Kohji Shibayama

Plasmapheresis in treatment of human T-lymphotropic virus type-I associated myelopathy.

In 11 of 18 patients with human T-lymphotropic virus type-I (HTLV-I) associated myelopathy (HAM) gait, sensory, and/or sphincter disturbance improved with plasmapheresis (4 to 6 sessions in 2 weeks), and the effects were maintained for 2 to 4 weeks. Plasmapheresis lowered the titre of HTLV-I antibody in serum but not in cerebrospinal fluid, and change of HTLV-I antibody titres did not correlate with the effects of plasmapheresis. These results suggest that plasmapheresis is useful treatment, at least in producing a temporary improvement, in patients with HAM, and that some humoral factor(s), but not HTLV-I antibody, may be important in the pathogenesis of HAM.

Presence of serum anti-human T-lymphotropic virus type I (HTLV-I) IgM antibodies means persistent active replication of HTLV-I in HTLV-I-associated myelopathy

We investigated serum IgM antibodies against human T-lymphotropic virus type I (HTLV-I) in 29 HTLV-I associated myelopathy (HAM) patients and 34 HTLV-I carriers, using western blot analysis. Anti-HTLV-I IgM was detected in all 6 post-transfusional HAM patients and in 19 of 23 (83%) HAM patients with no history of blood transfusion, but in only 4 of 21 (19%) HTLV-I carriers. In HAM patients, HTLV-I proviral DNA integrated into peripheral blood lymphocyte (PBL) was detected by Southern blot analysis in all of the 6 (100%) and 18 of the 23 (78%). In contrast, it was detected in only 2 of 25 (8%) HTLV-I carriers. For the serum anti-HTLV-I IgM and HTLV-I provirus in PBL, the differences between the HAM and HTLV-I carriers were statistically significant (P less than 0.01). Our data indicate that the increased HTLV-I proviral DNA in PBL is produced by the persistent active replication of HTLV-I in HAM. Furthermore, Southern blot analysis showed intense bands in HAM patients with histories of blood transfusion, in whom the progression of the disease had been rapid. We conclude that the persistent active replication of HTLV-I is an important factor in the pathogenesis of HAM.

Active production of anti-human T-lymphotropic virus type I (HTLV-I) IgM antibody in HTLV-I-associated myelopathy

We investigated the presence of anti-human T-lymphotropic virus type I (HTLV-I) IgM in sera and cerebrospinal fluid from patients with HTLV-I-associated myelopathy (HAM) by Western blot analysis. Analyses of 36 serum samples revealed that most patients (31/36; 86.1%) had anti-HTLV-I IgM, whereas only four of 23 (17.4%) HTLV-I carriers had it. In studies of cerebrospinal fluid, anti-HTLV-I IgM was detected in 24 of 36 (66.7%) HAM patients, whereas none was detected in nine HTLV-I carriers. The differences were statistically significant (p less than 0.01). These results suggest that persistent active replication of HTLV-I occurs in the central nervous system as well as in the peripheral blood of HAM patients, and may contribute to the development of HAM.

Interferon-alpha treatment in HTLV-I-associated myelopathy: Studies of clinical and immunological aspects

We treated 17 patients with HTLV-I-associated myelopathy (HAM) with interferon-alpha (IFN-alpha) in an open, nonrandomized, uncontrolled study. They were administered 1.5-9.0 x 10(6) international units of IFN-alpha daily for 4 weeks, and 4 patients showed a marked clinical response, 7 showed a moderate response and the others did not show any clinical response. Increased unstimulated (spontaneous) peripheral blood lymphocyte (PBL) proliferation was observed in all patients who were measured lymphocyte transformation. Spontaneous PBL proliferation was significantly inhibited by IFN-alpha treatment (P less than 0.01), whereas anti-HTLV-I-antibodies did not show any significant changes. Likewise, decreased stimulation indices to phytohemagglutinin (SI) due to increased spontaneous PBL proliferation were significantly increased after IFN-alpha treatment (P less than 0.01). In the patients who showed marked clinical responses, the changes of SI in IFN-alpha treatment were higher than those in other patients. These data indicate that further studies are warranted for evaluation of IFN-alpha treatment of HAM in a randomized, controlled study.

LONG-TERM FOLLOW-UP OF IMMUNOMODULATION IN TREATMENT OF HTLV-I-ASSOCIATED MYELOPATHY

tick bites and health problems over the preceding five years. Blood samples were tested for B burgdorferi antibody by indirect ELISA at the microbiology department, Charing Cross Hospital, London. 32 of the 33 workers were men and the age range was 22-63. Of the 33 Nature Conservancy workers 27 recorded tick bites, while all 10 Red Deer Commission workers had been frequently bitten, several over 18-28 years. Symptoms previously described in Lyme disease

Heparin treatment in patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy: A preliminary study

Ten patients with HTLV-I-associated myelopathy (HAM) were treated in an uncontrolled preliminary trial of heparin. In 7 patients, motor dysfunction improved substantially and the effect continued for more than a month after the discontinuation of therapy. Sensory and urinary disturbances also improved in 3 of 4 and in 2 of 10 patients, respectively. Heparin did not alter the subsets of peripheral blood lymphocytes nor the titers of anti-HTLV-I antibodies in serum and cerebrospinal fluid. Spontaneous proliferation of peripheral blood lymphocytes, however, was depressed significantly (P < 0.05) in all cases. Heparin therapy has some advantages in cost, ease of administration and fewer side effects compared to other therapies such as plasmapheresis and interferon-alpha. We conclude that heparin can be administered safely to HAM, and that a double-blind placebo-controlled trial is warranted to determine its efficacy in HAM.

Central motor conduction time in patients with HTLV-1 associated myelopathy

ABSTRACT— Transcranial electrical stimulation of the motor cortex was performed in 7 patients with human T‐lymphotropic virus type‐I associated myelopathy (HAM) and 15 normal subjects. The mean value of central motor conduction time (CCT) for the thenar and hypothenar muscles in patients with HAM was not different from that in normal subjects. In contrast, mean CCT value for the tibialis anterior and gastrocnemius muscles in patients with HAM was 8.54‐10.34 ms longer than the value in normal subjects. These findings indicate that the lesion of pyramidal tract involvement in patients with HAM is mainly localized in the descending corticomotoneuron pathways at the thoracic spinal cord level. This technique could be used in a clinical study without untoward side effects, and may be valuable in detecting clinically silent lesions involving the pyramidal tract.