Central Nervous System ; pathology ; Humans ; Infant ; Leigh Disease ; pathology ; physiopathology

OBJECTIVETo investigate the value of functional magnetic resonance imaging (MRI) in sequential evaluation of patients with Leigh syndrome.

METHODSTwo patients with Leigh syndrome underwent diffusion weighted imaging (DWI), perfusion weighted imaging (PWI) and proton magnetic resonance spectroscopy ((1)H-MRS).

RESULTSThe brain lesions showed hyperintensity on DWI, lactate doublet peak on MRS and hyperperfusion in the patients at baseline, and maintained a hyperintensity on DWI and hyperperfusion in the absence of lactate doublet peak on MRS at follow-up 1 year later. DWI still revealed persistent hyperintensity in the brain lesions in one patient 2 years later.

CONCLUSIONFunctional MRI can sensitively highlight the characteristics of brain lesions in patients with Leigh syndrome, and can therefore be used to evaluate the sequential changes of the brain lesions.

Brain ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Leigh Disease ; pathology ; Magnetic Resonance Imaging ; methods

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.
Brain/pathology/ultrastructure ; Female ; Humans ; Infant ; Kidney/pathology/ultrastructure ; Leigh Disease/*pathology ; Liver/pathology/ultrastructure ; Mitochondrial Encephalomyopathies/pathology ; Muscles/pathology

Asian Continental Ancestry Group ; Genotype ; Humans ; Leigh Disease ; genetics ; pathology ; Phenotype ; Retrospective Studies

A case of Leigh's disease (subacute necrotizing encephalomyelopathy) is reported with such noteworthy features as early onset, dystonia, paraparesis the presence of low attenuation areas in both basal ganglias on computerized tomography of the brain and the presence of a high signal intensity in both basal ganglias in T2 weighted image by MR. The electron microscopic findings of muscle biopsy are suggestive of pleoconial mitochondrial myopathy.
Basal Ganglia/pathology ; Case Report ; Dystonia/diagnosis/*etiology ; Energy Metabolism ; Human ; Infant ; Leigh Disease/*diagnosis/metabolism/pathology ; Male ; Muscles/pathology

Leigh's syndrome, which is characterised by progressive neurodegeneration involving the brainstem and basal ganglia, belongs to a family of disorders classified as mitochondrial myopathies. It is most commonly transmitted by an autosomal recessive mode of inheritance, but can sometimes occur in a mitochondrial pattern. It typically presents during infancy with developmental delay and deterioration of brainstem function. Respiratory failure is the common cause of death and postoperative morbidity in patients with Leigh's disease. Herein, we report the case of a 17-year-old female patient with Leigh's syndrome who underwent general anaesthesia for a tracheostomy, which was performed in view of the patient's requirement for long-term ventilation and frequent toileting for secretions. Her respiratory complications included central hypoventilation secondary to brainstem involvement, and obstructive sleep apnoea due to obesity and muscle dystonia. She was hospitalised for acute respiratory decompensation secondary to hospital-acquired pneumonia. We review the anaesthetic implications of this disease and discuss its impact on preoperative, intraoperative and postoperative management.
Adolescent ; Anesthesia, General ; methods ; Anesthetics ; therapeutic use ; Dystonia ; pathology ; Female ; Humans ; Hypoventilation ; complications ; diagnosis ; Leigh Disease ; complications ; drug therapy ; Mitochondria ; pathology ; Postoperative Complications ; Sleep Apnea, Obstructive ; complications ; Ventilation

This study reviews a case of mitochondrial respiratory chain complex I deficiency due to the 10191T>C mutation in mitochondrial ND3 gene. The previously healthy boy progressively presented with blepharoptosis, weakness, epilepsy and motor regression at age 6 years. Elevated blood lactate and pyruvate were observed. Brain magnetic resonance imaging showed symmetrical lesions in the basal ganglia. Leigh syndrome was thus confirmed. The protein from the mitochondria and genomic DNA of the boy and his parents was collected from peripheral blood leucocytes for the activity test for mitochondrial complex I to V and genetic analysis. The results showed the activity of complex I (33.1 nmol /min in 1 milligram mitochondrial protein) was lower than normal reference value (44.0±5.4 nmol /min in 1 milligram mitochondrial protein). The ratio of complex I to citrate synthase (19.8%) was also lower than normal reference value (48%±11%). The activities of complexes II to V were normal. 10191T>C mutation in ND3 gene of mitochondria was identified in the boy. 10191T>C mutation and complex I deficiency were not detected in his parents. At present, he is 16 years old, and of normal intelligence with spastic paralysis in both lower extremities after treatment. It is concluded that a Chinese boy with isolated complex I deficiency due to 10191T>C mutation in ND3 gene was firstly diagnosed by peripheral leukocytes mitochondrial respiratory chain enzyme assay and gene analysis. This study can provide clinical data for the nosogenesis of Leigh syndrome.
Adolescent ; Brain ; pathology ; Electron Transport Complex I ; deficiency ; genetics ; Humans ; Leigh Disease ; genetics ; Magnetic Resonance Imaging ; Male ; Mitochondrial Diseases ; genetics ; Mutation

OBJECTIVETo report a Chinese Han family with two patients of Leigh syndrome (LS) and to scan the mutation in mitochondrial DNA(mtDNA).

METHODSThe clinical features and the laboratory findings were summarized. Mitochondrial DNA chip and direct sequencing were performed to detect the mutation in entire mtDNA.

RESULTSFailure of thrive, psychomotor retardation, hypotonia and weakness, cerebellar ataxia, and seizure were the main manifestations of the family. Brain magnetic resonance imaging (MRI) showed lesions at midbrain, periaqueductal gray matter, dentate nuclei of cerebellar and thalami. The levels of lactic acid and pyruvate were mildly abnormal. The mutation of ND5*13513 G to A was identified in the LS family.

CONCLUSIONPatients with ND5*13513 G to A mutation may have a characteristic clinical course and ND5 *13513 G to A might be a preferential candidate mutation of Leigh syndrome.

Base Sequence ; Child, Preschool ; DNA, Mitochondrial ; genetics ; Electron Transport Complex I ; genetics ; Female ; Humans ; Infant ; Leigh Disease ; diagnostic imaging ; genetics ; pathology ; physiopathology ; Magnetic Resonance Imaging ; Male ; Mitochondrial Proteins ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Tomography, X-Ray Computed

To analyzed the progression of white matter maturation and white matter pathology, MR imaging of the brain was obtained in 38 children with delayed development. Children with developmental delay showed a high incidence of MR abnormalities(34/38, 89.5%). Delayed pattern of myelination and gray-white matter differentiation was seen in 13 patients. Twenty-two patients had white matter patholgy, including 14 with white matter hypoplasia, seven with focal small infarction, five with periventricular leukomalacia, and three with high signal intensities on T2 weighted image. Associated structural abnormalities were also evaluated. The most common lesions in decreasing frequency were cerebral atrophy and dysgenesis of the corpus callosum, pachygyria and/or polymicrogyria, porencephalic cyst and Leigh's disease. Twenty-three of 34 children had multiple abnormalities on MRI. The MRI was useful in depicting the progression of myelination and other white matter lesions, and serial follow-up MR is recommended for patients with delayed or lack of myelination and gray-white matter differentiation.
Abnormalities, Multiple ; Atrophy ; Brain* ; Child* ; Corpus Callosum ; Follow-Up Studies ; Humans ; Incidence ; Infant, Newborn ; Infarction ; Leigh Disease ; Leukomalacia, Periventricular ; Lissencephaly ; Magnetic Resonance Imaging* ; Myelin Sheath ; Pathology ; Polymicrogyria ; White Matter*

OBJECTIVETo analyze clinical and imaging features and genetic characteristics of Leigh syndrome with emergent pulmonary edema.

METHODThe clinical features and imaging data of 2 cases (1 male, 1 female) seen in Anhui Provincial Children's Hospital from 2012 to 2014 were analyzed and summarized. Venous blood samples were sent to Guangzhou Jinyu Medical Examination Center for genetic analysis. Peripheral blood DNA was extracted and amplified, then sent to a sequencing facility for presence of genetic mutation by comparing with the reference sequence (NC_012920.1).

RESULT(1) The first patient was a 7 months old boy. The second patient was a 7 months and 21 days old girl. They were presented with abnormal respiration and pulmonary hemorrhage required mechanical ventilation. The first patient had a similar attack after 4 months of his birth, whose psychomotor development was normal, and no abnormal neurological findings. The value of blood lactate was 1.58 mmol/L. The value of pyruvic acid was 0.25 mmol/L. The value of cerebrospinal fluid lactate was 6. 4 mmol/L, which was an abnormal increase. The second patient had abnormal nervous system development, which included motor development retardation and hypotonia. The value of blood lactate was 6. 8 mmol/L, pyruvic acid was 0.31 mmol/L. Cerebrospinal fluid lactate was 8.2 mmol/L. (2) Imaging data: chest X-ray revealed double lung effusion. Bilateral caudate nucleus and lentiform nucleus had high signal, and bilateral internal capsule forelimbs were affected in DWI sequence of head MRI. Hemispheres, basal ganglia, cerebral peduncle, cerebellum, pons, and splenium of corpus callosum had multiple abnormal signals in head MRI of the second patient. NAA peak showed significantly reduced lesion area in magnetic resonance blood-flow scanning, and Cho peak increased significantly, which were double lactate-peak. (3) Genetic testing: ATPase6 m.9185 t > C mutation was found in case 1 that was consistent with Leigh syndrome pathogenesis. Hybrid mutations (m. 10191 t > C) in mitochondrial DNA was found in case 2. Two cases with the diagnosis of Leigh syndrome was clear. They were given combined therapy, such as mechanical ventilation, limited fluid to alleviate lung exudation, coenzyme Q10, and L-carnitine. The illness of case 1 relapsed after discharge. But in case 2, there was no improvement. They both died after treatment was given up.

CONCLUSIONNeurological symptoms were common in Leigh syndrome, in which acute lung hemorrhage was rarely reported. Timely ventilator support can temporarily save lives, but fatality rate is high and prognosis is poor.

Brain ; pathology ; Carnitine ; therapeutic use ; DNA, Mitochondrial ; Female ; Genetic Testing ; Hemorrhage ; etiology ; Humans ; Infant ; Lactic Acid ; Leigh Disease ; complications ; genetics ; Lung Diseases ; etiology ; Magnetic Resonance Imaging ; Male ; Mutation ; Pyruvic Acid