Early sequential development of infective dermatitis, human T cell lymphotropic virus type 1-associated myelopathy, and adult T cell leukemia/lymphoma.

We describe a patient with human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis who developed HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T cell leukemia/lymphoma at 16 years of age. Long inverse polymerase chain reaction was used to demonstrate monoclonal integration of proviral DNA in the lymphomatous skin lesion.

[Chronic progressive cervical myelopathy with HTLV-I infection: variant form of HAM/TSP].

We report four patients with slowly progressive cervical myelopathy. The four patients had several features in common; 1) progressive cervical myelopathy with a duration of several months to years, 2) abnormal lesions in the cervical to upper thoracic cord levels with or without gadolinium enhancement, 3) anti-HTLV-I antibodies were positive both in serum and CSF, 4) high levels of HTLV-I proviral load in PBMC. The calculated risk of HAM/TSP in two patients showed a high value, comparable to those of HAM/TSP, and higher than those of healthy HTLV-I carrier. Because the clinical and laboratory findings of these four cases show similarities to those of HAM/TSP, we propose that these four cases may be a variant form of HAM/TSP.

Epitope analysis of the cerebrospinal fluid IgG in HTLV-I associated myelopathy patients using phage display method.

We, for the first time, analyzed the binding motifs of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with a phage library displaying 12-mer random peptides. As a result, the sequences highly homologous to HTLV-I gp46 192-199, 237-243 and 255-261 were the common linear epitopes of high affinity- IgG exclusively detected in both CSF and sera of the patients. These IgG responses were confirmed with corresponding HTLV-I peptides and serum antibody titers significantly correlated with disease severity or duration. Gp46 237-243 has not been detected in previous enzyme-linked immunosorbent assay (ELISA) studies using bound longer peptides, suggesting the usefulness of the phage display method.

[A woman with Sezary syndrome developed HTLV-1-associated myeloneuropathy. The reported case supports the theory of etiological connection]. / Kvinna med Sézarys syndrom utvecklade HTLV-1-associerad myeloneuropati. Rapporterat fall ger stöd för teori om orsakssamband.

The patient was a 58-year-old woman with a 10-year history of severely itching erythroderma, as well as enlarged lymph glands and circulating Sézary cells (i.e. Sézary's syndrome). Histological analysis of a skin biopsy revealed Pautrier's microabcesses with atypical lymphocytes characteristic of T-cell lymphoma. Her lymph glands were also found to contain atypical lymphocytes. Parallel to the skin disorder, the patient developed paraparesis with fainting strength of the musculature of the extremities. Ultimately, she was unable to walk. She had no feeling of vibration and had difficulties emptying her bladder. Babinski's sign was positive, bilaterally. Ten years before the present admission the patient's skin and blood lymphocytes were positive for sequences of human T-cell lymphoma virus-1 (HTLV-1) in a polymerase chain reaction (PCR). At the present admission, the patient presented a high titre of HTLV-1 antibodies both in the blood and cerebrospinal fluid on ELISA and Wesern blot analysis. The patient had been married to a man from Bolivia for 30 years. He was also strongly positive for HTLV-1 antibodies in blood. Adult T-leukemia (ATL) is common in areas where HTLV-1 is found endemically. ATL has skin symptoms similar to mycosis fungoides. The clinical findings in this patient indicate an etiological connection between some cases of T-cell lymphoma in the skin (Sézary's syndrome) and HTLV-1.

Chronic active VZV infection manifesting as zoster sine herpete, zoster paresis and myelopathy.

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.

Pathological and virological assessment of acute HTLV-I-associated myelopathy complicated with encephalopathy and systemic inflammation.

HTLV-I-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP), is a chronic inflammatory disease of the spinal cord. Acute cases are uncommon. We report the case of a 41-year-old woman with acute HAM/TSP complicated with encephalitis, an intense inflammatory reaction of the nervous system and lymphocytic infiltration of skeletal muscles, liver, salivary, adrenal and pituitary glands. The immunohistochemical studies of the lymphocytes surrounding blood vessels showed both B- and T-lymphocytes, in similar proportion, with both CD4- and CD8-positive cells. In addition, many perivascular and scattered macrophages were observed. Adult T-cell leukemia/lymphoma (ATL) was ruled out. The marrow aspirate was normal. Serial cerebrospinal fluid (CSF) analysis showed presence of HTLV-I antibodies, but without intrathecal synthesis of specific antibodies. Determination of HTLV-I viral loads demonstrated increased levels in the CSF relative to the peripheral blood and may be associated with widespread inflammation. The pathological and immunological findings may help understand the role of immune-reactive cells in the pathogenesis of HTLV-I-associated myelopathy.

Juvenile human T lymphotropic virus type 1-associated myelopathy.

We report the cases of 5 adolescents with human T lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis, acquired in all but 1 case from the mother. The first symptom in all patients was difficulty in running, which was present for many years before the final diagnosis was made. Follow-up showed an indolent progression, regardless of treatment strategy.

Diagnosis of HAM/TSP based on CSF proviral HTLV-I DNA and HTLV-I antibody index.

The contribution of human T-cell lymphotropic virus (HTLV-I) DNA by PCR in CSF and the intrathecal synthesis of antibodies to HTLV-I by the antibody index (AI) to the diagnosis of HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) were evaluated. Cases of spastic paraparesis compatible with HAM/TSP had increased AI for HTLV-I (60/73) and HTLV-I proviral sequences in CSF (25/27). Among 27 patients with other neurologic diseases, three had increased AI and another three had positive HTLV-I DNA in CSF. Thus, the combination of PCR for proviral DNA and AI for HTLV-I in CSF provides consistent criteria for the diagnosis of HAM/TSP.

Inflammatory myopathy on HTLV-I infection: case report.

We describe a 41 years old woman who 17 years ago presented hypotonia and proximal muscular weakness in the upper and lower limbs. On neurological examination, the biceps, triceps and Achilles reflexes were absent; the brachioradialis reflexes were decreased and the patellar reflexes were normal. There was bilateral Babinski sign. The remainder of the neurological examination was unremarkable. In the investigation a myopathic pattern was found in the electromyography. The nerve-conduction study was normal; a ELISA method for HTLV-I antibodies was positive in the blood and in the cerebral spinal fluid. The muscle biopsy showed inflammatory myopathy, compatible with polymyositis. This paper focuses the polymyositis in the beginning of an HTLV-I infection case.

Inflammatory myopathy on HTLV-I infection: case report

We describe a 41 years old woman who 17 years ago presented hypotonia and proximal muscular weakness in the upper and lower limbs. On neurological examination, the biceps, triceps and Achilles reflexes were absent; the brachioradialis reflexes were decreased and the patellar reflexes were normal. There was bilateral Babinski sign. The remainder of the neurological examination was unremarkable. In the investigation a myopathic pattern was found in the electromyography. The nerve-conduction study was normal; a ELISA method for HTLV-I antibodies was positive in the blood and in the cerebral spinal fluid. The muscle biopsy showed inflammatory myopathy, compatible with polymyositis. This paper focuses the polymyositis in the beginning of an HTLV-I infection case

HTLV-I associated myelopathy: clinical and epidemiological profile.

The prevalence of HTLV-I reaches 1.8% among blood donors in Salvador, and 40% among chronic myelopathy patients in the state of Bahia, Brazil. The present study shows the epidemiological and clinical picture of patients attending the HAM/TSP Outpatient Unit at the Foundation of Neurology and Neorusurgery (FNN). 114 patients had epidemiologic data collected and 51 of these patients, who had regularly attended the HAM/TSP Unit for at least 1 year, were evaluated for signs, symptoms and disease progression. Most of the 114 patients were female (70%), of African descent, and with a mean age of 51. Sexually transmitted diseases and blood transfusion were the most common risk factors. Paraparesis with spasticity was the predominant sign (85%), bladder dysfunction occurred in 75%, intestinal dysfunction was recorded in 48%. Sensory examination was normal in 50% of the cases studied. The patients' functional status, as measured by the Kurtzke Disability Scale, during the 1 year observation period changed only in early disease. Steroid therapy with prednisone was the most commonly used treatment in this group.

[A case of HTLV-I associated myelopathy with abnormal patchy MRI lesions in the spinal cord].

We report a case of HTLV-I associated myelopathy (HAM) with a spinal cord MRI showing abnormal multifocal and patchy lesions. A 50-year-old woman suffering from progressive paraparesis was admitted to our hospital. HTLV-I antibodies in the serum and CSF were positive, and a diagnosis of HAM was made. Her T2 weighted spinal cord MRI showed scattered areas of high signal intensity from the cervical to the thoracic cord. The lesions were enhanced with gadolinium-DTPA on T1 weighted imaging. Atrophy of the thoracic cord has been reported in many patients with HAM. In rare cases, T2 weighed thoracic cord MRI showed diffuse high signal intensity. The pattern of high signal intensity in our case, however, was multifocal and patchy, thus differing from the findings of previous reports. And we believe this is the first such report. This case suggests that the MRI of HAM patient may show multifocal and scattered lesions in the spinal cord.

Neuropathology of HTLV-1-associated myelopathy (HAM/TSP).

In order to clarify pathogenesis of HAM/TSP, we performed a detailed neuropathologic analysis of seven autopsy patients with HAM/TSP. Inflammatory infiltrates of mononuclear cells and degeneration of myelin and axons were noted in the middle to lower thoracic spinal cords and were continuously extended to the entire spinal cord. Horizontal distribution of inflammatory lesions was symmetric at any spinal levels. Immunohistochemical analysis demonstrated T-cell dominance. The numbers of CD4+ T cells and CD8+ T cells were equally present in patients with shorter clinical course. Apoptosis of helper/inducer T cells were observed in the presence of TIA1+ cytotoxic T cells in these active inflammatory lesions. Inflammatory infiltrates were markedly decreased and CD8+/TIA1- T cells were predominated over CD4+ cells in patients with prolonged clinical course. HTLV-1 proviral DNA amounts in the freshly frozen spinal cord measured by quantitative PCR were well correlated with the numbers of infiltrated CD4+ cells. In situ PCR of HTLV-1 proviral DNA using multi-primary pairs demonstrated the presence of HTLV-1 infected cells exclusively in the mononuclear infiltrates of perivascular areas. From these findings, it is suggested that the target of the inflammatory process seen in HAM/TSP lesions may be HTLV-1 infected CD4+ T cells infiltrating the spinal cord.

[A case of rapidly progressive HTLV-I-associated myelopathy (HAM)].

We report a 65-year-old woman with HAM who showed rapid progression of the clinical symptoms. The initial symptom was lumbago and she became unable to walk within 4 months after the onset of the lumbago. When seen on admission, she had flaccid paraplegia and areflexia was seen in the lower extremities with positive Babinski and Chaddock reflexes. She had numbness below the level of the navel, vibratory sensation was decreased in both lower limbs, and there was a hyperesthesic zone at the tenth thoracic vertebral level. She had a difficulty in urination and defecation. Laboratory examination revealed elevated anti-HTLV-I antibody titers both in serum (4,096x by PA method) and in cerebrospinal fluid (CSF) (4,096x). The levels of IgG and neopterin in CSF were also increased to 16.6 mg/dl (normal: < 5 mg/dl) and 360.3 pmol/ml (normal: < 30 pmol/ml), respectively. HTLV-I messenger RNA positive cells were detected in 0.1% to 0.01% of cells in CSF by in situ hybridization using an oligonucleotide probe labelled with alkaline phosphatase. Spinal cord MRI detected neither spinal cord compression nor vascular diseases. She was treated with 1,000 mg methylprednisolone for 3 days intravenously, followed by 60 mg oral prednisolone therapy. In several days after receiving the treatments, her muscle tonus became spastic and deep tendon reflexes in the legs became brisk. The hyperesthesia at the tenth thoracic vertebral level and numbness below the level of the navel were also gradually improved. Subsequently, her clinical features were consistant with those of the typical HAM. Therefore, the patient was diagnosed as rapidly progressive HAM. The initial phase of rapidly progressive HAM patients had been described only from clinical history. These patients had common characteristic clinical features, such as older age at onset, relatively severe motor dysfunction, high titers of anti-HTLV-I antibody in CSF, and increased levels of neopterin and IgG in CSF, when compared with those of other HAM patients. The clinical course and laboratory findings in the present patient were compatible with those in the previous cases reported as rapidly progressive HAM. This patient showed flaccid paraplegia and areflexia which have rarely been seen in HAM patients. However, these symptoms were changed to spastic and hyperactive after prednisolone therapy. We speculate that inflammation in the spinal cord in this patient was severe enough to spread to the dorsal root, and disturbed the afferent pathway from the peripheral to the central nervous system. This inflammatory reaction might be suppressed by prednisolone to facilitate the recovery of the afferent pathway, which led to the typical clinical symptoms of HAM.

Anterior horn cell degeneration in polymyositis associated with human T lymphotropic virus Type-1 in patients from Barbados.

Anterior horn cell degeneration has only occasionally been noted in patients with tropical spastic paraparesis associated with human T lymphotropic virus type-1 (HTLV-1) infection. We report on three adult patients with HTLV-1-associated polymyositis who had clinical evidence of anterior horn cell degeneration. One patient had moderate proximal weakness and muscle wasting in all four limbs, while two had mild upper limb weakness with more profound proximal weakness and wasting in the lower limbs. In all three patients, electromyographic findings were compatible with motor unit loss and muscle biopsies showed mononuclear inflammatory cell infiltration; muscle biopsies in two patients showed features of denervation. Immunoglobulin G (IgG) antibodies to HTLV-1 were detected by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western immunoblot in serum and cerebrospinal fluid in all three patients. In two, cell cultures were established from peripheral blood lymphocytes and HTLV-1 antigen was identified by immunofluorescence and the ELISA antigen-capture technique using an anti-p19 HTLV-1 mouse monoclonal antibody. The three cases illustrate the variety of neuromuscular disease, other than spastic paraparesis, that may occur in HTLV-1 infection. In some cases of HTLV-1-associated polymyositis, anterior horn cell degeneration may make a significant contribution to the muscle atrophy observed.

The association of antibodies against human T cell lymphotropic virus type I (HTLV-I) pX gene mutant products with HTLV-I-associated myelopathy/tropical spastic paraparesis.

Antibodies specific for the products of the human T cell lymphotropic virus type I (HTLV-I) pX frame-shift mutants were studied by ELISA. The serum IgG antibodies to the synthetic peptide corresponding to one nucleotide insertion at position 7784 were significantly more common in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients than in HTLV-I carriers who had neither HAM/TSP nor adult T cell leukemia (39% vs. 5%). The seropositivities to the other synthetic peptides, which corresponded to the one nucleotide deletion at position 7475 and the internal deletion of nt 7754-7819 and nt 7853-7936, were rare. A genetic study confirmed the presence of the responsible mutation of the pX gene in peripheral blood mononuclear cells and central nervous system tissue from HTLV-I-infected subjects with and without HAM/TSP. These results suggest that HTLV-I pX frame-shift mutants are expressed in vivo in HTLV-I carriers; they also induce antibodies. especially in those with HAM/TSP.

The value of CSF analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis.

Cerebrospinal fluid (CSF) and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/tropical spastic paraparesis), six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control) from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA). All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG). In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response) were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono- and polyspecific immune responses is discussed for these chronic neurological diseases.

HTLV-I associated myelopathy in Porto Alegre (Southern Brazil).

HTLV-I associated myelopathy/tropical spastic paraparesis (TSP/HAM) have been increasingly described in practically all regions of Brazil. Five confirmed and documented cases of patients with TSP/HAM in Rio Grande do Sul are reported; in all of them spastic paraparesis, neurogenic bladder and superficial and/or profound sensitive disorders were observed in variable degrees. One patient presented a relapsing-remitting course with a cerebellar ataxia (multiple sclerosis-like pattern). Everyone was submitted to clinical, serological, urodynamic, neurophysiologic and neuroradiologic investigation. The aim of this study was to present the southern region of Brazil as an area with significant endemicity for HTLV-I/II infection (prevalence of 0.42% between blood donors), and also to show the existence of patients with neurologic disease associated with this retrovirus.

The value of csf analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis

Amostras do líquido cefalorraquidiano (LCR) e soro de 17 pacientes brasileiros com HAM/TSP, seis com esclerose múltipla e seis com epilepsia idiopática (controle nao-inflamatório) foram analisadas para a presença de anticorpos para o vírus de sarampo, rubéola, varicela zoster e herpes simples pelo método de ELISA. Todos os casos de HAM/TSP e esclerose múltipla tinham resposta imune poliespecífica intratecal para sarampo e rubéola. Anticorpos específicos para sarampo e rubéola (resposta MRZ) foram observados em todos os pacientes com esclerose múltipla, mas nao nos controles com epilepsia idiopática. A relevância das respostas poliespecífica e monoespecífica é discutida para essas doenças neurológicas crônicas.