Download PDF
Journal of Pediatric Epilepsy 2018; 07(02): 045-051
DOI: 10.1055/s-0038-1668590
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Rasmussen's Encephalitis

Aimee F. Luat
1   Carman and Ann Adams Departments of Pediatrics and Neurology, Children's Hospital of Michigan, Detroit Medical Center Wayne State University School of Medicine, Detroit, Michigan, United States
› Author Affiliations
Further Information

Publication History

02 June 2018

20 June 2018

Publication Date:
03 September 2018 (online)

    Permissions and Reprints

Abstract

Rasmussen's encephalitis (RE) is a childhood epilepsy syndrome characterized by drug-refractory focal seizures especially epilepsia partialis continua, progressive hemiparesis, and neurocognitive decline. Diagnosis is mainly clinical and can be ambiguous during the early stages of the disease. Its underlying etiology is still elusive, but is suspected to be immune mediated. Treatment of seizures and disease progression is challenging, and although immunotherapy may delay its course, to date, surgical disconnection of the diseased hemisphere remains to be the only effective treatment providing seizure freedom in 60 to 85% of cases. The following review summarizes the current knowledge of the pathophysiology, clinical presentation, management, and treatment of RE.

Keywords

Rasmussen's encephalitis - surgery - immunotherapy
 

  • References

  • 1 Rasmussen T, Olszewski J, Lloydsmith D. Focal seizures due to chronic localized encephalitis. Neurology 1958; 8 (06) 435-445
    CrossrefPubMedGoogle Scholar
  • 2 Bien CG, Tiemeier H, Sassen R. , et al. Rasmussen encephalitis: incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins. Epilepsia 2013; 54 (03) 543-550
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Robitaille Y. Neuropathologic aspects of chronic encephalitis. In: Andermann F. , ed. Chronic Encephalitis and Epilepsy. Rasmussen's Syndrome. Boston: Butterworth-Heinemann; 1991: 79-110
    Google Scholar
  • 5 Bien CG, Bauer J, Deckwerth TL. , et al. Destruction of neurons by cytotoxic T cells: a new pathogenic mechanism in Rasmussen's encephalitis. Ann Neurol 2002; 51 (03) 311-318
    CrossrefPubMedGoogle Scholar
  • 6 Pardo CA, Vining EP, Guo L, Skolasky RL, Carson BS, Freeman JM. The pathology of Rasmussen syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies. Epilepsia 2004; 45 (05) 516-526
    CrossrefPubMedGoogle Scholar
  • 7 Li Y, Uccelli A, Laxer KD. , et al. Local-clonal expansion of infiltrating T lymphocytes in chronic encephalitis of Rasmussen. J Immunol 1997; 158 (03) 1428-1437
    PubMedGoogle Scholar
  • 8 Schwab N, Bien CG, Waschbisch A. , et al. CD8+ T-cell clones dominate brain infiltrates in Rasmussen encephalitis and persist in the periphery. Brain 2009; 132 (Pt 5): 1236-1246
    CrossrefPubMedGoogle Scholar
  • 9 Walter GF, Renella RR. Epstein-Barr virus in brain and Rasmussen's encephalitis. Lancet 1989; 1 (8632): 279-280
    PubMedGoogle Scholar
  • 10 Power C, Poland SD, Blume WT, Girvin JP, Rice GP. Cytomegalovirus and Rasmussen's encephalitis. Lancet 1990; 336 (8726): 1282-1284
    CrossrefPubMedGoogle Scholar
  • 11 Jay V, Becker LE, Otsubo H. , et al. Chronic encephalitis and epilepsy (Rasmussen's encephalitis): detection of cytomegalovirus and herpes simplex virus 1 by the polymerase chain reaction and in situ hybridization. Neurology 1995; 45 (01) 108-117
    CrossrefPubMedGoogle Scholar
  • 12 Vinters HV, Wang R, Wiley CA. Herpesviruses in chronic encephalitis associated with intractable childhood epilepsy. Hum Pathol 1993; 24 (08) 871-879
    CrossrefPubMedGoogle Scholar
  • 13 Rogers SW, Andrews PI, Gahring LC. , et al. Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis. Science 1994; 265 (5172): 648-651
    CrossrefPubMedGoogle Scholar
  • 14 Mantegazza R, Bernasconi P, Baggi F. , et al. Antibodies against GluR3 peptides are not specific for Rasmussen's encephalitis but are also present in epilepsy patients with severe, early onset disease and intractable seizures. J Neuroimmunol 2002; 131 (1–2): 179-185
    CrossrefPubMedGoogle Scholar
  • 15 Watson R, Jiang Y, Bermudez I. , et al. Absence of antibodies to glutamate receptor type 3 (GluR3) in Rasmussen encephalitis. Neurology 2004; 63 (01) 43-50
    CrossrefPubMedGoogle Scholar
  • 16 Watson R, Jepson JE, Bermudez I. , et al. Alpha7-acetylcholine receptor antibodies in two patients with Rasmussen encephalitis. Neurology 2005; 65 (11) 1802-1804
    CrossrefPubMedGoogle Scholar
  • 17 Yang R, Puranam RS, Butler LS. , et al. Autoimmunity to munc-18 in Rasmussen's encephalitis. Neuron 2000; 28 (02) 375-383
    CrossrefPubMedGoogle Scholar
  • 18 Alvarez-Barón E, Bien CG, Schramm J, Elger CE, Becker AJ, Schoch S. Autoantibodies to Munc18, cerebral plasma cells and B-lymphocytes in Rasmussen encephalitis. Epilepsy Res 2008; 80 (01) 93-97
    CrossrefPubMedGoogle Scholar
  • 19 Pardo CA, Nabbout R, Galanopoulou AS. Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES). Neurotherapeutics 2014; 11 (02) 297-310
    CrossrefPubMedGoogle Scholar
  • 20 Wirenfeldt M, Clare R, Tung S, Bottini A, Mathern GW, Vinters HV. Increased activation of Iba1+ microglia in pediatric epilepsy patients with Rasmussen's encephalitis compared with cortical dysplasia and tuberous sclerosis complex. Neurobiol Dis 2009; 34 (03) 432-440
    CrossrefPubMedGoogle Scholar
  • 21 Banati RB, Goerres GW, Myers R. , et al. [11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis. Neurology 1999; 53 (09) 2199-2203
    CrossrefPubMedGoogle Scholar
  • 22 Ramaswamy V, Walsh JG, Sinclair DB. , et al. Inflammasome induction in Rasmussen's encephalitis: cortical and associated white matter pathogenesis. J Neuroinflammation 2013; 10: 152
    PubMedGoogle Scholar
  • 23 Maroso M, Balosso S, Ravizza T. , et al. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med 2010; 16 (04) 413-419
    CrossrefPubMedGoogle Scholar
  • 24 Luan G, Gao Q, Zhai F, Chen Y, Li T. Upregulation of HMGB1, toll-like receptor and RAGE in human Rasmussen's encephalitis. Epilepsy Res 2016; 123: 36-49
    CrossrefPubMedGoogle Scholar
  • 25 Chin JH. Adenosine receptors in brain: neuromodulation and role in epilepsy. Ann Neurol 1989; 26 (06) 695-698
    CrossrefPubMedGoogle Scholar
  • 26 Luan G, Wang X, Gao Q. , et al. Upregulation of neuronal adenosine A1 receptor in human Rasmussen encephalitis. J Neuropathol Exp Neurol 2017; 76 (08) 720-731
    CrossrefPubMedGoogle Scholar
  • 27 Luan G, Gao Q, Guan Y. , et al. Upregulation of adenosine kinase in Rasmussen encephalitis. J Neuropathol Exp Neurol 2013; 72 (11) 1000-1008
    CrossrefPubMedGoogle Scholar
  • 28 Oguni HAF, Rasmussen TB. The natural history of the syndrome of chronic encephalitis and epilepsy: a study of the MNI series of fourty-eight cases. In: Andermann F. , ed. Chronic Encephalitis and Epilepsy. Boston: Butterworth-Heinemann; 1991: 7-35
    Google Scholar
  • 29 Villani F, Pincherle A, Antozzi C. , et al. Adult-onset Rasmussen's encephalitis: anatomical-electrographic-clinical features of 7 Italian cases. Epilepsia 2006; 47 (Suppl. 05) 41-46
    PubMedGoogle Scholar
  • 30 Dupont S, Gales A, Sammey S, Vidailhet M, Lambrecq V. Late-onset Rasmussen Encephalitis: A literature appraisal. Autoimmun Rev 2017; 16 (08) 803-810
    CrossrefPubMedGoogle Scholar
  • 31 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 (02) 418-424
    CrossrefPubMedGoogle Scholar
  • 32 Jaillon-Riviere V, Dupont S, Bertran F. , et al. Late onset Rasmussen's syndrome: clinical and therapeutic characteristics [Article in French]. Rev Neurol (Paris) 2007; 163 (05) 573-580
    CrossrefPubMedGoogle Scholar
  • 33 Bien CG, Widman G, Urbach H. , et al. The natural history of Rasmussen's encephalitis. Brain 2002; 125 (Pt 8): 1751-1759
    CrossrefPubMedGoogle Scholar
  • 34 Granata T, Gobbi G, Spreafico R. , et al. Rasmussen's encephalitis: early characteristics allow diagnosis. Neurology 2003; 60 (03) 422-425
    CrossrefPubMedGoogle Scholar
  • 35 Hennessy MJ, Koutroumanidis M, Dean AF. , et al. Chronic encephalitis and temporal lobe epilepsy: a variant of Rasmussen's syndrome?. Neurology 2001; 56 (05) 678-681
    CrossrefPubMedGoogle Scholar
  • 36 Bien CG, Elger CE, Leitner Y. , et al. Slowly progressive hemiparesis in childhood as a consequence of Rasmussen encephalitis without or with delayed-onset seizures. Eur J Neurol 2007; 14 (04) 387-390
    CrossrefPubMedGoogle Scholar
  • 37 Ravindra VM, Mazur MD, Mohila CA, Sweney MT, Hersh A, Bollo RJ. Rasmussen encephalitis with dual pathology in a patient without seizures: case report and literature review. Childs Nerv Syst 2015; 31 (11) 2165-2171
    CrossrefPubMedGoogle Scholar
  • 38 Frucht S. Dystonia, athetosis, and epilepsia partialis continua in a patient with late-onset Rasmussen's encephalitis. Mov Disord 2002; 17 (03) 609-612
    CrossrefPubMedGoogle Scholar
  • 39 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
    CrossrefPubMedGoogle Scholar
  • 40 Bien CG, Urbach H, Deckert M. , et al. Diagnosis and staging of Rasmussen's encephalitis by serial MRI and histopathology. Neurology 2002; 58 (02) 250-257
    CrossrefPubMedGoogle Scholar
  • 41 Fiorella DJ, Provenzale JM, Coleman RE, Crain BJ, Al-Sugair AA. (18)F-fluorodeoxyglucose positron emission tomography and MR imaging findings in Rasmussen encephalitis. Am J Neuroradiol 2001; 22 (07) 1291-1299
    PubMedGoogle Scholar
  • 42 Kuki I, Matsuda K, Kubota Y. , et al. Functional neuroimaging in Rasmussen syndrome. Epilepsy Res 2018; 140: 120-127
    CrossrefPubMedGoogle Scholar
  • 43 Mameniškienė R, Wolf P. Epilepsia partialis continua: a review. Seizure 2017; 44: 74-80
    CrossrefPubMedGoogle Scholar
  • 44 Longaretti F, Dunkley C, Varadkar S, Vargha-Khadem F, Boyd SG, Cross JH. Evolution of the EEG in children with Rasmussen's syndrome. Epilepsia 2012; 53 (09) 1539-1545
    CrossrefPubMedGoogle Scholar
  • 45 Rossi Sebastiano D, Visani E, Duran D. , et al. Epileptic spikes in Rasmussen's encephalitis: migratory pattern and short-term evolution. A MEG study. Clin Neurophysiol 2017; 128 (10) 1898-1905
    CrossrefPubMedGoogle Scholar
  • 46 Kravljanac R, Djuric M, Jovic N, Djordjevic M, Zamurovic D, Pekmezovic T. Etiology, clinical features and outcome of epilepsia partialis continua in cohort of 51 children. Epilepsy Res 2013; 104 (1–2): 112-117
    CrossrefPubMedGoogle Scholar
  • 47 Joe B, Goldsmith I, Yoshor D, Verma A. Successful treatment of epilepsia partialis continua by partial focal resection in a patient with Sturge-Weber syndrome. J Clin Neurophysiol 2005; 22 (05) 358
    PubMedGoogle Scholar
  • 48 Cornelius LP, Raju V, Lalapet RA. A case of epilepsia partialis continua due to linear nevus syndrome with hemimegalencephaly. J Pediatr Neurosci 2017; 12 (02) 203-205
    CrossrefPubMedGoogle Scholar
  • 49 Daghistani R, Widjaja E. Role of MRI in patient selection for surgical treatment of intractable epilepsy in infancy. Brain Dev 2013; 35 (08) 697-705
    CrossrefPubMedGoogle Scholar
  • 50 Wolf NI, Rahman S, Schmitt B. , et al. Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features. Epilepsia 2009; 50 (06) 1596-1607
    CrossrefPubMedGoogle Scholar
  • 51 Cohen BHCP, Copeland WC. POLG-Related Disorders. 2010; Available at: https://www-ncbi-nlm-nih-gov.proxy.lib.wayne.edu/books/NBK26471/ . Accessed May 5, 2018
    PubMedGoogle Scholar
  • 52 Gastaut H, Faidherbe J, Roger J. [5 case reports of unusual development of the hemiconvulsion-hemiplegiaepilepsy syndrome (HHE syndrome) in children]. Acta Neurol Psychiatr Belg 1962; 62: 177-192
    PubMedGoogle Scholar
  • 53 Nabbout R, Vezzani A, Dulac O, Chiron C. Acute encephalopathy with inflammation-mediated status epilepticus. Lancet Neurol 2011; 10 (01) 99-108
    CrossrefPubMedGoogle Scholar
  • 54 Freeman JL, Coleman LT, Smith LJ, Shield LK. Hemiconvulsion-hemiplegia-epilepsy syndrome: characteristic early magnetic resonance imaging findings. J Child Neurol 2002; 17 (01) 10-16
    CrossrefPubMedGoogle Scholar
  • 55 Longo D, Paonessa A, Specchio N. , et al. Parry-Romberg syndrome and Rasmussen encephalitis: possible association. Clinical and neuroimaging features. J Neuroimaging 2011; 21 (02) 188-193
    CrossrefPubMedGoogle Scholar
  • 56 Shah JR, Juhász C, Kupsky WJ. , et al. Rasmussen encephalitis associated with Parry-Romberg syndrome. Neurology 2003; 61 (03) 395-397
    CrossrefPubMedGoogle Scholar
  • 57 El-Kehdy J, Abbas O, Rubeiz N. A review of Parry-Romberg syndrome. J Am Acad Dermatol 2012; 67 (04) 769-784
    CrossrefPubMedGoogle Scholar
  • 58 Paprocka J, Jamroz E, Adamek D, Marszal E, Mandera M. Difficulties in differentiation of Parry-Romberg syndrome, unilateral facial sclerodermia, and Rasmussen syndrome. Childs Nerv Syst 2006; 22 (04) 409-415
    CrossrefPubMedGoogle Scholar
  • 59 Olson HE, Lechpammer M, Prabhu SP. , et al. Clinical application and evaluation of the Bien diagnostic criteria for Rasmussen encephalitis. Epilepsia 2013; 54 (10) 1753-1760
    CrossrefPubMedGoogle Scholar
  • 60 Grujic J, Bien CG, Pollo C, Rossetti AO. Vagus nerve stimulator treatment in adult-onset Rasmussen's encephalitis. Epilepsy Behav 2011; 20 (01) 123-125
    CrossrefPubMedGoogle Scholar
  • 61 San-Juan D, Calcáneo JdeD, González-Aragón MF. , et al. Transcranial direct current stimulation in adolescent and adult Rasmussen's encephalitis. Epilepsy Behav 2011; 20 (01) 126-131
    CrossrefPubMedGoogle Scholar
  • 62 Kang JS, Krakow K, Roggendorf J, Steinmetz H, Hilker R. Botulinum toxin treatment of epilepsia partialis continua. Mov Disord 2009; 24 (01) 141-143
    CrossrefPubMedGoogle Scholar
  • 63 Lozsadi DA, Hart IK, Moore AP. Botulinum toxin A improves involuntary limb movements in Rasmussen syndrome. Neurology 2004; 62 (07) 1233-1234
    CrossrefPubMedGoogle Scholar
  • 64 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
    CrossrefPubMedGoogle Scholar
  • 65 Varadkar S, Bien CG, Kruse CA. , et al. Rasmussen's encephalitis: clinical features, pathobiology, and treatment advances. Lancet Neurol 2014; 13 (02) 195-205
    CrossrefPubMedGoogle Scholar
  • 66 Vining EP, Freeman JM, Pillas DJ. , et al. Why would you remove half a brain? The outcome of 58 children after hemispherectomy-the Johns Hopkins experience: 1968 to 1996. Pediatrics 1997; 100 (2 Pt 1): 163-171
    CrossrefPubMedGoogle Scholar
  • 67 Lettori D, Battaglia D, Sacco A. , et al. Early hemispherectomy in catastrophic epilepsy: a neuro-cognitive and epileptic long-term follow-up. Seizure 2008; 17 (01) 49-63
    CrossrefPubMedGoogle Scholar
  • 68 Granata T, Andermann F. Rasmussen encephalitis. Handb Clin Neurol 2013; 111: 511-519
    PubMedGoogle Scholar
  • 69 Honavar M, Janota I, Polkey CE. Rasmussen's encephalitis in surgery for epilepsy. Dev Med Child Neurol 1992; 34 (01) 3-14
    PubMedGoogle Scholar
  • 70 Rasmussen T. Hemispherectomy for seizures revisited. Can J Neurol Sci 1983; 10 (02) 71-78
    Google Scholar
  • 71 Hartman AL, Cross JH. Timing of surgery in rasmussen syndrome: is patience a virtue?. Epilepsy Curr 2014; 14 (1, Suppl): 8-11
    CrossrefPubMedGoogle Scholar
  • 72 Granata T, Fusco L, Gobbi G. , et al. Experience with immunomodulatory treatments in Rasmussen's encephalitis. Neurology 2003; 61 (12) 1807-1810
    CrossrefPubMedGoogle Scholar
  • 73 Chinchilla D, Dulac O, Robain O. , et al. Reappraisal of Rasmussen's syndrome with special emphasis on treatment with high doses of steroids. J Neurol Neurosurg Psychiatry 1994; 57 (11) 1325-1333
    CrossrefPubMedGoogle Scholar
  • 74 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 (06) 1030-1036
    CrossrefPubMedGoogle Scholar
  • 75 Bahi-Buisson N, Villanueva V, Bulteau C. , et al. Long term response to steroid therapy in Rasmussen encephalitis. Seizure 2007; 16 (06) 485-492
    CrossrefPubMedGoogle Scholar
  • 76 Leach JP, Chadwick DW, Miles JB, Hart IK. Improvement in adult-onset Rasmussen's encephalitis with long-term immunomodulatory therapy. Neurology 1999; 52 (04) 738-742
    CrossrefPubMedGoogle Scholar
  • 77 Takahashi Y, Yamazaki E, Mine J. , et al. Immunomodulatory therapy versus surgery for Rasmussen syndrome in early childhood. Brain Dev 2013; 35 (08) 778-785
    CrossrefPubMedGoogle Scholar
  • 78 Andrews PI, Dichter MA, Berkovic SF, Newton MR, McNamara JO. Plasmapheresis in Rasmussen's encephalitis. Neurology 1996; 46 (01) 242-246
    CrossrefPubMedGoogle Scholar
  • 79 Antozzi C, Granata T, Aurisano N. , et al. Long-term selective IgG immuno-adsorption improves Rasmussen's encephalitis. Neurology 1998; 51 (01) 302-305
    CrossrefPubMedGoogle Scholar
  • 80 Bien CG, Gleissner U, Sassen R, Widman G, Urbach H, Elger CE. An open study of tacrolimus therapy in Rasmussen encephalitis. Neurology 2004; 62 (11) 2106-2109
    CrossrefPubMedGoogle Scholar
  • 81 Derry C, Dale RC, Thom M, Miller DH, Giovannoni G. Unihemispheric cerebral vasculitis mimicking Rasmussen's encephalitis. Neurology 2002; 58 (02) 327-328
    CrossrefPubMedGoogle Scholar