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In 2007, the detection of IgG antibodies against the N-methyl-d-aspartate receptor in young women with encephalopathy opened a new field in neurology: the study of encephalitides with antibodies directed against well-defined antigens on the surfaces of central nervous system neurons.1 In 2010, the Oxford ...

During the past 20 years, the clinical syndrome of behavioral variant frontotemporal dementia (bvFTD) has become better recognized, but it still represents a challenging diagnosis for many neurologists and psychiatrists, not to mention primary care physicians. Simultaneously, dramatic advances in our understanding of the neurobiological underpinnings of the ...

Original Investigation 
Bastien Joubert, MD; Margaux Saint-Martin, MSc; Nelly Noraz, PhD; Géraldine Picard, MSc; Veronique Rogemond, PhD; François Ducray, MD, PhD; Virginie Desestret, MD, PhD; Dimitri Psimaras, MD; Jean-Yves Delattre, MD, PhD; Jean-Christophe Antoine, MD; Jérôme Honnorat, MD, PhD

Importance  Autoantibodies against contactin-associated protein-like 2 (CASPR2) are observed in several neurological syndromes, including neuromyotonia (NMT), Morvan syndrome (MoS), and limbic encephalitis.

Objective  To characterize the clinical and biological presentations of patients with anti-CASPR2 antibodies in the cerebrospinal fluid (CSF).

Design, Setting, and Participants  We ...

Editorial: Contactin-Associated Protein-like 2 Antibodies; Christian G. Bien, MD
Original Investigation  FREE
Kamalini G. Ranasinghe, MBBS, PhD; Katherine P. Rankin, PhD; Peter S. Pressman, MD; David C. Perry, MD; Iryna V. Lobach, PhD; William W. Seeley, MD; Giovanni Coppola, MD; Anna M. Karydas, BA; Lea T. Grinberg, MD, PhD; Tal Shany-Ur, PhD; Suzee E. Lee, MD; Gil D. Rabinovici, MD; Howard J. Rosen, MD; Maria Luisa Gorno-Tempini, MD, PhD; Adam L. Boxer, MD, PhD; Zachary A. Miller, MD; Winston Chiong, MD, PhD; Mary DeMay, MD; Joel H. Kramer, PsyD; Katherine L. Possin, PhD; Virginia E. Sturm, PhD; Brianne M. Bettcher, PhD; Michael Neylan, BA; Diana D. Zackey, BA; Lauren A. Nguyen, MA; Robin Ketelle, MS, RN; Nikolas Block, BA; Teresa Q. Wu, BA; Alison Dallich, BS; Natanya Russek, BS; Alyssa Caplan, BA; Daniel H. Geschwind, MD, PhD; Keith A. Vossel, MD, MSc; Bruce L. Miller, MD
Includes: Supplemental Content

Importance  Clearer delineation of the phenotypic heterogeneity within behavioral variant frontotemporal dementia (bvFTD) will help uncover underlying biological mechanisms and improve clinicians’ ability to predict disease course and to design targeted management strategies.

Objective  To identify subtypes of bvFTD syndrome based on distinctive patterns of atrophy ...

Editorial: Behavioral Variant Frontotemporal Dementia; David S. Knopman, MD
Review 
Vivek Misra, MD; William J. Hicks, MD; Farhaan Vahidy, MD; Susan Alderman, RN; Sean I. Savitz, MD

Importance  Clinical trials are under way to test the safety and efficacy of different types of cell therapies in patients with ischemic stroke. The informed consent process for recruitment of patients with stroke in cell therapy trials is complex and requires extensive discussions on multiple aspects.

Observations...

Comment & Response 
S. Ali Nabavizadeh, MD

To the Editor I read with interest the evidence-based review by Jones and Cascino.1 The authors performed a systematic review of 27 studies with 3163 patients who underwent epilepsy surgery and demonstrated that magnetic resonance imaging–identified mesial temporal sclerosis is associated with a favorable outcome after surgery, ...

Comment & Response 
Gregory D. Cascino, MD; Amy L. Jones, MD

In Reply We thank Nabavizadeh for his interest in our article.1 We appreciate the importance of surgical technique in the care and management of patients with medial temporal lobe epilepsy (MTLE) associated with mesial temporal sclerosis (MTS). The operative strategy in 25 of the 27 studies appeared ...

Comment & Response 
Paolo Vitali, MD, PhD; Marina Pan, MD; Eduardo Caverzasi, MD

To the Editor The study by Eisenmenger et al1 published in JAMA Neurology explored the progression of diffusion-weighted imaging (DWI) hyperintensities in a large cohort (37 patients) of sporadic Creutzfeldt-Jakob disease (sCJD) over time by using a visual assessment approach previously applied by our group.2

Comment & Response 
Laura Eisenmenger, MD; Simon Mead, PhD; Harpreet Hyare, PhD

In Reply We thank Vitali and colleagues for their correspondence. We studied serial diffusion-weighted brain magnetic resonance imaging in sporadic Creutzfeldt-Jakob disease using a visual rating method.1 The rarity and very rapid clinical declines seen in this disease make serial imaging studies of a large patient sample ...

Correction  FREE

In the Original Investigation titled “Blood Biomarkers for Brain Injury in Concussed Professional Ice Hockey Players,”1 published online March 13, 2014, and also in the June 2014 print issue of JAMA Neurology, there were errors in Table 1 and Figure 2A. In Table 1, the upper ...

Editorial 
Nicolas Dupré, MD, MSc, FCRP(C); Guy Rouleau, MD, PhD, FRCP(C)

Huntington disease (HD) is a progressive disorder causing motor, cognitive, and psychiatric disturbances, with a mean age at onset of 35 to 44 years and a median survival time of 15 to 18 years.1 Although most cases have the classic triplet repeat expansion, HD specialists all follow ...

Original Investigation 
Paul K. Crane, MD, MPH; Laura E. Gibbons, PhD; Kristen Dams-O’Connor, PhD; Emily Trittschuh, PhD; James B. Leverenz, MD; C. Dirk Keene, MD, PhD; Joshua Sonnen, MD; Thomas J. Montine, MD, PhD; David A. Bennett, MD; Sue Leurgans, PhD; Julie A. Schneider, MD, MS; Eric B. Larson, MD, MPH
Includes: Supplemental Content

Importance  The late effects of traumatic brain injury (TBI) are of great interest, but studies characterizing these effects are limited.

Objective  To determine whether TBI with loss of consciousness (LOC) is associated with an increased risk for clinical and neuropathologic findings of Alzheimer disease (AD), Parkinson ...

Original Investigation 
Samuel Groeschel, MD; Jörn-Sven Kühl, MD; Annette E. Bley, MD; Christiane Kehrer, MD; Bernhard Weschke, MD; Michaela Döring, MD; Judith Böhringer, PhD; Johanna Schrum, MD; René Santer, PhD; Alfried Kohlschütter, PhD; Ingeborg Krägeloh-Mann, MD, PhD; Ingo Müller, PhD
Includes: Supplemental Content

Importance  Allogeneic hematopoietic stem cell transplantation (HSCT) has been the only treatment option clinically available during the last 20 years for juvenile metachromatic leukodystrophy (MLD), reported with variable outcome and without comparison with the natural course of the disease.

Objective  To compare the long-term outcome of ...

Original Investigation 
Louise-Laure Mariani, MD; Christelle Tesson, PhD; Perrine Charles, MD, PhD; Cécile Cazeneuve, MD; Valérie Hahn, MS; Katia Youssov, MD; Leorah Freeman, MD, PhD; David Grabli, MD, PhD; Emmanuel Roze, MD, PhD; Sandrine Noël, BSc; Jean-Noel Peuvion, BSc; Anne-Catherine Bachoud-Levi, MD, PhD; Alexis Brice, MD; Giovanni Stevanin, PhD; Alexandra Durr, MD, PhD
Includes: Supplemental Content

Importance  Huntington disease (HD), a prototypic monogenic disease, is caused by an expanded CAG repeat in the HTT gene exceeding 35 units. However, not all patients with an HD phenotype carry the pathological expansion in HTT, and the positive diagnosis rate is poor.

Objectives  To ...

Editorial: The Puzzle of Huntington Disease Phenocopies; Nicolas Dupré, MD, MSc, FCRP(C); Guy Rouleau, MD, PhD, FRCP(C)
Images in Neurology 
Tadeu A. Fantaneanu, MD; Shamik Bhattacharyya, MD; Tracey A. Milligan, MD; Page B. Pennell, MD

This case report describes a 57-year-old man with hemochromatosis and panhypopituitarism who presented with a 6-month history of word-finding difficulty, short-term memory loss, and rapidly cycling symptoms.

Comment & Response 
Daniel Weintraub, MD; Helen C. Kales, MD; Connie Marras, MD, PhD

In Reply We appreciate the thoughtful comments by Malaty et al regarding our recent publication in JAMA Neurology reporting an increased risk for mortality associated with antipsychotic use in Parkinson disease (PD).1 They noted that the study did not focus on patients with PD and psychosis specifically, ...

Comment & Response 
Irene A. Malaty, MD; Michael S. Okun, MD; Michael Jaffee, MD

To the Editor Weintraub et al1 recently published an article in JAMA Neurology on the mortality risk associated with antipsychotic use in Parkinson disease (PD). We do not deny that the collective evidence has strongly suggested that neuroleptics are associated with increased mortality in elderly populations and ...

Editorial 
Henry J. Kaminski, MD

With the initial identification in 1976 of antibodies directed toward the acetylcholine receptor (AChR) in the serum of patients with myasthenia gravis (MG),1 it became clear that upwards of 20% of patients with clinical and electrophysiological evidence of a neuromuscular disorder lacked such antibodies. Was this because ...

The emergence of oral-administered small molecules in multiple sclerosis (MS) therapeutics affords patients potential benefits of improved adherence, convenience, and increased effectiveness within a therapeutic area, which has otherwise benefited predominantly from injectable disease-modifying medicines for several decades. Switching from injectable to oral MS treatment may also improve ...

Original Investigation 
Ludwig Kappos, MD; David K. B. Li, MD; Olaf Stüve, MD; Hans-Peter Hartung, MD; Mark S. Freedman, MD; Bernhard Hemmer, MD; Peter Rieckmann, MD; Xavier Montalban, MD; Tjalf Ziemssen, MD; Brian Hunter, PhD; Sophie Arnould, PhD; Erik Wallström, MD; Krzysztof Selmaj, MD
Includes: Supplemental Content

Importance  This dose-blinded extension of the phase 2 BOLD (BAF312 on MRI Lesion Given Once Daily) Study in relapsing-remitting multiple sclerosis provides evidence on disease activity and safety of a range of siponimod doses for up to 24 months.

Objective  To assess the safety and efficacy ...

Editorial: Conclusions From the BOLD Phase 2 Extension Study of Siponimod; Edward R. Hammond, MD, PhD, MPH

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