Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: Non-aneurysmal subarachnoid haemorrhage (NASAH) accounts for less than 20% of spontaneous subarachnoid haemorrhage (SAH). However, its epidemiological characteristics, risk factors and aetiology remain poorly defined.

Methods: All patients with spontaneous SAH admitted to a neurosurgical centre in Sweden over a 3.5-year period were prospectively enrolled in a database. Epidemiological data, risk factors, Fisher grade and follow-up radiological findings were analysed, comparing NASAH cases to aneurysmal SAH (aSAH).

Results: A total of 1532 patients with SAH were included, of whom 377 (24.6%) were diagnosed with NASAH. Five NASAH patients exhibited microaneurysms in the perforating arteries (MAPAs) of the vertebrobasilar circulation, identified on follow-up cone-beam CT angiography. Gender distribution and Fisher grade presentation differed significantly between the NASAH and aSAH groups (p<0.001). Risk factors, such as smoking, hypertension and alcohol overuse, were significantly more common in aSAH than NASAH. Conversely, diabetes mellitus (DM) was more prevalent in NASAH than in aSAH (p<0.001).

Conclusions: This is the largest epidemiological study of NASAH to date. The observed incidence of NASAH was higher than in the previous reports, suggesting either underdiagnosis in earlier studies or a changing proportion of aSAH to NASAH cases. The distinct differences in population characteristics and risk factors suggest that NASAH and aSAH arise from fundamentally different pathophysiological mechanisms. DM emerged as a risk factor for NASAH, and MAPAs were identified as one of the underlying sources of haemorrhage in this subgroup.

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is increasingly used as a one-off disease-modifying therapy for aggressive forms of multiple sclerosis (MS). We report real-world effectiveness of AHSCT for MS in the UK.

Methods: This retrospective open-label study included patients with (pw)MS treated with AHSCT between 2002 and 2023 in 14 UK centres. Outcomes included relapse-free survival (RFS), MRI activity-free survival (MFS), progression-free survival (PFS) and no evidence of disease activity (NEDA-3). We assessed 6-month confirmed Expanded Disability Status Scale (EDSS) score progression or improvement compared with pre-treatment. Treatment-related mortality (TRM) was defined as death from any cause within 100 days post-autologous graft reinfusion.

Results: 364 pwMS were included (median age 40 years; 58% female). Of these, 271 pwMS had adequate neurological follow-up data: 168 (62%) had relapsing-remitting MS (pwRRMS) and 103 (38%) had progressive MS (pwPMS). Median disease duration from symptom onset was 10 years (IQR 6-14), EDSS 6 (IQR 4.0-6.5) and follow-up from AHSCT 46 months. At 2 and 5 years from AHSCT, RFS was 94.6% and 88.6%; MFS 93.1% and 80.1%; PFS 83.5% and 62.4%; NEDA-3 72.3% and 46.2%. pwRRMS had significantly higher rates of PFS (p=0.007) and NEDA-3 (p=0.001) than pwPMS. RRMS was a predictor of EDSS improvement, whose prevalence was 24.2% at 2 years and 20.4% at 5 years. TRM was 1.4% (n=5/364).

Conclusions: In this cohort with high EDSS at baseline and including pwPMS, AHSCT led to durable remission of inflammatory activity and stabilisation or improvement of neurological disability, particularly in pwRRMS.

Background: Treatment of progression independent of relapse activity (PIRA) is a relevant unmet need in multiple sclerosis (MS), being only modestly affected by disease-modifying treatments (DMTs) which target predominantly adaptive immunity in the periphery. As chemotherapy administered during autologous haematopoietic stem cell transplantation (AHSCT) is bioavailable within the central nervous system (CNS), the hypothesis that AHSCT could affect long-term PIRA was explored in aggressive relapsing-remitting (RR)-MS.

Methods: Retrospective propensity-score matched study including RR-MS patients who received BEAM/ATG AHSCT or started natalizumab (NTZ, ie, controls) at our centre in Florence in the period 2007-2018.

Main outcome: cumulative proportion of patients with PIRA during NTZ treatment epoch (ie, censoring controls at NTZ discontinuation) and whole follow-up (NTZ-other[o]DMTs, that is, including switch from NTZ to alternative DMTs).

Results: Thirty RR-MS were included in each group; median follow-up duration was 106 (6-209) months. NTZ was discontinued by 29/30 patients, who subsequently started alternative DMTs. Cumulative proportion of patients with PIRA did not differ between the two groups during the NTZ treatment epoch (p=0.990), but it was lower in AHSCT-treated compared with NTZ-oDMTs treated patients over the whole follow-up, being 10% vs 21% at year 5, and 10% versus 49% at year 10, respectively (p=0.020). AHSCT was superior to NTZ on relapses and NEDA-3, and to NTZ-oDMTs on all the secondary outcomes analysed. Baseline age and Expanded Disability Status Scale independently predicted PIRA in the whole cohort.

Conclusion: Timely treatment with AHSCT or DMTs targeting inflammation in both the peripheral and CNS compartments might prevent long-term PIRA in aggressive RR-MS.

Over recent decades, various hypotheses and theoretical frameworks have been advanced to elucidate the aetiology of normal pressure hydrocephalus (NPH). This reversible neurological condition, characterised by the classical clinical triad of gait disturbance, urinary incontinence and cognitive impairment, represents a multifactorial interplay of pathophysiological processes that co-occur, rather than originating from a single, defined cause. Despite extensive research efforts, the precise aetiology and underlying pathophysiological pathways remain indeterminate. Contributory factors such as dysfunction of the glymphatic system, diminished arterial pulsatility, metabolic and osmotic dysregulation, astrogliosis and neuroinflammatory processes are acknowledged as critical in the pathogenesis of NPH. Recent advancements in the understanding of these pathophysiological aberrations have substantially refined the conceptualisation of the NPH phenotype, enhancing the predictive accuracy for cerebrospinal fluid diversion interventions. This review addresses the definition and classification of NPH and emphasises future research directions aimed at further elucidating the molecular and physiological mechanisms underlying the disease. A comprehensive understanding of this syndrome is critical for informed clinical decision-making and optimising therapeutic outcomes. With the global increase in ageing populations, accurately differentiating NPH from other neurodegenerative disorders and managing overlapping comorbidities has become increasingly significant.

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.