Therapeutic Advances in Neurological Disorders最新文献

Background: Cladribine (CLAD) stands as an oral disease modifying treatment (DMT) for multiple sclerosis (MS) patients, distinguished by its unique dosing regimen and mechanism of action. However, real-world data on its effectiveness remain limited, particularly regarding the clinical and therapeutical management beyond the 2-year treatment schedule.

Objectives: The aim of our study was to explore the effectiveness profile of CLAD in individuals with MS (pwMS). We assessed the proportion of patients achieving no evidence of disease activity (NEDA-3) status and identified variables associated with better outcomes.

Design: In this retrospective study, we collected clinical and magnetic resonance imaging (MRI) data of MS patients across 10 MS Clinics in Central Italy who started CLAD between 2018 and 2023.

Methods: We evaluated the annualized relapse rate (ARR) during treatment, and the proportion of patients who experienced relapses, radiological activity, and confirmed disability progression. Additionally, we estimated the proportion of patients achieving NEDA-3 among those with a minimum follow-up of 3 months and explored baseline variables associated with NEDA status.

Results: We collected data from 1094 patients with a mean follow-up of 25.1 months, of whom 79% completed the second CLAD cycle. The mean age was 37.7 years (SD 9.7), and the mean disease duration was 6.5 years, with 40.5% being treatment naïve. Despite a significant reduction of the ARR from 0.91 to 0.04 (p < 0.01) following CLAD treatment, 8.9% of patients presented at least one relapse, while 22.0% and 7.9% of patients experienced radiological activity or disability progression, respectively. Across the entire study cohort, 70.2% of patients maintained the NEDA-3 status. Younger age (HR = 0.98, p < 0.001) and higher expanded disability status scale score (HR = 1.11, p = 0.049) were associated with a higher risk of not achieving the NEDA-3 status. Additionally, we included 131 patients who were older than 50 years at the time of CLAD initiation. Among the cohort, 116 patients switched to another DMT after CLAD, primarily anti-CD20 monoclonal antibodies following disease reactivation.

Conclusion: This postmarketing experience confirms the effectiveness of CLAD in the treatment of pwMS, with a significant reduction in ARR and a high proportion of patients remaining free from disease activity. By contrast, some patients required an escalation strategy mainly with anti-CD20 monoclonal antibodies because of persisting disease activity.

Therapeutic plasma exchange (PLEX) is a powerful and fast-acting immunomodulating therapy that is underutilized for autoimmune neurological disorders. Here, we present the largest collection of real-world experiences with PLEX procedures to date in the treatment of autoimmune neurological conditions, supporting its safety and clinical benefits with patient cases and corresponding patient videos. Our collective real-world experience with PLEX spans over 67 years, 90,210 procedures, and includes nine double-blind randomized controlled and unblinded studies serving as principal investigators. Case histories and videos of our patients demonstrate when and how PLEX should be used, identify barriers to using PLEX, and ways to overcome these barriers. Specific protocol details are shared of how to treat an acute or chronic phase of a disease. If used appropriately and early in the disease course for both acute and chronic progressive phases, PLEX can safely change the trajectory of many autoimmune neurological disorders in both outpatient and inpatient settings.

Background: Switching disease-modifying therapies (DMTs) is common in relapsing-remitting multiple sclerosis (RRMS). Vertical switching to higher-efficacy agents generally outperforms horizontal switching within the same efficacy tier, yet horizontal switches remain frequent where escalation is impractical.

Objectives: To compare real-world outcomes after horizontal versus vertical DMT switches and to identify predictors of successful horizontal switching.

Design: Retrospective, registry-based observational study.

Methods: Adults with RRMS who switched DMTs in the MSBase Registry (2010-2023) were analyzed. Horizontal switches were defined as transitions within efficacy tiers, and vertical switches as transitions to a higher tier. Propensity score matching (1:1) generated balanced cohorts. Multivariable mixed-effects models with a random intercept for patients were used to evaluate associations with outcomes. The primary outcome was no evidence of disease activity (NEDA-3) during the treatment period; secondary outcomes included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) change, confirmed disability worsening (CDW), confirmed disability improvement (CDI), and progression independent of relapse activity (PIRA). Predictors of successful horizontal switching were explored using logistic regression.

Results: A total of 4934 matched switches (2467 pairs) were analyzed. Vertical switching achieved higher NEDA-3 rates than horizontal switching (45.8% vs 33.7%) and was associated with lower ARR, reduced CDW risk, and more frequent CDI; differences in EDSS progression and PIRA were not significant. Among horizontal switchers, 33.7% achieved NEDA-3. Success was associated with lower baseline EDSS, fewer prior relapses, and later-line switching. Outcomes varied by destination therapy: anti-CD20 agents had the highest success (≈50%), followed by cladribine (≈43%) and natalizumab (≈41%), whereas interferon and glatiramer acetate performed the poorest. Switches toward anti-CD20 therapies generally yielded better outcomes than other within-tier changes.

Conclusion: Vertical switching should be preferred when treatment modification is required, particularly for patients with active disease. However, a subset of patients can achieve disease stability after horizontal switching, especially those with lower disability and fewer prior relapses. The dynamics of horizontal switching may further influence outcomes, warranting prospective validation.

Background: Despite significant achievements in healthcare quality improvement for ischemic stroke and transient ischemic attack (TIA), the advancements and challenges of patient adherence to secondary prevention medications remain unclear.

Objectives: We aimed to investigate adherence rates of secondary prevention medication and identified the key determinants in Chinese patients with ischemic stroke or TIA.

Design: This is an observational study.

Methods: Using the China National Stroke Registry (CNSR) database from 2007 to 2018, this observational study included patients with ischemic stroke or TIA who were admitted to the hospital within 7 days of symptom onset. The study outcome was the patient adherence to secondary prevention medications, which was defined as the consistent use of prescribed antithrombotic, lipid-modulating, antidiabetic, and antihypertensive medications post-discharge using an "all-or-none" approach. We calculated adherence rates in 3 and 12 months. Logistic regression models were used to evaluate influencing factor patterns and challenges in the improvement of patient adherence.

Results: A total of 12,873 patients from CNSR I and 15,099 patients from CNSR III were included. Patient adherence rates for secondary prevention medications increased from 66.97% in CNSR I to 80.76% in CNSR III (p < 0.0001) in 3 months, and from 35.08% to 59.81% (p < 0.0001) in 12 months. Patient age, the National Institute of Health stroke scale score at admission, disease diagnosis, the Trial of Org 10172 in Acute Stroke Treatment classification, family income per capita, alcohol consumption, dyslipidemia history, hypertension history, diabetes history, and heart disease history appeared to exhibit a significant association with adherence.

Conclusion: In spite of the remarkable progress in patient adherence to secondary prevention of stroke from 2007 to 2018, challenges remain in sustaining quality improvement initiatives, necessitating further improvements by addressing disease severity, lifestyle, medical history, and socioeconomic factors.

Background: Lasmiditan, an oral 5-HT_1F receptor agonist, has been recently approved for acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, scarce data is available regarding effectiveness and tolerability in the real-world setting.

Objectives: To evaluate lasmiditan effectiveness and tolerability in the real-world setting in 16 Italian headache centers.

Design: LasmiDitan as Acute migRaine Treatment (DART) study is a prospective, multicentric, observational study.

Methods: We enrolled 58 participants with migraine (84.5% females, age 49.0 (45.2-52.9) years, 24.1% with chronic migraine) reporting 9.4 (7.4-11.3) monthly migraine days. Participants were instructed to treat their migraine attacks with oral lasmiditan 50 or 100 mg. Using an ad hoc electronic diary, participants prospectively collected migraine attack features at baseline and every 30 min after lasmiditan administration, up to 2 h post-dose. The primary outcome was 2-h pain freedom for the first-treated attack after lasmiditan intake. We also collected the occurrence of treatment-emergent adverse events (AE) after administration.

Results: Overall, participants treated 100 attacks, of which 58 first-treated attacks. Regarding first-treated attacks, 44.8% of subjects rated migraine intensity as severe at lasmiditan intake. Pain freedom 2-h post-dosing was reported in 32.8% (19/58) of individuals and was associated with baseline pain intensity, being higher in subjects treating a mild/moderate attack (p = 0.044). Conversely, it was not influenced by timing of intake (p = 0.375), dosage (p = 0.727), or previous triptan failure (p = 0.351). Regarding all-treated attacks, pain freedom 2-h post-dosing was 37.0% (37/100). At least one AE was reported by 53.4% of participants (31/58), predominantly asthenia, dizziness, somnolence, anxiety or agitation, and paresthesia. Tolerability was rated as good-to-excellent by 51.8% of subjects.

Conclusion: Our study supports clinical effectiveness of oral lasmiditan 50 and 100 mg for the treatment of acute migraine attacks. Lasmiditan effectiveness was not associated with the previous triptan failure and may therefore represent a valuable therapeutic option in subjects who did not benefit from, or have contraindications to, triptans.

Trail registration: The study was preregistered on clinicaltrial.gov, NCT05903040 (https://clinicaltrials.gov/study/NCT05903040?cond=migraine&intr=lasmiditan&rank=5).

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most frequently observed autoimmune neuropathy in patients with diabetes mellitus (DM). While intravenous immune globulin (IVIG) is a well-established treatment for CIDP, its efficacy in diabetic patients remains uncertain due to their exclusion from prior randomized trials, largely because of concerns about confounding diabetic axonal neuropathy.

Objectives: To evaluate the effectiveness of IVIG therapy in CIDP patients with diabetes mellitus (CIDP-DM) compared to those without diabetes (CIDP).

Design: Multi-center, prospective, observational study after at least 3 monthly infusions of IVIG therapy.

Methods: Thirty-six patients meeting diagnostic criteria for CIDP were enrolled and stratified into CIDP or CIDP-DM. All patients were followed for a minimum of 3 months after initiating IVIG therapy. Clinical outcomes were assessed at baseline (visit #1) and after 3 monthly IVIG infusions (visit #4) using the adjusted Inflammatory Neuropathy Cause and Treatment Disability Score, the Rasch-built Overall Disability Scale, and the Chronic Acquired Polyneuropathy Patient-reported Index, measured at baseline and at the point of maximal improvement.

Results: No significant differences were observed in clinical outcomes, treatment-related adverse events, or tolerance between CIDP and CIDP-DM groups, indicating comparable effectiveness of IVIG therapy. However, subgroup analyses revealed that longer duration of diabetes and elevated HbA1c levels were associated with delayed response to IVIG, likely due to cumulative axonal degeneration.

Conclusion: Despite the small number of enrolled patients, IVIG appears equally effective in CIDP patients with and without diabetes. Earlier initiation of IVIG treatment should be considered in CIDP-DM patients to mitigate potential delays in therapeutic response associated with a possibly chronic diabetic neuropathy-related component.

Background: Parenchymal hematoma (PH) is a common complication of acute ischemic stroke, particularly following reperfusion therapy.

Objective: This study aimed to explore the relationship between regional perfusion parameters and PH outcomes in stroke patients treated beyond the conventional time window.

Design: This retrospective cohort study included patients from the CHinese Acute tissue-Based imaging selection for Lysis In Stroke-Tenecteplase (CHABLIS-T) trials and the Huashan Hospital stroke registry.

Methods: Regional perfusion parameters were calculated within Alberta Stroke Program Early CT Score (ASPECTS)-defined regions of interest (ROIs). Mirror indices of cerebral blood flow (CBFmi), cerebral blood volume (CBVmi), and mean transit time were derived as the ratios of median perfusion values within ASPECTS-ROIs in the lesion and its contralateral hemisphere. Absolute time to maximum values for symptomatic ASPECTS-ROIs were also recorded. Logistic regression evaluated associations between perfusion parameters and PH outcomes, with predictive performance assessed using receiver operating characteristic (ROC) curves and area under the curve (AUC). Sensitivity analysis was conducted in patients receiving endovascular treatment (EVT) and in the trial-only population.

Results: Of 1010 patients screened, 313 met the inclusion criteria, and 54 developed PH. Multivariable stepwise logistic regression identified reduced CBFmi (adjusted odds ratios (aOR) = 0.07, 95% confidence interval (CI), 0.02-0.30, p < 0.001) and CBVmi (aOR = 0.11, 95% CI, 0.03-0.45, p = 0.002) in the lentiform nucleus as significant predictors of PH. ROC analysis showed good discriminative performance (AUC: CBFmi 0.71 (95% CI, 0.62-0.80), CBVmi 0.70 (95% CI, 0.61-0.79)). Sensitivity analysis in patients undergoing EVT and trial-only patients drew similar results.

Conclusion: Decreased CBFmi and CBVmi in the lentiform nucleus were independently associated with an elevated risk of PH, highlighting their potential utility in predicting hemorrhagic complications.

Trial registration: NCT04086147, NCT04516993.

Background: Patients with atrial fibrillation (AF) who survive spontaneous intracerebral hemorrhage (ICH) face competing risks of thromboembolism and recurrent bleeding.

Objectives: To evaluate the safety and efficacy of initiating oral anticoagulants versus avoiding anticoagulation in adults with AF after spontaneous ICH.

Design: Systematic review and meta-analysis of randomized-controlled clinical trials (RCTs).

Data sources and methods: We searched MEDLINE, Scopus, and ClinicalTrials.gov up to August 28, 2025, for eligible RCTs randomizing adults with AF and prior spontaneous ICH to start oral anticoagulation versus avoid anticoagulation. Efficacy outcomes included the occurrence of new ischemic stroke (primary) and ischemic major adverse cardiovascular events (MACE; secondary). Safety outcomes included recurrent ICH (primary), hemorrhagic-MACE, all-cause mortality at follow-up, and cardiovascular death (secondary). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects meta-analysis.

Results: Six RCTs were included, comprising 403 patients in the anticoagulation group and 395 in the avoid-anticoagulation group. Anticoagulants reduced the rates of new ischemic stroke (RR = 0.20; 95% CI: 0.06-0.72; I ² = 60%; number needed to treat = 9) and ischemic-MACE (RR = 0.41; 95% CI: 0.23-0.75; I ² = 32%). Anticoagulants were associated with higher rates of recurrent ICH (RR = 3.14; 95% CI: 1.41-7.01; I ² = 0%; number needed to harm = 19) and hemorrhagic-MACE (RR = 2.35; 95% CI: 1.32-4.21; I ² = 1%). All-cause mortality at 90 days (RR = 1.06; 95% CI: 0.69-1.64; I ² = 28%) and cardiovascular death (RR = 0.98; 95% CI: 0.34-2.87; I ² = 63%) did not differ between the two groups. Leave-one-out sensitivity analyses supported the overall direction of effects, with some attenuation when individual trials were omitted.

Conclusion: In AF survivors of spontaneous ICH, restarting oral anticoagulation lowers ischemic events but raises risks of recurrent ICH and major bleeding, without a clear early mortality difference. Potential benefits may outweigh risks in selected patients within a multidisciplinary framework. Adequately powered RCTs are needed to refine agent choice, timing, and patient selection.

Trial registration: PROSPERO CRD420251135299 (registered August 27, 2025).

Spinocerebellar ataxia type 3 (SCA3) is an inherited neurodegenerative disorder. Some of its clinical features resemble those of primary Parkinson's disease (PD), which can easily lead to misdiagnosis. There is currently no disease-modifying therapy available for SCA3, treatment is mainly symptomatic. Herein, we report a case of a young female patient with SCA3 who presented with Parkinsonian as the main manifestation and underwent globus pallidus internus (GPi) deep brain stimulation (DBS). This is a 36-year-old female patient. Her first symptoms occurred at the age of 28 in 2009, manifesting as gait abnormalities in the right lower limb. She was misdiagnosed with early-onset PD in 2011. Genetic testing showed abnormal numbers of CAG repeats (15/70) within the coding region of the ATXN3 genes. She was diagnosed with SCA3. The patient initially responded well to levodopa-based medication, but the treatment effects gradually attenuated over time, with the development of severe symptom fluctuations and dyskinesia in 2018. The patient underwent GPi-DBS surgery in the absence of cerebellar signs, cognitive, and mood disorders. Six-year postoperative follow-up results suggest that long-term GPi-DBS is effective for the control of dyskinesia, but the residual motor symptoms (parkinsonism and ataxia) had progressively worsened in the patient. Various targets have been reported to be selected for DBS treatment of SCA3, with substantial individual differences in treatment outcomes. This case emphasizes the importance of genetic testing for the diagnosis of SCA3 and provides a basis for personalized treatment of patients with SCA3.

Background: Oral corticosteroids (OCS) are commonly used in the management of autoimmune Myasthenia Gravis (MG), often in high doses for prolonged periods. Exposure to OCS is associated with significant and cumulative adverse effects. There is currently no universal consensus on the approach to OCS use in MG.

Objectives: To reach a multinational consensus on the appropriate use of OCS in MG, including the role of treatment approaches to minimize dose and support tapering.

Design: This modified Delphi study established consensus among a panel of 70 general neurologists/neuromuscular specialists from eight countries over two rounds of survey to establish best practice principles regarding the use of OCS in MG.

Methods: The current literature on OCS use in MG was reviewed. Topics of interest were identified, and a modified Delphi consensus process was created. A steering committee of six experts in MG proposed statements for testing with the wider panel over two rounds of surveys. Consensus was reached if at least 75% agreed or strongly agreed on a 4-point Likert scale.

Results: Consensus was achieved for all 37 final statements. These statements covered principles of OCS use, including a target for long-term use of ⩽5 mg/day; the role of biologic treatments in minimizing required OCS dose; the need for individualization of approach according to patient factors; and the need for detailed guidance regarding how and when to taper OCS dose.

Conclusion: These findings reinforce a shift in the management of MG, advocating for the judicious and sparing use of OCS against the backdrop of expanding therapeutic options. As additional evidence-based data emerge, these recommendations should be updated.