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DOI: 10.1055/s-0041-1739682
Sulthiame Impairs Mitochondrial Function In Vitro and May Trigger Onset of Visual Loss in Leber Hereditary Optic Neuropathy
Background/Purpose: Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder and characterized by acute or subacute painless visual loss. Environmental factors reported to trigger visual loss in LHON mutation carriers include smoking, heavy intake of alcohol, raised intraocular pressure, and some drugs, including carbonic anhydrase inhibitors.
The antiepileptic drug sulthiame (STM) is effective especially in focal seizures and widely used in pediatric epileptology. STM is a sulfonamide derivate and an inhibitor of mammalian carbonic anhydrase isoforms I-XIV.
Methods: Clinical observation, molecular genetic analysis, real-time respirometry.
Results: Two unrelated patients, an 8-year-old girl and an 11-year-old boy, with cryptogenic focal epilepsy, suffered binocular (#1) or monocular (#2) visual loss in close temporal connection with starting antiepileptic pharmacotherapy with STM. In both subjects, visual loss was due to LHON. We used real-time respirometry in fibroblasts derived from LHON patients to investigate the effect of STM on oxidative phosphorylation. Oxygen consumption rate in fibroblasts from a healthy control was not impaired by STM compared with a vehicle control. In contrast, fibroblasts carrying the m.14484T>C or the m.3460G>A LHON mutation displayed a drastic reduction of the respiration rate when treated with STM compared to vehicle control.
Conclusion: Our observations point to a causal relationship between STM treatment and onset or worsening of visual failure in two subjects with LHON rather than pure coincidence. Antiepileptic medication with STM may pose a risk for visual loss in LHON mutation carriers and should be avoided in these patients.
Publication History
Article published online:
28 October 2021
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