European Journal of Neurology最新文献

Background: New drug trials in drug resistant epilepsy are typically powered to detect changes in seizure frequency as the primary endpoint, without integrating other treatment-associated benefits and harms. We developed Epilepsy-DOOR, a consumer-codesigned outcome measure, which combines seizure frequency with quality of life and adverse event measures. This study evaluated Epilepsy-DOOR in previously completed phase 3 clinical trials of adjunctive brivaracetam in patients with drug resistant epilepsy.

Methods: Epilepsy-DOOR was derived for each participant who completed the randomised controlled trial of three Phase 3 trials of brivaracetam (N01252, N01253, N01254). Win odds were estimated for Epilepsy-DOOR and its individual components: change in seizure frequency, quality of life, and adverse event severity for treatment with brivaracetam over placebo for each dose in each study. Odds ratio was estimated for responder rate.

Results: In N01252, Epilepsy-DOOR demonstrated benefit of 100 mg brivaracetam (Win odds 1.42, 95% CI 1.03, 1.97) but not smaller doses over placebo, in line with the results when using responder rate (odds ratio 1.14, 95% CI 1.02, 1.29). In studies N01253 and N01254, benefit as assessed by Epilepsy-DOOR did not attain statistical significance, despite benefits at some doses when measuring seizure responder rate.

Conclusion: Epilepsy-DOOR showed similar effect sizes but slightly reduced power when compared with responder rate. This reduced power is due to the appropriate reflection of adverse events by Epilepsy-DOOR. Epilepsy-DOOR provides a more holistic measure of anti-seizure medication treatment effects, balancing relative benefits and harms, and has potential as a future endpoint in clinical trials in epilepsy.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare antibody-mediated inflammatory demyelinating disorder. In 2023, new international consensus diagnostic criteria were agreed. This study uses these criteria to describe epidemiological features of MOGAD in a population-based cohort of patients from south Wales, UK.

Methods: Retrospective review of case notes on all positive MOG-IgG results in South Wales between 01 January 2011 and 30 June 2024 was undertaken, 2023 diagnostic criteria applied and standardised clinical features recorded. Paediatric MOGAD was defined as age at onset < 16 years and adult MOGAD ≥ 16 years. The incidence period was between 01 January 2015 and 31 December 2023.

Results: Seventy-six prevalent cases were identified: 53 adults and 23 children. Minimum estimated prevalence of MOGAD in south Wales on 30 June 2024 was 76/1,974,110 population (3.85/100,000 population; 95% CI 3.03-4.82). Paediatric prevalence was 6.59/100,000 population (95% CI 4.18-9.89) and adult prevalence 3.26/100,000 population (95% CI 2.44-4.27). Sex ratio was almost equal in males and females. The most frequent presentations were optic neuritis in adults (62.3%) and ADEM in children (34.8%); 64.5% had a monophasic disease course over a median follow-up of 38 months (IQR 13-63). Mean annual incidence was 3.39 (95% CI 2.58-4.39) per million population.

Conclusions: This regional study provides updated prevalence and incidence rates for MOGAD since the introduction of 2023 diagnostic criteria in a stable south Wales, UK population.

Objectives: To investigate the prevalence of probable REM sleep behavior disorder (pRBD) in essential tremor (ET), identify associated risk factors, and evaluate its effects on motor and non-motor symptoms.

Methods: Clinical data were collected from 1297 ET patients across multicenter. pRBD was assessed using the RBD Questionnaire-Hong Kong (RBDQ-HK). Risk factors associated with pRBD were identified through multivariable logistic regression. Furthermore, a meta-analysis was conducted to synthesize existing estimates of pRBD/RBD prevalence in ET.

Results: In this study, pRBD was identified in 11.6% of ET patients. Meta-analysis yielded pooled prevalence estimates of 16% for pRBD (ES = 0.16, 95% CI [0.10-0.21]) and 14% for RBD (ES = 0.14, 95% CI [0.07-0.21]). ET patients with pRBD were older (59.89 ± 13.99 vs. 54.63 ± 16.59 years, p < 0.001) and had a later tremor onset (47.55 ± 15.98 vs. 43.15 ± 17.62 years, p = 0.007) compared with those without pRBD. ET-pRBD patients also exhibited a higher frequency of midline tremor (54.67% vs. 43.93%, p = 0.003), rest tremor (27.33% vs. 16.04%, p = 0.001), and elevated Non-Motor Symptom Scale (NMSS) scores (20.30 ± 18.50 vs. 10.43 ± 12.42, p < 0.001). Multivariable logistic regression identified lower educational attainment (OR = 0.93, p = 0.002) and higher NMSS scores (OR = 1.03, p < 0.001) as independent risk factors.

Conclusions: pRBD is prevalent in ET and independently associated with lower education and increased non-motor symptom burden. Recognition of pRBD may help identify an ET subgroup with distinctive clinical features.

Objective: To explore pathological findings on magnetic resonance imaging (MRI) and their diagnostic implications in early-stage neuroborreliosis (NB).

Method: Adult patients from the Danish neuroinfections cohort (DASGIB, 2015-2019) with confirmed NB, symptom duration < 6 months, and MRI performed within 14 days of diagnosis were included. MRIs were retrospectively reinterpreted by an unblinded neuroradiologist.

Results: In 116 patients, 123 MRIs were performed (99 brain, 44 spine, 46 with contrast). White matter lesions (WML) were common, but non-specific and associated with increasing age (p < 0.001). Six patients showed WML not typical for small vessel disease. Acute infarctions occurred in four patients. Encephalitis was clinically diagnosed in five patients; one showed brainstem FLAIR hyperintensities. In 45 contrast-enhanced brain scans, leptomeningeal enhancement was identified in 6 (13%) and cranial nerve enhancement in 29 (64%). There was poor correlation between facial palsy and enhancement. Spinal cord lesions (1.6-14 cm) were identified in 10 of 44 scans (23%) without symptoms of transverse myelitis. Among 13 contrast-enhanced spine scans, 8 showed leptomeningeal enhancement (61%), and 8 showed nerve root enhancement (61%). Most enhancements did not match symptoms.

Conclusion: Pathological findings were found in 35 of 46 patients with contrast-enhanced MRIs. Key findings included cranial nerve, spinal nerve root, and leptomeningeal enhancement-often without clinical correlation. Spinal cord lesions were relatively frequent; cerebral infarction was rare. While key findings can support the diagnosis, their absence does not exclude NB.

Background: Despite clear diagnostic criteria established in 2017, delivering and explaining the diagnosis of persistent postural-perceptual dizziness (PPPD) can be challenging.

Methods: We outline a step-by-step approach to clearly explain the diagnosis, underlying mechanisms and treatment options to patients with PPPD, followed by a brief overview of current treatment approaches. This approach is adapted from the Cambridge-Calgary Consultation Model and previous recommendations for functional neurological disorders but is mainly based on our expertise accrued over decades and input from patients with PPPD.

Results: The practical clinical framework for the assessment and management of PPPD includes structured history-taking, bedside examination and patient-centred communication strategies aimed at improving diagnostic confidence and therapeutic engagement.

Conclusion: Our experience indicates that the clinical approach used may shape patients' understanding, engagement and overall management trajectory in PPPD. Good communication is essential for the diagnosis and management of this condition.

Background: Cranial nerve involvement is a well-recognized feature in Guillain-Barré syndrome (GBS) but remains less well understood in chronic forms of autoimmune neuropathies. Earlier studies of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) were conducted before updated diagnostic criteria and the recognition of autoimmune nodopathy (AN), which may limit the interpretation of their findings.

Methods: We retrospectively analyzed 582 patients with chronic autoimmune neuropathies-CIDP (n = 431), multifocal motor neuropathy (MMN) (n = 64), anti-myelin-associated glycoprotein (MAG) neuropathy (n = 54), and AN (n = 33)-from 4 Korean and 1 UK centers. Patients with cranial nerve involvement were identified and described. CIDP patients with cranial nerve involvement (cranial+ CIDP) were compared with those without (cranial- CIDP).

Results: Cranial nerve involvement was observed in 8.8% (38/431) of CIDP and 24.2% (8/33) of AN patients but was absent in MMN (0/64) and anti-MAG neuropathy (0/54). Facial palsy was overall the most common manifestation (CIDP: 45%, AN: 50%). Patients with AN more frequently exhibited bilateral optic neuropathy (50%) and facial diplegia (38%), while CIDP patients more often showed trigeminal neuropathy and oculomotor nerve palsy (both 32%). Compared with cranial- CIDP, cranial+ CIDP patients were more often younger, of variant subtypes (especially multifocal), presented (sub)acutely with preceding infection/vaccination, followed by relapsing-remitting rather than progressive courses, and achieved greater improvement despite greater pre-treatment disability.

Conclusions: Cranial nerve involvement serves as a diagnostic clue in chronic autoimmune neuropathies, particularly in identifying AN and CIDP. Cranial+ CIDP appears to represent a distinct subset with partial overlap to GBS, suggesting unique underlying mechanisms.