Acute disseminated encephalomyelitis (ADEM)

Version: 2.1
Published: 08 July 2016
Condition for which Ig has an emerging therapeutic role.

This medical condition has either been superseded or has become inactive
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Specific Conditions
  • Acute disseminated encephalomyelitis
Indication for Ig Use
  • Monophasic ADEM unresponsive to corticosteroid therapy or where corticosteroids are contraindicated (e.g. suspicion of central nervous system infection).
  • Recurrent or multiphasic ADEM unresponsive to corticosteroid therapy or where corticosteroid therapy has become intolerable or is contraindicated.
Level of Evidence Evidence of probable benefit – more research needed (Category 2a)
Description and Diagnostic Criteria Acute disseminated encephalomyelitis (ADEM) is a monophasic inflammatory condition of the central nervous system that usually presents in children and young adults. It typically occurs following a viral prodrome with multifocal neurological disturbance and altered conscious state. ADEM usually follows a monophasic course, but patients may experience recurrence of the initial symptom complex (recurrent ADEM) or a second episode of ADEM (multiphasic ADEM). The majority make a full recovery.

ADEM is thought to have an autoimmune basis. Pathologic similarities to experimental allergic encephalomyelitis (EAE), an animal model of inflammatory demyelination, support this theory. It is postulated that a common antigen shared by an infectious agent and a myelin epitope results in an autoimmune response.

Patients show multiple demyelinating lesions on magnetic resonance imaging (MRI) in the deep and subcortical white matter. The differential diagnosis includes other inflammatory demyelinating disorders, such as multiple sclerosis, optic neuritis and transverse myelitis.

High-dose corticosteroids are first-line treatment of ADEM. Intravenous immunoglobulin (IVIg) has been used for patients who fail to respond to corticosteroid therapy or in patients where corticosteroids are contraindicated. Most patients with ADEM recover completely over a period of six weeks from onset.

There is no biological marker for ADEM. Diagnosis is by clinical recognition of the multifocal neurological disturbance and altered conscious state, with the typical magnetic resonance imaging (MRI) findings of demyelination.
Justification for Evidence Category Review of multiple case series of IVIg use for paediatric ADEM found that children with monophasic ADEM completely recovered after administration of IVIg or IVIg plus corticosteroids. In recurrent ADEM, children either completely recovered after IVIg, or showed improvement. Adults with monophasic or recurrent ADEM recovered after treatment with IVIg.
Diagnosis Requirements

A diagnosis must be made by a Neurologist.
Qualifying Criteria for Ig Therapy
Monophasic ADEM unresponsive to corticosteroid therapy or where corticosteroids are contraindicated (e.g. suspicion of central nervous system infection).
  • Symptomatic ADEM
AND
  • Unresponsive to corticosteroid therapy.
  • OR
  • Corticosteroid therapy is contraindicated.
Recurrent or multiphasic ADEM unresponsive to corticosteroid therapy or where corticosteroid therapy has become intolerable or is contraindicated.
  • Symptomatic ADEM
AND
  • Unresponsive to corticosteroid therapy.
  • OR
  • Corticosteroid therapy has become intolerable or is contraindicated.
Review Criteria for Assessing the Effectiveness of Ig Use
Monophasic ADEM unresponsive to corticosteroid therapy or where corticosteroids are contraindicated (e.g. suspicion of central nervous system infection).
  • Improvement in symptoms in comparison to previous assessment. 
Recurrent or multiphasic ADEM unresponsive to corticosteroid therapy or where corticosteroid therapy has become intolerable or is contraindicated.
Six-monthly review by a neurologist is required for recurrent or multiphasic ADEM. Cessation of treatment should be considered at each review.

Documentation of clinical effectiveness is necessary for continuation of IVIg therapy.
 

On review of the initial authorisation period

Clinical effectiveness of Ig therapy may be demonstrated by:
 
  • Improvement in relapse rate in comparison to pre-treatment levels.

On review of a continuing authorisation period

Clinical effectiveness of Ig therapy may be demonstrated by:
 
  • Improvement in symptoms and clinical course in comparison to the previous review assessment.
Dose
Monophasic ADEM unresponsive to corticosteroid therapy or where corticosteroids are contraindicated (e.g. suspicion of central nervous system infection).
  • Dose (IVIg) - up to 2 g/kg in 2 to 5 divided doses.
Up to three doses may be used for extended monophasic ADEM. After three months, if symptoms persist, an alternative diagnosis should be considered.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Dosing above 1 g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.
Recurrent or multiphasic ADEM unresponsive to corticosteroid therapy or where corticosteroid therapy has become intolerable or is contraindicated.
  • Induction Dose (IVIg) - up to 2 g/kg in 2 to 5 divided doses.
  • Maintenance Dose (IVIg) - 0.4–2 g/kg, 4–6 weekly.
Aim for the minimum dose to maintain optimal functional status and prevent relapses.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Dosing above 1 g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.
Bibliography
Andersen, JB, Rasmussen, LH, Herning, M, et al 2001, ‘Dramatic improvement of severe acute disseminated encephalomyelitis after treatment with intravenous immunoglobulin in a three-year-old boy’, Developmental Medicine & Child Neurology, vol. 43, no. 2, pp. 136–8.

Feasby, T, Banwell, B, Benstead, T, et al 2007, ‘Guidelines on the use of intravenous immune globulin for neurologic conditions’, Transfusion Medicine Reviews, vol. 2, no. 2, suppl. 1, pp. S57–107.

Finsterer, J, Grass, R, Stollberger, C, et al 1998, ‘Immunoglobulins in acute, parainfectious, disseminated encephalomyelitis’, Clinical Neuropharmacology, vol. 21, pp. 258–61.

Hahn, JS, Siegler, DJ & Enzmann, D 1996, ‘Intravenous gammaglobulin therapy in recurrent acute disseminated encephalomyelitis’, Neurology, vol. 46, no. 4, pp. 1173–4.

Kleiman, M & Brunquell, P 1995, ‘Acute disseminated encephalomyelitis: response to intravenous immunoglobulin?’ Journal of Child Neurology, vol. 10, no. 6, pp. 481–3.

Marchioni, E, Marinou-Aktipi, K, Uggetti, C, et al 2002, ‘Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis’, Journal of Neurology, vol. 249, no. 1, pp. 100–4.

Mariotti, P, Batocchi, AP, Colosimo, C, et al 2003, ‘Multiphasic demyelinating disease involving central and peripheral nervous system in a child’, Neurology, vol. 60, no. 2, pp. 348–9.

Nishikawa, M, Ichiyama, T, Hayashi, T, et al 1999, ‘Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis’, Paediatric Neurology, vol. 21, no. 2, pp. 583–6.

Pittock, SJ, Keir, G, Alexander, M, et al 2001, ‘Rapid clinical and CSF response to intravenous gamma globulin in acute disseminated encephalomyelitis’, European Journal of Neurology, vol. 8, no. 6, p. 725.

Pradhan, S, Gupta, RP, Shashank, S, et al 1999, ‘Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis’, Journal of the Neurological Sciences, vol. 165, no. 1, pp. 56–61.

Revel-Vilk, S, Hurvitz, H, Klar, A, et al 2000, ‘Recurrent acute disseminated encephalomyelitis associated with acute cytomegalovirus and Epstein-Barr virus infection’, Journal of Child Neurology, vol. 15, no. 6, pp. 421–4.

Sahlas, DJ, Miller, SP, Guerin, M, et al 2000, ‘Treatment of acute disseminated encephalomyelitis with intravenous immunoglobulin’, Neurology, vol. 54, no. 6, pp. 1370–2.