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Early and effective treatment of KCNQ 2 encephalopathy
Author(s) -
Pisano Tiziana,
Numis Adam L.,
Heavin Sinéad B.,
Weckhuysen Sarah,
Angriman Marco,
Suls Arvid,
Podesta Barbara,
Thibert Ronald L.,
Shapiro Kevin A.,
Guerrini Renzo,
Scheffer Ingrid E.,
Marini Carla,
Cilio Maria Roberta
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12984
Subject(s) - status epilepticus , carbamazepine , sodium channel blocker , encephalopathy , phenytoin , levetiracetam , anesthesia , topiramate , medicine , epilepsy , electroencephalography , anticonvulsant , seizure types , clobazam , pediatrics , psychology , sodium channel , sodium , psychiatry , chemistry , organic chemistry
Summary Objectives To describe the antiepileptic drug ( AED ) treatment of patients with early infantile epileptic encephalopathy due to KCNQ 2 mutations during the neonatal phase and the first year of life. Methods We identified 15 patients and reviewed the electroclinical, neuroimaging, and AED treatment data. Results Seizure onset was between 1 and 4 days of age with daily tonic asymmetric, focal and clonic seizures in nine patients and status epilepticus in the remaining six. Electroencephalography ( EEG ) showed multifocal epileptiform abnormalities in nine patients and a burst‐suppression pattern in six. All patients were trialed with adequate daily doses of several AED s before they reached seizure freedom. Six patients (40%) achieved seizure control within 2 weeks of carbamazepine ( CBZ ) administration and five (33%) were seizure‐free with phenytoin ( PHT ). The last four patients (27%) were successfully treated with topiramate ( TPM ) (two patients), levetiracetam ( LEV ) (one), and a combination of LEV with TPM (one). Most patients reached seizure freedom within the first year of life and remained seizure‐free thereafter. Twelve patients had moderate‐to‐severe developmental delay at follow‐up. However, the two patients whose seizures ceased within a few days of onset showed only mild cognitive impairment. Significance Our findings suggest that drugs acting on sodium channels including CBZ and PHT should be considered as first‐line treatment in patients with KCNQ 2 encephalopathy. Voltage‐gated sodium and potassium channels co‐localize at the neuronal membrane. Therefore, the efficacy of drugs acting as sodium‐channel blockers could be linked to their modulating effect on both channels. The type of KCNQ 2 mutation might influence AED response as well as developmental outcome. Early recognition of KCNQ 2 encephalopathy followed by the most appropriate and effective treatment may be important for reducing the neurodevelopmental impairment associated with this disorder.