post traumatic epilepsy

1. POST
TRAUMATIC
EPILEPSY
DR.SHAMEEJ MUHAMED KV
SENIOR RESIDENT NEUROSURGERY
GMC CALICUT

2.  Epilepsy are the most commonly encountered
neurological disorders.
DEFENITION OF EPILEPSY
1. Conceptual Definition – which are useful for patient
communication & neurology education
2.Operational Definition-which can be used in clinical practice
&research
YOUMANS& WINN

4. Introduction
 TBI accounts for 10-20% of symptomatic epilepsy in
the general population and 6% of all epilepsy.
 TBI refers to a brain injury caused by an external
mechanical force.
 Posttraumatic epilepsy (PTE) is defined as a recurrent
seizure disorder secondary to traumatic brain injury
(TBI).

5.  Prevention of the development of PTE is a major
challenge in medicine.
 Identification of critical molecular, cellular, and
network characteristics predicting epileptogenesis with
TBI remains incomplete.
 As epileptogenesis occurs only in a subpopulation of
subjects, biomarkers for predicting risk for
epileptogenesis are needed.

6. Post traumatic seizures
 1.Immediate, Contact, or Concussive seizures (IPTS)-
which occur within 24 hours after injury
 2.Early (EPTS), Acute Symptomatic- Seizures those
occurring with in 1 week
• Late (LPTS), Remote Symptomatic-which occur after one
week after injury. Two or more unprovoked seizures
after 1 week

7.  Immediate and early seizures belong to the group of
provoked seizures
 they do not define epilepsy since they are not due to
underlying a pathogenic mechanism that chronically
predisposes the patient to manifest epileptic seizures
 Post-traumatic epilepsy is determined by the
presence of late seizures and therefore unprovoked.

8. Epidemology
 Post-traumatic epilepsy (PTE) is the most frequent cause
of epilepsy in young adults as they are more at risk of the
exposure to head injury
 Estimated proportion of presumed causes of incident
epilepsy related to TBI range between 2% and 16% in
European Countries.
 Early PTSs frequency comprised between 2.6% and
16.9%.
 Annegers et al have published a prospective study with a
follow-up of over 10 years, reporting an average PTE
/LPTS frequency of 2.1% in TBI patients; the percentage
was significantly higher (12%) if considering only subjects
with severe TBI.

10.  Children
 EPTS: 0.2 to 9.8%.
 EPTS more common than LPTS
 Younger children at increased risk of both
 Younger children more likely to have status
epilepticus

11. Risk factors
EPTS
 GCS <10
 Contusion
 Depressed fracture
 SDH EDH ICH
 Penetrating injury
 need of surgery
 infant age
 amnesia lasting more than 30 minutes,
 history of chronic alcoholism
 Seizure <24 h of injury (IPTS)

12. RISK FACTORS FOR LPTS
 Penetrating Injury
 Intracranial Hematoma (ICH)
 Compound Depressed Fracture
 EPTS
 Age over 35
 transient amnesia which lasts more than 24 hours
 male gender
 the presence of early PTSs as a risk factor for late PTSs

13.  Jennet et al showed that the presence of compound
depressed skull fractures was associated to a higher
general risk of early and late PTSs.
 Compound Depressed Fracture
 Early Seizures >50%
PTA >24 hours
 Dural Tearing 20-40%
 Focal Signs 5-20%
 None <3%

14.  Jennet. TB Head Injury 2005.
ICH
Intradural
Extradural
Operated NotOperated Operated
 45% 23% 22%

15. Risks - Penetrating injury
~ 50% over 15 years
 20% of adults within two years of TBI
 Risk remains high for >5 years
 Risk factors:
 GCS
 Motor deficit/ Aphasia
 EPTS
 Infection

16. Clinical types of seizures
 Generalized-onset or secondarily generalized
seizures
– Nonpenetrating TBI
– Children
 Partial-onset seizures
– Adults
– EPTS
– Focal lesions on CT
– Penetrating TBI

17. Clinical types of seizures
 Transient behavioral change
 Reminiscent of CPS
 Sterotyped behaviours
 Without the hypersynchronous EEG activity
 Mild TBI
 Respond to carbamazepine
 NES(non epileptic seizures)
Episodic behavioral events that superficially
resemble epileptic attacks
– 33 – 40%
– Milder injury
– Usually manifestations of other conversion disorders
– Psychiatric histories that predate TBI

18. LOCALIZATION
 Temporal 54%
 Frontal 33%
 Occipital 3%
 Parietal 5%
 The clinical characteristics of the seizures depend on the location
of the lesion and the precocity of the secondary generalization.
 In patients with a history of trauma in childhood (less than five
years) can manifest mesial temporal lobe epilepsies, as a trauma
in the temporal region at an early age can induce the
appearance of mesial temporal sclerosis
 Status epilepticus (SE) at onset is not uncommon; Jennett
calculated a frequency of 10% in patients with PTSs .
 The infant population undoubtedly has a higher probability of SE
compared to the adult one.

19. COURSE (NATURAL
HISTORY)
EPTS
 Only 50% patients have a recurrence
 25% only 2-3 seizures
LPTS
 20% of people who have a single LPTS never
have any further seizures
 50-66% have seizure onset within first 1 year
 75-80% have seizures by the end of 2nd year
 About half the patients who develop LPTS have 3 or
fewer seizures and go into spontaneous remission
thereafter

20.  LPTS
 Remission over 3 years
– 35% became seizure-free
– 21% had > 1 seizure per week
 After 5 years
– mild TBI no longer increased risk
– moderate or severe TBI or penetrating TBI remain at
increased risk

21.  Increased risk of recurrence/ persistence
• Partial seizures
• Seizure frequency within the first year
• Combined seizure patterns
• AED noncompliance
• Alcohol abuse
• Seizures began later after injury

22. PATHOGENESIS
IPTS &EPTS are considered direct reactions of a brain
damage & they are correlated to
1. altered vessel regulation of the local
cerebral blood flow,
2. alteration of the hematic-encephalic
barrier
3. increase of the intracranial pressure
with focal or diffuse presence of
ischemic, hemorrhagic, inflammatory
or necrotic damage

23.  animal models of PTE have suggested that late
seizures are caused by two main pathogenic pathways:
 Oxidative Stress Mechanisms
 Excitotoxic Mechanisms - Neuronal Hyper Excitability

24. mechanism of oxidative
stress
 trauma is accompanied by a leakage of red blood cells,
 formation of free radicals mediated by the iron contained
in hemoglobin;
 these free radicals react with the methylene groups in the
double lipid layer of neuronal membranes
 lipid peroxidation of the neuronal membranes and
mitochondria and the alteration of the function of the
sodium/ potassium pump ATPase activity.
 The result of this sequence of events is a reduction of the
chronic convulsive threshold of a group of neuronal cells.

25. EXCITOTOXIC
MECHANISM
Is explained by the extra cellular increase of excitatory amino acids
immediately after injury, with increased levels of glutamate and
aspartatic acid
 These traumatized cells tend to assume excitatory aminoacids more
readily than controls and present increased expression of the
sodium-coupled neutral amino acid transporters subtypes 1 (SNAT1)
and subtypes 2 (SNAT 2) .
 Traumatized in vitro cells tend to form axonal sprouting with a
higher immunoreactivity to GAP 43 (Grown Associated Protein).
 These cells show an altered excitability, evidenced by the presence of
synaptic potentials with prolonged post-synaptic components

26.  Other factors
• Altered calcium-mediated second messenger
activity
• Changes in ionotropic receptor function and
composition
• Altered endogenous neuro protectant activity
• TBI-induced cortical dysplasia

27. MODELS FOR EPILEPTOGENESIS
• Ferric chloride model
• Kindling model
These animal models of designed to mimic three broad
classes of epileptic disorders : temporal lobe epilepsy ,
epilepsy associated with a brain malformation & focal
epilepsy

28. Kindling
 are stimulus induced of temporal lobe epilepsy
 Application of brief trains of weak electrical stimulation
over brain until a seizure is observed
 Over a prolonged period of time spontaneous
seizures eventually appear
 Kindling occurs best in neuroplastic areas of brain,
amygdala
 Agents that retard or abort the kindling process are
considered antiepileptogenic
 Agents that suppress or block seizures in fully
“kindled” brain are anticonvulsant

29. Therapeutic relevance
Anticonvulsant
 Phenytoin (PHT)
 Carbamazepine (CBZ)
 Topiramate (TPM)
 Lamotrigine (LTG)

30. Ferrous Chloride Model
 The use of focal application of ferrous chloride as a model of
epilepsy arose from the observation that deposits of iron on
brain tissue after head trauma or stroke can be a risk factor to
develop epilepsy
 Ferrous chloride is injected in the cortex or amygdala of the
rat,after 5 to 7 days, more than 90% of the spontaneous seizures.
 Histologic analysis of 6 weeks after the injection show neuronal
loss,activated astroglial cells, iron-positive macrophages, and
fibro-blasts surrounding the iron deposit.
 Some of the surviving layer V pyramidal neurons stain positive
for iron, with loss of dendritic spines and decreased dendritic
branchingThe latter anatomic findings have clear
implications for synaptic excitability.
 Interest-ingly, most of AEDs available are effective in
controlling the seizures induced by ferrous chloride

31. DIAGNOSIS
 In patients with seizures at a short distance from cranial trauma it is
necessary to exclude other potential causes of provoked seizures
 A trauma patient often presents conditions of metabolic and
circulatory instability, with high probability of alteration in the
biochemicaL parameters, such as hyponatremia, which may lower the
epileptogenic threshold.
 EEG:- EEG in a patient with TBI is useful for the localization of the
lesion focus and for the measurements of the extent of damage,
but it is not able to define the probability to develop epilepsy
 more than 20% of patients with PTE have a negative EEG during the
first three months after injury

32. Neuroimaging
 Brain MRI represents the study of choice
 It allows a better anatomy definition of the brain and
gives the exact outcome of any post-traumatic lesion.
 T2-weighted images and gradient echo sequences may
well highlight the presence of hemosiderin deposits
that have a potential epileptogenic role.
 Messori et al. through the analysis of T2 images from
more than 130 patients, showed how a precocious
formation of a gliotic scar around a hemosiderin
deposit reduces the risk of PTE.

33. Treatment and prophylaxis -
EPTS
 The manifestation of immediate or early seizures can
affect the patient’s prognosis
 since it may increase the cerebral perfusion pressure
and the intracranial pressure.
 The prophylactic therapy of PTE is mainly intended to
block or delay epileptogenic mechanisms established
after TBI
 AED given during the first 24 hours reduce the
occurrence of early seizures significantly

34.  CHOICE OF AED:- While choosing AED, the cognitive,
motor and psychological problems related to TBI should
be kept in mind
Phenytoin is more cost-effective than
levetiracetam at all reasonable prices and at all clinically
plausible reductions in post-TBI seizure
potential.(Cotton, et al. J Trauma 2011.
 Though with increased hypersensitivity phlebitis
hypotension arrhythmia drug interactions of PHT
compared to LVM , which has predictable
pharmacokinetic, does not require drug monitoring but
with a greater tendency to persistence of epileptiform
EEG abnormalities,evidence favours PHT

35.  Carbamazepine (CBZ); only one true RCT reported and
this showed a good efficacy in the prevention of early
PTSs, but not in the late ones.
 VPA however with less capacity to prevent early PTSs
compared with PHT.

36.  The use of antiepileptic drugs (AEDs) at an early stage
in order to prevent PTE is rather controversial.
 The results of RCTs seem to show a moderate effect
only on early PTEs, not on the late ones.
 Temkin et al demonstrated that an early administration
of PHT prevented EPTS in an excellent way, while it did
not prevent the complete onset of LPTSs both during
the first year of therapy and in the following years
without therapy

37.  In general, the recommendations for drug prophylaxis
of EPTS provide Phenytoin as frontline drug,
 Levetiracetam &Carbamazepine as second choice
drugs;
 Phenobarbital and Valproate are not considered
indicated for PTS prophylaxis.
 No AED is effective in preventing LPTS

38. Treatment and prophylaxis -
LPTS
• No AED is effective in preventing LPTS
• Standard AEDs are effective for treatment
• Treatment guidelines similar to any other epileptic
patients
• Choice of AED – Cognitive effects , drug interaction &
efficacy

39.  Treatment LPTS
 Focal epilepsy:- CBZ extended release/ OXC/ PHT/LTG
 Generalized epilepsy:- VPA/ PHT/ OXC/ LTG
 • AED substitution is indicated
• Failure of seizure control
• Adverse drug reaction
• Cognitive decline

40. Prophylaxis in adults
Recommendation
 Level II
 Prophylactic use of phenytoin or valproate is not
recommended for preventing LPTS
 Anticonvulsants are indicated to decrease the
incidence of EPTS (within 7 days of injury)
 EPTS is not associated with worse outcomes.

41. Prophylaxis in Children
 Phenytoin vs placebo
 No significant differences in incidence of EPTS
 (phenytoin = 7% vs. placebo = 5%)
 Ineffective in reducing incidence of LPTS
 Phenytoin does not reduce EPTS or LPTS in children

42. Prophylaxis in Children
Recommendation
 Level III
Prophylactic treatment with phenytoin may be
considered to reduce the incidence of EPTS in pediatric
patients with severe TBI
 Level II
Prophylactic use of antiseizure therapy is not
recommended for children with severe TBI for
preventing LPTS

43. SURGICAL TREATMENT OF PTE
-Refractory PTE with a well localized seizure focus can
be considered for epilepsy surgery.
-Results are especially good for unilateral temporal lobe
injury.
-However, multifocal lesions are common, many of which
could be epileptogenic. Invasive monitoring may be
required.
-Risk of additional deficits is probably higher.

44. REFERENCES
 YOUMANN &WINN
 Post-Traumatic Epilepsy: Review Edward Cesnik, Ilaria
Casetta, Enrico Granieri* Department of Medical and
Surgical Sciences of Communication and Behaviour,
University of Ferrara, Italy(Journal of Neurology &
Neurophysiology)
 BRAIN INJURY MEDICINE:-PRINCIPLES &PRACTICE.
 GREENBERG

45.  THANK U