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

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*

BACKGROUNDLeigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients.

METHODSSixty-five unrelated cases (35 men and 30 women) who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography (CT) scan or magnetic resonance imaging (MRI). The differential diagnosis of organic acidurias and fatty acid beta-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA (T8993G, T8993C, T9176C, A8344G, A3243G) were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 (26.2%) of the patients. The diagnosis was confirmed by autopsy in 6 (9.2%) patients.

RESULTSThe patients had various forms of metabolic encephalomyopathy. Fifty-nine (90.8%) of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty (30.8%) patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases (7.7%). Of these, the A8344G mutation was detected in 2 patients. The T8993G, T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) families by DNA sequencing. A G604C mutation was identified in 6 (9.2%) patients. The genotypes of 52 patients remained unknown.

CONCLUSIONSLeigh syndrome presents as a diverse array of clinical features and can result from specific mutations in nuclear or mitochondrial DNA. In this study, SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) out of 65 patients with Leigh syndrome. It indicates that SURF1 mutations might be a common cause of Leigh syndrome in China. The etiology of Leigh syndrome in Chinese patients represents a persistent challenge to clinicians.

Adolescent ; Child ; Child, Preschool ; Cytochrome-c Oxidase Deficiency ; genetics ; Female ; Humans ; Infant ; Infant, Newborn ; Leigh Disease ; genetics ; metabolism ; pathology ; therapy ; Male ; Membrane Proteins ; Mitochondrial Proteins ; Mutation ; Proteins ; genetics ; Retrospective Studies ; Treatment Outcome

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