBJECTIVE: To investigate individual base rate risk for verbal memory loss following ATL in patients who have pathologically verified mild, moderate, or severe HS. PATIENTS AND METHODS: One hundred fifteen patients with unilateral temporal lobe epilepsy (68 with left-sided and 47 with right-sided epilepsy) were included. Acquisition, retrieval, and recognition components of verbal memory, as measured by the California Verbal Learning Test, were assessed before and after ATL. Postoperatively, the degree of neuronal loss and reactive gliosis of the hippocampus was assessed via a 3-tiered rating system establishing mild, moderate, and severe pathologic features. Patients with preoperative magnetic resonance imaging-based evidence of lesions outside the mesial temporal area (side of surgical resection) were excluded. RESULTS: Neither seizure laterality nor severity of HS was associated with preoperative verbal memory performance. Postoperatively, the left-sided ATL group demonstrated significant decline across the acquisition (P<.01), retrival (P<.001), and recognition (P<.001) verbal memory components compared with the right-sided ATL group. Patients who underwent left-sided ATL and had mild HS displayed the largest magnitude and percentage proportion of postoperative decline across all verbal memory components. However, 28 (48%) of the 58 patients who underwent left-sided ATL and who had moderate and severe HS displayed statistically reliable declines on retrieval aspects of verbal memory. Most patients undergoing right-sided ATL, regardless of the extent of hippocampal pathologic features, displayed no postoperative memory change. CONCLUSIONS: Substantial individual heterogeneity of memory outcome exists across groups of patients undergoing ATL, with various degrees of pathologically verified HS. Patients undergoing left-sided ATL who have mild HS seem at greatest risk for broad-spectrum verbal memory decline. However, when examining outcome on a patient-by-patient basis, many patients undergoing left-sided ATL who have moderate to severe HS were also vulnerable to verbal memory loss. This risk seems selective to a retrieval-based aspect of verbal memory
— id: 74098, year: 2002, vol: 59, page: 1895, stat: Journal Article,

Factor structure of the CVLT in epilepsy patients: relationship to hippocampal volume and seizure focus
Banos, JH; Martin, RC; Faught, RE; Knowlton, RC; Kuzniecky, RI
2001 ;16(8):716-717, Archives of clinical neuropsychology
— id: 104859, year: 2001, vol: 16, page: 716, stat: Journal Article,

Rasmussen's Encephalitis
Counce D; Limdi N; Kuzniecky R
2001 Nov;3(6):555-563, Current treatment options in neurology
When the diagnosis of Rasmussen's encephalitis is being considered, it is important to rapidly exclude other causes of epilepsia partialis continua and hemiparesis. Although there is no good data from randomized trials of different immune-related therapies, treatment with immunoglobulin G (IgG), steroids, or plasmapheresis is advocated as first-line therapy. It is not unreasonable to institute at least two treatment options (eg, IgG followed by plasmapheresis) if response to the first treatment is poor. Functional hemispherectomy and its variants are associated with a lower long-term complication rate
— id: 74100, year: 2001, vol: 3, page: 555, stat: Journal Article,

Magnetic resonance spectroscopic imaging in temporal lobe epilepsy: neuronal dysfunction or cell loss?
Kuzniecky, R; Palmer, C; Hugg, J; Martin, R; Sawrie, S; Morawetz, R; Faught, E; Knowlton, R
2001 Dec;58(12):2048-2053, Archives of neurology
BACKGROUND: Magnetic resonance spectroscopy (MRS) has demonstrated consistent metabolic abnormalities in temporal lobe epilepsy. The reason for decreases in N-acetylated compounds are thought to be related to neuronal hippocampal cell loss as observed in hippocampal sclerosis. However, mounting evidence suggest that the N-acetylated compound decreases may be functional and reversible. OBJECTIVE: To establish whether the metabolic changes measured by MRS correlate to hippocampal cell loss in temporal lobe epilepsy. SUBJECTS AND METHODS: We prospectively performed quantitative hippocampal MR imaging volumetry and MRS imaging in 33 patients with intractable mesial temporal lobe epilepsy who were undergoing surgery. A neuronal-glial ratio of cornu ammonis and fascia dentata was obtained and correlated while validating the pathologic analysis by comparisons with specimens of age-matched autopsy control-case hippocampus (n = 14). RESULTS: The neuronal-glial ratio of the patient group was statistically significantly lower than in the control group for the cornu ammonis region (P<.001). Correlations of hippocampal volumes with cornu ammonis and neuronal-glial ratios revealed a significant interdependence (P<.01). However, correlations of the resected hippocampal creatine-N-acetylated compound ratio with the cornu ammonis or fascia dentata neuronal-glial ratios showed no significant interdependence (P>.8). CONCLUSIONS: Our findings support the concept that the metabolic dysfunction measured by MRS imaging and the hippocampal volume loss detected by MR imaging volumetry do not have the same neuropathologic basis. These findings suggest that the MRS imaging metabolic measures reflect neuronal and glial dysfunction rather than neuronal cell loss as previously assumed
— id: 139942, year: 2001, vol: 58, page: 2048, stat: Journal Article,

Bilateral hippocampal atrophy: consequences to verbal memory following temporal lobectomy
Martin, R C; Sawrie, S M; Knowlton, R C; Bilir, E; Gilliam, F G; Faught, E; Morawetz, R B; Kuzniecky, R
2001 Aug 28;57(4):597-604, Neurology
BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected 60 patients with TLE who had undergone ATL (left = 31, right = 29). They determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices from three-dimensional MRI acquisition. Hippocampal volumes were defined as atrophic if the volumes were below 2 SD for control subjects. Bilateral hippocampal atrophy was present in 10 patients with left TLE and 11 patients with right TLE. The authors assessed acquisition, retrieval, and recognition components of verbal memory both before and after ATL. RESULTS: Groups did not differ across age, education, intelligence, age at seizure onset, or seizure duration. Seizure-free rates after ATL were 70% or higher for all groups. Before surgery, patients with left TLE displayed worse verbal acquisition performance compared with patients with right TLE. Patients with left TLE with bilateral hippocampal volume loss displayed the lowest performance across all three memory components. After surgery, both groups of patients with left TLE exhibited worse verbal memory outcome compared with patients with right TLE. Bilateral hippocampal atrophy did not worsen outcome in the patients with right TLE. A higher proportion of patients with left TLE with bilateral hippocampal atrophy experienced memory decline compared with the other TLE groups. CONCLUSION: Bilateral hippocampal atrophy in the presence of left TLE is associated with worse verbal memory before and after ATL compared with patients with unilateral hippocampal volume loss or right TLE with bilateral hippocampal volume loss
— id: 139944, year: 2001, vol: 57, page: 597, stat: Journal Article,

Comparative cognitive effects of carbamazepine and gabapentin in healthy senior adults
Martin, R; Meador, K; Turrentine, L; Faught, E; Sinclair, K; Kuzniecky, R; Gilliam, F
2001 Jun;42(6):764-771, Epilepsia
PURPOSE: This study compared the cognitive effects of carbamazepine (CBZ) and gabapentin (GBP) in healthy senior adults by using a randomized, double-blind crossover design. METHODS: Thirty-four senior adults were randomized to receive one of the two drugs followed by a 5-week treatment period. A 4-week washout phase preceded initiation of the second drug. Antiepileptic drugs (AEDs) were titrated to target doses of either CBZ (800 mg/day) or GBP (2,400 mg/day). Primary outcome measures were standardized neuropsychological tests of attention/vigilance, psychomotor speed, motor speed, verbal and visual memory, and the Profile of Mood State (POMS), yielding a total of 17 variables. Each subject received cognitive testing at predrug baseline, end of first drug phase, end of second drug phase, and 4 weeks after completion of the second drug phase. RESULTS: Fifteen senior adults (mean age, 66.5 years; range, 59-76 years) completed the study. Seniors completing the study did not differ significantly from noncompleting seniors in terms of demographic features or baseline cognitive performances. Fifteen of the 19 seniors not completing the study dropped out while receiving CBZ. Adverse events were frequently reported for both AEDs, although they were more common for CBZ. Mean serum levels for the completers were within midrange clinical doses (CBZ, 6.8 microg/ml; GBP, 7.1 microg/ml). Significant differences between CBZ and GBP were found for only one of 11 cognitive variables, with better attention/vigilance for GBP, although the effect was modest. Performances on the nondrug average were significantly better on 45% of cognitive variables compared with CBZ and 36% compared with GBP. The overall pattern of means favored GBP over CBZ on 15 of 17 (p < 0.001), nondrug over CBZ on 17 of 17 (p < 0.0000), and nondrug over GBP on eight of 17 (NS). CONCLUSIONS: Mild cognitive effects were found for both AEDs compared with the nondrug average condition. The magnitude of difference between the two AEDs across the cognitive variables was modest. Self-reported mood was not significantly affected by either AED. However, overall tolerability and side-effect profile of CBZ were poorer than those of GBP in senior adults at doses and titration rates reported in this study
— id: 139946, year: 2001, vol: 42, page: 764, stat: Journal Article,

Correlation of scalp EEG and 1H-MRS metabolic abnormalities in temporal lobe epilepsy
Maton, B; Gilliam, F; Sawrie, S; Faught, E; Hugg, J; Kuzniecky, R
2001 Mar;42(3):417-422, Epilepsia
PURPOSE: To correlate the interictal spike field and region of seizure onset with the distribution of 1H-MRS abnormalities in temporal lobe epilepsy (TLE) and improve our understanding of the clinical significance of 1H-MRS abnormalities. METHODS: Scalp electroencephalogram (EEG) monitoring and proton magnetic resonance spectroscopy (1H-MRS) results were correlated in 31 consecutive patients with TLE. RESULTS: Lateralized 1H-MRS-based hippocampal abnormalities were recorded in 95% of the patients with unilateral interictal spikes, with a high degree of concordance for the lateralization side (90%). In 64% of the patients with normal or bilateral interictal EEG spikes, 1H-MRS provided lateralizing information. Bilateral 1H-MRS abnormalities, with or without lateralization, were 3 times more frequent than bitemporal EEG spikes. Anterior predominance of the 1H-MRS abnormalities was more frequent in patients with anterior temporal EEG spiking (50%), than in patients without this EEG distribution (18%). Similar association was noted between distribution of 1H-MRS abnormalities and region of EEG seizure onset. CONCLUSIONS: Our results show a moderate level of concordance between the distribution of 1H-MRS and EEG abnormalities. 1H-MRS identifies abnormalities contralateral to the predominant seizure focus more often than does EEG and may provide lateralizing information in patients with nonlateralizing interictal EEG
— id: 139949, year: 2001, vol: 42, page: 417, stat: Journal Article,

Reproducibility of proton magnetic resonance spectroscopy imaging measurements of normal human hippocampus at 1.5 T: clinical implications
Maton, B; Londono, A; Sawrie, S; Knowlton, R; denHollander, J; Kuzniecky, R
2001 Apr;11(2):194-201, Journal of neuroimaging
The authors investigate the reproducibility of metabolite signals measured with proton magnetic resonance spectroscopy (1H-MRS) acquired from the human hippocampus in controls and in a phantom. Two 1H-MRS studies separated by 3 weeks were performed in 8 healthy volunteers and in a phantom. N-acetyl compounds (NA), choline (Ch), and creatine (Cr) peak areas and ratios were measured and compared using percentage variation, and Pearson Correlation Coefficient at the level of every voxel, the level of 1 hippocampus (5 voxels), and the level of 2 hippocampi (10 voxels). Sensitivity for observing clinically significant between-session 1H-MRS changes was evaluated using the reliable change index. Reproducibility measures for metabolite peak areas were only moderately concordant with percentage variation ranging from 14% to 20% for NA, Cho, and Cr. Stability was much improved when NA ratios and sum of multiple voxels were considered. Between-session NA/(Cho + Cr) changes greater than 22%, 12%, and 10% in one given participant can be detected with a 90% confidence interval when considered at the single-voxel level, the level of a single hippocampus, or the level of both hippocampi, respectively. Left-right asymmetry indices showed similar and limited inter-hemispheric asymmetry in repeated examination. This study suggests that 1H-MRS reproducibility performance is adequate for the study and monitoring of human hippocampus function when NA ratios and the sum of multiple voxels are considered. Individual metabolite peaks and single-voxel measurements have low reproducibility at 1.5 T and should be used only with clearly established statistical parameters
— id: 139948, year: 2001, vol: 11, page: 194, stat: Journal Article,

Postictal stability of proton magnetic resonance spectroscopy imaging (1H-MRSI) ratios in temporal lobe epilepsy
Maton, B; Londono, A; Sawrie, S; Knowlton, R; Martin, R; Kuzniecky, R
2001 Jan 23;56(2):251-253, Neurology
Interictal proton (1H) MRS is increasingly used for seizure lateralization in patients with temporal lobe epilepsy (TLE). Studies reporting postictal 1H-MRS metabolite changes in patients with TLE are few and contradictory. The authors prospectively performed interictal and postictal proton magnetic resonance spectroscopy imaging (1H-MRSI) studies in seven patients with TLE. The authors found no consistent changes in metabolite peak area ratios between studies, suggesting that 1H-MRS ratios remain stable between interictal and postictal state in TLE
— id: 139950, year: 2001, vol: 56, page: 251, stat: Journal Article,

Verbal retention lateralizes patients with unilateral temporal lobe epilepsy and bilateral hippocampal atrophy
Sawrie, S M; Martin, R C; Gilliam, F; Knowlton, R; Faught, E; Kuzniecky, R
2001 May;42(5):651-659, Epilepsia
PURPOSE: To examine the lateralization utility of preoperative verbal retention in patients with and without bilateral hippocampal atrophy. METHODS: The sample consisted of 74 patients with EEG-defined unilateral temporal lobe epilepsy (TLE) who had also undergone volumetric magnetic resonance imaging (MRI). Verbal retention was operationalized by the Logical Memory percentage retention subtest (LM%) of the Wechsler Memory Scale. Patients were divided into groups with (a) bilaterally normal hippocampal volumes, (b) unilateral atrophy, or (c) bilateral atrophy. Two different thresholds (empirically derived vs. normative) were used to lateralize on the basis of LM%. LM% lateralization was then examined by group using chi2, sensitivity, positive predictive values, and odds ratios. Analyses were also conducted separately in the subset of patients who were seizure free after surgery. RESULTS: Mean LM% performance was significantly lower in patients with left versus right TLE in the subset with bilateral hippocampal atrophy (p = 0.018), but not in patients with a normal MRI (p = 0.918) or unilateral atrophy (p = 0.087). The odds of a correct lateralization by LM% increased from 1.67 in patients with normal MRI to 36.11 in patients with bilateral hippocampal atrophy. The power of a right and left lateralization prediction by LM% was 100% and 75%, respectively, in patients with bilateral hippocampal atrophy. Similar results were obtained when analysis was restricted to patients who were seizure free after surgery. CONCLUSIONS: Preoperative verbal retention as measured by LM% may provide meaningful lateralization information in patients who are difficult to lateralize via MRI
— id: 139947, year: 2001, vol: 42, page: 651, stat: Journal Article,

Relationships among hippocampal volumetry, proton magnetic resonance spectroscopy, and verbal memory in temporal lobe epilepsy
Sawrie, S M; Martin, R C; Knowlton, R; Faught, E; Gilliam, F; Kuzniecky, R
2001 Nov;42(11):1403-1407, Epilepsia
PURPOSE: To examine the relationship between hippocampal volumes, 1H magnetic resonance spectroscopy (MRS)-identified hippocampal metabolic function, and verbal memory in patients with unilateral mesial temporal lobe epilepsy (MTLE). METHODS: Hippocampal volumes, 1H MRS-derived hippocampal creatine to N-acetylaspartate (Cr/NAA), and verbal memory assessment were obtained preoperatively in 22 patients (six right, 16 left) with EEG-defined unilateral MTLE. RESULTS: Left hippocampal volume correlated significantly with left hippocampal Cr/NAA (r=-0.549, p < 0.01), whereas right volume correlated significantly with right Cr/NAA (r=-0.478, p < 0.05). Verbal memory correlated significantly with left hippocampal Cr/NAA (r=-0.594, p < 0.01), but not with left hippocampal volume or right hippocampal measures. CONCLUSIONS: Hippocampal volumes and 1H MRS-derived metabolite ratios are statistically related, but share only a small percentage of variance, suggesting separate but related pathophysiologic processes. Left hippocampal Cr/NAA appears to be more sensitive to verbal memory function than volumes
— id: 139943, year: 2001, vol: 42, page: 1403, stat: Journal Article,

Mutations in the X-linked filamin 1 gene cause periventricular nodular heterotopia in males as well as in females
Sheen, V L; Dixon, P H; Fox, J W; Hong, S E; Kinton, L; Sisodiya, S M; Duncan, J S; Dubeau, F; Scheffer, I E; Schachter, S C; Wilner, A; Henchy, R; Crino, P; Kamuro, K; DiMario, F; Berg, M; Kuzniecky, R; Cole, A J; Bromfield, E; Biber, M; Schomer, D; Wheless, J; Silver, K; Mochida, G H; Berkovic, S F; Andermann, F; Andermann, E; Dobyns, W B; Wood, N W; Walsh, C A
2001 Aug 15;10(17):1775-1783, Human molecular genetics
Periventricular heterotopia (PH) is a human neuronal migration disorder in which many neurons destined for the cerebral cortex fail to migrate. Previous analysis showed heterozygous mutations in the X-linked gene filamin 1 (FLN1), but examined only the first six (of 48) coding exons of the gene and hence did not assess the incidence and functional consequences of FLN1 mutations. Here we perform single-strand conformation polymorphism (SSCP) analysis of FLN1 throughout its entire coding region in six PH pedigrees, 31 sporadic female PH patients and 24 sporadic male PH patients. We detected FLN1 mutations by SSCP in 83% of PH pedigrees and 19% of sporadic females with PH. Moreover, no PH females (0/7 tested) with atypical radiographic features showed FLN1 mutations, suggesting that other genes may cause atypical PH. Surprisingly, 2/24 males analyzed with PH (9%) also carried FLN1 mutations. Whereas FLN1 mutations in PH pedigrees caused severe predicted loss of FLN1 protein function, both male FLN1 mutations were consistent with partial loss of function of the protein. Moreover, sporadic female FLN1 mutations associated with PH appear to cause either severe or partial loss of function. Neither male could be shown to be mosaic for the FLN1 mutation in peripheral blood lymphocytes, suggesting that some neurons in the intact cortex of PH males may be mutant for FLN1 but migrate adequately. These results demonstrate the sensitivity and specificity of DNA testing for FLN1 mutations and have important functional implications for models of FLN1 protein function in neuronal migration
— id: 139945, year: 2001, vol: 10, page: 1775, stat: Journal Article,

Gray matter heterotopia
Barkovich, A J; Kuzniecky, R I
2000 Dec 12;55(11):1603-1608, Neurology
Gray matter heterotopia are common malformations of cortical development. From a clinical perspective, affected patients are best divided into three groups: subependymal, subcortical, and band heterotopia (also called double cortex). Symptomatic women with subependymal heterotopia typically present with partial epilepsy during the second decade of life; development and neurologic examinations up to that point are typically normal. Symptoms in men with subependymal heterotopia vary, depending on whether they have the X-linked or autosomal form. Men with the X-linked form more commonly have associated CNS and visceral anomalies; their development is typically abnormal. Symptomatic men with the autosomal variety have clinical courses similar to symptomatic women. Both men and women with subcortical heterotopia typically have congenital fixed neurologic deficits and develop partial epilepsy during the second half of the first decade of life. The more extensive the subcortical heterotopia, the greater the deficit; bilateral heterotopia are almost invariably associated with severe developmental delay or mental retardation. In general, band heterotopia are seen exclusively in women; men with a mutation of the related gene (called XLIS or DCX) usually die in utero or have a much more severe brain anomaly. Symptoms in affected women vary from normal to severe developmental delay or mental retardation; the severity of the syndrome is related to the thickness of the band of arrested neurons. Nearly all affected patients that come to medical attention have epilepsy, with partial complex and atypical absence epilepsy being the most common syndromes. Some of the more severely affected patients develop attacks
— id: 104808, year: 2000, vol: 55, page: 1603, stat: Journal Article,

Gender, Memory, and Hippocampal Volumes: Relationships in Temporal Lobe Epilepsy
Bengtson M; Martin R; Sawrie S; Gilliam F; Faught E; Morawetz R; Kuzniecky R
2000 Apr;1(2):112-119, Epilepsy & behavior
Previous research has suggested bilateral hippocampal support for verbal memory in women with early left-hemisphere injury and that women experience better verbal memory outcome following anterior temporal lobectomy (ATL). The present study investigated two issues: (1) Do women have better verbal memory outcome following ATL compared with men? (2) Are verbal memory abilities differentially supported by the right and left hippocampus in males and females? Verbal memory performance [Wechsler Memory Scale: Logical Memory (LM) savings score] was assessed in 70 patients who underwent ATL. MRI volumetric measurements of the left and right hippocampus were performed. No LM savings score difference was found between groups preoperatively although a statistically significant gender effect (P < 0.04) was found for postoperative LM savings scores. Females displayed better postoperative memory performance, regardless of side of surgery. Preoperative verbal memory performance was not associated with right or left hippocampal volumes in either left or right ATL females, although the right hippocampus was positively associated with memory performance for left ATL males. Hippocampal volumes were not associated with postoperative LM savings scores for any group. Results suggest that prose recall was only modestly influenced by gender and that bilateral hippocampal support for prose recall was not present in our female patients
— id: 74097, year: 2000, vol: 1, page: 112, stat: Journal Article,

Predictive value of MRI-identified mesial temporal sclerosis for surgical outcome in temporal lobe epilepsy: an intent-to-treat analysis
Gilliam, F; Faught, E; Martin, R; Bowling, S; Bilir, E; Thomas, J; Morawetz, R; Kuzniecky, R
2000 Aug;41(8):963-966, Epilepsia
PURPOSE: Magnetic resonance imaging (MRI) accurately identifies mesial temporal sclerosis (MTS), but prediction of successful surgical outcome ranges from 62% to 96% in published studies. Prior investigations only used patients who had received anterior temporal lobectomy (ATL), potentially overestimating the predictive value of MRI-identified MTS (MRI-MTS). METHODS: The authors performed an intent-to-treat analysis of 90 consecutive patients assessed for possible ATL, including 13 who did not undergo ATL because of inconclusive intracranial ictal EEG. Four (31%) of these 13 patients had unilateral mesial temporal abnormalities on their MRIs. RESULTS: The positive predictive value of MRI-MTS for seizure cessation decreased from 0.69 to 0.63 after adjustment for these additional false positive results. Four previous studies had revealed a positive predictive value of 0.75 (0.72 after similar adjustment). CONCLUSIONS: The authors conclude that the predictive value of MRI-MTS for outcome from ATL may be overestimated by small retrospective studies of highly selected postoperative patients
— id: 139953, year: 2000, vol: 41, page: 963, stat: Journal Article,

Adult myoclonic epilepsy: a distinct syndrome of idiopathic generalized epilepsy
Gilliam, F; Steinhoff, B J; Bittermann, H J; Kuzniecky, R; Faught, E; Abou-Khalil, B
2000 Oct 10;55(7):1030-1033, Neurology
The authors present 11 cases of idiopathic generalized epilepsy that began in adulthood at a mean age of 39 years. All patients had myoclonic jerks, five had absence seizures, and nine had infrequent generalized tonic-clonic seizures. A majority had a family history of seizures. EEG in all patients showed generalized epileptiform abnormalities, whereas neuroimaging and neurologic examination results were normal. This series appears to represent a previously undescribed idiopathic generalized epilepsy syndrome of adult myoclonic epilepsy
— id: 139952, year: 2000, vol: 55, page: 1030, stat: Journal Article,

Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment
Guerreiro, M M; Andermann, E; Guerrini, R; Dobyns, W B; Kuzniecky, R; Silver, K; Van Bogaert, P; Gillain, C; David, P; Ambrosetto, G; Rosati, A; Bartolomei, F; Parmeggiani, A; Paetau, R; Salonen, O; Ignatius, J; Borgatti, R; Zucca, C; Bastos, A C; Palmini, A; Fernandes, W; Montenegro, M A; Cendes, F; Andermann, F
2000 Jul;48(1):39-48, Annals of neurology
Two familial X-linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X-linked transmission. On the other hand, the pedigrees of 2 families ruled out X-linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X-linked syndrome of cortical maldevelopment
— id: 139954, year: 2000, vol: 48, page: 39, stat: Journal Article,

Occipitoparietal epilepsy, hippocampal atrophy, and congenital developmental abnormalities
Lawn, N; Londono, A; Sawrie, S; Morawetz, R; Martin, R; Gilliam, F; Faught, E; Kuzniecky, R
2000 Dec;41(12):1546-1553, Epilepsia
PURPOSE: Diagnostic uncertainty may arise in patients with occipitoparietal epilepsy when there is neuroimaging evidence of a posterior quadrant lesion and coexistent hippocampal abnormalities ('dual pathology'). It is not known whether hippocampal atrophy (HA) in these patients results from seizure propagation to temporolimbic structures or whether it is part of the pathological process underlying the occipitoparietal epilepsy. Clarification of this issue may have a significant bearing on the management of these patients. METHODS: We studied 20 patients with occipitoparietal epilepsy and neuroimaging or pathologic evidence of a congenital developmental abnormality. Normalized hippocampal volumes were obtained in all patients. The medical records and video-EEG recordings were analyzed to correlate the MRI findings with clinical data, seizure semiology, and EEG findings. RESULTS: HA was found in seven patients (35%). Neuroimaging abnormalities concordant with the side of HA were seen in all cases. There was clinical or EEG evidence of temporal spread in 12 patients. There was no correlation between the presence of HA and temporal lobe spread. The only clinical factor associated with HA in this series was a younger age of seizure onset. CONCLUSIONS: HA in patients with occipitoparietal epilepsy due to congenital developmental abnormalities is most likely to be a marker of a more widespread process related to a common pathogenesis during prenatal or perinatal development. HA in these patients is unlikely to be the result of secondary spread from an extrahippocampal focus. Surgical treatment should be tailored toward the primary epileptogenic zone rather the site of seizure spread
— id: 139951, year: 2000, vol: 41, page: 1546, stat: Journal Article,

Significance of interictal temporal lobe delta activity for localization of the primary epileptogenic region
Geyer, J D; Bilir, E; Faught, R E; Kuzniecky, R; Gilliam, F
1999 Jan 1;52(1):202-205, Neurology
Because interictal temporal lobe delta activity (TLDA) has been described in 30 to 90% of patients with temporal lobe epilepsy (TLE) but has not been investigated in patients with extratemporal epilepsy, we sought to determine the localizing significance of TLDA. We compared the presurgical interictal scalp EEG results of 47 consecutive patients who received extratemporal resection (40 frontal and 7 parietal-occipital) for intractable epilepsy with 43 consecutive patients who received anterior temporal lobectomy. We defined lateralized TLDA as runs of lower than 4-Hz waveforms that were easily distinguished from the background rhythms and were maximal at electrodes T4, F8, and T6 or T3, F7, and T5. The lateralized TLDA was subcategorized as temporal intermittent rhythmic delta activity (TIRDA) or temporal intermittent polymorphic delta activity (TIPDA). A chi-square test was used to determine the association of the lobe of the epileptogenic zone with TIRDA and TIPDA. We found TIRDA in 12 (28%) and TIPDA in 8 (19%) patients in the temporal lobe group, and TIRDA in 2 (4%) and TIPDA in 9 (19%) patients in the extratemporal group. TIRDA was strongly associated with TLE (p < 0.003), whereas TIPDA occurred at an equal rate in both groups. Similar to anterior temporal epilepsy, lateralized TIPDA is present in up to 20% of patients with extratemporal epilepsy. The presence of TIRDA strongly suggests TLE but may infrequently occur in extratemporal epilepsy. Caution should be used when using lateralized TLDA as a presurgical localizing finding
— id: 139967, year: 1999, vol: 52, page: 202, stat: Journal Article,

Ambulatory EEG monitoring
Gilliam, F; Kuzniecky, R; Faught, E
1999 Mar;16(2):111-115, Journal of clinical neurophysiology
Advances in computer technology offer increased capabilities for ambulatory EEG monitoring. The technical specifications of currently available ambulatory EEG machines reasonably approximate inpatient EEG equipment. However, the evolution of ambulatory EEG from 3-channel analog cassette recordings to reformatable 32-channel digital devices with computer-assisted spike and seizure detection raises several unresolved issues. Should patients with nondiagnostic routine EEG receive ambulatory EEG? Is ambulatory EEG as accurate for patients with unclear clinical diagnoses as inpatient video-EEG monitoring? If the diagnostic yield of ambulatory EEG is less than inpatient monitoring, do outpatient savings still make the technique cost-effective? This article reviews the development of ambulatory EEG and the investigations of its clinical utility. An evidence-based analysis explores the benefits and limitations of ambulatory EEG, and offers aspects of its use which require additional clinical research
— id: 139963, year: 1999, vol: 16, page: 111, stat: Journal Article,

Patient-oriented outcome assessment after temporal lobectomy for refractory epilepsy
Gilliam, F; Kuzniecky, R; Meador, K; Martin, R; Sawrie, S; Viikinsalo, M; Morawetz, R; Faught, E
1999 Sep 11;53(4):687-694, Neurology
OBJECTIVE: To determine patient-oriented outcome after anterior temporal lobectomy (ATL) for refractory epilepsy. BACKGROUND: Health-related quality of life (HRQOL) is an important component of the assessment of outcome from epilepsy surgery, but prior controlled studies of the effect of surgery on HRQOL are inconclusive. Direct assessment of the effect of surgery on patient concerns of living with epilepsy has not been reported. METHODS: We used reliable and valid instruments to compare HRQOL and patient concerns of 125 patients who had received an ATL more than than one year previously to a clinically similar group of 71 patients who were awaiting ATL. All patients were selected for surgery based on similar criteria. We also used bivariate correlation analysis and multivariate regression modeling to determine the association of traditional outcome variables with HRQOL. RESULTS: Patients who had undergone ATL reported significantly less concern of living with epilepsy in 16 of 20 items of the EFA Concerns Index and better HRQOL in 8 of 11 scales of the Epilepsy Surgery Inventory-55. Regression analysis in the postoperative group demonstrated that mood status, employment, driving, and antiepileptic drug (AED) cessation, but not seizure-free status or IQ, were associated with better HRQOL. CONCLUSIONS: Our findings support a positive affect of ATL on patient concerns and HRQOL in refractory temporal lobe epilepsy, although longitudinal studies are needed to corroborate these results. Mood, employment, driving ability, and AED use are important postoperative predictors of HRQOL
— id: 139959, year: 1999, vol: 53, page: 687, stat: Journal Article,

Characterization of mutations in the gene doublecortin in patients with double cortex syndrome
Gleeson, J G; Minnerath, S R; Fox, J W; Allen, K M; Luo, R F; Hong, S E; Berg, M J; Kuzniecky, R; Reitnauer, P J; Borgatti, R; Mira, A P; Guerrini, R; Holmes, G L; Rooney, C M; Berkovic, S; Scheffer, I; Cooper, E C; Ricci, S; Cusmai, R; Crawford, T O; Leroy, R; Andermann, E; Wheless, J W; Dobyns, W B; Walsh, C A
1999 Feb;45(2):146-153, Annals of neurology
Mutations in the X-linked gene doublecortin, which encodes a protein with no dear structural homologues, are found in pedigrees in which affected females show 'double cortex' syndrome (DC; also known as subcortical band heterotopia or laminar heterotopia) and affected males show X-linked lissencephaly. Mutations in doublecortin also cause sporadic DC in females. To determine the incidence of doublecortin mutations in DC, we investigated a cohort of eight pedigrees and 47 sporadic patients with DC for mutations in the doublecortin open reading frame as assessed by single-stranded conformational polymorphism analysis. Mutations were identified in each of the eight DC pedigrees (100%), and in 18 of the 47 sporadic DC patients (38%). Identified mutations were of two types, protein truncation mutations and single amino acid substitution mutations. However, pedigrees with DC displayed almost exclusively single amino acid substitution mutations, suggesting that patients with these mutations may have less of a reproductive disadvantage versus those patients with protein truncation mutations. Single amino acid substitution mutations were tightly clustered in two regions of the open reading frame, suggesting that these two regions are critical for the function of the Doublecortin protein
— id: 139964, year: 1999, vol: 45, page: 146, stat: Journal Article,

Acute psychotic symptoms induced by topiramate
Khan, A; Faught, E; Gilliam, F; Kuzniecky, R
1999 Jun;8(4):235-237, Seizure
The incidence of psychosis during clinical trials of topiramate was 0.8%, not significantly different from the rate for placebo or reported rates of psychosis in patients with refractory epilepsy. We observed psychotic symptoms in five patients soon after initiation of topiramate therapy. We performed a retrospective chart review of the first 80 patients who began on topiramate after approval for clinical use, between January and April 1997. Symptoms suggestive of psychosis, including hallucinations and delusions, were sought for analysis. Cognitive effects such as psychomotor slowing, confusion, and somnolence were not included. Five patients developed definite psychotic symptoms 2 to 46 days after beginning topiramate. Dosages at symptom onset were 50-400 mg/day. Symptoms included paranoid delusions in four patients and auditory hallucinations in three. Symptoms of psychosis and other psychiatric symptoms resolved quickly with discontinuation of topiramate in three patients, dose reduction from 300 to 200 mg/day in one and with inpatient treatment and neuroleptics in another. One patient had a history of auditory hallucinations, one of aggressive and suicidal thoughts, but three had no significant psychiatric history. Physicians should be aware of the possibility of psychotic symptoms, even in patients without a previous psychiatric history, when prescribing topiramate. Symptoms resolve quickly with discontinuation
— id: 139962, year: 1999, vol: 8, page: 235, stat: Journal Article,

Magnetic resonance spectroscopy in focal epilepsy: 31P and 1H spectroscopy
Kuzniecky, R
1999 Jul;155(6-7):495-498, Revue neurologique
Magnetic resonance spectroscopy (MRS) is rapidly becoming a clinical and research tool in epilepsy. Animal studies have demonstrated metabolic abnormalities in the interictal and ictal state showing energy depletion and changes in neuronal compounds. Similarly, clinical studies have demonstrated consistent abnormalities involving energy (31P) and cellular dependent (1H) compounds. Phosphorus MRS (31P) shows lateralizing metabolic dysfunction in approximately 65-75 p. 100 of patients with temporal lobe epilepsy (PCr/Pi). Proton MRS (1H) using single-voxel or chemical shift imaging has demonstrated a high sensitivity in lateralizing temporal lobe epilepsy (65-96 p. 100) with bilateral changes seen in 35-45 p. 100 of patients. The role of MRS in extra-temporal lobe epilepsy is less accurate because of the spatial limitations of current techniques. Further advances in this field promise to improve the clinical utility of MRS in epilepsy
— id: 139961, year: 1999, vol: 155, page: 495, stat: Journal Article,

Quantitative MRI in temporal lobe epilepsy: evidence for fornix atrophy
Kuzniecky, R; Bilir, E; Gilliam, F; Faught, E; Martin, R; Hugg, J
1999 Aug 11;53(3):496-501, Neurology
OBJECTIVE: To investigate whether the fornix and mamillary bodies, being part of the limbic system, are abnormal in patients with mesial temporal lobe epilepsy (MTLE). BACKGROUND: The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. This system is implicated in complex functions, including memory and emotion, and in diseases such as MTLE. METHODS: The authors performed volumetric measurements of hippocampus, amygdala, fornix, and mamillary bodies in 50 patients with MTLE and compared the results with normal controls and patients with extratemporal lobe epilepsy. RESULTS: Control (n = 17) measurements of the amygdala, hippocampus, and fornix revealed larger volumes of the right hemisphere structures (p < 0.001). Normalized fornix volumes revealed atrophy in 86% of studies concordant with hippocampal atrophy in all cases but one. Similarly, the mean hippocampal and fornix volumes for the group discriminated the epileptogenic temporal lobe (p < 0.001). Limbic volumes were normal in all patients with extratemporal lobe epilepsy. CONCLUSIONS: Quantitative MRI findings support the concept that MTLE is not a process limited to the hippocampus but also involves other interrelated limbic system structures, in particular, the fornix
— id: 139960, year: 1999, vol: 53, page: 496, stat: Journal Article,

Temporal lobe developmental malformations and hippocampal sclerosis: epilepsy surgical outcome
Kuzniecky, R; Ho, S S; Martin, R; Faught, E; Morawetz, R; Palmer, C; Gilliam, F
1999 Feb;52(3):479-484, Neurology
BACKGROUND: Temporal lobe developmental malformations coexist with mesial temporal sclerosis in the form of dual pathology with a high frequency of bilateral amygdala or hippocampal abnormalities. OBJECTIVE: The aim of this study was to correlate and compare the MRI findings and the surgical outcome in patients with temporal lobe developmental malformations (n = 20) and isolated mesial temporal sclerosis (n = 36). METHODS: MRI-based normalized volumetry of the amygdala and hippocampal formation in patients with unilateral temporal lobe developmental malformations and isolated mesial temporal sclerosis who underwent temporal lobe resections was performed. Seizure outcome was compared between groups at follow-up. RESULTS: The frequency of bilateral hippocampal or amygdala atrophy (p < 0.04) and combined hippocampal-amygdala atrophy (p < 0.02) was higher in patients with temporal lobe developmental malformations. Although no significant difference in postsurgical seizure-free status was found between the temporal lobe developmental malformations and isolated mesial temporal sclerosis groups (70% versus 91%), patients with temporal lobe developmental malformations and bilateral amygdala or hippocampal-amygdala atrophy had a significantly worse outcome (p < 0.02). CONCLUSION: Bilateral hippocampal atrophy is frequent in patients with temporal lobe developmental malformations. However, it is the presence of bilateral amygdala or amygdalo-hippocampal atrophy that is associated with a higher risk of seizure recurrence
— id: 139965, year: 1999, vol: 52, page: 479, stat: Journal Article,

Predictive value of 1H MRSI for outcome in temporal lobectomy
Kuzniecky, R; Hugg, J; Hetherington, H; Martin, R; Faught, E; Morawetz, R; Gilliam, F
1999 Sep 11;53(4):694-698, Neurology
OBJECTIVE: To investigate the predictive value of 1H MRSI for outcome in patients with mesial temporal lobe epilepsy (MTLE). BACKGROUND: 1H MRSI has been shown to be highly sensitive in the lateralization of temporal lob epilepsy. METHODS: The authors analyzed the relationship between the 1H MRSI findings and surgical outcome in 40 consecutive patients who underwent temporal lobe surgery for MTLE. Outcome at a mean of 24 months (range 18 to 40 months) was classified as seizure free or not seizure free. RESULTS: At follow-up, 78% of patients were seizure free. Correlations showed no predictive value for the creatine/N-acetylated compound (Cr/NA) ratio of the operated temporal lobe and outcome. However, a relationship was found between surgical failure and the Cr/NA ratio of the nonoperated temporal lobe and with a Cr/NA ratio in the nonoperated lobe above 1.21 in patients with bilateral abnormalities (p < 0.01). CONCLUSIONS: Preoperative elevations in the Cr/NA ratio in the nonoperated temporal lobe or the presence of higher metabolic ratios contralateral to the proposed surgery are associated with surgical failure. The predictive value of 1H MRSI absolute metabolite concentrations for outcome in MTLE requires further investigation
— id: 139958, year: 1999, vol: 53, page: 694, stat: Journal Article,

Effects of topiramate, lamotrigine and Gabapentin on cerebral GABA in healthy humans
Kuzniecky, RI; Martin, R; Hetherington, H; Gilliam, F; Faught, E
1999 ;40(1):244-244, Epilepsia
— id: 104860, year: 1999, vol: 40, page: 244, stat: Journal Article,

Hippocampal volumetry in occipito parietal epilepsy
Londono, AC; Black, L; Swarie, S; Gilliam, F; Faught, E; Kuzniecky, RI
1999 ;40(1):249-249, Epilepsia
— id: 104861, year: 1999, vol: 40, page: 249, stat: Journal Article,

Cognitive correlates of 1H MRSI-detected hippocampal abnormalities in temporal lobe epilepsy
Martin, R C; Sawrie, S; Hugg, J; Gilliam, F; Faught, E; Kuzniecky, R
1999 Dec 10;53(9):2052-2058, Neurology
OBJECTIVES: To examine associations between 1H magnetic resonance spectroscopic imaging (1H MRSI)-detected hippocampal creatine to N-acetylaspartate (Cr/NAA) ratios and neuropsychological measures sensitive to mesial temporal lobe function. BACKGROUND: The measurement of 1H MRSI-detected hippocampal metabolites has proved effective in determining extent and lateralization of neuronal damage. However, relationships between 1H MRSI-detected hippocampal metabolic abnormalities and specific areas of cognitive functioning have received limited attention compared to other studies using MRI volumetry or cerebral blood flow techniques. METHODS: We analyzed right and left hippocampal Cr/NAA ratios in 46 adult mesial temporal lobe epilepsy patients (32 left, 14 right) by 1H MRSI at high magnetic field (4.1 T). We examined the relationship between the right and left Cr/NAA hippocampal ratios to measures of verbal and visual memory, intelligence, attention, visuoperception, and confrontation naming. RESULTS: Measures of episodic verbal memory (n = 33) and visual confrontation naming (n = 46) were selectively associated with left hippocampal metabolic function (p<0.004), whereas neuronal function of the right hippocampal region was strongly associated with performance on a measure of facial recognition (n = 46; p<0.02). CONCLUSIONS: This study shows that specific areas of cognitive function are related to hippocampal neuronal metabolic abnormalities as detected by spectroscopic imaging. The current study indicates that 1H MRSI offers a complimentary technique to structural imaging studies in the study of mesial temporal lobe epilepsy and may enhance understanding of the role of hippocampal function in complex cognitive systems
— id: 139955, year: 1999, vol: 53, page: 2052, stat: Journal Article,

Cognitive consequences of coexisting temporal lobe developmental malformations and hippocampal sclerosis
Martin, R; Dowler, R; Gilliam, F; Faught, E; Morawetz, R; Kuzniecky, R
1999 Sep 11;53(4):709-715, Neurology
OBJECTIVE: To characterize patterns of cognitive functioning in a well-defined group of patients with MRI-identified coexisting left temporal lobe developmental malformations (TLDM) and mesial temporal sclerosis (MTS), and to examine neuropsychological outcome in this dual-pathology group following epilepsy surgery. METHODS: Cognitive functioning in patients with left TLDM and MTS (n = 15) was compared with patients with isolated left MTS (n = 40). TLDM and MTS were identified by high-quality MRI protocol. Patients were administered a battery of neuropsychology tests as part of their presurgical workup for possible epilepsy surgery. Unilateral temporal lobe resection was performed on 10 of the dual-pathology patients and 34 of the isolated MTS patients. Postoperative cognitive performance was also assessed. RESULTS: Both groups displayed impairments in verbal and visual memory, language, and academic achievement. Performance on measures of psychometric intelligence, executive function, and attention were not impaired and were similar between groups. Presence of dual pathology was associated with a significantly less efficient verbal encoding strategy on the word list learning task. Postoperatively, declines were noted for both groups across tasks of verbal memory and language. Groups were not different significantly in terms of neuropsychological outcome after surgery. CONCLUSION: Patients with coexisting TLDM and MTS have impaired cognitive functioning similar to MTS patients-in particular, with regard to episodic memory and language deficits. Temporal lobe resection produces similar cognitive changes in both groups
— id: 139957, year: 1999, vol: 53, page: 709, stat: Journal Article,

Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults
Martin, R; Kuzniecky, R; Ho, S; Hetherington, H; Pan, J; Sinclair, K; Gilliam, F; Faught, E
1999 Jan 15;52(2):321-327, Neurology
OBJECTIVE: To study the acute and steady-state cognitive effects of three new antiepileptic drugs (AEDs): gabapentin, lamotrigine, and topiramate. BACKGROUND: Several newer antiepileptic medications approved recently by the Food and Drug Administration are gaining attention as efficacious alternatives to established AEDs. Greater tolerability with fewer side effects are reported in some. However, the potential cognitive effects of these newer AEDs have received limited attention. METHODS: Healthy young adults randomized to either of the three drugs were administered tests of attention, psychomotor speed, language, memory, and mood at baseline (predrug), acute single-dose period, and after 2 and 4 weeks on the drug. RESULTS: Compared with baseline, the topiramate group had selective, statistically significant declines on measures of attention and word fluency at acute doses, whereas the other two AED groups had no performance changes. At the 2- and 4-week test periods, only the topiramate subjects continued to display neurocognitive effects from drug administration. CONCLUSIONS: Results demonstrate potential acute and steady-state adverse cognitive effects for topiramate, whereas minimal effects were displayed for either gabapentin or lamotrigine in young healthy adults
— id: 139966, year: 1999, vol: 52, page: 321, stat: Journal Article,

Surgical outcome of cortical dysplasia: An actuarial analysis
Powell, TW; Faught, RE; Gilliam, F; Morawitz, R; Kuzniecky, RI
1999 ;40(2):207-208, Epilepsia
— id: 104862, year: 1999, vol: 40, page: 207, stat: Journal Article,

Increasing the accuracy of seizure focus localization using repeat Tc-99m HMPAO ICTAL SPECT
San Pedro, EC; Kuzniecky, RI; Mountz, JM
1999 ;213P(2):1135-1135, Radiology
— id: 104863, year: 1999, vol: 213P, page: 1135, stat: Journal Article,

Subjective versus objective memory change after temporal lobe epilepsy surgery
Sawrie, S M; Martin, R C; Kuzniecky, R; Faught, E; Morawetz, R; Jamil, F; Viikinsalo, M; Gilliam, F
1999 Oct 22;53(7):1511-1517, Neurology
OBJECTIVE: To examine subjective versus objective memory change after anterior temporal lobectomy (ATL). METHODS: A prospective, controlled study. Controls included 39 unoperated patients with intractable temporal lobe epilepsy (TLE) who were administered a series of cognitive and health-related quality of life measures at baseline and at 12-month follow-up intervals. The surgery sample included 65 patients with intractable, focal TLE who had undergone either a right or left ATL. These patients were tested preoperatively and at 6-month follow-up intervals. Subjective and objective memory change was quantified using a newly developed methodology to control for practice effect and regression to the mean. RESULTS: Measures of subjective and objective memory change were not significantly related in the surgery sample. Prevalence of significant subjective memory decline 1 year after surgery ranged from 3 to 7%, whereas prevalence of significant objective memory decline ranged from 26 to 55%. Postoperative levels of emotional distress significantly predicted self-reported memory decline 1 year after ATL. Postoperative medication side effect and seizure outcome were also related significantly to subjective memory change in patients who had undergone left ATL. CONCLUSIONS: Subjective and objective memory change after temporal lobectomy are not related. Complaints of significant memory decline after ATL are infrequent and may serve as a marker for depression or other mood disorder rather than organically based memory decline
— id: 139956, year: 1999, vol: 53, page: 1511, stat: Journal Article,

Neural network modeling of verbal memory and hippocampal function: A quantitative MRI-MRS study
Sawrie, SM; Martin, RC; Gilliam, FG; Faught, E; Maton, B; Hugg, JW; Kuzniecky, RI
1999 ;40(2):45-45, Epilepsia
— id: 104864, year: 1999, vol: 40, page: 45, stat: Journal Article,

Temporal lobe pH(i) and IQ: No consistent correlation
Anderson, B; Elgavish, GA; Chu, WJ; Simor, T; Martin, RC; Hugg, JW; Kuzniecky, RI
1998 ;26(2):75-79, Intelligence
Medial temporal lobe pH(i) and IQ were compared in 33 men and women undergoing evaluation for epilepsy surgery. No consistent correlation between medial temporal lobe pH(i) and IQ measures was observed. pH(i) measures from the two hemispheres were poorly correlated. We were unable to replicate the report of Rae, et al. (1996) of a significant positive correlation between brain pH(i) and IQ.
— id: 104865, year: 1998, vol: 26, page: 75, stat: Journal Article,

Guidelines for neuroimaging evaluation of patients with uncontrolled epilepsy considered for surgery
Berkovich, AJ; Berkovic, SF; Cascino, GD; Chiron, C; Duncan, JS; Gadian, DG; Jackson, GD; Kuzniecky, RI; McLachlan, RS; Meencke, HJ; Palmini, A; Sadzot, B; Stefan, H; Theodore, WH; Comm on Neuroimaging of the Int League Against
1998 ;39(12):1375-1376, Epilepsia
— id: 104866, year: 1998, vol: 39, page: 1375, stat: Journal Article,

Volumetric MRI of the limbic system: anatomic determinants
Bilir, E; Craven, W; Hugg, J; Gilliam, F; Martin, R; Faught, E; Kuzniecky, R
1998 Mar;40(3):138-144, Neuroradiology
The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. It is involved in complex functions including memory and emotion and in diseases such as temporal lobe epilepsy. Volume measurements of the amygdala and hippocampus have been used reliably to study patients with temporal lobe epilepsy but have not extended to other limbic structures. We performed volume measurements of hippocampus, amygdala, fornix and mamillary bodies in healthy individuals. Measurements of the amygdala, hippocampus, fornix and mamillary bodies revealed significant differences in volume between right and left sides (P < 0.001). The intraclass coefficient of variation for measurements was high for all structures except the mamillary bodies. Qualitative image assessment of the same structures revealed no asymmetries between the hemispheres. This technique can be applied to the study of disorders affecting the limbic system
— id: 139973, year: 1998, vol: 40, page: 138, stat: Journal Article,

Symptomatic occipital lobe epilepsy
Kuzniecky, R
1998 ;39 Suppl 4:S24-S31, Epilepsia
Symptomatic occipital lobe epilepsy is increasingly recognized among patients with partial-onset seizures. Although traditional clinical and electroencephalographic criteria had defined occipital lobe epilepsy in the past, new neuroimaging techniques and the recognition of specific syndromes associated with occipital lobe epilepsy have improved the diagnosis and management of these patients. These syndromes include, among others, lesional occipital lobe epilepsy (congenital vs. acquired), MELAS, and epilepsy with bilateral occipital calcifications. The diagnosis of symptomatic occipital lobe epilepsy is improving as functional and structural neuroimaging techniques enable the detection of subtle abnormalities in such patients. This has had a direct impact on the correct classification of patients with benign occipital lobe epilepsy, basilar migraine, and symptomatic occipital lobe epilepsy. The common clinical symptoms, EEG patterns, and neuroimaging findings of these patients are discussed
— id: 139974, year: 1998, vol: 39 Suppl 4, page: S24, stat: Journal Article,

Topiramate increases cerebral GABA in healthy humans
Kuzniecky, R; Hetherington, H; Ho, S; Pan, J; Martin, R; Gilliam, F; Hugg, J; Faught, E
1998 Aug;51(2):627-629, Neurology
Topiramate (TOP) is a novel anticonvulsant drug with multiple mechanisms of action used in the treatment of epilepsy. Measurements of cerebral GABA were obtained in six controls using 1H MRS at baseline and at 3 and 6 hours following the administration of 3 mg/kg of TOP. Brain GABA concentrations rose by 72% at 3 hours and by 64% at 6 hours compared with baseline (p < 0.004). This study demonstrates that TOP significantly increases human cerebral GABA concentrations in healthy individuals
— id: 139970, year: 1998, vol: 51, page: 627, stat: Journal Article,

Relative utility of 1H spectroscopic imaging and hippocampal volumetry in the lateralization of mesial temporal lobe epilepsy
Kuzniecky, R; Hugg, J W; Hetherington, H; Butterworth, E; Bilir, E; Faught, E; Gilliam, F
1998 Jul;51(1):66-71, Neurology
OBJECTIVES: To determine the relative utility of 1H MRSI and hippocampal volumetry for the lateralization of mesial temporal lobe epilepsy (MTLE) in patients with intractable epilepsy. BACKGROUND: MTLE is the most common partial-onset seizure disorder in patients undergoing temporal lobe epilepsy surgery. MR volumetry and spectroscopy are reliable preoperative imaging techniques for the lateralization of MTLE. METHODS: We analyzed the 1H MRSI and hippocampal formation volumes preoperatively in 30 consecutive patients who had undergone temporal lobectomy. RESULTS: Volumetry correctly lateralized the side of surgery in 93% of patients and 1H MRSI did so in 97% of patients. Incorrect lateralization occurred by volumetry in two patients and by 1H MRSI in one patient. Concordance between all MRI modalities was 73%. Pearson's analysis revealed no correlation between the degree of hippocampal volume loss and the creatine-to-N-acetylated-compounds ratio. CONCLUSIONS: Volumetry and 1H MRSI correctly lateralized most patients with MTLE and complement each other in final lateralization. The lack of correlation between the severity of volume loss and the degree of metabolic disturbance suggests that the techniques examine distinct pathophysiologic processes in MTLE
— id: 139971, year: 1998, vol: 51, page: 66, stat: Journal Article,

Improved health care resource utilization following video-EEG-confirmed diagnosis of nonepileptic psychogenic seizures
Martin, R C; Gilliam, F G; Kilgore, M; Faught, E; Kuzniecky, R
1998 Oct;7(5):385-390, Seizure
The economic burden of epilepsy is well recognized. However, empirical investigation establishing costs associated with the diagnosis and treatment of non-epileptic psychogenic seizures (NEPS) is lacking. We studied 20 patients with video/EEG monitoring-confirmed NEPS to determine the effect of definitive diagnosis and treatment on medical costs and utilization. A medical resource utilization questionnaire and inpatient medical chart review were employed to calculate utilization information. Medication usage, outpatient visits, emergency room admissions, and diagnostic testing over a 6-month pre-diagnosis and a 6-month post-diagnosis period were compared. There was an 84% average reduction in total seizure-related medical charges in the 6 months following NEPS diagnosis. Average diagnostic testing charges declined 76%, average medication charges decreased 69%, outpatient clinic visits declined 80%, and emergency room visits reduced by 97%. A majority of patients obtaining a definitive inpatient video/EEG-seizure-monitoring-confirmed NEPS diagnosis experience substantial reductions in health care utilization and dollar costs
— id: 139969, year: 1998, vol: 7, page: 385, stat: Journal Article,

Individual memory change after anterior temporal lobectomy: a base rate analysis using regression-based outcome methodology
Martin, R C; Sawrie, S M; Roth, D L; Gilliam, F G; Faught, E; Morawetz, R B; Kuzniecky, R
1998 Oct;39(10):1075-1082, Epilepsia
PURPOSE: To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression-based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome. METHODS: Memory change was operationalized using regression-based change norms in a group of left (n = 53) and right (n = 48) ATL patients. All patients were administered tests of episodic verbal (prose recall, list learning) and visual (figure reproduction) memory, and semantic memory before and after ATL. RESULTS: ATL patients displayed a wide range of memory outcome across verbal and visual memory domains. Significant performance declines were noted for 25-50% of left ATL patients on verbal semantic and episodic memory tasks, while one-third of right ATL patients displayed significant declines in immediate and delayed episodic prose recall. Significant performance improvement was noted in an additional one-third of right ATL patients on delayed prose recall. Base rate change was similar between the two ATL groups across immediate and delayed visual memory. Approximately one-fourth of all patients displayed clinically meaningful losses on the visual memory task following surgery. Robust relationships between preoperative memory measures and nonstandardized change scores were attenuated or reversed using standardized memory outcome techniques. CONCLUSIONS: Our results demonstrated substantial group variability in memory outcome for ATL patients. These results extend previous research by incorporating known effects of practice and regression to the mean when addressing meaningful neuropsychological change following epilepsy surgery. Our findings also suggest that future neuropsychological outcome studies should take steps towards controlling for regression-to-the-mean before drawing predictive conclusions
— id: 139968, year: 1998, vol: 39, page: 1075, stat: Journal Article,

Contribution of neuropsychological data to the prediction of temporal lobe epilepsy surgery outcome
Sawrie, S M; Martin, R C; Gilliam, F G; Roth, D L; Faught, E; Kuzniecky, R
1998 Mar;39(3):319-325, Epilepsia
PURPOSE: We empirically examined the contribution of neuropsychological data to the prediction of postoperative seizure control relative to base rate information in an existing series of patients undergoing anterior temporal lobectomy (ATL). METHODS: A discriminant function predicting surgery outcome (seizure-free vs. non-seizure-free) was computed separately for samples of patients with left (n = 79) and right (n = 62) temporal lobectomy (LATL, RATL). Predictor variables included 14 measures tapping five neurocognitive domains. The predicted base rates were compared with the actual base rates in the two samples. Finally, overall predictive accuracy was examined in optimal versus suboptimal ATL patients. RESULTS: The base rate of seizure freedom in the LATL group was 74.70%; that in the RATL group was 66.10%. The predictive function for the LATL group achieved a hit rate of 80.00% and a positive predictive power of 92.11%. The function for the RATL group achieved a hit rate of 83.33% and a positive predictive power (PPP) of 89.66%. The overall predictive accuracy for the optimal group was only 55%, but that in the suboptimal group was 72%. CONCLUSIONS: Neuropsychological data used in a multivariate statistical fashion may be able to offer an incremental increase in the prediction of postoperative seizure freedom relative to existing base rates of surgery success in patients with ATL epilepsy. The use of neuropsychological data may be of greatest predictive value in a population of ATL candidates with suboptimal findings with a lower base rate of postoperative seizure freedom, but may actually reduce predictive accuracy in a group of ATL candidates from an optimal population with an already high base rate of surgical success
— id: 139972, year: 1998, vol: 39, page: 319, stat: Journal Article,

Recommendations for neuroimaging of patients with epilepsy
Barkovich, AJ; Berkovic, SF; Cascino, GD; Chiron, C; Duncan, JS; Gadian, DG; Jackson, GD; Kuzniecky, RI; McLachlan, RS; Meencke, HJ; Palmini, A; Sadzot, B; Stefan, H; Theodore, WH
1997 ;38(11):1255-1256, Epilepsia
— id: 104867, year: 1997, vol: 38, page: 1255, stat: Journal Article,

ILAE neuroimaging commission recommendations for neuroimaging of patients with epilepsy
Berkovic, SF; Duncan, JS; Barkovich, A; Cascino, G; Chiron, C; Engel, J; Gadian, D; Jackson, G; Kuzniecky, R; McLachlan, R; Meencke, H; Palmini, A; Reynolds, EH; Sadzot, B; Stefan, H; Theodore, W; Wolf, P
1997 ;38(11):1-2, Epilepsia
These guidelines are intended to apply to patients with a clear diagnosis of epilepsy. They have been specifically formulated for the management of newly diagnosed patients and those with chronic epilepsy who have not been fully evaluated, and are not designed for the full investigation of patients for possible surgical treatment. Therefore, these recommendations are dedicated to computed tomography (CT) and magnetic resonance imaging (MRI) but not to functional imaging techniques. $$:
— id: 104868, year: 1997, vol: 38, page: 1, stat: Journal Article,

Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: A double-blind, concentration-response design clinical trial
Beydoun, A; Sackellares, JC; Shu, V; Bornhofen, JH; Borreson, T; Browne, TR; Cascino, GD; Deaton, R; Devinsky, O; Drake, ME; Fromm, GH; Gallagher, BB; Griggs, WL; Hirschorn, KA; Homan, RW; Kaplan, L; Krauss, GL; Kuzniecky, RI; Chi, WL; Mamdani, MB; McPherson, SL; Mirza, WU; Morris, GL; Murray, KR; Pakainis, A; Penovich, P; Ramsay, RE; Rask, C; Risinger, MW; Rogin, JB; Roos, K; Tennison, M; Thadani, V; Valeriano, JP; Weisberg, LA
1997 JAN ;48(1):182-188, Neurology
This is the first randomized, double-blind, parallel-group, multicenter trial that evaluated the efficacy of divalproex sodium monotherapy by comparing seizure frequency in 143 patients with poorly controlled partial epilepsy randomly assigned to high (80 to 150 mu g/mL; 555 to 1,040 mu mol/L) or low (25 to 50 mu g/mL; 175 to 345 mu mol/L) plasma valproate groups, There was a statistically significant reduction from baseline in the 8-week frequency of complex partial (p = 0.001) and secondarily generalized tonic-clonic seizures (p = 0.018) for patients in the high, compared with the low, plasma valproate group. Compared with baseline, there was a 30% median reduction in complex partial seizures for patients in the high group and a 19% increase for those in the low group. The median reduction for secondarily generalized tonic-clonic seizures was 70% for patients in the high group compared with a 22% increase in the low group. Adverse events that occurred significantly more frequently in the high group included tremors, thrombocytopenia, alopecia, asthenia, diarrhea, vomiting, and anorexia. This study demonstrates the efficacy of divalproex sodium as monotherapy for the treatment of partial-onset seizures and supports its role as one of the first-line antiepileptic drug treatments for patients with partial epilepsy
— id: 104284, year: 1997, vol: 48, page: 182, stat: Journal Article,

Cognitive adverse effects of topiramate
Faught, E; Kuzniecky, RI; Gilliam, F; Kamin, M
1997 ;48(3):43006-43006, Neurology
— id: 104869, year: 1997, vol: 48, page: 43006, stat: Journal Article,

Association of combined MRI, interictal EEG, and ictal EEG results with outcome and pathology after temporal lobectomy
Gilliam, F; Bowling, S; Bilir, E; Thomas, J; Faught, E; Morawetz, R; Palmer, C; Hugg, J; Kuzniecky, R
1997 Dec;38(12):1315-1320, Epilepsia
PURPOSE: Magnetic resonance imaging, interictal scalp EEG, and ictal scalp EEG each have been shown to localize the primary epileptic region in most patients with mesial-basal temporal lobe epilepsy (MBTLE), but the association of surgical outcome and pathology with each combination of these test results is not known. METHODS: We reviewed the MRI, interictal scalp EEG, and ictal scalp EEG results of 90 consecutive patients with MBTLE. Twelve patients were excluded from the analysis because inconclusive bitemporal intracranial EEG results precluded anterior temporal lobectomy (ATL); none had concordant MRI and interictal scalp EEG results. We compared all combinations of presurgical MRI, interictal EEG, and ictal EEG results to seizure outcome and tissue pathology in the 78 patients who underwent an ATL. RESULTS: Forty-eight (61%) patients had concordant lateralized MRI and interictal EEG temporal lobe abnormalities, with no discordant ictal EEG results; 77% of these patients were seizure-free after ATL. Concordance of MRI and interictal EEG abnormalities correlated with seizure cessation (p < 0.05), compared to all combinations with discordant or nonlateralizing MRI and interictal EEG results. Mesial temporal sclerosis (MTS) was confirmed pathologically in about 80% of both groups (p = 0.5). Outcome in patients with concordant MRI and ictal EEG with nonlateralizing interictal EEG was significantly worse than combinations with concordant MRI and interictal EEG (p < 0.02). CONCLUSIONS: Compared to other combinations of test results, concordance of MRI and interictal EEG is most closely associated with surgical outcome in MBTLE. However, most selected patients have pathologic confirmation of MTS regardless of test results or outcome. This information may be useful for planning the presurgical evaluation of patients with medically intractable MBTLE
— id: 139975, year: 1997, vol: 38, page: 1315, stat: Journal Article,

Patient-validated content of epilepsy-specific quality-of-life measurement
Gilliam, F; Kuzniecky, R; Faught, E; Black, L; Carpenter, G; Schrodt, R
1997 Feb;38(2):233-236, Epilepsia
PURPOSE: To study the effects of epilepsy from the patients' perspective and assist determination of content validity of health-related quality-of-life (HRQOL) measures. METHODS: We asked 81 consecutive patients with moderately severe epilepsy to list in order of importance their concerns of living with recurrent seizures. To minimize investigator bias, patients completed the procedure in a private setting without staff involvement. RESULTS: Twenty-four distinct domains were generated by the patients. Concerns about driving (64%), independence (54%), employment (51%), social embarrassment (36%), medication dependence (33%), mood/stress (32%), and safety (31%) each were listed by > 30% of patients. Driving was listed as the most important concern by 28% of patients, followed by employment (21%), independence (9%), safety (6%), antiepileptic-drug side effects (5%), seizure unpredictability (5%), and seizure aversion (5%). CONCLUSIONS: The effect of epilepsy on HRQOL is not vague or obscure from the patients' perspective but is defined by a limited number of domains. Independence is an important concern that may not be evaluated adequately by currently available HRQOL instruments
— id: 139982, year: 1997, vol: 38, page: 233, stat: Journal Article,

Epilepsy surgery outcome: comprehensive assessment in children
Gilliam, F; Wyllie, E; Kashden, J; Faught, E; Kotagal, P; Bebin, M; Wise, M; Comair, Y; Morawetz, R; Kuzniecky, R
1997 May;48(5):1368-1374, Neurology
The effect of extratemporal and temporal lobe cortical resection on children with intractable epilepsy is not well understood. We evaluated a comprehensive array of outcome variables in 33 consecutive children who received epilepsy surgery at 12 years of age or younger. Twenty-two (67%) children were seizure-free, three (9%) had a greater than 90% reduction in seizures, and four had no improvement. Antiepileptic drugs (AEDs) were not required in 10 (30%) children and were reduced in number in another 10. Six (29%) of 21 tested children had an improvement of greater than 10 points in Verbal or Performance IQ after surgery, while one (4%) had a decrease greater than 10 points in Verbal IQ. One mild hemiparesis and one inferior quadrantanopsia occurred; both were anticipated. We used the Child Health Questionnaire (CHQ), a valid and reliable instrument for children, to assess health-related quality of life (HRQOL). Six of 12 subscale scores of the CHQ were significantly lower in the surgical group compared with 410 age-matched control subjects. Parents were satisfied with surgical results in 28 (85%) cases. Pathologic tissue diagnosis and site of resection were not associated significantly with any outcome measure. We conclude that surgery eliminates seizures and reduces AED requirements in most children with intractable epilepsy selected by currently available methods. Further investigation is needed to establish the nature and significance of inferior scores in the surgical group in the HRQOL domains of physical function, general health, and self-esteem
— id: 139979, year: 1997, vol: 48, page: 1368, stat: Journal Article,

Bilateral parasagittal parietooccipital polymicrogyria and epilepsy
Guerrini, R; Dubeau, F; Dulac, O; Barkovich, A J; Kuzniecky, R; Fett, C; Jones-Gotman, M; Canapicchi, R; Cross, H; Fish, D; Bonanni, P; Jambaque, I; Andermann, F
1997 Jan;41(1):65-73, Annals of neurology
We describe 9 patients with a bilateral malformation of cortical development, centered around the parasagittal and mesial aspects of the parietooccipital cortex, with magnetic resonance imaging findings suggestive of polymicrogyria. No familial distribution or etiologic factors were identified. Location in a watershed area between anterior and posterior cerebral arteries suggests postmigratory perfusion failure as the underlying cause. In most patients the malformation was detected by magnetic resonance imaging after computed tomography scans with 10-mm-thick sections were considered normal. Seizures, present in all, had started between the ages of 20 months and 15 years (mean, 9 years) and were intractable in 7. Complex partial seizures with or without minor automatisms were the most frequent ictal pattern. In only 4 patients these were preceded by symptoms indicating posterior onset. Interictal electroencephalograms showed both diffuse and bilateral parietooccipital or temporal abnormalities. The range of IQ scores indicated average intelligence to mild retardation. Several patients presented deficits on neuropsychological tasks requiring performance under time constraints, suggesting that the malformation may result in cognitive slowing. Early diagnosis of this malformation may be difficult because of the lack of neurological signs, relatively late seizure onset, difficulty in localizing seizure onset, and inability to recognize the cortical abnormality on computed tomography scans
— id: 139984, year: 1997, vol: 41, page: 65, stat: Journal Article,

Magnetic resonance and functional magnetic resonance imaging: tools for the study of human epilepsy
Kuzniecky, R
1997 Apr;10(2):88-91, Current opinion in neurology
The development of new magnetic resonance imaging base neuroimaging techniques is increasing the utility and the importance of magnetic resonance imaging in the investigation of patients with epilepsy. Recent advances in magnetic resonance imaging, magnetic resonance spectroscopy and functional magnetic resonance imaging are not only providing relevant clinical information regarding human epilepsy but are also revealing important insights into its basic mechanisms. In the present review the role of these new technologies is discussed in the context of their clinical utility
— id: 139980, year: 1997, vol: 10, page: 88, stat: Journal Article,

Occipital lobe developmental malformations and epilepsy: clinical spectrum, treatment, and outcome
Kuzniecky, R; Gilliam, F; Morawetz, R; Faught, E; Palmer, C; Black, L
1997 Feb;38(2):175-181, Epilepsia
PURPOSE: Cortical developmental malformations (CDM) are increasingly recognized in association with epilepsy. We describe 10 patients (age range 14-35 years) with symptomatic occipital lobe epilepsy and CDM. METHODS: Neurologic, neuroophthalmologic and electrophysiologic studies were performed. Patients had MRI, SPECT, and in some cases intracranial EEG investigators. RESULTS: Mean age of seizure onset was 8 years. We noted strong correlations between the presence of visual auras, the scalp EEG pattern, and the subtype of underlying pathology. Magnetic resonance imaging (MRI) showed CDM in all patients, with polymicrogyria and focal dysplasia being the most frequent malformations. Despite the presence of occipital lobe structural malformations in all patients, visual field deficits were present in only 2. Those who underwent cortical resections were seizure-free or showed major improvement at a mean follow-up of 3.5 years. CONCLUSIONS: Intracranial stimulation studies and the low frequency of pre- and postoperative deficits suggest that some degree of cortical visual reorganization may occur in patients with occipital lobe malformations. Occipital lobe CDM should be sought as a cause of symptomatic occipital lobe epilepsy even though they may become symptomatic after childhood
— id: 139983, year: 1997, vol: 38, page: 175, stat: Journal Article,

Intrinsic epileptogenesis of hypothalamic hamartomas in gelastic epilepsy
Kuzniecky, R; Guthrie, B; Mountz, J; Bebin, M; Faught, E; Gilliam, F; Liu, H G
1997 Jul;42(1):60-67, Annals of neurology
Hypothalamic hamartomas and gelastic seizures are often associated with cognitive deterioration, behavioral problems, and poor response to anticonvulsant treatment or cortical resections. The origin and pathophysiology of the epileptic attacks are obscure. We investigated 3 patients with this syndrome and frequent gelastic seizures. Ictal single-photon emission computed tomography performed during typical gelastic seizures demonstrated hyperperfusion in the hamartomas, hypothalamic region, and thalamus without cortical or cerebellar hyperperfusion. Electroencephalographic recordings with depth electrodes implanted in the hamartoma demonstrated focal seizure origin from the hamartoma in 1 patient. Electrical stimulation studies reproduced the typical gelastic events. Stereotactic radiofrequency lesioning of the hamartoma resulted in seizure remission without complications 20 months after surgery. The functional imaging findings, electrophysiological data, and results of radiofrequency surgery indicate that epileptic seizures in this syndrome originate and propagate from the hypothalamic hamartoma and adjacent structures
— id: 139976, year: 1997, vol: 42, page: 60, stat: Journal Article,

Proton spectroscopic imaging at 4.1 tesla in patients with malformations of cortical development and epilepsy
Kuzniecky, R; Hetherington, H; Pan, J; Hugg, J; Palmer, C; Gilliam, F; Faught, E; Morawetz, R
1997 Apr;48(4):1018-1024, Neurology
We used proton magnetic resonance spectroscopic imaging (MRSI) at 4.1 tesla in patients with malformations of cortical development (MCDs) and epilepsy. We compared the spectroscopic results with normative data using 2 SDs (95% confidence) above normal values for detection of significant abnormalities for creatine-N-acetylated compounds (Cr/NA) ratio and choline-N-acetylated compounds (Cho/NA). The results were correlated with clinical, EEG, and histologic findings. Patients with focal cortical dysplasia showed significant metabolic abnormalities in correspondence with the structural lesions, whereas patients with heterotopia and polymicrogyria demonstrated no subcortical MRSI abnormalities. Significant correlations were found between the metabolic abnormalities and the frequency of seizures but not with the degree of interictal EEG discharges. Quantitative neuronal and glial cell counts revealed no statistically significant correlation between cell loss and the abnormal metabolic ratios in those who underwent surgery. These preliminary findings suggest that MRSI-based metabolic abnormalities in patients with MCDs are variable and are likely to be associated with complex cellular mechanisms involving the regulation of NA, total Cr content, and Cho
— id: 139981, year: 1997, vol: 48, page: 1018, stat: Journal Article,

Supplementary sensorimotor area epilepsy. Seizure localization, cortical propagation and subcortical activation pathways using ictal SPECT
Laich, E; Kuzniecky, R; Mountz, J; Liu, H G; Gilliam, F; Bebin, M; Faught, E; Morawetz, R
1997 May;120 ( Pt 5):855-864, Brain
We studied clinical signs, EEGs and ictal cerebral blood flow by single-photon emission computed tomography (SPECT) in eight patients with intractable supplementary sensorimotor area (SSMA) seizures. SPECT scans were performed after injection of the regional cerebral blood flow tracer [99mTc]HMPAO (hexametylpropylene amine oxime) early in the ictal phase (2-5 s after seizure onset). Ictal SPECT demonstrated unilateral predominance of hyper-perfusion of the SSMA in all patients, concordant with either lateralizing clinical signs, lateralization of ictal scalp EEG or with the site of ictal onset of seizures, obtained from intracranial electrodes. Two distinctive cortical blood-flow propagation patterns were identified in SSMA seizures. The type I pattern consisted of primary involvement of the ipsilateral SSMA and dorsal premotor and motor cortex. The type II pattern consisted of bilateral but asymmetric mesial frontal propagation. Ictal contraversive head and eye movements were associated with a type I propagation pattern (P < 0.03). Activation of subcortical structures led to variable hyper-perfusion of the basal ganglia and thalamus. Contralateral cerebellar hyperperfusion was observed in all cases. We conclude that ictal SPECT is a useful method for seizure localization in patients with SSMA epilepsy. The observed heterogeneity of clinical features in SSMA epilepsy correlates with propagation to, and activation of, specific cortical structures, and is consistent with known anatomical interconnections between the SSMA, ipsilateral cortical and transcallosal cortical structures
— id: 139978, year: 1997, vol: 120 ( Pt 5), page: 855, stat: Journal Article,

Identification of a recombination event narrowing the Lafora disease gene region
Maddox, L O; Descartes, M; Collins, J; Keating, J; Rosenfeld, S; Palmer, C; Carroll, A J; Kuzniecky, R
1997 Jul;34(7):590-591, Journal of medical genetics
Patients affected with progressive myoclonus epilepsy of the Lafora type present during late adolescence with a characteristic EEG pattern and Lafora bodies seen on skin biopsy. The critical region for the Lafora gene has been localised to chromosome 6q24 flanked by the dinucleotide repeat markers D6S292 and D6S420. This study for linkage of markers from the candidate gene region was performed in a previously unpublished family affected with Lafora disease. EEG and skin biopsy evaluation for Lafora bodies were performed on five of eight family members followed for seizure activity. Haplotype and linkage analysis of DNA from five family members were carried out using the nine dinucleotide repeat markers reported in the common region of homozygosity by Serratosa et al in 1995. The present study of an additional family affected by Lafora disease has narrowed the 17 cM critical region for the Lafora disease gene on chromosome 6q24 to a 4 cM region flanked by markers D6S308 and D6S311
— id: 139977, year: 1997, vol: 34, page: 590, stat: Journal Article,

Is the intracellular pH different from normal in the epileptic focus of patients with temporal lobe epilepsy? A 31P NMR study
Chu, W J; Hetherington, H P; Kuzniecky, R J; Vaughan, J T; Twieg, D B; Faught, R E; Gilliam, F G; Hugg, J W; Elgavish, G A
1996 Sep;47(3):756-760, Neurology
We performed in vivo 31P NMR spectroscopic studies of human brain on a 4.1 T whole-body NMR system. Based on a control group of 20 healthy volunteers, the normal pHi was 7.05 (SD, 0.06; SEM, 0.01) in the left temporal lobe and 7.04 (SD, 0.04; SEM, 0.01) in the right temporal lobe. We also studied a patient group consisting of 13 individuals with unilateral temporal lobe epilepsy. The mean pHi was 7.02 (SD, 0.04; SEM, 0.01) in the ipsilateral lobe and 7.02 (SD, 0.05; SEM, 0.01) in the contralateral lobe. These results clearly show that no statistically significant difference in pHi is observed between the two lobes, either in normal controls or in patients. Also, no significant pHi difference exists between the control group and the patient group. Lateralization in each of the 13 patients with unilateral epilepsy, based on their individual pHi difference between the ipsilateral lobe and contralateral lobe (delta pHi), showed that three patients were nondiagnostic cases because their delta pHis were not significantly different from zero (< or = 0.02), five patients showed small delta pHis consistent with their clinical lateralization, whereas the remaining five patients showed delta pHi-based lateralization opposite to the clinical findings. These results seem to indicate an essentially random distribution around delta pHi = 0 within a very small experimental error of +/-0.02 pH units. pHi obtained from eight different areas in each of the 13 unilateral patients also did not show any significantly nonzero delta pHi values. These results led to the conclusion that even at the excellent spectral resolution and reproducibility of the 4.1 T machine (typical SD of 0.05 pH units), no significant pHi effect, induced by temporal lobe epilepsy, could be detected. Therefore, in this study, delta pHi does not appear to be a clinically useful tool for the lateralization of epileptic foci in patients with temporal lobe epilepsy
— id: 139985, year: 1996, vol: 47, page: 756, stat: Journal Article,

Altered brain sodium channel transcript levels in human epilepsy
Lombardo, A J; Kuzniecky, R; Powers, R E; Brown, G B
1996 Jan;35(1-2):84-90, Brain research. Molecular brain research
Normal, and perhaps pathological, characteristics of neuronal excitability are related to the distribution and density of voltage-gated ion channels such as the sodium channel. We studied normal and epileptic human brain using the ligase detection reaction to measure the relative quantities of mRNAs encoding sodium channel subtypes 1 and 2. Normal brains exhibited characteristic 1:2 ratios which varied by brain region, but the ratios were invariate among individuals. These normal values were altered as much as threefold in anatomically corresponding regions of epileptic brain tissues. Changes of this magnitude in such a highly conserved value support a potential role for sodium channels in the pathophysiology of epilepsy
— id: 139986, year: 1996, vol: 35, page: 84, stat: Journal Article,

Proton nuclear magnetic resonance spectroscopic imaging of human temporal lobe epilepsy at 4.1 T
Hetherington, H; Kuzniecky, R; Pan, J; Mason, G; Morawetz, R; Harris, C; Faught, E; Vaughan, T; Pohost, G
1995 Sep;38(3):396-404, Annals of neurology
We performed proton magnetic resonance spectroscopic imaging (MRSI) at high magnetic field (4.1 T) to study N-acetylaspartate, creatine, and choline levels in the brains of normal control subjects and patients with intractable temporal lobe epilepsy. We compared the results of MRSI to those of other presurgical techniques to determine the sensitivity of this method in the lateralization of the epileptic focus. The normal hippocampal creatine-N-acetylaspartate ratio was 0.71 +/- 0.14 with no differences between left and right. Using the mean control hippocampal creatine-N-acetylaspartate ratio plus 2 standard deviations to identify statistically significant changes, we found lateralizing metabolic abnormalities corresponding to the operated temporal lobe in all patients. Four patients (40%) had contralateral abnormalities, and 2 of them had bilateral independent seizure onset confirmed by intracranial electroencephalographic studies. Statistically significant increases in the choline-N-acetylaspartate ratio in comparison to healthy volunteers were observed in 8 of the 10 patients. With the creatine-N-acetylaspartate ratio, MRSI demonstrated a 100% sensitivity compared to magnetic resonance imaging, which identified pathology in 70% of the patients. These findings suggest that proton MRSI yields a distinctive metabolic profile in patients with temporal lobe epilepsy and is sensitive in detecting bilateral metabolic abnormalities in some patients. These preliminary findings suggest that MRSI is more sensitive than magnetic resonance imaging in the lateralization of epileptic foci in temporal lobe epilepsy
— id: 139988, year: 1995, vol: 38, page: 396, stat: Journal Article,

TEMPORAL-LOBE EPILEPSY LOCALIZATION BY H-1 MRSI AT 4.1T WITH FOLLOW-UP AFTER SURGERY
HUGG, JW; KUZNIECKY, RI; HETHERINGTON, HP; MASON, GF; PAN, JW; MORAWETZ, RB; GILLIAM, FG; FAUGHT, RE
1995 ;36(8):A1-A1, Epilepsia
— id: 104870, year: 1995, vol: 36, page: A1, stat: Journal Article,

Discordant occurrence of cerebral unilateral heterotopia and epilepsy in monozygotic twins
Kuzniecky, R; Gilliam, F; Faught, E
1995 Nov;36(11):1155-1157, Epilepsia
Cerebral developmental malformations are increasingly recognized as a cause of epilepsy. Magnetic resonance imaging (MRI) has advanced our understanding of these disorders and their relation to epilepsy. We report the occurrence of discordant unilateral heterotopia and epilepsy in monozygotic twins. The affected individual developed intractable focal seizures at age 16 years. Mild cognitive difficulties had been present in early life. Evaluation showed right hemisphere EEG epileptogenic abnormalities, and the MRI scan showed massive right hemisphere heterotopia. EEG and MRI examinations in the patient's twin brother were normal. These findings suggest that the development of some developmental brain malformations and epilepsy is strongly influenced by nongenetic factors such as an environmental insult
— id: 139987, year: 1995, vol: 36, page: 1155, stat: Journal Article,

Frontal and central lobe focal dysplasia: clinical, EEG and imaging features
Kuzniecky, R; Morawetz, R; Faught, E; Black, L
1995 Feb;37(2):159-166, Developmental medicine & child neurology
The authors studied 11 patients with developmental malformations and seizures originating from the frontal and central regions. Patients with centrally located seizures had primary involvement of the face or mouth; clonic activity involving the limb was also seen. Seizures among those with frontal lesions were primarily unilateral or bilateral tonic motor. Secondary generalized tonic-clonic seizures preceded by focal manifestations occurred infrequently in those with central localization, but were not rare in the frontal group. MRI revealed abnormalities in 10 patients, nine of whom underwent surgical resection with good results. Focal cortical dysplasia may be the underlying epileptogenic abnormality in young patients with clinical features suggestive of central or frontal cortical involvement
— id: 139989, year: 1995, vol: 37, page: 159, stat: Journal Article,

Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on first 67 patients exiting a controlled study. First International Vagus Nerve Stimulation Study Group
George, R; Salinsky, M; Kuzniecky, R; Rosenfeld, W; Bergen, D; Tarver, W B; Wernicke, J F
1994 May-Jun;35(3):637-643, Epilepsia
Vagus nerve stimulation (VNS) has demonstrated a significant anticonvulsant effect in preclinical studies, in pilot studies in humans, and in the acute phase of a multicenter, double-blinded, randomized study. After completion of a 14-week, blinded, randomized study, with 31 receiving high (therapeutic) VNS and 36 receiving low (less or noneffective) VNS, 67 patients elected to continue in an open extension phase. During the extension phase, all 67 patients received high VNS. Seizure frequency during the 3-month treatment blocks was compared with a 12-week baseline. For both groups, all periods of high VNS demonstrated a significant decrease in seizure frequency (p < 0.01 level) as compared with baseline. For the 16-18-month period of VNS, data were available for 26 of the 31 patients randomized to high VNS. This group achieved a 52.0% mean seizure frequency percentage reduction as compared with baseline. For those converted from low to high VNS, data were available for 24 of the 36 patients at the 16-18-month time period. This group reported a mean seizure frequency percentage reduction of 38.1% as compared with baseline. No significant change in the safety/side effect profile was reported during long-term follow-up. The previously reported side effects of hoarseness/voice change, coughing, and paresthesia (sensation in neck and jaw) continued to occur during VNS. These side effects were well tolerated. During the follow-up period, 1 patient died of thrombotic thrombocytopenic purpura (TTP) and 5 patients discontinued treatment because of unsatisfactory efficacy
— id: 139991, year: 1994, vol: 35, page: 637, stat: Journal Article,

Familial diffuse cortical dysplasia
Kuzniecky, R
1994 Mar;51(3):307-310, Archives of neurology
Two brothers are described with a syndrome characterized by mental retardation, atypical absence, atonic and generalized tonic-clonic seizures, and bilateral symmetrical slow spike and wave discharges on electroencephalograms. Magnetic resonance imaging revealed dysplastic cortex probably representing pachygyria primarily over the parietal regions bilaterally in both patients. The presence of an identical clinical, electroencephalographic, and cortical developmental abnormality on imaging studies in these brothers suggests that a genetic mechanism may play a role in some developmental disorders of the cerebral cortex
— id: 139992, year: 1994, vol: 51, page: 307, stat: Journal Article,

The congenital bilateral perisylvian syndrome: imaging findings in a multicenter study. CBPS Study Group
Kuzniecky, R; Andermann, F
1994 Jan;15(1):139-144, AJNR. American journal of neuroradiology
PURPOSE: To describe the neuroimaging findings and the clinical features in patients with the congenital bilateral perisylvian syndrome. PATIENTS AND METHODS: Evaluation including history, general and neurologic examinations, electroencephalogram, chromosomal studies, and imaging data were reviewed in 31 patients. Pathologic material was available in two patients. RESULTS: All patients had similar neurologic dysfunction, primarily pseudobulbar paresis. Dysarthria and severe restriction of tongue movements were present in all. Motor milestones were delayed in 75% of the patients and language milestones in all. Mild to moderate intellectual deficits were documented in 75% of patients (full-scale IQ = 70). Pyramidal signs were observed in 70%. Seizures were present in 87% and were intractable to medical therapy in half of this group. MR revealed bilateral perisylvian and perirolandic malformations with exposure of the insula. The malformations were symmetrical in 80% of cases. Pathologic correlation revealed four layered polymicrogyria in the affected areas. CONCLUSIONS: The congenital bilateral perisylvian syndrome is a homogeneous clinical-radiologic entity. The underlying abnormality is probably polymicrogyria
— id: 139994, year: 1994, vol: 15, page: 139, stat: Journal Article,

Infantile spasms: an early epileptic manifestation in some patients with the congenital bilateral perisylvian syndrome
Kuzniecky, R; Andermann, F; Guerrini, R
1994 Oct;9(4):420-423, Journal of child neurology
We report four patients with infantile spasms and the congenital bilateral perisylvian syndrome. Onset of spasms occurred during the first 6 months of life. Response to corticotropin treatment was prompt and resulted in resolution of seizures in all patients. Epilepsy developed in the four children after an interval of 2 to 12 years. Developmental outcome was variable; three were severely restricted and one was married and lived independently. Imaging studies revealed bilateral perisylvian lesions characteristic of polymicrogyria. Infantile spasms may be the presenting seizure type in some patients with the congenital bilateral perisylvian syndrome
— id: 139990, year: 1994, vol: 9, page: 420, stat: Journal Article,

The epileptic spectrum in the congenital bilateral perisylvian syndrome. CBPS Multicenter Collaborative Study
Kuzniecky, R; Andermann, F; Guerrini, R
1994 Mar;44(3 Pt 1):379-385, Neurology
We studied the frequency, clinical and EEG characteristics, and outcome of the epileptic syndrome in 31 patients with a congenital neurologic syndrome characterized by pseudobulbar palsy, cognitive deficits, and bilateral perisylvian polymicrogyria. Seizures were present in 27 of 31 patients (87%) and usually began between the ages of 4 and 12 years; they commonly consisted of atypical absence, atonic/tonic, and generalized tonic-clonic seizures. Partial attacks were present in 26%. EEG demonstrated generalized spike and wave abnormalities and, less frequently, multifocal discharges, predominantly in centro-parietal regions. Seizures were poorly controlled in 65%, with the remaining patients well controlled. Seven patients underwent callosotomy, which resulted in seizure improvement. This study indicates that the epileptic spectrum in this syndrome is broad but follows predictable patterns. Callosotomy is a valuable treatment strategy in those with intractable drop attacks
— id: 139993, year: 1994, vol: 44, page: 379, stat: Journal Article,

HOW MANY SEIZURES SHOULD BE OBSERVED BY EEG VIDEO MONITORING TO CONCLUDE THAT ALL SEIZURES ARISE FROM ONE SITE
FAUGHT, E; BRADLEY, EL; KUZNIECKY, RI
1993 ;43(4):A287-A287, Neurology
— id: 104871, year: 1993, vol: 43, page: A287, stat: Journal Article,

Felbamate monotherapy for partial-onset seizures: an active-control trial
Faught, E; Sachdeo, R C; Remler, M P; Chayasirisobhon, S; Iragui-Madoz, V J; Ramsay, R E; Sutula, T P; Kanner, A; Harner, R N; Kuzniecky, R
1993 Apr;43(4):688-692, Neurology
We evaluated felbamate (FBM) monotherapy in 111 patients with uncontrolled partial-onset seizures in a multicenter, double-blind, parallel-group trial. During the 56-day baseline period, patients had at least eight partial-onset seizures and received one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients received either FBM 3,600 mg/d or valproate (VPA) 15 mg/kg/d. The baseline AED at therapeutic levels was discontinued by one-third decrements on study days 1, 14, and 28 and the sub-therapeutic AED, if any, was discontinued completely on study day 1. Study endpoints were completion of 112 study days or fulfilling one or more escape criteria. Criteria for escape relative to baseline were (1) twofold increase in monthly seizure frequency, (2) twofold increase in highest 2-day seizure frequency, (3) single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or (4) significant prolongation of GTCs. The primary efficacy variable was the number of patients in each treatment group who met escape criteria. Thirty-seven patients on VPA and 18 on FBM met escape criteria (p < 0.001). Even when we considered FBM dropouts to have fulfilled escape criteria and VPA dropouts to have completed the 112-day trial, the treatment difference remained statistically significant (p = 0.039) in favor of FBM. Adverse experiences with FBM were all mild or moderate in severity. The frequency of adverse experiences was much lower during monotherapy. FBM monotherapy was effective in the treatment of partial-onset seizures with or without secondarily generalized seizures and demonstrated a favorable safety profile
— id: 139998, year: 1993, vol: 43, page: 688, stat: Journal Article,

Congenital bilateral perisylvian syndrome: study of 31 patients. The CBPS Multicenter Collaborative Study
Kuzniecky, R; Andermann, F; Guerrini, R
1993 Mar 6;341(8845):608-612, Lancet
Advances in neuroimaging techniques have enabled the recognition of developmental malformations of the brain during life. Careful correlation of clinical and imaging features has identified several new syndromes. We have studied 31 patients with a congenital neurological syndrome characterised by pseudobulbar palsy, cognitive deficits, and bilateral perisylvian abnormalities on imaging studies. All patients had diplegia of the facial pharyngeal, and masticatory muscles, of variable severity. Some patients had slight dysarthria, whereas others were unable to speak. 85% of patients had mental retardation, ranging from mild to severe. Epilepsy was present in 27 (87%) and commonly consisted of atypical absence, atonic/tonic, tonic-clonic seizures, and, less frequently, partial attacks. Seizures were poorly controlled in 55%. Magnetic resonance imaging showed bilateral perisylvian cortical malformations consistent with polymicrogyria, confirmed at necropsy. Division of the corpus callosum in several patients resulted in seizure improvement. This congenital bilateral perisylvian syndrome can be clinically diagnosed and confirmed by imaging studies. Further studies are necessary to elucidate its cause
— id: 140000, year: 1993, vol: 341, page: 608, stat: Journal Article,

Predictive value of magnetic resonance imaging in temporal lobe epilepsy surgery
Kuzniecky, R; Burgard, S; Faught, E; Morawetz, R; Bartolucci, A
1993 Jan;50(1):65-69, Archives of neurology
The predictive value of magnetic resonance imaging (MRI) was assessed by a prospective study of 34 patients selected for surgical treatment of temporal lobe epilepsy. The MRIs were interpreted using standardized visual diagnostic criteria and the imaging findings were correlated with the surgical outcome. Lateralized MRI abnormalities were found in 25 (74%) of 34 patients. Significant associations were found between either the presence of a restricted foreign-tissue lesion or hippocampal atrophy and an excellent surgical outcome. An abnormal MRI had an 82% predictive value and a normal MRI had a 56% predictive value for surgical success. A history of febrile convulsions and the presence of hippocampal atrophy best predicted outcome (predictive value, 86%). These results suggest that specific MRI findings in candidates for temporal lobe epilepsy surgery are predictive of surgical outcome. The information provided by MRI may be of value for counseling patients prior to surgical intervention
— id: 140001, year: 1993, vol: 50, page: 65, stat: Journal Article,

Ictal 99mTc HM-PAO brain single-photon emission computed tomography in electroencephalographic nonlocalizable partial seizures
Kuzniecky, R; Mountz, J M; Thomas, F
1993 Apr;3(2):100-102, Journal of neuroimaging
A 9-year-old child with intractable focal epilepsy was studied for possible surgical treatment. Multiple electroencephalographic studies did not localize the epileptic focus. An ictal single-photon emission computed tomography (SPECT) study with technetium 99m-hexamethylpropyleneamineoxime demonstrated a focal area of hyperperfusion. Through three-dimensional, functional to anatomical image-matching techniques, the focus was overlaid on the magnetic resonance image localizing the cortical convolution responsible for the epileptogenic focus. Subdural electroencephalographic studies performed for seizure localization and functional mapping confirmed this location. This case emphasized the usefulness of ictal SPECT scans in patients with seizures nonlocalizable by electroencephalography being evaluated for epilepsy surgery
— id: 139997, year: 1993, vol: 3, page: 100, stat: Journal Article,

Ictal single-photon emission computed tomography demonstrates localized epileptogenesis in cortical dysplasia
Kuzniecky, R; Mountz, J M; Wheatley, G; Morawetz, R
1993 Oct;34(4):627-631, Annals of neurology
We investigated the use of ictal single-photon emission computed tomography (SPECT) in 2 children with intractable epilepsy. Ictal scalp electroencephalographic studies failed to localize the epileptic focus and interictal data demonstrated widespread lateralized abnormalities. Ictal SPECT studies with technetium 99m-hexamethylpropyleneamineoxime demonstrated focal areas of hyperperfusion in the frontal lobes. Resection of the abnormal areas shown by SPECT was carried out despite evidence of large areas of epileptogenesis demonstrated by scalp and subdural electroencephalographic studies. Pathological material revealed cortical dysplasia. Ictal SPECT provides functional evidence for localized epileptogenesis in focal cortical dysplasia
— id: 139995, year: 1993, vol: 34, page: 627, stat: Journal Article,

Magnetic resonance imaging in childhood intractable partial epilepsies: pathologic correlations
Kuzniecky, R; Murro, A; King, D; Morawetz, R; Smith, J; Powers, R; Yaghmai, F; Faught, E; Gallagher, B; Snead, O C
1993 Apr;43(4):681-687, Neurology
We conducted a retrospective single-blind study assessing the value of MRI in 44 children surgically treated for partial epilepsy, and correlated the MRI findings with the pathology in all cases. MRI revealed abnormalities in concordance with the clinical and electroencephalographic data in 84% of patients. Developmental neuronal migration pathology was present in 25% of patients and was relatively more common in the sensorimotor cortex. There was hippocampal sclerosis in 50% of patients with temporal lobe resection; however, only two of the 10 children with hippocampal sclerosis were below the age of 12 years. Similarly, ganglio-glial tumors were more common than astrocytomas in children below age 12. These results indicate that MRI is sensitive in the detection of pathologic abnormalities in most pediatric candidates for epilepsy surgery, and that the distribution and type of pathology appear to be age related in this population
— id: 139999, year: 1993, vol: 43, page: 681, stat: Journal Article,

Epilepsia partialis continua due to cortical dysplasia
Kuzniecky, R; Powers, R
1993 Oct;8(4):386-388, Journal of child neurology
We describe a child with progressive neurologic deterioration and epilepsia partialis continua of the right extremities. Magnetic resonance imaging suggested cortical dysplasia of the left frontal region including the central sensorimotor cortex. Subdural grid recordings showed widespread ictal activity and frequent interictal discharges from the motor cortex. A tailored resection was performed, and histologic analysis confirmed cortical dysplasia. This case demonstrates that cortical dysplasia may be the underlying cause in some cases of childhood epilepsia partialis continua of the progressive type
— id: 139996, year: 1993, vol: 8, page: 386, stat: Journal Article,

In vivo 31P nuclear magnetic resonance spectroscopy of human temporal lobe epilepsy
Kuzniecky, R; Elgavish, G A; Hetherington, H P; Evanochko, W T; Pohost, G M
1992 Aug;42(8):1586-1590, Neurology
We performed localized 31P nuclear magnetic resonance (NMR) 1H-image-guided in vivo spectroscopy to study regional high-energy phosphate levels in the brains of normal controls and in patients with intractable unilateral temporal lobe epilepsy. We did not observe differences in intracellular pH between controls and patients. The phosphocreatine/inorganic phosphate ratio was reduced by 50% in the epileptogenic temporal lobe compared with controls (p less than 0.005) and by 35% when compared with the unaffected contralateral temporal lobe (p less than 0.05). We did not observe differences in the ratio of phosphomonoesters to phosphodiesters between controls and patients. These findings suggest that in vivo 31P NMR spectroscopy yields a distinctive interictal metabolic profile in patients with intractable unilateral temporal lobe epilepsy and may permit noninvasive lateralizing evidence of the seizure focus
— id: 140003, year: 1992, vol: 42, page: 1586, stat: Journal Article,

Antiepileptic drug treatment after temporal lobe epilepsy surgery: a randomized study comparing carbamazepine and polytherapy
Kuzniecky, R; Rubin, Z K; Faught, E; Morawetz, R
1992 Sep-Oct;33(5):908-912, Epilepsia
Temporal lobectomy is an effective treatment in selected patients with medically intractable temporal lobe epilepsy (TLE). Postoperative antiepileptic drug (AED) treatment guidelines have not been established, and patients are often treated with polytherapy postoperatively. We prospectively randomized 40 patients undergoing temporal lobectomy to monotherapy with carbamazepine (CBZ, 20) or to continuation of their presurgical polytherapy (20) to assess the efficacy and safety of each regimen during the first year after operation. No significant differences between groups were noted with respect to seizure recurrence rate and type or time of recurrence. Patients in the polytherapy group had a 30% incidence of drug-related side effects as compared with only 10% in the CBZ group. These results suggest that after temporal lobectomy for intractable epilepsy, patients can be safely treated with CBZ monotherapy and that treatment with multiple AEDs is not necessary
— id: 140002, year: 1992, vol: 33, page: 908, stat: Journal Article,

Bilateral porencephalic defect and bilateral perisylvian polymicrogyria
Andermann, F; Andermann, E; Palmini, A; Kuzniecky, R
1991 Nov;13(6):464-464, Brain & development (Tokyo)
— id: 140004, year: 1991, vol: 13, page: 464, stat: Journal Article,

Hippocampal sclerosis in temporal lobe epilepsy demonstrated by magnetic resonance imaging
Berkovic, S F; Andermann, F; Olivier, A; Ethier, R; Melanson, D; Robitaille, Y; Kuzniecky, R; Peters, T; Feindel, W
1991 Feb;29(2):175-182, Annals of neurology
The value of magnetic resonance imaging in the detection of hippocampal sclerosis has been controversial. We studied 10 patients aged 22.5 +/- 6.0 years with intractable temporal lobe epilepsy selected because of a history of a prolonged childhood convulsion, which is characteristic of a group of patients in whom hippocampal sclerosis is a constant finding. All 10 patients showed reduction in size of one hippocampus associated with increased signal intensity on T2-weighted magnetic resonance images. These changes were reliably detected on coronal spin-echo images, perpendicular to the long axis of the hippocampus. Appreciation of the normal imaging anatomy of the hippocampus allowed correct interpretation of the relative changes in signal intensities of the hippocampus and adjacent temporal horn on sequential echo images. The side of the abnormal hippocampus on magnetic resonance imaging accorded with the electroencephalographic localization in all 10 patients, and with the lateralization of the early convulsions in all 6 patients where this was known. Temporal lobectomy was performed in all 10 patients. Hippocampal sclerosis was confirmed in the 3 patients in whom hippocampal tissue was available for histological examination. The value of this technique was reinforced by the excellent postoperative results, with 80% being seizure free at a mean follow-up time of 33 +/- 4 months
— id: 140008, year: 1991, vol: 29, page: 175, stat: Journal Article,

Electroencephalographic correlations of extracranial and epidural electrodes in temporal lobe epilepsy
Kuzniecky, R; Faught, E; Morawetz, R
1991 May-Jun;32(3):335-340, Epilepsia
Thirty patients with medically intractable complex partial seizures of temporal lobe origin, but no structural abnormalities on neuroradiologic investigations, had both extracranial (scalp) and epidural EEG recordings. Fifteen patients (50%) had localized, unilateral, ictal, scalp EEGs, but one of these had bilateral independent temporal seizure onset according to epidural recordings. Of the 15 patients in whom scalp EEGs were non-localizing, 12 had well-localized epidural ictal EEGs, and 3 had multifocal or bilateral independent temporal ictal recordings. Epidural recordings provide information for determination of site of onset of temporal lobe seizures in selected patients
— id: 140006, year: 1991, vol: 32, page: 335, stat: Journal Article,

Cortical dysplasia in temporal lobe epilepsy: magnetic resonance imaging correlations
Kuzniecky, R; Garcia, J H; Faught, E; Morawetz, R B
1991 Mar;29(3):293-298, Annals of neurology
Cortical dysplasia has been documented in histological specimens surgically removed for treatment of refractory temporal lobe epilepsy. We studied 10 patients with cortical dysplasia and complex partial seizures who underwent temporal lobectomy. Magnetic resonance imaging revealed abnormalities in 5 of the patients who had microscopically detectable major abnormalities. Magnetic resonance imaging revealed an abnormal cortical-white matter architectonic pattern in 2 patients with moderate cortical dysplasia. In the remaining 3 patients, magnetic resonance imaging findings were unremarkable. These observations suggest that magnetic resonance imaging is sensitive in the detection of certain dysplastic lesions in temporal lobe epilepsy. Preoperative identification of these abnormalities by magnetic resonance imaging may permit early and optimal surgical treatment in patients with refractory epilepsy
— id: 140007, year: 1991, vol: 29, page: 293, stat: Journal Article,

Lateralization of epileptic foci by magnetic resonance imaging in temporal lobe epilepsy
Kuzniecky, R; Suggs, S; Gaudier, J; Faught, E
1991 Nov;1(4):163-167, Journal of neuroimaging
A retrospective single-blind study was carried out to assess the reliability of magnetic resonance imaging (MRI) for determining lateralization of the electrographic focus in 45 patients with intractable temporal lobe epilepsy. With strictly defined MRI diagnostic criteria, the electroencephalographic (EEG) focus was correctly lateralized in 86% of patients. Excluding patients with structural lesions, the criteria provided for correct lateralization of the epileptogenic focus in 78% and false lateralization in 5%. Hippocampal atrophy on T1-weighted images and increased signal intensity from mesial structures on T2-weighted scans were highly reliable for lateralization. Postoperative outcome did not differ between the patients with normal and those with abnormal findings on MRI, but the group sample was inadequate to assess the issue of surgical outcome. These findings suggest that with appropriate techniques and strictly defined diagnostic criteria, MRI can provide reliable seizure lateralization in patients with intractable temporal lobe epilepsy
— id: 140005, year: 1991, vol: 1, page: 163, stat: Journal Article,

Akinetic mutism caused by bilateral anterior cerebral tuberculous obliterative arteritis
Fesenmeier, J T; Kuzniecky, R; Garcia, J H
1990 Jun;40(6):1005-1006, Neurology
— id: 140010, year: 1990, vol: 40, page: 1005, stat: Journal Article,

Intracranial EEG electrodes
Kuzniecky, R; Faught, E
1990 Jun;40(6):1009-1010, Neurology
— id: 140009, year: 1990, vol: 40, page: 1009, stat: Journal Article,

Surgical treatment of epilepsy: initial results based upon epidural electroencephalographic recordings
Kuzniecky, R; Faught, E; Morawetz, R
1990 Jun;83(6):637-639, Southern medical journal
We describe our initial results in 50 consecutive patients who had investigation for possible surgical treatment of intractable focal epilepsy. Forty-three were investigated using intracranial epidural or foramen ovale electrodes. Forty-five had cortical resection (43 temporal, one frontal, and one parietal). Thirty-two patients who had resection have been followed up for 6 months to 4 years, and 29 (90%) have had good results. Our findings suggest that epidural recordings are valuable in patients with epilepsy who are being considered for surgical resection. They offer an alternative to depth intracerebral investigations in the majority of patients
— id: 140011, year: 1990, vol: 83, page: 637, stat: Journal Article,

Bilateral central macrogyria: epilepsy, pseudobulbar palsy, and mental retardation--a recognizable neuronal migration disorder
Kuzniecky, R; Andermann, F; Tampieri, D; Melanson, D; Olivier, A; Leppik, I
1989 Jun;25(6):547-554, Annals of neurology
The neuronal migration disorders comprise several morphological entities that are recognizable during life using current imaging techniques. We studied 4 patients who had a characteristic bilateral central rolandic and sylvian macrogyria. The patients had pseudobulbar palsy with oromotor incoordination and developmental delay and were mildly retarded. Minor seizures developed between the ages of 8 and 9 years. Subsequently, atonic drop attacks became the predominant epileptic pattern. Epileptogenic electrographic abnormalities were secondary generalized or multifocal. The lesions were detected by computed tomography and magnetic resonance imaging in all patients. Bilateral symmetrical areas of thick cortex surrounding a large sulcus were seen. This syndrome consists of specific clinical, imaging, electroencephalographic, and epileptic features. It can be suspected clinically and confirmed by imaging studies. Callosotomy in two patients helped the intractable seizures
— id: 140013, year: 1989, vol: 25, page: 547, stat: Journal Article,

Myoclonus epilepsy and ragged-red fibres (MERRF). 2. Electrophysiological studies and comparison with other progressive myoclonus epilepsies
So, N; Berkovic, S; Andermann, F; Kuzniecky, R; Gendron, D; Quesney, L F
1989 Oct;112 ( Pt 5):1261-1276, Brain
Electrophysiological studies (EEG, evoked potentials, nerve conduction and EMG) in 13 patients with myoclonus epilepsy with ragged red fibres (MERRF) are presented. The most notable findings are the presence of atypical irregular generalized spike and wave discharges arising from an abnormal EEG background (9 patients), focal epileptiform abnormalities (6 patients) most commonly over the occipital regions and giant cortical SEPs (4 of 6 patients tested). Similar findings of disturbed EEG background activity, generalized spike and wave discharges and giant cortical SEPs appear to be shared by the group of diseases characterized by progressive myoclonus epilepsy
— id: 140012, year: 1989, vol: 112 ( Pt 5), page: 1261, stat: Journal Article,

Familial myopathy with changes resembling inclusion body myositis and periventricular leucoencephalopathy. A new syndrome
Cole, A J; Kuzniecky, R; Karpati, G; Carpenter, S; Andermann, E; Andermann, F
1988 Oct;111 ( Pt 5):1025-1037, Brain
Five of 6 male siblings were affected by a progressive myopathy beginning in early childhood. Muscle biopsies in all patients showed the characteristic changes of inclusion body myositis. Computerized tomography and magnetic resonance imaging revealed a markedly abnormal appearance of cerebral white matter in the 4 affected patients tested, but clinical and other laboratory examinations failed to demonstrate evidence of central white matter dysfunction. Muscle biopsies and brain imaging were normal in all clinically unaffected family members. On the basis of the genetics, muscle biopsy findings and cerebral white matter changes, we conclude that this constellation represents a hitherto undescribed syndrome
— id: 140014, year: 1988, vol: 111 ( Pt 5), page: 1025, stat: Journal Article,

Focal cortical dysplasia
Kuzniecky, R
1988 Sep;69(3):478-478, Journal of neurosurgery
— id: 140015, year: 1988, vol: 69, page: 478, stat: Journal Article,

Focal cortical myoclonus and rolandic cortical dysplasia: clarification by magnetic resonance imaging
Kuzniecky, R; Berkovic, S; Andermann, F; Melanson, D; Olivier, A; Robitaille, Y
1988 Apr;23(4):317-325, Annals of neurology
Focal cortical myoclonus is rare. Obvious causes include tumor or atrophy involving the motor strip, but in some cases no cause is apparent. We present 4 patients who started to have focal myoclonus in childhood. All had focal motor seizures as well, and one had recurrent focal motor status epilepticus. All 4 had a mild progressive hemiparesis. Electrographic investigations showed focal epileptic discharges in the contralateral rolandic areas. Radiological studies were unrevealing, but magnetic resonance showed rolandic lesions in 3 patients. At surgery, abnormally wide gyri were found in the distribution demonstrated by magnetic resonance. The pathological substrate was focal cortical dysplasia. All patients have improved considerably following surgery. These findings suggest that focal myoclonus may be due to a rolandic neuronal migration disorder. Visualization of these lesions by magnetic resonance permits development of a surgical strategy leading to optimal treatment of these medically intractable epileptic disorders
— id: 140017, year: 1988, vol: 23, page: 317, stat: Journal Article,

Magnetic resonance imaging of meningio-angiomatosis
Kuzniecky, R; Melanson, D; Robitaille, Y; Olivier, A
1988 May;15(2):161-164, Canadian journal of neurological sciences
We report the case of a patient with meningio-angiomatosis, a rare disorder of the cerebral cortex often associated with Von Recklinghausen's neurofibromatosis. Previous reports have described a variety of radiological findings but in general they have been of little value in the diagnosis of this disorder. We describe the magnetic resonance image, which identified a well-defined lesion. The imaging techniques are reviewed
— id: 140016, year: 1988, vol: 15, page: 161, stat: Journal Article,

Magnetic resonance imaging in temporal lobe epilepsy: pathological correlations
Kuzniecky, R; de la Sayette, V; Ethier, R; Melanson, D; Andermann, F; Berkovic, S; Robitaille, Y; Olivier, A; Peters, T; Feindel, W
1987 Sep;22(3):341-347, Annals of neurology
A retrospective single-blind study assessing the value of magnetic resonance imaging (MRI) in 48 patients treated surgically for temporal lobe epilepsy was carried out. The imaging findings were correlated with the surgical findings in all cases. Abnormal MRI signals were detected in 34 of 48 (71%) epileptic patients and in 3 of 48 (6.2%) normal or disease control subjects. Twelve patients had structural foreign-tissue lesions, all detected by MRI. Of 14 patients with severe gliosis of the neocortex and/or mesial temporal structures, 11 had abnormal MRI scans. In patients with mild or moderate gliosis of mesial temporal structures, 6 of 12 had abnormal MRI scans. These results indicate that MRI is a sensitive technique for localizing foreign-tissue lesions, mesial temporal sclerosis, and gliosis in patients with intractable temporal lobe seizures
— id: 140018, year: 1987, vol: 22, page: 341, stat: Journal Article,

Carotid-ophthalmic aneurysm: an uncommon cause of acute monocular blindness
Kuzniecky, R; Melmed, C; Schipper, H
1987 Apr 1;136(7):727-728, CMAJ (Canadian Medical Association Journal)
— id: 140020, year: 1987, vol: 136, page: 727, stat: Journal Article,

Benign occipital epilepsy: a family study
Kuzniecky, R; Rosenblatt, B
1987 Jul-Aug;28(4):346-350, Epilepsia
Benign occipital epilepsy is a newly recognized form of partial epilepsy in children. It is characterized by motor seizures preceded in some cases by visual symptoms and a relatively benign course. We present three siblings with this condition and a fourth with the EEG abnormalities. A family study including 25 relatives demonstrated a typical EEG abnormality in 26% of relatives. These EEG changes were more evident in younger members. These findings suggest an autosomal dominant pattern for the EEG abnormalities with age-dependent expression and variable penetrance of the seizure disorder
— id: 140019, year: 1987, vol: 28, page: 346, stat: Journal Article,