Brain communications最新文献

{"title":"Epidemiology, disease evolution and economic burden of amyotrophic lateral sclerosis in France using the French national health data system.","authors":"Philippe Corcia, Katie Stenson, Agathe Doutriaux, Hicham Hadjrabia, François Boer, Seham Issa, Sophie Marguet, Frederic Bernard, Enkhgerel Nasanbat, Gregoire Nowacki, Gérard de Pouvourville, Philippe Couratier","doi":"10.1093/braincomms/fcaf292","DOIUrl":"10.1093/braincomms/fcaf292","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis is a rare neurodegenerative disease that requires multidisciplinary care, resulting in extensive healthcare resource utilization. No study has explored the prevalence of amyotrophic lateral sclerosis or characterized associated healthcare resource utilization in France, despite its high burden on people living with amyotrophic lateral sclerosis, caregivers and the healthcare system. Herein, we conducted a France-wide retrospective study to describe the epidemiology, disease course and economic burden of amyotrophic lateral sclerosis. People living with amyotrophic lateral sclerosis were identified from the French population from 2012 to 2019 using the French national health data system. A milestone and symptom-based staging algorithm was developed to categorize the incident cohort into early, mid and late stages. Data were extracted on epidemiology, demographic and clinical characteristics and clinical treatments. Healthcare resource utilization and costs were analysed for amyotrophic lateral sclerosis cases and matched non-amyotrophic lateral sclerosis controls and at disease stages. Events of interests were identified, and a competing risk analysis was conducted. Comparative statistics were performed using paired <i>t</i>-test, ANOVA and χ<sup>2</sup> test. We identified 18 289 incident amyotrophic lateral sclerosis cases, 56.1% of whom were male. The average age at diagnosis was 68.4 (± 12.5) years. In 2019, the estimated incidence and prevalence were 3.5/100 000 person-years and 11.0/100 000 persons, respectively. All-cause hospitalizations were higher among people at mid stage (1.66 person-years) and late stage (2.82 person-years) than among people at early stage (1.46 person-years) and for the amyotrophic lateral sclerosis cases (1.98 person-years) than for the matched non-amyotrophic lateral sclerosis controls (0.45 person-years). Home hospitalization and rehabilitation admission were more prevalent among people in later stages. The rate of out-patient and ambulatory consultations to all specialties was 13.8 person-years for people at early and mid stages and 11.1 person-years for people at late stage and 13.0 and 8.7 person-years for the amyotrophic lateral sclerosis cases and the matched non-amyotrophic lateral sclerosis controls, respectively. Direct costs increased as the disease progressed and were also higher for the amyotrophic lateral sclerosis cases than for the matched non-amyotrophic lateral sclerosis controls. Amyotrophic lateral sclerosis imposes a significant health burden through incremental healthcare resource utilization across all stages that increases with disease progression. Out-patient and ambulatory resource consumption decreased as the disease progressed to a more severe form, accompanied by a corresponding increase in in-patient services. These findings shed light on the complex needs of people living with amyotrophic lateral sclerosis and the continued need for more efficacious ","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf292"},"PeriodicalIF":4.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered putamen connectivity in patients with neurological post-COVID condition.","authors":"Lars S Schlenker, Tim J Hartung, Pia Klabunn, Katia Schwichtenberg, Josephine Heine, Lucas Adam, Christiana Franke, Carsten Finke","doi":"10.1093/braincomms/fcaf291","DOIUrl":"10.1093/braincomms/fcaf291","url":null,"abstract":"<p><p>Although the exact aetiology of the post-COVID condition is still under investigation, there is increasing evidence for white matter pathology in patients with persistent cognitive and fatigue symptoms following an infection with SARS-CoV-2. Still, to date there are no studies that investigated the white matter connectome in patients with post-COVID condition. Based on previous findings, we analyzed the structural connectome of these patients, with a focus on the thalamus and basal ganglia. In this cross-sectional study, 43 patients (34 women, 9 men) and 41 (33 women, 8 men) healthy control participants underwent structural MRI, including T1-weighted and diffusion weighted imaging, as well as a comprehensive neuropsychological and psychiatric assessment. The cognitive assessment included verbal and visual long-term memory, working memory, attention, processing speed, executive control, verbal fluency and spatial navigation. Fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions, depression and anxiety were assessed with the Beck Depression Inventory II and the Beck Anxiety Inventory, respectively. MRI data was analyzed using probabilistic tractography, reconstructing 100 million streamlines per participant, to create individual connectomes. Connectome alterations were assessed using graph theory by calculating node strength and betweenness centrality for the thalamus and basal ganglia. We then analyzed group differences in these measures between patients and control participants with the Mann-Whitney-U-test. For significant alterations, we explored associations between graph measures, fatigue and cognition, depression and anxiety using spearman correlations. We identified significantly increased node strength of the putamen (<i>U</i> = 589, <i>p</i> _FDR = 0.036), which was significantly associated with the fatigue severity in patients (<i>ρ</i> = 0.33, <i>P</i> = 0.045) but not in control participants (<i>ρ</i> = 0.11, <i>P</i> = 0.509). Betweenness centrality of the putamen was increased in patients with post-COVID condition (<i>U</i> = 620, <i>P</i> = 0.019) but was not associated with fatigue (<i>ρ</i> = 0.07, <i>P</i> = 0.685). Neither node strength nor betweenness centrality of the putamen was associated with cognitive performance, depression or anxiety scores. Patients with post-COVID condition exhibit structural connectome alterations that are associated with fatigue severity. Such structural white matter pathology may thus contribute to post-COVID pathophysiology. In addition, putamen connectivity could be a neural correlate of post-COVID fatigue.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf291"},"PeriodicalIF":4.5,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional connectivity of vestibular graviceptive to sensory and motor circuits.","authors":"Julian Conrad, Laurenz Eberle, Bernhard Baier, Rainer Boegle, Marianne Dieterich, Andreas Zwergal","doi":"10.1093/braincomms/fcaf290","DOIUrl":"10.1093/braincomms/fcaf290","url":null,"abstract":"<p><p>Processing of vestibular graviceptive signals from the inner ear is essential for spatial perception, bipedal stance, locomotion, and navigation in a three-dimensional world. Acute unilateral ischaemic lesions along the central vestibular pathways lead to deficits of gravitational processing which can be quantified as perceptual tilts of the subjective visual vertical (SVV). For ipsiversive and contraversive directional tilts, dichotomous networks were documented from the brainstem to the thalamus. In the current lesion-network mapping study, we asked whether this dichotomy of directional tilts of gravitational processing is maintained at the cortical level. 107 patients with acute right-hemispheric infarcts (mean age 66 years, ±13 years) in the territory of the middle cerebral artery were included in the study. To examine the association of tilts of the SVV with lesion locations, support-vector regression lesion-symptom mapping (SVR-LSM) was used with tilt of the SVV as a continuous variable. Analyses were carried out for ipsi- and contraversive tilts separately. In addition, we performed disconnectome mapping and SVR-LSM-disconnectome analyses by referencing lesions to a normative connectome detect structural networks associated with SVV tilts. Similarly, functional connectivity mapping was used to determine the functional networks associated with SVV tilts. The SVR-LSM with the functional maps revealed the statistical association between SVV tilt and functional networks. The SVR-LSM analysis demonstrated distinct clusters associated with either ipsi- or contraversive SVV tilts. Ipsiversive tilt clusters were centered around the parieto-(retro)-insular opercular cortex [PIVC, retroinsular area (Ri), posterior insular long gyrus (Ig), parietal operculum (OP2-3)]. The contraversive tilt cluster showed additional involvement of the motor system (basal ganglia) and the ventral prefrontal cortex (Brodman area BA44, inferior frontal gyrus). In lesions with ipsiversive tilts, a disconnection of fronto-insular tracts and the arcuate fascicle was found. Contraversive tilt related disconnection was observed in the superior longitudinal fascicle (SLFII) and the medial temporal cortex (perirhinal, entorhinal cortex). Cortico-fugal connections could be traced down via the thalamus to the cerebellum and vestibular nuclei. The functional networks associated with ipsiversive and contraversive tilts showed a similar pattern: more restricted in the core vestibular and ocular motor cortical network for ipsiversive tilts, additional involvement of the motor system for contraversive tilts. Thus, the current data demonstrate partly separated cortical networks for gravitational processing associated with directional SVV tilts. These could imply differential routes of vestibular input for sensory and motor processing.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf290"},"PeriodicalIF":4.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migraine and functional neurological disorder (FND)-a review of comorbidity and potential overlap.","authors":"Jon Stone, Jan Coebergh, Lujain Khoja, Matthew Butler, Timothy R Nicholson, David W Dodick","doi":"10.1093/braincomms/fcaf288","DOIUrl":"10.1093/braincomms/fcaf288","url":null,"abstract":"<p><p>Migraine and functional neurological disorder (FND) are two of the most common conditions in neurological practice. It is assumed that the two conditions have distinct underlying mechanisms. However, it can be clinically challenging to disentangle their relative contributions to a patient's symptoms. In addition, apart from the relationship between persistent postural perceptual dizziness (PPPD) and migraine, the frequency of co-occurrence has not been characterized in detail. Contemporary conceptualizations of FND have driven a re-evaluation of its relationship to other neurological disorders, including migraine. We carried out a narrative review of the literature examining the co-occurrence of migraine and FND. We also explored their comorbidities, aetiological risk factors and mechanisms, focusing especially on areas of potential overlap. Our review suggests increased frequency of migraine in people with functional seizures compared to epilepsy, but data from people with functional motor symptoms is mixed. Robust epidemiological studies evaluating the frequency of FND in migraine are lacking. Similar to other neurological disorders, migraine is an established trigger of FND. Female gender, adverse childhood experiences and comorbid psychiatric and functional disorders, such as irritable bowel syndrome and fibromyalgia, are more common in both conditions than in controls, but perhaps more so in FND. Mechanistic research in both conditions highlights converging frameworks of dysregulated allostatic/stress responses in the context of predictive processing models of the brain. This has implications for pharmaceutical and rehabilitation treatments. The relationship between migraine and FND is poorly studied. An overview of their overlap offers a model of non-dualistic thinking within a clinical neuroscience framework for future studies.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf288"},"PeriodicalIF":4.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare <i>PANK2</i> variants and pantothenate-kinase-associated neurodegeneration in the Dominican Republic.","authors":"Badri N Vardarajan, Pedro Sanchez Roa, Christine Y Kim, Peter Stoeter, Diones Rivera Mejia, Alexander Houck, Amanda Chan, Dolly Reyes-Dumeyer, Angel Piriz, Robert Fee, Francisco Blanco-Abinader, Francisco A Roedan, Elizabeth Rice, Samantha Christenson, Rebecca Chiu, Tamil I Gunasekaran, Rafael A Lantigua, Clifton Dalgard, Serge Przedborski, Richard Mayeux","doi":"10.1093/braincomms/fcaf286","DOIUrl":"10.1093/braincomms/fcaf286","url":null,"abstract":"<p><p>Pantothenate-kinase-associated neurodegeneration (PKAN) is a rare, autosomal recessive neurological disorder characterized by the progressive degeneration of specific regions in the brain and is invariably fatal. Several individuals in families affected by PKAN were known to live in an isolated region in a southwestern province of the Dominican Republic and had been previously studied. Forty-six individuals with PKAN in 34 families were evaluated for disease manifestations using the PKAN-Disease Rating Scale and the Leiter-3 Cognitive and Neuropsychological assessment. We completed whole genome sequencing in the 46 affected individuals and their 80 unaffected relatives. Haplotype analysis was used to identify shared genetic patterns among individuals with the mutation to identify common ancestral and founder effects. The classic form of PKAN was observed in 22 individuals with moderate-to-severe oromandibular dystonia and limb dystonia and onset in early childhood. The atypical form was observed in 24 individuals with Parkinsonism, dystonia, cognitive deficits, and later onset of disease. A <i>PANK2</i> variant, chr20:3907977: A:G <i>(c.680A</i>  <i>></i>  <i>G, p.Y227C),</i> was homozygous among 42 affected individuals equally divided by disease form. There were 59 heterozygous carriers of this variant among parents and relatives of the affected individuals. Four individuals from two families were compound heterozygotes for <i>c.680A</i>  <i>></i>  <i>G</i> and chr20:3918728: C:T (<i>c.1594C</i>  <i>></i>  <i>T).</i> Haplotype analyses revealed shared patterns across families and of African origin consistent with founder effects for <i>c.680A</i>  <i>></i>  <i>G</i> and <i>c.1594C</i>  <i>></i>  <i>T</i>, likely introduced to the island 25-35 generations earlier. The frequency of heterozygous carriers of <i>c.680A</i>  <i>></i>  <i>G</i> allele among individuals of Dominican ancestry living in New York was 0.18% but was 0.8% among individuals living in the Dominican Republic, significantly higher than the reported frequency for all causal <i>PANK2</i> mutations worldwide. This investigation confirmed likely founder mutations in <i>PANK2</i> associated with the classic and atypical forms of PKAN in 34 families in an isolated region of the Dominican Republic. Compound heterozygosity was observed in four individuals from two families. The heterozygous frequency of <i>c.680A</i>  <i>></i>  <i>G</i> was exceptionally high in the Dominican population compared with worldwide data. Founder mutations in such communities offer a unique opportunity to set up relevant, affordable and accessible genetic counselling and screening.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf286"},"PeriodicalIF":4.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligodendrogliomas: findings after classifying the same cohort using pre- and post-World Health Organization (WHO) 2021 criteria.","authors":"Maria Angeles Vaz-Salgado, Juan M Sepulveda, Julie Earl, Jacqueline Gutierrez, Yolanda Ruano, Hector Pian, Diana Cantero, Aurelio Hernández-Lain","doi":"10.1093/braincomms/fcaf265","DOIUrl":"10.1093/braincomms/fcaf265","url":null,"abstract":"<p><p>The 2021 World Health Organization (WHO) classification includes the presence of isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion for oligodendrogliomas. The objective of this study was to evaluate the impact of the introduction of this classification in a cohort of oligodendrogliomas. A total of 182 cases with an initial diagnosis of oligodendroglioma by histological criteria were identified, including Grades 2 and 3 and oligoastrocytoma (initial cohort). Subsequently, IDH mutation and 1p/19q codeletion were determined and were present in a total of 91 cases (reclassified cohort). The clinical evolution of both cohorts was analyzed. The mean age was 45 years (14-75), 65% were Grade 2 and 22% were oligoastrocytomas. Complete resection was performed in 47% and biopsy in 7%. After surgery, 50% received radiotherapy, 30% chemotherapy and 36% did not receive adjuvant therapy. In the reclassified cohort, there were no statistically significant differences between Grade 2 and Grade 3 oligodendrogliomas, the median overall survival (OS) in Grade 2 was 13.3 years [95% confidence interval (CI) 8.2-18.4] and 12 years in Grade 3 (95% CI 5.6-18.3). However, in the initial cohort, significant differences were found according to tumour grade. Even in cases without adjuvant treatment, the median OS was 12 years. Compared with this data, the median OS for the cohort that did not meet IDH mutation and 1p/19q codeletion criteria was 7.52 years (95% CI 4.67-10.38). Molecular classification allows a more accurate selection of oligodendrogliomas and implies cases with a better prognosis, regardless of the grade and treatment received. These data should be taken into account in clinical practice and clinical trials.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf265"},"PeriodicalIF":4.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Respiratory sensitivity is reduced in functional neurological disorder and associated with higher somatoform dissociation.","authors":"Natascha Stoffel, Petr Sojka, Nicolas Gninenko, Michael Mouthon, Laure von der Weid, Tereza Serranová, Selma Aybek","doi":"10.1093/braincomms/fcaf283","DOIUrl":"10.1093/braincomms/fcaf283","url":null,"abstract":"<p><p>Abnormal interoception-the processing of internal bodily signals-has been increasingly recognized as a key factor in the pathophysiology of functional neurological disorder. While evidence suggests reduced cardiac interoceptive accuracy in functional neurological disorder, other interoceptive domains, such as respiratory processing, remain largely unexplored. Here, we introduce a novel respiratory resistance sensitivity task to assess respiratory interoception and metacognition in functional neurological disorder. Additionally, we investigate the relationship between respiratory interoception and other interoceptive or clinical variables, including somatoform dissociation as a potential inverse correlate of interoception. Using the respiratory resistance sensitivity task, respiratory interoceptive sensitivity and metacognition were assessed, along with the response time and the decision precision for identifying the obstructed breath in the respiratory task in patients with mixed functional neurological disorder (<i>N</i> = 43) and age- and sex-matched healthy controls (<i>N</i> = 48). Drift diffusion modelling was applied to response times and discrimination decisions to assess sensory evidence accumulation. Additionally, interoceptive self-reports (multidimensional assessment of interoceptive awareness and the interoceptive accuracy scale) were collected. Associations between interoceptive measures, symptom severity, and the Somatoform Dissociation Questionnaire were analysed. Patients with functional neurological disorder showed reduced respiratory sensitivity (<i>P</i>  <i>=</i> 0.032, <i>d</i> = 0.47) and interoceptive self-report scores (<i>P</i>  <i>=</i> 0.0004, <i>d</i> = 0.79 and <i>P</i>  <i>=</i> 0.018, <i>d</i> = 0.65, respectively) compared to controls, whereas metacognition and decision precision did not differ between groups. In the functional neurological disorder group, respiratory sensitivity and metacognitive performance were negatively associated with somatoform dissociation scores (<i>r</i> = -0.38, <i>P</i> = 0.011 and <i>r</i> = -0.36, <i>P</i> = 0.017, respectively). While no group difference was found for the response time, we did identify a negative correlation with response time and respiratory sensitivity (<i>r</i> = -0.27, <i>P</i> = 0.013) and reduced drift rate in patients with 89% posterior probability. Further, perceived breathlessness (<i>r</i> = -0.24, <i>P</i> = 0.026) was negatively associated with the task performance. This study provides first evidence of impaired respiratory interoception in patients with functional neurological disorder. We were able to demonstrate a moderate-sized group difference in a large cohort, using a valid respiratory task, that is, associated with clinical variables such as self-reported severity of somatoform symptoms. Further, reduced drift rates for patients with functional neurological disorder indicated less efficient sensory evidence accumulation, while indifferent bo","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf283"},"PeriodicalIF":4.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12342147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF and blood neuronal injury biomarkers in spinal bulbar muscular atrophy and amyotrophic lateral sclerosis 4.","authors":"Pashtun Shahim, Abdullah AlQahtani, Angela D Kokkinis, Narjis Kazmi, Marie Ezuma-Ngwu, Jahan Misra, George Harmison, Nicole Benoit, Melina Jones, Elizabeth Howe, Alice B Schindler, Galen O Joe, Christopher Grunseich","doi":"10.1093/braincomms/fcaf275","DOIUrl":"10.1093/braincomms/fcaf275","url":null,"abstract":"<p><p>Spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis 4 (ALS4) are two forms of motor neuron disease characterized by clinically slow disease progression. Based on the current limited human studies, the contribution of central nervous neurodegeneration to these diseases and the rate of clinical progression is unclear. Neuronal proteins glial fibrillary acidic protein (GFAP), neurofilament light (NfL) chain, or Total-tau measured in either cerebrospinal fluid or blood could serve as sensitive markers of neurodegeneration. We studied 56 adult participants (32 SBMA, 7 ALS4, and 17 controls) who were enrolled at the National Institutes of Health, of whom 22 (10 SBMA, 7 ALS4, and 5 controls) underwent paired CSF and serum sampling, and of whom 6 participants were assessed longitudinally up to 24 months from initial visit. An additional 7 controls completed CSF sampling only. CSF GFAP, NfL chain, and Total-tau correlated with corresponding levels in serum (<i>r</i> = 0.74, <i>r</i> = 0.47, and <i>r</i> = 0.70, respectively). CSF GFAP was increased in patients with SBMA (median, 8840 pg/mL, interquartile range (IQR) 5780-10489) as compared to controls (median, 5315 pg/mL, IQR 1822-6657; <i>P</i> = 0.029) but not compared with ALS4 (median, 5015 pg/mL, IQR 3172-9803; <i>P</i> = 0.31). Patients with SBMA had increased concentrations of CSF NfL chain (median, 719 pg/mL, IQR 483-773) as compared to ALS4 (median, 307 pg/mL, IQR 187-629; <i>P</i> = 0.034) or controls (median, 395 pg/mL, IQR 307-497; <i>P</i> = 0.024). In contrast, serum concentrations of either biomarker did not differ significantly between SBMA, ALS4, or controls. Higher CSF GFAP and NfL chain levels were associated with lower SBMA Functional Rating Scale scores (<i>r</i> = -0.49 and <i>r</i> = -0.42, respectively). Over the course of 24 months, the average change in SBMA Functional Rating Scale was -0.83 points, while the changes in CSF GFAP and NfL chain were progressive (increased 1.4-fold and 1.3-fold, respectively). Our data suggest that SBMA patients have increased concentrations of CSF GFAP and NfL chain as compared to ALS4 and controls, and higher levels of these biomarkers are associated with disease severity. Importantly, these results indicate that SBMA is associated with progressive neurodegeneration and that either CSF GFAP or NfL chain may be useful for patient stratification and monitoring treatment effects in clinical trials.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf275"},"PeriodicalIF":4.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous mammalian models for Alzheimer's disease and dementia.","authors":"Madeleine Ford, Frank J Gunn-Moore, Mark P Dagleish","doi":"10.1093/braincomms/fcaf287","DOIUrl":"10.1093/braincomms/fcaf287","url":null,"abstract":"<p><p>Globally, the human population is ageing, and, consequently, the prevalence of major neurocognitive disorders is increasing, resulting in a greater need for novel dementia therapeutic interventions. Animal models are invaluable in studying underlying pathological processes in human diseases and with evidence for rising life expectancy in many domesticated animals studies have investigated neurocognitive disorders in several non-human species. Rodents have been used extensively as animal models, but this review will examine published literature suggesting candidate non-laboratory animal models for studying dementia, especially human Alzheimer's disease. Comparison of the physiological, pathological and clinical features of companion animals, farm animals and marine mammals shows that although many animals develop amyloid plaques and, to lesser degree, hyperphosphorylated tau protein, very few develop neurofibrillary tangles or neuronal loss to the same extent as humans with Alzheimer's disease. Several hypotheses are proposed as to why, as yet, no animals have been found to spontaneously develop Alzheimer's disease-like pathology to the same level as humans but highlight specific aspects where these models may be useful if developed further.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf287"},"PeriodicalIF":4.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Optical coherence tomography with voxel-based morphometry: a new tool to unveil focal retinal neurodegeneration in multiple sclerosis.","authors":"","doi":"10.1093/braincomms/fcaf269","DOIUrl":"10.1093/braincomms/fcaf269","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/braincomms/fcad249.].</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 4","pages":"fcaf269"},"PeriodicalIF":4.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}