Evidence for Association

Biologic Plausibility

Chapter 3 provided a detailed discussion of the historic and scientific evidence that establishes a relation between vaccines and the development of demyelinating diseases of the CNS. In summary, it is biologically plausible that injection of an inactivated virus, bacterium, or live attenuated virus might induce an autoimmune response in the susceptible host, either by deregulation of the immune response, by nonspecific activation of T cells directed against myelin proteins, or by autoimmunity triggered by sequence similarities to host proteins such as those of myelin. The latter mechanism might evoke a response to a self-antigen (molecular mimicry) (Fujinami and Oldstone, 1989).

Case Reports, Case Series. and Uncontrolled Observational Studies

Reports in the literature of cases that clinically resemble ADEM include one described by Schlenska (1977). A 36-year-old woman developed lethargy, slurred speech, nystagmus, hemihypesthesia, decreased sensation along several thoracic dermatomes, and pyramidal tract signs 5 days after receiving a tetanus toxoid booster. She had good recovery over an 11-month period with no further episodes. Another report by Schwarz et al. (1988) describes a 21-year-old man who developed coma with midbrain signs after tetanus toxoid administration on two occasions 2.5 years apart. Latencies from the time of toxoid administration to the onset of symptoms were 7 and 8 days, respectively.

Several case reports describing transverse myelitis after tetanus booster administration were found in the literature. In 1977, Whittle and Roberton described a 7-month-old girl who developed flaccid paraparesis 6 days after receiving DT and OPV. Read et al. (1992) described a 50-year-old man who developed flaccid legs, areflexia, and a sensory level at T-6 12 days after receiving a tetanus booster. A magnetic resonance imaging study showed no lesions in the brain, suggesting that this lesion was indeed limited to the spinal cord. In a case described by Topaloglu et al. (1992), an 11-year-old girl developed spastic paraparesis, bilateral papillitis, and visual defects 3 days after receiving a booster of tetanus toxoid. An 11-month follow-up showed no recurrence of symptoms, and there was total recovery except for the persistence of pale optic disks. This does suggest disease in multiple foci, as is seen in ADEM, but the time interval between immunization and disease was too brief to suggest a mechanism analogous to experimental allergic encephalomyelitis. Two pertinent case reports of transverse myelitis were found in VAERS (submitted between November



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