Neurology最新文献

Objectives: Neuronal autoantibodies are linked to cognitive impairment in neurologic diseases and can be associated with tumors. In patients with cancer, IgA/IgM N-Methyl-D-Aspartate receptor (NMDAR) autoantibodies are most common, yet their clinical relevance is unclear. We assessed cognitive function in cancer patients with serum NMDAR autoantibodies and compared the results with matched controls.

Methods: For this cross-sectional case-control study in Germany, we recruited 1,055 patients with cancer and tested for neuronal serum autoantibodies. Cognitive assessment was performed blinded to antibody status and after excluding patients with potential confounders of cognitive dysfunction. The tests included verbal memory (Rey Auditory Verbal Learning Test), visuospatial memory (Rey-Osterrieth Complex Figure), and working memory.

Results: Fifty-six patients with IgA/IgM NMDAR autoantibodies (median age 61.0 years [28.0-86.0], 35.7% female) were matched 1:1 to autoantibody-negative patients by age, sex, cancer type, and stage. Autoantibody-positive patients showed impairments in verbal memory (mean score ± SD: 9.7 ± 3.6 vs 11.4 ± 3.2; p = 0.01; Cohen d = 0.49), visuospatial memory (19.4 ± 7.0 vs 22.6 ± 5.6; p = 0.01; d = 0.50), and working memory (6.2 ± 1.9 vs 7.0 ± 2.1; p = 0.04; d = 0.40). Memory function decreased with increasing IgA NMDAR autoantibody levels. Both groups performed similarly on measures of attention, executive function, and verbal fluency.

Discussion: Serum NMDAR autoantibodies are associated with isolated memory deficits in patients with cancer and might serve as a potential biomarker for cancer-related cognitive impairment.

A 41-year-old, left-handed man was admitted to the hospital for workup of a 3-week history of headache, constant vertigo, diplopia, and left hemiparesis. An initial diagnosis was made, and the patient was treated with symptomatic improvement. He was discharged and then presented a few weeks later with recurrence of his symptoms which required additional diagnostic workup. This ultimately led to a diagnosis of a rare disorder. In this case report, we outline his clinical course and our reasoning at each step which led to our eventual definitive diagnosis.

Background and objectives: Cerebral small vessel disease (cSVD) is a major contributor to stroke and dementia, often beginning decades before clinical symptoms appear. While MRI markers offer critical insight into cSVD burden, blood-based biomarkers may offer a more accessible complement to neuroimaging. We investigated whether plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are associated with MRI markers of cSVD in middle-aged adults and whether they are associated with longitudinal progression.

Methods: We conducted a retrospective analysis of prospectively collected data from the UK Biobank cohort. Participants aged 40-60 years at baseline (2006-2010) with plasma biomarker measurements and follow-up MRI scans (2014-2019) were included. Individuals with prevalent neurologic conditions were excluded. We assessed 3 MRI markers of cSVD: white matter hyperintensities (WMHs), fractional anisotropy (FA), and mean diffusivity (MD). Three analytical approaches were used: associations between baseline biomarkers and future MRI markers, associations between baseline biomarkers and longitudinal MRI changes, and correlations between longitudinal biomarker and MRI changes. Robust regression models were adjusted for age, sex, and cerebrovascular risk factors.

Results: Among 5,270 participants (mean age 54.2 ± 7.8 years; 53.4% female), higher baseline GFAP levels were significantly associated with all 3 MRI cSVD markers-WMH volume (β = 0.06, 95% CI 0.01-0.10, p = 0.014), FA (β = 0.08, 95% CI 0.03-0.13, p = 0.001), and MD (β = 0.14, 95% CI 0.09-0.18, p < 0.001)-after a follow-up of 9 years. Among 1,317 participants with longitudinal MRI data, baseline GFAP was associated with progression of FA (β = 0.012, 95% CI 0.001-0.023, p = 0.033) and MD (β = 0.020, 95% CI 0.003-0.038, p = 0.025) over 3 years. NfL was not significantly associated with any MRI cSVD marker. Longitudinal changes in both biomarkers showed no significant associations with concurrent MRI progression.

Discussion: Plasma GFAP levels were associated with subsequent changes in white matter integrity among middle-aged adults, suggesting potential utility as an early indicator of cSVD vulnerability. These associations, observed nearly a decade after biomarker measurement, highlight GFAP's potential for long-term risk stratification. Blood-based biomarkers may support earlier identification of individuals at heightened risk of cSVD, enabling preventive strategies when interventions may be most effective.

Background and objectives: "Motor reserve" refers to the brain's dynamic resilience against dopaminergic degeneration in Parkinson disease (PD). However, its clinical significance remains unclear because of critical limitations, including the lack of data on its longitudinal trajectories. Using Parkinson's Progression Markers Initiative data with serial dopamine transporter (DAT) imaging from the drug-naive stage, we investigated its trajectories, determinants, and prognostic implications.

Methods: This retrospective observational cohort study assessed motor reserve using 2 complementary approaches. The residual-based approach calculated deviations in Movement Disorders Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3 scores from expected values derived from a linear regression model incorporating putamen DAT specific binding ratio (putamen SBR), age, sex, and disease duration. The interaction-based approach extended this model by introducing interaction terms between putamen SBR and each factor, analyzing the corresponding β coefficients. We examined motor reserve's cross-sectional associations with clinical parameters, its mediation effects, and its longitudinal trajectories-up to 4 years-based on DAT imaging data availability, while identifying factors influencing its changes. Finally, we assessed its impact on long-term prognosis using Cox proportional hazards and linear mixed-effects models (LMEMs).

Results: We included 566 drug-naive patients with PD (median age 62.3 [interquartile range 56.3-69.6] years; 33.7% female). At baseline, regular physical activity was significantly associated with motor reserve in both approaches, with mediation analysis indicating that motor reserve largely mediated the effect of physical activity on motor symptom improvement. Longitudinally, adequate medication and sustained regular physical activity levels were strongly associated with a slower early-years decline in motor reserve. It is important to note that early-years average motor reserve, not the baseline value, was a strong predictor of long-term motor outcomes (Cox: Hoehn/Yahr stage 3, hazard ratio = 0.50, 95% CI 0.37-0.66; LMEMs: MDS-UPDRS Part 3 score, fixed-effects standardized interaction coefficient = -0.57, 95% CI -0.79 to -0.35). These findings were further validated through propensity score matching.

Discussion: Maintaining motor reserve in the early years after diagnosis strongly predicts favorable long-term motor outcomes, with adequate treatment and regular physical activity-both modifiable factors-supporting this maintenance. Because our study includes early-stage, drug-naive PD, further research in later stages is warranted.

Trial registration information: ClinicalTrials.gov (NCT01141023). A link to the trial registry page is clinicaltrials.gov/ct2/show/NCT01141023.