Enfermedades por virus lentos del sistema nervioso central: ¿un nexo fisiopatogénico común? Vías hacia nuevos enfoques terapéuticos / Slow virus diseases of the central nervous system: a common physiopathogenic nexus? Paths towards new therapeutic approaches

Las enfermedades por virus lentos del sistema nervioso central (SNC) son aquellas en las que el periodo de incubación previo a las manifestaciones clínicas es muy prolongado y se mide en meses e incluso en años. Nos proponemos revisar la concepción actual existente sobre la fisiopatogénesis de estas enfermedades, con el fin de abrir el debate sobre nuevos enfoques terapéuticos, dado el oscuro pronóstico y el escaso éxito de los tratamientos actuales para ellas. El enfoque clásico ante cualquier enfermedad infecciosa es el de actuar frente al patógeno. En este artículo expondremos el importante papel que puede desempeñar el sistema inmune en estas afecciones y, por tanto, la posibilidad de un enfoque terapéutico desde el punto de vista de la inmunomodulación. Nuestra opinión es que los pacientes quizá se beneficien de combinar la estrategia clásica antiviral (inosiplex, ribavirina, IFN-alfa) con el uso de inmunomoduladores del tipo de la pentoxifilina, o de los nuevos que se describen (hormona estimulante de los melanocitos alfa [MSH-alfa], dexanabinol). Mientras, no existan fármacos antivirales específicos de cada uno de estos patógenos, los inmunomoduladores podrían aportar un beneficio clínico como fármacos adyuvantes o paliativos. Esto supondría, no sólo una innovación en el tratamiento de estas enfermedades, sino también un cambio en la concepción del enfoque terapéutico, poniendo al sistema inmune en el mismo plano de importancia que el propio virus (AU)

[Atherosclerosis and chronic persistent virus infection]. / Ateroskleroz i khronicheskaia persistentnaia virusnaia infectsiia.

Clinical, epidemiological and serological data as well as literature reviews were used to formulate and substantiate a concept on the presence of cause-sequel (etiological) relation between chronic persistent (slow) infection caused by the Epstein-Barr herpes virus (chronic infectious mononucleosis) and atherosclerosis. Detailed findings of the etiologic agent of atherosclerosis makes it possible to plan principally new ways of its diagnosis, treatment and prophylaxis.

Prion dementia without characteristic pathology.

Gerstmann-Sträussler syndrome (GSS) was diagnosed in a family with presenile dementia by prion protein gene analysis. Extensive histological examination of the brain of an affected individual from this family showed no characteristic features of GSS or Creutzfeldt-Jakob disease (CJD). Thus "spongiform encephalopathy" (GSS or CJD) cannot always be excluded on neuropathological grounds in an individual dying of a dementing condition, and the true prevalence of these diseases is likely to be underestimated. Screening by prion protein gene analysis will help to determine the full clinical and neuropathological phenotype in familial cases. This observation may be relevant to the assessment of possible transmission of bovine spongiform encephalopathy to man.

[The role of maternal virus-specific cytotoxic T-lymphocytes in the immunopathology of congenital influenza infection in mice]. / Rol' materinskikh virusspetsificheskikh tsitotoksicheskikh T-limfotsitov v immunopatologii pri vrozhdennoi grippoznoi infektsii u myshei.

Using 51Cr isotope label it was demonstrated that a very low per cent of syngeneic lymphocytes derived from healthy donors and inoculated in the blood stream of uninfected or influenza virus-infected pregnant mice is found in fetuses before delivery. Similar results were obtained after inoculation of virus-specific cytotoxic lymphocytes (CTL) into uninfected pregnant mice. After inoculation into the blood stream of infected pregnant mice of virus-specific CTL their migration into fetuses before delivery increases, being most marked in 25-30% of mice. Intravenous inoculation of excess CTL (10(6) cells) to infected pregnant mice resulted in rapid development of signs of slow influenza infection in the progeny with typical clinical picture and histopathological lesions in organs and tissues. Large doses (10(7)-10(8) cells) of CTL inoculated into the blood stream cause higher reduction and death of fetuses and increase the rate of stillbirths. The role of maternal virus-specific CTL in the pathogenesis of experimental congenital and especially slow influenza infection is discussed.

Gerstmann-Sträussler-Scheinker disease. I. Extending the clinical spectrum.

We present the clinical findings in affected members of a large kindred with Gerstmann-Sträussler-Scheinker disease. Sixty-four patients exhibited progressive ataxia, dementia, and parkinsonian features. Inheritance appears to be autosomal dominant. Impaired smooth-pursuit eye movements, defective short-term memory, clumsiness of the hands, and ataxia of gait develop in the late 30s to early 60s. Eye movement abnormalities are characteristic of cerebellar dysfunction. Dementia progresses gradually over several years. Later, rigidity and bradykinesia appear and, at this stage, there is often psychosis or severe depression with rapid weight loss. Death occurs in 6 months to 2 years after onset of rigidity. Magnetic resonance imaging in 2 affected individuals showed cerebellar atrophy. There is decreased T2 signal in the basal ganglia, consistent with iron deposition.

Diagnosis of Gerstmann-Sträussler syndrome in familial dementia with prion protein gene analysis.

The polymerase chain reaction was used to screen DNA samples from 12 unrelated individuals with various familial dementias and ataxias for mutation in part of the prion protein (PrP) gene, an abnormality that occurs in individuals with the spongiform encephalopathies, Gerstmann-Sträussler syndrome (GSS) and Creutzfeldt-Jakob disease. 2 members of a family in whom GSS was not previously suspected had a 0.15 kb insertion of similar size to that found in another kindred with pathologically proven spongiform encephalopathy. GSS may be more common than is currently realised; PrP gene analysis is potentially useful for diagnosis and genetic counselling in familial dementias and ataxias.

[Juvenile spongiform encephalopathy with unusual pathomorphologic findings]. / Encefalopatia spongiforme giovanile con insoliti reperti patomorfologici.

A 27-year-old man presented disturbances of gait and language, quickly followed by intellectual deterioration, tetraplegia, anarthria and myoclonus. Histological examination of a cerebral biopsy showed not only cortical changes consistent with the diagnosis of Creutzfeldt-Jakob disease, but also many amyloid-plaques with variable morphology. The diagnostic interpretation of the case particularly as to concern his relationship to s.c. Gerstmann-Strüssler syndrome is discussed.

Fragile X expression in Martin-Bell syndrome, intellectually normal individuals, and neoplasia, interpreted by a viral hypothesis.

We present data on fragile X expression in lymphocytes obtained from the following patients: a university student, an infertile couple, 6 of 22 prostatic cancer patients, a meningioma patient, and members of families with meningioma and familial gliomas. All patients were of normal intelligence. In addition, we report 3 cases of central nervous system (CNS) tumors in more typical fragile X families. We suggest that the fragile X expression as well as the clinical findings may be caused by a viral (or similar) infection. The virus may require a receptor protein coded by one allele of a gene on the X chromosome.