Pharmacogenomics in epilepsy

Balestrini, Simona; Sisodiya, Sanjay M.

doi:10.1016/j.neulet.2017.01.014

Cited by 124 publications

(111 citation statements)

References 180 publications

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“…There are many patients who have used CIM for only short periods of time and still have a severe cognitive outcome, and IQ/DQ scores after 5 years of disease ranged over 60 IQ/DQ points for participants who had used CIM for almost the complete duration of that period. It is very likely that other genetic factors have a substantial influence on cognitive outcomes and also on responses to CIM, as multiple genetic modifiers have already been implicated to influence SCN1A phenotypes and responses to antiepileptic medication in general . Further research investigating the role of other genetic modifiers and pharmacogenetics is needed.…”

Section: Discussionmentioning

confidence: 99%

“…It is very likely that other genetic factors have a substantial influence on cognitive outcomes and also on responses to CIM, as multiple genetic modifiers have already been implicated to influence SCN1A phenotypes [18][19][20]33 and responses to antiepileptic medication in general. 41 Further research investigating the role of other genetic modifiers and pharmacogenetics is needed. However, even if CIM use is responsible for only a small part of cognitive decline, it should still be avoided to optimize disease courses in individual patients.…”

Section: F I G U R E 2 Duration Of Contraindicated Medication (Cim) Umentioning

confidence: 99%

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Influence of contraindicated medication use on cognitive outcome in Dravet syndrome and age at first afebrile seizure as a clinical predictor in SCN1A‐related seizure phenotypes

et al. 2018

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Summary Objective Pathogenic variants in SCN1A can give rise to extremely variable disease severities that may be indistinguishable at their first presentation. We aim to find clinical features that can help predict the evolution of seizures into Dravet syndrome and clinical features that predict cognitive outcome in Dravet syndrome. We specifically investigate the role of contraindicated medication (CIM) as a possible modifier of cognitive decline. Methods A cohort of 164 Dutch participants with SCN1A‐related seizures was evaluated. Clinical data were collected from medical records and semistructured telephone interviews. Cognitive function was classified by a child neurologist, neuropsychologist, and clinical geneticist. Several clinical variables, including duration of CIM use in the first 5 years of disease, were evaluated in univariate and multivariate analyses. Results A longer duration of CIM use in the first 5 years after seizure onset was significantly associated with a worse cognitive outcome at time of inclusion, and with lower interpolated intelligence quotient/developmental quotient scores after the first 5 years of disease in Dravet syndrome patients. CIM use remained a significant predictor for cognitive outcome in a multivariate regression model, as did age at the first observation of developmental delay and age at first afebrile seizure. Age at first afebrile seizure was the most accurate predictor for evolution of seizures into Dravet syndrome for the complete cohort. Significance Our data suggest that a longer CIM use in the first 5 years of disease can have negative effects on cognitive outcome in Dravet syndrome. An early diagnosis is essential to avoid these drugs. Furthermore, we identified age at first afebrile seizure as an important predictor for evolution of seizures into Dravet syndrome and for the severity of Dravet syndrome, which can be used to counsel parents of young patients with SCN1A‐related seizures.

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Section: Discussionmentioning

confidence: 99%

Section: F I G U R E 2 Duration Of Contraindicated Medication (Cim) Umentioning

confidence: 99%

Influence of contraindicated medication use on cognitive outcome in Dravet syndrome and age at first afebrile seizure as a clinical predictor in SCN1A‐related seizure phenotypes

et al. 2018

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“…The pharmacokinetic properties of various AEDs, as well as treatment response, safety, and tolerability, can be affected by racial differences. For example, metabolism of many AEDs is mediated by cytochrome P450 (CYP), and variant alleles of CYP2C9 and CYP2C19 can lead to significant differences in AED serum concentrations . The CYP2C9*3 mutation is common among Asian populations and can cause delayed phenytoin clearance, resulting in increased toxicity .…”

Section: Introductionmentioning

confidence: 99%

“…For example, metabolism of many AEDs is mediated by cytochrome P450 (CYP), and variant alleles of CYP2C9 and CYP2C19 can lead to significant differences in AED serum concentrations. 27,28 The CYP2C9*3 mutation is common among Asian populations and can cause delayed phenytoin clearance, resulting in increased toxicity. 29 Similarly, Asian patients with human leukocyte antigen HLA-B*1502 are at greater risk for carbamazepine-induced severe cutaneous adverse reactions.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of perampanel in generalized and focal to bilateral tonic‐clonic seizures: A comparative study of Asian and non‐Asian populations

Nishida¹,

Lee

et al. 2019

Epilepsia

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Summary Perampanel is an approved adjunctive treatment for focal seizures with or without focal to bilateral tonic‐clonic (FBTC) seizures and generalized tonic‐clonic (GTC) seizures. We compared efficacy and safety of perampanel vs placebo in Asian and non‐Asian populations in a post hoc analysis of pooled data from 5 randomized phase 3 studies. Patients (≥12 years old) with focal + FBTC seizures received perampanel 2, 4, 8, or 12 mg or placebo; patients with GTC seizures received perampanel 8 mg or placebo (titration: 4‐6 weeks; maintenance: 13 weeks). Efficacy endpoints included median percentage change in FBTC or GTC seizure frequency per 28 days and 50% responder rate relative to baseline. Median percentage change in FBTC seizure frequency was significantly greater for perampanel 8 and 12 mg than placebo in the Asian population (median difference from placebo: −30.32%, P = 0.0017; −30.06%, P = 0.0008, respectively) and perampanel 4, 8, and 12 mg in the non‐Asian population (−35.07%, P = 0.0001; −37.78%, P < 0.0001; −34.53%, P < 0.0001, respectively). In both populations, median percentage change in GTC seizure frequency was significantly greater for perampanel 8 mg than placebo (median difference from placebo: Asian, −37.37%, P = 0.0139; non‐Asian, −27.04%, P = 0.0006). The 50% responder rates were significantly greater than placebo for perampanel 8 and 12 mg for FBTC seizures (Asian: 58.0%, P = 0.0017 and 58.6%, P = 0.0013, respectively; non‐Asian: 59.3%, P < 0.0001 and 54.3%, P = 0.0050, respectively) and perampanel 8 mg for GTC seizures (Asian: 57.6%, P = 0.0209; non‐Asian: 68.8%, P = 0.0329). Pooled FBTC/GTC seizure data showed generally similar patterns of response to perampanel in both populations. The most frequent treatment‐related adverse events were fatigue, irritability, dizziness, somnolence, and headache. Perampanel was effective, well tolerated, and can be considered a therapeutic option for FBTC/GTC seizures in Asian populations.

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“…Such biomarkers might improve a patient‐tailored choice of treatment strategies based on individual coupling profile in the interictal EEG of patients (Balestrini & Sisodiya, ), and further demonstrate that an EEG which appears normal at first glance does not necessarily need to be normal (Maheshwari et al . ).…”

mentioning

confidence: 99%

Disclosing hidden information in the electroencephalogram using advanced signal analytical techniques

Lüttjohann

2017

The Journal of Physiology

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Pharmacogenomics in epilepsy

Cited by 124 publications

References 180 publications

Influence of contraindicated medication use on cognitive outcome in Dravet syndrome and age at first afebrile seizure as a clinical predictor in SCN1A‐related seizure phenotypes

Influence of contraindicated medication use on cognitive outcome in Dravet syndrome and age at first afebrile seizure as a clinical predictor in SCN1A‐related seizure phenotypes

Efficacy and safety of perampanel in generalized and focal to bilateral tonic‐clonic seizures: A comparative study of Asian and non‐Asian populations

Disclosing hidden information in the electroencephalogram using advanced signal analytical techniques

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