Neuroimaging of Mitochondrial Cytopathies

Abstract

Mitochondrial diseases are a complex and heterogeneous group of genetic disorders that occur as a result of either nuclear DNA or mitochondrial DNA pathogenic variants, leading to a decrease in oxidative phosphorylation and cellular energy (ATP) production. Increasing knowledge about molecular, biochemical, and genetic abnormalities related to mitochondrial dysfunction has expanded the neuroimaging phenotypes of mitochondrial disorders. As a consequence of this growing field, the imaging recognition patterns of mitochondrial cytopathies are continually evolving. In this review, we describe the main neuroimaging characteristics of pediatric mitochondrial diseases, ranging from classical to more recent and challenging features. Due to the increased knowledge about the imaging findings of mitochondrial cytopathies, the pediatric neuroradiologist plays a crucial role in the diagnosis and evaluation of these patients.

The combination of whole‐exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders

“…[2][3][4] By the end of 2018, a total of 6310 phenotypes were included in the Online Mendelian Inheritance in Man (OMIM), 5 of which approximately 3963 are neurological disorders (NDs). Mitochondrial hereditary diseases, 6,7 hereditary metabolic diseases, 8 and neurocutaneous syndromes, such as neurofibromatosis and tuberous sclerosis, 9 also manifest as nervous system diseases. Mitochondrial hereditary diseases, 6,7 hereditary metabolic diseases, 8 and neurocutaneous syndromes, such as neurofibromatosis and tuberous sclerosis, 9 also manifest as nervous system diseases.…”

“…NDs are divided into central nervous system disorders and peripheral nervous system disorders. Mitochondrial hereditary diseases, hereditary metabolic diseases, and neurocutaneous syndromes, such as neurofibromatosis and tuberous sclerosis, also manifest as nervous system diseases. NDs are highly heterogeneous, and the probabilities of diagnostic rate of NDs in 5 years and not being diagnosed in more than 6 years are 33% and 15%, respectively …”

Selective symmetrical necrotizing encephalopathy secondary to primary mitochondrial disorder in a cat

“…This pattern is consistent with the brain MRI of PMD‐affected human patients and is compatible with astrogliosis, vasculopathy, and cystic malacic lesions 29 observed at histopathology. In neuroimaging of humans, PMD‐related lesions show a more restricted diffusion in diffusion‐weighted imaging (DWI) 29‐32 . The usefulness of DWI to better investigate microstructural alteration in the brain of animals affected by PMDs is not yet defined.…”

“…In the few previously published MRI descriptions of PMDs in veterinary medicine, 14,15,19 no postcontrast enhancement has been reported. In MRI of the brain in PMD‐affected human patients, contrast enhancement rarely is described 29,30,33 . When present, enhancement seems to be associated with vasculopathy and white matter rarefaction 34 .…”

“…In neuroimaging of humans, PMD‐related lesions show a more restricted diffusion in diffusion‐weighted imaging (DWI). 29 , 30 , 31 , 32 The usefulness of DWI to better investigate microstructural alteration in the brain of animals affected by PMDs is not yet defined. In our case, DWI sequences were not acquired because they are not available in a low‐field MRI system.…”