Complex I deficiency

> Literature review

Complex I is the largest complex of the respiratory chain and isolated deficiencies are the most common enzymatic defect of the oxidative phosphorylation disorders. Deficiencies result in a wide variety of Mitochondrial disorders ranging from lethal neonatal disease to adult onset neurodegenerative disorders. These patients have a reduction/deficiency of NADH-Coenzyme Q reductase.

On brain imaging all patients have T2 hyperintense lesions of the brainstem. This may involve the ventral midbrain, dorsal midbrain, dorsal pons, ventral medulla oblangata, or dorsal medulla oblangata. 90% of patients have at least 1 striatal anomaly (putamen or caudate). 1/3 of patients have thalamic increased T2 signal (all of whom had a striatal anomaly). Caudate lesions are seen in 1/2 of patients with mitochondrial (mtDNA) mutations vs 10% of patients with nuclear mutations. 40% of patients with mtDNA mutations have cortical grey matter stroke lesions with this finding not being seen in patients with nuclear mutations. On the other hand a supratentorial leukoencephalopathy is seen in over 1/2 of patients with nuclear mutations but none in mtDNA mutations. Cerebellar T2 hyperintensities are seen in 45% of patients. Cerebellar atrophy is seen only in patients with mtDNA mutations. Patients may have elevated lactate on MRS.

Complex I deficiency secondary to NUBPL mutation results in sharply defined decreased T1, increased T2 lesions of the corpus callosum that expand the corpus initially and then thin it. They have multifocal (sometimes confluent) periventricular/deep white matter lesions that may be continuous with the corpus callosal lesions. These white matter lesions progress to volume loss as if the cavitated white matter lesions have collapsed. The subcortical U fibres are spared. They may also have increased T2 signal of the cerebellar cortex which progresses to atrophy with secondary pontine atrophy.