Clinical features, treatment and prognosis of Rasmussen encephalitis in 21 children_Journal of Epilepsy

Authors：

JI Taoyun ^1,2 , WANG Ruofan ^1,2 , LIU Qingzhu ¹ , WANG Shuang ^1,2 , YU Hao ¹ , LIU Chang ¹ , SUN Yu ¹ , WANG Wen ¹ , YU Guojing ¹ , WANG Dongming ¹ , WU Ye ^1,2 , JIANG Yuwu ^1,2 , LIU Xiaoyan ^1,2 ,  CAI Lixin ¹

1. Pediatric Epilepsy Center, Peking University First Hospital, Beijing 100034, China;
2. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China;

Corresponding author：

CAI Lixin, Email: cailx1010@hotmail.com

Keywords：

Rasmussen encephalitis; Epilepsia partialis continua; Hemispheric disconnection; Focal motor seizures

DOI：

10.7507/2096-0247.202205012

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Objective To summarize the clinical phenotype, electrophysiological characteristics, imaging characteristics, surgical treatment and prognosis of Rasmussen encephalitis (RE), so as to deepen the understanding of the disease. Methods The clinical data of patients with RE who underwent surgical therapy from October 2014 to October 2019 at Children's Epilepsy Center in Peking University First Hospital were retrospectively reviewed. Demographic characteristics, seizure forms, electroencephalogram (EEG), cranial nuclear magnetic resonance (MRI), operative methods as well as surgical outcomes evaluated by Engel classification during follow-up of the subjects were collected and analyzed. Results Totally 21 pediatric patients were enrolled, including 8 males and 13 females. The age at onset was (5.0±2.0) years old, the age at the time of surgery was (6.9±2.7) years old, and the disease duration at the time of surgery was (1.7±1.3) years. Twenty (20/21, 95.2%) patients had focal motor seizures, and 10 (10/21, 47.6%) patients had 2 or 3 forms of focal motor seizures. Fifteen patients (15/21, 71.4%) had epilepsia partialis continua (EPC), which occurred (0.7±0.6) years after the onset. All patients had hemiplegia, which appeared at (0.9±0.6) years after the onset. All patients showed a slow rhythm at their affected hemispheres during the EEG monitoring and 4 of them also showed slow rhythm at the contralateral hemispheres as the disease progressed. All patients had epileptiform discharges at the involved hemisphere, and 6 patients also had independent epileptiform discharges on the contralateral side. All 21 patients underwent hemispheric disconnection. The duration of follow-up was 2 to 7 years, and all patients achieved Engel class I after the surgery. The neurological dysfunction recovered to varying degrees during the postoperative period. Conclusion RE mostly occurs around the school age. Focal motor seizures are the main manifestations and the most common onset symptoms. With the progress of the disease, the condition of patients worsened gradually. The EEG of patients was mainly characterized by broad slow wave and spike wave in the affected hemisphere. Some patients can also have bilateral involvement, which was obviously asymmetrical. Through surgical treatment, the patients all achieved good results in terms of seizures and development.

Citation： JI Taoyun, WANG Ruofan, LIU Qingzhu, WANG Shuang, YU Hao, LIU Chang, SUN Yu, WANG Wen, YU Guojing, WANG Dongming, WU Ye, JIANG Yuwu, LIU Xiaoyan, CAI Lixin. Clinical features, treatment and prognosis of Rasmussen encephalitis in 21 children. Journal of Epilepsy, 2022, 8(5): 400-406. doi: 10.7507/2096-0247.202205012 Copy

1.	Bien CG, Widman G, Urbach H, et al. The natural history of Rasmussen’s encephalitis. Brain, 2002, 125(Pt 8): 1751-1759.
2.	Pardo CA, Vining EPG, Guo L, et al. The pathology of Rasmussen’s syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies. Epilepsia, 2004, 45(5): 516-526.
3.	陈帅, 王一松, 关宇光, 等. Rasmussen脑炎的病因及发病机制研究现状. 转化医学电子杂志, 2015, 2(10): 121-125.
4.	Xinghui He, Fan Chen, Yifan Zhang, et al. Upregulation of adenosine A2A receptor and downregulation of GLT1 is associated with neuronal cell death in Rasmussen's encephalitis. Brain Pathol, 2020, 30(2): 246-260.
5.	Bien CG, Granata T, Antozzi C, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain, 2005, 128(Pt 3): 454-471.
6.	Bhatjiwale MG, Polkey C, Cox TC, et al. Rasmussen’s encephalitis: neuroimaging findings in 21 patients with a closer look at the basal ganglia. Pediatr Neurosurg, 1998, 29(3): 142-148.
7.	Leach JP, Chadwick DW, Miles JB, et al. Improvement in adult-onset Rasmussen’s encephalitis with long-term immunomodulatory therapy. Neurology, 1999, 52(4): 738-742.
8.	Gray F, Serdaru M, Baron H, et al. Chronic localised encephalitis (Rasmussen’s) in an adult with epilepsia partialis continua. J Neurol Neurosurg Psychiatry, 1987, 50(6): 747-751.
9.	Hart YM, Andermann F, Fish DR, et al. Chronic encephalitis and epilepsy in adults and adolescents: a variant of Rasmussen’s syndrome? Neurology, 1997, 48(2): 418-424.
10.	Cay-Martinez KC, Hickman RA, McKhann Ii GM, et al. Rasmussen encephalitis: an update. Semin Neurol, 2020, 40(2): 201-210.
11.	Ambrosino P, Freri E, Castellotti B, et al. Kv7. 3 compound heterozygous variants in early onset encephalopathy reveal additive contribution of C-terminal residues to PIP2-dependent Kt channel gating. Mol Neurobiol, 2018, 55(08): 7009-7024.
12.	Longaretti F, Dunkley C, Varadkar S, et al. Evolution of the EEG in children with Rasmussen’s syndrome. Epilepsia, 2012, 53(09): 1539-1545.
13.	Granata T, Gobbi G, Spreafico R, et al. Rasmussen’s encephalitis: early characteristics allow diagnosis. Neurology, 2003, 60(03): 422-425.
14.	Wagner J, Schoene-Bake JC, Bien CG, et al. Automated 3D MRI volumetry reveals regional atrophy differences in Rasmussen encephalitis. Epilepsia, 2012, 53(04): 613-621.
15.	Chiapparini L, Granata T, Farina L, et al. Diagnostic imaging in 13 cases of Rasmussen’s encephalitis: can early MRI suggest the diagnosis? Neuroradiology, 2003, 45(03): 171-183.
16.	S Larionov, R König, H Urbach, et al. MRI brain volumetry in Rasmussen encephalitis: the fate of affected and "unaffected" hemispheres. Neurology, 2005, 64(5): 885-887.
17.	D J Fiorella, J M Provenzale, R E Coleman, et al. (18)F-fluorodeoxyglucose positron emission tomography and MR imaging findings in Rasmussen encephalitis. AJNR Am J Neuroradiol, 2001, 22(7): 1291-1299.
18.	Hart YM, Cortez M, Andermann F, et al. Medical treatment of Rasmussen’s syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Neurology, 1994, 44(6): 1030-1036.
19.	Andrews PI, Dichter MA, Berkovic SF, et al. Plasmapheresis in Rasmussen’s encephalitis. Neurology, 1996, 46(1): 242-246.
20.	Antozzi C, Granata T, Aurisano N, et al. Long-term selective IgG immuno-adsorption improves Rasmussen’s encephalitis. Neurology, 1998, 51(1): 302-305.
21.	Bien CG, Gleissner U, Sassen R, et al. An open study of tacrolimus therapy in Rasmussen encephalitis. Neurology, 2004, 62(11): 2106-2109.
22.	Liba Z, Sedlacek P, Sebronova V, et al. Alemtuzumab and intrathecal methotrexate failed in the therapy of Rasmussen encephalitis. Neurol Neuroimmunol Neuroinflamm, 2017, 4(4): e354.
23.	Thilo B, Stingele R, Knudsen K, et al. A case of Rasmussen encephalitis treated with rituximab. Nat Rev Neurol, 2009, 5(8): 458-462.
24.	Lagarde S, Villeneuve N, Trébuchon A, et al. Anti-tumor necrosis factor alpha therapy (adalimumab) in Rasmussen’s encephalitis: an open pilot study. Epilepsia, 2016, 57(6): 956-966.
25.	Kebir H, Carmant L, Fontaine F, et al. Humanized mouse model of Rasmussen’s encephalitis supports the immune-mediated hypothesis. J Clin Invest, 2018, 128(5): 2000-2009.
26.	Bien CG, Schramm J. Treatment of rasmussen encephalitis half a century after its initial description: promising prospects and a dilemma. Epilepsy Res, 2009, 86(2-3): 101-112.
27.	Skirrow C, Cross JH, Owens R, et al. Determinants of IQ outcome after focal epilepsy surgery in childhood: a longitudinal casecontrol neuroimaging study. Epilepsia, 2019, 60(5): 872-884.
28.	Jonas R, Nguyen S, Hu B, et al. Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes. Neurology, 2004, 62(10): 1712-1721.
29.	Basheer SN, ConnollyMB, Lautzenhiser A, et al. Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function. Epilepsia, 2007, 48(1): 133-140.
30.	Thomas SG, Daniel RT, Chacko AG, et al. Cognitive changes following surgery in intractable hemispheric and sub-hemispheric pediatric epilepsy. Childs Nerv Syst, 2010, 26(8): 1067-1073.
31.	Granata T, Matricardi S, Ragona F, et al. Hemispherotomy in Rasmussen encephalitis: long-term outcome in an Italian series of 16 patients. Epilepsy Res, 2014, 108(06): 1106-1119.

1. Bien CG, Widman G, Urbach H, et al. The natural history of Rasmussen’s encephalitis. Brain, 2002, 125(Pt 8): 1751-1759.
2. Pardo CA, Vining EPG, Guo L, et al. The pathology of Rasmussen’s syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies. Epilepsia, 2004, 45(5): 516-526.
3. 陈帅, 王一松, 关宇光, 等. Rasmussen脑炎的病因及发病机制研究现状. 转化医学电子杂志, 2015, 2(10): 121-125.
4. Xinghui He, Fan Chen, Yifan Zhang, et al. Upregulation of adenosine A2A receptor and downregulation of GLT1 is associated with neuronal cell death in Rasmussen's encephalitis. Brain Pathol, 2020, 30(2): 246-260.
5. Bien CG, Granata T, Antozzi C, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain, 2005, 128(Pt 3): 454-471.
6. Bhatjiwale MG, Polkey C, Cox TC, et al. Rasmussen’s encephalitis: neuroimaging findings in 21 patients with a closer look at the basal ganglia. Pediatr Neurosurg, 1998, 29(3): 142-148.
7. Leach JP, Chadwick DW, Miles JB, et al. Improvement in adult-onset Rasmussen’s encephalitis with long-term immunomodulatory therapy. Neurology, 1999, 52(4): 738-742.
8. Gray F, Serdaru M, Baron H, et al. Chronic localised encephalitis (Rasmussen’s) in an adult with epilepsia partialis continua. J Neurol Neurosurg Psychiatry, 1987, 50(6): 747-751.
9. Hart YM, Andermann F, Fish DR, et al. Chronic encephalitis and epilepsy in adults and adolescents: a variant of Rasmussen’s syndrome? Neurology, 1997, 48(2): 418-424.
10. Cay-Martinez KC, Hickman RA, McKhann Ii GM, et al. Rasmussen encephalitis: an update. Semin Neurol, 2020, 40(2): 201-210.
11. Ambrosino P, Freri E, Castellotti B, et al. Kv7. 3 compound heterozygous variants in early onset encephalopathy reveal additive contribution of C-terminal residues to PIP2-dependent Kt channel gating. Mol Neurobiol, 2018, 55(08): 7009-7024.
12. Longaretti F, Dunkley C, Varadkar S, et al. Evolution of the EEG in children with Rasmussen’s syndrome. Epilepsia, 2012, 53(09): 1539-1545.
13. Granata T, Gobbi G, Spreafico R, et al. Rasmussen’s encephalitis: early characteristics allow diagnosis. Neurology, 2003, 60(03): 422-425.
14. Wagner J, Schoene-Bake JC, Bien CG, et al. Automated 3D MRI volumetry reveals regional atrophy differences in Rasmussen encephalitis. Epilepsia, 2012, 53(04): 613-621.
15. Chiapparini L, Granata T, Farina L, et al. Diagnostic imaging in 13 cases of Rasmussen’s encephalitis: can early MRI suggest the diagnosis? Neuroradiology, 2003, 45(03): 171-183.
16. S Larionov, R König, H Urbach, et al. MRI brain volumetry in Rasmussen encephalitis: the fate of affected and "unaffected" hemispheres. Neurology, 2005, 64(5): 885-887.
17. D J Fiorella, J M Provenzale, R E Coleman, et al. (18)F-fluorodeoxyglucose positron emission tomography and MR imaging findings in Rasmussen encephalitis. AJNR Am J Neuroradiol, 2001, 22(7): 1291-1299.
18. Hart YM, Cortez M, Andermann F, et al. Medical treatment of Rasmussen’s syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Neurology, 1994, 44(6): 1030-1036.
19. Andrews PI, Dichter MA, Berkovic SF, et al. Plasmapheresis in Rasmussen’s encephalitis. Neurology, 1996, 46(1): 242-246.
20. Antozzi C, Granata T, Aurisano N, et al. Long-term selective IgG immuno-adsorption improves Rasmussen’s encephalitis. Neurology, 1998, 51(1): 302-305.
21. Bien CG, Gleissner U, Sassen R, et al. An open study of tacrolimus therapy in Rasmussen encephalitis. Neurology, 2004, 62(11): 2106-2109.
22. Liba Z, Sedlacek P, Sebronova V, et al. Alemtuzumab and intrathecal methotrexate failed in the therapy of Rasmussen encephalitis. Neurol Neuroimmunol Neuroinflamm, 2017, 4(4): e354.
23. Thilo B, Stingele R, Knudsen K, et al. A case of Rasmussen encephalitis treated with rituximab. Nat Rev Neurol, 2009, 5(8): 458-462.
24. Lagarde S, Villeneuve N, Trébuchon A, et al. Anti-tumor necrosis factor alpha therapy (adalimumab) in Rasmussen’s encephalitis: an open pilot study. Epilepsia, 2016, 57(6): 956-966.
25. Kebir H, Carmant L, Fontaine F, et al. Humanized mouse model of Rasmussen’s encephalitis supports the immune-mediated hypothesis. J Clin Invest, 2018, 128(5): 2000-2009.
26. Bien CG, Schramm J. Treatment of rasmussen encephalitis half a century after its initial description: promising prospects and a dilemma. Epilepsy Res, 2009, 86(2-3): 101-112.
27. Skirrow C, Cross JH, Owens R, et al. Determinants of IQ outcome after focal epilepsy surgery in childhood: a longitudinal casecontrol neuroimaging study. Epilepsia, 2019, 60(5): 872-884.
28. Jonas R, Nguyen S, Hu B, et al. Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes. Neurology, 2004, 62(10): 1712-1721.
29. Basheer SN, ConnollyMB, Lautzenhiser A, et al. Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function. Epilepsia, 2007, 48(1): 133-140.
30. Thomas SG, Daniel RT, Chacko AG, et al. Cognitive changes following surgery in intractable hemispheric and sub-hemispheric pediatric epilepsy. Childs Nerv Syst, 2010, 26(8): 1067-1073.
31. Granata T, Matricardi S, Ragona F, et al. Hemispherotomy in Rasmussen encephalitis: long-term outcome in an Italian series of 16 patients. Epilepsy Res, 2014, 108(06): 1106-1119.

Journal of Epilepsy

Clinical features, treatment and prognosis of Rasmussen encephalitis in 21 children

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