PMC8281247_01
Brain computed tomography shows calcifications of bilateral basal ganglia, thalamus (A,B), and cerebellar dentate nuclei (C).
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F1
Brain computed tomography (CT) showed calcifications of the bilateral basal ganglia, thalamus, and cerebellar dentate nuclei (Figure 1).
(A) At age 12 years, magnetic resonance imaging (MRI) revealed hyperintense on T1-weighted images and hypointense or hyperintense on T2-weighted images in the bilateral basal ganglia and thalamus (white arrowhead), which were coincident with areas showing calcifications on computed tomography. Some lesions were slightly hypointense or isointense on T1-weighted images, with T2 hyperintense in the bilateral internal capsule and periventricular areas (yellow arrowhead). (B) At age 19 years, MRI showed mild brain atrophy, but the lesions of bilateral internal capsule and periventricular areas (yellow arrowhead) did not change significantly compared to those in the previous MRI. (C-E) At age 22, 24, and 26 years, MRI showed no change in the lesions of bilateral internal capsule and periventricular areas (yellow arrowhead). Brain atrophy showed no obvious change.
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F2
T2-weighted images in the bilateral basal ganglia, thalamus, and cerebellar dentate nuclei, which were coincident with areas showing calcifications in the CT images. The other lesions were slightly hypointense or isointense on T1-weighted images, with T2 hyperintense in the bilateral internal capsule and periventricular areas (Figure 2A). There were four episodes in the following 6 years. MRI showed mild brain atrophy, but the lesions did not change significantly compared to those in the previous MRI (Figure 2B). At the age of 22 years, his EEG showed generalized, low-to-medium amplitude, 3- to 4-Hz spike-and-wave discharge, and lesions in the MRI were unchanged (Figure 2C). MRI showed no change in the lesions (Figure 2D). MRI were the same as before (Figure 2E). Magnetic resonance spectroscopy (MRS) revealed no lactate peaks.
(A) Chronology of the major clinical features. EEG, electroencephalography; CT, computed tomography; MRI, magnetic resonance imaging; EMG, electromyography; MoCA, Montreal Cognitive Assessment; MMSE, Mini-Mental State Examination; RBFs, ragged blue fibers; SSV, strongly succinate dehydrogenase-reactive vessel; COX, cytochrome C oxidase; NGS, next-generation sequencing; nDNA, nuclear DNA; mtDNA, mitochondrial DNA. (B) Pedigree of the family showing clinically and genetically affected members (black squares).
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F3
At age 26 years, he visited our clinic with the abovementioned symptom (Figure 3).
(A) Hematoxylin and eosin staining demonstrates no obvious abnormalities. (B) Modified Gomori trichrome staining shows no ragged red fibers. (C) Succinate dehydrogenase (SDH) staining shows several ragged blue fibers (asterisks). (D) Cytochrome C oxidase (COX) staining shows plenty of COX-deficient fibers (asterisks). (E) COX-SDH staining shows occasional COX-negative and SDH-positive fibers in blue. (F) SDH staining shows atypical strongly SDH-reactive vessels (arrows).
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F4
C oxidase (COX) staining revealed abundant COX-deficient fibers. COX-SDH staining showed only occasional COX-negative and SDH-positive fibers in blue (Figure 4). mtDNA testing of blood and muscle biopsy sample was performed, which detected a known m.5549G>A mutation in the MT-TW gene.