Leber hereditary optic neuropathy (LHON)
Which are the symptoms?
In most LHON patients, visual impairment is the only significant clinical manifestation. However, cardiac conduction disorders (preexcitation syndromes and prolonged QT interval), musculoskeletal and neurological disorders (reflex disorders, mild cerebellar ataxia, movement disorders, peripheral neuropathies) were found in some families. In addition, some patients, especially women, with LHON confirmed by genetic molecular analysis show symptoms and signs of multiple sclerosis (including changes in cerebrospinal fluid and white matter confirmed by MRI), while at the same time they show severe and progressive optic neuropathy typical of LHON. The significance of this association is still not entirely clear: population studies have not shown a higher prevalence of mtDNA mutations in patients with multiple sclerosis. Therefore, it is possible that the apparent link between LHON and MS is no more than the mere prevalence of the two diseases. However, an underlying change in mtDNA may worsen the prognosis of optic neuritis in patients with multiple sclerosis.
How is it diagnosed?
In terms of differential diagnosis, there are many case reports of LHON associated with clinical features suggestive of MS. Given the heterogeneity of Leber's views, both in terms of patient age and clinical characteristics, we believe that mtDNA analysis should be performed for any form of bilateral optic neuropathy in which it is impossible to establish an accurate etiological diagnosis. This is especially true for forms of progressive atypical optic neuritis, at whatever age it occurs, in the absence of obvious signs of associated systemic pathology; for hereditary optic neuropathies such as Kier's disease; in selected cases of optic atrophy of the child, even in the first years of life, if there are no other signs of defined malformation syndromes.
How is it treated?
There is currently no therapy that has been shown to be effective in treating LHON, including the addition of vitamins and other cofactors and the use of steroids. In some cases, visual and neurological repair has been described using idebenone, a quinone analog, but more experience is required to obtain meaningful results. Various neuroprotective therapies are also very promising, but even so, are still under consideration. Some preventive measures, notably abstaining from smoking and drinking alcohol, are the only measures that are certainly considered beneficial in preventing disease.