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PO18-WE-44 Alternatives to valproic acid in juvenile myoclonic epilepsy
19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339
and hypertensive encephalopathy 18%. With rectal diazepam, the mean time to control seizure was 5 minutes and was effective in all patients with clinical response seen in 0.5–9 minutes. Intravenousl Midazolam mean time to control was recorded at 7 minutes and 33 seconds. This was effective in 14 of 15 (93%) subjects with clinical response noted within 5 seconds up to 10 minutes. The buccal route responded similarly with the intravenous Midazolam group with cessation of seizures in 12 of 13 (92%) children. Comparing seizure duration with time to control the attack using the Pearson Correlation found to be not significant. Also noted was the increased recurrence of seizures using intravenous midazolam. Conclusion: Buccal Midazolam is safe, effective in seizure control It is easily administered with fewer seizure recurrence. However, there was no statistical significance in seizure termination between the three treatment group. PO18-WE-41 Prevalence of the serum autoantibodies in the first seizure and after long term treatment with antiepileptic drugs in epileptic patients M.R. Najafi1 , M. Zare1 , E. Vaziri1 , M.R. Aghaghazvini2 , M. Reisifar3 . 1 Neurology, Isfahan University Of Medical Sciences, Isfahan, Islamic Republic of Iran; 2 Isfahan Center of Public Health Training and Resea, Isfahan, Islamic Republic of Iran; 3 INRC, Isfahan, Islamic Republic of Iran Purpose: Epileptic seizures have been proposed to be associated with some aberrant immune system functions. Increased prevalence of autoantibodies is a frequent finding in patients with epilepsy. Anti-epileptics therapy also has been proposed to affect autoantibodies levels. The exact contribution of each of the neurological disorders themselves, or subsequent treatment with anti-convulasants on the induction of autoantibodies has not been elucidated yet. The aim of this study was to determine the prevalence of autoantibodies in patients experiencing their first seizure and compare it with those who have been under chronic antiepileptic therapy and with normal controls. Methods: The frequency of antinuclear antibodies (ANA), anticardiolipin antibodies (aCL) and anti-B2-glycoprotein I immunoglobulin G class antibodies were studied in the sera of 64 epileptic patients who had been under chronic antiepileptic therapy for a minimum of six monthes, in 41 patients who had experienced their first seizure and in 75 apparently healthy controls. Results: The prevalence of autoantibodies were significantly higher in seizure patients compared with normal controls (P < 0.054). The prevalence of autoantibodies were 7.3, 7.8 and 1.3% in first seizure, chronic anticonvulsant receiving and normal subjects respectively. ANA was the most frequent autoantibody in all groups. The frequency of autoantibodies did not statistically differed between newly diagnosed and chronically treated epileptic patients. Conclusion: The result of this study shows that increased prevalence of autoantibodies can be seen both before and after long term epilepsy treatment. According to these results, the presence of autoantibodies can not totally be attributed to anticonvulsants side effects. The exact influence, if any, of anti-epileptics on the induction of auto-immunity remain to be cleared. PO18-WE-42 Salivary testosterone and 8-OHDG levels in epileptic patients under chronic valproate therapy M.R. Najafi, M.R. Aghaye-Ghazvini, Z. Gabari, M. Zare. Medical Science, Isfahan, Islamic Republic of Iran Objective: Long-term exposure to valproic acid has been reported to result in, among other side effects, hyperandrogenism and oxidative stress in patients [1,2]. The aim of this study was to investigate the salivary testosterone and 8-OHDG levels, as markers of androgens and oxidative stress statues, in women who had been under chronic valproate treatment. Saliva sampling was selected because it is a
S255
non-invasive, stress-free technique and enables multiple sampling. Previous studies have shown that testosterone concentration in saliva is in good correlation with the serum free testosterone, and therefore salivary testosterone provides a reliable method for determination of physiologically active testosterone. Methods: We studied concentrations of salivary testosterone in 33 women under chronic valproate treatment and 7 healthy female controls. Salivary 8-OHDG was also measured in 17 patients and 6 controls (male and female). Results: Salivary testosterone concentrations in valproate-treated women (28.3±4.1, mean ± S.E.M., pg/ml), showed no statistically differences in concentrations compared with the healthy controls (27.6±0.9 pg/ml). Only one of the valproate receiving patients had salivary testosterone levels above upper reference values (55 pg/ml). salivary 8-OHDG levels were 2.96±1.08 and 1.15±0.47 in patients and healthy controls respectively (ng/mL, mean ± S.E.M.). No statistically differences in 8-OHDG concentrations was also observed between these two groups. Conclusion: Chronic valproate treatment does not appear to cause a significant increase in the salivary testosterone or 8-OHDG levels. Study of a larger number of patients and control groups may be needed to reveal the possible effects of valproate therapy on androgens and redox state of treated patients. PO18-WE-43 Correlation between duration of fenitoin usage and BMD in epileptic patients E. Setyarini, J.E.W. Rahardjo, M.H. Machfoed. Neurology, Airlangga University, Dr. Soetomo General Hospital, Surabaya, Indonesia Purpose: Epilepy is a common health disease which need at least 2 years of medication or even for a whole life time. A long period of anti epileptic medication, especially phenytoin, will decrease convulsion, but on the other side, it might increase bone metabolic disorder, started from osteopenia until osteoporosis. Bone metabolic disorder caused by phenytoin has not got any attention optimally in epileptic patients. According to the American Neurologist survey, it was found that only 28% of 624 neurologist, who performed bone densitometry examination routinely, after giving phenytoin. The use of phenytoin more than 5 years will cause the decrease of bone mineral density and the increase of bone fracture especially the femur and lumbal. The purpose of this study is to prove correlation between duration of phenytoin use and BMD. Method: The study was performed at neurological outpatients of dr. Soetomo Hospital from December 1, 2008 until January 31, 2009. The study sample was epileptic patients who used phenytoin and fulfilled both inclusion and exclusion criteria. Bone density examination was performed to the femur by using Dual X-ray Absorptiometry (DXA) scan. Correlation between phenytoin use duration and BMD was performed by mean of Pearson test. Result: Correlation coefficient between the phenytoin use duration and BMD as follows: • Columna femur was −0.676 (p = 0.000) • Trochanter femur was −0.749 (p = 0.000) • Intertrochanter femur was −0.712 (p = 0.000) • Total femur was −0.730 (p = 0.000) • Ward’s femur was −0.785 (p = 0.000) Conclusion: This study conclude that there was a negative correlation between duration of phenytoin use and BMD. PO18-WE-44 Alternatives to valproic acid in juvenile myoclonic epilepsy I. Kuzmanovski, E. Cvetkovska. Clinic of Neurology, Skopje, Republic of Macedonia Introduction: Juvenile myoclonic epilepsy (JME) is genetically determined, common idiopathic generalized syndrome, accounting for 5–10% of all epilepsy cases. It is characterised by triad of myoclonic jerks, generalized tonic-clonic seizures and absences.
S256
19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339
Purpose: The aim of the study was to evaluate the efficacy of alternative drugs when first-line valproic acid (VPA) fails in juvenile myoclonic epilepsy (JME). Material: 23 patients with JME in whom seizure control was insufficient (13) or experienced side effects (10) on VPA, were started with different drugs according to patient-specific variables. In three patients with only persistent myoclonias, clonazepam was added. In patients with uncontrolled myoclonias and tonic-clonic seizures we introduced: lamotrigine (LTG) in 10, topiramate (TPM) in 3, levetiracetam (LEV) in 3 and phenobarbital (PB) in 4 of them. Observational period was 6 months. Results: CNZ was effective in all 3 patients in suppressing myoclonias. In LTG group one patient drop out because of rush and another because of worsening of tremor when LTG added to VPA. Of remaining 8 patients, 3 were seizure free and in 2 marked reductions occurred. Worsening was observed in 2 and 1 without effect. TPM was effective in 1, LEV in 2 and PB in 2 of patients. Conclusion: In JME patients, in whom VPA failed, LTG, LEV and TPM of newer AEDs, but not to forget CNZ and PB in selected patients, could be useful therapeutic agents. PO18-WE-45 Surveillance of Croatian pregnant women with epilepsy and effects of antiepileptic drugs exposure in their offspring S. Miskov1 , R. Gjergja Juraski2 , A. Fucic3 , T. Ivicevic Bakulic4 , I. Mikula1 , L.J. Cvitanovic-Sojat2 , J. Bosnjak1 , V. Demarin1 . 1 Neurology, University Hospital Sisters of Mercy, Zagreb, Croatia; 2 Neuropediatrics, University Hospital Sisters of Mercy, Zagreb, Croatia; 3 Institute for Medical Research/Occupational Health, Zagreb, Croatia; 4 Obstetrics and Gynecology, University Hospital Sisters of Mercy, Zagreb, Croatia Purpose: The aim was to follow up pregnancies exposed to AED and their offspring in order to assess teratogenic and neurodevelopmental effect of particular AED of newer generation. Methods: The study is prospective surveillance of pregnancies in Croatian women with epilepsy from May 2003 to May 2009. The data about pregnancy planning, folate supplementation, seizure frequency and AED therapy were obtained. The results were compared with healthy controls (mother/newborn pairs). Results: We have surveyed 68 pregnancies from 52 women: 91% (62/68) were exposed to monotherapy: 33 to lamotrigine (LTG): 19 live-births (LB), 2 premature deliveries (one with motor delay), 3 spontaneous abortions (SA), 1 artificial abortion, 1 intrauterine death and 7 ongoing pregnancies (OP). Eleven LB and 2 SA were exposed to carbamazepine (CBZ), 1 LB was under phenitoine (PHT) and 1 under phenobarbiton (PB) with EPH gestosis/peripartal asphyxia. One LB and 1 preterm LB with ASD, severe psychomotor delay and epilepsy was exposed to gabapentine (GBP), 5 LB and 1 OP were under valproic acid (VP). Two pregnancies were under meprobamate (MPB): 1 LB and 1 SA. Six pregnancies were exposed to polytherapy: 1 LB, 1 SA and 1 OP to topiramate (TPM) and VP, 1 still-birth to CBZ and PB, 1 LB with intrauterine growth retardation and dysmorphism to TPM, CBZ, PHT, and 1 OP to VP and clonazepam (CZP). Four pregnancies without AED resulted in healthy LB. About 35% of women have planned their pregnancy, but only 20% took folic acid periconceptionaly. Conclusion: We have surveyed pregnancies exposed to LTG, VP, PHT, PB, GBP, TMP, CBZ, MPB and CZP. AED polytherapy resulted in larger proportion of complications. Adequate preconceptional counseling in women with epilepsy resulted in higher proportion of pregnancy planning and folic acid intake. Further follow up of all live-births till school age will be provided.
PO18-WE-46 Step one: study on the treatment of elderly patients with older and newer anti-epileptic drugs, interim report on recruitment and drop-out rates 1 G. Kramer ¨ , K.J. Werhahn2 , E. Trinka3 . 1 Medical, Swiss Epilepsy Center, Z¨ urich, Switzerland; 2 Neurology, University Medicine, Mainz, Germany; 3 Neurology, Medical University Hospital, Innsbruck, Austria
Purpose: New onset focal epilepsy occurs frequently in the elderly, yet, randomised controlled studies on antiepileptic treatment are scarce. Lamotrigine (LTG) and gabapentin are of equal efficacy but better tolerability compared to CBZ standard release. Retention is not different to LTG when CBZ slow-release is used. In this trial Levetiracetam (LEV) is compared to CBZ-SR and LTG. Method: STEP-ONE is a randomized, double-blind, multicenter study. Patients aged 60 years or above with new onset focal epilepsy (either at least one seizure and spike discharges on EEG or a relevant lesion on CT/MRI or a total of 2 spontaneous seizures) are eligible and those with symptomatic epileptic seizures due to acute (<2 weeks) brain injuries are excluded. Patients receive CBZ-SR, LTG or LEV in a parallel group design over 58 weeks (6 weeks titration and 52 weeks maintenance, target 400, 100, 1000 mg, respectively). Results: N = 212 (of 360) patients have been included so far. The drop-out rate is 38%. Drop-out reasons include: 25% patients personal request, 19% side effects on lowest daily dose (CBZ-SR 200 mg, LTG 50 mg, and LEV 500 mg), 33% newly occurring medical conditions. There were no unexpected drug-related serious adverse events. Conclusion: Retention is comparable to previous trials. Antiepileptic treatment in the elderly requires slow titration on low target dosages. Data with standard CBZ and faster titration or high target dosages should be interpreted with caution. Special drug trial designs are needed for the elderly. Recruitment of elderly people is difficult but study adherence is good. PO18-WE-47 A case of toxic hepatitis developing during phenytoin treatment H.N. Gune ¨ s¸ 1 , G. Gune ¨ s¸ 2 , T.K. Yoldas¸ 1 . 1 Neurology, Dıskapı ¸ Y.B. Training and Research Hospital, Ankara, Turkey; 2 Internal Medicine, Ufuk University, Faculty of Medicine, Ankara, Turkey Purpose: Idiosyncratic reactions such as lymphadenopathy, liver toxicity and hematological and dermatological side effects may be encountered during treatment of epilepsy with the widely-used phenytoin. The hepatotoxicity usually appears following six weeks of drug use in a dose-dependent manner. Case: A 30-year-old man with no history of epilepsy or liver disease presented at the emergency neurology outpatients department following a generalized tonic clonic seizure. The first intervention included phenytoin loading followed by maintenance treatment (Phenytoin 17 mg/kg infusion and 300 mg/day in 3 doses po as maintenance). The patient started to have liver enzyme (AST, ALT) elevations on the second day of maintenance phenytoin treatment. Following other tests, the phenytoin treatment was stopped with a preliminary diagnosis of phenytoin-related liver toxicity. The liver enzyme levels gradually decreased during follow-up and approached normal limits. Conclusion: Some articles report that phenytoin-related liver toxicity starts at least one week after initial drug usage. The elevation of liver enzymes from the second day of phenytoin use in our case is interesting as it indicates that phenytoin-related liver toxicity can be seen with low doses and at an early stage.
and hypertensive encephalopathy 18%. With rectal diazepam, the mean time to control seizure was 5 minutes and was effective in all patients with clinical response seen in 0.5–9 minutes. Intravenousl Midazolam mean time to control was recorded at 7 minutes and 33 seconds. This was effective in 14 of 15 (93%) subjects with clinical response noted within 5 seconds up to 10 minutes. The buccal route responded similarly with the intravenous Midazolam group with cessation of seizures in 12 of 13 (92%) children. Comparing seizure duration with time to control the attack using the Pearson Correlation found to be not significant. Also noted was the increased recurrence of seizures using intravenous midazolam. Conclusion: Buccal Midazolam is safe, effective in seizure control It is easily administered with fewer seizure recurrence. However, there was no statistical significance in seizure termination between the three treatment group. PO18-WE-41 Prevalence of the serum autoantibodies in the first seizure and after long term treatment with antiepileptic drugs in epileptic patients M.R. Najafi1 , M. Zare1 , E. Vaziri1 , M.R. Aghaghazvini2 , M. Reisifar3 . 1 Neurology, Isfahan University Of Medical Sciences, Isfahan, Islamic Republic of Iran; 2 Isfahan Center of Public Health Training and Resea, Isfahan, Islamic Republic of Iran; 3 INRC, Isfahan, Islamic Republic of Iran Purpose: Epileptic seizures have been proposed to be associated with some aberrant immune system functions. Increased prevalence of autoantibodies is a frequent finding in patients with epilepsy. Anti-epileptics therapy also has been proposed to affect autoantibodies levels. The exact contribution of each of the neurological disorders themselves, or subsequent treatment with anti-convulasants on the induction of autoantibodies has not been elucidated yet. The aim of this study was to determine the prevalence of autoantibodies in patients experiencing their first seizure and compare it with those who have been under chronic antiepileptic therapy and with normal controls. Methods: The frequency of antinuclear antibodies (ANA), anticardiolipin antibodies (aCL) and anti-B2-glycoprotein I immunoglobulin G class antibodies were studied in the sera of 64 epileptic patients who had been under chronic antiepileptic therapy for a minimum of six monthes, in 41 patients who had experienced their first seizure and in 75 apparently healthy controls. Results: The prevalence of autoantibodies were significantly higher in seizure patients compared with normal controls (P < 0.054). The prevalence of autoantibodies were 7.3, 7.8 and 1.3% in first seizure, chronic anticonvulsant receiving and normal subjects respectively. ANA was the most frequent autoantibody in all groups. The frequency of autoantibodies did not statistically differed between newly diagnosed and chronically treated epileptic patients. Conclusion: The result of this study shows that increased prevalence of autoantibodies can be seen both before and after long term epilepsy treatment. According to these results, the presence of autoantibodies can not totally be attributed to anticonvulsants side effects. The exact influence, if any, of anti-epileptics on the induction of auto-immunity remain to be cleared. PO18-WE-42 Salivary testosterone and 8-OHDG levels in epileptic patients under chronic valproate therapy M.R. Najafi, M.R. Aghaye-Ghazvini, Z. Gabari, M. Zare. Medical Science, Isfahan, Islamic Republic of Iran Objective: Long-term exposure to valproic acid has been reported to result in, among other side effects, hyperandrogenism and oxidative stress in patients [1,2]. The aim of this study was to investigate the salivary testosterone and 8-OHDG levels, as markers of androgens and oxidative stress statues, in women who had been under chronic valproate treatment. Saliva sampling was selected because it is a
S255
non-invasive, stress-free technique and enables multiple sampling. Previous studies have shown that testosterone concentration in saliva is in good correlation with the serum free testosterone, and therefore salivary testosterone provides a reliable method for determination of physiologically active testosterone. Methods: We studied concentrations of salivary testosterone in 33 women under chronic valproate treatment and 7 healthy female controls. Salivary 8-OHDG was also measured in 17 patients and 6 controls (male and female). Results: Salivary testosterone concentrations in valproate-treated women (28.3±4.1, mean ± S.E.M., pg/ml), showed no statistically differences in concentrations compared with the healthy controls (27.6±0.9 pg/ml). Only one of the valproate receiving patients had salivary testosterone levels above upper reference values (55 pg/ml). salivary 8-OHDG levels were 2.96±1.08 and 1.15±0.47 in patients and healthy controls respectively (ng/mL, mean ± S.E.M.). No statistically differences in 8-OHDG concentrations was also observed between these two groups. Conclusion: Chronic valproate treatment does not appear to cause a significant increase in the salivary testosterone or 8-OHDG levels. Study of a larger number of patients and control groups may be needed to reveal the possible effects of valproate therapy on androgens and redox state of treated patients. PO18-WE-43 Correlation between duration of fenitoin usage and BMD in epileptic patients E. Setyarini, J.E.W. Rahardjo, M.H. Machfoed. Neurology, Airlangga University, Dr. Soetomo General Hospital, Surabaya, Indonesia Purpose: Epilepy is a common health disease which need at least 2 years of medication or even for a whole life time. A long period of anti epileptic medication, especially phenytoin, will decrease convulsion, but on the other side, it might increase bone metabolic disorder, started from osteopenia until osteoporosis. Bone metabolic disorder caused by phenytoin has not got any attention optimally in epileptic patients. According to the American Neurologist survey, it was found that only 28% of 624 neurologist, who performed bone densitometry examination routinely, after giving phenytoin. The use of phenytoin more than 5 years will cause the decrease of bone mineral density and the increase of bone fracture especially the femur and lumbal. The purpose of this study is to prove correlation between duration of phenytoin use and BMD. Method: The study was performed at neurological outpatients of dr. Soetomo Hospital from December 1, 2008 until January 31, 2009. The study sample was epileptic patients who used phenytoin and fulfilled both inclusion and exclusion criteria. Bone density examination was performed to the femur by using Dual X-ray Absorptiometry (DXA) scan. Correlation between phenytoin use duration and BMD was performed by mean of Pearson test. Result: Correlation coefficient between the phenytoin use duration and BMD as follows: • Columna femur was −0.676 (p = 0.000) • Trochanter femur was −0.749 (p = 0.000) • Intertrochanter femur was −0.712 (p = 0.000) • Total femur was −0.730 (p = 0.000) • Ward’s femur was −0.785 (p = 0.000) Conclusion: This study conclude that there was a negative correlation between duration of phenytoin use and BMD. PO18-WE-44 Alternatives to valproic acid in juvenile myoclonic epilepsy I. Kuzmanovski, E. Cvetkovska. Clinic of Neurology, Skopje, Republic of Macedonia Introduction: Juvenile myoclonic epilepsy (JME) is genetically determined, common idiopathic generalized syndrome, accounting for 5–10% of all epilepsy cases. It is characterised by triad of myoclonic jerks, generalized tonic-clonic seizures and absences.
S256
19th World Congress of Neurology, Poster Abstracts / Journal of the Neurological Sciences 285 S1 (2009) S155–S339
Purpose: The aim of the study was to evaluate the efficacy of alternative drugs when first-line valproic acid (VPA) fails in juvenile myoclonic epilepsy (JME). Material: 23 patients with JME in whom seizure control was insufficient (13) or experienced side effects (10) on VPA, were started with different drugs according to patient-specific variables. In three patients with only persistent myoclonias, clonazepam was added. In patients with uncontrolled myoclonias and tonic-clonic seizures we introduced: lamotrigine (LTG) in 10, topiramate (TPM) in 3, levetiracetam (LEV) in 3 and phenobarbital (PB) in 4 of them. Observational period was 6 months. Results: CNZ was effective in all 3 patients in suppressing myoclonias. In LTG group one patient drop out because of rush and another because of worsening of tremor when LTG added to VPA. Of remaining 8 patients, 3 were seizure free and in 2 marked reductions occurred. Worsening was observed in 2 and 1 without effect. TPM was effective in 1, LEV in 2 and PB in 2 of patients. Conclusion: In JME patients, in whom VPA failed, LTG, LEV and TPM of newer AEDs, but not to forget CNZ and PB in selected patients, could be useful therapeutic agents. PO18-WE-45 Surveillance of Croatian pregnant women with epilepsy and effects of antiepileptic drugs exposure in their offspring S. Miskov1 , R. Gjergja Juraski2 , A. Fucic3 , T. Ivicevic Bakulic4 , I. Mikula1 , L.J. Cvitanovic-Sojat2 , J. Bosnjak1 , V. Demarin1 . 1 Neurology, University Hospital Sisters of Mercy, Zagreb, Croatia; 2 Neuropediatrics, University Hospital Sisters of Mercy, Zagreb, Croatia; 3 Institute for Medical Research/Occupational Health, Zagreb, Croatia; 4 Obstetrics and Gynecology, University Hospital Sisters of Mercy, Zagreb, Croatia Purpose: The aim was to follow up pregnancies exposed to AED and their offspring in order to assess teratogenic and neurodevelopmental effect of particular AED of newer generation. Methods: The study is prospective surveillance of pregnancies in Croatian women with epilepsy from May 2003 to May 2009. The data about pregnancy planning, folate supplementation, seizure frequency and AED therapy were obtained. The results were compared with healthy controls (mother/newborn pairs). Results: We have surveyed 68 pregnancies from 52 women: 91% (62/68) were exposed to monotherapy: 33 to lamotrigine (LTG): 19 live-births (LB), 2 premature deliveries (one with motor delay), 3 spontaneous abortions (SA), 1 artificial abortion, 1 intrauterine death and 7 ongoing pregnancies (OP). Eleven LB and 2 SA were exposed to carbamazepine (CBZ), 1 LB was under phenitoine (PHT) and 1 under phenobarbiton (PB) with EPH gestosis/peripartal asphyxia. One LB and 1 preterm LB with ASD, severe psychomotor delay and epilepsy was exposed to gabapentine (GBP), 5 LB and 1 OP were under valproic acid (VP). Two pregnancies were under meprobamate (MPB): 1 LB and 1 SA. Six pregnancies were exposed to polytherapy: 1 LB, 1 SA and 1 OP to topiramate (TPM) and VP, 1 still-birth to CBZ and PB, 1 LB with intrauterine growth retardation and dysmorphism to TPM, CBZ, PHT, and 1 OP to VP and clonazepam (CZP). Four pregnancies without AED resulted in healthy LB. About 35% of women have planned their pregnancy, but only 20% took folic acid periconceptionaly. Conclusion: We have surveyed pregnancies exposed to LTG, VP, PHT, PB, GBP, TMP, CBZ, MPB and CZP. AED polytherapy resulted in larger proportion of complications. Adequate preconceptional counseling in women with epilepsy resulted in higher proportion of pregnancy planning and folic acid intake. Further follow up of all live-births till school age will be provided.
PO18-WE-46 Step one: study on the treatment of elderly patients with older and newer anti-epileptic drugs, interim report on recruitment and drop-out rates 1 G. Kramer ¨ , K.J. Werhahn2 , E. Trinka3 . 1 Medical, Swiss Epilepsy Center, Z¨ urich, Switzerland; 2 Neurology, University Medicine, Mainz, Germany; 3 Neurology, Medical University Hospital, Innsbruck, Austria
Purpose: New onset focal epilepsy occurs frequently in the elderly, yet, randomised controlled studies on antiepileptic treatment are scarce. Lamotrigine (LTG) and gabapentin are of equal efficacy but better tolerability compared to CBZ standard release. Retention is not different to LTG when CBZ slow-release is used. In this trial Levetiracetam (LEV) is compared to CBZ-SR and LTG. Method: STEP-ONE is a randomized, double-blind, multicenter study. Patients aged 60 years or above with new onset focal epilepsy (either at least one seizure and spike discharges on EEG or a relevant lesion on CT/MRI or a total of 2 spontaneous seizures) are eligible and those with symptomatic epileptic seizures due to acute (<2 weeks) brain injuries are excluded. Patients receive CBZ-SR, LTG or LEV in a parallel group design over 58 weeks (6 weeks titration and 52 weeks maintenance, target 400, 100, 1000 mg, respectively). Results: N = 212 (of 360) patients have been included so far. The drop-out rate is 38%. Drop-out reasons include: 25% patients personal request, 19% side effects on lowest daily dose (CBZ-SR 200 mg, LTG 50 mg, and LEV 500 mg), 33% newly occurring medical conditions. There were no unexpected drug-related serious adverse events. Conclusion: Retention is comparable to previous trials. Antiepileptic treatment in the elderly requires slow titration on low target dosages. Data with standard CBZ and faster titration or high target dosages should be interpreted with caution. Special drug trial designs are needed for the elderly. Recruitment of elderly people is difficult but study adherence is good. PO18-WE-47 A case of toxic hepatitis developing during phenytoin treatment H.N. Gune ¨ s¸ 1 , G. Gune ¨ s¸ 2 , T.K. Yoldas¸ 1 . 1 Neurology, Dıskapı ¸ Y.B. Training and Research Hospital, Ankara, Turkey; 2 Internal Medicine, Ufuk University, Faculty of Medicine, Ankara, Turkey Purpose: Idiosyncratic reactions such as lymphadenopathy, liver toxicity and hematological and dermatological side effects may be encountered during treatment of epilepsy with the widely-used phenytoin. The hepatotoxicity usually appears following six weeks of drug use in a dose-dependent manner. Case: A 30-year-old man with no history of epilepsy or liver disease presented at the emergency neurology outpatients department following a generalized tonic clonic seizure. The first intervention included phenytoin loading followed by maintenance treatment (Phenytoin 17 mg/kg infusion and 300 mg/day in 3 doses po as maintenance). The patient started to have liver enzyme (AST, ALT) elevations on the second day of maintenance phenytoin treatment. Following other tests, the phenytoin treatment was stopped with a preliminary diagnosis of phenytoin-related liver toxicity. The liver enzyme levels gradually decreased during follow-up and approached normal limits. Conclusion: Some articles report that phenytoin-related liver toxicity starts at least one week after initial drug usage. The elevation of liver enzymes from the second day of phenytoin use in our case is interesting as it indicates that phenytoin-related liver toxicity can be seen with low doses and at an early stage.