TY - JOUR
T1 - Rasmussen's encephalitis
T2 - Clinical features, pathobiology, and treatment advances
AU - Varadkar, Sophia
AU - Bien, Christian G.
AU - Kruse, Carol A.
AU - Jensen, Frances E.
AU - Bauer, Jan
AU - Pardo, Carlos A.
AU - Vincent, Angela
AU - Mathern, Gary W.
AU - Cross, J. Helen
N1 - Funding Information:
The collaboration leading to this work was initiated at an international conference on Rasmussen's encephalitis in Oct, 2010, sponsored by the RE Children's Project ( www.rechildrens.org ). GWM was supported in part by NIH RO1NS38992 and the RE Children's Project (Seth Wohlberg). CAK was supported in part by NIH R01CA125244-01A2 and R01CA154256, the Joan S Holmes Memorial Research Fund, and the RE Children's Project. All authors have received travel and conference support from the RE Children's Project. We would like to thank Deirdre Pinto, Associate Researcher, RE Children's Project, for her very helpful comments on the manuscript.
Funding Information:
SV has sat on Advisory Panels for Eisai and received honoraria for speaking engagements from Cyberonics (Zaventem, Belgium) and Eisai (Hatfield, UK) with remuneration paid to her department. CGB gave scientific advice to Eisai (Frankfurt, Germany) and UCB (Monheim, Germany), undertook industry-funded travel with support of Eisai (Frankfurt, Germany), UCB (Monheim, Germany), Desitin (Hamburg, Germany), and Grifols (Frankfurt, Germany), and obtained honoraria for speaking engagements from Eisai (Frankfurt, Germany), UCB (Monheim, Germany), Desitin (Hamburg, Germany), Diamed (Köln, Germany), Fresenius Medical Care (Bad Homburg, Germany). His employer (Krankenhaus Mara, Bielefeld, Germany) runs a lab for the detection of autoantibodies; external senders are charged for antibody diagnostics. He received research support from Diamed (Köln, Germany), Fresenius Medical Care (Bad Homburg, Germany), Astellas Pharma (München, Germany) and Octapharma (Langenfeld, Germany). CAK was partly supported by NIH RO1CA125244-01A2 and RO1CA154256 , the Joan S Holmes Memorial Research Fund, and the RE Children's Project. FEJ has investigator-initiated research grants from Eisai Inc (USA) and Lundbeck (Deerfield, USA). CAP and JB have no conflicts of interest to declare. AV and Oxford University hold patents and receive royalties and payments for antibody assays. AV is a consultant for Athena Diagnostics (Worcester, USA) and received a grant from Euroimmun AG (Wimbledon, UK). GWM was partly supported by NIH RO1NS38992 and the RE Children's Project (Seth Wohlberg). JHC holds an endowed Chair through University College London (London, UK). She has sat on Advisory Panels for Eisai (Hatfield, UK) and Viropharma (Maidenhead, UK) for which remuneration has been paid to her department. She has received money to the Department as an educational grant from UCB (Slough, UK) and Eisai (Hatfield, UK) for a Clinical Training Fellowship in Epilepsy. She holds grants for research from Action Medical Research, Epilepsy Research UK, and the Great Ormond Street Hospital Children's Charity, and she co-supervises a PhD student funded by Vitaflo (Liverpool, UK). She worked as Clinical Advisor to the update of the NICE guidelines on the diagnosis and management of epilepsy (2009–12) for which remuneration was made to her department.
PY - 2014/2
Y1 - 2014/2
N2 - Rasmussen's encephalitis is a rare chronic neurological disorder, characterised by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. Neuropathological and immunological studies support the notion that Rasmussen's encephalitis is probably driven by a T-cell response to one or more antigenic epitopes, with potential additional contribution by autoantibodies. Careful analysis of the association between histopathology and clinical presentation suggests that initial damage to the brain is mediated by T cells and microglia, suggesting a window for treatment if Rasmussen's encephalitis can be diagnosed early. Advances in neuroimaging suggest that progression of the inflammatory process seen with MRI might be a good biomarker in Rasmussen's encephalitis. For many patients, families, and doctors, choosing the right time to move from medical management to surgery is a real therapeutic dilemma. Cerebral hemispherectomy remains the only cure for seizures, but there are inevitable functional compromises. Decisions of whether or when surgery should be undertaken are challenging in the absence of a dense neurological deficit, and vary by institutional experience. Further, the optimum time for surgery, to give the best language and cognitive outcome, is not yet well understood. Immunomodulatory treatments seem to slow rather than halt disease progression in Rasmussen's encephalitis, without changing the eventual outcome.
AB - Rasmussen's encephalitis is a rare chronic neurological disorder, characterised by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. Neuropathological and immunological studies support the notion that Rasmussen's encephalitis is probably driven by a T-cell response to one or more antigenic epitopes, with potential additional contribution by autoantibodies. Careful analysis of the association between histopathology and clinical presentation suggests that initial damage to the brain is mediated by T cells and microglia, suggesting a window for treatment if Rasmussen's encephalitis can be diagnosed early. Advances in neuroimaging suggest that progression of the inflammatory process seen with MRI might be a good biomarker in Rasmussen's encephalitis. For many patients, families, and doctors, choosing the right time to move from medical management to surgery is a real therapeutic dilemma. Cerebral hemispherectomy remains the only cure for seizures, but there are inevitable functional compromises. Decisions of whether or when surgery should be undertaken are challenging in the absence of a dense neurological deficit, and vary by institutional experience. Further, the optimum time for surgery, to give the best language and cognitive outcome, is not yet well understood. Immunomodulatory treatments seem to slow rather than halt disease progression in Rasmussen's encephalitis, without changing the eventual outcome.
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U2 - 10.1016/S1474-4422(13)70260-6
DO - 10.1016/S1474-4422(13)70260-6
M3 - Review article
C2 - 24457189
AN - SCOPUS:84892489621
VL - 13
SP - 195
EP - 205
JO - The Lancet Neurology
JF - The Lancet Neurology
SN - 1474-4422
IS - 2
ER -