Margherita Nosadini1, Shekeeb S Mohammad2, Francesco Corazza1, Ezia Maria Ruga3, Kavitha Kothur2, Giorgio Perilongo3, Anna Chiara Frigo4, Irene Toldo1, Russell C Dale2, Stefano Sartori1. 1. Paediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy. 2. Neuroimmunology Group, Institute for Neuroscience and Muscle Research, Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Sydney, Australia. 3. Department of Paediatrics, University of Padua, Padua, Italy. 4. Department of Cardiac, Thoracic and Vascular Sciences, Biostatistics, Epidemiology and Public Health Unit, University of Padua, Padua, Italy.
Abstract
AIM: To conduct a systematic literature review on patients with biphasic disease with herpes simplex virus (HSV) encephalitis followed by anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHOD: We conducted a case report and systematic literature review (up to 10 December 2016), focused on differences between herpes simplex encephalitis (HSE) and anti-NMDAR encephalitis phases, age-related characteristics of HSV-induced anti-NMDAR encephalitis, and therapy. For statistical analyses, McNemar's test, Fisher's test, and Wilcoxon rank sum test were used (two-tailed significance level set at 5%). RESULTS: Forty-three patients with biphasic disease were identified (31 children). Latency between HSE and anti-NMDAR encephalitis was significantly shorter in children than adults (median 24 vs 40.5d; p=0.006). Compared with HSE, anti-NMDAR encephalitis was characterized by significantly higher frequency of movement disorder (2.5% vs 75% respectively; p<0.001), and significantly lower rate of seizures (70% vs 30% respectively; p=0.001). Compared with adults, during anti-NMDAR encephalitis children had significantly more movement disorders (86.7% children vs 40% adults; p=0.006), fewer psychiatric symptoms (41.9% children vs 90.0% adults; p=0.025), and a slightly higher median modified Rankin Scale score (5 in children vs 4 in adults; p=0.015). During anti-NMDAR encephalitis, 84.6 per cent of patients received aciclovir (for ≤7d in 22.7%; long-term antivirals in 18.0% only), and 92.7 per cent immune therapy, but none had recurrence of HSE clinically or using cerebrospinal fluid HSV polymerase chain reaction (median follow-up 7mo). INTERPRETATION: Our review suggests that movement disorder may help differentiate clinically an episode of HSV-induced anti-NMDAR encephalitis from HSE relapse. Compared with adults, children have shorter latency between HSE and anti-NMDAR encephalitis and, during anti-NMDAR encephalitis, more movement disorder, fewer psychiatric symptoms, and slightly more severe disease. According to our results, immune therapy given for HSV-induced anti-NMDAR encephalitis does not predispose patients to HSE recurrence.
AIM: To conduct a systematic literature review on patients with biphasic disease with herpes simplex virus (HSV) encephalitis followed by anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHOD: We conducted a case report and systematic literature review (up to 10 December 2016), focused on differences between herpes simplex encephalitis (HSE) and anti-NMDARencephalitis phases, age-related characteristics of HSV-induced anti-NMDARencephalitis, and therapy. For statistical analyses, McNemar's test, Fisher's test, and Wilcoxon rank sum test were used (two-tailed significance level set at 5%). RESULTS: Forty-three patients with biphasic disease were identified (31 children). Latency between HSE and anti-NMDARencephalitis was significantly shorter in children than adults (median 24 vs 40.5d; p=0.006). Compared with HSE, anti-NMDARencephalitis was characterized by significantly higher frequency of movement disorder (2.5% vs 75% respectively; p<0.001), and significantly lower rate of seizures (70% vs 30% respectively; p=0.001). Compared with adults, during anti-NMDARencephalitischildren had significantly more movement disorders (86.7% children vs 40% adults; p=0.006), fewer psychiatric symptoms (41.9% children vs 90.0% adults; p=0.025), and a slightly higher median modified Rankin Scale score (5 in children vs 4 in adults; p=0.015). During anti-NMDARencephalitis, 84.6 per cent of patients received aciclovir (for ≤7d in 22.7%; long-term antivirals in 18.0% only), and 92.7 per cent immune therapy, but none had recurrence of HSE clinically or using cerebrospinal fluid HSV polymerase chain reaction (median follow-up 7mo). INTERPRETATION: Our review suggests that movement disorder may help differentiate clinically an episode of HSV-induced anti-NMDARencephalitis from HSE relapse. Compared with adults, children have shorter latency between HSE and anti-NMDARencephalitis and, during anti-NMDARencephalitis, more movement disorder, fewer psychiatric symptoms, and slightly more severe disease. According to our results, immune therapy given for HSV-induced anti-NMDARencephalitis does not predispose patients to HSE recurrence.
Authors: Thaís Armangue; Marianna Spatola; Alexandru Vlagea; Simone Mattozzi; Marc Cárceles-Cordon; Eloy Martinez-Heras; Sara Llufriu; Jordi Muchart; María Elena Erro; Laura Abraira; German Moris; Luis Monros-Giménez; Íñigo Corral-Corral; Carmen Montejo; Manuel Toledo; Luis Bataller; Gabriela Secondi; Helena Ariño; Eugenia Martínez-Hernández; Manel Juan; Maria Angeles Marcos; Laia Alsina; Albert Saiz; Myrna R Rosenfeld; Francesc Graus; Josep Dalmau Journal: Lancet Neurol Date: 2018-07-23 Impact factor: 44.182