perinatal asphyxia is a significant cause of brain damage in the human newborns and can result in long - term neurodevelopmental disability . neonatal seizures are important risk factors for impaired neurodevelopment in neonatal hypoxic - ischemic encephalopathy ( hie ) . most studies of neonatal seizures depend on clinically diagnosed seizures . however , increased use of continuous electroencephalographic ( eeg ) monitoring has clarified the fact that seizures in newborns are often subclinical and that neonatologists have difficulties in distinguishing seizures from nonseizure spells . there had been conflicts as to the importance of seizures that are electrographic without clinical manifestations as compared with those that manifest obvious clinical signs . previous studies found a clear relationship between seizure load and injury on magnetic resonance imaging ( mri ) . however , little is known regarding frequency of seizure , its distribution , its time of onset and seizure expression , and their relationship to mri brain injury during therapeutic hypothermia ( th ) . our aim was to determine the value of video - eeg monitoring in newborns with hie treated by hypothermia through determination of eeg background , prevalence of seizures during th , determination of eeg patterns that can predict mri brain injury and value of detection , and treatment of subclinical seizures . this work was conducted on 39 full - term newborns with hie admitted to the neonatal intensive care unit ( nicu ) of al hada and taif military hospitals , saudi arabia . their gestational ages ranged from 37 to 40 weeks with a mean of 38  1.8 . their weights ranged from 3.1 to 3.8 kg with a mean of 3.32  0.56 , 46% were males and 54% were females . all cases were subjected to th with whole - body cooling according to standard protocols . inclusion criteria for th included : 
 gestational age at birth 36 weeks.any of the following : 
 ph < 7.0 of cord or first blood gasbase deficit > 12 of cord or first blood gas10-min agar score < 5 . 

  gestational age at birth 36 weeks . any of the following : 
 ph < 7.0 of cord or first blood gasbase deficit > 12 of cord or first blood gas10-min agar score < 5 . 
  ph < 7.0 of cord or first blood gas base deficit > 12 of cord or first blood gas 10-min agar score < 5 . exclusion criteria included premature babies known or suspected cases of metabolic disorders and congenital anomalies . th was initiated as early as possible after birth with whole - body cooling ( target temperature 33.5c ) for 72 h followed by rewarming over 6 h. antiepileptic drugs were used to control seizures according to guidelines . sedation was done for all patients using continuous infusion of morphine in a dose of ( 1025 g / kg / h ) all over cooling to prevent any abnormal movement . newborns with seizure were subdivided into two groups : group 1 included newborns with a treatment of both types of ( clinical and subclinical ) seizures ( 12 cases ) . group 2 included newborns with the treatment of clinical seizures only ( 7 cases ) . a nicoletone eeg monitor was used to record continuous video - eeg recordings for 72 h. it started early after birth . eeg background at the onset of the recording was classified into one of five patterns : ( 1 ) transient discontinuity for less than one - half of the recording is considered normal for gestational age . ( 2 ) excessively discontinuous , with an existence of discontinuity for more than one - half of the recording . ( 3 ) depressed and undifferentiated , there is an absence of faster frequencies with persistence of a low background activity . there is also often a suppression of amplitude ( 515 v ) , and the tracing may be more discontinuous that would be expected for gestational age . ( 4 ) burst suppression ( bs ) pattern is characterized by periods of excessively suppressed background ( 5 v ) interrupted by bursts of abnormal activity . ( 5 ) extremely low voltage , with amplitude < 5 v or with no perceptible cerebral activity . a repetitive rhythmic activity of > 10 s duration identifies an electrographic seizure , with a sharp beginning , middle , and end with clear evolution . these features are important in differentiating of ictal rhythmic discharges from artifacts [ figure 2 ] . when electrographic seizure activity was continued for at least half an hour or recurs for at least one - half of 13 h recording time , status epilepticus ( se ) was identified . burst suppression pattern in severe birth asphyxia showing severely suppressed background activity with intermittent bursts of normal activity seizure pattern showing a repetitive , rhythmic , and stereotyped activity of > 10 s duration with a sharp beginning , middle , and end with clear evolution neonates were imaged with conventional t1-weighted , t2-weighted , and diffusion - weighted imaging sequences . basal ganglia / thalamus score < 2 and watershed score <3 identify normal to mild mri injury . basal ganglia / thalamus score 2 or watershed pattern 3 identifies moderate to severe mri injury . data were analyzed with spss , and variables were analyzed with t - test and chi - square . specificity and sensitivity were used to assess the prognostic value of eeg background patterns at different intervals . linear regression analysis was used to test the relationship between the duration of seizure patterns and mri scores . a nicoletone eeg monitor was used to record continuous video - eeg recordings for 72 h. it started early after birth . eeg background at the onset of the recording was classified into one of five patterns : ( 1 ) transient discontinuity for less than one - half of the recording is considered normal for gestational age . ( 2 ) excessively discontinuous , with an existence of discontinuity for more than one - half of the recording . ( 3 ) depressed and undifferentiated , there is an absence of faster frequencies with persistence of a low background activity . there is also often a suppression of amplitude ( 515 v ) , and the tracing may be more discontinuous that would be expected for gestational age . ( 4 ) burst suppression ( bs ) pattern is characterized by periods of excessively suppressed background ( 5 v ) interrupted by bursts of abnormal activity . ( 5 ) extremely low voltage , with amplitude < 5 v or with no perceptible cerebral activity . a repetitive rhythmic activity of > 10 s duration identifies an electrographic seizure , with a sharp beginning , middle , and end with clear evolution . these features are important in differentiating of ictal rhythmic discharges from artifacts [ figure 2 ] . when electrographic seizure activity was continued for at least half an hour or recurs for at least one - half of 13 h recording time , status epilepticus ( se ) was identified . burst suppression pattern in severe birth asphyxia showing severely suppressed background activity with intermittent bursts of normal activity seizure pattern showing a repetitive , rhythmic , and stereotyped activity of > 10 s duration with a sharp beginning , middle , and end with clear evolution neonates were imaged with conventional t1-weighted , t2-weighted , and diffusion - weighted imaging sequences . basal ganglia / thalamus score < 2 and watershed score <3 identify normal to mild mri injury . basal ganglia / thalamus score 2 or watershed pattern 3 identifies moderate to severe mri injury . data were analyzed with spss , and variables were analyzed with t - test and chi - square . linear regression analysis was used to test the relationship between the duration of seizure patterns and mri scores . all clinical characteristics were not significantly associated with brain injury in mri [ table 1 ] . clinical characteristics of newborns in relation to brain injury at the beginning of cooling , no one of newborns whom background was normal had moderate to severe injury . in 12 newborns whom background pattern was excessively discontinuous , 9 ( 75% ) had normal or mild injury and 3 ( 25% ) had moderate to severe injury . bs or extremely low - voltage pattern was found in 16 newborns , 10 ( 62.5% ) had moderate to severe injury and 6 ( 37.5% ) newborns had a normal mri or only a mild injury . eeg improved in all six newborns with bs or extremely low - voltage pattern by 1218 h of recording and background normalized by the middle of cooling [ table 2 ] . electroencephalographic background during cooling in relation to magnetic resonance imaging brain injury during this interval , one newborn whom eeg improved from a discontinuous pattern to a normal one at the beginning of cooling had moderate to severe mri injury . during the middle of cooling , no one of the remaining newborns with a normal eeg had moderate to severe injury . among the 11 infants with a discontinuous eeg pattern , the background had moderate to severe injury in ( 2/11 , 18% ) . all newborns ( 7/7 , 100% ) with bs or extremely low - voltage patterns had moderate to severe injury [ table 2 ] . among the 11 infants whom background was normal furthermore , among the 15 infants with an excessively discontinuous pattern , 2 ( 13% ) of them showed moderate to severe mri injury . compared to all five infants ( 100% ) whom background had bs or extremely low voltage [ table 2 ] . the same two newborns whom background was normal ( 13% ) at this time point showed moderate to severe injury . after rewarming , all six infants with bs or extremely low - voltage patterns had moderate to severe injury [ table 2 ] . seizures recurred during the middle of cooling in two infants and during rewarming in another two . among the 12 infants with electrographic seizures , 5 infants ( 42% ) did not show a clinical correlate ( subclinical seizure ) . among the five infants with subclinical seizure , three of them showed subclinical se . all three infants with se showed bs or extremely low - voltage patterns with the start of cooling . patients with moderate to severe mri injury had isolated or recurrent seizures more frequently than those with no or mild injury ( 47% vs. 21% , p = 0.05 ) , and the se was seen only in infants with moderate to severe injury ( p = 0.01 ) [ table 3 ] . background of electroencephalographic , seizures , status epilepticus , and outcome of magnetic resonance imaging brain outcome a normal eeg background at the start of cooling was more predictive of a favorable mri outcome than at later time points with a specificity of 100% and 80% , respectively . bs pattern or extremely low - voltage background is of a prognostic value for moderate to severe injury that increased from the start of cooling ( 75% specificity ) to the middle of cooling and later ( 100% specificity ) [ table 4 ] . electroencephalographic background sensitivity and specificity during and after cooling for moderate to severe magnetic resonance imaging brain injury there were no differences between groups regarding clinical characteristics . the duration ( median  standard deviation ) of seizure patterns was 42  83 min in group 1 , compared with 86  134 min in group 2 [ figure 3 ] . no significant difference in duration was found between the groups using linear regression . there was a significant relationship between the duration of seizure patterns and mri scores in linear regression analysis in group 1 [ figure 4 ] . duration of seizure patterns for the clinical and subclinical seizure treatment group 1 and the clinical seizure treatment group 2 . the vertical lines indicate the limit lines : ranges relationship between duration of seizure patterns and magnetic resonance imaging scores ( linear regression ) in group 1 at the beginning of cooling , no one of newborns whom background was normal had moderate to severe injury . in 12 newborns whom background pattern was excessively discontinuous , 9 ( 75% ) had normal or mild injury and 3 ( 25% ) had moderate to severe injury . bs or extremely low - voltage pattern was found in 16 newborns , 10 ( 62.5% ) had moderate to severe injury and 6 ( 37.5% ) newborns had a normal mri or only a mild injury . eeg improved in all six newborns with bs or extremely low - voltage pattern by 1218 h of recording and background normalized by the middle of cooling [ table 2 ] . during this interval , one newborn whom eeg improved from a discontinuous pattern to a normal one at the beginning of cooling had moderate to severe mri injury . during the middle of cooling , no one of the remaining newborns with a normal eeg had moderate to severe injury . among the 11 infants with a discontinuous eeg pattern , the background had moderate to severe injury in ( 2/11 , 18% ) . all newborns ( 7/7 , 100% ) with bs or extremely low - voltage patterns had moderate to severe injury [ table 2 ] . among the 11 infants whom background was normal , 2 ( 18% ) of them showed moderate to severe mri injury . furthermore , among the 15 infants with an excessively discontinuous pattern , 2 ( 13% ) of them showed moderate to severe mri injury . compared to all five infants ( 100% ) whom background had bs or extremely low voltage [ table 2 ] . the same two newborns whom background was normal ( 13% ) at this time point showed moderate to severe injury . after rewarming , all six infants with bs or extremely low - voltage patterns had moderate to severe injury [ table 2 ] . seizures recurred during the middle of cooling in two infants and during rewarming in another two . among the 12 infants with electrographic seizures , 5 infants ( 42% ) did not show a clinical correlate ( subclinical seizure ) . among the five infants with subclinical seizure , three of them showed subclinical se . all three infants with se showed bs or extremely low - voltage patterns with the start of cooling . patients with moderate to severe mri injury had isolated or recurrent seizures more frequently than those with no or mild injury ( 47% vs. 21% , p = 0.05 ) , and the se was seen only in infants with moderate to severe injury ( p = 0.01 ) [ table 3 ] . background of electroencephalographic , seizures , status epilepticus , and outcome of magnetic resonance imaging brain outcome a normal eeg background at the start of cooling was more predictive of a favorable mri outcome than at later time points with a specificity of 100% and 80% , respectively . bs pattern or extremely low - voltage background is of a prognostic value for moderate to severe injury that increased from the start of cooling ( 75% specificity ) to the middle of cooling and later ( 100% specificity ) [ table 4 ] . electroencephalographic background sensitivity and specificity during and after cooling for moderate to severe magnetic resonance imaging brain injury there were no differences between groups regarding clinical characteristics . the duration ( median  standard deviation ) of seizure patterns was 42  83 min in group 1 , compared with 86  134 min in group 2 [ figure 3 ] . there was a significant relationship between the duration of seizure patterns and mri scores in linear regression analysis in group 1 [ figure 4 ] . duration of seizure patterns for the clinical and subclinical seizure treatment group 1 and the clinical seizure treatment group 2 . the vertical lines indicate the limit lines : ranges relationship between duration of seizure patterns and magnetic resonance imaging scores ( linear regression ) in group 1 some complicating factors are encountered during th in the form of sedation and clinical changes that occur during cooling . brain mri provides structural details only and its sensitivity for hie in the first few days of life is of a limited value . video - eeg monitoring is considered the gold standard test for assessment of brain functions and for detection of subclinical seizure in neonatal hie . previous studies for prediction of seizures were based on clinically diagnosed seizures , confirmed by intermittent eeg recordings . subclinical seizures constitute about two - thirds of neonatal seizures and require video - eeg monitoring to be diagnosed . continuous video - eeg monitoring is considered the most accurate test for neonatal seizure detection . the potential of neuroprotective therapies , such as hypothermia , has raised the importance of accurate prediction of outcome in the first hours of life . our study showed that none of the clinical characteristics were associated with brain injury in mri . these data were concordant with that reported by murray et al . , 2009 , who reported neither the condition at birth nor the degree of metabolic acidosis reliably predicts the occurrence of seizures . throughout all treatment periods , a normal eeg was associated with no or mild mri brain injury . at the start of cooling , a normal eeg background had better predictive value ( 100% specificity ) than at later time points ( 80% specificity ) . over the first 24 h of monitoring , only one newborn with moderate to severe mri injury showed improvement in the eeg background from excessively discontinuous to normal . , 1982 , holmes and lombroso , 1993 , and nash et al . , 2011 , who reported that normal eeg background at the start of cooling had better predictive value than at later time points with a specificity of 100% and 93% , respectively . however , bs pattern or extremely low - voltage background is of a prognostic value for moderate to severe injury that increased from the start of cooling ( 75% specificity ) to middle of cooling and later ( 100% specificity ) , reflecting six newborns with these patterns at the start of recording who were protected from further injury by middle of cooling . similar results were reported by nash et al . , 2011 and biagioni et al . abnormal eeg background activity continuous for 24 h or more or getting worse denotes poor prognosis . good prognostic features include improvement of eeg background activity in the form of increase in voltage , decrease in discontinuity , or appearance of sleep - wake cycles within 1224 h after birth . in our study , by the 2 day of life coinciding with the time of middle of cooling , a bs or extremely low - voltage eeg becomes of high predictive value for detection of moderate to severe mri injury . 2010 , studied the effect of cooling on amplitude - integrated eeg in infants with asphyxia . he found that a severely abnormal eeg background pattern in the cooled infants was not specific for abnormal developmental outcome until the 2 day of life . serial eegs are preferred to single recordings so that persistence of abnormalities can be determined . single recordings may have little significance ; however , if the pattern persists for several weeks , it may be of more prognostic value . as an example , an eeg obtained soon after birth can show significant abnormalities due to stress of birth ; these abnormalities may disappear completely within a few days and thus have little clinical significance . severity of neonatal eeg abnormalities correlates with the severity of neurological insult to the neonate . this makes eeg in this age group a valuable tool in predicting outcome of at - risk neonates . markedly abnormal and normal eegs have the greatest reliability in predicting poor and good outcomes , respectively . between these two extremes , there are many background patterns with different prognostic values that are difficult to use with different studies giving varying results . in such conditions , other neuroimaging studies and previous studies concluded that during the first 24 h of life , the eeg background had a poor prognostic value . previous studies in noncooled infants with hie are in favor of our results . in our study , the majority of infants ( 75% ) with an excessively discontinuous pattern after rewarming had no or only mild mri injury . , 2002 , who found that a discontinuous eeg pattern early in life is sometimes associated with poor outcome . the discrepancy from our results can be attributed to different methods used , different definitions in the literature for excessively discontinuous background , and effect of hypothermia . improvement of neurological sequelae necessitates rapid detection and treatment of seizures , which will depend on continuous eeg monitoring . in our study , furthermore , wusthoff et al . , 2011 , found 65% of participants had electrographic seizures during or immediately after treatment with hypothermia . these findings are consistent with the  prehypothermia  literature , which describes seizures in 22%64% , suggesting that hypothermia as employed for hie does not substantially affect the incidence of seizures . in our study , continuous video - eeg revealed 5 of 12 patients ( 42% ) with seizure activity did not show clinical seizure . among those five patients , three patients had subclinical se . in a previous study conducted by murray et al . , 2008 , on 51 full - term neonates with hie , he showed that only 34% of the electrographic seizures on video - eeg monitoring had clinical evidence . high incidence of seizures had been reported in our patients despite the effect of hypothermia in reduction of seizures in experimental studies . furthermore , srinivasakumar et al . , 2013 , stated that th was associated with a reduced seizure burden in infants with mild and moderate injury but not in those with severe injury . this discrepancy may be attributed to the different nature of cooling in animal models that is deep and early . in many studies , detection of seizure in newborns however , most seizures are subclinical and can be missed without continuous eeg monitoring . however , clinical observation alone can not differentiate between actual seizures and movements mimic seizures in infants . in our study , all newborns with se had severely abnormal mri while not all newborns with isolated or recurrent seizures were associated with moderate to severe brain injury . these findings are in concordance of other authors who reported that newborns with se had a significantly worse outcome in comparison to newborns with recurrent seizures . furthermore , we were able to show that immediate treatment of clinical and subclinical seizure patterns detected in eeg results in a reduction of total duration of seizure patterns , and there is a significant association between duration of seizure patterns detected in the eeg and severity of brain injury as seen on mri . the finding that treatment of clinical and subclinical seizures results in a reduction of total seizure duration supports the hypothesis that subclinical seizures should be treated . in most nicus doing eeg monitoring , treatment of subclinical seizures is recommended . whether this policy has a positive impact on prognosis has not yet proven , but there is some evidence for the best outcome for treating infants . there are some limitations to our study ; we used mri as a short - term outcome measure and long - term outcome is not known in our patients . although cooling does not affect the prognostic value of mri in newborns with hie , long - term developmental follow - up of our patients to confirm our results is recommend finally , we did not include a control group in our study as the protocol in our unit to subject any case fulfilling the criteria of th to early cooling . this was based on safety and benefits of th as well as the lack of other effective therapies . further studies are recommended to clarify that eeg patterns are attributed to either brain injury or therapeutic intervention ( hypothermia and medications ) . we can conclude that eeg monitoring in newborns with hie is very crucial in seizure management and prognosis . a trend was found for a reduction in the duration of seizure patterns when clinical and subclinical seizures were treated . this trend and the significant association of seizure duration and severity of brain injury found on mri scans suggest that recognition and treatment of neonatal seizures ( clinical and subclinical ) in infants with hie can reduce brain injury . there are no conflicts of interest .
background : the values of electroencephalography ( eeg ) in neonatal hypoxic - ischemic encephalopathy ( hie ) during therapeutic hypothermia ( th ) are still uncertain.aims:the aim of this study is to detect eeg background , the prevalence of seizures during cooling , and to determine different eeg patterns that can predict brain injury in magnetic resonance imaging ( mri).patients and methods : thirty - nine newborns with hie were subjected to th . 
 continuous monitoring by video - eeg was carried out throughout cooling and during rewarming . 
 mri was done for all newborns after rewarming . 
 the predictive value of eeg background for mri brain injury was evaluated at 6-h intervals during cooling and rewarming.results:at all - time intervals , normal eeg was associated with no or mild mri brain injury . at the beginning of cooling , normal background was more predictive of a favorable mri outcome than at later time points . 
 after 24 h of monitoring , diffuse burst suppression and depressed patterns had the greatest prognostic value . in most patients , a discontinuous pattern was not associated with poor prognosis . 
 thirty - one percent developed electrical seizures , and 8% developed status epilepticus . 
 seizures were subclinical in 42% . 
 there is a significant association between duration of seizure patterns detected on the eeg and severity of brain injury on mri.conclusions:continuous eeg monitoring in newborns with hie under cooling has a prognostic value about early mri brain injury and identifies electrographic seizures , approximately 50% of which are subclinical . 
 treatment of clinical and subclinical seizure results in a reduction of the total duration of seizure pattern supports the hypothesis that subclinical seizures should be treated .