Journal of Neurology最新文献

Background: Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences.

Methods: A cohort study spanning 10 years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits.

Results: Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304 days, IQR 1433-3274) indicated favorable outcomes in both groups.

Conclusion: This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.

Background: Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington's disease (HD). To date, however, there has been no longitudinal study exceeding 3 years examining either its serial dynamics or predictive power in HD. We aimed to conduct the first such study.

Methods: Serum NfL was sampled using ultrasensitive immunoassay at four timepoints across a 14-year period in a cohort of HD gene carriers (n = 21) and controls (n = 14). Gene carriers were premanifest at baseline. Clinical features of HD were evaluated by Unified Huntington's Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A/B task, Symbol Digit Modalities Task and semantic/phonemic fluency tasks.

Results: 14/21 HD gene carriers converted to prodromal or manifest disease by the final timepoint ("converters"). At baseline and each subsequent timepoint, NfL levels were higher in converters than in non-converters and controls (p = < 0.001-0.03, η_p² = 0.25-0.66). The estimated rate of change in NfL was higher in converters than in non-converters (p = 0.03) and controls (p = 0.001). Baseline NfL was able to discriminate converters from non-converters (area under curve = 1.000, p = 0.003). A higher rate of change in NfL was predictive of more severe motor (UHDRS-TMS p = 0.007, β = 0.711, R² = 0.468) and cognitive deficits (MoCA p = 0.007, β = - 0.798, R² = 0.604; Trail B, p = 0.007, β = 0.772, R² = 0.567; phonemic fluency p = 0.035, β = - 0.632, R² = 0.345).

Conclusions: Our data suggest that (1) NfL longitudinal dynamics in premanifest/transitional HD are non-constant; rising faster in those closer to disease onset, and (2) NfL can identify individuals at risk of conversion to manifest disease and predict clinical trajectory, > 10 years from disease onset.

Background and objectives: Although recent meta-analyses have shown that the association between physical activity (PA) and the risk of developing Parkinson's disease (PD) is influenced by gender differences, a growing number of studies are revealing the general applicability of this association across genders. This study aimed to reassess the association and dose-response relationship between PA and PD risk in populations.

Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted in this study from inception to February 1, 2024, without language restrictions. Stratified analyses were conducted to explore the association between PA and PD risk, combining multivariate-adjusted effect estimates via random-effects models, and to validate the dose-response relationship between the two.

Results: This study included 21 observational studies, comprising 13 cohort studies and 8 case-control studies. The pooled analysis revealed that PA significantly reduced the risk of developing PD [relative risk (RR) = 0.77, 95% CI 0.70-0.85]. In addition, the dose-response analysis revealed both linear and nonlinear associations, with linear results indicating a 9% reduction in PD risk for every 10 MET-h/wk increase in PA. The study also demonstrated that the protective effect of PA against PD was significant for both sexes. Moreover, no statistically significant effects of PA on preventing PD were observed in individuals with a BMI > 26 (RR = 0.35, 95% CI 0.12-1.02) or in Asian populations (RR = 0.78, 95% CI 0.60-1.01); however, the trends suggest potential protective effects, warranting further investigation. Sensitivity analyses confirmed the robustness of these findings.

Conclusion: This meta-analysis produced substantial evidence to reaffirm the protective effect of high PA on PD across various population groups and the inverse dose-response relationship with PD risk, and to validate the protective effect of PA among different demographic groups.

Background: The wearing-off phenomenon is a key driver of medication change for patients with Parkinson's disease (PD) treated with levodopa. Common first-line options include increasing the levodopa dose or adding a catechol-O-methyltransferase (COMT) inhibitor, but there are no trials comparing the efficacy of these approaches. We evaluated the effectiveness of adjunct opicapone versus an additional 100 mg levodopa dose in PD patients with early wearing-off using pooled data from 2 randomized studies.

Methods: The ADOPTION study program included two similarly designed 4-week, open-label studies conducted in South Korea (NCT04821687) and Europe (NCT04990284). Patients with PD, treated with 3-4 daily doses of levodopa therapy and with signs of early wearing-off were randomized (1:1) to adjunct opicapone 50 mg or an additional dose of levodopa 100 mg. Patient-level data from the two studies were pooled.

Results: The adjusted mean [SE] change from baseline to week 4 in absolute OFF time (key endpoint) was - 62.8 min [8.8] in the opicapone group and - 33.8 min [9.0] in the levodopa 100 mg group, the difference significantly favoring opicapone (- 29.0 [- 53.8, - 4.2] min, p = 0.02). Significant differences in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III subscore (- 4.1 with opicapone vs - 2.5 with levodopa 100 mg), also favored opicapone (- 1.7 [- 3.3, - 0.04], p < 0.05). Dyskinesia was the most frequently reported adverse event (opicapone 7.2% vs. levodopa 100 mg 4.2%).

Conclusions: In these short-term trials, introducing adjunct opicapone was more effective at reducing OFF time than adding another 100 mg levodopa dose in PD patients with early signs of wearing-off.

Objective: To evaluate the reliability, responsiveness, and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in patients with lysosomal storage disorders (LSDs) who present with neurological symptoms, and quantify the threshold for a clinically meaningful change.

Methods: We analyzed data from three clinical trial cohorts (IB1001-201, IB1001-202, and IB1001-301) of patients with Niemann-Pick disease type C (NPC) and GM2 Gangliosidoses (Tay-Sachs and Sandhoff disease) comprising 122 patients and 703 visits. Reproducibility was described as re-test reliability between repeat baseline visits or baseline and post-treatment washout visits. Responsiveness was determined in relation to the Investigator's, Caregiver's, and Patient's Clinical Global Impression of Improvement (CGI-I). The CGI-I data was also used to quantify a threshold for a clinically meaningful improvement on the SARA scale. Using a qualitative methods approach, patient/caregiver interviews from the IB1001-301 trial were further used to assess a threshold of meaningful change as well as the breadth of neurological signs and symptoms captured and evaluated by the SARA scale.

Results: The Inter-Class Correlation (ICC) was 0.95 or greater for all three trials, indicating a high internal consistency/reliability. The mean change in SARA between repeat baseline and post-treatment washout visit assessments in all trials was -0.05, SD 1.98, i.e., minimal, indicating no significant differences, learning effects or other systematic biases. For the CGI-I responses and change in SARA scores, Area Under the Curve (AUC) values were 0.82, 0.71, and 0.77 for the Investigator's, Caregiver's, and Patient's CGI-I respectively, indicating strong agreement. Further qualitative analyses of the patient/caregiver interviews demonstrated a 1-point or greater change on SARA to be a clinically meaningful improvement which is directly relevant to the patient's everyday functioning and quality of life. Changes captured by the SARA were also paralleled by improvement in a broad range of neurological signs and symptoms and beyond cerebellar ataxia.

Conclusion: Qualitative and quantitative data demonstrate the reliability and responsiveness of the SARA score as a valid measure of neurological signs and symptoms in LSDs with CNS involvement, such as NPC and GM2 Gangliosidoses. A 1-point change represents a clinically meaningful transition reflecting the gain or loss of complex function.

Background: Neuro-otological factors that influence changes in spontaneous nystagmus (SN) during vertigo attacks in Ménière's disease (MD) remain unclear.

Objective: To identify neuro-otological factors that might influence the initial direction of SN and the directional change of SN.

Methods: A prospective, observational study of 22 patients with definite MD to evaluate the initial direction and directional change of SN during vertigo attacks, endolymphatic hydrops (EH) volume, and the function of horizontal semicircular canal and hearing levels.

Results: SN consistently began as irritative in 17 of 22 cases, and 9 of 17 cases showed a definite change in direction after onset. SN consistently began as paralytic in 5 of 22 cases, and 3 of 5 cases showed a definite change in direction after onset. Subjects in the irritative initial SN group had less severe degrees of hearing loss, smaller cochlear and vestibular EH volume than the paralytic initial SN group (P = 0.017, < 0.001, and 0.009, respectively). Subjects in the SN direction change group had significantly smaller maximum slow phase velocity, percentage of caloric weakness and canal paresis than the no SN direction change group (P = 0.001, 0.006, and 0.001, respectively). Simple logistic regression analysis showed that smaller EH volume was significantly associated with initial irritative SN (OR = 0.867, 95% CI 0.762-0.988, P = 0.032) and that the degree of canal paresis was negatively associated with the presence of directional change of SN (OR = 0.022, 95% CI 0.002-0.289, P = 0.004).

Conclusions: The morphology of EH and canal paresis may independently affect the characteristics of SN in patients with MD.