Nikolaos Mitsoudis

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.

Social cognitive impairment significantly impacts the quality of life in multiple sclerosis (MS). This study investigated the structural, clinical and functional predictors of emotion recognition in 48 MS patients (26 Relapsing–Remitting, 22 Progressive) and 40 matched healthy controls (HCs). All participants were assessed for emotion recognition (Reading the Mind in the Eyes Test [RMET]). The MS cohort was additionally assessed for information processing speed (IPS) (Symbol Digit Modalities Test [SDMT]) and cognitive reserve (CR) (Cognitive Reserve Index questionnaire [CRIq]). Confounding clinical variables were quantified, including physical disability (Expanded Disability Status Scale [EDSS]), fatigue (Modified Fatigue Impact Scale [MFIS]) and affective symptoms (Depression Anxiety and Stress Scale [DASS‐21]). Regional cortical volumes were extracted utilizing 3T MRI automated parcellation. Patients with Progressive MS exhibited profound emotion recognition deficits compared to HCs ( p = 0.006). Multivariate regression identified IPS (β = 0.352) and CR (β = 0.289) as the only significant independent predictors of RMET accuracy. These functional variables statistically eclipsed the influence of focal anterior insular atrophy, perceived fatigue and mood symptoms. Emotion recognition impairment in MS is primarily driven by two independent, additive predictors: IPS and CR. Together, these functional determinants outweigh the influence of focal macroscopic cortical damage, fatigue and mood symptoms.

Neuroprotection in childhood developmental and epileptic encephalopathies may require approaches, distinct from adult brain injury models of neuroprotection, with a primary focus on preservation of synaptic density rather than prevention of cellular necrosis. There is growing evidence to indicate early-life seizures activate complement cascade proteins C1q and C3. Subsequently, localized microglia may excessively phagocytose structurally intact synaptic neurons disrupting normal brain maturation. This review incorporates kinetic models of neuro-immune interactions based on human histopathology from epileptogenic tissues and quantitative neuro-immune biomarkers to provide suggestions that complement-mediated synaptic pruning may contribute to structural network disruption and cognitive decline in pediatric epilepsy. While standard anti-seizure medications effectively stabilize electrical activity, they do not mitigate underlying neuro-inflammatory responses. Consequently, targeted pharmacological inhibition of the complement microglia axis may provide a potential disease modifying strategy to protect developing neural circuits. The translational feasibility of using targeted complement inhibitors should be evaluated addressing critical challenges such as central nervous system drug delivery across the blood–brain barrier, immunosuppression management and the application of non-invasive biomarkers to define the precise therapeutic window for intervention.

This review characterizes VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) as a prototype of adult-onset autoinflammation that challenges traditional autoimmune paradigms. Driven by constitutive activation of innate myeloid cells via Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1) mutations, VEXAS affects the nervous system in approximately 6–10% of cases. We identify the peripheral nervous system as the primary target (70%), typically manifesting as refractory axonal polyneuropathy, while central involvement may present as neutrophilic meningoencephalitis. Crucially, we highlight the "hematologic paradox"—hyperinflammation co-occurring with macrocytic anemia rather than thrombocytosis—as the key biomarker distinguishing VEXAS from vasculitic mimics, necessitating early genetic sequencing for targeted clone suppression.

Background/Objectives: Neuromyelitis Optica Spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system with a globally heterogeneous prevalence/ To estimate the prescription-based prevalence of NMOSD in Greece and determine the use of long-term immunotherapies and concomitant medications in these patients. Methods: We analyzed anonymized prescription records from the national prescription database, dating from 1 January 2017 to 1 May 2024. The administrative point prevalence of NMOSD in Greece on 1 January 2022 was calculated according to the national census conducted in late 2021. Results: We identified 219 cases of NMOSD and a 1:6.8 male-to-female ratio. The point prevalence on 1 January 2022 was 1.97 per 100,000, with the highest detected in the region of Crete, and the lowest in the regions of Eastern Macedonia and Thrace. The mean age of people with NMOSD on that date was 51.3 years old. Azathioprine was the most frequently prescribed maintenance immunotherapy, while antidepressants were the most common concomitant medications prescribed. Polypharmacy was observed in 28.9% of the identified cases. Conclusions: We hereby present the prescription drug use of people with NMOSD in Greece in the era just before the introduction of NMOSD-specific immunotherapy in Greece.

The revised 2024 McDonald criteria recognize the optic nerve as a fifth topographical location for dissemination in space (DIS), raising critical questions regarding its diagnostic utility and technical requirements. To analyze this new inclusion, we provide a focused review and illustrate its clinical significance through a case series of three patients where optic nerve assessment was critical for diagnosis. We analyze the operationalization of key diagnostic tools, including optical coherence tomography (OCT) (defining retinal nerve fiber and ganglion cell layer thinning thresholds and inter-eye asymmetry, assessed outside acute neuritis), visual evoked potentials (VEPs) (P100 latency criteria), and 3T orbital magnetic resonance imaging (MRI) (using fat-suppressed T2/short-tau inversion recovery (STIR) and post-gadolinium sequences). Furthermore, we specify how dissemination in time (DIT) was met (presence of CSF-specific oligoclonal bands or new T2/gadolinium-enhancing lesions) and how key mimics (e.g., myelin oligodendrocyte glycoprotein antibody disease (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), ischemic/hereditary neuropathies) were excluded via antibody testing and clinical/laboratory findings. The analysis suggests that the 2024 multiple sclerosis (MS) criteria, by recognizing the optic nerve, may enhance diagnostic sensitivity. In our cohort, multimodal optic nerve assessment was essential to meet DIS criteria, successfully expediting the MS diagnosis and treatment initiation. This multimodal approach also highlights the optic nerve's potential as a source for quantitative biomarkers and a target for future neuroprotective strategies. We conclude that including the optic nerve as a DIS site represents a major diagnostic advance. The presented cases underscore the practical application of the 2024 criteria, stressing the importance of comprehensive evaluation, but also highlighting the critical need for careful exclusion of mimics, vigilance to avoid overdiagnosis, and the necessity of standardized acquisition protocols and robust normative databases for generalizing this approach.

Plasticity is a fundamental property of the brain that enables the nervous system to respond appropriately to internal and external stimuli. It primarily involves changes at the synaptic level, mediated by a wide array of molecules, ultimately leading to cognitive and behavioral changes. This review critically contrasts the developmental timing and mechanisms of plasticity in Autism spectrum disorder (early hyperplasticity and excitation–inhibition imbalance) versus Schizophrenia (adolescent overpruning and NMDAR hypofunction) and evaluates evidence for interventions that harness plasticity to improve cognitive and behavioral outcomes. Preclinical and small clinical studies suggest that interventions targeting plasticity-related pathways may improve specific cognitive and behavioral domains. However, effects appear to be symptom-domain-specific and protocol-dependent and larger randomized controlled trials are needed to confirm efficacy. Cognitive remediation for Schizophrenia has been associated with improved executive function and increased hippocampal volume, while virtual reality-based training for Autism spectrum disorder has shown gains in attention and planning skills. By highlighting both molecular mechanisms and therapeutic strategies, this review aims to provide an integrated perspective on how plasticity-targeted interventions could be optimized across neurodevelopmental and neuropsychiatric disorders.