Signs associated with Leigh syndrome range from a near absence of abnormalities to severe neurologic problems. Central nervous system is frequently affected. The clinical signs include motor and /or intellectual retardation/regression, brainstem dysfunction, including respiratory abnormalities and abnormal eye movement (nystagmus and ophthalmoparesis) [1,2].
Sometimes, atypical neurologic abnormalities present to suggest Leigh syndrome, and this condition is known as Leigh-like syndrome ; endocrine abnormalities, cardiac abnormalities, and gastroenterologic problem are some examples .
A diagnosis of Leigh syndrome is based on clinical signs and symptoms, metabolic abnormalities, and neuroimaging findings . Leigh syndrome is characterized by almost identical brain changes: focal, bilateral symmetric lesions associated with demyelination, vascular proliferation and gliosis .
The gray matter
The abnormal histopathology in central gray matter is a major indication of Leigh syndrome. Lesions are most consistently observed in the brain stem gray matter and usually occur in both sides. They are delineated and spread into the white matter. These lesions are spongy and show an intense capillary proliferation. Vacuoles enclosed by membrane(s) also present in lesions. The most severe lesions can lead to cavitation and tissue collapse .
The white matter
White matter is well preserved in most cases, but abnormal white matter can be found in cerebra and cerebellum. The abnormalities include sponginess, deficient myelin formation, myelin loss, abundant presence of lipid-laden macrophages, capillary proliferation, prominent gliosis, and eventually axonal loss. Myelin sheaths and dendrites degenerate before axons and cell bodies do. The optic nerves and tracts are often demyelinated and scarred up .
Ragged red fibers are usually associated with mitochondrial disease and can be found in some Leigh syndrome patients. Mitochondria accumulate in skeletal muscle fibers when oxygen level is abnormally low. The staining with Gomori modified Trichrome gives the red color .