Trans-synaptic degeneration in the optic pathway. A study in clinically isolated syndrome and early relapsing-remitting multiple sclerosis with or without optic neuritis

Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our study was to investigate the relationship between inflammation and neurodegeneration and to achieve evidence of trans-synaptic degeneration in the optic pathway in MS at clinical onset

Alemtuzumab as rescue therapy in case of multiple sclerosis rebound following Natalizumab break: Clinical case and literature review

Introduction: Natalizumab break exposes multiple sclerosis (MS) patients to a high risk of disease reactivation or rebound, whose prevention and treatment constitute a clinical challenge. Case presentation: We describe a dramatic case of MS rebound, characterized by the development of severe neurological and psychiatric symptoms, following natalizumab break. Alemtuzumab rapidly and completely suppressed brain inflammation as demonstrated by clinical and radiological findings. Conclusions: Our case further adds to the available literature evidence on Alemtuzumab as first-choice rescue therapy following Natalizumab discontinuation

Decreased platelet number in multiple sclerosis during alemtuzumab infusion: A common, transient and clinically silent phenomenon

Background The cause and clinical significance of the transient decrease in platelet (PLT) count observed in relapsing remitting multiple sclerosis (RRMS) during alemtuzumab administration remain undefined. The aim of this study was to analyse the kinetics and clinical relevance of early onset thrombocytopaenia in alemtuzumab-treated RRMS. Methods A total of 26 patients with RRMS were included in a longitudinal study. Blood samples were collected immediately before the first alemtuzumab infusion (D0), and after 3 days (D3), 28 days (D28) and 49 days (D49). PLT, red blood cell (RC), leucocyte and lymphocyte counts, haemoglobin (Hb) concentration and haematocrit (Htc) were measured. Patients with MS were clinically evaluated every day of drug infusion and then at D28 and D49 to verify the presence of signs or symptoms suggestive of thrombocytopaenia. Results PLT number significantly decreased at D3 ( p < 0.005) and was associated with a decrease in RC count ( r : 0.53, p < 0.01), Hb ( r : 0.42, p = 0.05) and Htc ( r : 0.53, p < 0.01). A progressive reversion of PLT number to normal values was observed at D28 and D49. A mild thrombocytopaenia was observed in 12 patients (46.2%), 8 of which (66.6%) had PLT nadir values at D3, and 4 (33.3%) at D28. No sign or symptom suggestive of thrombocytopaenia was observed. A strong correlation between pretreatment and nadir PTL counts ( r : 0.59, p < 0.005) was observed; indeed, mild thrombocytopaenia was observed more frequently in these patients with a baseline PTL count lower than 230 × 10 9 /L (83.3% versus 42.9%, p < 0.05). Conclusions The early PLT decrease in alemtuzumab-treated patients is transient, mild, not associated with clinically relevant events and is probably related to the cytokine-released syndrome. Notwithstanding this, our findings suggest the opportunity for PLT monitoring during infusion and in the following 2 months, since a decrease in PLT count may occur

NEDA-3 status including cortical lesions in the comparative evaluation of natalizumab versus fingolimod efficacy in multiple sclerosis

Background: Cortical lesions (CLs) are typical of multiple sclerosis (MS) and have been recently incorporated in MS diagnostic criteria. Thus, the ‘no evidence of disease activity’ (NEDA) definition should now include CLs. The aim of this study was to evaluate the NEDA3 + CL status in natalizumab- or fingolimod-treated relapsing remitting MS (RMS) patients. Methods: Natalizumab- or fingolimod-treated RMS patients were enrolled in a 2-year longitudinal study based on clinical and magnetic resonance imaging (MRI) evaluations performed respectively biannually and annually. CLs were detected by double inversion recovery. The NEDA3 + CL condition was evaluated at baseline (T0) and at the end of the first (T1) and second (T2) year. Results: Of the 137 RMS patients included in the study, 86 were propensity-matched. At T2, the annualized relapse rate was lower on natalizumab ( p = 0.021), but the effect on white matter lesions ( p = 0.29) and the proportion of NEDA-3 patients ( p = 0.14) were similar in the two treatment arms. At T2, 11.6% natalizumab- and 62.8% fingolimod-treated patients had new CLs ( p < 0.001) and a higher proportion of natalizumab-treated patients (55.8% versus 11.6%, p < 0.001) achieved the NEDA3 + CL status (hazard ratio 5.2, p < 0.001). Conclusion: The incorporation of CLs in the NEDA-3 definition highlighted the higher efficacy of natalizumab versus fingolimod in suppressing disease activity in RMS patients

Supplementary Material 3, MSJ779951_supplementary_material_3 – Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset

<p>Supplementary Material 3, MSJ779951_supplementary_material_3 for Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset by Marco Puthenparampil, Antonio Zito, Giorgia Pantano, Lisa Federle, Erica Stropparo, Silvia Miante, Giustina De Silvestro, Mario Plebani and Paolo Gallo in Multiple Sclerosis Journal</p