Central Nervous System Imaging in Mitochondrial Disorders

Abstract

Imaging of central-nervous-system (CNS) abnormalities is important in patients with mitochondrial disorders (MCDs) since the CNS is the organ second most frequently affected in MCDs and some of them are potentially treatable. Clinically relevant imaging techniques for visualization of CNS abnormalities in MCDs are computed tomography, magnetic resonance imaging, and MR-spectroscopy. The CNS abnormalities in MCDs visualized by imaging techniques include stroke-like lesions with cytotoxic or vasogenic edema, laminar cortical necrosis, basal ganglia necrosis, focal or diffuse white matter lesions, focal or diffuse atrophy, intra-cerebral calcifications, cysts, lacunas, hypometabolisation, lactacidosis, hemorrhages, cerebral hypo- or hyperperfusion, intra-cerebral artery stenoses, or moyamoya syndrome. The CNS lesions may proceed with or without clinical manifestations, why neuroimaging should be routinely carried out in all MCDs to assess the degree of CNS involvement. Some of these lesions may remain unchanged for years, some may show contiguous spread and progression, but some may even disappear, spontaneously or in response to medication. Dynamics of Stroke-like lesions may be positively influenced by L-arginine, dichloracetate, steroids, edavarone, or antiepileptics. Symptomatic treatment of CNS abnormalities in MCD patients may positively influence their outcome.

Neuroimaging in Mitochondrial Disorders

“…White matter changes are frequently observed in association with many syndromes related to idiopathic developmental delay [62,63]. Clinically, leukoencephalopathies are clinically characterized by the predominance of motor disturbances, with slow neurological deterioration and a low (but not absent) incidence of seizures.…”

The use of neuroimaging in the diagnosis of mitochondrial disease

“…Once diagnosis has been confirmed, a further application of neuroimaging is the evaluation of therapeutic interventions (for examples on putative agents, see Finsterer [2009]). For example, 7 of 11 mitochondrial patients treated for 1 week with dichloroacetate (DCA) demonstrated reduced brain levels of lactate and increased NAA [De Stefano et al, 1995].…”

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

“…Elevations of brain lactate occur when mitochondrial dysfunction results in a shift in cellular ATP production from oxidative phosphorylation towards anaerobic glycolysis. On MRI, a variety of characteristic brain structural abnormalities are observed with mitochondrial disorder (Finsterer 2009;Saneto et al 2008). The widespread availability of these noninvasive imaging tools provides a valuable means of screening for brain-specific abnormalities that may reflect mitochondrial dysfunction in ASD.…”