Neurology and Therapy最新文献

Alzheimer's disease (AD) remains the most common form of dementia in elderly populations. Accurately diagnosing early forms of dementia and AD remains a significant clinical challenge, especially in fast-paced primary care settings. Informant-based questionnaires that rely on close caregivers of the patients, such as the Informant Questionnaire on Cognitive Decline in the Elderly, the Ascertain Dementia 8-Item, the Quick Dementia Rating System, and the Alzheimer's Questionnaire, have recently been shown to be a valuable supplement to current standards of diagnosis, such as performance-based tests. This review aimed to explore the key characteristics of various informant-based questionnaires and evaluate their efficacy in the medical setting. Analysis of each test demonstrated that informant-based assessments show a strong ability to detect cognitive impairment early on in its pathology and can highlight gradual decline over time, compared with the single-timeframe evaluations that performance-based tests provide. Informant-based questionnaires are also able to circumvent challenges associated with the patient's education level, language, and other cultural biases, thus making them useful in diverse populations. When used in conjunction with performance tests, informant-based tests can significantly streamline the diagnostic process for dementia and enhance management and treatment strategies. Further research is advised to effectively integrate these tests into routine clinical practice and establish a new standard of care.

Introduction: While clinical trials have established the efficacy of immunoglobulin (Ig) to treat chronic inflammatory demyelinating polyneuropathy (CIDP), real-world data are limited. This study evaluated real-world effectiveness of Ig among patients with CIDP in terms of progressive use of assistive devices as a proxy for deteriorating clinical disability.

Methods: Adults diagnosed with CIDP by a neurologist from 1/2015 to 11/2021 and with a documented nerve conduction study were identified using linked medical and pharmacy claims and electronic medical record (EMR) data in the United States (US). Patients receiving Ig were propensity score matched to patients without Ig. Claims for assistive devices were used as a proxy for disability and assessed over 6-month baseline and follow-up periods. Deterioration was defined as ≥ 1 post-index claim for an assistive device indicating a higher level of disability than observed at baseline. Changes in anticonvulsant, antidepressant, and opioid use were assessed as secondary outcomes.

Results: The study sample comprised 1302 Ig-treated and non-Ig-treated matched pairs (mean age 61 years and ~ 40% female). Approximately 40% fewer Ig-treated patients had ≥ 1 level of deterioration (3.3% vs. 5.4%, p = 0.0104) and ≥ 2 levels of deterioration (3.1% vs. 5.1%, p = 0.0079) in assistive device use. Anticonvulsant (48.0-44.8%) and opioid use (39.2-33.3%; both p < 0.0001) decreased from baseline to follow-up in Ig-treated patients but remained unchanged for non-Ig-treated patients. Among patients with baseline opioid use, a higher proportion of Ig-treated patients had opioid improvement over the post-index period (41.5% vs. 32.1%, p = 0.0021).

Conclusion: Our findings support the effectiveness of Ig therapy in CIDP. The benefits of Ig seen in clinical trials of maintained or improved disability scores appear to be reflected in the real world by less deterioration in assistive device use and lesser use of anticonvulsants, antidepressants, and opioids.

Introduction: Donanemab has been developed as an amyloid-targeting therapy (ATT) for mild cognitive impairment (MCI) and mild dementia due to Alzheimer's disease (AD). In registration trials involving donanemab, a treat‑to‑clearance approach was used, in which patients discontinued ATT when amyloid plaque levels decreased below a predefined threshold, which differs from previously available symptomatic treatments for AD. Our study explored care partners' perceptions regarding ATT and treat‑to‑clearance.

Methods: This was a cross-sectional, qualitative interview study. Care partners of individuals with MCI or mild dementia due to AD participated in online semi-structured interviews about their perceptions regarding the impact of MCI or mild dementia diagnoses due to AD, the burden of supporting, and use/cessation of ATT. The qualitative data from the interviews were analyzed using a thematic approach.

Results: The participants were 22 care partners (5 male/17 female), and their median age was 59 (range 35-81) years. The most common relationships between care partners and the individuals with AD were child (50.0%) and spouse/partner (45.5%); 68.2% of the care partners lived with the individuals with AD. Thematic analysis identified three major classifications (Thoughts regarding therapy; Treat‑to‑clearance; and Burdens of support), along with 15 themes and five sub-themes. Care partners expressed experiencing mental burden and time constraints, while treat‑to‑clearance could save care partners' time by reducing hospital waiting time and alleviating financial burden. Confirming the clearance of amyloid β plaques provided care partners with a sense of relief, while they remained concerned about the potential progression of AD symptoms and sought follow-up care after stopping treatment.

Conclusions: These results suggest that providing clear explanations and facilitating shared decision-making when introducing ATT, as well as introducing follow-up care and long-term evidence after stopping treatment, are needed.

Introduction: Oral corticosteroids (OCS) are commonly used to control symptoms in patients with myasthenia gravis (MG). Long-term high-dose OCS use is associated with serious side effects, but the real-world clinical impact of high-dose OCS in patients with MG is not well understood. The main objectives of this study were to evaluate healthcare resource utilization and clinical complications associated with high-dose versus low-dose OCS use in Japanese patients with MG.

Methods: A retrospective cohort study was performed using JMDC, a Japanese claims database. Patients with newly diagnosed MG (incident cases) were identified, and the date of the first diagnosis of MG was defined as the index date. Patients were stratified into two groups by OCS dose level (high-dose OCS ≥ 7.5 mg/day; low-dose OCS < 7.5 mg/day; based on the average dose in the population during the follow-up). Patient characteristics, treatments, long-term hospitalization (≥ 10 days cumulative per year), and corticosteroid-related complications were assessed.

Results: Of 2107 patients with an incident MG diagnosis, 576 were on OCS (high-dose OCS, 210; low-dose OCS, 366) during the follow-up period. There were no obvious differences in baseline comorbidities between the high- and low-dose OCS groups. A significant increase in long-term hospitalization was observed in the high-dose OCS versus the low-dose OCS group (adjusted odds ratio [95% CI], 1.832 [1.180, 2.845], P = 0.007). A greater proportion of patients in the high-dose OCS group versus the low-dose OCS group received ≥ 1 course per year of in-hospital intravenous immunoglobulin (34.8% vs. 15.3%), plasma exchange therapy (16.2% vs. 8.2%), and intravenous methylprednisolone pulse therapy (33.3% vs. 24.0%). The incidence of new complications such as diabetes, osteoporosis, osteoporotic fractures, neuropsychiatric disease, and sepsis was significantly (P < 0.05) higher with high- versus low-dose OCS.

Conclusion: Use of high-dose OCS in patients with MG was associated with adverse outcomes, including increased rates of long-term hospitalizations and clinical complications.

Introduction: High-dose intravenous methylprednisolone (IVMP) is effective in treating generalized myasthenia gravis (gMG), but early-stage transient aggravation and MG crisis can occur. This study evaluated the safety and efficacy of efgaitigimod in combination with different doses of IVMPs in patients with severe gMG.

Methods: This was a single-center, retrospective cohort study that retrospectively collected patients with myasthenia gravis who presented to Hebei Myasthenia Gravis Diagnosis and Treatment Center from December 2023 to May 2024, divided into IVMP monotherapy (1000 mg, Group A, n = 20) or efgartigimod combined with IVMP: 1000 mg (Group B, n = 7), 500 mg (Group C, n = 10), or 250 mg (Group D, n = 20). Patients received efgartigimod (10 mg/kg) intravenously on days 1 and 8 while receiving IVMP. Efficacy was assessed via quantitative myasthenia gravis (QMG) scores at baseline, week 2, and week 12.

Results: Groups A, C, and D demonstrated progressive QMG reductions over 12 weeks. Group B showed a week 12 QMG rebound (vs. week 2) but remained below baseline. At week 2, Group A had significantly less QMG improvement than Group B (p = 0.004), which was not different from group C/D. After 12 weeks, no significant difference was found among the groups (p = 0.639). Transient exacerbations and adverse events were significantly higher in Group A versus C/D.

Conclusion: Efgartigimod combined with 250 mg IVMP is associated with improvement of symptoms, reduction of transient exacerbations, and adverse event rates compared with higher IVMP doses or IVMP monotherapy, offering a promising regimen for severe gMG.

Trial registration: Chinese Clinical Trial Registry (Chictr2400080921).

Introduction: Cognitive adverse events are a common issue in patients receiving later-generation antiseizure medications (ASMs). In this study, we assessed the long-term effects of cenobamate on cognitive endpoints in patients with drug-resistant focal epilepsy.

Methods: In this retrospective, observational study, the clinical records of adult patients who received cenobamate as part of the Spanish Expanded Access Program were reviewed. Seizure frequency, concomitant ASM usage, and data from 20 neuropsychological tests were collected at 6 and 18 months after cenobamate initiation.

Results: Among 14 patients included in the study, eight (57%) had daily seizures at baseline, three (21%) had seizures at least weekly, and three (21%) had seizures at least monthly. The median number of prior ASMs was 10; the median number of concomitant ASMs was three. The median cenobamate dose was 12.5 mg/day at baseline, 200 mg/day at month 6, and 250 mg/day at month 18. At month 18, 10 patients (71%) had at least a 50% reduction in seizure frequency, seven (50%) had at least a 90% reduction, and two (14%) achieved seizure freedom. Significant improvements in cognitive scores from baseline to month 18 were observed for verbal episodic memory (two measures; p = 0.016 and p = 0.0013), visuospatial episodic memory (p = 0.014), and processing speed (p = 0.0018). The mean number of concomitant ASMs (p = 0.0018) and the concomitant ASM drug load (p = 0.0001) decreased significantly between baseline and month 18. The sum of the ratios of prescribed daily dose/daily defined dose (total ratio of defined daily dose) for all concomitant ASMs (p < 0.0001), for perampanel (p = 0.017), and for sodium channel blockers (p = 0.0003) also decreased between baseline and month 18.

Conclusion: In this exploratory, real-world study, we observed significant improvements in seizure frequency, concomitant ASM usage, and cognition at up to 18 months of cenobamate treatment in patients with drug-resistant focal epilepsy.

Introduction: Since 2018 subcutaneous immunoglobulin (SCIg) has been approved for the maintenance treatment of chronic inflammatory demyelinating polyneuropathy (CIDP). However, comprehensive real-world data for long-term SCIg treatment are scarce for CIDP and especially for other immune-mediated neuropathies such as multifocal motor neuropathy (MMN).

Methods: In this observational study, 62 patients with CIDP and 13 with MMN were analyzed. Patients had been receiving regular intravenous immunoglobulin (IVIg) and transitioned to an equivalent weekly dose of SCIg. A comprehensive set of biographical, clinical, and paraclinical data were compared between the time of the switch and after 12 months.

Results: Subcutaneous administration was continued by 84% of the patients with CIDP and 77% of the patients with MMN for at least 12 months. Patients were clinically and electroneurographically stable over a period of 12 months under SCIg therapy and treatment satisfaction and preference was high. Nevertheless, intensified treatment especially by increasing the SCIg dose was necessary in a relevant proportion of both groups (31% of patients with CIDP and 40% of patients with MMN). The proportion of patients with concomitant autoimmune disease was higher in patients with CIDP with intensified treatment.

Conclusions: SCIg is an effective alternative maintenance treatment for patients with CIDP and MMN who have previously responded to IVIg. Switching to an equivalent weekly dose of SCIg as a replacement for monthly IVIg is both feasible and effective in most patients. Nevertheless, about one-quarter of patients require an increased dose of subcutaneous immunoglobulin, which is well tolerated and often preferred to allow continuation of this treatment modality.

Introduction: In 2013, the "MS in the 21st Century" (MS21) initiative established a consensus statement for multiple sclerosis (MS) standards of care, with an overall vision including "Full access to personalised treatment, with reimbursement, to achieve freedom from disease." This update considers progress made since 2013 and priority areas for further improvement.

Methods: A Delphi process with two rounds of anonymised voting was used to develop updated consensus statements based on three key themes: (1) optimising current MS care provision; (2) facilitating shared decision-making and patient education; and (3) continuing MS research and development. Voting panels (n = 30), including people living with MS (PwMS), MS patient advocacy group (PAG) representatives and healthcare professionals (HCPs) indicated agreement using a sliding scale [1 (strongly disagree) to 5 (strongly agree)] and free-text feedback. Statements were revised after each voting round, with the consensus threshold set a priori as ≥ 75% agreement. There was a 70% response rate at each round of voting, with respondents representing 13 countries.

Results: Seven original principles were expanded to 14, with emerging themes including unmet care needs in ageing PwMS, MS prevention, and treatments for progressive MS and remyelination. The top priority for both HCPs and PwMS/PAG representatives was "access to quick and decisive treatment after diagnosis."

Conclusion: For PwMS to be unburdened by symptoms, professionals and stakeholders within the MS community should work together to meet the updated MS21 vision, including access to appropriate care, greater PwMS involvement in decisions, and further research and development to address unmet needs in MS.