Inmunohistoquímica de los cambios degenerativos del sistema nervioso central en paraparesias esp sticas asociadas al virus linfotrópico humanoTtipol(HTLV-l) / Immunohistochemistry of degenerative changes in the central nervous system in spastic paraparesis associated to human T lymphotropic virus type I (HTLV-I)

Background: Human T lymphotropic virus type I is associated with tropical spastic paraparesis, that is a chronic and progressive disease which damages specially the cortiespinal tracts. The pathogenesis of this degenerative process remains unknown. Aim: To identify histopathological aspects that could suggest a pathogenic hypothesis we studied immunohistochemical features in spinal cords obtained from patients that died due to progressive spastic paraparesis. Patients and Methods: Five males and five females, who died between 1990 and 2000, with a mean age of 52 years and mean disease duration of 8.6, were studied. All had a complete clinical and virological diagnosis. Samples were obtained from the frontal motor cortex and spinal cord (cervical, dorsal and lumbar segments), were fixed in formol (10 percent), included in paraffin, and stained with Haematoxylin and Luxol-fast-blue. Immunohistochemical study was made with anti-neurofilament antibodies 1:100 (M0762, DAKO), anti-APP 1:20 (Rabbit Pre Amyloid protein 51-2700 ZYMED), anti-tau 1:100 (A0024DAKO) and anti-ubiquitine 1:50 (NCL UBIQm Novocastra). Results: All cases had demyelinization and axonal loss in the cortico-spinal tracts; distal and segmental demyelinization of Goll tract; axonal thickening, amyloid precursor protein deposits in the white matter; tau protein aggregation in the spinal cord oligodendrocytes; axonal ubiquitination of sensitive and motor tracts, and subcortical white matter. Neurona! injury was absent. Conclusions: The systematic damage of motor and sensitive tracts of the spinal-cord and the absence of neurona! damage, defines a degenerative process limited to axons. This central axonopathie could be caused by a disturbance of axoplasmic transport.

Incremento de la actividad metaloproteinásica y de sus inhibidores en el líquido cefalorraquídeo, en pacientes con paraparesia espástica tropical / Increased activity of matrix metalloproteinases and their tissue inhibitors in cerebrospinal fluid of patients with HTLV-1 associated tropical spastic paraparesis

Background: Proteolytic modifications of neuronal surfaces and the surrounding extracellular matrix are very important in neuronal development and regeneration. Increased activity of matrix metalloproteinases (MMPs) and their tissue inhibitors, due to secretion by macrophages and lymphocytes, occur in inflammatory processes that disrupt the blood brain barrier. However, neurons and microglia can also secrete these enzymes. Aim: To identify the type of MMP present in the cerebrospinal fluid (CSF) and changes in the expression of tissue inhibitors of metalloproteinases (TIMPs) in patients with HTLV-1 associated tropical spastic paraparesis. Patients and methods: CSF samples from 12 patients with HTLV-1 associated tropical spastic paraparesis and 12 healthy controls were obtained by an atraumatic lumbar puncture. The presence of MMPs was measured by zymography and the relative amounts of TIMPs were measured by immunowestern blot. Results: In the CSF of both controls and patients, a similar gelatinolytic band corresponding to proMMP-2 (latent form) was observed. In 83.3 percent of patients with HTLV 1 associated tropical spastic paraparesis, the MMP-9 was also present. TIMP-1, TIMP-2 and TIMP-3 were elevated 2.24 ñ 0.72, 3.85 ñ 1.38 and 5.89 ñ 3.4 fold, respectively, in the CSF of patients as compared to controls. Conclusions: Patients with HTLV-1 associated tropical spastic paraparesis have elevated activity of MMP-9 and levels of TIMPs in the CSF, when compared to healthy controls