Journal of Neurology最新文献

Background: Huntington's disease (HD) is caused by CAG trinucleotide expansion on chromosome 4, leading to mutant Huntingtin production. Premanifest carriers show no obvious clinical signs, and early symptoms progress slowly. Fluid biomarkers like neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), measurable in cerebrospinal fluid and serum (sNfL, sGFAP), offer potential predicting HD progression.

Objective: To assess the role of sGFAP and sNfL and clinical biomarkers in different disease stages and correlate with disease progression.

Methods: HD mutation carriers were categorized into clinical stages according to their motor symptoms and functional capacities. The Unified HD Rating Scale, cognitive assessments and olfactory tests were used to characterize the patients clinically. Furthermore, sNfL and sGFAP levels were assessed.

Results: We consecutively included 44 HD mutation carriers (13 premanifest HD (preHD), 18 in early (early HD) and 13 in advanced (advanced HD) disease stages) and 19 healthy controls (HC). Advanced HD patients performed worse on all clinical tasks and had higher sGFAP and sNfL levels compared to other groups (all p values < 0.05). We did not find difference in sGFAP levels between the preHD, early HD and HC group  (all p values > 0.05). In contrast, sNfL levels differed significantly between preHD and early HD, and HC (all p values < 0.05). ROC curve analysis revealed that the AUC of sGFAP (0.970) exhibited superior discriminatory accuracy compared to sNfL (0.791) levels in separating advanced from early HD patients. By contrast, ROC curve analysis revealed that the AUC of sNFL (0.988) exhibited superior discriminatory accuracy compared to sGFAP (0.609) levels in separating all HD mutation carriers from HC.

Conclusions: Our study indicates that sNfL can detect changes in very early and premanifest HD stages, whereas sGFAP showed differences in more advanced stages only.

Objectives: To determine whether extending anti-CGRP mAb treatment beyond 3 years influences migraine course, we analyzed migraine frequency during the first month of treatment discontinuation following three 12-month treatment cycles (Ts).

Methods: This multicenter, prospective, real-world study enrolled 212 patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who completed three consecutive Ts of subcutaneous anti-CGRP mAbs. Discontinuation periods (D1, D2, D3) were defined as the first month after T1, T2, and T3, respectively. The primary endpoint was the ≥ 50% response rate at D3 compared to D2. Secondary endpoints included changes in monthly migraine days (MMD), monthly headache days (MHD), monthly analgesic intake (MAI), numerical rating scale (NRS), Headache Impact Test-6 (HIT-6), ≥ 50% response rate at D3 versus D1 and D2, and relapse rates to CM or medication overuse.

Results: At D3 vs. D2, significant improvements (p < 0.001) were observed in the ≥ 50% response rate (77.8% vs. 53.8%), MMD (- 2.1 ± 1.7), MHD (- 2.9 ± 2.4), MAI (- 2.6 ± 2.4), NRS (- 0.7 ± 1.3), and HIT-6 (- 7.2 ± 5.9), with lower relapse rates to CM (2.3% vs. 18%) and medication overuse (1.3% vs. 10.1%). Compared to D1, D3 demonstrated greater benefits (p < 0.001) in MMD (- 2.6 ± 1.9), MHD (- 5.8 ± 3.3), MAI (- 4.9 ± 3.4), NRS (- 1 ± 1.6), and HIT- 6 (- 9.4 ± 7), alongside higher ≥ 50% response rates (77.8% vs. 25%) and reduced relapses to CM (2.3% vs. 67.7%) and medication overuse (1.3% vs. 34.2%).

Discussion: Three years of anti-CGRP mAb treatment revealed a progressive increase in the proportion of ≥ 50% responders (D1: 25%; D2: 53.8%; D3: 77.8%) and substantial reductions in migraine burden, suggesting that prolonged treatment may favorably modify migraine course.

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.