An observational longitudinal study of congenital myasthenic syndromes.

Congenital Myasthenic Syndromes (CMS) are a group of inherited disorders characterised by fatigable muscle weakness. There are currently no validated outcome measures in CMS. We conducted a prospective exploratory observational study in 49 CMS patients.

Deep Learning Modeling to Differentiate Multiple Sclerosis From MOG Antibody-Associated Disease.

Background And Objectives: Multiple sclerosis (MS) is common in adults while myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is rare. Our previous machine-learning algorithm, using clinical variables, ≤6 brain lesions, and no Dawson fingers, achieved 79% accuracy, 78% sensitivity, and 80% specificity in distinguishing MOGAD from MS but lacked validation. The aim of this study was to (1) evaluate the clinical/MRI algorithm for distinguishing MS from MOGAD, (2) develop a deep learning (DL) model, (3) assess the benefit of combining both, and (4) identify key differentiators using probability attention maps (PAMs).

Outcomes After Acute Plasma Exchange for Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Background And Objectives: Data on the plasma exchange (PLEX) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are limited. Herein, we evaluate outcomes after PLEX in MOGAD.

Methods: This international multicenter retrospective cohort study included patients from 18 tertiary care centers in 6 countries.

Long-Term Efficacy and Safety of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder From the SAkuraMoon Open-Label Extension Study.

Background And Objectives: Satralizumab (SAT), an interleukin-6 receptor inhibitor, reduced the risk of protocol-defined relapse (PDR) vs placebo (PBO) with a favorable safety profile in patients with neuromyelitis optica spectrum disorder (NMOSD) in 2 pivotal phase 3 trials, SAkuraSky and SAkuraStar. We evaluated the long-term safety and efficacy of SAT in patients with NMOSD in the single-arm, open-label, rollover study SAkuraMoon.

Methods: Patients who completed the double-blind periods (DBPs) and open-label extensions (OLEs) of SAkuraSky and SAkuraStar were enrolled in SAkuraMoon, where they continued receiving subcutaneous SAT 120 mg 4 times a week (Q4W) ± immunosuppressive therapy.

Myasthenic syndromes: mistaking genetic for acquired.

Congenital myasthenic syndromes (CMS) are a rare, heterogeneous group of disorders caused by pathogenic variants in genes encoding proteins essential for neuromuscular transmission. variants are among the most common causes of CMS and one of the subtypes that may worsen with pyridostigmine. We report two patients who presented in adulthood with fatigable limb girdle weakness, initially diagnosed with seronegative myasthenia gravis, who slowly progressed over time despite escalating treatment and eventually needed intensive care admission.

The impact of autoimmune comorbidities on the onset attack recovery in adults with AQP4-NMOSD and MOGAD.

Background: Aquaporin-4 neuromyelitis optica spectrum disorder (AQP4-NMOSD) often coexists with other autoimmune diseases (AIDs), whereas such comorbidities are less common in myelin oligodendrocyte glycoprotein antibody disease (MOGAD). This study investigates the impact of additional AIDs on early relapse recovery and disability in patients with AQP4-NMOSD and MOGAD.

Methods: This retrospective study included patients aged > 16 years with AQP4-NMOSD (n = 175) or MOGAD (n = 221), who were followed at a nationally commissioned Oxford service and categorized based on the presence of at least one AID.

Case report on severe myelin oligodendrocyte glycoprotein antibody-associated disease relapse after ectopic pregnancy and laparoscopic medical abortion: relevance of peripheral inflammation for demyelinating disease activity.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare neurological condition. Tubal ectopic pregnancy is an important cause of maternal morbidity and mortality worldwide. Regular pregnancy has a disease-modifying effect on MOGAD, with an increased relapse rate postpartum.

Analysis of infection rates in neuromyelitis optica spectrum disorder: Comparing satralizumab treatment in SAkuraMoon, post-marketing, and US-based health claims data.

Satralizumab showed a comparable safety profile versus placebo in 2 pivotal neuromyelitis optica spectrum disorder (NMOSD) studies. We analyzed infection rates with long-term satralizumab treatment in the open-label study, SAkuraMoon, and in a post-marketing setting (PMS), comparing frequencies with US-based health claims real-world data (US-RWD). Incidence rates of infection per 100 patient-years (IR/100 PY) were analyzed in the SAkura studies (clinical cut-off date: 31 January 2023).

Structures of the human adult muscle-type nicotinic receptor in resting and desensitized states.

Muscle-type nicotinic acetylcholine receptor (AChR) is the key signaling molecule in neuromuscular junctions. Here, we present the structures of full-length human adult receptors in complex with Fab35 in α-bungarotoxin (αBuTx)-bound resting states and ACh-bound desensitized states. In addition to identifying the conformational changes during recovery from desensitization, we also used electrophysiology to probe the effects of eight previously unstudied AChR genetic variants found in patients with congenital myasthenic syndrome (CMS), revealing they cause either slow- or fast-channel CMS characterized by prolonged or abbreviated ion channel bursts.

Sleep-related hypermotor epilepsy in a patient with myelin-oligodendrocyte-glycoprotein antibody disease.

Unusual seizure phenotypes in myelin-oligodendrocyte-glycoprotein (MOG) seropositive patients have previously been reported, although so far, no cases of sleep-related hypermotor epilepsy (SHE). In our case, a patient with a diagnosis of MOG antibody-associated disease (MOGAD) began reporting unusual sleep disturbances; video-audio documentation was in keeping with the clinical diagnosis of SHE. MRI brain was normal at the time of the assessment for seizures.

Smoking status and vascular risk factors as predictors of disability in AQP4-NMOSD and MOGAD.

Background: Smoking and vascular risk factors (VRFs) are reported to have adverse effects in multiple sclerosis but data are limited in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). This study aimed to measure their impact on disability.

Methods: Smoking status was defined as never, past or current smokers and VRF comprised of ⩾1: hypertension, dyslipidemia, high body mass index or diabetes.

Multiple autoimmunity: neuromyelitis optica spectrum disorder with Lambert-Eaton myasthenic syndrome.

A 56-year-old woman with a background of neuromyelitis optica spectrum disorder associated with aquaporin-4 antibodies (AQ4-NMOSD) treated with azathioprine, presented with a 2-month history of declining mobility, weight loss and hoarse voice. She had a history of autoimmune thyrotoxicosis and treated hypertension. Given her smoking history, the initial clinical concern was of malignancy.

More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis.

Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we integrated these three modalities to portray an enriched representation of the brain's core-periphery organization and explore its alterations in PwMS. In this retrospective cross-sectional study, we selected PwMS and healthy controls with complete multimodal brain MRI acquisitions from 13 European centers within the MAGNIMS network.

Association of the Cervical Canal Area With Disability and Progression in People With Multiple Sclerosis.

Background And Objectives: In multiple sclerosis (MS), brain reserve serves as a protective factor against cognitive impairment. Previous research has suggested a structural counterpart in the spine-spinal cord reserve-seemed to be associated with physical disability. This study aimed to investigate the potential of the cervical canal area (CCaA) as a proxy for spinal cord reserve in a multicentric cohort of people with MS (PwMS).

Assessing the Utility of ColabFold and AlphaMissense in Determining Missense Variant Pathogenicity for Congenital Myasthenic Syndromes.

Background/objectives: Congenital myasthenic syndromes (CMSs) are caused by variants in >30 genes with increasing numbers of variants of unknown significance (VUS) discovered by next-generation sequencing. Establishing VUS pathogenicity requires in vitro studies that slow diagnosis and treatment initiation. The recently developed protein structure prediction software AlphaFold2/ColabFold has revolutionized structural biology; such predictions have also been leveraged in AlphaMissense, which predicts ClinVar variant pathogenicity with 90% accuracy.

Cerebral cortical encephalitis in adults with myelin oligodendrocyte glycoprotein antibody-associated disease: A national case series.

Background And Purpose: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a relatively recently described disease, most commonly presenting with optic neuritis and longitudinally extensive transverse myelitis. Cerebral cortical encephalitis is a rare manifestation of MOGAD.

Methods: We identified patients presenting with cerebral cortical encephalitis with positive MOG antibodies in serum across a large specialized service.

Using disease-modifying treatments in multiple sclerosis: Association of British Neurologists (ABN) 2024 guidance.

The Association of British Neurologists last published guidelines on disease-modifying treatment (DMT) in multiple sclerosis (MS) in 2015. Since then, additional DMTs have been licensed and approved for prescribing within the National Health Service for relapsing-remitting MS, early primary progressive MS and active secondary progressive MS. This updated guidance provides a consensus-based approach to using DMTs.

Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap.

Background And Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS.

275th ENMC international workshop: Seronegative myasthenia gravis: An update paradigm for diagnosis and management, 9-11 February 2024, Hoofddorp, the Netherlands.

The 275th ENMC workshop on the diagnosis and management of seronegative myasthenia gravis (SNMG) was held on February 9-11, 2024. The participants included experts in the field of adult and pediatric MG together with patient representatives. This workshop aimed to redefine SNMG in view of recent diagnostic and therapeutic updates and to identify patient unmet needs.

Brain reserve and physical disability in secondary progressive multiple sclerosis.

Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS.

The influence of MOGAD on diagnosis of multiple sclerosis using MRI.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS.