Annals of Clinical and Translational Neurology

BackgroundDopa-responsive dystonia is caused by pathogenic variants in the GCH1 gene. Although its clinical features and reduced penetrance are known, in vivo metabolic and structural alterations in symptomatic (sMC) and asymptomatic mutation carriers (aMC) remain poorly understood. ObjectivesTo characterize volumetric and neurometabolic brain changes of GCH1 mutation carriers and explore their relationship with clinical severity. MethodsWe studied 20 sMC, 5 aMC, and 25 mutation-free healthy c...

IntroductionThe 2024 McDonald criteria incorporate the central vein sign (CVS) and paramagnetic rim lesions (PRL) as supportive imaging biomarkers for MS diagnosis. While susceptibility-weighted-imaging (SWI) and T2*-weighted echo-planar-imaging (EPI) are generally used to assess CVS/PRL, their relative performance remains unclear. This study compared high-resolution isotropic-T2*-EPI with non-isotropic SWI for CVS/PRL detection. Materials and MethodsIn this multi-centre study, 21 patients with...

An overlap syndrome of myositis and/or myocarditis associated with myasthenia gravis (MG) has emerged as a life-threatening immune-related adverse event (irAE) in cancer patients treated with immune checkpoint inhibitors (ICIs). This syndrome closely resembles a rare form of idiopathic inflammatory myopathy (IIM) seen in a subset of MG patients. In this systematic review, we searched PubMed for reports of concurrent MG and IIM as well as ICI-related overlap syndromes. By integrating clinical, se...

In LGMDR1-Calpain-3 related, as in all muscular dystrophies, clinical trial monitoring remains a challenge due to the lack of reliable biomarkers. This study assessed IL-32 concentrations in both serum and urine, uncovering a marked increase in patients compared to healthy controls. Serum IL-32 levels were especially elevated in young adults, suggesting a possible link to the early and more active phases of disease onset. Meanwhile, urinary IL-32 levels showed consistent elevation across all age...

ATP1A3-related syndromes represent a continuously expanding clinical spectrum and present with an extraordinarily wide range of symptoms. New phenotypes continue to emerge, posing ongoing challenges for both diagnosis and development of treatments. In this context, telemedicine offers a unique opportunity to greatly expand outreach to patients. Remote, high-resolution assessments help refine phenotypic characterization and the identification of novel and intermediate phenotypes. In this study w...

IntroductionNeurodegenerative dementia syndromes are severely debilitating, progressive and increasing in incidence with an ageing population. A treatable differential diagnosis to neurodegenerative dementia is autoimmune encephalitis (AE), but AE patients are often misdiagnosed, delaying treatment. Previous work in the Netherlands has shown that 0.8% of patients with suspected neurodegenerative dementia suffer from AE. In Sweden, there is considerable variability in the prevalence of AE, possib...

PurposeMyasthenia gravis (MG) is a rare neuromuscular disease. In-person appointments in specialized centers are not readily available, especially on short notice. The purpose of this study was to analyze patient-specialist communication through a telemedical platform. MethodsIn a randomized controlled study 45 MG patients were observed over three months. The intervention group (N=30) was monitored via a mobile application ( app) that enabled chat function and assessed MG-specific outcome measu...

BackgroundChronic autoimmune diseases such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Multifocal Motor Neuropathy (MMN), and Thyroid Eye Disease (TED) impose a considerable burden on affected individuals. Patient-reported outcome measures (PROMs)--both disease-specific and generic--are widely used to assess functioning, quality of life, and treatment effects in these populations. However, most PROMs currently lack reference values derived from the general population, limiting t...

ObjectiveDuchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder for which monitoring biomarkers are urgently needed. We aimed to evaluate whether proteins in serum can accurately monitor patients function within the duration of a clinical trial. MethodsIn this study, we evaluated longitudinal serum proteins of DMD patients participating to the FOR-DMD clinical trial, comparing daily and intermittent corticosteroid regimens in boys aged 4-8 years at baseline. Using the aptamer...

Adenylosuccinate synthetase 1 (ADSS1) myopathy is an ultra-rare disease characterized by progressive muscle dysfunction. The objective of this investigation was to employ a non-invasive biomarker approach to phenotype (fine-)motor skills, speech production and cognition in adults with ADSS1 myopathy. Five individuals with ADSS1 myopathy and five age-sex-matched healthy controls (HCs) underwent a comprehensive multimodal evaluation. Assessments included, (i) evaluation of motor performance, (ii) ...

Background and objectives STXBP1-related disorder (STXBP1-RD), caused by pathogenic variants in the STXBP1 gene, is a rare neurodevelopmental condition, characterized by early-onset seizures, developmental delay, intellectual disability (ID), and prominent motor dysfunction. Despite the high prevalence of motor symptoms, systematic gait characterization remains limited. We therefore aimed to quantitively assess gait in individuals with STXBP1-RD. Methods In this cross-sectional study, we include...

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by reduced expression of the survival motor neuron (SMN) protein. In addition to affecting motor neuron survival, SMN deficiency impacts multisystem physiology and neurotransmission. Dopaminergic dysfunction has been reported in mouse models of SMA, leading to postural and locomotor impairments that improve upon treatment with L-DOPA and benserazide. However, whether altered dopamine metabolism contributes to clinical sympto...

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterised by progressive neurological disability and heterogeneous symptom trajectories. Current clinical monitoring methods, including magnetic resonance imaging (MRI) and episodic neurological assessments, provide limited insight into subtle disease progression and functional changes. Digital health technologies integrating multimodal biosignals and behavioural assessments may enable continuous monitoring and personalised rehab...

Background / ObjectivesWe investigated whether the interthalamic adhesion (IA), a midline structure connecting the thalami, is altered in MS and associated with thalamic damages and cognition. MethodsWe prospectively included 32 clinically isolated syndrome/early MS, 31 RRMS, 31 PPMS patients, and 103 matched controls. All underwent anatomical 3T MRI and completed a comprehensive cognitive battery. IA presence, subtype, and volume were assessed by two blinded readers. Thalamic nuclei and other ...

ObjectiveTo replicate and extend recent findings suggesting that higher serum alpha-linolenic acid (ALA) levels are associated with reduced disease activity and progression in multiple sclerosis (MS). MethodsWe reanalysed clinical trial data from 85 people with MS, who had serum ALA, magnetic resonance imaging (MRI), and clinical (EDSS, PASAT) assessments collected for two years, with additional follow-up at 12-years. Linear and mixed models were used to assess the relationship between ALA and ...

Artificial intelligence (AI) is increasingly being integrated into healthcare, particularly in data-intensive chronic diseases that rely on longitudinal monitoring and shared decision-making. Multiple sclerosis is a prototypical example of such care, but real-world benefit will depend on whether people accept AI support in different clinical roles. We conducted a cross-sectional, web-based survey among 241 people with MS (pwMS) to assess comfort with AI across eight clinical domains and to ident...

BackgroundAnti-seizure medications (ASMs) are widely used in neonatal intensive care, but there is limited evidence for their safety and long-term outcomes. Phenobarbital is the only ASM generally recommended for use in neonates, but it has been linked with adverse effects in infants. Other anti-seizure medications, such as fosphenytoin, levetiracetam, and midazolam are used off-label in this population. MethodsWe performed a retrospective observational study of 18,548 infants in intensive care...

BackgroundDisorders affecting the spinal cord (myelopathies) can cause severe disability. Despite diagnostic advances, approximately 12-18% of myelopathy cases continue to elude an etiological diagnosis, hampering effective treatment. MethodsThis retrospective, multicenter, tertiary care cohort study conducted from 2014 to 2025 evaluated archived biofluids from patients with IM, known autoimmune myelitis, or other neurological diseases (ONDs). Proteome-wide phage display was used to discover no...

BackgroundThe prodromal phase of multiple sclerosis (MS) is increasingly recognized, but most studies have focused on isolated symptoms or static comorbidity counts, leaving the evolving structure of pre-onset disease burden underexplored. ObjectiveTo characterize dynamic disease trajectories preceding MS onset through longitudinal network modeling. MethodsHealth data from 10,273 MS patients and 47,167 matched controls in Sweden were analyzed. Disease co-occurrence networks were constructed fo...

While 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is an established biomarker in amyotrophic lateral sclerosis (ALS), the metabolic correlates of motor neuron disease motor variants remain poorly defined. This is why we investigated patterns of cerebral glucose metabolism across the spectrum of motor neuron disorders (MND), including progressive muscular atrophy (PMA), primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS). We retrospectively included 18 PMA, ...