Medical Specialties Commons^™

Enzyme Replacement Therapies: What Is The Best Option?, Azam Safary, Mostafa Akbarzadeh Khiavi, Rahimeh Mousavi, Jaleh Barar, Mohammad Rafi

Department of Neurology Faculty Papers

Despite many beneficial outcomes of the conventional enzyme replacement therapy (ERT), several limitations such as the high-cost of the treatment and various inadvertent side effects including the occurrence of an immunological response against the infused enzyme and development of resistance to enzymes persist. These issues may limit the desired therapeutic outcomes of a majority of the lysosomal storage diseases (LSDs). Furthermore, the biodistribution of the recombinant enzymes into the target cells within the central nervous system (CNS), bone, cartilage, cornea, and heart still remain unresolved. All these shortcomings necessitate the development of more effective diagnosis and treatment modalities against LSDs. …

Lateralized Hippocampal Oscillations Underlie Distinct Aspects Of Human Spatial Memory And Navigation., Jonathan Miller, Andrew J. Watrous, Melina Tsitsiklis, Sang Ah Lee, Sameer A. Sheth, Catherine A. Schevon, Elliot H. Smith, Michael R. Sperling, Ashwini Sharan, Ali Akbar Asadi-Pooya, Gregory A. Worrell, Stephen Meisenhelter, Cory S. Inman, Kathryn A. Davis, Bradley Lega, Paul A. Wanda, Sandhitsu R. Das, Joel M. Stein, Richard Gorniak, Joshua Jacobs

Department of Neurology Faculty Papers

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in …

Stroke Severity Affects Timing: Time From Stroke Code Activation To Initial Imaging Is Longer In Patients With Milder Strokes., Kimberly T. Kwei, John W. Liang, Natalie Wilson, Stanley Tuhrim, Mandip Dhamoon

Department of Neurology Faculty Papers

Optimizing the time it takes to get a potential stroke patient to imaging is essential in a rapid stroke response. At our hospital, door-to-imaging time is comprised of 2 time periods: the time before a stroke is recognized, followed by the period after the stroke code is called during which the stroke team assesses and brings the patient to the computed tomography scanner. To control for delays due to triage, we isolated the time period after a potential stroke has been recognized, as few studies have examined the biases of stroke code responders. This "code-to-imaging time" (CIT) encompassed the time …

Efficacy And Safety Of Eslicarbazepine Acetate Monotherapy In Patients Converting From Carbamazepine., Ladislav Pazdera, Michael R. Sperling, Jay H. Harvey, Maria C. Sam, Laura A. Strom, David Blum, Todd Grinnell, Hailong Cheng

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate the influence of prior use of carbamazepine (CBZ) and other antiepileptic drugs (AEDs) with a putatively similar mechanism of action (inhibition of voltage-gated sodium channels; VGSCs) on seizure outcomes and tolerability when converting to eslicarbazepine acetate (ESL), using data pooled from 2 controlled conversion-to-ESL monotherapy trials (studies: 093-045, 093-046).

METHODS: Adults with treatment-resistant focal (partial-onset) seizures were randomized 2:1 to ESL 1600 or 1200 mg once daily. The primary efficacy endpoint was study exit (meeting predefined exit criteria related to worsening seizure control) versus an historical control group. Other endpoints included change in seizure frequency, responder rate, …

Effects Of Adjunctive Eslicarbazepine Acetate On Serum Lipids In Patients With Partial-Onset Seizures: Impact Of Concomitant Statins And Enzyme-Inducing Antiepileptic Drugs., Scott Mintzer, Robert T. Wechsler, Joanne B. Rogin, Barry E. Gidal, Matthias Schwab, Elinor Ben-Menachem, Mar Carreño, Patrício Soares Da Silva, Joana Moreira, Yan Li, David Blum, Todd Grinnell

Department of Neurology Faculty Papers

PURPOSE: To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences.

SUBJECTS AND METHODS: We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period.

KEY FINDINGS: In total, 426 and 1021 placebo- and ESL-treated …

Closed-Loop Stimulation Of Temporal Cortex Rescues Functional Networks And Improves Memory., Youssef Ezzyat, Paul A. Wanda, Deborah F. Levy, Allison Kadel, Ada Aka, Isaac Pedisich, Michael R. Sperling, Ashwini Sharan, Bradley C. Lega, Alexis Burks, Robert E. Gross, Cory S. Inman, Barbara C. Jobst, Mark A. Gorenstein, Kathryn A. Davis, Gregory A. Worrell, Michal T. Kucewicz, Joel M. Stein, Richard Gorniak, Sandhitsu R. Das, Daniel S. Rizzuto, Michael J. Kahana

Department of Neurology Faculty Papers

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target …

Electrical Stimulation Modulates High Γ Activity And Human Memory Performance., Michal T. Kucewicz, Brent M. Berry, Vaclav Kremen, Laura R. Miller, Fatemeh Khadjevand, Youssef Ezzyat, Joel M. Stein, Paul Wanda, Michael R. Sperling, Richard Gorniak, Md, Kathryn A. Davis, Barbara C. Jobst, Robert E. Gross, Bradley Lega, S Matt Stead, Daniel S. Rizzuto, Michael J. Kahana, Gregory A, Worrell

Department of Neurology Faculty Papers

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We …

Consensus Guidelines For Newborn Screening, Diagnosis And Treatment Of Infantile Krabbe Disease., Jennifer M. Kwon, Dietrich Matern, Joanne Kurtzberg, Lawrence Wrabetz, Michael H. Gelb, David A. Wenger, Can Ficicioglu, Amy T. Waldman, Barbara K. Burton, Patrick V. Hopkins, Joseph J. Orsini

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurodegenerative genetic disorder caused by deficiency of galactocerebrosidase. Patients with the infantile form of Krabbe disease can be treated at a presymptomatic stage with human stem cell transplantation which improves survival and clinical outcomes. However, without a family history, most cases of infantile Krabbe disease present after onset of symptoms and are ineligible for transplantation. In 2006, New York began screening newborns for Krabbe disease to identify presymptomatic cases. To ensure that those identified with infantile disease received timely treatment, New York public health and medical systems took steps to accurately diagnose and rapidly …

Timing Of Vessel Imaging For Suspected Large Vessel Occlusions Does Not Affect Groin Puncture Time In Transfer Patients With Stroke., John W. Liang, Laura Stein, Natalie Wilson, Johanna T. Fifi, Stanley Tuhrim, Mandip S. Dhamoon

Department of Neurology Faculty Papers

BACKGROUND: Access to endovascular therapy (ET) in cases of acute ischemic stroke may be limited, and rapid transfer of eligible patients to hospitals with endovascular capability is needed.

OBJECTIVE: To determine the optimal timing of diagnostic CT angiography to confirm large vessel occlusion (LVO).

METHODS: Of 57 emergency department transfers to Mount Sinai Hospital (MSH) for possible ET from January 2015 through March 2016, 39 (68%) underwent ET, among whom 22 (56%) had CT angiography before transfer and 17 (44%) had CT angiography on arrival. We compared mean outside hospital arrival to groin puncture (OTG) time between the two groups …

Sex Differences In Outcomes After Stroke In Patients With Diabetes In Ontario, Canada., Mandip S. Dhamoon, John W. Liang, Limei Zhou, Melissa Stamplecoski, Moira K. Kapral, Baiju R. Shah

Department of Neurology Faculty Papers

BACKGROUND: Outcomes after stroke in those with diabetes are not well characterized, especially by sex and age. We sought to calculate the sex- and age-specific risk of cardiovascular outcomes after ischemic stroke among those with diabetes.

METHODS: Using population-based demographic and administrative health-care databases in Ontario, Canada, all patients with diabetes hospitalized with index ischemic stroke between April 1, 2002, and March 31, 2012, were followed for death, stroke, and myocardial infarction (MI). The Kaplan-Meier survival analysis and Fine-Gray competing risk models estimated hazards of outcomes by sex and age, unadjusted and adjusted for demographics and vascular risk factors.

RESULTS: …

Advances In The Diagnosis, Immunopathogenesis And Therapies Of Igm-Anti-Mag Antibody-Mediated Neuropathies., Marinos Dalakas

Department of Neurology Faculty Papers

Polyneuropathy with immunoglobulin M (IgM) monoclonal gammopathy is the most common paraproteinemic neuropathy, comprising a clinicopathologically and immunologically distinct entity. The clinical spectrum spans from distal paresthesias and mild gait imbalance to more severe sensory ataxia, with falls and a varying degree of distal sensorimotor deficits. In approximately 75% of patients, the monoclonal IgM immunoreacts with myelin-associated glycoprotein (MAG) and sulfoglucuronyl glycosphingolipid (SGPG), or other peripheral nerve glycolipids that serve as antigens. These antibodies are considered pathogenic because IgM and complement are deposited on the myelin sheath, splitting the myelin lamellae, while adoptive transfer of patients' IgM into susceptible host …

Lacosamide And Levetiracetam Have No Effect On Sharp-Wave Ripple Rate, Jan Kudlacek, Jan Chvojka, Antonin Posusta, Lubica Kovacova, Seung Bong Hong, Shennan A. Weiss, Md, Phd, Kamila Volna, Petr Marusic, Jakub Otahal, Premysl Jiruska

Department of Neurology Faculty Papers

Pathological high-frequency oscillations are a novel marker used to improve the delineation of epileptogenic tissue and, hence, the outcome of epilepsy surgery. Their practical clinical utilization is curtailed by the inability to discriminate them from physiological oscillations due to frequency overlap. Although it is well documented that pathological HFOs are suppressed by antiepileptic drugs (AEDs), the effect of AEDs on normal HFOs is not well known. In this experimental study, we have explored whether physiological HFOs (sharp-wave ripples) of hippocampal origin respond to AED treatment. The results show that application of a single dose of levetiracetam or lacosamide does not …

Intermediate-Term Risk Of Stroke Following Cardiac Procedures In A Nationally Representative Data Set., Laura Stein, Alison Thaler, John W. Liang, Stanley Tuhrim, Amit S. Dhamoon, Mandip S. Dhamoon

Department of Neurology Faculty Papers

BACKGROUND: Studies on stroke risk following cardiac procedures addressed only perioperative and long-term risk following limited higher-risk procedures, were poorly generalizable, and often failed to stratify by stroke type. We calculated stroke risk in the intermediate risk period following cardiac procedures compared with common noncardiac surgeries and medical admissions.

METHODS AND RESULTS: The Nationwide Readmissions Database contains readmission data for 49% of US admissions in 2013. We compared age-adjusted stroke readmission rates up to 90 days postdischarge. We used Cox regression to calculate hazard ratios, up to 1 year, of stroke risk comparing transcatheter aortic valve replacement versus surgical aortic …

Interaction Of Rna-Binding Protein Hur And Mir-466i Regulates Gm-Csf Expression., Jing Chen, William Adamiak, Ganlei Huang, Ulus Atasoy, Abdolmohamad M. Rostami, Shiguang Yu

Department of Neurology Faculty Papers

Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by T helper 17 (Th17) cells plays an essential role in autoimmune diseases. Transcriptional regulation of Th17 cell differentiation has been extensively studied, but post-transcriptional regulation of Th17 cell differentiation has remained less well characterized. The RNA-binding protein HuR functions to promote the stability of target mRNAs via binding the AU-rich elements of the 3' untranslated region (3'UTR) of numerous pro-inflammatory cytokines including IL-4, IL-13, IL-17 and TNF-α. However, whether HuR regulates GM-CSF expression in Th17 cells has not been fully investigated. Here we showed that HuR conditional knockout (KO) Th17 cells have decreased GM-CSF …

Widespread Theta Synchrony And High-Frequency Desynchronization Underlies Enhanced Cognition., E. A. Solomon, J. E. Kragel, Michael R. Sperling, Ashwini Sharan, G. Worrell, M. Kucewicz, C. S. Inman, B. Lega, K. A. Davis, J. M. Stein, B. C. Jobst, K. A. Zaghloul, S. A. Sheth, D. S. Rizzuto, M. J. Kahana

Department of Neurology Faculty Papers

The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, …

Evaluation Of Perampanel As Monotherapy For Focal Seizures: Experience From Open-Label Extension Studies, Patrick Kwan, Scott Mintzer, Antonio Laurenza, Anna Patten, Karen Cartwright, Formerly: Eisai Ltd.

Department of Neurology Faculty Papers

Perampanel, a selective, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, is approved for adjunctive treatment of focal seizures, with or without secondarily generalized seizures, and for primary generalized tonic–clonic seizures in patients with epilepsy aged ≥ 12 years. Perampanel was recently approved for monotherapy use for focal seizures in the U.S.A. Anti-seizure drug monotherapy may be preferable to polytherapy, which is generally associated with increased toxicity, non-compliance, and cost. Here, we report cases where patients had converted to perampanel monotherapy during open-label extension (OLEx) portions of 9 Phase II and III studies. Of 2245 patients who enrolled in the OLEx studies, …

Fremanezumab For The Preventive Treatment Of Chronic Migraine., Stephen D. Silberstein, David W. Dodick, Marcelo E. Bigal, Paul P. Yeung, Peter J. Goadsby, Tricia Blankenbiller, Melissa Grozinski-Wolff, Ronghua Yang, Yuju Ma, Ernesto Aycardi

Department of Neurology Faculty Papers

BACKGROUND: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two fremanezumab dose regimens with placebo for the prevention of chronic migraine.

METHODS: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), fremanezumab monthly (675 mg at baseline and 225 mg at …

Spectrophotometric Analysis Of Thrombolytic Activity: Sata Assay, Masumeh Zamanlu, Morteza Eskandani, Reza Mohammadian, Nazila Entekhabi, Mohammad Rafi, Mehdi Farhoudi

Department of Neurology Faculty Papers

Introduction: Measurement of thrombolytic activity i.e. clot lysis is crucial for research and development of novel thrombolytics. It is also a key factor in assessment of the effectiveness of conventionally used thrombolytic agents in the clinic, which are the choice effective therapies for myocardial infarction and ischemic stroke. Previous methods used for the assessment of thrombolytic activity are often associated with some drawbacks such as being costly, time-consuming, complication and low accuracy. Here, we introduce a simple, economic, relatively accurate and fast method of spectrophotometric analysis of thrombolytic activity (SATA) assay, standardized by tissue plasminogen activator (tPA), which can quantitatively …

Bimodal Coupling Of Ripples And Slower Oscillations During Sleep In Patients With Focal Epilepsy., Inkyung Song, Iren Orosz, Inna Chervoneva, Zachary J. Waldman, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Noriko Salamon, Richard Gorniak, Sandra Dewar, Anatol Bragin, Jerome Engel, Michael R. Sperling, Richard Staba, Shennan A. Weiss

Department of Neurology Faculty Papers

OBJECTIVE: Differentiating pathologic and physiologic high-frequency oscillations (HFOs) is challenging. In patients with focal epilepsy, HFOs occur during the transitional periods between the up and down state of slow waves. The preferred phase angles of this form of phase-event amplitude coupling are bimodally distributed, and the ripples (80-150 Hz) that occur during the up-down transition more often occur in the seizure-onset zone (SOZ). We investigated if bimodal ripple coupling was also evident for faster sleep oscillations, and could identify the SOZ.

METHODS: Using an automated ripple detector, we identified ripple events in 40-60 min intracranial electroencephalography (iEEG) recordings from 23 …

Induction Of Peripheral Tolerance In Ongoing Autoimmune Inflammation Requires Interleukin 27 Signaling In Dendritic Cells, Rodolfo Thome, Jason N. Moore, Elisabeth R. Mari, Javad Rasouli

Department of Neurology Faculty Papers

Peripheral tolerance to autoantigens is induced via suppression of self-reactive lymphocytes, stimulation of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Interleukin (IL)-27 induces tolerogenic DCs and Treg cells; however, it is not known whether IL-27 is important for tolerance induction. We immunized wild-type (WT) and IL-27 receptor (WSX-1) knockout mice with MOG_35-55 for induction of experimental autoimmune encephalomyelitis and intravenously (i.v.) injected them with MOG_35-55 after onset of disease to induce i.v. tolerance. i.v. administration of MOG^35-55 reduced disease severity in WT mice, but was ineffective in Wsx^-/- mice. IL-27 signaling in DCs was …

Acute Stroke Multimodal Imaging: Present And Potential Applications Toward Advancing Care., Ivan Matos Diaz, John W. Liang, L. Velickovic Ostojic, Aaron P. Tansy

Department of Neurology Faculty Papers

In the past few decades, the field of acute ischemic stroke (AIS) has experienced significant advances in clinical practice. A core driver of this success has been the utilization of acute stroke imaging with an increasing focus on advanced methods including multimodal imaging. Such imaging techniques not only provide a richer understanding of AIS in vivo, but also, in doing so, provide better informed clinical assessments in management and treatment toward achieving best outcomes. As a result, advanced stroke imaging methods are now a mainstay of routine AIS practice that reflect best practice delivery of care. Furthermore, these imaging methods …

Erenumab (Amg 334) In Episodic Migraine: Interim Analysis Of An Ongoing Open-Label Study., Messoud Ashina, David Dodick, Peter J. Goadsby, Uwe Reuter, Stephen Silberstein, Feng Zhang, Julia R. Gage, Sunfa Cheng, Daniel D. Mikol, Robert A. Lenz

Department of Neurology Faculty Papers

OBJECTIVE: To assess long-term safety and efficacy of anti-calcitonin gene-related peptide receptor erenumab in patients with episodic migraine (EM).

METHODS: Patients enrolled in a 12-week, double-blind, placebo-controlled clinical trial (NCT01952574) who continued in an open-label extension (OLE) study will receive erenumab 70 mg every 4 weeks for up to 5 years. This preplanned interim analysis, conducted after all participants had completed the 1-year open-label follow-up, evaluated changes in monthly migraine days (MMD), achievement of ≥50%, ≥75%, and 100% reductions, Headache Impact Test (HIT-6) score, Migraine-Specific Quality of Life (MSQ), Migraine Disability Assessment (MIDAS), and safety. Data reported as observed without …

The Rna-Binding Protein Hur Contributes To Neuroinflammation By Promoting C-C Chemokine Receptor 6 (Ccr6) Expression On Th17 Cells., Jing Chen, Jennifer L. Martindale, Carole Cramer, Myriam Gorospe, Ulus Atasoy, Paul D. Drew, Shiguang Yu

Department of Neurology Faculty Papers

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA …

Ibrutinib Unmasks Critical Role Of Bruton Tyrosine Kinase In Primary Cns Lymphoma., Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S. Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S. Tabar, Cameron W. Brennan, Igor T. Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Antonio Omuro, Elena Pentsova, Alissa A. Thomas, Elina Tsyvkin, Ariela Noy, M. Lia Palomba, Paul Hamlin, Craig S. Sauter, Craig H. Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C. Lallana, Vaios Hatzoglou, Anne S. Reiner, Philip H. Gutin, Jason T. Huse, Katherine S. Panageas, Thomas G. Graeber, Nikolaus Schultz, Lisa M. Deangelis, Ingo K. Mellinghoff

Department of Neurology Faculty Papers

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated …

Debate On Human Aging And Lifespan, Mohammad Rafi, Abass Alavi

Department of Neurology Faculty Papers

The issue of human lifespan has long been a matter of controversy among scientists. In spite of the recent claim by Dong et al that human lifespan is limited to 115 years, with the mounting improvements in biotechnology and scientific understanding of aging, we may be confident that aging will slow down over the course of the current century extending human longevity much longer than 115 years.

Tia1 Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia Promote Phase Separation And Alter Stress Granule Dynamics., Ian R. Mackenzie, Alexandra M. Nicholson, Mohona Sarkar, James Messing, Maria D. Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B. Perkerson, Aishe Kurti, Billie J. Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R. Hsiung, Charles Krieger, Melissa E. Murray, Masato Kato, John D. Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A. Zivkovic, Veronica Hirsch-Reinshagen, Raymond P. Roos, Stephan Züchner, Neill R. Graff-Radford, Ronald C. Petersen, Richard J. Caselli, Zbigniew K. Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W. Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B. Boylan, J. Paul Taylor, Rosa Rademakers

Department of Neurology Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10

Resolution Of Occlusive Carotid Artery Thrombus Treated With Anticoagulation As Demonstrated On Duplex Ultrasonography., Laura Stein, John W. Liang, Jesse Weinberger

Department of Neurology Faculty Papers

BACKGROUND AND PURPOSE: While the majority of cerebral ischemic events due to carotid occlusive disease result from atherosclerotic plaque rupture, intraluminal carotid artery thrombus occasionally occurs in patients without preexisting carotid atherosclerosis. Identification of nonatherosclerotic thrombus as the cause of the carotid occlusive disease can obviate the need for an interventional procedure, and resolution of thrombus can be monitored with B-mode duplex ultrasonography.

METHODS: We reviewed 3 patients treated on The Mount Sinai Hospital Stroke Unit with anticoagulation for nonatherosclerotic carotid thrombi and followed with serial Doppler ultrasonogrpahy for resolution of thrombus.

RESULTS: Occlusive carotid thrombus was successfully treated in …

Connecting The Brain To Itself Through An Emulation., Mijail D. Serruya

Department of Neurology Faculty Papers

Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as in vitro culture preparations or in vivo ectopic construct organoids. Arrays of modules can be constructed as early stage whole brain emulators, following canonical …

Presurgical Thalamic "Hubness" Predicts Surgical Outcome In Temporal Lobe Epilepsy., Xiaosong He, Gaelle E. Doucet, Dorian Pustina, Michael R. Sperling, Ashwini D. Sharan, Joseph I. Tracy

Department of Neurology Faculty Papers

OBJECTIVE: To characterize the presurgical brain functional architecture presented in patients with temporal lobe epilepsy (TLE) using graph theoretical measures of resting-state fMRI data and to test its association with surgical outcome.

METHODS: Fifty-six unilateral patients with TLE, who subsequently underwent anterior temporal lobectomy and were classified as obtaining a seizure-free (Engel class I, n = 35) vs not seizure-free (Engel classes II-IV, n = 21) outcome at 1 year after surgery, and 28 matched healthy controls were enrolled. On the basis of their presurgical resting-state functional connectivity, network properties, including nodal hubness (importance of a node to the network; …

Single-Fiber Electromyography In The Orbicularis Oculi Muscle In Patients With Ocular Myasthenia Gravis Symptoms: Does Abnormal Jitter Predict Response To Treatment?, Goran Rakocevic, Mark Moster, Mary Kay Floeter

Department of Neurology Faculty Papers

BACKGROUND: Seronegative ocular myasthenia gravis (OMG) is diagnosed by ocular symptoms with supporting SFEMG, typically of frontalis or extensor digitorum muscles. We aimed to determine the sensitivity and specificity of orbicularis oculi SFEMG to diagnose and exclude myasthenia gravis and predict response to therapy.

METHODS: Orbicularis oculi SFEMG studies were conducted in 142 consecutive patients with symptoms and/or findings of OMG and negative AChR antibody during the period of 5 years. Retrospective chart review was conducted 2 years after the SFEMG to determine whether treatments were given and responses to treatment.

RESULTS: Orbicularis oculi SFEMG was abnormal in 31 patients …