Kenneth Robert Alper, M.D.

Ibogaine and the inhibition of acetylcholinesterase
Alper, Kenneth; Reith, Maarten E A; Sershen, Henry
2012 Feb 15;139(3):879-882, Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE: Ibogaine is a psychoactive monoterpine indole alkaloid extracted from the root bark of Tabernanthe iboga Baill. that is used globally in medical and nonmedical settings to treat drug and alcohol addiction, and is of interest as an ethnopharmacological prototype for experimental investigation and pharmaceutical development. The question of whether ibogaine inhibits acetylcholinesterase (AChE) is of pharmacological and toxicological significance. MATERIALS AND METHODS: AChE activity was evaluated utilizing reaction with Ellman's reagent with physostigmine as a control. RESULTS: Ibogaine inhibited AChE with an IC(50) of 520+/-40muM. CONCLUSIONS: Ibogaine's inhibition of AChE is physiologically negligible, and does not appear to account for observations of functional effects in animals and humans that might otherwise suggest the possible involvement of pathways linked to muscarinic acetylcholine transmission
— id: 150565, year: 2012, vol: 139, page: 879, 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,

Emotional recognition in depressed epilepsy patients
Brand, Jesse G; Burton, Leslie A; Schaffer, Sarah G; Alper, Kenneth R; Devinsky, Orrin; Barr, William B
2009 Jul;15(3):333-338, Epilepsy & behavior
The current study examined the relationship between emotional recognition and depression using the Minnesota Multiphasic Personality Inventory, Second Edition (MMPI-2), in a population with epilepsy. Participants were a mixture of surgical candidates in addition to those receiving neuropsychological testing as part of a comprehensive evaluation. Results suggested that patients with epilepsy reporting increased levels of depression (Scale D) performed better than those patients reporting low levels of depression on an index of simple facial recognition, and depression was associated with poor prosody discrimination. Further, it is notable that more than half of the present sample had significantly elevated Scale D scores. The potential effects of a mood-congruent bias and implications for social functioning in depressed patients with epilepsy are discussed
— id: 101883, year: 2009, vol: 15, page: 333, 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,

Self-reported Versus Clinician Rated Depression and Anxiety in Psychogenic Nonepileptic Seizures
Murphy, KE; Barr, WB; Brand, JG; Karantzoulis, S; Bender, HA; Alper, K
2009 ;23(4):61-61, Clinical neuropsychologist
— id: 125471, year: 2009, vol: 23, page: 61, stat: Journal Article,

The ibogaine medical subculture
Alper, Kenneth R; Lotsof, Howard S; Kaplan, Charles D
2008 Jan 4;115(1):9-24, Journal of ethnopharmacology
AIM OF THE STUDY: Ibogaine is a naturally occurring psychoactive indole alkaloid that is used to treat substance-related disorders in a global medical subculture, and is of interest as an ethnopharmacological prototype for experimental investigation and possible rational pharmaceutical development. The subculture is also significant for risks due to the lack of clinical and pharmaceutical standards. This study describes the ibogaine medical subculture and presents quantitative data regarding treatment and the purpose for which individuals have taken ibogaine. MATERIALS AND METHODS: All identified ibogaine 'scenes' (defined as a provider in an associated setting) apart from the Bwiti religion in Africa were studied with intensive interviewing, review of the grey literature including the Internet, and the systematic collection of quantitative data. RESULTS: Analysis of ethnographic data yielded a typology of ibogaine scenes, 'medical model', 'lay provider/treatment guide', 'activist/self-help', and 'religious/spiritual'. An estimated 3414 individuals had taken ibogaine as of February 2006, a fourfold increase relative to 5 years earlier, with 68% of the total having taken it for the treatment of a substance-related disorder, and 53% specifically for opioid withdrawal. CONCLUSIONS: Opioid withdrawal is the most common reason for which individuals took ibogaine. The focus on opioid withdrawal in the ibogaine subculture distinguishes ibogaine from other agents commonly termed 'psychedelics', and is consistent with experimental research and case series evidence indicating a significant pharmacologically mediated effect of ibogaine in opioid withdrawal
— id: 78350, year: 2008, vol: 115, page: 9, 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,

Localizing epileptogenic regions in partial epilepsy using three-dimensional statistical parametric maps of background EEG source spectra
Alper, Kenneth; Raghavan, Manoj; Isenhart, Robert; Howard, Bryant; Doyle, Werner; John, Roy; Prichep, Leslie
2008 Feb 1;39(3):1257-1265, Neuroimage
This preliminary study sought to localize epileptogenic regions in patients with partial epilepsy by analysis of interictal EEG activity utilizing variable resolution electromagnetic tomography (VARETA), a three-dimensional quantitative electroencephalographic (QEEG) frequency-domain distributed source modeling technique. The very narrow band (VNB) spectra spanned the frequency range 0.39 Hz to 19.1 Hz, in 0.39 Hz steps. These VNB spectra were compared to normative data and transformed to provide Z-scores for every scalp derivation, and the spatial distributions of the probable EEG generators of the most abnormal values were displayed on slices from a probabilistic MRI atlas. Each voxel was color-coded to represent the significance of the deviation relative to age appropriate normative values. We compared the resulting three-dimensional images to the localization of epileptogenic regions based on invasive intracranial EEG recordings of seizure onsets. The VARETA image indicated abnormal interictal spectral power values in regions of seizure onset identified by invasive monitoring, mainly in delta and theta range (1.5 to 8.0 Hz). The VARETA localization of the most abnormal voxel was congruent with the epileptogenic regions identified by intracranial recordings with regard to hemisphere in all 6 cases, and with regard to lobe in 5 cases. In contrast, abnormal findings with routine EEG agreed with invasive monitoring with regard to hemisphere in 3 cases and with regard to lobe in 2 cases. These results suggest that analysis of background interictal EEG utilizing distributed source models should be investigated further in clinical epilepsy
— id: 76455, year: 2008, vol: 39, page: 1257, stat: Journal Article,

Emotional recognition ability in patients with epileptic vs. non-epileptic seizures
Brand, JG; Barr, WB; Schaffer, SG; Burton, LA; Alper, KR; Devinsky, O
2008 SEP ;22(4):747-747, Clinical neuropsychologist
— id: 104236, year: 2008, vol: 22, page: 747, stat: Journal Article,

A psychodynamic understanding of conversion nonepileptic seizures in a young woman with acquired blindness
Soffer, Jocelyn; Alper, Kenneth R; Basch, Samuel
2008 Jul;13(7):575-584, CNS spectrums
— id: 95756, year: 2008, vol: 13, page: 575, stat: Journal Article,

Gender and major depression in a sample of epilepsy patients
Wolkin, JR; Barr, WB; Alper, KR; Zemon, V; Devinsky, O
2008 SEP ;22(4):747-747, Clinical neuropsychologist
— id: 104237, year: 2008, vol: 22, page: 747, stat: Journal Article,

The use of ibogaine in the treatment of addictions
Alper, Kenneth R; Lotsof, Howard S
Psychedelic medicine: New evidence for hallucinogenic substances as treatments (Vol 2) Westport, CT, US: Praeger Publishers/Greenwood Publishing Group, 2007,
Ibogaine is a naturally occurring iboga alkaloid, a chemical taxonomic category presently known to contain approximately 80 naturally occurring and synthetic compounds, some of which reportedly reduce the self-administration of drugs of abuse and opiate withdrawal symptoms in animal models and humans (Alper et al. 2001). Ibogaine is isolated from the root bark of Tabernanthe iboga native to West Central Africa, where it has been used as a religious sacrament for centuries (Fernandez 1982; Goutarelet al. 1993) before it was observed in the United States and Europe to have apparent effects on opioid withdrawal and other drug dependence syndromes. As reviewed in this chapter, major published scientific evidence for ibogaine's effectiveness includes reduced drug self-administration and withdrawal in animals, and case reports and open-label trials in humans. From a pharmacological standpoint, ibogaine is interesting because it appears to have a novel mechanism of action that is different from other existing pharmacotherapeutic approaches to addiction. The question of ibogaine's mechanism of action is important because its ultimate significance may be a paradigm for understanding the neurobiology of addiction as well as the development of new medications. The sections of this chapter address the following ibogaine topics: History; Pharmacology; Subjective effects; Evidence of efficacy; Learning, memory, and addiction; Clinical use of ibogaine; and Future research. Acute opioid withdrawal is the indication for which ibogaine has most frequently been given (Alper et al. 1999 and 2001; Frenken 2001), which distinguishes the ibogaine subculture from subcultures involving other hallucinogenic drugs. It is a clinically robust phenomenon that can be appreciated by a lay clinical observer and produces a relatively clear outcome occurring within a limited time frame. The lay individuals involved in the ibogaine subculture are very likely to be capable of making valid clinical observations regarding the absence or presence of the signs of acute opioid withdrawal. To apply the term 'triangulation' as a validating principle in the clinical medical context, it is interesting that a similar effect of ibogaine in acute opiate withdrawal is evident in the animal model, the numerous and consistent accounts of subculture participants, and published case series. The ibogaine medical subculture reflects that drug users actively seek alternatives to present treatment options despite medical risk, expense, and possible legal prosecution. The patient has primacy in the moral and ethical hierarchy of medicine, and it is fitting to end this chapter with a quote posted to an Internet message board from a patient reflecting on ibogaine treatment. The sense of marginalization, and affirmation of a belief in a real pharmacological effect, is familiar to anyone experienced with talking with ibogaine treatment providers or individuals who have been treated.
— id: 4641, year: 2007, vol: , page: 43, stat: Chapter,

Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports
Alper, Kenneth; Schwartz, Kelly A; Kolts, Russell L; Khan, Arif
2007 Aug 15;62(4):345-354, Biological psychiatry
BACKGROUND: Clinical trial data provide an approach to the investigation of the effects of psychopharmacological agents, and psychiatric disorders themselves, on seizure threshold. METHODS: We accessed public domain data from Food and Drug Administration (FDA) Phase II and III clinical trials as Summary Basis of Approval (SBA) reports that noted seizure incidence in trials of psychotropic drugs approved in the United States between 1985 and 2004, involving a total of 75,873 patients. We compared seizure incidence among active drug and placebo groups in psychopharmacological clinical trials and the published rates of unprovoked seizures in the general population. RESULTS: Increased seizure incidence was observed with antipsychotics that was accounted for by clozapine and olanzapine, and with drugs indicated for the treatment of OCD that was accounted for by clomipramine. Alprazolam, bupropion immediate release (IR) form, and quetiapine were also associated with higher seizure incidence. The incidence of seizures was significantly lower among patients assigned to antidepressants compared to placebo (standardized incidence ratio = .48; 95% CI, .36- .61). In patients assigned to placebo, seizure incidence was greater than the published incidence of unprovoked seizures in community nonpatient samples. CONCLUSIONS: Proconvulsant effects are associated with a subgroup of psychotropic drugs. Second-generation antidepressants other than bupropion have an apparent anticonvulsant effect. Depression, psychotic disorders, and OCD are associated with reduced seizure threshold
— id: 74108, year: 2007, vol: 62, page: 345, stat: Journal Article,

Psychotropic complementary medicines
Alper, K. R; Glick, S. D
2006 ;188:587- Jun, British journal of psychiatry
Comments on the article by U. Werneke et al (see record #200602224-005) that reviewed the complementary medicines routinely encountered in psychiatric practice, their effectiveness, potential adverse effects and interactions. The current authors state that Werneke et al's review contains substantive errors and omissions regarding the iboga alkaloid ibogaine and its synthetic congener 18-methoxycoronaridine (18-MC).
— id: 64678, year: 2006, vol: 188, page: 587, stat: Journal Article,

Correlation of PET and qEEG in normal subjects
Alper, Kenneth R; John, E Roy; Brodie, Jonathan; Gunther, Wilfred; Daruwala, Raoul; Prichep, Leslie S
2006 Apr 30;146(3):271-282, Psychiatry research
Positron emission tomography (PET) and quantitative electroencephalography (qEEG) were obtained in 15 normal male subjects with eyes closed at rest. Correlations between qEEG variables and regional metabolism were examined as an approach to investigating the metabolic and neuroanatomical basis of the generation of the EEG. Analogous to the neurometric approach to qEEG, a normative 2-fluoro-deoxyglucose voxel data base was developed for the PET image. The PET image was transformed to an idealized cylindrical set of coordinates to allow registration with the Talairach stereotactic atlas. PET regions of interest for the thalamus, the left and right temporal lobes, the medial frontal cortex and the dorsolateral prefrontal cortex were defined using Talairach coordinates and correlated to the QEEG. Salient findings included a negative correlation of thalamic metabolism to alpha power and a positive correlation of medial frontal cortical metabolism to delta EEG power. The significance of these findings is discussed with reference to the existing literature on the physiology of the generation of the EEG
— id: 67000, year: 2006, vol: 146, page: 271, 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,

Nonepileptic seizures treatment workshop summary
LaFrance, W Curt Jr; Alper, Kenneth; Babcock, Debra; Barry, John J; Benbadis, Selim; Caplan, Rochelle; Gates, John; Jacobs, Margaret; Kanner, Andres; Martin, Roy; Rundhaugen, Lynn; Stewart, Randy; Vert, Christina
2006 May;8(3):451-461, Epilepsy & behavior
In May 2005, an international, interdisciplinary group of researchers gathered in Bethesda, MD, USA, for a workshop to discuss the development of treatments for patients with nonepileptic seizures (NES). Specific subgroup topics that were covered included: pediatric NES; presenting the diagnosis of NES, outcome measures for NES trials; classification of NES subtypes; and pharmacological treatment approaches and psychotherapies. The intent was to develop specific research strategies that can be expanded to involve a large segment of the epilepsy and psychiatric treatment communities. Various projects have resulted from the workshop, including the initial development of a prospective randomized clinical trial for NES
— id: 71629, year: 2006, vol: 8, page: 451, stat: Journal Article,

QEEG source localization of epileptiform foci
Prichep, LS; Alper, K
2006 NOV 23 ;54(1):28-29, Neuropsychobiology
— id: 69291, year: 2006, vol: 54, page: 28, stat: Journal Article,

Rates of invalid MMPI-2 responding in patients with epileptic and nonepileptic seizures
Barr, WB; Larson, E; Alper, K; Devinsky, O
2005 SEP ;46(11):60-60, Epilepsia
— id: 59584, year: 2005, vol: 46, page: 60, stat: Journal Article,

Localizing epileptic foci using variable resolution electromagnetic tomography (VARETA)
Alper, K; Raghavan, M; Prichep, L; Isenhart, R; Howard, B; John, R
2004 AUG-SEP ;45(3):114-115, Epilepsia
— id: 49018, year: 2004, vol: 45, page: 114, stat: Journal Article,

Obsessive-compulsive symptoms in patients with temporal lobe epilepsy
Isaacs, Keren L; Philbeck, John W; Barr, William B; Devinsky, Orrin; Alper, Kenneth
2004 Aug;5(4):569-574, Epilepsy & behavior
The goals of this work were to: (1) determine the prevalence of clinically significant obsessive-compulsive (OC) symptoms in patients with temporal lobe epilepsy (TLE), (2) characterize the differences in self-reported OC symptoms in patients with TLE and a normative control group, and (3) compare the severity of OC symptoms in right and left hemisphere TLE patients. Patients with TLE (n=30) were administered the Obsessive-Compulsive Inventory (OCI). As a group, patients with TLE had a higher prevalence of OC symptoms than the nonpatient normative sample. In addition, TLE patients exhibited elevated scores on all but 3 of the 16 OCI scales and subscales. There were no reliable differences in OC symptoms in patients with right versus left hemisphere seizure foci, although the right hemisphere patients tended to score higher on both scales of the OCI
— id: 55970, year: 2004, vol: 5, page: 569, stat: Journal Article,

Treatment of psychosis, aggression, and irritability in patients with epilepsy
Alper KR; Barry JJ; Balabanov AJ
2002 Oct;3(5S):13-18, Epilepsy & behavior
Psychosis, irritability, and aggression in persons with epilepsy are frequently the focus of clinical intervention. These neuropsychiatric symptoms may occur due to the bidirectional relationship between psychosis and epilepsy, in which the potential etiopathogenic mechanisms are believed to be closely related to the seizure disorder itself and also may result from underlying brain injury or behavioral intolerance of antiepileptic or other medication. Epileptic patients are at heightened risk for mood disorders, psychotic disorders, and delerium. The possible lowering of seizure threshold by psychotropic drugs should not contraindicate appropriate use of psychotropic agents, and risk may be minimized by the selection of agents not associated with a relatively high likelihood of altering seizure threshold. Behavioral toxicity of antiepileptic drugs (AEDs) is addressed by selection of alternative agents, and some AEDs appear to possess positive psychotropic effects. The use of antipsychotic, antidepressant, and other psychotropic agents in psychosis, irritability, and aggression in epilepsy is discussed, including dosage ranges, major side effects, and potential interactions between antieplieptic and psychotropic medication
— id: 39289, year: 2002, vol: 3, page: 13, stat: Journal Article,

Premorbid psychiatric risk factors for postictal psychosis: In reply
Alper, Kenneth R; Devinsky, Orrin; Boylan, Laura
2002 ;14(4):465-466 Fal, Journal of neuropsychiatry & clinical neurosciences
Responds to G. C. Fong et al's comments (see record 2002-06521-015) on K. Alper et al's article (see record 2001-09677-006) which reported interest in the relationship between seizure cluster characteristics, presence of mood disorder among first- and second-decree relatives, and postictal psychosis. The current authors agree that the approach would be useful. (PsycINFO Database Record (c) 2007 APA, all rights reserved)
— id: 80779, year: 2002, vol: 14, page: 465, stat: Journal Article,

Adaptation to repeated cocaine administration in rats
Binienda, Zbigniew K; Pereira, Frederico; Alper, Kenneth; Slikker, William Jr.; Ali, Syed F
Cellular and molecular mechanisms of drugs of abuse II: Cocaine, substituted amphetamines, GHB, and opiates New York, NY, US: New York Academy of Sciences, 2002,
(from the chapter) Quantitative electroencephalogram (EEG) studies in cocaine-dependent human patients show deficits in slow-wave brain activity, reflected in diminished EEG power in the delta and theta frequency bands. In the present study, electrophysiological measures were monitored in 10 nonanesthetized, adult male Sprague-Dawley rats via bipolar, epidural electrodes implanted over the somatosensory cortex. Control electrocorticograms (ECoG) were recorded twice within a two-week interval to establish a baseline. Rats were subsequently injected daily with cocaine HCl at 15 mg/kg, i.p., for two weeks. The ECoG was recorded during a 1-h session one day after the last injection. Total concentrations of dopamine (DA) and its metabolites were assayed in caudate nucleus (CN) and frontal cortex (FC) using HPLC/EC. Compared with controls, marked increases in DA concentrations were observed in both regions. The DA turnover decreased significantly. The power spectra, obtained by use of a fast Fourier transformation, revealed a significant decrease in slow-wave delta frequency bands following repeated exposure to cocaine. These data are consistent with reported findings in humans that repeated exposures to cocaine result in a decrease in slow-wave brain activity. Further studies are necessary to establish whether regional alterations in blood flow and metabolic activity may underlie such observations.
— id: 4557, year: 2002, vol: , page: 172, stat: Chapter,

Adaptation to repeated cocaine administration in rats
Binienda, Zbigniew K; Pereira, Frederico; Alper, Kenneth; Slikker, William Jr; Ali, Syed F
2002 Jun;965:172-179, Annals of the New York Academy of Sciences
Quantitative electroencephalogram (EEG) studies in cocaine-dependent human patients show deficits in slow-wave brain activity, reflected in diminished EEG power in the delta and theta frequency bands. In the present study, electrophysiological measures were monitored in 10 nonanesthetized, adult male Sprague-Dawley rats via bipolar, epidural electrodes implanted over the somatosensory cortex. Control electrocorticograms (ECoG) were recorded twice within a two-week interval to establish a baseline. Rats were subsequently injected daily with cocaine HCl at 15 mg/kg, i.p., for two weeks. The ECoG was recorded during a 1-h session one day after the last injection. Total concentrations of dopamine (DA) and its metabolites were assayed in caudate nucleus (CN) and frontal cortex (FC) using HPLC/EC. Compared with controls, marked increases in DA concentrations were observed in both regions. The DA turnover decreased significantly. The power spectra, obtained by use of a fast Fourier transformation, revealed a significant decrease in slow-wave delta frequency bands following repeated exposure to cocaine. These data are consistent with reported findings in humans that repeated exposures to cocaine result in a decrease in slow-wave brain activity. Further studies are necessary to establish whether regional alterations in blood flow and metabolic activity may underlie such observations
— id: 47446, year: 2002, vol: 965, page: 172, stat: Journal Article,

Outcome related electrophysiological subtypes of cocaine dependence
Prichep, Leslie S; Alper, Kenneth R; Sverdlov, Lev; Kowalik, Sharon C; John, E R; Merkin, Henry; Tom, Mee Lee; Howard, Bryant; Rosenthal, Mitchell S
2002 Jan;33(1):8-20, Clinical electroencephalography
We previously described the existence of two quantitative EEG (QEEG) subtypes of cocaine dependent males, identified at baseline, displaying differential proneness to relapse. The current study expands the population to include females and enhances the measure set to include both QEEG and somatosensory EP (SEP) features. Fifty-seven cocaine dependent adults (16 F, 41 M) were evaluated 5-14 days after last cocaine use, while in residence at a drug-free therapeutic community. The median length of stay in treatment (continued abstinence) was 25 weeks. Using a small subset of QEEG and SEP baseline features, three subtypes (CLUS) were identified. CLUS 2 (n = 25) and CLUS 3 (n = 23) replicated the published subtypes, while CLUS 1 (n = 9) was previously undescribed. Cluster membership was significantly associated with length of stay in treatment (chi 2 = 13.789, P < 0.001), but not with length of exposure to crack cocaine or to any demographic or clinical features. Seventy-eight percent of CLUS 1 and 65% of CLUS 3 left treatment < or = 25 weeks, whereas 80% of CLUS 2 remained in treatment > 25 weeks. The existence of outcome related subtypes may reflect: [1] differential neurophysiological vulnerability, 'traits,' predisposing individuals to cocaine addiction; or [2] differential neurosensitivity, 'states,' due to the effects of chronic cocaine exposure, and associated differences in treatment outcome. Using Variable Resolution Electrical Tomographic Analysis (VARETA), the mathematically most probable neuroanatomical source of the scalp recorded EEG data was localized. Computation of VARETA on the baseline Cluster profiles suggest significant differences in the underlying pathophysiology of these subtypes
— id: 68150, year: 2002, vol: 33, page: 8, stat: Journal Article,

Premorbid psychiatric risk factors for postictal psychosis
Alper K; Devinsky O; Westbrook L; Luciano D; Pacia S; Perrine K; Vazquez B
2001 Fall;13(4):492-499, Journal of neuropsychiatry & clinical neurosciences
Postictal psychosis (PIP) is a common and clinically significant sequela of inpatient epilepsy monitoring. A series of 622 patients with complex partial epilepsy undergoing video-EEG evaluations as candidates for epilepsy surgery were evaluated, by structured psychiatric interview, for individual and family psychiatric histories, depression, anxiety, and features of personality disorders. No patient had psychotic symptoms at baseline. Twenty-nine developed a PIP episode during monitoring. The a priori hypotheses were that patients with PIP would have higher baseline schizotypal and paranoid personality ratings and a greater prevalence of histories of psychiatric treatment and family history of psychotic illness. However, only a higher prevalence of mood disorder among first- and second-degree relatives distinguished the patients who developed PIP on logistic regression analyses (odds ratio=3.49, P=0.001). Possible mechanisms linking vulnerability toward mood disorders and the development of psychotic symptoms in epilepsy are discussed
— id: 26525, year: 2001, vol: 13, page: 492, stat: Journal Article,

Ibogaine: a review
Alper KR
2001 ;56(11):1-38, Alkaloids. Chemistry & biology
— id: 26577, year: 2001, vol: 56, page: 1, stat: Journal Article,

A contemporary history of ibogaine in the United States and Europe
Alper KR; Beal D; Kaplan CD
2001 ;56(11):249-281, Alkaloids. Chemistry & biology
— id: 26575, year: 2001, vol: 56, page: 249, stat: Journal Article,

Nondominant hemisphere lesions and conversion nonepileptic seizures
Devinsky O; Mesad S; Alper K
2001 Summer;13(3):367-373, Journal of neuropsychiatry & clinical neurosciences
To explore the hypothesis that lateralized hemispheric dysfunction may contribute to the development of conversion symptoms, the authors studied frequency of unilateral cerebral physiological or structural abnormalities in 79 consecutive patients with conversion nonepileptic seizures (C-NES), who were also compared with two groups of epilepsy patients without C-NES. Sixty (76%) of the C-NES patients had unilateral cerebral abnormalities on neuroimaging, of which 85% were structural. Ictal or interictal epileptiform abnormalities on EEG were found in 78% of C-NES patients and focal slowing in another 10%. Fifty (63%) of the C-NES patients had both structural and epileptiform abnormalities. Among the 60 with unilateral abnormalities, 43 (71%) had right hemisphere structural lesions or physiologic dysfunctions (C-NES>non-C-NES, P<0.02). This study supports prior studies and clinical observations that cerebral dysfunction can contribute to the pathogenesis of conversion disorder, and that nondominant hemisphere dysfunction may play a greater role
— id: 34414, year: 2001, vol: 13, page: 367, stat: Journal Article,

Progression of postictal to interictal psychosis
Tarulli A; Devinsky O; Alper K
2001 Nov;42(11):1468-1471, Epilepsia
PURPOSE: To describe a case series of patients with both postictal psychosis (PIP) and chronic interictal psychosis (IIP). METHODS: We retrospectively reviewed the records of 43 patients with PIP from a comprehensive epilepsy center to find evidence of both PIP and IIP in the same patient. RESULTS: Six (13.9%) of the 43 patients met all the criteria for both PIP and IIP. Five of our six patients had multiple documented PIPs before they became chronically psychotic. The range of length of time between PIP and IIP was 7 to 96 months. Postictal and interictal psychotic behavior was similar or identical in five of six cases. CONCLUSIONS: The results of this study suggest a progression from PIP to IIP: there is a similarity between the symptoms of the two psychoses, a history of multiple PIPs before the first IIP, and a period of months to years between PIP and IIP onset
— id: 34411, year: 2001, vol: 42, page: 1468, stat: Journal Article,

Ibogaine in acute opioid withdrawal. An open label case series
Alper KR; Lotsof HS; Frenken GM; Luciano DJ; Bastiaans J
2000 ;909:257-259, Annals of the New York Academy of Sciences
— id: 11582, year: 2000, vol: 909, page: 257, stat: Journal Article,

Psychotropic medication use in patients with epilepsy: effect on seizure frequency
Gross A; Devinsky O; Westbrook LE; Wharton AH; Alper K
2000 Fall;12(4):458-464, Journal of neuropsychiatry & clinical neurosciences
Physicians are often reluctant to use psychotropic medications in epilepsy patients with psychiatric disorders because of concern over the potential risk for lowering seizure threshold. This study assesses retrospectively the impact of psychotropic medications on seizure frequency in 57 patients seen consecutively at an epilepsy center. During psychotropic drug therapy, seizure frequency decreased in 33% of patients, was unchanged in 44%, and increased in 23%. Mean seizure frequency was not statistically different between pre-treatment and treatment periods (t = 0.23, df = 56). Simultaneous adjustments in antiepileptic drug regimen could not account for the findings. Results support the position that psychotropic medications, introduced slowly in low to moderate doses, can be safely used in epilepsy patients with comorbid psychiatric pathology during the regular course of clinical care
— id: 34417, year: 2000, vol: 12, page: 458, stat: Journal Article,

Emotional outbursts and post-traumatic stress disorder during intracarotid amobarbital procedure
Masia SL; Perrine K; Westbrook L; Alper K; Devinsky O
2000 Apr 25;54(8):1691-1693, Neurology
Severe emotional outbursts (SEOs) during intracarotid amobarbital procedures (IAP) rarely jeopardize preoperative language and memory testing. Four of four patients (100%) with outbursts had experienced significant emotional trauma (three were raped and one witnessed a decapitation), compared with 26 of 546 patients (4.8%) without outbursts (chi2 = 69.8, p < 0. 0001). Evocative injections were ipsilateral to seizure focus. IAP may disrupt emotional balance in some traumatized patients. Counseling may prevent SEOs
— id: 34420, year: 2000, vol: 54, page: 1691, stat: Journal Article,

The EEG and cocaine sensitization: a hypothesis
Alper KR
1999 Spring;11(2):209-221, Journal of neuropsychiatry & clinical neurosciences
The author presents the hypothesis that reduced delta EEG power observed in cocaine withdrawal is related to changes in dopamine (DA) transmission related to cocaine sensitization. Evidence for this hypothesis includes the topographic anatomical correspondence between the putative site of delta generation and the cortical terminal field of the mesotelencephalic DA system, as well as the laminar distribution and ultrastructural features of DA terminals in frontal cortex that appear to be adapted to the modulation of the delta rhythm, a global forebrain EEG mode. The effect of DA on membrane conductances of individual pyramidal neurons also suggests that DA exerts a significant influence on delta power by modulating the transition between global and local EEG modes. Access to a neural correlate of sensitization via noninvasive EEG methodology could be useful in investigating the relationship of stimulant sensitization to the clinical syndrome of cocaine dependence
— id: 12016, year: 1999, vol: 11, page: 209, stat: Journal Article,

Treatment of acute opioid withdrawal with ibogaine
Alper KR; Lotsof HS; Frenken GM; Luciano DJ; Bastiaans J
1999 Summer;8(3):234-242, American journal on addictions
Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting
— id: 11952, year: 1999, vol: 8, page: 234, stat: Journal Article,

Psychosis after epilepsy surgery
Bromfield, EB; Devinsky, O; Fricchione, GL; Frumin, M; Mesad, SM; Alper, K; Dickey, C
1999 ;40(4):242-242 FAL, Epilepsia
— id: 104275, year: 1999, vol: 40, page: 242, stat: Journal Article,

Prediction of treatment outcome in cocaine dependent males using quantitative EEG
Prichep LS; Alper KR; Kowalik SC; Vaysblat LS; Merkin HA; Tom M; John ER; Rosenthal MS
1999 Mar 1;54(1):35-43, Drug & alcohol dependence
This study investigates the existence of outcome related neurophysiological subtypes within a population of abstinent cocaine dependent adults. We have previously reported and replicated the existence of a distinctive quantitative EEG (QEEG) profile in such a population, and demonstrated the persistence of this pattern at one and six month follow-up evaluations. This profile is characterized by significant deficits of absolute and relative delta and theta power, and excess of relative alpha power, as compared with age expected normal values. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. In the current study, 35 adult males with DSM-III-R cocaine dependence, were evaluated while residents of a drug-free residential therapeutic community, 5-15 days after last use of crack cocaine. Using multivariate cluster analysis, two neurophysiological subtypes were identified from the baseline QEEGs; Cluster 1 characterized by significant deficits of delta and theta activity, significant excess of alpha activity and more normal amounts of beta activity (alpha CLUS) and Cluster 2 characterized by deficits of delta, more normal amounts of theta and anterior excess of alpha and beta activity beta CLUS). No significant relationships were found between QEEG subtype membership and length of exposure to cocaine, time since last use of cocaine or any demographic characteristics. Further, no significant relationships were found between the commonly reported comorbid clinical features of depression and anxiety and subtype membership. However, a significant relationship was found between QEEG subtype membership and length of stay in treatment, with members of the alpha CLUS retained in treatment significantly longer than members of the beta CLUS
— id: 7429, year: 1999, vol: 54, page: 35, stat: Journal Article,

Correlation of qEEG with PET in schizophrenia
Alper K; Gunther W; Prichep LS; John ER; Brodie J
1998 ;38(1):50-56, Neuropsychobiology
PET relative metabolism was correlated with quantitative EEG in 9 schizophrenic patients. The PET metabolic regions of interest were the frontal lobes, thalamus and basal ganglia, and right and left temporal lobes. Significant positive correlations were seen for the frontal lobes and delta EEG power, and alpha power with subcortical metabolism. The physiologic plausibility of those correlations is discussed with reference to the possible effect of neuroleptic medication
— id: 7481, year: 1998, vol: 38, page: 50, stat: Journal Article,

Persistent QEEG abnormality in crack cocaine users at 6 months of drug abstinence
Alper KR; Prichep LS; Kowalik S; Rosenthal MS; John ER
1998 Jul;19(1):1-9, Neuropsychopharmacology
The major objective of this study was to examine the persistence of abnormal quantitative EEG (qEEG) measures over a six month time interval in subjects in strictly supervised drug free residential treatment for crack cocaine dependence. Seventeen subjects were assessed with qEEG at five to 10 days, one month and six months following their last use of cocaine. No significant changes were noted over time in abnormal qEEG measures, which included deficits of absolute and relative power in the delta band and increased relative alpha power. The persistence of qEEG abnormality in crack cocaine withdrawal suggests a persistent neurobiologic alteration resulting from chronic cocaine exposure. The specificity of the qEEG findings is discussed, and an interpretation is suggested with reference to the hypothesis of neural sensitization in cocaine dependence
— id: 7480, year: 1998, vol: 19, page: 1, stat: Journal Article,

Olfactory reference syndrome in a patient with partial epilepsy
Devinsky O; Khan S; Alper K
1998 Apr;11(2):103-105, Neuropsychiatry neuropsychology & behavioral neurology
A 49-year-old man with right temporal lobe epilepsy developed the chronic delusion that his body emitted a foul odor (olfactory reference syndrome). Before the delusional symptoms, he had partial seizures with unpleasant olfactory hallucinations. Subsequently ictal olfactory symptoms abated but a disabling delusional syndrome developed. The only prior case of the olfactory reference syndrome in a patient with epilepsy had a right frontal lesion. The case further supports the association of right hemisphere lesions and delusional disorders
— id: 7322, year: 1998, vol: 11, page: 103, stat: Journal Article,

Dissociation in epilepsy and conversion nonepileptic seizures
Alper K; Devinsky O; Perrine K; Luciano D; Vazquez B; Pacia S; Rhee E
1997 Sep;38(9):991-997, Epilepsia
PURPOSE: We examined the dimensionality of the item content of the Dissociative Experiences Scale (DES) in relation to the clinical diagnosis of conversion nonepileptic seizures (C-NES) versus complex partial epilepsy (CPE). METHODS: The DES was administered to a sex- and age-matched sample of 132 patients with C-NES and 169 with CPE and was factor analyzed with principal components analysis (PCA) with varimax rotation. RESULTS: The mean total DES score was 15.1 in the C-NES group and 12.7 in the CPE group (p = 0.079). The factors obtained by PCA differentiated the CPE and C-NES groups more strongly than did the total DES score. The factor accounting for the most variance, interpreted as 'depersonalization-derealization,' was significantly greater in C-NES than CPE (p = 0.005). An 'absorption-imaginative involvement' factor, which included some of the clinical features of posttraumatic stress disorder was elevated only in subjects reporting histories of childhood abuse (p = 0.001) regardless of the diagnosis of CPE or C-NES. An 'amnestic' factor appearing to represent memory problems related to neurologic impairment showed a trend toward elevation in CPE (p = 0.056) and may have confounded the CPE versus C-NES distinction using total DES scores. CONCLUSIONS: The DES has separate underlying dimensions that appear to relate distinctively to depersonalization and derealization, childhood trauma, and neurologic impairment. The heterogeneous item content of the DES is a potential confound that should be appreciated when this instrument is used to study dissociation in neuropsychiatric populations
— id: 12132, year: 1997, vol: 38, page: 991, stat: Journal Article,

Clinical profile of patients with epileptic and nonepileptic seizures
Devinsky O; Sanchez-Villasenor F; Vazquez B; Kothari M; Alper K; Luciano D
1996 Jun;46(6):1530-1533, Neurology
Epileptic seizures (ES) and nonepileptic seizures (NES) often coexist in patients with treatment-refractory seizures. There are few data on ictal features of these different seizure types in the same patient. We identified 20 patients with ES from a group of 99 NES patients (ES/NES) and compared this group with patients with only ES or NES. All 20 ES/NES patients developed NES after ES. Clinical features of NES clearly differed from ES in 18 of 20 cases. In patients with ES/NES their ES were similar to seizures in patients with only ES, and their NES were similar to spells in patients with only NES. ES/NES patients were similar to ES patients in electrodiagnostic and neuroimaging studies, and similar to NES patients in psychiatric interviews and inventories. The clinical manifestations of ES and NES in the same patient are usually different. Both types of events may be stereotypic and can be distinguished and characterized during video-EEG recording. Determining what events are more prevalent or disturbing is critical. Psychiatric and antiepileptic drug treatment may be provided accordingly
— id: 12601, year: 1996, vol: 46, page: 1530, stat: Journal Article,

Neurometric QEEG studies of crack cocaine dependence and treatment outcome
Prichep LS; Alper K; Kowalik SC; Rosenthal M
1996 ;15(4):39-53, Journal of addictive diseases
This paper presents an overview of the quantitative electrophysiological (QEEC) research on cocaine dependence conducted at Brain Research Laboratories of New York University Medical Center. These studies have demonstrated that subjects with DSM-III-R cocaine dependence (without dependence on any other substance) evaluated in the withdrawal state, have replicable abnormalities in brain function when evaluated at baseline (approximately 5 to 10 days after last crack cocaine use), which are still seen at one and six month follow-up evaluations. These abnormalities were characterized by significant excess of relative alpha power and deficit of absolute and relative delta and theta power. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. In addition, QEEC subtypes were identified within the population of cocaine dependent subjects at baseline, and these subtypes were found to be significantly related to subsequent length of stay in treatment. The relationship between these QEEG findings and the neuropharmacology of cocaine dependence is discussed
— id: 12667, year: 1996, vol: 15, page: 39, stat: Journal Article,

Quantitative electroencephalographic characteristics of crack cocaine dependence
Prichep LS; Alper KR; Kowalik S; Merkin H; Tom M; John ER; Rosenthal MS
1996 Nov 15;40(10):986-993, Biological psychiatry
This study replicates preliminary findings reporting a quantitative electroencephalographic (QEEG) profile of crack cocaine dependence in abstinence. All subjects (n = 52) met criteria for DMS-III-R cocaine dependence (in the form of crack), and were residing in a drug-free therapeutic community. Baseline QEEG evaluations were conducted at intake (5-10 days after last use of crack, and at follow-up (1 month after last reported use). Previous findings of significant excess of relative alpha power and deficit of absolute and relative delta and theta power were replicated in this expanded group. Abnormalities were greater in anterior than posterior regions, and disturbances in interhemispheric relationships were also observed. Further, QEEG showed little change in the interval between the first and second evaluations. This QEEG profile may reflect persistent alterations in neurotransmission as a possible consequence of chronic cocaine exposure
— id: 12472, year: 1996, vol: 40, page: 986, stat: Journal Article,

Social and medical outcome of nonepileptic seizures
ABRAMSON, H; BARKAN, M; ALPER, K; PERRINE, K; DEVINSKY, O
1995 NOV ;36(22):H9-H9, Epilepsia
— id: 52681, year: 1995, vol: 36, page: H9, stat: Journal Article,

Psychiatric classification of nonconversion nonepileptic seizures
Alper K; Devinsky O; Perrine K; Vazquez B; Luciano D
1995 Feb;52(2):199-201, Archives of neurology
OBJECTIVE: To determine the frequency and type of non-conversion nonepileptic seizures (NES). BACKGROUND: Although conversion disorder is the most common psychiatric disorder among patients with NES, many patients with nonepileptic paroxysmal behavioral events have other psychiatric disorders, with natural histories and treatments different from those of conversion disorder. DESIGN: Retrospective review of a series of consecutive admissions for video-electroencephalography monitoring. All patients identified with NES were interviewed by a psychiatrist. Patients with conversion and other psychiatric disorders were divided into separate groups. SETTING: A comprehensive epilepsy center. RESULTS: Twenty-one patients evaluated for possible epileptic seizures had a psychiatric disorder other than conversion that accounted for their events. Among these patients, Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) anxiety disorders (n = 9) were the most common diagnosed category, followed by all forms of psychotic disorders (n = 7) and impulse control problems in the setting of attention deficit disorder residual type (n = 2). In contrast to 71 patients with conversion NES seen over the same period of time, the non-conversion group showed no female predominance and the nonconversion patients were significantly less likely than the conversion patients to have been physically or sexually abused in childhood or adolescence. CONCLUSIONS: These results support the validity of the nosologic distinction of nonconversion from conversion NES and suggest that DSM-III-R anxiety disorders are an important diagnostic confound in clinical epilepsy
— id: 12805, year: 1995, vol: 52, page: 199, stat: Journal Article,

DISSOCIATION IN PATIENTS WITH EPILEPTIC AND NONEPILEPTIC SEIZURES
ALPER, K; DEVINSKY, O; PERRINE, K; LUCIANO, D; VAZQUEZ, B; PACIA, S; ABRAMSON, H
1995 OCT ;36(4):640-640, Epilepsia
— id: 104295, year: 1995, vol: 36, page: 640, stat: Journal Article,

Postictal psychosis: a case control series of 20 patients and 150 controls
Devinsky O; Abramson H; Alper K; FitzGerald LS; Perrine K; Calderon J; Luciano D
1995 Mar;20(3):247-253, Epilepsy research
We compared clinical data, EEG, and video-EEG studies in a consecutive series of 20 patients with postictal psychosis (PP) to 150 consecutive epilepsy patients with complex partial (CPS) or generalized tonic-clonic (GTCS) seizures but without PP. There was a lucid interval between last seizure and onset of psychosis ranging from 2.3 to 72 h (mean, 25 h). Duration of PP ranged from 16 to 432 h (mean, 83 h). Age, sex, epilepsy type (partial vs. generalized), and history of febrile seizures were similar in the PP and control groups. Patients with PP had more frequent GTCS during monitoring than controls (2.8 vs. 1.3; P < 0.001). Patients with PP were more likely to have a history of encephalitis (P < 0.0001) and psychiatric hospitalization (P < 0.002). More patients with PP had bilateral interictal epileptiform discharges during monitoring than controls (P < 0.0002). Postictal psychosis most often develops in patients with bilateral dysfunction following a cluster of GTCS
— id: 6818, year: 1995, vol: 20, page: 247, stat: Journal Article,

DEPRESSION AND ANXIETY IN PATIENTS WITH NONEPILEPTIC VERSUS EPILEPTIC SEIZURES
DONOFRIO, N; PERRINE, K; ALPER, K; ABRAMSON, H; DEVINSKY, O
1995 NOV ;36(22):H11-H11, Epilepsia
— id: 52682, year: 1995, vol: 36, page: H11, stat: Journal Article,

ABUSE HISTORY AND ICTAL SEMIOLOGY OF NONEPILEPTIC PSYCHOGENIC SEIZURES
LUCIANO, D; BARKEN, M; DEVINSKY, O; PERRINE, K; ALPER, K
1995 NOV ;36(22):645-645, Epilepsia
— id: 86669, year: 1995, vol: 36, page: 645, stat: Journal Article,

Quantitative EEG characteristics of children exposed in utero to cocaine
Prichep LS; Kowalik SC; Alper K; de Jesus C
1995 Jul;26(3):166-172, Clinical electroencephalography
Quantitative EEGs (QEEGs) were evaluated in a group of 6 school age children with in utero cocaine exposure. Their QEEGs showed significant deviations from age expected normal values. Further, the QEEG profile of brain dysfunction seen in these children was extremely similar to that previously reported in a large population of crack cocaine dependent adults. These abnormalities were characterized by significant excess of relative power in the alpha frequency band, and deficits of absolute and relative power in the delta and theta bands. Characteristic disturbances in interhemispheric relationships were also present. The similarities between the QEEG profiles of those adults with chronic exposure and children with prenatal exposure suggests that the brain dysfunction reflected in the QEEG is not a result of a transient change in neurotransmission, but a more profound alteration which persists in these children at school age. Further study is required to extend these findings to a larger group of children, and to investigate the potential relationship between these neurophysiological abnormalities and the developmental, behavioral and co-morbid features observed in such children
— id: 6948, year: 1995, vol: 26, page: 166, stat: Journal Article,

QEEG in hemophiliacs with HIV infection
Riedel RR; Alper K; Bulau P; Brackmann HH; Niese D; Schieck U; Gunther W
1995 Apr;26(2):84-91, Clinical electroencephalography
Conventional visual analysis of the EEG was performed on 320 hemophiliacs infected with HIV, who spanned the range of the Walter Reed (WR) system for classifying clinical stage of HIV infection, and on 50 HIV seronegative hemophiliac controls. Intermittent or paroxysmal slowing was the conventional EEG abnormality most commonly seen in early stages of HIV infection (stages WR1 and 2), with increased focal epileptiform activity and generalized slowing appearing in patients with the full clinical syndrome of AIDS (WR6). Slowing of the manually measured alpha rhythm was noted in stages WR2 and above. Quantitative EEG (qEEG) was obtained in a subset of 103 male HIV seropositive male hemophiliacs and 35 male HIV seronegative hemophiliac controls. The principal findings were a progressive relative increase in theta power with a tendency towards an anterior topographic distribution, and a progressive decline of spectral power in fast alpha relative to slow alpha with increasing severity of HIV disease. Significant qEEG differences from controls were apparent in WR2 subjects (seropositive with lymphadenopathy and without other constitutional symptoms), and were relatively greater in WR3-6 subjects. These results suggest sensitivity of qEEG to early CNS involvement with HIV infection
— id: 6729, year: 1995, vol: 26, page: 84, stat: Journal Article,

Nonepileptic seizures
Alper K
1994 Feb;12(1):153-173, Neurologic clinics
A review of the literature on epileptic seizures (NES) is presented, a common clinical entity that can be reliably diagnosed if suggestion and video-EEG monitoring are combined with an appreciation of the phenomenology of epileptic and nonepileptic events. Axis I psychiatric disorders with symptoms such as anxiety or dissociation should be considered in the differential diagnosis of NES
— id: 63288, year: 1994, vol: 12, page: 153, stat: Journal Article,

HIV ANTIBODY TESTING AND CLIENT RETENTION IN THE THERAPEUTIC-COMMUNITY - A PRELIMINARY-REPORT OF PHOENIX-HOUSE
GONZALEZ, I; ROSENTHAL, MS; BIGLER, MO; ALPER, K; GERINGER, W
1994 SEP-OCT ;11(5):481-488, Journal of substance abuse treatment
This report describes the current approach to testing for the human immunodeficiency virus (HIV) antibody at Phoenix House, a large therapeutic community (TC) in the northeastern United States, and presents findings on retention of clients who have been tested for HIV antibodies and notified of their HIV serostatus. A total of 240 clients were tested while in treatment at Phoenix House between April 1988 and July 1992. Of these, 51 tested HIV positive. An additional 76 clients had tested positive for HIV antibodies prior to entering treatment. The difference in length of treatment stay between those who tested negative while in treatment and those who tested positive while at Phoenix House was not significant (t = 0.41, df = 238, p > .683). Although clients who tested seronegative during treatment were found to remain in treatment a significantly longer amount of time than the total population of seropositive clients (t = 4.54, df = 314, p < .001), those who learned of their seropositive status while in treatment remained in the program longer than clients who entered treatment aware of their seropositivity (t = 4.08, df = 125, p < .001). These findings suggest that acute reactions of the knowledge of seropositivity did not determine most premature terminations. The use of a small group, a core technical element of the TC, may have provided a favorable context for the task of HIV counseling and testing
— id: 52307, year: 1994, vol: 11, page: 481, stat: Journal Article,

Diminished cerebral metabolic response to motor stimulation in schizophrenics: a PET study
Guenther, W; Brodie, J D; Bartlett, E J; Dewey, S L; Henn, F A; Volkow, N D; Alper, K; Wolkin, A; Cancro, R; Wolf, A P
1994 ;244(3):115-125, European archives of psychiatry & clinical neuroscience
Positron emission tomography (PET) and the deoxyglucose method were used to measure cerebral metabolism in 14 normals and 13 schizophrenics at rest and during performance of simple and complex finger-movement sequences. The normals, but not the schizophrenics, showed significant metabolic activation in mesial frontal and contralateral sensorimotor and premotor regions during the complex movement. The relative metabolism of schizophrenics was significantly lower than normal in frontal regions and higher than normal in thalamus and basal ganglia under all scanning conditions. The results suggest that schizophrenics may have a brain dysfunction which limits their capacity to produce a focal metabolic response to stimulation in several functionally distinct brain regions
— id: 76242, year: 1994, vol: 244, page: 115, stat: Journal Article,

Quantitative electrophysiological characteristics and subtyping of schizophrenia
John ER; Prichep LS; Alper KR; Mas FG; Cancro R; Easton P; Sverdlov L
1994 Dec 15;36(12):801-826, Biological psychiatry
Quantitative descriptors of resting electroencephalogram (EEG) (QEEG) and event-related potentials (QERP) to visual and auditory stimuli were obtained from normal subjects and 94 chronic schizophrenic patients on medication, 25 chronic schizophrenics off medication, and 15 schizophrenics with no history of medication. These schizophrenic groups showed a high incidence of neurometric features that were significantly deviant from normative values. Multivariate discriminant analysis using these features successfully separated the schizophrenic patients from normals with high accuracy in independent replication. The data from the medicated group were subjected to cluster analysis. Newly developed algorithms were used for objective selection of the most effective set of variables for clustering and the optimum number of clusters to be sought. Five clusters were obtained, containing roughly equivalent proportions of the sample with markedly different QEEG profiles. The whole sample was then classified into these clusters. Each cluster contained patients both on and off medication, but patients who had never been medicated were classified into only three of these clusters. No significant clinical or demographic differences were found between members of the five clusters; however, clear differences in QERP profiles were seen. These results are described in detail and possible physiological and pharmacological implications are discussed
— id: 6653, year: 1994, vol: 36, page: 801, stat: Journal Article,

Quantitative EEG correlates of cognitive deterioration in the elderly [published erratum appears in Neurobiol Aging 1994 May-Jun;15(3):391]
Prichep LS; John ER; Ferris SH; Reisberg B; Almas M; Alper K; Cancro R
1994 Jan-Feb;15(1):85-90, Neurobiology of aging
We report on the quantitative analysis of the EEG (QEEG), using the Neurometric method, in large samples of normal elderly; normal subjectively impaired elderly; patients with mild cognitive impairment; patients presenting with a continuum of primary cognitive deterioration from mild to moderately severe as measured by the Global Deterioration Scale (GDS), compatible with dementia of the Alzheimer's type (DAT). Neurometric QEEG measures were found to be a sensitive index of degree of cognitive impairment, especially reflected in increased absolute and relative power in the theta band, with delta increasing in later stages of deterioration. While these abnormalities were widespread, neither localized or lateralized, MANOVA's for GDS and relative power in theta reached highest significance in a bilateral temporo-parietal arc. A possible relationship between hippocampal dysfunction, cognitive deterioration, and theta abnormalities is discussed in relation to these findings. The results suggest that Neurometric QEEG features are sensitive to the earliest presence of subjective cognitive dysfunction and might be useful in the initial evaluation of patients with suspected dementia, as well as in estimating the degree of cognitive deterioration in DAT patients
— id: 6488, year: 1994, vol: 15, page: 85, stat: Journal Article,

Nonepileptic seizures and childhood sexual and physical abuse
Alper K; Devinsky O; Perrine K; Vazquez B; Luciano D
1993 Oct;43(10):1950-1953, Neurology
Nonepileptic seizures (NES) must be distinguished from epilepsy to avoid the adverse effects of unnecessary antiepileptic drugs and to initiate appropriate psychiatric treatment. A higher frequency of prior sexual abuse has been suspected in NES, although no prospective controlled study has compared patients with NES and epilepsy. A series of patients with conversion disorder presenting as epilepsy and 140 patients with complex partial epilepsy (CPE) without evidence of conversion were selected from a series of consecutive admissions to a comprehensive epilepsy center. The groups did not differ with respect to age, years of education, race, or marital status, but the percentage of women was greater in the conversion NES group (73.2%) than in the CPE control group (50.7%; p < 0.002). The frequency of a history of sexual or physical abuse was greater in the NES group (32.4%) than in the CPE controls (8.6%; p < 0.000). Severity of sexual but not physical abuse was significantly greater in the NES group relative to controls (p < 0.05). There was a trend for a closer relationship of the perpetrator of sexual abuse to the victim among the NES patients compared with CPE controls (p < 0.1). These results support the impression that childhood abuse is more common among patients with conversion NES than with epilepsy, and suggests that in some cases childhood abuse may be a contributory pathogenetic factor
— id: 56494, year: 1993, vol: 43, page: 1950, stat: Journal Article,

Treatment resistant depression in a case of minor head injury: an electrophysiological hypothesis
Mas F; Prichep LS; Alper K
1993 Jul;24(3):118-122, Clinical electroencephalography
A relatively small but highly concordant literature suggests that manic depressive psychoses may include familial as well as nonfamilial subtypes. The latter, which appears to be an acquired form, follows brain injury of various etiology, displays EEG abnormalities and tends to respond well to anticonvulsant therapy. In this study we postulate an extension of this dichotomy to a larger spectrum of affective disorder, including milder but 'treatment resistant' forms often associated with a high degree of dysfunction. Central to this hypothesis is information gathered from the longitudinal study of a well defined case in which precise clinical and electrophysiological data have been obtained at critical junctures. This data also leads us to suggest the existence of a latent vulnerability to psychosocial stressors in a subgroup of minor head injured patients. Once triggered, the resulting psychopathological state may be clinically indistinguishable from similar but etiologically distinct conditions. However, they respond poorly, if at all, to the treatments usually effective for mood disorders, often causing puzzlement and frustration among clinicians as well as mounting hopelessness in patients. This organic mood disorder subtype, which can be described as 'neuro-sensitization mood disorder,' may be identified by combining a thorough history, including perinatal events and putative brain injury, with electrophysiological data consisting of quantitative EEG (QEEG) in association with evoked potentials. In cases with positive findings, anticonvulsants such as carbamazepine, clonazepam and valproic acid can be a treatment of choice
— id: 6447, year: 1993, vol: 24, page: 118, stat: Journal Article,

Nonepileptic seizures during apparent sleep
Thacker K; Devinsky O; Perrine K; Alper K; Luciano D
1993 Apr;33(4):414-418, Annals of neurology
We report 12 patients with nonepileptic seizures (NESs) documented with video-electroencephalographic monitoring during apparent sleep. There were 7 females and 5 males, ages 11 to 67 years (mean, 33 yr). In all patients there was a well-organized posterior alpha rhythm present immediately before onset of clinical changes despite the appearance of sleep. Patients later 'confirmed' that these attacks occurred during sleep. Features of these episodes were typical of NESs and none were associated with ictal or postictal electroencephalographic changes other than muscle and movement artifact. Provocative testing with suggestion confirmed the nonepileptic nature of these episodes in 9 patients. Three patients had epileptiform discharges during prolonged interictal recordings and 1 had a documented complex partial seizure. Our findings indicate that reports of seizures during sleep are not uncommon among patients with NESs
— id: 13192, year: 1993, vol: 33, page: 414, stat: Journal Article,

Juvenile myoclonic epilepsy: Clinical features and factors related to misdiagnosis
Vazquez B; Devinksy O; Luciano D; Alper K; et al
1993 ;6(4):233-238, Journal of epilepsy
Identified 37 patients (aged 11-57 yrs) with juvenile myoclonic epilepsy (JME) out of 740 consecutive epilepsy patients. Only 3 were initially diagnosed with JME. Factors leading to misdiagnosis included warnings (auras) suggesting partial seizures before generalized tonic-clonic seizures (GTCS), confusion between absence and complex partial seizures, failure of patients to spontaneously report or for physicians to obtain a history of myoclonic jerks, and failure to report myoclonic jerks to medical personnel despite specific questioning. Psychiatric disorders were common: depression occurred in 9 Ss and panic disorder in 7 Ss. Following diagnosis, 86% of Ss were seizure-free on antiepileptic drugs. To improve diagnostic sensitivity, Ss with epilepsy should be routinely questioned about the occurrence of myoclonic seizures, and JME should not be excluded because patients report nonspecific warnings before GTCS.
— id: 8160, year: 1993, vol: 6, page: 233, stat: Journal Article,

Quantitative electroencephalography. A new approach to the diagnosis of cerebral dysfunction in systemic lupus erythematosus
Ritchlin CT; Chabot RJ; Alper K; Buyon J; Belmont HM; Roubey R; Abramson SB
1992 Nov;35(11):1330-1342, Arthritis & rheumatism
OBJECTIVE. Neuropsychiatric manifestations are common in patients with systemic lupus erythematosus (SLE), but accurate diagnosis is often difficult. We conducted a prospective study to determine the utility of neurometric quantitative electroencephalography (QEEG) as an indicator of cerebral dysfunction in SLE patients. METHODS. Fifty-two SLE patients were divided into 4 groups based on the results of neuropsychiatric evaluations. These included patients with objective evidence of neuropsychiatric SLE (NPSLE), patients with neuropsychiatric symptoms, patients with no evidence of NPSLE, and patients with a prior history of NPSLE. All QEEG findings were compared with data in an age-regressed normative database and with findings in an independent sample of normal subjects. RESULTS. QEEG sensitivity was 87%, and specificity was 75%. QEEG results were abnormal in 74% of the SLE patients with neuropsychiatric symptoms and in 28% of the patients with no evidence of active NPSLE. QEEG profiles varied as a function of the severity and type of neuropsychiatric manifestation present. Within this patient population, QEEG was more sensitive than magnetic resonance imaging, computed tomography scanning, or conventional EEG. CONCLUSION. Neurometric QEEG may be a sensitive indicator of cerebral dysfunction in patients with NPSLE and can differentiate patients with diverse neuropsychiatric manifestations. When combined with a careful clinical history and evaluation, QEEG provides information that may be useful for the early detection of NPSLE and for serial evaluation of disease activity and treatment efficacy
— id: 9743, year: 1992, vol: 35, page: 1330, stat: Journal Article,

Quantitative EEG correlates of crack cocaine dependence
Alper KR; Chabot RJ; Kim AH; Prichep LS; John ER
1990 Dec;35(2):95-105, Psychiatry research
Evidence for a distinctive syndrome of neuroadaptation in cocaine dependence has accumulated from behavioral, neurophysiological, and preclinical and clinical pharmacological studies. The authors report on the results of a preliminary investigation of the quantitative electroencephalographic (QEEG) correlates of severe DSM-III-R crack cocaine dependence in seven patients abstinent from cocaine for 1 to 68 days. The major QEEG finding was increased absolute and relative alpha power. Increased alpha power has also been reported in multiple previous studies of depressed patients. This series of crack-dependent patients showed significant depressive morbidity; four patients attempted suicide subsequent to initiating their use of crack and the group mean (+/- SD) Beck Depression Scale score was 18.9 (+/- 6.5). These results complement other studies that support the concept of neuroadaptation to chronic cocaine exposure. Prospective studies correlating QEEG measures with subsequent response to pharmacological interventions for cocaine dependence should be considered
— id: 14267, year: 1990, vol: 35, page: 95, stat: Journal Article,