Initial Experiences with Proton MR Spectroscopy in Treatment Monitoring of Mitochondrial Encephalopathy

PURPOSE: Mitochondrial encephalopathy (ME) is a rare disorder of energy metabolism. The disease course can roughly be evaluated by clinical findings. The purpose of this study was to evaluate metabolic spectral changes using proton MR spectroscopy (MRS), and to establish a way to monitor ME by neuroimaging. MATERIALS AND METHODS: Proton MRS data were retrospectively reviewed in 12 patients with muscle biopsy-confirmed ME (M : F = 7 : 5, Mean age = 4.8 years). All received 1H-MRS initially and also after a ketogenic diet and mitochondrial disease treatment cocktail (follow up average was 10.2 months). Changes of N-acetylaspartate/creatine (NAA/Cr) ratio, choline/creatine (Cho/Cr) ratio, and lactate peak in basal ganglia at 1.2 ppm were evaluated before and after treatment. Findings on conventional T2 weighted MR images were also evaluated. RESULTS: On conventional MRI, increased basal ganglia T2 signal intensity was the most common finding with ME (n = 9, 75%), followed by diffuse cerebral atrophy (n = 8, 67%), T2 hyperintense lesions at pons and midbrain (n = 4, 33%), and brain atrophy (n = 2, 17%). Lactate peak was found in 4 patients; 2 had disappearance of the peak on follow up MRS. Quantitative analysis showed relative decrease of Cho/Cr ratio on follow up MRS (p = 0.0058, paired t-test, two-tailed). There was no significant change in NAA/Cr ratio. CONCLUSION: MRS is a useful tool for monitoring disease progression or impro-vement in ME, and decrease or disappearance of lactate peak and reduction of Cho/Cr fraction were correlated well with improvement of clinical symptoms.

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.