BMJ Neurology Open最新文献

Background: We previously reported a scale to assess the disease progression rate in patients with amyotrophic lateral sclerosis (ALS), the forced vital capacity decline pattern scale (FVC-DiP). In this study, we investigated the association between FVC-DiP scores and neurofilament light chain (NfL) in the serum and cerebrospinal fluid (CSF) in patients with ALS.

Methods: We performed a retrospective study to examine the association between NfL levels and the rate of disease progression (N=41). The disease progression rate was assessed using three methods: the FVC-DiP score determined using the percentage of predicted FVC (%FVC) and disease duration at the %FVC measurement, the rate of decline in the ALS Functional Rating Scale Revised (ALSFRS-R) score (ΔFS) and the rate of decline in the %FVC (Δ%FVC).

Results: The FVC-DiP scores were significantly correlated with NfL levels in both the serum and CSF (serum, R²=0.274, p<0.001; CSF, R²=0.274, p=0.001). Patients assessed as rapidly progressing by the FVC-DiP had high NfL levels, and patients assessed as slowly progressing had low NfL levels. In the group with a low ΔFS and/or Δ%FVC, although the disease progression rate assessed by the FVC-DiP may have differed from the assessments obtained using the ALSFRS-R and/or %FVC, the correlation between FVC-DiP scores and serum NfL levels remained consistent.

Conclusions: The FVC-DiP was significantly associated with NfL levels in the serum and CSF, suggesting that the FVC-DiP is a reasonable scale to assess the rate of ALS progression.

Background: Published evidence is limited on the clinical burden of juvenile myasthenia gravis (JMG). We aimed to assess epidemiology and the clinical characteristics of JMG in England.

Methods: We performed a retrospective analysis of patients with newly diagnosed JMG identified in England via primary care and hospital data between 2010 and 2019.

Results: 32 children (aged 2-17 years) with newly diagnosed JMG were included. Prevalence of JMG ranged from 2.2 (95% CI 1.5 to 3.1) in 2012 to 2.5 (95% CI 1.8 to 3.4) per 100 000 in 2018. The annual incidence ranged from 0.8 (95% CI 0.1 to 5.7) in 2015 to 3.8 (95% CI 1.6 to 9.0) per million per year in 2017. Incidence fluctuated in females from 1.6 (95% CI 0.2 to 11.3) in 2016 to 6 (95% CI 2.3 to 16.1) per million per year in 2018. Overall, 20 patients received first acetylcholinesterase inhibitors or corticosteroids with no prior therapy during the study period. During the follow-up period (median, 3.3 years), 17 patients (53.1%) with JMG experienced a hospitalisation. No deaths were observed.

Conclusions: This study confirms the rarity of JMG in England, with steady incidence and prevalence rates over a decade. Further research is required to assess unmet needs in JMG therapy and the importance of effective treatments for this condition.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by motor symptoms. However, approximately half of patients with PD exhibit signs of dementia within a decade of diagnosis. While deficits in working memory and visuospatial abilities are recognised as hallmarks of cognitive decline in PD, these populations are rarely studied using detailed cognitive tools that link cognitive impairments to formal theoretical models, such as the theory of visual attention (TVA).

Methods: This cross-sectional study addresses this gap by employing the TVA whole report paradigm to assess visual processing in a cohort of patients with PD, both with and without cognitive impairment. Participants were divided based on their Montreal Cognitive Assessment (MoCA) scores into two PD groups (n=25 each) and a healthy control group (n=25).

Results: Our principal finding is that the visual processing speed (C) and visual short-term memory capacity (K) are significantly diminished in patients with PD with MoCA scores below 26 (Analysis of variance, p=0.016 for C and p<0.001 for K), while no notable differences were observed between controls and patients with PD with MoCA scores of 26 or above. Using a generalised linear model to assess the impact of factors such as age, gender and disease duration, we discovered that the C-parameter was significantly influenced by age, while the K-parameter was notably affected by gender.

Conclusion: TVA parameters demonstrate their suitability for detecting cognitive deficits in PD. Given their independence from motor and non-motor symptoms, TVA parameters may prove to be valuable tools for early diagnosis and longitudinal monitoring of cognitive deficits in individual patients with PD.

Background: Endovascular catheters and devices used for thrombectomy in patients who had a stroke can damage the vessel lumen leading to microthrombi. During stroke recanalisation, microthrombi could migrate distally and occlude cerebral microvasculature, potentially limiting the benefit of recanalisation therapy.

Objectives: To describe vascular injury occurring after endovascular therapy (EVT), with stent retrievers (SR) and direct aspiration (DA), to open up avenues for further improvement of EVT technique.

Methods: SR and DA were performed according to clinical procedures in extracranial vessels in a swine model of thromboembolic arterial occlusion. Treated vessels were collected at 2 hours or 3 days post-EVT to assess respectively acute injury and early healing (remnant vascular injury) as assessed by Evans-Blue (EB) dye exclusion. The presence of microthrombi was quantified using scanning electron microscopy. Markers of coagulation activation were measured periprocedurally in plasma.

Results: Both SR and DA induced vascular injury. SR tended to result in larger EB positive areas than DA at 2 hours (99.5 vs 84.5; p=0.072) which reached statistical significance at day 3 (78.6 vs 48.6; p=0.040) post-EVT. Both EVT methods similarly yielded microthrombi in treated areas which were still observed at 3 days post-EVT. In addition, both EVT methods immediately increased systemic plasma levels of complexes of intrinsic-pathway coagulation activation: thrombin, Factor IX and Factor Xa:Antithrombin.

Conclusions: In this preclinical thromboembolic model, SR thrombectomy and DA lead to acute vascular injury, yield microthrombi and trigger contact activation of the coagulation system. At 3 days after intervention, healing remains incomplete, showing remnant vascular injury in the treated arteries, especially in SR thrombectomy.

There is increasing interest in the role of platform trials, where several investigational products targeting disease modification in Parkinson's Disease can be assessed in parallel. Indeed, several initiatives are currently gearing up across North America and Europe to conduct such studies. However, to date, little attention has been paid to ongoing efforts that already exist in Australia and look soon to expand across to New Zealand as part of greater collaboration. This viewpoint will highlight some of these ongoing efforts addressing the challenges and potential solutions for delivering successful studies.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a widely applied therapy in Parkinson's disease (PD). Occasionally, postoperative worsening of gait or balance occurs, even in the face of a persistently gratifying appendicular symptom improvement. The characteristics vary considerably, and the risk factors for this postoperative gait or balance worsening are largely unknown. We systematically investigated the literature for all cases of gait or balance worsening after STN-DBS in PD and explored its characteristics and determinants. In consecutive populations with best medical treatment as the control group, we also explored its incidence.

Methods: We searched PubMed, Embase and Cochrane. We considered all cases occurring between 1 month after surgery (to exclude immediate postoperative complications as most likely cause) and 12 months after surgery (to exclude disease progression).

Results: From 2719 entries, we included 20 studies (n=1010 operated patients). Freezing of gait and falls were the most commonly reported symptoms. The first worsening of symptoms occurred between 3 and 6 months after surgery. Modulation of pedunculopontine afferents was more likely associated with worsening of gait and balance. In controlled trials with consecutive patients, 24 cases (15.9%) were reported, compared with 5.8% with best medical treatment (p=0.0013).

Conclusions: Gait or balance worsening after STN-DBS is a complex phenomenon that cannot readily be explained by mere disease progression. The multifactorial nature warrants further study in gait labs and through advanced imaging techniques. Future studies should also estimate the actual incidence, which we could not establish as we excluded cohorts without any reported cases.

Background: Intravenous thrombolysis for acute minor ischaemic strokes did not provide any benefit in the recent TEMPO-2 trial. In general, single antiplatelet agents are used to improve the outcomes after thrombolysis. This systematic review was done to assess the impact of dual antiplatelet therapy (DAPT) after thrombolysis in patients with minor stroke.

Materials and methods: A literature search was performed on PubMed, The Cochrane Library and Science Direct for articles between 2016 and 2024. All studies included patients with minor stroke, aged ≥18 years, National Institutes of Health Stroke Scale score of ≤5 (or 3) and those who received thrombolysis prior to DAPT. The primary endpoint was modified Rankin Scale (mRS) score of 0-1 at 90 days. The quality of the studies was assessed using the Newcastle Ottawa Scale. Risk ratios (RRs) were calculated, and subgroup analysis was done.

Results: Only 4 out of 4364 studies originally retrieved met the inclusion criteria and were included. The analysis showed that the mRS score improvement at 90 days was almost similar in both DAPT and single antiplatelet therapy (SAPT) groups (RR 1.09; 95% CI (0.98, 1.21), p=0.11). Risk of symptomatic intracranial haemorrhage (SICH) (RR 0.65; 95% CI (0.11, 3.97), p=0.64) and stroke recurrence (RR 0.88; 95% CI (0.44, 1.78), p=0.64) was reduced with DAPT compared with SAPT without any major significance.

Conclusion: While these findings could not establish the superiority of DAPT over SAPT, DAPT showed slightly better results in functional outcomes, reducing the risk of stroke recurrence and SICH after thrombolysis in patients with minor stroke.

Prospero registration number: CRD42024593717.

Background: Higher-level gait disorders (HLGDs) are slow, unsteady neurological GDs in older people. GDs can reduce quality of life (QoL) and cause depression. This has not been investigated in HLGD even though some HLGD causes are treatable, potentially affecting associated problems. We aimed to investigate gait and balance confidence, depressive symptoms and QoL in HLGD.

Methods: In a population (n=3769, 65-84y), 798 reported gait impairment (questionnaire) and were clinically examined together with 249 age- and sex-matched controls. Gait property groups were formed: 'HLGD', 'other neurological GD', 'non-neurological GD' or 'no GD'. Swedish Falls Efficacy Scale (FES(S)), Modified Gait Efficacy Scale (mGES), Euro Quality of Life 5-Dimension 5-Level index, Euro Quality of Life Visual Analogue Scale (EQ VAS) and Geriatric Depression Scale-15 (GDS-15) were compared.

Results: In the general population, 38% had GDs, of which 16% (n=87/561) were HLGDs, giving an HLGD prevalence of 5.8%; 26% (n=145/561) were other neurological GDs; and 59% (n=329/561) non-neurological GDs. HLGD had more depressive symptoms than non-neurological GD and no GD (GDS-15 HLGD, 3.9±3.4; non-neurological GD, 2.5±2.8; no GD, 1.4±2.0; p<0.05), lower EQ VAS (HLGD, 63±17; non-neurological GD, 71±18; no GD, 82±14; p<0.001), lower gait confidence (mGES HLGD, 60±22; non-neurological GD, 74±21; no GD, 90±13; p<0.001) and lower balance confidence (FES(S) HLGD, 93±32; non-neurological GD, 111±25; no GD, 124±13; p<0.001).

Conclusions: HLGDs are common and associated with reduced QoL, reduced confidence in gait and balance, and depressive symptoms, emphasising awareness of mental health among older people with slow unsteady gait.

Background: Misdiagnosis of idiopathic intracranial hypertension (IIH) is prevalent and potentially harmful. We evaluated the diagnostic process of IIH and the impact of implementing a National Guideline (NG) on IIH management to improve patient care.

Method: In this observational retrospective study, we retrieved data on diagnostic investigations, duration, errors and causes for suspecting IIH from patients referred to the Danish Headache Center by suspected new-onset IIH from January 2020 to September 2022. We compared outcomes by final diagnosis (true vs disproven IIH) and the period before and after implementation of the NG. Level of significance was Bonferroni adjusted to p<0.002.

Results: 96 patients were referred. We confirmed IIH in 27 (28%) and disproved IIH in 69 (72%) whose final diagnoses were predominantly headache disorders (70%) and pseudo-papilloedema (12%). True IIH was discovered by optic disc oedema (n=25, none detected by neurologists); neuroimaging indicating elevated intracranial pressure (n=1) or a typical clinical phenotype (n=1) aided little but often elicited IIH suspicion suggesting anchoring bias with premature closure. Misdiagnosis affected 11% (n=11). Diagnostic workup was more comprehensive and faster in true IIH (p<0.001). Mismanagement dropped by implementation of the NG (from 44% to 20%, p=0.02).

Conclusion: Optic disc oedema is the most predictive determinant of true IIH; neuroimaging and phenotype alone have poor diagnostic value and introduce bias. Fundus exam is urgent and decisive in suspected IIH and should guide diagnostic strategy to mitigate unnecessary investigations and preserve vision. An NG reduced diagnostic errors and optimised the diagnostic process.

Background: N-methyl-D-aspartate receptor antibody encephalitis (NMDAR-Ab-E) can have an onset during, after or prior to a pregnancy. In animal models, transplacental NMDAR immunoglobulin G transfer can affect neurodevelopment. In contrast, clinical reports of mothers affected by NMDAR-Ab-E typically are reassuring. We systematically reviewed maternal, infant and childhood clinical data pertaining to NMDAR-Ab-E with an onset before, during or after pregnancy and compared this to our single autoimmune neurology centre experience.

Methods: After pre-registration on PROSPERO (CRD42023408447), we searched PubMed and Scopus for NMDAR-Ab-E case reports/series with an onset before, during or after pregnancy (last search 19/10/2023). We extracted maternal, neonatal and childhood outcomes using an idealised checklist to derive summary statistics.

Results: After quality control, we identified 66 pregnancies in 61 women from 48 reports or series. 72% of women recovered with minimal or no neurological deficits, comparable to non-pregnancy-associated NMDAR-Ab-E. Likewise, 80% of pregnancies resulted in live births with a single neonatal death reported. Data on neonatal outcome measures were frequently unreported, and childhood follow-up was provided in only 60%. Our centre's experience is consistent: 3/4 mothers recovered with no functional deficits and 7/8 children without evidence of compromise at a median follow-up of 2 years.

Conclusions: Current evidence does not overall suggest unfavourable maternal, fetal or childhood outcomes after NMDAR-Ab-E. However, the available sample is small, predominantly single case reports with modest follow-up, lacks standardisation, and data are often incomplete. Future approaches should address these caveats: developing multi-centre collaboration towards an international registry.