Abstract

SO.14.07

Seizures following subconjunctival 5-FU therapy

René Höhn1, Julia Lamparter1, Daniel Herzog1, Stefan Klimpe2, Norbert Pfeiffer1, Urs Voßmerbäumer1
1Universitäts-Augenklinik Mainz, 2Neurologie, Universitätsklinikum Mainz

Objective
Antiproliferative treatment following glaucoma surgery includes subconjunctival 5-fluorouracil (5-FU) injections as a routine procedure. Cumulative dosage during the postoperative period is adjusted to individual needs ranging from 5 to 75 mg.
Results
We report the case of a 68 year old male caucasian patient who underwent uneventful trabeculectomy with intraoperative application of Mitomycin C. 5mg 5-FU were given subconjunctivally on postoperative day 4. Few minutes later, a generalized, tonic and clonic seizure occurred lasting for 3 minutes. A second seizure happened 3 hours later. However epilepsy was hitherto unknown in this patient nor did his medical history give any hints as to such a condition. Known systemic conditions included arterial hypertension, coronary heart disease, congenital aortic coarctation, hyperlididemia and prostate hyperplasia. Neurologic examination including electroencephalography and cranial imaging revealed spike wave complexes, but no specific focus. 13 days later 5 mg 5-FU were twice applied without complications under anticonvulsive therapy. When trabeculectomy was performed on the fellow eye three months later, 5 mg 5-FU were again applied to prevent bleb scarring without obvious complications. Upon a 5-hour interval after the second injection, two more grand-mal convulsions occurred despite anticonvulsive therapy with gabapentin.
Conclusions
5-fluorouracil is a pyrimidine antimetabolite that blocks DNA synthesis and inhibits RNA processing and function. Neurotoxicity is not known as a common side effect and clinical incidence is <1%, manifesting as encephalopathy or cerebellar syndrome following systemic therapy. However, seizures are described in only a few cases, the exact pathway is not understood. Acute damage to neuronal cells by induction of apoptosis from systemic 5-FU has been demonstrated in an animal model as well as delayed damage to myelinated tracts. Our patient presented with a first seizure following a single subconjunctival injection of 5 mg 5-FU. Despite anticonvulsive therapy seizures recurred after reapplication on the fellow eye. After discontinuation of 5-FU, no more epileptic episode occurred. All known seizures of this patient were temporally associated to the injection. To the best of our knowledge this is the first report of epileptic seizures following subconjunctival 5-FU application.

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