Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) have both overlapping and distinct MRI lesion features, which vary with imaging timing. This study identified distinguishing MRI characteristics using paired MRIs at clinical attack and remission.

Methods: We retrospectively identified Mayo Clinic patients with MOGAD and MS that: (1) fulfilled respective diagnostic criteria; (2) had paired attack (≤30 days) and remission MRI scans (≥12 months) without interval attacks. MRIs were compared between groups for key features.

Results: We included 43 patients with MOGAD (median age 31 years (range, 3-67); 63% female) and 49 patients with MS (median age 39 years (range, 17-65); 65% female). Resolution of at least one T2-lesion differentiated MOGAD from MS (sensitivity, (95% CI 77% to 100%), specificity, (95% CI 86% to 99%); Youden's index (YI)=0.90). Resolution of at least two T2-lesions indicated MOGAD (sensitivity 62% (95% CI 41% to 79%); specificity, 100% (95% CI 94% to 100%); YI=0.62). MOGAD patients were more likely to have normal MRI scans at follow-up compared with MS (brain 14/44 (32%) vs 0/60 (0%), p<0.001; spine 21/27 (78%) vs 7/36 (19%), p<0.001). In addition, the presence of T1-hypointense, ovoid periventricular T2, and enhancing lesions were more common in MS versus MOGAD at attack and remission and in the spine, longitudinally extensive T2 lesions were more common in MOGAD attacks (8/27 (30%)).

Conclusion: Paired MRI at attack and remission revealed distinctive characteristics of MOGAD and MS, with greater diagnostic value at remission driven by the discriminating power of T2-lesion resolution. In MOGAD patients with initial parenchymal involvement, a 1-year follow-up MRI may aid diagnosis and serve as a new baseline.

Background: The pathogenic mechanisms underlying autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A), a central nervous system disorder associated with GFAP autoimmunity, remain controversial. The present study aimed to investigate the potential role of the intrathecal reactivation of Epstein-Barr virus (EBV) in patients with GFAP-A.

Methods: EBV-DNA levels were measured in the cerebrospinal fluid (CSF) and blood samples of 14 patients with GFAP-A and 28 patients with other disorders. IgM and IgG antibodies against EBV viral capsid antigen (VCA) and IgG antibodies against early antigen (EA) were also measured in serum samples.

Results: EBV-DNA was detected in the CSF samples in 10 of the 14 patients with GFAP-A and in 1 of the 28 patients in the disease control group, with a significant difference between the two groups (71.4% vs 3.6%; p<0.0001). Conversely, EBV-DNA was not detected in the blood of the 13 patients with GFAP-A. In patients with GFAP-A, the CSF-EBV-DNA level was significantly associated with the worst modified Rankin scale score during the acute phase (r_s=0.6143, p=0.0194). Serum antibody profiling revealed evidence of past EBV infection, with VCA-IgG positivity and VCA-IgM and/or EA-IgG negativity observed in 92.9% of the patients with GFAP-A.

Conclusion: The study findings suggest that GFAP autoimmunity is associated with intrathecal EBV reactivation.

Background: Multiple sclerosis (MS) is the most common neuroimmunological disease in young adults. Data on its clinical onset before the age of 18 (paediatric-onset MS (POMS)) are limited.

Methods: This observational study present data on >1000 POMS compared with adult-onset MS (AOMS) and analysed patients regarding diagnostic delay, initial symptoms and long-term outcome using generalised additive models and adjustment for relevant confounders.

Results: The results showed a diagnostic delay and a higher proportion of women with POMS vs AOMS. Sensory (57%) and visual (48%) disturbances were the most common initial symptoms of POMS. Relapse rates were higher in POMS than in AOMS within the first 15 years after the clinical onset. The proportion of patients reaching an Expanded Disability Status Scale (EDSS) score of 3.0 by 15 years was lower in POMS (41%) than in AOMS (age-dependent, 48%-71%). A plateau phase in EDSS was observed in patients with POMS after age 40, which was not seen in those with AOMS. This plateau phase was responsible for the equalisation of the EDSS score with advanced age between POMS and AOMS. Cerebellar and polysymptomatic symptoms at clinical onset and male sex were predictors of higher EDSS scores in POMS, whereas in AOMS, pyramidal dysfunction was a predictor of worse outcomes.

Conclusions: This largest and longest follow-up study of POMS to date revealed that women are more likely to develop MS at younger ages and experience different symptoms than men. Patients with POMS tend to have higher relapse rates but may recover more quickly from relapses and experience a more stable disease course later in life.

Background: The purpose of this study was to clarify the usefulness of the 'hot cross bun' sign (HCBS) as a diagnostic imaging marker in a large cohort of patients with multiple system atrophy (MSA) and spinocerebellar ataxia (SCA).

Methods: This multicentre study included 97 patients with neuropathologically confirmed MSA, and 105 patients with genetically confirmed SCA. Neuroimaging features, including HCBS and middle cerebellar peduncle (MCP) hyperintensities, were assessed. HCBS was graded from 0 to 2: 0, none; 1, only a vertical hyperintense line; and 2, a cruciform hyperintense line. The neuropathological correlates of HCBS were evaluated in 15 patients with MSA with ≤3 months between MRI and autopsy.

Results: In patients with a disease duration <3 years, grade 1 or 2 HCBS was detected in 100% patients with MSA with predominant cerebellar ataxia (MSA-C) and 39.0% with SCA; whereas grade 2 HCBS was observed in 50% with MSA-C and 2.4% with SCA. Moreover, the coexistence of grade 2 HCBS and MCP hyperintensities exhibited a specificity of 100%. A neuropathological assessment revealed myelin loss, alpha-synuclein aggregates and astrocytic reaction in the MCP, transverse fibres, central zone between longitudinal fasciculi and raphe nucleus, with relative preservation in the longitudinal fasciculi and medial lemniscus in patients with MSA and grade 2 HCBS.

Conclusions: Grade 1 or 2 HCBS is a highly sensitive finding in patients with MSA-C, and the observation of grade 2 HCBS within 3 years of motor symptom onset has excellent specificity for discriminating MSA-C from SCA, especially when accompanied by MCP hyperintensities.

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.