Journal of Neurology, Neurosurgery, and Psychiatry最新文献

Background: Patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) encephalitis are typically elderly men that often carry human leucocyte antigen (HLA)-DRB1*07:01 (≈90%). Herein, we aimed to investigate whether patients with atypical demographic profiles or not carrying DRB1*07:01 have distinct clinical manifestations and outcome.

Methods: Retrospective chart review of LGI1-Ab patients diagnosed at the French Reference Centre and three other European centres.

Results: Among 238 patients included, median age at onset was 66 years (IQR: 60-73), 65% were male, 89% carried DRB1*07:01 and 10% DRB1*04:02, another known secondary HLA association. We identified three age groups (young, typical, old) based on percentiles of age distribution. Young (≤51 years) patients were less commonly male (35%, p=0.004), while faciobrachial dystonic seizures (FBDS; 65%, p=0.047) and hyponatraemia (64%, p=0.046) were more frequent in old (≥79 years) patients. Old patients experienced poor outcome (modified Rankin Scale [mRS] >2 at last follow-up) more frequently (64%, p<0.001). There were no significant differences between males and females. DRB1*07:01 non-carriers were younger (p=0.005) and less frequently male (47%, p=0.044), while non-carriers of both DRB1*07:01 and DRB1*04:02 experienced poor outcome more commonly (64%, p=0.005). Older age (adjusted OR: 1.08, 95% CI [1.02 to 1.14], p=0.008), higher mRS at nadir (4.22 [2.46-7.24], p<0.001) and DRB1*07:01 non-carrier status (8.39 [1.88-37.44], p=0.005) were independently associated with poor outcome. Moreover, older age (1.08 [1.04-1.11], p<0.001), FBDS (2.20 [1.17-4.13], p=0.014) and hyponatraemia (2.30 [1.22-4.34], p=0.010) were associated with severe encephalitis (mRS >3 at nadir).

Conclusions: Age appears to be the main driver of clinical presentation, severity and outcome in LGI1-Ab encephalitis. Remarkably, DRB1*07:01 non-carriers are younger, more commonly female and experience poorer prognosis, reflecting a distinct pathophysiology.

Deep brain stimulation (DBS) is a surgical treatment for medication-resistant motor symptoms in Parkinson's disease (PD), involving the implantation of electrodes in subcortical targets, primarily the subthalamic nucleus (STN) and internal globus pallidus (GPi). While DBS is effective for motor control, psychiatric factors significantly impact postoperative quality of life. This narrative review aimed to summarise early (<2 weeks) psychiatric adverse events (AEs) following DBS in PD, addressing the prevalence of these events, their effects on pre-existing psychiatric symptoms and the influence of targeting and DBS parameters on these symptoms. A comprehensive search was performed across multiple databases, identifying 148 relevant studies, among which 55 focused on early psychiatric outcomes. Methodological diversity was noted, with 97% of studies concentrating on bilateral STN DBS. Our findings indicate that early postoperative psychiatric AEs are common, primarily occurring within days postsurgery and often transient. These AEs show improvement with parametric adjustments or the introduction of psychiatric medications. Notably, the role of the STN and GPi extends beyond motor control to emotional regulation, emphasising the importance of monitoring psychiatric outcomes in DBS patients. This review highlights the need for increased awareness and management strategies for early psychiatric complications in the context of DBS therapy, ultimately contributing to enhanced patient care and outcomes in advanced PD stages. Future studies should focus on standardising the evaluation of psychiatric AEs and exploring preventive strategies to minimise their occurrence post-DBS. PROSPERO registration number CRD42020184000.

Background: Resective epilepsy surgery is an established clinical intervention, but the cost-effectiveness at a national healthcare level is uncertain. This study evaluates the cost-effectiveness of resective epilepsy surgery compared with medical management in adults from national healthcare and personal social services perspectives.

Methods: A de novo decision analytic model was developed, comprising a 1-year decision tree and lifetime Markov model to evaluate lifetime costs and quality-adjusted life years (QALYs). Data were obtained from UK epilepsy surgery centres to evaluate the costs of preoperative assessment and the probability of undergoing resection after presurgical evaluation. Other clinical inputs were obtained from a systematic literature review. The main outcome of the analysis was the incremental cost-effectiveness ratio (ICER), with a cost-effectiveness threshold set at £20 000 cost per QALY gained.

Results: Data from 762 patients informed preoperative evaluation costs and the probability of undergoing epilepsy surgery after presurgical evaluation. The total lifetime cost of epilepsy treatment for people who had surgical treatment was £56 911, compared with £32 490 for medical management. Total QALYs per person for surgery were 15.91 and 13.76 for medical management. Resective epilepsy surgery was shown to be cost-effective with an ICER of £11 348 per QALY gained.

Conclusions: Our data inform and strengthen recommendations to prioritise referral of those with drug-refractory epilepsy to surgical centres. We provide a health economic rationale for the development and support of resective epilepsy surgery programmes across national healthcare systems.

Objectives: Early-onset Parkinson's disease (EOPD) is an increasingly serious disorder, yet there is currently a scarcity of epidemiological data and reports on this disease worldwide.

Methods: By using data from the 2021 Global Burden of Disease Study, we analysed the number of incident cases, prevalent cases and years lived with disability (YLDs) for EOPD (diagnosis after the age of 20 years and before the age of 50 years) from 1990 to 2021, along with their corresponding age-standardised rates. Additionally, we calculated the average annual percent change of the age-standardised rates and analysed the negative correlation between smoking and the disability-adjusted life years (DALYs) burden for EOPD.

Results: From 1990 to 2021, the incidence, prevalence and YLDs associated with EOPD have tripled globally. Most countries have seen a consistent increase in the age-standardised incidence and prevalence rates of this disease, especially those with high-middle Socio-Demographic Index scores. In 2021, smoking contributed to a 9.03% decrease in the global burden of DALYs, a decline from -14.14% in 1990.

Conclusions: EOPD is increasing at an alarming rate worldwide, necessitating the attention of global health organisations and the implementation of effective intervention measures to address this serious challenge.

Background: Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can share similar features, posing diagnostic challenges. In this study, we identified sets of conventional MRI lesion distribution criteria proposed for disease differentiation and investigated their clinical utility.

Methods: We searched five electronic databases for English-written and peer-reviewed diagnostic accuracy studies that included brain MRI at least. Hierarchical and univariate random-effects logistic regression models were employed for diagnostic accuracy meta-analysis. Heterogeneity was explored with subgroup analyses. Certainty of evidence was assessed using the GRADEpro tool.

Results: Three sets of criteria ('Matthews', 'Cacciaguerra', 'MS lesion checklist') were investigated in 11 studies (2008 patients; MS, n=1037; NMOSD, n=842; MOGAD, n=129), with low applicability concerns. Overall pooled sensitivity and specificity of the Matthews brain MRI criteria (MS vs seropositive-NMOSD differentiation) were 0.92 (0.86 to 0.96) and 0.85 (0.79 to 0.90), respectively, with higher diagnostic values in non-Caucasian populations and during follow-up. Pooled sensitivity and specificity of the Cacciaguerra brain-spinal cord criteria (seropositive-NMOSD vs MS differentiation) were 0.96 (0.76 to 0.99) and 0.83 (0.71 to 0.90), respectively. The MS lesion checklist (MS vs NMOSD/MOGAD differentiation) had lower diagnostic accuracy measures (sensitivity, specificity: 0.74, 0.79, respectively). The Matthews criteria provided the strongest moderate certainty evidence and also showed high pooled diagnostic accuracy for MS versus seronegative-NMOSD (sensitivity: 0.93 (0.84 to 0.97)); specificity: 0.90 (0.80 to 0.95)) and for MS versus MOGAD differentiation (sensitivity: 0.86 (0.81 to 0.90); specificity: 0.87 (0.76 to 0.93)).

Conclusions: Lesion distribution criteria can accurately discriminate between MS, NMOSD and MOGAD. Further optimised validation studies, and revisions or extensions may support sustained implementation.

Prospero registration number: CRD42023472178.

Background: Functional motor disorders (FMD) cause long-term disability and economic burden. There is a need for multidisciplinary interventions to manage both motor and non-motor symptoms. We aim to evaluate the clinical and economic effects of integrating digital telemedicine into multidisciplinary FMD management.

Methods: This single-blind, randomised controlled trial involved patients with FMD. They were randomly assigned to receive 5-day multidisciplinary rehabilitation with either a digital telemedicine or a standard care programme. The digital telemedicine group received remote management and wearable sensors. A blinded evaluator assessed primary and secondary outcomes at baseline, post-treatment, 12-week and 24-week follow-ups. The primary outcomes were changes in motor symptoms. The secondary outcomes were changes in non-motor symptoms, quality of life (QoL) and mobility in unsupervised settings. The incremental cost-effectiveness ratio (ICER) and quality-adjusted life years (QALYs) were calculated at 24 weeks.

Results: Of the total of 62 patients, half made up the digital telemedicine group (n=31, 40.82% female, mean age 42.55±12.65 years) and half the standard care group (n=31, 59.18% female, mean age 43.77±14.44 years). The mental QoL score for the standard care group was lower (p=0.045) and declined compared with the digital telemedicine group (p=0.034), with lower scores at follow-up (p=0.03). At 24 weeks, the ICER (€5503/QALY) showed that digital telemedicine, despite higher initial costs, yielded 0.037 additional QALYs and reduced healthcare use during follow-up.

Conclusions: Despite similar improvements in motor symptoms in both groups, digital telemedicine offers an effective adjunct to maintain mental health QoL and reduces healthcare costs in the long-term management of FMD.

Trial registration number: ClinicalTrials.gov ID: NCT05345340.

Introduction: Late-onset multiple sclerosis (LOMS) now comprises over 10% of MS diagnoses in contemporary cohorts. The effectiveness of disease-modifying therapies (DMTs) in LOMS is unclear. We aimed to establish the comparative effectiveness of moderate-high-efficacy versus low-efficacy DMTs in LOMS.

Methods: Using data from the MSBase registry, this multicentre cohort study included people with MS with symptom onset after age 50. Covariates were balanced using inverse-probability-treatment-weighting (IPTW). Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP), confirmed disability improvement (CDI), relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA).

Results: Of 1032 participants, 472 received moderate-high-efficacy DMTs and 560 received low-efficacy DMTs. IPTW-weighted ARR was 0.06 for moderate-high-efficacy and 0.09 for low-efficacy DMTs, corresponding to an ARR ratio of 0.68 (95% CI 0.50 to 0.93, p=0.01). HR for time to first relapse was 0.66 (95% CI 0.47 to 0.91, p=0.01) in favour of moderate-high-efficacy DMTs.Among 856 participants with adequate follow-up, 37% experienced CDP over a median of 4.43 years, with most events (83.6%) attributable to PIRA. The HR for time to CDP was 0.78 (p=0.08) and RAW was 0.69 (p=0.31) in favour of moderate-high-efficacy DMTs, though neither reached statistical significance. There was no difference in CDI or PIRA.

Conclusion: Moderate-high-efficacy DMTs reduced relapse risk in LOMS. Relapse activity was low. CDP was common and driven by PIRA. Although the CDP and RAW results did not reach statistical significance, the overall findings support the initial use of moderate-high-efficacy DMTs in LOMS.

Background: Evidence on relapse activity in relapsing-remitting multiple sclerosis (RRMS) after assisted reproductive technology (ART) treatment differs. We investigated whether relapse activity increased after ART initiation.

Methods: Women with RRMS from the Danish MS Registry who underwent ART treatment from 1995 to 2018 were eligible. The annualised relapse rate (ARR) and corresponding 95% CI at 3 and 9 months post-ART initiation versus 12 months pre-ART were investigated using a negative binomial regression model. Analyses were stratified for live births within 12 months post-ART and disease-modifying therapy (DMT) use pre-ART. Clinical and demographic factors associated with relapse risk were identified.

Results: At ART initiation, 162 women, median age 33 years (IQR: 30-37), median Expanded Disability Status Scale score 1.5 (IQR: 1.0-2.5) were included; 55 (34.0%) were exposed to DMT. 27 relapses were recorded (ARR (95% CI) 0.17 (0.11 to 0.26)) at 12 months pre-ART; 7 relapses and 0.17 (0.08 to 0.36) at 3 months post-ART initiation, and 16 relapses and 0.13 (0.08 to 0.23) at 9 months post-ART initiation. When stratified by ART outcomes, relapse counts in subgroups became small. Women continuing DMT at ART initiation showed a statistically non-significant increase in ARR at 3 months post-ART.

Conclusions: Women with RRMS in Denmark did not, on average, have increased relapse activity at 3 and 9 months post-ART initiation compared with 12 months pre-ART. Women with disease activity pre-ART initiation may have a potentially elevated relapse risk post-ART.

Background: Few studies have investigated patient-reported non-motor outcomes after stroke in young adults. We aimed to assess their prevalence and patterns in this population to identify unmet needs.

Methods: This prospective cohort study included consecutive patients (aged <55) admitted to University College London (UCL) Hospitals Hyperacute Stroke Unit with ischaemic stroke or intracerebral haemorrhage (ICH) between 2017 and 2020. At 6 months, we collected data on eight non-motor domains (anxiety, depression, fatigue, sleep disturbance, pain interference, reduced social participation, bowel and bladder dysfunction). We assessed outcome co-occurrence, compared prevalence by modified Rankin Scale (mRS) score (favourable: 0-1 versus unfavourable: 2-5), and performed multivariable logistic regression to identify predictors of each adverse outcome and high non-motor outcome burden (≥3 adverse outcomes).

Results: We included 493/527 (94%) eligible patients (median age 48, IQR 41-52; 33% female; 82% ischaemic stroke). Fatigue (55%) reduced social participation (47%) and sleep disturbance (46%) were most common. Prevalence rates did not differ significantly by mRS score. 91% reported ≥1 adverse outcome; 27% reported ≥4. Anxiety was predicted by ICH (OR 1.92; 95% CI 1.11 to 3.33; p=0.019) and higher education levels (per decile increase in education deprivation, OR 1.12; 95% CI 1.03 to 1.22; p=0.012). Pain interference was predicted by admission stroke severity (per National Institutes of Health Stroke Scale 10-point increase, OR 1.54; 95% CI 1.05 to 2.25; p=0.025).

Conclusions: Adverse non-motor outcomes are common in young adults 6 months post-stroke, even in those with an mRS score of 0-1 (indicating a favourable functional recovery). Furthermore, non-motor outcomes rarely occur in isolation, highlighting the need for early and comprehensive screening, recognition and management.