Transcript Post Traumatic Epilepsy

Post Traumatic
Epilepsy
Sarah Wagers, MD
Assistant Professor University of
Louisville Department of Neurosurgery
Frazier Rehabilitation Institute
Robley Rex Veterans Administration
Neurorestorative
Asikainen said in 1998
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Recovery from a TBI involves dealing with
problems that can be physical, cognitive, or
psychological in nature. The development of
Posttraumatic Epilepsy(PTE) further complicates
recovery by means of physical and psychological
consequences of seizures as well as the
medications used for their treatment. Whereas
most posttraumatic symptoms show gradual
improvement over time, epilepsy is unique in
recurring suddenly and unexpectedly, leading to
a physical and psychological setback that can
negatively affect recovery and that has been
shown to worsen functional outcome
History
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Association of epilepsy and head injury has
been recognized since antiquity.
As far back as 3000 BC evidence that patients
surviving head injury went on to develop
epilepsy.
In early Renaissance clear descriptions of
epilepsy following head injury
1904-William Spratling- textbook Epilepsy and
Its Treatment-noted that trauma was cause of
epilepsy in 6.7% of patients
Epidemiology
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Trauma is one of the most common etiologies
for development of epilepsy- 20% of
symptomatic epilepsy.
Young adults and those with military injury
have the highest incidence.
Even today like the numbers in 1904- 6% of the
cases within the seizure population are
caused by trauma.
PTS will be observed in approximately 35%–
65% of patients with Penetrating TBI
Epidemiology
 Age
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of development of seizures
15-34 yrs- 30 % caused by trauma
<14-14%
>65-8%
Classification
Epileptic seizure- a clinical manifestation presumed
to result from an abnormal and excessive discharge
of a set of neurons in the brain. The clinical manifestation
consists of sudden and transitory abnormal phenomena,
which may include alterations of consciousness, motor,
sensory, autonomic, or psychic events, perceived by the
patient or an observer .
Epilepsy- is a condition characterized by
recurrent (2 or more) epileptic seizures, unprovoked by any
immediate identified cause .
Classification
 Post-traumatic
epilepsy (PTE) -disorder
characterized by recurrent late seizure
episodes not attributable to another
obvious cause in patients with TBI .
 PTS - single or recurrent seizures occurring
after TBI and are commonly classified into
early (< 1 week after TBI) and late (> 1
week after TBI).
Classification
 Controversy
over days 8-14 post injury,
probably more like early seizures than late
physiologically.
 In practice the term PTS and PTE are used
interchangeably, but the term PTE is
meant to be recurrent late seizures
Precipitants
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Causes that lead to seizures that would not
be considered PTE.
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hydrocephalus
sepsis
hypoxia
metabolic abnormalities
Space occupying lesions including hemorrhage
Alcohol
Drugs including prescription or
illegal/recreational
Precipitants
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Medications that possibly lower the seizure
threshold
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Buproprion
Tricylics
Data that SSRI’s could possible lead to increase,
but have been determined to be the safest
treatment for depression in TBI.
Clozapine
Antibiotics – quinolones and imipenem
lessen risk by ensuring appropriate dosing in ill patients
with reduced renal clearance.
Precipitants
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Dopamine agonists- amantadine and
bromocriptants -only anecdotal evidence.
Cocaine
High dose caffeine
Rarely amphetamine related drugs at
appropriate doses- methylphenidate and
dextroamphetamine do not increase risk of
seizures
Tramadol especially mixed with
antidepressants
Classification
 Focal
vs. Generalized –from the
Commission on Classification and
Terminology of the International League
Against Epilepsy
Classification
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Focal seizures without impairment of consciousness -Consciousness is not
impaired during these focal seizures. The patient can respond appropriately
to questions and commands and can remember events occurring during the
seizure. The principal types are the following:
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1. Motor seizures, which are characterized by localized stiffening or jerking of
the face or extremity on the same side of the body.
2. Somatosensory or special sensory seizures, which can include any sensory
modality including smell, taste (often unpleasant—e.g., a metallic sensation),
vision (such as flashing lights), hearing, or touch (such as paresthesias and
electrical sensations).
3. Autonomic seizures, which are relatively common and may include
changes in visceral sensation (e.g., in abdomen or chest) and change in
heart or breathing rates.
4. Psychic seizures in which patients report feelings of fear, depression, or
anxiety, or altered perceptions of time such as de´ ja` vu
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Classification
Focal Seizures
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Focal seizures with impairment of consciousness
Formerly called complex partial seizures, these seizures are
characterized by impairment of consciousness. Frequently,
the patient has automatisms, characterized by automatic
movements such as lip smacking, picking at bed sheets,
grunting, or more complex acts.
Complex partial seizures (CPS) usually last no longer than 3
min, with postictal confusion lasting 15 min or less. They may
begin as focal seizures without impairment of consciousness
(e.g., focal motor, focal sensory) and progress to
impairment of consciousness or have impairment of
consciousness from the start.
Classification
 Focal
onset evolving to a bilateral
convulsive seizure (e.g., tonic, clonic,
tonic-clonic)
 Focal seizures can evolve to a bilateral or
convulsive seizure. Patients may describe
an aura, which is a focal seizure
preceding loss of consciousness. Patients
may also experience a focal seizure with
impairment of consciousness before
evolution to a convulsive seizure.
Classification
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GENERALIZED SEIZURES (SEIZURES WITHOUT FOCAL ONSET)
Absence seizures
Usually classified as either typical absence (previously
known as petit mal) or atypical absence.
1. Typical absence seizures are characterized by abrupt
onset of impairment of awareness and responsiveness
lasting 3–20 sec. Return to awareness is immediate after the
seizure ends. There is no warning before the seizure and no
postictal confusion.
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The patient may report automatisms such as eye blinking and lip
smacking.
2. Atypical absence seizures are usually seen in children
with cognitive impairment as opposed to typical absence.
They may be associated with atonic and tonic seizures.
Classification
 Myoclonic
seizures
 Myoclonic seizures are characterized by
very brief bilateral synchronous jerks.
Consciousness is usually not impaired
unless there are successive myoclonic
seizures.
Classification
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Atonic seizures
Atonic seizures are characterized by a sudden loss
of postural tone with impairment of consciousness.
These seizures rarely last more than 1 min and
generally last less than 5 sec.
Tonic seizures
Tonic seizures are characterized by flexion or
extension of both the upper and lower extremities.
They generally last from 5–20 sec and are
common in patients with other neurologic
abnormalities
Classification
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Tonic-clonic seizures
Primary generalized tonic-clonic seizures are
not preceded by an aura and are
characterized by an initial tonic phase of
stiffening followed by a clonic phase of jerking
of the extremities. The seizure lasts about from
30 sec to 2 min.
It may be difficult to differentiate a primary
generalized tonic-clonic seizure from a
secondarily generalized seizure.
Classification
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Psychogenic nonepileptic seizures (PNES), often
called
Pseudoseizures or psychogenic seizures, are terms
used for episodic behavioral events, which
superficially resemble epileptic attacks but are not
associated with paroxysmal activity within the
brain. PNES must be differentiated from other
nonepileptic events such as syncopal episodes
and cardiac events.
PNES are common in neurologic settings and may
coexist with epileptic seizures in patients with
epilepsy
PTSD is significant risk factor for developing PNES.
Manifestations
 The
varied types of seizures that originate
in the frontal or temporal lobes and their
associated ictal or postictal alteration of
consciousness justify their consideration in
the differential diagnosis of any patient
with TBI with episodic changes in mental
status.
Manifestations
 Frontal
lobe epilepsy -may exhibit
complex, semipurposeful motor
automatisms such as kicking, screaming,
and thrashing episodes. Frontal lobe
interictal and postictal manifestations also
include cognitive or affective symptoms,
such as confusion, anger, hostility, and
hallucinations.
Manifestations
 Temporal
lobe origin- Complex partial
seizures may also present with emotional
symptoms such as fear or panic, followed
by periods of postictal confusion and
amnesia.
 Seizure-related aggression, however, is
rare. It is usually associated with postictal
confusion, particularly while the patient is
being restrained
Diagnosis
 The
presence of focal motor, sensory, or
language deficit of new onset should alert
the clinician to the possibility of a recent
unwitnessed PTS.
Diagnosis
 Todd’s
paralysis or postictal paresis (PP) is
defined as a transient focal deficit that
may follow a focal or tonic-clonic seizure
. It is a recognized postictal manifestation
of PTS. These do not reflect permanent
structural damage but rather represent
transient postictal disruption of function
that typically resolves within 24–48 hours.
Natural History
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Approximately one-half to two-thirds of
patients who suffer from PTS will experience
seizure onset within the first 12 months and
75%–80% by the end of the second year
following injury.
After 5 years, adults with mild TBI do not
appear to have a significantly increased risk
relative to the general population
Patients with moderate or severe TBI and PTBI
will remain at increased risk after this postinjury
duration
Recurrence
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It is increasingly evident that seizure
recurrence is a critical factor in determination
of subsequent disability and quality of life
(QOL)
Greater seizure frequency significantly
correlates with lower employment rates,
which in one study ranged from 57% among
patients who are seizure free for 3 months to
30% in patients with daily seizures.
As seizure frequency increased, health care
costs increased and measures of QOL
declined
Recurrence
 Recent
evidence suggests that although
patients with Early PTS will experience a
late seizure in 20%–30% of cases, seizure
onset after the first week is associated
with a much higher likelihood of a seizure
recurrence
 Immediate post-traumatic seizures (IPTS)
are generally believed to carry no or little
increased risk of recurrence
Recurrence
 Between
20% to 33% of patients with Late
PTS will experience frequent recurrences,
many refractory to conventional AED
therapy.
 Surgical intervention may be an option.
Complications
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Cognitive-cognitive deficits can persist in
between seizures.
Behavioral-higher incidence of psychiatric
related hospitalizations have been noted
among patients with PTS when compared
with nonepileptic controls with PTBI .
Mazzini et al. in 2003 issue of Epilepsia, found
that disinhibited behavior, irritability, and
aggressive behavior were significantly more
frequent and severe among rehabilitation in
patients with PTE when compared with
patients with TBI without seizures.
Complications
 Elevated
disorders
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prevalence of psychiatric
Depression- due to disability, memory
problems, being denied driver’s license,
stigmatization, perceived loss of control.
Depression itself can actually decrease the
seizure threshold.
Incidence of suicide is higher
Post-ictal psychosis-can last up to a week
Complications
 Staus
Epilepticus is the most clinically
significant manifestation of PTS and carries
the greatest risk of adverse outcome.
 The Working Group on Status Epilepticus
defines SE as more than 30 minutes of (a)
continuous seizure activity or (b) 2 or more
sequential seizures without full recovery of
consciousness in between.
Complications
 Status
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Epilepticus
usually attributable to another cause, such
as AED withdrawal; acute systemic or
neurologic injury, such as anoxic
encephalopathy or stroke; sepsis;
metabolic derangements; or a
combination of these conditions
 More
likely to be encountered as a PTS
manifestation in children
Management
 Prophylaxis-using
anti epileptic drugs in
patients who have not had a seizure
 Reasons they have been used
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Prevent seizure in the first few days when it
would have the greatest risk of secondary
injury such a increasing ICP
Medicolegal
Hopefully to prevent development of later
seizures.
Prophylaxis
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Thus far animal and human studies fail to
provide evidence that AED therapy
prevents the development of the PTS
focus or alters the course of seizure
recurrence.
Prophylaxis
 High
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Risk Patients
Patient Characteristics
History of chronic alcohol use
Age-children have lower risk of late PTS, but
higher rise of IPTS and EPTS.
Genetics-?family hx seizures and presence
of Apo E gene
High Risk Patients
 Injury
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characteristics
Penetrating injuries
More severe injury
Focal neurologic deficits
Depressed skull fracture
Recurrent bone/metal fragments
Rare in mild TBI, if do happen, need to rule
out other cause.
Prophylaxis
 No
studies have shown that AEDs prevent
late PTS, but some have shown evidence
of prevention of EPTS, but no difference in
death/neurological disability.
Treatment
 Decision
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to treat after first seizure
33% can be expected to have a second
within 3-5 years.
Weigh risks/benefits- avoiding a second
seizure vs. the risks of the medication
Treatment
 Goal
is to get control with just one
medication.
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Type of seizure
Route/frequency of medication
Expected adverse effects
Co-morbidities
Treatment
 Commonly
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used traditional medications
Carbamazipine, Valproic acid, Phenytoin
 2nd
generation/newer meds- few studies
on use. Fewer adverse events.
Adverse Effects of Medications
 See
Table
 Cognitive effects
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Older agents affect memory and cognition
especially Phenytoin, Carbamazepine
and Phenobarbital.
Can impair recovery in lab animals
Adverse Effects
 Because
PTS occur among a minority of
all patients with TBI, including severe TBI,
AED therapy broadly directed against
subclinical seizure activity among all
patients with TBI during recovery may be
more detrimental to neurological and
functional outcome than either seizures
alone or initiation of AED therapy after
seizure onset.
Trends
 Fewer
clinician treating prophylactically
beyond 7 days.
 Still frequent use of Phenytoin
 Frequent substitutions- Carbamazepine,
Valproic acid, Lamotrigine, Leviteracitam
Duration of treatment
 No
clinical studies
 Reasonable to discontinue after 2 years
seizure free
Surgical treatment
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Refractory to treatment even after treatment with
muItiple AEDs
Randomized study comparing surgical and
medical treatment for temporal lobe epilepsy, 58%
of surgically treated patients were free of disabling
seizures at 1 year vs only 8% of those assigned to
receive medical treatment.
Significant improvements in outcome were
observed in measures of QOL as well as a trend
with respect to social functioning
If PTS, more difficult to locate the seizure focus due
to the damage in the brain- not as affective as in
no traumatic.
Vagus Nerve Stimulator
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VNS is approved by the Food and Drug
Administration (FDA) for adjunctive treatment
of intractable partial seizures in patients
above 12 years old.
Based on controlled, randomized trials,
approximately 30% of these patients can be
expected to have at least a 50% decrease in
overall seizure frequency
Usually can reduce medications
Not studied in late PTS
Prognosis
 If
PTE- 50% in remission at 15 years post
trauma.
 Those with frequent seizures during the first
year have a lesser chance of obtaining
an extended remission.
References
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Zasler, ND; Katz, DI; Zafonte, RD. Brain Injury
Medicine Principle and Practice Second
Edition. 636-659. 2013
Lowenstein, DH. Epilepsy After Head Injury: An
Overview. Epilepsia, 50(Suppl. 2) 1528-1167.
2008
Seizures After TBI. TBI Model System Consumer
Information. 2010
Silver, JM; McAllister, TW; Yudofsky, SC.
Textbook of Traumatic Brain Injury. Second
Edition. 265-275. 2011.