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Spotlight on the May 18 Issue
José G. Merino
doi : 10.1212/WNL.0000000000011925
May 18, 2021; 96 (20)
Rational Utilization of Critical Care Services for Intracerebral Hemorrhage
Matthew B. Maas
doi : 10.1212/WNL.0000000000011926
May 18, 2021; 96 (20)
In Vivo Detection of Underlying SynucleinopathiesAre We There Yet?
David Irwin, Marie Saint-Hilaire
doi : 10.1212/WNL.0000000000011929
May 18, 2021; 96 (20)
Is OCT a Viable Tool to Monitor Disease-Modifying Treatments in RRMS Yet?
Ahmed T. Toosy, Kush Kapur, Kavita V. Nair
doi : 10.1212/WNL.0000000000011928
May 18, 2021; 96 (20)
IVIG and Small Fiber NeuropathyThe Ongoing Search for Evidence
Christopher H. Gibbons, Christopher Klein
doi : 10.1212/WNL.0000000000011921
May 18, 2021; 96 (20)
Novel Score for Stratifying Risk of Critical Care Needs in Patients With Intracerebral Hemorrhage
Roland Faigle, Bridget J. Chen, Rachel Krieger, Elisabeth B. Marsh, Ayham Alkhachroum, Wei Xiong, Victor C. Urrutia, Rebecca F. Gottesman
doi : 10.1212/WNL.0000000000011927
May 18, 2021; 96 (20)
Objective To develop a risk prediction score identifying patients with intracerebral hemorrhage (ICH) at low risk for critical care.
Contribution of Racial and Ethnic Differences in Cerebral Small Vessel Disease Subtype and Burden to Risk of Cerebral Hemorrhage Recurrence
Juan Pablo Castello, Marco Pasi, Jessica R. Abramson, Axana Rodriguez-Torres, Sandro Marini, Stacie Demel, Lee Gilkerson, Patryk Kubiszewski, Andreas Charidimou, Christina Kourkoulis, Zora DiPucchio, Kristin Schwab, M. Edip Gurol, Anand Viswanathan, Christopher D. Anderson, Carl D. Langefeld, Matthew L. Flaherty, Amytis Towfighi, Steven M. Greenberg, Daniel Woo, Jonathan Rosand, Alessandro Biffi
doi : 10.1212/WNL.0000000000011932
May 18, 2021; 96 (20)
Objective Black and Hispanic survivors of intracerebral hemorrhage (ICH) are at higher risk of recurrent intracranial bleeding. MRI-based markers of chronic cerebral small vessel disease (CSVD) are consistently associated with recurrent ICH. We therefore sought to investigate whether racial/ethnic differences in MRI-defined CSVD subtype and severity contribute to disparities in ICH recurrence risk.
Association Between Hemostatic Profile and MigraineA Mendelian Randomization Analysis
Yanjun Guo, Pamela M. Rist, Maria Sabater-Lleal, Paul de Vries, Nicholas Smith, Paul M Ridker, Tobias Kurth, Daniel I. Chasman
doi : 10.1212/WNL.0000000000011931
May 18, 2021; 96 (20)
Objective To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis.
Effect of Adrenomedullin on Migraine-Like Attacks in Patients With Migraine
Hashmat Ghanizada, Mohammad Al-Mahdi Al-Karagholi, Nanna Arngrim, Mette M?rch-Rasmussen, Christopher S. Walker, Debbie L. Hay, Messoud Ashina
doi : 10.1212/WNL.0000000000011930
May 18, 2021; 96 (20)
Objective To determine whether the IV infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients.
Association of Neighborhood Context, Cognitive Decline, and Cortical Change in an Unimpaired Cohort
Jack F.V. Hunt, Nicholas M. Vogt, Erin M. Jonaitis, William R. Buckingham, Rebecca L. Koscik, Megan Zuelsdorff, Lindsay R. Clark, Carey E. Gleason, Menggang Yu, Ozioma Okonkwo, Sterling C. Johnson, Sanjay Asthana, Barbara B. Bendlin, Amy J.H. Kind
doi : 10.1212/WNL.0000000000011918
May 18, 2021; 96 (20)
Objective To test the hypothesis that neighborhood-level disadvantage is associated with longitudinal measures of neurodegeneration and cognitive decline in an unimpaired cohort.
In Vivo Diagnosis of SynucleinopathiesA Comparative Study of Skin Biopsy and RT-QuIC
Vincenzo Donadio, Zerui Wang, Alex Incensi, Giovanni Rizzo, Enrico Fileccia, Veria Vacchiano, Sabina Capellari, Martina Magnani, Cesa Scaglione, Michelangelo Stanzani Maserati, Patrizia Avoni, Rocco Liguori, Wenquan Zou
doi : 10.1212/WNL.0000000000011935
May 18, 2021; 96 (20)
Objective To determine whether (1) immunofluorescence is a reproducible technique in detecting misfolded ?-synuclein in skin nerves and subsequently whether (2) immunofluorescence and real-time quaking-induced conversion (RT-QuIC) (both in skin and CSF) show a comparable in vivo diagnostic accuracy in distinguishing synucleinopathies from non-synucleinopathies in a large cohort of patients.
Modulation of Retinal Atrophy With Rituximab in Multiple Sclerosis
Jeffrey Lambe, Hunter Risher, Angeliki G. Filippatou, Olwen C. Murphy, Elias S. Sotirchos, Henrik Ehrhardt, Esther Ogbuokiri, Nicole Pellegrini, Brandon Toliver, Nicholas J. Luciano, Simidele Davis, Nicholas Fioravante, Ohemaa Kwakyi, Jerry L. Prince, Peter A. Calabresi, Kathryn C. Fitzgerald, Shiv Saidha
doi : 10.1212/WNL.0000000000011933
May 18, 2021; 96 (20)
Objective To investigate the effects of rituximab on retinal atrophy in patients with relapsing-remitting multiple sclerosis (RRMS), we performed serial optical coherence tomography (OCT) scans among a cohort of patients with RRMS on rituximab and compared rates of ganglion cell + inner plexiform layer (GCIPL) atrophy to those observed among age- and sex-matched glatiramer acetate (GA)–and natalizumab-treated patients with RRMS and healthy controls (HCs).
Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy
Margot Geerts, Bianca T.A. de Greef, Maurice Sopacua, Sander M.J. van Kuijk, Janneke G.J. Hoeijmakers, Catharina G. Faber, Ingemar S.J. Merkies
doi : 10.1212/WNL.0000000000011919
May 18, 2021; 96 (20)
Objective This is the first double-blind randomized controlled trial evaluating the efficacy and safety of IV immunoglobulin (IVIG) vs placebo in patients with idiopathic small fiber neuropathy (I-SFN).
Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis
Gregory S. Day, Melanie Y. Yarbrough, Peter K?rtvelyessy, Harald Prüss, Robert C. Bucelli, Marvin J. Fritzler, Warren Mason, David F. Tang-Wai, Claude Steriade, Julien Hébert, Rachel L. Henson, Elizabeth M. Herries, Jack H. Ladenson, A. Sebastian Lopez-Chiriboga, Neill R. Graff-Radford, John C. Morris, Anne Fagan
doi : 10.1212/WNL.0000000000011937
May 18, 2021; 96 (20)
Objective To determine whether neuronal and neuroaxonal injury, neuroinflammation, and synaptic dysfunction associate with clinical course and outcomes in antibody-mediated encephalitis (AME), we measured biomarkers of these processes in CSF from patients presenting with AME and cognitively normal individuals.
What Is the Role of the Cytosolic DNA Response in Neurodegeneration?
Eduardo Benarroch
doi : 10.1212/WNL.0000000000011944
May 18, 2021; 96 (20)
Value-Generating Exploratory Trials in Neurodegenerative Dementias
Lauren G. Friedman, Nicholas McKeehan, Yuko Hara, Jeffrey L. Cummings, Dawn C. Matthews, Jian Zhu, Richard C. Mohs, Deli Wang, Suzanne B. Hendrix, Melanie Quintana, Lon S. Schneider, Michael Grundman, Samuel P. Dickson, Howard H. Feldman, Judith Jaeger, Elizabeth C. Finger, J. Michael Ryan, Debra Niehoff, Susan L-J. Dickinson, Jessica T. Markowitz, Meriel Owen, Alessio Travaglia, Howard M. Fillit
doi : 10.1212/WNL.0000000000011774
May 18, 2021; 96 (20)
Drug development for Alzheimer disease and other neurodegenerative dementias, including frontotemporal dementia, has experienced a long history of phase 2 and phase 3 clinical trials that failed to show efficacy of investigational drugs. Despite differences in clinical and behavioral characteristics, these disorders have shared pathologies and face common challenges in designing early-phase trials that are predictive of late-stage success. Here, we discuss exploratory clinical trials in neurodegenerative dementias. These are generally phase 1b or phase 2a trials that are designed to assess pharmacologic effects and rely on biomarker outcomes, with shorter treatment durations and fewer patients than traditional phase 2 studies. Exploratory trials can establish go/no-go decision points, support proof of concept and dose selection, and terminate drugs that fail to show target engagement with suitable exposure and acceptable safety profiles. Early failure saves valuable resources including opportunity costs. This is especially important for programs in academia and small biotechnology companies but may be applied to high-risk projects in large pharmaceutical companies to achieve proof of concept more rapidly at lower costs than traditional approaches. Exploratory studies in a staged clinical development program may provide promising data to warrant the substantial resources needed to advance compounds through late-stage development. To optimize the design and application of exploratory trials, the Alzheimer's Drug Discovery Foundation and the Association for Frontotemporal Degeneration convened an advisory panel to provide recommendations on outcome measures and statistical considerations for these types of studies and study designs that can improve efficiency in clinical development.
Radiation-Induced Bilateral Oculomotor Nerve Palsy 20 Years After Radiation Treatment
Justin J. Grassmeyer, J. Americo Fernandes, Jason T. Helvey, Sachin Kedar
doi : 10.1212/WNL.0000000000011936
May 18, 2021; 96 (20)
Rare, Intradural, Double Draining Veins in a Spinal Dural Arteriovenous Fistula
Xiaodong Niu, Tongyu Wang, Cong Wu, Jin Li
doi : 10.1212/WNL.0000000000011955
May 18, 2021; 96 (20)
Pearls & Oy-sters: Cerebral Microbleeds Caused by Adrenocortical Adenoma-Related Primary Aldosteronism
Sun Min Lee, Yong Jun Choi, Kihwang Lee, Hyeung Kyoo Kim, Jin-Sun Park, Yong Cheol Lim, Jang-Hee Kim, So Young Moon
doi : 10.1212/WNL.0000000000011934
May 18, 2021; 96 (20)
Opinion & Special Articles: Shared Decision-Making During the COVID-19 PandemicThree Bullets in 3 Hemispheres
Tej D. Azad
doi : 10.1212/WNL.0000000000011811
May 18, 2021; 96 (20)
Patients with traumatic brain injury may be dependent on the decision-making of their families. Restrictive visitation policies implemented during the coronavirus disease 2019 (COVID-19) pandemic disproportionately affect these patients and their families. This narrative aims to illustrate this phenomenon and catalyze discussions regarding the need for careful evaluation of restrictive family visitation policies and exceptions that may be required for patients with brain injuries.
Teaching NeuroImages: Rare Adult-Onset Genetic Leukoencephalopathy
Pavankumar Rudrabhatla, Sekar Sabarish, Harikrishnan Ramachandran, Sruthi S. Nair
doi : 10.1212/WNL.0000000000011233
May 18, 2021; 96 (20)
Teaching Video NeuroImages: Jaw Clonus in Amyotrophic Lateral Sclerosis
Abeer Goel, Ritu Shree, Heena Kathuria, Sahil Mehta, Vivek Lal, Karthik Vinay Mahesh
doi : 10.1212/WNL.0000000000011127
May 18, 2021; 96 (20)
Editors' Note: In Vivo Distribution of ?-Synuclein in Multiple Tissues and Biofluids in Parkinson Disease
Aravind Ganesh, Steven Galetta
doi : 10.1212/WNL.0000000000011942
May 18, 2021; 96 (20)
Reader Response: In Vivo Distribution of ?-Synuclein in Multiple Tissues and Biofluids in Parkinson Disease
Christopher Gibbons, Vincenzo Donadio, Claudia Sommer, Rocco Liguori, Giuseppe Lauria Pinter, Raffaella Lombardi, Kathrin Doppler, Roy Freeman
doi : 10.1212/WNL.0000000000011941
May 18, 2021; 96 (20)
Author Response: In Vivo Distribution of ?-Synuclein in Multiple Tissues and Biofluids in Parkinson Disease
Thomas Beach, Lana M. Chahine, Charles H. Adler, Brit Mollenhauer
doi : 10.1212/WNL.0000000000011938
May 18, 2021; 96 (20)
Editors' Note: Longitudinal Changes of Brain Microstructure and Function in Nonconcussed Female Rugby Players
Aravind Ganesh, Steven Galetta
doi : 10.1212/WNL.0000000000011943
May 18, 2021; 96 (20)
Reader Response: Longitudinal Changes of Brain Microstructure and Function in Nonconcussed Female Rugby Players
Pashtun Shahim, Ramon Diaz-Arrastia
doi : 10.1212/WNL.0000000000011939
May 18, 2021; 96 (20)
Author Response: Longitudinal Changes of Brain Microstructure and Function in Nonconcussed Female Rugby Players
Kathryn Y. Manning, Ravi S. Menon
doi : 10.1212/WNL.0000000000011940
May 18, 2021; 96 (20)
Long-term Employment Outcomes After Epilepsy Surgery in Childhood
doi : 10.1212/WNL.0000000000011418
May 18, 2021; 96 (20)
Quality Improvement in NeurologyHeadache Quality Measurement Set
doi : 10.1212/WNL.0000000000011419
May 18, 2021; 96 (20)
