Post Traumatic EpilepsySarah Wagers, MDAssistant Professor University of Louisville Department of NeurosurgeryFrazier Rehabilitation InstituteRobley Rex Veterans AdministrationNeurorestorative

Asikainen said in 1998 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 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 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 of development of seizures

15-34 yrs- 30 % caused by trauma <14-14% >65-8%

ClassificationEpileptic seizure- a clinical manifestation presumedto result from an abnormal and excessive dischargeof a set of neurons in the brain. The clinical manifestationconsists 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 byrecurrent (2 or more) epileptic seizures, unprovoked by anyimmediate 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 Causes that lead to seizures that would not

be considered PTE. hydrocephalus sepsis hypoxia metabolic abnormalities Space occupying lesions including hemorrhage Alcohol Drugs including prescription or

illegal/recreational

Precipitants

Medications that possibly lower the seizure threshold 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 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 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:

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

ClassificationFocal Seizures

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 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. 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 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 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 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 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 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 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 prevalence of psychiatric

disorders 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 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- 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 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 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 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 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. Type of seizure Route/frequency of medication Expected adverse effects Co-morbidities

Treatment

Commonly 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

Older agents affect memory and cognitionespecially 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 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 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 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.