Annals of Neurology最新文献

{"title":"Oropouche Virus: An Emerging Neuroinvasive Arbovirus.","authors":"Daniel M Pastula, J David Beckham, Kenneth L Tyler","doi":"10.1002/ana.27139","DOIUrl":"https://doi.org/10.1002/ana.27139","url":null,"abstract":"<p><p>Oropouche virus (OROV) is an arthropod-borne virus (arbovirus) in the Orthobunyavirus genus and Peribunyaviridae viral family that is endemic to parts of South America, Central America, and the Caribbean. It has recently emerged in Cuba, and travel-imported cases are recently being reported in the United States and Europe. Typically maintained in a sylvatic cycle between certain forest sloths, non-human primates, birds, and mosquitoes, OROV disease outbreaks can occur in an urban cycle between certain biting midges and/or mosquitoes and humans. Clinically, approximately 60% of infections are symptomatic with an abrupt fever and non-specific influenza-like illness within 3 to 10 days. Many initial OROV infections can present similarly to chikungunya, dengue, and Zika virus infections. Interestingly, OROV infections can follow a biphasic course with recurrence of symptoms approximately 1 week after initial symptom onset. Concerningly, similar to Zika virus, it appears that vertical transmission of OROV may occur with potentially adverse effects on fetal development including miscarriages. Neuroinvasion of OROV occurs in animal models, and human cases of meningitis, encephalitis, and peri-infectious Guillain-Barré syndrome have all been reported. Diagnosis is either through detection of OROV nucleic acid, OROV immunoglobulin M, or OROV neutralizing antibodies in the serum and/or cerebrospinal fluid. No antiviral treatments are available, and there are no current vaccines. Preventing mosquito and biting midge bites is key. Neurologists should be aware of and report any potential neuroinvasive OROV disease cases to local/state/territorial health departments. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666481","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":"Cerebrovascular Function in Sporadic and Genetic Cerebral Small Vessel Disease.","authors":"Michael S Stringer, Gordon W Blair, Anna Kopczak, Danielle Kerkhofs, Michael J Thrippleton, Francesca M Chappell, Susana Muñoz Maniega, Rosalind Brown, Kirsten Shuler, Iona Hamilton, Daniela Jaime Garcia, Fergus N Doubal, Una Clancy, Eleni Sakka, Tetiana Poliakova, Esther Janssen, Marco Duering, Michael Ingrisch, Julie Staals, Walter H Backes, Robert van Oostenbrugge, Geert Jan Biessels, Martin Dichgans, Joanna M Wardlaw","doi":"10.1002/ana.27136","DOIUrl":"https://doi.org/10.1002/ana.27136","url":null,"abstract":"<p><strong>Objective: </strong>Cerebral small vessel diseases (SVDs) are associated with cerebrovascular dysfunction, such as increased blood-brain barrier leakage (permeability surface area product), vascular pulsatility, and decreased cerebrovascular reactivity (CVR). No studies assessed all 3 functions concurrently. We assessed 3 key vascular functions in sporadic and genetic SVD to determine associations with SVD severity, subtype, and interrelations.</p><p><strong>Methods: </strong>In this prospective, cross-sectional, multicenter INVESTIGATE-SVDs study, we acquired brain magnetic resonance imaging in patients with sporadic SVD/cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), including structural, quantitative microstructural, permeability surface area product, blood plasma volume fraction, vascular pulsatility, and CVR (in response to CO₂) scans. We determined vascular function and white matter hyperintensity (WMH) associations, using covariate-adjusted linear regression; normal-appearing white matter and WMH differences, interrelationships between vascular functions, using linear mixed models; and major sources of variance using principal component analyses.</p><p><strong>Results: </strong>We recruited 77 patients (45 sporadic/32 CADASIL) at 3 sites. In adjusted analyses, patients with worse WMH had lower CVR (B = -1.78, 95% CI -3.30, -0.27) and blood plasma volume fraction (B = -0.594, 95% CI -0.987, -0.202). CVR was worse in WMH than normal-appearing white matter (eg, CVR: B = -0.048, 95% CI -0.079, -0.017). Adjusting for WMH severity, SVD subtype had minimal influence on vascular function (eg, CVR in CADASIL vs sporadic: B = 0.0169, 95% CI -0.0247, 0.0584). Different vascular function mechanisms were not generally interrelated (eg, permeability surface area product~CVR: B = -0.85, 95% CI -4.72, 3.02). Principal component analyses identified WMH volume/quantitative microstructural metrics explained most variance in CADASIL and arterial pulsatility in sporadic SVD, but similar main variance sources.</p><p><strong>Interpretation: </strong>Vascular function was worse with higher WMH, and in WMH than normal-appearing white matter. Sporadic SVD-CADASIL differences largely reflect disease severity. Limited vascular function interrelations may suggest disease stage-specific differences. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646030","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":"Micro-Doses of DNP Preserve Motor and Muscle Function with a Period of Functional Recovery in Amyotrophic Lateral Sclerosis Mice.","authors":"Renjia Zhong, Demi L A Dionela, Nina Haeyeon Kim, Erin N Harris, John G Geisler, Lan Wei-LaPierre","doi":"10.1002/ana.27140","DOIUrl":"https://doi.org/10.1002/ana.27140","url":null,"abstract":"<p><strong>Objective: </strong>Mitochondrial dysfunction is one of the earliest pathological events observed in amyotrophic lateral sclerosis (ALS). The aim of this study is to evaluate the therapeutic efficacy of 2,4-dinitrophenol (DNP), a mild mitochondrial uncoupler, in an ALS mouse model to provide preclinical proof-of-concept evidence of using DNP as a potential therapeutic drug for ALS.</p><p><strong>Methods: </strong>hSOD1^G93A mice were treated with 0.5-1.0 mg/kg DNP through daily oral gavage from presymptomatic stage or disease onset until 18 weeks old. Longitudinal behavioral studies were performed weekly or biweekly from 6 to 18 weeks old. In situ muscle contraction measurements in extensor digitorum longus muscles were conducted to evaluate the preservation of contractile force and motor unit numbers in hSOD1^G93A mice following DNP treatment. Muscle innervation and inflammatory markers were assessed using immunostaining. Extent of protein oxidation and activation of Akt pathway were also examined.</p><p><strong>Results: </strong>DNP delayed disease onset; improved motor coordination and muscle performance in vivo; preserved muscle contractile function, neuromuscular junction morphology, and muscle innervation; and reduced inflammation and protein oxidation at 18 weeks old in hSOD1^G93A mice. Strikingly, symptomatic hSOD1^G93A mice exhibited a period of recovery in running ability at 20 cm/s several weeks after 2,4-dinitrophenol treatment started at disease onset, offering the first observation in disease phenotype reversal using a small molecule.</p><p><strong>Interpretation: </strong>Our results strongly support that micro-dose DNP may be used as a potential novel treatment for ALS patients, with a possibility for recovery, when used at optimal doses and time of intervention. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646034","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":"Elevated Cerebrospinal Fluid Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1 in Asymptomatic C9orf72 Hexanucleotide Repeat Expansion Carriers.","authors":"Elizabeth R Dellar, Iolanda Vendrell, Benazir Amein, David G Lester, Evan C Edmond, Katie Yoganathan, Thanuja Dharmadasa, Aitana Sogorb-Esteve, Roman Fischer, Kevin Talbot, Jonathan D Rohrer, Martin R Turner, Alexander G Thompson","doi":"10.1002/ana.27133","DOIUrl":"https://doi.org/10.1002/ana.27133","url":null,"abstract":"<p><strong>Objective: </strong>To identify biochemical changes in individuals at higher risk of developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) via C9orf72 hexanucleotide repeat expansion (HRE) heterozygosity.</p><p><strong>Methods: </strong>Cross-sectional observational study of 48 asymptomatic C9orf72 HRE carriers, 39 asymptomatic non-carrier controls, 19 people with sporadic ALS, 10 with C9orf72 ALS, 14 with sporadic FTD, and 10 with C9orf72 FTD. Relative abundance of 30 pre-defined cerebrospinal fluid biomarkers of ALS and FTD were compared in asymptomatic C9orf72 HRE carriers and age-matched non-carrier controls. Differential abundance of these proteins was quantified using data independent acquisition mass spectrometry or electro chemiluminescent assay for neurofilament light chain. Unbiased analysis of the entire cerebrospinal fluid proteome was then carried out.</p><p><strong>Results: </strong>Ubiquitin carboxyl-hydrolase isozyme L1 levels were higher in asymptomatic C9orf72 HRE carriers compared with age-matched non-carriers (log₂fold change 0.20, FDR-adjusted p-value = 0.034), whereas neurofilament light chain levels did not significantly differ. Ubiquitin carboxyl-hydrolase isozyme L1 levels remained elevated after matching of groups by neurofilament levels (p = 0.011), and after adjusting for age, sex, and neurofilament levels. A significant difference was also observed when restricting analysis to younger participants (<37) matched by neurofilament level (p = 0.007).</p><p><strong>Interpretation: </strong>Elevated cerebrospinal fluid ubiquitin carboxyl-hydrolase isozyme L1 levels in C9orf72 HRE carriers can occur in the absence of increased neurofilament levels, potentially reflecting either compensatory or pathogenic mechanisms preceding rapid neuronal loss. This brings forward the window on changes associated with the C9orf72 HRE carrier state, with potential to inform understanding of penetrance and approaches to prevention. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643518","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":"Sex-Specific Vulnerabilities to Subclinical Vascular Brain Injury in Early Late-Life: The Framingham Heart Study.","authors":"Wai-Ying Wendy Yau, Matthew R Scott, Rodica E Petrea, Rachel F Buckley, Daniel Kojis, Reisa A Sperling, Jasmeer P Chhatwal, Pauline Maillard, Hugo J Aparicio, Jose Rafael Romero, Charles S DeCarli, Alexa S Beiser, Sudha Seshadri","doi":"10.1002/ana.27135","DOIUrl":"https://doi.org/10.1002/ana.27135","url":null,"abstract":"<p><strong>Objective: </strong>Subclinical vascular brain injury is an increasingly recognized risk factor for stroke and dementia. Despite well-established sex differences in vascular risk and disease prevalence, the impact of sex on drivers of subclinical vascular brain injury remains unclear, presenting a barrier to developing sex-specific prevention guidelines. We aimed to establish the extent to which sex moderates associations between vascular risk factors and magnetic resonance imaging (MRI) measures of subclinical brain injury in stroke-free older adults.</p><p><strong>Methods: </strong>We leveraged cross-sectional data from 1,579 stroke- and dementia-free Framingham Heart Study Offspring participants at exam 8 (age 65.7 ± 8.8 years, 53% women). Vascular risks were assessed using components of the Framingham Stroke Risk Profile (FSRP) and diastolic blood pressure (DBP). White matter hyperintensity volume (WMH), total cerebral brain volume (TBV), and covert brain infarcts were quantified using MRI. We examined whether vascular risk factors were associated with MRI measures across the combined cohort, and then determined whether sex modified these associations.</p><p><strong>Results: </strong>Higher FSRP and specifically systolic blood pressure (SBP) were associated with greater WMH. These associations were stronger in women and remained after adjusting for menopause age and hormone therapy use. By contrast, diabetes and lower DBP were associated with smaller TBV primarily in men. The DBP-atrophy relationship was only observed in men with declining DBP or prior hypertension.</p><p><strong>Interpretation: </strong>Our findings highlight differential vulnerability to the impact of vascular risk factors on white matter health in women and global atrophy in men, supporting the development of sex-specific guidelines to better preserve vascular brain health in aging. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613176","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":"Automated and Interpretable Detection of Hippocampal Sclerosis in Temporal Lobe Epilepsy: AID-HS.","authors":"Mathilde Ripart, Jordan DeKraker, Maria H Eriksson, Rory J Piper, Siby Gopinath, Harilal Parasuram, Jiajie Mo, Marcus Likeman, Georgian Ciobotaru, Philip Sequeiros-Peggs, Khalid Hamandi, Hua Xie, Nathan T Cohen, Ting-Yu Su, Ryuzaburo Kochi, Irene Wang, Gonzalo M Rojas-Costa, Marcelo Gálvez, Costanza Parodi, Antonella Riva, Felice D'Arco, Kshitij Mankad, Chris A Clark, Adrián Valls Carbó, Rafael Toledano, Peter Taylor, Antonio Napolitano, Maria Camilla Rossi-Espagnet, Anna Willard, Benjamin Sinclair, Joshua Pepper, Stefano Seri, Orrin Devinsky, Heath R Pardoe, Gavin P Winston, John S Duncan, Clarissa L Yasuda, Lucas Scárdua-Silva, Lennart Walger, Theodor Rüber, Ali R Khan, Torsten Baldeweg, Sophie Adler, Konrad Wagstyl","doi":"10.1002/ana.27089","DOIUrl":"10.1002/ana.27089","url":null,"abstract":"<p><strong>Objective: </strong>Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure-freedom. We developed an open-source software to characterize and localize HS to aid the presurgical evaluation of children and adults with suspected TLE.</p><p><strong>Methods: </strong>We included a multicenter cohort of 365 participants (154 HS; 90 disease controls; 121 healthy controls). HippUnfold was used to extract morphological surface-based features and volumes of the hippocampus from T1-weighted MRI scans. We characterized pathological hippocampi in patients by comparing them to normative growth charts and analyzing within-subject feature asymmetries. Feature asymmetry scores were used to train a logistic regression classifier to detect and lateralize HS. The classifier was validated on an independent multicenter cohort of 275 patients with HS and 161 healthy and disease controls.</p><p><strong>Results: </strong>HS was characterized by decreased volume, thickness, and gyrification alongside increased mean and intrinsic curvature. The classifier detected 90.1% of unilateral HS patients and lateralized lesions in 97.4%. In patients with MRI-negative histopathologically-confirmed HS, the classifier detected 79.2% (19/24) and lateralized 91.7% (22/24). The model achieved similar performances on the independent cohort, demonstrating its ability to generalize to new data. Individual patient reports contextualize a patient's hippocampal features in relation to normative growth trajectories, visualise feature asymmetries, and report classifier predictions.</p><p><strong>Interpretation: </strong>Automated and Interpretable Detection of Hippocampal Sclerosis (AID-HS) is an open-source pipeline for detecting and lateralizing HS and outputting clinically-relevant reports. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613155","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":"Distinct Constructs Underlie Patient-Reported and Performance-Rated Outcomes after Stroke.","authors":"Julie A DiCarlo, Abhishek Jaywant, Perman Gochyyev, Anna K Bonkhoff, Richard Hardstone, Kimberly S Erler, Jessica Ranford, Alison Cloutier, Nathan Ward, Kelly L Sloane, Lee H Schwamm, Steven C Cramer, David J Lin","doi":"10.1002/ana.27129","DOIUrl":"https://doi.org/10.1002/ana.27129","url":null,"abstract":"<p><strong>Objective: </strong>Patient-reported outcome measures (PROMs), which capture patients' perspectives on the consequences of health and disease, are widely used in neurological care and research. However, it is unclear how PROMs relate to performance-rated impairments. Sociodemographic factors are known to affect PROMs. Direct damage to brain regions critical for self-awareness (i.e., parietal regions and the salience/ventral-attention network) may also impair self-report outcomes. This study examined the relationship between PROMs and performance-based measures in stroke survivors with arm motor impairments. We hypothesized that PROMs would be distinct from performance-based outcomes, influenced by sociodemographic factors, and linked to damage in brain circuits involved in self-perception.</p><p><strong>Methods: </strong>We longitudinally assessed 54 stroke survivors using patient-reported and performance-rated measures at 4 timepoints. We used factor analysis to reveal the outcome battery's factorial structure. Linear regression examined the association between classes of measures and sociodemographics. Voxel-lesion-symptom-mapping, region-of-interest-based analysis, and voxel-lesion-network-mapping investigated the relationship between classes of outcomes and stroke-related injury.</p><p><strong>Results: </strong>Performance-based and patient-reported measures formed distinct factors, consistent across recovery phases. Higher education (β1 = 0.36, p = 0.02) and income adequacy (β2 = 0.48, p = 0.05) were associated with patient-reported, but not performance-rated outcomes. Greater parietal lobe injury, irrespective of hemisphere, was associated with worse patient-reported outcomes; greater corticospinal tract injury related to worse performance-rated outcomes. Lesions with greater functional connectivity to the salience/ventral-attention network were associated with worse patient-reported outcomes (r = -0.35, p = 0.009).</p><p><strong>Interpretation: </strong>Our findings reveal important differences between performance-rated and patient-reported outcomes, each with specific associated factors and anatomy post-stroke. Incorporating sociodemographic and neuroanatomic characteristics into neurorehabilitation strategies may inform and optimize patient outcomes. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613157","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 96, Number 6, December 2024","authors":"","doi":"10.1002/ana.26708","DOIUrl":"https://doi.org/10.1002/ana.26708","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642224","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 Pure Arterial Malformations.","authors":"Linggen Dong, Ming Lv","doi":"10.1002/ana.27134","DOIUrl":"https://doi.org/10.1002/ana.27134","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613156","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":"Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial.","authors":"Sarah C Milne, Melissa Roberts, Shannon Williams, Jillian Chua, Alison C Grootendorst, Genevieve Agostinelli, Anneke C Grobler, Hannah L Ross, Amy Robinson, Kristen Grove, Gabrielle Modderman, Annabel Price, Megan Thomson, Libby Massey, Christina Liang, Kishore R Kumar, Kim Dalziel, Joshua Burns, Carolyn M Sue, Pubudu N Pathirana, Malcolm Horne, Nikki Gelfard, Helen Curd, David Szmulewicz, Louise A Corben, Martin B Delatycki","doi":"10.1002/ana.27130","DOIUrl":"https://doi.org/10.1002/ana.27130","url":null,"abstract":"<p><strong>Objective: </strong>Rehabilitation is thought to reduce ataxia severity in individuals with hereditary cerebellar ataxia (HCA). This multicenter, randomized controlled superiority trial aimed to examine the efficacy of a 30-week goal-directed rehabilitation program compared with 30 weeks of standard care on function, ataxia, health-related quality of life, and balance in individuals with an HCA.</p><p><strong>Methods: </strong>Individuals with an autosomal dominant or recessive ataxia (aged ≥15 years) were enrolled at 5 sites in Australia. Participants were randomized (1:1) to receive rehabilitation (6 weeks of outpatient physiotherapy followed by a 24-week home exercise program) (n = 39) or continued their usual activity (n = 37). The primary outcome measure was the motor domain of the Functional Independence Measure (mFIM) at 7 weeks. Secondary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the SF-36v2, assessed at 7, 18, and 30 weeks. Outcome assessors were blinded to treatment allocation.</p><p><strong>Results: </strong>Seventy-one participants (rehabilitation, 37; standard-care, 34) were included in the intention-to-treat analysis. At 7 weeks, mFIM (mean difference 2.26, 95% confidence interval [CI]: 0.26 to 4.26, p = 0.028) and SARA (-1.21, 95% CI: -2.32 to -0.11, p = 0.032) scores improved after rehabilitation compared with standard care. Compared with standard care, rehabilitation improved SARA scores at 30 weeks (mean difference -1.51, 95% CI: -2.76 to -0.27, p = 0.017), but not mFIM scores (1.74, 95% CI: -0.32 to 3.81, p = 0.098). Frequent adverse events in both groups were fatigue, pain, and falls.</p><p><strong>Interpretation: </strong>Goal-directed rehabilitation improved function at 7 weeks, with improvement in ataxia and health-related quality of life maintained at 30 weeks in individuals with HCA, beyond that of standard care. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613159","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}