Spectrum of clinical neuroimaging in mitochondrial disorders: a neuroanatomical approach

Mitochondrial disorders are a highly heterogeneous group of genetic diseases that impact pathways associated with the structure and function of the mitochondrion. Clinical presentations of mitochondrial disorders include a wide range of onset, progression, and spectrum of neurological symptoms – ranging from episodic, focal neurological deficits to gradual onset of developmental delays, sensorineural hearing loss, visual impairment, or ataxia. This variability provides clinicians with a diagnostic challenge in identifying suspicion of a mitochondrial disorder and prioritizing specific mitochondrial disorders within their differential. While next-generation sequencing of both the nuclear and mitochondrial genomes has aided identification of mitochondrial disorders, testing results are typically not available for weeks to months, and CSF and biochemical studies indicating possible mitochondrial disorder, such as elevated lactate, are nonspecific in differentiating between mitochondrial disorders and other neurogenetic diseases. Neuroimaging can serve as an early tool to help identify specific mitochondrial disorders; however, there are additional variability and overlap between disorders and other non-mitochondrial diseases. This review provides a framework in narrowing the mitochondrial differential by neuroanatomical localization on neuroimaging studies. We will highlight established neuroimaging patterns associated with mitochondrial disorders, review the role of MRS, and discuss the alternative non-mitochondrial etiologies associated with these findings.