Leber's hereditary optic neuropathy: the neurologist point of view

Summary Leber's hereditary optic neuropathy (LHON) is a neurodegenerative disorder that selectively affects the retinal ganglion cells (RGCs), consequently leading to optic atrophy and loss of central vision. The primary cause is a metabolic dysfunction of mitochondria due to mitochondrial DNA mutations affecting the respiratory complex I. Despite the metabolic defect is systemic and measurable in post-mitotic tissues, the disease is usually limited to the RGCs and leads to profoundly impaired vision. However, adjunctive neurological features may be present in a subset of LHON patients defining the so-called “plus” variant phenotype. The most frequent neurological features may be a multiple-sclerosis-like disease, basal ganglia involvement with dystonia or spastic dystonia and bilateral striatal necrosis, myoclonus, parkinsonism, peripheral neuropathy, migraine and sensorineural hypoacusia. Neurological exam, brain MRI, MR-spectroscopy and other ancillary exams may be needed to well characterize the “plus” phenotype of LHON patients. The genetic bases of these LHON “plus” cases are currently unclear, but private mtDNA mutations and nuclear genetic variants may be relevant.