RESUMEN
BACKGROUND: Alpers syndrome is one of the most common phenotypes of mitochondrial disorders in early childhood and has been associated with pathogenic mutations in POLG1. AIMS: To investigate the phenotypic-genotypic correlations in Alpers syndrome and to identify potential differences among patients with Alpers syndrome with or without pathogenic POLG1 mutations. METHODS: Patients with the phenotype of Alpers syndrome who were referred to our pediatric hospital during 1984-2007 and were diagnosed with mitochondrial encephalomyopathy underwent further biochemical, morphological and genetic investigations. RESULTS: A total of 19 patients were included in the study, of whom six had pathogenic POLG1 mutations including a novel mutation (c.907 G>A, p.Gly303Arg). Complete mtDNA sequencing in the subgroup without POLG1 mutations showed 5 novel and 5 very rare mtDNA variants considered as rare polymorphisms. Compared to POLG1(-) patients, the POLG1(+) patients more frequently had seizures at onset, which often became refractory. Ataxia and stroke-like episodes were much more common, while microcephaly and spasticity were encountered almost solely in the POLG1(-) group. Hepatic and ophthalmological involvement developed in 79% and 88% of patients, respectively. Most of the patients in both groups had predominant deficiency of complex I. In addition to the major degenerative changes in the cerebral cortex, the basal ganglia, thalamus and white matter were also involved to variable extent. CONCLUSION: Alpers syndrome is a heterogeneous syndrome that should be considered in patients with early-onset progressive cortical encephalopathy regardless of liver involvement. The phenotype is different depending on the presence or absence of POLG1 mutations.
Asunto(s)
Esclerosis Cerebral Difusa de Schilder/genética , Esclerosis Cerebral Difusa de Schilder/psicología , Adolescente , Edad de Inicio , Encéfalo/patología , Cardiomiopatías/complicaciones , Niño , Preescolar , ADN/genética , ADN Polimerasa gamma , ADN Polimerasa Dirigida por ADN/genética , Interpretación Estadística de Datos , Esclerosis Cerebral Difusa de Schilder/patología , Oftalmopatías/complicaciones , Femenino , Estudios de Seguimiento , Genotipo , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Inmunohistoquímica , Lactante , Discapacidad Intelectual/etiología , Hígado/metabolismo , Hígado/patología , Hepatopatías/complicaciones , Hepatopatías/patología , Masculino , Mitocondrias/metabolismo , Músculo Esquelético/patología , Mutación/genética , Neuroimagen , Fosforilación Oxidativa , Convulsiones/etiología , Caracteres SexualesRESUMEN
We report on a young girl with Alpers-Huttenlocher syndrome, as confirmed by mitochondrial polymerase gamma sequencing, who was treated with the classic (4 parts fat:1 part each of carbohydrate and protein) ketogenic diet after she presented with epilepsia partialis continua. She improved clinically, and her electroencephalogram improved dramatically. This is the first detailed report on the efficacy of the ketogenic diet in treating the epileptic encephalopathy of Alpers-Huttenlocher syndrome. We present a literature review of the utility of a ketogenic diet in mitochondrial disorders, and speculations as to why the diet may be helpful in Alpers-Huttenlocher syndrome.
Asunto(s)
Dieta Cetogénica , Esclerosis Cerebral Difusa de Schilder/dietoterapia , Anticonvulsivantes/uso terapéutico , Encéfalo/patología , Preescolar , Cognición/fisiología , Esclerosis Cerebral Difusa de Schilder/complicaciones , Esclerosis Cerebral Difusa de Schilder/psicología , Electroencefalografía , Epilepsia/complicaciones , Epilepsia/dietoterapia , Epilepsia/psicología , Resultado Fatal , Femenino , Humanos , Imagen por Resonancia Magnética , Midazolam/uso terapéutico , Destreza Motora/fisiología , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatologíaRESUMEN
Patients with medial temporal lobe epilepsy based on left hippocampal sclerosis often show severe verbal memory deficits. Recent studies suggest that memory formation in these patients may be reallocated to the right hemisphere owing to left hippocampal pathology. To test this hypothesis, we used functional magnetic resonance imaging to examine encoding-related activity of verbal items in temporal lobe epilepsy patients with left hippocampal sclerosis and patients with idiopathic epilepsy as a control group. Results demonstrated that patients with idiopathic epilepsy showed more activation in both left and right hippocampi. The temporal lobe epilepsy group showed enhanced activation in left fusiform gyrus. We discuss these results in terms of different strategy use by the groups.
Asunto(s)
Encéfalo/fisiopatología , Esclerosis Cerebral Difusa de Schilder/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Memoria , Habla , Adulto , Anciano , Encéfalo/patología , Mapeo Encefálico , Esclerosis Cerebral Difusa de Schilder/psicología , Epilepsia del Lóbulo Temporal/psicología , Femenino , Lateralidad Funcional , Alemania , Hipocampo/fisiopatología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: to assess the relationship between hypertension and cognitive function in elderly subjects. METHODS: 17 subjects with uncomplicated hypertension (nine male, eight female) and 27 control subjects with similar educational level and age (18 male, nine female) were studied. These individuals were recruited, according to strict selection criteria, from a random sample of 120 elderly subjects living in the community, who had a normal Mini Mental State score. An extensive neuropsychological test battery, sensitive to mild cognitive impairment, was administered in standard conditions to measure attention, concentration and judgement, psychomotor speed, memory and learning. Affective disorders were also evaluated. In all patients a computed tomography scan was performed. RESULTS: subjects with high blood pressure had lower mean levels of performance in attentional measures; tapping test (inhibition of incorrect answers), three words-three shapes test (attempts; incidental memory) and reaction time to multiple stimuli. They also scored worse in clusters 1 and 2 of the Hamilton rating scale for depression. Confluent white matter lesions were found in nine hypertensive subjects (52.9%) and five controls (18.5%; P = 0.0170). Lacunes were demonstrated in 11 hypertensive (64.7%) and four normotensive people (14.8%; P = 0.0007). In a multivariate analysis (logistic regression), three cognitive variables (tapping, Hamilton cluster 2 and Hamilton total score) remained significantly associated with hypertension, independently of the presence of cerebral lesions. CONCLUSIONS: in elderly otherwise normal hypertensive subjects, an attentional impairment may occur, which appears to be functional and possibly reversible rather than structural and progressive.
Asunto(s)
Presión Sanguínea/fisiología , Hipertensión/fisiopatología , Inteligencia/fisiología , Anciano , Anciano de 80 o más Años , Atención/fisiología , Daño Encefálico Crónico/diagnóstico , Daño Encefálico Crónico/fisiopatología , Daño Encefálico Crónico/psicología , Infarto Cerebral/diagnóstico , Infarto Cerebral/fisiopatología , Infarto Cerebral/psicología , Comorbilidad , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/psicología , Esclerosis Cerebral Difusa de Schilder/diagnóstico , Esclerosis Cerebral Difusa de Schilder/fisiopatología , Esclerosis Cerebral Difusa de Schilder/psicología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/psicología , Masculino , Recuerdo Mental/fisiología , Escala del Estado Mental , Pruebas Neuropsicológicas , Solución de Problemas/fisiología , Retención en Psicología/fisiología , Tomografía Computarizada por Rayos XRESUMEN
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary stroke disease linked to chromosome 19 q 12. We report on two families affected by this disease, which is characterised by recurrent subcortical ischaemic strokes, progressive pseudobulbar palsy, and presenile dementia. Neuroimaging revealed multiple deep infarcts and diffuse leukoencephalopathy. Diagnosis of CADASIL based on the typical clinical feature without vascular risk factors, the neuroradiological signs of extensive leukoencephalopathy, and the autosomal dominant pattern of inheritance. CADASIL might be an underestimated cause of familial stroke and should be considered in the differential diagnosis of hereditary stroke.
Asunto(s)
Aberraciones Cromosómicas/genética , Cromosomas Humanos Par 19 , Demencia por Múltiples Infartos/genética , Esclerosis Cerebral Difusa de Schilder/genética , Genes Dominantes/genética , Encéfalo/patología , Trastornos de los Cromosomas , Demencia por Múltiples Infartos/diagnóstico , Demencia por Múltiples Infartos/psicología , Diagnóstico Diferencial , Esclerosis Cerebral Difusa de Schilder/diagnóstico , Esclerosis Cerebral Difusa de Schilder/psicología , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Síndrome , Tomografía Computarizada por Rayos XRESUMEN
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO-SL) is a rare hereditary disease affecting both brain and bones. Skeletal symptoms begin in early adulthood and neuropsychiatric symptoms at approximately age 30. Progressive dementia associated with an accentuated frontal lobe syndrome handicaps the patients. The author describes inadequate psychosocial reactions of the spouses of 21 Finnish PLO-SL patients. The reactions included rejection and divorce in 8 cases and rejection without divorce in 1 case. Jealousy, violence, and alcoholism were common in male spouses. The author suggests that some of the spouses' negative psychosocial reactions may be lessened if the family is informed early about the nature of the disorder.
Asunto(s)
Actitud Frente a la Salud , Enfermedades del Desarrollo Óseo/genética , Esclerosis Cerebral Difusa de Schilder/genética , Familia , Matrimonio , Adulto , Enfermedades del Desarrollo Óseo/complicaciones , Enfermedades del Desarrollo Óseo/psicología , Demencia/etiología , Demencia/genética , Demencia/psicología , Esclerosis Cerebral Difusa de Schilder/complicaciones , Esclerosis Cerebral Difusa de Schilder/psicología , Divorcio , Femenino , Finlandia , Educación en Salud , Humanos , Celos , Masculino , Rechazo en Psicología , Factores Sexuales , ViolenciaRESUMEN
Psychopathological alterations caused by symmetrical basal ganglia sclerosis of different etiologies are described, involving cases with parathyroid gland/hormone dysfunction (some of them familial), patients after thyroidectomy, and patients with basal ganglia calcification of uncertain etiology. Initial symptomatology in a group of 62 patients is reported; chronic symptoms in another group of 35 patients were evaluated. Estimates of volume of the basal ganglia calcifications were made, in addition to precise topographical localizations by CT. In 40% the initial symptoms noted were psychiatric, compared with 50% who first presented neurological symptoms. In the group of chronic cases practically all showed intellectual impairment. There was a marked preponderance of organic affective syndromes (initially 21%, chronic 65%): the affective chronic patients can be subdivided into 37% depressive, 20% bipolar, 11% manic cases. We could find no direct relationships with regard to etiology, localization, volume or symptoms, except that extensive calcifications occur after parathyroid hormone deficiencies due to thyroidectomy and lead to more severe mental deterioration.