Acute Disseminated Encephalomyelitis Treatment & Management

  • Author: Robert Stanley Rust Jr, MD, MA; Chief Editor: B Mark Keegan, MD, FRCPC   more...
 
Updated: Nov 18, 2010
 

Medical Care

Acute disseminated encephalomyelitis (ADEM) is often treated with high-dose intravenous corticosteroids, to which it appears to be responsive. One common protocol is 20 mg/kg/d of methylprednisolone (maximum dose of 1 g/d) for 3-5 days. Improvement may be observed within hours but usually requires several days. An oral taper for 3 weeks or some other interval is sometimes appended. The chief alternative therapy is intravenous immune globulin (IVIG).[16] It is administered as 2 g/kg intravenously for 2-3 days. IVIG may be preferable in instances where meningo-encephalitis cannot be excluded based upon the hypothesis that corticosteroids might worsen the course of infection.[16]

Available published information concerning efficacy is inadequate to accurately assess much concerning the impact of either form of therapy, although it appears likely that both forms of therapy increase the pace of initial recovery. Whether these forms of therapy influence times to final outcome or extent of final recovery is not known.

Theoretically, very high-dose corticosteroids (30-50 mg/kg) administered intravenously at presentation to patients with transverse myelitis may be advantageous from the vantage point of its capacity to close the blood-brain barrier and limit swelling. Marked cord swelling may account for poor outcome in some cases of transverse myelitis because of circulatory impairment and cord infarction. The same argument may hold true for severe cerebral ADEM such as tends to arise in some young children (< 3 y old) who also may have marked permanent neurologic impairments after severe ADEM.

There is as yet no convincing evidence that treatment with the combination of intravenous corticosteroids and IVIG confers any advantage in such cases, although this approach is employed by some clinicians.

Severe ADEM has also been treated, apparently successfully, with such alternative approaches as (1) combination of intravenous corticosteroids and IVIG, (2) cyclosporin, (3) cyclophosphamide, or (4) plasma exchange/plasmapheresis[17, 18] . Greater understanding of trimolecular complex regulation, adhesion molecules, and inflammatory cytokines may permit development of more specific and effective ADEM therapies. The polymorphism of the human major histocompatibility complex and apparent heterogeneity of T cell response to autoantigens render this a daunting project, although anticytokines represent an intriguing avenue of therapeutic research.[19]

Taper-related recurrence occurs in as many as 3-5% of cases and usually responds to prolongation of taper. Similar phenomena occur in other postinfectious diseases, such as Guillain-Barré syndrome or opsoclonus-myoclonus. A subset of patients manifest repeated recurrences that prevent discontinuation of corticosteroids or necessitate changing to various steroid-sparing treatments such as cyclophosphamide or beta-interferons. This rare and interesting subgroup tends to have onset of disease before 6 years of age, and despite recurrence, these children do not manifest evidence for CSF immune profile (ie, IgG index, IgG synthetic rate, oligoclonal bands) abnormality. The relationship of this group to patients with ADEM or MS or some other form of inflammatory CNS illness remains unclear.

Non–taper-related recurrences occur in as many as 5% of children with ADEM. In such instances most children have just a single recurrence, although some prepubertal children manifest 2 or even 3 recurrences within a year or two of the initial bout but then manifest no further recurrences for follow-up intervals as long as 18 years. Although it has been suggested that IVIG administered in treatment of a single recurrence may prevent further recurrence, the evidence for this remains inconclusive because most children with a single recurrence of ADEM that are treated with corticosteroids also have no further recurrences.

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Surgical Care

Surgical treatment for severely elevated intracranial pressure has been undertaken for cases of AHLE, hemorrhagic brain purpura, and non-Reye syndrome, examples of what have been termed obscure encephalopathies of infancy. Some of these cases were likely examples of hyperacute ADEM. Surgical interventions have ranged from placement of pressure bolts to decompression of the intracranial fossae by unroofing of the cranium. Outcome of such interventions was mixed.

Although such severe cases were regularly noted in the medical literature from the 1920s until the mid 1970s, few examples have been noted since that time. Prevalence clearly has dramatically decreased. Because these severe cases often followed measles, mumps, and other diseases for which effective vaccines have been developed and because the disappearance of such cases has followed the availability and use of such vaccines (earlier disappearance in the United States and Western Europe, subsequent disappearance in Asia and the Middle East), this change in prevalence likely reflects the removal of pathogens that are provocative of such severe forms of ADEM.

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Consultations

Consultations with infectious disease specialists are occasionally warranted to consider alternative diagnoses. Pediatric intensivists generally become involved in severe cases for management of airway, breathing, and circulation.

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Activity

No clear restrictions on activity exist except as indicated by the severity of disease. The possible exceptions are ADEM-related postinfectious demyelinative syndromes, sometimes in association with the development of brain edema, that arise in the wake of illnesses such as brucellosis or malaria. In the case of acute brucellosis, recovery is clearly more rapid and relapse is less likely if patients are treated with enforced bedrest. This rule may also be true of the relapsing neurobrucellotic illnesses, including the types that closely resemble or are examples of ADEM. Although somewhat less clear in the case of cerebral malaria, little doubt exists that enforced bedrest with appropriate positioning (because of elevation of intracranial pressure) is of importance. In the case of cerebral malaria and in cases of the more severe varieties of neurobrucellosis, bedrest is often necessary because of the low mental status and weakness of such individuals.

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Contributor Information and Disclosures
Author

Robert Stanley Rust Jr, MD, MA  Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia School of Medicine; Chair-Elect, Child Neurology Section, American Academy of Neurology

Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Christopher Luzzio, MD  Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison School of Medicine and Public Health

Christopher Luzzio, MD is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Glenn Lopate, MD  Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Director of Neurology Clinic, St Louis ConnectCare; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa

Disclosure: Baxter Grant/research funds Other; Amgen Grant/research funds None

Selim R Benbadis, MD  Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Honoraria Speaking, consulting

Chief Editor

B Mark Keegan, MD, FRCPC  Assistant Professor of Neurology, College of Medicine, Mayo Clinic; Master's Faculty, Mayo Graduate School; Consultant, Department of Neurology, Mayo Clinic, Rochester

B Mark Keegan, MD, FRCPC is a member of the following medical societies: American Academy of Neurology, American Medical Association, and Minnesota Medical Association

Disclosure: Novartis Consulting fee Consulting; Bionest Consulting fee Consulting

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Fatal ADEM-related transverse myelitis in a 13-month-old.
Typical childhood ADEM in 7-year-old. Note tendency to involve gray-white junction, the fact that the lesion margins are less well defined than typical MS plaques, and that the deep white matter lesions are not oriented perpendicularly to the ventricular surface as is typical in MS.
Typical adolescent multiple sclerosis findings on MRI. Note the tendency of lesions to exhibit sharp margins, to be elongated, to occur in deep white matter or corpus callosum sparing the cortical gray-white junction, and to be oriented perpendicularly to the ventricular surface.
 
 
 
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