Neuroimaging characteristics of single Large-Scale mitochondrial DNA deletion syndromes

Single large-scale mitochondrial DNA deletion syndromes (SLSMDSs) are rare mitochondrial disorders that present a continuum of phenotypes, including Pearson syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. Neuroimaging findings in SLSMDSs are underreported, and their role in diagnosis and disease monitoring remains inadequately defined. This study aims to characterize clinical features and analyze neuroimaging findings, including spectroscopy and diffusion imaging, in patients with SLSMDSs.

A retrospective review of 11 patients diagnosed with SLSMDSs at a tertiary referral center between 2013 and 2024 was conducted. Clinical, genetic, and neuroimaging data were analyzed. MRI scans were reviewed for abnormalities in various brain regions, including white matter, basal ganglia, thalami, corpus callosum, cerebellum, and brainstem.

The cohort had a mean age of 8.3 years (63.6% female). MRI was normal in 4 patients. Among the remaining 7, symmetrical T2/FLAIR hyperintensities, with or without diffusion alterations, were frequently observed, involving the dorsal brainstem in 7/7 and the cerebellum in 6/7 of patients. Globi pallidi involvement was also present in 6 of 7 patients. MR basal ganglia spectroscopy demonstrated elevated lactate in 3 of 7 patients with available spectroscopy. Subcortical and deep white matter abnormalities were identified in 3 patients, sparing the periventricular regions. Imaging progression was noted in patients with serial studies (4 patients).

Neuroimaging in SLSMDSs typically demonstrates characteristic involvement of the dorsal brainstem, cerebellum, and basal ganglia, and may show diffusion alterations, a finding suggestive of metabolic injury. The observed pattern of subcortical white matter involvement with periventricular sparing may aid in differentiating this disorder from others. Normal imaging may be present in early or less severe disease. MRI, including diffusion imaging and spectroscopy, can support diagnosis and longitudinal monitoring.