The neuroimaging of Leigh syndrome: case series and review of the literature

Abstract

Leigh syndrome by definition is (1) a neurodegenerative disease with variable symptoms, (2) caused by mitochondrial dysfunction from a hereditary genetic defect and (3) accompanied by bilateral central nervous system lesions. A genetic etiology is confirmed in approximately 50% of patients, with more than 60 identified mutations in the nuclear and mitochondrial genomes. Here we review the clinical features and imaging studies of Leigh syndrome and describe the neuroimaging findings in a cohort of 17 children with genetically confirmed Leigh syndrome. MR findings include lesions in the brainstem in 9 children (53%), basal ganglia in 13 (76%), thalami in 4 (24%) and dentate nuclei in 2 (12%), and global atrophy in 2 (12%). The brainstem lesions were most frequent in the midbrain and medulla oblongata. With follow-up an increased number of lesions from baseline was observed in 7 of 13 children, evolution of the initial lesion was seen in 6, and complete regression of the lesions was seen in 3. No cerebral white matter lesions were found in any of the 17 children. In concordance with the literature, we found that Leigh syndrome follows a similar pattern of bilateral, symmetrical basal ganglia or brainstem changes. Lesions in Leigh syndrome evolve over time and a lack of visible lesions does not exclude the diagnosis. Reversibility of lesions is seen in some patients, making the continued search for treatment and prevention a priority for clinicians and researchers.

Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

“…Patients with Leigh syndrome are typically diagnosed after an acute metabolic crisis, with the concomitant presence of bilateral lesions detectable by brain MRI (25). Thus, the degenerative brain disease usually manifests before diagnosis.…”

Recessive mutations in VPS13D cause childhood onset movement disorders

“…The characteristics of the first MRI resemble Leigh syndrome MRI presentations, which consist of symmetrical T2 hyperintensities affecting the putamina, caudate heads, globus pallidus, thalamus, subthalamic nucleus, and brainstem (periaqueductal gray matter, pons, medulla); more rarely there is multifocal white matter involvement. 17 Interestingly, 3 patients in our cohort initially received a presumptive diagnosis of Leigh syndrome because of their imaging and clinical presentation, although the absence of sudden clinical deterioration, slow progression, and normal serum lactate levels did not support this diagnosis. Individual II-2 from Family 2 did have elevated cerebrospinal fluid lactate.…”

“…The striking brain MRI findings are wide‐ranging and include symmetrical caudate and putaminal hyperintense T2/ FLAIR signal or multifocal, widespread subcortical white matter involvement with a hypointense T2 signal in the basal ganglia and putaminal atrophy (see Fig ). The characteristics of the first MRI resemble Leigh syndrome MRI presentations, which consist of symmetrical T2 hyperintensities affecting the putamina, caudate heads, globus pallidus, thalamus, subthalamic nucleus, and brainstem (periaqueductal gray matter, pons, medulla); more rarely there is multifocal white matter involvement . Interestingly, 3 patients in our cohort initially received a presumptive diagnosis of Leigh syndrome because of their imaging and clinical presentation, although the absence of sudden clinical deterioration, slow progression, and normal serum lactate levels did not support this diagnosis.…”

Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients

“…These lesions included cortical atrophy, T2-signal hyperintensities or stroke-like lesions. Radiological involvement of the cortex, commonly reflected by global atrophy, was found in 12% of patients with Leigh syndrome regardless of genetic cause in one study 30. Neuropathology studies in Leigh syndrome suggest that the characteristic striatal and brainstem lesions are due to primary energy deprivation 22.…”