Brain最新文献

{"title":"How modular are modules in visual cortex?","authors":"Martin N Hebart","doi":"10.1093/brain/awaf100","DOIUrl":"https://doi.org/10.1093/brain/awaf100","url":null,"abstract":"This scientific commentary refers to ‘Visual feature processing in a large stroke cohort: evidence against modular organization’ by Lugtmeijer, Sobolewska et al. (https://doi.org/10.1093/brain/awaf009).","PeriodicalId":9063,"journal":{"name":"Brain","volume":"3 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618478","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":"MRI R2* captures inflammation in disconnected brain structures after stroke: a translational study.","authors":"Ismail Koubiyr, Takayuki Yamamoto, Laurent Petit, Nadège Dubourdieu, Elena Avignone, Elise Cozensa, Chloé Galmiche, Hikaru Fukutomi, Igor Sibon, Vincent Dousset, Michel Thiebaut de Schotten, Aude Panatier, Marion Tible, Thomas Tourdias","doi":"10.1093/brain/awaf082","DOIUrl":"https://doi.org/10.1093/brain/awaf082","url":null,"abstract":"<p><p>Ischemic strokes disrupt brain networks, leading to remote effects in key regions like the thalamus, a critical hub for brain functions. However, non-invasive methods to quantify these remote consequences still need to be explored. This study aimed to demonstrate that MRI-derived R2* changes can capture iron accumulation linked with inflammation secondary to stroke-induced disconnection. In order to link remote R2* changes to stroke-induced disconnection, we first conducted a secondary analysis of 156 prospectively included stroke patients who underwent MRI at baseline and 1-year follow-up. We mapped fibers disconnected by baseline infarcts to compare the R2* changes over 1 year according to the disconnectivity status in specific thalamic nuclei groups. We also identified the variables associated with elevated R2* at 1 year in a multivariate context through linear regressions. In parallel, to understand the biological underpinning of the remote R2* changes, we set up a translational mouse model through photothrombotic induction of focal cortical infarcts or sham procedures in 110 C57BL/6J mice. We explored the mice through combinations of in vivo MRI at 72h, 2-, 4-, and 8-weeks, histology, qPCR for gene expression, mass spectrometry for iron concentration quantification, and additional ex vivo high-resolution diffusion tensor imaging. In stroke patients, we found a significant increase of R2* within severely disconnected medial and lateral thalamic nuclei groups from baseline to 1 year. At the same time, no change occurred if these structures were not disconnected. We also showed that the disconnectivity status at baseline was significantly associated with R2* at follow-up, independently from confounders, establishing a direct and independent relationship between baseline disconnection and the subsequent R2* increase within the associated locations. In mice, we recapitulated the patients' conditions by observing increased R2* in the stroke groups, specifically within the disconnected thalamic nuclei. Such remote and focal R2* changes peaked at 2 weeks, preceding and correlating with longer-term atrophy at 8 weeks. We established that the remote R2* increase was spatially and temporally correlated with a significant increase of chemically determined iron load bound to ferritin within activated microglial cells. This study provides critical evidence that R2* is a sensitive marker of inflammation secondary to network disconnection, potentially informing future neuroprotective strategies targeting remote brain regions after stroke.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603771","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":"Modulating inhibitory synaptic plasticity to restore basal ganglia dynamics in Parkinson’s disease","authors":"Kiah A Spencer, Alexandra Boogers, Srdjan Sumarac, David B J Crompton, Leon A Steiner, Luka Zivkovic, Yijinmide Buren, Alexandre Boutet, Andres M Lozano, Suneil K Kalia, William D Hutchison, Alfonso Fasano, Luka Milosevic","doi":"10.1093/brain/awaf103","DOIUrl":"https://doi.org/10.1093/brain/awaf103","url":null,"abstract":"Parkinson’s disease is characterized, in part, by hypoactivity of direct pathway inhibitory projections from striatum to the globus pallidus internus (GPi) and indirect pathway inhibitory projections from globus pallidus externus (GPe) to the subthalamic nucleus (STN). In people with Parkinson’s disease (n=32), we explored the potential use of intracranial stimulation for eliciting long-term potentiation (LTP) of these underactive pathways to produce improvement of symptoms that persists beyond stimulation cessation. During GPi deep brain stimulation (DBS) surgery, we found strong evidence (p&amp;lt;.05; BF10&amp;gt;10) of increased amplitudes of hand movements and striato-GPi evoked potentials before versus after high-frequency microstimulation. In a small sample of outpatients with sensing-enabled GPi-DBS, we found anecdotal evidence (p&amp;lt;.10; BF10&amp;gt;1) of improved hand movements and attenuated beta frequency oscillations. In STN, enduring behavioural effects, potentiation of GPe-STN projections (intraoperative), and decreases to beta oscillations (extraoperative) were not observed. Our findings support that LTP-like effects in GPi may produce motor improvements that extend beyond stimulation cessation, while the lack of effects in STN suggests the need for optimizing stimulation paradigms for effective LTP induction. These findings nevertheless highlight the potential of LTP-based strategies for sustained therapeutic benefits, which may be useful for mitigating DBS side-effects and optimizing battery usage.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"31 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607988","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":"Parvalbumin neurons mediate neurological phenotypes of anti-NMDAR encephalitis.","authors":"Yi-Fan Feng, Zi-Ke Zeng, You Ni, Yue Hu, Ke-Xin Yang, Fang Cai, Qin-Ming Zhou, Ming Chen, Xiao-Na Zhu, Sheng Chen, Ji Hu","doi":"10.1093/brain/awae374","DOIUrl":"https://doi.org/10.1093/brain/awae374","url":null,"abstract":"<p><p>Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, often present with severe psychiatric symptoms, yet the neuropathological mechanisms underlying their cognitive deficits remain insufficiently understood. In this study, we constructed an animal model using anti-NMDAR IgG purified from the serum of patients with anti-NMDAR encephalitis, and we used IgG obtained from healthy individuals as a control. Daily administration of anti-NMDAR IgG into the medial prefrontal cortex (mPFC) of mice for 7 days resulted in cognitive impairments resembling clinical symptoms, which spontaneously resolved 30 days after discontinuing the injections. Immunohistochemical staining and electrophysiological testing of parvalbumin neurons in the mPFC treated with anti-NMDAR IgG revealed significant cellular morphological damage, reduced excitability, synaptic dysfunction and a loss of NMDAR antagonist-induced gamma oscillations. Application of optogenetic and pharmacogenetic techniques to activate parvalbumin neurons in the mPFC successfully reversed the cognitive impairments observed in the anti-NMDAR-IgG-treated mice. Single-cell sequencing of anti-NMDAR-IgG-treated parvalbumin neurons identified differentially expressed genes and pathways related to synapses and neuronal development, offering potential targets for therapeutic intervention. Additionally, we showed that these alterations in parvalbumin neurons were not confined to the mPFC, as similar changes were detected in the hippocampus after anti-NMDAR IgG injections. In summary, our findings elucidate distinct alterations in parvalbumin neurons during the pathogenesis of anti-NMDAR encephalitis, providing preclinical rationale for exploring approaches to modulate parvalbumin neuronal function to treat anti-NMDAR encephalitis.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603773","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":"Transcallosal inhibition does not influence subacute motor recovery in mild-to-moderate stroke","authors":"Emily Fokas, Myriam Taga, Leticia Hayes, Charalambos C Charalambous, Sharmila Raju, Ziyue Wang, Yongzhao Shao, Pietro Mazzoni, Valentin Stepanov, Els Fieremans, Heidi Schambra","doi":"10.1093/brain/awaf095","DOIUrl":"https://doi.org/10.1093/brain/awaf095","url":null,"abstract":"After stroke, upper extremity (UE) motor recovery may be mediated in part by transcallosal projections between hemispheres. The interhemispheric competition model posits that transcallosal inhibition (TI) from the contralesional hemisphere is abnormally strengthened following stroke and interferes with motor recovery. This model has recently been questioned. In this longitudinal study, we aimed to definitively confirm or refute a maladaptive role of contralesional TI in subacute motor recovery. We assessed 30 mild-to-moderately impaired subjects over the six months following ischemic stroke. We tracked contralesional TI and motor functions in the proximal and distal segments of the paretic UE. We used transcranial magnetic stimulation to examine the ipsilateral silent period (iSP) in an arm and hand muscle. We used quantitative and clinical testing to examine deficits in muscle strength, motor control, and individuation; UE segmental impairment; and UE activity limitation. We assessed the relationships of contralesional TI to motor functions in the subacute period. Despite recovery of most motor functions in the proximal and distal UE, contralesional TI was largely static and unrelated to recovery of any motor function. There were inconsistent associations between stronger TI, less hand impairment, and less activity limitation in the subacute period overall. We found no compelling evidence to suggest a maladaptive role of contralesional TI in UE motor recovery in mild-to-moderately impaired stroke subjects. The scattered associations between stronger TI and better levels of paretic UE function suggest a potential supportive role rather than a limiting one. These findings challenge the validity of the interhemispheric competition model in the subacute recovery period, and prompt reconsideration of neuromodulatory strategies that subacutely target contralesional TI.","PeriodicalId":9063,"journal":{"name":"Brain","volume":"2 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599800","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":"Reply: Why the threat of psychosocial reductionism to patients in psychiatry and medicine is rather ignored.","authors":"Thomas A Pollak","doi":"10.1093/brain/awaf092","DOIUrl":"https://doi.org/10.1093/brain/awaf092","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595753","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":"Why the threat of psychosocial reductionism to patients in psychiatry and medicine is rather ignored.","authors":"Thomas H J Molmans","doi":"10.1093/brain/awaf091","DOIUrl":"https://doi.org/10.1093/brain/awaf091","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596053","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":"Raised intracranial pressure alters cortical vascular function and cephalic allodynia","authors":"Olivia Grech, Eloisa Rubio-Beltran, Emily C Stanyer, Alejandro Labastida-Ramirez, Gareth G Lavery, Lisa J Hill, Philip R Holland, Alexandra J Sinclair","doi":"10.1093/brain/awae415","DOIUrl":"https://doi.org/10.1093/brain/awae415","url":null,"abstract":"Raised intracranial pressure (ICP) is associated with altered cerebral hemodynamics and cephalic pain. The relationship between the algetic response and cortical neurovascular changes in raised ICP is unclear. This study aimed to evaluate this relationship and determine if lowering ICP (using a glucagon like peptide-1 receptor agonist) could ameliorate the algetic response. We also sought to explore the role of calcitonin gene-related peptide in cephalic pain driven by raised ICP by inhibiting calcitonin gene-related peptide signalling and quantifying changes in the algetic response. In a rat model of raised ICP, created by intracisternal kaolin injection, mechanical thresholds were measured alongside steady-state potential and cerebral blood flow responses to spreading depolarisation. Nuclear magnetic resonance spectroscopy evaluated energetic substrates in animals with raised ICP ex-vivo. Glucagon like peptide-1 receptor agonist exenatide and calcitonin gene-related peptide receptor antagonist olcegepant were injected daily and measurements were repeated. Kaolin increased ICP [median (range) 15.96mmHg (8.97) n = 8] versus controls [6.02mmHg (1.79) n = 6 p = 0.0007]. Animals with raised ICP exhibited reduced mechanical thresholds (mean (SD) hind paw baseline: 5.78g (2.81), day 7: 3.34g (2.22) p &amp;lt; 0.001, periorbital baseline: 6.13g (2.07), day 7: 2.35g (1.91) n = 12 p &amp;lt; 0.001). Depolarisation and repolarisation durations were increased [depolarisation raised ICP: 108.81s (222.12) n = 11, controls: 37.54s (108.38) n = 9 p = 0.038, repolarisation raised ICP: 1824.26s (3499.54) n = 12, controls: 86.96s (140.05) n = 9 p&amp;lt;0.0001]. CBF change was also reduced (85.55% (30.84) n = 9) compared to controls (217.64% (37.70) n = 8 p &amp;lt; 0.0001). Substrates for cellular energetics (ADP, ATP and NAD+) were depleted in rodent brains with raised ICP (p = 0.009, p = 0.018, p = 0.011 respectively). Exenatide significantly lowered ICP (exenatide: 9.74mmHg (6.09) n = 19, vehicle: 18.27mmHg (6.67) n = 16 p = 0.004) and rescued changes in mechanical withdrawal. Exenatide recovered characteristic spreading depolarisation responses (depolarisation duration exenatide: 56.46s (25.10) n = 7, vehicle: 115.98s (58.80) n = 6 p = 0.033) [repolarisation duration exenatide: 177.55s (562.88) n = 7, vehicle: 800.85s (1988.67) n = 6 p = 0.002]. In the setting of raised ICP olcegepant prevented changes in periorbital mechanical thresholds. We conclude that raised ICP disrupted the cortical neurovascular responses, reduced algetic thresholds and depleted crucial energetic substrates. Exenatide reduced ICP, improving algetic thresholds and cortical neurovascular changes. Importantly, olcegepant alleviated the cerebral algesia, suggesting calcitonin gene-related peptide’s role in driving pain responses in elevated ICP. These studies support the rationale that reducing ICP improves cephalic pain in conditions of raised ICP. Furthermore, the data suggests that he","PeriodicalId":9063,"journal":{"name":"Brain","volume":"53 1","pages":""},"PeriodicalIF":14.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576250","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":"Broader anti-EBV TCR repertoire in multiple sclerosis: disease specificity and treatment modulation.","authors":"Tilman Schneider-Hohendorf, Christian Wünsch, Simon Falk, Catarina Raposo, Florian Rubelt, Hamid Mirebrahim, Hosseinali Asgharian, Ulrich Schlecht, Daniel Mattox, Wenyu Zhou, Eva Dawin, Marc Pawlitzki, Sarah Lauks, Sven Jarius, Brigitte Wildemann, Joachim Havla, Tania Kümpfel, Miriam-Carolina Schrot, Marius Ringelstein, Markus Kraemer, Carolin Schwake, Thomas Schmitter, Ilya Ayzenberg, Katinka Fischer, Sven G Meuth, Orhan Aktas, Martin W Hümmert, Julian R Kretschmer, Corinna Trebst, Ilka Kleffner, Jennifer Massey, Paolo A Muraro, Haiyin Chen-Harris, Catharina C Gross, Luisa Klotz, Heinz Wiendl, Nicholas Schwab","doi":"10.1093/brain/awae244","DOIUrl":"10.1093/brain/awae244","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) infection has long been associated with the development of multiple sclerosis (MS). Patients with MS have elevated titres of EBV-specific antibodies in serum and show signs of CNS damage only after EBV infection. Regarding CD8+ T cells, an elevated but ineffective response to EBV was suggested in MS patients, who present with a broader MHC-I-restricted EBV-specific T-cell receptor beta chain (TRB) repertoire compared to controls. It is not known whether this altered EBV response could be subject to dynamic changes, e.g. by approved MS therapies, and whether it is specific for MS. Peripheral blood TRB repertoire samples (n = 1317) of healthy donors (n = 409), patients with MS (n = 710) before and after treatment, patients with neuromyelitis optica spectrum disorder (n = 87), MOG antibody-associated disease (MOGAD) (n = 64) and Susac's syndrome (n = 47) were analysed. Apart from MS, none of the evaluated diseases presented with a broader anti-EBV TRB repertoire. In MS patients undergoing autologous haematopoietic stem-cell transplantation, EBV reactivation coincided with elevated MHC-I-restricted EBV-specific TRB sequence matches. Therapy with ocrelizumab, teriflunomide or dimethyl fumarate reduced EBV-specific, but not CMV-specific MHC-I-restricted TRB sequence matches. Together, these data suggest that the aberrant MHC-I-restricted T-cell response directed against EBV is specific to MS with regard to neuromyelitis optica, MOGAD and Susac's syndrome and that it is specifically modified by MS treatments interfering with EBV host cells or activated lymphocytes.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"933-940"},"PeriodicalIF":10.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632633","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":"Phase 2b program with sonlicromanol in patients with mitochondrial disease due to m.3243A>G mutation.","authors":"Jan Smeitink, Just van Es, Brigitte Bosman, Mirian C H Janssen, Thomas Klopstock, Grainne Gorman, John Vissing, Gerrit Ruiterkamp, Chris J Edgar, Evertine J Abbink, Rob van Maanen, Oksana Pogoryelova, Claudia Stendel, Almut Bischoff, Ivan Karin, Mahtab Munshi, Anne Kümmel, Lydia Burgert, Christianne Verhaak, Herma Renkema","doi":"10.1093/brain/awae277","DOIUrl":"10.1093/brain/awae277","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Mitochondrial disease incorporates a group of rare conditions with no approved treatment to date, except for Leber hereditary optic neuropathy. Therapeutic options to alleviate the symptoms of mitochondrial disease are urgently needed. Sonlicromanol is a promising candidate, as it positively alters the key metabolic and inflammatory pathways associated with mitochondrial disease. Sonlicromanol is a reductive and oxidative distress modulator, selectively inhibiting microsomal prostaglandin E1 synthase activity. This phase 2b program, aimed at evaluating sonlicromanol in adults with m.3243A&gt;G mutation and primary mitochondrial disease, consisted of a randomized controlled (RCT) study (dose-selection) followed by a 52-week open-label extension study (EXT, long-term tolerability, safety and efficacy of sonlicromanol). Patients were randomized (1:1:1) to receive 100 or 50 mg sonlicromanol or placebo twice daily (bid) for 28 days with a ≥2-week wash-out period between treatments. Patients who completed the RCT study entered the EXT study, wherein they received 100 mg sonlicromanol bid. Overall, 27 patients were randomized (24 RCT patients completed all periods). Fifteen patients entered the EXT, and 12 patients were included in the EXT analysis set. All patients reported good tolerability and favourable safety, with pharmacokinetic results comparable to the earlier phase 2a study. The RCT primary end point [change from placebo in the attentional domain of the cognition score (visual identification; Cogstate IDN)] did not reach statistical significance. Using a categorization of the subject's period baseline a treatment effect over placebo was observed if their baseline was more affected (P = 0.0338). Using this approach, there were signals of improvements over placebo in at least one dose in the Beck Depression Inventory (BDI, P = 0.0143), Cognitive Failure Questionnaire (P = 0.0113) and the depression subscale of the Hospital Anxiety and Depression Scale (P = 0.0256). Statistically and/or clinically meaningful improvements were observed in the patient- and clinician-reported outcome measures at the end of the EXT study [Test of Attentional Performance (TAP) with alarm, P = 0.0102; TAP without alarm, P = 0.0047; BDI somatic, P = 0.0261; BDI total, P = 0.0563; SF12 physical component score, P = 0.0008]. Seven of nine domains of RAND-Short Form-36-like SF-36 pain improved (P = 0.0105). Other promising results were observed in the Neuro-Quality of Life Short Form-Fatigue Scale (P = 0.0036), mini-Balance Evaluation Systems test (P = 0.0009), McGill Pain Questionnaire (P = 0.0105), EuroQol EQ-5D-5L-Visual Analog Scale (P = 0.0213) and EQ-5D-5L-Index (P = 0.0173). Most patients showed improvement in the Five Times Sit-To-Stand Test. Sonlicromanol was well-tolerated and demonstrated a favourable benefit/risk ratio for up to 1 year. Sonlicromanol was efficacious in patients when affected at baseline, as seen across a variety of clinically relevant domain","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":"896-907"},"PeriodicalIF":10.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581239","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}