How hypoxic brain injury and mitochondrial abnormalities may contribute to the pathogenesis of movement disorders, such as in our case, remains unknown. It is important to note that her abnormal movements occurred after birth and they were progressive. Reported secondary etiologies of a myoclonus and dystonia syndrome have included storage disorders, neurodegenerative diseases, drug-induced, toxic-metabolic conditions, inflammatory disorders, and traumatic or hypoxic insults to the brain.[18, 19] Our patient had multiple perinatal comorbidities (gestational toxemia, hypoglycemia, and postnatal sepsis) that resulted in resuscitation and likely brain hypoxia from the incident. It has been hypothesized that anoxic injury to the thalamus may underpin the abnormalities delaying the presentation of the movement disorders, such as in our case. Though she had a genetic confirmation of a complex I mitochondrial defect, which hypothetically could have contributed to the manifested syndrome, we cannot completely be sure that this is the underlying etiology. Whereas movement disorders reported in mitochondriopathies can be myoclonic and have been associated with seizures, our patient had only one of these known manifestations. Impaired mitochondrial function is known to impact biological processes that depend on energy and metabolism in structures with high metabolic activity, such as putamen, globus pallidus, and thalamus, and these have been reported in many neurological disorders, inclusive of both dystonia and myoclonus. Though we cannot be certain, we hypothesize the mitochondrial dysfunction in addition to the hypoxic brain injury were large contributors to the hyperkinetic movements in our case.
The mechanism of action of DBS in mitochondrial disorders remains uncertain, and the optimal stimulation target for similar syndromes continues to be debated. Described reports suggest benefits for movement disorders secondary to mitochondrial disease may occur even if surgery is not considered until long after symptom onset. The clear loss of the DBS benefit initially observed in our case suggests both a loss of DBS benefit and somewhat of a disease progression, at least for dystonia. Higher DBS settings need to be tried before considering dystonia to be unresponsive. Longer follow-up and blinded evaluations are required to confirm our short-term results and unblinded results and allow stronger conclusions. Although promising, DBS outcomes for secondary myoclonus and dystonia will require more study to better understand reasonable approaches to the application of this technology.