BACKGROUND: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. METHODS: A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. RESULTS: LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ± standard deviation, 2.79 ± 1.47 vs. 3.83 ± 1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ = 4.29, P = 0.04). CONCLUSIONS The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.
Acidosis, Lactic ; drug therapy ; mortality ; Adolescent ; Anticonvulsants ; therapeutic use ; Carbamazepine ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Lamotrigine ; therapeutic use ; Levetiracetam ; administration & dosage ; therapeutic use ; Male ; Mitochondrial Encephalomyopathies ; drug therapy ; mortality ; Oxcarbazepine ; therapeutic use ; Prospective Studies ; Retrospective Studies ; Stroke ; drug therapy ; mortality ; Topiramate ; therapeutic use ; Valproic Acid ; therapeutic use

INTRODUCTION: Simultaneous bilateral angle-closure glaucoma is a potentially blinding disease. From 2001 to 2007, over 100 cases of Topiramate-associated bilateral acute angle glaucoma (TA-ACG) were reported. We report the first known case in the Philippines.

CASE REPORT: A 42-year old Filipino woman diagnosed with migraine presented with the sudden blurring of vision, with generalized headache after her second dose of 25mg Topiramate. Visual acuity was decreased to 20/200 in each eye. Intraocular pressures  (IOP) were elevated to OD 50mmHg and OS 55mmHg with shallow anterior chambers and 360 degree angle closure on gonioscopy. Stat doses of mannitol, acetazolamide, brimonidine, and latanoprost were given. Topiramate was discontinued. Laser iridotomy was performed with note of an immediate drop in IOP to OD 24mmHg and OS 18 mmHg. On the day of discharge, the patient's third day of admission, IOP had returned to 12 mmHg OU and best-corrected vision had improved to 20/20 in both eyes. B-scan ultrasonography confirmed choroidal thickening in both eyes.

DISCUSSION: Topiramate associated acute angle closure glaucoma (TA-AACG) as an idiosyncratic adverse effect was first reported by Banta et al in July 20018 with shallow anterior chambers, relative lens thickening, and 360° ciliochoroidal detachments in both eyes on A- and B-scan ultrasonography. Angle-closure was believed to result from the anterior rotation of the ciliary process and not from pupillary block, rendering laser iridotomy ineffective. Signiñicant lens thickening has been shown in TA-AACG. It is thought to result in part from relaxation of the zonules due to anterior ciliary rotation and ciliary edema, and from a direct drug effect. Myopia resulting from this is characteristic of TA-AACG and may persist from days to weeks after discontinuation of topiramate. The management of TAAACG requires stopping the drug. As TA-AACG and transient myopia usually resolves within days to weeks after stopping Topiramate, medical treatment with topical cycloplegic agents, topical beta-blockers and oral pressure-lowering agents often suffice as an interim measure. However, more invasive options such as laser iridotomy should be considered when significant pupillary block angle closure is present.

SUMMARY: Topiramate may be associated with acute angle-closure glaucoma wherein, in the Filipino patient, pupillary block may be present and should be addressed by laser iridotomy when possible.

Human ; Female ; Glaucoma, Angle-closure ; Latanoprost ; Mydriatics ; Acetazolamide ; Intraocular Pressure ; Gonioscopy ; Topiramate ; Brimonidine Tartrate ; Mannitol ; Rotation ; Philippines ; Acceleratory Factor From Growth Hormone ; Prostaglandins F, Synthetic ; Fructose ; Migraine Disorders ; Visual Acuity ; Myopia ; Headache ; Ultrasonography ; Edema ; Anterior Chamber