Neurology

Chuck, Carlin C. BS*; Kim, Daniel BA*; Kalagara, Roshini BA; Rex, Nathaniel BS; Madsen, Tracy E. MD, PhD; Mahmoud, Leana PharmD; Thompson, Bradford B. MD; Jones, Richard N. ScD; Furie, Karen L. MD, MPH; Reznik, Michael E. MD

doi : 10.1212/WNL.0000000000012856

Volume 97(21), 23 November 2021, p e2054-e2064

Andexanet alfa was recently approved as a reversal agent for the factor Xa inhibitors (FXais) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. We aimed to explore potential clinical implications of andexanet alfa in FXai-associated ICH in this simulation study.

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CSF Synaptic Biomarkers in the Preclinical Stage of Alzheimer Disease and Their Association With MRI and PET: A Cross-sectional Study

Mila-Aloma, Marta MSc; Brinkmalm, Ann PhD; Ashton, Nicholas J. PhD; Kvartsberg, Hlin PhD; Shekari, Mahnaz MSc; Operto, Gregory PhD; Salvado, Gemma MSc; Falcon, Carles PhD; Gispert, Juan Domingo PhD; Vilor-Tejedor, Natalia PhD; Arenaza-Urquijo, Eider M. MSc; Grau-Rivera, Oriol PhD; Sala-Vila, Aleix PhD; Sanchez-Benavides, Gonzalo PhD; Gonzalez-de-Echavarri, Jose Maria MD; Minguillon, Carolina PhD; Fauria, Karine PhD; Ninerola-Baizan, Aida PhD; Perissinotti, Andres MD, PhD; Kollmorgen, Gwendlyn PhD; Suridjan, Ivonne PhD; Zetterberg, Henrik MD, PhD; Molinuevo, Jose Luis MD, PhD; Blennow, Kaj MD, PhD; Suarez-Calvet, Marc MD PhD; on behalf of the ALFA Study; on behalf of the ALFA Study; Beteta, Annabella MD; Cacciaglia, Raffaele PhD; Canas, Alba MS; Deulofeu, Carme PhD; Cumplido, Irene MSc; Dominguez, Ruth MS; Emilio, Maria MS; Fuentes, Sherezade MS; Hernandez, Laura MS; Huesa, Gema PhD; Huguet, Jordi PhD; Marne, Paula MS; Mench[spacing acute]on, Tania MS; Polo, Albina MD; Pradas, Sandra MS; Soteras, Anna MS; Vilanova, Marc BSc

doi : 10.1212/WNL.0000000000012853

Volume 97(21), 23 November 2021, p e2065-e2078

To determine whether CSF synaptic biomarkers are altered in the early preclinical stage of the Alzheimer continuum and associated with Alzheimer disease (AD) risk factors, primary pathology, and neurodegeneration markers.

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Association of CT-Based Hypoperfusion Index With Ischemic Core Enlargement in Patients With Medium and Large Vessel Stroke

Nomani, Ali Z. MD, MSc, FCPS; Kamtchum Tatuene, Joseph MD, MAS, MRes, FEBN; Rempel, Jeremy L. MD, FRCPC; Jeerakathil, Thomas MD, MSc, FRCPC; Winship, Ian R. BSc, PhD; Khan, Khurshid A. MD, FRCPC; Buck, Brian H. MD, FRCPC; Shuaib, Ashfaq MD, FRCPC; Jickling, Glen C. MD, MSc, FRCPC

doi : 10.1212/WNL.0000000000012855

Volume 97(21), 23 November 2021, p e2079-e2087

The rate of infarct core progression in patients with acute ischemic stroke is variable and affects outcome of reperfusion therapy. We evaluated the hypoperfusion index (HI) to estimate the initial rate of core progression in patients with medium vessel occlusion (MeVO) compared to large vessel occlusion (LVO) stroke and within a larger time frame since stroke onset.

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CT Hypoperfusion-Hypodensity Mismatch to Identify Patients With Acute Ischemic Stroke Within 4.5 Hours of Symptom Onset

Sporns, Peter B. MD*; Kemmling, Andre MD*; Minnerup, Heike MD, MSc*; Meyer, Lennart MD; Krogias, Christos MD; Puetz, Volker MD; Thierfelder, Kolja MD; Duering, Marco MD; Kaiser, Daniel MD; Langner, Soenke MD; Massoth, Christina MD; Brehm, Alex MD; Rotkopf, Lukas MD; Kunz, Wolfgang G. MD; Karch, Andre MD, MSc; Fiehler, Jens MD; Heindel, Walter MD; Schramm, Peter MD; Royl, Georg MD; Wiendl, Heinz MD; Psychogios, Marios MD; Minnerup, Jens MD

doi : 10.1212/WNL.0000000000012891

Volume 97(21), 23 November 2021, p e2088-e2095

To test the hypothesis that CT hypoperfusion-hypodensity mismatch identifies patients with ischemic stroke within 4.5 hours of symptom onset.

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Prevalence of Patent Foramen Ovale in a Cohort of Children With Cryptogenic Ischemic Stroke

Shih, Evelyn K. MD, PhD; Beslow, Lauren A. MD, MSCE; Natarajan, Shobha S. MD; Falkensammer, Christine B. MD; Messe, Steven R. MD*; Ichord, Rebecca N. MD*

doi : 10.1212/WNL.0000000000012892

Volume 97(21), 23 November 2021, p e2096-e2102

To determine the significance of patent foramen ovale (PFO) in childhood stroke, we compared PFO prevalence, PFO features, and stroke recurrence risk in 25 children with cryptogenic arterial ischemic stroke (AIS), 54 children with AIS from a known etiology, and 209 healthy controls.

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Natural History of Facioscapulohumeral Dystrophy in Children: A 2-Year Follow-up

Dijkstra, Jildou N. MD; Goselink, Rianne J.M. MD, PhD; van Alfen, Nens MD, PhD; de Groot, Imelda J.M. MD, PhD; Pelsma, Maaike MSc; van der Stoep, Nienke PhD; Theelen, Thomas MD, PhD; van Engelen, Baziel G.M. MD, PhD; Voermans, Nicol C. MD, PhD*; Erasmus, Corrie E. MD, PhD*

doi : 10.1212/WNL.0000000000012882

Volume 97(21), 23 November 2021, p e2103-e2113

Data on the natural history of facioscapulohumeral dystrophy (FSHD) in childhood are limited and critical for improved patient care and clinical trial readiness. Our objective was to describe the disease course of FSHD in children.

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Tissue 2-Hydroxyglutarate and Preoperative Seizures in Patients With Diffuse Gliomas

Ohno, Makoto MD, PhD*; Hayashi, Yoshiharu MEng*; Aikawa, Hiroaki PhD; Hayashi, Mitsuhiro MD, PhD; Miyakita, Yasuji MD, PhD; Takahashi, Masamichi MD, PhD; Matsushita, Yuko BSc; Yoshida, Akihiko MD, PhD; Satomi, Kaishi MD, PhD; Ichimura, Koichi MD, PhD; Hamada, Akinobu PhD; Narita, Yoshitaka MD, PhD

doi : 10.1212/WNL.0000000000012893

Volume 97(21), 23 November 2021, p e2114-e2123

Mutant isocitrate dehydrogenase (IDH) 1/2 gene products gain a new ability to produce D-2-hydroxyglutarate (D2HG). IDH1/2 mutations are thought to be associated with seizures owing to the structural similarity between D2HG and glutamate. However, the effects of D2HG on seizures in clinical settings are not fully understood. We sought to investigate the relationship between tissue 2-hydroxyglutarate (2HG) concentration and preoperative seizures using clinical samples.

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Defining Speech Subtypes in De Novo Parkinson Disease: Response to Long-term Levodopa Therapy

Rusz, Jan PhD; Tykalova, Tereza PhD; Novotny, Michal PhD; Zogala, David PhD; Sonka, Karel DSc; Ruzicka, Evzen DSc; Dusek, Petr PhD

doi : 10.1212/WNL.0000000000012878

Volume 97(21), 23 November 2021, p e2124-e2135

Patterns of speech disorder in Parkinson disease (PD), which are highly variable across individual patients, have not been systematically studied. Our aim was to identify speech subtypes in treatment-naive patients with PD and to examine their response to long-term dopaminergic therapy.

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Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines: A Systematic Review and Meta-analysis

Palaiodimou, Lina MD*; Stefanou, Maria-Ioanna MD*; Katsanos, Aristeidis H. MD; Aguiar de Sousa, Diana MD; Coutinho, Jonathan M. MD; Lagiou, Pagona MD; Michopoulos, Ioannis MD; Naska, Androniki PhD; Giannopoulos, Sotirios MD; Vadikolias, Konstantinos MD; Voumvourakis, Konstantinos I. MD; Papaevangelou, Vasiliki MD; Vassilakopoulos, Theodoros I. MD; Tsiodras, Sotirios MD; Tsivgoulis, Georgios MD

doi : 10.1212/WNL.0000000000012896

Volume 97(21), 23 November 2021, p e2136-e2147

There is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes.

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Fetal Familial Cerebral Cavernous Malformation With a Novel Heterozygous KRIT1 Variation

Cheng, Dan MD*; Shang, Xiang MBBS*; Gao, Wanli MD; Barkhof, Frederik MD, PhD; Liu, Yaou MD, PhD

doi : 10.1212/WNL.0000000000012852

Volume 97(21), 23 November 2021, p 986-988

To identify fetal familial cerebral cavernous malformation (CCM) and a novel variation.

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Opportunities for Understanding MS Mechanisms and Progression With MRI Using Large-Scale Data Sharing and Artificial Intelligence

Vrenken, Hugo PhD; Jenkinson, Mark BSc, BE, DPhil; Pham, Dzung L. PhD; Guttmann, Charles R.G. MD; Pareto, Deborah PhD; Paardekooper, Michel PhD; de Sitter, Alexandra PhD; Rocca, Maria A. MD; Wottschel, Viktor PhD; Cardoso, M. Jorge PhD; Barkhof, Frederik MD, PhD; on behalf of the MAGNIMS Study Group; on behalf of the MAGNIMS Study Group; de Stefano, Nicola MD, PhD; Garriga, Jaume Sastre-; Ciccarelli, Olga MD, PhD; Enzinger, Christian MD, PhD; Filippi, Massimo MD, PhD; Gasperini, Claudio MD, PhD; Kappos, Ludwig MD, PhD; Palace, Jacqueline MD, PhD; Rovira, Alex MD, PhD; Yousry, Tarek MD, PhD

doi : 10.1212/WNL.0000000000012884

Volume 97(21), 23 November 2021, p 989-999

Patients with multiple sclerosis (MS) have heterogeneous clinical presentations, symptoms, and progression over time, making MS difficult to assess and comprehend in vivo. The combination of large-scale data sharing and artificial intelligence creates new opportunities for monitoring and understanding MS using MRI. First, development of validated MS-specific image analysis methods can be boosted by verified reference, test, and benchmark imaging data. Using detailed expert annotations, artificial intelligence algorithms can be trained on such MS-specific data. Second, understanding disease processes could be greatly advanced through shared data of large MS cohorts with clinical, demographic, and treatment information. Relevant patterns in such data that may be imperceptible to a human observer could be detected through artificial intelligence techniques. This applies from image analysis (lesions, atrophy, or functional network changes) to large multidomain datasets (imaging, cognition, clinical disability, genetics). After reviewing data sharing and artificial intelligence, we highlight 3 areas that offer strong opportunities for making advances in the next few years: crowdsourcing, personal data protection, and organized analysis challenges. Difficulties as well as specific recommendations to overcome them are discussed, in order to best leverage data sharing and artificial intelligence to improve image analysis, imaging, and the understanding of MS.

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Perivascular and Subarachnoid Fluid-Attenuated Inversion Recovery Hyperintensities Related to Delayed Gadolinium Leakage After Stroke

Nistorec, Larisa MD; Renard, Dimitri MD; Parvu, Teodora MD

doi : 10.1212/WNL.0000000000012854

Volume 97(21), 23 November 2021, p 1000-1001

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Clinical Reasoning: An Unusual Case of Acute Psychosis and Tetraparesis in a Young Zambian Man

Zimba, Stanley MBChB, MMED, STP; Chishimba, Lorraine MBChB; Chomba, Mashina MBChB; Saylor, Deanna MD, MHS

doi : 10.1212/WNL.0000000000012468

Volume 97(21), 23 November 2021, p 1002-1005

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Pearls and Oy-sters: Symmetric Numbness and Paresthesia Due to Stroke-like Episode in an Adolescent Male With MELAS

Vassar, Rachel MD; Mehta, Nehali MD

doi : 10.1212/WNL.0000000000012611

Volume 97(21), 23 November 2021, p 1006-1008

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Teaching NeuroImage: Basal Ganglia T1 Hyperintensity and SWI Signal Diabetic Striatopathy in an 18-Year-Old Man With Type 1 Diabetes Mellitus

Tencer, Jaclyn MD; Yum, Sabrina W. MD

doi : 10.1212/WNL.0000000000012489

Volume 97(21), 23 November 2021, p e2148-e2149

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Teaching Video NeuroImage: An Uncommon Cause of Hearing Loss

Siddiqui, Waleed Tariq MD, MPH; Byrne, Maria MD

doi : 10.1212/WNL.0000000000012469

Volume 97(21), 23 November 2021, p e2150-e2151

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Editors' Note: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis

Lewis, Ariane MD; Galetta, Steven MD

doi : 10.1212/WNL.0000000000012897

Volume 97(21), 23 November 2021, p 1009

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Reader Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis

Pollak, Thomas A.; Pruss, Harald; Bechter, Karl; Najjar, Souhel; Vincent, Angela

doi : 10.1212/WNL.0000000000012898

Volume 97(21), 23 November 2021, p 1009-1010

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Author Response: Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis

Dalmau, Josep; Guasp, Mar; Graus, Francesc

doi : 10.1212/WNL.0000000000012899

Volume 97(21), 23 November 2021, p 1010

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