CARBAMAZEPINE TOXICITY WITH COMPLETE OPHTHALMOPLEGIA

Abstract Background Carbamazepine (CMZ) is an anti-epileptic with a wide spectrum of clinical use (management of: bipolar disorder1, impulse control disorder2, trigeminal neuralgia3), however it has low margin of therapeutic range and toxicity is common if overdosed. Aim Describe a rare case of complete ophthalmoplegia (CO) from CMZ toxicity together with literature review. Method Literature search on PubMed, Google Scholar with keywords of 'carbamazepine toxicity', 'ophthalmoplegia', 'gaze paralysis' from inception to September 2023. Cases with inadequate data, and non-English reports were excluded. Case A 68-year-old gentleman with known history of chronic alcoholism, epilepsy and trigeminal neuralgia on CMZ 400mg 2 time-per-day, was admitted for unsteadiness. He drink 2 cans of beers daily. There were no other neurological symptoms. Clinical examination show that he was slow but able to follow instruction. CO with vertical, horizontal doll’ s eye test are impaired. No ptosis, pupil is reactive. No other focal neurological deficit. Blood investigations and computed tomography brain were normal. CMZ level was raised at 20 mg/L (normal: 6-12 mg/L). Patient improve drastically upon cessation of CMZ. CO resolved on day 3, rechecked CMZ level was 3 mg/L. He claimed that he was taking extra 3 CMZ tablets for his trigeminal neuralgia pain. Discussion CO from CMZ toxicity is very rare, with only 5 cases from literature search (Table 1)4,5,6,7,8. In all cases, carbamazepine level was >/= 20 mg/L. Most patients has mild drowsiness, only 2 with stupors. CO resolved within 3-4 days in 80% of cases. One patient died from CMZ toxicity. Majority were managed with cessation of CMZ, one case had gastric lavage and charcoal. The mechanism of CMZ causing CO is unknown. CMZ’ s vestibular depressant effect on the vestibulo- oculomotor system may contribute to ophthalmoplegia6. The use of physostigmine to reverse amitriptyline induced ophthalmoplegia suggests a cholinergic mechanism on brainstem causing ophthalmoplegia9. The anticholinergic effects of CMZ may act on similar pathways to cause ophthalmoplegia.6 Alcohol accelerates the absorption of CMZ and increases the area under the concentration-time curve for single doses, it may potentiate toxicity10,11 CMZ toxicity has to be treated seriously. Cessation of the medication, hydration, activated charcoal and hemodialysis can be considered. References 1.Chen, CH., Lin, SK. 'Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes'. BMC Psychiatry 12, 47 (2012). https://doi.org/10.1186/1471-244X-12-47. 2.Huband N., Ferriter M., Nathan R., Jones H. 'Antiepileptics for aggression and associated impulsivity'. Cochrane Database Syst. Rev. 2010;2010:CD003499. 3.Gambeta E, Chichorro JG, Zamponi GW. 'Trigeminal neuralgia: An overview from pathophysiology to pharmacological treatments'. Mol Pain. 2020 Jan-Dec; 16:1744806920901890. 4.Noda S, Umezaki H. 'Carbamazepine-induced ophthalmoplegia'. Neurology. 1982 Nov;32(11):1320. 5.Mullally WJ. 'Carbamazepine-induced ophthalmoplegia'. Arch Neurol. 1982 Jan;39(1):64. 6.Ng K, Silbert PL, Edis RH. 'Complete external ophthalmoplegia and asterixis with carbamazepine toxicity'. Aust N Z J Med. 1991 Dec;21(6):886-7. 7.Wijdicks EF, Arendt C, Bazzell MC. 'Postoperative ophthalmoplegia and ataxia due to carbamazepine toxicity facilitated by diltiazem'. J Neuroophthalmol. 2004 Mar;24(1):95. 8.Salcman M, Pippenger CE. 'Acute carbamazepine encephalopathy'. JAMA. 1975; 231(9):915 9.Spector RH, Schnapper R. 'Amitriptyline-induced ophthalmoplegia'. Neurology. 1981 Sep;31(9):1188- 90. 10.Seymour JF. 'Carbamazepine overdose. Features of 33 cases'. Drug Saf. 1993 Jan;8(1):81-8. 11.Piekoszewski W, Florek E, Szpak D, Kramer L, Jawień W. 'Carbamazepine intoxication in alcohol dependent epileptic patients'. Pharmacol Rep. 2010 Mar-Apr;62(2):398-404.