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Pediatric-onset multiple sclerosis (MS, POMS) accounts for 3-5% of all MS cases and is characterized by a highly inflammatory profile, often warranting treatment with high-efficacy agents. Our aim is to present real-world data of a series of 18 Hellenic POMS patients treated with natalizumab (NTZ) either as adolescents or as adults, after high disease activity has efficiently subsided. Clinical and imaging/laboratory data from 18 POMS patients who have received at least one NTZ infusion were selected in this single-center retrospective observational study. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques. Eighteen patients with a mean age of disease onset of 15.3 ± 2.4 years were treated with NTZ with a mean of 51.7 ± 46.4 infusions, 6 as adolescents and 12 as adults. 22.2% were treatment naïve. At the end of the observational period, patients of both groups remained relapse-free, with no radiological activity and significantly reduced disability accumulation. No evidence of disease activity (NEDA)-3 status was achieved in 66.7% of all patients, 58.3% in the adult-treated, and 83.3% in the adolescent-treated POMS patients. NTZ was generally well tolerated. Only 5 adverse events were observed, in 3 patients who were carriers of the HLA-DRB1*15 (HLA-DRB1*15/HLA-DRB1*11 and HLA-DRB1*15/HLA-DRB1*13 genotypes), 1 homozygous for the HLA-DRB1*03 allele and 1 heterozygous for HLA-DRB1*04 and HLA-DRB1*16 alleles. NTZ is highly efficacious and mostly safe for POMS patients with high disease activity in all age groups. The role of immunogenetics in personalized patient evaluation and treatment needs to be further investigated.

The process of ageing is characteristic of multicellular organisms associated with late stages of the lifecycle and is manifested through a plethora of phenotypes. Its underlying mechanisms are correlated with age-dependent diseases, especially neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and multiple sclerosis (MS) that are accompanied by social and financial difficulties for patients. Over time, people not only become more prone to neurodegeneration but they also lose the ability to trigger pivotal restorative mechanisms. In this review, we attempt to present the already known molecular and cellular hallmarks that characterize ageing in association with their impact on the central nervous system (CNS)’s structure and function intensifying possible preexisting pathogenetic conditions. A thorough and elucidative study of the underlying mechanisms of ageing will be able to contribute further to the development of new therapeutic interventions to effectively treat age-dependent manifestations of neurodegenerative diseases.

Hereditary angioedema (HAE) related to C1 esterase-inhibitor deficiency activates the classic complement pathway and results to edematous crises. Although HAE is usually associated with multiple immunoregulatory disorders, neurologic manifestations are rare.We report on the case study of a 33-year-old man diagnosed with HAE (SERPIN1G gene mutation) and multiple sclerosis (MS), followed up for at least 6 years. After a first clinical attack of HEA with scrotal edema, MS disease exacerbation was observed. Treatment with glatiramer acetate could not prevent either MS or HAE clinical attacks with recurrent exacerbations been observed. Remission of MS and significant amelioration of HAE attacks were achieved under fingolimod treatment.Herein we provide long term evaluation of an extremely rare case of concomitant existence of HAE and MS and present the effects of MS current disease-modifying therapies in HAE attacks. Our case highlights the possible effect of fingolimod in immunoregulatory-mechanisms implicated in both diseases.

Background: Blood–brain barrier dysfunction in active multiple sclerosis (MS) lesions leads to pathological changes of cerebrospinal fluid (CSF). Theoretically, CSF analyses could help to predict relapse recovery and the course of disability. In this monocentric study, we investigated the impact of CSF findings assessed during the first relapse of MS on the short-term course of disability. Methods: We performed a retrospective observational study including MS patients with available CSF data after onset of first MS relapse. Clinical symptoms had to be accompanied by gadolinium-enhanced lesion on magnetic resonance imaging. Expanded Disability Status Scale (EDSS) assessments at timepoint of relapse and after relapse recovery were studied to analyze disability. A two-step multivariate linear regression analysis adjusted for EDSS at spinal tab, duration of symptoms, sex, time until post relapse EDSS assessment, immunotherapy post relapse, and relapse treatment with glucocorticoids/plasma exchange to predict relapse associated disability was run. Results: In the first step of the regression model, pathological albumin quotient (QAlb) [regression coefficient 0.50, 95% confidence interval (CI) (0.07–0.92), p = 0.02, n = 99] and CSF protein concentration [regression coefficient 0.84, 95% CI (0.33–1.35), p = 0.001, n = 99] predicted EDSS after relapse recovery. In the second step, the sum score of both predictors [range 0–2; n per value: 0 ( n = 73), 1 ( n = 10), 2 ( n = 15)] confirmed the negative impact on course of disability after relapse [regression coefficient 0.38, 95% CI (0.13–0.62), p = 0.003, n = 98]. In this final multivariate linear regression model ( p 2 0.34), also EDSS at lumbar puncture [regression coefficient 0.58, 95% CI (0.35–0.81), p Discussion: Our study conducted in MS patients during first relapse confirmed that both increased CSF protein concentration and pathological QAlb have a negative impact on EDSS after relapse. As secondary finding, we identified time from symptom onset to lumbar puncture as predictor of disability recovery after relapse.

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of highly active relapsing-remitting multiple sclerosis (MS). The principal adverse effect is the development of secondary autoimmune disorders during the immune reconstitution period after alemtuzumab, with autoimmune thyroid disease (AITD) being the most common. To define the type, timing and course of AITD after alemtuzumab treatment for MS we analyzed clinical and serologic data from 31 patients (follow-up range 8 to 58 months). Hashimoto thyroiditis (HT) with positive anti-TPO and/or anti-Tg antibodies was present at baseline in four patients. Of note, one of them 13 months after the first dose developed mild hyperthyroidism [stimulating TRAbs: 1,8U/L, normal range:40 U/L) as well as anti-Tg antibodies. Seven cases of HT with positive anti-TPO/anti-Tg antibodies were documented, of which one developed hypothyroidism. During follow-up, two successful pregnancies were recorded. The first, a 32-year-old woman, developed HT with hypothyroidism 12 months after the first cycle of alemtuzumab and gave birth to a healthy boy 22 months following last dose. The second, a 31-year-old woman, developed GD hyperthyroidism during the first trimester of pregnancy and was started on PTU that was stopped in the beginning of the second trimester. TRAbs titer declined and a healthy girl was delivered. Contrary to published literature, we recorded frequent occurrence of GD with fluctuating and unpredictable course requiring block and replace ATD regimen. This is suggestive of alternating stimulating and inhibitory TRAbs, while further studies are needed to understand the underlying mechanisms responsible for Th1-Th2 balance and cytokine pathways towards AITD. Pretreatment screening and careful follow-up allow for early diagnosis and treatment. Finally, concerning future pregnancies post-alemtuzumab it is important to address the risk for secondary AITD in women of childbearing age in conjunction with their treating obstetrician.