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Longitudinal analysis of regional brain changes in anti-NMDAR encephalitis: a case report
BACKGROUND: Anti-NMDA receptor encephalitis is an immune-mediated disorder characterized by antibodies against the GluN1 subunit of the NMDA receptor that is increasingly recognized as a treatable cause of childhood epileptic encephalopathy. In adults, the disorder has been associated with reversibl...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554978/ https://www.ncbi.nlm.nih.gov/pubmed/34706674 http://dx.doi.org/10.1186/s12883-021-02446-8 |
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author | Nillo, Ryan M. Broce, Iris J. Uzgil, Besim Singhal, Nilika S. Glastonbury, Christine M. Hess, Christopher P. Barkovich, James A. Desikan, Rahul S. Sugrue, Leo P. |
author_facet | Nillo, Ryan M. Broce, Iris J. Uzgil, Besim Singhal, Nilika S. Glastonbury, Christine M. Hess, Christopher P. Barkovich, James A. Desikan, Rahul S. Sugrue, Leo P. |
author_sort | Nillo, Ryan M. |
collection | PubMed |
description | BACKGROUND: Anti-NMDA receptor encephalitis is an immune-mediated disorder characterized by antibodies against the GluN1 subunit of the NMDA receptor that is increasingly recognized as a treatable cause of childhood epileptic encephalopathy. In adults, the disorder has been associated with reversible changes in brain volume over the course of treatment and recovery, but in children, little is known about its time course and associated imaging manifestations. CASE PRESENTATION: A previously healthy 20-month-old boy presented with first-time unprovoked seizures, dysautonomia, and dyskinesia. Paraneoplastic workup was negative, but CSF was positive for anti-NMDAR antibodies. The patient’s clinical condition waxed and waned over a 14-month course of treatment with first- and second-line immunotherapies (including steroids, IVIG, rituximab, and cyclophosphamide). Serial brain MRIs scans obtained at 5 time points spanning this same period showed no abnormal signal or enhancement but were remarkable for cycles of reversible regional cortical volume loss. All scans included identical 1-mm resolution 3D T1-weighted sequences obtained on the same 3 T scanner. Using a novel longitudinal processing stream in FreeSurfer6 (Reuter M, et. al, Neuroimage 61:1402–18, 2012) we quantified the rate of change in cortical volume at each vertex (% volume change per month) between consecutive scans and correlated these changes with the time course of the patient’s treatment and clinical response. We found regionally specific changes in cortical volume (up to 7% per month) that preferentially affected the frontal and occipital lobes and paralleled the patient’s clinical course, with clinical decline associated with volume loss and clinical improvement associated with volume gain. CONCLUSIONS: Our results suggest that reversible cortical volume loss in anti-NMDA encephalitis has a regional specificity that mirrors many of the clinical symptoms associated with the disorder and tracks the dynamics of disease severity over time. This case illustrates how quantitative morphometric techniques can be applied to clinical imaging data to reveal patterns of brain change that may provide insight into disease pathophysiology. More widespread application of this approach might reveal regional and temporal patterns specific to different types of autoimmune encephalitis, providing a tool for diagnosis and a surrogate marker for monitoring treatment response. |
format | Online Article Text |
id | pubmed-8554978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-85549782021-10-29 Longitudinal analysis of regional brain changes in anti-NMDAR encephalitis: a case report Nillo, Ryan M. Broce, Iris J. Uzgil, Besim Singhal, Nilika S. Glastonbury, Christine M. Hess, Christopher P. Barkovich, James A. Desikan, Rahul S. Sugrue, Leo P. BMC Neurol Case Report BACKGROUND: Anti-NMDA receptor encephalitis is an immune-mediated disorder characterized by antibodies against the GluN1 subunit of the NMDA receptor that is increasingly recognized as a treatable cause of childhood epileptic encephalopathy. In adults, the disorder has been associated with reversible changes in brain volume over the course of treatment and recovery, but in children, little is known about its time course and associated imaging manifestations. CASE PRESENTATION: A previously healthy 20-month-old boy presented with first-time unprovoked seizures, dysautonomia, and dyskinesia. Paraneoplastic workup was negative, but CSF was positive for anti-NMDAR antibodies. The patient’s clinical condition waxed and waned over a 14-month course of treatment with first- and second-line immunotherapies (including steroids, IVIG, rituximab, and cyclophosphamide). Serial brain MRIs scans obtained at 5 time points spanning this same period showed no abnormal signal or enhancement but were remarkable for cycles of reversible regional cortical volume loss. All scans included identical 1-mm resolution 3D T1-weighted sequences obtained on the same 3 T scanner. Using a novel longitudinal processing stream in FreeSurfer6 (Reuter M, et. al, Neuroimage 61:1402–18, 2012) we quantified the rate of change in cortical volume at each vertex (% volume change per month) between consecutive scans and correlated these changes with the time course of the patient’s treatment and clinical response. We found regionally specific changes in cortical volume (up to 7% per month) that preferentially affected the frontal and occipital lobes and paralleled the patient’s clinical course, with clinical decline associated with volume loss and clinical improvement associated with volume gain. CONCLUSIONS: Our results suggest that reversible cortical volume loss in anti-NMDA encephalitis has a regional specificity that mirrors many of the clinical symptoms associated with the disorder and tracks the dynamics of disease severity over time. This case illustrates how quantitative morphometric techniques can be applied to clinical imaging data to reveal patterns of brain change that may provide insight into disease pathophysiology. More widespread application of this approach might reveal regional and temporal patterns specific to different types of autoimmune encephalitis, providing a tool for diagnosis and a surrogate marker for monitoring treatment response. BioMed Central 2021-10-27 /pmc/articles/PMC8554978/ /pubmed/34706674 http://dx.doi.org/10.1186/s12883-021-02446-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Case Report Nillo, Ryan M. Broce, Iris J. Uzgil, Besim Singhal, Nilika S. Glastonbury, Christine M. Hess, Christopher P. Barkovich, James A. Desikan, Rahul S. Sugrue, Leo P. Longitudinal analysis of regional brain changes in anti-NMDAR encephalitis: a case report |
title | Longitudinal analysis of regional brain changes in anti-NMDAR encephalitis: a case report |
title_full | Longitudinal analysis of regional brain changes in anti-NMDAR encephalitis: a case report |
title_fullStr | Longitudinal analysis of regional brain changes in anti-NMDAR encephalitis: a case report |
title_full_unstemmed | Longitudinal analysis of regional brain changes in anti-NMDAR encephalitis: a case report |
title_short | Longitudinal analysis of regional brain changes in anti-NMDAR encephalitis: a case report |
title_sort | longitudinal analysis of regional brain changes in anti-nmdar encephalitis: a case report |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554978/ https://www.ncbi.nlm.nih.gov/pubmed/34706674 http://dx.doi.org/10.1186/s12883-021-02446-8 |
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