Atypical clinical and MRI features in Leber hereditary optic neuropathy: a case series of four patients

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder typically presenting with subacute, painless, bilateral vision loss in young individuals. While often recognizable, atypical presentations can complicate diagnosis. Notably, optic nerve lesions on MRI are uncommon in LHON and are typically associated with inflammatory optic neuropathies, increasing the risk of misdiagnosis.

We retrospectively analyzed four patients who initially presented with suspected optic neuritis but were later diagnosed with LHON. Demographic, genetic, clinical, and multimodal data were retrieved from medical records.

The series included two adolescent males, a 51-year-old man, and a 52-year-old woman. All experienced subacute, bilateral vision loss and were later found to carry pathogenic LHON mutations. However, their initial presentations were misleading. The two adult patients presented beyond the typical age of onset; one was initially diagnosed with glaucoma due to increased intraocular pressure, while the other had a history of Fahr's syndrome. One adolescent reported ocular pain with eye movements and showed a relative afferent pupillary defect, mimicking optic neuritis. Two patients lacked typical fundoscopic findings suggestive of LHON. MRI findings further complicated the diagnosis: all patients showed T2-FLAIR hyperintensities of the optic nerves with contrast enhancement, and in three cases abnormalities extended posteriorly to the chiasm and optic tracts on follow-up MRI.

MRI abnormalities involving the optic pathway do not exclude LHON and may be present in atypical cases. LHON should be considered in all patients presenting with bilateral subacute visual loss, even when clinical or imaging features suggest alternative diagnoses.