Leber hereditary optic neuropathy (LHON)
General description
Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by acute or subacute vision loss due to optic nerve atrophy. The onset of visual impairment usually occurs between ages 20-40 but can affect individuals of any age. It often starts in one eye and progresses to the other within weeks. Triggers like smoking, alcohol, or certain antibiotics can precipitate symptoms in previously unaffected carriers.
LHON follows a maternal inheritance pattern, with reduced penetrance, affecting about 50% of males and 10% of females carrying the mutation. Over 90% of cases are linked to one of three mitochondrial DNA (mtDNA) mutations (m.11778>A, m.3460G>A, or m.14484T>C), which affect the complex I subunit of the respiratory chain.
While LHON primarily involves optic nerve damage, some individuals may experience additional symptoms, such as tremors, peripheral neuropathy, movement disorders, cardiac conduction abnormalities (e.g., Wolff-Parkinson-White syndrome), and multiple sclerosis-like symptoms. These extraocular manifestations are referred to as "LHON plus."
Optic nerve
-
Optic nerve
MRI shows coronal T2WI/STIR hyperintensity in the bilateral optic nerves, with occasional involvement of the optic chiasm. In the acute to subacute phase, contrast enhancement is observed in the bilateral optic nerves, while in the chronic phase, optic nerve atrophy is noted.
Basal ganglia and brainstem
-
Caudate nucleus
-
Putamen
-
Globus pallidus
-
Brainstem
Although imaging findings can vary among patients, Leber plus syndrome typically presents with bilateral T2WI/FLAIR hyperintensities in the basal ganglia and brainstem.
White matter lesion
-
CerebrumCerebral white matter
-
CerebellumCerebellar white matter
Occasionally, T2WI/FLAIR may show patchy high signals in the cerebral white matter, cerebellum, and brainstem, making differentiation from multiple sclerosis challenging.