Tuesday, October 24, 2023

Vinpocetine for GABR mutations

Mandelenaki D, Juvené E, Gederer D, Aeby A. Precision medicine: Vinpocetine as a potential treatment for GABRG2-related epilepsy. Epileptic Disord. 2023 Jun;25(3):383-389. doi:10.1002/epd2.20015. Epub 2023 May 25. PMID: 37536979.


Introduction: Pathogenic variants of the GABRG2 gene, encoding a GABAA receptor subunit, have been associated with various epileptic syndromes and drug-resistant epilepsy. Vinpocetine has been previously reported efficacious in a patient harboring a GABRB3 pathogenic variant, encoding another GABAA receptor subunit.

Case presentation: We describe a patient with GABRG2-related drug-resistant epilepsy who improved after vinpocetine treatment. An 8-year-old boy with a family history of epilepsy was diagnosed with early onset absence epilepsy at 6 months of age and was treated unsuccessfully with sodium valproate and ethosuximide. At 6 years of age, he developed generalized tonic-clonic seizures and increasing absences despite lamotrigine add-on as well as learning difficulties. Brain MRI was normal and video-EEG telemetry showed multiple myoclonic absences. An epilepsy gene panel analysis showed a GABRG2 pathogenic variant, c.254 T > A p.(Ile85Lys) (NM_198903.2), inherited from the proband's father. Seizures were resistant to several medications. After treatment with vinpocetine add-on, the patient showed a dramatic initial response, further reduction of seizures, and improvement of his cognitive functions.

Conclusion: This case illustrates that vinpocetine could be considered in drug-resistant epilepsies related to GABRG2 in accordance with the principles of precision medicine.

Billakota S, Andresen JM, Gay BC, Stewart GR, Fedorov NB, Gerlach AC, Devinsky O. Personalized medicine: Vinpocetine to reverse effects of GABRB3 mutation. Epilepsia. 2019 Dec;60(12):2459-2465. doi: 10.1111/epi.16394. Epub 2019 Nov 22. PMID: 31755996; PMCID: PMC7004153.


Objective: To screen a library of potential therapeutic compounds for a woman with Lennox-Gastaut syndrome due to a Y302C GABRB3 (c.905A>G) mutation.

Methods: We compared the electrophysiological properties of cells with wild-type or the pathogenic GABRB3 mutation.

Results: Among 1320 compounds, multiple candidates enhanced GABRB3 channel conductance in cell models. Vinpocetine, an alkaloid derived from the periwinkle plant with anti-inflammatory properties and the ability to modulate sodium and channel channels, was the lead candidate based on efficacy and safety profile. Vinpocetine was administered as a dietary supplement over 6 months, reaching a dosage of 20 mg three times per day, and resulted in a sustained, dose-dependent reduction in spike-wave discharge frequency on electroencephalograms. Improved language and behavior were reported by family, and improvements in global impression of change surveys were observed by therapists blinded to intervention.

Significance: Vinpocetine has potential efficacy in treating patients with this mutation and possibly other GABRB3 mutations or other forms of epilepsy. Additional studies on pharmacokinetics, potential drug interactions, and safety are needed.

Gjerulfsen CE, Mieszczanek TS, Johannesen KM, Liao VWY, Chebib M, Nørby HAJ, Gardella E, Rubboli G, Ahring P, Møller RS. Vinpocetine improved neuropsychiatric and epileptic outcomes in a patient with a GABRA1 loss-of-function variant. Ann Clin Transl Neurol. 2023 Aug;10(8):1493-1498. doi: 10.1002/acn3.51838. Epub 2023 Jul 11. PMID: 37434477; PMCID: PMC10424645.


Vinpocetine is a synthetic derivative of the alkaloid vincamine and has been used as a dietary supplement for decades. Following a positive report of the use of vinpocetine in a patient with a loss-of-function GABRB3 variant, we here describe another patient with a loss-of-function GABRA1 variant (p.(Arg112Gln)) who benefited from vinpocetine treatment. This patient was diagnosed with autism spectrum disorder, psychiatric complications, and therapy-resistant focal epilepsy. Upon add-on treatment with 40 mg vinpocetine daily for 16 months, the patient experienced an overall improved quality of life as well as seizure freedom. Our findings corroborate that vinpocetine can attenuate epilepsy-associated behavioral issues in patients with loss-of-function GABAA receptor gene variants.

Monday, October 16, 2023

Febrile seizures

 In a matter of seconds, Kelly Herrmann’s son Howie went from sleeping in her arms to having a seizure.

She recognized he was having a seizure but didn’t know why.

“I was holding him, and he started to turn blue and stopped breathing. I honestly thought he was dying in my arms,” she said.

Earlier in the day, Howie’s day care called Herrmann and said he had a fever. Little did Herrmann or her husband Seth Moser know, a fever in children sometimes causes what’s known as a febrile seizure.

Febrile seizure, explained

Mohamad Saifeddine, M.D., is a pediatric neurology specialist at Sanford Health in Sioux Falls, South Dakota. He said sometimes a febrile seizure can be caused from a brain infection but oftentimes, like in Howie’s case, it’s caused from a fever.

“A febrile seizure is a seizure that happens in the setting of fever. That means the seizure itself is abnormal firing of electricity in the brain, that spreads throughout the brain and causes the child to have different movements and being unconscious,” he said.

How common are febrile seizures?

Dr. Saifeddine said it’s actually a very common condition in children, particularly in children between the ages of one and a half years old to three years of age.

“Statistically, it’s up to 2-5% of kids actually going to have at least one febrile seizure in their lifetime,” he said.

These types of seizures typically last one to two minutes, but “it can be shorter and unfortunately it can be longer,” Dr. Saifeddine explained.

Related: Stroke or seizure? It can be a fine line between the two

If a seizure lasts longer than three to five minutes, it’s called a “status.” Meaning, the prolonged seizure is not stopping by itself.

“That’s when we need to ask or seek medical help for any parents. That’s when parents should come to the ER or call 911,” he said.

What if my child is having a febrile seizure?

According to Dr. Saifeddine, the most important thing a parent can do when their child is having a seizure, whether it’s febrile or not, “is to put the child on their side.”

“Do not put anything in their mouth, and make sure that the child doesn’t have something sharp or hard under their head, so if the child is actually seizing, meaning they’re having whole-body jerking, they won’t hit their head with something that can injure themself,” he said.

He said it can be an extremely difficult thing to remember to do, but he recommends someone checks the time while the child is having the seizure.

“If the seizure is more than two or three minutes and the child is not waking up, somebody (then) has to call 911.”

‘It was confusing and also a relief’

When Howie was having his febrile seizure, Hermann rushed over to her neighbors, Howie still blue in her arms, and asked them to call 911.

Thankfully, when the ambulance arrived, Howie’s febrile seizure had stopped. The EMT explained to Herrmann that Howie most likely had a febrile seizure, and that it was very common.

Seek care: Well child visits important for children of all ages

Herrmann, having never heard of a febrile seizure or that it’s often caused by a fever, had questions swirling.

“If it was so common, how did I not know what that was? His fever was so low. It 100.4, and even in the ambulance, it was still only 100.5 or so. So, in my mind it just didn’t make sense, because yes, he had a fever, but just barely. It wasn’t anything too high,” Hermann said.

“So, it was like a relief, but also I was still confused. I was still worried that something was wrong. I was worried he was going to have another one. Despite learning more from the care team, it was still really confusing and scary,” she added.

Howie is home and doing just fine, a relief to is entire family.

Herrmann said her take home message for parents is to know febrile seizures exist and be prepared if their child has one.

“Don’t put anything in their mouth, and try to keep the airway open. Pay attention to how long it’s lasting, because if it lasts a really long time, that can be a problem.”