Clinical features, investigations, and outcomes of pediatric limbic encephalitis:   A multicenter study

Saraswathy Sabanathan; Omar Abdel-Mannan; Kshitij Mankad; Ata Siddiqui; Krishna Das; Lucinda Carr; Christin Eltze; Michael Eyre; Jon Gadian; Cheryl Hemingway; Marios Kaliakatsos; Rachel Kneen; Deepa Krishnakumar; Bryan Lynch; Amitav Parida; Thomas Rossor; Micheal Taylor; Evangeline Wassmer; Sukhvir Wright; Ming Lim; Yael Hacohen

doi:10.1002/acn3.51494

Clinical features, investigations, and outcomes of pediatric limbic encephalitis: A multicenter study

Saraswathy Sabanathan
, Omar Abdel-Mannan
, Kshitij Mankad
, Ata Siddiqui
, Krishna Das
, Lucinda Carr
, Christin Eltze
, Michael Eyre
, Jon Gadian
, Cheryl Hemingway
, Marios Kaliakatsos
, Rachel Kneen
, Deepa Krishnakumar
, Bryan Lynch
, Amitav Parida
, Thomas Rossor
, Micheal Taylor
, Evangeline Wassmer
, Sukhvir Wright
, Ming Lim^*

Yael Hacohen

^*Corresponding author for this work

Evelina London Children's Healthcare
University College London
Gt. Ormond St. Hospital for Children
King's College London
King's College Hospital NHS Foundation Trust
Royal Liverpool Children's NHS Trust
Addenbrooke’s Hospital
Children’s University Hospital
Birmingham Children's Hospital
Leeds Children’s Hospital

Research output: Contribution to journal › Article › peer-review

20 Citations (SciVal)

22 Downloads (Pure)

Abstract

Objectives: To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). Methods: In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. Results: Twenty-five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow-up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32%), and extra-limbic changes with claustrum involvement in 9/25 (38%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti-NMDAR Abs, and 2/15 positive for anti-Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti-GAD antibodies. Initial immune therapy included steroids in 23/25 (92%), intravenous immunoglobulin (IVIg) in 14/25 (56%), and plasma exchange in 7/25 (28%). The commonest second-line treatment was rituximab in 15/25 (60%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow-up, 13/25 (52%) had refractory seizures and 16/25 (64%) had memory impairment. Six children (24%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long-term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. Interpretation: A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.

Original language	English
Pages (from-to)	67-78
Number of pages	12
Journal	Annals of Clinical and Translational Neurology
Volume	9
Issue number	1
Early online date	11 Jan 2022
DOIs	https://doi.org/10.1002/acn3.51494
Publication status	Published - Jan 2022

Bibliographical note

© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Funding: MRC Clinical Academic Research Partnership. Grant Number: MR/T024437/1; British Paediatric Neurology Association. Grant Number: GN2835; Action Medical Research; Berkeley Foundation's A. W. Pidgley Memorial Clinical Research Training Fellowship. Grant Number: ABN/182533; MS Society; Association of British Neurologists

Funding

Cheryl Hemingway has received educational and travel grants from Merck Serono and Bayer and Biogen. Omar Abdel‐mannan is funded by an Association of British Neurologists, MS Society, and The Berkeley Foundation's A. W. Pidgley Memorial Clinical Research Training Fellowship (ABN/182533). Michael Eyre is supported by Action Medical Research and the British Paediatric Neurology Association (GN2835). Cheryl Hemingway is funded by an MRC Clinical Academic Research Partnership grant (MR/T024437/1) Yael Hacohen is funded by the UK MS Society (Award number 92). Ming Lim receives research grants from Action Medical Research, the DES society, GOSH charity, National Institute for Health Research, MS Society, and SPARKS charity; receives research support grants from the London Clinical Research Network and Evelina Appeal; has received consultation fees from CSL Behring, Novartis and Octapharma; received travel grants from Merck Serono.

Access to Document

10.1002/acn3.51494Licence: CC BY 3.0

Clinical features, investigations, and outcomes of pediatric limbic encephalitis
© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 2.06 MBLicence: CC BY 3.0

Cite this

Sabanathan, S., Abdel-Mannan, O., Mankad, K., Siddiqui, A., Das, K., Carr, L., Eltze, C., Eyre, M., Gadian, J., Hemingway, C., Kaliakatsos, M., Kneen, R., Krishnakumar, D., Lynch, B., Parida, A., Rossor, T., Taylor, M., Wassmer, E., Wright, S., ... Hacohen, Y. (2022). Clinical features, investigations, and outcomes of pediatric limbic encephalitis: A multicenter study. Annals of Clinical and Translational Neurology, 9(1), 67-78. https://doi.org/10.1002/acn3.51494

@article{57ab902a17eb4c5483b4259edafbf9ef,

title = "Clinical features, investigations, and outcomes of pediatric limbic encephalitis: A multicenter study",

abstract = "Objectives: To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). Methods: In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. Results: Twenty-five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow-up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60\%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32\%), and extra-limbic changes with claustrum involvement in 9/25 (38\%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti-NMDAR Abs, and 2/15 positive for anti-Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti-GAD antibodies. Initial immune therapy included steroids in 23/25 (92\%), intravenous immunoglobulin (IVIg) in 14/25 (56\%), and plasma exchange in 7/25 (28\%). The commonest second-line treatment was rituximab in 15/25 (60\%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow-up, 13/25 (52\%) had refractory seizures and 16/25 (64\%) had memory impairment. Six children (24\%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long-term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. Interpretation: A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.",

author = "Saraswathy Sabanathan and Omar Abdel-Mannan and Kshitij Mankad and Ata Siddiqui and Krishna Das and Lucinda Carr and Christin Eltze and Michael Eyre and Jon Gadian and Cheryl Hemingway and Marios Kaliakatsos and Rachel Kneen and Deepa Krishnakumar and Bryan Lynch and Amitav Parida and Thomas Rossor and Micheal Taylor and Evangeline Wassmer and Sukhvir Wright and Ming Lim and Yael Hacohen",

note = "{\textcopyright} 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding: MRC Clinical Academic Research Partnership. Grant Number: MR/T024437/1; British Paediatric Neurology Association. Grant Number: GN2835; Action Medical Research; Berkeley Foundation's A. W. Pidgley Memorial Clinical Research Training Fellowship. Grant Number: ABN/182533; MS Society; Association of British Neurologists ",

year = "2022",

month = jan,

doi = "10.1002/acn3.51494",

language = "English",

volume = "9",

pages = "67--78",

journal = "Annals of Clinical and Translational Neurology",

issn = "2328-9503",

publisher = "Wiley",

number = "1",

}

Sabanathan, S, Abdel-Mannan, O, Mankad, K, Siddiqui, A, Das, K, Carr, L, Eltze, C, Eyre, M, Gadian, J, Hemingway, C, Kaliakatsos, M, Kneen, R, Krishnakumar, D, Lynch, B, Parida, A, Rossor, T, Taylor, M, Wassmer, E , Wright, S, Lim, M & Hacohen, Y 2022, 'Clinical features, investigations, and outcomes of pediatric limbic encephalitis: A multicenter study', Annals of Clinical and Translational Neurology, vol. 9, no. 1, pp. 67-78. https://doi.org/10.1002/acn3.51494

TY - JOUR

T1 - Clinical features, investigations, and outcomes of pediatric limbic encephalitis

T2 - A multicenter study

AU - Sabanathan, Saraswathy

AU - Abdel-Mannan, Omar

AU - Mankad, Kshitij

AU - Siddiqui, Ata

AU - Das, Krishna

AU - Carr, Lucinda

AU - Eltze, Christin

AU - Eyre, Michael

AU - Gadian, Jon

AU - Hemingway, Cheryl

AU - Kaliakatsos, Marios

AU - Kneen, Rachel

AU - Krishnakumar, Deepa

AU - Lynch, Bryan

AU - Parida, Amitav

AU - Rossor, Thomas

AU - Taylor, Micheal

AU - Wassmer, Evangeline

AU - Wright, Sukhvir

AU - Lim, Ming

AU - Hacohen, Yael

N1 - © 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding: MRC Clinical Academic Research Partnership. Grant Number: MR/T024437/1; British Paediatric Neurology Association. Grant Number: GN2835; Action Medical Research; Berkeley Foundation's A. W. Pidgley Memorial Clinical Research Training Fellowship. Grant Number: ABN/182533; MS Society; Association of British Neurologists

PY - 2022/1

Y1 - 2022/1

N2 - Objectives: To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). Methods: In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. Results: Twenty-five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow-up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32%), and extra-limbic changes with claustrum involvement in 9/25 (38%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti-NMDAR Abs, and 2/15 positive for anti-Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti-GAD antibodies. Initial immune therapy included steroids in 23/25 (92%), intravenous immunoglobulin (IVIg) in 14/25 (56%), and plasma exchange in 7/25 (28%). The commonest second-line treatment was rituximab in 15/25 (60%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow-up, 13/25 (52%) had refractory seizures and 16/25 (64%) had memory impairment. Six children (24%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long-term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. Interpretation: A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.

AB - Objectives: To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). Methods: In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. Results: Twenty-five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow-up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32%), and extra-limbic changes with claustrum involvement in 9/25 (38%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti-NMDAR Abs, and 2/15 positive for anti-Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti-GAD antibodies. Initial immune therapy included steroids in 23/25 (92%), intravenous immunoglobulin (IVIg) in 14/25 (56%), and plasma exchange in 7/25 (28%). The commonest second-line treatment was rituximab in 15/25 (60%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow-up, 13/25 (52%) had refractory seizures and 16/25 (64%) had memory impairment. Six children (24%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long-term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. Interpretation: A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.

UR - https://www.scopus.com/pages/publications/85122684539

UR - https://onlinelibrary.wiley.com/doi/10.1002/acn3.51494

U2 - 10.1002/acn3.51494

DO - 10.1002/acn3.51494

M3 - Article

AN - SCOPUS:85122684539

SN - 2328-9503

VL - 9

SP - 67

EP - 78

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

IS - 1

ER -