Didier Smadja

HTLV-1 proviral load in peripheral blood mononuclear cells quantified in 100 HAM/TSP patients: A marker of disease progression☆

A high proviral load of human T cell lymphotropic virus type 1 (HTLV-1) in peripheral blood mononuclear cells (PBMCs) has been reported in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of the present study was to investigate the role of HTLV-1 proviral load in PBMCs (expressed as the number of copies per 10(6) PBMCs) in HAM/TSP disease course. One hundred consecutive HAM/TSP patients were recruited and assigned on the basis of the disability score and disease duration to either a rapid (n=38) or a slow (n=62) progression group. Thirty-four asymptomatic HTLV-1 carriers were also included. HTLV-1 proviral load was quantified in all HAM/TSP patients and asymptomatic subjects. The mean HTLV-1 proviral load was 6-fold lower in asymptomatic carriers than in HAM/TSP patients (18,224+/-24,811 vs. 107,905+/-96,651, p<0.0001) and significantly higher in rapid progression patients than in slow progression patients (146,469+/-98,943 vs. 84,270+/-87,912, p=0.0002). HTLV-1 proviral load in HAM/TSP patients was independent of age at the time of study, age at onset, and disease duration, and was not related to ophthalmological-associated disease or Chisholm grade. A high level of pulmonary lymphocytosis correlated with high HTLV-1 proviral load level (p=0.01). Our results suggest that the level of HTLV-1 proviral load in PBMCs parallels the course of HTLV-1 infection, being low in asymptomatic carriers and high and very high, respectively, in slow and rapid progression HAM/TSP patients. The magnitude of the HTLV-1 proviral load in PBMCs can be used as a biological marker of disease progression and could be a useful marker of disease activity in the monitoring of therapeutic trials.

Human T Lymphotropic Virus Type I (HTLV-I) Proviral Load in Cerebrospinal Fluid: A New Criterion for the Diagnosis of HTLV-I–Associated Myelopathy/Tropical Spastic Paraparesis?

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is associated with accumulation of HTLV-I-infected T cells in the central nervous system (CNS). However, data on HTLV-I proviral load in the CNS at the asymptomatic stage are still lacking. We measured HTLV-I proviral load in cerebrospinal fluid (CSF) cells from 17 patients with HAM/TSP and 25 asymptomatic carriers. The percentage of HTLV-I-infected cells in CSF cells and the CSF cell : peripheral blood mononuclear cell HTLV-I proviral load ratio were always >10% and >1, respectively, in the patients with HAM/TSP but were always <10% and <1, respectively, in the asymptomatic carriers. We propose that determination of HTLV-I proviral load in CSF cells should be included as a new parameter for the diagnosis of HAM/TSP.

Ossification of the ligamenta flava with severe myelopathy in a black patient. A case report.

Study Design. A case of symptomatic ossification of ligamenta flava in a black man from Martinique (French West Indies) is reported. Objectives. To show that ossification of ligamenta flava may be observed in racial groups other than Japanese people and that the postoperative prognosis of symptomatic ossification of ligamenta flava is not always excellent. Summary of Background Data. Ossification of ligamenta flava causing slowly progressive myelopathy or radiculopathy is rare. It usually occurs in the lower thoracic spine. Ossification of ligamenta flava has mainly been described as occurring in Japanese people and very rarely in Caucasians. Diagnosis is based on a computed tomographic scan or magnetic resonance imaging, and postoperative prognosis is usually good. Methods. Low thoracic ossification of ligamenta flava was diagnosed in a black man from Martinique, based on the computed tomographic scan data and on the histopathologic examination of the removed tissue. The patient was clinically evaluated before and 1 year after the operation. A postoperative computed tomographic scan was performed. A magnetic resonance image was not available in this case. Results. The patient exhibited severe subacute myelopathy. After decompression, the neurologic recovery was incomplete. A postoperative computed tomographic scan showed complete excision of ossification of ligamenta flava and decompression of the spinal cord. Conclusions. Ossification of ligamenta flava may occur in black people. An incomplete postoperative recovery may be observed in such cases of unusual subacute compressive myelopathy.

Un nouveau cas d'ataxie cérébelleuse à anticorps anti-GAD traité par corticoïdes et initialement séronégatif

INTRODUCTION Cerebellar ataxia with antiglutamic acid decarboxylase antibodies (GAD-ab) is an exceptional newly recognized autoimmune disorder. The cerebellar ataxia may occur in isolation or be associated with stiff man syndrome another rare GAD-Ab induced disorder of central nervous system. EXEGESIS A 38-year-old woman with a past history of Graves disease presented with insidious cerebellar symptoms including ataxic gait, dysmetria, dysarthria, and oscillopsia. A thorough survey of markers of paraneoplastic cerebellar ataxia and collagen diseases was negative. Her serum contained high level of GAD-ab (647.2 U/ml) and MRI evidenced pure cerebellar atrophy leading to diagnosis of autoimmune cerebellar ataxia. Under corticosteroids, cerebellar symptoms partially improved, but serum GAD-ab titre dramatically decreased. CONCLUSION Testing for GAD-ab may be indicated in patients with idiopathic cerebellar ataxia, particularly mature women with organ-specific autoimmune diseases. Corticosteroids must be started to prevent irreversible cerebellar atrophy.

Communication brèveUn nouveau cas d'ataxie cérébelleuse à anticorps anti-GAD traité par corticoïdes et initialement séronégatifA new case of cerebellar ataxia with anti-GAD antibodies treated with corticosteroids and initially seronegative

INTRODUCTION Cerebellar ataxia with antiglutamic acid decarboxylase antibodies (GAD-ab) is an exceptional newly recognized autoimmune disorder. The cerebellar ataxia may occur in isolation or be associated with stiff man syndrome another rare GAD-Ab induced disorder of central nervous system. EXEGESIS A 38-year-old woman with a past history of Graves disease presented with insidious cerebellar symptoms including ataxic gait, dysmetria, dysarthria, and oscillopsia. A thorough survey of markers of paraneoplastic cerebellar ataxia and collagen diseases was negative. Her serum contained high level of GAD-ab (647.2 U/ml) and MRI evidenced pure cerebellar atrophy leading to diagnosis of autoimmune cerebellar ataxia. Under corticosteroids, cerebellar symptoms partially improved, but serum GAD-ab titre dramatically decreased. CONCLUSION Testing for GAD-ab may be indicated in patients with idiopathic cerebellar ataxia, particularly mature women with organ-specific autoimmune diseases. Corticosteroids must be started to prevent irreversible cerebellar atrophy.