Nervous System Diseases Commons^™

Remarkable Seizure Reduction With Trofinetide Treatment In An Adult With Rett Syndrome: A Case Report, Semihan Adegbite, Pooneh Memar Ardestani, Maromi Nei

Department of Neurology Faculty Papers

No abstract provided.

Objective Oculomotor, Vestibular, Reaction Time, And Cognitive Signatures Of Vestibular Migraine, Claire E. J. Ceriani, Alexandr Braverman, Alexander Kiderman

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate oculomotor, vestibular, reaction time, and cognitive (OVRT-C) function in patients with vestibular migraine (VM) using objective eye-tracking-based metrics and to identify patterns of dysfunction relative to healthy controls.

BACKGROUND: Vestibular migraine is a common yet underdiagnosed cause of vertigo. Diagnosis remains primarily clinical, because objective neurologic and vestibular findings are often absent or inconsistent. Quantitative methods capable of capturing the multisystem manifestations of VM may improve objective characterization of the disorder.

METHODS: Participants with a clinical diagnosis of vestibular migraine were recruited from a tertiary headache center and assessed using a battery of OVRT-C tests administered with …

Editorial: Clinical Imaging, Neurophysiological, Neuropathology And Neuroethics Studies On Disorders Of Consciousness, Coma Mechanisms, And Theories Of Consciousness: A Unifying Attempt, Diego Iacono, Manuel Trachsel, Thanh Phan, Charlène Aubinet

Department of Neurology Faculty Papers

No abstract provided.

Apolipoprotein E4 And Its Later-Life Health Effects On The Multiple Sclerosis Population, Dean Zeldich, Chia Hsin Cheng, Yi Guan, Sriman Narain, Bang-Bon Koo

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer's Disease, accelerates cognitive decline and neuroinflammatory processes, including blood-brain-barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.

METHODS: MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic …

Promising Effects Of Car T-Cell Therapy In Refractory Stiff Person Syndrome And A Hopeful Future For All Neuroautoimmunities, Marinos Dalakas

Department of Neurology Faculty Papers

Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases. The CD19 CAR T cells-targeting those CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts-are now extensively explored in refractory neuroautoimmunities with promising benefits based on case series in patients with myasthenia gravis (MG), stiff person syndrome (SPS), neuromyelitis, myositis, and multiple sclerosis; some patients …

Botulinum Toxin In Stiff Person Syndrome: How Useful Is It In Helping Muscle Stiffness And Spasms?, Marinos Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Reaching International Consensus On The Definition Of Refractory Migraine Using The Delphi Method, Jennifer Robblee, Fawad A. Khan, Michael J. Marmura, Hope L. O'Brien, Lawrence D. Robbins, Marielle K. Samaha, Morris Levin, Simona Sacco, Raffaele Ornello, Stephanie J. Nahas, Heike Hesse, Annika Ehrlich, Adam S. Sprouse-Blum, Christina Sun-Edelstein, Bronwyn Jenkins, Elizabeth K, Seng, Shivang Joshi, Meredith J. Barad, Mi Ji Lee, Sheena K. Aurora, Mario Fernando Prieto Peres

Department of Neurology Faculty Papers

Aim: Despite its frequency in tertiary headache centers, the International Classification of Headache Disorders, 3rd edition (ICHD-3) does not include refractory migraine. Multiple definitions have been proposed with a recent 2020 proposal for both refractory migraine and resistant migraine by the European Headache Federation (EHF). The aim is to reach an international consensus on the definition of refractory migraine.

Methods: This study is a Delphi consensus carried out by a group of international experts in headache medicine. Following a focus group, a panel of 20 experts and one facilitator reviewed the EHF proposed criteria to build upon their definitions. The …

Immediate-Use Rescue Medication And The Epilepsy Monitoring Unit: Experiences From An Expert Panel, Evelyn K. Shih, Brin E. Freund, Michael R. Sperling, Danielle A. Becker, Proleta Datta, Sandra Dewar, Edward Faught, Tracy Glauser, R. Edward Hogan, Randa Jarrar, Andres M. Kanner, David King-Stephens, Rebecca E. Matthews, Patricia Penovich, M. Scott Perry, Eric B. Segal, Joseph Sirven, John M. Stern, James W. Wheless, Enrique Carrazana, Adrian L. Rabinowicz, William O. Tatum

Department of Neurology Faculty Papers

BACKGROUND: People with epilepsy (PWE) may experience seizure clusters, broadly defined as ≥2 seizures that occur in close proximity. In epilepsy monitoring units (EMUs), seizure clusters can spontaneously occur during long-term videoelectroencephalogram monitoring (LTVEM) or as a result of antiseizure medication dose adjustments. In this survey, we examined the experiences and practices of expert clinicians with seizure clusters in EMUs.

METHODS: A 55-item survey was sent to members of an Epilepsy Education Council who are epilepsy experts. Items described experiences, treatment practices, and negative outcomes with seizure clusters in EMUs.

RESULTS: Of the 15 experts (aged 43-77 y), 14 are …

Comparative Outcomes Of Coil Embolization And Surgical Clipping In Elderly Patients With Subarachnoid Hemorrhage: A Systematic Review And Meta-Analysis, Yohanna Idsabella Rossi, Gabriel Bolner, Jonathan Costa Dall'acqua, Fabiana Dolovitsch De Oliveira, Lucas V. Zacaria, Taís L. Denicol, Michel Frudit, Natália Vasconcellos De Oliveira Souza

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Elderly patients with subarachnoid hemorrhage (SAH) face a disproportionately high burden of morbidity and mortality. While endovascular coiling is often favored in this population, direct comparisons with surgical clipping are limited. We conducted a meta-analysis to compare outcomes of clipping versus coiling in SAH patients aged ≥ 60 years.

METHODS: A systematic search of PubMed, Embase, and Cochrane databases identified studies comparing the two treatments in this age group. The primary outcome was a composite of unfavorable outcomes (modified Rankin Scale [mRS] > 2 and mortality). Secondary outcomes included mortality, favorable outcome (mRS 0-2), rebleeding, and hospital length …

Multiple Subcortical And Subcortico-Cortico Dynamic Network Reconfigurations Characterize Focal-To-Bilateral Tonic-Clonic Seizures, Shilpi Modi, A. Ankeeta, Walter Hinds, Michael R. Sperling, Xiaosong He, Joseph I. Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with focal to bilateral tonic-clonic seizures (FBTCS+) a more severe form of the disorder. Evidence has underscored the critical role of the thalamus, mesial temporal region, basal ganglia and cerebellum, along with the cortex, in the propagation, termination, and modulation of seizure activity. We examined time variant patterns of interaction within and between 7 cortical and 4 subcortical systems in 55 healthy controls and 56 patients with TLE (n = 40 with FBTCS+ and 15 without), isolating those patterns most distinctive of FBTCS+ utilizing tools from dynamic network neuroscience on …

Stress And Seizures: The October 7th Experience, Alon Doron, Firas Fahoum, Lilach Goldstein

Department of Neurology Faculty Papers

OBJECTIVE: Stress is a frequently self-reported seizure trigger in patients with epilepsy (PWE), with studies regarding this issue having conflicting results. On October 7th, 2023, a large-scale military invasion accompanied by massive rocket launches against Israel, including Tel Aviv, occurred, providing an opportunity to investigate the role of acute stress in provoking seizures.

METHODS: All adults who presented to the emergency department (ED) of Tel Aviv Sourasky Medical Center between January 1st, 2017, and February 29th, 2024, and were diagnosed with seizures were included. Data were collected using MDClone, a data acquisition tool. The overall seizure-related ED admissions were compared …

Cenobamate Use In Pregnancy: A Case Report, Tiara Paul, Maromi Nei

Department of Neurology Faculty Papers

No abstract provided.

Management Of Parkinson's Disease Psychosis: First-Line Antipsychotic Selection And Rationale For Continuing, Combining, Or Switching, Stuart H. Isaacson, Henry Nasrallah, Rajesh Pahwa, Gustavo Alva, Daniel Kremens, Stephen M. Stahl

Department of Neurology Faculty Papers

INTRODUCTION: The past decade has seen a paradigm shift in the evaluation and management of Parkinson's disease psychosis (PDP), with the first approval of an antipsychotic in the US in 2016. An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Clozapine and quetiapine use can be limited by provoking Parkinson's disease (PD) nonmotor symptoms of somnolence and hypotension. Quetiapine may also be limited by its risk in cognitive impairment. Pimavanserin is not associated with these symptoms. …

Seizure Freedom And Reducing The Risk Of Sudden Unexpected Death In Patients With Focal Epilepsy Treated With Cenobamate Or Other Antiseizure Medications, Michael R. Sperling, William E. Rosenfeld, John Watson, Pavel Klein

Department of Neurology Faculty Papers

People with epilepsy who have uncontrolled seizures are at increased risk of all-cause mortality, injuries, comorbidities, mood and psychosocial disorders, and diminished quality of life. For those with focal epilepsy, focal to bilateral tonic-clonic seizures (FBTCS) pose the greatest risk for sudden unexpected death in epilepsy (SUDEP), a leading cause of premature mortality in people with epilepsy. Cenobamate is a third-generation antiseizure medication with demonstrated efficacy in controlling focal seizures, including FBTCS, in people with drug-resistant epilepsy. Treatment with cenobamate in clinical trials was associated with a reduction in all-cause mortality to a rate statistically indistinguishable from that seen in …

Immunogenetic Studies In Patients With Gad-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes And Klk10 -Gene Variants, Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).

METHODS: We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.

RESULTS: Two genes expressed in immune and neuronal tissues were identified: the ORAI1 that codes for a calcium release–activated channel protein with a role in the …

Il-7rα On Cd4+ T Cells Is Required For Their Survival And The Pathogenesis Of Experimental Autoimmune Encephalomyelitis, Gholamreza Azizi, Bram Van Den Broek, Larissa Ishikawa, Hamed Naziri, Reza Yazdani, Guang-Xian Zhang, Bogoljub Ciric, Mohamad Rostami

Department of Neurology Faculty Papers

BACKGROUND: The IL-7 receptor alpha (IL-7Rα) binds both IL-7 and thymic stromal lymphopoietin (TSLP). IL-7Rα is essential for the development and survival of naive CD4+ T cells and their differentiation to effector/memory CD4+ T cells. Mice lacking IL-7Rα have severe lymphopenia and are resistant to experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. However, it has been reported that IL-7Rα on peripheral CD4+ T cells is disposable for their maintenance and EAE pathogenesis, which does not align with the body of knowledge on the role of IL-7Rα in the biology of CD4+ T cells. Given that a definitive study …

Apomorphine Titration With And Without Anti-Emetic Pretreatment In Patients With Parkinson’S Disease Experiencing Off Episodes: A Modified Delphi Panel, Stuart H. Isaacson, Richard Dewey, Robert A. Hauser, Daniel Kremens, Rajeev Kumar, Mark Lew, William Ondo, Fernando Pagan, Kelly E. Lyons, Rajesh Pahwa

Department of Neurology Faculty Papers

INTRODUCTION: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed.

METHODS: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment. During Round 1, a panel of 9 US movement disorder specialists rated the appropriateness of prescribing apomorphine therapy with and without antiemetic pretreatment across 192 patient scenarios and were able to review their scores in relation to other scores. During the Round 2, consensus was defined for each scenario as …

Magnetic Resonance Imaging Signs Of Idiopathic Intracranial Hypertension, Dagmar Beier, Johanne Juhl Korsbæk, Gabriel Bsteh, Stefan Macher, Wolfgang Marik, Berthold Pemp, Hsiangkuo Yuan, Areeba Nisar, Lisbeth Høgedal, Laleh Dehghani Molander, Snorre Malm Hagen, Christoph Patrick Beier, Simon Bang Kristensen, Rigmor Højland Jensen

Department of Neurology Faculty Papers

IMPORTANCE: The magnetic resonance imaging (MRI) criteria currently used to diagnose idiopathic intracranial hypertension (IIH) are based on expert opinion and have limited accuracy. Additional neuroimaging signs have been proposed and used with contradictory results; thus, prospective evidence is needed to improve diagnostic accuracy.

OBJECTIVE: To provide evidence-based, accurate MRI signs for IIH diagnosis.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted from January 2018 to May 2021 with 3 validation cohorts at 2 Danish headache centers and with 3 independent international cohorts. Consecutive patients with suspected IIH were enrolled. Eligibility required the clinical suspicion of IIH, age …

Sustained Response To Atogepant In Episodic Migraine: Post Hoc Analyses Of A 12-Week Randomized Trial And A 52-Week Long-Term Safety Trial, Richard Lipton, Stephanie J. Nahas, Patricia Pozo-Rosich, Tanya Bilchik, Peter Mcallister, Michelle Finnegan, Yingyi Liu, Natty Chalermpalanupap, Brett Dabruzzo, David Dodick

Department of Neurology Faculty Papers

BACKGROUND: Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment.

METHODS: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety …

Comparative Efficacy, Quality Of Life, Safety, And Tolerability Of Atogepant And Rimegepant In Migraine Prevention: A Matching-Adjusted Indirect Comparison Analysis, Cristina Tassorelli, Kateryna Onishchenko, Rashmi B. Halker Singh, Molly Duan, Laure Dupont-Benjamin, Matthew Hemstock, Corey Voller, Peter Mcallister, Stephanie J. Nahas, Pranav Gandhi, Jessica Ailani

Department of Neurology Faculty Papers

BACKGROUND: Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice.

METHODS: An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly …

Objectivity, Practicality, And Significance Of Practice Guidelines For The Practicing Neurologists: What We Learnt From Consensus Criteria In Cidp, Myasthenia Gravis And Inflammatory Myopathies, Marinos C. Dalakas

Department of Neurology Faculty Papers

The value of practice guidelines in the three most common autoimmune neuromuscular disorders, namely Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Myasthenia Gravis (MG) and Autoimmune Inflammatory Myopathies (AIM), has been extensively debated regarding their usefulness in clinical practice, objectivity and universal value considering that guidelines are also established regionally in certain countries. This commentary highlights common concerns on how guidelines are presently generated, pointing out: (a) non-sufficient diversity among Task-Force members to identify and address not only routine clinical and electrophysiology issues but also immunology, imaging, pathology, biomarkers, epidemiology or treatment economics; (b) Task-Force being often comprised by the same or …

Genetics Of Functional Seizures; A Scoping Systematic Review, Ali A. Asadi-Pooya, Mark Hallett, Nafiseh Mirzaei Damabi, Khatereh Fazelian Dehkordi

Department of Neurology Faculty Papers

Background: Evidence on the genetics of functional seizures is scarce, and the purpose of the current scoping systematic review is to examine the existing evidence and propose how to advance the field.

Methods: Web of science and MEDLINE were searched, from their initiation until May 2023. The following key words were used: functional neurological disorder(s), psychogenic neurological disorder(s), functional movement disorder(s), psychogenic movement disorder(s), functional seizures(s), psychogenic seizure(s), nonepileptic seizure(s), dissociative seizure(s), or psychogenic nonepileptic seizure(s), AND, gene, genetic(s), polymorphism, genome, epigenetics, copy number variant, copy number variation(s), whole exome sequencing, or next-generation sequencing.

Results: We identified three original studies. …

How To Manage The Initiation Of Apomorphine Therapy Without Antiemetic Pretreatment: A Review Of The Literature, Stuart H. Isaacson, Richard B. Dewey, Rajesh Pahwa, Daniel E. Kremens

Department of Neurology Faculty Papers

Introduction

Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods

To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.

Results

Three studies were identified as …

Delta Oscillation Coupled Propagating Fast Ripples Precede Epileptiform Discharges In Patients With Focal Epilepsy, Shennan A. Weiss, Laurent Sheybani, Nitish Seenarine, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Jerome Engel Jr., Michael R. Sperling, Yuval Nir, Richard J. Staba

Department of Neurology Faculty Papers

Epileptiform spikes are used to localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Pathological fast ripple (FR, 200–600 Hz) are biomarkers of epileptogenic brain, and we postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo intracranial EEG (iEEG) recordings from a cohort of 46 patients we found that, in the seizure onset zone (SOZ), propagating FR were more often followed by an epileptiform spike, as compared with non-propagating FR (p < 0.05). Propagating FR had a distinct frequency and larger power (p < 1e-10) and were more strongly phase coupled to the peak of iEEG delta oscillation, which likely correspond with the DOWN states during non-REM sleep (p < 1e-8), than non-propagating FR. While FR propagation was rare, all FR occurred with the highest probability within +/− 400 msec of epileptiform spikes with superimposed high-frequency oscillations (p < 0.05). Thus, a sub-population of epileptiform spikes in the SOZ, are preceded by propagating FR that are coordinated by the DOWN state during non-REM sleep.

Individualised Prediction Of Drug Resistance And Seizure Recurrence After Medication Withdrawal In People With Juvenile Myoclonic Epilepsy: A Systematic Review And Individual Participant Data Meta-Analysis, Remi Stevelink, Dania Al-Toma, Floor E. Jansen, Herm J. Lamberink, Ali A. Asadi-Pooya, Mohsen Farazdaghi, Gonçalo Cação, Sita Jayalakshmi, Anuja Patil, Çiğdem Özkara, Şenay Aydın, Joanna Gesche, Christoph P. Beier, Linda J. Stephen, Martin J. Brodie, Gopeekrishnan Unnithan, Ashalatha Radhakrishnan, Julia Höfler, Eugen Trinka, Roland Krause, Emanuele Cerulli Irelli, Carlo Di Bonaventura, Jerzy P. Szaflarski, Laura E. Hernández-Vanegas, Monica L. Moya-Alfaro, Yingying Zhang, Dong Zhou, Nicola Pietrafusa, Nicola Specchio, Giorgi Japaridze, Sándor Beniczky, Mubeen Janmohamed, Patrick Kwan, Marte Syvertsen, Kaja K. Selmer, Bernd J. Vorderwülbecke, Martin Holtkamp, Lakshminarayanapuram G. Viswanathan, Sanjib Sinha, Betül Baykan, Ebru Altindag, Felix Von Podewils, Juliane Schulz, Udaya Seneviratne, Alejandro Viloria-Alebesque, Ioannis Karakis, Wendyl J. D'Souza, Josemir W. Sander, Bobby P. C. Koeleman, Willem M. Otte, Kees P. J. Braun

Department of Neurology Faculty Papers

BACKGROUND: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.

METHODS: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on …