Neurology Commons^™

Automated Fiber Tract Reconstruction For Surgery Planning: Extensive Validation In Language-Related White Matter Tracts., Matteo Mancini, Sjoerd B. Vos, Vejay N. Vakharia, Aidan G. O'Keeffe, Karin Trimmel, Frederik Barkhof, Christian Dorfer, Salil Soman, Gavin P. Winston, Chengyuan Wu, John S. Duncan, Rachel Sparks, Sebastien Ourselin

Department of Neurosurgery Faculty Papers

Diffusion MRI and tractography hold great potential for surgery planning, especially to preserve eloquent white matter during resections. However, fiber tract reconstruction requires an expert with detailed understanding of neuroanatomy. Several automated approaches have been proposed, using different strategies to reconstruct the white matter tracts in a supervised fashion. However, validation is often limited to comparison with manual delineation by overlap-based measures, which is limited in characterizing morphological and topological differences. In this work, we set up a fully automated pipeline based on anatomical criteria that does not require manual intervention, taking advantage of atlas-based criteria and advanced acquisition protocols …

Erenumab In Chronic Migraine: Patient-Reported Outcomes In A Randomized Double-Blind Study., Richard B. Lipton, Stewart J. Tepper, Uwe Reuter, Stephen Silberstein, Walter F. Stewart, Jon Nilsen, Dean K. Leonardi, Pooja Desai, Sunfa Cheng, Daniel D. Mikol, Robert Lenz

Department of Neurology Faculty Papers

OBJECTIVE: To determine the effect of erenumab, a human monoclonal antibody targeting the calcitonin gene-related peptide receptor, on health-related quality of life (HRQoL), headache impact, and disability in patients with chronic migraine (CM).

METHODS: In this double-blind, placebo-controlled study, 667 adults with CM were randomized (3:2:2) to placebo or erenumab (70 or 140 mg monthly). Exploratory endpoints included migraine-specific HRQoL (Migraine-Specific Quality-of-Life Questionnaire [MSQ]), headache impact (Headache Impact Test-6 [HIT-6]), migraine-related disability (Migraine Disability Assessment [MIDAS] test), and pain interference (Patient-Reported Outcomes Measurement Information System [PROMIS] Pain Interference Scale short form 6b).

RESULTS: Improvements were observed for all endpoints in …

Cervical Posterior Longitudinal Ligament Ossification : Microscopy-Assisted Anterior Corpectomy And Fusion., Wanyi Wang, Tao Ding, James Harrop, Huilin Yang, Xiaofeng Gu, Dehong Feng, Yafeng Zhang, Hao Liu, Fenglin Tang, Yuntao Xue, Miao Lu, Chao Wu

Department of Neurosurgery Faculty Papers

OBJECTIVE: To explore the clinical efficacy and safety of microscopy-assisted anterior corpectomy and fusion for cervical ossification of the posterior longitudinal ligament (OPLL).

METHODS: A retrospective review of 32 cervical OPLL patients who underwent microscopy-assisted anterior corpectomy and fusion from June 2012 to March 2017 was carried out. Patients were evaluated with outcome metrics: Japanese Orthopaedic Association (JOA) scores (17 points method), visual analog scale (VAS), and radiographic parameters of the lordotic angle. The complications during treatment and follow-up were recorded.

RESULTS: This study included 32 patients (15 males and 17 females) with a mean age of 58.3 ± 2.9 …

Re-Code Dcm (Research Objectives And Common Data Elements For Degenerative Cervical Myelopathy): A Consensus Process To Improve Research Efficiency In Dcm, Through Establishment Of A Standardized Dataset For Clinical Research And The Definition Of The Research Priorities, Benjamin M. Davies, Danyal Z. Khan, Oliver D. Mowforth, Angus G.K. Mcnair, Toto Gronlund, Angelos G. Kolias, Lindsay Tetreault, Michelle L. Starkey, Iwan Sadler, Ellen Sarewitz, Delphine Houlton, Julia Carter, Sukhvinder Kalsi-Ryan, Bizhan Aarabi, Brian K. Kwon, Shekar N. Kurpad, James Harrop, Jefferson R. Wilson, Robert Grossman, Armin Curt, Michael G. Fehlings, Mark R.N. Kotter

Department of Neurosurgery Faculty Papers

Study Design: Mixed-method consensus process.

Objectives: Degenerative cervical myelopathy (DCM) is a common and disabling condition that arises when mechanical stress damages the spinal cord as a result of degenerative changes in the surrounding spinal structures. RECODE-DCM (REsearch Objectives and Common Data Elements for Degenerative Cervical Myelopathy) aims to improve efficient use of health care resources within the field of DCM by using a multi-stakeholder partnership to define the DCM research priorities, to develop a minimum dataset for DCM clinical studies, and confirm a definition of DCM.

Methods: This requires a multi-stakeholder partnership and multiple parallel consensus development processes. It …

Lewy Body Dementia Association's Research Centers Of Excellence Program: Inaugural Meeting Proceedings., Bethany Peterson, Melissa Armstrong, Douglas Galasko, James E. Galvin, Jennifer Goldman, David Irwin, Henry Paulson, Daniel Kaufer, James Leverenz, Angela Lunde, Ian G. Mckeith, Andrew Siderowf, Angela Taylor, Katherine Amodeo, Matt Barrett, Kimiko Domoto-Reilly, John Duda, Stephen Gomperts, Neill Graff-Radford, Samantha Holden, Lawrence Honig, Daniel Huddleston, Carol Lippa, Irene Litvan, Carol Manning, Karen Marder, Charbel Moussa, Chiadi Onyike, Fernando Pagan, Alexander Pantelyat, Victoria Pelak, Kathleen Poston, Joseph Quinn, Irene Richard, Liana S. Rosenthal, Marwan Sabbagh, Douglas Scharre, Sharon Sha, Holly Shill, Yasar Torres-Yaghi, Tina Christie, Todd Graham, Ian Richards, Mike Koehler, Brad Boeve

Department of Neurology Faculty Papers

The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator's meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or …

Human Verbal Memory Encoding Is Hierarchically Distributed In A Continuous Processing Stream., Michal T. Kucewicz, Krishnakant Saboo, Brent M. Berry, Vaclav Kremen, Laura R. Miller, Fatemeh Khadjevand, Cory S. Inman, Paul Wanda, Michael R. Sperling, Richard Gorniak, Kathryn A. Davis, Barbara C. Jobst, Bradley Lega, Sameer A. Sheth, Daniel S. Rizzuto, Ravishankar K. Iyer, Michael J. Kahana, Gregory A. Worrell

Department of Neurology Faculty Papers

Processing of memory is supported by coordinated activity in a network of sensory, association, and motor brain regions. It remains a major challenge to determine where memory is encoded for later retrieval. Here, we used direct intracranial brain recordings from epilepsy patients performing free recall tasks to determine the temporal pattern and anatomical distribution of verbal memory encoding across the entire human cortex. High γ frequency activity (65-115 Hz) showed consistent power responses during encoding of subsequently recalled and forgotten words on a subset of electrodes localized in 16 distinct cortical areas activated in the tasks. More of the high …

Study Of The Cytological Features Of Bone Marrow Mesenchymal Stem Cells From Patients With Neuromyelitis Optica., Chunsheng Yang, Yang Yang, Li Ma, Guang-Xian Zhang, Fu-Dong Shi, Yaping Yan, Guoqiang Chang

Department of Neurology Faculty Papers

Neuromyelitis optica (NMO) is a refractory autoimmune inflammatory disease of the central nervous system without an effective cure. Autologous bone marrow‑derived mesenchymal stem cells (BM‑MSCs) are considered to be promising therapeutic agents for this disease due to their potential regenerative, immune regulatory and neurotrophic effects. However, little is known about the cytological features of BM‑MSCs from patients with NMO, which may influence any therapeutic effects. The present study aimed to compare the proliferation, differentiation and senescence of BM‑MSCs from patients with NMO with that of age‑ and sex‑matched healthy subjects. It was revealed that there were no significant differences in …

Guidelines Of The International Headache Society For Controlled Trials Of Acute Treatment Of Migraine Attacks In Adults: Fourth Edition., Hans-Christoph Diener, Cristina Tassorelli, David W. Dodick, Stephen Silberstein, Richard B. Lipton, Messoud Ashina, Werner J. Becker, Michel D. Ferrari, Peter J. Goadsby, Patricia Pozo-Rosich, Shuu-Jiun Wang, Jay Mandrekar

Department of Neurology Faculty Papers

The quality of clinical trials is an essential part of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of the Guidelines for controlled trials of drugs in migraine. Scientific and clinical developments in headache medicine led to second and third editions in 2000 and 2012, respectively. The current, fourth edition of the Guidelines retains the structure and much content from previous editions. However, it also incorporates evidence from clinical trials published after the third edition as well as feedback from meetings with regulators, …

Development And Validation Of The Fsiq-Rms: A New Patient-Reported Questionnaire To Assess Symptoms And Impacts Of Fatigue In Relapsing Multiple Sclerosis, Stacie Hudgens, René Schüler, Jonathan Stokes, Sonya Eremenco, Elke Hunsche, Thomas P. Leist

Department of Neurology Faculty Papers

Objectives: A new patient-reported outcome (PRO) instrument to measure fatigue symptoms and impacts in relapsing multiple sclerosis (RMS) was developed in a qualitative stage, followed by psychometric validation and migration from paper to an electronic format.

Methods: Adult patients with relapsing-remitting multiple sclerosis (RRMS) were interviewed to elicit fatigue-related symptoms and impacts. A draft questionnaire was debriefed in cognitive interviews with further RRMS patients, and revised. Content confirmation interviews were conducted with patients with progressive-relapsing multiple sclerosis (PRMS) and relapsing secondary-progressive multiple sclerosis (RSPMS). Psychometric analyses used data from adult patients with different RMS subtypes and matched non-RMS controls in …

A Closer Look At Arsa Activity In A Patient With Metachromatic Leukodystrophy., Kathleen Doherty, S. Barron Frazier, Matthew Clark, Anna Childers, Sumit Pruthi, David A. Wenger, Jessica Duis

Department of Neurology Faculty Papers

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease mainly caused by a deficiency of arylsulfatase A activity. The typical clinical course of patients with the late infantile form includes a regression in motor skills with progression to dysphagia, seizures, hypotonia and death. We present a case of a 4-year-old female with rapidly progressive developmental regression with loss of motor milestones, spasticity and dysphagia. MRI showed volume loss and markedly abnormal deep white matter. Enzymatic testing in one laboratory showed arylsulfatase A activity in their normal range. However, extraction of urine showed a large increase in sulfatide excretion in …

Early Progression Of Krabbe Disease In Patients With Symptom Onset Between 0 And 5 Months., Maria L. Beltran-Quintero, Nicholas A. Bascou, Michele D. Poe, David A. Wenger, Carlos A. Saavedra-Matiz, Matthew J. Nichols, Maria L. Escolar

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurological disorder caused by a deficiency in the lysosomal enzyme, β-galactocerebrosidase, resulting in demyelination of the central and peripheral nervous systems. If left without treatment, Krabbe disease results in progressive neurodegeneration with reduced quality of life and early death. The purpose of this prospective study was to describe the natural progression of early onset Krabbe disease in a large cohort of patients.

METHODS: Patients with early onset Krabbe disease were prospectively evaluated between 1999 and 2018. Data sources included diagnostic testing, parent questionnaires, standardized multidisciplinary neurodevelopmental assessments, and neuroradiological and neurophysiological tests.

RESULTS: We …

Hemi-Eses Associated With Agenesis Of The Corpus Callosum And Normal Cognition., Mahmoud Mohammadi, Safoura Kowkabi, Ali Akbar Asadi-Pooya, Reza Azizi Malamiri, Reza Shervin Badv

Department of Neurology Faculty Papers

• Corpus callosum plays the important role in bilateral synchronous expression of focal discharges of ESES.
• Sparing dominant hemisphere form continuous spike and slow waves during sleep accounts for normal cognitive scores.
• Early detection and treatment of ESES have a great impact on cognitive and language scores and final prognosis.

Gitelman Syndrome: A Rare Cause Of Seizure Disorder And A Systematic Review., Muhammad Asim Shahzad, Maryam Mukhtar, Asrar Ahmed, Waqas Ullah, Rehan Saeed, Mohsin Hamid

Abington Jefferson Health Papers

Gitelman syndrome is one of the few inherited causes of metabolic alkalosis due to salt losing tubulopathy. It is caused by tubular defects at the level of distal convoluted tubules, mimicking a thiazide-like tumor. It usually presents in late childhood or in teenage as nonspecific weakness, fatigability, polyuria, and polydipsia but very rarely with seizures. It is classically associated with hypokalemia, hypomagnesemia, hypocalciuria, hyperreninemia, and hyperaldosteronism. However, less frequently, it can present with normal magnesium levels. It is even rarer to find normomagnesemic patients of GS who develop seizures as the main complication since hypomagnesemia is considered the principal etiology …

Combination Therapy With Fingolimod And Neural Stem Cells Promotes Functional Myelination, Yuan Zhang, Xin-Yu Lu, Ze-Qin Ye, Bogoljub Ciric, Cun-Gen Ma, A. M. Rostami, Xing Li, Guang-Xian Zhang

Department of Neurology Faculty Papers

Myelination, which occurs predominantly postnatally and continues throughout life, is important for proper neurologic function of the mammalian central nervous system (CNS). We have previously demonstrated that the combination therapy of fingolimod (FTY720) and transplanted neural stem cells (NSCs) had a significantly enhanced therapeutic effect on the chronic stage of experimental autoimmune encephalomyelitis, an animal model of CNS autoimmunity, compared to using either one of them alone. However, reduced disease severity may be secondary to the immunomodulatory effects of FTY720 and NSCs, while whether this therapy directly affects myelinogenesis remains unknown. To investigate this important question, we used three myelination …

Repeat Neuro-Imaging In Patients Presenting With Traumatic Extra-Axial Intracranial Hemorrhage, Austin Saline, Anthony Stefanelli, Md, Omaditya Khanna, Md, Sol Feuerwerker, Somnath Das, Evan Selzer

Phase 1

Introduction: The management of extra-axial intracranial hemorrhage patients is complicated and lacks a systemic algorithm to determine the timing and necessity of head computed tomography (HCT). However, repeat HCTs weakly predict the need for an intervention after mild traumatic brain injury (TBI).

Objective: This study focused on assessing the safety, efficacy, and necessity of obtaining serial HCTs in patients presenting with subdural hemorrhages.

Methods: A retrospective chart review was conducted of patients with subdural hemorrhages and a GCS between 13-15 on admission (n=116). The total number of HCTs, time between repeat HCTs, duration of hospital stay, and factors necessitating surgery …

Improving Door-To-Groin Time For Stroke-Alert Patients Arriving At Tjuh, Megan Carney, Mackenzie O'Connor, Robin Dharia, Md

Phase 1

Introduction: Due to the large number of endovascular-eligible acute ischemic stroke patients, the urgent nature of effective stroke treatment protocols has become increasingly recognized at TJUH. Due to the hospital’s unique situation with two city blocks between the ER and endovascular lab, in-hospital factors remain a significant reason for the delay of treatment.

Objective: The purpose was to conduct a quality-assurance trial to determine whether standardizing imaging modalities for inpatient and ER stroke-alert patients at our institution would improve door-to-puncture times.

Methods: After implementation of the new stroke alert protocol, data were prospectively collected for six months for two groups …

Network Influence Of The Cerebellum For Predicting Dbs Response In Patients With Advanced Parkinson’S Disease, Lucy Li, Jennifer Muller, Sara Thalheimer, Mackenzie D. Silverman, Mahdi Alizadeh, Tsao-Wei Liang, Kelly Layton, Daniel Kremens, Victor Romo, Feroze Mohamed, Chengyuan Wu

Phase 1

Introduction: Deep brain stimulation (DBS) is a treatment option for reducing motor symptoms in patients with Parkinson’s Disease (PD) when first-line medication becomes ineffective. Existing literature has hypothesized that the clinical outcome of DBS may depend on brain connectivity profiles of the stimulation site to distant brain regions. However, the potential of brain connectivity profiles to predict response to DBS in PD remains unclear.

Objective: This study aimed to investigate how changes in structural and functional connectivity may relate to patient response to DBS, through the examination of brain network changes using graph theory.

Methods: Ten patients with advanced PD …

The Insula And Its Epilepsies, Barbara C. Jobst, Jorge Gonzalez-Martinez, Jean Isnard, Philippe Kahane, Nuria Lacuey, Samden D. Lahtoo, Dang K. Nguyen, Chengyuan Wu, Fred Lado

Department of Neurosurgery Faculty Papers

Insular seizures are great mimickers of seizures originating elsewhere in the brain. The insula is a highly connected brain structure. Seizures may only become clinically evident after ictal activity propagates out of the insula with semiology that reflects the propagation pattern. Insular seizures with perisylvian spread, for example, manifest first as throat constriction, followed next by perioral and hemisensory symptoms, and then by unilateral motor symptoms. On the other hand, insular seizures may spread instead to the temporal and frontal lobes and present like seizures originating from these regions. Due to the location of the insula deep in the brain, …

Hemispheric Regional Based Analysis Of Diffusion Tensor Imaging And Diffusion Tensor Tractography In Patients With Temporal Lobe Epilepsy And Correlation With Patient Outcomes., Mahdi Alizadeh, Lauren Kozlowski, Jennifer Muller, Neha Ashraf, Shiva Shahrampour, Feroze B. Mohamed, Chengyuan Wu, Ashwini Sharan

Department of Neurosurgery Faculty Papers

Imaging in the field of epilepsy surgery remains an essential tool in terms of its ability to identify regions where the seizure focus might present as a resectable area. However, in many instances, an obvious structural abnormality is not visualized. This has created the opportunity for new approaches and imaging innovation in the field of epilepsy, such as with Diffusion Tensor Imaging (DTI) and Diffusion Tensor Tractography (DTT). In this study, we aim to evaluate the use of DTI and DTT as a predictive model in the field of epilepsy, specifically Temporal Lobe Epilepsy (TLE), and correlate their clinical significance …

Quantitative Clinical And Autoimmune Assessments In Stiff Person Syndrome: Evidence For A Progressive Disorder., Goran Rakocevic, Harry Alexopoulos, Marinos C. Dalakas

Department of Neurology Faculty Papers

BACKGROUND: Stiff Person Syndrome (SPS) is an under-diagnosed disorder that affects mobility and the quality of life of affected patients. The aim of the study is to describe the natural history of SPS, the extent of accumulated disability and the associated clinical and immunological features in patients followed for up to 8 years in a single center.

METHODS: Our collective cohort included 57 SPS patients. Additionally, 32 of these patients were examined every 6 months for a two-year period in a longitudinal study protocol, to assess disease progression using quantitative measures of stiffness and heightened sensitivity.

RESULTS: The most frequent …

Randomized Trial Of Polychromatic Blue-Enriched Light For Circadian Phase Shifting, Melatonin Suppression, And Alerting Responses., J. P. Hanifin, S. W. Lockley, K. Cecil, K. West, M. Jablonski, B. Warfield, M. James, M. Ayers, B. Byrne, E. Gerner, C. Pineda, M. Rollag, G. C. Brainard

Department of Neurology Faculty Papers

Wavelength comparisons have indicated that circadian phase-shifting and enhancement of subjective and EEG-correlates of alertness have a higher sensitivity to short wavelength visible light. The aim of the current study was to test whether polychromatic light enriched in the blue portion of the spectrum (17,000 K) has increased efficacy for melatonin suppression, circadian phase-shifting, and alertness as compared to an equal photon density exposure to a standard white polychromatic light (4000 K). Twenty healthy participants were studied in a time-free environment for 7 days. The protocol included two baseline days followed by a 26-h constant routine (CR1) to assess initial …

Rheumatoid Meningitis Sine Arthritis., Cathy Lee-Ching, Lawrence C. Kenyon, Matthew Berk, Chantel Park

Department of Medicine Faculty Papers

Rheumatoid meningitis is a rare and very serious extra-articular manifestation of rheumatoid arthritis. We present a case of a 7()year-old female with no history of arthritis who developed stroke-like symptoms, seizures, psychosis and compulsive behavior. Serial brain magnetic resonance images (MRI) over four months demonstrated progressive interhemispheric meningeal thickening. She had mild lymphocytic pleocytosis on the cerebrospinal fluid analysis and serum anti-cyclic citrullinated peptide antibodies resulted positive in high titers. She underwent a brain biopsy showing necrotizing granulomas consistent with rheumatoid meningitis. Her symptoms resolved with treatment with glucocorticoids and cyclophosphamide. She has not been diagnosed with rheumatoid arthritis even …

Genome-Wide Mega-Analysis Identifies 16 Loci And Highlights Diverse Biological Mechanisms In The Common Epilepsies., Bassel Abou-Khalil, Pauls Auce, Andreja Avbersek, Melanie Bahlo, David J. Balding, Thomas Bast, Larry Baum, Albert J. Becker, Felicitas Becker, Bianca Berghuis, Samuel F. Berkovic, Katja E. Boysen, Jonathan P. Bradfield, Lawrence C. Brody, Russell J. Buono, Ellen Campbell, Gregory D. Cascino, Claudia B. Catarino, Gianpiero L. Cavalleri, Stacey S. Cherny, Krishna Chinthapalli, Alison J. Coffey, Alastair Compston, Antonietta Coppola, Patrick Cossette, John J. Craig, Gerrit-Jan De Haan, Peter De Jonghe, Carolien G.F. De Kovel, Norman Delanty, Chantal Depondt, Orrin Devinsky, Dennis J. Dlugos, Colin P. Doherty, Christian E. Elger, Johan G. Eriksson, Thomas N. Ferraro, Martha Feuch, Ben Francis, Andre Franke, Jacqueline A. French, Saskia Freytag, Verena Gaus, Eric B. Geller, Christian Gieger, Tracy Glauser, Simon Glynn, David B. Goldstein, Hongsheng Gui, Youling Guo, Kevin F. Haas, Hakon Hakonarson, Kerstin Hallmann, Sheryl Haut, Erin L. Heinzen, Ingo Helbig, Christian Hengsbach, Helle Hjalgrim, Michele Iacomino, Andrés Ingason, Jennifer Jamnadas-Khoda, Michael R. Johnson, Reetta Kälviäinen, Anne-Mari Kantanen, Dalia Kasperavičiūte, Dorothee Kasteleijn-Nolst Trenite, Heidi E. Kirsch, Robert C. Knowlton, Bobby P.C. Koeleman, Roland Krause, Martin Krenn, Wolfram S. Kunz, Ruben Kuzniecky, Patrick Kwan, Dennis Lal, Yu-Lung Lau, Anna-Elina Lehesjoki, Holger Lerche, Costin Leu, Wolfgang Lieb, Dick Lindhout, Warren D. Lo, Iscia Lopes-Cendes, Daniel H. Lowenstein, Alberto Malovini, Anthony G. Marson, Thomas Mayer, Mark Mccormack, James L. Mills, Nasir Mirza, Martina Moerzinger, Rikke S. Møller, Anne M. Molloy, Hiltrud Muhle, Mark Newton, Ping-Wing Ng, Markus M. Nöthen, Peter Nürnberg, Terence J. O’Brien, Karen L. Oliver, Palotie Palotie, Faith Pangilinan, Sarah Peter, Slavé Petrovski, Annapurna Poduri, Michael Privitera, Rodney Radtke, Sarah Rau, Philipp S. Reif, Eva M. Reinthaler, Felix Rosenow, Josemir W. Sander, Thomas Sander, Theresa Scattergood, Steven C. Schachter, Christoph J. Schankin, Ingrid E. Scheffer, Bettina Schmitz, Susanne Schoch, Pak C. Sham, Jerry J. Shih, Graeme J. Sills, Sanjay M. Sisodiya, Lisa Slattery, Alexander Smith, David F. Smith, Michael C. Smith, Philip E. Smith, Anja C.M. Sonsma, Doug Speed, Michael R. Sperling, Bernhard J. Steinhoff, Ulrich Stephani, Remi Stevelink, Konstantin Strauch, Pasquale Striano, Hans Stroink, Rainer Surges, K. Meng Tan, Liu Lin Thio, G. Neil Thomas, Marian Todaro, Rossana Tozzi, Maria S. Vari, Ellen P.G. Vining, Frank Visscher, Sarah Von Spiczak, Nicole M. Walley, Yvonne G. Weber, Zhi Wei, Judith Weisenberg, Christopher D. Whelan, Peter Widdess-Walsh, Markus Wolff, Wolking Wolking, Wanling Yang, Federico Zara, Fritz Zimprich

Department of Neurology Faculty Papers

The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the …

Levels Of Par-1 Kinase Determine The Localization Of Bruchpilot At The Drosophila Neuromuscular Junction Synapses., Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh P. Wairkar

Farber Institute for Neuroscience Faculty Papers

Functional synaptic networks are compromised in many neurodevelopmental and neurodegenerative diseases. While the mechanisms of axonal transport and localization of synaptic vesicles and mitochondria are relatively well studied, little is known about the mechanisms that regulate the localization of proteins that localize to active zones. Recent finding suggests that mechanisms involved in transporting proteins destined to active zones are distinct from those that transport synaptic vesicles or mitochondria. Here we report that localization of BRP-an essential active zone scaffolding protein in Drosophila, depends on the precise balance of neuronal Par-1 kinase. Disruption of Par-1 levels leads to excess accumulation of …

Medial Temporal Lobe Functional Connectivity Predicts Stimulation-Induced Theta Power., E. A. Solomon, J. E. Kragel, R. Gross, B. Lega, M. R. Sperling, G. Worrell, S. A. Sheth, K. A. Zaghloul, B. C. Jobst, J. M. Stein, S. Das, R. Gorniak, C. S. Inman, S. Seger, D. S. Rizzuto, M. J. Kahana

Department of Neurology Faculty Papers

Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked increases in theta (5-8 Hz) power, particularly when stimulation was applied in or adjacent to white matter. Stimulation tended …

Triggers, Protectors, And Predictors In Episodic Migraine., Michael J. Marmura

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: A wide variety of triggers prompt attacks in episodic migraine. Although experimental triggers such as glyceryl trinitrate reliably produce migraine, natural triggers are much less predictable and vary in importance between individuals. This review describes the most common triggers in episodic migraine and provides strategies for managing them in clinical practice.

RECENT FINDINGS: Multiple migraine attack triggers have been established based on patient surveys, diary studies, and clinical trials. Stress, menstrual cycle changes, weather changes, sleep disturbances, alcohol, and other foods are among the most common factors mentioned. Clinical studies have verified that fasting, premenstrual periods in …

Spinal Infections: From Prevention To Cure, James Harrop

Department of Neurosurgery Faculty Papers

AOSpine North America (AOSNA) is honored to have the ability to present this focused issue on spinal infections. As we are all aware, spinal infections are a prevalent part of our daily treatment regimen as spine surgeons—whether these infections are in our elective practice or emergencies.

Distinct Role Of Il-27 In Immature And Lps-Induced Mature Dendritic Cell-Mediated Development Of Cd4, Fang Zhou, Guang-Xian Zhang, A. M. Rostami

Department of Neurology Faculty Papers

Interleukin-27 (IL-27) plays an important role in regulation of anti-inflammatory responses and autoimmunity; however, the molecular mechanisms of IL-27 in modulation of immune tolerance and autoimmunity have not been fully elucidated. Dendritic cells (DCs) play a central role in regulating immune responses mediated by innate and adaptive immune systems, but regulatory mechanisms of DCs in CD4⁺ T cell-mediated immune responses have not yet been elucidated. Here we show that IL-27 treated mature DCs induced by LPS inhibit immune tolerance mediated by LPS-stimulated DCs. IL-27 treatment facilitates development of the CD4⁺ CD127⁺3G11⁺ regulatory T cell subset …

Ketamine For Refractory Headache: A Retrospective Analysis., Eric S. Schwenk, Amir C. Dayan, Ashwin Rangavajjula, Marc C. Torjman, Mauricio G. Hernandez, Clinton G. Lauritsen, Stephen D. Silberstein, William B. Young, Eugene R. Viscusi

Department of Anesthesiology Faculty Papers

BACKGROUND AND OBJECTIVES: The burden of chronic headache disorders in the United States is substantial. Some patients are treatment refractory. Ketamine, an N-methyl-D-aspartate antagonist, provides potent analgesia in subanesthetic doses in chronic pain, and limited data suggest it may alleviate headache in some patients.

METHODS: We performed a retrospective study of 61 patients admitted over 3 years for 5 days of intravenous therapy that included continuous ketamine to determine responder rate and patient and ketamine infusion characteristics. Pain ratings at 2 follow-up visits were recorded. An immediate responder was a patient with decrease of 2 points or greater in the …

Therapeutic Effect Of Rho Kinase Inhibitor Fsd-C10 In A Mouse Model Of Alzheimer's Disease., Qing-Fang Gu, Jie-Zhong Yu, Hao Wu, Yan-Hua Li, Chun-Yun Liu, Ling Feng, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma

Department of Neurology Faculty Papers

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer's disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long-term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long-term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD-C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin-1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of …