Background Neuromyelitis Optica Spectrum Disorder (NMOSD) is a severe autoimmune-mediated inflammatory condition affecting the central nervous system. While various factors, such as immunotherapy regimens, influence the risk of relapse, the predictive significance of aquaporin-4 immunoglobulin G (AQP4-IgG) status is still debated. Identifying the determinants of disease severity and factors associated with relapse is essential for the development of personalized therapeutic strategies. Objective This study aims to identify risk factors associated with relapse in patients diagnosed with serum AQP4 antibody-positive NMOSD. Additionally, it seeks to examine the impact of various traditional immunotherapy regimens and the different titres of AQP4-IgG on the relapse rates in these patients. Design This retrospective cohort study, conducted across multiple centers, examined longitudinal data from 314 seropositive AQP4-IgG NMOSD patients treated at seven medical centers from January 2014 to June 2024. Methods This study used annualized relapse rate (ARR) as the outcome measure. Kaplan-Meier, logistic regression, and Cox regression were used to assess the risk factors for relapse. The specific titers of AQP4-IgG were classified into different subgroups: negative, low-positive, moderate-positive, and high-positive. The relapse rate was compared among different AQP4-IgG titers and treatment patterns (tacrolimus, mycophenolate mofetil, azathioprine, oral glucocorticoid-only, or no medication). Results We reviewed 314 AQP4-IgG positive (median [IQR] age at onset: 45.0 [33.0, 54.0] years; 86.0% female) NMOSD inpatients and outpatients. The median disease duration was 47 (26, 84) months. The median relapse-free survival period for patients with NMOSD was 30 months. AQP4-IgG seropositive status (OR =6.75,95% CI 2.95-15.46,P<0.001)during the disease course and multisystem involvement at initial onset (OR =1.89,95% CI 1.025-3.486,P = 0.041) were identified as independent risk factors for relapse. Patients who received standardized immunotherapy during remission (OR = 0.05,95% CI 0.02-0.14,P<0.001) demonstrated a significantly reduced risk of relapse. In contrast, the median relapse time for patients treated solely with oral glucocorticoids was comparable to that of untreated controls (HR=0.92, 95% CI 0.68-1.23, P=0.561). Patients who achieved seronegative status during observation exhibited the longest median interval between relapses. Seroconversion to AQP4-IgG negativity (HR=0.40,95%CI 0.21-0.75,P=0.005) during observation was associated with a reduction in both relapse frequency and annualized relapse rate (ARR). Conclusion The implementation of standardized immunotherapy markedly decreased the incidence of relapse in patients with NMOSD. Multisystem involvement at initial onset and AQP4-IgG seropositive status during the course of the disease were predictive of a higher likelihood of relapse.
Non-ischemic cerebral enhancing (NICE) lesions are exceptionally rare complications of neuroendovascular procedures and have been reported predominantly after intracranial interventions, with only one previous case following extracranial carotid stenting. We report a second such case. A woman in her mid-thirties with inactive Takayasu arteritis underwent long-segment extracranial stenting of asymptomatic stenoses of the left common (CCA) and internal carotid (ICA) arteries using three overlapping stents. Eighteen days after the procedure, she developed new-onset headache; MRI showed a small left parieto-occipital hemorrhage and multiple ipsilateral NICE lesions. Serial MRI over 10 months demonstrated asynchronous NICE lesion behavior, with simultaneous emergence, regression, and persistence of ipsilateral and contralateral foci. Their non-ischemic morphology and the absence of clinical, laboratory, CSF, or vascular imaging evidence of active vasculitis argued against a Takayasu-related origin. Despite fluctuating lesion burden, she developed no persistent neurological deficits and required no long-term immunosuppressive therapy. Mild headaches and a one-day cluster of focal sensory seizures occurred, with no recurrence under low-dose lamotrigine. This case provides further evidence that NICE lesions are not confined to intracranial procedures and may also follow extracranial carotid stenting, showing highly variable lesion dynamics. The continued appearance of new lesions up to 308 days after stenting suggests persistent microembolization or delayed inflammatory manifestation of initially occult embolic deposits rather than a purely one-time periprocedural event. The divergence between radiological lesion burden and clinical severity further suggests that management should be guided primarily by the clinical course and that conservative management may be appropriate in clinically stable patients.
Background Immune Reconstitution Therapies (IRTs) represent a distinct class of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS), mainly characterized by transient as opposed to continuous immunosuppression. Dedicated guidelines on the long-term management of this class of drugs are lacking. Objectives This study aimed to define the positioning of IRTs, specifically Cladribine tablets, addressing patient selection, family planning, and long-term therapeutic strategies. Design An expert consensus study conducted between March and July 2025. Methods The Hellenic Academy of Neuroimmunology (HELANI) convened a Steering Committee and a 19-neurologist expert panel, selected among academic centers, public neurology departments and private hospitals/practices. Α three-round process was followed, comprising statement drafting, blinded online voting, and a face-to-face consensus meeting. Consensus required >80% agreement on a 5-point Likert scale. Results Of 24 initial assertions, 23 were retained for the final consensus framework. 22 achieved full consensus regarding both clinical principle and application. The panel established “Timely” high-efficacy intervention as the preferred treatment approach. Cladribine tablets were identified as the only IRT with sufficient data to support use in patients aged >55 years and was considered as appropriate for family planning without treatment interruption. One statement (vaccinations) was removed due to insufficient evidence. Regarding long-term management, consensus was achieved on the validity of re-treating clinically stable patients after Year 4; however, opposite views regarding the timing of re-treatment were expressed, advocating both continued maintenance and disease activity-driven approaches. Notably, Neurofilament Light (NfL) testing was unanimously rejected (0% agreement) as a standard monitoring tool. Conclusion This consensus establishes a framework for the timely Use and long-term management of IRTs. Cladribine serves as a central pillar, offering advantages in family planning and older populations, while re-treatment paradigms require personalized timing.
Background Symptomatic intracranial atherosclerotic stenosis (sICAS) represents a frequent cause of recurrent acute ischemic stroke (AIS). Although lipoprotein(a) [Lp(a)] is an established risk factor for atherosclerosis, its association with sICAS and large-artery atherosclerotic (LAA) stroke has been scarcely investigated in Caucasians. Objectives To investigate the association between serum Lp(a) levels and sICAS, and secondarily evaluate their association with LAA stroke. Design Cross-sectional, single-center observational study. Methods We enrolled consecutive patients with AIS. Multivariable logistic regression assessed the association between serum Lp(a) levels and sICAS. Discriminative performance was assessed using receiver operating characteristic (ROC) analysis; associations between Lp(a) and LAA stroke were evaluated in secondary models. Results Among 407 consecutive AIS patients, 43 (10.6%) had sICAS. Higher Lp(a) levels were independently associated with sICAS after multivariable adjustment. Each 1-unit increase in log 10 -transformed Lp(a) was associated with approximately 3-fold increased odds of sICAS (adjusted odds ratio [aOR]: 3.34; 95% CI: 1.78-6.25; p<0.001), and each 10 nmol/L increase in Lp(a) conferred a 5% increase in sICAS odds (aOR: 1.05; 95% CI: 1.02-1.08; p=0.003). Lp(a) levels ≥75 nmol/L were associated with approximately 3-fold higher odds of sICAS (aOR: 3.16; 95% CI: 1.56-6.41; p=0.001). In ROC analysis, an Lp(a) cutoff of 53.8 nmol/L demonstrated a high negative predictive value (93%), but a low positive predictive value (19%) for sICAS. In secondary analyses, higher Lp(a) levels were also independently associated with LAA stroke. Conclusion Elevated Lp(a) levels were independently associated with sICAS and LAA stroke in our cross-sectional study. The cutoff of 53.8 nmol/L was associated with a low likelihood of sICAS, warranting external validation. Lp(a) may serve as a routinely available biomarker for etiologic risk stratification in AIS, rather than as a stand-alone diagnostic marker.
Background Satralizumab, an interleukin-6 receptor monoclonal antibody, is approved for aquaporin-4 IgG (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorder (NMOSD). However, real-world evidence remains limited, particularly regarding treatment initiation during acute attacks, transitions from B-cell-depleting therapies, and safety during pregnancy. Objectives To evaluate the real-world effectiveness and safety of satralizumab in AQP4-IgG–seropositive NMOSD and to assess outcomes across key clinical scenarios. Design A multicenter retrospective observational study. Methods This study evaluated 36 patients with AQP4-IgG-seropositive NMOSD treated with satralizumab. Primary clinical evaluations included changes in the annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS) scores, alongside safety profiles. Special clinical scenarios, including the feasibility of initiation during acute attacks, outcomes in patients with persistent disease activity despite prior B-cell-depleting therapies, and exposure during pregnancy, were also evaluated. Results Over a median follow-up of 16.7 months, 97.2% of patients remained relapse-free. The overall median ARR decreased from 0.3 to 0.0 ( p < 0.001), and the median EDSS score decreased by 0.5 points ( p = 0.001). Patients initiating satralizumab during acute attacks (n = 10) demonstrated significantly greater EDSS score reductions compared with those initiating during remission (n = 26) (median change: -1.5 vs 0.0, p < 0.001), with no significant difference in ARR reductions. Furthermore, 6 patients with persistent disease activity on prior B-cell-depleting therapies achieved sustained clinical stability after transitioning to satralizumab. Adverse events occurred in 22.2% of patients, predominantly comprising mild upper respiratory tract infections. Notably, 1 patient exposed to satralizumab during early pregnancy remained relapse-free without severe maternal or obstetric complications; the neonate developed mild pneumonia and a 2-mm atrial septal defect, both of which were managed conservatively. Conclusion Satralizumab maintained low relapse rates and facilitated EDSS score reductions, even following B-cell-depleting therapy failure. Pronounced EDSS improvements with acute-phase initiation likely reflect concomitant rescue therapies and natural recovery. Single-case pregnancy exposure provides preliminary safety insights, requiring broader registry validation. These findings expand real-world evidence for satralizumab across diverse clinical scenarios.
