Abstracts

Rationale: Mutations in the protocadherin 19 (PCDH19) gene cause epilepsy and mental retardation limited to females (EFMR) or Dravet-like syndromes. Especially in the first years of life epilepsy is known to be highly pharmaco-resistant, still there is no concept how to treat these patients. In this retrospective study we analyzed effectiveness of antiepileptic therapy in patients with PCDH19-mutations. Methods: Retrospective analysis of 32 patients aged 2-19 years (mean age: 9.3 years) with PCDH19-mutations. All patients were female and suffered from epilepsy with variable seizure types, mostly generalized tonic-clonic seizures (84%), with clusters of seizures (97%), starting at the mean age of 9.5 months (range: 4-20). Most of them showed a mild to severe mental retardation (88%) with predominantly autistic behavioral problems (53%). Results: Antiepileptic drugs administered were carbamazepine (CBZ, n=19), clobazam (CLB, n=16), clonazepam (CZP, n=7), ethosuximide (ESM, n=1), gabapentin (GBP, n=1), lacosamide (LCM, n=2), lamotrigine (LTG, n=16), levetiracetam (LEV, n=25), lorazepam (LZP, n=1), nitrazepam (NZP, n=1), oxcarbazepine (OXC, n=12), phenobarbital (PB, n=16), phenytoin (PHT, n=9), pregabalin (PGB, n=1), rufinamide (RFN, n=5), sulthiame (STM, n=6), stiripentol (STP, n=4), topiramate (TPM, n=16), valproate (VPA, n=25), vigabatrin (VGB, n=5) and zonisamide (ZNS, n=2). Patients received overall an average of six different antiepileptic drugs (range: 1-11). In addition, three girls received steroids, two girls ketogenic diet (KD), and one girl received a vagus nerv stimulator (VNS). Seizure reduction lasting for at least 3 months was achieved with CBZ (32%), CLB (94%), CZP (43%), LTG (31%), LEV (44%), LZP (1/1), OXC (33%), PB (50%), PHT (11%), RFN (40%), STM (17%), STP (50%), TPM (31%), VPA (44%), VGB (20%) and ZNS (2/2), as well as with ketogenic diet (1/3) and VNS (1/1). 12 patients (38%) became seizure free for at least 3 months, two of them for almost four years. Aggravation was observed with CBZ (5%), LCM (1/2), LTG (6%) and OXC (8%). Conclusions: The most effective drug in patients with PCDH19-mutations resulted to be CLB, followed by PB, STP, VPA, LEV, CZP and RFN. Although epilepsy in PCDH19 mutations is known to be pharmaco-resistant, more than a third of the patients became seizure free at least for 3 months, some up to almost four years, although a possible age-dependent spontaneous seizure remission has to be considered. Few cases of aggravation are reported for CBZ, LCM, LTG and OXC, and none for PHT. Although PCDH19 is the second frequent Dravet-associated gene, therapy concept in patients with PCDH19 mutations might be different than in classical Dravet syndrome, where sodium channel blockers are known to cause frequent aggravation. Further data are needed to evaluate the effect of specific antiepileptic drugs to define rational treatment concepts in patients with PCDH19 mutations.