Journal of Neurology最新文献

Background and purpose: Lobar intracerebral hemorrhage (ICH) is associated with a high risk of recurrence, particularly in elderly patients, where cerebral amyloid angiopathy (CAA) is often the primary cause. Diagnostic markers of CAA-related ICH, including subarachnoid hemorrhage (SAH) and finger-like projection (FLP), have recently been developed. Here, we aimed to explore the associations between SAH, FLP and the risk of ICH recurrence in lobar ICH patients.

Methods: We analyzed data from consecutive lobar ICH patients using the method of cohort study. We divided them into 4 groups on the basis of the presence or absence of SAH and FLP on CT imaging. The Cox regression model and competing risk model were used to analyze the associations of SAH and FLP with the risk of ICH recurrence at 1 year.

Results: In total, 353 patients with lobar ICH (median age 74 [62, 81] years, 57.2% male) were included in our study. During follow-up, recurrence occurred in 34 patients (10.6%), and 90 patients (28.1%) died. The competing risk model revealed that patients in the SAH + FLP- (HR 2.88, 95% CI 1.12-7.44, p = 0.03) and SAH + FLP + (HR 8.38, 95% CI 3.40-20.66, p < 0.001) groups had higher risks of ICH recurrence within 1 year than did those in the SAH-FLP- group.

Conclusion: SAH is an important predictor of ICH recurrence, and this predictive ability is further enhanced when FLP is present. These findings suggest that SAH, especially with FLP, can be a valuable tool for assessing prognosis in lobar ICH patients.

Introduction: The large-scale approval of anti-amyloid monoclonal antibodies for treating Alzheimer's disease (AD) has raised concerns about their safety due to treatment-emergent amyloid-related imaging abnormalities (ARIA).

Methods: We present two cases of patients diagnosed with mild cognitive impairment due to AD who were enrolled in the GRADUATE I clinical trial. They received subcutaneous gantenerumab every two weeks during the study period.

Results: Both patients experienced recurrent ARIA-Effusion/Edema type (ARIA-E). One developed symptomatic and severe ARIA, leading to hospitalization and study withdrawal. We report a long follow-up post-randomization (65 and 54 months), during which the adverse events did not appear to have a negative impact on disease progression. Additionally, one patient had a negative amyloid-PET over a year after treatment cessation.

Discussion: These cases suggest that recurrent ARIA-E do not inevitably lead to accelerated progression, instead, may relate to possible long-term benefits. The mechanisms underlying these findings warrant further real-life evidence.

Introduction: While cerebral amyloid angiopathy is likely responsible for intracerebral hemorrhage (ICH) occurring in superficial (grey matter, vermis) cerebellar locations, it is unclear whether hypertensive arteriopathy (HA), the other major cerebral small vessel disease (cSVD), is associated with cerebellar ICH (cICH) in deep (white matter, deep nuclei, cerebellar peduncle) regions. We tested the hypothesis that HA-associated neuroimaging markers are significantly associated with deep cICH compared to superficial cICH.

Patients and methods: Brain MRI scans from consecutive non-traumatic cICH patients admitted to a referral center were analyzed for cSVD markers. Clinical risk factors, left ventricular hypertrophy (LVH, a marker of hypertensive end-organ damage), and neuroimaging markers were compared between patients with deep and superficial cICH in univariate and multivariable models.

Results: Hypertension and LVH were more common among 83 (64%) patients with deep cICH compared to 46 (36%) with superficial cICH. HA-related markers such as peri-basal ganglia white matter hyperintensity pattern, deep lacunes, severe basal ganglia enlarged perivascular spaces, and deep cerebral microbleeds (CMBs) were more common among those with deep vs. superficial cICH. Strictly lobar CMBs were less common among patients with deep cICH, whereas mixed-location CMBs were more common. After multivariable adjustment, LVH (aOR 4.06, 95% CI [1.22-13.50], p = 0.02), deep lacunes (aOR 6.02, 95% CI [1.46-24.89], p = 0.01), and strictly lobar CMBs (aOR 0.09, 95% CI [0.02-0.45], p < 0.01) remained significantly associated with deep cICH.

Discussion and conclusion: Because HA-associated markers are significantly associated with deep cICH, it is likely HA is the dominant underlying microangiopathy of this ICH subtype.

Plasma tau phosphorylated at threonine 181 (p-tau181) and 217 (p-tau217) have demonstrated high accuracy for Alzheimer's disease (AD) diagnosis, defined by CSF/PET amyloid beta (Aβ) positivity, but most studies have been performed in research cohorts, limiting their generalizability. We studied plasma p-tau217 and p-tau181 for CSF Aβ status discrimination in a cohort of consecutive patients attending an academic memory clinic in Spain (July 2019-June 2024). All patients had CSF AD biomarkers performed as part of their routine clinical assessment. Aβ positivity was defined with a local cut-off of CSF Aβ_1-42 < 600 pg/mL; in patients with borderline Aβ_1-42 values or when there was a mismatch between the Aβ and the T status (T + if CSF p-tau181 ≥ 65 pg/mL), a ratio Aβ_1-42/Aβ_1-40 < 0.07 was used. Plasma p-tau217 and p-tau181 were measured retrospectively, from blood samples collected at first visit, with Fujirebio Lumipulse and Quanterix Simoa assays, respectively. We included 468 patients (mean age 67 years, 50% female, 61% Aβ positive). Plasma p-tau217 outperformed plasma p-tau181 in discriminating CSF Aβ status (AUC 0.95 vs 0.90, p = 0.005). A 97.5% sensitivity and specificity plasma p-tau217 algorithm, classifying patients into three groups of Aβ probability (Low, Intermediate and High), resulted in 67% of patients in the Low and High groups, having their Aβ status predicted (as negative and positive, respectively) with 96% accuracy. The remaining 33% in the Intermediate group were candidates to undergo CSF/PET testing. A model with a 10% variation in p-tau217 levels yielded small changes in accuracy (95%). In conclusion, plasma p-tau217 could have discriminated CSF Aβ status in two-thirds of patients with very high accuracy in a memory clinic cohort. These results support the implementation of plasma p-tau217 as an initial diagnostic tool in memory clinics for AD diagnosis, reducing the need for more invasive/expensive testing.

Introduction: The current literature on the prevalence and potential association between disease-modifying therapies (DMTs) and cancer risk in the MS population has yielded mixed findings.

Methods: This study aimed to estimate cancer prevalence and cancer risk in patients with MS (PwMS) under prolonged DMT exposure. Database search include: MEDLINE PUBMED, SCOPUS, and Google Scholar.

Results: A total of 13 studies involving 333,779 PwMS were included, reporting cancer events over periods ranging from 6 to 32 years. The aggregated pooled prevalence of cancer events in MS patients receiving disease-modifying therapies (DMTs) was 3.8% (95% CI 2.6, 5.2%), with substantial heterogeneity (I² = 99.7%, p = 0). Two studies compared cancer events in MS patients who received DMTs versus those who did not. The relative risk of cancer associated with DMTs was 0.8 (95% CI 0.59-1.31, I² = 93.6%, p = 0.53), indicating no significant increase in cancer risk due to DMTs. Breast and basal cell carcinomas had a high prevalence (18.4% and 11.3, respectively) in PwMS under DMTs.

Conclusion: This study reports a 3.8% pooled prevalence of cancer in PwMS receiving DMTs. The findings of this study suggest that DMTs alone do not increase cancer risk in PwMS. Breast cancer and basal cell carcinoma had the highest prevalence among the different types of cancer.

Fluid biomarkers play important roles in many aspects of neurodegenerative diseases, such as Huntington's disease (HD). However, a main question relates to how well levels of biomarkers measured in CSF are correlated with those measured in peripheral fluids, such as blood or saliva. In this study, we quantified levels of four neurodegenerative disease-related proteins, neurofilament light (NfL), total tau (t-tau), glial fibrillary acidic protein (GFAP) and YKL-40 in matched CSF, plasma and saliva samples from Huntingtin (HTT) gene-positive individuals (n = 21) using electrochemiluminescence assays. In addition, salivary levels of NfL, t-tau, and GFAP were quantified from a larger cohort (n = 95). We found both positive and negative correlations in the levels of these biomarkers among different biofluids. Most notably, in contrast to the significant positive correlations observed between CSF and plasma levels for NfL and GFAP, we detected significant negative correlations between the CSF and saliva levels of NfL and GFAP. With regard to clinical measures, both plasma and CSF levels of NfL were significantly positively correlated with Total Motor Score and chorea, whereas saliva levels of NfL showed significant correlations in the opposite direction. Additional correlations between salivary biomarkers with clinical data, adjusting for age, sex and CAG repeat length, confirmed that salivary NfL was significantly negatively associated with chorea scores in manifest HD, but not premanifest (PM), individuals. In contrast, salivary t-tau was positively associated with measures of cognition in PM participants. These findings suggest that salivary levels of NfL and t-tau proteins may exemplify non-invasive biomarkers for disease symptoms at different stages of illness. Further, these findings highlight the notion that different forms of disease proteins exist in different biological fluids.

Positional downbeat nystagmus (pDBN) is a common finding in dizzy patients, with etiologies ranging from benign paroxysmal positional vertigo (BPPV) to central vestibular lesions. Although peripheral pDBN often presents with distinct clinical features that differentiate it from BPPV, diagnosing its etiology can be challenging. A thorough clinical evaluation, including the physical characteristics of the nystagmus, response to positional maneuvers, and neurological findings, is often sufficient to diagnose conditions that provoke pDBN such as anterior canal BPPV, atypical posterior canal BPPV, and central causes. However, when the diagnosis remains uncertain, a brain MRI focusing on the posterior fossa is required. In human lesion models, the vestibulocerebellum (nodulus and uvula) is commonly implicated in pDBN. Central causes of positional vertigo include vascular events, tumors, immune mediated, toxicity, and demyelinating diseases. Ultimately, a significant number of cases will remain without a clear etiology despite extensive workup. Clinicians should be vigilant for signs suggesting central vestibular dysfunction at follow-up in cases of apparently refractory BPPV. The aim of this work is to provide a comprehensive overview of pDBN and offer a logical approach to its assessment, along with recommendations for future research directions.

Background: Conventional medical management, while essential, cannot address all multifaceted consequences of Parkinson's disease (PD). This pilot study explores the potential of a co-designed creative arts therapy on health-related quality of life, well-being, and pertinent non-motor symptoms.

Methods: We conducted an exploratory pilot study with a pre-post design using validated questionnaires. Eight individuals with PD participated in the program. The investigated intervention was a 10-week creative arts therapy with weekly 90-120-min sessions, guided by three creative therapists. Participants were allowed to autonomously select from multiple creative media based on their personal preferences. Explored co-primary outcomes included health-related quality of life (PDQ-39), well-being (ICECAP-A), anxiety/depression (HADS), executive functioning (BRIEF-A), resilience/mental flexibility (FIT-60), and self-efficacy (GSES). We used paired sample t tests for pre-post analysis of the co-primary outcomes and Wilcoxon signed-rank tests for PDQ-39 sub-scores. We also included aesthetic responsiveness (AReA) and healthcare consumption (IMCQ adapted for PD) questionnaires reported as descriptive statistics.

Results: The results showed a significant reduction in anxiety and an increase in well-being. We also observed a slight improvement in cognitive functioning. Finally, we noted a reduction in healthcare consumption (fewer visits at neurologists, specialized PD nurses, and allied healthcare professionals).

Conclusion: These findings cautiously suggest that our co-designed, multi-media creative arts therapy has the potential to increase well-being and reduce anxiety, while reducing healthcare consumption. These preliminary findings support the need for a larger, randomized controlled trial to explore the therapeutic potential of creative arts therapy in PD care.