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1.  Monitoring in non-traumatic coma. Part II: Electroencephalography. 
Archives of Disease in Childhood  1988;63(8):895-899.
Forty eight comatose children had electroencephalograms (EEG) recorded during the acute phase of their illnesses. These were classified according to a simple grading system and the findings correlated with the presence of seizures, deep coma, minimum cerebral perfusion pressure, and eventual neurological outcome. Serial EEGs proved important, particularly when slow activity was seen initially. None of the 20 patients who showed low amplitude EEG activity or electrocerebral silence at any stage of the acute illness did well. Discharges were seen in only 13 of the 29 patients with seizures and their presence did not correlate with outcome except in five patients with a distinctive pattern of discharges, none of whom had a good outcome. EEG findings associated with poor outcome did not always correlate with the clinical assessment of deep coma, emphasising the difficulties of neurological evaluation in these patients. Five of the patients with cerebral perfusion pressures greater than 42 mm Hg had a poor outcome that was predicted by serial EEGs. In nine patients with a minimum cerebral perfusion pressure in the borderline range 38-42 mm Hg the EEG was useful as an indication of the outcome. The EEG reflects changes in cerebral function which may be due to multifactorial or repeated insults. An EEG is therefore important in both the initial assessment and as an indicator of the neurological outcome, particularly in those patients in whom the cerebral perfusion pressure has apparently been adequate or within the borderline range.
PMCID: PMC1778981  PMID: 3415324
2.  Changing trends in incidence and aetiology of childhood acute non-traumatic coma over a period of changing malaria transmission in rural coastal Kenya: a retrospective analysis 
BMJ Open  2012;2(2):e000475.
Objectives
Recent changes in malaria transmission have likely altered the aetiology and outcome of childhood coma in sub-Saharan Africa. The authors conducted this study to examine change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood non-traumatic coma over a 6-year period.
Design
Retrospective analysis of prospectively collected data.
Setting
Secondary level health facility: Kilifi, Coast, Kenya.
Participants
Children aged 9 months to 13 years admitted with acute non-traumatic coma (Blantyre Coma Score =2) between January 2004 and December 2009 to Kilifi District Hospital, Kenya. Exclusion criteria: delayed development, epilepsy and sickle cell disease.
Results
During the study period, 665 children (median age 32 (IQR 20–46) months; 46% were girls) were admitted in coma. The incidence of childhood coma declined from 93/100 000 children in 2004 to 44/100 000 children in 2009. There was a 64% overall drop in annual malaria-positive coma admissions and a 272% overall increase in annual admissions with encephalopathies of undetermined cause over the study period. There was no change in case death of coma. Vomiting, breathing difficulties, bradycardia, profound coma (Blantyre Coma Score=0), bacteraemia and clinical signs of meningitis were associated with increased risk of death. Seizures within 24 h prior to admission, and malaria parasitaemia, were independently associated with survival, unchanging during the study period.
Conclusion
The decline in the incidence and number of admissions of childhood acute non-traumatic coma is due to decreased malaria transmission. The relative and absolute increase in admissions of encephalopathy of undetermined aetiology could represent aetiologies previously masked by malaria or new aetiologies.
Article summary
Article focus
This study examines change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood acute non-traumatic coma over a 6-year period of documented change in malaria transmission in rural coastal Kenya.
Key messages
There is an overall decline in childhood coma presentation over the study period, with a significant drop in malaria-positive coma admissions.
There is relative and absolute increase in coma admissions of undetermined aetiology.
There is an urgent need to examine for the role of viruses, metabolic derangements, vascular pathologies and other conditions in the aetiology of childhood non-traumatic coma.
Strengths and limitations of this study
The study is based on prospectively collected data in a setting where recommended standard clinical care is consistent and for which the catchment area is well delineated.
A number of children with acute coma likely die before arrival in hospital, and a few others are seen in a smaller hospital, which refers most of their comatose patients to the hospital in the study. Thus, the incidence figures are minimum incidences, likely an underestimation of the actual incidence.
doi:10.1136/bmjopen-2011-000475
PMCID: PMC3323808  PMID: 22466156
3.  Impact of Continuous EEG Monitoring on Clinical Management in Critically Ill Children 
Neurocritical care  2011;15(1):70-75.
Background
Continuous EEG (cEEG) monitoring is being used with increasing frequency in critically ill patients, most often to detect non-convulsive seizures. While cEEG is non-invasive and feasible in the critical care setting, it is also expensive and labor intensive, and there has been little study of its impact on clinical care. We aimed to determine prospectively the impact of cEEG on clinical management in critically ill children.
Methods
Critically ill children (non-neonates) with acute encephalopathy underwent cEEG. Study enrollment and data collection were prospective.
Results
100 children were studied. EEG monitoring led to specific clinical management changes in 59 children. These included initiating or escalating anti-seizure medications in 43 due to seizure detection, demonstrating that a specific event (subtle movement or vital sign change) was not a seizure in 21, or obtaining urgent neuroimaging that led to a clinical change in 3. In the remaining 41 children, cEEG ruled out the presence of non-convulsive seizures but did not lead to a specific change in clinical management.
Conclusions
EEG monitoring led to changes in clinical management in the majority of patients, suggesting it may have an important role in management of critically ill children. Further study is needed to determine whether the management changes elicited by cEEG improve outcome.
doi:10.1007/s12028-010-9380-z
PMCID: PMC3134111  PMID: 20499208
Seizure; Status epilepticus; Pediatric; Critically Ill; Electroencephalogram; EEG monitoring
4.  Seizures in 204 comatose children: incidence and outcome 
Intensive Care Medicine  2012;38(5):853-862.
Purpose
Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain.
Methods
cEEG (one to three channels) was performed for a median 42 h (range 2–630 h) in 204 unventilated and ventilated children aged ≤15 years (18 neonates, 61 infants) in coma with different aetiologies. Outcome at 1 month was independently determined and dichotomized for survivors into favourable (normal or moderate neurological handicap) and unfavourable (severe handicap or vegetative state).
Results
Of the 204 patients, 110 had clinical seizures (CS) before cEEG commenced. During cEEG, 74 patients (36 %, 95 % confidence interval, 95 % CI, 32–41 %) had electroencephalographic seizures (ES), the majority without clinical accompaniment (non-convulsive seizures, NCS). CS occurred before NCS in 69 of the 204 patients; 5 ventilated with NCS had no CS observed. Death (93/204; 46 %) was independently predicted by admission Paediatric Index of Mortality (PIM; adjusted odds ratio, aOR, 1.027, 95 % CI 1.012–1.042; p < 0.0005), Adelaide coma score (aOR 0.813, 95 % CI 0.700–0.943; p = 0.006), and EEG grade on admission (excess slow with >3 % fast, aOR 5.43, 95 % CI 1.90–15.6; excess slow with <3 % fast, aOR 8.71, 95 % CI 2.58–29.4; low amplitude, 10th centile <9 µV, aOR 3.78, 95 % CI 1.23–11.7; and burst suppression, aOR 10.68, 95 % CI 2.31–49.4) compared with normal cEEG, as well as absence of CS at any time (aOR 2.38, 95 % CI 1.18–4.81). Unfavourable outcome (29/111 survivors; 26 %) was independently predicted by the presence of ES (aOR 15.4, 95 % CI 4.7–49.7) and PIM (aOR 1.036, 95 % CI 1.013–1.059).
Conclusion
Seizures are common in comatose children, and are associated with an unfavourable outcome in survivors. cEEG allows the detection of subtle CS and NCS and is a prognostic tool.
doi:10.1007/s00134-012-2529-9
PMCID: PMC3338329  PMID: 22491938
Seizures; Status epilepticus; Coma; Child; Outcome; Medicine & Public Health; Pain Medicine; Emergency Medicine; Intensive / Critical Care Medicine; Pneumology/Respiratory System; Pediatrics; Anesthesiology
5.  Electrographic Status Epilepticus is Associated with Mortality and Worse Short-Term Outcome in Critically Ill Children 
Critical care medicine  2013;41(1):210-218.
Objectives
Electrographic seizures (ES) and electrographic status epilepticus (ESE) are common in critically ill children. We aimed to determine whether ES and ESE are associated with higher mortality or worse short-term neurologic outcome.
Design
Prospective observational study.
Setting
Pediatric intensive care unit of a tertiary children’s hospital.
Patients
Non-neonatal children admitted to a pediatric intensive care unit (PICU) with acute encephalopathy underwent continuous electroencephalographic (cEEG) monitoring. EEGs were scored as (1) no seizures, (2) ES, or (3) ESE. Covariates included age, acute neurologic disorder category, prior neurodevelopmental status, sex, and EEG background category. Outcomes were mortality and worsening of Pediatric Cerebral Performance Category (PCPC) from pre-admission to PICU discharge. Chi-squared analysis, Fisher’s exact test, and multivariable logistic regression were used to evaluate the associations between ES or ESE and mortality or short-term neurologic outcome, using odds ratios (OR) and 95% confidence intervals (95%CI).
Interventions
None
Main Results
Two hundred children underwent cEEG. Eighty-four (42%) had seizures which were categorized as ES in 41 (20.5%) and ESE in 43 (21.5%). Thirty-six subjects (18%) died and 88 subjects (44%) had PCPC worsening. In multivariable analysis ESE was associated with an increased risk of mortality (OR 5.1; 95%CI 1.4, 18, p=0.01) and PCPC worsening (OR 17.3; 95%CI 3.7, 80, p<0.001) while ES was not associated with an increased risk of mortality (OR 1.3; 95%CI 0.3, 5.1; p=0.74) or PCPC worsening (OR 1.2; 95%CI 0.4, 3.9; p=0.77).
Conclusions
ESE, but not ES, is associated with mortality and worse short-term neurologic outcome in critically ill children with acute encephalopathy.
doi:10.1097/CCM.0b013e3182668035
PMCID: PMC3531581  PMID: 23164815
EEG Monitoring; Seizure; Status Epilepticus; Pediatric; Outcome; Non-Convulsive Seizure
6.  Predictors and incidence of posttraumatic seizures in children and adolescents after brain injury 
Clinics and Practice  2012;2(3):e66.
The present study evaluates the incidence of early and late seizures after head injury in patients under 18 years old. Factors correlating with a high risk of developing posttraumatic seizures were identified. Such risk factors were the severity of the head trauma and a Glasgow Coma Scale of 3–8. In contrast to many studies, we observed that the incidence of posttraumatic seizures was significantly higher in patients older than 12 years old (12–16 and 12–18). Most of the late seizures were paroxysmal electroencephalography (EEG) discharges diagnosed on a snapshot-EEG during the follow-up examination of the patients without clinical symptoms. We suppose that EEG-examination in head injured children is important to identify patients with epileptic potentials without clinical symptoms. Epileptic patterns of the EEG could worsen the diagnosis and clinical outcome of the children in accordance to studies performed in the adult population.
doi:10.4081/cp.2012.e66
PMCID: PMC3981315  PMID: 24765465
posttraumatic seizures; early seizures; late seizures; anticonvulsive therapy.
7.  Phenobarbitone, neonatal seizures, and video-EEG 
Aims: To evaluate the effectiveness of phenobarbitone as an anticonvulsant in neonates.
Methods: An observational study using video-EEG telemetry. Video-EEG was obtained before treatment was started, for an hour after treatment was given, two hours after treatment was given, and again between 12 and 24 hours after treatment was given. Patients were recruited from all babies who required phenobarbitone (20–40 mg/kg intravenously over 20 minutes) for suspected clinical seizures and had EEG monitoring one hour before and up to 24 hours after the initial dose. An EEG seizure discharge was defined as a sudden repetitive stereotyped discharge lasting for at least 10 seconds. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes. Seizures were categorised as EEG seizure discharges only (electrographic), or as EEG seizure discharges with accompanying clinical manifestations (electroclinical). Surviving babies were assessed at one year using the Griffiths neurodevelopmental score.
Results: Fourteen babies were studied. Four responded to phenobarbitone; these had normal or moderately abnormal EEG background abnormalities and outcome was good. In the other 10 babies electrographic seizures increased after treatment, whereas electroclinical seizures reduced. Three babies were treated with second line anticonvulsants, of whom two responded. One of these had a normal neurodevelopmental score at one year, but the outcome for the remainder of the whole group was poor.
Conclusion: Phenobarbitone is often ineffective as a first line anticonvulsant in neonates with seizures in whom the background EEG is significantly abnormal.
doi:10.1136/fn.86.3.F165
PMCID: PMC1721395  PMID: 11978746
8.  Observations on comatose survivors of cardiopulmonary resuscitation with generalized myoclonus 
BMC Neurology  2005;5:14.
Background
There is only limited data on improvements of critical medical care is resulting in a better outcome of comatose survivors of cardiopulmonary resuscitation (CPR) with generalized myoclonus. There is also a paucity of data on the temporal dynamics of electroenephalographic (EEG) abnormalities in these patients.
Methods
Serial EEG examinations were done in 50 comatose survivors of CPR with generalized myoclonus seen over an 8 years period.
Results
Generalized myoclonus occurred within 24 hours after CPR. It was associated with burst-suppression EEG (n = 42), continuous generalized epileptiform discharges (n = 5), alpha-coma-EEG (n = 52), and low amplitude (10 μV <) recording (n = 1). Except in 3 patients, these EEG-patterns were followed by another of these always nonreactive patterns within one day, mainly alpha-coma-EEG (n = 10) and continuous generalized epileptiform discharges (n = 9). Serial recordings disclosed a variety of EEG-sequences composed of these EEG-patterns, finally leading to isoelectric or flat recordings. Forty-five patients died within 2 weeks, 5 patients survived and remained in a permanent vegetative state.
Conclusion
Generalized myoclonus in comatose survivors of CPR still implies a poor outcome despite advances in critical care medicine. Anticonvulsive drugs are usually ineffective. All postanoxic EEG-patterns are transient and followed by a variety of EEG sequences composed of different EEG patterns, each of which is recognized as an unfavourable sign. Different EEG-patterns in anoxic encephalopathy may reflect different forms of neocortical dysfunction, which occur at different stages of a dynamic process finally leading to severe neuronal loss.
doi:10.1186/1471-2377-5-14
PMCID: PMC1190185  PMID: 16026615
9.  Electroencephalographic Monitoring in the Pediatric Intensive Care Unit 
Continuous EEG monitoring is used with increasing frequency in critically ill children to provide insight into brain function and to identify electrographic seizures. EEG monitoring use often impacts clinical management, most often by identifying electrographic seizures and status epilepticus. Most electrographic seizures have no clinical correlate, and thus would not be identified without EEG monitoring. There is increasing data that electrographic seizures and electrographic status epilepticus are associated with worse outcome. Seizure identification efficiency may be improved by further development of quantitative EEG trends. This review describes the clinical impact of EEG data, the epidemiology of electrographic seizures and status epilepticus, the impact of electrographic seizures on outcome, the utility of quantitative EEG trends for seizure identification, and practical considerations regarding EEG monitoring.
doi:10.1007/s11910-012-0330-3
PMCID: PMC3569710  PMID: 23335026
EEG; EEG monitoring; seizure; status epilepticus; intensive care unit; critical care
10.  Absence of early epileptiform abnormalities predicts lack of seizures on continuous EEG 
Neurology  2012;79(17):1796-1801.
Objective:
To determine whether the absence of early epileptiform abnormalities predicts absence of later seizures on continuous EEG monitoring of hospitalized patients.
Methods:
We retrospectively reviewed 242 consecutive patients without a prior generalized convulsive seizure or active epilepsy who underwent continuous EEG monitoring lasting at least 18 hours for detection of nonconvulsive seizures or evaluation of unexplained altered mental status. The findings on the initial 30-minute screening EEG, subsequent continuous EEG recordings, and baseline clinical data were analyzed. We identified early EEG findings associated with absence of seizures on subsequent continuous EEG.
Results:
Seizures were detected in 70 (29%) patients. A total of 52 patients had their first seizure in the initial 30 minutes of continuous EEG monitoring. Of the remaining 190 patients, 63 had epileptiform discharges on their initial EEG, 24 had triphasic waves, while 103 had no epileptiform abnormalities. Seizures were later detected in 22% (n = 14) of studies with epileptiform discharges on their initial EEG, vs 3% (n = 3) of the studies without epileptiform abnormalities on initial EEG (p < 0.001). In the 3 patients without epileptiform abnormalities on initial EEG but with subsequent seizures, the first epileptiform discharge or electrographic seizure occurred within the first 4 hours of recording.
Conclusions:
In patients without epileptiform abnormalities during the first 4 hours of recording, no seizures were subsequently detected. Therefore, EEG features early in the recording may indicate a low risk for seizures, and help determine whether extended monitoring is necessary.
doi:10.1212/WNL.0b013e3182703fbc
PMCID: PMC3475619  PMID: 23054233
11.  Continuous noninvasive monitoring of barbiturate coma in critically ill children using the Bispectral™ index monitor 
Critical Care  2007;11(5):R108.
Introduction
Traumatic brain injury and generalized convulsive status epilepticus (GCSE) are conditions that require aggressive management. Barbiturates are used to lower intracranial pressure or to stop epileptiform activity, with the aim being to improve neurological outcome. Dosing of barbiturates is usually guided by the extent of induced burst-suppression pattern on the electroencephalogram (EEG). Dosing beyond the point of burst suppression may increase the risk for complications without offering further therapeutic benefit. For this reason, careful monitoring of EEG parameters is mandatory. A prospective study was conducted to evaluate the usefulness of the bispectral index suppression ratio for monitoring barbiturate coma.
Methods
A prospective observational pilot study was performed at a paediatric (surgical) intensive care unit, including all children with barbiturate-induced coma after traumatic brain injury or GCSE. The BIS™ (Bispectral™ index) monitor expresses a suppression ratio, which represents the percentage of epochs per minute in which the EEG was suppressed. Suppression ratios from the BIS monitor were compared with suppression ratios of full-channel EEG as assessed by quantitative visual analysis.
Results
Five patients with GCSE and three patients after traumatic brain injury (median age 11.6 years, range 4 months to 15 years) were included. In four patients the correlation between the suppression ratios of the BIS and EEG could be determined; the average correlation was 0.68. In two patients, suppression ratios were either high or low, with no intermediate values. This precluded determination of correlation values, as did the isoelectric EEG in a further two patients. In the latter patients, the mean ± standard error BIS suppression ratio was 95 ± 1.6.
Conclusion
Correlations between suppression ratios of the BIS and EEG were found to be only moderate. In particular, asymmetrical EEGs and EEGs with short bursts (less than 1 second) may result in aberrant BIS suppression ratios. The BIS monitor potentially aids monitoring of barbiturate-induced coma because it provides continuous data on EEG suppression between full EEG registrations, but it should be used with caution.
doi:10.1186/cc6138
PMCID: PMC2556759  PMID: 17897479
12.  Electroencephalographic monitoring during hypothermia after pediatric cardiac arrest 
Neurology  2009;72(22):1931-1940.
Background:
Hypoxic ischemic brain injury secondary to pediatric cardiac arrest (CA) may result in acute symptomatic seizures. A high proportion of seizures may be nonconvulsive, so accurate diagnosis requires continuous EEG monitoring. We aimed to determine the safety and feasibility of long-term EEG monitoring, to describe electroencephalographic background and seizure characteristics, and to identify background features predictive of seizures in children undergoing therapeutic hypothermia (TH) after CA.
Methods:
Nineteen children underwent TH after CA. Continuous EEG monitoring was performed during hypothermia (24 hours), rewarming (12–24 hours), and then an additional 24 hours of normothermia. The tolerability of these prolonged studies and the EEG background classification and seizure characteristics were described in a standardized manner.
Results:
No complications of EEG monitoring were reported or observed. Electrographic seizures occurred in 47% (9/19), and 32% (6/19) developed status epilepticus. Seizures were nonconvulsive in 67% (6/9) and electrographically generalized in 78% (7/9). Seizures commenced during the late hypothermic or rewarming periods (8/9). Factors predictive of electrographic seizures were burst suppression or excessively discontinuous EEG background patterns, interictal epileptiform discharges, or an absence of the expected pharmacologically induced beta activity. Background features evolved over time. Patients with slowing and attenuation tended to improve, whereas those with burst suppression tended to worsen.
Conclusions:
EEG monitoring in children undergoing therapeutic hypothermia after cardiac arrest is safe and feasible. Electrographic seizures and status epilepticus are common in this setting but are often not detectable by clinical observation alone. The EEG background often evolves over time, with milder abnormalities improving and more severe abnormalities worsening.
GLOSSARY
= burst suppression;
= cardiac arrest;
= cardiopulmonary resuscitation;
= developmental delay;
= fentanyl;
= fosphenytoin;
= hypoxic ischemic encephalopathy;
= levetiracetam;
= lorazepam;
= midazolam;
= nonconvulsive seizures;
= nonconvulsive status epilepticus;
= negative predictive value;
= phenobarbital;
= periodic epileptiform discharge;
= pediatric intensive care unit;
= positive predictive value;
= status epilepticus;
= sudden infant death syndrome;
= seizures;
= therapeutic hypothermia;
= vecuronium;
= valproic acid;
= ventricular tachycardia.
doi:10.1212/WNL.0b013e3181a82687
PMCID: PMC2690970  PMID: 19487651
13.  Early EEG Improvement after Ketogenic Diet Initiation 
Epilepsy research  2011;94(1-2):94-101.
Purpose
This study examines electroencephalographic (EEG) changes in children with medication resistant epilepsy treated with the ketogenic diet (KD).
Methods
Routine EEGs were obtained prior to KD initiation, then one month and three months later. Changes in EEG background slowing and frequency of interictal epileptiform discharges (IEDs) were evaluated using power spectrum analysis and manual determination of spike index. KD responders were compared to non-responders to determine if baseline or early EEG characteristics predicted treatment response (>50% seizure reduction) at three months.
Results
Thirty-seven patients were evaluated. No differences in baseline EEG features were found between responder groups. Frequency of IEDs declined in 65% of patients as early as one month, by a median of 13.6% (IQR 2-33). Those with a ten percent or greater improvement in IED frequency at one month were greater than six times more likely to be KD responders (OR 6.5 95% CI 0.85 to 75. p=0.03). Qualitative and quantitative measures of EEG background slowing improved in the whole cohort, but did not predict responder status.
Conclusion
Baseline predictors of KD response remain elusive. Most patients experienced a reduction in IEDs and improvement in EEG background slowing after KD initiation. Reduction of IEDs at one month strongly predicted KD responder status at three months.
doi:10.1016/j.eplepsyres.2011.01.012
PMCID: PMC3062190  PMID: 21345653
Ketogenic Diet; EEG; spike index; power spectrum analysis
14.  Video-EEG monitoring in newborns with hypoxic-ischemic encephalopathy treated with hypothermia 
Neurology  2011;76(6):556-562.
Background:
Therapeutic hypothermia (TH) is becoming standard of care in newborns with hypoxic-ischemic encephalopathy (HIE). The prognostic value of the EEG and the incidence of seizures during TH are uncertain.
Objective:
To describe evolution of EEG background and incidence of seizures during TH, and to identify EEG patterns predictive for MRI brain injury.
Methods:
A total of 41 newborns with HIE underwent TH. Continuous video-EEG was performed during hypothermia and rewarming. EEG background and seizures were reported in a standardized manner. Newborns underwent MRI after rewarming. Sensitivity and specificity of EEG background for moderate to severe MRI brain injury was assessed at 6-hour intervals during TH and rewarming.
Results:
EEG background improved in 49%, remained the same in 38%, and worsened in 13%. A normal EEG had a specificity of 100% upon initiation of monitoring and 93% at later time points. Burst suppression and extremely low voltage patterns held the greatest prognostic value only after 24 hours of monitoring, with a specificity of 81% at the beginning of cooling and 100% at later time points. A discontinuous pattern was not associated with adverse outcome in most patients (73%). Electrographic seizures occurred in 34% (14/41), and 10% (4/41) developed status epilepticus. Seizures had a clinical correlate in 57% (8/14) and were subclinical in 43% (6/14).
Conclusions:
Continuous video-EEG monitoring in newborns with HIE undergoing TH provides prognostic information about early MRI outcome and accurately identifies electrographic seizures, nearly half of which are subclinical.
doi:10.1212/WNL.0b013e31820af91a
PMCID: PMC3053178  PMID: 21300971
15.  Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest 
Critical Care  2010;14(5):R173.
Introduction
Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome.
Methods
From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC).
Results
Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2).
Conclusions
Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.
doi:10.1186/cc9276
PMCID: PMC3219275  PMID: 20920227
16.  Presurgical EEG-fMRI in a complex clinical case with seizure recurrence after epilepsy surgery 
Epilepsy surgery has improved over the last decade, but non-seizure-free outcome remains at 10%–40% in temporal lobe epilepsy (TLE) and 40%–60% in extratemporal lobe epilepsy (ETLE). This paper reports a complex multifocal case. With a normal magnetic resonance imaging (MRI) result and nonlocalizing electroencephalography (EEG) findings (bilateral TLE and ETLE, with more interictal epileptiform discharges [IEDs] in the right frontal and temporal regions), a presurgical EEG-functional MRI (fMRI) was performed before the intraoperative intracranial EEG (icEEG) monitoring (icEEG with right hemispheric coverage). Our previous EEG-fMRI analysis results (IEDs in the left hemisphere alone) were contradictory to the EEG and icEEG findings (IEDs in the right frontal and temporal regions). Thus, the EEG-fMRI data were reanalyzed with newly identified IED onsets and different fMRI model options. The reanalyzed EEG-fMRI findings were largely concordant with those of EEG and icEEG, and the failure of our previous EEG-fMRI analysis may lie in the inaccurate identification of IEDs and wrong usage of model options. The right frontal and temporal regions were resected in surgery, and dual pathology (hippocampus sclerosis and focal cortical dysplasia in the extrahippocampal region) was found. The patient became seizure-free for 3 months, but his seizures restarted after antiepileptic drugs (AEDs) were stopped. The seizures were not well controlled after resuming AEDs. Postsurgical EEGs indicated that ictal spikes in the right frontal and temporal regions reduced, while those in the left hemisphere became prominent. This case suggested that (1) EEG-fMRI is valuable in presurgical evaluation, but requires caution; and (2) the intact seizure focus in the remaining brain may cause the non-seizure-free outcome.
doi:10.2147/NDT.S47099
PMCID: PMC3732198  PMID: 23926432
EEG-fMRI; focus localization; presurgical evaluation; epilepsy surgery
17.  Impact of amplitude-integrated EEG on the clinical care for neonates with seizures 
Pediatric neurology  2012;46(1):32-35.
Amplitude-integrated EEG (aEEG) was introduced relatively recently into neonatal intensive care in the U.S.A. We aimed to evaluate whether aEEG has changed clinical care for neonates with seizures. All 202 neonates treated for seizures at our hospital from 2002 to 2007 were included in this study. Neonates monitored with aEEG (n=67) were compared to a contemporary control group of neonates who were not monitored, despite aEEG availability (n=57), and a historical control group of neonates treated for seizures before aEEG was introduced in our NICU (n=78). 82% of those treated with phenobarbital (137/167) continued treatment after discharge, with no difference among the groups. Adjusted for gestational age and length of stay, there was also no difference among groups in the number of neuroimaging studies or number of anticonvulsants per patient. Fewer patients in the aEEG group, compared to contemporary controls (n=16/67 vs. 29/57, p=0.001) or historical controls (n=38/78, p=0.002), were diagnosed clinically with seizures without electrographic confirmation. We conclude that introducing aEEG did not increase neuroimaging tests, nor did it alter anticonvulsant use. However, diagnostic precision for neonatal seizures improved after aEEG introduction, as fewer neonates were treated for seizures based solely on clinical findings, without electrographic confirmation.
doi:10.1016/j.pediatrneurol.2011.11.004
PMCID: PMC3246404  PMID: 22196488
neonatal seizures; electroencephalography; amplitude-integrated EEG; aEEG; EEG; hypoxic ischemic encephalopathy; phenobarbital
18.  Physiologic and prognostic significance of "alpha coma". 
A patient with posthypoxic "alpha coma" is described whose EEGs were recorded before coma, within two hours following the onset of coma and after recovery. The differences observed between the alpha activity during coma and that seen before and after suggest that the alpha activity during coma and the physiologic alpha rhythm are different phenomena. This case, as well as others reported, also suggests that "alpha coma" resolving in the first 24 hours following hypoxia may have a better prognosis than "alpha coma" detected after the first day, and stresses the need for EEG monitoring begun in the immediate period following hypoxia in order to assess accurately the prognostic significance of this EEG pattern in the early stages of postanoxic encephalopathy. The aetiology of "alpha coma" also affects outcome. The survival rate appears higher in patients with respiratory arrest than in those with combined cardiopulmonary arrest.
PMCID: PMC1027482  PMID: 6886700
19.  The prognostic value of electroencephalography in epilepsy: a long-term follow-up study 
Neurology International  2010;2(2):e18.
Predicting the evolution of epilepsy is of obvious importance for patients and their families. Value of electroencephalography (EEG) is extensively used in the diagnosis of epilepsy yet its role as a prognostication method remains unclear. The aim of the present retrospective study is to investigate the relationship between serial EEG recordings and long-term clinical and social outcomes in a cohort of patients with epilepsy. Thirty-nine epileptic patients were monitored clinically and with repeat EEG recordings for more than 15 years. All patients who initially had epileptiform discharges ended up with poor or moderate seizure control whereas more than half of the patients with normal initial recordings had good clinical outcomes and satisfactory social adjustment. Deterioration of the recordings over time was associated with unfavourable results in a significant proportion of patients (90%), while stable or improved EEG findings predicted a favourable outcome. It is concluded that serial EEG recordings can be used in the prognostic evaluation of epilepsy.
doi:10.4081/ni.2010.e18
PMCID: PMC3093201  PMID: 21577332
epilepsy; prognosis; electroencephalography; epilepsy outcome; seizure control; social adaptation.
20.  Prolonged refractory status epilepticus following acute traumatic brain injury: a case report of excellent neurological recovery 
Critical Care  2005;9(6):R725-R728.
Introduction
Refractory status epilepticus (RSE) secondary to traumatic brain injury (TBI) may be under-recognized and is associated with significant morbidity and mortality.
Methods
This case report describes a 20 year old previously healthy woman who suffered a severe TBI as a result of a motor vehicle collision and subsequently developed RSE. Pharmacological coma, physiological support and continuous electroencephalography (cEEG) were undertaken.
Results
Following 25 days of pharmacological coma, electrographic and clinical seizures subsided and the patient has made an excellent cognitive recovery.
Conclusion
With early identification, aggressive physiological support, appropriate monitoring, including cEEG, and an adequate length of treatment, young trauma patients with no previous seizure history and limited structural damage to the brain can have excellent neurological recovery from prolonged RSE.
doi:10.1186/cc3884
PMCID: PMC1414004  PMID: 16280070
21.  Clinical and EEG response to anticonvulsants in neonatal seizures. 
Archives of Disease in Childhood  1989;64(4 Spec No):459-464.
During a two year period prospective continuous electroencephalographic (EEG) monitoring of 275 infants identified seizure activity in 55 cases, 31 of whom were treated with anticonvulsant drugs on clinical grounds. EEG and clinical response was complete in only two and equivocal in another six. Clinical response with persistent EEG seizures occurred in 13 and neither clinical nor EEG response in 10. There was no significant improvement in the generally poor neurological outcome compared with that in 24 infants whose seizures were not treated because of limited or absent clinical manifestations. Background EEG abnormality (as an index of associated cerebral dysfunction) was a guide to potential lack of response to anticonvulsant drugs; it was also predictive of subsequent clinical outcome irrespective of treatment. This study shows that commonly used anticonvulsant drugs (phenobarbitone, paraldehyde, phenytoin, and diazepam) have little effect on seizure control or neurological outcome in neonatal seizures associated with haemorrhagic, hypoxic, or ischaemic cerebral lesions. In view of the variable clinical appearance of EEG seizure activity, continuous EEG monitoring should be an essential feature of further study of neonatal anticonvulsant treatment.
PMCID: PMC1592048  PMID: 2730114
22.  Nonconvulsive seizures are common in critically ill children 
Neurology  2011;76(12):1071-1077.
Background:
Retrospective studies have reported the occurrence of nonconvulsive seizures in critically ill children. We aimed to prospectively determine the incidence and risk factors of nonconvulsive seizures in critically ill children using predetermined EEG monitoring indications and EEG interpretation terminology.
Methods:
Critically ill children (non-neonates) with acute encephalopathy underwent continuous EEG monitoring if they met institutional clinical practice criteria. Study enrollment and data collection were prospective. Logistic regression analysis was utilized to identify risk factors for seizure occurrence.
Results:
One hundred children were evaluated. Electrographic seizures occurred in 46 and electrographic status epilepticus occurred in 19. Seizures were exclusively nonconvulsive in 32. The only clinical risk factor for seizure occurrence was younger age (p = 0.03). Of patients with seizures, only 52% had seizures detected in the first hour of monitoring, while 87% were detected within 24 hours.
Conclusions:
Seizures were common in critically ill children with acute encephalopathy. Most were nonconvulsive. Clinical features had little predictive value for seizure occurrence. Further study is needed to confirm these data in independent high-risk populations, to clarify which children are at highest risk for seizures so limited monitoring resources can be allocated optimally, and to determine whether seizure detection and management improves outcome.
doi:10.1212/WNL.0b013e318211c19e
PMCID: PMC3068008  PMID: 21307352
23.  Thiopentone induced coma after severe birth asphyxia. 
Archives of Disease in Childhood  1986;61(11):1084-1089.
The aim of this study was to determine the feasibility of inducing a prolonged coma in severely asphyxiated newborn babies by the infusion of high dose thiopentone. In six severely asphyxiated babies the electroencephalograph (EEG) and blood pressure were monitored continuously. Thiopentone was infused at a rate sufficient to suppress completely the EEG providing the mean blood pressure remained above 35 mm Hg; it was continued until there was no evidence of cerebral oedema for 24 hours. In two the infusion was stopped prematurely because of hypotension that was unresponsive to treatment. In the other four a deep coma was maintained for a median duration of 127 hours. All developed pharmacodynamic tolerance to the thiopentone and showed non-linear elimination kinetics. Three babies died; the three survivors have moderate to severe handicap. It was concluded that with full intensive care it is possible to induce a deep coma; the outcome does not seem to be improved, however, and the incidence of complications was high.
PMCID: PMC1778119  PMID: 3789788
24.  Dynamic timecourse of typical childhood absence seizures: EEG, behavior and fMRI 
Absence seizures are 5–10 second episodes of impaired consciousness accompanied by 3–4Hz generalized spike-and-wave discharge on electroencephalography (EEG). The timecourse of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from 9 pediatric patients. We investigated behavior concurrently using a continuous performance task (CPT) or simpler repetitive tapping task (RTT). EEG time-frequency analysis revealed abrupt onset and end of 3–4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex >5s before seizure onset, followed by profound fMRI decreases continuing >20s after seizure end. This timecourse differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long lasting sequence of fMRI changes in absence seizures, which are not detectible by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.
doi:10.1523/JNEUROSCI.5101-09.2010
PMCID: PMC2946206  PMID: 20427649
EEG-fMRI; Thalamus; Absence epilepsy; HRF; Attention; Orbitofrontal cortex
25.  Approach to the patient with transient alteration of consciousness 
Neurology. Clinical Practice  2012;2(3):179-186.
Summary
Evaluating transient impairment of consciousness is critical to diagnose epileptic seizures, syncope, parasomnias, organic encephalopathies, and psychogenic nonepileptic seizures. Effective evaluation of episodic unconscious events demands interactive interviewing of the patient and witnesses of the events, with judgment as to historians' observational abilities. When generalized tonic-clonic seizures have been witnessed by medical staff or other reliable observers, a search for concomitant nonconvulsive events and for comorbid illnesses often elucidates diagnoses unsuspected by the referring physician. Consultation for stupor-coma should not miss a potentially reversible acute severe encephalopathy, particularly when reversibility requires timely therapy. Perspicacious analyses of complex cognitive-motor phenomena support judicious application of diagnostic procedures, including brief or prolonged EEG and video-EEG, EKG tilt-table testing, EKG loop monitoring, and brain imaging.
doi:10.1212/CPJ.0b013e31826af1be
PMCID: PMC3613203  PMID: 23634366

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