of vision. Brain MRIs after the second and third vaccine doses revealed large lesions occupying the left occipital lobe and right parieto-occipital region, respectively. The lesions displayed hypointense signals on T2-weighted MRIs. Histologic examination and immunoperoxidase staining were consistent with demyelinating disease. Testing for oligoclonal IgG bands in the cerebrospinal fluid (CSF) and examination for intrathecal hepatitis B surface antibodies were not performed after the third dose of vaccine. Improvement of the condition was noted after treatment with dexamethasone. Brain MRIs performed at follow-up visits 1 year and 2.5 years after the onset of the initial episode showed almost complete resolution of the previous findings.

Tourbah et al. (1999) reported a 31-year-old man (patient 5 in the article) with vertigo and paresthesia in hands and legs 2 weeks after the first injection of hepatitis B vaccine. The symptoms resolved in 10 days. The patient presented with asthenia, vertigo, paresthesia, and left hemihypoesathesia after the second dose of a hepatitis B vaccine. The symptoms resolved in 10 days. The symptoms reappeared 7 days after receiving a booster dose of hepatitis B vaccine. A brain MRI after the first dose showed multiple T2-weighted high-intensity signals. An MRI after the third dose showed high signal lesions T2-weighted images involving arcuate fibers of both hemispheres, periventricular and subcortical white matter, corpus callosum and cerebellar white matter, and cortex.

Weight of Mechanistic Evidence

The two publications described above, when considered together, presented clinical evidence suggestive but not sufficient for the committee to conclude the vaccine may be a contributing cause of ADEM after vaccination against hepatitis B. The mechanistic evidence contributing to the analysis includes a clinical picture consistent with ADEM, and recurrence of symptoms after revaccination with hepatitis B vaccine where new white matter disease was associated with each revaccination. In the publications described above all of the patients recovered with steroids. In addition, a brain biopsy performed by Konstantinou et al. (2001) showed demyelin-ation. Furthermore, Konstantinou et al. (2001) did not observe oligoclonal bands in the CSF. Neither publication reported the development of antibodies to HBsAg.

Autoantibodies, T cells, and molecular mimicry may contribute to the symptoms of ADEM; however, the publications did not provide evidence linking these mechanisms to hepatitis B vaccine.

The committee assesses the mechanistic evidence regarding an association between hepatitis B vaccine and ADEM as low-intermediate based on two cases.



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