Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

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

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; …