Annals of Clinical and Translational Neurology

IntroductionMagnetic resonance spectroscopy (MRS) of the brain offers significant potential for monitoring metabolic alterations associated with neurological pathologies. However, to date, its application has predominantly been limited to research settings and a select number of clinical centers. This study aimed to assess the diagnostic accuracy of brain MRS in detecting various neurological diseases. MethodsBrain MRS examinations conducted at public hospitals affiliated with Shiraz University...

ObjectiveTo define the diagnostic utility and clinicopathologic features correlating with anti-cytosolic 5'-nucleotidase 1A (NT5C1A) antibody positivity in idiopathic inflammatory myopathies (IIMs). Methods4987 patients had anti-NT5C1A status clinically tested between 2014 and 2019 in the Washington University neuromuscular clinical laboratory. Using clinicopathologic information available for 630 of these patients, we classified them as inclusion body myositis (IBM), dermatomyositis, antisynth...

The role of inflammation in cortical superficial siderosis (cSS), a marker of cerebral amyloid angiopathy (CAA) linked to high hemorrhage risk, is unclear. We examined 14 patients with cSS using 3T post-contrast vessel wall MRI (VWI) and CSF analysis. Although only 31% met current CAA-ri criteria, 86% showed vessel wall enhancement or sulcal hyperintensities near cSS, frequently extending beyond. Four patients with follow-up VWI demonstrated corticosteroid-responsive regression of inflammation. ...

The visual evoked potential (VEP) patterns of optic neuritis are known to often differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) but have been less reported in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This study aimed to characterize the VEP pattern in MOGAD and evaluate its utility in distinguishing MOGAD from MS and NMOSD. We retrospectively reviewed the clinical manifestations and VEP findings in patients with MS (n = 29...

GNE myopathy is a rare autosomal recessive skeletal muscle disorder characterized by progressive distal muscle weakness, typically starting in the lower legs and gradually involving proximal muscle groups. It is an autosomal recessive disease, caused by biallelic variants in GNE. To date, over 350 causative GNE variants have been reported, however, establishing genotype-phenotype correlation remains difficult due to clinical heterogeneity and limited patient numbers. In this study, we describe 2...

IntroductionCerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage and cognitive impairment in the elderly. Though definitive diagnosis requires post-mortem pathological analysis, clinical and radiographic criteria allow for noninvasive, in vivo diagnosis. We sought to validate the new ICD-10-CM diagnostic code for CAA with respect to the recently updated Boston criteria, version 2.0. MethodsWe conducted a retrospective study of inpatient and outpatient encounters at a ...

ObjectiveTo describe the safety and efficacy of risdiplam in non-sitter adult patients with 5q spinal muscular atrophy (SMA). MethodsType 2 SMA adult patients, who were not eligible for nusinersen, were offered risdiplam through the expanded access program. Patients were followed up with a battery of scales and clinical measures. ResultsSix non-sitter patients (17 - 46 years old) were treated with risdiplam. One patient reported mild adverse events (dyspepsia and headache). After one year of t...

IntroductionMyasthenia gravis (MG) is a chronic autoimmune neuromuscular disease primarily affecting extraocular, bulbar, axial, and proximal extremity muscle groups. However, a subgroup of patients experience distal extremity weakness, known as distal myasthenia gravis (DMG). Despite its longtime observation, DMGs clinical and demographic features remain poorly understood. This scoping review aims to summarise current evidence regarding the demographic, clinical, and diagnostic features of auto...

Charcot-Marie-Tooth disease type 1E (CMT1E) is a rare, autosomal dominant peripheral neuropathy caused by missense variants, deletions, and truncations within the peripheral myelin protein-22 (PMP22) gene. CMT1E phenotypes vary depending on the specific variant, ranging from mild to severe, and there is little natural history and phenotypic progression data on individuals with CMT1E. Patients with CMT1E were evaluated during initial and follow-up visits at sites within the Inherited Neuropathy C...

ObjectivesTo examine whether the dynamic range of 1.25% low-contrast visual acuity (LCVA) measurement in MS patients with optic neuritis (ON) can be improved by using the Early Treatment Diabetic Retinopathy Study (ETDRS) letter scoring method. MethodsLCVA was tested using 2.5% and 1.25% low contrast ETDRS-style 4m Sloan letter charts. When [&ge;]20 letters were read correctly, the letter score was equal to letter count plus 30. If <20 letters were read correctly, the letter score was equal to ...

Background and ObjectivesSporadic inclusion body myositis (IBM) is the most common acquired myopathy in individuals over age 50. The disorder is slowly progressive and while many therapies have been investigated, response has generally been poor. Clinical heterogeneity may influence treatment responsiveness; however, data regarding heterogeneity in IBM is limited and often conflicting. We aim to identify clinically distinct subgroups within a large IBM cohort, as well as prognostic factors for d...

ObjectivesMultiple sclerosis (MS) is a complex autoimmune neurological disorder that frequently impacts vision. One of the most frequent initial presentations of MS is acute vision loss due to optic neuritis, an acute disorder caused by MS involvement with the optic nerve. While vision impairment is often the first sign of MS, it can occur or recur at any time during the patients course. In this study, we aim to develop and evaluate machine learning models to predict vision impairment in patient...

BackgroundEBV infection is thought to play a central role in the development of Multiple Sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk. ObjectiveTo examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk. MethodsPubmed was searched using the terms "multiple sclerosis" AND "Epstein Barr virus", "multiple sclerosis" AND EBV, "clinically isolated syndrome" AND "Epstein Bar...

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...

ObjectiveA multi-center, prospective, cross-sectional natural history study to define the clinical phenotype of Andersen-Tawil syndrome, validate its current diagnostic criteria, explore genotype-phenotype correlations, and establish clinically relevant endpoints for use in therapeutic trials. MethodsParticipants were followed at yearly intervals for two years. Outcome measures included attack frequency and duration, neurophysiological exercise testing and interictal muscle strength. Cardiac en...

ImportanceThe risk of multiple sclerosis (MS) is significantly influenced by polygenic inheritance. Polygenic risk scores (PRS) for MS can help identify high-risk individuals and stratify populations for clinical trials. However, most genome-wide association studies (GWAS) have been conducted in populations of European ancestry, raising questions about the accuracy of these PRS in other ancestries. ObjectiveTo determine whether a PRS for MS can effectively stratify individuals of non-European a...

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by homozygous loss of the SMN1 gene. Copy number of the nearly identical paralog, SMN2, correlates with disease severity. SMN2 is the primary modifier of SMA, with only a few other modifiers reported. We reviewed the literature of rare siblings affected by SMA that show discordance in clinical presentation despite having the same number of SMN2 copies, which predicts the presence of genetic modifiers. We further recruited a sibl...

ObjectiveReport outcomes on patients with Multiple Sclerosis (MS) and related disorders with COVID-19 illness. MethodsFrom March 16 to April 30th, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center (MSCC) were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by review of in-patient hospital records. ResultsWe identified 76 patients (55 with relapsing MS of which 9 had pediatric-o...

BackgroundDifferentiating demyelinating from axonal polyneuropathies is essential for accurate diagnosis and treatment. We hypothesized that multiparametric quantitative MRI (qMRI) of peripheral nerves can differentiate demyelination from axonal loss. This retrospective study leveraged genetically defined demyelinating and axonal polyneuropathies to test this concept. MethodsMultiparametric qMRI data of proximal (sciatic) and distal (tibial) nerves were acquired on 3T MRI, including magnetizati...

BackgroundIdiopathic inflammatory myopathies (IIMs) are a group of rare acquired muscular diseases. In healthy muscle, myofibers do not express major histocompatibility complex (MHC) class I and II. It was established that MHC-I positive immunostaining, although non-specific, is a marker for IIM diagnosis, while the significance of MHC-II immunostaining remains unclear. The present study investigates the expression of MCH-II in myofibers and capillaries of IIM muscles, taking into account the cu...