Postgrad Med J: first published as 10.1136/pgmj.45.524.392 on 1 June 1969. Downloaded from Postgrad. med. J. (June 1969) 45, 392-400. Para-infectious and post-vaccinal encephalomyelitis P. B. CROFT The Tottenham Group ofHospitals, London, N.15 Summary of neurological disorders following vaccinations of The incidence of encephalomyelitis in association all kinds (de Vries, 1960). with acute specific fevers and prophylactic inocula- The incidence of para-infectious and post-vaccinal tions is discussed. Available statistics are inaccurate, encephalomyelitis in Great Britain is difficult to but these conditions are of considerable importance estimate. It is certain that many cases are not -it is likely that there are about 400 cases ofmeasles notified to the Registrar General, whose published encephalitis in England and Wales in an epidemic figures must be an underestimate. In addition there year. is a lack of precise diagnostic criteria and this aspect The pathology of these neurological complications will be considered later. In the years 1964-66 the is discussed and emphasis placed on the distinction mean number of deaths registered annually in between typical perivenous demyelinating encepha- England and Wales as due to acute infectious litis, and the toxic type of encephalopathy which encephalitis was ninety-seven (Registrar General, occurs mainly in young children. 1967). During the same period the mean annual The clinical syndromes occurring in association number of deaths registered as due to the late effects with measles, chickenpox and German measles are of acute infectious encephalitis was seventy-four- considered. Although encephalitis is the most fre- this presumably includes patients with post-encepha-copyright. quent complication, myelitis and polyradiculitis also litic Parkinsonism. During this 3-year period there occur. There is evidence that 'uncomplicated were five deaths from post-vaccinial encephalitis, measles' is associated with brain involvement in the while the mean number of deaths registered annually prodromal phase. Similar para-infectious disorders as due to 'encephalitis, myelitis and encephalomye- occur in association with other infections including litis, excluding acute infectious encephalitis' was 110. smallpox and influenza. To put these figures into perspective, in 1966 The post-vaccinal types of encephalomyelitis are 612 deaths were registered as due to motor neurone also considered with particular reference to post- disease, 836 to disseminated sclerosis, 7363 to motor http://pmj.bmj.com/ vaccinial encephalitis and rabies post-vaccinal vehicle traffic accidents and 18,554 to primary encephalitis. carcinoma of the lung. The pathogenesis of these disorders is discussed During 1966 the number of deaths from encepha- and it is concluded that there is direct viral invasion litis certified as secondary to infectious diseases was of the nervous system, followed by an antigen- fifteen for measles encephalitis (out of a total of antibody reaction. At times virus may remain latent eighty deaths attributed to measles) and two for within the nerve cell without destroying it. chickenpox encephalitis (from a total of seventeen on September 29, 2021 by guest. Protected deaths due to chickenpox). Introduction Notifications of infectious diseases in 1966 in- Although the majority of cases of encephalitis and cluded 343,642 cases ofmeasles, eighty-three cases of other neurological disorders which occur in associ- acute infectious encephalitis and 114 cases of post- ation with acute viral infections such as measles, infectious encephalitis. Miller (1964) estimated the develop some days after the onset of the exanthem, incidence of measles encephalitis as 1 per 1000 and in a few patients the neurological disorder is either this agrees with other figures (Miller, Stanton & simultaneous with or precedes the development Gibbons, 1956). On this basis one would have of the rash. It is, thus, more logical to describe these expected over 340 cases of measles encephalitis in conditions as para-infectious rather than post- 1966, and of course not all cases of measles are infectious. Similarly, although the encephalitis notified. The figure of 114 cases of post-infectious following vaccination against smallpox (post- encephalitis of all kinds in 1966 is certainly much vaccinial encephalitis) is the typical example of below the true incidence. encephalitis as a sequel to prophylactic inoculations, The death rate in measles encephalitis has varied the tern post-vaccinal should be used for the range but has often been estimated at about 20 % (McNair Postgrad Med J: first published as 10.1136/pgmj.45.524.392 on 1 June 1969. Downloaded from Para-infectious andpost-vaccinal encephalomyelitis 393 Scott, 1967). If, making allowance for non-notifica- pathy oftoxic type characterized by cerebral oedema, tion, there were up to 400 cases of measles encepha- vacuolization of neurones and neuronal degenera- litis in 1966, deaths from this disorder should have tion, especially in the cortex. This syndrome occurs been about eighty. This contrasts with the fifteen mainly in children under 2 years, but may occur in patients actually registered as having died from older children. Acute encephalopathy is also found measles encephalitis. in fatal cases of para-infectious neurological illness However inaccurate the statistics may be, it is in young children. Lyon, Dodge & Adams (1961) clear that post-infectious encephalitis and encephalo- described similar cases in infants and children, myelitis is a significant problem in the United without obvious precipitating cause, though in most Kingdom, as it is in the United States, where about cases there was a febrile illness of variable and 30 % of the total cases of encephalitis are in the post- unidentified type. The lesions in post-vaccinal and infectious group (McNair Scott, 1967). para-infectious encephalopathy resemble those fol- lowing status epilepticus, anoxic episodes or severe Pathology hypoglycaemia. For many years a distinction has been drawn between primary polioclastic encephalitis, involving Clinical aspects predominantly neurones of the grey matter, and due There are many reviews of the neurological to direct invasion by virus (e.g. rabies and arbovirus), syndromes occurring after vaccination and in and secondary myelinoclastic leuco-encephalitis. association with acute viral infections. Miller et al. Here the myelin sheaths of the white matter are the (1956) made a detailed study of the literature at that main site of damage with axis cylinders less affected, time, and discussed their own experience, while the and neurones largely spared (Miller, 1961). The review of McNair Scott (1967) included more recent second group is often, but not always, a sequel to a work. viral infection. Miller et al. (1956) emphasized that although the The early work of Tumbull & McIntosh (1926) majority of patients under consideration had showed that in post-vaccinial encephalitis the usual encephalitis, in some the spinal cord was the main underlying process is one of perivenous demyelina- site of the disease. Polyradiculitis was less common copyright. tion, mainly in relation to small veins in the white than these forms of central nervous system involve- matter. Similar changes were found in encephalitis ment. associated with measles, chickenpox and rubella In the para-infectious groups of disorders, the (Miller et al., 1956). distribution of the various syndromes was as follows Further studies led de Vries (1960) to consider (Table 1): that the classical change in post-vaccinial encepha- TABLE 1. Distribution of the various syndromes litis is one of perivenous demyelination, witlh an associated microglial reaction-'microglia encepha- German http://pmj.bmj.com/ litis'. In this type of encephalitis, which commonly Measles Chickenpox measles occurs 5-15 days after vaccination, the illness runs Encephalitis (%) 96 90 92 an acute course, and if recovery occurs there are Myelitis (Y.) 3 3 4 often few sequelae, though permanent neurological Polyradiculitis (%) 1 7 4 deficit is more common when the disorder is pri- latent marily a myelitis. Similar changes are found in the The average period between the acute infection and the neurological illness was shortest for para-infectious group of neurological disorders, and on September 29, 2021 by guest. Protected also in sporadically occurring acute disseminated rubella and longest for varicella, while measles held encephalomyelitis. an intermediate position. With each infectious In some patients acute haemorrhagic leuco- disease the latent period was shortest for cases of encephalitis occurs and Russell (1955) argued that encephalitis and longest for those of polyradiculitis this, and acute disseminated encephalomyelitis, are (Table 2). variants of a single pathological process. She referred TABLE 2. Latent period (days) to the literature on experimental allergic encephalitis German and discussed the possibility that the naturally Measles Chickenpox measles occurring acute disseminated encephalomyelitis and Encephalitis 4-7 6-3 3-8 acute haemorrhagic leuco-encephalitis are due to a Myelitis 5.5 8-3 6-7 process based on an allergic response to an antigenic Polyradiculitis 9 0 11-3 8-7 stimulus. de Vries (1960) emphasized that some children with There was a wide range of latent periods, and post-vaccinial encephalitis do not show the typical mention has already been made of the occasional demyelinating changes, but instead an encephalo- patient in whom the