epilepsy is one of the most prevalent neurological diseases , and it affects approximately 0.5%-0.8% of children . despite the prescription of appropriate antiepileptic medication , approximately 10%-30% of children with epilepsy do not respond to treatment . refractory epilepsy is defined as the failure to control seizures with the use of two or more anticonvulsant drugs . an acceptable approach for patients with intractable seizures is multiple antiepileptic drug therapy rather than monotherapy . the outcome of seizures in children with refractory epilepsy has been improved by new - generation antiepileptic drugs . vigabatrin was formulated in 1975 by a purposeful effort to create a substance that can increase the levels of gamma - aminobutyric acid ( gaba ) , an inhibitory neurotransmitter . vigabatrin destroys gaba transaminase ( gaba - t ) irreversibly inhibiting the activity of the enzyme in the nervous system tissue and cerebrospinal fluid ( csf ) as well as enhancing presynaptic gaba , which leads to seizure improvement . the structure of vigabatrin is similar to that of gaba , so it can selectively interfere with gaba - t activity and prevent gaba decomposition . oral vigabatrin is absorbed quickly and almost completely ; it has a linear pharmacokinetic profile with a maximum concentration achieved within 2 h after administration . vigabatrin has been used as a first - line treatment of children with infantile spasms aged between one month and 2 years and as an add - on therapy for adolescents with intractable complex partial epilepsy in over 50 countries . long - term vigabatrin therapy is considered to be safe and well tolerated ; the most common side effects are a self - limiting headache , somnolence , weight gain and visual field defects . there have been no detailed investigations on the efficacy of vigabatrin in iranian children with various seizure types . this study was designed to determine the efficacy of vigabatrin in iranian children with intractable epilepsy and its adverse effects . from november 2011 to october 2012 , 73 children with refractory epilepsy who visited the pediatric neurology clinics of the children s medical center or mofid children s hospital were enrolled in this study . children aged below 18 years with epilepsy refractory to previous aeds ( > 2 conventional and new aeds ) were included in the study . children with neurodegenerative diseases or hypersensitivity to anticonvulsants were excluded from the study . after receiving written consent from the patients , initial assessments such as disease history ( type , onset , etiology , and the frequency of seizures ; previous treatment period ; and type of aed used ) , physical examination ( general and neurological ) , seizures were confirmed and quantified monthly based on reports from parents , observing videos taken by parents , and direct observation at the hospital before and after treatment . diffuse and continuous paroxysmal epileptic discharges were considered severely abnormal when they accounted for > 50% of the eeg readings and were considered mildly or moderately abnormal when they accounted for > 25% of the eeg readings . next , the children were administered an initial oral dose of vigabatrin ( 4050 mg / kg / day ) that was divided into 2 or 3 doses ; vigabatrin was administered in addition to their previous medication ( > 2 new , conventional , or concurrent aeds ) . vigabatrin doses were adjusted to a maximum dose of 100 mg / kg / day based on the level of seizure response . during the follow - up period , a response was defined as a stable seizure frequency or severity or a > 50% reduction in seizure frequency . the primary and secondary outcomes of the study were defined as the efficacy of vigabatrin , three and six months after initiation . the study was approved by the ethics committee of shahid beheshti university of medical sciences , and was registered in the iranian registry of clinical trials ( irct number : irct2012091210508n3 ) . a total of 73 patients were enrolled in the study , but only 67 children reached the final stage . details of the patient characteristics are listed in table 1 . of these last patients , 41 ( 61.2% ) were male and 26 ( 38.8% ) female . they ranged in age from three months to 13 years with an average of 3.1 [ standard deviation ( sd ) : 2.6 ] years . the age of seizure onset ranged from one day to five years , and the mean age at seizure onset was 8.57 ( sd : 12.8 ) months . the daily frequency of seizures varied from one attack every three months to 29 attacks per day with an average of 6.61 ( sd : 5.9 ) seizures per day . the patients had used a minimum of three and a maximum of 16 antiseizure medications , with an average number of 5.0 ( sd : 2.89 ) prior to this study . primidon , sodium valproate , phenobarbital , carbamazepine , phenytoin , and topiramate were the most commonly used concomitant drugs . vigabatrin was administered at a minimum dose of 40 mg/ kg / day and at a maximum dose of 100 mg / kg / day ; the mean dose was 76.6 ( sd : 22.6 ) mg / kg / day . patient characteristics in children with refractory epilepsy the primary outcome , efficacy of vigabatrin after three months , was assessed by daily seizure frequency , which decreased by 56% to 2.9 ( sd : 5.2 ) per day . the secondary outcome , efficacy after six months , was a 54.5% decline in daily seizure frequency to 3.0 ( sd : 5.3 ) per day ( fig . there was significant difference between seizure frequency three ( p=0.001 ) and six months ( p=0.001 ) after the initiation of vigabatrin therapy compared with baseline , and there was no significant difference between the daily seizure frequency at three and six months ( p=0.6 ) . seizure reduction at the three- and six - months follow - up frequency reduction : seizure frequency decline percent toward initial frequency improvement : seizure severity reduction percent toward initial severity in terms of the primary outcome and based on the severity and duration of seizures , 45 ( 67.2% ) patients were classified as responders with the greatest responses observed in patients with partial , infantile spasms and generalized tonic - clonic seizures . there was no significant correlation between the type of seizure and drug response at this time point ( p=0.4 ) . regarding the secondary outcome , the seizure severity of 38 ( 56.7% ) patients was reduced by > 50% with the greatest reductions observed in patients with infantile , partial spasms and generalized tonic - clonic seizures . the type of seizure was significantly correlated with drug response at this time point ( p=0.008 ) . no significant difference was observed between seizure severity and decline in seizure duration at the three- and six - month follow - up ( p=0.39 ) . after six months of vigabatrin therapy , minor side effects were observed in nine ( 13.4% ) patients including somnolence [ 3 ( 4.5% ) ] , horse laugh [ 1 ( 1.5% ) ] , urinary stones [ 1 ( 1.5% ) ] , increased appetite [ 1 ( 1.5% ) ] , and abnormal electroretinographic ( erg ) pattern [ 3 ( 4.5% ) ] . the three patients who had an abnormal erg pattern were all taking vigabatrin at a dose of 5070 mg / kg ; the drug was discontinued in these patients and they were examined again three months after discontinuation . at this time , two had a normal erg pattern , but one had an abnormal erg pattern . this study proved that vigabatrin has significant efficacy in reducing the frequency , duration , and severity of pediatric seizures . daily seizures were reduced by 56% and 54.5% after three and six months of vigabatrin therapy . the responder rate , which means a reduction of > 50% in seizure severity and duration , was 67.2% and 56.7% at three and six months of vigabatrin therapy , respectively . the reported overall response rate for vigabatrin as an adjunctive therapy in intractable epilepsy differs , and ranges from 33% to 67% for partial epilepsy and 16% to 76% for infantile spasms . turanli reported that vigabatrin reduced seizure frequency by 50% in 31.2% of children with intractable seizures , which is lower than the response reported in this study . a possible explanation for this discrepancy may be the fact that the mean final follow - up in turanli s study was approximately 23.8 months , which is much longer than the six - month period used in our study . many studies have shown that the effects of antiepileptic drugs are reduced over time because of decreased receptor sensitivity resulting in pharmacokinetic tolerance . an important finding of our study was that 80% of patients with tuberous sclerosis had complete seizure improvement with vigabatrin therapy . this result is in agreement with hancock et al , who reported that vigabatrin ceased infantile spasms in 54% of infants without tuberous sclerosis compared with 95% of infants with tuberous sclerosis . in this study , we found that partial , infantile spasms and generalized tonic - clonic seizures showed the greatest response to vigabatrin therapy . visudtibhan reported a similar efficacy of approximately 76% for vigabatrin in the treatment of infantile spasms . in turanli s study , vigabatrin resulted in > 50% reduction in 33.3% of patients with partial seizures and 30.6% of those with generalized seizures , and there was no significant difference between these seizure types . in a clinical trial performed by guberman , 58% of patients with partial seizures treated with vigabatrin achieved a reduction of > 50% in daily seizure frequency versus baseline . based on our results , we suggest that vigabatrin therapy could be an appropriate therapy for partial epilepsies that are refractory to other treatments . our patients who showed a > 50% reduction in seizures , were administered vigabatrin at a dose of approximately 75 mg / kg / day , whereas turanli achieved the same effect at 61.5 mg / kg / day . after six months of vigabatrin therapy a few minor side effects were observed in nine ( 13.4% ) patients including somnolence , horse laugh , urinary stones , increased appetite , and an abnormal erg pattern . our adverse effect rate was lower than the 18% complication rate ( increased appetite , obesity , visual field defects , alopecia , drowsiness , skin rash , behavioral changes , hirsutism , and increased liver enzymes ) found among turanli s patients . guberman reported weight gain and behavior problems in 12% of his cases . in the present study , another important finding was that two children presented with a horse laugh as a vigabatrin effect . this complication is consistent with that reported by amirsalari et al , who found that loud laughing was a side effect in 16% of patients undergoing vigabatrin therapy . based on erg examinations , only three ( 4.5% ) children developed visual impairment at the end of the six - month treatment . our findings are consistent with those of turanli et al . , who confirmed visual field defects in 3.6% of children by erg . this study confirms the short - term efficacy and safety of vigabatrin in children with refractory epilepsies . future investigations with a longer evaluation period are needed to study the prolonged efficacy of vigabatrin .
objectiveapproximately one - third of all children with epilepsy do not achieve complete seizure improvement . 
 this study evaluated the efficacy of vigabatrin in children with intractable epilepsy.methodsfrom november 2011 to october 2012 , 73 children with refractory epilepsy ( failure of seizure control with the use of two or more anticonvulsant drugs ) who were referred to the children s medical center and mofid children s hospital were included in the study . 
 the patients were treated with vigabatrin in addition to their previous medication , and followed - up after three to four weeks to determine the daily frequency , severity , and duration of seizures in addition to any reported side effects.findingsof the 67 children , 41 ( 61.2% ) were males and 26 ( 38.8% ) females , their age ranging from three months to 13 years with an average of 3.1 [ standard deviation ( sd ) , 2.6 ] years . 
 the mean daily frequency of seizures at baseline was 6.61 ( sd , 5.9 ) seizures per day . 
 vigabatrin reduced the seizure frequency 2.9 ( sd , 5.2 ) ( 56% decline ) and 3.0 ( sd , 5.3 ) ( 54.5% decline ) per day after three and six months of treatment , respectively . 
 a significant difference was observed between seizure frequencies at three ( p<0.001 ) and six months ( p<0.001 ) after vigabatrin initiation compared with the baseline . 
 somnolence [ 3 ( 4.5% ) ] , horse laugh [ 1 ( 1.5% ) ] , urinary stones [ 1 ( 1.5% ) ] , increased appetite [ 1 ( 1.5% ) ] , and abnormal electroretinographic pattern [ 3 ( 4.5% ) ] were the most common side effects in our patients.conclusionthis study confirms the short - term efficacy and safety of vigabatrin in children with refractory epilepsies .