Tolosa-Hunt syndrome: analysis of 24 cases.
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Biomedical subjects
Publications and source records attributed to T Hemachudha.
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Encephalitis and polyneuritis occurring after rabies vaccination are believed to be immunologically mediated. We studied antibody responses to neural antigens in 36 patients with major neurologic complications, 25 with minor complications, and 39 with no complications after immunization with a brain-derived, Semple rabies vaccine. Patients with major complications had significantly elevated levels of antibody to brain white matter as compared with the other groups (P less than 0.001). Assays for antibody to selected central nervous system antigens showed that high levels of serum and cerebrospinal fluid antibody to myelin basic protein correlated with the presence of major neurologic complications (both central and peripheral nervous systems). The level of antibody to cerebroside correlated best with the number of injections of vaccine, but like antibody to myelin basic protein, the antibody to cerebroside was present in the cerebrospinal fluid of patients with major complications. Some patients with major complications also had antibodies directed to the gangliosides GD1b and GT1b. No antibodies to myelin-associated glycoprotein were detected in any of the samples. These data implicate myelin basic protein as an encephalitogen in these autoimmune diseases of the human nervous system, but suggest that immune responses to cerebroside and certain gangliosides may have an augmentative role in severe disease.
We studied 61 patients with complications of Semple-type postexposure rabies immunization. Thirty-six had neurologic signs, and 25 had only fever, headache, or myalgia. Thirty-two patients had CNS complications, and 4 had an acute peripheral neuropathy. Disease was acute and monophasic in 33, but 3 patients had progressive disease, including 1 patient with a relapsing-remitting course. No clinical features, including CSF content of myelin basic protein, were prognostic indicators. In three of six patients with encephalomyelitis, lymphocytes showed a proliferative response to myelin.
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Previous studies in Thailand and Tunisia have shown that one injection of dog pre-exposure rabies vaccine does not produce a lasting antibody titre in a significant group of animals. We therefore duplicated the Thai study in a small North American community using healthy, owned dogs. A tissue culture vaccine of known high antigenicity was given intramuscularly as one primary injection and antibody titres were determined by the rapid fluorescent focus inhibition test on days 14, 30, 60, 180 and 360. Titres were less than 0.5 i.u./mL in 27% of dogs bled at 2 months, 24% at 6 months, and in 33% one year after the primary vaccination. In rabies endemic regions, it may be hazardous to rely on the previous vaccine history of a biting dog when making post-exposure management decisions. A retrospective study of antibody levels in previously vaccinated dogs in North America also indicated that a single injection of vaccine often failed to result in adequate titres.
Serum cytokines were compared by enzyme-linked immunosorbent assay among (i) 28 patients with rabies, (ii) 13 patients with non-fatal encephalitis due to other viruses, (iii) 16 patients with immune-mediated neurological diseases, and (iv) 15 patients with non-viral central nervous system infections and non-HTLV-I progressive spastic paraparesis. Levels of soluble interleukin 2 receptor (S-IL2R) were comparable in groups (i)-(iii). Fewer paralytic (1/6) than encephalitic (12/22) rabies patients had elevated S-IL2R. Only one patient with rabies and one with non-fatal viral encephalitis (group ii) had elevated S-CD8. Interleukin 6 (IL-6) was elevated in 5/22 rabies patients with encephalitis and in 0/6 paralytic rabies patients. Four individuals in groups (ii) and (iii) had elevated IL-6. Patterns of cytokine responses in group (iv) were similar to those in groups (i)-(iii). The results suggest defects in immune responsiveness in paralytic rabies.
Rabies caused by fox bite is uncommon, most cases being caused by bite of rabid dogs (95%). We report a 45-year-old lady with rabies encephalomyelitis caused by bite of a rabid wild fox (Vulpes vulpes), a species prevalent in the Deccan plateaus of Central India. Though foxes are known to be susceptible to rabies, literature on the pathological changes caused by fox bite rabies in humans is scarce. Unlike the mild histological alterations described in canine rabies, a florid encephalitic process evolved in fox bite rabies, in our case, with intense microglial reaction, neuronophagia and perivascular inflammatory infiltrates despite clinical manifestation as a paralytic rabies. Immunostaining using polyclonal antibodies to the rabies viral nucleocapsid antigen and to the whole virion demonstrated high viral load within neurons with extensive spread along dendritic arborization and axonal tracts. Genomic sequence analysis demonstrated close homology with canine virus strain with only minor variations.