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Background and Objective: A population-based study is reported of MS in French Afro-Caribbeans (FAC) in Martinique. FAC are descendants of interracial mating that occurred between French Caucasians and black Africans in the 17th and the 18th centuries., Methods: The authors surveyed the entire island of Martinique (area 1,128 km(2), population 357,000) between November 1997 and October 1999., Results: Sixty-two patients (46 females, 16 males, ratio 2.9:1) were identified with definite or probable disease by the Poser criteria. Prevalence for all patients on December 31, 1998, was 17.4/10(5) (95% CI 13.1 to 21.7) and 14.3/10(5) (95% CI 10.4 to 18.2) for clinically definite cases (n = 51). Age range of patients on prevalence day was 17 to 73 years (mean +/- SD 39 +/- 11.3 years). Mean age at onset was 31.2 +/- 11 years. Overall, 9.7% had primary progressive disease and 19.4% had benign MS. A low proportion of definite and probable MS cases had oligoclonal bands in CSF (50.9%). Seventeen patients, 13 of whom were alive on prevalence day, had a relapsing form of neuromyelitis optica., Conclusion: The island of Martinique appears to have a low to medium prevalence of MS. MS was almost unknown in FAC in Martinique until the late 1970s. The apparent recent increase may be explained by improved recognition of patients, increased availability of MRI for diagnosis, increased disease awareness among physicians, increased survival of MS patients, or an actual increase in disease frequency.

Purpose: The objective of this study is to describe the clinical and immunological aspects observed in patients with both human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis and ocular dryness., Methods: In 15 such patients, clinical and biological examinations completed with a biopsy of secondary salivary glands were performed to assess the etiology of the ocular dryness., Results: Histological study of the biopsy specimens indicated that 80% of the patients had grade 3 or grade 4 lesions, according to the Chisholm scale. Polyclonal hypergammaglobulinemia was found in 60% of patients and lymphocytic alveolitis in 80%. Three patients had past medical history of chronic uveitis., Conclusions: All findings in these patients were compatible with Sjögren's syndrome; however, no immunological disorders characteristic of the syndrome were found. Tests for antinuclear antibodies and rheumatoid factor proved negative in all cases.

Background: Screening for human T-lymphotropic virus type I (HTLV-I) antibodies in volunteer blood donors has been systematic in the French West Indies since 1989. Western blot-indeterminate results are commonly obtained. The significance of these indeterminate serologic patterns in HTLV-I-endemic areas is still unclear., Study Design and Methods: During a 2-year period, 9759 blood donors were tested for HTLV-I antibodies. The epidemiologic features of HTLV-I-seropositive, -seroindeterminate, and -seronegative donors were compared. A lookback investigation was performed for the HTLV-I-seropositive donors, and the HTLV-I-seroindeterminate individuals were followed up., Results: Thirty-nine donors (0.4%) were HTLV-I seropositive and 49 (0.5%) were seroindeterminate. The age and sex ratio characteristics of the seroindeterminate donors are divergent from those of the HTLV-I-seropositive group and are more like those of the seronegative population. However, during the study period, three cases of seroconversion after an initial seroindeterminate profile were reported. Two cases were detected through follow-up of 38 HTLV-I-seroindeterminate donors over a mean of 8 months (2-24 months). The third seroconverter belonged to the HTLV-I-seropositive group and was identified through lookback investigation. This case is atypical, with p19 reactivity for several months before HTLV-I seropositivity., Conclusion: These findings indicate that, although HTLV-I-seroindeterminate donors mainly are HTLV-I-noninfected, the rate of seroconversion in a repeat blood donor population from an endemic region must be taken into consideration. Moreover, the case of delayed seroconversion observed in this study suggests the difficulty of counseling seroindeterminate blood donors in endemic regions.

Human T cell leukemia virus type I (HTLV-I) sequences were sought in labial salivary glands of patients with HTLV-I-associated myelopathy or tropical spastic paraparesis and of seropositive neurologically healthy carriers. HTLV-I proviral DNA was found by polymerase chain reaction amplification in DNA extracted from lip biopsies of every patient. Viral RNA was found by in situ hybridization in the acini epithelium, as well as in lymphocytic infiltrates. This observation suggests that HTLV-I expression in labial salivary glands could participate in the inflammatory lesions observed in these patients. Some seronegative patients with Sjögren's syndrome or dryness syndrome were also positive for viral transactivator tax DNA (41% in Martinique and 16% in non-HTLV-I-endemic region). Despite histologic signs of lymphocytic infiltration, no viral expression was found in the labial salivary glands of these patients.

A prospective incidence study was carried out in the French Caribbean island of Martinique between May 1st 1994 and April 31st 1995. incidence was 80.6 (77.7 when standardized with 1990 U.S. population). This incidence was higher than that observed in the Swiss canton of Geneva where the same methodology was used. The individualized risk factors of first provoked and unprovoked seizures in Martinique were alcoholism, head trauma and cerebro-vascular accidents.

Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. One hundred and eighty four index patients with autosomal dominant cerebellar ataxia type I were screened for this mutation. We found expansion in 109 patients from 30 families of different geographical origins (15%) and in two isolated cases with no known family histories (2%). The SCA2 chromosomes contained from 34 to 57 repeats and consisted of a pure stretch of CAG, whereas all tested normal chromosomes (14-31 repeats), except one with 14 repeats, were interrupted by 1-3 repeats of CAA. As in other diseases caused by unstable mutations, a strong negative correlation was observed between the age at onset and the size of the CAG repeat (r = -0.81). The frequency of several clinical signs such as myoclonus, dystonia and myokymia increased with the number of CAG repeats whereas the frequency of others was related to disease duration. The CAG repeat was highly unstable during transmission with variations ranging from -8 to +12, and a mean increase of +2.2, but there was no significant difference according to the parental sex. This instability was confirmed by the high degree of gonadal mosaicism observed in sperm DNA of one patient.

A 37 year-old man had headaches for 10 days, then a single tonic-clonic seizure and coma due to an extensive cerebral venous thrombosis. In spite of full-dose heparin treatment for 7 days, the clinical picture worsened along with increasing edema on CT-Scan. Direct thrombolytic treatment was then performed using transvenous catheterization and instillation of Urokinase (2.6 MU over 4 days). A near complete repermeabilization of the sinuses was obtained and the patient improved dramatically in a few days. The only adverse effect of Urokinase was hematuria. Based on our experience and review of the literature which includes 26 previous cases, direct thrombolytic therapy appears to be a relatively safe procedure. This treatment should be considered in a patient with extensive dural sinus thrombosis which fails to respond to heparin treatment.

We report a new syndrome that we call "recurrent optic neuromyelitis with endocrinopathies" in eight Antillean women from Martinique and Guadeloupe Ocular involvement was either monocular or binocular, whereas myelopathy was acute or subacute. In seven patients, myelopathic symptoms recurred, and in six patients, visual problems recurred. Spinal cord involvement was a consistent band-like pseudo-syringomyelic dissociated sensory loss. All eight patients had endocrinopathies consisting of amenorrhea, galactorrhea, diabetes insipidus, hypothyroidism, or hyperphagia. Spinal cord MRI revealed cavitation-like images. Various immunosuppressant treatments had little effect on the uniformly deteriorating course, ending in blindness and paraplegia. Six patients died within 5 years of onset, and an autopsy in one patient showed multiple demyelinizing lesions of the spinal cord with thickened blood vessels walls without evidence of inflammation. These cases appear to constitute a syndrome distinct from MS and from classic Devic's syndrome, not only because of the association with endocrinopathies but because of the stereotypy of the recurrences, the absence of MRI lesions in the cerebral white matter, and the unusual image of cavitation of the spinal cord. The syndrome is also distinct from HTLV-I-associated paraparesis, which is endemic in the West Indies.

To investigate whether HTLV-I induces the development of complement-dependent cytotoxic antibodies in humans, sera of asymptomatic HTLV-I carriers and of patients suffering from tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) or adult T cell leukaemia (ATL) were used in a cytotoxicity assay against a panel of target cells. This panel included uninfected cell lines (CEM, Jurkat, Molt and H9), cell lines chronically infected with HTLV-I (MT2, MT4, C9IPL and HUT102), as well as lines H36 (H9 infected with HTLV-I), H9-IIIB (H9 infected with HIVms) and H9-MN (H9 infected with HIMVMN). HTLV-I+ sera induced lysis of H36 and of lines expressing HTLV-I antigens in the presence of rabbit complement, but did not lyse cells in presence of human complement. The HTLV-I+ sera also failed to lyse the HTLV-I- lines and H9 cells, suggesting that lysis was specific for HTLV-I. H36 cell lysis was prevented by IgG depletion of the sera and by dialysis of rabbit complement against EGTA or EDTA. Rabbit complement-dependent cytotoxic antibodies were present in the sera of 14/14 HTLV-I-infected individuals; the highest titres were predominantly found in the sera of the TSP/HAM patients. Such antibodies were also detected in 5/5 individuals coinfected with HIV-1 and HTLV-I, although no cytotoxic antibody could be found against HIV-infected cells. Vice versa, sera of HIV-1-infected individuals did not exert a lytic effect in the presence of complement (of human or rabbit origin) against HIV-1- or HTLV-I-infected cells. Incubation of the sera of four HTLV-I-infected patients with HTLV-I env-specific synthetic peptides demonstrated that some of the complement-dependent cytotoxic antibodies recognized epitopes located on gp46 between amino acids 190 and 209. There is no correlation of rabbit complement-dependent cytotoxic HTLV-I antibodies with the development of disease.

Autosomal dominant cerebellar ataxias (ADCAs) are a group of neurodegenerative disorders that are clinically and genetically heterogeneous. We report here a genetic linkage study, with five chromosome 12q markers, of three Martinican families with ADCA type 1, for which the spinocerebellar ataxia 1 (SCA1) locus was excluded. Linkage to the SCA2 locus was demonstrated with a maximal lead score of 6.64 at theta = 0.00 with marker D12S354. Recombinational events observed by haplotype reconstruction demonstrated that the SCA2 locus is located in an approximately 7-cM interval flanked by D12S105 and D12S79. Using the z(max)-1 method, multipoint analysis further reduced the candidate interval for SCA2 to a region of 5 cM. Two families shared a common haplotype at loci spanning 7 cM, which suggests a founder effect, whereas a different haplotype segregated with the disease in the third family. Finally, a mean anticipation of 12+/-14 years was found in parent-child couples, with no parental sex effect, suggesting that the disease might be caused by an expanded and unstable triplet repeat.

The objective of this study is to describe the clinical and immunological aspects observed in patients with both "tropical spastic paraparesis/HTLV-I associated myelopathy" (TSP/HAM) and ocular dryness. In 10 such patients clinical and biological examinations completed with a biopsy of secondary salivary glands were performed to assess the etiology of the ocular dryness. According to the Chisholm's scale, 70% of the patients had a biopsy grade 3 or grade 4. Polyclonal hypergammaglobulinemia was found in 90% of patients and lymphocytic alveolitis in 80%. Three patients had past medical history of chronic uveltis. All the findings were compatible with Sjögren's syndrome, however no characteristic immunological disorders were found. Antinuclear antibodies and rheumatoid factor proved negative in all cases.

The purpose of this study was to confirm that ophthalmological features seen in patients in Martinique, French West Indies, could be linked to infection by HTLV-I. The authors studied 93 HTLV-I infected patients divided into 70 patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 23 asymptomatic HTLV-I carriers. They did a complete ophthalmological examination with an assessment of lacrymal secretion by means of three tests: Shirmer 1, break-up time and rose Bengal. Some patients had a biopsy of secondary salivary glands. When possible, detection of HTLV-I antibodies was carried out in the aqueous humor. In 45 of the 93 patients (48.4%) the presence of dry keratoconjunctivitis was recorded. In 22 of these 45 cases, a biopsy of the secondary salivary glands showed the presence of lymphoplasmocytoid infiltrations comparable to the glandular changes that occur with Gougerot-Sjögren syndrome. Among the 93 patients, 15 cases of uveitis were noted (16.1%) with 13 cases of anterior uveitis and 11 cases of vitritis. The inflammation was bilateral in 9 cases (9/15 = 60%). Two cases of cotton wool spots, 3 cases of abnormalities in the distribution of the retinal pigment and 7 cases of corneal lesions were also noted. Higher levels of anti-HTLV-I antibodies were detected in the aqueous humor of 3 patients with uveitis. The coexistence of dry eye (keratoconjunctivitis), uveitis and retinal microangiopathy in patients who are suffering from HAM/TSP could suggest the involvement of an autoimmune or immunological mechanism in the physiopathology of the illness.

Human T-cell leukemia virus type I (HTLV-I) is associated with a large spectrum of clinical manifestation including adult T-cell leukemia (ATL) and tropical spastic paraparesis or HTLV-I-associated myelopathy (TSP/HAM). In most cases, however, infected patients remain asymptomatic. The participation of the immune system in the pathogenesis of TSP/HAM has been suggested. In this study the IgG antibody response of HTLV-I-infected individuals has been investigated using both ELISA with a panel of nuclear and cytoplasmic proteins and peptides known to be recognized by antibodies from patients with various systemic autoimmune diseases, and immunoprecipitation of ribonucleoproteins from HeLa cell extracts. The results were compared with the reactivity of sera from individuals with non-HTLV-I-related neurological diseases and healthy blood donors. Raised levels of autoantibodies reacting with several nuclear and cytoplasmic antigens were found in TSP/HAM and ATL patients. In asymptomatic HTLV-I-seropositive individuals, both the prevalence and level of IgG antibodies were lower and directed only against a restricted set of antigens. The mechanism of induction of these antibodies still remains obscure. However, the results show that a significant autoimmune response exists in these patients and it may contribute to the pathogenesis of the disease.

We searched for the presence of human T-cell leukemia virus type I (HTLV-I) sequences in central nervous system and muscle lesions of 3 patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and 3 patients with HTLV-I-associated polymyositis. Proviral DNA coding for the Tax protein was found by polymerase chain reaction amplification in DNA extracted from lesions of every patient with TSP/HAM or HTLV-I-associated polymyositis. In contrast, viral RNA was found occasionally by in situ hybridization in muscle lesions of some patients with polymyositis, but was never found in central nervous system lesions of TSP/HAM patients.

Myositis linked to HTLV-1 is unfrequent. Over a period of 8 years, 14 patients with inflammatory myopathy were diagnosed in Martinique. Seven were seropositive for HTLV 1 antibody; the clinical and pathological data of whom are presented herein. Five patients presented with polymyositis, two with dermatomyositis. All seven patients had extra-muscular clinical features including neuropathy (4/7) and myelopathy (6/7), resulting in a quite peculiar clinical picture. Muscle biopsy showed a neurogenic process combined with myositic changes in 3/7 patients. Corticotherapy led to dramatic improvement in only one case, but with no sustained effect. HTLV 1 may be considered the etiological agent of this form of dermato-polymyositis, characterized by a clearly distinctive clinico-pathological picture, and a poor response to corticotherapy. As in the case of tropical spastic paraparesis/HTLV 1 associated myelopathy, careful assessment of non-steroidal therapy is now warranted.

A 34 year old woman with AIDS presented with adynamia and obsessive-compulsive behaviour. CT scan revealed bilateral toxoplasmic lesions involving basal ganglia. The neuropsychological picture resolved under specific antitoxoplasmic treatment. However, relapse of toxoplasmosis occurred in associating with the same behavioral changes. This is the first case of such a syndrome due to infectious lesions, and in which improvement through transient, was observed.

The main neurological manifestation due to Human T-Cell Lymphotropic Virus type (HTLV1) infection is a chronic spastic paraparesis called HTLV1-associated paraparesis (HAP). Since 1985, we observed in Martinique (French West Indies) 276 cases of HAP. Among them, 70 patients fulfilled clinical, electrophysiological or histological criteria of associated peripheral nervous system involvement (42/70), myositis (8/70), or both (20/70). Muscle biopsy revealed neurogenic atrophy of muscle fibers or myositic changes in 41/70. Neuromuscular involvement was only mild in 19/70. On the other hand, 25 patients presented with a syndrome mimicking amyotrophic lateral sclerosis, and 7 other patients with features of polymyositis. This study shows that neurological manifestations associated to HTLV1 infection may be more complex than the well-known chronic spastic paraparesis, since 25.4% of the HAP Martinican patients exhibit neuropathic or myositic features.

Spinocerebellar ataxia 2 (SCA2) is one of the loci for the clinically and genetically heterogeneous group of autosomal dominant type I cerebellar ataxias. After initial linkage to chromosome 12q in Cuban families, SCA2 was shown to be the gene responsible for the disease in Italian, Tunisian, French-Canadian, Austrian-Canadian and Martinican kindreds with dominant ataxia, and the candidate interval was reduced to 6.4 cM between markers D12S84 and D12S79. Comparison of patients from families of different geographical origins clearly demonstrates the clinical interfamilial variability of the clinical signs which reaches statistical significance for the frequency of extrapyramidal rigidity, postural tremor and dementia. The most striking difference between the 29 Martinican SCA2 patients and those with SCA1 on chromosome 6p or SCA3/MJD on chromosome 14q is the greater frequency of hyporeflexia in the former. A mean 12.5 year anticipation is observed, with a more rapid clinical course of the disease in successive generations, indicating that an expanded trinucleotide repeat probably constitutes the underlying molecular mechanism.

The susceptibility of NK cell-mediated cytolysis was compared between 5 human HTLV-I-transformed T cell lines and 10 newly established IL-2-dependent HTLV-I-infected lines. None of the cell lines were killed after 4 hr incubation with normal PBMC. However, after 20 hr, 3 HTLV-I-transformed lines were significantly lysed. All the HTLV-I-infected lines, except 2, weakly inhibited the NK cell-mediated lysis of K562 targets. They showed a reduced ability to bind normal PBMC as compared with control NK-sensitive T cell lines. The IL-2-dependent lines remained unaffected by PBMC from HTLV-I-infected individuals, including the autologous donors. In contrast to the HTLV-I-transformed lines, they were weakly lysed or not lysed at all by LAK cells and only 5 were killed by ADCC with HTLV-I+ sera and normal PBMC. Taken together, the results show that IL-2-dependent HTLV-I-infected T cells strongly resist NK cell-mediated cytolysis at a post-binding level and suggest that such cells may escape in vivo from non-specific, MHC-unrestricted cellular cytotoxicity.

Objectives: The most common neurological picture associated with HTLV-1 infection is a slowly progressive spastic paraplegia often involving nerve and muscle inflammation. We report here six cases of inflammatory vasculitis of the nervous system observed among HTLV-1 infected patients., Methods: HTLV-1 infection was diagnosed in 6 female patients, mean age 58 years (range 40-77 years) using ELISA, Western blot or polymerase chain reaction., Results: All 6 patients presented a pyramidal syndrome which was associated with peripheral neuropathy in 3, myositis in 1 and a sicca syndrome in 3. Two groups of patients could be identified. In 3 patients, the neurological picture was typical of HTLV infection; pathology examination of biopsy material revealed necrozing vasculitis. In 3 other patients, the clinical course was particularly rapid, highly suggestive of anterior spinal artery infarction, associated, in 2, with a major inflammatory syndrome., Conclusion: These 6 cases demonstrate that vasculitis can be associated with HTLV-1 infection as has been observed in HIV-infected patients. In certain cases, clinical signs of vasculitis may be lacking while in others they may dominate the clinical manifestations.

The humoral immune response in sera from 30 human T cell lymphotropic virus type I (HTLV-I)-positive individuals from Martinique in the French West Indies was studied. The subjects were subdivided into those suffering from TSP/HAM and those being asymptomatic. In general, TSP/HAM patient sera seemed to contain more virus-specific antibodies than did the sera from the asymptomatic subjects. Three of the 13 TSP/HAM sera and 1 of the 17 asymptomatic sera contained HTLV-I-specific IgM antibodies, whereas 6 and 5 sera, respectively, contained IgA antibodies. By correlating the ability of patient sera to inhibit HTLV-I-induced syncytia with their antibody reactivity in ELISA to 42 synthetic peptides, together corresponding to the entire envelope glycoprotein of HTLV-I, a number of putative neutralizing domains were identified. Eight synthetic peptides representing the regions with the highest coefficient of correlation between neutralizing titer and ELISA reactivity were employed to specifically adsorb potentially neutralizing antibodies, and were also used directly, without sera, in the syncytium-neutralizing test. By those techniques, three novel and two previously described domains that seemed to contain neutralizing epitopes were identified. Two of the novel neutralizing sites resided in the external glycoprotein (gp46) and were contained within amino acids 53-75 and 287-311, respectively, and one was located in the transmembrane glycoprotein (gp21) within amino acids 346-368. Our findings may have implications for the rational design of subunit vaccines for prevention of and/or alteration of the clinical outcome of HTLV-I-related diseases.

We present the results of ophthalmologic examinations of a consecutive series of 30 patients with HTLV-I associated myelopathy. This is the first ophthalmologic prospective study reported outside the Japanese endemic area. Twenty-one of the patients (70%) had kerato-conjunctivitis sicca in addition to accessory salivary gland lymphocytary infiltration in 7. Two cases of uveo-papillitis, 1 case of cotton-wool spots and 3 cases of retinochoroidal degeneration were also observed. Moreover, an aliquot of the aqueous humour was collected from the anterior chamber in 5 patients and showed high titer of HTLV-I antibodies for the 2 patients with uveo-papillitis. We propose different hypotheses to explain the physiopathologic characteristics of these features.

The human T-lymphotropic retrovirus type I (HTLV-1), isolated in 1980, has been shown to be responsible for two distinct systemic diseases: adult T-cell leukemia and HTLV associated myelopathy (HAM). Recently, an ever increasing number of publications have described other disorders associated with HAM. We report a case of uveitis-optic disc neuritis which, to our knowledge, had not been previously described. The fact that both uvea and optic disc were inflamed would suggest that immune-mediated reactions are involved in the pathogenesis of HAM.

A peptide library of HTLV-I Env and Tax proteins was constructed in yeast in order to characterize which domains of these proteins are immunogenic in HTLV-I-infected individuals. Five yeast colonies (A to E) were selected using HTLV-I positive plasma, and one yeast colony (F) was selected using rabbit anti-Tax sera. Plasmid DNA present in each positive clone was recovered and sequenced. Overlapping clones A to E covered the C-terminal part of the gp46 exterior glycoprotein (aa 197 to 305) and were all glycosylated. Clone F encoded the C-terminal 25 aa of Tax (aa 329-353). Recombinant peptides were recognized by more than 40% of the HTLV-I positive human sera, confirming that they are major immunodominant domains. We studied the antibody response to each recombinant peptide in patients with TSP/HAM and asymptomatic carriers. Higher absorbance values were obtained with sera from TSP/HAM patients than from asymptomatic carriers, but the difference between the two groups was not statistically significant. Our study confirms that the COOH-terminal region of gp46 is highly immunogenic in HTLV-I-infected individuals and demonstrates a new immunogenic epitope of the Tax protein.

The authors report a case of intradural posterolateral spinal arachnoid cyst diagnosed by Magnetic Resonance Imaging (MRI) in a 59-year-old woman. Ten years before, she started to suffer from burning sensation of the left lower limb aggravated by head movements. Physical examination was normal except a sensory dissociation below T10. A myelography was considered as normal. Three years later, motor disturbances occur with progressive weakness. Examination showed asymmetrical spastic paraparesis with a right predominance. On MRI, the spinal cord was displaced at T6-T7 level by a posterior intradural mass with a similar signal than CSF; furthermore, at this level, there was an intramedullary hyposignal on T1 weighted sections. The diagnosis of spinal intradural arachnoid cyst was confirmed at surgery. Microscopic examination of the cyst wall showed fibrous tissue with mild lymphocytic infiltration. Rapid recovery of legs weakness followed, but abnormalities of spinothalamic functions persisted. The clinical characteristics and the MRI data are discussed. The authors conclude that this arachnoid cyst had an inflammatory origin.

Numerous epidemiological studies showed that The occurrence of multiple sclerosis (MS) was the result of genetic factors varying by ethnic group as well as geographical and environmental factors. It is difficult to estimate exactly the prevalence of MS among black Africans. Nevertheless it's possible to state that the disease is rare but present among those populations. Among black Americans prevalence of MS seems related to the degree of mixture with white population. Among West Indians the occurrence of MS is closely related to an environmental factor acquired in Europe before 15 years of age. Those data confirm the existence during childhood and adolescence of a critical period during which an environmental factor is acquired in regions of high prevalence for MS.

To date, 271 cases of HTLV1-associated paraplegia have been observed in Martinique (French West Indies). The clinical picture consisted mostly in a spastic paraparesis or paraplegia with sphincter disturbances (80%) and lower limbs pains (60%). The severity of the disease appeared variable: after a mean disease duration of 6.5 years, 40% of the patients could walk without help, 35% used a single crutch, and 25% used a couple of crutches or were confined to a wheelchair. A variable neuromuscular component was observed in 70 cases (25.4%). In 38 cases, the peripheral signs (SIGNS) or the myositis were only mild. In contrast, 25 patients presented with severe amyotrophy evoking amyotrophic lateral sclerosis, and 7 other had features of dermatopolymyositis. Lastly, an extra-neural spreading of the disease was extremely frequent, including lymphocytic alveolitis (76%), sicca syndrome (69%) and more rarely uveitis, arthritis or vasculitis.

The human T-cell leukaemia virus type 1 was the first human retrovirus to be isolated in 1980 by R. Gallo and coworkers. As its name indicates, this virus is responsible for adult T-cell leukaemia. In 1985, the neurological manifestations associated with this disease were isolated from the tropical spastic paraplegia group in Martinique. Since that time, such manifestations have been reported in non-tropical countries in other foci of viral endemia and sporadically outside these regions. These neurological manifestations are totally independent of the haematological manifestations with which they are virtually never associated. Frequent in areas of viral endemia, they may be encountered in other countries open to human migrations, where they are too often overlooked.

The human retrovirus HTLV-1 (Human T-cell Lymphotrophic Virus) is responsible for malignant proliferations of mature T lymphocytes. It is also now implicated in neurological disorders dominated by spastic paraplegia. A study of 140 cases of lumbar and root pain enabled us to identify 8 of apparently idiopathic atypical lumbar and root pain which led to the discovery of a positive HTLV-1 serology performed routinely. These cases were remarkable in terms of the rarity and minimal extent of spinal cord signs and of Lasegue's sign, their duration of more than a year and the existence of neurological signs indicative of central involvement. In 2 patients there was secondary progression to a spastic paraparesis. It would appear that the neurotropism of HTLV-1 virus is not limited to the central nervous system but that it can also involve the peripheral nervous system as indicated by certain cases in the literature as well as those collected in Martinique, an endemic area for the virus. Rheumatologists should be aware of this possibility when confronted with such cases of atypical lumbar and root pain and should seek the existence of an HTLV-1 virus infection among other viral etiologies, in particular when the patient concerned comes from an endemic area.

In most cases the only manifestation of nervous system pathology associated with HTLV-1 infection is spastic paraplegia. The virus is transmitted by breast-feeding from mother to child, by transfusion of contaminated blood (or by syringes of intravenous drug addicts) or sexually from husband to wife. Paraplegia usually begins progressively after the age of 30 years by motor and sphincteral disorders, followed by a phase of stabilization. Other clinical entities, such as pseudo-LAS syndromes, polymyositis, lymphocytic alveolitis, vasculitis or meningitis, may coexist or show varying degrees of expression. There is no treatment capable of modifying the course of the disease, but corticosteroids are worth trying, notably in the initial stages of paraplegia and in polymyositis.

Debilitating disorders of the nervous system have a relatively high prevalence in the tropics, a geographic region that is often deficient in specialists in the fields of neurology and epidemiology. During World War II, attention was called to a possible nutritional origin for most of these diseases. Recently, however, human T lymphotropic virus type I (HTLV-I), formerly linked only to a rare form of leukemia (adult T cell leukemia), has been associated with a spastic paraplegia observed mostly in tropical areas and referred to as tropical spastic paraparesis. This entity is also observed in nontropical areas endemic for HTLV-I, including Japan, South America, and the southern United States. Viruses of the HTLV family are being associated increasingly with pathology in humans. The pathogenesis of HTLV-I-associated tropical spastic paraparesis remains to be understood. However, future research is expected to favor a multidisciplinary approach, with exciting potential insights derived from the fields of neurology, immunology, and infectious diseases. The aim of this review is to summarize contemporary research related to the viral etiology of this clinical entity.

Several authors have demonstrated the presence of antibodies against the HTLV-I retrovirus in patients with MS. Considerable controversy exists regarding the etiologic significance, if any, of this finding, but the presence of these antibodies in the blood or CSF of MS patients has led to reconsideration of that diagnosis in certain cases. It is recommended that, before the diagnosis of MS is changed to that of HTLV-I-associated chronic myelitis, at least 2 of the following abnormalities be present: (1) clinical or electrophysiologic involvement of peripheral nerve or muscle; (2) the presence of oligoclonal bands in the serum; (3) the presence in blood or CSF of lymphocytes with multilobed nuclei; (4) a positive serologic test for syphilis; (5) the presence of a sicca syndrome; and (6) the presence of pulmonary lymphocytic alveolitis.

HTLV-I is a type C human retrovirus, endemic in Japan, central Africa, South America and the Caribbean, which causes adult T cell leukemia/lymphoma and chronic progressive paraparesis. Some neurological patients with chronic progressive myelopathies, but seronegative for HTLV-I have been reported in Martinique. We performed polymerase chain reaction (PCR), to look for the presence of HTLV-I genomic sequences in those patients. Two primers were chosen for gag and tax genes. Liquid hybridization was performed on the amplified products using an internal 32p labelled oligonucleotide as a probe. The hybridized material was run on a 6% polyacrylamide gel. Forty-three of forty-four seropositive subjects analysed as "positive controls" were positive for gag, but only 16/29 for tax. Twenty HTLV-I seronegative neurological patients with a symptomatology suggesting HAM/TSP were tested: 18 were found positive for at least one of the 2 oligonucleotide pairs. Two "negative controls": Moya-Moya and vascular brain failure were found negative. 8/9 subjects with uninterpretable WB were also studied by PCR, and 8 were found positive for at least one oligo pair. Our conclusion is that PCR methodology is able to detect genetic information related to HTLV-I in a number of cases where classical serology is negative.