Abstract
Background
To realize the clinical characteristics of long QT syndrome (LQTS) caused by antiseizure medicines (ASMs), and to improve the prevention and management of ASM-acquired QT syndrome.
Case presentation
A case of ASM-acquired QT syndrome was diagnosed and relevant literature was reviewed. The case was a 7-year-old boy who presented with a sudden onset of panic followed by changes in consciousness, with or without convulsions, lasting from tens of seconds to 3 min. The patient then received antiepileptic treatment with valproic acid, levetiracetam and oxcarbazepine and was seizure free for about a year. However, on August 12, 2021, his illness flared up again. Electroencephalogram (EEG) showed the background activity was slow, and no obvious epileptic discharge was detected. But electrocardiogram (ECG) showed a surprisingly prolonged QT interval (770 ms). Torsades de Pointes was found during Holter monitoring, while electrolyte levels were normal. The ECG recordings gradually returned to normal after stop** ASMs. For literature search, only 21 related papers were obtained after reading titles and full-texts of 105 English-language papers retrieved using keywords "acquired QT interstitial syndrome/acquired Long QT Syndrome (aLQTS)" and "anti-epileptic seizure drugs/ASMs", in the databases of Wanfang, CNKI, Pubmed, and other databases, from publication year 1965 to October 26, 2021. There are 12 types of drug-acquired LQTS caused by ASMs, most of which are Na+ blockers, but LQTS caused by oxcarbazepine had not been reported previously.
Conclusions
ASMs such as oxcarbazepine can cause acquired LQTS. When Na+ or K+ channel blockers are used clinically, ECG should be reviewed regularly and abnormal ECG should be intervened in time to reduce iatrogenic accidents in patients with epilepsy.
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Background
Long QT syndrome (LQTS) is a rare and often preventable cause of sudden cardiac death in young adults. Its prevalence is about 1/2500 [1]. According to the Practice Guidelines of the American Academy of Neurology, the risk of sudden unexpected death in epilepsy (SUDEP) in children is 0.22/1000 [2], accounting for 7%-17% of the mortality of patients with epilepsy. QT prolongation has been identified as one of the main mechanisms of SUDEP, as it is associated with fatal arrhythmias. This condition may be further aggravated by antiepileptic treatment. Although the exact pathophysiological mechanism of SUDEP remains uncertain, there are growing concerns on the impairment of cardiac function, including arrhythmias caused by seizures. In addition, the potential role of antiepileptic seizure medicines (ASMs) has been proposed [3]. Although clinical data suggest that the use of most antiepileptic drugs does not cause an additional risk of QT prolongation, there is a lack of sufficient evidence that these drugs are completely risk-free for all patients [4]. At present, about 10 types of ASMs have been reported to induce acquired LQTS [5,6,7]. However, LQTS caused by oxcarbazepine has not been reported before, and there is no consensus on ASMs associated with ECG changes and an arrhythmia risk. To advance the understanding of the ASM-acquired LQTS and improve the management of this condition, we report a case of oxcarbazepine-induced LQTS, combined with a review of related literature.
Case presentation
General information
The patient was a 13-year-old boy. In November 2015 at the age of 7, he experienced the first seizure, manifested as a sudden fear-like performance without an obvious cause in the awake state, followed by systemic rigidity, accompanied by limb twitching, which lasted for about 2–3 min, and the attack relieved naturally. Then the patient was sent to the local hospital, but the specific treatment was not clear. On March 9, 2016, the patient had a similar seizure. The presentation was the same as before, sometimes accompanied by secondary generalized tonic–clonic seizures. He was diagnosed as epilepsy (focal motor seizures with impaired awareness and focal progression to bilateral tonic–clonic seizures). On March 25, 2016, valproic acid treatment was given, with the dose gradually increasing to 5 ml, q12h (24 kg, 16 mg/kg per day). On July 20, 2016, seizures still occurred, and the therapy was changed to valproic acid + levetiracetam. On May 13, 2017, seizures occurred again, with condition of attention deficit hyperactivity disorder. Valproic acid (same as before) + oxcarbazepine (0.075, q12h initial dose, gradually increased to 0.15, q12h) treatment was given to the patient. This therapy continued for 1 year and 3 months till August 2018, when the patient’s family refused to adjust the drug dose for the fear of side effects, but the patient still had one seizure every 5-12 months. On August 12, 2021, the clinical attack appeared again, showing sudden unconsciousness. The patient denied vomiting, chest tightness, chest pain or other symptoms before and after the attack. ECG recording in a third-level grade-A hospital in ** ASMs, a time significantly longer than the 5–7-h half-life (5–9 h in children) of the ASMs. This may be associated with valproic acid. On the 10th day, ECG showed normal activity, which indicates that the diLQTS caused by ASMs was reversible.
Conclusions
Although the diLQTS caused by ASMs is extremely rare, there is still a high clinical risk and medical risk; therefore, during the diagnosis and treatment of epilepsy, we should pay more attention to identifying LQTS and analyzing its relationship with seizures. ASMs such as oxcarbazepine can cause acquired long QT syndrome. ECG should be reviewed regularly particularly when Na+ or K+ channel blockers are used, and abnormal ECG should be intervened in time to reduce iatrogenic accidents in patients with epilepsy.
Availability of data and materials
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Abbreviations
- ASMs:
-
Antiepileptic seizure medicines
- diLQTS:
-
Drug-induced LQTS
- LQTS:
-
Long QT Syndromes
- TdP:
-
Torsade de pointes
- VSD:
-
Voltage sensor domain
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We appreciate the patient and his family for their support and understanding of the manuscript.
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XY was responsible for data sorting and document compilation, Professor JZ was responsible for guiding and revising the literature, HC revised the paper, and other authors were responsible for data collection. All authors read and approved the final manuscript.
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This case report complied with the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Jiangxi Children's Hospital (JXSETYY-YXKY-20220064). Written informed consent was obtained from the patient’s guardian.
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Yu, X., Zha, J., Yi, Z. et al. Case report of antiseizure medicine-induced long QT syndrome and a literature review. Acta Epileptologica 4, 39 (2022). https://doi.org/10.1186/s42494-022-00102-3
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DOI: https://doi.org/10.1186/s42494-022-00102-3