Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients

Summary Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I HTLV-1] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-1 DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-1 infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients. These findings demonstrate an immune reaction to HTLV-I in the CNS of HAM patients, thus confirming the association of infection and CNS disease. The demonstration of intrathecal HTLV-I antibody production also proved useful for the differential diagnosis of MS or HAM, especially in patients from areas endemic for HTLV-I.Abbreviations DTPA diethylenetriaminepentaacetic acid - ELISA enzyme-linked immunosorbent assay - HAM HTLV-I-associated myelopathy - HTLV-I human T-cell leukemia virus type I - MRI magnetic resonance imaging - MS multiple sclerosis - PBMC peripheral blood mononuclear cells - PCR polymerase chain reaction - RIPA radioimmune precipitation assay - SDS sodium dodecyl sulfate - TSP tropical spastic paraparesis