Luis Cartier R

Resonancia Magnética de médula espinal y cerebro en el correlato clínico de la paraparesia espástica progresiva que se asocia al virus humano linfotrópico tipo-I (HTLV-I)

Background: The spastic paraparesis associated to HTLV-1 causes degenerative pyramidal tract lesions of the spinal cord and affects cortical-nuclear connections in the brain. Aim: To report the findings of magnetic resonance imaging in patients with spastic paraparesis. Material and methods: A magnetic resonance imaging of the brain and spinal cord was performed in 30 patients (24 females), mean age and evolution of 56 and 12 years respectively, with a clinical and virological diagnosis of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Results: No patient had abnormal signals in the spinal cord parenchyma. However, an atrophy of the dorsal segment was observed in 87% of patients. Patients with the highest degree of atrophy showed a higher degree of functional impairment. Eleven patients had spinal cord conus atrophy, associated to neurogenic bladder or impotency. In 80% of patients, hyperintense subcortical white matter images in DP, T2 and Flair, mostly bi frontal, were detected. In half of them, small rounded and isolated images were observed. In the other half, eight or more images, generally larger and occasionally confluent, were found. Ten of 12 patients with confluent brain lesions showed different degrees of cognitive impairment. No patient had lesions in the corpus callosus, periventricular white matter, pons, medulla oblongata or cerebellum. Conclusions: Most patients with tropical spastic paraparesis have alterations in brain or spinal cord magnetic resonance imaging. The magnetic resonance lesions are concordant with functional impairment. The characteristics of the imaging in TSP/HAM patients can be helpful in the differential diagnosis of patients with paraparesis (Rev Med Chile 2006; 134: 1011-20). (Key words: Human T-lymphotropic virus 1; Magnetic resonance imaging; Paraparesis, tropical spastic)

Inmunohistoquímica de los cambios degenerativos del sistema nervioso central en paraparesias espásticas asociadas al virus linfotrópico humanoTtipol(HTLV-l)

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%), included in paraffin, and stained with Haematoxylin and Luxol-fast-blue. Immunohistochemical study was made with anti-neurofilament antibodies 1:100 (MO762, DAKO), anti-APP 1:20 (Rabbit Pre Amyloid protein 51-2700 ZYMED), antitau 1:100 (A0024 DAKO) 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. Neuronal injury was absent. Conclusions: The systematic damage of motor and sensitive tracts of the spinal-cord and the absence of neuronal damage, defines a degenerative process limited to axons. This central axonopathie could be caused by a disturbance of axoplasmic transport (Rev Med Chile 2007; 135: 1139-46). (Key words: Axonal injury, diffuse; Human T-lymphotropic virus; Paraparesis, tropical spastic)

Proteína Tax (HTLV-I), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP

Human T-cell lymphotropic virus type I (HTLV-I) isa retrovirus that influences cellular metabolism modifying biological responses. This results inoncogenic, degenerative or inflammatory changes. The myelopathy associated to HTLV-I ortropical spastic paraparesia (HAM/TSP) is a mainly degenerative response to the virus infection.On the other hand, Sjogren syndrome has an inflammatory appearance. Theimmunohistochemical study of CD-4, CD-8 and CD45 lymphocytes, metalloproteinase MMP-9and viral Tax protein in pathological samples of salivary glands may help to differentiateprimary from viral Sicca syndrome.

Leucemia linfoma T del adulto en Chile.: Estudio clínico-patológico y molecular de 26 pacientes

Background: Adult T cell leukemia lymphoma is a lymphoproliferative syndrome etiologically associated to human T cell lymphotropic virus type I. Aim: To describe the clinical and laboratory features of 26 Caucasian Chilean patients, with HTLV-I positive adult T-cell leukemia lymphoma (ATLL). Material and methods: Diagnostic criteria included clinical features, cell morphology, immunophenotype, HTLV-I serology and/or DNA analysis by Southern blot or PCR. Results: According to the clinical presentation, 12 cases had the acute ATLL form, 6 had a lymphoma, 4 the chronic form and 4 had smoldering ATLL. The median presentation age was 50 years, younger than the Japanese patients, but significantly older than patients from other South American countries (eg Brasil, Jamaica, Colombia). The main clinical features: lymphadenopathy, skin lesions and hepatosplenomegaly, were similar in frequency to those of patients from other countries, except for the high incidence of associated neurological disease. Tropical Spastic Paraparesis (TSP) in our series of ATLL, was seen in one third of the patients (8/26). A T-cell immunophenotype was shown in all 26 cases and HTLV-I serology was positive in 25/26 patients. Molecular analysis on the seronegative patient showed clonal integration of proviral HTLV-I DNA into the lymphocytes DNA, and thus he may have been a poor responder to the retroviral infection. Proviral DNA integration was also demonstrated in 15/16 patients being clonal in 10, polyclonal in 3 (all smoldering cases) and oligoclonal in one. Conclusions: ATLL in Chile has similar clinical and laboratory features than the disease in other parts of the world, except for a younger age than Japanese patients but older than those from other Latin American countries and a high incidence of patients with associated TSP. Detailed morphological and immunophenotypic analysis of the abnormal circulating lymphocytes, together with the documentation of HTLV-I by serology and/or DNA analysis are key tests for the identification of this disease.

Atrofia cerebelosa por el virus JC en un paciente con SIDA

La leucoencefalopatia multifocal progresiva es un proceso desmielinizante del SNC, que se caracteriza por la lisis de los oligodendrocitos infectados por el virus JC. La inmunodeficiencia es un factor predisponente para adquirir la enfermedad y al menos el 5% de los pacientes con SIDA pueden desarrollar una LMP. Entre pacientes infectados con VIH tambien se ha descrito una lisis de las celulas granulosas del cerebelo y atrofia cerebelosa, atribuida a una variante del virus JC. Se presenta un hombre de 37 anos portador de VIH, que consulta por vertigos posturales, seguidos de alteraciones de la marcha y un sindrome cerebeloso, palabra escandida, hiperreflexia, reflejos pendulares, Babinski y un leve deterioro cognitivo. La RM cerebral mostro areas de hiperintensidad en T2 de la substancia blanca en los hemisferios cerebrales, en los talamos y en estructuras bulbo-protuberanciales, asociadas a una atrofia incipiente del cerebelo. El LCR era normal, salvo la PCR positiva para el VJC. El paciente estaba con terapia antiretroviral que se mantuvo. Una segunda RM, ocho meses despues, mostro leve aumento de las lesiones de los hemisferios cerebrales, de la protuberancia y del hemisferio cerebeloso izquierdo, pero se habia incrementado la atrofia de la corteza cerebelosa. Despues de dos anos, el paciente ha mantenido el sindrome cerebeloso, que unido a la detencion clinica de la enfermedad y ala atrofia del cerebelo, sugieren que este paciente pudiera tener una doble infeccion por VJC tanto de la variedad tipica como de la mutante. Este seria el primer caso de atrofia cerebelosa por el VJC pesquisado en Chile.

Caídas y alteraciones de la marcha en los adultos mayores

There is a higher frequency of falls in the elderly than in young people, due to age related physiological changes in gait. There is a lower amplitude of pelvic movements that affects gait efficiency. Equilibrium is also disturbed since the trunk assumes the leadership of gait, displacing the pelvis. Many diseases of elderly individuals, such as Parkinson disease, spastic paraparesis, cerebrovascular accidents or neuropathies, further impair the gait. Therefore, after the age of 65, all falls must be considered symptomatic (Rev Med Chile 2002; 130: 332-7)

Paraparesia espástica progresiva asociada a HTLV-I en Chile: Estudio y seguimiento de 121 pacientes por diez años

Se revisan las paraparesias espasticas progresivas del adulto (PEPAs) producidas por el HTLV-I, en 121 pacientes chilenos. Se analizan los aspectos epidemiologicos, clinicos, diagnosticos, las enfermedades asociadas, y la patogenia. El seguimiento de los pacientes durante varios anos permitio definir el perfil evolutivo, establecer las causas de muerte y estudiar el comportamiento del virus. De los casos con anatomia patologica surgieron hipotesis, que han permitido definir mecanismos de dano, sustentados en estudios inmunohistoquimicos. Se pudo confirmar que la enfermedad del SNC es un proceso degenerativo, vinculado a una axonopatia central que expresa fallas del transporte axoplasmico, que afecta particularmente la via corticoespinal, aunque existe un compromiso mas extenso mielo-encefalico. Ademas, el virus es capaz de producir una enfermedad multisistemica, que puede comprometer simultaneamente el sistema nervioso, el sistema hematologico, las glandulas exocrinas, el parenquima hepatico, pulmonar, muscular y oseo.

Forma familiar de la enfermedad de Creutzfeldt-Jakob: marcadores genéticos en 4 familias chilenas

brain of affected individuals. Chile has a prevalence of CJD that is more than twice than in the rest of the world and has the highest rate of familial forms. These later forms are associated with the heterozygocity of codon 200 of PrP protein gene. Aim: To search susceptibility genetic markers of CJD in members of families affected by CJD. Material and methods: A blood sample was obtained from 50 individuals pertaining to four families affected by CJD. DNA from peripheral mononuclear cells was amplified by polymerase chain reaction and sequenced for the gene that codifies PrP protein. Results: In family A, 21 of 23 members were homozygotes for codon 129 (Met/Met) and eight were simultaneously heterozygotes for codon 200 (Glu/Lys). In family B, six of nine members were homozygotes for codon 129, five were heterozygotes for codon 200 and four had both mutations. In family C, the four analyzed subjects were homozygotes for codon 129 and two were simultaneously heterozygotes for codon 200. In family D, nine of 14 members were homozygotes for codon 129 and two were simultaneously homozygotes for codon 200. No family had polymorphisms for codon 219. Conclusions: Thirty two percent of analyzed subjects were homozygotes for codon 129 and heterozygotes for codon 200, condition that defines the genetic susceptibility to acquire CJD. The dominant tendency of these genotypes could explain the higher incidence of CJF in Chile (Rev Med Chile 2006; 134: 1116-22).

Incremento de la actividad metaloproteinásica y de sus inhibidores en el líquido cefalorraquídeo, en pacientes con paraparesia espástica tropical

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% 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 ± 0.72, 3.85 ± 1.38 and 5.89 ± 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. (Rev Med Chile 2000; 128: 585-92).

Síndrome de meningitis y retención urinaria

The Meningitis-Retention Syndrome associates aseptic meningitis and neurogenic bladder, with a vesical dysfunction that outlasts meningitis widely. Urodynamic assessment shows a detrusor palsy with normal function of the external sphincter. We report a 24-year-old male admitted for headache, fever, myalgias and acute urinary retention, which was diagnosed as a urinary tract infection. Worsening of symptoms and slight meningeal signs prompted for a lumbar puncture that yielded a cerebrospinal fluid with 94 lymphocytes, in which etiological evaluation was inconclusive. Meningeal syndrome and myalgia subsided by the fifth day, while urinary retention persisted. A magnetic resonance imaging of the brain and spinal cord done at the fifth day, showed high intensity signals in basal ganglia and central spinal cord, not altered by contrast. These images disappeared in the imaging control performed two months later. Bladder dysfunction lasted at least until the second month of follow up.