BMJ Neurology Open最新文献

Background: Ocrelizumab, a humanised anti-CD20 monoclonal, is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS). The long-term safety of B-cell depletion in RRMS, however, is uncertain and there are no data on dose reduction of ocrelizumab as a risk mitigation strategy. This study aimed to evaluate the effectiveness and safety of reducing ocrelizumab dose from 600 to 300 mg in patients with RRMS.

Method: Data were collected through the Townsville neurology service. Following the standard randomised controlled trial regimen of 600 mg every 6 months for 2 years, sequential patients consented to dose reduction to 300 mg every 6 months. Patients were included if they were diagnosed with RRMS and received at least one reduced dose of ocrelizumab. Relapse, disability progression, new MRI lesions, CD19⁺ cell counts and immunoglobulin concentrations were analysed.

Results: A total of 35 patients, treated with 177 full and 107 reduced doses, were included. The mean follow-up on reduced dose was 17 (1-31) months. We observed no relapses or new MRI activity in the cohort receiving the reduced dose, accompanied by persistent CD19+B cell depletion (≤0.05×10⁹/L). Mean IgG, IgA and IgM levels remained stable throughout the study. No new safety concerns arose.

Conclusions: In this single-centre observational study, dose reduction of ocrelizumab from 600 to 300 mg every 6 months after 2 years appeared to maintain efficacy in terms of new inflammatory disease activity. A randomised trial may be warranted to confirm this and explore the impact of dose reduction on long-term safety.

Background: Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation.

Methodology: Next-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias.

Results: We here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification.

Conclusion: Dystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.

Introduction: Recently, there have been a few reports of atypical post-coronavirus disease 2019 (COVID-19) myelopathy manifesting tract-specific lesions similar to those due to vitamin B₁₂ deficiency. However, the precise characteristics of imaging or clinical course remain not well understood.

Methods: A retrospective analysis of the clinical and imaging characteristics of four patients who were referred to our hospital with a unique post-COVID-19 myelopathy was performed.

Results: Four-to-six weeks following COVID-19 infection in the summer of 2023, four middle-aged men developed paraparesis, hypo/dysesthesia and bladder/bowel disturbance, suggesting myelopathy. Although spinal MRI showed no abnormalities in the early stages, tract-specific longitudinal lesions along the dorsal and lateral columns became apparent as the symptoms progressed. Owing to the lack of MRI findings at the early stage, all cases were challenging to diagnose. However, the patients remained partially responsive to aggressive immunosuppressive therapies, even in the advanced stage.

Discussion: We termed these tract-specific longitudinal lesions in the presented case series 'Grasshopper sign' because brain coronal and spine axial MRI findings looked like a grasshopper's antennae and face. Early identification of the characteristic MRI abnormality could allow for early intervention using intensive immunosuppressive therapy, which could improve patient outcomes.

Background: Mitochondrial diseases in adults are generally chronic conditions with a wide spectrum of severity contributing to disease burden and healthcare resource utilisation. Data on healthcare resource utilisation in mitochondrial diseases are limited.

Objectives: We performed a retrospective longitudinal study to investigate the clinical drivers of hospitalisation in adult patients with mitochondrial diseases to better understand healthcare resource utilisation.

Methods: We recruited participants from our specialised Mitochondrial Disease Clinic in Sydney, Australia between September 2018 and December 2021. We performed a retrospective chart review for the period 2013-2022 considering emergency department (ED) and/or hospital admission notes, as well as discharge summaries. We used multiple linear regression models to examine the association between the type of presenting symptom(s) and duration of hospital stay and frequency of admissions, while adjusting for relevant covariates.

Results: Of the 99 patients considered, the duration of hospitalisation ranged from 0 to 116 days per participant and the number of admissions ranged from 0 to 21 per participant. Participants with one or more mitochondrial disease-associated admissions constituted 52% of the study cohort. 13% of the participants presented to the ED without requiring an admission and 35% never attended the ED or required a hospital admission during this period. Neurological (p<0.0001), gastroenterological (p=0.01) and symptoms categorised as 'other' (p<0.0001) were the main presentations driving the total number of days admitted to hospital. A statistically significant association was evident for the number of admissions and all types of presenting symptoms (p<0.0001).

Conclusion: There are variable reasons for hospitalisation in adults with mitochondrial diseases, with neurological and gastroenterological presentations being associated with prolonged and complex hospitalisation. A better understanding of clinical drivers such as these allows for better informed and well-coordinated management aimed at optimising healthcare resource utilisation.

Background: A critical first step in managing functional neurological disorder (FND) is a positive diagnosis and clear explanation using an understandable illness model. Multidisciplinary group education sessions are one way to achieve this, with some evidence they improve understanding, confidence in diagnosis and outcomes with further treatment. In many conditions, illness perceptions and stigma affect distress, functioning, quality of life and engagement. Exploring relationships between these factors could lead to deeper understanding of the impact of education.

Methods: Questionnaires assessing illness perceptions, quality of life, mood, anxiety, comorbidities, treatment engagement and stigma (both experienced and anticipated) were completed before, immediately and 1 month after a multidisciplinary online group education session for FND at a regional neurosciences centre. Free-text data on causal attributions and needs were also collected.

Results: 166 patients attended online education sessions from January 2022 to July 2023; 61 (37%) completed presession surveys, 42 (25%) completed postsession and 35 (21%) completed 1 month postsession surveys. Patients reported multiple comorbidities, poor quality of life, functioning and high levels of stigma. Illness perception scores indicated FND as threatening, mysterious and unpredictable, with low personal or treatment control over symptoms. Illness coherence/understanding (mean difference 2.27, p<0.01, 95% CI 1.22 to 4.23) and engagement (mean difference 2.42, p<0.01, 95% CI 0.46 to 4.36) increased after the session. There were no significant changes in stigma, distress, sense of control or anticipated discrimination. Free-text analysis revealed stress and trauma as the most common causal attributions, followed by physical illnesses. Patients requested personalised formulations, practical disability advice, help with explaining the condition to others (eg, employers), peer support and treatment.

Conclusion: Multidisciplinary group FND education sessions potentially improve patient understanding and engagement. Clinicians should consider the possible benefits of personalised formulations and linking to practical and peer support. Further work assessing illness perceptions is needed, such as adapting measures for FND.

Introduction: Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness. However, the interplay between affective arousal and changes in interoceptive processing at the onset of dissociative seizures is not well understood.

Methods: Using retrospective routine data obtained from video-electroencephalography telemetry in a university hospital epilepsy monitoring unit, we investigate ictal changes in cardiac indices of autonomic arousal and heartbeat evoked potentials (HEPs) in 24 patients with dissociative seizures.

Results: Results show autonomic arousal during seizures with increased heart rate and a shift towards sympathetic activity. Compared with baseline, ictal HEP amplitudes over central and right prefrontal electrodes (F8, Fz) were significantly less pronounced during seizures, suggesting diminished cortical representation of interoceptive information. Significant correlations between heart rate variability measures and HEPs were observed at baseline, with more sympathetic and less parasympathetic activity related to less pronounced HEPs. Interestingly, these relationships weakened during seizures, suggesting a disintegration of autonomic arousal and interoceptive processing during dissociative seizures. In a subgroup of 16 patients, MRI-based cortical thickness analysis found a correlation with HEP amplitudes in the left somatosensory association cortex.

Conclusions: These findings possibly represent an electrophysiological hint of how autonomic arousal could negatively impact bodily awareness in dissociative seizures, and how these processes might be related to underlying brain structure.

Background: We aimed to determine whether sodium valproate (VPA) should be contraindicated in all mitochondrial diseases, due to known VPA-induced severe hepatotoxicity in some mitochondrial diseases.

Methods: We systematically reviewed the published literature for mitochondrial DNA (mtDNA) and common nuclear genotypes of mitochondrial diseases using PubMed, Ovid Embase, Ovid Medline and MitoPhen databases. We extracted patient-level data from peer-reviewed articles, published until July 2022, using the Human Phenotype Ontology to manually code clinical presentations for 156 patients with genetic diagnoses from 90 publications.

Results: There were no fatal adverse drug reactions (ADRs) in the mtDNA disease group (35 patients), and only 1 out of 54 patients with a non-POLG mitochondrial disease developed acute liver failure. There were fatal outcomes in 53/102 (52%) POLG VPA-exposed patients who all harboured recessive mutations.

Conclusions: Our findings confirm the high risk of severe ADRs in any patient with recessive POLG variants irrespective of the phenotype, and therefore recommend that VPA is contraindicated in this group. However, there was limited evidence of toxicity to support a similar recommendation in other genotypes of mitochondrial diseases.

The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures multicentre randomised controlled trial is the largest, fully-powered study to test the clinical and cost-effectiveness of a psychotherapeutic intervention in this population. We also explored predictors or moderators of outcomes and investigated mechanisms of change in therapy. In this current review of findings, we discuss issues related to the design of the trial and consider the study's nested qualitative studies which were undertaken not only to shed light on the original research questions but to provide insights and recommendations for other researchers in the field of functional neurological disorder. Finally, we consider issues relating to the possible clinical application of our study findings.

Introduction: Cases of nitrous oxide (N₂O)-induced myeloneuropathy are increasing at UK hospitals. At our centre, a dedicated ambulatory care pathway, endorsed nationally, was established to treat and monitor patients with N₂O-myeloneuropathy in 2021 and refined through three audit cycles. We analysed the outcomes of patients on this pathway to better understand factors associated with non-engagement. Alongside, a novel approach using WhatsApp for questionnaire delivery was trialled in an attempt to improve engagement with treatment.

Methods: Patients on the N₂O ambulatory care pathway were identified from MDT meeting lists from 9 September 2022 to 25 April 2023. Clinical data were collected via electronic clinical records, including the most recent neurological examination and reason for discharge from the pathway. Patients identified from MDT lists from 27 January 2023 to 14 March 2023 were approached to participate in weekly 12-item surveys, delivered via WhatsApp. This was approved as a service development project with approval for WhatsApp use given by the chief clinical information officer.

Results: 35/56 (62.5%) patients were discharged from ambulatory care due to non-attendance and 17/56 (30.4%) completed their treatment course. The median time from initial presentation to discharge was 49 days. 24/40 (60.0%) of patients with a final neurological examination documented had a residual deficit, with objective sensory deficits most common. 12 patients were approached to receive weekly questionnaires via WhatsApp. 5/8 who expressed interest returned a consent form. All participants were withdrawn due to non-response or participant choice. 1/5 returned more than two surveys.

Conclusion: Despite poor participation in surveys delivered via WhatsApp, novel approaches are needed to improve engagement with patients on the N₂O ambulatory care pathway.

Background: The study aimed to elucidate the prevalence of nitrous oxide (N2O) usage in patients with unexplained venous thromboembolism (VTE), highlighting the potential association with hyperhomocysteinaemia (HHcy).

Methods: We conducted a retrospective study at the Royal London Hospital, examining cases of N2O-related VTE from March to August 2023. Among 50 patients identified, four (8%) had recent unprovoked VTE. Patient data were collected based on N2O ambulatory emergency care pathway admissions.

Results: Among the 50 patients identified, four (8%) had recent or concurrent VTE. Three were male (75%), with an ethnic distribution of 50% Asian or Asian British and 50% Black or Black British. Patients were distributed across quintiles of the index of multiple deprivation. All had actual or functional vitamin B12 deficiency.

Discussion: The association between N2O use and VTE requires further investigation, though a plausible mechanism involving HHcy has been proposed. Clinicians should be vigilant for VTE in N2O users, especially those presenting with unexplained symptoms. VTE prophylaxis may be worth considering, particularly if continued exposure to nitrous oxide is anticipated.

Conclusion: N2O misuse may increase the risk of VTE, warranting attention from healthcare providers. Further research is needed to elucidate this association and inform preventive strategies. Public awareness about the risks of N2O remains essential.