MELAS with diffuse degeneration of the cerebral white matter: Report of an autopsy case

Abstract

Up to now diffuse white matter demyelination of the cerebrum has been reported in only a few cases of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). Here we document an autopsy case with this rare neuropathology. Most MELAS cases are diagnosed antemortem by A3243G transition of mitochondrial DNA. While cerebral damage including necrotic foci in the cerebral cortex are common findings in MELAS, prominent white matter involvement best characterizes this MELAS case. There were numerous necrotic foci, varying in size and chronological stage, in the cerebral white matter. In the areas of the white matter without necrotic foci, there was diffuse fibrillary gliosis with the loss of axons and oligodendrocytes. The gliosis was dominant in the deep white matter, sparing the U-fiber. The cerebral cortex showed diffuse cortical atrophy with few scattered necrotic foci. Distribution of the cerebral lesions does not coincide with the territory of blood supply. The vascular wall presented only slight to mild hyalinosis. We assumed a common pathogenesis to the cortical lesions and the white matter change. The pathogenesis of the present diffuse cerebral lesions may not be just secondary to circulatory disturbance but partly due to metabolic abnormality.

Voxelwise Analysis of Diffusion Tensor Imaging and Structural MR Imaging in Patients with the m.3243A>G Mutation in Mitochondrial DNA

“…Some previous imaging 31,32 and neuropatholog- ic 9,33 studies on MELAS syndrome also suggest that both gray and white matter are affected, and that white matter involvement is not only secondary to cortical damage. 9,33 Brain glucose and oxygen metabolism were previously assessed with positron-emission tomography in 28 of the 29 subjects also participating in this study. 34 The cerebral metabolic rate of oxygen is universally decreased in the gray and white matter of patients with the m.3243AϾG mutation, whereas the metabolic rate of glucose is decreased with a predilection for the posterior parts of the brain.…”

“…The most commonly described neuropathologic features of the MELAS syndrome are multifocal necrotic foci in the cerebral cortex and predominantly subcortical white matter gliosis. 8,9 However, the classic MELAS syndrome is relatively rare, and most patients with m.3243AϾG mutation present with other symptoms of mitochondrial disease, such as sensorineural hearing impairment, diabetes mellitus, myopathy, or cognitive impairment. 10 The large variation in the clinical phenotypes is at least partly due to heteroplasmy of the mutation (ie, the co-occurrence of the 2 alleles within mitochondria, cells, and tissues).…”

Leukoencephalopathies in Mitochondrial Disorders: Clinical and MRI Findings

“… 12‐14 WMLs and their clinical presentation are usually not the initial manifestation of the disease. Single patients may present with diffuse gliosis of the cerebral and cerebellar white matter with cactus formation of the Purkinje cells, 15,16 which may be prominent in single patients 17 . In the areas of necrotic foci, diffuse fibrillary gliosis with loss of axons and oligodendrocytes can be found 16 .…”

“…Single patients may present with diffuse gliosis of the cerebral and cerebellar white matter with cactus formation of the Purkinje cells, 15,16 which may be prominent in single patients 17 . In the areas of necrotic foci, diffuse fibrillary gliosis with loss of axons and oligodendrocytes can be found 16 . Patients may additionally present with calcifications of the basal ganglia, cystic lesions, and laminar cortical necrosis 12 .…”

“…Loss of myelin and fibrous gliosis of the subcortical and deep white matter may be also seen on cerebral CT 19 . Neuropathologic studies may show multiple old or new necrotic foci in the cerebrum and cerebellum 16,20 . Histologic work‐up of acute foci revealed neuronal loss and sponginess 20 .…”