Results of a magnetic resonance imaging (MRI) study published in JIMD Reports show that patients with mitochondrial diseases may experience greater white matter hyperintensity (WMH) burden over time.
Though the study did not include individuals with mutations in the TK2 gene, these findings may hold relevance for thymidine kinase 2 deficiency (TK2d) and other mitochondrial diseases. Individuals with TK2d, for example, may experience central nervous system involvement that is detectable via imaging studies.
WMHs are brain lesions detected on MRI that are associated with an elevated risk of stroke, cognitive difficulties and death. While most cases are caused by cerebral small-vessel disease, mitochondrial diseases can also cause WMHs to form.
The study included 36 individuals with mitochondrial disease, 16 (44%) of whom had the m.3243A>G mutation in their mitochondrial DNA, a variant that often causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Of the participants, 15 were followed for a median of six years.
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At baseline, all supratentorial regions of the brain, which are responsible for numerous high-level processes, had detectable WMHs.
Over follow-up, the total WMH volume rose by 97%, and the total brain lesion volume increased fourfold. The periventricular region of the brain, which plays a role in neuroendocrine regulation, showed the greatest change over time. Nevertheless, global Fazekas scores, a measure of WMH burden, remained fairly low and did not fluctuate significantly.
Analysis of follow-up imaging revealed that women had a greater WMH burden than men. In addition, those with the m.3243A>G variant had a larger total WMH volume than those with other variants. However, the researchers found no difference in WMH burden by history of stroke-like episodes or brain symptoms.
Overall, these changes were greater than what would be expected from vascular causes alone.
“These findings emphasize the importance of systematic MRI follow-up,” the researchers concluded. “Advanced imaging approaches may further support earlier detection of progression, identification of high-risk patients and monitoring of treatment response.”
Limitations of the study include the relatively small sample size, including a low number of patients with mutations in nuclear DNA genes such as TK2.
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