Clinical:Leigh's disease

Leigh's disease -- also known as Leigh syndrome, or, more descriptively, subacute necrotizing encephalomyelopathy -- is a progressive neurodegenerative disorder of infancy and childhood (but older patients and rare adult cases are recognized). Common clinical findings include signs of dysfunction of the brainstem or basal ganglia such as respiratory abnormalities, nystagmus, ataxia, dystonia, and hypotonia. MRI often shows hyperintensity of the basal ganglia and thalamus. The characteristic neuropathologic finding is symmetric necrotic lesions distributed along the brainstem, diencephalon, and basal ganglia. Degeneration in and around the cerebellar dentate nuclei are also quite common. Loss of Purkinje cells in the cerebellum, accompanied by profuse 'torpedo' formations highlighted by neurofilament immunohistochemistry, can also be seen. Although deep gray structures are most frequently involved, symmetric necrotic lesions as far superior as the cerebral white matter and as far inferior as the spinal cord can be seen. The pathophysiology involves failure of oxidative metabolism within the mitochondria of the developing brain due to a variety of molecular defects. Inheritance can be X-linked recessive, autosomal recessive, or maternal, depending on the responsible defect. In X-linked cases, mutations of the E1 subunit of pyruvate dehydrogenase complex (PDHC) are often present.

References

1. Greenfield's Neuropathology (8th edition, 2008, Hodder Arnold). Edited by Love S, Louis DN, Ellison DW. p. 608-9.

2. Neuropathology: A reference text of CNS pathology (2nd edition, 2004, Elsevier). Edited by Ellison D, Love S, Chimelli L et al. p. 142-5.