Neurology and Therapy最新文献

Introduction: In clinical practice, switching between preventive treatments is common in patients with chronic migraine when efficacy is insufficient or tolerability is poor. With the advent of more targeted therapies, such as onabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies, treatment options have expanded, yet evidence to guide sequencing decisions remains limited. The aim of this study was to investigate the real-world effectiveness of switching between onabotulinumtoxinA and erenumab and vice versa in patients with chronic migraine who showed inadequate response to their initial preventive treatment.

Methods: This retrospective real-world study included patients with chronic migraine treated at the Headache Center, Charité-Universitätsmedizin Berlin between October 2022 and December 2024. Eligible patients had received both onabotulinumtoxinA and erenumab in sequence, switching as a result of insufficient efficacy or tolerability. A very good response was defined as a ≥ 50% reduction in monthly headache days in the third month after the switch.

Results: Out of 632 screened patients, 78 met the inclusion criteria (84.6% female; mean age 43 ± 14 years). Of these, 54 switched from onabotulinumtoxinA to erenumab, and 24 from erenumab to onabotulinumtoxinA. A very good response was observed in 14 patients (17.9%): 10/54 (18.5%) after switching to erenumab and 4/24 (16.7%) after switching to onabotulinumtoxinA.

Conclusion: Sequential preventive treatment with onabotulinumtoxinA and erenumab resulted in a very good response in about one-fifth of patients. Although both treatments target the CGRP pathway, their distinct mechanisms of action may still provide benefit when switching therapies after initial failure.

This review summarizes current concepts in our understanding of stroke anatomy, pathophysiology of cerebral hypoperfusion, and collateral circulation. It also provides an evidence-based update in stroke trials and treatments assessed using PRISMA guidelines. Intravenous thrombolysis, endovascular thrombectomy for anterior circulation strokes, blood pressure control after endovascular thrombectomy, and medical management principles are discussed. Endovascular thrombectomy and medical therapy improves functional independence at 90 days in anterior circulation strokes even in late windows up to 24 h post symptom onset regardless of infarct core size. Intensive systolic blood pressure control acutely post thrombectomy is associated with harm and worse outcomes. This review also provides an evidence-based update on neurorehabilitation strategies with emerging interventions such as brain-computer interface and robotics having the potential to maximize neuroplasticity for potential improvement and recovery post stroke.

Introduction: Parkinson's disease is the second most common neurodegenerative disorder. In advanced Parkinson's disease, subcutaneous (SC) infusion therapies represent minimally invasive and reversible treatment options. In the United Kingdom (UK), licensed SC infusion therapies include apomorphine and foslevodopa-foscarbidopa; both represent effective and generally well-tolerated therapies, although uncertainties regarding their relative efficacy, safety and costs remain.

Methods: The relative efficacy and safety of apomorphine and foslevodopa-foscarbidopa was assessed via Bucher indirect treatment comparison (ITC) of TOLEDO (NCT02006121) and M15-736 (NCT04380142) data, with findings used to support a cost-minimisation analysis (CMM). Thirteen outcomes were evaluated. Efficacy and safety outcomes were measured as mean differences and risk differences, respectively. The CMM, conducted from a UK healthcare payer perspective, considered treatment acquisition and concomitant therapy costs over a 6.34-year horizon (obtained from a published observational study).

Results: Bucher ITC results provided evidence for a comparable efficacy for apomorphine and foslevodopa-foscarbidopa in advanced Parkinson's disease. ITCs also indicated comparable safety, although a trend in favour of apomorphine was identified for hallucinations and most infusion site reactions assessed. The CMM demonstrated a clear per-patient cost benefit for apomorphine versus foslevodopa-foscarbidopa (£120,173.70), primarily driven by lower drug acquisition costs.

Conclusion: The main difference between UK licensed SC infusion therapies for advanced Parkinson's disease relates to cost as opposed to clinical outcome, with some evidence for improved tolerability of apomorphine. This supports the continued use of apomorphine as first-line SC infusion treatment for advanced Parkinson's disease in UK clinical practice.

Introduction: The pathogenesis of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) remains uncertain. Our work sought to examine the cortical gyrification pattern and its corresponding functional connectivity alterations, along with the underlying neurotransmitter information, in LID of PD.

Methods: We included 30 PD patients with LID (PD-LID group), 30 without LID (PD-NLID group), and 30 age- and gender-matched healthy controls (HC group). Regional cortical gyrification computed by local gyrification index (LGI) and seed-based resting-state functional connectivity (RSFC) were employed. We adopted the JuSpace toolset to further validate whether the spatial patterns in RSFC changes were linked with specific neurotransmitters.

Results: Compared to PD-NLID, PD-LID demonstrated lower regional LGI in the right inferior frontal gyrus (rIFG) (pars opercularis) and decreased RSFC between the rIFG and the left inferior parietal lobule (IPL). The decreased RSFC was correlated with the spatial distribution of the serotonin transporter (SERT) in the serotonergic system. In particular, the level of rIFG (pars opercularis) LGI was negatively related to the severity of LID and demonstrated good performance in detecting patients with PD-LID.

Conclusion: Our main findings indicated that the hypogyrification of rIFG and its corresponding functional connectivity reduction with left IPL, as well as the underlying serotonergic neurotransmitter distribution, could underlie the neurobiological underpinnings of LID.

Introduction: Migraine headache not only is associated with high levels of suffering but also represents a considerable socioeconomic challenge. It is linked to various psychological and physiological impairments, including sensorimotor and somatosensory dysfunction, like those observed in other persistent pain syndromes. This study aims to determine whether individuals with high-frequency episodic (HFEM) or chronic migraine (CM) exhibit differences in somatosensory perception compared to healthy individuals and to explore potential correlations with neuropsychological features.

Methods: Using a cross-sectional design, we assessed individuals with HFEM or CM (n = 45) and healthy controls (n = 25) using quantitative sensory testing (QST), conditioned pain modulation testing and neuropsychological questionnaires such as the Central Sensitization Inventory (CSI) and the Toronto Alexithymia Scale (TAS-20).

Results: Data from 45 participants (39 females) with HFEM or CM and a healthy control group of 25 individuals (21 female) were analysed. Median (range) number of monthly headache days of was 12.3 (6) in the migraine group. Statistically significant differences were found only in the assessment of central sensitization (p < 0.0010) but not for QST parameters. Correlations with QST parameters were generally weak, only the wind-up ratio (WUR) showing weak to moderate monotonic associations with both emotion- and somatosensory-associated parameters.

Conclusion: Overall, the results provided no evidence of significant differences between the migraine and healthy control groups. The lack of significant differences might be attributed to methodological limitations. However, the comprehensive and standardized implementation of QST strictly following the protocol of the German Research Network on Neuropathic Pain (DFNS), the selection of robust questionnaires, uniform diagnostic criteria and rigorous statistical analysis represent methodological strengths and support the validity of the results. Nevertheless, these findings, which partly contrast with existing literature, may reflect limitations of the sample and methodology and should be interpreted with caution.

Introduction: Risdiplam, an oral splicing modifier for the survival motor neuron-2 gene (SMN2), is approved for treating spinal muscular atrophy (SMA). While its safety and efficacy have been demonstrated in global trials, there are limited real-world data on its safety in Japanese patients with SMA. This all-case postmarketing surveillance (PMS) study aimed to assess the safety and usage patterns of risdiplam in Japan.

Methods: This 12-month interim analysis is part of an ongoing PMS study that includes Japanese patients with SMA who have received risdiplam. The full observation period for this PMS is 24 months from the initiation of risdiplam treatment. Safety data, including adverse drug reactions (ADRs), were collected from case report forms (CRFs) submitted by participating healthcare facilities. ADRs were coded using the MedDRA/J classification.

Results: This study included 538 patients with SMA from 259 institutions in Japan between August 2021 and August 2022. The median age (minimum-maximum) at enrolment was 22.5 (0-83) years, and 51.5% of patients were male. SMA type II (47.2%) and III (27.9%) were the most common phenotypes. The median treatment duration was 366.0 days, and 86.1% of patients continued risdiplam treatment. ADRs were reported in 112 patients (20.8%), while serious ADRs were reported in eight patients (1.5%). The most common ADRs (classified by MedDRA System Organ Class) were gastrointestinal disorders in 86 (16.0%) patients (diarrhoea in 43 [8.0%], faeces soft in 23 [4.3%] and stomatitis in 10 [1.9%] patients). Exploratory analysis suggested that advanced age, comorbidities and concomitant medication use might be associated with an increased incidence of gastrointestinal ADRs.

Conclusions: This 12-month interim analysis of PMS data indicated that risdiplam was well tolerated among Japanese patients with SMA, consistent with previous clinical trial findings. A comprehensive evaluation of the safety and efficacy of risdiplam will be provided in the final 24-month analysis.

Introduction: Alzheimer's disease (AD) is among the costliest of illnesses for the elderly, placing a significant burden on healthcare systems and caregivers. Despite the depth of evidence, reviews lack a holistic assessment of such costs, falling short of illustrating unmet medical needs. The objective of this review was to therefore characterize the total societal economic burden of AD, broken down by care setting and disease severity.

Methods: A targeted literature search of systematic reviews, cost-of-illness, and observational studies published between 2013 and 2024 was conducted on MEDLINE and Embase to identify articles reporting the economic burden of AD. Grey literature was hand-searched. Both direct and indirect costs were assessed, including societal burdens not often reported by AD-specific cost-of-illness studies such as financial delinquencies.

Results: In total, 81 articles were reviewed in depth, including 20 systematic reviews and 61 studies or reports. Findings consistently demonstrated that societal costs of AD or dementia typically increased by at least 50% between consecutive severity levels, increasing with disease progression. Informal caregiving often comprised close to half of societal costs, regardless of care setting, disease severity, or region. While studies reporting costs of mild cognitive impairment (MCI) were limited, the economic burden reported for this stage was appreciable compared to mild AD. Evidence for the impact of AD, as early as MCI, on quality of life (e.g., emotional and mental strain) and personal financial management capabilities was also identified.

Conclusion: This review provides a comprehensive overview, from studies spanning over more than a decade, of the substantial societal economic burden associated with AD, across cost categories, care settings, disease stages, and regions. This review may be used to inform health economic evaluations of novel interventions with potential to reduce the enormous and growing global economic burden of AD and dementia.

Introduction: Branch atheromatous disease (BAD) is a common subtype of acute ischemic stroke characterized by atherosclerosis. Patients with BAD are highly prone to early neurological deterioration. Intravenous thrombolysis can restore blood flow. We investigated the efficacy of tenecteplase (TNK) intravenous thrombolysis in BAD treatment.

Methods: We retrospectively examined data from patients with BAD admitted to 13 hospitals in Zhengzhou between January 2020 and December 2024. Participants were categorized into TNK and dual antiplatelet therapy (DAPT) groups. Propensity score matching was performed to reduce subgroup heterogeneity.

Results: We included 1980 patients (TNK: 621, DAPT: 1359) matched in 522 pairs of participants. After propensity score matching, intravenous TNK administration within 4.5 h of stroke onset was associated with reduced early neurological deterioration (unadjusted odds ratio [OR] = 1.796, 95% confidence interval [CI]: 1.303-2.477, P < 0.001) and improved clinical outcomes 90 days post-stroke. In the TNK group, more patients achieved good functional prognosis (modified Rankin scale [mRS] 0-1; unadjusted OR = 0.648, 95% CI 0.506-0.830, P < 0.001) and were functionally independent (mRS 0-2) at 90 days post-stroke (unadjusted OR = 0.725, 95% CI 0.546-0.963, P = 0.026). The dependence rate (mRS ≥ 4) in the TNK group was significantly lower than that in the DAPT group (unadjusted OR = 1.576, 95% CI 1.062-2.339, P = 0.024). Mortality (unadjusted OR = 2.351, 95% CI 0.605-9.143; P = 0.217), symptomatic intracranial hemorrhage (unadjusted OR = 0.595, 95% CI 0.215-1.650; P = 0.319), and other bleeding events (unadjusted OR = 1.371, 95% CI 0.680-2.764; P = 0.378) did not differ significantly.

Conclusion: TNK intravenous thrombolysis may be a safe and effective treatment for patients with BAD.

Introduction: Injectable drugs, including interferon-beta and glatiramer acetate (collectively referred to as BRACE), dimethyl fumarate (DMF), and teriflunomide (TER) are commonly used as initial disease-modifying therapies (DMTs) for multiple sclerosis (MS), especially in patients with favorable prognostic profiles. Despite their continued use, real-world comparative data on long-term treatment persistence and comprehensive disease control remain limited.

Methods: This retrospective study analyzed 400 patients initiating BRACE (n = 132), DMF (n = 130), or TER (n = 138) between 2014 and 2024 in routine clinical practice. Persistence was defined as treatment continuation without interruptions for ≥ 6 months. Effectiveness was evaluated using cumulative no evidence of disease activity (NEDA)-2 and NEDA-3 status. NEDA-2 included the absence of clinical relapses and confirmed disability progression; NEDA-3 additionally required the lack of MRI activity. Loss of NEDA status was marked from the first occurrence of any criterion failure.

Results: Injectables showed significantly higher discontinuation rates (70.5%) compared to patients with TER (42.0%) and DMF (48.5%) (p < 0.001), with divergence evident after year 3. Median time to discontinuation was 3.55 years for BRACE, 4.88 years for TER, and 5.78 years for DMF. No significant differences were observed in NEDA-2 or NEDA-3 survival. Patients with TER showed higher NEDA-2 rates at 1 year (87%) than DMF (74%) and BRACE (77%) (p < 0.05), but this difference was not sustained over time.

Conclusions: In real-world practice, oral therapies tend to be associated with better long-term persistence than injectables, while effectiveness measured by cumulative NEDA-3 remains comparable. These findings highlight the role of patient-centered factors such as tolerability and administration route in treatment adherence, supporting cumulative NEDA as a meaningful outcome in clinical decision-making.

Cladribine tablets (CladT) for relapsing multiple sclerosis help reset the immune system with short treatment courses over 2 years. This analysis of MAGNIFY-MS contrasted clinical outcomes with changes in immune cells, proteins and genes over 2 years in 270 participants. Most immune cells decreased 3 months after starting CladT. Gradual recovery was seen in naïve, regulatory, and transitional B cells starting at month (M)3 and M6. Gene activity related to immune response changes was also reported. Fewer cells producing pro-inflammatory signals and more cells producing anti-inflammatory signals were detected by M24. Immunoglobulin levels mostly remained normal, and a marker of neuroaxonal damage (serum neurofilament light chain) was decreased. Significant reductions in lesion count occurred from M2 onwards. Annualised relapse rate was 0.11 (95% confidence interval: 0.09, 0.15). Over 90% of participants were free of 6-month confirmed disability progression, around 87% had no confirmed progression on 9-hole peg test and timed 25-foot walk. No significant correlations were seen between clinical parameters and lymphocyte dynamics. The safety profile was consistent with previous studies. These findings provide evidence of CladT rebalancing the immune system towards a more homeostatic and less pathogenic state.