A Primer on Leigh's disease: a progressive, midline, symmetric, necrotizing neurodegenerative syndrome

For those of you taking your neuropathology subspecialty boards on September 10, 2009 (all 20 of you!), you should know that it will cost you $1800. You should also know something about Leigh's disease. I can't help you with the $1800; but I can give you some information about 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, as seen in these images from the University of Cincinnati College of Medicine. The characteristic neuropathologic finding is symmetric necrotic lesions distributed along the brainstem, diencephalon, and basal ganglia. Characteristically, some neurons are intact within the areas of partial necrosis. 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 north as the cerebral white matter and as far south 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.

That should pretty much cover you for the exam. Good luck!

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.