| Specific Conditions |
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| Indication for Ig Use |
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| 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 steroid therapy or in patients where steroids 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 MRI findings of demyelination. The International Paediatric MS Study Group (IPMSSG) criteria must be used for diagnosis (Krupp, LB, Tardieu, M, Amato, MP, et al 2013). |
| Justification for Evidence Category |
On review of multiple case series of intravenous immunoglobulin (IVIg) use for paediatric acute disseminated encephalomyelitis (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. Data from the International Pediatric MS Study Group (IPMSSG) in 2014 confirms this view. |
| 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
AND
Recurrent or multiphasic ADEM unresponsive to steroid therapy or where corticosteroid therapy has become intolerable or is contraindicated
This indication is for patients with recurrent or multiphasic ADEM, if patients relapse within six months of cessation of Ig therapy, an application can be submitted under the indication: Relapse of patients with recurrent or multiphasic ADEM within six months of commencement of trial off immunoglobulin therapy.
AND
Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Relapse of patients with recurrent or multiphasic ADEM within six months of commencement of trial off immunoglobulin therapy
ADEM patients with clinical and radiological evidence of relapse within six months of ceasing Ig therapy may qualify under this indication.
Where a relapse event does occur, a diagnosis of multiple sclerosis (MS) or neuromyelitis optica spectrum disorder should also be considered and MS disease modifying therapies or other therapies considered.
Review by a neurologist is required every six months. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. |
| Review Criteria for Assessing the Effectiveness of Ig Use |
Monophasic ADEM unresponsive to corticosteroid therapy or where corticosteroids are contraindicated
Review is not mandated for this indication however the following criteria may be useful in assessing the effectiveness of therapy.
Recurrent or multiphasic ADEM unresponsive to steroid therapy or where corticosteroid therapy has become intolerable or is contraindicated
A maximum of 12 months treatment is permitted under this indication. Review by a neurologist is required at six months to assess response to therapy.
Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Clinical effectiveness of Ig therapy may be assessed by: On review of the initial authorisation period
On review of a continuing authorisation period
If the patient relapses within six months of ceasing Ig therapy (with clinical and radiological evidence of relapse), patients may qualify under the indication Relapse of patients with recurrent or multiphasic ADEM within six months of commencement of trial off immunoglobulin therapy. Where a relapse event does occur, a diagnosis of multiple sclerosis (MS) or neuromyelitis optica spectrum disorder should also be considered and MS disease modifying therapies or other therapies considered. Relapse of patients with recurrent or multiphasic ADEM within six months of commencement of trial off immunoglobulin therapy
IVIg should be used for a maximum period of six months (induction plus five maintenance cycles) before determining whether the patient has responded. If there is no benefit after this treatment, IVIg therapy should be abandoned.
Review by a neurologist is required every six months. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Clinical effectiveness of Ig therapy may be assessed by: On review of the initial authorisation period
On review of a continuing authorisation period
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| Dose |
Monophasic ADEM unresponsive to corticosteroid therapy or where corticosteroids are contraindicated
Up to three doses (induction plus up to two follow-up doses) may be used for extended monophasic ADEM. After three months, if symptoms persist, an alternative diagnosis or therapy should be considered.
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. Recurrent or multiphasic ADEM unresponsive to steroid therapy or where corticosteroid therapy has become intolerable or is contraindicated
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. Relapse of patients with recurrent or multiphasic ADEM within six months of commencement of trial off immunoglobulin therapy
Aim for the minimum dose to maintain optimal functional status and prevent relapses.
Refer to the current product information sheet for further information on dose, administration and contraindications.ions. |
| Bibliography |
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| 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:S1, pp. S57–107. http://www.sciencedirect.com/science/article/pii/S088779630700003X 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 and Enzmann, D, 1996, ‘Intravenous gammaglobulin therapy in recurrent acute disseminated encephalomyelitis’, Neurology, vol. 46, no. 4, pp. 1173–4. https://www.ncbi.nlm.nih.gov/pubmed/8780119 Krupp, LB, Tardieu, M, Amato, MP, et al 2013, ‘International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions’, Multiple Sclerosis Journal, vol. 19, pp. 1261–1267. https://www.ncbi.nlm.nih.gov/pubmed/23572237 Kleiman, M and Brunquell, P, 1995, ‘Acute disseminated encephalomyelitis: response to intravenous immunoglobulin?’, Journal of Child Neurology, vol. 10, no. 6, pp. 481–3. http://journals.sagepub.com/doi/pdf/10.1177/088307389501000612 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. https://www.ncbi.nlm.nih.gov/pubmed/11954856 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. http://www.neurology.org/content/60/2/348.short 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. http://www.sciencedirect.com/science/article/pii/S0887899499000429 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, pp. 725. http://onlinelibrary.wiley.com/doi/10.1046/j.1468-1331.2001.00195.x/abstract |