The UK SMA Patient Registry, established in 2008, is an online database into which individuals living with spinal muscular atrophy (SMA) in the United Kingdom and Ireland can enter information about their or their child's condition. In April 2022, the registry implemented a range of patient-reported outcome measures (PROMs) to contribute to Managed Access Agreement (MAA) data collection supporting the national regulatory review of recently emerged SMA treatments Nusinersen and Risdiplam. The registry simultaneously launched a 3-year study in collaboration with the national Adult SMA REACH and SMA REACH UK clinical networks, aiming to collect longitudinal PROMs data at 6-month intervals from 100 patients receiving each respective treatment during the MAA data collection period. As of June 2025, the registry received 3764 PROMs questionnaire submissions from 363 patients and caregivers. EQ-5D-5L data showed adult patients' reporting of moderate-to-extreme anxiety and depression did not directly correspond to their self-reported motor function ability. EQ VAS data showed SMA type 1, 2 and 3 patients reported similar average levels of overall health, regardless of motor function ability. The registry's collected PROMs data, aligned with SMA REACH clinical data, was submitted to national regulatory authorities in December 2023, with a further report submitted in May 2025. The study demonstrated the successes of implementing PROMs to support MAA data collection and marked an important milestone for patients' voices to contribute to SMA therapy evaluation through a patient registry. The study data emphasises that patient-reported data complements and offers an alternate perspective to clinical real-world data.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder resulting from progressive degeneration and loss of motor neurones in the spinal cord. Current standards of care guidelines focus on a multidisciplinary approach and include recommendations for nine different aspects of care. Although intended for use in all patients with SMA, the guidelines are focused on paediatric best practices and evidence regarding care provision in adults with SMA remains limited. This cross-sectional analysis of a longitudinal registry cohort of adults with SMA study aimed to evaluate the clinical features and corresponding care provision to assess alignment with current care guidelines. Data from 426 patients with genetically confirmed SMA were analysed, including information on respiratory function, bulbar involvement, musculoskeletal complications and daily living support. Results demonstrated a high prevalence of respiratory impairment, bulbar dysfunction, contractures and significant limitations in activities of daily living. However, the care provision observed in this adult cohort did not consistently reflect the recommended standards outlined in the established SMA standards of care recommendations. In particular, gaps were noted in access to respiratory support, physiotherapy and nutritional management. These findings suggest that the application of current standards of care to the adult population is inconsistent. There is a need for improved translation of care provision into adult services to ensure comprehensive and equitable management of SMA across the lifespan.

ABSTRACTIntroduction/AimsAn increased risk of low trauma fractures is well documented in children and adolescents with duchenne muscular dystrophy (DMD). There is limited evidence regarding the fracture incidence of adults with DMD. The aim of this study was to examine radiologically confirmed fractures in adults with DMD and review bone health monitoring.MethodsThis was a retrospective review of all adult males ≥ 16 years with DMD under the care of adult physicians in the West of Scotland (2013–2022). Information regarding fractures, bone health monitoring, and bisphosphonate therapy was collected.ResultsThirty‐six men (median age at first visit 18.8 years) with DMD were included. Twelve were taking corticosteroids at first review, and a further 12 had previously been taking corticosteroids that were discontinued in childhood or adolescence. The fracture incidence rate was higher in the corticosteroid group (888.9 per 10,000 person years (95% CI 242.2–2275.9)) than in those not on corticosteroids (156.3 per 10,000 person years (95% CI 32.2–456.6)). Eighteen had lateral spine radiographs for vertebral fracture assessment and 15 had a DXA scan for bone density assessment during the follow‐up period.DiscussionThe fracture incidence in adult men with DMD is more than double that of UK men aged 18–49 years old, with an even higher incidence in those treated with corticosteroids. Fewer than half of the study population underwent bone monitoring. There is a need for enhanced clinical guidance for the monitoring and management of osteoporosis during transition and throughout adulthood.

The 2025 update of the Association of British Neurologists guidelines for the management of autoimmune myasthenia gravis (MG) emphasises several points that are distinct from the 2015 guidelines based on recent research and publications. The main differences from the previous guidelines are: (1) The recommendation to prescribe daily steroids rather than the alternate day regimen is now standard practice. (2) There is a clear emphasis on the beneficial effects of early thymectomy. (3) Randomised controlled trial evidence now supports early use of rituximab (within 1 year of generalised disease onset), although the evidence is less robust, but still likely to be useful, in established treatment-refractory MG. (4) Finally, several clinical trials have been published for newer targeted therapies in MG, predominantly those that inhibit the complement and neonatal Fc gamma receptor pathways, the roles of which are being slowly established especially in patients unresponsive to conventional therapy.

Multiple-acyl-CoA-dehydrogenase deficiency (MADD) is a rare metabolic disorder affecting fatty acid and amino acid metabolism. Local experience and evolving literature highlights a paucity of genetically confirmed cases. A retrospective analysis of patients attending the West of Scotland neuromuscular service with a working diagnosis of late-onset MADD was undertaken. Nineteen cases were identified with median onset age of 52 years and female predominance. 8/19 presented with rhabdomyolysis and 11/19 with a subacute myopathy over mean 12.6 months. 14/19 had evidence of a provoking factor prior to clinical presentation and 16/19 had current sertraline use. All cases had abnormal acylcarnitine profiles in keeping with a MADDlike profile and abnormal skeletal muscle biopsies. Abnormal lipid accumulation was seen in 14/19, ranging from mild increase in lipid droplet size to gross lipid excess in seven cases. 4/19 were heterozygous for likely pathogenic ETFDH gene variants; no second variants were identified within the limits of testing available. All showed variable improvement following riboflavin therapy, advice on nutrition and advice on sertraline discontinuation. We suggest a late-onset MADD-like myopathy is much more common in the cohort than primary genetic MADD. Non-genetic and acquired factors may be causative, in keeping with the evolving literature.

BackgroundWe report our experience of patients with generalised myasthenia gravis (gMG) treated with efgartigimod, an neonatal Fc receptor antagonist, under the Early Access to Medicine Scheme (EAMS) in the UK.MethodsData from all UK patients treated with efgartigimod under the EAMS July 2022 to July 2023 were collected retrospectively. Efgartigimod was administered as per the ADAPT protocol (consisting of a treatment cycle of four infusions at weekly intervals with further cycles given according to clinical need).Results48 patients with acetylcholine receptor antibody-positive gMG were treated in 12 centres. Most (75%) were female and most had a disease duration of over 10 years. The average MG-Activities of Daily Living (ADL) score at baseline was 11.2. Most (72.9%) patients had undergone thymectomy. 77.0% were taking prednisolone at baseline. All patients had used non-steroidal immunosuppressant treatments, the average number tried was 2.6 (range 1–6). 51% had received rituximab. 54.2% of patients required regular intravenous immunoglobulin/plasma exchange.75% of patients had a mean reduction in the MG-ADL of≥2 points in the first cycle and this remained stable throughout the study. The mean intracycle reduction in the MG-ADL score in the first, second, third and fourth cycles were −4.6 to –3.9, −3.4 and −4.2, respectively. Side effects were generally mild. No rescue treatments were required. At the end of the study, 96% of patients remained on efgartigimod.ConclusionEfgartigimod is a safe and effective treatment for patients with refractory, treatment-resistant gMG.

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members.

BACKGROUND:The m.3243A>G variant is the commonest mitochondrial (mt) DNA pathogenic variant and a frequent cause of mitochondrial disease. Individuals present with a variety of clinical manifestations from diabetes to neurological events resembling strokes. Due to this, patients are commonly cared for by a multidisciplinary team. OBJECTIVES:This project aimed to identify patients with confirmed mt.3243A>G-related mitochondrial disease attending the Muscle Clinic at Queen Elizabeth University Hospital in Glasgow. We explored potential correlates between clinical phenotypes and mtDNA heteroplasmy levels, HbA1c levels, body mass index, and specific clinical manifestations. We investigated if there were discrepancies between non-neurological speciality labelling in clinical records and individuals' phenotypes. METHODS:Data were gathered from the West of Scotland electronic records. Phenotypes were ascertained by a clinician with expertise in mitochondrial disorders. Statistical analyses were applied to study relationships between tissue heteroplasmy, HbA1c and clinical phenotypes including body mass index (BMI). RESULTS:Forty-six individuals were identified from 31 unrelated pedigrees. Maternally inherited diabetes and deafness was the prominent syndromic phenotype (48%). A significant association was found between overall number of symptoms and bowel dysmotility (p < 0.01). HbA1c was investigated as a predictor of severity with potential association seen. Although used widely as a prognosticator, neither corrected blood nor urine mtDNA heteroplasmy levels were associated with increased number of symptoms. In 74.1% of records, syndromic phenotypes were incorrectly used by non-neurological specialities. CONCLUSIONS:This m.3243 A > G patient cohort present with marked clinical heterogeneity. Urine and blood heteroplasmy levels are not reliable predictors of disease severity. HbA1c may be a novel predictor of disease severity with further research required to investigate this association. We infer that prognosis may be worse in patients with low BMIs and in those with bowel dysmotility. These results underscore a multidisciplinary approach and highlight a problem with inaccurate use of the existing nomenclature.

The UK SMA Patient Registry collects patient-reported outcome measures (PROMs) from individuals living with spinal muscular atrophy (SMA) in the UK and Ireland. In 2022, PROMs collection was introduced in the registry to supplement clinical and genetic data held therein. PROMs capture the perspectives of adults and caregivers of young people living with SMA about the impact of their condition and treatment, their quality of life and activities of daily living. Importance of the patient voice is increasingly recognised and valued. Currently, SMA therapies Nusinersen and Risdiplam are available in the UK via managed access agreements (MAAs). The collection of clinical and patient-reported data will inform review of treatment impact by UK regulatory authorities. In collaboration with clinical networks Adult SMA REACH and SMA REACH UK, the registry aims to collect PROMs data of 100 Nusinersen and 100 Risdiplam patients. PROMs will be aligned with Adult SMA REACH and SMA REACH clinical data, anonymised, analysed and submitted to regulatory authorities for consideration as part of the treatment MAAs. Registration in the UK SMA Patient Registry is patient-initiated through a secure online portal. Patients are invited to complete questionnaires about their condition and PROMs: EQ-5D; Patient Global Impression of Change; SMA Independence Scale (SMAIS-ULM); and a free-text box. Enabled through patient consent and data sharing agreements, patient-level PROMs data is shared with each patient's SMA REACH clinic and with the SMA REACH coordination teams. In clinic, the data informs patient care. At project coordination level, PROMs are aligned with clinical data collected by SMA REACH. At the time of abstract submission, the registry has 642 participants: 443 adults (16+years); 199 paediatric (<16years). PROMs have been completed by 205 adults and by the caregivers of 80 paediatric patients. The fraction of PROMs able to be aligned with Adult SMA REACH and SMA REACH clinical data is growing and will be presented. The UK SMA Patient Registry represents a well-defined cohort of individuals with SMA and is a valuable tool for the collection of SMA real-world data reported by treated and treatment-naïve patients. Expansion of the registry to collect PROMs supports UK SMA data collection and supplements Adult SMA REACH and SMA REACH clinical data, assisting in therapy evaluation by regulatory authorities.

A previously healthy 27-year-old man was admitted to the acute neurology ward with events involving his face, throat and upper limb, which video telemetry later confirmed were refractory focal seizures. He also had progressive pyramidal features, dysarthria and ataxia. MR scans of the brain identified progressive bilateral basal ganglia abnormalities, consistent with Leigh syndrome. However, extensive laboratory and genetic panels did not give a unifying diagnosis. A skeletal muscle biopsy showed no histopathological abnormalities on routine stains. Sequencing of the entire mitochondrial genome in skeletal muscle identified a well-characterised pathogenic variant (m.10191T>C in MT-ND3; NC_012920.1) at 85% heteroplasmy in skeletal muscle. We discuss the clinical and molecular diagnosis of an adult presenting with Leigh syndrome, which is more commonly a paediatric presentation of mitochondrial disease, and how early recognition of a mitochondrial cause is important to support patient care.

Multiple-acyl-CoA-dehydrogenase deficiency (MADD) is caused by recessive pathogenic variants in genes encoding the alpha and beta subunits of electron transfer flavoprotein (ETF) and ETF-coenzymeQ oxioreductase. Sunebo and colleagues recently described a MADD cohort, highlighting a paucity of genetic diagnoses and possible association with sertraline. This led us to review all 18 patients known to the West of Scotland adult neurology service who were being treated with riboflavin for a working diagnosis of late-onset MADD. 4/18 (22%) had a single heterozygous likely pathogenic or pathogenic ETFDH variant. Age at onset was 21 to 80y, with mean 52y. 8/18 presented with rhabdomyolysis, all with recognised precipitants. The remainder presented with (sub)acute progressive weakness. Detailed dietary assessments were not undertaken but unhealthy and/or restricted diets were often described. 15/18 (83%) were on sertraline at presentation. 13/18 (72%) had significant increases in C4>C18 acylcarnitines with patterns suggestive of MADD. 2/18 had patterns compatible with MADD or carnitine palmitoyltransferase-2 (CPT-2) deficiency, the latter was excluded genetically. 3/18 has more subtle patterns (C4>C10). For 10 of 14 patients where urine organic acids were analysed, these were suggestive of, or consistent with, MADD. Review of 17 skeletal muscle biopsies revealed abnormal lipid deposition in 15/17, ranging from increased lipid droplet size in a proportion of fibres in 5 cases through to coalescent lipid vacuoles in a majority of fibres in 5 cases. There was no correlation between extent of lipid pathology and age, or presence of ragged-red or COX-deficient fibres. All patients improved clinically and biochemically with riboflavin supplementation, though the extent varied. A late-onset MADD-like condition is much more common in our neurology cohort than primary genetic MADD and is likely multifactorial.

The Glasgow Genomic laboratory offers a 36 gene rhabdomyolysis and metabolic myopathy panel. Test criteria were developed by clinicians but not strictly enforced. Evaluation of 74 consecutive referrals found testing varied according to patients’ Health Board of residence from 0 to 27 patients tested/million population. 6 (8.1%) had definitive diagnoses with likely pathogenic or pathogenic variants (5 RYR1, 1 CAPN3). One had an RYR1 VUS and positive in-vitro contracture test. Clinical details were evaluated in 69 adults. In the two largest Health Boards there were 22.4 patients tested/million population with a pickup rate of definitive genetic diagnoses of 11%, compared with 6.5 tested/million population with a pickup rate of 5% in the rest of Scotland. 60% and 68% respectively fitted test criteria. 32 of 57 cases (56%) referred by clinicians involved in designing the test criteria fitted these, compared with 11 of 12 (92%) other referrals. All 5 probands with RYR1 associated rhabdomyolysis, and 2 relatives with exercise induced pigmenturia, were fit males, with cycling a trigger in all but one. Variant carrying female relatives were asymptomatic or had exercise related myalgia. 4 of 46 non-RYR1 rhabdomyolysis cases were triggered by cycling and 3 by spin classes. One RYR1 associated single rhabdomyolysis case would have been missed by strict application of test criteria, as peak CK was below the 10,000IU/L criterion. However, CK remained elevated, and the investigation pathway suggested referral to a muscle clinic. Persistently elevated CK should be added to test criteria. Both diagnoses (RYR1, CAPN3) in the possible metabolic myopathy group would have been missed if test criteria were adhered to. Variability in clinician awareness and adherence to test criteria likely contribute to the postcode lottery in access to testing. It is unclear why diagnostic pickup varies by patient postcode, and unclear whether the association of RYR1 rhabdomyolysis with cycling is real.

Background The diagnosis of patients with mutations in the VCP gene can be complicated due to their broad phenotypic spectrum including myopathy, motor neuron disease and peripheral neuropathy. Muscle MRI guides the diagnosis in neuromuscular diseases (NMDs); however, comprehensive muscle MRI features for VCP patients have not been reported so far. Methods We collected muscle MRIs of 80 of the 255 patients who participated in the “VCP International Study” and reviewed the T1-weighted (T1w) and short tau inversion recovery (STIR) sequences. We identified a series of potential diagnostic MRI based characteristics useful for the diagnosis of VCP disease and validated them in 1089 MRIs from patients with other genetically confirmed NMDs. Results Fat replacement of at least one muscle was identified in all symptomatic patients. The most common finding was the existence of patchy areas of fat replacement. Although there was a wide variability of muscles affected, we observed a common pattern characterized by the involvement of periscapular, paraspinal, gluteal and quadriceps muscles. STIR signal was enhanced in 67% of the patients, either in the muscle itself or in the surrounding fascia. We identified 10 diagnostic characteristics based on the pattern identified that allowed us to distinguish VCP disease from other neuromuscular diseases with high accuracy. Conclusions Patients with mutations in the VCP gene had common features on muscle MRI that are helpful for diagnosis purposes, including the presence of patchy fat replacement and a prominent involvement of the periscapular, paraspinal, abdominal and thigh muscles.

A 61-year-old man developed progressive head drop, gait disturbance, shortness of breath, night sweats and weight loss. Investigations led to a treatable diagnosis. This report documents the clinicopathological conference at the 43rd Edinburgh Clinical Neurology course 2022.