Annals of Clinical and Translational Neurology最新文献

{"title":"Medication Use in Multiple Sclerosis: A Population-Based Comparison With the General Danish Population.","authors":"Josefine Windfeld-Mathiasen, Henrik Horwitz, Ida M Heerfordt, Elisabeth Framke, Melinda Magyari","doi":"10.1002/acn3.70155","DOIUrl":"https://doi.org/10.1002/acn3.70155","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the overall use of prescription medications among individuals with multiple sclerosis compared to the general population, with a focus on treatments beyond disease-modifying therapies.</p><p><strong>Methods: </strong>We conducted a nationwide, registry-based study in Denmark. All residents with a diagnosis of multiple sclerosis aged 20-80 years and alive on January 1, 2023, were included and followed for 1 year. Each patient was matched with 10 individuals from the general population based on age, sex, and residence. Prescription data were obtained from the Danish National Prescription Registry and categorized using the Anatomical Therapeutic Chemical classification. Relative risks of medication use were calculated.</p><p><strong>Results: </strong>A total of 14,491 individuals with multiple sclerosis and 144,910 matched controls were included. Patients with multiple sclerosis had significantly higher use of several therapeutic drug classes, including analgesics (51% vs. 33%; RR: 1.56, 95% CI: 1.52-1.60), agents for constipation (12% vs. 3%; RR: 4.61, 95% CI: 4.36-4.88), spasmolytics, and urological medications. Among specific drugs, the most pronounced differences were observed for modafinil (RR: 323.33, 95% CI: 228.67-457.19), baclofen (RR: 36.51, 95% CI: 33.33-39.99), and fesoterodine (RR: 36.36, 95% CI: 18.66-70.87). In contrast, individuals with multiple sclerosis had lower usage of antidiabetic medications and treatments for chronic obstructive pulmonary disease.</p><p><strong>Interpretation: </strong>This large, population-based study reveals extensive use of medications targeting symptoms and comorbidities in individuals with multiple sclerosis. These insights can guide healthcare providers in optimizing patient management, addressing overlooked treatment needs, and improving overall care.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efgartigimod Combined With Steroid Treatment for HAM/TSP: A Case Report","authors":"Jiahui Zeng,&nbsp;Wotu Tian,&nbsp;Jingran Yang,&nbsp;Yanping Yang,&nbsp;Li Cao,&nbsp;Xinghua Luan","doi":"10.1002/acn3.70156","DOIUrl":"10.1002/acn3.70156","url":null,"abstract":"<p>HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological disorder with limited treatment options. We report a 54-year-old female with decade-long, progressive HAM/TSP, previously refractory to rituximab, who experienced worsening spastic paraparesis and neurogenic bladder dysfunction. She showed remarkable improvement in spasticity, bladder function, and quality of life following combination therapy with efgartigimod and corticosteroids. This case highlights efgartigimod's potential as an adjunctive therapy for refractory HAM/TSP, suggesting a new immune modulation strategy and warranting further research into combination treatments.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1937-1941"},"PeriodicalIF":3.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: Clinical Imaging Features of Sporadic and Genetic Frontotemporal Lobar Degeneration TDP-43 A and B","authors":"Sergi Borrego-Écija,&nbsp;Cèlia Cruz-Escalera,&nbsp;Agnes Perez-Millán,&nbsp;Jordi Juncà-Parellà","doi":"10.1002/acn3.70159","DOIUrl":"10.1002/acn3.70159","url":null,"abstract":"&lt;p&gt;We read with great interest the article “Clinical Imaging Features of Sporadic and Genetic Frontotemporal Lobar Degeneration TDP-43 A and B” by Coulborn et al. [&lt;span&gt;1&lt;/span&gt;]. The notion that some sporadic forms of frontotemporal lobar degeneration (FTLD) are the counterpart to genetic forms of FTLD is critically important. In recent years, research cohorts of genetic FTD, such as the Genetic Frontotemporal Initiative (GENFI) and the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD), have contributed to the expansion of our knowledge of the phenotypes of genetic FTLD. This knowledge could be further extended to sporadic cases if genetic and sporadic cases of FTLD that share the same molecular subtype also share the same clinical and neuroimaging phenotype. For example, we know that FTLD-TDP subtype A cases due to &lt;i&gt;GRN&lt;/i&gt; mutations lead to a specific phenotype characterized by asymmetric fronto-temporo-parietal atrophy [&lt;span&gt;2&lt;/span&gt;]. Could cases with the same pattern of atrophy, but lacking GRN mutations, indicate the presence of FTLD-TDP subtype A?&lt;/p&gt;&lt;p&gt;The authors conclude that clinical and neuroimaging phenotypes are influenced not only by neuropathological subtype but also, to some extent, by genotype. However, we observed that, particularly for FTLD-TDP A cases, this conclusion seems to be driven mainly by the inclusion of &lt;i&gt;C9orf72&lt;/i&gt; cases within that group. When considering only sporadic and &lt;i&gt;GRN&lt;/i&gt; cases, these subtypes appear to share many clinical and neuroimaging similarities. This discrepancy may result from the classification methodology used in the study [&lt;span&gt;3&lt;/span&gt;], rather than the more recent classification proposed by Mackenzie and Neumann [&lt;span&gt;4&lt;/span&gt;]. In their work, it is highlighted that certain &lt;i&gt;C9orf72&lt;/i&gt; cases might exhibit neuropathological features consistent with both TDP-43 subtype A and B. This mixed classification of the neuropathology of &lt;i&gt;C9orf72&lt;/i&gt; expansion carriers is problematic and not desirable. For this reason, they proposed some additional neuropathological features that, in our expertise, lead to the reclassification of most of the &lt;i&gt;C9orf72&lt;/i&gt; carriers as FTLD-TDP subtype B pathology. This leads us to consider that, when &lt;i&gt;C9orf72&lt;/i&gt; carriers are excluded from the equation, the similarities between sporadic and genetic FTLD-TDP A cases are considerable. Of note, these similarities have also been found at the transcriptomic level [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In conclusion, we consider that sporadic and genetic FTLD-TDP cases indeed share relevant phenotypic features. From our point of view, the work of Coulborn et al. [&lt;span&gt;1&lt;/span&gt;] also points in that direction, but the inclusion of cases with &lt;i&gt;C9orf72&lt;/i&gt; as TDP43 subtype A might blur the message.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Sergi Borrego-Écija:&lt;/b&gt; conceptualization, writing – original draft, writing – review and editing. &lt;b&gt;Cèlia Cruz-Escalera:&lt;/b&gt; writing – review and editing, validation. &lt;b&gt;Agnes Perez-Millán:&lt;/b&gt; wr","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 10","pages":"2164-2165"},"PeriodicalIF":3.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Diagnostic Value of Visual Evoked Potentials in Chronic Disorders of Consciousness","authors":"Letizia Clementi,&nbsp;Francesca Giulia Magnani,&nbsp;Filippo Barbadoro,&nbsp;Camilla Ippoliti,&nbsp;Martina Cacciatore,&nbsp;Davide Sattin,&nbsp;Valeria Pingue,&nbsp;Benedetta Cazzulani,&nbsp;Jorge Navarro,&nbsp;Elena Schiaffi,&nbsp;Laura Grigoletti,&nbsp;Cristina Rosazza,&nbsp;Anna Nigri,&nbsp;Matilde Leonardi,&nbsp;Davide Rossi Sebastiano","doi":"10.1002/acn3.70102","DOIUrl":"10.1002/acn3.70102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In chronic disorders of consciousness (DOCs), the distinction between vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) is as crucial as it is challenging. Evoked potentials (EPs) and event-related potentials (ERPs) are helpful, but some limitations prevent their consistent use in the routine diagnostic process. This study investigated the value of EPs and ERPs in 146 adult chronic DOC patients (82 VS/UWS and 64 MCS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All the patients underwent multimodal neurophysiological assessments, including flash-visual evoked potentials (f-VEPs), somatosensory EPs (SEPs), auditory EPs (AEPs), auditory ERPs, as well as a behavioral assessment using the Coma Recovery Scale-revised (CRS-r). We classified EPs and ERPs for the presence/absence of cortical responses, and then we performed an unsupervised cluster analysis to identify recurrent patterns. We then explored their occurrence in VS/UWS and MCS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>VS/UWS patients showed fewer cortical responses to all modalities than MCS. Cluster analysis revealed groups 1, 2, and 3, which included patients without detectable cortical responses to ERPs and f-VEPs, patients with cortical responses to f-VEPs but not to ERPs, and patients with ERPs, respectively. Groups 2 and 3 had similar demographics and CRS-r scores, which were higher than those of patients in group 1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our data suggest that f-VEPs may be as effective as ERPs for diagnosing MCS. This is a significant finding, as f-VEPs likely reflect brain injury of a lesser extent and the conservation of cortical areas pivotal for consciousness, highlighting the prominence of f-VEPs for identifying MCS in chronic DOC patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1875-1885"},"PeriodicalIF":3.9,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Challenge: The Case of a 70-Year-Old Man Who Presents With Progressive Vision Loss and Headaches","authors":"Malya Sahu,&nbsp;Rohini Samudralwar","doi":"10.1002/acn3.70089","DOIUrl":"10.1002/acn3.70089","url":null,"abstract":"<p>A 70-year-old presents with 6 weeks of progressive bilateral vision loss and headaches. He was also recently treated for presumed sciatica. His exam on admission is notable for poor visual acuity (no light perception), optic nerve atrophy bilaterally with swelling and disc hemorrhage on the left eye and left foot drop. MRI orbits reveals diffusion restriction and enhancement of bilateral optic nerves extending into the optic chiasm. He undergoes bilateral temporal artery biopsy due to concern for giant cell arteritis and high-dose steroids with no improvement in vision and both biopsies are normal. Ultimately, full neuro-axis imaging reveals evidence of leptomeningeal enhancement of the cerebellum, cervical and thoracic spine, and cauda equina nerve roots, as well as bilateral posterior semicircular canal enhancement and developing hydrocephalus. A CNS diagnosis is made via lumbar puncture, though ultimately the patient eventually expires in the hospital.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1944-1946"},"PeriodicalIF":3.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOTCH2NLC Repeat Expansions in Parkinsonian Disorders: Clinical and Neuroimaging Characteristics.","authors":"Han-Lin Chiang, Kang-Yang Jih, Cheng-Tsung Hsiao, Fu-Pang Chang, Justus Chunyu Chen, Yi-Chu Liao, Yih-Ru Wu, Yi-Chung Lee","doi":"10.1002/acn3.70147","DOIUrl":"https://doi.org/10.1002/acn3.70147","url":null,"abstract":"<p><strong>Objective: </strong>Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder caused by NOTCH2NLC GGC repeat expansions, with heterogeneous clinical manifestations, including parkinsonism. Recent studies have identified NOTCH2NLC repeat expansions in patients with Parkinson's disease (PD) and atypical parkinsonism (aPM), suggesting a potential genetic contribution. However, it remains unclear whether such cases represent NIID-related parkinsonism or typical PD. To address this, we screened NOTCH2NLC repeat expansions in a parkinsonian cohort and analyzed associated clinical and neuroimaging features.</p><p><strong>Methods: </strong>We examined 1017 unrelated patients with PD, 115 with aPM, 11 with multiple system atrophy, six with progressive supranuclear palsy, three with dementia with Lewy bodies, and 321 healthy controls. NOTCH2NLC GGC repeat expansions were detected using repeat-primed PCR and amplicon length analysis. Clinical data and neuroimaging findings were comprehensively reviewed.</p><p><strong>Results: </strong>Pathological NOTCH2NLC repeat expansions were identified in four patients with aPM and none with PD or in controls, with significantly higher frequency in aPM than in PD. An additional affected family member was also identified. All five patients showed clinical or neuroimaging features suggestive of NIID, including white matter hyperintensities in the paravermis and/or corticomedullary junction, curvilinear hyperintensities on diffusion-weighted imaging. Skin biopsies in two patients revealed eosinophilic, p62-positive intranuclear inclusions in the sweat gland cells and fibroblasts. No patient responded well to levodopa. TRODAT scans revealed normal findings in three patients, symmetric dopaminergic deficits in one, and asymmetric deficits in another.</p><p><strong>Interpretation: </strong>NOTCH2NLC repeat expansions appear to be more frequently associated with aPM with NIID-like features than with typical PD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Interleukin-6 Levels and Timing of Acute Ischemic Stroke Onset","authors":"Robert G. Kowalski,&nbsp;Aurélie Ledreux,&nbsp;John E. Violette,&nbsp;Whitney Paustian,&nbsp;Stefan Sillau,&nbsp;John A. Thompson,&nbsp;Robert T. Neumann,&nbsp;David Ornelas,&nbsp;Andrew A. Monte,&nbsp;Layne Dylla,&nbsp;Adit A. Ginde,&nbsp;Andra M. Farcas,&nbsp;Christina M. Coughlan,&nbsp;William J. Jones,&nbsp;James C. Grotta,&nbsp;Michael W. Graner","doi":"10.1002/acn3.70138","DOIUrl":"10.1002/acn3.70138","url":null,"abstract":"<p>Intravenous thrombolysis is the most widely available effective ischemic stroke treatment, but is approved only if given within 4.5 h from stroke onset. Many patients are not treated because stroke onset time is unknown. We evaluated the cytokine interleukin 6 (IL-6) in circulating blood after acute ischemic stroke (AIS). Results show IL-6 is elevated as early as 26 min after stroke and increases over 24 h. The IL-6 levels can estimate when the stroke occurred with 80% sensitivity and 74% specificity. With refinement, a point-of-care blood test for IL-6 during stroke could substantially increase the number of stroke patients eligible for thrombolysis.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1926-1931"},"PeriodicalIF":3.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal Autonomic Biomarkers Predict Phenoconversion in Pure Autonomic Failure.","authors":"S Koay, E Vichayanrat, F Bremner, F Valerio, R Mackenzie, G Chiaro, G Ingle, P McNamara, L Watson, J N Panicker, M P Lunn, C Mathias, V Iodice","doi":"10.1002/acn3.70140","DOIUrl":"https://doi.org/10.1002/acn3.70140","url":null,"abstract":"<p><strong>Background: </strong>Pure autonomic failure (PAF) presents with autonomic failure without other neurological features. A third develop central neurological features, fulfilling criteria for multiple system atrophy (MSA) and Lewy body diseases (LBD), including Parkinson's disease and Dementia with Lewy bodies. We hypothesized multimodal autonomic biomarkers would identify differences between PAF, MSA, and LBD, and predict phenoconversion in patients presenting with PAF.</p><p><strong>Methods: </strong>This observational cohort study included 391 alpha-synucleinopathy patients evaluated with cardiovascular autonomic testing, plasma noradrenaline, pupillometry, autonomic symptom, and quality-of-life questionnaires. PAF patients were monitored for the emergence of central neurological features. Logistic regression modeling was used to identify autonomic biomarkers at initial assessment that predicted future phenoconversion.</p><p><strong>Results: </strong>Patients with PAF had more severe orthostatic hypotension, lower supine plasma noradrenaline, and frequent sympathetic pupillary deficits at initial assessment than MSA and LBD. 50/194 (26%) with PAF phenoconverted to MSA or LBD after a median of 13 years, with normal pupils, heart rate response to deep breathing ≥ 10 bpm, and supine plasma noradrenaline ≥ 200 pg/mL predicting future phenoconversion to MSA or LBD, with younger age at presentation and higher supine plasma noradrenaline levels associated with conversion to MSA.</p><p><strong>Conclusion: </strong>In patients presenting with PAF, normal pupillary function and supine plasma noradrenaline levels with intact cardiovagal responses were red flags for future phenoconversion. Younger patients with higher supine plasma noradrenaline levels were more likely to convert to MSA rather than LBD. A non-invasive multimodal autonomic assessment can help differentiate between alpha-synucleinopathies and predict phenoconversion from PAF to MSA or LBD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeat Expansions in PLIN4 Cause Autosomal Dominant Vacuolar Myopathy With Sarcolemmal Features","authors":"Laura Llansó,&nbsp;Igor Stevanovski,&nbsp;Germán Morís,&nbsp;Roger Collet-Vidiella,&nbsp;Alba Segarra-Casas,&nbsp;Lidia González-Quereda,&nbsp;Benjamín Rodríguez-Santiago,&nbsp;Pia Gallano,&nbsp;Rodrigo Alvarez,&nbsp;Ana Vesperinas,&nbsp;Rosa Blanco,&nbsp;Beatriz San-Millán,&nbsp;Carmen Navarro,&nbsp;Isabel Illa,&nbsp;Gianina Ravenscroft,&nbsp;Ira W. Deveson,&nbsp;Eduard Gallardo,&nbsp;Montse Olivé","doi":"10.1002/acn3.70146","DOIUrl":"10.1002/acn3.70146","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aim to describe and characterize two unrelated Spanish families suffering from an autosomal dominant autophagic vacuolar myopathy caused by repeat expansions in <i>PLIN4</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the clinical phenotype and muscle imaging, and performed a genetic workup that included exome sequencing, muscle RNAseq, and long-read genome sequencing. Muscle pathology was assessed by means of histochemistry, electron microscopy, PLIN4, p62, LC3, and NBR1 immunofluorescence and/or western blotting. Detailed characterization of autophagic vacuoles was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients presented around the age of 30 with mild proximal weakness followed by prominent distal weakness in lower legs, eventually spreading to other muscle groups. Muscle biopsies showed unique pathological features characterized by numerous rimmed vacuoles that displayed sarcolemmal features and were located beneath the sarcolemma and within the cytoplasm. Ultrastructural studies showed autophagic vacuoles, replications, and loops of the basal lamina and tubulofilamentous sarcoplasmic inclusions. p62 and NBR1 co-localized with PLIN4 at the sarcolemma and vacuoles. LC3 immunoreactivity and other lysosomal markers were increased at the vacuoles. Targeted long-read sequencing of <i>PLIN4</i> in affected individuals revealed a single expanded allele of 39 × 99 bp repeats in family 1 and of 37 × 99 bp repeats in family 2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We characterize two new families suffering from an autosomal dominant myopathy carrying repeat expansions in <i>PLIN4</i>. Subsarcolemmal p62 expression is a powerful although nonspecific marker of this disease. No correlation between the size of the expansion and clinical severity can be clearly established. <i>PLIN4</i> expansions should be considered in the diagnosis of autosomal dominant vacuolar myopathies, especially when sarcolemmal features are present.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 10","pages":"2136-2151"},"PeriodicalIF":3.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous Monitoring of Bladder Dysfunction in People With Multiple Sclerosis: Wearables for the Bladder","authors":"Valerie J. Block,&nbsp;Shane Poole,&nbsp;Leah McIntyre,&nbsp;Nikki Sisodia,&nbsp;Chelyn Park,&nbsp;Gabby Joseph,&nbsp;Michelle E. Van Kuiken,&nbsp;Anne M. Suskind,&nbsp;Riley Bove","doi":"10.1002/acn3.70112","DOIUrl":"10.1002/acn3.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bladder dysfunction affects over 85% of people with multiple sclerosis (PwMS), yet current assessment methods are limited to periodic in-clinic evaluations or subjective patient reports, failing to capture real-world symptom fluctuations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To evaluate the feasibility and validity of using a novel remote bladder ultrasound device for home monitoring of bladder dysfunction in PwMS, comparing remote measurements with standard clinical assessments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-two women with MS participated in this 3-month pilot study. Participants were asked to use the wearable ultrasound device at home for at least 3–5 days a month. Remote device measurements were compared with standard clinical data for post-void residual (rPVR vs. cPVR) and urinary frequency (rFrequency vs. 3-day bladder diary frequency). Agreement between measures was assessed using Bland–Altman analyses and correlation coefficients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants were middle-aged (mean 51.5 years; SD 9.3) with mild–moderate disability (median EDSS 4.0) and mostly relapsing MS (72.7%). Study retention was high (86.4%; 19/22), with mean device utilization of 14.1 days. Good agreement was seen between rPVR and cPVR (mean difference = 32.1 mL, SD = 38.6; 95% limits of agreement: −43.6, 107.9). The rFrequency measure also demonstrated a strong correlation with patient-reported frequency (ICC = 0.81, Pearson's <i>r</i> = 0.793, <i>p</i> = 0.002). Visualization of remote monitoring data revealed substantial day-to-day variability in bladder symptoms not captured by traditional assessments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This pilot study demonstrates the feasibility and preliminary validity of using wearable ultrasound technology for remote monitoring of bladder dysfunction in PwMS. The ability to capture real-world symptom variations could transform assessment and management approaches, enabling more personalized and responsive care strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 9","pages":"1865-1874"},"PeriodicalIF":3.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}