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JOURNAL READING

September 2014

POSTTRAUMATIC EPILEPSY AND


TREATMENT
Chen JWY, Ruff RL, Eavey R, Wasterlain CG. Posttraumatic epilepsy and

treatment. Journal of Rehabilitation Research & Development. volume 46, number


6, 2009

Ellen J. S. Riry
2008-83-023
Pembimbing:
dr. Semuel Wagiu, Sp.S, M.Ked
Dibawakan dalam rangka tugas kepaniteraan klinik
di Bagian Neurologi Faktultas Kedokteran
Universitas Pattimura
Ambon

ABSTRACT
Posttraumatic epilepsy (PTE) : major long-term
complication of traumatic brain injury (TBI) within 5
years
Risk :
53% penetrating TBI
10-25% combat-associated closed-head trauma with positive brain
imaging
5% moderately severe closed-head injury without imaging finding

Partial seizures may manifest with subtle behavioral


alterations mistaken for manifestations of postraumatic
stress disorder and improperly treated
Sudden unexpected death in epilepsy : among 20-40 y.o
Seizures social stigma optimal seizure control is
essential
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DEFINITION

Epilepsy = all groups of syndrome characterized with


temporary paroxysm disorder of brain function.
(Dorland's Illustrated Medical Dictionary)
Other definition: disease of brain defined by any of the
following conditions:
at least 2 unprovoked seizures occuring greater than 24 hours
apart
1 unprovoked seizure and a probability of futher seizures similar
to the general recurrence risk (at least 60%) after 2 unprovoked
seizures, occuring over the next 10 years
diagnosis of an epilesy syndrome

INTRODUCTION
Definition of Posttraumatic Epilepsy
Traditional definition of epilepsy : 2 or more unprovoked
seizures after a head injury >1 week after the head
injury
86% patients with 1 unprovoked posttraumatic seizure
experienced a 2nd seizure within 2 years
Patient with 1 unprovoked posttraumatic seizure
extremely high risk of developing PTE
Other definition: 1 or more unprovoked seizure late head
injury need an early treatment
Seizures that occur within the first 7 days after TBI are
defined as provoked seizures
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Risk of Posttraumatic Epilepsy After Traumatic Brain


Injury
The probability of PTE significantly correlates with the
severity of injury
In general, TBI divided into:
Mild
Moderate
Severe

Multivariate analysis high risk of PTE:


depressed skull fracture,
brain contusion,
intracranial hemorrhage,
coma duration,
low Glasgow Coma Scale score, and
Older age

Patient with mild TBI : Presence of early seizure NOT


increase the risk of PTE
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Risk of Posttraumatic Epilepsy in Veterans


with Traumatic Brain Injury
Risk factor for developing PTE : After penetrating
head injury retained metal fragments,
intracranial hemorrhage, chronic neurolgical
deficits, brain parenchyma loss

Natural History of Posttraumatic Epilepsy


PTE presents with different seizure frequency and
may evolve into remission or develop into
intractable seizures.
Frequent seizures in the first year after penetrating
head injury suggest a reduced chance of remission

POSTTRAUMATIC EPILEPSY IN
CONTEXT OF OIF/OEF
Medical Cost of Posttraumatic Epilepsy
Max latent period of PTE : 20 years after TBI
Uncontrolled seizures can be fatal :
Seizures seizures
Aspirate during seizures pneumonia and
damage to the airways and lungs
Disrupt blood pressure and heart control sudden
death
Disrupt respiratory and blood temperature control
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Socioeconomic Cost of Posttraumatic


Epilepsy
Seizures = social stigma compromise society
Sudden unexpected death in epilepsy : 20-40 y.o
Uncontrolled seizures become refractory to
medications
Optimal seizure control = essential for the physical
and emotional health
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Risk of Posttraumatic Epilepsy in OIF/OEF


Veterans with Traumatic Brain Injury
risk for developing PTE varies type of TBI
cerebral injury can be seen on clinical imaging
the risk = 10-25%
potential risk 5%
repeated events of minimal TBI increases the risk
of PTE : unknown
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Nonconvulsive Seizures
partial seizure manifest with subtle behavioral
alterations mistaken for apathy catatonia or PTSD
presentation of a complex partial seizure could be
featureless
for early detection : every clinican who treats patients
with TBI is aware of this condition.
EEG is often needed to establish a diagnosis of nonconvulsive seizure
the most recent report : identified a little over 32.000
injuries and around 5.500 individuals with TBI
the number of PTE cases will increase if hostilities
continue
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Table 1

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Table 2

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POSTTRAUMATIC EPILEPSY
TREATMENT
Introduction
clinicians routinely use new and effective
AEDs with different mechanisms of actions
other option : sugical evaluation Epilepsy
Monitoring Unit (EMU)
specialists consider resection surgery to
remove the seizure focus to be standard of
care in patients with epilepsy that is refractory
to medical treatment alone.

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Prevention
a number of published uncontrolled,
unblinded observational studies have
investigated the effect of AEDs in preventing
PTE:

phenobarbital (PB) + phenytoin (PHT)


phenytoin (PHT)
phenobarbital (PB)
valproic acid (VPA)

Only PB+PHT showed a marked difference


between the treated and untreated groups
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Most of researchers did not reproduce the


beneficial effects of prophylactic treatment
with AEDs in several randomized trials using
PHT, PHT+PB, or carbamazepine (CBZ) with
follow-up periods of 3 months to 5 years
Cochrane review 2.036 patients
prophylactic treatment with PHT or CBZ was only
effective in reducing the risk of early provoked
seizures after TBI
no beneficial effect in the prevention of PTE with
AED treatment
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Role of AEDs After Traumatic Brain Injury


AED prophylaxis seems to be effective in
controlling the early provoked seizures not
the late and PTE
The results to date do not support
prophylactic use of AEDs in patients with TBI
before the development of PTE

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Potential Pitfalls of Using Or Not Using AED


Prophylaxis After Traumatic Brain Injury
clinical study: difficult to tease out AED cognitive side
effects from the direct effects of TBI and from AED
inhibition of recovery of brain function after TBI
another limiting factor: heterogeneity of patient
populations
the timing of AED treatment after TBI : varies among
studies
the different types of seizures further complicate the
heterogeneity issue
nonepileptic seizures might be misdiagnosed as PTE
and the patient could be unnecessarily treated with
AED
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Epileptogenesis
Basic Aspects
epileptogeneis describes the molecular, cellular,
and network processes
far from fully understood
have emerged based on ressearch using various
results from animal models of epilepsy
An injury to the superficial layers of GABAergic
neurons in TBI could tilt the dedicated balance
between the excitatory and inhibitory neurons
toward hyperexcitability

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other observation : once the kindling process is


fully established permanent due to certain
irreversible changes in the anatomical structures
and physiological functions from molecular to
network levels
agents that inhibit or reverse epileptogenesis :
antiepileptogenic agents
in contrast, drugs that reduce hyperexcitability :
anticonvulsant use to control seizure
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Onset
theory : 1 critical issue in PTE prophylaxis is
initiation of antiepileptogenic therapy before the
epileptogenesis process starts, or at least before it
escalates to an irreversible stage
Principle : TBI could set the process of
epileptogenesis inmotion, and many other
accessory factors will also determine whether
epileptogeneis could complete its course of
developing PTE

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Genetic Propensity for Posttraumatic Epilepsy


genetic defects mostly in primary generalized
epilepsies
could be viewed as genetic propensity for developing
the phenotype (the epilepsy) when the other cofactors
are present
the increased risk independent of the APOE 4
allele's effect on the functional outcome
role of APOE 4 allele in epileptogenesis : unclear

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PRELIMINARY GUIDELINES FOR DETECTION


OF AND THERAPY FOR POSTTRAUMATIC
EPILEPSY

Early Treatment
AED prophylaxis effective in controlling the early
provoked seizure AED up to 1 week after TBI :
advisable
initiated as early as possible
longterm AED after TBI : not recommended
the possibility that some AEDs might have a negative
effect on the recovery of brain function after TBI
???
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Indication for Diagnostic Studies


for early seizure detection after TBI EEG
screening during the first 2 years
which patient should receive AED therapy :
unclear
what clinical parameters to guide the
continuation or termination of therapy :
unclear
if subtle clinical presentations correlate with
the epileptiform discharges on EEG
recordings initiation of AED therapy

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Pharmacotherapy
PTE in patient (+) initiate AED therapy
following the general guidelines used for other
types of acquired epilepsy.
monotherapy or polytherapy (at least 2 AEDs
of different pharmacological mechanisms)
follow the general treatment principles
using the least amount of AED
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Indications for Surgery


inpatient video EEG monitoring, PET scan, brain MRI
with epilepsy protocols
futher evaluations : depth/grid intracranial electrodes,
funtional MRI, cortical functional mapping with
electrocorticography
perform the Wada test
evaluate patients who are refractory but fail surgical
evaluations for placement of a deep brain stimulator
or vagus nerve stimulator
consider patients who fail vagus nerve stimulation and
deep brain stimulation for enrollment in investigational
procedures
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CONCLUSIONS
PTE might represent a large, complex
problem that should not be ignored
any plans to address the problem should
be coordinated with existing polytrauma
and TBI programs
experts are available within the VA to
evaluate the problem and design efficient,
proactive solutions
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THANK YOU.

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