Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: Whether statin use after spontaneous intracerebral haemorrhage (ICH) increases the risk of recurrent ICH is uncertain.

Methods: In the setting of the Multicentric Study on Cerebral Haemorrhage in Italy we followed up a cohort of 30-day ICH survivors, consecutively admitted from January 2002 to July 2014, to assess whether the use of statins after the acute event is associated with recurrent cerebral bleeding.

Results: 1623 patients (mean age, 73.9±10.3 years; males, 55.9%) qualified for the analysis. After a median follow-up of 40.5 months (25th to 75th percentile, 67.7) statin use was not associated with increased risk of recurrent ICH either in the whole study group (adjusted HR, 0.99; 95% CI 0.64 to 1.53) or in the subgroups defined by haematoma location (deep ICH, adjusted HR, 0.74; 95% CI 0.35 to 1.57; lobar ICH, adjusted HR, 1.09; 95% CI 0.62 to 1.90), intensity of statins (low-moderate intensity statins, adjusted HR, 0.93; 95% CI 0.58 to 1.49; high-intensity statins, adjusted HR, 1.48; 95% CI 0.66 to 3.31) and use of statins before the index event (adjusted HR, 0.66; 95% CI 0.38 to 1.17).

Conclusions: Statin use appears to be unrelated to the risk of ICH recurrence.

Background: Whether telomere length (TL), an indicator of biological ageing, reflects Alzheimer's disease (AD)-related neuropathological change remains unclear. We investigated the relationships between TL, in vivo AD pathologies, including cerebral beta-amyloid and tau deposition, and cognitive outcomes in older adults.

Methods: A total of 458 older adults were included, encompassing both cognitively normal (CN) individuals and those cognitively impaired (CI), with the CI group consisting of individuals with mild cognitive impairment or AD dementia. All participants underwent clinical and neuropsychological assessments, amyloid positron emission tomography (PET) scan and DNA extraction for measuring TL at baseline. A subset of participants (n=140) underwent tau PET scan. At follow-up, the participants underwent neuropsychological assessments annually for up to 4 years.

Results: Overall, longer TL was associated with greater brain tau deposition (B=0.139, 95% CI 0.040, 0.238) and a faster decline in global cognition (B = - 0.371, 95% CI - 0.720, -0.023). In the subgroup analysis, the association between longer TL and greater in vivo AD pathologies, as well as faster cognitive decline, was observed particularly in the CI group. Mediation analysis suggested that longer TL was associated with cognitive decline through increased tau deposition in the CI group.

Conclusion: Our finding suggests that older adults with relatively longer TL, particularly in the CI group, may have greater in vivo AD pathologies and experience more rapid cognitive decline, potentially mediated by brain tau deposition. Further studies are necessary to elucidate the biological links underlying these associations.

Background: Deterioration in naming function is a common sequelae after epilepsy surgery in the language-dominant temporal lobe but information on recovery and long-term outcome is scarce. We, therefore, assessed short-term and long-term outcome of object naming in patients undergoing surgery in the temporal lobe and determined factors affecting deterioration and recovery of naming function.

Method: Object naming (Boston naming test) before surgery, at early follow-up (FU, 6-12 months) and late FU (≥2 years) was assessed in people with epilepsy (PWE) undergoing resections in the language-dominant left and non-dominant right temporal lobe.

Results: Sixty-six patients with left temporal lobe epilepsy (LTLE) and 87 control patients with right temporal lobe epilepsy (RLTE) were included. At early FU, 28 patients with LTLE (42%) and three patients with RTLE (3%) showed a significant naming decline. In patients with LTLE, risk for deterioration increased with lower verbal memory before surgery, older age at seizure onset and was particularly high with posterior temporal resections (≥40 mm from the temporal pole) and seizure onset >16 years. Of the patients with LTLE with early naming decline, 11 patients (39%) recovered fully in their naming abilities at late FU, averaging almost 10 years. Recovery was associated with the degree of postoperative naming decline at early FU. PWE with a decline of less than 10 items (<20%) had a good prognosis of recovery at late FU. Postoperative seizure control had no significant effect on recovery.

Conclusions: In our cohort, less than 50% of PWE showed significantly deteriorated naming function after resection of the dominant temporal lobe. If a decline occurred, it appeared to recover to a certain degree and remained as a permanent deficit in 26% of the patients. Long-term outcome of visual object naming can be predicted by the degree of early postoperative decline.

Antimyelin-associated glycoprotein (MAG) neuropathy is a rare autoimmune demyelinating peripheral neuropathy caused by IgM autoantibodies targeting MAG. The typical presentation is that of a slowly progressive, distal, length-dependent, predominantly sensory, sometimes ataxic neuropathy, frequently accompanied by upper limb tremor. Distal motor weakness may subsequently occur. The clinical presentation may vary and rarely be consistent with that of typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), as well as have an aggressive and rapidly disabling course. The diagnosis of anti-MAG neuropathy is based on the detection of anti-MAG antibodies through ELISA or western blot analysis, primarily in presence of an IgM monoclonal gammopathy. Anti-MAG neuropathy may occur without or with haematological malignancy. Electrophysiology is characteristic of a predominantly distal demyelinating neuropathy. Intravenous immunoglobulins and plasma exchange have unproven benefits, but may provide short-term effects. Cytotoxic therapies are commonly used, although without an evidence base. Rituximab, an anti-B-cell monoclonal antibody was studied in two randomised controlled trials, neither of which achieved their primary outcome. However, a meta-analysis of these two studies demonstrated improvement of disability at 8-12 months. A recent trial with lenalidomide was interrupted prematurely due to a high rate of venous thromboembolism. There are currently two ongoing trials with Bruton's tyrosine kinase inhibitors. Symptom control is otherwise frequently needed. Outcome measures used for other inflammatory neuropathies present limitations in anti-MAG neuropathy. International registries such as the planned IMAGiNe study may, in future, provide answers to the many remaining questions.

Background: Neuroaxonal loss occurs in the early stages of multiple sclerosis (MS), but whether it results from early inflammatory brain damage or an ongoing neurodegenerative process remains unclear. We hypothesise that genetic and childhood environmental risk factors for MS may already have an impact on neurodevelopment before the typical age of onset for MS in the general population.

Methods: We examined associations and interactions of genetic and environmental risk factors for MS with brain MRI outcomes, including volumetric (n=5350) and diffusion data (n=5649), at ages 9 and 13 years in a large, population-based childhood cohort without MS diagnoses. Polygenic risk scores (PRSs) were used to assess genetic burden, with rs10191329 as a marker of MS severity. Environmental factors at age 5 included Epstein-Barr virus (EBV) serology, vitamin D status, body mass index, duration of outdoor activities, and household parental smoking.

Results: Genetic data were available for 2817 and 2970 participants with volumetric and diffusion data, respectively. The MS-PRS was positively associated with EBV viral capsid antigen titres among EBV-positive children (β=0.15, p=2.98×10^-6). A negative association was observed between the MS-PRS and subcortical grey matter volume (β=-0.03, p=0.014). Interaction between the MS-PRS and household parental smoking was negatively linked to total brain (β=-0.21, p=0.025) and thalamic volumes (β=-0.22, p=0.003), where a higher MS-PRS and household smoking were associated with lower volumes. No associations were observed for rs10191329 with brain outcomes.

Conclusions: Genetic and environmental risk factors for MS interact to influence brain volumes in childhood, suggesting a potential window for preventing MS in genetically susceptible individuals by reducing exposure to household smoking.

Background: Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories.

Methods: Within the framework of the Big MS Data network, we merged data from the Observatoire Français de la Sclérose en Plaques, the Swedish and Italian MS registries, and MSBase. We identified patients with PPMS that started DMT or were never treated during the observed period. Subpopulations with comparable baseline characteristics were selected by propensity score matching. Disability outcomes were analysed in time-to-recurrent event analyses, which were repeated in subclasses with different disability trajectories determined by latent class mixed models.

Results: Of the 3243 included patients, we matched 739 treated and 1330 untreated patients with a median follow-up of 3 years after pairwise censoring. No difference in the risk of confirmed disability worsening (CDW) was observed between the groups in the fully matched dataset (HR 1.11, 95% CI 0.97 to 1.23, p=0.127). However, we found a lower risk for CDW among the class of treated patients with an aggressive disability trajectory (n=360, HR 0.68, 95% CI 0.50 to 0.92, p=0.014).

Conclusions: In line with previous studies, our data suggest that DMT does not ameliorate disability worsening in PPMS, in general. However, we observed a beneficial effect of DMT on disability worsening in patients with aggressive predicted disability trajectories.

Background: Alexander disease is an autosomal dominant leukodystrophy caused by heterozygous pathogenic variants in the glial fibrillar acidic protein (GFAP) gene. Although increasingly recognised, there is evidence that Alexander disease, particularly later-onset disease, is significantly underdiagnosed and its true prevalence is unknown (the only population-based prevalence was estimated at one in 2.7 million). Using the extensive UK Biobank dataset, we analysed the frequency of pathogenic and likely pathogenic variants, GFAP variants, within the UK population and identified clinical and radiological phenotypes linked to these variants.

Methods: Pathogenic, likely pathogenic and GFAP variants of uncertain significance were identified in the UK Biobank whole-exome sequencing data (n=4 70 000). Demographic information, previous medical history-including symptoms associated with Alexander disease-collected from self-reported data and hospital records, family history and various MRI metrics were compared between variant carriers and controls.

Results: We identified 36 unique pathogenic and likely pathogenic GFAP variants in 106 carriers, yielding a carrier frequency of approximately 1 in 4435. Modelling based on the UK population estimated a prevalence of 6.8 per 100 000. Carriers of pathogenic and likely pathogenic GFAP variants had higher odds of bladder dysfunction (OR 3.17, p<0.0001), upper airway dysfunction (OR 7.82, p=0.004) and psychiatric conditions (OR 1.51, p=0.04). Additionally, carriers were more likely to report a paternal history of dementia (OR 2.79, p<0.0001). MRI data revealed significant atrophy in brainstem regions among variant carriers.

Conclusion: Pathogenic and likely pathogenic GFAP variants are more prevalent in the general population than previously expected and are associated with clinical and radiological characteristics of Alexander disease. This study indicates that Alexander disease may be under-reported, misdiagnosed, or exhibit reduced penetrance.

Background: To delineate the clinical characteristics and outcomes of late-onset myelin oligodendrocyte glycoprotein antibody-associated disease (LO-MOGAD) and compare them with those of early-onset MOGAD (EO-MOGAD).

Methods: This observational cohort study included 199 adult patients with MOGAD. We reviewed the patients' demographic and clinical data and performed comparative analyses between EO-MOGAD and LO-MOGAD (onset age 18-50 and ≥50 years, respectively).

Results: Among the 199 patients, 42 had LO-MOGAD. Compared with patients with EO-MOGAD, those with LO-MOGAD patients exhibited a significantly higher incidence of optic neuritis both at the initial attack (66.67% vs 43.31%, p=0.007) and throughout all attacks (72.15% vs 52.51%, p=0.001). Over a similar disease duration, patients with LO-MOGAD exhibited significantly fewer relapsing courses (45.16% vs 70.97%), higher Expanded Disability Status Scale (EDSS) and visual functional system scores at the last visit (all p<0.05). Compared with patients with EO-MOGAD, those with LO-MOGAD had a significantly lower risk of relapse (HR 0.512, 95% CI 0.268 to 0.978, p=0.034), but higher risks of reaching EDSS ≥2 (HR 2.893, 95% CI 1.524 to 5.494, p<0.001) and visual acuity ≤0.6 (HR 3.097, 95% CI 1.073 to 8.937, p=0.022). Immunosuppressive therapies significantly reduced the annualised relapse rates of patients with LO-MOGAD, although adverse events leading to drug discontinuation and hospitalisation were observed.

Conclusions: Compared with patients with EO-MOGAD, patients with LO-MOGAD exhibited fewer relapsing courses but worse disability outcomes and should be actively treated.

Background: It remains imperative to discover the time course that cardiovascular risk factors influence neurodegeneration in males and females and decipher whether the apolipoprotein (APOE) genotype mediates this relationship. Here we perform a large-scale evaluation of the influence of cardiovascular risk and obesity on brain volume in males and females in different age groups.

Methods: 34 425 participants between the ages of 45 and 82 years were recruited from the UK Biobank database https://www.ukbiobank.ac.uk. T1-weighted structural MR images (n=34 425) were downloaded locally for all participants, and voxel-based morphometry was performed to characterise the volumetric changes of the whole brain. The influence of Framingham cardiovascular risk (general cardiovascular risk), abdominal subcutaneous adipose tissue, and visceral adipose tissue volume (obesity) on cortical grey matter volume across different decades of life was evaluated with voxel-wise analysis.

Results: In males, cardiovascular risk and obesity demonstrated the greatest influence on lower grey matter volume between 55-64 years of age. Female participants showed the greatest effect on lower grey matter volume between 65-74 years of age. Associations remained significant in APOE ε4 carriers and APOE ε4 non-carriers when evaluated separately.

Conclusions: The strongest influence of cardiovascular risk and obesity on reduced brain volume was between 55-64 years of age in males, whereas women were most susceptible to the detrimental effects of cardiovascular risk a decade later between 65-74 years of age. Here we elucidate the timing that targeting cardiovascular risk factors and obesity should be implemented in males and females to prevent neurodegeneration and Alzheimer's disease development.