BMJ Neurology Open最新文献

Background: The m.3243A>G mitochondrial DNA variant is the most common cause of adult mitochondrial disease and is associated with a heterogeneous clinical phenotype. The retina and optic nerve are among the most metabolically active tissues, making them vulnerable to mitochondrial dysfunction. Optical coherence tomography (OCT) studies have demonstrated retinal nerve fibre layer (RNFL) thinning in mitochondrial and other neurodegenerative diseases. We investigated whether temporal RNFL thinning is associated with central nervous system (CNS) involvement in individuals with the m.3243A>G variant.

Methods: High-resolution OCT was used to assess peripapillary RNFL thickness and perform macular segmentation. Participants were categorised into normal RNFL (n=14) or temporal RNFL thinning (n=15) groups. Demographic data, mean-corrected m.3243A>G heteroplasmy, Newcastle Mitochondrial Disease Adult Scale (NMDAS) scaled scores and NMDAS neurological traits were compared.

Results: Temporal RNFL thinning was significantly associated with neurological features (Fisher's exact test, p=0.027). In multivariable analysis, RNFL thinning and age were independent predictors of neurological involvement. Macular OCT revealed concomitant thinning of the ganglion cell-inner plexiform (GC-IPL) complex in the RNFL thinning group, with preservation of outer retinal layers, supporting primary retinal ganglion cell vulnerability. No significant associations were found between RNFL thinning and m.3243A>G heteroplasmy or NMDAS scaled scores.

Conclusion: Temporal RNFL thinning, accompanied by GC-IPL loss, is associated with neurological involvement in m.3243A>G-related mitochondrial disease, supporting its potential as a non-invasive biomarker of CNS dysfunction. Longitudinal studies are needed to determine whether these retinal changes are progressive and predictive of neurological decline.

Background: Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) impose psychological burdens on patients. Chronic illnesses create challenges for both patients and their partners, who also play a crucial role in managing disease-related stress. Despite its relevance, little is known about the role of dyadic coping (DC) in these conditions. This study investigates DC in NMOSD and MOGAD, aiming to provide clinical recommendations.

Methods: The CoMMOnsense-Study is a cross-sectional, prospective study of 59 NMOSD and 50 MOGAD patients and their respective partners, recruited from 15 centres of the German Neuromyelitis Optica Study Group registry. Participants completed self-report questionnaires on DC, depression, anxiety and quality of relationship. Correlation analyses were performed to compare findings based on antibody status. Subsequently, multivariate regression analyses were conducted to identify relevant predictors of DC.

Results: Patients with NMOSD and MOGAD demonstrated higher levels of depressive symptoms (NMOSD: p=0.007; MOGAD: p=0.023) and stress communication scores (NMOSD: p=0.022; MOGAD: p=0.013) than their partners. Negative coping was low across all subgroups (Stanine 1). Despite high DC and relationship quality, discrepancies were observed in the coping perceptions between partners.

Conclusions: Coping is highly shared within partnerships affected by NMOSD and MOGAD, while discrepancies in coping perceptions and protective buffering suggest the presence of unfavourable coping mechanisms. Reducing protective buffering and illness-related distortions shows potential areas for enhancing DC.

Background: Despite advances in multiple sclerosis (MS) management, the need for more accurate biomarkers remains critical. Conventional MRI, while essential for diagnosis, prognosis and disease monitoring, has limitations in capturing the full complexity of disease progression. This paper aims to identify biomarkers likely to be available in clinical practice by 2028, define a prospective organisational follow-up model for patients with MS, explore organisational requirements and propose solutions to facilitate their implementation. These insights aim to inform and anticipate future discussions among policymakers regarding the adoption of prospective biomarkers into clinical practice.

Methods: A multimethod qualitative design was employed, including a systematic literature review of 82 studies, two modified Delphi consensus processes and semistructured interviews with nine neurologists and three healthcare programming experts, applying the Structural, Technological, Organisational and Professional (STOP) framework. The STOP framework was used to assess structural, technological, organisational and professional requirements and to explore solutions.

Results: The research identified a prospective organisational follow-up model that integrates the most probable prospective biomarkers into clinical practice. The prospective organisational follow-up model defined an optimal testing frequency of Serum Neurofilament Light Chain and Glial Fibrillar Acidic Protein every 6 months, as well as Cognitive Tests and Optical Coherence Tomography every 12 months. Combining biomarkers and aligning them with MRI was seen as beneficial. Despite the validation of the model through a modified Delphi consensus process based on organisational feasibility and economic sustainability, structural and organisational challenges need to be addressed to ensure smoother integration into clinical practice.

Conclusions: This article aims to define an organisational model for the integration of prospective biomarkers into clinical follow-up in MS. It also explores potential strategies to facilitate their transition from research settings to routine clinical practice. The proposed approach provides a framework with potential for replication across various care pathways.

Background: Factors such as age and stroke severity are commonly used to predict poststroke functional outcomes and tailor stroke rehabilitation therapy. However, the role of personality in stroke rehabilitation and its influence on functional outcomes is unclear. This review aims to assess whether an association exists between personality and poststroke functional outcomes.

Methods: We searched Medline, AMED, APA PsychINFO, CENTRAL, CINAHL and Scopus for studies published between database inception and 22 October 2024. Studies were included if they recruited adults with stroke, used a validated method to assess personality and poststroke functional outcomes and were published in a peer-reviewed journal.

Results: Five studies were identified (n=424): four cohort and one cross-sectional. There were no major concerns regarding risk of bias. Methods of assessing personality and poststroke functional outcome both varied, with Eysenck's Personality Questionnaire and Barthel Index being the most frequently used. Extroversion, openness and lie-tendency were associated with improved poststroke functional outcomes, while type D personality was negatively associated with poststroke functional outcomes.

Conclusions: There is some evidence for an association between personality and poststroke functional outcomes, but this is limited by the small number of relevant studies and small sample sizes. Further studies are needed to investigate this potential relationship.

Prospero registration number: CRD42024592518.

Introduction: Statin therapy is known to reduce subsequent cardiovascular events in patients who had an ischaemic stroke and transient ischaemic attack (TIA). However, its effectiveness and safety in frail older adults with a recent stroke or TIA are uncertain, leading to variations in clinical practice. 'StAtins in Frail oldEr patients with ischemic Stroke or Transient ischemic attack-the Randomized Controlled Trial' (SAFEST-RCT) aims to investigate the effectiveness of initiating versus not initiating statin therapy in this vulnerable population, to optimise secondary prevention strategies.

Methods and analysis: This multicentre, prospective, randomised, open-label study aims to enrol 612 frail adults ≥70 years with a recent acute ischaemic stroke or TIA across 22 Dutch hospitals. The study compares prescribing versus not prescribing statins in terms of health-related quality of life, major adverse cardiovascular event-free survival and societal costs over a 2-year follow-up period.

Ethics and dissemination: The SAFEST-RCT protocol was approved by the Ethics Committee of Amsterdam UMC. It complies with the Declaration of Helsinki and is classified as a healthcare evaluation. Recruitment began in March 2025. Results will be published in open access journals, presented at conferences, shared via the Dutch Brain Injury Association and integrated into national guidelines to support implementation in routine care.

Trial registration number: NCT06785727.

Background: Functional neurological disorder (FND) is a common cause of neurological disability with symptoms spanning motor, sensory and cognitive domains. While effective treatments exist, the impact of symptom chronicity on treatment outcomes is unclear. This systematic review and meta-analysis investigated whether longer symptom duration influences treatment outcomes across FND phenotypes: functional movement disorders, functional/dissociative seizures (FDS) and mixed presentations.

Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO and grey literature were systematically searched till 29 June 2024. Studies were included if they involved adult FND participants undergoing any intervention and evaluated symptom change, function and health-related quality of life (HrQoL). Studies were excluded with <10 participants, missing symptom duration data or irrelevant outcomes. Two reviewers independently extracted data and assessed risk of bias. Meta-analyses used random effects models, subgroup analyses and univariate meta-regression to examine associations with symptom chronicity.

Results: 63 studies met inclusion criteria; 27 studies (885 participants) were meta-analysed. Longer symptom duration modestly reduced improvements in motor symptoms (-3.24 points/year, scale: 0-100) and physical HrQoL (-1.2 points/year, scale: 0-100). Global improvements (mean Clinical Global Impression-Change 2.43, 95% CI: 2.28 to 2.59, scale: 1-7) and mental HrQoL gains (mean Short Form-Mental Component Summary +5.04 points, 95% CI: 1.67 to 8.41) were observed irrespective of chronicity. FDS frequency reduced after psychotherapy in eight of nine studies, even with prolonged symptoms.

Conclusions: Symptom chronicity modestly reduced motor and physical HrQoL improvements, but did not negate meaningful gains across a range of outcomes. Early diagnosis and treatment are critical for better outcomes, but remain beneficial in chronic stages.

Background: Tumefactive demyelinating lesions (TDLs) are rare, large demyelinating lesions of the central nervous system that can mimic brain tumours in radiological appearance. They have been observed across multiple demyelinating diseases. Previous studies have suggested that antibody profiles may correlate with distinct clinical or imaging characteristics, but detailed comparisons between antibody-defined subgroups in TDLs remain limited.

Methods: We retrospectively analysed 30 patients with confirmed TDLs. Demographic, clinical, imaging and laboratory data were collected, and patients were stratified by myelin oligodendrocyte glycoprotein (MOG) and N-methyl-D-aspartic acid receptor (NMDAR) antibody results. Lesion characteristics were evaluated on brain MRI, and outcomes were assessed by modified Rankin Scale at last follow-up. Statistical comparisons were made between antibody-positive and antibody-negative subgroups.

Results: Among TDLs subgroups, MOG+ patients had elevated cerebrospinal fluid white cell counts and showed greater lesion volume reduction on follow-up MRI than MOG- patients. NMDAR+ patients showed elevated levels of systemic inflammatory markers compared with NMDAR- counterparts. Regardless of antibody status, most TDLs patients responded well to immunotherapy, with 86.7% achieving a favourable outcome.

Conclusions: TDLs represent a heterogeneous inflammatory syndrome. MOG and NMDAR antibodies influence the clinical and laboratory characteristics of TDL patients but have limited impact on prognosis.

Background: Disproportionately fewer females with Parkinson's disease (PD) undergo deep brain stimulation surgery (DBS). Some data show worse depression, anxiety, and quality of life (QOL) in females with PD. Investigations into these gender disparities, or the effect of DBS on these non-motor symptoms, remain limited.

Methods: 61 PD patients across seven UK DBS centres were recruited for the Clinical Response of Impulsive behaviours to deep brain Stimulation in PD (CRISP) prospective cohort study. Questionnaires measured primary outcomes of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and QOL (Parkinson's Disease Questionnaire-39) before and 6 months after bilateral subthalamic nucleus DBS, and secondary outcomes of predictors of postoperative changes in mood.

Results: Females were disproportionately under-referred for DBS (28% of cohort). Baseline depression and anxiety were similar between genders. While DBS significantly improved overall anxiety (p<0.001), females reported significantly more postoperative anxiety than males (median score 7 vs 1.5, Cohen's d=0.33, p=0.009). Postoperatively, only males experienced a significant reduction in moderate depression, by 29% (p=0.004) (12% in females). QOL improved significantly by similar proportions, thus significantly worse QOL in females preoperatively was sustained as 9.12% worse postoperatively (Cohen's d=0.75, p=0.02). Preoperatively, females reported significantly worse mobility, social support, and pain; postoperatively, the significant difference in mobility was sustained. Longer PD duration, worse QOL, and mobility predicted postoperative depression (R² =0.156, p=0.003), while female gender and reduced social support predicted postoperative anxiety (R²=0.23, p<0.001).

Conclusions: DBS showed clinical efficacy for non-motor PD symptoms across genders, evidencing the need to close the gender gap in DBS. Analysis by gender highlighted significant disparities and postoperative predictors that provide impetus for tailored DBS counselling.

Background: The updated International Panel's diagnostic criteria for multiple sclerosis (2024 revision of McDonald criteria) have for the first time included the optic nerve as the fifth location for dissemination in space (DIS) criterion. The new requirement consists of evidence of significant retinal asymmetry. However, this can be challenging in the acute phase in absence of optic disc swelling. Here, we have investigated the sensitivity of retinal asymmetry over time, from the acute to the chronic phase of optic neuritis.

Methods: This observational study analysed longitudinal optical coherence tomography (OCT) images of 25 patients with optic neuritis and 5 healthy controls. Spectral domain OCT scans were obtained from the macula and optic disc. The peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell (mGCL) and inner plexiform layers (mIPL) were measured in the acute (≤7 days), subacute (between 1 and 12 weeks) and chronic (>3 months) phase.

Results: The OCT measurements showed progressive thinning in pRNFL and mGCIPL layers as the disease progressed. In the acute phase, the sensitivity of the pRNFL was 69% (due to optic disc swelling) and for the mGCPL 27%. In the chronic phase, sensitivity levels increased up to 76% (pRNFL) and 88% (mGCIPL) due to atrophy.

Conclusions: A clear understanding of the temporal dynamics of diagnostic findings is important. For OCT, the highest diagnostic sensitivity is achieved for the mGCIPL in the chronic phase. This should be taken into account for timing the test in patients where the acquisition of optic nerve involvement is essential for DIS.

Background: Criteria-led transfer allows transfer of select stroke patients to inpatient rehabilitation without rehabilitation physician review, which may be a barrier for timely transfers.

Objective: Primary: determine the proportion of patients transferred via criteria-led transfer and waitlist time. Secondary: determine the number of unplanned 30-day acute hospital representations and readmissions from inpatient rehabilitation, and number of daily allied health contacts while waitlisted.

Method: A single-centre retrospective analysis was conducted on all patients transferred from the acute stroke unit to inpatient rehabilitation in 2023.

Results: 178 (79%) patients successfully used criteria-led transfer, 22 (9.5%) did not meet criteria and the remainder attended inpatient rehabilitation via a separate pathway. Median waitlist time (in days) was shorter for criteria led transfer patients compared with those who did not meet criteria (3 (1-5) vs 5 (3-8), p=0.005). Emergency department representation rates were lower in the criteria-led transfer cohort (30 (16.9%) vs 8 (36.3%), p=0.03) compared with those who did not meet criteria. No difference in readmission rates was seen (p=0.22). Waitlisted patients received 1 (0.5-1.5) allied health reviews daily.

Conclusions: Criteria-led transfer is associated with shorter waitlist times for transfer to rehabilitation without increased adverse events. Further research is needed to determine result generalisability.