Therapeutic Advances in Neurological Disorders最新文献

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.

Background: The role of gut microbiota in multiple sclerosis (MS) has become increasingly important, intestinal dysbiosis with reduced production of short-chain fatty acids (SCFA) being the prevailing paradigm. However, the direction of causality, that is, whether intestinal changes are cause or consequence of chronic central nervous system inflammation, remains to be elucidated. Previous studies have focused on long-term MS patients. Alteration in fecal SCFA concentrations in early MS, particularly during relapses, remains to be extensively studied.

Objectives: To compare fecal SCFA concentrations in patients with a first diagnosis of MS with those in patients with long-term MS and in healthy controls (HCs).

Design: Prospective cohort study.

Methods: The prospective case-control study was conducted on relapsing-remitting MS (RRMS) patients at the time of first, acute relapse without ongoing immunotherapy (Early-RRMS). Clinical and demographic parameters, as well as fecal SCFA concentrations (measured by gas chromatography) were collected. The parameters were compared with those of matched RRMS patients under different, long-term immunotherapy (Late-RRMS) and HCs.

Results: SCFA concentrations of propionate, butyrate, isobutyrate, valerate, and isovalerate were not significantly different between the early-RRMS cohort and HCs, but were lower in the late-RRMS cohort.

Conclusion: The findings indicate that reduction in SCFA levels is exclusively observed in patients with RRMS during the further course of the disease and not at the onset. Decrease in SCFA concentration may be rather consequence or related to neurodegeneration than linked to the first demyelinating event. Further investigation related to disease trajectories of immunomodulatory or neuroprotective treatments are required.

Background: With the development of highly effective disease-modifying treatments, vaccinations are becoming increasingly important in people with neurological autoimmune diseases. However, questions regarding the safety and efficacy of vaccinations under immunotherapy remain.

Objective: To provide recommendations on types and timing of vaccinations for people with neuroimmunological diseases under different immunotherapies.

Design: Our study presents a German evidence-based expert consensus on vaccination under immunotherapies in neurological autoimmune diseases.

Methods: Based on literature research, a consortium of experts evaluated the quality of evidence, integrated clinical experience, and responded to a questionnaire determining an agreement (>75%) on statements concerning vaccination upon immune therapies in neuroimmunological diseases.

Results: The specific humoral and cellular response to vaccination can be compromised under alemtuzumab, azathioprine, cladribine, cyclophosphamide, CD19/CD20 antibodies (inebilizumab, ocrelizumab, ofatumumab, rituximab, ublituximab), dimethyl fumarate/diroximel fumarate, FcRn inhibitors (efgartigimod, rozanolixizumab), complement C5 inhibitors (eculizumab, ravulizumab, zilucoplan), interleukin-6 receptor antibodies (tocilizumab, satralizumab), intravenous immunoglobulins, long-term steroid administration, methotrexate, mitoxantrone, mycophenolate mofetil, tacrolimus, teriflunomide, tumor necrosis factor-α blockers, and sphingosine-1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, siponimod), as well as after autologous stem cell transplantation. The lymphocyte count can have an influence here. Overall, it is generally advisable to complete vaccination before starting immunotherapy. However, in the case of an active inflammatory disease course with possible irreversible neurological deficits, a delay in therapy initiation until immunization has been completed cannot be justified. The application of live vaccines is contraindicated for most therapies and is only recommended after a strict risk-benefit assessment.

Conclusion: Vaccinations are necessary for individuals on immunotherapy to reduce the risk of infections and the associated risk of worsening neurological autoimmune diseases. However, the humoral and cellular vaccination response may be impaired under immunotherapy necessitating close monitoring. Here, we provide applicable recommendations to optimize immunization for individuals receiving immunotherapy due to a neurological autoimmune disease.

The development and successful clinical application of engineered T cells expressing synthetic chimeric antigen receptors (CARs) represents a milestone in cancer therapy. This approach optimizes physiological in vivo T-cell activation against specific target antigens expressed on defined cell subsets with the goal of their deep and sustained depletion. Significant progress has been made in redesigning CAR T-cell constructs to improve patient safety, therapeutic efficacy, and accessibility. Efforts have also focused on streamlining manufacturing to improve availability and reduce costs, two critical challenges to widespread adoption. Beyond hematologic malignancies, CAR T-cell therapies are now increasingly being repurposed to tackle B-cell-mediated autoimmune diseases (AIDs). This is primarily achieved through broad B-cell depletion, but more targeted approaches-such as the selective elimination of autoantibody-producing B-cell subpopulations-are also being explored. Important considerations in their implementation are identifying the most pertinent patient groups, tailoring their treatment up to the point of CAR-infusion, and following up on their unique toxicity-profile. In the context of neurological AIDs-including refractory myasthenia gravis, Lambert-Eaton syndrome, multiple sclerosis, and stiff-person syndrome-early clinical experience suggests promising efficacy and tolerability, leading to a growing number of registered clinical trials. In this review, we provide an overview of the mechanism and evolution of CAR T-cell therapy, highlighting why its application in AIDs, particularly in neurology, represents a highly promising therapeutic strategy.

Background: There is no standardized treatment for acquired amyloid polyneuropathy (AAP) in domino liver transplant (DLT) recipients.

Objectives: Our objective is to analyze the efficacy and safety of patisiran for the treatment of AAP in DLT recipients.

Design: We performed a postauthorization prospective longitudinal study of DLT recipients with AAP who received patisiran treatment for 22 months.

Methods: The primary endpoint was change in the Neuropathy Impairment Scale (NIS) from baseline. Other assessments included neurophysiologic study, quantitative sensory testing, 10 m walking test, and quality of life and disability questionnaires. As safety parameters we analyzed evidence of graft rejection, immunosuppression levels, and renal and cardiac adverse effects.

Results: Four patients were recruited. The mean NIS at baseline was 8.5 ± 2.08. All patients presented clinical improvement after 22 months of treatment, with a mean NIS of 4.75 ± 2.27 points. The mean change from baseline in the NIS was -3.75 ± 0.71 (95% CI: -0.47 to 7.97). The use of patisiran was not associated with cardiovascular or renal side effects. No patient presented relevant changes in immunosuppression levels or graft rejection.

Conclusion: Our study suggests that patisiran may improve neurological manifestations in DLT recipients with AAP, producing no relevant adverse effects.

Background: Although migraine is the second most prevalent form of headache, its preventive treatment has some contraindications and complications. It has been postulated that lacosamide reacts with collapsin response mediator protein 2 and prevents its phosphorylation, inhibiting calcitonin gene-related peptide release in the trigeminal system, which might have a role in migraine management.

Objective: Our study aimed mainly to evaluate the efficacy and safety of lacosamide as an alternative medication to topiramate for the prevention of migraine, especially in patients who had contraindications to topiramate and other approved antiseizure medications used for migraine prevention.

Design: Our study included two parallel groups: the lacosamide and the topiramate groups.

Methods: We recruited episodic migraine patients between the ages of 18 and 65; the lacosamide group received lacosamide 50 mg once daily for 1 week, then twice daily from the 8th day till the 90th day); while the topiramate group received topiramate 50 mg once daily for 1 week, then 50 mg twice daily from the 8th day till the 90th day.

Results: There was not a statistically significant difference between the lacosamide and topiramate in the absolute change in monthly migraine days (MMD) at 90 days with p-value 0.34, there was no significant difference between lacosamide and topiramate groups regarding the percentage of patients with ⩾50% reduction in the baseline migraine days frequency in the last 4 weeks of the treatment period with a p-value 0.11. In total, 14.0 (4.7%) patients in the lacosamide group and 24.0 (8.0%) in the topiramate group stopped treatment prematurely due to intolerance to drug-related adverse effects, hazard ratio 2.83, 95% confidence interval (1.34-4.72), p-value 0.03.

Conclusion: In episodic migraine patients, the regular use of lacosamide 50 mg Bid for 3 months yielded reductions in the MMD, migraine days that required acute medications, and Headache Impact Test-6 score comparable to those achieved using topiramate 50 mg Bid. Lacosamide was more tolerable than topiramate in episodic migraine patients.

Trial registration: Prospectively registered on clinicaltrials.gov, NCT06243692-January 29, 2024; https://clinicaltrials.gov/study/NCT06243692.