RESUMO
Leigh syndrome is an inherited neurodegenerative disorder of infancy that typically manifests between 3 and 12 months of age. The common neurological manifestations are developmental delay or regression, progressive cognitive decline, dystonia, ataxia, brainstem dysfunction, epileptic seizures, and respiratory dysfunction. Although the disorder is clinically and genetically heterogeneous, the histopathological and radiological features characteristically show focal and bilaterally symmetrical, necrotic lesions in the basal ganglia and brainstem. The syndrome has a characteristic histopathological signature that helps in clinching the diagnosis. We discuss these unique findings on autopsy and radiology in a young infant who succumbed to a subacute, progressive neurological illness suggestive of Leigh syndrome. Our case highlights that Leigh syndrome should be considered in the differential diagnosis of infantile-onset, subacute neuroregression with dystonia and seizures, a high anion gap metabolic acidosis, normal ketones, elevated lactates in blood, brain, and urine, and bilateral basal ganglia involvement.
Assuntos
Humanos , Masculino , Lactente , Doença de Leigh/patologia , Autopsia , Gânglios da Base/anormalidades , Dano Encefálico Crônico/patologia , Doenças Neurodegenerativas , Diagnóstico Diferencial , Manifestações NeurológicasRESUMO
We describe the long-term clinical outcome of a patient with Leigh-like syndrome presenting as an early onset encephalopathy and peripheral neuropathy caused by the T8993G mutation in the mitochondrial DNA (mtDNA). Clinical follow-up for 20 years revealed a peculiar pattern of slow disease progression, characterized by the addition of new minor deficits, while worsening of previous symptoms was mild. Brain MRI revealed cerebellar atrophy, diffuse demyelination of corona radiata and parietal white matter, and bilateral and symmetrical putaminal lesions. The proportion of mutant mtDNAs in blood was 72% (+/-0.02%) and in skeletal muscle was 81% (+/-0.4%). Leigh-like syndrome caused by the T8993G mtDNA mutation is a progressive disease, although not necessarily associated with an aggressive clinical course.
Assuntos
DNA Mitocondrial/genética , Doença de Leigh/genética , Doença de Leigh/fisiopatologia , ATPases Mitocondriais Próton-Translocadoras/genética , Adulto , Análise Química do Sangue , Encéfalo/patologia , Análise Mutacional de DNA , Progressão da Doença , Seguimentos , Genes Mitocondriais , Humanos , Doença de Leigh/patologia , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/química , Mutação de Sentido Incorreto , Síndrome , Adulto JovemRESUMO
Acute necrotizing encephalopathy was initially reported in Japanese children. The rapid evolution and symmetrical brain lesions seen in the brainstem, cerebellum and specially in the thalamus characterize the disease. We studied a 7-month-old-girl, who presented with two episodes of rapid loss of consciousness and paresis without metabolic disturbances. At the first time she had a rapid improvement, but at the second episode the course was fulminant and in two days she lapsed into a clinical state of brain death. The magnetic resonance studies showed symmetrical lesions in the thalamus and additional lesions involving the brainstem and the cerebellum.
Assuntos
Encéfalo/patologia , Doença de Leigh/patologia , Evolução Fatal , Feminino , Humanos , Lactente , Imageamento por Ressonância MagnéticaRESUMO
A encefalopatia necrotizante aguda foi descrita inicialmente em crianças japonesas e se caracteriza por rápida evolução e lesões simétricas no tronco encefálico, cerebelo e especialmente nos tálamos. Avaliamos uma menina de 7 meses de idade, que apresentou dois episódios de depressão da consciência de rápida instalação e paresias, sem alterações metabólicas. Houve uma rápida melhora na primeira crise, porém o segundo episódio foi fulminante, tendo evoluído para estado de morte encefálica em dois dias. Os estudos de ressonância magnética mostraram lesões simétricas nos tálamos e acometimento também do tronco encefálico e cerebelo.
Acute necrotizing encephalopathy was initially reported in Japanese children. The rapid evolution and symmetrical brain lesions seen in the brainstem, cerebellum and specially in the thalamus characterize the disease. We studied a 7-month-old-girl, who presented with two episodes of rapid loss of consciousness and paresis without metabolic disturbances. At the first time she had a rapid improvement, but at the second episode the course was fulminant and in two days she lapsed into a clinical state of brain death. The magnetic resonance studies showed symmetrical lesions in the thalamus and additional lesions involving the brainstem and the cerebellum.
Assuntos
Feminino , Humanos , Lactente , Encéfalo/patologia , Doença de Leigh/patologia , Evolução Fatal , Imageamento por Ressonância MagnéticaAssuntos
Insuficiência de Crescimento/etiologia , Doença de Leigh/diagnóstico , Gânglios da Base/patologia , Pré-Escolar , Insuficiência de Crescimento/fisiopatologia , Globo Pálido/patologia , Humanos , Doença de Leigh/etiologia , Doença de Leigh/patologia , Doença de Leigh/fisiopatologia , Imageamento por Ressonância Magnética , MasculinoRESUMO
A 30 months-old boy developed bilateral nistagmus, tremor, gait disturbance, hypotonia and disartria. The diagnose of Leigh encephalopathy was suggested on the basis of clinical, neuroimaging and laboratory findings. Computed tomography and magnetic resonance imaging (MRI) at an early stage revealed bilateral and symmetric lesions in the putamen, appearing as hyperintense signal on T2-weighted images. Twelve months later a relatively large hypertense area in the posterior brainstem was observed. At this stage, the patient exhibited marked deterioration, dystonic manifestations, rigidity and respiratory disturbances. He died 6 months later for respiratory arrest during bronconeumonic infection. We believe MRI is a valuable means to allow assessment of the evolution of the disease.
Assuntos
Doença de Leigh/diagnóstico , Imageamento por Ressonância Magnética , Pré-Escolar , Diagnóstico Diferencial , Evolução Fatal , Humanos , Doença de Leigh/patologia , Masculino , Putamen/patologiaRESUMO
Os autores revêem a literatura atual acerca das enfermidades neurológicas relacionadas aos distúrbios das mitocôndrias. Inicialmente, recordam-se os conceitos fisiológicos desta organela, caracterizando-se a seguir, de forma genérica, sua disfunçåo sob o ponto de vista clínico e laboratorial. Descrevem-se especificamente as principais neuromitocondriopatias primárias (oftalmoplegia extrínseca progressiva, síndrome de KearnsSayre, MERRF, MELAS, NARP, atrofia óptica de Leber, MiMyCa, MINGIE/POLIP, síndrome de Pearson, síndrome de Leigh, doença de Alpers) e secundárias (doença de Menkes, miopatia da AZT, doença de Parkinson). Por fim, säo tecidas consideraçöes acerca das principais abordagens terapêuticas nestas afecçöes