Need for developing a standardized case definition and guidelines for encephalitis/acute disseminated encephalomyelitis as adverse events following immunization:
Among the various events reported as adverse outcomes following immunizations, neurologic adverse events following immunization (AEFI) are perhaps the most severe, and also perhaps the most difficult to address. The multifaceted presentation of neurologic illness, and relative lack of familiarity with the approach to and diagnosis of neurologic disease by many clinicians, makes neurologic AEFI some of the most challenging issues in clinical vaccinology. Further, the severity of central and peripheral nervous system events in individual patients often heightens the concern when such illnesses are associated with antecedent immunizations.
To improve comparability of vaccine safety data, the Brighton Collaboration Encephalomyelitis/ADEM Working Group has developed a case definition and guidelines for encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM), applicable in study settings with different availability of resources, in health care settings that differ by availability of and access to health care, and in different geographic regions.
The estimated incidence of encephalitis, in general, has varied widely, and is dependent upon age, demographics, season, causative agent, and presence of epidemic illness. Nearly all previous studies on encephalitis have been hospital-based. Estimates of viral encephalitis rates have ranged from 0.08/100,000 population in national passive surveillance studies [1] to 1–6 cases per 100,000 in hospital-based studies to 7.4 cases per 100,000 in one population-based study [2], [3], [4]. The incidence of encephalitis has generally been lower than that of aseptic meningitis, and children are at higher risk than adults. Case-fatality rates and incidence of severe neurologic sequelae also vary, dependent upon study methods and underlying etiologic agent. Population-based and hospital-based estimates of neurologic sequelae have ranged from 0.35 to 2.7 per 100,000 cases, with case fatality rates from 1 to 10% [2], [3], [4], [5]. Certain agents are associated with higher case fatality rates; mortality rates of up to 33% have been reported with Herpes simplex encephalitis [6].
The underlying causes of acute encephalitis/myelitis are legion, and include infectious, toxic, neoplastic, autoimmune, and metabolic etiologies [7], [8], [9], [10], [11], [12], [13]. Most cases of encephalitis are thought to be infectious in nature, and may be attributed to a number of different viral, bacterial, fungal, and parasitic agents [7], [8], [9], [10]. Toxic and metabolic agents may lead to a chemical encephalitis [10], [11], while neoplasm may lead to either neoplastic or paraneoplastic encephalitis [6]. Finally, various autoimmune conditions may lead to acute encephalitis [10]. Immunizations may very rarely lead to acute encephalitis, particularly in the setting of live-attenuated viral vaccines [14], [15], [16]. However, the introduction of immunizations has served to reduce the incidence of encephalitic complications in several viral and bacterial infections [17], [18], [19], [20]. In more than 70% of cases of acute encephalitis, however, a demonstrable etiologic agent is unable to be identified [13], presumably due to the broad range of possible underlyi
