Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: Detection of immunoglobulin G targeting myelin oligodendrocyte glycoprotein (MOG-IgG) is the mainstay of laboratory diagnosis of MOG antibody-associated disease. Laboratory biomarkers have the potential to predict disease course and activity, thus informing prompt therapeutic decisions to minimise relapse-associated disability accrual.

Methods: This systematic review with meta-analysis was registered in PROSPERO (CRD42024554429). MEDLINE, Embase and Scopus databases were searched. Random-effects or mixed-effects modelling was performed and OR or HR with 95% CIs reported.

Results: 106 studies with ≥1710 individuals were included. A relapsing course was associated with persistent seropositivity on serial samples collected ≥3 months apart (OR 2.7 (95% CI 1.8 to 4.0), p<0.0001), lower likelihood of seroreversion to negative status (HR 0.19 (95% CI 0.14 to 0.26), p<0.0001) and delayed seroreversion compared with monophasic participants (median 19 years vs 2.5 years, p<0.0001). Acute disseminated encephalomyelitis was associated with a non-relapsing course (OR 0.049 (95% CI 0.0029 to 0.84), p=0.037). Serum MOG-IgG titre-negative, low positive or clear positive-discriminated disease state: attack was associated with clear positive titre (OR 3.6 (95% CI 2.6 to 5.0), p<0.0001), but not negative titre (OR 0.073 (95% CI 0.028 to 0.19), p<0.0001). Cerebrospinal fluid (CSF) leucocytosis (≥5 cells/µL) was associated with attack (OR 3.1 (95% CI 1.7 to 5.9), p=0.0004). Neither serum glial fibrillary acidic protein nor neurofilament light chain correlated with disease activity. Novel biomarkers of disease course and activity have also been assessed qualitatively.

Conclusions: MOG-IgG serostatus and titre and CSF leucocytosis are biomarkers of disease course and activity. The findings provide rationale for serial serum MOG-IgG testing at an interval of 3-6 months in the first 12 months of disease to assist in relapse risk stratification.

Prospero registration number: CRD42024554429.

Background: Epilepsy affects 22.2% of people with intellectual disability compared with 1% of the general population. This study aims to identify characteristics associated with epilepsy-caused deaths in adults with intellectual disability and epilepsy in England.

Methods: We conducted a retrospective population-based analysis of all deaths of adults with intellectual disability and epilepsy reviewed by the English Learning from Lives and Deaths programme (2016-2021). Deaths were classified by whether epilepsy was the primary cause or not. Demographic, clinical and care-related variables were analysed using multivariable Cox regression for associations with age at death and factors linked to epilepsy-related mortality.

Results: Epilepsy was the primary cause of death in 1584 (16.2%) of 9756 deaths of people with intellectual disability and epilepsy. These individuals died at a significantly younger median age than those who died of other causes (56 vs 62 years; p<0.001). Epilepsy and non-epilepsy-related deaths in this population were more common among people with moderate-to-profound intellectual disability (p<0.001) and those of African or Asian ethnicity (p<0.001). Risk factors included poor quality of care, service gaps and lack of annual health checks (p<0.001). Psychiatry and speech and language therapy (SALT) input was protective.

Conclusion: Epilepsy-related deaths in intellectual disability may cause earlier mortality because of pervasive health inequalities and missed prevention opportunities. Targeted interventions, including annual health checks, improved multidisciplinary care access, improved inclusion of ethnic minorities, and integration of specialist psychiatric and SALT support may increase length of life. Systemic service redesign is required to reduce avoidable epilepsy-related mortality.

Background: Increased chronological age correlates with reduced relapse rates and increased disability in multiple sclerosis (MS). Biological age may better capture ageing's impact on MS and might accelerate due to MS itself. Establishing accelerated biological ageing in adults is complicated by normal ageing and comorbidities. Telomere length, a well-recognised biological ageing marker, is shortened in adults with MS and associated with disability. Demonstrating accelerated biological ageing in paediatric-onset MS (POMS) would strengthen the hypothesis that MS drives premature biological ageing. This study aimed to determine if telomere length differs in POMS compared to age-similar healthy controls.

Methods: We performed a cross-sectional case-control study of whole blood samples and clinical data from The US Network of Pediatric MS Centers. Real-time quantitative PCR measured telomere length, expressed as a telomere to somatic DNA ratio (T/S ratio). T/S ratio was compared between cases and age-similar healthy controls using multivariate regression analysis adjusting for chronological age, sex, race, ethnicity, tobacco exposure, socioeconomic status and body mass index.

Results: We analysed 300 POMS cases and 200 controls. The unadjusted mean T/S ratios were 1.66 (SD 0.32) for cases and 1.71 (SD 0.29) for controls (mean difference -0.05, 95% CI -0.10 to 0.01, p=0.08). After adjusting for key covariables with face validity, POMS participants had a mean 0.086 shorter T/S ratio than controls (95% CI 0.015 to 0.157, p=0.018).

Conclusions: POMS participants demonstrated shorter telomeres than age-similar controls in a multivariable model adjusting for sociodemographic variables, suggesting that MS may contribute to accelerated biological ageing.

Background: Heterozygous variants in SLC12A6 have recently been shown to cause dominant Charcot-Marie-Tooth disease (CMT). We aim to characterise the phenotype of patients with previously reported and novel heterozygous variants in the gene and understand any genotype-phenotype correlation.

Methods: Patients were clinically and genetically assessed in sites from Europe, Australia, Brazil and the USA. All patients underwent whole exome or whole genome sequencing. Variants were classified using American College of Medical Genetics and Genomics criteria.

Results: Twenty-three individuals from 13 families carried nine variants classified either as pathogenic/likely pathogenic or variants of uncertain significance segregating in multiple family members, including five novel variants. Forty-eight percent (11/23) were male with a mean age of disease onset of 15.7 years (range 1-45 years). Clinical phenotype varied dramatically with genotype; Arg207His and Ser647Pro caused a severe childhood-onset, sensory and motor, conduction-slowing neuropathy, whereas Gly552Asp caused a mild, adult-onset, sensory-predominant neuropathy, Thr991Ala an infantile-onset motor neuropathy, and the Met282Lys/Gly286Cys locus a complex, axonal neuropathy.

Conclusions: Heterozygous variants in SLC12A6 can cause CMT of all clinical phenotypes, severity and age of onset, depending on the genotype. Such phenotypic diversity has not been described for any other CMT gene, and more work is needed to understand disease mechanisms to guide future therapeutic options.

Background: Severe forms of generalised (GD) or cervical dystonia (CD) can be effectively treated with deep brain stimulation (DBS) of the globus pallidus interna (GPi). However, objectively assessing DBS effectiveness remains challenging.

Objective: To identify objective biomarkers of GPi-DBS effectiveness using a minimalistic three-dimensional (3D) kinematic motion capture system in patients with dystonia.

Methods: This retrospective longitudinal study analysed kinematic data from 14 patients before and after GPi-DBS: 7 with GD (3 females; mean age, 34.1±16.5 years; mean Burke-Fahn-Marsden (BFM) 32.9±14.1) and 7 with CD (4 females; mean age, 46.2±9.8 years; mean BFM 10.4±4.4). Parameters included barycentre displacement length, volume, velocity, angular velocity and power spectral density (PSD) in low-frequency (delta and theta) bands. Dystonia severity was assessed using the BFM scale.

Results: In the pooled cohort, GPi-DBS significantly reduced dystonia severity, with mean BFM scores decreasing from 21.6±15.4 preoperatively to 14.1±13.1 postoperatively (p=0.011, permutation test). In subgroup analyses, BFM scores decreased significantly in the CD group (p=0.015), while a non-significant trend toward improvement was observed in the GD group (p=0.076). Kinematic analysis in the pooled cohort demonstrated a robust reduction in barycentre angular velocity (p<0.001), whereas other parameters were not significantly modified. In the CD subgroup, additional significant reductions were observed in displacement length, velocity and PSD amplitudes in both frequency bands (all p<0.01). Multivariate regression analysis demonstrated that kinematic improvements in barycentre displacement length, velocity, angular velocity and PSD in delta and theta bands were significantly associated with clinical improvements (all p<0.05).

Conclusions: 3D kinematic analysis provides objective biomarkers of GPi-DBS effectiveness in dystonia. Despite differing response patterns, kinematic features remain informative across phenotypes supporting their use in individualised outcome assessment.

Background: Estimators of biological age, such as epigenetic clocks, are promising biomarkers for neurological disorders where the risk significantly increases with age, such as Parkinson's disease (PD). The purpose of this study was to prospectively investigate whether epigenetic age acceleration can predict PD risk, age at PD onset and time to phenoconversion.

Methods: We conducted a prospective, nested case-control study within the Nurses' Health Study, including participants who provided two blood samples before being diagnosed with PD. DNA methylation profiles were obtained from 75 individuals who developed PD, 79 individuals who developed prodromal features suggestive of PD and 154 age-matched controls. We estimated epigenetic age acceleration using six different epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, DunedinPACE and the cortical epigenetic clock) and assessed their associations with PD risk, age at PD onset and time to PD onset.

Results: Epigenetic age acceleration was not consistently associated with a higher PD risk, using estimates of biological ageing neither in the first sample (collected a median of 19 years before PD onset) nor in the second sample (collected a median of 8 years before PD onset). These results remained similar in multivariable models adjusted for smoking status, physical activity, body mass index, caffeine intake, alcohol intake and Mediterranean diet score. Furthermore, epigenetic age acceleration was not associated with earlier age at PD onset or time to PD phenoconversion.

Conclusions: In our study, epigenetic clock-based biomarkers do not reliably predict PD risk, age at PD onset or time to PD phenoconversion.

Lecanemab is an anti-amyloid monoclonal antibody, recently approved in the UK as a treatment for mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease (AD) in adults who are apolipoprotein E ε4 gene (APOE4) heterozygotes or non-carriers.A group of UK neurologists, old age psychiatrists and geriatricians with expertise in AD convened to agree appropriate use recommendations for lecanemab in UK clinical practice. The primary focus of these recommendations is safety.Eligibility criteria for lecanemab in the UK include (a) a clinical diagnosis of MCI or mild dementia due to AD, (b) the presence of amyloid-β pathology, confirmed using approved methods (ie, an amyloid positron emission tomography scan or cerebrospinal fluid assay) and (c) APOE4 heterozygous or non-carrier status. Eligibility screening should be conducted in secondary care and those identified as being potentially eligible for lecanemab should be referred to a specialist centre for confirmation of the likely pathological diagnosis, APOE4 counselling and testing and a multidisciplinary consensus decision regarding treatment eligibility. Lecanemab is administered as an intravenous infusion every 2 weeks, and those eligible for treatment should have brain magnetic resonance imaging (MRI) scans prior to the 1st, 5th, 7th and 14th infusions. Specific guidance is provided for safety monitoring and management of potential adverse reactions, including amyloid-related imaging abnormalities and infusion-related reactions.The introduction of lecanemab into UK clinical practice provides an important opportunity to improve services for all people living with dementia, not just those eligible for lecanemab treatment.