Efficacy, Tolerability, and Retention of Antiseizure Medications in PRRT2-Associated Infantile Epilepsy
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Efficacy, Tolerability, and Retention of Antiseizure Medications in PRRT2-Associated Infantile Epilepsy. / Doring, Jan H.; Saffari, Afshin; Bast, Thomas; Brockmann, Knut; Ehrhardt, Laura; Fazeli, Walid; Janzarik, Wibke G.; Klabunde-Cherwon, Annick; Kluger, Gerhard; Muhle, Hiltrud; Pendziwiat, Manuela; Moller, Rikke S.; Platzer, Konrad; Santos, Joana Larupa; Schroter, Julian; Hoffmann, Georg F.; Kolker, Stefan; Syrbe, Steffen.
In: Neurology: Genetics, Vol. 8, No. 5, 200020, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Efficacy, Tolerability, and Retention of Antiseizure Medications in PRRT2-Associated Infantile Epilepsy
AU - Doring, Jan H.
AU - Saffari, Afshin
AU - Bast, Thomas
AU - Brockmann, Knut
AU - Ehrhardt, Laura
AU - Fazeli, Walid
AU - Janzarik, Wibke G.
AU - Klabunde-Cherwon, Annick
AU - Kluger, Gerhard
AU - Muhle, Hiltrud
AU - Pendziwiat, Manuela
AU - Moller, Rikke S.
AU - Platzer, Konrad
AU - Santos, Joana Larupa
AU - Schroter, Julian
AU - Hoffmann, Georg F.
AU - Kolker, Stefan
AU - Syrbe, Steffen
PY - 2022
Y1 - 2022
N2 - Background and ObjectivesPathogenic variants in PRRT2, encoding for the proline-rich transmembrane protein 2, were identified as the main cause of self-limiting sporadic and familial infantile epilepsy. Reported data on treatment response to antiseizure medications (ASMs) in defined monogenic epilepsies are limited. The aim of this study was to evaluate the treatment response of ASMs in children with monogenic PRRT2-associated infantile epilepsy.MethodsA multicenter, retrospective, cross-sectional cohort study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology criteria. Inclusion criteria were occurrence of infantile seizures and genetic diagnosis of likely pathogenic/pathogenic PRRT2 variants.ResultsTreatment response data from 52 individuals with PRRT2-associated infantile epilepsy with a total of 79 treatments (defined as each use of an ASM in an individual) were analyzed. Ninety-six percent (50/52) of all individuals received ASMs. Levetiracetam (LEV), oxcarbazepine (OXC), valproate (VPA), and phenobarbital (PB) were most frequently administered. Sodium channel blockers were used in 22 individuals and resulted in seizure freedom in all but 1 child, who showed a reduction of more than 50% in seizure frequency. By contrast, treatment with LEV was associated with worsening of seizure activity in 2/25 (8%) treatments and no effect in 10/25 (40%) of treatments. LEV was rated significantly less effective also compared with VPA and PB. The retention rate for LEV was significantly lower compared with all aforementioned ASMs. No severe adverse events were reported, and no discontinuation of treatment was reported because of side effects.DiscussionIn conclusion, a favorable effect of most ASMs, especially sodium channel blockers such as carbamezepine and OXC, was observed, whereas the efficacy and the retention rate of LEV was lower in PRRT2-associated childhood epilepsy. Tolerability in these young children was good for all ASMs reported in the cohort.
AB - Background and ObjectivesPathogenic variants in PRRT2, encoding for the proline-rich transmembrane protein 2, were identified as the main cause of self-limiting sporadic and familial infantile epilepsy. Reported data on treatment response to antiseizure medications (ASMs) in defined monogenic epilepsies are limited. The aim of this study was to evaluate the treatment response of ASMs in children with monogenic PRRT2-associated infantile epilepsy.MethodsA multicenter, retrospective, cross-sectional cohort study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology criteria. Inclusion criteria were occurrence of infantile seizures and genetic diagnosis of likely pathogenic/pathogenic PRRT2 variants.ResultsTreatment response data from 52 individuals with PRRT2-associated infantile epilepsy with a total of 79 treatments (defined as each use of an ASM in an individual) were analyzed. Ninety-six percent (50/52) of all individuals received ASMs. Levetiracetam (LEV), oxcarbazepine (OXC), valproate (VPA), and phenobarbital (PB) were most frequently administered. Sodium channel blockers were used in 22 individuals and resulted in seizure freedom in all but 1 child, who showed a reduction of more than 50% in seizure frequency. By contrast, treatment with LEV was associated with worsening of seizure activity in 2/25 (8%) treatments and no effect in 10/25 (40%) of treatments. LEV was rated significantly less effective also compared with VPA and PB. The retention rate for LEV was significantly lower compared with all aforementioned ASMs. No severe adverse events were reported, and no discontinuation of treatment was reported because of side effects.DiscussionIn conclusion, a favorable effect of most ASMs, especially sodium channel blockers such as carbamezepine and OXC, was observed, whereas the efficacy and the retention rate of LEV was lower in PRRT2-associated childhood epilepsy. Tolerability in these young children was good for all ASMs reported in the cohort.
KW - PAROXYSMAL KINESIGENIC DYSKINESIA
KW - PRRT2
KW - MUTATIONS
KW - LEVETIRACETAM
KW - GUIDELINES
KW - PHENOTYPE
KW - VARIANTS
U2 - 10.1212/NXG.0000000000200020
DO - 10.1212/NXG.0000000000200020
M3 - Journal article
C2 - 36187725
VL - 8
JO - Neurology: Genetics
JF - Neurology: Genetics
SN - 2376-7839
IS - 5
M1 - 200020
ER -
ID: 323857591