HTLV-1 and the Peripheral Nervous System
HTLV-1 and the Peripheral Nervous System
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, NewYork-Presbyterian Hospital, Cornell Campus. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.
Synopsis: Human T-cell lymphotropic virus type I (HTLV-1) is a human retrovirus and the etiologic agent for a progressive neurological disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although masked by the more prominent myelopathy, involvement of the peripheral nervous system also occurs.
Source: Grindstaff P, Gruener G. The Peripheral Nervous System Complications of HTLV-1 Myelopathy (HAM/TSP) Syndromes. Semin Neurol. 2005;25;315-327.
Human T-cell lymphotropic virus type 1 (HTLV-1), a human retrovirus, is the etiologic agent for a slowly progressive thoracic myelopathy with back and leg pain, ambulatory difficulties, spastic paraparesis, and urinary frequency or incontinence. Some HTLV-1 individuals demonstrate leg weakness with sensory ataxia, symptoms of painful sensory neuropathy, distal sensory impairment, and depressed deep tendon reflexes, and have been designated the ataxic group, in contrast to the former spastic group. Both were formerly encompassed under the rubric Jamaican neuropathy because the condition was first described in the Jamaican population. Subsequently, Tropical Spastic Paraparesis (TSP) became the designation for the spastic group and, more recently, with recognition of the etiologic role of HTLV-1 in TSP, the World Health Organization has agreed that HTLV-1-associated myelopathy (HAM) be termed HAM/TSP, as they are the same entity. Less well publicized is involvement of the neuromuscular system with HTLV-1, the subject of this review.
Autopsy studies have documented anterior horn cell involvement in HAM/TSP patients, and case reports describe individuals with amyotrophic lateral sclerosis (ALS)-like syndromes. Most, however, have some atypical clinical, pathological (biopsy), or laboratory feature suggesting a diagnosis other than ALS and, even absent any such indication, the association may be coincidental. Nonetheless, the overlap suggests that HTLV-1 testing may be appropriate in patients felt to have motor neuron disease.
Peripheral neuropathy occurs in HTLV-1 individuals; one series documenting a 6.3% incidence of an axonal or mixed axonal demyelinating primarily sensory neuropathy among 335 infected patients. Sural nerve biopsy (n = 5) revealed perivascular infiltrates and axonal degeneration in 2 each, and demyelinating changes in one. Other large series report a higher incidence of subclinical neuropathy, approaching 50%, based on electrodiagnostic studies. Clinically, however, approximately 15% of HTLV-1 patients may have symptomatic peripheral neuropathy.
Both inflammatory and noninflammatory myopathy is described in HTLV-1, including pathologically documented inclusion body myositis, polymyositis and dermatomyositis. But in no instance is there any unique clinical or pathological feature to distinguish the condition from anything other than coincident overlap of 2 diseases. Response to corticosteroid treatment is also reported in some of these patients.
Commentary
Myelopathy develops in only 1-2% of individuals infected with HTLV-1. Risk factors for its development vary between populations and with host genetic background, but include HTLV-1 provirus load, certain HLA alleles, and certain HTLV-1 tax subgroups. HTLV-1 patients from Kagoshima, (Kyushu Island, southwestern Japan), who developed HAM/TSP, demonstrated a 10-fold greater median provirus load in peripheral blood mononuclear cells compared to asymptomatic HTLV-1-seropositive carriers. Increased risk of progression to disease was similarly associated with high HTLV-1 provirus load (Nagai M, et al. J Neurovirol. 1998;4:586-593), as was progression of motor disability (Takenouchi N, et al. J Neurovirol. 2003;9:29-35). Genetic background appears to be of consequence in developing HAM/TSP. Provirus load in seropositive asymptomatic carriers in genetic relatives of patients with HAM/TSP is significantly higher than that of non-HAM/TSP-related asymptomatic carriers (Nagai et al ibid). In Kagoshima, outcome of HTLV-1 infection is associated with HLA alleles DRB1*0101, B*5401, A*02 and Cw*08 (Jeffery, KJ, et al. J Immunol. 2000;165:7278-7284), and HLA-A*02 and Cw*08 genes are each independently associated with lower HTLV-1 provirus load and with protection from HAM/TSP. Increased susceptibility to HAM/TSP is associated with HLA-DRB1*0101 and B*5401 and with HTLV-1 tax gene sequence variation (Furukawa Y, et al. J Infect Dis. 2000;182:1343-1349). Hence, host genetic factors and HTLV-1 subgroups are independent factors in the risk of developing HAM/TSP.
Human T-cell lymphotropic virus type I (HTLV-1) is a human retrovirus and the etiologic agent for a progressive neurological disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).Subscribe Now for Access
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