RESUMEN
Subacute sclerosing panencephalitis (SSPE) is a progressive, essentially untreatable, disease of the nervous system. When first described in the 20th Century, it was characterized more for its neuropathological features than for its pathophysiology or cause. It was not until the 1960s that a clear relationship to the measles virus was established. It is now thought that this uncommon infectious encephalopathy is caused by a "slow," altered or persistent form of the wild measles virus which has harbored in the nervous system for years. Then a "breakout" occurs and the more lytic and virulent organisms produce the progressive and spreading inflammatory and destructive lesions which are confined to the nervous system. Epidemiological study of the disease confirms its relationship to measles. In the years since the development of national measles immunization programs, there has been a dramatic decline in the incidence of measles exanthem and until recently a corresponding decline in the incidence of SSPE. In recent years there has been a mild to moderate increase in cases of SSPE as reported to the USA/International SSPE Registry. As yet, there has not been a totally effective treatment. The purpose of this paper is to give an overall review on SSPE and its relationship to measles. This review will include a prospectus of its history, considerations as to its etiology, correlation of clinicopathological features, and thoughts on the past and present epidemiology and treatment.
Asunto(s)
Encéfalo/patología , Encéfalo/virología , Sarampión/virología , Panencefalitis Esclerosante Subaguda/patología , Panencefalitis Esclerosante Subaguda/virología , Adolescente , Preescolar , HumanosAsunto(s)
Enfermedades Desmielinizantes/diagnóstico , Degeneración Nerviosa , Enfermedades del Sistema Nervioso/diagnóstico , Adolescente , Encéfalo/patología , Niño , Preescolar , Enfermedades Desmielinizantes/etiología , Diagnóstico Diferencial , Humanos , Lactante , Enfermedades del Sistema Nervioso/etiologíaRESUMEN
We report the first observation of a chromosome abnormality in a patient with typical juvenile ceroid-lipofuscinosis (NCL), who was found to have an apparently balanced translocation between chromosomes 10 and 18 [t(10;18)(q22.1;q21.1)]. Since juvenile NCL was previously mapped to 16p12, this report raises the possibility of heterogeneity in this form of NCL.
Asunto(s)
Cromosomas Humanos Par 10 , Cromosomas Humanos Par 18 , Lipofuscinosis Ceroideas Neuronales/genética , Lipofuscinosis Ceroideas Neuronales/patología , Translocación Genética , Niño , Bandeo Cromosómico , Mapeo Cromosómico , Femenino , Humanos , Cariotipificación , Linfocitos/patología , Linfocitos/ultraestructura , Masculino , Microscopía Electrónica , Lipofuscinosis Ceroideas Neuronales/clasificación , Vacuolas/patología , Vacuolas/ultraestructuraRESUMEN
We analyzed National Registry data from 575 patients with subacute sclerosing panencephalitis (SSPE) in the United States to assess changes in patient characteristics and SSPE epidemiology. Racial proportions have changed in recent years with an increasing number of Hispanic patients reported in relation to a constant black:white ratio; however, the male:female ratio of approximately 2:1 has remained. The most striking feature of the data is the rapid decline in SSPE incidence. Corresponding to this decrease is an increase in the proportion of cases following measles vaccination. There also is a shorter incubation period for SSPE following vaccination than after measles infection.
Asunto(s)
Panencefalitis Esclerosante Subaguda/epidemiología , Femenino , Humanos , Masculino , Vacuna Antisarampión , Panencefalitis Esclerosante Subaguda/etnología , Panencefalitis Esclerosante Subaguda/microbiología , Estados UnidosRESUMEN
The neuronal ceroid lipofuscinoses are clinical disorders associated with the accumulation of autofluorescent waxy pigments within cells of several different tissues. Such syndromes always have neurological manifestations. Variations in clinical course, genetics, pathogenesis, and possibly treatment occur in each of the several forms listed under this category. Ten subtypes have now been recognized: (1) chronic, juvenile (Batten type); (2) acute, late infantile (Bielschowsky type); (3) subacute-chronic, adult (Kufs type); (4) acute, infantile (Santavuori-Haltia type); (5) congenital (Norman-Wood type); (6) acute, adult (Zeman-Dyken type); (7) acute-subacute childhood (Bielschowsky variant); (8) chronic, childhood with pervasiveness (Edathodu-Dyken type); (9) chronic, infantile with autism (Dyken type); and (10) chronic, juvenile with ataxia and spasticity (Dyken type). By far the most common of these are the first four disorders listed. It is proposed that this present classification of neuronal ceroid lipofuscinosis is more comprehensive than previous ones and fails to support the hypothesis that this disorder represents a unitary disease process, rather than different diseases with similar characteristics. At present, each of the neuronal ceroid lipofuscinosis types are of unknown etiology.
Asunto(s)
Lipofuscinosis Ceroideas Neuronales/clasificación , HumanosRESUMEN
Neuronal ceroid-lipofuscinoses (NCL) represent diseases of different types. Each variety of NCL may have its own clinical course, genetics, pathogenesis, and treatment. Four disorders are presently accepted as examples of NCL. These include the chronic juvenile or Batten type, the acute late infantile or Bielschowsky type, the chronic or subacute adult Kufs type, and the acute infantile or Santavuori-Haltia type. Seventy patients with clinical and pathological features of NCL have been studied over 20 years; 62 of these fit into one of the above categories, but 8 are atypical and present nosologic problems. Recognized as examples of atypical NCL are 1) chronic congenital or Norman-Wood type, 2) acute adult or Zeman-Dyken type, 3) acute childhood or Bielschowsky variant, 4) chronic childhood (Edathodu-Dyken) type, with pervasiveness, 5) chronic infantile (Dyken) type with autism, and 6) chronic juvenile (Dyken) type with ataxia. It is proposed that our present classification of NCL be based on differentiating clinical dynamics and characteristics, age-of-onset, and morphological and pathological criteria. Although genetic characteristics are now recognized, these are of autosomal recessive or autosomal dominant type. No differentiating biochemical differences have been established to aid in the nosology of these diseases.
Asunto(s)
Lipofuscinosis Ceroideas Neuronales/clasificación , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Linfocitos/ultraestructura , Masculino , Microscopía Electrónica , Lipofuscinosis Ceroideas Neuronales/sangre , Lipofuscinosis Ceroideas Neuronales/patología , Orgánulos/ultraestructura , SíndromeRESUMEN
Five patients afflicted with subacute sclerosing panencephalitis were studied with computed tomography and magnetic resonance imaging. Computed tomography documented changes of nonspecific cerebral atrophy and low attenuation in the subcortical white matter. Magnetic resonance imaging revealed bilateral, symmetric, and diffuse abnormal increased signal in the white matter of the cerebral hemispheres with normal posterior fossa structures in 4 of 5 patients. Magnetic resonance imaging was superior to computed tomography in demonstrating the total extent of abnormality and may be the imaging modality of choice for this childhood disease.
Asunto(s)
Imagen por Resonancia Magnética , Panencefalitis Esclerosante Subaguda/diagnóstico , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Atrofia , Encéfalo/patología , Niño , Femenino , Humanos , MasculinoRESUMEN
A patient with the hyperornithinemia, hyperammonemia, homocitrullinuria syndrome is described. This patient represents the 12th documented case of this rare, presumably autosomal recessive condition. Increased levels of ammonia, ornithine and homocitrulline were demonstrated in blood and cerebrospinal fluid. The blood ammonia concentration could be lowered by supplementation of the diet with low doses of arginine. High doses of arginine precipitated seizures, although plasma levels of arginine and ornithine were not altered. The uptake of ornithine by the particulate fraction of the patient's fibroblasts was lower than that of controls, but still measurable. It is suggested that HHH patients have a partial impairment of the uptake of ornithine by mitochondria.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Aminoácidos/metabolismo , Amoníaco/metabolismo , Citrulina/análogos & derivados , Ornitina/metabolismo , Transporte Biológico , Preescolar , Citrulina/orina , Fibroblastos/metabolismo , Estudios de Seguimiento , Humanos , Cinética , Masculino , Trastornos Psicomotores/metabolismo , Convulsiones/metabolismo , SíndromeRESUMEN
Ictal phenomena were studied during three separate six-hour video/polygraphic recording sessions in 10 patients with infantile spasms; 1,079 spasms occurred. Frequency during wakefulness (7.7 spasms/hour) was greater than that during sleep (2.5 spasms/hour); 46.6% of spasms occurred in clusters. Spasms were composed of one or more of three phases: a myoclonic contraction, a tonic contraction, and/or an arrest of activity. The most common types were myoclonic-tonic (40.3%) and myoclonic alone (36.3%). When classified by postural motor phenomena, 41.6% were "flexor", 16.3% "extensor", 39.0% "mixed", and 3.1% "arrest" alone. Electrographic monitoring revealed that myoclonic contractions were associated with an initial paroxysmal event. Tonic contractions and arrests were usually associated with suppression of electroencephalographic activity with or without rhythmic activity. Knowledge of these clinical and electrographic features is important for diagnosis and evaluation of proposed treatments.
Asunto(s)
Electroencefalografía , Espasmos Infantiles/fisiopatología , Corteza Cerebral/fisiopatología , Preescolar , Potenciales Evocados , Femenino , Humanos , Lactante , Masculino , Monitoreo Fisiológico , Fases del Sueño/fisiologíaRESUMEN
Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease of childhood that is due to a persistent measles infection. Owing to a nationwide immunization program in the United States, the incidence has decreased considerable, coexistent with the decline in natural measles infection. The disease, now fully understood, still represents a great international problem. Clinical presentation, etiology, pathogenesis, prevention, and treatment are updated in this article.
Asunto(s)
Panencefalitis Esclerosante Subaguda/diagnóstico , Adolescente , Amantadina/uso terapéutico , Anticuerpos Antivirales/líquido cefalorraquídeo , Encéfalo/patología , Niño , Preescolar , Electroencefalografía , Femenino , Humanos , Inosina Pranobex/uso terapéutico , Masculino , Virus del Sarampión/inmunología , Cuidados Paliativos , Sistema de Registros , Población Rural , Panencefalitis Esclerosante Subaguda/epidemiología , Panencefalitis Esclerosante Subaguda/terapia , Proteínas Virales/inmunologíaRESUMEN
Although valproic acid (VPA) is used to treat infantile spasms, VPA's efficacy in infantile spasms has not been determined in a controlled study. This study evaluated the effect of VPA on infantile spasms in patients who had not responded to adrenocorticotropin (ACTH) and corticosteroid therapy. The hypotheses were tested using a double-blind, randomized controlled crossover design. Twenty-one patients were randomly assigned to either the baseline-valproate-placebo treatment or the baseline-placebo-valproate treatment groups. Based on a repeated measures analysis of variance test, the valproate group had lower total mean spasm frequency levels than the placebo group. However, this difference did not remain after the crossover; the difference was due to the initial administration of valproate and placebo. When the spasm index was analyzed, the valproate treatment was found to have lower mean spasm index scores than the baseline treatments (p less than 0.03). No short-term toxic effects were observed in any patient. We conclude that short-term VPA therapy has a beneficial effect even on chronic infantile spasm patients who have failed to respond to ACTH/corticosteroid therapy.
Asunto(s)
Espasmos Infantiles/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Ensayos Clínicos como Asunto , Método Doble Ciego , Esquema de Medicación , Electroencefalografía , Humanos , Lactante , Distribución AleatoriaRESUMEN
Subacute sclerosing panencephalitis (SSPE) is a rare central nervous system degenerative disease that occurs primarily in children and adolescents. It is believed to be caused by a measles-like virus. Initial symptoms usually present as a variety of personality changes followed by myoclonus with progression of mental and motor deterioration, which leads to death within a few months to years. New experimental treatment with inosiplex has been shown to be helpful for patients stricken with this progressive neurological disease. A response to inosiplex therapy is best in patients with a slowly progressing form of the disease. Inosiplex treatment is safe with few adverse effects. The duration of treatment appears to be lifelong since many patients relapse when inosiplex therapy is discontinued. This article reviews the etiology, pathogenesis, and experimental treatment of SSPE.
Asunto(s)
Inosina Pranobex/uso terapéutico , Inosina/análogos & derivados , Panencefalitis Esclerosante Subaguda/tratamiento farmacológico , Amantadina/uso terapéutico , Animales , Humanos , Inosina Pranobex/farmacología , Inosina Pranobex/toxicidad , Panencefalitis Esclerosante Subaguda/diagnóstico , Panencefalitis Esclerosante Subaguda/etiologíaRESUMEN
Twenty-four computed tomographic scans of 12 patients with confirmed subacute sclerosing panencephalitis were studied using standardized techniques of radiological assessment. Abnormalities encountered were of four types--(1) lateral ventricular dilatation, (2) cerebral cortical atrophy and sylvian fissure widening, (3) low parenchymal attenuation, and (4) brainstem atrophy and cerebellar atrophy--and of varying degrees. The abnormalities correlated best with the stage and duration of disease, but not necessarily well with the patient's mental state. The fewest radiological abnormalities were encountered in the acute or early stages, whereas more signs of parenchymal disturbances in the form of low attenuations emerged during intermediate periods. Chronic periods were accompanied by atrophic changes in the form of cortical atrophy, ventricular dilatation, and brainstem cerebellar atrophy.
Asunto(s)
Panencefalitis Esclerosante Subaguda/diagnóstico por imagen , Femenino , Humanos , Masculino , Tomografía Computarizada por Rayos XRESUMEN
We studied the probability of survival of subacute sclerosing panencephalitis (SSPE) patients prognostically stratified into rapidly and slowly developing SSPE, nontreatment, and inosiplex-treated groups. Based on life table analysis, survival did not differ between treated and untreated patients with rapidly developing SSPE. The cumulative survival rates were significantly (p less than 0.05) higher and the mortality rate significantly lower in the slowly developing inosiplex-treated group.
Asunto(s)
Inosina Pranobex/uso terapéutico , Inosina/análogos & derivados , Panencefalitis Esclerosante Subaguda/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Panencefalitis Esclerosante Subaguda/mortalidadRESUMEN
Subacute sclerosing panencephalitis is a central nervous system degenerative disease that rapidly progresses to death in most untreated cases. In this study we compare the level of neurological disability longitudinally in a group of SSPE patients receiving inosiplex (Isoprinosine) treatment (12) to a historical control group of untreated patients (15). The mean ND did not differ between the groups from onset of SSPE through 21 months. From two years through four and one-half years the inosiplex group had significantly lower ND compared to the nontreatment group. The subjects were then divided into four subgroups: Group 1, rapidly progressing SSPE, not treated; Group 2, slowly progressing SSPE, not treated; Group 3, rapidly progressing SSPE, inosiplex treated; and Group 4 slowly progressing SSPE, inosiplex treated. The rapidly developing groups did not differ in ND at any time. The slowly developing treated group had significantly lower ND than the slowly developing untreated group from two and one-half years to four and one-half years after onset of SSPE. These findings suggest that inosiplex is effective in the slowly developing or chronic form of SSPE.
Asunto(s)
Inosina Pranobex/uso terapéutico , Inosina/análogos & derivados , Panencefalitis Esclerosante Subaguda/tratamiento farmacológico , Adolescente , Niño , Preescolar , Evaluación de la Discapacidad , Femenino , Humanos , Estudios Longitudinales , Masculino , Examen Neurológico , Pronóstico , Panencefalitis Esclerosante Subaguda/complicacionesRESUMEN
We studied a 3-month-old boy who had opsoclonus in association with acute bacterial meningitis. The CSF IgG and IgM were elevated acutely, gradually returning to normal with clinical improvement. Correspondingly, CSF cytomorphology showed excessive plasmocytosis and a higher proportion of reactive lymphocytes than expected in an acute bacterial meningitis. These abnormalities in CSF cytology are effects of an abnormal immune response in the CNS, and provide evidence to support an immunopathic basis to opsoclonus.