J Neurol Neurosurg Psychiatry 2004;75:i22-i28 doi:10.1136/jnnp.2003.034256
INFLAMMATORY/POST-INFECTIOUS ENCEPHALOMYELITIS
L Bennetto, N Scolding
Author Affiliations: Institute of Clinical Neurosciences, Department of Neurology, University of Bristol, Frenchay Hospital, Bristol, UK
Spontaneous recovery is the rule, usually over a course of weeks to months. ADEM tends to have a more severe initial course but much better ultimate recovery than MS. Historically fatal disease was common, with reported mortality rates as high as 30–50% as recently as 1948 in European children with post-vaccination ADEM. The outlook this millennium appears much brighter, with three recent studies encompassing 150 children with ADEM reporting no deaths. One of these studies followed up their 35 cases for a mean 5.8 years and found that the majority completely recovered in a few weeks. Twenty patients had no long term impairment; permanent neurological deficits included motor dysfunction (six patients, severe in three), cognitive impairment (four patients), visual loss (four patients), and behavioural problems (four patients). Epilepsy developed in three patients but persisted in only one with extended follow up. A recent study of 40 adult patients with ADEM reported two mortalities, suggesting that adult ADEM may presently have a slightly worse prognosis than childhood ADEM.
Treatment options
Corticosteroids are widely considered to be an effective first line treatment for ADEM. Intravenous methylprednisolone 1 g daily for at least three days is advised. While expert opinion and several convincing reports support this regimen, the natural history of ADEM of course features spontaneous improvement, and it is difficult therefore to be absolutely certain of its benefits. The recent trend towards improved survival in reported case series of ADEM may, however, reflect increased use of corticosteroids, intravenous methylprednisolone in particular. The rationale for corticosteroid use is their ability to reduce inflammation, decrease oedema, and seal the blood–brain barrier, which should decrease the further influx of active immune cells and humoral factors, contributing to demyelination. In some cases, cessation of steroid treatment has been followed by a relapse, possibly forming the basis of MDEM. As a relapse suggestive of MDEM is most likely shortly after ADEM it would seem prudent to prescribe a 1–2 month oral prednisolone taper.
Plasma exchange is recommended in patients who respond poorly to intravenous corticosteroids. There have also been several reports of impressive responses to plasma exchange; however, some of these have been confounded by the co-administration of corticosteroids and cyclophosphamide. More importantly a randomised, controlled, crossover trial of true versus sham plasma exchange for attacks of severe CNS demyelination resistant to corticosteroid treatment in 22 patients showed that 42% of patients had moderate or greater neurological improvement in the plasma exchange arm compared with just 6% of the patients receiving sham treatment (statistically significant). Although this study only had one patient with ADEM, the other conditions treated under the remit of “severe CNS demyelination”—MS, Marburg variant MS, acute transverse myelitis, neuromyelitis optica—are sufficiently similar and occasionally indistinguishable from ADEM in the acute phase to represent a reasonable rationale for treatment at present. This study used a course of seven plasma exchanges over 14 days, but improvement is frequently observed after the first exchange.
Intravenous immunoglobulin (IVIG) has also been used with success in a few cases of ADEM. While the evidence behind its use in ADEM is probably weaker than that of plasma exchange, there are several neuro-inflammatory conditions where IVIG has a proven effect and is often considered a more convenient alternative to plasma exchange. At present it should be reserved for ADEM that fails to respond to corticosteroid treatment and where plasma exchange is contraindicated or impractical. There have been suggestions based on subtle pathogenetic differences that IVIG may be preferable to plasma exchange in cases of post-vaccination encephalomyelitis, but this is not proven. Intravenous cyclophosphamide has also been used in the past with some apparent success but has not gained widespread recommendation.
In severe cases of ADEM, and particularly acute haemorrhagic leucoencephalomyelitis, cerebral oedema can occur and should be treated with combinations of mannitol and hyperventilation. If these conservative measures fail then more drastic measures such as craniotomy can be considered.
ADEM has been known to relapse into MDEM following routine vaccinations and it would seem sensible to avoid vaccinations (or other immune stimulation) for at least six months following a diagnosis of ADEM.
