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FP29-WE-02 Effects of fetal antiepileptic drug exposure on verbal vs. nonverbal cognitive outcomes at age 3 years
19th World Congress of Neurology, Free Paper Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S57–S154
experiences of treatment with LCM with a follow-up of at least 3 months were investigated. Methods: Of 84 patients with focal epilepsies, age 17–70, mean 40±12.1 years, sex: 46.4% female, 100–600 dosis range mean, 29.7±95.5 seizure control, responder rate and side effects prospectively were documented in two epilepsy centers for 3 months observation period up to now. Patients suffered from epilepsy for years and were treated with concomitant drugs in 78.6%. Results: The responder rate was 38.1%. The retention rate was 88.1%. Side effects occurred in 34.5%: dizziness 20%, tiredness 6.0%, ataxia 4.8%, blurred vision 4.8%. Discussion: LM was effective in a considerable number of patients with difficult to treat focal epilepsies. No severe side effects were observed, dizziness was the most reported side effect. In addition to three months observation, six months follow-up including high dosing will be reported. FP29-WE-02 Effects of fetal antiepileptic drug exposure on verbal vs. nonverbal cognitive outcomes at age 3 years K.J. Meador1 , M. Cohen2 , N. Browning3 , G.A. Baker4 , J. ClaytonSmith5 , P. Pennell1 , L. Kalayjian6 , J. Liporace7 , M. Privitera8 , A. Kanner9 , D. Combs-Cantrell10 , D.W. Loring1 . 1 Neurology, Emory University, Atlanta, United States; 2 Neurology, Medical College of Georgia, Augusta, United States; 3 EMMES Corporation, Rockville, United States; 4 Neurological Science, University of Liverpool, Liverpool, United Kingdom; 5 University of Manchester, Manchester, United Kingdom; 6 Neurology, University of Southern California, Los Angeles, United States; 7 Riddle Health Care, Media, United States; 8 Neurology, University of Cincinnati, Cincinnati, United States; 9 Neurology, Rush University Medical Center, Chicago, United States; 10 North Texas Epilepsy Center, Irving, United States Purpose: We recently reported that fetal exposure to valproate impairs IQ compared to other commonly used antiepileptic drugs (AEDs). In this investigation, we examined the differential effects of fetal AED exposure on verbal vs. nonverbal cognitive measures. Methods: The NEAD Study is an ongoing prospective observational multicenter study in the USA and UK, which has enrolled pregnant women with epilepsy on AED monotherapy from 1999 to 2004. The purpose of the investigation is to determine if differential longterm neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). This report compares the verbal vs. nonverbal cognitive outcomes in 234 children at 3 years/old. Index scores for the following cognitive domains were calculated (using subscores of Differential Ability Scales and Preschool Language Scale-4): Expressive Language, Receptive Language, Visuomotor-Construction, and Non-verbal Intellectual Ability. Primary analysis used children who completed testing. Linear regression models were used to examine group differences, adjusting for covariates: AED, maternal IQ, pregnancy average AED dose, AED/dose and AED/maternal IQ interactions, maternal and gestational age, and preconception folate. The effects of multiple additional covariates were also examined. Results: Children exposed in utero to valproate had markedly lower expressive (91 vs. 101–104, p < 0.0001) and receptive (89 vs. 97– 101, p < 0.0001) language scores, but only slightly lower visuomotorconstructive (100 vs. 102–107, p = 0.03) and non-verbal intellectual abilities (97 vs. 102–105, p = 0.02). Conclusions: The findings are consistent with prior studies and suggest that normal language development and cerebral lateralization are particular susceptible to in utero valproate exposure. Women of childbearing potential who require AEDs should be advised of this risk. The underlying mechanisms and the risk of many AEDs remain uncertain.
S103
FP29-WE-03 Clinical outcomes and immune effects of antiepileptic drug use in HIV-infected patients P. Vivithanaporn1 , C. Power1 , K. Lee2 , R. Seimienuk2 , H.B. Krentz2 , F. Maingat1 , M.J. Gill2 . 1 Department of Medicine, University of Alberta, Edmonton, Canada; 2 Southern Alberta Clinic, Calgary, Canada Purpose: Antiepileptic drugs (AEDs) are widely prescribed to HIV/AIDS patients receiving antiretroviral therapies (ARTs) although the spectrum of AED use and their adverse effects remain uncertain. Here we investigated AED use and their effects within a centralized HIV community clinic and in vitro effect of AEDs on T cell proliferation and viral replication. Methods: Clinical characteristics, laboratory findings, and demographic features of all patients receiving AEDs at the Southern Alberta Clinic, Calgary, from 2001 to 2007 were analyzed. In patients on stable ART regimens, the effects of AEDs on virologic and immunologic parameters were analyzed. Cultured HIV-infected and uninfected T cells were assessed in terms of viral replication and proliferation with exposure AEDs. Results: 166 AED-treated patients were identified within a total 1345 HIV/AIDS patients. The major AED indications included peripheral neuropathy/neuropathic pain, seizure/epilepsy and mood disorder. AED types included: calcium (gabapentin/pregabalin) (45%) and sodium (phenytoin, carbamazepine, lamotrigine) (32%) channel blockers, valproate (16%), and Other (7%). Although the overall frequency of abnormal liver function tests was 16% and cumulative dosages of AEDs was found to be high, liver or virologic failure was not observed. Among patients on stable ART regimens CD4+ T cell counts rose over 12 months in groups receiving either sodium and calcium channel blockers (p < 0.05). In vitro proliferation assay showed that valproate suppressed proliferation of HIV-infected and uninfected T cells whereas gabapentin and phenytoin did not affect T cell proliferation. In contrast, none of the AEDs exerted effects on viral production in terms of reverse transcriptase activity. Conclusions: AEDs were prescribed for multiple indications without major adverse effects in this population. Immune status in patients receiving sodium or calcium channel blocking drugs was improved despite large cumulative AED doses. FP29-WE-04 Can epilepsy awareness programmes improve drug compliance of patients in New Delhi, India? M.B. Singh1 , A. Srivastava1 , V. Singh2 , M. Aggarwal2 . 1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India; 2 College of Nursing, All India Institute of Medical Sciences, New Delhi, India Purpose of the study: Developing countries struggle with poor health infrastructure and limited resources. Allocation of funds demands a clear demonstration of an area of deficiency. We planned this study to highlight the role of patient education and awareness programmes amongst epilepsy patients in improving compliance to antiepileptic drugs (AEDs). Materials and methods: A descriptive cross sectional survey was done in 231 epilepsy patients/caregivers of epilepsy patients following-up in Neurology OPD, AIIMS, New Delhi, using a structured questionnaire for a period of 6 months. This questionnaire was developed, validated and pilot-run before being used. Univariate analysis using chi square test and Fisher’s exact test and logistic regression were performed. Significance was considered at p < 0.05. Results: Out of 231 epileptic patients, 86 (37.23%) reported noncompliance. Patients living in urban areas, having generalized tonic clonic seizures and without any past history of noncompliance were more compliant. Frequency of seizures was negatively correlated with compliance. Local non-availability of medicines was the strongest predictor of noncompliance (37.21%). Other reasons
experiences of treatment with LCM with a follow-up of at least 3 months were investigated. Methods: Of 84 patients with focal epilepsies, age 17–70, mean 40±12.1 years, sex: 46.4% female, 100–600 dosis range mean, 29.7±95.5 seizure control, responder rate and side effects prospectively were documented in two epilepsy centers for 3 months observation period up to now. Patients suffered from epilepsy for years and were treated with concomitant drugs in 78.6%. Results: The responder rate was 38.1%. The retention rate was 88.1%. Side effects occurred in 34.5%: dizziness 20%, tiredness 6.0%, ataxia 4.8%, blurred vision 4.8%. Discussion: LM was effective in a considerable number of patients with difficult to treat focal epilepsies. No severe side effects were observed, dizziness was the most reported side effect. In addition to three months observation, six months follow-up including high dosing will be reported. FP29-WE-02 Effects of fetal antiepileptic drug exposure on verbal vs. nonverbal cognitive outcomes at age 3 years K.J. Meador1 , M. Cohen2 , N. Browning3 , G.A. Baker4 , J. ClaytonSmith5 , P. Pennell1 , L. Kalayjian6 , J. Liporace7 , M. Privitera8 , A. Kanner9 , D. Combs-Cantrell10 , D.W. Loring1 . 1 Neurology, Emory University, Atlanta, United States; 2 Neurology, Medical College of Georgia, Augusta, United States; 3 EMMES Corporation, Rockville, United States; 4 Neurological Science, University of Liverpool, Liverpool, United Kingdom; 5 University of Manchester, Manchester, United Kingdom; 6 Neurology, University of Southern California, Los Angeles, United States; 7 Riddle Health Care, Media, United States; 8 Neurology, University of Cincinnati, Cincinnati, United States; 9 Neurology, Rush University Medical Center, Chicago, United States; 10 North Texas Epilepsy Center, Irving, United States Purpose: We recently reported that fetal exposure to valproate impairs IQ compared to other commonly used antiepileptic drugs (AEDs). In this investigation, we examined the differential effects of fetal AED exposure on verbal vs. nonverbal cognitive measures. Methods: The NEAD Study is an ongoing prospective observational multicenter study in the USA and UK, which has enrolled pregnant women with epilepsy on AED monotherapy from 1999 to 2004. The purpose of the investigation is to determine if differential longterm neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). This report compares the verbal vs. nonverbal cognitive outcomes in 234 children at 3 years/old. Index scores for the following cognitive domains were calculated (using subscores of Differential Ability Scales and Preschool Language Scale-4): Expressive Language, Receptive Language, Visuomotor-Construction, and Non-verbal Intellectual Ability. Primary analysis used children who completed testing. Linear regression models were used to examine group differences, adjusting for covariates: AED, maternal IQ, pregnancy average AED dose, AED/dose and AED/maternal IQ interactions, maternal and gestational age, and preconception folate. The effects of multiple additional covariates were also examined. Results: Children exposed in utero to valproate had markedly lower expressive (91 vs. 101–104, p < 0.0001) and receptive (89 vs. 97– 101, p < 0.0001) language scores, but only slightly lower visuomotorconstructive (100 vs. 102–107, p = 0.03) and non-verbal intellectual abilities (97 vs. 102–105, p = 0.02). Conclusions: The findings are consistent with prior studies and suggest that normal language development and cerebral lateralization are particular susceptible to in utero valproate exposure. Women of childbearing potential who require AEDs should be advised of this risk. The underlying mechanisms and the risk of many AEDs remain uncertain.
S103
FP29-WE-03 Clinical outcomes and immune effects of antiepileptic drug use in HIV-infected patients P. Vivithanaporn1 , C. Power1 , K. Lee2 , R. Seimienuk2 , H.B. Krentz2 , F. Maingat1 , M.J. Gill2 . 1 Department of Medicine, University of Alberta, Edmonton, Canada; 2 Southern Alberta Clinic, Calgary, Canada Purpose: Antiepileptic drugs (AEDs) are widely prescribed to HIV/AIDS patients receiving antiretroviral therapies (ARTs) although the spectrum of AED use and their adverse effects remain uncertain. Here we investigated AED use and their effects within a centralized HIV community clinic and in vitro effect of AEDs on T cell proliferation and viral replication. Methods: Clinical characteristics, laboratory findings, and demographic features of all patients receiving AEDs at the Southern Alberta Clinic, Calgary, from 2001 to 2007 were analyzed. In patients on stable ART regimens, the effects of AEDs on virologic and immunologic parameters were analyzed. Cultured HIV-infected and uninfected T cells were assessed in terms of viral replication and proliferation with exposure AEDs. Results: 166 AED-treated patients were identified within a total 1345 HIV/AIDS patients. The major AED indications included peripheral neuropathy/neuropathic pain, seizure/epilepsy and mood disorder. AED types included: calcium (gabapentin/pregabalin) (45%) and sodium (phenytoin, carbamazepine, lamotrigine) (32%) channel blockers, valproate (16%), and Other (7%). Although the overall frequency of abnormal liver function tests was 16% and cumulative dosages of AEDs was found to be high, liver or virologic failure was not observed. Among patients on stable ART regimens CD4+ T cell counts rose over 12 months in groups receiving either sodium and calcium channel blockers (p < 0.05). In vitro proliferation assay showed that valproate suppressed proliferation of HIV-infected and uninfected T cells whereas gabapentin and phenytoin did not affect T cell proliferation. In contrast, none of the AEDs exerted effects on viral production in terms of reverse transcriptase activity. Conclusions: AEDs were prescribed for multiple indications without major adverse effects in this population. Immune status in patients receiving sodium or calcium channel blocking drugs was improved despite large cumulative AED doses. FP29-WE-04 Can epilepsy awareness programmes improve drug compliance of patients in New Delhi, India? M.B. Singh1 , A. Srivastava1 , V. Singh2 , M. Aggarwal2 . 1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India; 2 College of Nursing, All India Institute of Medical Sciences, New Delhi, India Purpose of the study: Developing countries struggle with poor health infrastructure and limited resources. Allocation of funds demands a clear demonstration of an area of deficiency. We planned this study to highlight the role of patient education and awareness programmes amongst epilepsy patients in improving compliance to antiepileptic drugs (AEDs). Materials and methods: A descriptive cross sectional survey was done in 231 epilepsy patients/caregivers of epilepsy patients following-up in Neurology OPD, AIIMS, New Delhi, using a structured questionnaire for a period of 6 months. This questionnaire was developed, validated and pilot-run before being used. Univariate analysis using chi square test and Fisher’s exact test and logistic regression were performed. Significance was considered at p < 0.05. Results: Out of 231 epileptic patients, 86 (37.23%) reported noncompliance. Patients living in urban areas, having generalized tonic clonic seizures and without any past history of noncompliance were more compliant. Frequency of seizures was negatively correlated with compliance. Local non-availability of medicines was the strongest predictor of noncompliance (37.21%). Other reasons