a 2-year - old girl presented with partial seizures that manifested as twitching of the left angle of the mouth and jerking of the left upper limb but usually did not result in a loss of consciousness . the child s motor and cognitive development were within the normal ranges . at the age of 3 years , she was referred to our center with the aim of achieving control of her seizures . brain magnetic resonance imaging ( mri ) showed focal cortical dysplasia in the right centroparietal region ( figure 1a ) , while interictal tc - ethyl cysteinate dimer single - photon emission computed tomography ( spect ) did not detect any abnormalities ( data not shown ) . a , at the age of 3 years , a t2-weighted mri scan showed focal cortical dysplasia in the right centroparietal region (  ) . b , on day 2 after admission , a t2-weighted mri image showed a high signal intensity lesion (  ) adjacent to the focal cortical dysplasia lesion . c , apparent diffusion coefficient mapping also showed a high signal intensity lesion in the same region . d , the high signal intensity lesion (  ) was located close to the right insular cortex ( left ) . on day 69 , the high signal intensity lesion had diminished in size , and the patient s cluster seizures had improved ( right ) . dimer spect detected hyperperfusion in a region containing the high signal intensity lesion seen on mri , which was located close to the right insular cortex . interictal tc - ethyl cysteinate dimer spect performed on day 68 did not detect any abnormalities . mri indicates magnetic resonance imaging ; spect , single - photon emission computed tomography . at the age of 10 years and 5 months , the patient was admitted because of a sudden worsening of her seizures . on admission , she was taking phenytoin ( 250 mg / d ) in combination with valproate ( 400 mg / d ) . an ictal eeg showed rhythmic fast waves arising from the right central region , which sometimes evolved into diffuse slow waves corresponding to asymmetric bilateral tonic seizures ( left > right ) . the patient s seizures did not respond to the intravenous administration of midazolam , lidocaine , and phenobarbital . on the second day after admission , t2-weighted mri and apparent diffusion coefficient mapping revealed a high signal intensity lesion adjacent to the focal cortical dysplasia lesion ( figure 1b - d , left ) . diffusion - weighted imaging also revealed a high signal intensity lesion in the same region ( data not shown ) . an eeg performed at the onset of the seizure showed rhythmic fast waves arising from the right central region . ten seconds after the onset of the seizure , when the epileptic activity evolved into diffuse slow waves , the patient s baseline sinus heart rate of about 100 beats / min suddenly dropped to 40 to 50 beats / min , and she started to exhibit an idioventricular rhythm . immediately after the seizure activity disappeared , the patient s cardiac rhythm returned to a normal sinus rhythm ( figure 2 ) . oxygen desaturation ( an oxygen saturation value of < 92% ) due to apnea ( defined as breath arrest lasting > 10 seconds ) also occurred after the appearance of ictal bradycardia . cardiac assessments , including continuous 24-hour ambulatory electrocardiography ( ecg ) monitoring and echocardiography , did not detect any abnormalities between the seizures . a , an eeg performed at seizure onset showed rhythmic fast waves arising from the right central region . b , about 10 seconds after seizure onset , when the patient s epileptic activity evolved into diffuse slow waves , her baseline sinus heart rate of about 100 beats / min suddenly dropped to 40 to 50 beats / min and then exhibited an idioventricular rhythm . c , after the seizure activity disappeared ( 68 seconds after onset ) , the patient s cardiac rhythm returned to a normal sinus rhythm . between 3 and 5 days after the patient s admission , the frequency of her seizures increased to 5 to 10 an hour . the patient s ictal bradycardia and apnea were usually accompanied by seizures , despite the prompt discontinuation of phenytoin and lidocaine . the idioventricular rhythm was observed in about half of the seizures . on the sixth day after admission , when a brief period of ictal asystole occurred , barbiturate ( sodium thiopental ) therapy was started while the patient was under mechanical ventilation . the frequency of the patient s seizures decreased to once or twice an hour after the initiation of the barbiturate therapy ( 5 mg / kg / h ) , and her ictal bradycardia subsided . after the continuous intravenous infusion of sodium thiopental for 48 hours , the dose was gradually reduced . however , the patient s bradycardia was less severe than it had been previously , her heart rate only fell to around 60 to 70 beats / min , and she did not develop cardiac arrhythmia . on the 25th day after admission , ictal spect performed on day 27 showed hyperperfusion in the area containing both the focal cortical dysplasia lesion and the high signal intensity lesion seen on mri ( figure 1e ) . the frequency of the patient s seizures was reduced via the continuous infusion of midazolam and high - dose phenobarbital , and hence , her ictal bradycardia subsided again . interictal spect performed on day 68 did not reveal any abnormalities ( figure 1e ) . on day 69 , the high - intensity lesion adjacent to the focal cortical dysplasia lesion was found to have diminished in size on follow - up mri ( figure 1d , right ) . interictal f - fluorodeoxyglucose positron emission tomography / computed tomography was performed 2 months after discharge and detected hypometabolism in the right centroparietal region but not in the right insular cortex ( data not shown ) . she underwent surgery at the age of 13 years and 1 month , and the lesion was partially resected . after surgery , the patient had infrequent partial seizures that were similar to those observed before surgery but no longer developed cluster seizures . ictal bradycardia is considered to be rare in children because there have only been a few reported pediatric cases . however , a recent study found that ictal bradycardia occurred in 8.2% of the pediatric patients with epilepsy admitted to a pediatric epilepsy monitoring unit . another comparative study reported that ictal bradycardia occurred more often in children ( 23.8% of pediatric seizures ) than in adults ( 7.3% of adult seizures ) . in adults , ictal bradycardia was found to be more strongly associated with seizures originating from the temporal lobe , while in children it was more prevalent in patients having seizures of extratemporal origin . the risk factors for ictal bradycardia include seizure clustering , having suffered with epilepsy for a long period , taking multiple antiepileptic drugs , a younger age at seizure onset , and refractory epilepsy . the propagation of seizure activity into the autonomic centers that regulate the cardiovascular system is assumed to be the leading mechanism of ictal bradycardia . in 1990 , oppenheimer and cechetto demonstrated that stimulation of the left insular cortex evoked bradycardia in rats . the same authors later showed that perioperative stimulation of the insular cortex tended to result in heart rate changes ( left insular cortex : bradycardia and right insular cortex : tachycardia ) in patients with epilepsy . although conflicting results have been obtained regarding the left- or right - sided predominance of ictal bradycardia , several other studies have suggested that the insular cortex plays an important role in cardiac regulation in humans . however , to the best of our knowledge , there has only been 1 case report of ictal bradycardia due to an insular cortex lesion , which involved a 3-year - old girl with focal cortical dysplasia in her right insular cortex . 
  some antiepileptic drugs , such as carbamazepine , lamotrigine , phenytoin , and lidocaine , are known to act as sodium channel blockers and can have side effects that affect the cardiac conduction system . our patient was receiving phenytoin and lidocaine for her cluster seizures when the first episode of ictal bradycardia occurred . however , phenytoin and lidocaine are unlikely to have caused the bradycardia experienced in the present case due to ( 1 ) the prolonged ( > 2 weeks ) persistence of the bradycardia , despite the prompt discontinuation of the above - mentioned drugs and ( 2 ) the absence of cardiac arrhythmia between seizures according to continuous 24-hour ambulatory ecg monitoring . focal cortical dysplasia constitutes the most important cause of intractable localization - related epilepsy in childhood . a recent study reported that ictal spect is useful for defining the epileptic zone in a high proportion of children with focal cortical dysplasia who undergo surgical evaluation . in our patient , the high signal intensity lesion seen on t2-weighted mri image appeared when the patient had cluster seizures and diminished in size as her seizures improved , suggesting that these mri changes were related to seizure clustering . ictal spect detected hyperperfusion in the area containing the high signal intensity lesion depicted on mri , which was located very close to the right insular cortex . the ictal bradycardia experienced by our patient might have been caused by the following mechanism : repetitive seizure activity might have expanded from the hyperperfusion zone into the right insular cortex , which controls cardiac rhythm , resulting in ictal bradycardia . the autonomic alterations and heart rate changes seen during epilepsy are complex and are not fully understood . although the presence of hyperperfusion on ictal spect might represent zones of seizure propagation , there have not been any reports about the ictal spect findings of patients with ictal bradycardia . in our patient , ictal spect demonstrated hyperperfusion in an area that was close to the insular cortex but did not involve the insular cortex itself . subtraction ictal spect coregistered to mri analysis also failed to detect ictal hyperperfusion in the right insular cortex ( data not shown ) . one possible reason for this is that the patient s bradycardia was less severe at the time of the ictal spect study than it had been previously . although the seizures experienced by the patient after the injection of the radiotracer used for the spect produced similar symptoms and paroxysmal eeg discharges to the previous seizures , the bradycardia induced was mild ( the patient s heart rate only fell to 60 - 70 beats / min ) and did not lead to cardiac arrhythmia . thus , seizures involving more severe ictal bradycardia might have been found to involve the insular cortex on spect . in this study , ictal and interictal spect were performed during the patient s cluster seizures ( day 27 ) , when ictal bradycardia was observed , and on day 68 , when the ictal bradycardia had gone into remission . however , no ictal spect scans were performed after the patient s ictal bradycardia went into remission because she did not experience seizures often during the follow - up period . comparing the 2 ictal spect scans might have helped us to clarify the origin of the patient s ictal bradycardia and why her ictal bradycardia was transient . further studies with ictal spect are necessary to elucidate the pathophysiology of ictal bradycardia in patients with epilepsy , providing that clinical conditions allow it .
ictal bradycardia , which is considered to be one of the causes of sudden unexplained death in epilepsy , is rare . a 10-year - old girl with focal cortical dysplasia in her right centroparietal region developed transient ictal bradycardia during cluster seizures . 
 brain magnetic resonance imaging demonstrated a high signal intensity lesion adjacent to the focal cortical dysplasia lesion . 
 ictal 99mtc - ethyl cysteinate dimer single - photon emission computed tomography ( spect ) detected hyperperfusion in an area containing the high signal intensity lesion , which was located close to the insular cortex . since the hyperperfusion zone observed on spect was considered to reflect seizure propagation , it is possible that the ictal bradycardia experienced in the present case was caused by the following mechanism : the repetitive seizure activity caused the high - intensity lesion seen on mri to expand into the right insular cortex , which controls cardiac rhythm , resulting in ictal bradycardia .