Smallpox and smallpox vaccination is reviewed from the Departments of Neurology, Yale University School of Medicine, New Haven, CT, and University of New Mexico School of Medicine, Albuquerque. Neurological complications of smallpox vaccination are a postvaccinial encephalopathy (PVE) in children under 2 years of age and postvaccinial encephalomyelitis (PVEM) in recipients over 2 years. Past experience showed that the mortality of PVEM was 10 to 50%. The neuropathology of PVEM suggests an immune-mediated illness. Many unanswered questions need to be addressed regarding the risks of PVEM and PVE after smallpox vaccination with newer vaccines, neuroimaging findings, the prevention of these complications, and optimal therapy. [1]

COMMENT. The risks of the smallpox vaccine are reviewed in an editorial [2]. Rates of PVEM vary from 1 in 4000 to 1 in 80,000 after primary vaccination, and from 1 in 50,000 to 1 in 450,000 after revaccination. Long-term disabilities of survivors may reach 30%. A vaccination campaign involving a previously unvaccinated population less than 35 years of age would carry the highest risk of neurologic complications. In addition, approximately 10% of the US population has some immunodeficiency, resulting in a greater risk of cutaneous dissemination.

The outcome of acute disseminated encephalomyelitis (ADEM) in a long-term follow-up study of 84 pediatric patients is covered in Ped Neur Briefs Nov 2002;16:81-82. Childhood ADEM affects boys more frequently than girls, and recovery occurs in 90%. Residual disability in 10% is not related to MRI lesions at onset but it is correlated with the occurrence of optic neuritis. MRI shows bilateral, asymmetrical involvement of white matter of frontal and parietal lobes, lesions in deep grey matter including the thalamus, and corpus callosum and periventricular demyelination. The location of pathology based on MRI findings was similar to that described in ADEM following smallpox vaccination [3]. Turnbull and Mcintosh (1926) published the first description of the encephalomyelitis following vaccination against smallpox in 7 cases in London. These authors emphasized involvement of the ventral half of the pons. In Holland about the same time, 139 cases of post-vaccinial encephalomyelitis with 41 deaths were reported (Bouman and Bok (1927). Case-reports of similar lesions to post-vaccinial ADEM soon appeared following varicella (1927), measles (1926), influenza (1930), and smallpox (1927). An increase in strength of the vaccine and primary vaccination of many older children and adolescents were considered responsible for the epidemic of post-vaccinial cases in Great Britain and Holland in the years 1923-6. Glanzmann (1927) was the first to suggest that post-vaccinial ADEM was due to an antigen-antibody reaction.

Human monkeypox virus infection. The recent outbreak of Human Monkeypox Virus disease in Midwestern States and the governmental decision to recommend smallpox vaccination to persons exposed to prairie dogs or Gambian giant rats, pets linked to the infection, provide neurologists with an additional reason to consider the implications of smallpox vaccination. Human monkeypox is a rare zoonotic viral disease that occurs primarily in the rain forest of central and west Africa. Person-to-person spread may occur. The incubation period is up to 21 days. Fatalities in Africa have ranged from one percent to 10% of cases. Most patients seen in the US have experienced a prodrome of fever, headaches, myalgia, chills and sweats, followed by a nonproductive cough in one-third. A papular rash developed at one to 10 days after onset of fever and it progressed to vesiculation, pustulation, umbilication and crusting. Lesions occurred on head, trunk and extremities, including palms and soles. In the US, among 22 cases contracted from pet prairie dogs no fatalities have been reported. (Conover CS, Illinois Department of Public Health, Springfield, IL, June 8, 2003).