Table 2.
In vitro selected compounds (IVSCs) for the treatment of patients with potassium channel-associated pediatric epilepsies.
| Patient # | Pathogenic variant | In vitro functional properties | Drug tested in vitro | ASMs before IVSC start | Age of IVSC start (years, months) | Frequency of seizures before IVSC start | IVSC applied | IVSC last dose (mg/kg) | IVSC last plasma level | IVSC side effects | Follow-up (years, months)/Notes | Ongoing ASMs | Ongoing frequency of seizure | EEG modification | Modification of other features |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Kv7.2-G310S | LoF | GBP | VPA, LEV | 7,7 | monthly | GBP | 26 | 5.7 mg/L | None | 6,2 | GPB, VPA. LEV suspended |
seizure free | better background activity, decrease of epileptiform activity | improved interaction and communication |
| 2 | Kv7.2-D535E | LoF | GBP | TPM, CZP | 6,2 | monthly seizures; daily spasms | GBP | 9.6 | N.A. | Increase of seizure frequency | 3,10 / GBP suspended after 1 month, introduced CBZ | CBZ | seizure free | unchanged | improvement of attention and participation |
| 3 | Kv7.3-V359L + K v7.3-D542N | LoF | GBP | GVG | 10,3 | daily | GBP | 28 | 3.4 mg/L | None | 3,4 | GBP. GVG suspended |
seizure free | reduction of epileptiform activity | reduction of irritability, improved head-trunk control, walking with support, interaction with environment |
| 4 | Kv3.1-V425M | GoF | FLX | VPA, LEV | 4,5 | febrile seizures in cluster | FLX | 0.24 | 137 ng/mL | None | 5,6 | FLX, LEV. VPA suspended |
seizure free | better background activity, decrease of epileptiform activity | improvement in behavior, participation in school and social activities |
| 5 | KNa1.1 S937G | GoF | FLX | OXC, CZP | 18,3 | daily | FLX | 1.2 | 412.6 ng/mL | None | 3,1 | FLX, OXC, CZP | seizure free | normal background, disappearance of epileptic activity | active social life |
| 6 | KNa1.1 R262Q | GoF | FLX | OXC, VPA, CBD | 5,0 | daily | FLX | 0.8 | 447.5 ng/mL | Worsening of behavior disorder | 4,5 / FLX suspended after 10 months | VNS, VPA, OXC, CZP | persistent seizures | unchanged | unchanged |
ASMs: cannabidiol (CBD), carbamazepine (CBZ), clonazepam (CZP), fluoxetine (FLX), gabapentin (GBP), vigabatrin (GVG), levetiracetam (LEV), oxcarbazepine (OXC), topiramate (TPM), vagus nerve stimulation (VNS), valproate (VPA).