Canadian Journal of Neurological Sciences最新文献

Background: A critical step toward determining eligibility for experimental and clinical treatment with anti-amyloid therapies in Alzheimer's disease (AD) is to select appropriate subjects having a high likelihood of being Aβ+. We propose a clinical biomarker composite score, named Clinical β-Amyloid Positivity Prediction Score Plus (CAPS Plus), for Aβ+ prediction in people presenting with clinical Alzheimer's syndrome including both prodromal and mild AD.

Methods: The original CAPS incorporated scores from the neuropsychiatry inventory questionnaire, mini-mental state examination score loss per year and Fazekas score. Plasma p-tau-217, a novel addition to CAPS, was measured using the Simoa HD-X with the AlzPATH p-tau217 Advantage Plus assay. To incorporate p-tau-217 into CAPS Plus, an intra-cohort cut-off (>0.698 pg/ml) for p-tau217 was generated using logistic regression and Yoden's index. CAPS Plus had a maximum score of 5, with those ≥4 indicating a high probability of being Aβ+. The accuracy of CAPS Plus was computed through logistic regression and area under the receiver operating characteristic curve (AUROC) analysis.

Results: Of n = 44 patients, n = 25 (57%) were Aβ+. Plasma p-tau-217 was significantly higher in the Aβ+ subgroup (1.36 vs 0.46 pg/mL, p < 0.0001). The AUROC was 0.89 for a CAPS Plus score of 4 or more, suggesting excellent discrimination and improving the accuracy of the original CAPS (0.86). CAPS Plus has a notably better specificity (89%) than the original CAPS (80%) and p-tau-217 alone (74%).

Conclusion: CAPS Plus is potentially a useful screening tool for enrollment in anti-Aβ therapy and clinical trials for AD, specifically addressing people with prodromal and mild AD.

Objectives: Early diagnosis of amyotrophic lateral sclerosis (ALS) is essential for treatment initiation and symptom management, yet it remains challenging due to nonspecific symptoms and the lack of reliable diagnostic biomarkers. Although conventional MRI sequences such as T2* weighted and fluid-attenuated inversion recovery (FLAIR) have shown potential in identifying upper motor neuron abnormalities, their diagnostic utility in ALS is not well established. This study aimed to evaluate the sensitivity and specificity of brain T2* weighted and FLAIR MRI sequences in diagnosing ALS using prospectively collected data and to assess associations with disease severity.

Methods: Data were analyzed from 20 patients with ALS and 20 healthy controls enrolled at the Edmonton site of the Canadian ALS Neuroimaging Consortium 1 (CALSNIC-1) study. Single-slice 2D axial susceptibility-weighted echo planar imaging (SWEPI) and FLAIR images were independently rated by a blinded neurologist and radiologist for signs of corticospinal tract and motor cortex abnormalities. Sensitivity and specificity were calculated, and linear regression was used to examine associations with ALS Functional Rating Scale-Revised (ALSFRS-R) scores.

Results: T2* weighted and FLAIR MRI sequences showed high specificity (0.95 and 0.85, respectively) but low sensitivity (both 0.25) for ALS diagnosis. No significant correlation was found between imaging abnormalities and ALSFRS-R scores. Inter-rater reliability was poor (κ = 0.25 for SWEPI; κ = 0.14 for FLAIR).

Conclusion: While T2* weighted and FLAIR MRI sequences may have some specificity for ALS, our study suggests they are not sufficiently sensitive to be used as reliable diagnostic tools for ALS.

Background: Ocrelizumab (OCR) and rituximab (RTX) are anti-CD20 monoclonal antibodies (CD20Mabs) used in the treatment of relapsing multiple sclerosis (RMS). While both are effective at reducing relapses and new MRI lesions in clinical trials, real-world data on discontinuation rates and reasons for stopping therapy are limited.

Methods: This observational retrospective chart review included patients from two MS clinics in British Columbia, Canada. RMS patients treated with at least one infusion of OCR or RTX between January 2017 and March 2023 were included. Primary outcomes were reasons for discontinuation and discontinuation rates, with a secondary outcome of time to discontinuation.

Results: In total, 881 RMS patients were included, with 478 on OCR and 403 on RTX. A total of 16.9% of patients on OCR and 14.9% on RTX discontinued therapy over 1643 and 694 patient-years, respectively (p = 0.46). Reasons for discontinuation included: side effects (33.3%), insurance coverage (17.0%) and clinical or radiological disease activity (11.3%). Discontinuation rates at 12, 24 and 36 months were 3.5%, 8.2% and 12.5% for OCR, and 6.4%, 14.8% and 22.2% for RTX, respectively (p = 0.0089). Median time to discontinuation was 21 months on OCR and 11.5 months on RTX (p < 0.0001). On Cox regression analysis, treatment with RTX was the only variable associated with discontinuation (hazard ratio 1.72, 95% CI 1.20-2.45).

Conclusion: Discontinuation rates of CD20Mabs were low, and the most common reason for stopping was side effects. Although not designed for comparison, our study suggests RMS patients may persist longer on OCR than RTX.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by fatigable weakness and increased perioperative vulnerability. Postoperative myasthenic crisis, defined as respiratory failure requiring prolonged ventilation or re-intubation, remains a feared complication after surgical procedures such as thymectomy. The efficacy of preoperative interventions such as intravenous immunoglobulin (IVIg) and plasmapheresis remains uncertain. This review examines the evidence supporting risk stratification tools and immunomodulatory strategies to prevent postoperative myasthenic crisis. A comprehensive literature review was conducted focusing on studies evaluating the incidence, risk factors and preventive strategies for postoperative myasthenic crisis in MG patients. Particular emphasis was placed on clinical predictive models and randomized trials assessing preoperative IVIg and plasmapheresis. Recent data suggest the incidence of postoperative myasthenic crisis has declined to below 10%, largely due to advances in surgical technique and perioperative care. Established risk factors include bulbar involvement, reduced pulmonary function and prior crises. Risk prediction models such as the Leuzzi and Kanai scores offer clinically useful stratification. While older retrospective studies favored preoperative plasmapheresis, meta-analyses and randomized trials have yielded mixed results. Randomized trials of IVIg have shown no significant benefit in well-controlled patients, and both interventions carry notable risks and costs. Current evidence does not support the routine use of IVIg or plasmapheresis prior to surgery in all MG patients. A targeted, risk-based approach guided by validated predictive models is recommended to minimize unnecessary interventions and health care system costs.

Background: Chronic subdural hematoma (cSDH) is a prevalent neurosurgical condition, particularly in the elderly. In cases of surgical evacuation, there is conflicting evidence regarding the impact of early versus late mobilization on patient outcomes.

Method: To understand the current state of the literature, we performed a comprehensive systematic review of studies comparing early and late mobilization protocols in cSDH patients following surgical evacuation. We conducted a supplementary meta-analysis to assess the effects of early versus late mobilization for recurrence and postoperative complication outcomes.

Results: Of the 1295 identified articles, 4 studies comprising 622 patients were included. Early mobilization (EM) was typically defined as ambulation ≤ 48 hours post-surgery and late mobilization as bed rest for ≥48 hours or more, though definitions varied between studies. EM did not increase cSDH recurrence in any study. Two studies reported decreased medical complications in the EM group. Two studies suggested a shorter hospital stay with EM, and one study reported significantly better functional recovery on follow-up. A supplementary meta-analysis did not find any significant differences in recurrence or medical complications across studies.

Conclusion: EM after cSDH surgery may reduce postoperative complications and potentially improve recovery without appearing to affect recurrence rates. However, data interpretation was limited by heterogeneous study designs, definitions of mobilization and outcome measures. Further multicenter trials with consistent protocols and outcome scales are warranted to further establish optimal mobilization strategies.