Yael Hacohen1, Yukihiro Nishimoto2, Yuki Fukami3, Bethan Lang1, Patrick Waters1, Ming J Lim1,4, Nobuhiro Yuki3,5, Angela Vincent1. 1. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK. 2. Department of Pediatrics, Wakayama National Hospital, Wakayama, Japan. 3. Department of Medicine, Yong Loo Ling School of Medicine, National University of Singapore, Singapore, Singapore. 4. Children's Neurosciences, Evelina London Children's Hospital, at Guy's and St Thomas' NHS Foundation Trust, King's Health Partners Academic Health Science Centre, London, UK. 5. Department of Physiology, Yong Loo Ling School of Medicine, National University of Singapore, Singapore, Singapore.
Abstract
AIM: Central nervous system (CNS) autoantibodies have been reported in a range of neuroimmune diseases, but there has not been a systematic evaluation of autoantibodies in paediatric patients with brainstem encephalitis. METHOD: Serum samples from 57 children (40 male, 17 female, median age 12y, range 0.6-18y) with a diagnosis of brainstem encephalitis were tested retrospectively for antibodies to GQ1b, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), N-methyl-D-aspartate receptor, LGI1, CASPR2, glycine receptor (GlyR), DPPX, and the voltage gated potassium channel (VGKC)-complex. RESULTS: Disease localized to the brainstem was seen in 19 patients: Bickerstaff's brainstem encephalitis (n=14) and clinically isolated syndrome (n=5). Polyfocal presentation was seen in 38 children, with predominantly white matter disease in 18 patients and grey matter in 20 patients. CNS surface antibodies were found in 22/57 patients (two patients with double positivity): GQIb (n=6), NMDAR (n=7), GlyR (n=5), MOG (n=5), and one AQP4. Three patients were positive for VGKC-complex antibodies. All patients were negative for antibodies to DPPX and the VGKC-complex antigens LGI1, CASPR2, and contactin-2. Although there were some partial differences in the presentations, the clinical features and outcomes did not relate clearly to the presence or absence of specific antibodies. INTERPRETATION: As determined retrospectively, 39% of patients had cell surface antibodies. The results did not suggest any relationship with treatment or outcomes obtained but it is possible that specific antibody detection could be a helpful guide to more intensive immunotherapies in some cases.
AIM: Central nervous system (CNS) autoantibodies have been reported in a range of neuroimmune diseases, but there has not been a systematic evaluation of autoantibodies in paediatric patients with brainstem encephalitis. METHOD: Serum samples from 57 children (40 male, 17 female, median age 12y, range 0.6-18y) with a diagnosis of brainstem encephalitis were tested retrospectively for antibodies to GQ1b, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), N-methyl-D-aspartate receptor, LGI1, CASPR2, glycine receptor (GlyR), DPPX, and the voltage gated potassium channel (VGKC)-complex. RESULTS: Disease localized to the brainstem was seen in 19 patients: Bickerstaff's brainstem encephalitis (n=14) and clinically isolated syndrome (n=5). Polyfocal presentation was seen in 38 children, with predominantly white matter disease in 18 patients and grey matter in 20 patients. CNS surface antibodies were found in 22/57 patients (two patients with double positivity): GQIb (n=6), NMDAR (n=7), GlyR (n=5), MOG (n=5), and one AQP4. Three patients were positive for VGKC-complex antibodies. All patients were negative for antibodies to DPPX and the VGKC-complex antigens LGI1, CASPR2, and contactin-2. Although there were some partial differences in the presentations, the clinical features and outcomes did not relate clearly to the presence or absence of specific antibodies. INTERPRETATION: As determined retrospectively, 39% of patients had cell surface antibodies. The results did not suggest any relationship with treatment or outcomes obtained but it is possible that specific antibody detection could be a helpful guide to more intensive immunotherapies in some cases.
Authors: Jonathan Douglas Santoro; Daniel V Lazzareschi; Cynthia Jane Campen; Keith P Van Haren Journal: J Neurol Date: 2017-11-24 Impact factor: 4.849
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