Anti-CD20 treatment and neutrophil function in central nervous system demyelinating diseases.

INTRODUCTION: A contribution of neutrophil granulocytes to the pathogenesis of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) is recognized. Anti-CD20 treatments applied in these diseases are associated with infectious complications and neutropenia. No data is available about functional characteristics of neutrophils obtained from patients with anti-CD20 treatments. METHODS: In neutrophils isolated from 13 patients with anti-CD20 treatment (9 MS, 4 NMOSD), 11 patients without anti-CD20 treatment (9 MS, 2 NMOSD) and 5 healthy controls, we analyzed chemotaxis, production of reactive oxygen species (ROS), phagocytosis, and formation of neutrophil extracellular traps (NET) in vitro. RESULTS: Chemotaxis and ROS production were found unchanged between patients with and without anti-CD20 treatment or between patients and healthy controls. We found a higher proportion of non-phagocytosing cells in patients without anti-CD20 treatment compared to patients with anti-CD20 treatment and healthy controls. As compared to healthy controls, a higher proportion of neutrophils from patients without anti-CD20 treatments underwent NET formation, either unstimulated or stimulated with phorbol 12-myristate 3-acetate for 3 h. In about half of patients with anti-CD20 treatment (n = 7), NET formation of unstimulated neutrophils occurred already within 20 min of incubation. This was not observed in patients without anti-CD20 treatment and healthy controls. CONCLUSION: Anti-CD20 treatment in MS and NMOSD patients does not alter chemotaxis and ROS production of neutrophils in vitro but might restore their impaired phagocytosis in these diseases. Our study reveals a predisposition to early NET formation in vitro of neutrophils obtained from patients with anti-CD20 treatment. This may contribute to associated risks of neutropenia and infections.

Acute transverse myelitis in childhood: A single centre experience from North India.

BACKGROUND: Acute transvers myelitis (ATM) is a rare and disabling condition in childhood. There are only few reports of clinical profile, prognosis and predictors of ATM from developing countries. OBJECTIVE: To study the clinical profile of children with ATM and predictors of its outcome. METHOD: Retrospective analysis of children <12 years of age diagnosed with ATM over a period of 6 years from a tertiary care institute. RESULTS: Thirty six children (21 boys, median age-7.5 years) were diagnosed with ATM. Weakness was symmetrical at onset in 27 (75%) children with progression over a median of 2 days (IQR 1-5 days). Severe weakness at onset with lower limb power ≤ 1/5 on MRC scale was present in 27 (75%), a sensory level in 25(69.4%) and bladder dysfunction in 31(86.1%) children. MRI showed longitudinal extensive myelitis (LETM) in 27 (75%) children and the thoracic cord was most commonly affected [18 (50%)]. On a median follow up of 35 months (range IQR 11-57 months); 15 (41.7%) were non ambulatory or required assistance to walk. Severe weakness at onset with power ≤ 1 on MRC scale, spinal shock, respiratory muscle weakness, mechanical ventilation, greater mean time to diagnosis and treatment was associated with bad outcome. ATM was a monophasic illness in all, except in 3 children; all with neuromyelitis optica spectrum disorder. Progression to multiple sclerosis was not seen in any child in our cohort. CONCLUSION: In this series of childhood ATM from North India, the disease was severe, monophasic and involved long segments (≥ 3) of cord in majority. Nearly half the children remain dependent on follow up. Delayed diagnosis and delayed initiation of steroid therapy was associated with poor outcome.