Annals of Clinical and Translational Neurology最新文献

{"title":"Remarkable Recovery After Delayed High-Dose Methylprednisolone in a Rare Case of Penetrating Spinal Cord Injury.","authors":"Honghong Wang, Shuang Liu, Jiale Wang, Kaiyang Xue, Shenwei Li, Zhongheng Du","doi":"10.1002/acn3.70405","DOIUrl":"https://doi.org/10.1002/acn3.70405","url":null,"abstract":"<p><p>Traumatic spinal cord injury (TSCI) caused by sharp-force penetration is exceptionally rare, and the use of high-dose methylprednisolone (MP) remains highly controversial, especially beyond the conventional 8-h treatment window. This case report describes a 30-year-old male with acute incomplete TSCI following a knife stab wound to the right neck. Despite no initial improvement, high-dose MP (1000 mg/day for 3 days, tapered thereafter) was initiated 40 h post-injury, along with mannitol. Remarkable neurological recovery was observed, including independent ambulation by post-injury day 25. Follow-up MRI showed significant hematoma absorption. This case suggests that delayed high-dose MP may benefit selected TSCI patients, particularly those with penetrating mechanisms and ongoing secondary injury. It highlights the potential for extending the therapeutic window in specific scenarios and supports the need for further research into individualized treatment strategies for TSCI.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758004","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":"Reply to Letter: \"Limitations of Complement Activity Assays as Biomarkers for Ravulizumab Therapeutic Monitoring\" by Saccà and Pelto Regarding \"Inhibition of Classical and Alternative Complement Pathway by Ravulizumab and Eculizumab\".","authors":"Lea Gerischer, Jutta Schroeder-Braunstein, Guido Wabnitz, Andreas Meisel","doi":"10.1002/acn3.70403","DOIUrl":"https://doi.org/10.1002/acn3.70403","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727731","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":"Prodromal Lewy Body Disorder Features in REM Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy.","authors":"Daniel Weintraub, Michele K York, Roseanne Dobkin, Anuprita R Nair, Ryan Kurth, David-Erick Lafontant, Chelsea Caspell-Garcia, Roy N Alcalay, Ethan G Brown, Lana M Chahine, Christopher Coffey, Tatiana Foroud, Douglas Galasko, Karl Kieburtz, Kenneth Marek, Kalpana Merchant, Brit Mollenhauer, Kathleen L Poston, Andrew Siderowf, Cristina Simonet, Tanya Simuni, Caroline M Tanner, Thomas F Tropea, Aleksandar Videnovic","doi":"10.1002/acn3.70399","DOIUrl":"https://doi.org/10.1002/acn3.70399","url":null,"abstract":"<p><strong>Objective: </strong>Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal state for Lewy body disorders and exhibits biological heterogeneity that may influence clinical expression and progression. We examined clinical features in individuals with iRBD and biomarker-defined synucleinopathy.</p><p><strong>Methods: </strong>Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, multi-center observational study. Participants included polysomnogram (PSG)-confirmed iRBD individuals who were cerebrospinal fluid (CSF) α-synuclein seed amplification assay positive with no clinical diagnosis of Parkinson's disease or dementia with Lewy bodies, along with robust healthy controls (HCs). Clinical and biological features of prodromal PD and DLB, including mild cognitive impairment (MCI), subthreshold parkinsonism, and a range of neuropsychiatric, autonomic, and sensory symptoms, were assessed.</p><p><strong>Results: </strong>Compared with HCs (N = 136), iRBD participants (N = 197) demonstrated worse cognitive performance, including a lower cognitive summary score (p < 0.0003, effect size = 0.41), and higher odds of subthreshold parkinsonism (OR = 24.5), and neuropsychiatric (OR = 3.5), autonomic (OR = 7.2) and sensory symptoms (OR = 13.2). Common features included hyposmia (75%), pain (54%), urinary problems (52%), constipation (49%), lightheadedness (40%) and anxiety (36%), whereas rates of MCI (32%), subthreshold parkinsonism (27%) and psychosis (7%) were lower. iRBD participants with abnormal dopamine transporter imaging had higher anxiety scores and antidepressant use. Although only 10% met criteria for prodromal DLB due to the requirement for MCI, most exhibited multi-domain impairment.</p><p><strong>Interpretation: </strong>iRBD with synucleinopathy is associated with multi-domain clinical impairment before clinical neurodegenerative disease diagnosis, supporting broad clinical assessment in early biomarker-defined synuclein disease.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147757994","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":"Safety and Tolerability of Givinostat: Evidence From Real-World and Clinical Practice.","authors":"Marika Pane, Anna Capasso, Chiara Arpaia, Adele D'Amico, Emilio Albamonte, Federica Trucco, Maria Sframeli, Riccardo Masson, Francesca Magri, Luca Bello, Romina Venditti, Claudia Dosi, Michela Catteruccia, Michele Tosi, Claudio Bruno, Sonia Messina, Giacomo Comi, Elena Pegoraro, Valeria A Sansone, Eugenio Mercuri","doi":"10.1002/acn3.70397","DOIUrl":"https://doi.org/10.1002/acn3.70397","url":null,"abstract":"<p><strong>Objective: </strong>The aim of our study was to establish the prevalence of adverse events in a real-world setting in boys living with Duchenne muscular dystrophy (DMD) treated with givinostat as part of an Expanded Access Program (EAP) in Italy.</p><p><strong>Methods: </strong>The cohort included 90 ambulant boys, with age when treatment started between 6 and 23 years (mean 10.1 years, SD: 3.2 years) and with a follow up between 6.0 and 14.6 months (mean 10.6 months; SD 2.6 months).</p><p><strong>Results: </strong>Platelets count decrease and triglyceride levels increase were the most common adverse events, followed by diarrhea. A dose reduction was needed in 38 of the 90 boys following thrombocytopenia (n = 34), diarrhea (n = 2), and hypertriglyceridemia (n = 4), with two of the boys presenting both thrombocytopenia and hypertriglyceridemia. Eleven of the 38 boys with initial dose reduction (10 with thrombocytopenia and 1 with hypertriglyceridemia) required an additional dose reduction for persistence of values outside the threshold, with one of them discontinuing treatment because of persistent hypertriglyceridemia even with the lowest dose.</p><p><strong>Interpretation: </strong>Our results confirm the safety profile observed in the pivotal study providing further evidence of the management of the drug in a real-world setting. In our experience, treatment with givinostat was well managed by maintaining a strict monitoring. This was facilitated by allowing families to perform blood tests in local labs, reducing the stress and burden of frequent visits to the hospital.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715404","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":"Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy in Idiopathic Intracranial Hypertension Patients Treated with GLP-1 Receptor Agonists.","authors":"Faisal A Al-Harbi, Mohanad A Alkuwaiti, Yazeed B Alaql, Ahmed K Alsaif, Ahmed A Alessa, Meshari Ayed Alharbi, Mohammed Alfalah, Saud A Alnaaim, Sajjad M AlHaddad, Ahmed Y Azzam","doi":"10.1002/acn3.70406","DOIUrl":"https://doi.org/10.1002/acn3.70406","url":null,"abstract":"<p><strong>Introduction: </strong>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant weight-reducing effects and may offer benefits in idiopathic intracranial hypertension (IIH); however, recent concerns about the risk of non-arteritic anterior ischemic optic neuropathy (NAION) have emerged. Hence, this study was designed to examine the relationship between GLP-1 RA use and optic outcomes in IIH patients.</p><p><strong>Methods: </strong>This study used the TriNetX Global Collaborative Network to perform a retrospective propensity score-matched cohort study. It involved GLP-1 RA exposure status to classify adult patients with IIH. Further, it applied propensity score matching (PSM) on demographics, comorbidities, and medications. In this study, the primary outcome was incident NAION; the secondary outcome was optic atrophy. Cox proportional hazards regression, time-stratified analyses, and multiple testing corrections were performed.</p><p><strong>Results: </strong>From 144,678 IIH patients, 15,567 matched pairs were analyzed. GLP-1 RA use demonstrated significantly decreased NAION risk (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.24-0.93, p = 0.027) and optic atrophy risk (HR 0.78, 95% CI 0.64-0.94, p = 0.009). Time-stratified analyses have demonstrated protective associations across all evaluated time windows. The optic atrophy finding remained significant after Bonferroni correction, while NAION remained significant after false discovery rate correction. Subgroup analysis revealed stronger protective associations in non-diabetic patients (risk ratio 0.53, 95% CI 0.41-0.68) compared to diabetic patients (risk ratio 0.76, 95% CI 0.58-0.99).</p><p><strong>Conclusions: </strong>GLP-1 RA utilization among IIH patients was associated with a reduced risk of NAION and optic atrophy. These findings align with the proposed pathway linking GLP-1 RA-induced weight reduction to lower intracranial pressure and papilledema reduction in IIH patients; residual confounding cannot be ruled out, and prospective studies are needed to confirm these associations.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696905","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":"Aquaporin-4 in Narcolepsy Type 1: Investigation of Perivascular Fluid Movement in Sleep Disorders.","authors":"Jonas Ranke, Petra Steinacker, Steffen Halbgebauer, Patrick Oeckl, Geert Mayer, Markus Otto","doi":"10.1002/acn3.70398","DOIUrl":"https://doi.org/10.1002/acn3.70398","url":null,"abstract":"<p><p>Narcolepsy type 1 (NT1) is caused by the loss of hypocretin-1 leading to excessive daytime sleepiness and cataplexy. Additionally, disrupted nighttime sleep has become an increasingly recognized feature of NT1. As the glymphatic fluid movement has been linked to sleep architecture, we investigated cerebrospinal fluid (CSF) Aquaporin-4 (AQP4) as potential biomarker for perivascular fluid exchange processes in 133 NT1 patients, 145 patients with other sleeping disorders, and 62 controls. NT1 patients showed lower CSF AQP4 concentrations compared to both control groups (p < 0.0001 and p = 0.01). AQP4 levels were correlated to the CSF hypocretin-1 levels. These data suggest potential brain fluid barrier alterations in NT1.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687164","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":"Predictive Ability of Plasma p-tau217 for β-Amyloid Status: A Prospective Multicenter Study.","authors":"Miquel Massons, Nuria Guillen, Jordi Sarto, Neus Falgàs, Sergi Borrego-Écija, Diana Esteller-Gauxax, Magda Castellví, Adrià Tort-Merino, Agnès Pérez-Millan, Anna Antonell, Josep M Augè Fradera, Gerard Piñol, Iolanda Riba, Anna Carnes-Vendrell, Marta Cullell, Maria Teresa Osuna, Lorena Bajo, Teresa Romero, Eva Bonjoch, Joan Bello, Susana Fernández, Marta Balagué, Isabel Gómez-Ruiz, Anuncia Boltes, Claustre Pont, Raquel Cuevas, Sara Carrillo, Laura Iglesias, Teresa Maria Casadevall Codina, Lorena Grau Guinea, Fernando Jose Espada, Raquel Sánchez-Valle, Mircea Balasa, Albert Lladó","doi":"10.1002/acn3.70387","DOIUrl":"https://doi.org/10.1002/acn3.70387","url":null,"abstract":"<p><strong>Objective: </strong>Plasma tau phosphorylated at threonine 217 (p-tau217) measured with fully automated platforms has shown high accuracy for Alzheimer's disease (AD) diagnosis, but real-world multicenter data remain limited. We aimed to validate the diagnostic performance of p-tau217 for identifying AD pathology in a real-world multicenter cohort across seven memory clinics in Catalonia (Spain), with only one tertiary hospital with prior experience in AD blood-based biomarkers.</p><p><strong>Methods: </strong>In this prospective multicenter study, consecutive patients with cognitive impairment undergoing routine cerebrospinal fluid (CSF) biomarker testing were included. Plasma samples were collected following a standardized pre-analytical protocol and analyzed centrally using the Lumipulse G p-tau217 assay (Fujirebio). Diagnostic accuracy for Aβ status was assessed overall and across sites.</p><p><strong>Results: </strong>A total of 185 participants were included. Plasma p-tau217 showed excellent accuracy for CSF-defined Aβ status (AUC 0.916) with consistent performance across centers. Using a single cut-off, diagnostic accuracy reached 84.9%, which prompted the use of a dual-threshold strategy to improve overall performance and to classify p-tau217 values into low, intermediate, and high probability categories of Aβ positivity. When applying a strict model with 97.5% sensitivity and specificity (cut-offs 0.146/0.486 pg/mL), 42.7% of participants fell within the intermediate zone, whereas the remaining 57.3% were confidently classified with 95.3% accuracy.</p><p><strong>Interpretation: </strong>In a real-world multicenter memory-clinic cohort, plasma p-tau217 measured on a fully automated platform accurately discriminated CSF Aβ status and enabled reliable rule-in/rule-out classification in over half of patients. These findings support its broader clinical use as an initial diagnostic tool for AD.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669429","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":"Network Localization of Fatigue in Multiple Sclerosis","authors":"Olli Likitalo,&nbsp;Jaakko Kungshamn,&nbsp;Albert Bellmunt-Gil,&nbsp;Silvia Tommasin,&nbsp;Abhineet Ojha,&nbsp;Matias Viitala,&nbsp;Juho Aaltonen,&nbsp;Jyrki Lötjönen,&nbsp;Juha Koikkalainen,&nbsp;Pauli Ylikotila,&nbsp;Patrizia Pantano,&nbsp;Merja Soilu-Hänninen,&nbsp;Juho Joutsa","doi":"10.1002/acn3.70241","DOIUrl":"10.1002/acn3.70241","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fatigue is among the most common symptoms and one of the main factors determining the quality of life in multiple sclerosis (MS). However, the neurobiological mechanisms underlying fatigue are not fully understood. Here we studied lesion locations and their connections in individuals with MS, aiming to identify brain networks associated with fatigue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>38 MS patients with and 21 without fatigue were included in the study. Association between fatigue and lesion locations was investigated using voxel-lesion symptom mapping and lesion connectivity using lesion network mapping. The findings were tested in two independent datasets, including (1) MS patients scanned using resting-state functional connectivity MRI (rs-fcMRI) (<i>n</i> = 199) and (2) individuals with stroke lesions (<i>n</i> = 85).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were no specific anatomical MS lesion locations significantly associated with fatigue, but lesions associated with fatigue were connected to a common network with peak positive connectivity to the right premotor cortex and negative connectivity to the left temporal pole (<i>p</i>\u0000 _FWE &lt; 0.05). Of the two identified network nodes, connectivity from the premotor cortex to multiple other brain regions was significantly associated with MS fatigue severity in the independent dataset of MS patients (<i>p</i> &lt; 0.05). The MS fatigue network was also reproducible in poststroke fatigue (spatial correlation <i>r</i> = 0.57, permutation test <i>p</i> = 0.02), again showing that lesion connectivity to the premotor cortex, but not the temporal pole, was associated with fatigue (<i>p</i> = 0.04).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results show that fatigue in MS localizes to a brain network, lending insight into the neural substrates of fatigue.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 4","pages":"676-687"},"PeriodicalIF":3.9,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538393","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":"Real-World Investigation of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disease","authors":"Li-Tsung Lin,&nbsp;Hui-An Lin,&nbsp;Sheng-Feng Lin","doi":"10.1002/acn3.70246","DOIUrl":"10.1002/acn3.70246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Satralizumab, a monoclonal antibody targeting the interleukin-6 receptor, has demonstrated efficacy in clinical trials for neuromyelitis optica spectrum disorder (NMOSD). However, its real-world effectiveness and safety compared to conventional immunosuppressive therapies remain uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified patients diagnosed with NMOSD in the TriNetX federated health research platform between January 2018 and April 2024. This international platform was accessed via Taipei Medical University. Patients were followed for 1 month to 3 years. A 1:1 propensity-score matching (PSM) analysis balanced baseline characteristics between the satralizumab and conventional immunosuppressant groups. Risk ratios (RRs) were calculated for relapse risk and safety outcomes, including sepsis, respiratory infection, urinary tract infection, anemia, neutropenia, and mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 220 patients received satralizumab, while 1744 received conventional immunosuppressants. After PSM, 218 patients remained in each group. Satralizumab was associated with a significantly lower relapse risk at 1 month (RR: 0.38, 95% CI 0.21–0.66), 3 months (RR: 0.43, 95% CI 0.28–0.66), 6 months (RR: 0.50, 95% CI 0.33–0.70), 9 months (RR: 0.62, 95% CI 0.46–0.83), 12 months (RR: 0.63, 95% CI 0.47–0.83), 24 months (RR: 0.60, 95% CI 0.42–0.86) and 36 months (RR: 0.52, 95% CI 0.32–0.83). Across all follow-up intervals, numbers needed to treat were consistently between 4 and 9. No significant differences were observed in infection rates, anemia, neutropenia, or mortality between the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Satralizumab demonstrated superior efficacy in reducing NMOSD relapse rates compared to conventional immunosuppressants while maintaining a comparable safety profile.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 4","pages":"665-675"},"PeriodicalIF":3.9,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511323","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":"Reduced Muscular Carnosine in Proximal Myotonic Myopathy—A Pilot 1H-MRS Study","authors":"Alexander Gussew,&nbsp;Maryam Kargaran,&nbsp;Maik Rothe,&nbsp;Andreas Deistung,&nbsp;Dietrich Stoevesandt,&nbsp;Walter A. Wohlgemuth,&nbsp;David Strube,&nbsp;Thomas Kendzierski,&nbsp;Anna Katharina Kölsch,&nbsp;Maurits Gerhard Abraham Heuschen,&nbsp;Markus Otto,&nbsp;Alexander Mensch","doi":"10.1002/acn3.70263","DOIUrl":"10.1002/acn3.70263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Myotonic dystrophy type 2 (proximal myotonic myopathy, PROMM) is a progressive multisystem disorder with muscular symptoms (proximal weakness, pain, myotonia) and systemic manifestations such as diabetes mellitus, cataracts, and cardiac arrhythmias. A hallmark feature is the selective degeneration of type-II fibers, likely driven by chronic myotonia and sustained metabolic stress. In this study, proton magnetic resonance spectroscopy (¹H-MRS) was applied to assess intramuscular carnosine as a potential noninvasive marker of type-II fiber integrity, alongside extramyocellular lipids (EMCL) and intracellular pH. We hypothesized that carnosine would be reduced in PROMM as a consequence of type-II fiber loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seventy participants (27 genetically confirmed PROMM patients, 43 healthy volunteers) underwent localized ¹H-MRS of the quadriceps muscle at 3 T using a short-TE PRESS sequence. To ensure reliable carnosine quantification, spectra with voxel fat fraction ≥ 40% were excluded, yielding a final cohort of 19 patients and 19 matched healthy volunteers. Metabolites were quantified relative to total creatine, and exploratory correlations were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PROMM patients showed significantly reduced carnosine compared with healthy volunteers (−50%, 0.05 ± 0.03 vs. 0.10 ± 0.05; <i>p</i> = 0.0022) and markedly elevated EMCL (threefold, 150.6 ± 80.5 vs. 48.6 ± 38.4; <i>p</i> = 0.0007). Intracellular pH did not differ between groups. Exploratory analysis revealed a negative correlation between carnosine and EMCL (<i>r</i> = −0.50, <i>p</i> = 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This pilot study demonstrates that ¹H-MRS can detect reduced intramuscular carnosine in PROMM, consistent with selective type-II-fiber loss. Carnosine thus emerges as a potential in vivo biomarker of fiber-type-specific degeneration. Validation in larger, longitudinal cohorts is warranted to establish its clinical and translational relevance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 4","pages":"788-795"},"PeriodicalIF":3.9,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595426","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}