Journal of Neurology最新文献

Objective: The diagnosis of paraneoplastic neurologic syndromes (PNS) requires exclusion of alternative etiologies. However, the spectrum of alternative diagnoses encountered during PNS workup ("better explanations") has not been systematically examined. We aimed to characterize this spectrum.

Methods: Retrospective population-based study in Friuli-Venezia-Giulia (Italy). Among 878 consecutive patients tested for PNS antibodies at a centralized tertiary center serving three hospitals (2009-2017), alternative diagnoses were identified. Results of a logistic regression model were used to develop the PNS DDx Score.

Results: Among 661 patients with alternative diagnoses, median age was 66 years, and 51% were male. CNS involvement predominated in 397 patients (60%), peripheral in 215 (33%), and extra-nervous system in 49 (7%). Etiologic diagnosis was reached in 269 with central involvement, including degenerative (97, 36%), autoimmune (47, 17%), and vascular (37, 14%). In peripheral presentations, a diagnosis was reached in 112 and included autoimmune (51, 45%), toxic-metabolic (40, 36%), and vasculitis (11, 10%). PNS antibody testing increased by 96% from 2009 to 2017; diagnostic yield remained low (7% vs. 8%). Intermediate-risk or other syndromes (OR 7.97, CI95% 3.07-23.80; OR 192.82 CI95%, 66.11-739.59) and low-risk/absence of tumor (OR 6.90, CI95% 2.75-18.92) were associated with alternative diagnoses, whereas increasing age (OR 0.95, CI95% 0.92-0.97) was inversely associated. These variables (age, syndrome, and tumor type) were incorporated in the PNS DDx Score.

Conclusion: Alternative diagnoses during PNS workup are common in patients < 55 years and those without high-risk syndromes. The PNS DDx Score can be used to identify patients at risk of misdiagnosis.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel noninvasive therapy for Parkinson's disease (PD). Randomized controlled trials (RCTs) have reported inconsistent results on their effects. This meta-analysis evaluated the efficacy of taVNS on motor and gait outcomes in PD.

Methods: This systematic review followed the PRISMA guidelines and was registered in PROSPERO (CRD420251184160). The RCTs evaluating taVNS in patients with PD were systematically searched in PubMed, the Cochrane Central Register of Controlled Trials, Embase, CNKI, VIP, and Wanfang databases up to October 15, 2025. The primary outcomes were motor function, gait ability, and gait parameters. Data were pooled using a fixed-effects model and expressed as mean differences (MD) with 95% confidence intervals (CI); random-effects models were additionally applied as sensitivity analyses. Risk of bias and methodological quality were assessed using the Cochrane RoB 2 tool and the Physiotherapy Evidence Database (PEDro) scale, and the certainty of evidence was evaluated with the GRADE framework.

Results: A total of 7 RCTs involving 183 patients with PD were included. The meta-analysis showed that taVNS significantly improved motor function (MDS-UPDRS Part III: MD =  - 2.64, 95% CI - 4.23 to - 1.05, P < 0.001) and increased stride length (MD = 0.13 m, 95% CI 0.05-0.22, P < 0.001), whereas its effect on gait speed was not statistically significant. The overall risk of bias was low; however, due to the relatively small sample sizes, the certainty of evidence was rated as moderate according to the GRADE framework.

Conclusion: taVNS may provide modest benefits for PD, with improvements observed in motor function and stride length, but no clear effect on gait speed. Given the limited evidence, larger high-quality trials are needed to confirm its clinical value.

Background: Impaired speech due to dysarthria significantly impacts quality of life. Patient-reported outcomes (PROs) offer critical insight into the lived experience of communication disability and are central to regulatory frameworks for patient-focused drug development.

Objectives: To develop and validate the Dysarthria Impact Scale (DIS), a brief PRO designed to assess the impact of motor speech disorders on quality of life across neurological conditions.

Methods: A multi-site, cross-sectional study was conducted with 244 participants, including individuals with Huntington's disease, Parkinson's disease, hereditary ataxias, and head and neck cancer, and healthy controls. The 22-item DIS was developed using expert input and patient feedback and evaluated alongside reference tools (Voice Handicap Index and SF-36). Item reduction procedures yielded two shorter versions (DIS-17 and DIS-6). Validity, reliability, and sensitivity/specificity analyses were performed, and minimal clinically important differences (MCIDs) were estimated using distribution-based methods.

Results: All DIS versions showed strong convergent validity with the VHI (r = -0.85) and SF-36 (r = 0.72) and were correlated with blinded perceptual speech ratings. DIS-17 and DIS-6 achieved comparable sensitivity (0.93 and 0.88) and specificity (0.84 and 0.86, respectively). Test-retest reliability was high (r = 0.98), with estimated MCIDs and within-subject variability provided. Group differences were observed, with lower DIS scores in ataxia and Parkinson's disease compared to Huntington's disease.

Conclusions: The DIS is a valid, reliable, and practical PRO for quantifying the impact of dysarthria on quality of life. Longitudinal responsiveness remains to be established.

Patients with Parkinson's disease (PD) exhibit delayed saccades and saccadic hypometria; Still, the diagnostic yield of saccadic parameters is limited in clinical settings. We hypothesized that, as motor fluctuations, fluctuations would also be documented on saccadic parameters, and these could serve as a feasible interpretative measure for clinical application. This cross-sectional study evaluated a prospectively recruited de novo cohort of 114 patients with PD in South Korea, collected from February 2022 to August 2024. All participants performed horizontal and vertical saccades following a target that alternately appeared on a light bar every 2 s. The mean, standard deviation, and coefficient of variation (CV) of saccadic latency, amplitude, and velocity were analyzed. Dynamic time warping (DTW) was applied to assess the temporal variability of saccadic sequences, including control-deviation DTW (CD-DTW) and population-variability DTW (PV-DTW). The data were compared to those obtained from 70 age- and sex-matched healthy participants. Patients with PD showed a higher CV of saccadic amplitude, both horizontally (p < 0.001) and vertically (p < 0.001), compared with the healthy controls. Latency-, amplitude-, and velocity-based CV and CD-DTW features positively correlated with age and MDS-UPDRS-III. Receiver operating characteristic curve analysis showed that the logistic regression model combining CD-DTW and CV for horizontal saccadic amplitude had the highest discriminatory power (area under the curve of 0.848 [95% confidence interval = 0.777-0.908]; false discovery rate-adjusted q = 0.039). Patients with PD showed a higher saccadic variability than healthy controls, which was correlated with the severity of motor symptoms. Saccadic variability, as well as bradykinesia observed in the extremities, likely reflects the sequence effect of PD. Therefore, saccadic analyses may aid in PD diagnosis and severity assessment.

Background: Cognitive testing provides an essential marker of brain function. Despite the widespread availability of technology, cognitive testing in contemporary practice largely remains rooted in the manual administration and scoring of analog materials. Here we introduce telehealth enabled neuropsychological testing (TENT): browser-based, videoconference-integrated software for examiner-led cognitive assessment.

Methods: TENT incorporates a battery of tasks assessing memory, language, processing speed, attention and executive functions. We used TENT to conduct remote, telehealth-based assessments in 531 healthy volunteers, and validated the software in a sample of 452 individuals with drug-resistant epilepsy (DRE) and 392 individuals with newly diagnosed seizures. TENT-acquired measures were compared against clinically acquired, in-person, traditional cognitive measures where available. Participant user experience feedback was obtained in a subset of participants.

Results: Comparison of healthy volunteers and DRE participants yielded a pattern of cognitive compromise characteristic of chronic, drug-resistant epilepsy. TENT data was sensitive to demographic and clinical parameters (e.g., age, antiseizure medication load, lateralised structural pathology, age at seizure onset) known to affect aspects of cognition. Correlations between TENT data and reference in-person measures were comparable to published test-retest coefficients for the reference measures. Participant user experience was overall positive.

Conclusions: TENT modernizes traditional neuropsychological testing by providing for human-led cognitive assessments that exploit the benefits of technology-assisted testing and can be used for remote assessment. It offers a modular, normed and standardized system applicable across a range of neuropsychological conditions, providing reach, convenience, efficiencies and data richness. This approach draws upon the strengths of the traditional assessment model while modernizing contemporary neuropsychological practice.

Background: Stroke is the world's second-leading cause of death, with ischemic events accounting for nearly 9 of 10 cases. Rapid endovascular treatment (EVT) is now standard, yet the benefit of giving intravenous tPA beforehand ("bridging therapy") remains uncertain. One reason: tPA often shifts the clot distally-thrombus migration (TM)-a phenomenon seen in roughly one-fifth of large-vessel strokes that can complicate the procedure but has also been linked to better outcomes. This study evaluates how TM influences clinical outcomes, aiming to clarify whether tPA adds value in patients who receive EVT.

Methods: A comprehensive literature search was conducted across various databases until April 2025 to identify relevant articles. The quality was assessed using the NOS tool and the analysis was performed using RevMan 5 software. Primary outcomes of interest were favorable functional outcomes (modified Rankin Scale score 0-2) and mortality 90 days after stroke.

Results: Thirteen studies (n = 6,198 patients) were identified fulfilling our research question. Thrombus migration was significantly associated with favourable neurological outcomes (mRS 0-2) at 90 days (OR = 1.43; P = 0.025). TM showed no significant impact on other outcomes, including 90-day mortality (OR = 0.86; P = 0.15), symptomatic intracranial hemorrhage (sICH) (OR = 1.12; P = 0.54), any ICH (OR = 1.25; P = 0.4), NIHSS change at discharge (MD = 0.36; P = 0.18) and successful reperfusion rates (TICI 2b-3) (OR = 0.69; P = 0.0686).

Conclusions: Thrombus migration during mechanical thrombectomy was associated with better 90-day functional outcomes. Although thrombus migration might affect complete revasculrization, it may offer clinical benefits by restoring blood flow to larger brain territories.

Background: Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) have emerged as quantitative biomarkers of intrathecal humoral immune activity and are now included in diagnostic criteria for multiple sclerosis (MS). The aim of this study was to evaluate the relationship between quantitative and qualitative KFLC parameters and intrathecal immunoglobulin synthesis in MS.

Methods: In this retrospective monocentric study, paired CSF and serum samples from 242 neurological patients, 171 with MS, were analyzed. KFLC, IgG and IgM concentrations were measured by turbidimetry and intrathecal synthesis was assessed using established linear and nonlinear indices. IgG and KFLC oligoclonal bands (OCB) were detected by isoelectric focusing followed by immunoblotting. Alternative K-index thresholds were explored and the independent contribution of IgG and IgM intrathecal fractions was assessed using multivariable regression models.

Results: K-index positivity showed a strong association with intrathecal IgG synthesis and IgG OCB in MS patients (all p < 0.0001) and was independent of age and sex. Multivariable analysis demonstrated that the K-index was independently associated with IgG (p < 0.0001), but not IgM (p = 0.738) intrathecal synthesis. Qualitative KFLC oligoclonality was frequently observed in patients with IgG OCB (89.19%).

Conclusions: KFLC are confirmed as a valuable complementary biomarker to IgG OCB in MS. K-index values should be evaluated in conjunction with clinical features, imaging data, and ongoing or prior treatments, as KFLC levels may be dynamic and treatment sensitive, with a potential risk of misclassification in diagnostically borderline cases.

Existing research suggests a weak, inconsistent link between self-reported cognitive concerns (SCC) and performance-based measures of cognitive dysfunction in people with multiple sclerosis (pwMS). This study aimed to evaluate for a non-linear relationship between SCC and cognitive impairment in pwMS. A consecutive sample of 933 pwMS routinely completed the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery at a Canadian neuropsychiatry clinic between 2020 and 2025. Covariates included age, sex, Expanded Disability Status Scale scores, disease duration, disease course, Wechsler Test of Adult Reading scores, and Hospital Anxiety and Depression Scale sub-scale scores. Cognitive impairment was defined as ≥ 3 MACFIMS raw scores ≥ 1.5 SD below matched normative data. Using a grid search to identify a breakpoint in Perceived Deficits Questionnaire (PDQ) scores (to assess SCC), a segmented logistic regression analysis was undertaken to predict cognitive impairment from PDQ scores, controlling for covariates. Mean participant age was 43.34 years (SD 10.89), 75.12% were female, median EDSS was 2.00 (IQR 1.50-3.50), and 46.73% had cognitive impairment. PDQ scores ≥ 50 independently predicted increased odds of cognitive impairment (OR = 1.92, 95% CI [1.22-3.02], p = 0.0052), while PDQ scores < 50 were not associated with cognitive impairment (OR = 1.03, 95% CI [0.87-1.21], p = 0.75). In conclusion, above a critical threshold, SCC indicate increased odds of cognitive impairment.

Background: Secondary progressive multiple sclerosis (SPMS) encompasses heterogeneous phenotypes that may or may not exhibit disease activity.

Objectives: To characterize a cohort of non-relapsing SPMS (nrSPMS) identified through a data-driven definition adapted from the HERCULES trial criteria, compared with neurologist-defined (ND) SPMS.

Methods: Relapsing MS patients were retrospectively extracted from the Italian Multiple Sclerosis Register (RISM). ND was defined according to clinical criteria for SPMS and the HERCULES cohort adapting the trial inclusion criteria. Progression independent from relapse activity (PIRA) and relapse-associated worsening (RAW) events were assessed. Diagnostic performances of SPMS definitions were evaluated.

Results: Among 20,306 patients, 866 (4.26%) were classified as SPMS by ND and 1603 (7.89%) by HERCULES criteria. The HERCULES group included older patients, less likely to relapse post-conversion. PIRA occurred in 88.8% of ND and 88.5% of HERCULES-defined cases, with a shorter median time to first PIRA in the latter. The HERCULES definition showed high specificity (93.4%) and low sensitivity (37.6%).

Conclusions: HERCULES-adapted criteria identified a subgroup of 7.9% nrSPMS patients in the real-world cohort of RISM, characterized by fewer post-conversion relapses and earlier PIRA onset. These findings reinforce the value of applying standardized algorithmic definitions of SPMS in registry-based studies.

Background: Serum neurofilament light chain (sNfL) has emerged as a biomarker reflecting neuroaxonal damage. The role of sNfL in predicting clinical outcome and guiding therapeutic management in multiple sclerosis (MS) is an ongoing research topic. We sought to evaluate sNfL utility for the prediction of achieving No Evidence of Disease Activity-3 (NEDA-3) among MS patients.

Methods: We conducted a prospective cohort study including MS patients with a single sNfL measurement at first clinical evaluation. Follow-up was performed every 6 months/clinical relapse and included clinical and MRI evaluation. The main outcome was NEDA-3 achievement during follow-up. sNfL levels were measured, using single-molecule-array (SIMOA) assay. sNfL age- and BMI-normalized Z-scores > 1.5 were defined as high. Linear regression analyses were performed to identify predictors of baseline sNfL Z-score and multivariable Cox proportional hazard regression models were used to evaluate predefined outcomes.

Results: We included 125 patients [age at sNfL measurement:40 ± 12, 30% men, 82% relapsing-remitting and 18% progressive MS]:37 treatment-naïve patients, 88 patients under Disease-Modifying-Treatment (DMT) with 19.1 (Interquartile Range:12.1-24.5) months median follow-up. Prior DMT use [β:-0.93; 95%CI:-1.48- -0.38 p-value:0.001] was negatively associated with baseline sNfL Z-scores. Gadolinium-enhancing lesions were associated with higher sNfL Z-scores [adjusted standardized linear regression coefficient-β:0.68; 95%CI:0.03-1.32; p-value:0.036], contrary to T2-weighted lesion activity (β:0.40; 95%CI:0.17-0.94; p-value:0.232). In treatment-naive patients, high sNfL Z-scores were associated with lower probability of achieving NEDA-3 during follow-up [hazard-ratio:0.35; 95%CI:0.13-0.96; p-value:0.041].

Conclusions: This study demonstrated that gadolinium-enhancing lesions, indicative of active inflammation, are associated with elevated sNfL Z-scores, contrary to T2-weighted lesion-activity and highlights the prognostic value of sNfL in achieving NEDA-3 in treatment-naive patients.