Annals of Neurology最新文献

{"title":"Loss of TDP-43 Splicing Repression Occurs in Myonuclei of Inclusion Body Myositis Patients","authors":"Chiseko Ikenaga MD, PhD,&nbsp;Andrew B. Wilson PhD,&nbsp;Katherine E. Irwin MS,&nbsp;Aswathy Peethambaran Mallika PhD,&nbsp;Collin Kilgore MS,&nbsp;Irika R. Sinha MS,&nbsp;Elizabeth H. Michelle MD,&nbsp;Jonathan P. Ling PhD,&nbsp;Philip C. Wong PhD,&nbsp;Thomas E. Lloyd MD, PhD","doi":"10.1002/ana.27167","DOIUrl":"10.1002/ana.27167","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy with muscle pathology characterized by endomysial inflammation, rimmed vacuoles, and cytoplasmic mislocalization of transactive response DNA-binding protein 43 (TDP-43). We aimed to determine whether loss of TDP-43 splicing repression led to the production of “cryptic peptides” that could be detected in muscle biopsies as a useful biomarker for IBM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used an antisera against a neoepitope encoded by a TDP-43-dependent cryptic exon within hepatoma-derived growth factor-like protein 2 (<i>HDGFL2</i>) for immunohistochemical analysis on muscle biopsy samples of 122 patients with IBM, 181 disease controls, and 16 healthy controls without abnormal muscle pathology. In situ hybridization was also utilized to detect the localization of cryptic <i>HDGFL2</i> transcripts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found cryptic <i>HDGFL2</i> peptides localized within myonuclei from muscle biopsies in 79 of 122 patients with IBM (65%), and this staining correlated with TDP-43 depletion. In contrast, cryptic <i>HDGFL2</i> immunoreactivity was absent in 197 muscle biopsies from a variety of disease controls, except for 2 patients with vacuolar myopathies. Notably, we show that cryptic <i>HDGFL2</i> transcripts are accompanied by the detection of cryptic <i>HDGFL2</i> in muscle fibers of IBM without rimmed vacuoles and TDP-43 aggregates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Together, our findings establish that loss of TDP-43 splicing repression occurs in myonuclei of IBM skeletal muscle and suggest that detection of cryptic peptides in muscle biopsies may be a useful biomarker. We suggest that a therapeutic strategy designed to restore TDP-43 function should be considered to attenuate the degeneration of skeletal muscle in this devastating disease. ANN NEUROL 2025;97:629–641</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 4","pages":"629-641"},"PeriodicalIF":8.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930092","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":"Phenotype Spectrum of TRPM3-Associated Disorders","authors":"Laura Jolitz,&nbsp;Ingo Helbig MD,&nbsp;Mark P. Fitzgerald MD PhD,&nbsp;Sarah McKeown Ruggiero MS, CGC,&nbsp;Stacey Cohen MS, CGC,&nbsp;Chloe Angelini,&nbsp;Elena Vallespin,&nbsp;Vincent Michaud MD,&nbsp;Anna Gerasimenko,&nbsp;Benjamin Cogne,&nbsp;Bertrand Isidor,&nbsp;Boris Keren,&nbsp;David Dyment DPhil, MD,&nbsp;Delphine Heron MD,&nbsp;Helena Gásdal Karstensen PhD,&nbsp;Inge Cuppen MD, PhD,&nbsp;John Christodoulou MB, PS, PhD,&nbsp;Meredith Wilson,&nbsp;Nicole J. Lake MSc, PhD,&nbsp;Saskia Biskup MD, PhD,&nbsp;Steffen Syrbe MD,&nbsp;Takayasu Mori MD, PhD,&nbsp;Lena-Luise Becker MD,&nbsp;Angela M. Kaindl MD, PhD","doi":"10.1002/ana.27141","DOIUrl":"10.1002/ana.27141","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Monoallelic variants in the transient receptor potential melastatin-related type 3 gene (<i>TRPM3</i>) have been associated with neurodevelopmental manifestations, but knowledge on the clinical manifestations and treatment options is limited. We characterized the clinical spectrum, highlighting particularly the epilepsy phenotype, and the effect of treatments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed retrospectively the phenotypes and genotypes of 43 individuals with <i>TRPM3</i> variants, acquired from GeneMatcher and collaborations (n = 21), and through a systematic literature search (n = 22). We included all patients with a pathogenic <i>TRPM3</i> variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age at the time of the study was 10 years, with a preponderance of girls (60%) versus boys (40%). Frequent findings were developmental delay and/or intellectual disability (93%), global or axial hypotonia (77%), ocular involvement (70%), musculoskeletal anomalies (65%), and dysmorphic features (58%). Epilepsy was diagnosed in 31 patients (72%), classified in all as developmental and epileptic encephalopathy with or without spike wave activation in sleep (DEE/DEE-SWAS). Patients with the variant p.Val1002Met (n = 24) significantly more often had developmental delay and epilepsy. The most effective anti-seizure medication was primidone. All treated patients showed an improvement in seizure frequency, motor and speech development, and/or learning capability with this drug.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Developmental delay/intellectual disability and epilepsy are dominant phenotypic features in patients with <i>TRPM3</i> variants. Given that epilepsy can negatively impact development, screening for awake and sleep electroencephalogram abnormalities and other manifestations are essential to offer early intervention. The TRPM3 channel blocker primidone has shown promising effects and should be considered in every child with a <i>TRPM3</i> gain-of-function variant. ANN NEUROL 2025;97:561–570</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 3","pages":"561-570"},"PeriodicalIF":8.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918714","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":"Perfusion and Electrophysiological Changes in MELAS.","authors":"Baris Alten, Catherine J Chu, Natalia S Rost, Melissa A Walker","doi":"10.1002/ana.27176","DOIUrl":"https://doi.org/10.1002/ana.27176","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906459","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":"Annals of Neurology: Volume 97, Number 1, January 2025","authors":"","doi":"10.1002/ana.26973","DOIUrl":"https://doi.org/10.1002/ana.26973","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 1","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143120454","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":"Prediction of Central Post-Stroke Pain by Quantitative Sensory Testing","authors":"Susanna Asseyer MD,&nbsp;Eleni Panagoulas MD,&nbsp;Jana Maidhof MD,&nbsp;Kersten Villringer MD,&nbsp;Esra Al PhD,&nbsp;Xiuhui Chen MD,&nbsp;Thomas Krause MD,&nbsp;Samyogita Hardikar PhD,&nbsp;Arno Villringer MD,&nbsp;Gerhard Jan Jungehülsing MD","doi":"10.1002/ana.27138","DOIUrl":"10.1002/ana.27138","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Among patients with acute stroke, we aimed to identify those who will later develop central post-stroke pain (CPSP) versus those who will not (non-pain sensory stroke [NPSS]) by assessing potential differences in somatosensory profile patterns and evaluating their potential as predictors of CPSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a prospective longitudinal study on 75 acute stroke patients with somatosensory symptoms, we performed quantitative somatosensory testing (QST) in the acute/subacute phase (within 10 days) and on follow-up visits for 12 months. Based on previous QST studies, we hypothesized that QST values of cold detection threshold (CDT) and dynamic mechanical allodynia (DMA) would differ between CPSP and NPSS patients before the onset of pain. Mann–Whitney <i>U</i>-tests and mixed analysis of variances with Bonferroni corrections were performed to compare z-normalized QST scores between both groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 26 patients (34.7%) developed CPSP. In the acute phase, CPSP patients showed contralesional cold hypoesthesia compared to NPSS patients (<i>p</i> = 0.04), but no DMA differences. Additional exploratory analysis showed NPSS patients exhibit cold hyperalgesia on the contralesional side compared to the ipsilesional side, not seen in CPSP patients (<i>p</i> = 0.011). A gradient-boosting approach to predicting CPSP from QST patterns before pain onset had an overall accuracy of 84.6%, with a recall and precision of 75%. Notably, both in the acute and the chronic phase, approximately 80% of CPSP and NPSS patients showed bilateral QST abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Cold perception differences between CPSP and NPSS patients appear early post stroke before pain onset. Prediction of CPSP through QST patterns seems feasible. ANN NEUROL 2025;97:507–520</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 3","pages":"507-520"},"PeriodicalIF":8.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890635","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":"Optimal Cerebral Blood Flow Thresholds for Ischemic Core Estimation Using Computed Tomography Perfusion and Diffusion-Weighted Imaging.","authors":"Nakhoon Kim, Wi-Sun Ryu, Sue Young Ha, Jun Yup Kim, Jihoon Kang, Sung Hyun Baik, Cheolkyu Jung, Moon-Ku Han, Hee-Joon Bae, Longting Lin, Mark Parsons, Beom Joon Kim","doi":"10.1002/ana.27169","DOIUrl":"https://doi.org/10.1002/ana.27169","url":null,"abstract":"<p><strong>Objective: </strong>Computed tomography perfusion (CTP) imaging is crucial in quantifying cerebral blood flow (CBF) and thereby making an endovascular treatment (EVT) after large vessel occlusion. However, CTP is prone to overestimating the ischemic core. We sought to delineate the optimal regional CBF (rCBF) thresholds of pre-EVT CTP.</p><p><strong>Methods: </strong>We collected acute ischemic stroke patients due to large vessel occlusion who achieved successful recanalization with baseline CTP, immediate post-EVT diffusion-weighted image (DWI) within 3 hours, and delayed post-EVT DWI between 24 and 196 hours. Core volumes estimated by CTP at various rCBF thresholds were validated against immediate and delayed DWI lesion volumes.</p><p><strong>Results: </strong>A total of 175 acute large vessel occlusion patients were included. Baseline CTP was taken in a median of 24 minutes (interquartile range [IQR] 21-31 minutes) after arrival; after the CTP, groin puncture in a median of 37 minutes (IQR 28-52 minutes), immediate post-EVT DWI scans in a median of 1.6 hours (IQR 0.8-2.1 hours), and delayed DWI scans in a median of 89 hours (IQR 69-106 hours). The correlations between the rCBF thresholds were the best at rCBF <22% for immediate DWI (0.64; 95% CI 0.55-0.73) and at rCBF <30% for delayed DWI (0.69; 95% CI 0.61-0.76). The interval between CTP and recanalization was inversely correlated with the overestimation of ischemic core volume compared with the subsequent DWI.</p><p><strong>Interpretation: </strong>Optimal rCBF thresholds for estimating ischemic core using CTP depend significantly on the timing of DWI post-EVT and CTP to recanalization delay. The optimal rCBF thresholds for ischemic core estimation may vary depending on the clinical setting. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890630","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":"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}