Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: High-efficacy disease-modifying therapies (HETs) have substantially improved multiple sclerosis (MS) management, yet ongoing cognitive decline remains a concern. This study aims to assess Symbol Digit Modalities Test (SDMT) changes in patients with stable relapsing-remitting MS (RRMS) treated with HETs and to evaluate the role of baseline MRI biomarkers as predictors of SDMT changes.

Methods: Consecutive patients with RRMS treated with HETs underwent clinical, SDMT and MRI assessment at baseline with SDMT and clinical re-evaluation after 24 months. Patients presenting relapses or MRI activity (new T2 and/or gadolinium-enhancing lesions) during follow-up were excluded. Cognitive changes were defined using the 90% CI regression-based reliable change index methodology accounting for sex, age, education and baseline score. Baseline MRI examination included three-dimensional-sagittal Fluid Attenuated Inversion Recovery (FLAIR), T1-Magnetization Prepared - RApid Gradient Echo (T1-MPRAGE) and quantitative susceptibility mapping (QSM) for paramagnetic rim lesions (PRLs) and QSM-isointense lesions (ISO) assessment. Univariate and multivariable regression analyses were performed to predict SDMT changes.

Results: 90 patients (mean age: 40.3 years, median Expanded Disability Status Scale: 2.0) were included. PRLs were present in 46 (51.1%) patients. After 24 months, 13 (14.4%) patients showed SDMT decline and 8 (8.9%) showed improvement. At multivariable analyses, PRLs were associated with higher risk of SDMT decline (β: 2.70, p: 0.02, OR: 14.82) while higher ISO lesion volumes were weakly associated with SDMT improvement (β: 0.07, p: 0.01, OR: 1.07).

Conclusions: SDMT decline and improvement are detectable in patients with RRMS without clinical or MRI activity over 2 years. PRLs seem to predict SDMT decline in MS, underscoring the critical role of compartmentalised chronic inflammation in disease progression.

Background: Robust epidemiological data regarding population incidence and prevalence of functional neurological disorder (FND) would be helpful with regards to resource allocation and planning for this disorder, particularly given high symptom burden and high healthcare utilisation. We therefore aimed to systematically review and synthesise available data on FND incidence and prevalence.

Methods: PubMed was searched to identify original research articles that reported on the incidence or prevalence of FND. Risk of bias assessment for each study was conducted. Incidence and prevalence rates of FND were additionally estimated by extrapolating data from low risk of bias studies on functional seizures alone.

Results: Thirty-nine articles were included. Nineteen reported on FND incidence, 21 reported on prevalence. Comparison between studies was difficult due to methodological differences and significant heterogeneity of incidence and prevalence estimates was found. The incidence of FND was estimated at 10-22/100 000, while minimum prevalence of FND was estimated at 80-140/100 000, with a possible range of 50-1600/100 000. Incidence of paediatric FND was estimated to be between 1 and 18/100 000.

Conclusions: The range of incidence and prevalence varies widely across studies, with significant heterogeneity among studies and most studies likely provide underestimates due to methodological challenges. However, using our best method as a conservative estimate, there are likely a minimum of 50-100 000 people with FND in the UK, as an example country. Given that FND appears to be more prevalent than many other well-known and well-funded neurological disorders, incidence and prevalence data suggested here indicate the need for greater research and clinical funding allocation to FND programmes.

Background: We quantify the loss of working years for people with epilepsy compared with the general population and consider variation by aetiology, psychiatric comorbidity, sex and age.

Methods: This population-based cohort study included all individuals aged 18-65 years living in Denmark from 1995 to 2018. Using nationwide registers since 1977, we identified people with epilepsy and obtained information on the main source of income or employment for each year during follow-up from 1995 to 2020. The main outcome was number of working years lost in people with epilepsy compared with the general population of same sex and age, capturing both working life lost due to permanent (death, disability pension, early retirement) and temporary (unemployment, sick leave) factors.

Results: The study comprised 5 466 140 individuals, including 74 980 (1.4%) with epilepsy. In people with epilepsy, the number of working years was on average reduced by 6.6 (95% CI: 6.5 to 6.7) years compared with the general population, largely due to disability pension (4.8 years, 95% CI: 4.7 to 4.9) and premature death (1.6 years, 95% CI: 1.6 to 1.7). Loss of working life was more pronounced in those with a presumed underlying aetiology (9.0 years (95% CI: 8.9 to 9.2) vs 5.4 years (95% CI: 5.2 to 5.5) in those with unknown aetiology), those with psychiatric comorbidity (14.5 years (95% CI: 14.2 to 14.7) vs 5.6 years (95% CI: 5.5 to 5.7) in those without), men (7.2 years (95% CI: 7.1 to 7.3) vs 5.9 (95% CI: 5.8 to 6.0) years in women) and people with early onset of epilepsy (eg, 11.5 years (95% CI: 11.3 to 11.7) among those with onset <20 years).

Conclusions: Epilepsy was associated with significant loss of working life resulting from both disability and premature death.

Background: Limited data are available on the global rates of paediatric multiple sclerosis. Here, we report on the estimated worldwide prevalence of paediatric MS.

Methods: We included paediatric prevalence data in 2020-2022 (Multiple Sclerosis International Federation Atlas of MS) and the prevalence of child neurologists (International Child Neurology Association). Data were split into prevalence bands per 100 000. Countries were classified by the WHO Region and World Bank Income. Descriptive analyses were performed. An estimated worldwide prevalence rate was calculated from the 2020-2022 paediatric prevalence data, which was adjusted to reduce outliers' impact and to reflect worldwide income distribution. The Atlas of MS data was obtained via survey of coordinators from the countries who use different tracking methods including national registries vs crude estimates.

Results: Paediatric data were available in 24% (53/219) countries (38 higher and 15 lower income) with 31 420 total paediatric MS cases. In 2022, 67% (10/15) of lower income countries reported prevalence bands of '<1.0' compared with 34% (13/38) of higher income countries. Only 7% (1/15) of lower income countries reported prevalence bands '≥3.1'compared with 34% (13/38) of higher income countries. The rates of child neurologists positively correlated with the prevalence band. In 2020-2022, the estimated global prevalence (crude) was 2.53/100 000 (95% CI 2.51 to 2.56), with an adjusted prevalence rate of 1.48/100 000 (95% CI 1.45 to 1.51).

Conclusions: Access to epidemiology data from resource-limited countries is challenging including surveillance for case ascertainment. Increased resources and standard methodologies will facilitate the understanding of rare disease epidemiology.

Background: Whether bridging thrombolysis with tenecteplase is beneficial compared with thrombectomy alone in patients who had a stroke with large-vessel occlusion remains unclear.

Methods: This is a causal inference study of observational data from the trials SWIFT DIRECT and EXTEND-IA TNK Parts 1 and 2 applying target trial emulation. We compared patients receiving thrombectomy alone to patients receiving tenecteplase 0.25 mg/kg or 0.40 mg/kg before thrombectomy. The primary outcome was functional independence (modified Rankin Scale (mRS) of 0-2) at 90 days. Secondary outcomes included improvement over the full ordinal mRS scale, freedom of disability (mRS 0-1), mortality and occurrence of symptomatic intracranial haemorrhage. The average causal treatment effect was estimated via inverse probability of treatment weighting and G-Computation. We calculated standardised risk differences (SRDs) and adjusted (common) ORs (a(c)ORs).

Results: Of 377 patients included in the target trial, 187 received thrombectomy alone and 190 tenecteplase before thrombectomy. Tenecteplase before thrombectomy did not increase the probability of patients achieving functional independence (SRD 0.04 (95% CI -0.06 to 0.13)) but resulted in a significant improvement in the mRS overall (acOR 1.56 (95% CI 1.07 to 2.23)) and in a higher probability of freedom from disability (SRD 0.10 (95% CI 0.01 to 0.20)). The probability for improvement of functional outcomes was further increased in patients treated within 140 min after onset (ordinal mRS acOR 1.63 (95% CI 1.04 to 2.56)). No significant differences in safety outcomes were observed between the two groups.

Conclusion: Tenecteplase before thrombectomy compared with thrombectomy alone did not increase the probability of functional independence but resulted in significant improvement over the full mRS scale. This improvement was most evident in patients treated early.

Background: Data regarding long-term recovery from autoimmune encephalitis (AE) remain limited.

Methods: This retrospective observational study investigated outcomes in 182 patients who met the 2016 criteria for definite AE. Recovery data were available in 172 patients. Follow-up data at ≥24 months post-attack were available for 119. Recovery trajectory, residual symptoms, outcome predictors and causes of post-AE death were assessed.

Results: Of 172 patients, 138 (80%) achieved good recovery (modified Rankin Scale (mRS) ≤2) with a median recovery time of 4 months (95% CI: 2 to 6 months). Recovery varied by associated neural antibody, with the best recovery observed in leucine-rich glioma-inactivated 1 (97% good recovery, median recovery time 0 (0 to 2) months). Paraneoplastic AE (p=0.007), severe attacks (eg, mRS ≥4 at attack, p=0.007) and cerebrospinal fluid pleocytosis (p=0.005) were associated with a lower likelihood of good recovery, while seizure presentation (p=0.026) was associated with better recovery. Despite good recovery, several residual symptoms persisted ≥24 months post-AE, including cognitive deficits (53%), seizures (26%), depression (23%), sleep disorders (25%), brainstem/cerebellar symptoms (13%), other movement disorders (14%) and autonomic symptoms (12%). Predictors of long-term sequelae included disabling cognitive deficit at onset and delayed immunotherapy for post AE-dementia, and medial temporal atrophy as well as escalation to cyclophosphamide therapy for both drug-resistant epilepsy and chronic depression. Of 182 patients, 20 (11%) died; the most common cause of death was progression of AE (6/20 (30%)).

Conclusion: While the majority of patients achieved functional independence after AE, several residual symptoms persisted. Several clinical and paraclinical features were associated with long-term sequelae.

Background: Since their introduction in 2015, directional leads have practically replaced conventional leads for deep brain stimulation (DBS) in Parkinson's disease (PD). Yet, the benefits of directional DBS (dDBS) over omnidirectional DBS (oDBS) remain unclear. This meta-analysis and systematic review compares the literature on dDBS and oDBS for PD.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Database searches included Pubmed, Cochrane (CENTRAL) and EmBase, using relevant keywords such as 'directional', 'segmented', 'brain stimulation' and 'neuromodulation'. The screening was based on the title and abstract.

Results: 23 papers reporting on 1273 participants (1542 leads) were included. The therapeutic window was 0.70 mA wider when using dDBS (95% CI 0.13 to 1.26 mA, p=0.02), with a lower therapeutic current (0.41 mA, 95% CI 0.27 to 0.54 mA, p=0.01) and a higher side-effect threshold (0.56 mA, 95% CI 0.38 to 0.73 mA, p<0.01). However, there was no relevant difference in mean Unified Parkinson's Disease Rating Scale III change after dDBS (45.8%, 95% CI 30.7% to 60.9%) compared with oDBS (39.0%, 95% CI 36.9% to 41.2%, p=0.39), in the medication-OFF state. Median follow-up time for dDBS and oDBS studies was 6 months and 3 months, respectively (range 3-12 for both). The use of directionality often improves dyskinesia, dysarthria, dysesthesia and pyramidal side effects. Directionality was used in 55% of directional leads at 3-6 months, remaining stable over time (56% at a mean of 14.1 months).

Conclusions: These findings suggest that stimulation parameters favour dDBS. However, these do not appear to have a significant impact on motor scores, and the availability of long-term data is limited. dDBS is widely accepted, but clinical data justifying its increased complexity and cost are currently sparse.

Prospero registration number: CRD42023438056.

Background: The causative genes for over 60% of inherited peripheral neuropathy (IPN) remain unidentified. This study endeavours to enhance the genetic diagnostic rate in IPN cases by conducting screenings focused on non-coding repeat expansions.

Methods: We gathered data from 2424 unrelated Japanese patients diagnosed with IPN, among whom 1555 cases with unidentified genetic causes, as determined through comprehensive prescreening analyses, were selected for the study. Screening for CGG non-coding repeat expansions in LRP12, GIPC1 and RILPL1 genes was conducted using PCR and long-read sequencing technologies.

Results: We identified CGG repeat expansions in LRP12 from 44 cases, establishing it as the fourth most common aetiology in Japanese IPN. Most cases (29/37) exhibited distal limb weakness, without ptosis, ophthalmoplegia, facial muscle weakness or bulbar palsy. Neurogenic changes were frequently observed in both needle electromyography (97%) and skeletal muscle tissue (100%). In nerve conduction studies, 28 cases primarily showed impairment in motor nerves without concurrent involvement of sensory nerves, consistent with the phenotype of hereditary motor neuropathy. In seven cases, both motor and sensory nerves were affected, resembling the Charcot-Marie-Tooth (CMT) phenotype. Importantly, the mean CGG repeat number detected in the present patients was significantly shorter than that of patients with LRP12-oculopharyngodistal myopathy (p<0.0001). Additionally, GIPC1 and RILPL1 repeat expansions were absent in our IPN cases.

Conclusion: We initially elucidate LRP12 repeat expansions as a prevalent cause of CMT, highlighting the necessity for an adapted screening strategy in clinical practice, particularly when addressing patients with IPN.

Background: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age.

Methods: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS.

Results: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women.

Conclusions: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.