Wainwright Seizures in Pediatrcis TBI - uwmedicine.org · 9/16/2018 1 Recognizing & Managing Seizures in Pediatric TBI Mark Wainwright MD PhD Herman and Faye Sarkowsky Professor of

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Recognizing & Managing Seizures in Pediatric TBI

Mark Wainwright MD PhD

Herman and Faye Sarkowsky Professor of Neurology

Division Head, Pediatric Neurology

University of Washington

UW Medicine EMS & Trauma 2018 Conference

September 17 and 18, 2018

Objectives

• To understand the approach to recognition of seizures after TBI

• Understand the contribution of seizures to secondary neurologic injury after TBI

• Review the evidence for treatment of seizures and specific treatment approaches

Definitions and Epidemiology

• Impact seizures – occur within minutes

• Early post-traumatic seizures – within 7 days

• Last post-traumatic seizures – after 7 days

• Incidence of PTS in children range from 5.5 to 45%

• Higher when continuous EEG used for detection

• Most common risk factors for PTS

• Younger age; Severe TBI; Subdural Hemorrhage; Inflicted TBI

• Consensus guidelines for the management of severe TBI support 7 day prophylaxis with an antiepileptic drug

Arndt D et al., (2016) J Child Neurol 31:46-56; Keenan et a., (2004) Pediatrics 114:633-639

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Current Pediatric Recommendations

• Prophylactic treatment with phenytoin may be considered to reduce the incidence of early posttraumatic seizures (PTS) in pediatric patients with severe TBI.

• Strength of Recommendation: Weak

• Quality of Evidence: Low,

• 2018 update pending

Anticonvulsant selection and EEG use is not uniform in the management of severe TBI; pathways reduce this variability

Kurz J et al., Pediatr Crit Care Med 2016; 17:649–657

• Approaches and Decisions in Acute Pediatric TBI (ADAPT) trial

• 43 Centers; 98% response rate

TBI shortens life expectancy particularly in the young

McMillan T et al., J Neurol Neurosurg Psychiatry 2011;82:931e935

More than 40% of

adolescents and adults

admitted with TBI are dead 13

years later

• Death rate in younger adults (ages

15-54) 1 year post injury

significantly higher compared to

community controls (17.4 vs 2.4

per 1000 per year)

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Long-term mortality is higher in patients with post-traumatic epilepsy

Ussk J et al., Neurology 2018;91:e878-e883.

Age, abusive mechanism, subdural hemorrhage all contribute to risk for post-traumatic seizures

Bennett K et al., (2017) Pediatr Crit Care Med 18:54-63

• Abuse or assault most common in young children

• PTS diagnosed in 543 (25%) of 2,122 cases of severe TBI

• PTS present in 51% of assault cases vs 21% PTS in other

mechanisms

Seizures, clinical and electrographic exacerbate acute neurologic injury

• Clinical Observation• In patients with ICH, nonconvulsive seizures are associated with

greater mass effect and shift, worsening of NIHSS scores, and trend towards worse outcome (Vespa 2003)

• Expanding hemorrhages and trend towards worse outcome in another (Claassen 2007)

• Seizure related herniation in patients with CNS infections (Solomon 2002; Idro 2005)

• Biochemistry (microdialysis)• Seizures cause glutamate spikes on microdialysis, elevated

glycerol (membrane breakdown), elevated lactate (Vespa 1998, 2002, 2007)

• Seizures cause elevations in CBF, ICP (animals and humans), lactate, and metabolic demand

• Neurophysiology• Seizures may trigger peri-injury depolarizations

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18 month old, difficult to awaken after a nap at daycare

metabolic acidosis

Decerebrate posturing

Key mechanisms

Open questions

• Do seizures injure the brain after traumatic brain injury?

• Clinical seizures, electrographic seizures or both?

• Does treatment of seizures improve outcome?

• If so, what is the best treatment?

• What are the risk factors for and the causes of remote (months to years later)?

• Can these seizures be prevented by early management after TBI?

• Which patients should be treated?

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Suspect non-convulsive seizures in children with abusive head trauma

Hasbani et a., Pediatr Crit Care Med. 2013; 14: 709–715.

• Electrographic seizures were entirely

nonconvulsive in 8 of 12 children (67%)

• EEG background (disorganized) and

neuroimaging evidence of ischemia were

associated with the presence of electrographic

seizures (p = 0.05)

Abnormal neuroimaging also increase the risk for long-term development of epilepsy after moderate or severe TBI

Keret et al., Seizure 58 (2018) 29–34

Abnormal neuroimaging is associated with increased risk for seizures after abusive head trauma and risk for poor outcome

Goldstein J et al., Neurocrit Care 2011 15:63-9

Seizures were associated with increased risk for

death or inpatient rehabilitation

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Seizure severity is associated with hypoxic ischemic injury in abusive head trauma

Dingman A. et al., Pediatric Neurology 82 (2018) 29–35

58 children with severe TBI due to abusive head trauma

Electrographic seizures in 51.2%

Hypoxic-ischemic injury (by MRI) in 77.4%

Wainwright et al., Ann Neurol 2004 56:61-67 (perinatal asphyxia)

Somera et al., Epilepsia 2007 48:1785-1800 (early-life seizures)

Lloyd et al., J Neuroinflammation 2008 5:28 (traumatic brain injury)

Somera et al., Brain Res 2009 1282:162-172 (early life seizures)

Blood brain barrier breakdown as mechanism of post-traumatic epilepsy

Piao C. et al., Exp Neurol 273 (2015) 288–300; J Cereb Blood Flow Metab 2018

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“25 month old F, now lethargic, most likely from Ativan given in ED”

Courtesy L. Hirsch MD

Courtesy L. Hirsch MD

Interim Summary

• Electrographic seizures are common after moderate and severe TBI

• Abusive head trauma particularly high risk

• Need continuous EEG monitoring for 1-2 days

• Children with a high seizure burden are at risk for hypoxic ischemic injury and need imaging

• Seizures may worsen neurologic outcome

• Seizure pathways reduce variability in management

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Cochrane Review Data: Low quality evidence that treatment with an anticonvulsant drug reduces the risk for post-traumatic seizures or post-traumatic epilepsy

Thompson K, et al., Cochrane Systematic Review - Intervention Version published: 10 August 2015

• 10 trials involving 2326 people in 12 published articles

• Early treatment with a traditional antiepileptic drug (phenytoin or carbamazepine) may reduce the risk of early post‐traumatic seizures

• No effect on late seizures or mortality• Evidence should ‘interpreted with caution’

Prevalence of early clinical seizures despite treatment with levetiracetam is approximately 20%

Chung M and O’Brien N., Pediatr Crit Care Med2016; 17:150–156

• Prevalence in children with TBI who do not receive seizure prophylaxis (20–53%)

• Rate in children treated with phenytoin (2–15%)

2003 Pediatric Traumatic Brain Injury Guidelines

• 18 chapters• No standards (level I)• 4 guidelines (level II)• 14 options (level III)• Impact unknown• Adherence unknown• Barrier factors unknown

Adelson et al., 2003 Pediatr Crit Care Med 4(3) Suppl

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2012 Brain Trauma Foundation Update

• 27 new publications included• 25 publications from 2003 guidelines were

excluded• Hampered by lack of systematic approach to

data collection

• Levels of recommendation changed to ‘Level I’ ‘Level II’, and ‘ Level III’.

• New chapters on Neuromonitoring and Neuroimaging

Kochanek P et al., 2012 Pediatr Crit Care Med 14(Suppl) S1-82

Pediatric Guidelines Adherence and Outcomes Study (PEGASUS)

Harborview Medical Center

Objectives and Hypotheses

• To characterize national variation in adherence to the pediatric TBI guidelines, and to examine the relationship between adherence and outcomes.

• To identify remediable high priority provider and organizational factors which impact adherence and outcomes

• To test the hypothesis that adherence to specific clinical indicators during the first 72 hr after admission is associated with improved discharge survival and neurologic outcome

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Inclusion criteria and data abstraction

• Patients ages 0-17 yr with severe TBI• ≥ one ICD-9 discharge diagnosis code: 800.0-801.9, 803.0-804.9, 850.0-854.1,

959.01, 950.1-950.3, and 995.55• Minimum AIS ≥ 3• Postresuscitation GCS ≤ 8• Alive with ETT in ICU ≥ 48 hr after ICU admission• Abnormal head CT• Trauma history

• Data abstracted from the EMR and sorted by location• Pre-hospital • Emergency Department• OR• ICU

• 236 subjects identified ages 8.0 (SD, 6.3 yr)

Measures of guideline adherence

• Created 16 clinical indicators • Number and type for each location determined a priori

– 5 PH– 5 ED– 10 OR– 14 ICU

• For some indicators at time component was included• Primary outcome

– Association of adherence across all locations with mortality and discharge GOS

• Secondary outcomes– Association with the location-specific adherence to indicators

Key findings associated with better outcome

• Maintenance of CPP > 40 mm Hg in the first 72 hr in OR and ICU

• Avoidance of pre-hospital hypoxia• Early nutrition• Hyperventilation in the absence of cerebral herniation

– Associated with mortality in the presence of herniation

Vavilla MS et al., Crit Care Med. (2014) 42:2258-66

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6% lower hazard of death for every percentage point increase in adherence

Outcomes for children with traumatic brain injury can be improved by implementing a cooperative program of accepted best practice

• Retrospective study of 123 pediatric patients with severe TBI

• Primary outcome; rate of categorised discharge disposition before and after introduction of a pediatric neurocritical care program in 2005

• Assessed adjusted outcome as a function of initial injury severity

Pineda et al., Lancet Neurol 2012 http://dx.doi.org/10.1016/S1474-4422(12)70269-7

Outcomes improved across the range of initial injury severity

Pineda et al., Lancet Neurol 2012 http://dx.doi.org/10.1016/S1474-4422(12)70269-7

After PNCP

Before PNCP

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Summary and clinical implications• TBI shortens life expectancy, mainly in the young• Post-traumatic epilepsy is associated with an increase in mortality• Mechanisms are not known• Young age, abusive head trauma and subdural hemorrhage all add to

risk• Treat severe TBI cases empirically with anticonvulsant [phenytoin 20

mg/kg load then 5 mg/kg/day ➗ bid or leviteracetam 30 mg/kg loading dose, then maintenance with 30-60 mg/kg/day

• Approach seizures as another second insult like hypoxia and hypotension

• Manage patients with continuous EEG monitoring; don’t rely on the neurologic exam to exclude seizures

• Create a pathway for management of TBI• Follow the guidelines and adhere to them• Create a seizure pathway

Recognizing & Managing Seizures in Pediatric TBI

Mark Wainwright MD PhD

Herman and Faye Sarkowsky Professor of Neurology

Division Head, Pediatric Neurology

University of Washington

Thankyou