Neurology and Therapy最新文献

Introduction: Real-world data are required to provide a greater understanding of the impact of ofatumumab on the ability to mount an effective immune response following the receipt of approved COVID-19 vaccinations. This retrospective real-world analysis aimed to describe the humoral immune response to COVID-19 vaccination during ofatumumab treatment in patients with multiple sclerosis (MS).

Methods: Data from patients with MS treated with ofatumumab who were fully vaccinated against COVID-19 infection were abstracted from medical charts at four clinical sites in the USA. Patient characteristics and humoral response were summarized descriptively. Differences in humoral response were documented on the basis of vaccination status during ofatumumab treatment (i.e., after full vaccination and after booster vaccination) and prior disease-modifying treatment (DMT) exposure (i.e., DMT naïve, prior anti-CD20/sphingosine 1-phosphate [S1P] therapy, prior non-anti-CD20/S1P therapy). The sample size precluded formal statistical analysis.

Results: Thirty-eight patients were included. The mean (standard deviation) duration of ofatumumab treatment upon data collection was 20.4 (4.6) months (treatment ongoing for 35 [92%] patients). Definitive humoral response after full vaccination was documented for 34 patients, of whom 20 (60%) were seropositive. Definitive humoral response after booster vaccination was documented among five patients, of whom three (60%) were seropositive. Among patients who were DMT naïve prior to ofatumumab (n = 15), 73% were seropositive; among patients exposed to prior anti-CD20/S1P therapy (n = 14), 33% were seropositive; and among patients exposed to prior non-anti-CD20/S1P therapy (n = 9), 56% were seropositive. Patients naïve to DMT had been living with an MS diagnosis for a shorter duration than those experienced with DMTs.

Conclusion: Patients with MS receiving ongoing treatment with ofatumumab can mount a positive humoral response to a COVID-19 vaccination. Prior treatment with anti-CD20 or S1P DMTs may be a risk factor for lower humoral response.

This article has been co-authored by a patient living with hereditary transthyretin (ATTRv) amyloidosis and a neurologist. This rare, progressive disease is associated with impairment of multiple organ systems, including the nerves, heart, and the gastrointestinal tract, forcing patients to live with and adapt to a range of debilitating symptoms. Here, the patient and physician discuss how the symptoms of ATTRv amyloidosis profoundly impact day to day life, the difficulties with identifying the disease, and how this effects the diagnosis experience. In recent years, significant advancements have been made in the treatment and management of ATTRv amyloidosis. However, the authors highlight the urgency of increasing awareness of the disease among the wider medical community, as well as in patients who notice the symptoms, to ensure that earlier diagnosis and appropriate treatment are achieved.

Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impairs cognitive and functional abilities, placing a substantial burden on both patients and caregivers. Current symptomatic treatments fail to halt the progression of AD, highlighting the urgent need for more effective disease-modifying therapies (DMTs). DMTs under development are classified as either passive or active on the basis of their mechanisms of eliciting an immune response. While this review will touch on active immunotherapies, we primarily focus on anti-amyloid beta monoclonal antibodies (mAbs), a form of passive immunotherapy, discussing their multifaceted role in AD treatment and the critical factors influencing their therapeutic efficacy. With two mAbs now approved and prescribed in the clinical setting, it is crucial to reflect on the lessons learned from trials of earlier mAbs that have shaped their development and contributed to their current success. These insights can then guide the creation of even more effective mAbs, ultimately enhancing therapeutic outcomes for patients with AD while minimizing adverse events.

Background: Post-stroke depression (PSD) is a prevalent psychiatric complication in stroke patients, severely reducing quality of life and delaying social recovery in stroke survivors. Clinical studies have shown that acupuncture can be used as an alternative approach for PSD. The aim of this study was to examine the safety, efficacy, and electroencephalogram (EEG) mechanism of acupuncture in treating PSD patients.

Methods: From October 28, 2022 to May 16, 2023, this single-center, single-blind, randomized clinical trial was conducted at the Second Affiliated Hospital of Nanchang University. A total of 56 eligible subjects were assigned in a random manner, with an equal distribution between two groups: the manual acupuncture (MA) group and the sham acupuncture (SA) group. The primary outcome was the Hamilton Depression Scale-24 (HAMD-24); the secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI), the National Institutes of Health Stroke Scale (NIHSS), the Barthel index, EEG power spectrum, and EEG imaginary coherent (iCOH).

Results: Compared to the SA group, the MA group exhibited significant improvements in HAMD-24, NIHSS, PSIQ, and Barthel index at week 6. The total improvement rate was 85.71% in the MA group and 28.57% in the SA group. After 6 weeks of treatment, the alpha and beta bands power spectrum increased significantly, while the delta and theta bands power spectrum decreased significantly in the MA group compared to the SA group. The iCOH analysis showed that the MA group had significantly higher functional connectivity in the four bands than the SA group.

Conclusions: Acupuncture might be regarded as an adjunctive treatment for PSD patients with improvements in their neurological deficits, sleep quality, and depression. Meanwhile, the mechanism of acupuncture in treating PSD patients may be through decreasing the slow wave power spectrum and increasing the fast wave power spectrum, and enhancing brain functional connectivity.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2200065112/2022-10-28).

Introduction: The goal of this economic model is to estimate an economically justifiable price (EJP) for using donanemab for the treatment of early symptomatic Alzheimer's disease (AD) in the United States based on clinical data from the phase 3 TRAILBLAZER-ALZ 2 trial (NCT04437511).

Methods: We adapted an AD Markov state-transition model developed by the Institute for Clinical and Economic Review to estimate the EJP for donanemab at different willingness-to-pay (WTP) thresholds from the health care system perspective and the societal perspective as co-base cases.

Results: Assuming a WTP threshold of $150,000 per quality-adjusted life-year (QALY) gained, the model estimates a 1-year (13-dose) EJP for donanemab of $80,538 from the health care system perspective and $91,126 from the societal perspective; at a WTP threshold of $100,000 per QALY gained, the model estimates a 1-year (13-dose) EJP for donanemab of $44,691 from the health care system perspective and $55,419 from the societal perspective. Mean total treatment costs per patient at the $150,000 per QALY gained EJP derived from the health care system perspective were estimated at $77,812 based on the average number of doses of donanemab patients received in the co-base case analysis. One-way sensitivity analysis (OWSA) indicated that treatment efficacy, disease severity at the time of treatment initiation, and duration of treatment effect were the main drivers of the potential EJP.

Conclusions: Results from this modeling simulation informed by the TRAILBLAZER-ALZ 2 study support an EJP for limited-duration treatment with donanemab that exceeds per-dose list prices for currently available amyloid-targeting therapies, implying potentially lower lifetime costs and better value for money.

Optical coherence tomography angiography (OCT-A) is a state-of-the-art imaging technique for the retinal vasculature to accurately segment the capillary network and assign it to retinal layers. OCT-A is a promising technique to better understand neurological diseases with visual system manifestations, such as multiple sclerosis (MS), and to identify and characterize vascular biomarkers. Initial studies suggested vascular changes in MS and its differential diagnoses such as myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Here we review clinical and technical aspects of OCT-A imaging and discuss the potential for the MS field as well as barriers that need to be overcome before OCT-A can be established in clinical application.

Introduction: Open traumatic brain injury (OTBI) is associated with high mortality and morbidity; however, the classification of these injuries and the determination of patient prognosis remain uncertain, hindering the selection of optimal treatment strategies. This study aimed to develop and validate a novel OTBI classification system and a prognostic model for poor prognosis.

Methods: This retrospective study included patients with isolated OTBI who received treatment at three large medical centers in China between January 2020 and June 2022 as the training set. Data on patients with OTBI collected at the Fuzong Clinical Medical College of Fujian Medical University between July 2022 and June 2023 were used as the validation set. Clinical parameters, including clinical data at admission, radiological and laboratory findings, details of surgical methods, and prognosis were collected. Prognosis was assessed through a dichotomized Glasgow Outcome Scale (GOS). A novel OTBI classification was proposed, categorizing patients based on a combination of intracranial hematoma and midline shift observed on imaging, and logistic regression analyses were performed to identify risk factors associated with poor prognosis and to investigate the association between the novel OTBI classification and prognosis. Finally, a nomogram suitable for clinical application was established and validated.

Results: Multivariable logistic regression analysis identified OTBI classification type C (p < 0.001), a Glasgow Coma Scale score (GCS) ≤ 8 (p < 0.001), subarachnoid hemorrhage (SAH) (p = 0.004), subdural hematoma (SDH) (p = 0.011), and coagulopathy (p = 0.020) as independent risk factors for poor prognosis. The addition of the OTBI classification to a model containing all the other identified prognostic factors improved the predictive ability of the model (Z = 1.983; p = 0.047). In the validation set, the model achieved an area under the curve (AUC) of 0.917 [95% confidence interval (CI) = 0.864-0.970]. The calibration curve closely approximated the ideal curve, indicating strong predictive performance of the model.

Conclusions: The implementation of our proposed OTBI classification system and its use alongside the other prognostic factors identified here may improve the prediction of patient prognosis and aid in the selection of the most suitable treatment strategies.

Background: Despite considerable evidence for the efficacy and safety of stiripentol in Dravet syndrome (DS), some aspects of stiripentol use remain challenging in clinical practice, such as dose titration and the adjustment of concomitant antiseizure medications (ASMs) to prevent potential adverse effects.

Aim: To (1) provide practical recommendations on the initiation of stiripentol treatment in patients with DS, (2) evaluate its effectiveness in the patient, and (3) guide the management of drug interactions and other aspects of treatment monitoring.

Methods: Six Spanish neurologists (the authors) with expertise in the management of pediatric and adult patients with DS held a meeting in early 2024 to develop expert recommendations regarding the use of stiripentol in DS, based on a review of the literature and their common clinical experience.

Results: According to these recommendations, stiripentol can be administered to patients with DS of any age, although its initiation and titration vary according to age group. Individualized adjustment of concomitant ASMs, such as valproic acid and clobazam or drugs specifically for DS (i.e., fenfluramine), at initiation and during stiripentol treatment, can mitigate drug interactions, thereby increasing the long-term tolerability of stiripentol treatment. In specific cases, stiripentol doses of > 50 mg/kg/day may be contemplated, and acute stiripentol administration may be considered to control refractory status epilepticus. Blood tests should be performed before starting stiripentol, at 3, 6, and 12 months after starting treatment, and then annually, except in the event of adverse effects, when additional testing may be necessary. Most adverse effects can be adequately managed by adjusting concomitant medications.

Conclusion: These practical recommendations may be easily adapted for use in different countries, and should increase physicians' confidence in the initiation and monitoring of stiripentol treatment, thus facilitating effective management of patients with DS and improving clinical outcomes.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) have a profound impact on patients' quality of life (QoL), with progressive declines occurring as the disease advances. This systematic review aims to summarize the published evidence on patient-reported outcomes (PROs) in individuals with MCI due to AD and mild AD dementia. Comprehensive searches were conducted across five major databases to identify studies reporting on utility values, disutilities, and QoL measures in these patient populations. A total of 23 studies were included that utilized various QoL assessment tools, including EQ-5D (n = 14), SF-36/SF-12 (n = 4), and QOL-AD (n = 11). Reported EQ-5D scores ranged from 0.81 to 0.92 for patients with MCI and from 0.67 to 0.85 for those with mild AD, indicating a noticeable decline in QoL as the disease progresses. QOL-AD scores ranged from 33.8 to 42.5 for MCI and from 32.4 to 38.1 for mild AD, equally reflecting the greater impairment in QoL with disease advancement. Interventions were generally associated with smaller declines in PROs compared to placebo, suggesting a positive impact of treatment in mitigating QoL deterioration. The findings underscore the significant QoL differences between MCI and mild AD, emphasizing the potential benefit of early intervention to preserve QoL and delay disease progression. This review highlights the importance of continued research to better understand QoL in patients with MCI and mild AD dementia, particularly in terms of capturing comprehensive patient-reported outcomes and evaluating the effectiveness of interventions over time. These findings can contribute to a more informed approach in clinical practice and support decision-making in the management of early-stage AD.

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.