Annette O Nusbaum, M.D.

Phase II clinical trial of lapatinib in children and adults with NF2-related tumors
Karajannis M.A.; Ballas M.; Ayanru I.; Orrico A.; Nusbaum A.; Hagiwara M.; Roland T.; Golfinos J.; Allen J.
2010 ;12(6):ii43-ii43, Neuro-oncology
PURPOSE: Lapatinib is an orally active receptor tyrosine kinase inhibitor that reversibly inhibits EGFR and ErbB2. We have recently shown that EGFR and ErbB2 are consistently expressed and activated in vestibular schwannomas (VS) in patients with NF2 and that lapatinib is active in a preclinical VS model. This study aims to determine the response rate to lapatinib in children and adults with VS and other NF2-related tumors. EXPERIMENTAL DESIGN: A 2-stage clinical trial design was used and NF2 patients > 3 years of age with progressive NF2-related tumors including VS, meningiomas and ependymomas were eligible. Lapatinib was administered continuously for 28-day courses. MRIs of the brain and spine, including volumetric tumor analysis, as well as audiograms were performed at baseline and after every 3rd course. Primary endpoint was defined as a decrease of at least 15% in tumor volume. RESULTS: At the time of submission, enrollment on the first trial stage has been completed with 9 eligible patients. Two patients discontinued protocol therapy after 3 courses due to progression. One of 3 evaluable patients to date had a 16.6% reduction in tumor volume of his VS after 3 courses. The remaining 6 patients continue on trial. CONCLUSION: A full report of tolerance and activity will be reported on the first 9 patients, but preliminary response data suggests that lapatinib may have anti-tumor activity against VS in NF2 patients. Predefined study response criteria on stage 1 were met to allow enrollment of 8 additional patients on stage 2 of this trial
— id: 135615, year: 2010, vol: 12, page: ii43, stat: Journal Article,

Superior turbinate pneumatization in patients with chronic rhinosinusitis: prevalence on paranasal sinus CT
Kanowitz, Seth J; Nusbaum, Annette O; Jacobs, Joseph B; Lebowitz, Richard A
2008 Oct;87(10):578-579, Ear, nose & throat journal
With the availability of high-resolution computed tomography (CT), a great deal of attention has been paid to the anatomy of the paranasal sinuses. But while investigators have focused on the osteomeatal complex and its relation to chronic rhinosinusitis, there has been little discussion of the superior turbinate. Although a few anatomic studies have tried to quantify pneumatization of the superior turbinate, the prevalence of this finding on radiography is not well addressed in the literature. We prospectively studied 100 consecutively presenting patients who underwent coronal CT of the paranasal sinuses (200 sides) for the evaluation of symptoms of chronic rhinosinusitis at an academic tertiary referral center to determine the prevalence of pneumatization of the superior turbinate. We found evidence of pneumatization in 44 of the 200 sides, for a prevalence of 22%. In all, pneumatized superior turbinates were found in 27 patients (27%)-bilaterally in 17 (17%) and unilaterally in 10 (10%)
— id: 92166, year: 2008, vol: 87, page: 578, stat: Journal Article,

Bone deposition/generation with LeFort III (midface) distraction
Jensen, John N; McCarthy, Joseph G; Grayson, Barry H; Nusbaum, Annette O; Eski, Muhittin
2007 Jan;119(1):298-307, Plastic & reconstructive surgery
BACKGROUND: It is essential to critically assess bone deposition in midface distraction. The aim of this study was to characterize the quality and volume of bone deposition at specific osteotomy sites following midface distraction. METHODS: At approximately 6 months after distraction, computed tomographic scans with three-dimensional reconstruction were obtained on 10 craniosynostosis syndromal patients who had undergone LeFort III osteotomy and midface distraction. Patient age ranged from 37 to 109 months (mean, 63.7 months) and the distractions ranged from 7 to 15 mm. Both the reconstructed scans and axial cuts were independently evaluated by four blinded observers (two plastic surgeons, an orthodontist, and a radiologist) and graded for bone deposition in predetermined anatomical sites correlated to the osteotomy. RESULTS: The authors found that variable bony bridging occurred at all sites along the osteotomy, but bone deposition was most reliably seen at the pterygomaxillary buttress and nasofrontal junction. In addition, the medial orbital walls tended to show greater consistency in bone deposition than the lateral orbital walls, and deposition at the zygomatic arches was shown to be least likely to occur. The technique of evaluation and the clinically significant findings are discussed. CONCLUSIONS: Bony deposition occurs more reliably in the medial facial skeleton following LeFort III osteotomy, and osteotomy through the zygomatic body was more likely to result in deposition than one through the arch
— id: 73825, year: 2007, vol: 119, page: 298, stat: Journal Article,

Dynamic sagittal half-Fourier acquired single-shot turbo spin-echo MR imaging of the temporomandibular joint: initial experience and comparison with sagittal oblique proton-attenuation images
Wang, E Y; Mulholland, T P; Pramanik, B K; Nusbaum, A O; Babb, J; Pavone, A G; Fleisher, K E
2007 Jun-Jul;28(6):1126-1132, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Our aim was to assess dynamic half-Fourier acquired single-shot turbo spin-echo (HASTE) MR imaging of the temporomandibular joint (TMJ) using parallel imaging, in comparison with static proton density (Pd) imaging. MATERIALS AND METHODS: Thirty-four TMJs from 17 subjects (7 volunteers, 10 patients) were imaged in a multichannel head coil on a 1.5 T magnet by using a 35-second dynamic sagittal HASTE acquisition (TR/TE, 1180/65 msec; matrix, 128 x 128; section thickness, 7 mm; 30 images) and sagittal oblique Pd in closed- and open-mouthed positions (TR/TE, 1800/12 msec; matrix, 256 x 256; section thickness, 2 mm; 15 sections). Images were reviewed by 3 readers and rated for confidence of disk position, presence of motion artifact, range of motion, and presence of disk displacement on a 5-point scale. Consensus review of cases was also performed to assess disk dislocation and limited range of motion. RESULTS: More static examinations were rated as having motion artifact (19.6% versus 6.9%, P=.016), limited range of motion (30.4% versus 17.7%, P=.016), and disk dislocations (31.4% versus 22.6%, P=.071). Confidence ratings were higher on dynamic examinations (4.11 versus 3.74, P=.018). Chi-squared tests demonstrated no significant difference in consensus reviews of the 2 examination types. CONCLUSION: Dynamic HASTE TMJ MR imaging is a time-efficient adjunct to standard MR imaging protocols, producing fewer motion artifacts, additional range of motion information, and a dynamic assessment of disk position, when compared with static imaging. Further study is needed to evaluate the role of this sequence in diagnosing disk displacement
— id: 73383, year: 2007, vol: 28, page: 1126, stat: Journal Article,

MR imaging and proton spectroscopy of neuronal injury in late-onset GM2 gangliosidosis
Inglese, Matilde; Nusbaum, Annette O; Pastores, Gregory M; Gianutsos, John; Kolodny, Edwin H; Gonen, Oded
2005 Sep;26(8):2037-2042, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Despite the ubiquity of G(M2) gangliosides accumulation in patients with late-onset G(M2) gangliosidosis (G(M2)G), the only clinical MR imaging-apparent brain abnormality is profound cerebellar atrophy. The goal of this study was to detect the presence and assess the extent of neuroaxonal injury in the normal-appearing gray and white matter (NAGM and NAWM) of these patients. METHODS: During a single imaging session, 9 patients with late-onset G(M2)G and 8 age-matched normal volunteers underwent the following protocol: (1) T1- and T2-weighted and fluid-attenuated inversion recovery MR images, as well as (2) multivoxel proton MR spectroscopy (1H-MR spectroscopy) to quantify the distribution of the n-acetylaspartate (NAA), creatine (Cr), and choline (Cho), were obtained. RESULTS: The patients' NAA levels in the thalamus (6.5 +/- 1.9 mmol/L) and NAWM (5.8 +/- 2.1 mmol/L) were approximately 40% lower than the controls' (P = .003 and P = .005), whereas the Cr and Cho reductions ( approximately 30% and approximately 26%) did not reach significance (P values of .06-.1). All cerebellar metabolites, especially NAA and Cr, were much (30%-90%) lower in the patients, which reflects the atrophy. CONCLUSION: In late-onset G(M2)G, NAA decreases are detectable in NAGM and NAWM even absent morphologic (MR imaging) abnormalities. Because the accumulation of G(M2) gangliosides can be reduced pharmacologically, 1H-MR spectroscopy might be a sensitive and specific for detecting and quantifying neuroaxonal injury and monitoring response to emerging treatments
— id: 61242, year: 2005, vol: 26, page: 2037, stat: Journal Article,

Correlation of apparent diffusion coefficient with neuropsychological testing in temporal lobe epilepsy
Lui, Yvonne W; Nusbaum, Annette O; Barr, William B; Johnson, Glyn; Babb, James S; Orbach, Darren; Kim, Alice; Laliotis, Georgia; Devinsky, Orrin
2005 Aug;26(7):1832-1839, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: Patients with nonlesional temporal lobe epilepsy have long been known to have abnormalities of memory. Recently, these patients have been shown to have increased diffusivity in the hippocampus. We hypothesized that in these patients, a negative correlation would exist between diffusivity measures of the mesial temporal lobe and performance on neuropsychological tests. METHODS: Twenty presurgical patients with temporal lobe epilepsy and 20 age- and sex-matched healthy controls underwent MR imaging of the brain. Apparent diffusion coefficient region of interest measures were taken in both hippocampi and parahippocampal gyri by 2 independent observers. Mean whole brain diffusivity was calculated. All patients completed neuropsychological testing. Electroencephalogram and pathology results were collected. Patients and controls were compared with respect to each apparent diffusion coefficient measure. In patients, apparent diffusion coefficients ipsilateral and contralateral to the seizure focus were compared. Associations were assessed between diffusivity measures and neuropsychological scores. RESULTS: Eleven patients had right-sided seizure foci and 9 had left-sided seizure foci. Patients demonstrated higher apparent diffusion coefficient values than controls over the whole brain, in the hippocampi, and in the parahippocampal gyri (P < .05). Patients demonstrated higher apparent diffusion coefficient within the ipsilateral hippocampus (1.19 +/- 0.22 x 10(-3) s/mm2) and parahippocampal gyrus (1.02 +/- 0.12 x 10(-3) s/mm2) compared with the contralateral side (1.02 +/- 0.16 x 10(-3) s/mm2 and 0.96 +/- 0.09 x 10(-3) s/mm2, respectively) (P < .05). Negative correlations were seen between hippocampal apparent diffusion coefficients and multiple memory tests (P < .05). CONCLUSION: Quantitative diffusion measurements in the hippocampus correlate with memory dysfunction in patients with temporal lobe epilepsy
— id: 57871, year: 2005, vol: 26, page: 1832, stat: Journal Article,

Diffusion tensor MR imaging of gray matter in different multiple sclerosis phenotypes
Nusbaum, Annette O
2002 Jun-Jul;23(6):899-900, AJNR. American journal of neuroradiology
— id: 96884, year: 2002, vol: 23, page: 899, stat: Journal Article,

Regional and global changes in cerebral diffusion with normal aging
Nusbaum AO; Tang CY; Buchsbaum MS; Wei TC; Atlas SW
2001 Jan;22(1):136-142, AJNR. American journal of neuroradiology
BACKGROUND AND PURPOSE: We used quantitative diffusion MR imaging to investigate the microstructural changes that occur in white matter during normal aging in order to identify regional changes in anisotropy and to quantify global microstructural changes by use of whole-brain diffusion histograms. METHODS: Full diffusion tensor MR imaging was performed in 20 healthy volunteers, 20 to 91 years old. Thirteen subjects also underwent high-resolution T1-weighted imaging, so that diffusion images could be coregistered and standardized to normal coordinates for statistical probability mapping. Relative anisotropy (RA) was calculated, as was linear regression of RA with age for each pixel; pixels with a significant correlation coefficient were displayed. For histographic analysis, the average apparent diffusion coefficient (ADC) histograms were calculated on a pixel-by-pixel basis. Subjects were divided into two equal groups by the median age (55 years) of the population and plotted for statistical comparison. RESULTS: Regional analysis showed statistically significant decreases in RA with increasing age in the periventricular white matter, frontal white matter, and genu and splenium of the corpus callosum, despite the absence of signal abnormalities on visual inspection of conventional images. Significant increases in RA were found in the internal capsules bilaterally. ADC histograms showed higher mean ADC and reduced peak height and skew in the older age group on group comparisons. CONCLUSION: Quantitative diffusion histograms correlate with normal aging and may provide a global assessment of normal age-related changes and serve as a standard for comparison with neurodegenerative diseases
— id: 27834, year: 2001, vol: 22, page: 136, stat: Journal Article,

Differential amygdala activation during emotional decision and recognition memory tasks using unpleasant words: an fMRI study
Tabert MH; Borod JC; Tang CY; Lange G; Wei TC; Johnson R; Nusbaum AO; Buchsbaum MS
2001 ;39(6):556-573, Neuropsychologia
This study used fMRI to examine the response of the amygdala in the evaluation and short-term recognition memory of unpleasant vs. neutral words in nine right-handed healthy adult women. To establish specificity of the amygdala response, we examined the fMRI BOLD signal in one control region (visual cortex). Alternating blocks of unpleasant and neutral trials were presented. During the emotional decision task, subjects viewed sets of three unpleasant or three neutral words while selecting the most unpleasant or neutral word, respectively. During the memory task, subjects identified words that were presented during the emotional decision task (0.50 probability). Images were detrended, filtered, and coregistered to standard brain coordinates. The Talairach coordinates for the center of the amygdala were chosen before analysis. The BOLD signal at this location in the right hemisphere revealed a greater amplitude signal for the unpleasant relative to the neutral words during the emotional decision but not the memory task, confirmed by Time Course x Word Condition ANOVAs. These results are consistent with the memory modulatory view of amygdala function, which suggests that the amygdala facilitates long-term, but not short-term, memory consolidation of emotionally significant material. The control area showed only an effect for Time Course for both the emotional decision and memory tasks, indicating the specificity of the amygdala response to the evaluation of unpleasant words. Moreover, the right-sided amygdala activation during the unpleasant word condition was strongly correlated with the BOLD response in the occipital cortex. These findings corroborate those by other researchers that the amygdala can modulate early processing of visual information in the occipital cortex. Finally, an increase in subject's state anxiety (evaluated by questionnaire) while in the scanner correlated with amygdala activation under some conditions
— id: 27833, year: 2001, vol: 39, page: 556, stat: Journal Article,

Quantitative diffusion measurements in focal multiple sclerosis lesions: correlations with appearance on TI-weighted MR images
Nusbaum AO; Lu D; Tang CY; Atlas SW
2000 Sep;175(3):821-825, American journal of roentgenology
OBJECTIVE: Relative hypointensity on T1-weighted MR imaging has been suggested as a putative disability marker. The purpose of our study was to determine if there are quantifiable diffusion differences among focal multiple sclerosis lesions that appear differently on conventional T1-weighted MR images. We hypothesized that markedly hypointense lesions on unenhanced T1-weighted images would have significantly increased diffusion compared with other lesions, and enhancing portions of lesions would have different diffusion compared with nonenhancing lesions. SUBJECTS AND METHODS: Average apparent diffusion coefficient (ADC) was calculated for 107 lesions identified on T2-weighted images in 16 patients with multiple sclerosis and was compared with the ADC of normal white matter in 16 age- and sex-matched control subjects. Seventy-five nonenhancing lesions (29 isointense, 46 hypointense) and 32 enhancing lesions (6 isointense, 26 hypointense) were categorized on the basis of unenhanced T1-weighted MR imaging. RESULTS: Hypointense and isointense nonenhancing lesions both showed significantly higher ADC than normal white matter (p < 0.0001). Hypointense nonenhancing lesions showed higher ADC values than isointense nonenhancing lesions (p < 0.0001). Diffusion in enhancing portions of enhancing lesions was decreased when compared with nonenhancing portions. CONCLUSION: Quantitative diffusion data from MR imaging differ among multiple sclerosis lesions that appear different from each other on T1-weighted images. These quantitative diffusion differences imply microstructural differences, which may prove useful in documenting irreversible disease
— id: 27835, year: 2000, vol: 175, page: 821, stat: Journal Article,

Whole-brain diffusion MR histograms differ between MS subtypes
Nusbaum AO; Tang CY; Wei T; Buchsbaum MS; Atlas SW
2000 Apr 11;54(7):1421-1427, Neurology
OBJECTIVE: To determine whether quantitative whole-brain MR diffusion histograms in patients with MS differ from those of normal control subjects. BACKGROUND: MRI detects macroscopic cerebral lesions in MS, but the white matter lesion burden on MRI correlates imperfectly to clinical disability. Previous reports have further suggested abnormalities in white matter of MS patients with no visible lesions on conventional MRI. METHODS: A total of 25 subjects (13 with MS [9 relapsing-remitting, 4 secondary progressive] and 12 healthy control subjects) underwent diffusion-weighted echoplanar MRI encompassing the entire brain. The average apparent diffusion coefficient (ADCave, or diffusion trace) was calculated on a pixel-by-pixel basis after segmentation of intracranial space from calvarium and extracranial soft tissues. Whole-brain ADCave histograms were calculated and plotted for statistical comparison. RESULTS: Mean whole-brain MR ADCave in MS patients was elevated and histograms were shifted to higher values compared with normal control subjects. Mean whole-brain ADCave of secondary progressive patients was shifted to higher values compared with relapsing-remitting patients. Whole-brain ADCave histograms of relapsing-remitting patients showed no significant difference from normal control subjects. CONCLUSION: Whole-brain MR diffusion histograms may quantitate overall cerebral lesion load in patients with MS and may be able to discern differences between clinical subgroups
— id: 27836, year: 2000, vol: 54, page: 1421, stat: Journal Article,

Correlation between the degree of contrast enhancement and the volume of peritumoral edema in meningiomas and malignant gliomas
Holodny AI; Nusbaum AO; Festa S; Pronin IN; Lee HJ; Kalnin AJ
1999 Nov;41(11):820-825, Neuroradiology
Peritumoral edema and contrast enhancement of brain tumors are both thought to be due to breakdown of the blood-brain barrier (BBB); however, the exact mechanism by which these two phenomena occur and whether there is a quantitative or etiological relationship is not known. Our purpose was to determine whether the relationship between the breakdown of the BBB, defined radiologically as the degree of contrast enhancement, and the volume of surrounding edema is different for high-grade gliomas and meningiomas. We analyzed 13 meningiomas and 23 gliomas. A direct linear relationship between the degree of contrast enhancement (dC) and volume of peritumoral edema (V) with a high correlation coefficient (R = 0.66, P = 0.0006) was established for gliomas. A mathematical relationship between dC and V could not be established for meningioma. The findings for gliomas offer indirect radiological evidence that the defect in the BBB which causes edema is quantitatively and etiologically related to the defect in the BBB responsible for contrast enhancement. For meningiomas, the lack of a relationship between dC and V implies either that the mechanisms responsible for formation of edema and contrast enhancement are fundamentally different or that a physical barrier in certain meningiomas limits propagation of edema into the adjacent white matter
— id: 27839, year: 1999, vol: 41, page: 820, stat: Journal Article,

Pial involvement in Wegener's granulomatosis shown on MRI
Nusbaum AO; Morgello S; Atlas SW
1999 Nov;41(11):847-849, Neuroradiology
Involvement of the brain and meninges is rare in Wegener's granulomatosis (WG); it has been reported in 1.2-8 % of patients. Meningeal involvement in WG has been reported in imaging as being confined to the dura mater, and is thought to represent granulomatous infiltration. We present a case of WG with abnormal pial enhancement and involvement of the perivascular spaces on MRI, pathologically proven to represent granulomatous infiltration due to the primary disease rather than to infection
— id: 27838, year: 1999, vol: 41, page: 847, stat: Journal Article,

Recurrence of a deep neck infection: a clinical indication of an underlying congenital lesion
Nusbaum AO; Som PM; Rothschild MA; Shugar JM
1999 Dec;125(12):1379-1382, Archives of otolaryngology, head & neck surgery
OBJECTIVE: To discuss the computed tomographic (CT) and clinical findings of those entities that may present as recurrent deep neck infections. PATIENTS AND METHODS: Twelve patients with recurrent deep neck infections and CT scans were retrospectively identified since 1990. Their CT scans and medical histories were reviewed. The diagnosis was pathologically confirmed in all cases. RESULTS: The CT scans revealed an abscess or a localized infected cyst in the deep soft tissues of the neck, with varying degrees of associated inflammatory change in the adjacent soft tissues. The diagnoses in these cases included 1 first branchial cleft cyst, 3 second branchial cleft cysts, 1 third branchial cleft cyst, 2 fourth branchial cleft cysts, 2 infected lymphangiomas, 2 thyroglossal duct cysts, and 1 cervical thymic cyst. CONCLUSIONS: Most deep neck infections are the result of suppurative adenitis. The location of the primary focus is usually from the mucosa of the upper aerodigestive tract or from an odontogenic source. Less common causes are perforations due to a foreign body, thrombophlebitis of the internal jugular vein, or osteomyelitis of the spine. Recurrences in these situations are unusual. Less commonly, congenital lesions can present as deep neck infections, and recurrences are common. Our cases suggest that the recurrence of a deep neck infection should alert the physician to the possibility of an underlying congenital lesion and that CT is helpful in the early recognition of these lesions
— id: 27837, year: 1999, vol: 125, page: 1379, stat: Journal Article,

Isolated vagal nerve palsy associated with a dissection of the extracranial internal carotid artery
Nusbaum AO; Som PM; Dubois P; Silvers AR
1998 Nov-Dec;19(10):1845-1847, AJNR. American journal of neuroradiology
A 40-year-old man had paralysis of the right vocal cord. Imaging showed a dissection of the extracranial internal carotid artery, and physical examination disclosed paresis of the right side of the soft palate. To our knowledge, this is only the second report of carotid dissection presenting as an isolated vagal neuropathy. Most often, multiple lower cranial nerves are involved. The CT, MR imaging, and MR angiographic findings are presented and the topic is reviewed
— id: 27840, year: 1998, vol: 19, page: 1845, stat: Journal Article,

Pneumoretroperitoneum secondary to an open reduction and internal fixation of a femoral fracture: case report
Maldjian PD; Nusbaum AO
1997 Jun;63(6):504-505, American surgeon
We present a case of pneumoretroperitoneum detected on computed tomography that resulted from open reduction and internal fixation of a femoral fracture. Retroperitoneal air has many etiologies. These range from the clinically insignificant to the potentially catastrophic, if not recognized promptly. We present a case of retroperitoneal air secondary to open reduction and internal fixation of a femoral fracture. To our knowledge, this association has not previously been described
— id: 27841, year: 1997, vol: 63, page: 504, stat: Journal Article,