Therapeutic Advances in Neurological Disorders最新文献

Background: Cerebrovascular events are a potentially serious complication of giant cell arteritis (GCA) with intracranial involvement. However, diagnosing GCA in this context remains challenging, as classical clinical features may be absent.

Objectives: To identify characteristic cerebellar infarct patterns associated with intracranial GCA and to differentiate them from other common causes of posterior circulation stroke.

Design: Multicenter retrospective study.

Methods: A total of 125 patients with cerebellar infarctions of various etiologies were included. Among these, 19 patients had confirmed intracranial GCA. Infarct patterns were compared to those seen in strokes of cardioembolic origin (n = 42), arterio-arterial embolism from proximal vertebral artery atherosclerosis (n = 13), local atherosclerotic stenosis of the V4 segment (n = 21), and vertebral artery dissection (n = 30). Infarct topography was assessed using acute-phase diffusion-weighted magnetic resonance imaging. Sensitivity and specificity were calculated for individual imaging features.

Results: Distinct imaging signatures were observed in patients with GCA. A "corona-like" infarct pattern, defined by sparing of the medial branch of the proximal posterior inferior cerebellar artery (PICA), demonstrated a sensitivity of 79% and a specificity of 64%. A patchy infarct pattern, characterized by scattered non-confluent lesions, was present in 53% of GCA cases and showed high specificity (93%). When both features were present, specificity increased to 98% and sensitivity was reduced to 47%.

Conclusion: Our findings reveal a distinct cerebellar infarct pattern associated with intracranial GCA, characterized by a corona-like configuration and patchy lesions predominantly involving the lateral PICA territory. Recognition of this imaging phenotype may enhance diagnostic accuracy in challenging cases and facilitate the timely initiation of immunosuppressive therapy.

Background: Converging lines of preclinical evidence support the neuroprotective properties of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in Parkinson's disease (PD). Nevertheless, results from randomized-controlled clinical trials (RCTs) remain conflicting.

Objectives: To assess the safety and efficacy of GLP-1 RAs in PD.

Design: Systematic review and meta-analysis of randomized placebo-controlled clinical trials.

Data sources and methods: A systematic search of MEDLINE and Scopus databases was conducted on October 7, 2025, for randomized placebo-controlled clinical trials investigating GLP-1 RAs in adults with PD. Risk of bias was evaluated using the Cochrane Collaboration risk-of-bias (RoB2) tool.

Results: Four RCTs comprising 667 PD patients (377 receiving GLP-1 RAs) were included. Between baseline and end-of-treatment, no differences were observed in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score change between GLP-1 RA- and placebo-treated patients in either off-medication (standardized mean difference (SMD): -0.16; 95% CI: -0.64 to 0.32; p = 0.52) or on-medication states (SMD: -0.13; 95% confidence interval (CI): -0.51 to 0.25; p = 0.49). No significant differences were uncovered in other MDS-UPDRS subscores, Non-Motor Symptoms Scale, Montreal Cognitive Assessment, or Parkinson's Disease Questionnaire scores. The risk of serious adverse events and odds of treatment discontinuation were similar between groups, but GLP-1 RAs were associated with an increased risk of weight loss compared to placebo (risk ratio: 1.44; 95% CI: 1.04-1.99; p = 0.03).

Conclusion: GLP-1 RAs were not associated with improvements in motor or non-motor domains of PD. However, robust preclinical evidence and promising findings in select subpopulations warrant further RCTs to evaluate their neuroprotective potential, prioritizing long-acting and brain-penetrant agents that effectively engage central GLP-1 circuits for PD treatment.

Registration: The pre-specified protocol of the present systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration ID: CRD420251008703).

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has shown promising results in treating pharmaco-resistant essential tremor (ET). This incisionless, image-guided technique targets the ventralis intermedius nucleus of the thalamus with precision, sparing surrounding eloquent tissue.Objective: This study aims to assess the efficacy of MRgFUS thalamotomy in improving tremor among ET patients, as objectively measured by a tri-axis accelerometer, and to compare these objective measures with the conventional Clinical Rating Scale for Tremor (CRST).Design: Prospective observational study.

Methods: Ten ET patients (aged 68.1 ± 11.8 years) received the MRgFUS treatment. Improvements in tremor severity were assessed using primary (CRST), with additional measurements of kinematic feature obtained from a tri-axis accelerometer. Correlations between accelerometer-derived kinematic features and CRST scores were evaluated.

Results: Significant improvement in tremor severity was observed in the cohort, as measured by both the accelerometer and CRST (paired Student's t test, p < 0.05) before and 1 day after the treatment. A moderate-to-strong correlation was found between accelerometer measurements and CRST scores.

Conclusion: The tri-axis accelerometer provides an effective means of monitoring tremor reduction following MRgFUS and correlated well to the clinical scales like CRST. This study supports the feasibility of accelerometer-based monitoring in clinical practice for MRgFUS assessment.

Background: Basilar artery occlusion (BAO) is a rare but devastating form of ischaemic stroke, with high rates of disability and mortality. While randomized trials have demonstrated the benefit of mechanical thrombectomy (MT) in BAO, the optimal first-line technique - aspiration, stent retriever, or a combined approach - remains undefined.

Objectives: This multicentre study aimed to provide a three-way comparison of MT techniques in terms of efficacy, safety and subgroup-specific outcomes.

Design: A retrospective observational study.

Methods: We prospectively included 517 consecutive patients with acute isolated BAO treated with MT across seven comprehensive stroke centres between January 2019 and December 2023. Patients were grouped by first-line technique: aspiration (n = 200), stent retriever (n = 260), or combined approach (n = 57). The primary outcome was favourable functional outcome at 90 days (mRS 0-3). Inverse probability weighting (IPW) adjusted for baseline imbalances. Secondary outcomes included successful recanalization, excellent outcome (mRS 0-1), functional independence (mRS 0-2), mortality, symptomatic intracranial haemorrhage (sICH) and haemorrhagic transformation (HT). Predefined subgroup analyses were performed.

Results: After adjustment, 90-day outcomes were similar across groups. Stent retrievers achieved higher recanalization rates (RR 1.86 vs aspiration, p < 0.001), while the combined technique was associated with less HT (RR 0.39 vs aspiration, p = 0.008). In patients ⩾80 years, stent-retriever use led to better outcomes than aspiration (39.2% vs 18%; p = 0.021). No other significant subgroup interactions were found.

Conclusion: While overall functional outcomes were comparable, stent retrievers yielded superior recanalization and the combined technique reduced haemorrhagic complications. Technique selection may benefit from individualized, anatomy-driven decision-making. Randomized studies are warranted.

What is this summary about? This is a plain language summary of an article published in The Lancet Neurology in 2024. The article describes the results of the ADHERE clinical study, which involved people with chronic inflammatory demyelinating polyradiculoneuropathy, or CIDP for short. CIDP is a rare autoimmune disease that affects nerves in the arms and legs. There is a need for new treatment options for CIDP that reduce symptoms, are convenient to take, and have manageable side effects. What happened in this study? In this study, researchers looked at how well efgartigimod worked in people with CIDP and the side effects people had during the study. Stage A of the study aimed to find people who had signs of reduced symptoms and disability after receiving efgartigimod. People received weekly injections of efgartigimod under the skin (subcutaneous). Stage B compared efgartigimod with a placebo treatment to find out how well efgartigimod worked and the side effects that people had. What were the results? Overall, 66% of all participants in ADHERE showed signs of clinical improvement after receiving efgartigimod. Half of these people had first signs of clinical improvement in about 22 days. Compared to a placebo, people who received efgartigimod had a reduced risk of CIDP symptoms getting worse or returning (relapsing). More people who received efgartigimod were able to carry out their daily activities and maintained grip strength than those who took a placebo. Most side effects that people developed during the study were mild or moderate. What do the results mean? In this study, people who received efgartigimod had stable or improving symptoms for up to 48 weeks, while more people who received a placebo had worsening strength, disability, and quality of life. Subcutaneous injections of efgartigimod may offer a more convenient option for people with CIDP compared with current treatments.

Multi-system comorbidities are common in patients with multiple sclerosis (PwMS) and significantly influence the disease's presentation and progression. A comorbidity is defined as an illness other than the specific disease of interest (in this case, MS). Generally, chronic or recurrent conditions are included, while transient conditions such as infection or concussion are excluded. Certain modifiable metabolic diseases in PwMS, such as hypertension, diabetes, dyslipidemia, and modifiable health factors such as smoking, alcohol, and obesity, are also considered part of MS comorbidity in this review, since these are risk factors not only for poor outcomes in MS but also for other vascular comorbidities in PwMS. Cohort studies and clinical trials have reported that comorbidity could have multiple adverse effects on MS. The purpose of this review is to summarize studies investigating modifiable risk factors of comorbidity of MS, as well as multiple body system comorbidities in MS, focusing on the influence these comorbidities have on MS outcomes. We aim to emphasize that the management of MS involves not only disease-modifying therapy, but also requires controlling and preventing modifiable risk factors for comorbidities and appropriate treatment of comorbidities, as these interventions may be equally crucial in improving the prognosis of MS.

Hereditary spastic paraplegia (HSP) groups rare, clinically and genetically heterogeneous neurodegenerative disorders, characterized by progressive lower-limb spasticity and weakness. Over the past decades, diagnostic strategies have evolved from pure clinical assessment to the integration of molecular tools, with next-generation and long-read sequencing (LRS) substantially increasing diagnostic yield and refining genotype-phenotype correlations. Neuroimaging provides complementary information, especially in specific subtypes such as SPG11 and SPG15, supporting diagnosis and guiding testing. Treatment has historically focused on symptomatic care, including physiotherapy, antispastic agents, and botulinum toxin, with dalfampridine explored for gait improvement in selected patients. More recently, research has expanded into disease-modifying avenues, such as drug repurposing (e.g., statins in SPG5, menatetrenone in ALS2) and early gene-based interventions in ultra-rare subtypes. At the same time, advances in technology, ranging from quantitative imaging and digital gait analysis to induced pluripotent stem cell models and artificial intelligence, are beginning to influence both clinical management and trial design. This review traces the trajectory of HSP care from its historical foundations to present standards and emerging innovations, outlining how technological progress is shaping realistic prospects for future therapeutic strategies.

Background: The prognostic significance of resting heart rate (HR) in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) after endovascular treatment (EVT) remains to be elucidated.

Objectives: To determine whether HR is differentially associated with functional outcomes in patients dichotomized by anterior (ACS) or posterior circulation stroke (PCS) after successful reperfusion.

Design: A multicenter retrospective cohort study.

Methods: We retrospectively analyzed consecutive successfully recanalized LVO-AIS patients with complete HR recordings at admission, 30 min, 12 h, 24 h, and 48 h post-EVT. A good outcome was defined as modified Rankin Scale (mRS) 0-2 for ACS or mRS 0-3 for PCS at 3 months. Binary logistic regression and receiver operating characteristic analyses were used to assess associations and predictive performance.

Results: Among 505 patients (362 ACS, 143 PCS), lower HR at 12, 24, and 48 h post-EVT was independently associated with good outcomes in both groups. HR showed higher predictive accuracy for PCS (AUC: 0.872-0.885) than for ACS (AUC: 0.732-0.762).

Conclusion: HR following EVT independently predicts functional outcome in LVO patients, demonstrating stronger predictive value for PCS than ACS. These results highlight the potential of HR monitoring in post-EVT management.

Chimeric antigen receptor T-cell (CAR-T) therapy has become an established treatment for several haematological malignancies in relapse and is being evaluated for new indications. An important clinical challenge associated with the use of CAR-T therapy, however, is the common development of neurotoxicity. Different neurotoxicity syndromes have been reported. The best-known form of CAR-T neurotoxicity is immune effector cell-associated neurotoxicity syndrome, which can be associated with various findings on magnetic resonance imaging (MRI), including cerebral oedema and leptomeningeal enhancement. Other manifestations of neurotoxicity include movement disorders, myelopathy, cranial nerve palsies and ischaemic strokes. MRI plays a key role in the diagnosis and management of patients with suspected neurotoxicity. It can be used to support the diagnosis, exclude differential diagnoses and forms part of the grading of neurotoxicity. Other roles for MRI after CAR-T therapy include assessment of potential longer-term effects of therapy and neurotoxicity, and the evaluation of patients with emerging indications for CAR-T therapy. We recommend performing a baseline MRI brain prior to CAR-T therapy where feasible, as this greatly aids in the interpretation of neuroimaging findings. Here, we discuss the established and potential roles of neuroimaging in the context of neurotoxicity secondary to CAR-T therapy.

Background: The quality and clinical outcomes of mechanical thrombectomy (MT) performed at thrombectomy-capable stroke centers (TSCs) versus comprehensive stroke centers (CSCs) remain insufficiently characterized.

Objective: To compare MT outcomes between TSCs and CSCs and to develop and externally validate an online tool for individualized prognosis and decision support.

Design: Retrospective cohort study including derivation and external validation cohorts from multiple stroke centers.

Method: Patients with anterior circulation large vessel occlusion who underwent MT within 24 h were analyzed. Inverse probability of treatment weighting (IPTW) and multivariable logistic regression estimated the effects of stroke center certification. Sensitivity analyses using alternative model specifications, patient subsets, and predefined subgroups assessed robustness and heterogeneity. A prognostic model was developed using least absolute shrinkage and selection operator regression after IPTW, externally validated using 2023-2024 data from different centers, and deployed as a Shiny-based online tool predicting 90-day modified Rankin Scale outcomes (0-2 for independence, 0-5 for survival).

Results: The median age was 69 years (interquartile range (IQR) 60-77) in the derivation cohort (n = 975) and 72 years (IQR 64-80) in the validation cohort (n = 484). Functional outcomes and survival probabilities were similar between cohorts. After IPTW and adjustment, logistic regression showed CSCs were associated with higher 3-month survival (OR, 1.70 (95% CI: 1.31-2.22)). Sensitivity and subgroup analyses validated findings. The online prediction model, incorporating eight variables, demonstrated strong discriminative ability for functional outcomes (C-statistic 0.77 (95% CI: 0.73-0.81)) and survival (C-statistic 0.77 (95% CI: 0.71-0.82).

Conclusion: CSCs were significantly associated with a higher probability of survival compared to TSCs, while no significant difference was observed in favorable functional outcomes. An online multivariable model could predict clinical outcomes and guide decision-making between TSCs and CSCs in routine clinical practice.