To describe a case of Leber hereditary optic neuropathy (LHON) mimicking neuromyelitis optica spectrum disorder (NMOSD).

LHON is an inherited mitochondrial disorder caused by point mutations in mitochondrial DNA genes (most commonly MTND1, MTND4, MTND6), which ultimately results in retinal ganglion cell apoptosis and demyelination/atrophy of the optic nerves, chiasm, and tracts. LHON typically affects young males and presents with sudden unilateral painless central vision loss, progressing to bilateral vision impairment within weeks to months, though it is not uncommon for vision loss to be bilateral at onset. Case reports of “LHON plus” syndromes have described patients with bilateral optic neuropathy plus extra-ophthalmologic manifestations, including cardiac conduction abnormalities, dystonia, and longitudinally extensive transverse myelitis (LETM).

Case report

This is a 34-year-old man with a stepwise neurologic decline over five years. He first developed left then right leg spastic paresis, followed by urinary and fecal retention, then years later experienced sudden onset of binocular painless visual impairment (could see movements) and bilateral upper extremity weakness/spasticity. MRI demonstrated an enhancing, T2 FLAIR hyperintense, longitudinally extensive lesion from the medulla to the lower cervical spinal cord. He was treated with solumedrol pulses and PLEX, without improvement. Extensive lab workup was unremarkable, including CSF and serum aquaporin-4 and MOG antibodies. Whole genome sequencing later detected a pathogenic mitochondrial DNA mutation (14484T>C) in the MTND6 gene, associated with LHON.

This is a case of LHON presenting first with myelopathic signs including spastic paraplegia and bowel/bladder dysfunction, followed years later by bilateral painless optic neuropathy, progressing to spastic quadriplegia. A few similar cases of bilateral optic neuropathy and LETM have been described, and even fewer cases of cord involvement preceding vision symptoms. It is important to consider LHON in the differential for seronegative NMOSD, as both can present with bilateral vision impairment and LETM.