31 results on '"Omar I. Khan"'
Search Results
2. Interictal spikes in developing rats cause long-standing cognitive deficits
- Author
-
Omar I. Khan, Qian Zhao, Forrest Miller, and Gregory L. Holmes
- Subjects
Learning ,Memory ,Water maze ,Apoptosis ,BrdU ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Frequent interictal spikes are a common finding in the electroencephalograms of children with epileptic encephalopathies. While it is well recognized that interictal spikes are a biological marker of seizures and can lead to transitory cognitive impairment, whether interictal spikes can result in long-standing adverse effects on learning and memory in children is not known. Here we investigated the consequences of interictal spikes in rat pups without seizures on long-term learning and memory. Rat pups were given a low dose of flurothyl for 4h for 10 days during continuous electroencephalographic monitoring. Rats developed interictal spikes without seizures while age-matched controls under similar testing conditions had few interictal spikes. When rats were tested as adults, there was impairment in reference memory in the probe test of the Morris water maze, reference memory impairment in the four-trial radial-arm water maze and impaired long-term potentiation. Early-life interictal spikes resulted in impaired new cell formation and decreased cell counts in the hippocampus but did not cause an increase in apoptosis. This study, for the first time demonstrates that interictal spikes in rat pups without seizures can result in long-standing spatial cognitive impairment. Our findings suggest that suppressing IIS may be as important as treating seizures during brain development.
- Published
- 2010
- Full Text
- View/download PDF
3. Neurotoxicity following CD19/CD28ζ CAR T-cells in children and young adults with B-cell malignancies
- Author
-
Haneen Shalabi, Staci Martin, Bonnie Yates, Pamela L Wolters, Claire Kaplan, Hannah Smith, Christopher R Sesi, Jennifer Jess, Mary Anne Toledo-Tamula, Kari Struemph, Cindy P Delbrook, Omar I Khan, Crystal L Mackall, Daniel W Lee, and Nirali N Shah
- Subjects
Cancer Research ,Young Adult ,Oncology ,Adolescent ,Neoplasms ,T-Lymphocytes ,Antigens, CD19 ,Humans ,Neurotoxicity Syndromes ,Neurology (clinical) ,Child ,Immunotherapy, Adoptive ,Pediatric Neuro-Oncology - Abstract
Background Neurotoxicity is an established toxicity of CD19 CAR T-cell therapy; however, there is little information on neurotoxicity in children, adolescents, and young adults (CAYA) receiving CD19/CD28ζ CAR T-cells for B-cell malignancies. Methods We analyzed neurotoxicity of CD19/CD28ζ CAR T-cells in CAYA treated on a phase I study (NCT01593696). Assessments included daily inpatient monitoring, caregiver-based neuro-symptom checklist (NSC), exploratory neurocognitive assessments, clinically-indicated imaging, CSF analysis, and systematic cytokine profiling, outcomes of which were associated with cytokine release syndrome (CRS) and treatment response postinfusion. Patients with active CNS leukemia were included. Results Amongst 52 patients treated, 13 patients had active CNS leukemia at infusion. Neurotoxicity was seen in 11/52 (21.2%) patients, with an incidence of 29.7% (11/37) in patients with CRS. Neurotoxicity was associated with the presence and severity of CRS. Those with neurotoxicity had higher levels of peak serum IL-6, IFNγ, and IL-15. Additionally, CNS leukemia was effectively eradicated in most patients with CRS. Pilot neurocognitive testing demonstrated stable-to-improved neurocognitive test scores in most patients, albeit limited by small patient numbers. The NSC enabled caregiver input into the patient experience. Conclusions This is the first systematic analysis of neurotoxicity utilizing a CD19/CD28ζ CAR construct in CAYA, including in those with active CNS involvement. The experience demonstrates that the neurotoxicity profile was acceptable and reversible, with evidence of anti-leukemia response and CNS trafficking of CAR T-cells. Additionally, neurocognitive testing, while exploratory, provides an opportunity for future studies to employ systematic evaluations into neurotoxicity assessments and validation is needed in future studies.
- Published
- 2023
4. SPARTAN: a spectral and information theoretic approach to partial-scan.
- Author
-
Omar I. Khan, Michael L. Bushnell, Suresh Kumar Devanathan, and Vishwani D. Agrawal
- Published
- 2007
- Full Text
- View/download PDF
5. A Neural Net Branch Predictor to Reduce Power.
- Author
-
Rajamani Sethuram, Omar I. Khan, Hari Vijay Venkatanarayanan, and Michael L. Bushnell
- Published
- 2007
- Full Text
- View/download PDF
6. Aliasing Analysis of Spectral Statistical Response Compaction Techniques.
- Author
-
Omar I. Khan and Michael L. Bushnell
- Published
- 2006
- Full Text
- View/download PDF
7. Spectral Analysis for Statistical Response Compaction During Built-In Self-Testing.
- Author
-
Omar I. Khan and Michael L. Bushnell
- Published
- 2004
- Full Text
- View/download PDF
8. Racial and Ethnic Differences in Antiseizure Medications Among People With Epilepsy on Medicaid
- Author
-
Wyatt P. Bensken, Guadalupe Fernandez Baca Vaca, Philip M. Alberti, Omar I. Khan, Timothy H. Ciesielski, Barbara C. Jobst, Scott M. Williams, Kurt C. Stange, Martha Sajatovic, and Siran M. Koroukian
- Subjects
Neurology (clinical) - Abstract
Background and ObjectivesBeing on a newer, second-, and third-generation antiseizure medication (ASM) may represent an important marker of quality of care for people with epilepsy. We sought to examine whether there were racial/ethnic differences in their use.MethodsUsing Medicaid claims data, we identified the type and number of ASMs, as well as the adherence, for people with epilepsy over a 5-year period (2010–2014). We used multilevel logistic regression models to examine the association between newer-generation ASMs and adherence. We then examined whether there were racial/ethnic differences in ASM use in models adjusted for demographics, utilization, year, and comorbidities.ResultsAmong 78,534 adults with epilepsy, 17,729 were Black, and 9,376 were Hispanic. Overall, 25.6% were on older ASMs, and being solely on second-generation ASMs during the study period was associated with better adherence (adjusted odds ratio: 1.17, 95% confidence interval [CI]: 1.11–1.23). Those who saw a neurologist (3.26, 95% CI: 3.13–3.41) or who were newly diagnosed (1.29, 95% CI: 1.16–1.42) had higher odds of being on newer ASMs. Importantly, Black (0.71, 95% CI: 0.68–0.75), Hispanic (0.93, 95% CI: 0.88–0.99), and Native Hawaiian and Other Pacific Island individuals (0.77, 95% CI: 0.67–0.88) had lower odds of being on newer ASMs when compared with White individuals.DiscussionGenerally, racial and ethnic minoritized people with epilepsy have lower odds of being on newer-generation ASMs. Greater adherence by people who were only on newer ASMs, their greater use among people seeing a neurologist, and the opportunity of a new diagnosis point to actionable leverage points for reducing inequities in epilepsy care.
- Published
- 2023
9. Neurotoxicities associated with checkpoint inhibitors: Two case reports and a review of the literature
- Author
-
Andrea B. Apolo, Nicole N. Davarpanah, Martha Quezado, Lisa M. Cordes, Lauren B. Reoma, Avindra Nath, Billel Gasmi, and Omar I. Khan
- Subjects
medicine.medical_specialty ,Immune checkpoint inhibitors ,encephalitis ,lcsh:Medicine ,Ipilimumab ,Case Report ,Case Reports ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Peripheral nerve ,neurotoxicity ,medicine ,ipilimumab ,Intensive care medicine ,nivolumab ,lcsh:R5-920 ,Palsy ,business.industry ,lcsh:R ,Limbic encephalitis ,Aseptic meningitis ,General Medicine ,medicine.disease ,aseptic meningitis ,checkpoint inhibitor ,030220 oncology & carcinogenesis ,Nivolumab ,lcsh:Medicine (General) ,business ,Encephalitis ,medicine.drug - Abstract
We report a case of nivolumab‐induced delayed‐onset aseptic meningitis and a case of limbic encephalitis and peripheral nerve palsy with toxicity relapse 6 months after initial presentation. The atypical presentations contribute to our knowledge of these rare events and reinforce the necessity for vigilant monitoring and a multidisciplinary treatment approach.
- Published
- 2019
10. Influence of Research Continuity on Physician-Scientists’ Career Success
- Author
-
Jenna Brownrout, Omar I. Khan, Avindra Nath, Taylor Gordon, Wyatt P. Bensken, Gina Norato, Catherine Squirewell, and John D. Heiss
- Subjects
Medical education ,Research ,education ,Neurology Residency ,Scopus ,Quarter (United States coin) ,Research Personnel ,United States ,Late career ,Career Mobility ,Research career ,Interquartile range ,Physicians ,Workforce ,Humans ,Neurology (clinical) ,Psychology ,Training period ,Research Article - Abstract
ObjectiveTo determine if maintaining continuity in research topic and method from early to late career yields a greater likelihood of physician-scientists’ research career success; that is, achieving research independence and producing impactful publications.MethodsTo explore the effect of maintaining continuity in research, 108 neurology residency graduates (2000–2010) from former medical scientist training programs at the highest National Institute of Neurological Disorders and Stroke– and NIH-funded institutions were identified. Through comparison of PhD dissertations with postgraduate work, research continuity was deemed present if there was evidence of continuity in research topic and method. With publicly available SCOPUS, PubMed, and NIH RePORT data, the correlation that degree of continuity had with h-indices, number of grants awarded, and R01 acquisition was examined.ResultsNearly half of the graduates were classified as noncontinuous (45%), fewer than a quarter as somewhat continuous (22%), and roughly a third as very continuous (32%). The data demonstrated that research continuity increased the ability to acquire a R01, with 83% of R01 or R21 recipients having very continuous research. Very continuous graduates also had higher median number of grants received (2 [interquartile range (IQR) 1–3]) and a higher median h-index (17 [IQR 10.5–20]) compared to the somewhat continuous and noncontinuous groups.ConclusionsThis study highlights research continuity as an important and modifiable variable during the training period of physician-scientists and one that may improve their career success and promote greater retention within the workforce.
- Published
- 2021
11. A framework for health equity in people living with epilepsy
- Author
-
Wyatt P, Bensken, Philip M, Alberti, Omar I, Khan, Scott M, Williams, Kurt C, Stange, Guadalupe Fernandez-Baca, Vaca, Barbara C, Jobst, Martha, Sajatovic, and Siran M, Koroukian
- Subjects
Epilepsy ,Health Equity ,Neurology ,Humans ,Neurology (clinical) ,Healthcare Disparities ,United States - Abstract
Epilepsy is a disease where disparities and inequities in risk and outcomes are complex and multifactorial. While most epilepsy research to date has identified several key areas of disparities, we set out to provide a multilevel life course model of epilepsy development, diagnosis, treatment, and outcomes to highlight how these disparities represent true inequities. Our piece also presents three hypothetical cases that highlight how the solutions to address inequities may vary across the lifespan. We then identify four key domains (structural, socio-cultural, health care, and physiological) that contribute to the persistence of inequities in epilepsy risk and outcomes in the United States. Each of these domains, and their core components in the context of epilepsy, are reviewed and discussed. Further, we highlight the connection between domains and key areas of intervention to strive towards health equity. The goal of this work is to highlight these domains while also providing epilepsy researchers and clinicians with broader context of how their work fits into health equity.
- Published
- 2022
12. Future Directions of Training Physician–Scientists
- Author
-
Omar I. Khan, John D. Heiss, Wyatt P. Bensken, and Avindra Nath
- Subjects
Adult ,Male ,Biomedical Research ,020205 medical informatics ,media_common.quotation_subject ,Translational research ,02 engineering and technology ,Training (civil) ,Article ,Education ,03 medical and health sciences ,0302 clinical medicine ,Physicians ,Political science ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Humans ,Conversation ,Attrition ,Health Workforce ,030212 general & internal medicine ,Academic medicine ,media_common ,Education, Medical ,business.industry ,General Medicine ,Middle Aged ,Public relations ,medicine.disease ,Research Personnel ,United States ,Workforce ,Female ,business ,Forecasting - Abstract
In academic medicine, the attrition of the physician-scientist workforce has been significantly discussed for the past three decades, with substantial attention and funding targeted to stop this attrition and attempt to reinvigorate the workforce. Despite these concerns and efforts, the attrition has not been stopped or even significantly slowed, and thus a further understanding of the physician-scientist workforce is needed with a closer look at how this workforce is measured and quantified. Through reviewing three methods by which physician-scientists are identified and understood, limitations in these definitions arise, leading to the basic question: Who qualifies to be a physician-scientist? Answering this question may lead to developing more comprehensive and less restrictive approaches when qualifying and measuring the physician-scientist workforce and appreciating the varying contributions physicians make to research. Through suggesting an expanded appreciation of these research contributions, recognition of collaboration, and funding models that support both of these aspects, the authors hope to add to the conversation by challenging traditional approaches and encouraging movement toward forward-looking definitions that encourage and promote all physicians to engage with research. This reimagining of physician-scientists will result not just in a remeasuring of the workforce but, subsequently, in strengthening the clinical and translational research continuum as well.
- Published
- 2019
13. Convection-Enhanced Delivery of Muscimol in Patients with Drug-Resistant Epilepsy
- Author
-
John D. Heiss, Omar I. Khan, Davis P. Argersinger, John A. Butman, Susumu Sato, and William H. Theodore
- Subjects
Adult ,Male ,Drug Resistant Epilepsy ,Electroencephalography ,Convection ,03 medical and health sciences ,Epilepsy ,chemistry.chemical_compound ,0302 clinical medicine ,Infusion Procedure ,medicine ,Humans ,Epilepsy surgery ,Research—Human—Clinical Trials ,medicine.diagnostic_test ,Muscimol ,business.industry ,GABAA receptor ,Brain ,medicine.disease ,Magnetic Resonance Imaging ,Crossover study ,Infusions, Intraventricular ,chemistry ,030220 oncology & carcinogenesis ,Anesthesia ,Anticonvulsants ,Female ,Surgery ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background Minimally invasive therapies for drug-resistant epilepsy (DRE) have been advocated. A study of convection-enhanced delivery (CED) of muscimol, a GABAA receptor agonist, was previously completed in non-human primates. Objective To investigate the safety and anti-epileptic effects of intracerebral muscimol infusion into the epileptic focus of patients with DRE. Methods In this phase 1 clinical trial, 3 adult patients with DRE underwent CED into the seizure focus of artificial CSF vehicle followed by muscimol for 12 to 24 h each using a crossover design. Basic pathophysiology of the epileptic focus was examined by assessing the infusions' effects on seizure frequency, electroencephalogram (EEG) spike-wave activity, and power-spectral EEG frequency. Results Inter-ictal neurological function remained normal in all patients. Pathological examination of resected specimens showed no infusion-related brain injuries. Seizure frequency decreased in 1 of 3 patients during muscimol infusion but was unchanged in all patients during vehicle infusion. Mean beta frequencies did not differ significantly before, during, or after infusion periods. Infused fluid provided insufficient MRI-signal to track infusate distribution. In the 2 yr after standard epilepsy surgery, 1 patient had temporary reduction in seizure frequency and 2 patients were seizure-free. Conclusion CED of muscimol into the epileptic focus of patients with DRE did not damage adjacent brain parenchyma or adversely affect seizure surgery outcome. This study did not confirm that intracerebral muscimol infusion effectively suppressed seizures. A surrogate tracer is recommended to track infusion distribution to the epileptic focus and surrounding structures in future studies using CED to suppress the seizure focus.
- Published
- 2018
14. Physician-scientists in neurology
- Author
-
Alexandra K. Hansen, John D. Heiss, Omar I. Khan, Avindra Nath, Gina Norato, and Wyatt P. Bensken
- Subjects
Financing, Government ,medicine.medical_specialty ,Biomedical Research ,Index (economics) ,MEDLINE ,Scopus ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Neurologists ,030212 general & internal medicine ,Publishing ,Impact factor ,business.industry ,Financing, Organized ,United States ,National Institutes of Health (U.S.) ,Family medicine ,Cohort ,Workforce ,Portfolio ,Neurology (clinical) ,Journal Impact Factor ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveThe objective of this study was to evaluate the methods by which neurology physician-scientists are quantified through applying author-level metrics to commonly used definitions when discussing funding efforts aimed at the attrition of the physician-scientist workforce.MethodsNeurology residency alumni from institutions with the highest National Institute of Neurological Disorders and Stroke funding were identified for 2003–2005, and their funding records, publishing history, and impact factor (h-index) were obtained via the NIH Research Portfolio Online Reporting Tools and Scopus Author Profile. The group differences of total publications, yearly publication rate, and h-index between R01-funded, non-R01-funded, and nonfunded individuals were analyzed via analysis of variance models, and a publications-per-research hour rate was calculated and similarly compared across groups.ResultsFrom 15 programs, and from a total of 252 neurologists, 186 were identified as having demonstrated an interest in research. The mean h-index, yearly publication rate, and cumulative number of publications were significantly higher in those who eventually received an R01 grant compared to those without R01 funding and those with no research funding. Within the top 50 performers by yearly publication rate, there was an equal mix of the 3 groups of neurologists: R01 (19, 38%), non-R01 (15, 30%), and nonfunded (16, 32%). Those who were nonfunded (10% research effort) had an estimated 4.9 publications per 1,000 research hours compared to 3.0 for those with non-R01 (40% research effort) funding and 3.2 for those with R01 funding (80% research effort).ConclusionsWhile eventual R01 grant and early career funding pathways were confirmed as important components of higher h-index and larger publication numbers, the classic definition of a physician-scientist was questioned through these findings. Those presumed to be without funding and generally excluded from the physician-scientist pool because of lack of protected research time, in some instances, outperformed their R01-funded colleagues and had a higher publications-per-research hour than those with an R01 and those with non-R01 funding, when estimating a 10% research effort. This reflects a potentially erroneous assumption and indicates the important contribution of these neurologists.
- Published
- 2018
15. Preoperative prediction of temporal lobe epilepsy surgery outcome
- Author
-
Sungyoung Auh, Conrad V. Kufta, Alexander Jow, Daniel M. Goldenholz, William H. Theodore, Sara K. Inati, Susumu Sato, Anto Bagic, and Omar I. Khan
- Subjects
Adult ,Male ,Subset Analysis ,medicine.medical_specialty ,Time Factors ,Kaplan-Meier Estimate ,Electroencephalography ,Article ,03 medical and health sciences ,0302 clinical medicine ,Seizures ,medicine ,Humans ,Epilepsy surgery ,Ictal ,030212 general & internal medicine ,Prospective cohort study ,Proportional Hazards Models ,Retrospective Studies ,Sclerosis ,medicine.diagnostic_test ,Proportional hazards model ,Hazard ratio ,Odds ratio ,Anterior Temporal Lobectomy ,Prognosis ,Magnetic Resonance Imaging ,Surgery ,Logistic Models ,Treatment Outcome ,Epilepsy, Temporal Lobe ,Neurology ,Preoperative Period ,Female ,Neurology (clinical) ,Radiology ,Psychology ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Purpose There is controversy about relative contributions of ictal scalp video EEG recording (vEEG), routine scalp outpatient interictal EEG (rEEG), intracranial EEG (iEEG) and MRI for predicting seizure-free outcomes after temporal lobectomy. We reviewed NIH experience to determine contributions at specific time points as well as long-term predictive value of standard pre-surgical investigations. Methods Raw data was obtained via retrospective chart review of 151 patients. After exclusions, 118 remained (median 5 years follow-up). MRI-proven mesial temporal sclerosis (MTSr) was considered a separate category for analysis. Logistic regression estimated odds ratios at 6-months, 1-year, and 2 years; proportional hazard models estimated long-term comparisons. Subset analysis of the proportional hazard model was performed including only patients with commonly encountered situations in each of the modalities, to maximize statistical inference. Results Any MRI finding, MRI proven MTS, rEEG, vEEG and iEEG did not predict two-year seizure-free outcome. MTSr was predictive at six months (OR=2.894, p=0. 0466), as were MRI and MTSr at one year (OR=10.4231, p=0. 0144 and OR=3.576, p=0. 0091). Correcting for rEEG and MRI, vEEG failed to predict outcome at 6 months, 1year and 2 years. Proportional hazard analysis including all available follow-up failed to achieve significance for any modality. In the subset analysis of 83 patients with commonly encountered results, vEEG modestly predicted long-term seizure-free outcomes with a proportional hazard ratio of 1.936 (p=0.0304). Conclusions In this study, presurgical tools did not provide unambiguous long-term outcome predictions. Multicenter prospective studies are needed to determine optimal presurgical epilepsy evaluation.
- Published
- 2016
16. Hospital Resource Utilization in Epilepsy: Disparities in Rural vs Urban Care
- Author
-
Wyatt P. Bensken, Gina Norato, and Omar I. Khan
- Subjects
Epilepsy ,business.industry ,Environmental health ,Hospital discharge database ,Illness severity ,Medicine ,Facility type ,business ,medicine.disease ,Resource utilization - Abstract
SummaryObjectiveThis study assessed differences in resource utilization during epilepsy and seizure related hospitalizations in urban versus rural environments, to identify potential disparities in care for people living with epilepsy in rural communities.MethodsA 10 year (2001 to 2011) state-wide hospital discharge database was used. Cost, length of stay, illness severity, and procedure use were compared between urban facilities, rural facilities, and epilepsy centers. Comparison across three separate years helped to identify differences between facility type as well as to assess practices changes within facilities over time.ResultsAverage total charges between the three types of facilities was significantly different, with epilepsy centers having the highest average charge per patient, followed by urban and rural facilities (corrected p-values < 0.001). Illness severity was similar between the three groups, with the exception that epilepsy centers had a higher proportion of major severity cases. Length of stay remained fairly consistent across all three years for epilepsy centers (mean: 4.75 days), while decreasing for urban facilities (means: 4.39 to 3.72) and ultimately decreasing for rural facilities (mean: 3.31 to 3.09). Rates of procedure utilization revealed CT scan use persisted longer at rural facilities compared to urban facilities, while EEG and vEEG was low at rural facilities. vEEG was relatively restricted to epilepsy centers and had an initial substantial rise in use over the years and was associated with corresponding greater surgical procedure rates.SignificanceThis study indicates a measurable difference between epilepsy centers, urban facilities, and rural facilities in cost and procedure utilization while caring for patients during epilepsy- and seizure-related hospitalizations. If these conclusions are valid, they support that persons living with epilepsy who live in rural communities and utilize these services receive care that is considered suboptimal when compared to urban centers or epilepsy centers.
- Published
- 2019
17. Fatal encephalopathy with wild-type JC virus and ruxolitinib therapy
- Author
-
Richard W. Childs, Lauren B. Reoma, Daniel S. Reich, Christopher Trindade, Erin S Beck, Avindra Nath, Jamie Solis, Omar I. Khan, Marta Quezado, Stephen M. Hewitt, Phuong Vu, Maria Chiara Monaco, Marta Garcia Montojo, Kory R. Johnson, and Govind Nair
- Subjects
0301 basic medicine ,Adolescent ,medicine.medical_treatment ,viruses ,Encephalopathy ,JC virus ,medicine.disease_cause ,Virus ,Article ,03 medical and health sciences ,0302 clinical medicine ,Fatal Outcome ,Nitriles ,medicine ,Humans ,Janus Kinases ,Neurotropic virus ,Brain Diseases ,Base Sequence ,business.industry ,Progressive multifocal leukoencephalopathy ,virus diseases ,Immunosuppression ,medicine.disease ,Virology ,JC Virus ,030104 developmental biology ,Pyrimidines ,Neurology ,Lytic cycle ,nervous system ,Pyrazoles ,Female ,Neurology (clinical) ,business ,Meningitis ,030217 neurology & neurosurgery - Abstract
Objective JC virus (JCV) infection is a lytic infection of oligodendrocytes in progressive multifocal leukoencephalopathy; less common forms of central nervous system manifestations associated with JCV infection include granule cell neuronopathy, encephalopathy, and meningitis. Presented is the first case of fatal JCV encephalopathy after immunosuppressive therapy that included ruxolitinib. Methods Postmortem analysis included next generation sequencing, Sanger sequencing, tissue immunohistochemistry, and formalin-fixed hemisphere 7T magnetic resonance imaging. Results JCV DNA isolated from postmortem tissue samples identified a novel 12bp insertion that altered the transcription site binding pattern in an otherwise "wild-type virus," which has long been thought to be the nonpathogenic form of JCV. Anti-VP1 staining demonstrated infection in cortical neurons, hippocampal neurons, and glial and endothelial cells. Interpretation This expands the spectrum of identified JCV diseases associated with broad-spectrum immunosuppression, including JAK-STAT inhibitors, and sheds light on an additional neurotropic virus strain of the archetype variety. ANN NEUROL 2019;86:878-884.
- Published
- 2019
18. 021 Fludarabine-induced subacute, often fatal leukoencephalopathy: a case series
- Author
-
Amine Awad, Julie Albert, Avindra Nath, Lydia Albjerg, Richard W. Childs, Omar I. Khan, Jamie Solis, and Elizabeth Bartrum
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,Neurotoxicity ,medicine.disease ,Fludarabine ,White matter ,Transplantation ,Leukoencephalopathy ,Psychiatry and Mental health ,medicine.anatomical_structure ,Blurred vision ,medicine ,Surgery ,Histopathology ,Neurology (clinical) ,medicine.symptom ,business ,Pathological ,medicine.drug - Abstract
Fludarabine, a purine agonist, is associated with a rare dose-dependent risk of severe and often fatal neurotoxicity. Referencing the clinical course of seven such patients, we report the clinical, radiological, and pathological findings in one patient who developed a fatal leukoencephalopathy to highlight potential mechanisms of fludarabine-induced neurotoxicity. Of the seven cases, one presented with paraparesis, two with cognitive impairment, and four with blurred vision; five cases were fatal, with a variable time course of symptom onset and progression. All patients had unexplained progressive, symmetric leukoencephalopathy on serial brain MRIs. One patient underwent post-mortem neuropathological examination; she was a 49-year-old female with severe aplastic anaemia and myelodysplastic syndrome who had received fludarabine at 25 mg/m2 for five days prior to stem cell transplantation. Thirteen days later, she developed rapidly-progressive cognitive deterioration and motor weakness. Serial brain MRIs showed extensive leukoencephalopathy extending into the midbrain and pons bilaterally. She passed away at day 39 post-transplant. Histopathology revealed diffuse, gross softening of the white matter and microscopic evidence of a demyelinating process with diffuse myelin loss, axonal injury, and spheroid formation. Electron microscopy revealed abnormally proliferative, reticulated, densely packed endoplasmic reticulum, suggesting a toxic, progressive demyelinating process.
- Published
- 2019
19. A comparison of continuous video-EEG monitoring and 30-minute EEG in an ICU
- Author
-
Justin Montanye, Gregory L. Holmes, Richard E. Nordgren, Alendia Hartshorn, Vijay M. Thadani, Rod C. Scott, Richard P. Morse, Christina J. Azevedo, Mark A. Natola, Krzysztof A. Bujarski, Juan C. Gonzalez, Omar I. Khan, Barbara C. Jobst, and Stephen D. Surgenor
- Subjects
Adult ,Brain Diseases ,Icu patients ,Epilepsy ,medicine.diagnostic_test ,business.industry ,Medical record ,Videotape Recording ,Video EEG monitoring ,Electroencephalography ,General Medicine ,Monitoring seizure ,Eeg recording ,Intensive Care Units ,Neurology ,Eeg data ,Anesthesia ,Mental state ,Humans ,Medicine ,Neurology (clinical) ,business ,Monitoring, Physiologic ,Retrospective Studies - Abstract
Aim. To determine whether there is added benefit in detecting electrographic abnormalities from 16-24 hours of continuous video-EEG in adult medical/surgical ICU patients, compared to a 30-minute EEG.Methods. This was a prospectively enroled non-randomized study of 130 consecutive ICU patients for whom EEG was requested. For 117 patients, a 30-minute EEG was requested for altered mental state and/or suspected seizures; 83 patients continued with continuous video-EEG for 16-24 hours and 34 patients had only the 30-minute EEG. For 13 patients with prior seizures, continuous video-EEG was requested and was carried out for 16-24 hours. We gathered EEG data prospectively, and reviewed the medical records retrospectively to assess the impact of continuous video-EEG.Results. A total of 83 continuous video-EEG recordings were performed for 16-24 hours beyond 30 minutes of routine EEG. All were slow, and 34% showed epileptiform findings in the first 30 minutes, including 2% with seizures. Over 16-24 hours, 14% developed new or additional epileptiform abnormalities, including 6% with seizures. In 8%, treatment was changed based on continuous video-EEG. Among the 34 EEGs limited to 30 minutes, almost all were slow and 18% showed epileptiform activity, including 3% with seizures. Among the 13 patients with known seizures, continuous video-EEG was slow in all and 69% had epileptiform abnormalities in the first 30 minutes, including 31% with seizures. An additional 8% developed epileptiform abnormalities over 16-24 hours. In 46%, treatment was changed based on continuous video-EEG.Conclusion. This study indicates that if continuous video-EEG is not available, a 30-minute EEG in the ICU has a substantial diagnostic yield and will lead to the detection of the majority of epileptiform abnormalities. In a small percentage of patients, continuous video-EEG will lead to the detection of additional epileptiform abnormalities. In a sub-population, with a history of seizures prior to the initiation of EEG recording, the benefits of continuous video-EEG in monitoring seizure activity and influencing treatment may be greater.
- Published
- 2014
20. Prospective longitudinal overnight video-EEG evaluation in Phelan-McDermid Syndrome
- Author
-
Thomas Gaughan, Andrea L. Gropman, Omar I. Khan, Owen M. Rennert, Precilla D'Souza, Audrey Thurm, Xiangping Zhou, Riley Kessler, Ashura W. Buckley, Ninette Cohen, Sara K. Inati, and Jill Leon
- Subjects
0301 basic medicine ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Chromosomes, Human, Pair 22 ,Population ,Video Recording ,Neurological examination ,Chromosome Disorders ,Electroencephalography ,Cohort Studies ,03 medical and health sciences ,Behavioral Neuroscience ,Epilepsy ,0302 clinical medicine ,Seizures ,Medicine ,Humans ,Prospective Studies ,Wakefulness ,education ,Aged ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Seizure types ,Middle Aged ,medicine.disease ,030104 developmental biology ,Phenotype ,Neurology ,Autism spectrum disorder ,Mutation ,Female ,Neurology (clinical) ,Chromosome Deletion ,business ,Sleep ,Developmental regression ,030217 neurology & neurosurgery ,Natural history study - Abstract
Objective Phelan–McDermid Syndrome (PMS) is a rare genetic condition associated with loss of function mutations, including deletions, in the chromosome 22q13 region. This PMS phenotype includes intellectual disability, often minimal to absent verbal skills, and other neurologic features including autism spectrum disorder and seizures. Reports indicate seizures and abnormal electroencephalograms (EEGs) in this population, but previous studies do not describe EEG findings during sleep or prognostic value of abnormal EEG over any time period. Methods During a natural history study, 16 consecutively enrolled participants (mean age 10 years) with PMS underwent both routine (approximately 25 min) and overnight (average 9.65 h) video-EEG, in addition to genetic testing, neurodevelopmental assessment, neurological examination, and epilepsy phenotyping. Over 240 h of EEG, data was recorded. Comparison of findings from the routine EEG was made with prolonged EEG acquired during awake and sleep the same night. In a subset of nine participants, the overnight EEG was repeated one or more years later to observe the natural evolution and prognostic value of any abnormalities noted at baseline. Results A history of epilepsy, with multiple seizure types, was confirmed in seven of the 16 participants, giving a prevalence of 43.8% in this cohort. All but one EEG was abnormal (15 of 16), and 75% (12 of 16) showed epileptiform activity. Of these, only 25% of participants (3 of 12) showed definitive epileptiform discharges during the routine study. Overnight EEGs (sleep included) did not show any clinical events consistent with seizures or electrophic seizures, however, overnight EEG showed either more frequent and/or more definitive epileptiform activity in 68.75% (11 of 16) participants. All seven of the 16 participants who had previously been diagnosed with epilepsy showed epileptiform abnormalities. In addition to a wide range of epileptiform activity observed, generalized slowing with poor background organization was frequently noted. Follow-up EEG confirmed persistence of abnormal discharges, but none of the abnormal EEGs showed evolution to electrographic seizures. Clinically, there was no emergence of epilepsy or significant developmental regression noted in the time frame observed. Conclusions This is the first and most abundant prolonged awake and sleep video-EEG data recorded in a PMS cohort to date. The importance of overnight prolonged EEGs is highlighted by findings from this study, as they can be used to document the varied topographies of EEG abnormalities in conditions such as PMS, which are often missed during routine EEG studies. While the long-term significance of the EEG abnormalities found (beyond 1 year) remains uncertain despite their persistence over time, these findings do underscore the current clinical recommendation that overnight prolonged EEG studies (with sleep) should be conducted in individuals with PMS.
- Published
- 2017
21. Characterization of atypical language activation patterns in focal epilepsy
- Author
-
Elizabeth S. Duke, Eva K. Ritzl, William H. Theodore, William D. Gaillard, Madison M. Berl, Omar I. Khan, Susumu Sato, Irene Dustin, Leigh N. Sepeta, and Lauren A. Zimmaro
- Subjects
Epilepsy ,Variation (linguistics) ,Neurology ,Frontal lobe ,medicine.diagnostic_test ,medicine ,Neurology (clinical) ,Functional magnetic resonance imaging ,Psychology ,medicine.disease ,Neuroscience ,Language network ,Temporal lobe - Abstract
Objective Functional magnetic resonance imaging is sensitive to the variation in language network patterns. Large populations are needed to rigorously assess atypical patterns, which, even in neurological populations, are a minority.
- Published
- 2014
22. Toxoplasmosis encephalitis with immune-reconstitution inflammatory syndrome in an allogeneic stem cell transplant patient: a case report
- Author
-
Minoo Battiwalla, G T Brown, Austin John Barrett, Robert L. Danner, Omar I. Khan, Sawa Ito, Maura Manion, M E Gatti-Mays, Lauren Bowen, and Avindra Nath
- Subjects
0301 basic medicine ,Biopsy ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Immune system ,Immune reconstitution inflammatory syndrome ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,medicine ,Seroprevalence ,Humans ,Transplantation, Homologous ,Inflammation ,Transplantation ,biology ,business.industry ,Toxoplasma gondii ,Brain ,Hematology ,medicine.disease ,biology.organism_classification ,Virology ,Trimethoprim ,Magnetic Resonance Imaging ,Toxoplasmosis ,030104 developmental biology ,Graft-versus-host disease ,Treatment Outcome ,Immune System ,Immunology ,Encephalitis ,Interleukin-2 ,Female ,business ,030217 neurology & neurosurgery ,medicine.drug ,Stem Cell Transplantation - Abstract
Toxoplasma gondii is a ubiquitous intracellular parasite with an estimated seroprevalence of 22.5% in US residents aged 12 and older. Seroprevalence reaches 95% in some low-altitude countries with hot, humid climates.1 Although seroprevalence is relatively common, invasive toxoplasmosis involving the central nervous system (CNS), lung, liver and myocardium after stem cell transplantation (SCT), provoked by defective cellular immunity, is infrequent (0.2–7.6%), especially in the era of sulfamethoxazole/trimethoprim (Bactrim) prophylaxis.2, 3, 4 In HIV-positive patients with toxoplasmic encephalitis (TE), the T-cell response can lead to rare instances of an immune reconstitution inflammatory response (IRIS).5, 6 Here we describe the first documented case of IRIS in a SCT recipient.
- Published
- 2016
23. Increased In Vivo Expression of an Inflammatory Marker in Temporal Lobe Epilepsy
- Author
-
Robert B. Innis, William H. Theodore, Masahiro Fujita, Yi Zhang, Omar I. Khan, Shmuel Appel, Irene Dustin, William C. Kreisl, Jussi Hirvonen, Victor W. Pike, and Cheryl L. Morse
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Hippocampus ,ta3112 ,Article ,Temporal lobe ,Young Adult ,Epilepsy ,Receptors, GABA ,Translocator protein ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Cerebrum ,Inflammation ,Hippocampal sclerosis ,Fusiform gyrus ,biology ,business.industry ,Biological Transport ,Human brain ,Middle Aged ,medicine.disease ,ta3124 ,Pyrimidines ,medicine.anatomical_structure ,Epilepsy, Temporal Lobe ,Gene Expression Regulation ,Case-Control Studies ,Positron-Emission Tomography ,biology.protein ,Female ,business ,Biomarkers ,Parahippocampal gyrus - Abstract
Animal studies and clinical observations suggest that epilepsy is associated with inflammation. Translocator protein (TSPO) (18 kDa), a marker of inflammation, is increased in vitro in surgical samples from patients with temporal lobe epilepsy. TSPO can be measured in the living human brain with PET and the novel radioligand 11C-PBR28. In this study, we sought to determine whether in vivo expression of TSPO is increased ipsilateral to the seizure focus in patients with temporal lobe epilepsy. Methods: Sixteen patients with unilateral temporal lobe epilepsy and 30 healthy subjects were studied with 11 CPBR28 PET and MRI. Uptake of radioactivity after injection of 11 C-PBR28 was measured from regions of interest drawn bilaterally onto MR images. Brain uptake from ipsilateral and contralateral hemispheres was compared using a paired-samples t test. Results: We found that brain uptake was higher ipsilateral to the seizure focus in the hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and choroid plexus but not in other brain regions. This asymmetry was more pronounced in patients with hippocampal sclerosis than in those without. Conclusion: We found increased uptake of radioactivity after injection of 11C-PBR28 ipsilateral to the seizure focus in patients with temporal lobe epilepsy, suggesting increased expression of TSPO. Studies in larger samples are required to confirm this finding and determine the clinical utility of imaging TSPO in temporal lobe epilepsy.
- Published
- 2012
24. Age-Dependent Mesial Temporal Lobe Lateralization in Language FMRI
- Author
-
Marko Wilke, William D. Gaillard, William H. Theodore, Omar I. Khan, Benjamin Xu, Madison M. Berl, Meera Mehta, Sara K. Inati, Xiaozhen You, Leigh N. Sepeta, Irene Dustin, and Alison Austermuehle
- Subjects
Adult ,Male ,medicine.medical_specialty ,Aging ,Adolescent ,Decision Making ,Electroencephalography ,Audiology ,Statistical parametric mapping ,050105 experimental psychology ,Lateralization of brain function ,Article ,Functional Laterality ,Temporal lobe ,03 medical and health sciences ,Epilepsy ,Young Adult ,0302 clinical medicine ,Functional neuroimaging ,medicine ,Image Processing, Computer-Assisted ,Humans ,0501 psychology and cognitive sciences ,Neuropsychological assessment ,Child ,Language ,Retrospective Studies ,medicine.diagnostic_test ,05 social sciences ,medicine.disease ,Magnetic Resonance Imaging ,Temporal Lobe ,Oxygen ,Neurology ,Female ,Neurology (clinical) ,Psychology ,Functional magnetic resonance imaging ,Neuroscience ,psychological phenomena and processes ,030217 neurology & neurosurgery - Abstract
Summary Objective Functional magnetic resonance imaging (fMRI) activation of the mesial temporal lobe (MTL) may be important for epilepsy surgical planning. We examined MTL activation and lateralization during language fMRI in children and adults with focal epilepsy. Methods One hundred forty-two controls and patients with left hemisphere focal epilepsy (pediatric: epilepsy, n = 17, mean age = 9.9 ± 2.0; controls, n = 48; mean age = 9.1 ± 2.6; adult: epilepsy, n = 20, mean age = 26.7 ± 5.8; controls, n = 57, mean age = 26.2 ± 7.5) underwent 3T fMRI using a language task (auditory description decision task). Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8); regions of interest (ROIs) included MTL, Broca's area, and Wernicke's area. We assessed group and individual MTL activation, and examined degree of lateralization. Results Patients and controls (pediatric and adult) demonstrated group and individual MTL activation during language fMRI. MTL activation was left lateralized for adults, but less so in children (p's < 0.005). Patients did not differ from controls in either age group. Stronger left-lateralized MTL activation was related to older age (p = 0.02). Language lateralization (Broca's and Wernicke's) predicted 19% of the variance in MTL lateralization for adults (p = 0.001), but for not children. Significance Language fMRI may be used to elicit group and individual MTL activation. The developmental difference in MTL lateralization and its association with language lateralization suggests a developmental shift in lateralization of MTL function, with increased left lateralization across the age span. This shift may help explain why children have better memory outcomes following resection compared to adults.
- Published
- 2015
25. Learning About Teams by Participating in Teams
- Author
-
Diane Magrane, R. Kevin Grigsby, Yvette Pigeon, Jennifer Leadley, and Omar I. Khan
- Subjects
Patient Care Team ,Academic Medical Centers ,Models, Educational ,Teamwork ,Medical education ,Task management ,media_common.quotation_subject ,Team effectiveness ,Psychological safety ,General Medicine ,Team process ,United States ,Education ,Professional Competence ,Team learning ,Humans ,Effective team ,Narrative ,Diffusion of Innovation ,Program Development ,Psychology ,Retrospective Studies ,media_common - Abstract
As the work of academic health centers becomes increasingly oriented toward teams and collaboration, professional development in effective team skills becomes increasingly important. The authors sought to determine whether a transdisciplinary program for enhancing teamwork was effective in educating individual team members to translate lessons into productive outcomes of their own institutions' teams.Between 2006 and 2008, the authors used the Learning in Teams model of collaborative team development to design and implement two applications of a national professional development program for members of academic organizations' teams. The purpose of the program was to foster individual skill development in collaborative teamwork. Using pre/post surveys to determine changes in team functioning over the course of the program, the authors evaluated participants' perceptions of the effectiveness of their professional development programs' learning teams and of their home institutions' teams. They analyzed narrative reports of participants' institutional teams' progress for elements including team task management, member dynamics, and institutional outcomes.Pre/post self-assessments of team performance and participants' progress reports on their home teams revealed enhancement of team skills, including clarifying team charge, exploring team purpose, and evaluating team process. Program participants improved their team skills and enhanced productivity of their institutions' teams.The Learning in Teams model can support individual team skills development, enhance institutional team performance in academic health centers, and provide a basis for research in team skills development and team process improvement. It can be adapted to various programs to enhance skills in teamwork.
- Published
- 2010
26. Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study
- Author
-
Zenaide M.N. Quezado, Eva H. Baker, Wadih M. Zein, Aiyi Liu, Simona Bianconi, Omar I. Khan, Zhongjian Zhang, Goutam Chandra, Ning Miao, Kurt J. Griffin, Rafael C. Caruso, Anil B. Mukherjee, Sondra W. Levin, and Andrea L. Gropman
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Cysteamine Bitartrate ,Cysteamine ,Infantile neuronal ceroid lipofuscinosis ,Administration, Oral ,Pilot Projects ,Irritability ,Lipofuscin ,chemistry.chemical_compound ,Neuronal Ceroid-Lipofuscinoses ,medicine ,Humans ,Adverse effect ,business.industry ,PPT1 ,Infant ,Electroencephalography ,medicine.disease ,Surgery ,Acetylcysteine ,chemistry ,Child, Preschool ,Neuronal ceroid lipofuscinosis ,Drug Therapy, Combination ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Follow-Up Studies - Abstract
Summary Background Infantile neuronal ceroid lipofuscinosis is a devastating neurodegenerative lysosomal storage disease caused by mutations in the gene ( CLN1 or PPT1 ) encoding palmitoyl-protein thioesterase-1 (PPT1). We have previously reported that phosphocysteamine and N-acetylcysteine mediate ceroid depletion in cultured cells from patients with this disease. We aimed to assess whether combination of oral cysteamine bitartrate and N-acetylcysteine is beneficial for patients with neuronal ceroid lipofuscinosis. Methods Children between 6 months and 3 years of age with infantile neuronal ceroid lipofuscinosis with any two of the seven most lethal PPT1 mutations were eligible for inclusion in this pilot study. All patients were recruited from physician referrals. Patients received oral cysteamine bitartrate (60 mg/kg per day) and N-acetylcysteine (60 mg/kg per day) and were assessed every 6–12 months until they had an isoelectric electroencephalogram (EEG, attesting to a vegetative state) or were too ill to travel. Patients were also assessed by electroretinography, brain MRI and magnetic resonance spectroscopy (MRS), and electron microscopic analyses of leukocytes for granular osmiophilic deposits (GRODs). Children also underwent physical and neurodevelopmental assessments on the Denver scale. Outcomes were compared with the reported natural history of infantile neuronal ceroid lipofuscinosis and that of affected older siblings. This trial is registered with ClinicalTrials.gov, number NCT00028262. Findings Between March 14, 2001, and June 30, 2012, we recruited ten children with infantile neuronal ceroid lipofuscinosis; one child was lost to follow-up after the first visit and nine patients (five girls and four boys) were followed up for 8 to 75 months. MRI showed abnormalities similar to those in previous reports; brain volume and N-acetyl aspartic acid (NAA) decreased steadily, but no published quantitative MRI or MRS studies were available for comparison. None of the children acquired new developmental skills, and their retinal function decreased progressively. Average time to isoelectric EEG (52 months, SD 13) was longer than reported previously (36 months). At the first follow-up visit, peripheral leukocytes in all nine patients showed virtually complete depletion of GRODs. Parents and physicians reported less irritability, improved alertness, or both in seven patients. No treatment-related adverse events occurred apart from mild gastrointestinal discomfort in two patients, which disappeared when liquid cysteamine bitartrate was replaced with capsules. Interpretation Our findings suggest that combination therapy with cysteamine bitartrate and N-acetylcysteine is associated with delay of isoelectric EEG, depletion of GRODs, and subjective benefits as reported by parents and physicians. Our systematic and quantitative report of the natural history of patients with infantile neuronal ceroid lipofuscinosis provides a guide for future assessment of experimental therapies. Funding National Institutes of Health.
- Published
- 2014
27. Characterization of atypical language activation patterns in focal epilepsy
- Author
-
Madison M, Berl, Lauren A, Zimmaro, Omar I, Khan, Irene, Dustin, Eva, Ritzl, Elizabeth S, Duke, Leigh N, Sepeta, Susumu, Sato, William H, Theodore, and William D, Gaillard
- Subjects
Adult ,Male ,Adolescent ,Middle Aged ,Functional Laterality ,Temporal Lobe ,Article ,Frontal Lobe ,Young Adult ,Cross-Sectional Studies ,Acoustic Stimulation ,Child, Preschool ,Humans ,Female ,Epilepsies, Partial ,Prospective Studies ,Child ,Psychomotor Performance ,Language ,Retrospective Studies - Abstract
Functional magnetic resonance imaging is sensitive to the variation in language network patterns. Large populations are needed to rigorously assess atypical patterns, which, even in neurological populations, are a minority.We studied 220 patients with focal epilepsy and 118 healthy volunteers who performed an auditory description decision task. We compared a data-driven hierarchical clustering approach to the commonly used a priori laterality index (LI) threshold (LI0.20 as atypical) to classify language patterns within frontal and temporal regions of interest. We explored (n = 128) whether IQ varied with different language activation patterns.The rate of atypical language among healthy volunteers (2.5%) and patients (24.5%) agreed with previous studies; however, we found 6 patterns of atypical language: a symmetrically bilateral, 2 unilaterally crossed, and 3 right dominant patterns. There was high agreement between classification methods, yet the cluster analysis revealed novel correlations with clinical features. Beyond the established association of left-handedness, early seizure onset, and vascular pathology with atypical language, cluster analysis identified an association of handedness with frontal lateralization, early seizure onset with temporal lateralization, and left hemisphere focus with a unilateral right pattern. Intelligence quotient was not significantly different among patterns.Language dominance is a continuum; however, our results demonstrate meaningful thresholds in classifying laterality. Atypical language patterns are less frequent but more variable than typical language patterns, posing challenges for accurate presurgical planning. Language dominance should be assessed on a regional rather than hemispheric basis, and clinical characteristics should inform evaluation of atypical language dominance. Reorganization of language is not uniformly detrimental to language functioning.
- Published
- 2013
28. PET of serotonin 1A receptors and cerebral glucose metabolism for temporal lobectomy
- Author
-
John D. Heiss, Ashley R. Martinez, William H. Theodore, Omar I. Khan, Clarissa J. Liew, Sungyoung Auh, Irene Dustin, and Susumu Sato
- Subjects
Adult ,Male ,medicine.medical_treatment ,Electroencephalography ,Serotonin 5-HT1 Receptor Antagonists ,Neurosurgical Procedures ,Piperazines ,Article ,Temporal lobe ,Text mining ,Cyclohexanes ,Fluorodeoxyglucose F18 ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Ictal ,Anterior temporal lobectomy ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Retrospective cohort study ,Magnetic Resonance Imaging ,Temporal Lobe ,Glucose ,Positron emission tomography ,Anesthesia ,Positron-Emission Tomography ,Receptor, Serotonin, 5-HT1A ,Female ,business ,Nuclear medicine - Abstract
The objective of this study was to compare 5-hydroxytryptamine receptor 1A (5-HT1A) PET with cerebral metabolic rate of glucose (CMRglc) PET for temporal lobectomy planning. Methods: We estimated 5-HT1A receptor binding preoperatively with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (18F-FCWAY) PET and CMRglc measurement with 18F-FDG in regions drawn on coregistered MRI after partial-volume correction in 41 patients who had anterior temporal lobectomy with at least a 1-y follow-up. Surgery was tailored to individual preresection evaluations and intraoperative electrocorticography. Mean regional asymmetry values and the number of regions with asymmetry exceeding 2 SDs in 16 healthy volunteers were compared between seizure-free and non–seizure-free patients. 18F-FCWAY but not 18F-FDG and MRI data were masked for surgical decisions and outcome assessment. Results: Twenty-six of 41 (63%) patients seizure-free since surgery had significantly different mesial temporal asymmetries, compared with 15 non–seizure-free patients for both 18F-FCWAY (F1,39 = 5.87; P = 0.02) and 18F-FDG PET (F1,38 = 5.79; P = 0.021). The probability of being seizure-free was explained by both 18F-FDG and 18F-FCWAY PET, but not MRI, with a significant additional 18F-FCWAY effect ( χ 2 2 = 9.8796; P = 0.0072) after the probability of being seizure-free was explained by 18F-FDG. Although MRI alone was not predictive, any combination of 2 lateralizing imaging studies was highly predictive of seizure freedom. Conclusion: Our study provides class III evidence that both 5-HT1A receptor PET and CMRglc PET can contribute to temporal lobectomy planning. Additional studies should explore the potential for temporal lobectomy based on interictal electroencephalography and minimally invasive imaging studies.
- Published
- 2012
29. Cerebral blood flow and fMRI BOLD auditory language activation in temporal lobe epilepsy
- Author
-
Shmuel, Appel, Elizabeth S, Duke, Ashley R, Martinez, Omar I, Khan, Irene M, Dustin, Patricia, Reeves-Tyer, Madison B, Berl, Susumu, Sato, William D, Gaillard, and William H, Theodore
- Subjects
Adult ,Cerebral Cortex ,Male ,Brain Mapping ,Adolescent ,Middle Aged ,Magnetic Resonance Imaging ,Functional Laterality ,Article ,Oxygen ,Young Adult ,Epilepsy, Temporal Lobe ,Regional Blood Flow ,Cerebrovascular Circulation ,Image Processing, Computer-Assisted ,Humans ,Female ,Language ,Tomography, Emission-Computed - Abstract
Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), an important research and clinical tool, depends on relatively greater transient increases in (regional cerebral blood flow) rCBF than cerebral metabolic rate for oxygen during neural activity. We investigated whether reduced resting rCBF in patients with temporal lobe epilepsy affects BOLD signal during fMRI language mapping.We used [(15)O] water positron emission tomography (PET) to measure rCBF, and 3 Tesla echo planar imaging (EPI) BOLD fMRI with an auditory description decision task in 33 patients with temporal lobe epilepsy (16 men; mean age 33.6 ± standard deviation [SD] 10.6 years; epilepsy onset 14.8 ± 10.6 years; mean duration 18.8 ± 13.2 years; 23 left focus, 10 right focus). Anatomic regions drawn on structural MRI, based on the Wake Forest Pick Atlas, included Wernicke's area (WA), inferior frontal gyrus (IFG), middle frontal gyrus (MFG), and hippocampus (HC). Laterality indices (LIs), and asymmetry indices (AIs), were calculated on coregistered fMRI and PET.Twelve patients had mesial temporal sclerosis (seven on the left), two patients had a tumor or malformation of cortical development (both left), one patient a right temporal cyst, and 18 patients had normal MRI (14 left). Decreasing relative left WA CBF correlated with decreased left IFG voxel activation and decreasing left IFG LI. However, CBF WA AI was not related to left WA voxel activation itself or WA LI. There was a weak positive correlation between absolute CBF and fMRI activation in left IFG, right IFG, and left WA. Patients with normal and abnormal MRI did not differ in fMRI activation or rCBF AIs.Reduced WA rCBF is associated with reduced fMRI activation in IFG but not WA itself, suggesting distributed network effects, but not impairment of underlying BOLD response. Hypoperfusion in TLE does not affect fMRI clinical value.
- Published
- 2012
30. Serotonin 1A receptors, depression, and memory in temporal lobe epilepsy
- Author
-
William H, Theodore, Edythe A, Wiggs, Ashley R, Martinez, Irene H, Dustin, Omar I, Khan, Shmuel, Appel, Pat, Reeves-Tyer, and Susumu, Sato
- Subjects
Adult ,Male ,Depression ,Pyridines ,Brain ,Electroencephalography ,Middle Aged ,Neuropsychological Tests ,Verbal Learning ,Hippocampus ,Magnetic Resonance Imaging ,Functional Laterality ,Piperazines ,Article ,Cross-Sectional Studies ,Epilepsy, Temporal Lobe ,Memory ,Positron-Emission Tomography ,Receptor, Serotonin, 5-HT1A ,Humans ,Female - Abstract
Memory deficits and depression are common in patients with temporal lobe epilepsy (TLE). Previous positron emission tomography (PET) studies have shown reduced mesial temporal 5HT1A-receptor binding in these patients. We examined the relationships among verbal memory performance, depression, and 5HT1A-receptor binding measured with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (18FCWAY) PET in a cross-sectional study.We studied 40 patients (24 male; mean age 34.5 ± 10.7 years) with TLE. Seizure diagnosis and focus localization were based on ictal video-electroencephalography (EEG) recording. Patients had neuropsychological testing with Wechsler Adult Intelligence Score III (WAIS III) and Wechsler Memory Score III (WMS III) on stable antiepileptic drug (AED) regimens at least 24 h since the last seizure. Beck Depression Inventory (BDI) scores were obtained. We performed interictal PET with 18FCWAY, a fluorinated derivative of WAY 100635, a highly specific 5HT1A ligand, and structural magnetic resonance imaging (MRI) scans to estimate partial volume and plasma free fraction corrected 18FCWAY volume of distribution (V/f1).Hippocampal V/f1 was significantly lower in area ipsilateral than contralateral to the epileptic focus (73.7 ± 27.3 vs. 95.4 ± 28.4; p0.001). We found a significant relation between both left hippocampal 18FCWAY V/f1 (r = 0.41; p0.02) and left hippocampal volume (r = 0.36; p0.03) and delayed auditory memory score. On multiple regression, there was a significant effect of the interaction of left hippocampal 18FCWAY V/f1 and left hippocampal volume on delayed auditory memory, but not of either alone. High collinearity was present. In an analysis of variance including the side of the seizure focus, the effect of left hippocampal 18FCWAY V/f1 but not focus laterality retained significance. Mean BDI was 8.3 ± 7.0. There was a significant inverse relation between BDI and 18FCWAY V/f1 ipsilateral to the patient's epileptic focus (r = 0.38 p0.02). There was no difference between patients with a right or left temporal focus. There was no relation between BDI and immediate or delayed auditory memory.Our study suggests that reduced left hippocampal 5HT1A-receptor binding may play a role in memory impairment in patients with TLE.
- Published
- 2011
31. 6. Value of overnight EEG monitoring in the ICU
- Author
-
Barbara C. Jobst, Gregory L. Holmes, Christina J. Azevedo, Vijay M. Thadani, Juan C. Gonzalez, Richard E. Nordgren, Stephen D. Surgenor, Mark A. Natola, Omar I. Khan, Justin Montanye, Richard P. Morse, and Syed T. Arshad
- Subjects
medicine.medical_specialty ,Neurology ,business.industry ,Physiology (medical) ,Emergency medicine ,Medicine ,Neurology (clinical) ,business ,Eeg monitoring ,Value (mathematics) ,Sensory Systems - Published
- 2011
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.