Early differentiation of multiple system atrophy-parkinsonian subtype (MSA-P) from Parkinson’s disease (PD) remains challenging, particularly when autonomic dysfunction is absent during the early disease course. We report a 72-year-old woman who initially presented with asymmetric parkinsonism and was considered to have probable PD. Within the first five years, however, several red flags for an atypical parkinsonian syndrome became evident, including persistently poor levodopa responsiveness, relatively rapid motor progression, bilateral striatal hypometabolism on fluorodeoxyglucose positron emission tomography, and progressive posterior putaminal atrophy with iron deposition on serial magnetic resonance imaging. Definite orthostatic hypotension emerged approximately six years after motor onset, prompting revision of the diagnosis from PD to MSA-P. During the subsequent 18 months, dysphagia, severe dysarthria, recurrent falls, urinary retention, urinary incontinence, and a postvoid residual volume of 262 mL developed, together supporting clinically established MSA-P under the 2022 Movement Disorder Society criteria. At ten-year follow-up, the patient was semi-bedridden with marked postural deformity and complete loss of independent mobility. This case illustrates a delayed-dysautonomia phenotype in which diagnostic autonomic manifestations lagged behind motor and neuroimaging abnormalities by several years. It emphasizes the importance of early recognition of atypical red flags, repeated diagnostic reassessment, and longitudinal multimodal imaging when an apparent PD phenotype evolves atypically.
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.
