Identificación clínica y patológica de las diversas formas de la enfermedad de Creutzfeldt Jakob en Chile / Clinical and pathologic identification of different forms of Creutzfeldt Jakob disease in Chile

Background: The identification of clinical and pathological forms of Creutzfeldt Jakob Disease (CJD) started with the first cases of the disease. Genetic and biomolecular prion status assessment are allowing now a better classification. Aim: To identify the clinical forms of the disease that exist in Chile, based on clinical and neuropathological data. Patients and Methods: Review of records of 40 patients with CJD in whom a complete history, clinical details and neuropathological studies were available. Clinical aspects were grouped into five categories: behavioral and cognitive changes, sleep and alertness, visual impairment, motor disturbances, myoclonus and epilepsy. The neuropathological examination in each case allowed us to evaluate the damage of 13 areas of the central nervous system. Results: Five forms of CJD were identified. The classic form was present in 28 patients (70%), the Heidenhain form was present in five (12.5%), the ataxic form in four (10%), the form with Kuru plaques in two (5%) and the Vacuolar was present in one patient (2.5%). Conclusions: The variety and forms of CJD in Chile do not differ substantially from those found abroad.

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.

Proteína Tax ( HTLV-I ), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP / Viral Tax protein expression in salivary glands of patients infected with human t-cell lymphotropic virus type I and Sicca Syndrome

Background: Human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus that influences cellular metabolism modifying biological responses. This results in oncogenic, degenerative or inflammatory changes. The myelopathy associated to HTLV-I or tropical spastic paraparesia (HAM/TSP) is a mainly degenerative response to the virus infection. On the other hand, Sjögren syndrome has an inflammatory appearance. The immunohistochemical study of CD-4, CD-8 and CD45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein in pathological samples of salivary glands may help to differentiate primary from viral Sicca syndrome. Aim: To perform an immunohistochemical study of salivary glands of patients with HAM/TSP and Sicca syndrome and control subjects. Material and Methods: Pathological samples of salivary glands from 53 patients with HAM/TSP and Sicca syndrome and 10 control subjects, were studied. Immunohistochemistry was performed using antibodies against CD-4, CD-8 and CD-45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein. Results: Only in patients with HAM/TSP and Sicca syndrome, the presence of Tax protein was observed in CD-4 and CD-8 lymphocytes and in glandular acini. Conclusions: Patients infected with HTLV-I express Tax protein in salivary glands. This finding has diagnostic and pathogenic implications.

Hemorragias cerebrales y angiopatía amiloidea / Cerebral amyloid angiopathy in brains of patients dying of non traumatic cerebral hemorrhages

Background: Cerebral amyloid angiopathy is considered pathogenic in non traumatic cerebral lobar hemorrhages. Aim: To study the frequency of cerebral amyloid angiopathy in brains of patients dying of non traumatic cerebral hemorrhages. Material and methods: Thirty seven brains from patients, 25 men and aged 65ñ10 years old, with cerebral hemorrhages (14 lobar, 18 in basal ganglia and 5 in cerebellum or brainstem) were studied. As controls, the brains of 30 subjects, 14 men and aged 64ñ16 years old, dying of non neurological causes were studied. Deep and cortical vessels were stained with hematoxylin eosin, Gomori, Thioflavin T and Bodian. Definitive cerebral amyloid angiopathy was diagnosed when amyloid deposition was observed in the media of vessels. Results: Twenty six out of 32 patients dying of cerebral hemorrhage and 3 of 21 controls had chronic hypertension. Cerebral amyloid angiopathy was present in 19 of 37 brains of patients with cerebral hemorrhage and 13 of 30 control brains. In patients with hypertension, vascular changes independent of the location and volume of amyloid deposition, were observed. Such changes were dilatation, tortuousness, thickening of walls specially in muscular and adventitia and hyaline degeneration. Thirteen brains with hemorrhage had fibrinoid necrosis and 10 had microaneurysms. Conclusions: In this series of patients, cerebral amyloid deposition was unspecific and its role in the pathogenesis of cerebral hemorrhages was not confirmed. Hypertension was associated with vascular degenerative changes that can lead to cerebral hemorrhages

Mononeuropatía múltiple y vasculitis / Multiple mononeuropathy and vasculitis

Background: Seventy percent of vasculitis are neurologically expressed as multiple mononeuropathy (MM) or asymmetrical neuropathy (AN). Concurrent nerve and muscle biopsy increases the diagnostic accuracy of the disease. Aim: To define the pathological features of vascular damage in nerve and muscle in patients with MM or AN. Patients and methods: Between 1980 and 1997, 50 patients with a MM or AN diagnosis, based on neurological and neurophysiological findings, were studied at the Neurology Department of Hospital del Salvador. All underwent nerve and muscle biopsy (of the superficial peroneal nerve and the short peroneal muscle). Slices were stained with hematoxylin eosin, luxol fast blue and Gomori staining. Results: Forty two patients, aged 52 ñ 15 years old (29 female) had a vasculitis. These subjects with MM or AN associated to vasculitis, corresponded to 22 percent of neuropathies subjected to nerve biopsy at the Department in the study period. Thirty two cases (76 percent) had necrotizing arteritis, characterized by wall fibrinoid necrosis and lumen occlusion in large vessels (>100 microns), with Iymphoplasmocytic and macrophage infiltration. Ten cases showed an inflammatory reaction and endothelial proliferation without wall necrosis, specially in small epineural arteries. Vascular recanalization was found in 33 percent of cases. Diagnostic vascular changes were found in 87 percent of nerve biopsies and 53 percent of muscle biopsies. No definitive relationship between the intensity of vascular and nerve lesions was found. All muscle biopsies showed some degree of neurogenic atrophy and 5 had micro infarcts. Conclusions: Superficial peroneal nerve biopsy is diagnostic in most patients with MM or AN associated with vasculitis. Nerve and muscle biopsies are complementary in the diagnostic work up

Sindrome desmielinizante aislado del sistema nervioso central como expresión de una esclerosis múltiple tardía: estudio anatomoclínico de un caso / Isolated central nervous system cemyelinating syndrome as the clinical expression of a late multiple sclerosis: report of one case

We report a 56 years old male developed a transverse myelopathy with cuadriparesis,neurogenic bladder and a sensitive level at C4. Cerebral and spinal cord magnetic resonance imaging showed only one demyelinative lesion at the cervical level. Post morten neuropathological study showed segmental myelin loss without anatomical limits and with axonal preservation in the involved spinal cord segment. This lesion had the classical features of multiple sclerosis.The isolated lesion, the pathological findings and the delayed age of onset allow the definition of this case as an isolated nervous system demyelinative syndrome

Seroprevalencia del HTLV-I en familiares de pacientes con paraparesia espástica (HAM/TSP y PEP) / Seroprevalence of HTLV-I in the family of patients with spastic paraparesis (HAM/TSP and PEP)

The seroprevalence of HTLV-I was studied in parents, brothers, siblings and sexual partners of 147 patients with spastic paraparesis assocaited to HTLV-1 (HAM/TSP) and 84 patients with HTLV-1 negative spastic pararparesis (SP). Seroprevalence was 29.1 percent for HAM/SP and 0 percent for SP relatives (p<0.001); the last figure is similar to that of the general population. Seroprevalence in sexual partners was 65 percent, suggesting that sexual intercourse is the principal route of transmission. Likewise, seroprevalence in siblings of mothers with HAM/TSP or HTLV-1 positive was 17.6 percent, suggesting a high maternal transmission

Actividad de acetilcolinoesterasa en el cortex cerebral y nucleo de Meynert: estudio en cerebro humano normal / Acetylcholinesterase activity in the cerebral cortex and nucleus basalis of Meynert: study in the normal human brain

La actividad de acetilcolinoesterasa (AchE) es estudiada en 4 cerebros de pacientes sin patología neurológica ni psiquiátrica mediante el método de Karnovsky y Roots modificado. Se definen áreas AchE (+) en el hipocampo, donde se observan bandas de fibras aferentes a las capas piramidal y granulosa, así como somas neuronales AchE (+) en el sector CA1 y el subiculum. En el córtex frontal se reconoce un plexo de fibras AchE (+) relacionado con las capas III y V donde se observan neuronas piramidales con actividad AchE. En el córtex parietal la mayor actividad está relacionada a los somas de la capa III y a un haz de fibras en la capa I. En el núcleo basal de Meynert se aprecia gran cantidad de fibras y neuronas de 30 a 40 micrones AchE (+)

Estudio del núcleo basal de Meynert en hipoxia cerebral por para cardio-respiratorio / Study of the nucleus basalis of Meynert following cerebral hipoxia by cardio-respiratory arrest

Se estudia el cerebro de 2 mujeres de 18 y 26 años, fallecidas luego de una hipoxia cerebral por paro cardiorrespiratorio, y el de una paciente de 22 años sin patología neurológica. El caso de hipoxia que tenía el menor daño cortical, evidenció que su Núcleo de Meynert estaba proporcionalmente conservado. La seguna paciente con una extensa necrosis laminar de la corteza cerebral, desarrolló una degeneración del Núcleo de Meynert caracterizada por el menor tamaño y la pérdida de las neuronas. La observación se objetivó con un recuento de las neuronas mayores de 30 micrones en la región media del núcleo, que en el cerebro control fué de 369,6 (+ - 52,3); en el primer caso de 287,6 (+ - 58,7) N.S.); y en el segundo caso de 118,3 (+ - 36,3) p<0,005). También se midió el diámetro mayor de todas las neuronas en el sector de mayor densidad celular del Núcleo. El promedio fué de 30,8 (+ - 7,5) micrones en el control; 29,2 (= - 7,5) en el primer caso (NS); y 22,7 (+ - 6,7) en el segundo caso (p<0,01). Se postula que el Núcleo de Meynert se vería afectado por una degeneración retrógrada secundaria al daño cortical

Lipofuscinosis infantil tardía: estudio clínico-patológico de un caso esporádico y uno familiar / Late infant neuronal ceroid-lipofuscinosis: clinicopathological study of one familial and one sporadic cases

Se estudia una familia con tres hermanos afectados por lipofuscinosis ceroidea, cuya sintomatología se inicia alrededor de los 2 años, falleciendo al quinto año de vida. Los hallazgos neuropatológicos de uno de ellos se comparan con los de una paciente con lipofuscinosis ceroidea infantil tardía esporádica cuya sintomatología se inicia aproximadamente a los 2 años, pero con una evolución más prolongada, falleciendo a los 12 años de edad. A pesar de la diferente condición genética y evolución, los hallazgos neuropatológicos son esencialmente semejantes, caracterizadas por moderada atrofia cortical e intensa atrofia del cerebelo. En la microscopía se observan depósitos de lipofuscina de aspecto granuloso en la corteza, particularmente en las neuronas de las capas profundas y espongiosis de las capas superficiales, depósitos corpusculares en tálamo, subtálamo y sustancia nigra, pérdida acentuada de las neuronas de Purkinje con formaciones cactáceas de las dendritas y depósitos de lipofuscina, atrofia de las capas granular y molecular, desmielinización de las folias cerebelosas y palidez de los cordones laterales y posteriores en la médula

Degeneración espumosa de las neuronas del núcleo basal de Meynert en 20 casos de enfermedad de Creutzfeld-Jakob / Foamy neuronal degeneration in the nucleus basalis of Meynert in 20 cases of Creutzfeldt-Jakob disease

Se presenta el hallazgo en 20 casos de Enfermedad de Creutzfeldt-Jakob (ECJ) de una peculiar degeneración de las neuronas del núcleo basal de Meynert consistente en vacuolas citoplasmáticas que tienden a agregarse desplazando al núcleo y dando un aspecto "espumoso" a las neuronas. También se observan gránulos finos entre las vacuolas, así como en su interior, recordando la degeneración granulovacuolar del hipocampo. Estas alteraciones no se observan en 6 cerebros controles pareados por edad y sometidos al mismo procedimiento técnico. Se discute el significado de esta alteración y se sugiere que ella podría corresponder a un daño excitotóxico generado por la particular hiperexcitabilidad neuronal propia de la ECJ, posiblemente asociado a una degeneración retrógrada por lesión del terminal colinérgico cortical y a un déficit de factor de crecimiento nervioso