Neurology and Therapy最新文献

Introduction: Ischemic stroke is the second leading cause of mortality and a major contributor to disability worldwide. Hospital length of stay (LOS) is a marker of medical efficiency for stroke care. There is limited information on this issue in China. This study aimed to identify predictors of prolonged LOS and to assess whether a prolonged LOS benefits functional outcomes in patients with acute ischemic stroke (AIS) in China.

Methods: This secondary analysis of the Chinese Acute Ischemic Stroke Treatment Outcome Registry, a multicenter, prospective, hospital-based registry study, included patients diagnosed as AIS and admitted to a hospital within 3 days after AIS onset from May 2015 to October 2017. Participants were dichotomized as the normal LOS group (LOS ≤ 14 days) and the prolonged LOS group (LOS > 14 days). The outcomes were the proportions of poor outcome at 3 months and 12 months after stroke onset. Poor outcome was defined as a mRS score of 3-6.

Results: This study included 8171 patients (median age 64.0 years; 5367 male, 2804 female); 2968 (36.3%) patients had a prolonged LOS. Multivariable analysis identified independent predictors of prolonged LOS, including medical insurance, history of diabetes mellitus, stroke severity, use of anticoagulant agents, in-hospital infection complications, hemorrhagic events, and hospital region. A prolonged LOS was associated with a higher risk of poor outcome at 3 and 12 months after stroke, with this finding upheld in a propensity score-matched cohort as well as subgroup analyses stratified by stroke severity and age.

Conclusion: In this study, approximately one-third of patients with AIS experienced a prolonged LOS over 14 days. Independent predictors of prolonged LOS included medical insurance, history of diabetes mellitus, stroke severity, use of anticoagulant agents, in-hospital infection complications, hemorrhagic events, and hospital region. Extending the LOS beyond 14 days did not enhance the prognosis for patients with AIS. As an observational study, our research provided the foundation for further interventional studies. Graphical abstract available for this article.

Trial registration: ClinicalTrials.gov NCT02470624.

Introduction: Efficacy/tolerability of adjunctive brivaracetam (BRV) for focal-onset seizures (FOS) in patients aged ≥ 16 years was established in randomized controlled trials. This study aimed to evaluate the effectiveness of adjunctive BRV in patients (≥ 16 years) with FOS with/without focal to bilateral tonic-clonic seizures in daily clinical practice.

Methods: A 12-month, prospective, real-world, noninterventional study in nine European countries (EP0077/NCT02687711). BRV was prescribed per clinical practice and European Summary of Product Characteristics. Eligible patients had never received BRV before inclusion. Treating physicians made the decision to prescribe BRV, independently of study participation. Primary effectiveness outcome: BRV retention rate at 12 months; secondary effectiveness outcomes: 50% responder rate, seizure freedom.

Results: A total of 544 patients received ≥ 1 BRV dose (mean age: 43.6 years; 52.8% female; mean time since diagnosis: 22.7 years). Patients had a mean of 7.3 lifetime antiseizure medications (ASMs) and median of 3.7 FOS/28 days during 3-month retrospective baseline. Median total ASM drug load (including BRV) was 3.0 at BRV initiation (n = 539) and 3.3 at study end (n = 314). At 12 months, 57.7% of 541 patients remained on BRV, 60.4% of 230 were responders (≥ 50% seizure reduction since baseline), and 13.8% of 269 were seizure-free since BRV initiation. Historical levetiracetam use appeared not to impact retention rate (56.6% of 320 and 59.3% of 221 patients with and without historical levetiracetam use, respectively). 36.0% of 544 patients had drug-related treatment-emergent adverse events (TEAEs), mostly (≥ 5% of patients) drug ineffective (11.4%) and seizure (6.3%). The three most common drug-related TEAEs leading to permanent BRV discontinuation (of 544 patients) were drug ineffective (10.1%), seizure (5.1%), and behavior disorder (3.3%).

Conclusions: Adjunctive BRV was effective in clinical practice in patients with predominantly difficult-to-treat FOS, as shown by BRV retention rate of 57.7% at 12 months, which is in line with real-world retention rates for other new-generation ASMs.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.Ti v22 software.

Results: FARS-ADL concepts most frequently reported by individuals with SCA were difficulty walking (n = 7/7), falls (n = 6/7), speech difficulties (n = 4/7), and swallowing (n = 3/7). Individuals with SCA reported that all FARS-ADL items were relevant; Gait and Walking (n = 7/7), Bladder Function (n = 6/7), and Falling (n = 6/7) were considered extremely relevant. All HCPs (n = 8/8) reported that most FARS-ADL items were relevant to individuals with SCA; Quality of Sitting Position was considered least relevant. HCPs reported meaningful change as 1-2 point score change in individual FARS-ADL items (n = 7/7), 1-3 point change in total score (n = 6/6), and stability on any item and/or total score over ≥ 1 year, depending on SCA subtype (n = 5/8). Cognitive debriefing supported clarity and comprehension of FARS-ADL. Suggested improvements included refining response options for Dressing, Falling, Walking, and Bladder Function items.

Conclusion: The findings confirm the content validity of most FARS-ADL items for use in individuals with mild-to-moderate SCA1 and SCA3, and offer suggested improvements for response options.

Introduction: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is a severe, autosomal dominant disease resulting from multisystemic extracellular deposition of amyloid fibrils, leading to progressive organ damage and death. Sudoscan is a reproducible tool investigating sweat gland function and, indirectly, small nerve fiber impairment. The aim of this study was to evaluate any changes over time in electrochemical skin conductance (ESC) measured by Sudoscan in a cohort of late-onset patients with ATTRv from a single Italian center. Additionally, we investigated the role of Sudoscan as a marker of disease severity to confirm previous literature data.

Methods: We enrolled 61 patients with a late-onset ATTRv amyloidosis harboring different TTR variants with at least one clinical and instrumental evaluation including Sudoscan. Correlations with clinical data (including both clinical scales and questionnaires) were investigated to confirm the role of Sudoscan as a marker of disease severity. Moreover, a longitudinal analysis was performed in the subgroup of patients with at least 4 complete yearly evaluations (n = 23) to assess the role of Sudoscan as a marker of disease progression.

Results: At each yearly assessment, ESC values from both feet and hands significantly correlated with disease duration and neuropathy severity, as assessed by common clinical scales and questionnaires. No correlation was found with age at evaluation. Moreover, we observed a statistically significant change over time in ESC values measured at the feet (fESC) but not at the hands (hESC).

Conclusions: Sudoscan may represent a reliable marker of dysautonomia in ATTRv amyloidosis, displaying a potential role as a marker of both disease severity and progression. It could, therefore, serve as an outcome measure in future clinical trials. In addition, feet ESC seems to be a significant, independent predictor of autonomic dysfunction.

Migraine affects women three times more often than it does men, and various mechanisms may explain this incidence, including the key role of female sex hormones. Fluctuations in the levels of these hormones and their feedback control regulate the menstrual cycle, pregnancy, puerperium, perimenopause, and menopause. They can influence the occurrence and severity of migraine throughout the reproductive period. Of particular importance seems to be the perimenopausal period, which is associated with an increase in migraine, especially menstrual migraine, which is considered more disabling and less amenable to treatment than non-menstrual attacks. This article reviews the available evidence documenting the relationship between perimenopause, menopause, and migraine and diagnostic considerations in an attempt to determine the management of these periods of a woman's life. Special considerations, future directions, and unmet needs for perimenopausal and menopausal migraine are also discussed.

Introduction: Subjects with intellectual disability are usually excluded from clinical trials and there is limited evidence-based guidance for the choice of antiseizure medications in this vulnerable population. The study explored the effectiveness of brivaracetam (BRV) in people with epilepsy and intellectual disability.

Methods: BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST) was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The occurrence of adverse events (AEs) was also considered. Analyses by the presence and severity of intellectual disability were performed.

Results: Subjects with intellectual disability were 253 (24.6%) out of 1029 participants. The 12-month rates of seizure freedom were 18.4% and 10.3% in participants without and with intellectual disability, respectively; the corresponding values for seizure response were 40.0% and 28.9%. Intellectual disability was not an independent predictor of seizure outcomes. The rates of treatment discontinuation were 25.8% and 26.4% in participants without and with intellectual disability. respectively. There were no statistically significant differences in the rates of any AEs, somnolence, nervousness/agitation, and aggressiveness by the presence and degree of intellectual disability.

Conclusion: Brivaracetam can be a suitable treatment option and offer opportunities for clinical improvement in subjects with intellectual disability and uncontrolled seizures.

Lecanemab (Leqembi^©, Biogen), a humanized anti-amyloid-beta monoclonal antibody, has been approved for early-stage Alzheimer's disease (AD) in several countries, including the US and Japan. However, the European Medicines Agency (EMA) recently issued a negative opinion on its marketing authorization, reflecting concerns over the clinical value and manageability of anti-amyloid treatments. This decision highlights the ongoing disconnect between research advancements and clinical practice, where the focus on biological markers over tangible clinical improvements remains contentious. Despite promising biological effects, lecanemab's clinical outcomes have been modest, raising questions about its therapeutic role. The EMA's refusal underscores the need to address doubts surrounding the real-world effectiveness and safety of such treatments, especially concerning amyloid-related imaging abnormalities (ARIAs), a common side effect observed in clinical trials. The recent approval of lecanemab by the UK's Medicines and Healthcare products Regulatory Agency, despite the National Institute for Health and Care Excellence's rejection on cost-effectiveness grounds, further fuels the debate on the feasibility of anti-amyloid therapies. This commentary emphasizes the importance of real-world data on lecanemab's impact on cognitive decline, daily functioning, and side-effect management. As the global clinical use of lecanemab increases, continuous and standardized reporting on its outcomes is crucial for guiding future regulatory decisions and for potentially bridging the gap between research and practice in AD treatment.