Merino, Jose G. MD, MPhil; Editor-in-Chief, Neurology(R)
doi : 10.1212/WNL.0000000000012541
Volume 97(11), 14 September 2021, p 513-514
Wardlaw, Joanna M. MD, FRCR
doi : 10.1212/WNL.0000000000012540
Volume 97(11), 14 September 2021, p 515-516
Hershey, Linda A. MD, PhD; Tarawneh, Rawan MD
doi : 10.1212/WNL.0000000000012453
Volume 97(11), 14 September 2021, p 517-518
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.
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.
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.
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).
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).
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.
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.
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.
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.
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.
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
Salloway, Stephen MD, MS; Cummings, Jeffrey MD, ScD
doi : 10.1212/WNL.0000000000012451
Volume 97(11), 14 September 2021, p 543-544
Knopman, David S. MD; Perlmutter, Joel S. MD
doi : 10.1212/WNL.0000000000012452
Volume 97(11), 14 September 2021, p 545-547
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
Thompson, Austin R. BS; Ensrud, Erik R. MD
doi : 10.1212/WNL.0000000000012409
Volume 97(11), 14 September 2021, p 550
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
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
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
Camelo-Filho, Antonio Edvan MD*; Estephan, Eduardo de Paula MD, PhD*; Heise, Carlos Otto MD, PhD; Zanoteli, Edmar MD, PhD
doi : 10.1212/WNL.0000000000012180
Volume 97(11), 14 September 2021, p e1168-e1169
Ganesh, Aravind MD, DPhil, FRCPC; Galetta, Steven MD
doi : 10.1212/WNL.0000000000012544
Volume 97(11), 14 September 2021, p 555
Machado, Calixto
doi : 10.1212/WNL.0000000000012546
Volume 97(11), 14 September 2021, p 555-556
Vogrig, Alberto; Valente, Mariarosaria; Nilo, Annacarmen; Gigli, Gian Luigi
doi : 10.1212/WNL.0000000000012547
Volume 97(11), 14 September 2021, p 556
Abdo, Wilson F.; Van der Hoeven, Johannes G.
doi : 10.1212/WNL.0000000000012548
Volume 97(11), 14 September 2021, p 557
Ganesh, Aravind MD, DPhil, FRCPC; Galetta, Steven MD
doi : 10.1212/WNL.0000000000012549
Volume 97(11), 14 September 2021, p 557
Heldner, Mirjam R.
doi : 10.1212/WNL.0000000000012551
Volume 97(11), 14 September 2021, p 558-559
Zerna, Charlotte; Volny, Ondrej
doi : 10.1212/WNL.0000000000012550
Volume 97(11), 14 September 2021, p 559
Malhotra, Ajay; Khunte, Mihir
doi : 10.1212/WNL.0000000000012552
Volume 97(11), 14 September 2021, p 559-560
Zerna, Charlotte; Volny, Ondrej
doi : 10.1212/WNL.0000000000012553
Volume 97(11), 14 September 2021, p 560
doi : 10.1212/WNL.0000000000011945
Volume 97(11), 14 September 2021, p 561-563
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