Medical Specialties Commons^™

Erratum To: Characterizing Benefit From Temozolomide In Mgmt Promoter Unmethylated And Methylated Glioblastoma: A Systematic Review And Meta-Analysis, Iyad Alnahhas, Mouaz Alsawas, Appaji Rayi, Joshua D Palmer, Raju Raval, Shirley Ong, Pierre Giglio, Mohammad Hassan Murad, Vinay Puduvalli

Department of Neurology Faculty Papers

[This corrects the article DOI: 10.1093/noajnl/vdaa082.].

An Educational Workshop To Improve Neurology Resident Understanding Of Burnout, Substance Abuse, And Mood Disorders., Ryan Donaghy, Shiori Tomatsu, Patrick Kerns, Courtney White, Jeffrey Ratliff

Department of Neurology Faculty Papers

Introduction: Burnout, substance abuse, and mood disorders are prevalent among neurology residents. Increased recognition of concerning behaviors might encourage more access to mental health resources and reduce burnout.

Methods: We created an educational resource reviewing burnout, substance abuse, and mood disorders for neurology residents. This resource included an online module (control) and a role-play scenario offered only to one cohort (intervention). Online surveys assessed knowledge as well as confidence in the ability to recognize concerning behaviors. A practical assessment using a previously published "Stressed Resident" video was also conducted among resident cohorts.

Results: Of neurology residents, 18 participated in the …

Long-Term Efficacy And Tolerability Of Adjunctive Brivaracetam In Adults With Focal To Bilateral Tonic-Clonic (Secondary Generalized) Seizures: Post Hoc Pooled Analysis, Brian D Moseley, Svetlana Dimova, Sami Elmoufti, Cédric Laloyaux, Aliakbar Asadi-Pooya

Department of Neurology Faculty Papers

This post hoc analysis was conducted to evaluate the efficacy, tolerability, and health-related quality of life during long-term adjunctive brivaracetam (BRV) treatment in adult patients with focal to bilateral tonic-clonic seizures (FBTCS). Patients (≥ 16 years) were included in this post hoc analysis if they were randomized to BRV or placebo in double-blind, placebo-controlled (N01252 [NCT00490035], N01253 [NCT00464269], N01358 [NCT01261325]; core) trials, and received adjunctive BRV in the corresponding long-term follow-up (N01125 [NCT00175916], N01199 [NCT00150800], N01379 [NCT01339559]) trials, and reported FBTCS during the 8-week prospective baseline (core trial). Efficacy (concomitant levetiracetam excluded) and tolerability (concomitant levetiracetam included) were assessed from …

Evaluation Of Diazepam Nasal Spray In Patients With Epilepsy Concomitantly Using Maintenance Benzodiazepines: An Interim Subgroup Analysis From A Phase 3, Long-Term, Open-Label Safety Study., Eric B Segal, Daniel Tarquinio, Ian Miller, James W Wheless, Dennis Dlugos, Victor Biton, Gregory D Cascino, Jay Desai, R Edward Hogan, Kore Liow, Michael R Sperling, Blanca Vazquez, David F Cook, Adrian L Rabinowicz, Enrique Carrazana

Department of Neurology Faculty Papers

OBJECTIVE: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness.

METHODS: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen.

RESULTS: Among 175 patients enrolled by October 31, 2019, …

Aggressive Herpes Zoster In Young Patients With Multiple Sclerosis Under Dimethyl Fumarate: Significance Of Cd8, Maria Anagnostouli, Georgios Velonakis, Marinos Dalakas

Department of Neurology Faculty Papers

Dimethyl fumarate (DMF), approved for relapsing-remitting multiple sclerosis (RRMS), exerts immune-mediated mechanisms crucial for T-cell survival and migration, preferentially reducing CD8+ T cells.1 Although baseline absolute lymphocyte count (ALC) is considered the most critical predictor of developing lymphopenia,2 it was recently concluded that lymphocyte subset monitoring is not required for safety vigilance because T-cell subset reduction does not increase risks for serious infections.3 We present 2 young patients with RRMS, under DMF treatment, negative for HIV and SARSCoV-2 (by RT-PCR in nasal swab) and with normal follow-up white blood cell (WBC)/ALC counts, who developed severe herpes zoster (HZ) infection with …

Long Term Safety, Tolerability, And Efficacy Of Intracutaneous Zolmitriptan (M207) In The Acute Treatment Of Migraine., Stephanie J. Nahas, Nada Hindiyeh, Deborah I. Friedman, Nada Elbuluk, Donald J. Kellerman, Pamela K. Foreman, Peter Schmidt

Department of Neurology Faculty Papers

OBJECTIVE: To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine.

BACKGROUND: M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks.

METHODS: In this 6-12 month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48 h following treatment of a …

Automated Analysis Of Risk Factors For Postictal Generalized Eeg Suppression, Xiuhe Zhao, Laura Vilella, Liang Zhu, M R Sandhya Rani, Johnson P Hampson, Jaison Hampson, Norma J Hupp, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine Scott, Luke Allen, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo, Nuria Lacuey

Department of Neurology Faculty Papers

Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES. Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We …

Lack Of Observed Tolerance To Diazepam Nasal Spray (Valtoco®) After Long-Term Rescue Therapy In Patients With Epilepsy: Interim Results From A Phase 3, Open-Label, Repeat-Dose Safety Study., Gregory D. Cascino, Daniel Tarquinio, James W. Wheless, R. Edward Hogan, Michael R. Sperling, Kore Liow, Jay Desai, Charles Davis, Adrian L. Rabinowicz, Enrique Carrazana

Department of Neurology Faculty Papers

OBJECTIVE: Tolerance is a known consideration for maintenance use of benzodiazepines and other antiseizure drugs; however, clinical experience suggests that tolerance may not be anticipated with long-term intermittent use of benzodiazepines as rescue therapy. Diazepam nasal spray (Valtoco®) is a proprietary intranasal formulation approved for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Reported here are exploratory analyses investigating whether there was evidence of development of tolerance in an interim analysis of a long-term, phase 3, open-label safety study of diazepam nasal spray.

METHODS: …

Gad Antibody-Spectrum Disorders: Progress In Clinical Phenotypes, Immunopathogenesis And Therapeutic Interventions., Popianna Tsiortou, Harry Alexopoulos, Marinos Dalakas

Department of Neurology Faculty Papers

Antibodies against glutamic acid decarboxylase (GAD), originally linked to stiff person syndrome (SPS), now denote the “GAD antibody-spectrum disorders” (GAD-SD) that also include autoimmune epilepsy, limbic encephalitis, cerebellar ataxia and nystagmus with overlapping symptomatology highlighting autoimmune neuronal excitability disorders. The reasons for the clinical heterogeneity among GAD-antibody associated syndromes remain still unsettled, implicating variable susceptibility of GABAergic neurons to anti-GAD or other still unidentified autoantibodies. Although anti-GAD antibody titers do not correlate with clinical severity, very high serum titers, often associated with intrathecal synthesis of anti-GAD-specific IgG, point to in-situ effects of GAD or related autoantibodies within the central nervous …

Crispr-Mediated Rapid Generation Of Neural Cell-Specific Knockout Mice Facilitates Research In Neurophysiology And Pathology., Dan Xiao, Weifeng Zhang, Qing Wang, Xing Li, Yuan Zhang, Javad Rasouli, Giacomo Casella, Bogoljub Ciric, Mark Curtis, A M Rostami, Guang-Xian Zhang

Department of Neurology Faculty Papers

Inducible conditional knockout mice are important tools for studying gene function and disease therapy, but their generation is costly and time-consuming. We introduced clustered regularly interspaced short palindromic repeats (CRISPR) and Cre into an LSL-Cas9 transgene-carrying mouse line by using adeno-associated virus (AAV)-PHP.eB to rapidly knockout gene(s) specifically in central nervous system (CNS) cells of adult mice. NeuN in neurons and GFAP in astrocytes were knocked out 2 weeks after an intravenous injection of vector, with an efficiency comparable to that of inducible Cre-loxP conditional knockout. For functional testing, we generated astrocyte-specific Act1 knockout mice, which exhibited a phenotype …

Cardiovascular Disease Risk, Awareness, And Treatment In People With Epilepsy, Samuel W Terman, Carole E Aubert, Chloe E Hill, Jeremy Skvarce, James F Burke, Scott Mintzer

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate whether cardiovascular risk, risk awareness, and guideline concordant treatment differ in individuals with versus without epilepsy.

METHODS: This was a retrospective cross-sectional study using the National Health and Nutrition Examination Survey. We included participants ≥18 years for 2013-2018. We classified participants as having epilepsy if reporting ≥1 medication treating seizures. We calculated 10-year atherosclerotic cardiovascular disease (ASCVD) risk using the revised pooled cohort equation. We compared unadjusted and adjusted risk for participants with versus without epilepsy. We then assessed hypertension and diabetes disease awareness and control, plus statin guideline-concordance. We assessed mediators for both ASCVD risk and …

Can Early Treatment Of Twitcher Mice With High Dose Aavrh10-Galc Eliminate The Need For Bmt?, Mohammad Rafi, Paola Luzi, David A Wenger

Department of Neurology Faculty Papers

Introduction: Krabbe disease (KD) is an autosomal recessive disorder caused by mutations in the galactocerebrosidase (GALC) gene resulting in neuro-inflammation and defective myelination in the central and peripheral nervous systems. Most infantile patients present with clinical features before six months of age and die before two years of age. The only treatment available for pre-symptomatic or mildly affected individuals is hematopoietic stem cell transplantation (HSCT). In the animal models, combining bone marrow transplantation (BMT) with gene therapy has shown the best results in disease outcome. In this study, we examine the outcome of gene therapy alone.

Methods: Twitcher (twi) mice …

Anti-Sars-Cov-2 Antibodies Within Ivig Preparations: Cross-Reactivities With Seasonal Coronaviruses, Natural Autoimmunity, And Therapeutic Implications, Marinos Dalakas, Kleopatra Bitzogli, Harry Alexopoulos

Department of Neurology Faculty Papers

Introduction: Cross-reactivity to SARS-CoV-2 antigenic peptides has been detected on T-cells from pre-pandemic donors due to recognition of conserved protein fragments within members of the coronavirus's family. Further, preexisting antibodies recognizing SARS-CoV-2 with conserved epitopes in the spike region have been now seen in uninfected individuals. High-dose Intravenous Immunoglobulin (IVIg), derived from thousands of healthy donors, contains natural IgG antibodies against various antigens which can be detected both within the IVIg preparations and in the serum of IVIg-receiving patients. Whether IVIg preparations from pre-pandemic donors also contain antibodies against pre-pandemic coronaviruses or autoreactive antibodies that cross-react with SARS-CoV-2 antigenic epitopes, …

Seizure Clusters, Seizure Severity Markers, And Sudep Risk., Manuela Ochoa-Urrea, Nuria Lacuey, Laura Vilella, Liang Zhu, Shirin Jamal-Omidi, M R Sandhya Rani, Johnson P Hampson, Mojtaba Dayyani, Jaison Hampson, Norma J Hupp, Shiqiang Tao, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine Scott, Luke Allen, Brian K Gehlbach, Victoria Reick-Mitrisin, Stephan Schuele, Jennifer Ogren, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo

Department of Neurology Faculty Papers

Rationale: Seizure clusters may be related to Sudden Unexpected Death in Epilepsy (SUDEP). Two or more generalized convulsive seizures (GCS) were captured during video electroencephalography in 7/11 (64%) patients with monitored SUDEP in the MORTEMUS study. It follows that seizure clusters may be associated with epilepsy severity and possibly with SUDEP risk. We aimed to determine if electroclinical seizure features worsen from seizure to seizure within a cluster and possible associations between GCS clusters, markers of seizure severity, and SUDEP risk. Methods: Patients were consecutive, prospectively consented participants with drug-resistant epilepsy from a multi-center study. Seizure clusters were defined as …

Management Of Gliomas In Patients With Lynch Syndrome., Iyad Alnahhas, Appaji Rayi, Shirley Ong, Pierre Giglio, Vinay Puduvalli

Department of Neurology Faculty Papers

No abstract provided.

Development Of Optically Controlled "Living Electrodes" With Long-Projecting Axon Tracts For A Synaptic Brain-Machine Interface., Dayo O. Adewole, Laura A. Struzyna, Justin C. Burrell, James P. Harris, Ashley D. Nemes, Dmitriy Petrov, Reuben H. Kraft, H. Isaac Chen, Mijail D. Serruya, John A. Wolf, D. Kacy Cullen

Department of Neurology Faculty Papers

For implantable neural interfaces, functional/clinical outcomes are challenged by limitations in specificity and stability of inorganic microelectrodes. A biological intermediary between microelectrical devices and the brain may improve specificity and longevity through (i) natural synaptic integration with deep neural circuitry, (ii) accessibility on the brain surface, and (iii) optogenetic manipulation for targeted, light-based readout/control. Accordingly, we have developed implantable "living electrodes," living cortical neurons, and axonal tracts protected within soft hydrogel cylinders, for optobiological monitoring/modulation of brain activity. Here, we demonstrate fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of these tissue engineered constructs in vitro. …

Functional Seizures Are Not Less Important Than Epilepsy, A A Asadi-Pooya, Francesco Brigo, Benjamin Tolchin, Kette D. Valente

Department of Neurology Faculty Papers

Functional seizures (FS) are frequently encountered in neurology clinics, often affect young adults, and have significant negative impacts on many aspects of a person's life. In the current narrative review, we searched the literature regarding some of the consequences of FS (i.e., psychiatric comorbidities, social consequences, costs that are associated with the condition, cognitive impairment in patients with FS, the quality of life of the people with FS, and the increased risk of mortality that is associated with FS). Evidence shows that FS have significant negative consequences, comparable in their magnitude to those affecting patients with epilepsy. The clinical and …

Trsper: A Web-Based Application For Archimedes Spiral Analysis, Rogan Magee, Benjamin Yang, Jeff Ratliff

Department of Neurology Faculty Papers

Background: We built a web-based application of the Archimedes spiral exam that implements clinically validated spiral metrics and tested drawing instructions to define a clinical workflow.

Methods: We designed an HTML5 and Javascript implementation of the spiral exam to run on mobile touchscreen devices. We then recruited 10 volunteers each for 2 experiments designed to validate the programmed spiral metrics and assess how instructions or drawing implement affect the results. In task one, volunteers drew 5 spirals each while following 6 different instruction sets (n=30 spirals each, n=300 spirals total) that varied by support of the drawing hand and tracing …

Ifn-Β Acts On Monocytes To Ameliorate Cns Autoimmunity By Inhibiting Proinflammatory Cross-Talk Between Monocytes And Th Cells., Javad Rasouli, Giacomo Casella, Larissa Ishikawa, Rodolfo Thome, Alexandra Boehm, Adam Ertel, Carolina R Melo-Silva, Elisabeth R. Mari, Patrizia Porazzi, Weifeng Zhang, Dan Xiao, Luis J. Sigal, Paolo Fortina, Guang-Xian Zhang, A M Rostami, Bogoljub Ciric

Department of Neurology Faculty Papers

IFN-β has been the treatment for multiple sclerosis (MS) for almost three decades, but understanding the mechanisms underlying its beneficial effects remains incomplete. We have shown that MS patients have increased numbers of GM-CSF+ Th cells in circulation, and that IFN-β therapy reduces their numbers. GM-CSF expression by myelin-specific Th cells is essential for the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. These findings suggested that IFN-β therapy may function via suppression of GM-CSF production by Th cells. In the current study, we elucidated a feedback loop between monocytes and Th cells that amplifies autoimmune neuroinflammation, …

N2 Year In Review, Josep Dalmau, Marinos Dalakas, Dennis L Kolson, Friedemann Paul, Scott S Zamvil

Department of Neurology Faculty Papers

No abstract provided.

Burnout Among Healthcare Providers Of Covid-19; A Systematic Review Of Epidemiology And Recommendations, Mehrdad Sharifi, Ali Akbar Asadi-Pooya, Razieh Sadat Mousavi-Roknabadi

Department of Neurology Faculty Papers

Introduction: In the current systematic review, we intended to systematically review the epidemiology of burnout and the strategies and recommendations to prevent or reduce it among healthcare providers (HCPs) of COVID-19 wards, so that policymakers can make more appropriate decisions.

Methods: MEDLINE (accessed from PubMed), Science Direct, and Scopus electronic databases were systematically searched in English from December 01, 2019 to August 15, 2020, using MESH terms and related keywords. After reading the title and the abstract, unrelated studies were excluded. The full texts of the studies were evaluated by authors, independently, and the quality of the studies was determined. …

Inflammatory Myopathies: Update On Diagnosis, Pathogenesis And Therapies, And Covid-19-Related Implications., Marinos C. Dalakas

Department of Neurology Faculty Papers

The inflammatory myopathies constitute a heterogeneous group of acquired myopathies that have in common the presence of endomysial inflammation. Based on steadily evolved clinical, histological and immunopathological features and some autoantibody associations, these disorders can now be classified in five characteristic subsets: Dermatomyositis (DM) Polymyositis (PM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). Each inflammatory myopathy subset has distinct immunopathogenesis, prognosis and response to immunotherapies, necessitating the need to correctly identify each subtype from the outset to avoid disease mimics and proceed to early therapy initiation. The review presents the main clinicopathologic characteristics of each subset …

Time Cells In The Human Hippocampus And Entorhinal Cortex Support Episodic Memory., Gray Umbach, Pranish Kantak, Joshua Jacobs, Michael Kahana, Brad E. Pfeiffer, Michael R Sperling, Bradley Lega

Department of Neurology Faculty Papers

The organization of temporal information is critical for the encoding and retrieval of episodic memories. In the rodent hippocampus and entorhinal cortex, evidence accumulated over the last decade suggests that populations of "time cells" in the hippocampus encode temporal information. We identify time cells in humans using intracranial microelectrode recordings obtained from 27 human epilepsy patients who performed an episodic memory task. We show that time cell activity predicts the temporal organization of retrieved memory items. We also uncover evidence of ramping cell activity in humans, which represents a complementary type of temporal information. These findings establish a cellular mechanism …

Management Of Acute Ischemic Stroke., Franziska Herpich, Fred Rincon

Department of Neurology Faculty Papers

OBJECTIVES: Concise "synthetic" review of the state of the art of management of acute ischemic stroke.

DATA SOURCES: Available literature on PubMed.

STUDY SELECTION: We selected landmark studies, recent clinical trials, observational studies, and professional guidelines on the management of stroke including the last 10 years.

DATA EXTRACTION: Eligible studies were identified and results leading to guideline recommendations were summarized.

DATA SYNTHESIS: Stroke mortality has been declining over the past 6 decades, and as a result, stroke has fallen from the second to the fifth leading cause of death in the United States. This trend may follow recent advances in …

Contribution Of Left Supramarginal And Angular Gyri To Episodic Memory Encoding: An Intracranial Eeg Study., Daniel Y. Rubinstein, Liliana Camarillo-Rodriguez, Mijail D. Serruya, Nora A. Herweg, Zachary J. Waldman, Paul A. Wanda, Ashwini D. Sharan, Shennan A. Weiss, Michael R. Sperling

Department of Neurology Faculty Papers

The role of the left ventral lateral parietal cortex (VPC) in episodic memory is hypothesized to include bottom-up attentional orienting to recalled items, according to the dual-attention model (Cabeza et al., 2008). However, its role in memory encoding could be further clarified, with studies showing both positive and negative subsequent memory effects (SMEs). Furthermore, few studies have compared the relative contributions of sub-regions in this functionally heterogeneous area, specifically the anterior VPC (supramarginal gyrus/BA40) and the posterior VPC (angular gyrus/BA39), on a within-subject basis. To elucidate the role of the VPC in episodic encoding, we compared SMEs in the intracranial …

Challenges And Opportunities For Improving The Landscape For Lewy Body Dementia Clinical Trials., Jennifer G Goldman, Leah K Forsberg, Bradley F Boeve, Melissa J Armstrong, David J Irwin, Tanis J Ferman, Doug Galasko, James E Galvin, Daniel Kaufer, James Leverenz, Carol F Lippa, Karen Marder, Victor Abler, Kevin Biglan, Michael Irizarry, Bill Keller, Leanne Munsie, Masaki Nakagawa, Angela Taylor, Todd Graham

Department of Neurology Faculty Papers

Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson's disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body …

Thalamus And Focal To Bilateral Seizures: A Multiscale Cognitive Imaging Study., Lorenzo Caciagli, Luke A Allen, Xiaosong He, Karin Trimmel, Sjoerd B Vos, Maria Centeno, Marian Galovic, Meneka K Sidhu, Pamela J Thompson, Danielle S Bassett, Gavin P Winston, John S Duncan, Matthias J Koepp, Michael R Sperling

Department of Neurology Faculty Papers

OBJECTIVE: To investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality.

METHODS: FBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 …

Lgi1 Encephalitis With Squamous Lung-Cell Carcinoma: Resolution After Tumor Resection., Akash Virupakshaiah, Marinos Dalakas, Neeja Desai, Scott Mintzer, Jeffrey Ratliff

Department of Neurology Faculty Papers

Encephalitis with leucine-rich glioma-inactivated-1 (LGI1) immunoglobulin G (IgG) anti-bodies classically presents with cognitive impairment and characteristic faciobrachial dystonicseizures.1In a murine model, human LGI1 IgG caused reduction of Kv1.1 channels andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor receptors resulting in neuro-nal hyperexcitability indicating probable pathogenicity of LGI1 antibodies.2LGI1 autoimmu-nity is associated with malignancy in less than 10% of cases, including small cell lung cancer,prostate and colon cancer, squamous cell skin carcinoma, and neuroendocrine pancreaticcancer.3,4We present a case of LGI1 encephalitis only partially responsive to immunotherapywith eventual complete resolution after resection of a squamous cell lung carcinoma.

Eptinezumab For The Prevention Of Chronic Migraine: Efficacy And Safety Through 24 Weeks Of Treatment In The Phase 3 Promise-2 (Prevention Of Migraine Via Intravenous Ald403 Safety And Efficacy-2) Study., Stephen Silberstein, Merle Diamond, Nada A. Hindiyeh, David M. Biondi, Roger Cady, Joe Hirman, Brent Allan, Susan Pederson, Barbara Schaeffler, Jeff Smith

Department of Neurology Faculty Papers

BACKGROUND: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide-targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24 weeks of treatment.

METHODS: Patients received up to two 30-min IV administrations of eptinezumab 100 mg, 300 mg, or placebo separated by 12 weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day …

Absence-To-Bilateral-Tonic-Clonic Seizure: A Generalized Seizure Type., Sándor Beniczky, Guido Rubboli, Athanasios Covanis, Michael R Sperling

Department of Neurology Faculty Papers

OBJECTIVE: To test the hypothesis that absence seizures can evolve to generalized tonic-clonic seizures, we documented electroclinical features of this novel seizure type.

METHODS: In 4 large video-EEG databases, we identified recordings of seizures starting with impaired awareness that, without returning to baseline interictal state, evolved to generalized tonic-clonic seizures. We extracted the detailed semiologic and electrographic characteristics of these seizures, and we documented the clinical background, diagnoses, and therapeutic responses in these patients.

RESULTS: We identified 12 seizures from 12 patients. All seizures started with a period of impaired awareness and bursts of generalized spike or polyspike and slow-wave …