Gabriel Westman1, Azita Sohrabian2, Elisabeth Aurelius3, Clas Ahlm4, Silvia Schliamser5, Fredrik Sund6, Marie Studahl7, Johan Rönnelid2. 1. Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden. Electronic address: gabriel.westman@medsci.uu.se. 2. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 3. Unit of Infectious Diseases, Department of Medicine, Karolinska Institutet, Solna, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Solna, Sweden. 4. Department of Clinical Microbiology, Infectious Diseases, Umeå University, Umeå, Sweden. 5. Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden. 6. Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden. 7. Department of Infectious Diseases, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Abstract
BACKGROUND: Herpes simplex encephalitis (HSE) is a devastating disease, often leaving patients with severe disabilities. It has been shown that IgG anti-N-methyl-d-aspartate receptor (NMDAR) antibodies appear in approximately 25% of HSE patients and could be associated with impaired recovery of cognitive performance. OBJECTIVES: To characterize the prevalence of IgM and IgA anti-NMDAR antibodies in HSE patients, in relation to subsequent development of IgG anti-NMDAR and correlation to cognitive performance. STUDY DESIGN: A total of 48 subjects were included from a previously described cohort of patients with HSE verified by HSV-1 PCR. Cerebrospinal fluid (CSF) and serum samples drawn close to onset of disease, after 14-21 days of iv aciclovir treatment and after 90 days of follow-up, were analyzed for the presence of IgM and IgA anti-NMDAR, and related to IgG anti-NMDAR. Antibody levels were correlated to the recovery of cognitive performance, as estimated by the Mattis Dementia Rating Scale (MDRS), for a total of 24 months. RESULTS: In total, 27 of 48 (56%) study subjects were anti-NMDAR positive, defined as the presence of IgG (12/48, 25%), IgM (14/48, 29%) or IgA (13/48, 27%) antibodies in CSF and/or serum. IgM or IgA anti-NMDAR did not predict subsequent IgG autoimmunization and did not correlate to cognitive outcome. IgG anti-NMDAR serostatus, but not antibody titers, correlated to impaired recovery of cognitive performance. CONCLUSIONS: A majority of HSE patients develop IgG, IgM or IgA anti-NMDAR antibodies. However, the predictive value and clinical relevance of non-IgG isotypes remains to be shown in this setting.
BACKGROUND: Herpes simplex encephalitis (HSE) is a devastating disease, often leaving patients with severe disabilities. It has been shown that IgG anti-N-methyl-d-aspartate receptor (NMDAR) antibodies appear in approximately 25% of HSE patients and could be associated with impaired recovery of cognitive performance. OBJECTIVES: To characterize the prevalence of IgM and IgA anti-NMDAR antibodies in HSE patients, in relation to subsequent development of IgG anti-NMDAR and correlation to cognitive performance. STUDY DESIGN: A total of 48 subjects were included from a previously described cohort of patients with HSE verified by HSV-1 PCR. Cerebrospinal fluid (CSF) and serum samples drawn close to onset of disease, after 14-21 days of iv aciclovir treatment and after 90 days of follow-up, were analyzed for the presence of IgM and IgA anti-NMDAR, and related to IgG anti-NMDAR. Antibody levels were correlated to the recovery of cognitive performance, as estimated by the Mattis Dementia Rating Scale (MDRS), for a total of 24 months. RESULTS: In total, 27 of 48 (56%) study subjects were anti-NMDAR positive, defined as the presence of IgG (12/48, 25%), IgM (14/48, 29%) or IgA (13/48, 27%) antibodies in CSF and/or serum. IgM or IgA anti-NMDAR did not predict subsequent IgG autoimmunization and did not correlate to cognitive outcome. IgG anti-NMDAR serostatus, but not antibody titers, correlated to impaired recovery of cognitive performance. CONCLUSIONS: A majority of HSE patients develop IgG, IgM or IgA anti-NMDAR antibodies. However, the predictive value and clinical relevance of non-IgG isotypes remains to be shown in this setting.
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
Authors: Zachary Fitzpatrick; Gordon Frazer; Ashley Ferro; Simon Clare; Nicolas Bouladoux; John Ferdinand; Zewen Kelvin Tuong; Maria Luciana Negro-Demontel; Nitin Kumar; Ondrej Suchanek; Tamara Tajsic; Katherine Harcourt; Kirsten Scott; Rachel Bashford-Rogers; Adel Helmy; Daniel S Reich; Yasmine Belkaid; Trevor D Lawley; Dorian B McGavern; Menna R Clatworthy Journal: Nature Date: 2020-11-04 Impact factor: 49.962