Acute disseminated encephalomyelitis

Clinical symptoms

The typical features of acute disseminated encephalomyelitis are headache, drowsiness and fits, and one or more focal lesions producing hemisphere syndromes and disturbances of vision. In other cases, the clinical manifestations reflect damage either to the brainstem, optic nerves, or spinal cord, but each may be involved together and the peripheral nervous system is sometimes affected. These cases were more common before the advent of public health programmes which have reduced the frequency of predisposing exanthematous disorders, and fortunately they are seldom seen following vaccination itself, so that nowadays there is no distinct prodromal illness in most incident cases. Therefore, both in children and adults, a presumptive diagnosis of acute disseminated encephalomyelitis often has to be made in the absence of an identifiable cause.

However, a proportion of patients, especially adults, recovering from the initial episode, later relapse and follow a clinical course that is typical of multiple sclerosis. Thus it is important to recognize that multiple sclerosis may present in an encephalopathic form. In others situations, the illness remains monophasic but separate sites are involved sequentially and in a step-wise fashion, giving the appearance of a temporally disseminated illness. For this reason, it is unwise to consider symptoms evolving over several weeks as necessarily signifying a relapsing illness sufficient for the diagnosis of multiple sclerosis.

The hyperacute form of acute disseminated encephalomyelitis (Hurst 1941) is usually preceded by a non-specific respiratory infection 3–10 days before the onset of neurological symptoms. Young adult males are most commonly affected, complaining initially of headache or dizziness and progressing over hours through stages of disorientation, confusion, and drowsiness to coma. The rate of progress is such that events usually overtake the detection of focal signs, and this form of the disease is frequently fatal, although affected individuals may remain in a persistent vegetative state for several weeks and some survive with severe disability following treatments which reduce intracranial pressure. The combination of pyrexia and a marked cerebrospinal fluid pleocytosis with a predominantly neutrophil response mimics pyogenic infection of the central nervous system, but the course is not influenced by antimicrobial treatment.

Affected individuals develop headache, drowsiness, meningeal irritation, focal or generalized fits, and combinations of lesions indicating damage to the cerebrum, optic nerves, brainstem, or spinal cord about 10–20 days after the prodromal illness. The symptoms and signs evolve over the course of a few days.

Aetiology

Some of their cases may have arisen from direct viral infection of the nervous system and related disorders that were not then recognized. The Newcastle experience indicated that about 1 : 1000 children with exanthematous disorders develop acute disseminated encephalomyelitis, the risk being slightly higher with pertussis and scarlet fever than with measles and rubella. Nowadays, the majority of cases are encephalitic or multifocal.

Examination

Cerebrospinal fluid shows a mixed polymophonuclear and lymphocytic or predominantly mononuclear pleocytosis with raised protein and slight reduction in glucose; oligoclonal bands may be present.

Imaging

The magnetic resonance appearances of cerebral lesions in acute disseminated encephalomyelitis have been well described. In a series of 12 cases, including six adults and six children developing optic nerve, cerebral, brainstem, and cord disease, alone or in combination, following infection by mumps, varicella, mycoplasma, adenovirus, and non-specific respiratory infections, Kesselring et al. (1990) showed multifocal asymmetric white matter abnormalities in (generalized and clinically isolated) post-infectious demyelinating syndromes, which were indistinguishable from the lesions of multiple sclerosis, although many cases showed extensive and rather symmetric changes in the cerebral or cerebellar white matter and in the basal ganglia. More discriminating was the transient presence of oligoclonal bands in acute disseminated encephalomyelitis.

Serial or gadolinium–diethylenetriaminepentaacetic acid (DTPA)-enhanced scans are more useful and suggest that, whereas lesions persisting long after the clinical manifestations have resolved do not discriminate, the development of new lesions or the demonstration of areas with enhancement indicates disease activity, typical of multiple sclerosis and excluding acute monophasic demyelination.

Prognosis

While there is an appreciable mortality, the majority of patients survive and there is some evidence to suggest that the outcome is influenced by the early use of high-dose steroids, but this has not been formally evaluated. Despite surviving the acute illness, patients may be left with persistent neurological deficits.

It has been claimed that, in children, new episodes of central nervous system damage may occur 18 months after the initial episode in acute disseminated encephalomyelitis, but this interpretation assumed that multiple sclerosis does not occur in childhood, and cases of this type would not now be included in a series of patients with acute disseminated encephalomyelitis.

One reason for believing that acute disseminated encephalomyelitis arises from immune sensitization to brain antigens is that it has followed the use of vaccines containing central nervous system tissue. In its day, this form of the disease behaved much as other cases of acute disseminated encephalitis and the pathological features were also indistinguishable. Post-vaccinial encephalomyelitis has become a rare disorder following alterations in the preparation of this and other vaccines. The definitive series were collected several decades ago following episodes in which the need arose to vaccinate large numbers of individuals against smallpox as part of public-health measures. The 62 cases studied clinico-pathologically and reported by de Vries (1960) had been collected over 34 years and were necessarily severe. In all, the neurological illness developed within 21 days of vaccination and, in fatal cases, death occurred at, or soon after, 13 days.

In these hyperacute cases, the pathological findings mimic transitional forms of acute haemorrhagic or disseminated encephalomyelitis. The clinical illness starts with a vaccinial skin reaction and systemic symptoms which merge with the neurological manifestations, typically affecting the cerebrum but sometimes presenting as a myelitic disorder. Despite having a high mortality, post-vaccinial encephalomyelitis may recover spontaneously and completely.



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