Topiramate and visual loss in a patient carrying a Leber hereditary optic neuropathy mutation

Abstract

We describe a 43-year-old patient who experienced visual loss 4 years after beginning antiepileptic therapy with topiramate. Ophthalmological and neurological examinations led to a preliminary diagnosis of bilateral toxic optic neuritis. Mitochondrial genome sequence analysis detected a Leber hereditary optic neuropathy 11778G>A mutation. The possibility that topiramate might favor a conversion disease, alerts physicians to seek a history of blindness in patients undergoing chronic antiepileptic therapy.

Mitochondrial epilepsy in pediatric and adult patients

“…LHON : Only occasionally patients with LHON develop extra‐ocular manifestations including epilepsy . In some of these patients, epilepsy may precede the onset of ocular manifestations . Epilepsy may even start in early infancy and may present as myoclonic seizures .…”

“…Replacement of VPA by non‐mitochondrion‐toxic AEDs improves the outcome of these patients . Topiramate (TPM), which is known to inhibit an isoenzyme of the carboanhydrase, was accused to have triggered bilateral visual impairment in a patient with LHON . Except for dosages and management of rare pediatric electro‐clinical syndromes, differences between pediatric and adult mitochondrial epilepsy concerning AED treatment have not been reported.…”

Toxic optic neuropathies

“…Certain medications which were not previously known to be toxic have been reported to cause optic neuropathy in susceptible patients with preexisting dysfunction in mitochondrial metabolism [11,12]. Similarly, agents with known toxic effects to optic nerve were reported to exacerbate the preexisting mitochondrial optic neuropathies [13,14]. New case reports with toxic optic neuropathy can be anticipated in patients with congenital mitochondrial diseases, unless care is taken about the use of drugs that may interfere with mitochondrial metabolism in such patients [15].…”

MELAS syndrome due to the m.3291T>C mutation

“…Topiramate is an inhibitor of the mitochondrial carboanhydrase-VB. Topiramate has beneficial [5] and unfavourable effects [6] to mitochondria. As an inhibitor of the mitochondrial transition pore it has an anti-obesity effect but can be also effective in migraine and epilepsy.…”