Annals of Neurology最新文献

{"title":"Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease","authors":"Ethan G. Brown MD,&nbsp;Lana M. Chahine MD,&nbsp;Andrew Siderowf MD,&nbsp;Caroline Gochanour MS,&nbsp;Ryan Kurth MS,&nbsp;Micah J. Marshall MS,&nbsp;Chelsea Caspell-Garcia MS,&nbsp;Michael C. Brumm MS,&nbsp;Craig E. Stanley Jr PhD,&nbsp;Monica Korell MPH,&nbsp;Bridget McMahon BS,&nbsp;Maggie Kuhl BA,&nbsp;Kimberly Fabrizio BA,&nbsp;Laura Heathers BA,&nbsp;Luis Concha-Marambio PhD,&nbsp;Claudio Soto PhD,&nbsp;Sohini Chowdhury MA,&nbsp;Christopher S. Coffey PhD,&nbsp;Tatiana M. Foroud PhD,&nbsp;Tanya Simuni MD,&nbsp;Kenneth Marek MD,&nbsp;Caroline M. Tanner PhD,&nbsp;The Parkinson Progression Marker Initiative","doi":"10.1002/ana.27158","DOIUrl":"10.1002/ana.27158","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in longitudinal assessments and further biomarker evaluation including cerebrospinal fluid alpha-synuclein seed amplification assay (aSynSAA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As of January 29, 2024, 49,843 participants were sent an UPSIT and 31,293 (63%) completed it. Of UPSIT completers, 8,301 (27%) scored &lt;15th percentile. Of 1,546 who completed DAT-SPECT, 1,060 (69%) had DAT-SPECT binding &lt;100% expected for age and sex. Participants with an UPSIT &lt;10th percentile (n = 1,221) had greater likelihood of low DAT-SPECT binding compared to participants with an UPSIT in the 10th to 15th percentile (odds ratio, 3.01; 95% confidence interval, 1.85–4.91). Overall, 55% (198/363) of cases with UPSIT &lt;15th percentile and DAT-SPECT &lt;100% had positive aSynSAA, which increased to 70% (182/260) when selecting for more severe hyposmia (UPSIT &lt;10th percentile).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Remote screening for hyposmia and reduced DAT-SPECT binding identifies participants with a high proportion positive aSynSAA. Longitudinal data will be essential to define progression patterns in these individuals to ultimately inform recruitment into disease modification clinical trials. ANN NEUROL 2025;97:730–740</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"730-740"},"PeriodicalIF":8.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infundibulum of an Aberrant Accessory MCA Mimics Aneurysm","authors":"Wai Ting Lui MD,&nbsp;Tao Xiong MD,&nbsp;Bo Yang MD,&nbsp;Ning Ma MD","doi":"10.1002/ana.27171","DOIUrl":"10.1002/ana.27171","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"694-695"},"PeriodicalIF":8.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased White Matter Aerobic Glycolysis in Multiple Sclerosis","authors":"Matthew R Brier MD, PhD,&nbsp;Bradley Judge BS,&nbsp;Chunwei Ying PhD,&nbsp;Amber Salter PhD,&nbsp;Hongyu An PhD,&nbsp;Aakash Patel MS,&nbsp;Qing Wang PhD,&nbsp;Yong Wang PhD,&nbsp;Anne H Cross MD,&nbsp;Robert T Naismith MD,&nbsp;Tammie LS Benzinger MD, PhD,&nbsp;Manu S Goyal MD","doi":"10.1002/ana.27165","DOIUrl":"10.1002/ana.27165","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Despite treatments which reduce relapses in multiple sclerosis (MS), many patients continue to experience progressive disability accumulation. MS is associated with metabolic disruptions and cerebral metabolic stress predisposes to tissue injury and possibly impaired remyelination. Additionally, myelin homeostasis is metabolically expensive and reliant on glycolysis. We investigated cerebral metabolic changes in MS and when in the disease course they occurred, and assessed their relationship with microstructural changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study used combined fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) to measure cerebral metabolic rate of glucose and oxygen, thereby quantifying glycolysis. Twelve healthy controls, 20 patients with relapsing MS, and 13 patients with non-relapsing MS were studied. Relapsing patients with MS were treatment naïve and scanned pre- and post-initiation of high efficacy disease modifying therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In normal appearing white matter, we observed increased glucose utilization and reduced oxygen utilization in newly diagnosed MS, consistent with increased glycolysis. Increased glycolysis was greater in patients with a longer disease duration course and higher disability. Among newly diagnosed patients, different treatments had differential impacts on glucose utilization. Last, whereas hypermetabolism within lesions was clearly associated with inflammation, no such relationship was found within normal appearing white matter.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Increased white matter glycolysis is a prominent feature of cerebral metabolism in MS. It begins early in the disease course, increases with disease duration and is independent of microstructural evidence of inflammation in normal appearing white matter. Optimization of the metabolic environment may be an important component of therapies designed to reduce progressive disability. ANN NEUROL 2025;97:766–778</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"766-778"},"PeriodicalIF":8.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propranolol Reduces Parkinson's Tremor and Inhibits Tremor-Related Activity in the Motor Cortex: A Placebo-Controlled Crossover Trial","authors":"Anouk van der Heide PhD,&nbsp;Maaike Wessel MSc,&nbsp;Danae Papadopetraki MSc,&nbsp;Dirk E.M. Geurts MD, PhD,&nbsp;Teije H. van Prooije MD,&nbsp;Frank Gommans MD, PhD,&nbsp;Bastiaan R. Bloem MD, PhD,&nbsp;Michiel F. Dirkx MD, PhD,&nbsp;Rick C. Helmich MD, PhD","doi":"10.1002/ana.27159","DOIUrl":"10.1002/ana.27159","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Parkinson's disease (PD) resting tremor is thought to be initiated in the basal ganglia and amplified in the cerebello-thalamo-cortical circuit. Because stress worsens tremor, the noradrenergic system may play a role in amplifying tremor. We tested if and how propranolol, a non-selective beta-adrenergic receptor antagonist, reduces PD tremor and whether or not this effect is specific to stressful conditions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In a cross-over, double-blind intervention study, participants with PD resting tremor received propranolol (40 mg, single dose) or placebo (counter-balanced) on 2 different days. During both days, we assessed tremor severity (with accelerometry) and tremor-related brain activity (with functional magnetic resonance imaging), as well as heart rate and pupil diameter, while subjects performed a stressful cognitive load task that has been linked to the noradrenergic system. We tested for effects of drug (propranolol vs placebo) and stress (cognitive load vs rest) on tremor power and tremor-related brain activity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We included 27 PD patients with prominent resting tremor. Tremor power significantly increased during cognitive load versus rest (&lt;i&gt;F&lt;/i&gt;[1,19] = 13.8; &lt;i&gt;p&lt;/i&gt; = 0.001; &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msubsup&gt;\u0000 &lt;mi&gt;η&lt;/mi&gt;\u0000 &lt;mi&gt;p&lt;/mi&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/msubsup&gt;\u0000 &lt;/mrow&gt;&lt;/math&gt; = 0.42) and decreased by propranolol versus placebo (&lt;i&gt;F&lt;/i&gt;[1,19] = 6.4; &lt;i&gt;p&lt;/i&gt; = 0.02; &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msubsup&gt;\u0000 &lt;mi&gt;η&lt;/mi&gt;\u0000 &lt;mi&gt;p&lt;/mi&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/msubsup&gt;\u0000 &lt;/mrow&gt;&lt;/math&gt; = 0.25), but there was no interaction. We observed task-related brain activity in a stress-sensitive cognitive control network and tremor power-related activity in the cerebello-thalamo-cortical circuit. Propranolol significantly reduced tremor-related activity in the motor cortex compared to placebo (&lt;i&gt;F&lt;/i&gt;[1,21] = 5.3; &lt;i&gt;p&lt;/i&gt; = 0.03; &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 &lt;mrow&gt;\u0000 &lt;msubsup&gt;\u0000 &lt;mi&gt;η&lt;/mi&gt;\u0000 &lt;mi&gt;p&lt;/mi&gt;\u0000 &lt;mn&gt;2&lt;/mn&gt;\u0000 &lt;/msubsup&gt;\u0000 &lt;/mrow&gt;&lt;/math&gt; = 0.20), irrespective of cognitive load.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; I","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"741-752"},"PeriodicalIF":8.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinematic Rendering of Twig-Like Middle Cerebral Artery","authors":"Linggen Dong MD,&nbsp;Ming Lv MD","doi":"10.1002/ana.27173","DOIUrl":"10.1002/ana.27173","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"696-697"},"PeriodicalIF":8.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Utility of Long-Read Sequencing in Diagnosing Early Onset Parkinson's Disease","authors":"Kensuke Daida MD, PhD,&nbsp;Hiroyo Yoshino PhD,&nbsp;Laksh Malik MFS,&nbsp;Breeana Baker BSc,&nbsp;Mayu Ishiguro MD, PhD,&nbsp;Rylee Genner MS,&nbsp;Kimberly Paquette BA,&nbsp;Yuanzhe Li MD, PhD,&nbsp;Kenya Nishioka MD, PhD,&nbsp;Satoshi Masuzugawa MD,&nbsp;Makito Hirano MD, PhD,&nbsp;Kenta Takahashi MD, PhD,&nbsp;Mikhail Kolmogorov PhD,&nbsp;Kimberley J. Billingsley PhD,&nbsp;Manabu Funayama PhD,&nbsp;Cornelis Blauwendraat PhD,&nbsp;Nobutaka Hattori MD, PhD","doi":"10.1002/ana.27155","DOIUrl":"10.1002/ana.27155","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Variants in <i>PRKN</i> and <i>PINK1</i> are the leading cause of early-onset autosomal recessive Parkinson's disease, yet many cases remain genetically unresolved. We previously identified a 7 megabases complex structural variant in a pair of monozygotic twins using Oxford Nanopore Technologies (ONT) long-read sequencing. This study aims to determine if ONT long-read sequencing can detect a second variant in other unresolved early-onset Parkinson's disease (EOPD) cases with 1 heterozygous <i>PRKN</i> or <i>PINK1</i> variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ONT long-read sequencing was performed on EOPD patients with 1 reported <i>PRKN</i>/<i>PINK1</i> pathogenic variant, with onset age under 50. Positive controls included EOPD patients with 2 known <i>PRKN</i> pathogenic variants. Initial testing involved short-read targeted panel sequencing for single nucleotide variants and multiplex ligation-dependent probe amplification for copy number variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 47 patients were studied (<i>PRKN</i> “one-variant,” n = 23; <i>PINK1</i> “one-variant,” n = 12; <i>PRKN</i> “two-variants,” n = 12). ONT long-read sequencing identified a second pathogenic variant in 26% of <i>PRKN</i> “one-variant” patients (6/23), but none in <i>PINK1</i> “one-variant” patients (0/12). Detected variants included 1 complex inversion, 2 structural variant overlaps, and 3 duplications. In the <i>PRKN</i> “two-variants” group, both variants were identified in all patients (100%, 12/12).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>ONT long-read sequencing effectively identifies pathogenic structural variants in the <i>PRKN</i> locus missed by conventional methods. It should be considered for unresolved EOPD cases when a second variant is not detected through conventional approaches. ANN NEUROL 2025;97:753–765</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"753-765"},"PeriodicalIF":8.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annual Report from the Editor-in-Chief (2024)","authors":"Kenneth L Tyler","doi":"10.1002/ana.27163","DOIUrl":"https://doi.org/10.1002/ana.27163","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"1-12"},"PeriodicalIF":8.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143116684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Individuals in the Prodromal Phase of Parkinson's Disease: A Prospective Cohort Study","authors":"Mario H. Flores-Torres MD, PhD,&nbsp;Katherine C. Hughes PhD,&nbsp;Marianna Cortese MD, PhD,&nbsp;Albert Y. Hung MD, PhD,&nbsp;Brian C. Healy PhD,&nbsp;Michael A. Schwarzschild MD, PhD,&nbsp;Kjetil Bjornevik MD, PhD,&nbsp;Alberto Ascherio MD, ScD","doi":"10.1002/ana.27166","DOIUrl":"10.1002/ana.27166","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We prospectively evaluated how well combinations of signs and symptoms can identify individuals in the prodromal phase of Parkinson's disease (PD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study comprised 6,108 men who underwent repeated assessments of key prodromal features and were prospectively followed for the development of PD. Two composite measures of prodromal PD were evaluated: (i) the co-occurrence of constipation, probable rapid eye movement (REM) sleep behavior disorder (pRBD), and hyposmia, and (ii) the probability of prodromal PD based on the Movement Disorders Society (MDS) research criteria. We also examined the progression and heterogeneity of the prodromal PD phase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One hundred three individuals were newly diagnosed with PD over an average follow-up of 3.4 years. Men with constipation, pRBD, and hyposmia had a 23-fold higher risk of receiving a PD diagnosis in the subsequent 3 years, compared with men without these features (risk ratio [RR] = 23.35, 95% confidence interval [CI] = 10.62–51.33). The risk of PD was 21-fold higher in men with a probability of prodromal PD ≥ 0.8 compared with those with a probability &lt; 0.2 (RR = 21.96, 95% CI = 11.17–43.17). Both the co-occurrence of the 3 non-motor features and an MDS-based probability ≥ 0.8 had comparable predictive values, and both were stronger predictors of PD than any of the features individually. We identified 2 prodromal PD subtypes where RBD and visual color impairment were key discriminators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our study demonstrates that combinations of key signs and symptoms strongly predict future clinically manifest PD. These measures may be integrated into screening strategies to identify individuals who could be targeted for enrollment into PD prevention trials. ANN NEUROL 2025;97:720–729</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"720-729"},"PeriodicalIF":8.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Memoriam: Barry GW Arnason, MD (8/2/1933—7/17/2023)","authors":"Anthony T. Reder","doi":"10.1002/ana.27160","DOIUrl":"10.1002/ana.27160","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"13-14"},"PeriodicalIF":8.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association that Neuroimaging and Clinical Measures Have with Change in Arm Impairment in a Phase 3 Stroke Recovery Trial","authors":"Anne Schwarz PhD,&nbsp;Marc Feldman BS,&nbsp;Vu Le MS,&nbsp;Jesse Dawson MD,&nbsp;Charles Y. Liu MD, PhD,&nbsp;Gerard E. Francisco MD,&nbsp;Steven L. Wolf PhD, PT,&nbsp;Anand Dixit MD,&nbsp;Jen Alexander MSc,&nbsp;Rushna Ali MD,&nbsp;Benjamin L. Brown MD,&nbsp;Wuwei Feng MD,&nbsp;Louis DeMark DPT,&nbsp;Leigh R. Hochberg MD, PhD,&nbsp;Steven A. Kautz PhD,&nbsp;Arshad Majid MD,&nbsp;Michael W. O'Dell MD,&nbsp;Jessica Redgrave MD,&nbsp;Duncan L. Turner PhD, BSc,&nbsp;Teresa J. Kimberley PT, PhD,&nbsp;Steven C. Cramer MD","doi":"10.1002/ana.27156","DOIUrl":"10.1002/ana.27156","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Vagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS-REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment-related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Baseline magnetic resonance imaging (MRI) scans in the VNS-REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain). Eight clinical measures assessed at baseline were also evaluated (treatment group, age, race, gender, paretic side, pre-stroke dominant hand, time since stroke, and baseline Fugl-Meyer upper extremity score). Bivariate analyses compared each measure with the primary trial end point (change in Fugl-Meyer upper extremity score from baseline to end of 6 weeks of treatment) across all subjects, with secondary analyses examining trial groups separately.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;MRIs were available from 80 patients (age = 59.8 ± 9.5 years, 29 women). Across all patients, less white matter hyperintensities (&lt;i&gt;r&lt;/i&gt; = −0.25, &lt;i&gt;p&lt;/i&gt; = 0.028) at baseline was associated with larger Fugl-Meyer score change. In the VNS group, less white matter hyperintensities (&lt;i&gt;r&lt;/i&gt; = −0.37, &lt;i&gt;p&lt;/i&gt; = 0.018) and larger ipsilesional thalamus volume (&lt;i&gt;r&lt;/i&gt; = 0.33, &lt;i&gt;p&lt;/i&gt; = 0.046) were each associated with larger Fugl-Meyer score change. Analysis of covariance (ANCOVA) analyses tested the interaction that each baseline measure had with treatment group and found that the model examining white matter hyperintensities had a significant interaction term, indicating 2.3 less change in Fugl-Meyer Upper Extremity (FM-UE) points in the VNS group relative to the control group for each point increase in modified Fazekas scale.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Interpretation&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Neuroimaging measures are associated with extent of gains on the primary endpoint of a phase III stroke recovery trial. Among the neuroimaging measures examined, a measure of global brain heal","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"709-719"},"PeriodicalIF":8.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}