Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges

It is well known that <i>N</i>-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these...

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Main Authors: Anna Søgaard, Charlotte Aaberg Poulsen, Nadia Zeeberg Belhouche, Alberte Thybo, Siv Tonje Faret Hovet, Lykke Larsen, Christine Nilsson, Morten Blaabjerg, Mette Scheller Nissen
Format: Article
Language:English
Published: MDPI AG 2024-08-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/9/1953
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author Anna Søgaard
Charlotte Aaberg Poulsen
Nadia Zeeberg Belhouche
Alberte Thybo
Siv Tonje Faret Hovet
Lykke Larsen
Christine Nilsson
Morten Blaabjerg
Mette Scheller Nissen
author_facet Anna Søgaard
Charlotte Aaberg Poulsen
Nadia Zeeberg Belhouche
Alberte Thybo
Siv Tonje Faret Hovet
Lykke Larsen
Christine Nilsson
Morten Blaabjerg
Mette Scheller Nissen
author_sort Anna Søgaard
collection DOAJ
description It is well known that <i>N</i>-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively identified cases of post-HSE NMDARE in Denmark, using a national cohort database of autoimmune encephalitis (AE) and two regional databases of infectious encephalitis patients. We identified 80 post-HSE NMDARE cases in the literature, 66% being children, who more often presented movement disorders, decreased consciousness, and sleep disturbances compared to adults. Eight patients with post-HSE NMDARE were identified from the national cohort database of AE, none being children. Forty-four HSE patients were identified from the regional infectious encephalitis databases. Of these, 16 (36%) fulfilled the Graus criteria for probable/definite NMDARE, and eight (18%) presented a prolonged/relapsing disease course. Ten (23%) were tested for AE during hospitalization. Six (14%) had leftover cerebrospinal fluid available for retrospective autoantibody testing. One out of these six patients (17%) harbored NMDARE antibodies. Thus, in total, nine post-HSE NMDARE patients have been identified in Denmark from 2009 to 2021. Comparing the adult Danish patients to the literature, Danish patients were older, but the clinical phenotype and paraclinical findings were similar. Overall, the incidence of adult post-HSE NMDARE in the Region of Southern Denmark was 0.17 per million people per year and only 7% of adult HSE patients in the region were diagnosed with post-HSE NMDARE. Our findings suggest that adult patients are still underdiagnosed and the absence of pediatric cases diagnosed with post-HSE NMDARE in Denmark is highly concerning.
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spelling doaj-art-138659d8a5eb42a5ab3842a09836c1da2025-08-20T01:56:05ZengMDPI AGBiomedicines2227-90592024-08-01129195310.3390/biomedicines12091953Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future ChallengesAnna Søgaard0Charlotte Aaberg Poulsen1Nadia Zeeberg Belhouche2Alberte Thybo3Siv Tonje Faret Hovet4Lykke Larsen5Christine Nilsson6Morten Blaabjerg7Mette Scheller Nissen8Department of Clinical Research, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Nuclear Medicine, Odense University Hospital, 5000 Odense, DenmarkDepartment of Clinical Research, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Clinical Research, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Clinical Research, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Clinical Research, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Clinical Research, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Clinical Research, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Clinical Research, University of Southern Denmark, 5230 Odense, DenmarkIt is well known that <i>N</i>-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively identified cases of post-HSE NMDARE in Denmark, using a national cohort database of autoimmune encephalitis (AE) and two regional databases of infectious encephalitis patients. We identified 80 post-HSE NMDARE cases in the literature, 66% being children, who more often presented movement disorders, decreased consciousness, and sleep disturbances compared to adults. Eight patients with post-HSE NMDARE were identified from the national cohort database of AE, none being children. Forty-four HSE patients were identified from the regional infectious encephalitis databases. Of these, 16 (36%) fulfilled the Graus criteria for probable/definite NMDARE, and eight (18%) presented a prolonged/relapsing disease course. Ten (23%) were tested for AE during hospitalization. Six (14%) had leftover cerebrospinal fluid available for retrospective autoantibody testing. One out of these six patients (17%) harbored NMDARE antibodies. Thus, in total, nine post-HSE NMDARE patients have been identified in Denmark from 2009 to 2021. Comparing the adult Danish patients to the literature, Danish patients were older, but the clinical phenotype and paraclinical findings were similar. Overall, the incidence of adult post-HSE NMDARE in the Region of Southern Denmark was 0.17 per million people per year and only 7% of adult HSE patients in the region were diagnosed with post-HSE NMDARE. Our findings suggest that adult patients are still underdiagnosed and the absence of pediatric cases diagnosed with post-HSE NMDARE in Denmark is highly concerning.https://www.mdpi.com/2227-9059/12/9/1953<i>N</i>-methyl-D-aspartate receptor encephalitispost-viral autoimmune encephalitisherpes simplex virus 1 Encephalitisautoimmune encephalitisviral encephalitis
spellingShingle Anna Søgaard
Charlotte Aaberg Poulsen
Nadia Zeeberg Belhouche
Alberte Thybo
Siv Tonje Faret Hovet
Lykke Larsen
Christine Nilsson
Morten Blaabjerg
Mette Scheller Nissen
Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges
Biomedicines
<i>N</i>-methyl-D-aspartate receptor encephalitis
post-viral autoimmune encephalitis
herpes simplex virus 1 Encephalitis
autoimmune encephalitis
viral encephalitis
title Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges
title_full Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges
title_fullStr Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges
title_full_unstemmed Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges
title_short Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges
title_sort post herpetic anti nmdar encephalitis in denmark current status and future challenges
topic <i>N</i>-methyl-D-aspartate receptor encephalitis
post-viral autoimmune encephalitis
herpes simplex virus 1 Encephalitis
autoimmune encephalitis
viral encephalitis
url https://www.mdpi.com/2227-9059/12/9/1953
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