Therapeutic Advances in Neurological Disorders最新文献

Background: Non-ischemic cerebral enhancing (NICE) lesions are a rare complication following endovascular therapy (EVT) for cerebral aneurysms. Although first described in 2008, data on long-term outcome and treatment response remain limited.

Objectives: In this study, we investigated the long-term follow-up of patients with NICE lesions, including magnetic resonance imaging (MRI) findings, clinical course, and treatment.

Design: For this single-center ambispective observational study, we enrolled nine patients with NICE lesions after EVT for cerebral aneurysms.

Methods: We analyzed patients diagnosed with NICE lesions following EVT between 2008 and 2024 at the University Hospital of Augsburg. Data collection included patients' and procedural characteristics, clinical course, MRI findings, and response to immunotherapies.

Results: We present the long-term follow-up of five patients already published and four additional cases. Nine female patients (mean age at diagnosis 50.67 ± 11.82 (± standard deviation, SD) years) were identified and analyzed with a mean follow-up of 1659.44 ± 1426.87 (SD) days, ranging from 328 to 5223 days (cumulative follow-up of 40.92 patient-years). In total, 112 MRIs were available for evaluation. Eight patients developed symptoms at a mean of 11 ± 13.41 (SD) days post-EVT, one patient remained asymptomatic. New NICE lesions during follow-up were detected in six patients, five patients developed new or increasing symptoms. All patients received glucocorticosteroids with variable duration, six patients required additional immunotherapies. At final follow-up, all patients had a favorable outcome (modified Rankin Scale 0-1), though residual symptoms persisted in four of them.

Conclusion: Hitherto, this study presents the longest follow-up period of patients developing NICE lesions after EVT. NICE lesions may have a highly variable course regarding radiological and clinical characteristics, with potential for both clinical and radiological recurrence years after initial presentation. While immunosuppressive therapy appears effective, optimal treatment regimens and duration have yet to be determined. Our findings underline the importance of regular clinical and MRI controls for individual patient care in this rare condition.

Background: Migraine is a disabling neurovascular disorder characterized by recurrent attacks that lead to extracranial and visual involvement. Several studies have investigated the retinal vasculature features in individuals with migraine, but there have been conflicting results.

Objective: To evaluate retinal structure in migraine patients before (T0) and after 6-month therapy (T1) with anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs), using optical coherence tomography (OCT) imaging.

Design: A case-control and longitudinal study was conducted between January 2021 and December 2023, including 20 eyes from 10 healthy controls (HCs) and 32 eyes of 16 patients with migraine and treated with anti-CGRP mAbs according to AIFA criteria.

Methods: Patients underwent OCT angiography (OCT-A) to assess retinal vessel density (VD) and spectral-domain OCT (SD-OCT) to evaluate central retinal thickness, macular structure, and peripapillary retinal nerve fiber layer thickness. These parameters were assessed in both groups at T0 and again after 6 months (T1) as part of routine clinical care.

Results: All migraineurs exhibited a significant reduction in disease disability at T1, as assessed by clinical parameters. OCT data analysis revealed that individuals with migraine showed a significant increase in temporal retinal nerve fiber layer (RNFL) thickness and a reduction in nasal RNFL thickness compared to HCs. No differences in retinal circulation were observed between the groups at baseline. At T1, RNFL thickness remained sustained in the superior temporal sector, while the percentage VD of the superficial capillary plexus and radial peripapillary capillary significantly increased in the nasal perifoveal, inferior temporal, and hemi-inferior subregions.

Conclusion: Our study suggests that specific retinal structural changes could precede vascular dysfunction in migraine and can be detected early by combining SD-OCT and OCT-A acquisitions. Short-term treatment with anti-CGRP mAbs may exert neuroprotective effects, potentially preventing permanent ocular damage.

Trial registration: EyeHEAD Study (Trial registration number AIFA July/2024: IT 1735, www.aifa.gov.it/registro-studi-osservazionali).

Background: The novel criteria for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) have established imaging with nerve ultrasound (NUS) and magnetic resonance neurography (MRN) as complementary methods for CIDP diagnosis.

Objectives: Our goal was to investigate the role of MRN and NUS for CIDP monitoring.

Methods and design: We longitudinally examined 12 CIDP patients from 2016 to 2022 using NUS, MRN, nerve conduction studies (NCS), and clinical parameters (inflammatory neuropathy cause and treatment (INCAT)/overall disability sum score (ODSS)). NUS evaluated the cross-sectional area (CSA) of the median, ulnar, radial, tibial, fibular, and sural nerve as well as the intranerve CSA variability (INV_csa) of the tibial, fibular, ulnar, and median nerve, whereas MRN evaluated T2-weighted sequences of the fibular and tibial nerve at the popliteal fossa.

Results: Five patients showed clinical improvement/stability with corresponding improved or stable NCS/NUS parameters (number of nerves with increased CSA and INV_CSA). Seven deteriorating patients showed deteriorating NCS and either increasing or decreasing NUS markers possibly indicating inflammatory activity or degenerative CSA reduction. The difference ΔINCAT/ODSS_2022-2016 correlated positively with NUS ΔINV_CSA2022-2016 (p = 0.007, r = 0.731, n = 12) and with NUS ΔCSA_2022-2016 of the tibial nerve (p = 0.0005, r = 0.865, n = 12). Further, NUS-CSA of the tibial nerve in the popliteal fossa in 2016 correlated inversely with the difference of the INCAT/ODSS score (ΔINCAT/ODSS_2022-2016; r = -0.653; p = 0.033; n = 11). Finally, the Bland-Altman analyses for the tibial and fibular nerve showed a bias of -1.903 and 2.195 mm² (bias = NUS-CSA - MRN-CSA) accordingly revealing a difference between MRN and NUS measurements for deeper nerves.

Conclusion: CSA and INV_CSA of the tibial and fibular nerve can be used for monitoring in CIDP, and increased CSA of the tibial nerve is a good prognostic marker. MRN is more reliable for evaluating inflammation in proximal leg nerve segments.

Background: Inflammatory biomarkers, key predictors of ischemic stroke prognosis, may exhibit sex-specific predictive patterns.

Objectives: This study investigates sex-based differences in inflammatory biomarkers as predictors of 90-day clinical outcomes in acute ischemic stroke patients undergoing mechanical thrombectomy (MT).

Design: Multicenter retrospective study.

Methods: This study included 970 patients consecutively treated with MT for anterior circulation large vessel occlusion between 2016 and 2023. Inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP), systemic inflammation response index, and systemic immune-inflammation index, were measured on admission and 24-h post-MT. Inverse probability weighting was used to balance baseline characteristics between male and female patients. Least absolute shrinkage and selection operator regression and logistic regression were used to identify independent predictors of 90-day good functional outcomes (modified Rankin scale (mRS) score 0-2) and death, stratified by sex and age groups (<55 and ⩾55 years).

Results: In the male weighted population (516 patients), multivariable analysis showed that MLR (odds ratio (OR): 0.37, 95% confidence interval (CI): 0.13-0.95, p = 0.041), 24-h NLR (OR: 0.88, 95% CI: 0.83-0.94, p < 0.001), and 24-h MLR (OR: 0.33, 95% CI: 0.12-0.94, p < 0.001) were independent predictors of 90-day good functional outcome with age-specific differences noted. Twenty-four-hour MLR (OR: 5.05, 95% CI: 1.36-4.28, p = 0.047) and erythrocyte sedimentation rate (OR: 1.02, 95% CI: 1.01-1.04, p = 0.025) were independent predictors of death, respectively, for men <55 and men ⩾55 years. In the weighted female population (454 patients), 24-h NLR (OR: 0.89, 95% CI: 0.81-0.96, p = 0.007) and 24-h CRP (OR: 0.98, 95% CI: 0.97-0.99, p = 0.029) were independent predictors of good functional outcomes. Twenty-four-hour CRP was also an independent predictor of 90-day death (OR: 1.01, 95% CI: 1.00-1.02, p = 0.017) in women with no age-specific differences noted. Interaction analysis revealed significant sex-specific relationships for MLR and CRP but not for NLR.

Conclusion: This study highlights sex-based differences in the predictive value of widely available inflammatory biomarkers for stroke outcomes. MLR was a distinct predictor in men, while CRP was uniquely associated with outcomes in women. These findings underscore the need for sex-stratified approaches in stroke management and research.

Background: Outcomes after thymectomy differ greatly between non-thymomatous and thymomatous myasthenia gravis (MG), meriting an in-depth exploration.

Objective: To examine the treatment and prognosis of non-thymomatous and thymomatous MG patients after thymectomy.

Design: A multicenter, retrospective, case-control study focused on MG patients following thymectomy from November 2010 to January 2024. After propensity score matching, 284 patients (142 with non-thymomatous MG and 142 with thymomatous MG) were included, with a median follow-up of 2.94 years.

Methods: Four outcomes were examined: minimal manifestations status (MMS) or better at the final visit, sustained clinical response, postoperative myasthenic crisis, and long-term mortality. Kaplan-Meier, logistic regression, cox regression, nomogram, receiver operating characteristic curve, decision curve, and calibration curve analyses were used for assessment.

Results: Non-thymoma patients had a lower proportion of postoperative myasthenic crisis (5.6% vs 13.4%, p = 0.026) and long-term mortality (1.4% vs 9.9%, p = 0.002) but a higher proportion of sustained clinical response (66.2% vs 52.1%, p = 0.016) than thymoma patients. For both non-thymomatous and thymomatous MG, anti-acetylcholine receptor antibody (AChR-Ab) positivity was the independent predictor for MMS or better at the final visit (p = 0.048; p = 0.016) and sustained clinical response (p = 0.035; p = 0.037). Most severe Myasthenia Gravis Foundation of America (MGFA) classification and high-grade Masaoka histopathology were independent predictors for postoperative myasthenic crisis (p < 0.001; p = 0.010) and long-term mortality (p = 0.006; p = 0.014) for thymomatous MG. Postoperative prednisone combined with tacrolimus (Pred + TAC) was associated with achieving sustained clinical response (p = 0.026; p = 0.030) and prednisone tapering for both groups.

Conclusion: Non-thymomatous MG exhibited a more benign course with better outcomes. AChR-Ab positivity indicated a better prognosis for both groups, while thymomatous MG with severe MGFA classification and high-grade histopathology requires close monitoring and follow-up. Postoperative Pred + TAC could be an effective immunotherapy option for beneficial outcomes.

Background: Managing OFF episodes in patients with Parkinson's disease becomes increasingly challenging over time, making it critical to tailor treatment to each patient's needs and characteristics for effective care.

Objectives: Study CTH-301 assessed the long-term safety/tolerability and efficacy of sublingual apomorphine (SL-APO) for the on-demand treatment of OFF episodes.

Design: The findings from four post hoc analyses of Study CTH-301, conducted to understand factors influencing SL-APO retention and safety/tolerability, with a particular focus on oropharyngeal treatment-emergent adverse events (TEAEs) are reported.

Methods: The first analysis evaluated baseline variables differing between patients who completed the study and those who discontinued due to either lack of efficacy or adverse events to help define patients more likely to benefit from SL-APO therapy: The second and third analyses compared safety/tolerability between the subgroups of patients who were or were not receiving dopamine agonist (DA) treatment, and in those aged <70 or ⩾70 years at baseline, respectively. The fourth analysis examined oropharyngeal TEAEs.

Results: Patients in a younger age group, those experiencing morning akinesia or delayed ON, and those taking lower dose/fewer intakes of levodopa and concomitant DAs were more likely to benefit from SL-APO therapy. Patients taking concomitant DAs reported lower rates of DA-related TEAEs and a higher mean SL-APO optimal dose. Specific analyses in patients aged ⩾70 years indicated that this age group reported similar rates of TEAEs and a similar profile of the most common TEAEs compared with the group aged <70 years. A lower total daily dose of SL-APO was associated with a reduced risk of developing oropharyngeal TEAEs. Such events were mostly mild or moderate, occurring within the first months after SL-APO initiation, and generally resolved, with worsening being rare.

Conclusion: These analyses provided insights into retention and safety/tolerability of SL-APO, helping clinicians and patients make informed treatment decisions.

Multiple sclerosis (MS) is an autoimmune condition characterized by inflammatory demyelination that leads to irreversible neurological damage within the central nervous system (CNS). This review examines the therapeutic potential and clinical efficacy of cladribine tablets (CladT) for treating MS, focusing on the immune reconstitution mechanism and CNS effects. CladT represents a notable advance among disease-modifying therapies for MS due to its selective targeting of lymphocytes, resulting in sustained yet reversible immune modulation. This action leads to a substantial reduction in memory B cells while preserving the innate immune system and maintaining immunoglobulin levels, thereby mitigating the risks of secondary autoimmunity and infection. Cladribine appears to penetrate the blood-brain barrier, as indicated by cerebrospinal fluid (CSF) studies from parenteral cladribine use. In MS, CladT is associated with reductions in CSF immunological markers, such as oligoclonal bands and neurofilament light chain levels; it also mitigates acute and chronic inflammation, as evidenced, respectively, by consistent reductions in unique active lesions, and significant decrease in slowly expanding lesions in patients with predominant grey matter damage. These findings underscore the potential of CladT in reducing disability accumulation and improving long-term clinical outcomes in patients with highly active disease. By synthesizing data from clinical trials and real-world studies, this review underscores the effectiveness of CladT in reducing relapse rates, disability progression and magnetic resonance imaging-detected disease activity and emphasizes the importance of early high-efficacy treatment for optimizing long-term outcomes. Furthermore, emerging biomarkers are discussed as potential tools for predicting individual responses to therapy, thereby enabling more personalized treatment strategies. This review also provides valuable insights into the positive impact of CladT on quality of life measures, long-term outcomes and safety profile, all of which support the use of CladT in the evolving landscape of MS management.

Background: There is currently no established standard of care for recurrent glioblastoma (GBM). Re-irradiation (re-RT) and Bevacizumab (BEV) are both used in salvage treatment, but their combined efficacy remains uncertain.

Objectives: To evaluate whether combining re-irradiation with BEV improves survival outcomes compared to BEV alone in patients with recurrent high-grade gliomas (rHGG).

Design: Systematic review and meta-analysis of two-arm clinical trials.

Data sources and methods: A comprehensive literature search was conducted in Scopus, PubMed, Web of Science, and the Cochrane Library up to April 2024. Two independent reviewers assessed studies for eligibility and extracted data. Study quality was evaluated using the ROBINS-I and ROBINS-II tools. The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), toxicity, and prognostic factors.

Results: The meta-analysis demonstrated a significant improvement in OS with combined BEV and re-irradiation compared to BEV alone (hazard ratio (HR) 0.69, 95% confidence interval (CI: 0.56-0.85); p = 0.0005), corresponding to a 31% reduction in the risk of death. PFS also improved significantly (HR 0.64, 95% CI (0.45-0.90); p = 0.01). No significant increase in grade 3 toxicities was observed with the combination therapy. Subgroup analyses indicated that younger age and female gender were statistically associated with better OS, though the effect of age was modest and male gender was linked to poorer survival. Karnofsky performance status significantly influenced survival. Pulsed versus non-pulsed re-irradiation showed no differential effect on outcomes.

Conclusion: The combination of re-irradiation and BEV significantly improves both OS and PFS in patients with rHGG, without increasing severe toxicity. These findings support the safety and efficacy of the combined approach. Prospective trials are warranted to guide standardized treatment protocols.

Trial registration: This review was prospectively registered with PROSPERO (CRD42023463183).

Background: Acute ischemic stroke (AIS) is a leading cause of mortality and disability worldwide. Intravenous thrombolysis (IVT) improves recovery, but predicting outcomes remains challenging. Machine learning (ML) and biomarkers like ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein β (S100β), and neuron-specific enolase (NSE) may enhance prognostic accuracy.

Objectives: We aimed to assess the predictive value of serum brain injury biomarkers for 3-month outcomes in AIS patients treated with IVT, using an ML-based model.

Design: A multicenter prospective cohort study was conducted, enrolling AIS patients treated with recombinant tissue plasminogen activator from 16 hospitals.

Methods: Of 1580 patients, 1028 were included and divided into training (n = 571), testing (n = 243), and external validation (n = 214) cohorts. Thirty-three variables, including demographics, clinical data, and biomarkers (UCH-L1, S100β, NSE), were analyzed. Least Absolute Shrinkage and Selection Operator regression was used for feature selection, and six ML algorithms were tested. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), F1-score, calibration curve, and decision curve analysis.

Results: The light gradient boosting machines (LightGBM) model achieved the best performance in the training dataset (AUC: 0.846; F1-score: 0.789) and external validation dataset (AUC: 0.714). Eight critical predictors, including age, admission National Institutes of Health Stroke Scale (NIHSS) score, Trial of Org 10172 in Acute Stroke Treatment, white blood cell, finger blood glucose, UCH-L1, S100β, and NSE, were identified and incorporated into an ML model for clinical application. Shapley additive interpretation analysis enhances the interpretability of the model, with NIHSS score and NSE as top contributors. External validation confirmed good calibration and consistent net benefit across threshold probabilities (0.1-0.8).

Conclusion: Integrating serum biomarkers (UCH-L1, S100β, NSE) with ML significantly improves 3-month outcome prediction in AIS patients. The LightGBM model offers robust performance and clinical interpretability for individualized treatment planning.