Girl with rare CDD remained seizure-free for over 11 months
Fintepla treatment linked to response in single case report
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Brain scan images are displayed on a computer. A case report described more than 11 months of seizure freedom in a girl with CDD whose epilepsy evolved into an LGS pattern. (Image from iStock)
A girl with difficult-to-treat CDKL5 deficiency disorder (CDD), whose epilepsy later developed into Lennox–Gastaut syndrome (LGS), became seizure-free for more than 11 months after treatment with low-dose Fintepla (fenfluramine), suggesting this medication may be a potential option for similarly hard-to-treat seizures, according to a report from Japan.
After starting Fintepla, the patient’s caregivers said her seizures stopped. This came alongside a “dramatic” reduction in seizure-related anxiety. According to the report, the caregivers described the seizure freedom as “life-changing,” allowing more predictable daily care and fewer emergency visits.
“However, as a single observation it cannot establish efficacy,” researchers wrote in “Long-term response of fenfluramine in pediatric CDKL5 deficiency disorder with Lennox–Gastaut syndrome: A case report,” which was published in Brain and Development Case Reports. “Further studies are needed,” the researchers added.
CDD seizures are often hard to treat
CDD is caused by pathogenic variants in the CDKL5 gene that result in seizures usually beginning within the first three months of life, followed by delays in development. The types of seizures change over time and may evolve into LGS, a severe epilepsy syndrome. Treatment is limited because seizures are often resistant to the available antiseizure medications.
Here, the researchers described the case of a 13-year-old girl who was born at full term without birth complications and had no family history of epilepsy. Her first seizure occurred at 3 months of age and appeared as a generalized tonic seizure, which increases muscle tension, making muscles stiff throughout the body.
By 6 months, she developed other types of seizures, including generalized tonic-clonic seizures, which involve stiffening followed by rhythmic jerking; focal motor seizures, which involve only one part of the body; and focal impaired awareness seizures, during which a person is not fully aware of their surroundings. Later, she also developed repeated clusters of epileptic spasms.
An electroencephalogram (EEG), which measures the brain’s electrical activity, revealed hypsarrhythmia, an abnormal pattern associated with infantile epileptic spasm syndrome. Genetic testing found a variant in one copy of the CDKL5 gene that was not inherited from either parent, known as a de novo genetic variant.
Although this specific genetic variant was formally classified as being of uncertain significance because of limited evidence, its occurrence together with her clinical features strongly supported a diagnosis of CDD. She was treated with adrenocorticotropic hormone (ACTH), as well as several antiseizure medications, including carbamazepine, phenobarbital, zonisamide, and topiramate.
However, none of these treatments provided lasting control of her seizures. During this time, her development was delayed, and she also had severe delays in motor development, with poor control of her head and limited ability to follow objects with her eyes. Over the following years, doctors also tried a ketogenic diet, a high-fat, low-carbohydrate diet sometimes used for certain types of epilepsy, along with additional antiseizure medications.
Seizures stopped after Fintepla
By 13 years of age, she was taking valproate, levetiracetam, and lamotrigine but still experienced generalized tonic-clonic seizures every day and repeated clusters of epileptic spasms. Her EEG showed generalized slow spike-and-wave discharges — an abnormal electrical pattern characteristic of LGS — along with abnormal seizure-like electrical activity in multiple areas of the brain. Together with her seizure history, these findings supported the conclusion that her epilepsy had evolved into an LGS pattern.
Because her seizures remained severe despite many treatments, the doctors started Fintepla at 0.2 mg/kg/day. Soon after starting the medication, both her daily generalized tonic-clonic seizures and her clusters of epileptic spasms stopped completely. “All seizures completely resolved within a few days,” the researchers wrote.
Fintepla is approved to treat seizures associated with Dravet syndrome or LGS in patients ages 2 years and older. Its exact mechanism is not fully understood, but it is thought to act in part on serotonin signaling in the brain. Serotonin is a chemical messenger that helps nerve cells communicate, and changes in this signaling may help reduce seizures.
The girl has remained seizure-free for more than 11 months while continuing on the same dose of Fintepla. No clinically significant side effects were reported, and a follow-up EEG performed after six months showed the slow spike-and-wave pattern had disappeared and more normal background electrical activity was observed. Fintepla may be a “valuable option” for CDD-associated LGS, the researchers concluded.
