Leigh syndrome in an infant: autopsy and histopathology findings

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.

Encefalopatia necrotizante aguda: paciente com evolução recidivante e letal / Acute necrotizing encephalopathy: patient with a relapsing and lethal evolution

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.

Subacute necrotizing encephalopathy (Leigh's disease) in a child with particular reference to CT finding.

An example of subacute necrotizing encephalopathy, the fifth case in Thailand, was recorded. A 7-month-old boy presented clinically with vomiting, lethargy, respiratory difficulty, deteriorated consciousness, and hypotonia. The CT brain scan disclosed bilateral symmetrical radiolucencies in the basal ganglia, especially the lentiform nuclei, and thalami. Postmortem examination of these areas as well as the periaqueductal region revealed subacute necrotizing encephalopathy. It was characterized by necrosis, gliosis, and status spongiosus of the neuropil with relatively preserved neurons, and hyperplasia of small blood vessels as well as endothelium. As far as we are aware, the vast majority of abnormalities in the basal ganglia visualized by CT brain imaging often show calcific foci or high attenuation with asymmetrical distribution. Bilateral symmetrical lesions of low density are rare. We reported such an abnormality in a postmortem proven case of Leigh's disease. To recognize this finding should lead to correct antemortem diagnosis of the latter.

Mitocôndrias e doenças neurologicas / Mitochondrical and neurological diseases

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

Leigh's disease involving multiple organs

Leigh's disease is a rare progressive neurological disorder that is characterized light microscopically by focal spongy necrosis in the brain and electron microscopically by mitochondriopathy. We report an autopsy case of Leigh's disease that showed abnormalities in the liver, kidney and skeletal muscle as well as the central nervous system. The patient was an 18-month-old girl who has carried a diagnosis of cerebral palsy ever since her birth to a 20-year-old mother. The baby was generally hypertonic and mentally retarded. She died of severe metabolic acidosis. Postmortem examination showed growth retardation, fatty liver, fatty kidney and soft brain. Brain section showed multifocal softenings in the brainstem, basal ganglia and periventricular areas. Microscopically increased capillaries with endothelial proliferation, vacuolar degeneration and mild gliosis were seen in the brain. The axons were relatively preserved. Liver and kidneys showed microvesicular fatty change. Myofiber degeneration of the skeletal muscle was also noted. Electron microscopic examination showed markedly increased mitochondria in the parenchymal cells of the brain, liver and kidney. The mitochondria showed round to ovoid ballooned appearance including electron-dense core-like structures and pseudoinclusions of glycogen granules.