Successful Use of Quinidine to Treat Refractory Myoclonic and Astatic Seizures in a Patient with KCNT1 Variant
Abstract number :
2.311
Submission category :
12. Genetics / 12A. Human Studies
Year :
2021
Submission ID :
1826478
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:54 AM
Authors :
Marie-Christine Wright, MD, JD, MS - University of Toledo; Ajaz Sheikh - Neurology - University of Toledo; Imran Ali - Neurology - University of Toledo; Michael Nagel - Pediatric Neurology - Promedica Toledo Hospital; Naeem Mahfooz - Pediatric Neurology - University of Toledo
Rationale: We present successful use of quinidine sulfate for treatment of myoclonic and astatic seizures refractory to a regimen of multiple anti-epileptic drugs in a 2-year-old female with a heterozygous KCNT1 mutation, c.2797C >T (p.Arg933Cys), a variant of unknown significance. The use of quinidine sulfate, an anti-arrhythmic and anti-malarial drug, has been infrequently reported to treat epilepsy in other patients with KCNT1 mutations; success has been variable.
Methods: The patient’s seizures started at age 11 months. She had multiple daily generalized myoclonic and astatic seizures and an EEG abnormal for focal discharges in the midline (Fz/Cz) and right frontal (F4) region and ictal discharges of polyspike and 3–5 hertz spike and wave complexes which had bifrontal origin with bilateral secondary generalization (Fig 1). Her MRI brain was normal except for an incidental finding of 9 mm pineal cyst (Fig 2). Despite treatment with levetiracetam (41 mg/kg/d), valproate (21 mg/kg/d), and phenobarbital (4 mg/kg/d), her seizures continued to increase in frequency to 1–6 seizures per hour; in addition, she was experiencing intolerable mood side effects from levetiracetam and nightmares from phenobarbital. Quinidine sulfate was started at 100 mg t.i.d., titrated up to 200 mg t.i.d. one week later, and levetiracetam was weaned.
Results: Within one month of starting quinidine, the patient was no longer experiencing any clinical seizures and had normalization of EEG.
Conclusions: Mutations in the KCNT1 gene have been identified as gain of function mutations associated with autosomal dominant nocturnal frontal lobe epilepsy, or early infantile epileptic encephalopathy, and malignant migrating focal seizures of infancy. To date, our patient has achieved seizure-free status after being started on quinidine and has been simultaneously weaned off levetiracetam and phenobarbital. Thus, quinidine may be a viable option for treatment of patients with KCNT1 mutations who have myoclonic and astatic seizures refractory to traditional antiseizure medications. Additionally, the robust clinical response suggests that the mutation is likely to be clinically significant.
Funding: Please list any funding that was received in support of this abstract.: None.
Genetics