Journal of Neurology, Neurosurgery, and Psychiatry最新文献

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: 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: 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: 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.