Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis
IntroductionVery rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500904/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846126136400019456 |
|---|---|
| author | Sarah Jesse Marie Riemann Hauke Schneider Marius Ringelstein Marius Ringelstein Nico Melzer Niklas Vogel Lena Kristina Pfeffer Manuel A. Friese Kurt-Wolfram Sühs Dominica Hudasch Philipp Schwenkenbecher Albrecht Günther Christian Geis Jonathan Wickel Martin Lesser Annika Kather Frank Leypoldt Frank Leypoldt Justina Dargvainiene Robert Markewitz Klaus-Peter Wandinger Franziska S. Thaler Franziska S. Thaler Joseph Kuchling Katharina Wurdack Lidia Sabater Lidia Sabater Carsten Finke Jan Lewerenz |
| author_facet | Sarah Jesse Marie Riemann Hauke Schneider Marius Ringelstein Marius Ringelstein Nico Melzer Niklas Vogel Lena Kristina Pfeffer Manuel A. Friese Kurt-Wolfram Sühs Dominica Hudasch Philipp Schwenkenbecher Albrecht Günther Christian Geis Jonathan Wickel Martin Lesser Annika Kather Frank Leypoldt Frank Leypoldt Justina Dargvainiene Robert Markewitz Klaus-Peter Wandinger Franziska S. Thaler Franziska S. Thaler Joseph Kuchling Katharina Wurdack Lidia Sabater Lidia Sabater Carsten Finke Jan Lewerenz |
| author_sort | Sarah Jesse |
| collection | DOAJ |
| description | IntroductionVery rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E. Here, we aimed to investigate the frequency, long-term outcome, and immunological concomitants of ataxia in NMDAR-E.MethodsIn this observational study, patients with definite NMDAR-E with a follow-up of >12 months were recruited from the GENERATE registry. Cases with documented ataxia were analyzed in detail.ResultsIn 12 of 62 patients (19%), ataxia was documented. Bilateral cerebellar ataxia without additional focal CNS findings was found in four (one child and three adults); one of these was previously reported as a case with persistent cerebellar atrophy and ataxia. Two patients with bilateral cerebellar ataxia had additional focal neurological symptoms, optic neuritis and facial palsy. Two patients developed hemiataxia: one with diplopia suggesting brainstem dysfunction and the other probably resulting from cerebellar diaschisis due to contralateral status epilepticus. In all but the one developing cerebellar atrophy, cerebellar ataxia was transient and not associated with a worse long-term outcome. In all five patients with cerebellar ataxia tested, MOG, AQP-4, GluK2, and KLHL11 antibodies were negative. In two additional patients negative for both MOG and AQP-4 antibodies, ataxia was sensory and explained by cervical myelitis as part of multiple sclerosis (MS) manifesting temporal relation to NMDAR-E. One of the patients with bilateral ataxia with focal neurological deficits was also diagnosed with MS upon follow-up. Finally, in two patients, ataxia was explained by cerebral hypoxic damage following circulatory failure during an ICU stay with severe NMDAR-E.DiscussionAtaxia of different types is quite common in NMDAR-E. Cerebellar ataxia in NMDAR-E is mostly transient. NMDAR-E followed by persistent ataxia and cerebellar atrophy is very rare. Cerebellar ataxia in NMDAR-E may not be explained by concomitant KLHL11, MOG, AQP-4, or GluK2 autoimmunity. Of note, ataxia in NMDAR-E may result from treatment complications and, most interestingly, from MS manifesting in temporal association with NMDAR-E. |
| format | Article |
| id | doaj-art-76e8a5c2cf464bc9bbcf4e92a4798c07 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-76e8a5c2cf464bc9bbcf4e92a4798c072024-12-13T05:10:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15009041500904Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitisSarah Jesse0Marie Riemann1Hauke Schneider2Marius Ringelstein3Marius Ringelstein4Nico Melzer5Niklas Vogel6Lena Kristina Pfeffer7Manuel A. Friese8Kurt-Wolfram Sühs9Dominica Hudasch10Philipp Schwenkenbecher11Albrecht Günther12Christian Geis13Jonathan Wickel14Martin Lesser15Annika Kather16Frank Leypoldt17Frank Leypoldt18Justina Dargvainiene19Robert Markewitz20Klaus-Peter Wandinger21Franziska S. Thaler22Franziska S. Thaler23Joseph Kuchling24Katharina Wurdack25Lidia Sabater26Lidia Sabater27Carsten Finke28Jan Lewerenz29Department of Neurology, University Hospital Ulm, Ulm, GermanyDepartment of Neurology, University Hospital Ulm, Ulm, GermanyDepartment of Neurology, Augsburg University, Augsburg, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, GermanyDepartment of Neurology, Centre for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, GermanyDepartment of Neurology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, GermanyInstitute of Neuroimmunology and Multiple Sclerosis and Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyInstitute of Neuroimmunology and Multiple Sclerosis and Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanySection of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena, GermanySection of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena, GermanySection of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena, GermanyDepartment of Neurology, Carl Gustav Carus University Dresden, Dresden, GermanyDepartment of Neurology, Carl Gustav Carus University Dresden, Dresden, GermanyInstitute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lubeck, Germany0Department of Neurology, University Hospital Schleswig-Holstein, Kiel, GermanyInstitute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lubeck, GermanyInstitute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lubeck, GermanyInstitute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lubeck, Germany1Institute of Clinical Neuroimmunology, LMU University Hospital, LMU Munich, Munich, Germany2Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, Germany3Department of Neurology and Experimental Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany3Department of Neurology and Experimental Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany4Fundació de Recerca Biomèdica Clínic Barcelona-Institut d’Investigacions August Pi i Sunyer-Caixa Research Institute, Universitat de Barcelona, Barcelona, Spain5Spanish National Network for Research on Rare Diseases (CIBERER), Madrid, Spain2Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Munich, GermanyDepartment of Neurology, University Hospital Ulm, Ulm, GermanyIntroductionVery rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E. Here, we aimed to investigate the frequency, long-term outcome, and immunological concomitants of ataxia in NMDAR-E.MethodsIn this observational study, patients with definite NMDAR-E with a follow-up of >12 months were recruited from the GENERATE registry. Cases with documented ataxia were analyzed in detail.ResultsIn 12 of 62 patients (19%), ataxia was documented. Bilateral cerebellar ataxia without additional focal CNS findings was found in four (one child and three adults); one of these was previously reported as a case with persistent cerebellar atrophy and ataxia. Two patients with bilateral cerebellar ataxia had additional focal neurological symptoms, optic neuritis and facial palsy. Two patients developed hemiataxia: one with diplopia suggesting brainstem dysfunction and the other probably resulting from cerebellar diaschisis due to contralateral status epilepticus. In all but the one developing cerebellar atrophy, cerebellar ataxia was transient and not associated with a worse long-term outcome. In all five patients with cerebellar ataxia tested, MOG, AQP-4, GluK2, and KLHL11 antibodies were negative. In two additional patients negative for both MOG and AQP-4 antibodies, ataxia was sensory and explained by cervical myelitis as part of multiple sclerosis (MS) manifesting temporal relation to NMDAR-E. One of the patients with bilateral ataxia with focal neurological deficits was also diagnosed with MS upon follow-up. Finally, in two patients, ataxia was explained by cerebral hypoxic damage following circulatory failure during an ICU stay with severe NMDAR-E.DiscussionAtaxia of different types is quite common in NMDAR-E. Cerebellar ataxia in NMDAR-E is mostly transient. NMDAR-E followed by persistent ataxia and cerebellar atrophy is very rare. Cerebellar ataxia in NMDAR-E may not be explained by concomitant KLHL11, MOG, AQP-4, or GluK2 autoimmunity. Of note, ataxia in NMDAR-E may result from treatment complications and, most interestingly, from MS manifesting in temporal association with NMDAR-E.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500904/fullNMDAR-encephalitisataxiaoutcomecerebellummultiple sclerosisMOG antibody |
| spellingShingle | Sarah Jesse Marie Riemann Hauke Schneider Marius Ringelstein Marius Ringelstein Nico Melzer Niklas Vogel Lena Kristina Pfeffer Manuel A. Friese Kurt-Wolfram Sühs Dominica Hudasch Philipp Schwenkenbecher Albrecht Günther Christian Geis Jonathan Wickel Martin Lesser Annika Kather Frank Leypoldt Frank Leypoldt Justina Dargvainiene Robert Markewitz Klaus-Peter Wandinger Franziska S. Thaler Franziska S. Thaler Joseph Kuchling Katharina Wurdack Lidia Sabater Lidia Sabater Carsten Finke Jan Lewerenz Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis Frontiers in Immunology NMDAR-encephalitis ataxia outcome cerebellum multiple sclerosis MOG antibody |
| title | Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis |
| title_full | Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis |
| title_fullStr | Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis |
| title_full_unstemmed | Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis |
| title_short | Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis |
| title_sort | frequency characteristics and immunological accompaniments of ataxia in anti nmdar antibody associated encephalitis |
| topic | NMDAR-encephalitis ataxia outcome cerebellum multiple sclerosis MOG antibody |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500904/full |
| work_keys_str_mv | AT sarahjesse frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT marieriemann frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT haukeschneider frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT mariusringelstein frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT mariusringelstein frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT nicomelzer frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT niklasvogel frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT lenakristinapfeffer frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT manuelafriese frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT kurtwolframsuhs frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT dominicahudasch frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT philippschwenkenbecher frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT albrechtgunther frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT christiangeis frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT jonathanwickel frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT martinlesser frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT annikakather frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT frankleypoldt frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT frankleypoldt frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT justinadargvainiene frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT robertmarkewitz frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT klauspeterwandinger frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT franziskasthaler frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT franziskasthaler frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT josephkuchling frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT katharinawurdack frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT lidiasabater frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT lidiasabater frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT carstenfinke frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis AT janlewerenz frequencycharacteristicsandimmunologicalaccompanimentsofataxiainantinmdarantibodyassociatedencephalitis |