Journal of Neurology, Neurosurgery, and Psychiatry最新文献

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.

Background: We investigated the effectiveness of an Interdisciplinary Home-bAsed Reablement Programme (I-HARP) on improving functional independence, health and well-being of people with dementia, family carer outcomes and costs.

Method: A multicentre pragmatic parallel-arm randomised controlled trial compared I-HARP to usual care in community-dwelling people with mild to moderate dementia and their family carers in Sydney, Australia (2018-2022). I-HARP is a 4-month, home-based, dementia rehabilitation model delivered by an interdisciplinary team. Assessments were conducted at baseline (time-1), 4-month (time-2) and 12-month (time-3) follow-up. The primary outcome measure was the client's functional independence using the Disability Assessment for Dementia (DAD) scale at time-2, based on intention-to-treat analyses.

Result: Of 130 recruited client-carer dyads, 116 dyads (58/group) completed the trial. The I-HARP group were not significantly better in most outcome measures than usual care at both time-2 and time-3; with the only statistically significant difference being a reduction in home environment hazards at time-2. Post hoc subgroup analysis of 66 clients with mild dementia found significantly better functional independence in the intervention group compared with those in usual care: difference 8.99 on DAD (95% CI 1.21, 16.79) at time-2 and difference 12.16 (95% CI 1.93, 22.38) at time-3. Economic evaluation suggests potentially lower resource use in I-HARP compared with usual care, but the cost-effectiveness is uncertain.

Conclusion: Primary outcomes were not met for a population of people with dementia, with severity ranging from mild to moderate and severe. The I-HARP model appeared to benefit functional independence of participants with mild dementia, with potential cost savings.

Trial registration number: ACTRN12618000600246.

Background and objective: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing.

Methods: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region.

Results: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes.

Conclusions: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.

Background: Vitamin D (VitD) affects the risk of multiple sclerosis (MS), but the impact on disease activity is controversial. We assessed whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status at 2 years from disease-modifying treatment (DMT) start, and whether this association is causal or the result of confounding factors. Furthermore, we explored if a genetic predisposition to higher VitD levels affects the risk of disease activity.

Methods: 230 untreated relapsing-remitting MS patients underwent serum 25-OH-vitamin-D measurement, and the association between seasonally adjusted VitD and disease activity was tested. Modelling a Polygenic Risk Score from a Genome-Wide Association Study on ~400 000 individuals, we studied the impact of genetic predisposition to higher VitD on the NEDA-3 status in 1408 independent MS patients. Two-sample Mendelian randomisation (MR) was used to assess causality.

Results: Lower baseline VitD was associated with decreased probability of NEDA-3 at 2 years (p=0.019). Particularly, VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36, 95% CI 1.30 to 3.88, p=0.0037). Genetic predisposition to higher VitD levels was associated with delayed age at MS onset (p=0.018) and with a higher probability of NEDA-3 status (p=0.034). MR confirmed causality between VitD and the risk of disease activity (p=0.041).

Conclusions: VitD levels before DMT start affect the risk of disease activity in MS. Genetic predisposition to higher VitD levels confers a lower risk of disease activity and is associated with delayed MS onset. Our work prompts future prospective studies regarding VitD supplementation and lifestyle interventions to hamper disease activity in MS.