Neurology

Rissanen, Ina MD, PhD; Lucci, Carlo MD; Ghaznawi, Rashid MD; Hendrikse, Jeroen MD, PhD; Kappelle, L. Jaap MD, PhD; Geerlings, Mirjam I.; on behalf of the UCC-SMART-Study Group; on behalf of the UCC-SMART-Study Group; Visseren, Frank L.J. MD, PhD; Asselbergs, Folkert W. MD, PhD; Nathoe, Hendrik M. MD, PhD; Bots, Michiel L. MD, PhD; Emmelot- Vonk, Marielle H. MD, PhD; Jan de Borst, Gert MD, PhD; Leiner, Tim MD, PhD; de Jong, Pim A. MD, PhD; Lely, A. Titia MD, PhD; van der Kaaij, Niels P. MD, PhD; Ruigrok, Ynte M. MD, PhD; Verhaar, Marianne C. MD, PhD; Westerink, Jan MD, PhD

doi : 10.1212/WNL.0000000000012539

Volume 97(11), 14 September 2021, p e1063-e1074

To investigate the association of silent vascular lesions, imaging negative ischemia, and symptomatic cerebrovascular disease with long-term progression of brain atrophy and cerebrovascular lesions in patients with arterial disease.

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Reversible Ischemic Lesion Hypodensity in Acute Stroke CT Following Endovascular Reperfusion

Broocks, Gabriel MD; McDonough, Rosalie MD; Meyer, Lukas MD; Bechstein, Matthias MD; Kniep, Helge DiplIng; Schon, Gerhard MSc; Nawka, Marie Teresa MD; Fiehler, Jens MD; Hanning, Uta MD, MHBA; Sporns, Peter MD, MHBA; Barow, Ewgenia MD; Minnerup, Jens MD; Kemmling, Andre MD, MHBA

doi : 10.1212/WNL.0000000000012484

Volume 97(11), 14 September 2021, p e1075-e1084

In acute stroke, early ischemic lesion hypodensity on CT is considered the imaging hallmark of brain infarction, representing a state of irreversible tissue damage with a continual increase of net water uptake. This dogma, however, is challenged by rare cases of apparently reversed early lesion hypodensity after complete reperfusion. The purpose of this study was to investigate the occurrence of reversible ischemic edema after endovascular treatment.

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Alterations of Brain Metabolites in Adults With HIV: A Systematic Meta-analysis of Magnetic Resonance Spectroscopy Studies

Dahmani, Sophia*; Kaliss, Nicholas*; VanMeter, John W. PhD; Moore, David J. PhD; Ellis, Ronald J. MD, PhD; Jiang, Xiong PhD

doi : 10.1212/WNL.0000000000012394

Volume 97(11), 14 September 2021, p e1085-e1096

A meta-analysis of proton magnetic resonance spectroscopy studies to investigate alterations in brain metabolites in people with HIV (PWH), the relationship between metabolite alterations and combination antiretroviral therapy (cART), and the relationship between metabolite alterations and cognitive impairment.

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Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders

Sechi, Elia MD; Krecke, Karl N. MD; Messina, Steven A. MD; Buciuc, Marina MD; Pittock, Sean J. MD; Chen, John J. MD, PhD; Weinshenker, Brian G. MD; Lopez-Chiriboga, A. Sebastian MD; Lucchinetti, Claudia F. MD; Zalewski, Nicholas L. MD; Tillema, Jan Mendelt MD; Kunchok, Amy MD; Monaco, Salvatore MD; Morris, Padraig P. MD; Fryer, James P. MS; Nguyen, Adam; Greenwood, Tammy MS; Syc-Mazurek, Stephanie B. MD, PhD; Keegan, B. Mark MD; Flanagan, Eoin P. MD

doi : 10.1212/WNL.0000000000012467

Volume 97(11), 14 September 2021, p e1097-e1109

There are few studies comparing lesion evolution across different CNS demyelinating diseases, yet knowledge of this may be important for diagnosis and understanding differences in disease pathogenesis. We sought to compare MRI T2 lesion evolution in myelin oligodendrocyte glycoprotein immunoglobulin G (IgG)-associated disorder (MOGAD), aquaporin 4 IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD), and multiple sclerosis (MS).

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Association of Dipeptidyl Peptidase-4 Inhibitor Use and Amyloid Burden in Patients With Diabetes and AD-Related Cognitive Impairment

Jeong, Seong Ho MD*; Kim, Hye Ryun PhD*; Kim, Jeonghun PhD; Kim, Hankyeol MD; Hong, Namki MD; Jung, Jin Ho MD; Baik, Kyoungwon MD; Cho, Hanna MD, PhD; Lyoo, Chul Hyoung MD, PhD; Ye, Byoung Seok MD, PhD; Sohn, Young H. MD, PhD; Seong, Joon-Kyung PhD; Lee, Phil Hyu MD, PhD

doi : 10.1212/WNL.0000000000012534

Volume 97(11), 14 September 2021, p e1110-e1122

To investigate whether dipeptidyl peptidase-4 inhibitors (DPP-4i) have beneficial effects on amyloid aggregation and longitudinal cognitive outcome in diabetic Alzheimer disease-related cognitive impairment (ADCI).

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Association of Midlife Plasma Amyloid-[beta] Levels With Cognitive Impairment in Late Life: The ARIC Neurocognitive Study

Sullivan, Kevin J. PhD, MPH; Blackshear, Chad MS; Simino, Jeannette PhD; Tin, Adrienne PhD; Walker, Keenan A. PhD; Sharrett, A. Richey MD, DrPH; Younkin, Steven MD, PhD; Gottesman, Rebecca F. MD, PhD; Mielke, Michelle M. PhD; Knopman, David MD; Windham, B. Gwen MD; Griswold, Michael E. PhD; Mosley, Thomas H. PhD

doi : 10.1212/WNL.0000000000012482

Volume 97(11), 14 September 2021, p e1123-e1131

To evaluate the association between midlife plasma amyloid-[beta] (A[beta]1-42, A[beta]1-40, A[beta]42:A[beta]40) and risk of mild cognitive impairment (MCI) and dementia.

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Mortality in Patients With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study

Johnson, Emily L. MD; Krauss, Gregory L. MD; Kucharska-Newton, Anna PhD, MPH; Lam, Alice D. MD, PhD; Sarkis, Rani MD, MSc; Gottesman, Rebecca F. MD, PhD

doi : 10.1212/WNL.0000000000012483

Volume 97(11), 14 September 2021, p e1132-e1140

To determine the risk of mortality and causes of death in persons with late-onset epilepsy (LOE) compared to those without epilepsy in a community-based sample, adjusting for demographics and comorbid conditions.

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Clinical Course and Features of Seizures Associated With LGI1-Antibody Encephalitis

Smith, Kelsey M. MD; Dubey, Divyanshu MD; Liebo, Greta B. MD; Flanagan, Eoin P. MBBCh; Britton, Jeffrey W. MD

doi : 10.1212/WNL.0000000000012465

Volume 97(11), 14 September 2021, p e1141-e1149

To determine risk factors associated with clinical relapses and development of chronic epilepsy in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) immunoglobulin G encephalitis.

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Expanding Spectrum of Desmin-Related Myopathy, Long-term Follow-up, and Cardiac Transplantation

Shelly, Shahar MD*; Talha, Niaz MBBS*; Pereira, Naveen L. MD; Engel, Andrew G. MD; Johnson, Jonathan N. MD; Selcen, Duygu MD

doi : 10.1212/WNL.0000000000012542

Volume 97(11), 14 September 2021, p e1150-e1158

We aimed to determine the genetic and clinical phenotypes of patients with desmin-related myopathy and long-term outcomes after cardiac transplantation.

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Innovating Clinical Trials for Amyotrophic Lateral Sclerosis: Challenging the Established Order

van Eijk, Ruben P.A. MD, PhD; Nikolakopoulos, Stavros PhD; Roes, Kit C.B. PhD; Kendall, Lindsay MSc; Han, Steve S. MD, PhD; Lavrov, Arseniy MD, PhD; Epstein, Noam MD; Kliest, Tessa MSc; de Jongh, Adriaan D. MD; Westeneng, Henk-Jan MD; Al-Chalabi, Ammar MD, PhD; Van Damme, Philip MD, PhD; Hardiman, Orla MD, PhD; Shaw, Pamela J. MD, PhD; McDermott, Christopher J. MD, PhD; Eijkemans, Marinus J.C. PhD; van den Berg, Leonard H. MD, PhD

doi : 10.1212/WNL.0000000000012545

Volume 97(11), 14 September 2021, p 528-536

Development of effective treatments for amyotrophic lateral sclerosis (ALS) has been hampered by disease heterogeneity, a limited understanding of underlying pathophysiology, and methodologic design challenges. We have evaluated 2 major themes in the design of pivotal, phase 3 clinical trials for ALS-(1) patient selection and (2) analytical strategy-and discussed potential solutions with the European Medicines Agency. Several design considerations were assessed using data from 5 placebo-controlled clinical trials (n = 988), 4 population-based cohorts (n = 5,100), and 2,436 placebo-allocated patients from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. The validity of each proposed design modification was confirmed by means of simulation and illustrated for a hypothetical setting. Compared to classical trial design, the proposed design modifications reduce the sample size by 30.5% and placebo exposure time by 35.4%. By making use of prognostic survival models, one creates a potential to include a larger proportion of the population and maximize generalizability. We propose a flexible design framework that naturally adapts the trial duration when inaccurate assumptions are made at the design stage, such as enrollment or survival rate. In case of futility, the follow-up time is shortened and patient exposure to ineffective treatments or placebo is minimized. For diseases such as ALS, optimizing the use of resources, widening eligibility criteria, and minimizing exposure to futile treatments and placebo is critical to the development of effective treatments. Our proposed design modifications could circumvent important pitfalls and may serve as a blueprint for future clinical trials in this population.

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Quality Improvement in Neurology: Concussion Quality Measurement Set

Rose, Sean C. MD; Anderson, Wayne DO; Feinberg, Daniel MD; Ganesh, Aravind MD, DPhil, FRCPC; Green, Lauren DO; Jaffee, Michael MD; Kaplen, Michael Esq; Lorincz, Matthew MD, PhD; De Luigi, Arthur DO; Patel, Deepak MD; Tsao, Jack W. MD, DPhil; Lee, Erin; Webb, Adam MD

doi : 10.1212/WNL.0000000000012537

Volume 97(11), 14 September 2021, p 537-542

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Aducanumab, Amyloid Lowering, and Slowing of Alzheimer Disease

Salloway, Stephen MD, MS; Cummings, Jeffrey MD, ScD

doi : 10.1212/WNL.0000000000012451

Volume 97(11), 14 September 2021, p 543-544

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Prescribing Aducanumab in the Face of Meager Efficacy and Real Risks

Knopman, David S. MD; Perlmutter, Joel S. MD

doi : 10.1212/WNL.0000000000012452

Volume 97(11), 14 September 2021, p 545-547

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Area Postrema Syndrome as the Initial Presentation of Alexander Disease

Renaldo, Florence MD; Chalard, Francois MD; Valence, Stephanie MD, PhD; Burglen, Lydie MD, PhD; Rodriguez, Diana MD, PhD

doi : 10.1212/WNL.0000000000012462

Volume 97(11), 14 September 2021, p 548-549

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Two Mechanisms of Scapular Winging Visualized in a Patient With Parsonage-Turner Syndrome

Thompson, Austin R. BS; Ensrud, Erik R. MD

doi : 10.1212/WNL.0000000000012409

Volume 97(11), 14 September 2021, p 550

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Pearls & Oy-sters: Primary Cerebral Buerger Disease: A Rare Differential Diagnosis of Stroke in Young Adults

Kaiser, Daniel MD; Leonhardt, Georg K. MD; Weiss, Norbert MD; Radosa, Christoph G. MD; Linn, Jennifer MD; Gerber, Johannes C. MD; Puetz, Volker MD

doi : 10.1212/WNL.0000000000012140

Volume 97(11), 14 September 2021, p 551-554

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Clinical Reasoning: A 79-Year-Old Woman With Subacute Bilateral Visual Loss

Rossi, Simone MD; Amore, Giulia MD; Pensato, Umberto MD; D'Angelo, Roberto MD; Rinaldi, Rita MD; Guarino, Maria MD; Cortelli, Pietro MD, PhD

doi : 10.1212/WNL.0000000000012235

Volume 97(11), 14 September 2021, p e1159-e1165

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Teaching Video NeuroImage: Pupil-Sparing Infranuclear Third Nerve Palsy Pattern Caused by a Mesencephalic Stroke

Lahoz Fernandez, Paulo Eduardo MD; Brito, Vanessa de Sousa MD; Vieira Silveira, Coralia Gabrielle MD; Silva, Guilherme Diogo MD; Mutarelli, Eduardo Genaro MD, PhD, FAAN

doi : 10.1212/WNL.0000000000012189

Volume 97(11), 14 September 2021, p e1166-e1167

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