Rasmussen encephalitis

Version: 3.1
Published: 30 November 2023
Condition for which Ig use is in exceptional circumstances only

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Specific Conditions
  • Rasmussen encephalitis
Indication for Ig Use
  • Rasmussen encephalitis with concurrent steroid therapy unless contraindicated
Level of Evidence Evidence of probable benefit – more research needed (Category 2a)
Description and Diagnostic Criteria Rasmussen encephalitis is a chronic, progressive, focal encephalitis that is commonly accompanied by focal seizures, hemiparesis and cognitive decline. It is generally considered to be a disease of childhood, with most cases occurring in children younger than 10 years, although adult onset cases do occur. Conventional anticonvulsant therapy is usually ineffective and hemispherectomy may be helpful in the correct setting.
 
Generally there is an active progressive phase of the disease, often lasting some years, followed by quiescence and no further progression of disease. (Varadkar et al, 2014). Although historical data has generally reported seizure freedom only after functional hemispherectomy, some centres practise more aggressive immune therapies and report improved outcomes. Functional hemispherectomy provides the best opportunity of seizure freedom, however there will inevitably be post-surgical motor deficits, and often cognitive impairments post-hemispherectomy. Therefore it can be argued that aggressive early immune therapy may reduce the surgical sequelae of motor and cognitive deficits (The decision regarding when and if to perform hemispherectomy is challenging and discussed in Figure 4 of Varadkar et al 2014).
Justification for Evidence Category A number of retrospective case series, open label studies and one randomized controlled study (Bien et al, 2012) between 1996 and 2013. Hart YM et al (1996), Granata et al (2003) and Takahashi (2013) have reported benefit from immunomodulatory treatments including pulse steroids, intravenous immunoglobulin (IVIg), plasma exchange (PE) and tacrolimus. Benefit was seen in regard to reduced tissue and function loss and reduced chance of intractable epilepsy. A single case report described a good outcome with natulizumab (Bittner S et al, 2013). Early therapies may yield the best outcomes. Varadkar et al (2014) reported that immunomodulatory treatments seem to slow rather than halt disease progression without changing the eventual outcome. Patients are often left with intractable epilepsy for which functional hemispherectomy remains the only effective cure.
Diagnosis Requirements

A diagnosis must be made by a Neurologist.
Qualifying Criteria for Ig Therapy
  • Clinical features, EEG and MRI findings consistent with a diagnosis of Rasmussen encephalitis as per the European Consensus Statement (Bien, 2005)
  • OR
  • Two of typical clinical features, MRI changes or histopathology findings consistent with a diagnosis of Rasmussen encephalitis as per the European Consensus Statement (Bien, 2005)
AND
AND
  • Concurrent corticosteroid therapy
  • OR
  • Corticosteroid therapy is contraindicated
Review by a neurologist is required within six months of treatment and annually thereafter. It is recognised that the acute phase of Rasmussen encephalitis can last for at least 12 months followed by stabilisation of symptoms and residual disease. The aim of Ig therapy is to reduce the trajectory of deterioration in a progressive disease (Varadkar et al, 2014). Some patients will have aggressive and refractory disease, and in these cases hemispherectomy may be the preferred option (discussed in figure 4, Varadkar et al, 2014).
 
For patients on maintenance treatment, review by a neurologist is required at least annually. It is recognised that patients will typically reach a stabilisation phase 18 months to two years from onset, at which time, a trial of weaning should be considered.

Documentation of clinical effectiveness is necessary for continuation of IVIg therapy.
Review Criteria for Assessing the Effectiveness of Ig Use
Review by an neurologist is required within six months of treatment and annually thereafter. It is recognised that the acute phase of Rasmussen encephalitis can last for at least 12 months followed by stabilisation of symptoms and residual disease. The aim of Ig therapy is to reduce the trajectory of deterioration in a progressive disease (Varadkar et al, 2014). Some patients will have aggressive and refractory disease, and in these cases hemispherectomy may be the preferred option (discussed in figure 4, Varadkar et al, 2014).
 
For patients on maintenance treatment, review by a neurologist is required at least annually. It is recognised that patients will typically reach a stabilisation phase 18 months to two years from onset, at which time, a trial of weaning should be considered.
 
Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. 
 
Clinical effectiveness can be demonstrated by:
 

On review of the initial authorisation period

On review of a continuing authorisation period

  • Monitoring of the rate of deterioration of symptoms and disability compared to the qualifying assessment , including as measured by the adapted Modified Rankin Scale (MRS) score
  • AND
  • A trial of Ig weaning is planned for patients who have entered the residual stage of disease (permanent and stable neurologic deficits and continuing seizures) or a valid reason provided as to why a trial is not being planned or is contraindicated at this time
Dose
  • Induction Dose (IVIg) - 2 g/kg in divided doses over 2 to 5 days.
  • Maintenance Dose (IVIg) - 1 g/kg monthly as a single dose.
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
 
Refer to the current product information sheet for further information on dose, administration and contraindications.
 Dose Calculator
Bibliography
Bien, CG, Granata, T, Antozzi, C, et al 2005, ‘Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement’, Brain, vol. 128, PP. 454–71. https://www.ncbi.nlm.nih.gov/pubmed/15689357
                       
Bien, CG, Tiemeier, H, Sassen, R, et al 2013, ‘Rasmussen encephalitis: incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins’, Epilepsia, vol. 54, no. 3, pp. 543-50. https://www.ncbi.nlm.nih.gov/pubmed/23216622
 
Bittner, S, Simon, OJ, Göbel, K, et al 2013, ‘Rasmussen encephalitis treated with natalizumab’, Neurology, vol. 81, no. 4, pp. 395–397. https://www.ncbi.nlm.nih.gov/pubmed/23794679
 
Bonita, R & Beaglehole, R 1988, ‘Recovery of motor function after stroke’, Stroke, vol. 19, no. 12, pp. 1497-1500. https://www.ahajournals.org/doi/abs/10.1161/str.19.12.3201508
 
Caraballo, RH, Fortini, S, Cersósimo, R, Monges, S, Pasteris, MC, Gomez, M, et al 2013, ‘Rasmussen syndrome: an Argentinean experience in 32 patients’, Seizure, vol. 22, no. 5, pp. 360-7. https://www.ncbi.nlm.nih.gov/pubmed/23466213
 
Feasby, T, Barnwell, B, Benstead, T, et al 2007, ‘Guidelines on the Use of Intravenous Immune Globulin for Neurologic Conditions Transfusion Medicine Reviews’, vol. 21, no. 2, pp. S57-S107.
 
Granata, T, Gobbi, G, Spreafico, R, et al 2003, ‘Rasmussen's encephalitis: early characteristics allow diagnosis’, Neurology, vol. 60, no. 3, pp. 422-5. https://www.ncbi.nlm.nih.gov/pubmed/12578922
 
Hart, YM, Andermann, F, Fish, DR, Dubeau, F, Robitaille, Y, Rasmussen, T, et al 1997, ‘Chronic encephalitis and epilepsy in adults and adolescents: a variant of Rasmussen's syndrome?’, Neurology, vol. 48, no. 2, pp. 418-24. https://www.ncbi.nlm.nih.gov/pubmed/9040732
 
Ontario Regional Blood Coordinating Network (2016). Ontario Intravenous Immune Globulin (IVIG) Utilization Management Guidelines, Version 3.0. [online]. Available from: http://transfusionontario.org/en/download/ontario-intravenous-immune-globulin-ivig-utilization-management-guidelines-2/.
 
Rankin, J,1957, ‘Cerebral vascular accidents in patients over the age of 60’, Scottish Medical Journal, no. 2, pp. 200-15.
 
Stroke Engine Canada, 'The Modified Rankin Scale'. Available from  Modified Rankin Scale (MRS) – Strokengine
 
Takahashi, Y, Yamazaki, E, Mine, J, Kubota, Y, Imai, K, Mogami, Y, et al 2013, ‘Immunomodulatory therapy versus surgery for Rasmussen syndrome in early childhood’, Brain and Development, vol. 35, no. 8,pp. 778-85. https://www.ncbi.nlm.nih.gov/pubmed/23433490
 
UK Department of Health, 2011, ‘Clinical Guidelines for Immunoglobulin Use: Second Edition Update’, Available from: https://www.gov.uk/government/publications/clinical-guidelines-for-immunoglobulin-use-second-edition-update 
 
UK Department of Health, 2011, ‘Clinical Guidelines for Immunoglobulin Use: Second Edition Update’, Summary Poster. Available from: http://igd.mdsas.com/clinical-info/
 
Van Swieten, JC, Koudstaal, PJ, Visser, MC, Schouten, HJ, van Gijn, J, 1987, ‘Interobserver agreement for the assessment of handicap in stroke patients’, Stroke, vol. 19, no. 5, pp. 604-607. https://pdfs.semanticscholar.org/fba2/da6e4888b08ee79441937169c53f16aec218.pdf
 
Varadkar, S, Bien, CG, Kruse, CA, Jensen, FE, Bauer, J, Pardo, CA, et al 2014, ‘Rasmussen's encephalitis: clinical features, pathobiology, and treatment advances’,Lancet Neurology, vol. 13, no. 2, pp. 195-205. https://www.ncbi.nlm.nih.gov/pubmed/24457189