HTLV-I infection and neurological disease in Rio de Janeiro.

Fifty patients with chronic neurological diseases attending a clinic in Rio de Janeiro, Brazil, were examined for evidence of HTLV-I infection. Fifteen of 27 with progressive paraparesis of obscure origin had antibodies to HTLV-I in high titre in their serum samples, and 10 of 13 studied had antibodies in their cerebrospinal fluid. The clinical features of the antibody positive patients were similar to those of patients with HTLV-I associated myelopathy from other countries except that half of the Brazilian patients were white. Seven patients had multiple sclerosis and one of these had antibodies to HTLV-I in the serum. None of the eight patients with motor neuron disease and four with polymyositis had HTLV-I antibodies in their serum samples.     

Detection of human T-cell leukemia/lymphoma virus type I in a transfusion recipient with chronic myelopathy

A white man with a progressive spastic paraparesis that began 15 months after sustaining severe trauma in a motor vehicle accident was positive for antibodies to human T-lymphotropic virus type I (HTLV-I) by enzyme-linked immunosorbent assay. Serum antibody to HTLV-I was confirmed by Western blot and radioimmunoprecipitation assay. We detected specific proviral DNA in peripheral blood lymphocytes by the polymerase chain reaction. Because the incidence of HTLV-I is generally restricted to Southern Japan and Caribbean black populations, the most likely source of HTLV-I infection in this patient was multiple intraoperative blood transfusions. The relatively short interval between transfusion and development of HTLV-I-associated myelopathy is consistent with the more rapid evolution of this clinical syndrome compared with adult T-cell leukemia.     

Serum interleukin-2 concentrations in Guillain-Barré syndrome and chronic idiopathic demyelinating polyradiculoneuropathy: comparison with other neurological diseases of presumed immunopathogenesis

Serum concentrations of the cytokine interleukin-2 (IL-2) were quantitated by enzyme-linked immunosorbent assay in 42 patients with Guillain-Barré syndrome, 15 patients with chronic idiopathic demyelinating polyradiculoneuropathy, 37 patients with other neuropathies, 54 patients with other noninflammatory, nondemyelinating neurological disorders, and 26 healthy control subjects. We found markedly increased serum levels of IL-2 in patients with Guillain-Barré syndrome and to a much lesser extent, in patients with chronic idiopathic demyelinating polyradiculoneuropathy. Increased serum concentrations of IL-2 in patients with Guillain-Barré syndrome returned to normal in parallel with recovery from the disease. These findings suggest ongoing T-cell proliferation in patients with Guillain-Barré syndrome and some patients with chronic idiopathic demyelinating polyradiculoneuropathy. IL-2 levels were also raised in patients with active multiple sclerosis, myasthenia gravis, and herpes simplex encephalitis, and some patients with polymyositis, invoking T cells in the pathogenesis of these diseases.     

Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells

Six adult patients had a chronic progressive myelopathy that possessed the following features: high antibody titers to human T-lymphotropic virus type I (HTLV-I) in serum and cerebrospinal fluid (CSF); predominantly upper motor neuron disorder, symmetrical, with mild sensory and bladder disturbances; and presence of adult T-cell leukemia-like cells in both peripheral blood and CSF. We refer to this entity as HTLV-I-associated myelopathy (HAM). Electrophoretic studies of immunoglobulin G in CSF using Western blot analysis characteristically demonstrated p24 and p32 bands. Rates of intra-blood-brain barrier synthesis were determined and found increased in the patients with HAM. Corticosteroid treatment produced clinical improvement in all of 4 patients. A retrospective survey of CSF samples was carried out in 287 patients with neurological disorders, and 6 additional patients with HAM were identified.     

Absence of highly homologous sequence to HTLV-I in Japanese multiple sclerosis

We tried to detect HTLV-I-related sequences in Japanese patients with multiple sclerosis with a highly sensitive method that employs the polymerase chain reaction (PCR) of genomic DNA followed by Southern blot hybridization analysis. To amplify HTLV-I sequences, we used primers for LTR, pol, gag, and env coding regions. Fourteen patients with definite MS, 14 disease controls, 12 normal controls, and 3 patients with HTLV-I-associated myelopathy (HAM) were investigated. Results of particle aggregation assay for HTLV-I antibodies were negative in serum from all subjects except for the 3 HAM patients. Neither the 14 MS patients nor the 26 controls showed the presence of any highly homologous sequences to HTLV-I. We did observe faint signals for gag, pol, and env coding regions only at low stringent hybridization in some MS patients as well as some normal controls. The nucleotide sequence analysis of the faint bands was more homologous to major histocompatibility complex molecules than the HTLV-I genome.     

Plasmapheresis in neurology. Critical analysis of indications and protocols]

Therapeutic plasmapheresis (plasma exchange) in neurology is a matter of discussion. We review the main articles on clinical trials, both controlled and uncontrolled, trying to establish the efficacy and safety of the procedure. Humoral aspects involved in the genesis of the disorder play an important role for its indication in the present time. In myasthenia gravis indications for plasmapheresis are established: in the preparation for thymectomy, in patients with respiratory insufficiency and requiring respiratory prosthesis, after long immunosuppression therapy with rebound effect, when all other forms of therapy failed, and in neonatal myasthenia gravis with special technics. We discuss the indication of plasmapheresis in Guillain-Barré syndrome, multiple sclerosis, chronic inflammatory demyelinating polyneuromyelopathy, HTLV-1 myelopathy, HIV peripheral neuropathy and myelopathy, paraproteinemias, polymyositis, and dermatomyositis. Indications for other diseases are mentioned. Reference is made to the results we observed in 31 cases followed consecutively at Hospital dos Servidores, Rio de Janeiro, from June 1984 to June 1990. In our series 26 were myasthenic patients, 4 patients presented Guillain-Barré syndrome, and 1 multiple sclerosis. Therapeutic plasmapheresis protocols suggested by us are summarized.     

Unusual neurophysiological and immunological findings in myasthenia gravis: a case report

We describe the case of a male patient with ocular myasthenia gravis who developed a diabetic neuropathy similar to chronic inflammatory demyelinating polyradiculoneuropathy associated with transient generalized 'myokymic' discharges and distal weakness. He had antibodies against acetylcholine receptor and GQ1b ganglioside, but not anti-voltage-gated K(+) channel antibodies. Serial electrophysiological and immunological findings showed that diabetes was involved in the immune-mediated mechanism of peripheral neuropathy. We hypothesize that the concomitant appearance of distal motor weakness and decreased compound muscle action potentials upon repetitive nerve stimulation, together with increased distal motor latency and generalized peripheral nerve hyperexcitability, were all related to transient serum positivity to anti-GQ1b antibodies.     

Human T-cell lymphotropic virus type I and neurologic disease in Panama, 1985 and 1986

Human T-cell lymphotropic virus type I (HTLV-I) causes adult T-cell leukemia and has recently been associated with HTLV-associated myelopathy/tropical spastic paraparesis. The HTLV-I is endemic throughout the Caribbean basin and parts of South America, and HTLV-associated myelopathy/tropical spastic paraparesis also seems to be common in this area. This 2-year study, 1985 and 1986, was designed to evaluate the occurrence of HTLV-I infection in all newly diagnosed cases of selected neurologic diseases in Panama City, Panama. Six (8%) of 71 patients had antibody to HTLV-I detected by immunofluorescence, enzyme-linked immunosorbent assay, radioimmunoassay, and Western blot assays; 5 patients' conditions were diagnosed as spastic paraparesis, and all 5 were seropositive and also had HTLV-I antibody in cerebrospinal fluid. The remaining seropositive patient had multiple sclerosis, and no antibody was detected in her cerebrospinal fluid. Clinical and electrophysiologic studies indicated that HTLV-I-associated spastic paraparesis is a multifocal, primarily demyelinating disease that principally involves the spinal cord.     

Human T-lymphotropic virus type I antibodies in the serum of patients with tropical spastic paraparesis in the Seychelles

Tropical spastic paraparesis (TSP), a chronic myelopathy of unknown etiology, was studied in the Seychelles. Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus antibodies were determined using an enzyme-linked immunosorbent assay and confirmed with an indirect fluorescent antibody test in serum samples of 20 patients with TSP and 16 controls. Test results indicated that 17 patients (85%) and two controls (transverse myelopathy and clinically probable multiple sclerosis) were positive for HTLV-I. Serum samples of nine healthy controls and five with other neurologic diseases were negative for HTLV-I. No serum samples were positive for human immunodeficiency virus. Estimated relative risk for TSP in those subjects whose serum is positive for HTLV-I antibodies is 40. This result is highly statistically significant. Although primarily associated with adult T-cell leukemia and non-Hodgkin's lymphoma, HTLV-I could also be an etiologic agent of TSP.     

Neurological manifestations of gastrointestinal disorders, with particular reference to the differential diagnosis of multiple sclerosis

. Neurological manifestations of gastrointestinal disorders are described, with particular reference to those resembling multiple sclerosis (MS) on clinical or MRI grounds. Patients with celiac disease can present cerebellar ataxia, progressive myoclonic ataxia, myelopathy, or cerebral, brainstem and peripheral nerve involvement. Antigliadin antibodies can be found in subjects with neurological dysfunction of unknown cause, particularly in sporadic cerebellar ataxia ("gluten ataxia"). Patients with Whipple's disease can develop mental and psychiatric changes, suprancuclear gaze palsy, upper motoneuron signs, hypothalamic dysfunction, cranial nerve abnormalities, seizures, ataxia, myorhythmia and sensory deficits. Neurological manifestations can complicate inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease) due to vascular or vasculitic machanisms. Cases with both Crohn's disease and MS or cerebral vasculitis are described. Epilepsy, chronic inflammatory polyneuropathy, muscle involvement and myasthenia gravis are also reported. The central nervous system can be affected in patients with hepatitis C virus (HCV) infection because of vasculitis associated with HCV-related cryoglobulinemia. Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a disease caused by multiple deletions of mitochondrial DNA. It is characterized by peripheral neuropathy, ophthalmoplegia, deafness, leukoencephalopathy, and gastrointestinal symptoms due to visceral neuropathy. Neurological manifestations can be the consequence of vitamin B1, nicotinamide, vitamin B12, vitamin D, or vitamin E deficiency and from nutritional deficiency states following gastric surgery.     

Cold reactive antilymphocyte antibodies in neurological diseases.

Cold reactive (15 degrees C) antilymphocyte antibodies were detected in the sera of 33% of patients with multiple sclerosis, 50% with Guillain-Barré syndrome, 42% with myasthenia gravis, and 38% with polymyositis. We did not detect such antibodies against autologous cells in multiple sclerosis. In multiple sclerosis there was no correlation between the presence of antilymphocytic antibodies and disease activity or duration. In patients with multiple sclerosis, myasthenia gravis, and polymyositis there was no correlation between the presence of cold reactive antilymphocyte antibodies and abnormalities of T or B cell levels.     

HTLV-I-associated myelopathy: oligoclonal immunoglobulin G bands contain anti-HTLV-I p24 antibody

Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) and tropical spastic paraparesis belong to a new group of neurological diseases associated with retroviral infection. An HTLV-I-like virus has recently been implicated in multiple sclerosis as well. We studied paired cerebrospinal fluid and serum specimens from HAM and multiple sclerosis patients by isoelectric focusing and an isoelectric focusing HTLV-I p24 overlay technique to clarify the role of HTLV-I in these diseases. We detected oligoclonal bands by isoelectric focusing with silver-staining in cerebrospinal fluid, but not serum, from all 5 HAM and all 9 multiple sclerosis patients. An isoelectric focusing HTLV-I p24 overlay technique demonstrated anti-p24 antibody in HAM cerebrospinal fluid at a different pI distribution than that seen in paired serum, indicating local synthesis of anti-p24 antibody within the central nervous system. Oligoclonal bands in HAM cerebrospinal fluid corresponded in pI distribution to anti-p24 antibody activity, suggesting the presence of an ongoing HTLV-I infection in the central nervous system. Multiple sclerosis patients had no evidence of anti-HTLV-I activity by p24 radioimmunoprecipitation assay, Western immunoblots, or isoelectric focusing HTLV-I p24 overlay analysis. Our data support a role for HTLV-I as an etiological agent in HAM, but not in multiple sclerosis.     

AIDS-related vacuolar myelopathy is not associated with coinfection by human T-lymphotropic virus type I

Assessment of antibodies against human T-lymphotropic virus type I (HTLV-I) by enzyme-linked immunoassay, immunofluorescence, and Western blot was undertaken in patients with pathologically or clinically diagnosed acquired immunodeficiency syndrome-related vacuolar myelopathy to determine whether this retrovirus could be etiologically implicated in this disorder. No serological evidence for HTLV-I was found in the patients with vacuolar myelopathy, though 1 patient with an atypical myelopathy did have antibodies against HTLV-I.     

Predictive value of anti-GM1 ganglioside antibodies in neuromuscular diseases: a study of 180 sera

The incidence of anti-GM1 antibodies in the serum of 104 patients with neurological diseases, 35 patients with non-neurological diseases (NND) and 41 normal controls was determined by enzyme-linked immunosorbent assay (ELISA). Anti-GM1 antibodies were found in 90% of patients presenting with a motor neuropathy (all except one had multifocal conduction blocks). A large proportion (60%) of these patients displayed high antibody titer ranging from 101 to 788. A low incidence of anti-GM1 antibodies was found in the other groups of patients, i.e. 21% of amyotrophic lateral sclerosis (ALS), 26% of other neurological diseases (OND) and 23% of NND. High antibody titers ranging from 106 to 260 were found in two (5%) ALS patients, one (2%) OND patient (myasthenia gravis), and one (3%) NND patient (Waldenstr?m's disease). This study shows that high titers of anti-GM1 antibodies are found in a large proportion of patients with motor neuropathy with multifocal conduction blocks. This argues for a possible autoimmune origin of this neuropathy. We suggest that anti-GM1 antibody determination should be included systematically in the evaluation of all patients with motor neuron diseases and predominantly motor neuropathies.     

HTLV-I-associated myelopathy and polymyositis in a US native

A patient who had always lived in the United States had an HTLV-I infection and a chronic myelopathy clinically mimicking amyotrophic lateral sclerosis. Needle EMG and nerve conduction studies were consistent with anterior horn cell disease but muscle biopsy showed denervation and an inflammatory myopathy. Serum HTLV-I antibody tests were positive and HTLV-I DNA was present in peripheral leukocytes. This is the 1st reported US native with HTLV-I-associated myelopathy and polymyositis.     

Human T-cell lymphotropic virus type I (HTLV-I) confirmed by PCR-Southern blot and sequencing analysis in a woman with tropical spastic paraparesis

Abstract Human T-cell lymphotropic virus type I (HTLV-I) is a human retrovirus and the aetiological agent of a progressive neurological disease called tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), as confirmed by evidence accumulated in HTLV-I seroprevalence studies. TSP/HAM is rarely diagnosed in Italy, given the low prevalence of HTLV-I in the population. TSP/HAM begins insidiously in the fourth decade, mainly with spastic paraparesis of the lower extremities and positive Babinski reflex, as well as interfering with bowel and bladder functions. In this study we report the clinical, virological and haemato chemical data of a 54-year-old woman, born in the Ivory Cost, with symptoms suggestive of TSP. The presence of HTLV-I infection was demonstrated by the detection of antibodies in serum and in cerebrospinal fluid by immunoenzymatic assay and Western blot analysis. In addition, viral isolation was carried out in peripheral blood cells, and the presence of HTLV-I proviral DNA was confirmed by polymerase chain reaction/Southern blot and sequencing analysis. According to our results, HTLV-I testing might be useful when TSP/HAM is suspected.     

Presence of human T lymphotropic virus type I in two patients with progressive myelopathy in Puerto Rico

Two patients from Puerto Rico with progressive paraparesis had serum positive for human T lymphotropic virus type I (HTLV-I) antibodies by ELISA and Western blot, and one patient had HTLV-I antibodies in CSF by the ELISA method. Although the Caribbean basin is considered to be an endemic area for tropical spastic paraparesis, this is the first report of the isolation of HTLV-I antibodies in the serum and CSF of patients with chronic myelopathies in Puerto Rico.     

Ryanodine receptor autoantibodies in myasthenia gravis patients with a thymoma.

Sera from patients with myasthenia gravis were examined by Western blot for the presence of antibodies to proteins of the sarcoplasmic reticulum from rabbit skeletal muscle. Fourteen of 30 patients with myasthenia gravis and a thymoma had IgG autoantibodies to the calcium release channel of the sarcoplasmic reticulum (the ryanodine receptor), which plays a crucial role in the mechanism of excitation-contraction coupling in striated muscle. Ryanodine receptor autoantibodies were not detected in any of the 45 sera from patients with myasthenia gravis without a thymoma. Ryanodine receptor autoantibodies may have pathogenetic relevance in thymoma-associated myasthenia gravis.     

A study of three patients with amyotrophic lateral sclerosis and a polyneuropathy resembling CIDP

We report three patients with a syndrome that fulfilled clinical and laboratory criteria for definite chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who failed immunosuppressive treatment and eventually developed progressive amyotrophic lateral sclerosis (ALS). Mean disease duration was 23 months (13-38) before death. Two patients had a family history of ALS without mutations of the SOD1 gene. Postmortem examination in one patient showed an endoneurial infiltration of mononuclear cells in lumbar roots and distal and proximal peripheral nerves, mainly around myelinated fibers, with demyelination and axonal loss, consistent with CIDP. The spinal cord revealed severe neuronal loss in the anterior horn, axonal loss in the corticospinal tract, and large numbers of phagocytes in the anterior and lateral tracts, indicative of ALS. Whether demyelinating polyneuropathy was coincident with ALS or was a cause or consequence of motor neuron degeneration in these patients remains to be elucidated. This unusual combination may provide an important clue in elucidating the pathogenesis of ALS in some patients.     

Serum IgG and IgM anticardiolipin antibodies in neurological diseases

To determine whether anti-cardiolipin antibodies (ACA) are associated with multiple sclerosis (MS) or myasthenia gravis (MG), sera from 42 patients suffering from MS and from 21 patients with myasthenia were studied, using an enzyme-linked immunosorbent assay (ELISA). No significant difference in IgG or IgM immunoglobulin isotypes between the MS myasthenic patients and controls was found.