Current Treatment Options in Neurology

, Volume 14, Issue 4, pp 293–306 | Cite as

Treatment of Post-Traumatic Epilepsy

EPILEPSY (E WATERHOUSE, SECTION EDITOR)

Opinion statement

Post-traumatic epilepsy (PTE) due to traumatic brain injury is a diagnosis with multifactorial causes, diverse clinical presentations, and an evolving concept of management. Due to sports injuries, work-related injuries, vehicular accidents, and wartime combat, there is rising demand to understand the epidemiology, pathophysiology, diagnosis, prognosis, and treatment of PTE. PTE could occur at any time after injury and up to decades post-injury. The frontal and temporal lobes are the most commonly affected regions, and the resulting epilepsy syndrome is typically localization related. PTE should be actively considered as a diagnosis in any patient with a history of head trauma and episodic neurologic compromise regardless of how temporally remote the trauma occurred. The standard work-up includes a thorough history, neurological examination, neuroimaging, and electroencephalogram. Psychogenic nonepileptic seizures have a high comorbidity with seizures and need to be carefully excluded. PTE can spontaneously remit. For patients who do not go into remission, treatment for confirmed PTE includes antiepileptics, vagal nerve stimulator, and, when appropriate, surgical resection of an epileptogenic lesion. Lifestyle modification and counseling are critical for patients with PTE and should be routinely included in clinical management. The published evidence on the efficacy of various treatment modalities specific to PTE consists largely of retrospective studies and case reports. Despite a unique pathogenesis, the majority of current care parameters for PTE parallel those of standard care for localization-related epilepsy. The potential and need for rigorous clinical research in PTE continue to be in great demand.

Keywords

Traumatic brain injury Head injury Post-traumatic epilepsy Anticonvulsants Seizure Prophylaxis Seizure prevention Continuous EEG monitoring Neuromonitoring 

Introduction

Risk of post-traumatic epilepsy

Traumatic brain injury (TBI) occurs in at least 1.7 million patients per year in the United States, with approximately 80 % of these being mild TBI [1]. This is about 1.8 to 2.5 per 1,000 persons per year. About half a million people in the United States are hospitalized each year for TBI [2]. Approximately 135,000 patients per year in the United States present to the emergency department with head trauma from sports and recreation [1]. In veterans returning from recent wars in Iraq and Afghanistan, 6.7 % to 14.9 % were diagnosed with or self-reported TBI [3, 4]. One analysis approximated that 0.5 % of the entire population of deployed US troops in recent conflicts were likely to develop post-traumatic epilepsy (PTE) [5]. History of a previous TBI increases the likelihood of a repeat TBI, placing patients at a higher risk of developing PTE [6].

PTE is defined as two or more “unprovoked” or “late” seizures 7 days or greater after a TBI. Seizures that occur within the first 7 days after TBI are defined as “provoked” or “early” seizures and are not addressed in this article. The overall risk of developing PTE after TBI is dependent on the severity and mechanism of the injury. Our current understanding of the nature of PTE is based primarily on large retrospective studies of large clinical databases. Table 1 presents commonly used TBI classifications and associated risks of developing PTE
Table 1

Commonly used TBI classifications and associated risks of developing PTE

Type

Clinical presentation [7]

Modified Glasgow Coma Scale [42]

Risk of developing PTE [7]

Mild

Loss of consciousness and/or post-traumatic amnesia for <30 min with no skull fracture

13–15

0.7 %

Moderate

Loss of consciousness and/or post-traumatic amnesia lasting 30 min–24 h and/or skull fracture

9–12

1.2 %

Severe

Loss of consciousness and/or post-traumatic amnesia for >30 min and/or brain contusion, intracranial hematoma

3–8

10 %–12 %

PTE post-traumatic epilepsy, TBI traumatic brain injury

Evidence of damage on neuroimaging increases the risk of developing PTE by 10 % to 25 %. The likelihood of developing epilepsy for nonpenetrating moderately severe head injury without damage seen on CT or MRI is about 5 %. Other neuroimaging findings that significantly correlated with PTE were the degree of hydrocephalus and hypoperfusion of temporal lobes 1 year after trauma.

Intracranial hemorrhage increases risk for PTE by 10-fold [7]. In the Vietnam Head Injury study, 53 % of soldiers with penetrating head injury developed PTE. Half of those patients had persistent seizures 15 years after injury [8]. The risk of PTE after blast injury is not known at this point Additional risk factors for developing PTE may include seizures in the early and late stages after TBI, chronic alcoholism, age, severity of injury, length of post-traumatic amnesia, loss of consciousness, focal neurologic deficits, depressed skull fractures, cerebral contusions, retained bone and metal fragments, brain parenchyma loss, coma duration, low Glasgow Coma Scale, lesion location, and persistent focal electroencephalogram (EEG) abnormality [9, 10]. A family history may suggest a higher risk of PTE in patients with mild or severe TBI [11].

In one population-based study, 86 % of patients with one unprovoked post-traumatic seizure experienced a second seizure within 2 years [12]. This suggests that the risk of developing PTE in patients after one unprovoked post-traumatic seizure is extremely high. Seizure frequency in the first year after injury predicted future severity of seizures [8]. In Vietnam Head Injury study, 11 of 87 patients (12.6 %) developed late-onset seizures 15 to 35 years after PTE [13•]. This suggests that PTE can develop decades after initial trauma and that vigilant long-term medical follow-up is necessary.

Natural history of post-traumatic epilepsy

The seizure remission rate in PTE is about 25 % to 40 % in nonpenetrating head injury [14]. This is similar to the 20 % to 44 % remission rate found in an analysis of several studies examining newly diagnosed epilepsies in untreated populations [15]. This similarity suggests that the remission rate of PTE is currently no different than that of other newly diagnosed epilepsy syndromes, although the PTE data are older and may not take into account improved care.

Several large, retrospective cohort studies compared the mortality rate of moderate to severe TBI patients who survived beyond 1 year to a matched control population and found that patients with TBI were 22 to 37 times more likely to die of seizures [16, 17]. In a separate retrospective study, 27 % of patients with TBI and PTE died at 8 to 15 years after injury, compared with 10 % of matched patients with TBI only [18]. This underscores the importance of PTE prevention, early diagnosis, and treatment.

Diagnosis of post-traumatic epilepsy

The diagnosis of PTE includes a detailed history and physical examination (Fig. 1). Patients often do not consider certain incidences as head trauma (ie, sports-related head trauma, birth-related trauma, physical abuse with blows to the head). Focused questions specifically providing such examples should be asked. Evidence of head trauma can be found on examination from stigmata on the head and neurologic deficits. If the history of head trauma is established, the potential history of seizures should be explored with questions specifically asking for periods of unresponsiveness, altered awareness, disorientation, lost time, or staring. Explore for a history of motor manifestation such as automatisms, picking behavior, facial or limb twitching, or jerking. In a prospective case series, 50 % of moderate to severe TBI patients with seizures were found to be have nonconvulsive seizures. This diagnosis should be considered when a TBI patient is unresponsive [19].
Figure 1

Algorithm for post-traumatic epilepsy (PTE) diagnosis and treatment. EEG, electroencephalography; TBI, traumatic brain injury; VNS, vagus nerve stimulation.

Once the suspicion for seizures is established, further work-up includes an EEG and neuroimaging. MRI imaging should be done with gadolinium and GRE sequence to evaluate the presence of hemosiderin. When reviewing the images, the frontal and temporal lobes should receive close scrutiny, as these are the most affected regions in TBI and PTE. Video EEG monitoring with captured stereotypic events may be necessary if the routine EEG is unrevealing. In MRI-negative patients with potential temporal lobe epilepsy, hypometabolism on positron emission tomography (PET) may assist with diagnosis and surgical planning [20]. Frontal and temporal lobes are the most commonly affected areas, and neuropsychiatric testing can help establish deficits in any of those areas. For those patients who are potential epilepsy surgery candidates, additional testing may include intracranial EEG monitoring, WADA testing, functional MRI, SPECT (single photon emission CT), magnetoencephalography (MEG), and electrocorticography.

During the work-up for PTE, psychogenic nonepileptic seizures (PNES) need to be rigorously excluded in order to avoid unnecessary hospitalizations and medication administration. This is typically a diagnosis dependent on good clinical history and exclusion after a thorough epilepsy work-up. The occurrence of PNES can be quite high. In one retrospective study of 200 veterans and 700 civilians, PNES were identified in 25 % of veterans and 26 % of civilians admitted to the epilepsy monitoring unit (EMU). The delay from onset of spells to EMU diagnosis averaged 60.5 months for veterans and 12.5 months for civilians (P < 0.001) [21•]. Neurobehavioral sequelae of TBI, referred to by some as postconcussive syndrome, may also be confused clinically with PTE, as the two diagnoses share similar symptoms, including impaired attention, poor memory, disorientation, dizziness, irritability, or bizarre behavior [22].

Table 2 illustrates the current understanding of the mechanism of injury from TBI.
Table 2

Current understanding of the mechanism of injury from traumatic brain injury

Biomechanical

 Linear acceleration damaging gray matter and resulting in cortical contusions and hemorrhage

 Rotational head movement resulting in diffuse axonal injury and cerebral lesions and concussion

 Damage to deep gray matter nuclei and axonal tracts in the thalamus and brainstem

Neuroinflammatory response

 Microglial activation

 Upregulation of proinflammatory cytokines

 Blood–brain barrier breakdown

 Upregulation of cell adhesion molecules

 Leukocyte infiltration

 Vascular remodeling

 Hypoperfusion and cerebral edema

Treatment

Pharmacologic treatment

  • The American Academy of Neurology and the Brain Trauma Foundation both make the recommendation to initiate phenytoin in the acute setting of severe TBI to prevent provoked or early seizures. Valproic acid may be administered, although increased mortality may be associated with its use [23, 24, Class II]. Recent studies show that levetiracetam may also be used [25, 26•, Class III].

  • Beyond the first 7 days of severe TBI, prophylactic antiepileptic treatment should not be continued [23, 24, Class II].

  • In one population-based study, 86 % of patients with one unprovoked post-traumatic seizure experienced a second seizure within 2 years, suggesting that the risk of developing PTE in patients after one unprovoked post-traumatic seizure is extremely high [12]. Some physicians recommend antiepileptic therapy after the first unprovoked seizure (Class IV).

  • There is no evidence to support that glucocorticoids prevent the development of PTE [27].

Phenytoin (oral)

Standard dosage

300 to 400 mg/d with a goal of serum level 10 to 20 μg/mL.

Contraindications

Hypersensitivity to phenytoin or hydantoins.

Main drug interactions

Oral contraceptives, some antiretrovirals, coumadin, cefazolin, ciprofloxacin, clozapine, ethanol, some chemotherapies, HMG-CoA reductase inhibitors, valproic acid, felbamate.

Main side effects

Diplopia, ataxia, slurred speech, dizziness, drowsiness, rash, folic acid deficiency, osteomalacia, gingival hypertrophy, hypertrichosis, myelosuppression, Stevens-Johnson syndrome, suicidal ideation.

Pregnancy category

D.

Special points

Monitor serum drug level, creatinine, complete cell count, and liver function tests. Toxicity can result in ataxia and fall risk. Consider avoiding in patients with difficulty with ambulating.

Cost/cost-effectiveness

Inexpensive generic available.

Levetiracetam (oral)

Standard dosage

1,000 to 3,000 mg/d.

Contraindications

Hypersensitivity to levetiracetam.

Main drug interactions

Ketorolac, gingko.

Main side effects

Behavioral symptoms, anorexia, nausea, increased infections, neck pain, headache, asthenia, somnolence, suicidal ideation.

Pregnancy category

C.

Special points

Monitor creatinine at initiation. Levetiracetam can exacerbate irritability, which may be a preexisting condition in TBI patients.

Cost/cost-effectiveness

Inexpensive generic available.

Valproic acid (oral)

Standard dosage

10 to 60 mg/kg per day.

Contraindications

Hepatic disease or dysfunction, hypersensitivity to valproic acid, urea cycle disorders.

Main drug interactions

Lamotrigine, meropenem, ertapenem, primidone, imipenem, warfarin, naproxen, ketorolac, phenytoin, rufinamide, risperidone, olanzapine, acyclovir, felbamate, aspirin, antiretrovirals, phenobarbital, topiramate, carbamazepine, nimodipine, rifampin, erythromycin, mefloquine, amitriptyline, gingko.

Main side effects

Black box warnings for hepatotoxicity, teratogenicity, and pancreatitis; other side effects include sedation.

Pregnancy category

D.

Special points

Monitor serum drug level, liver function tests, ammonia, and platelets.

Cost/cost-effectiveness

Inexpensive generic available.

Phenobarbital (oral)

Standard dosage

20 to 180 mg/d.

Contraindications

Acute intermittent porphyria, hypersensitivity to barbiturates, severe liver dysfunction, dyspnea, sedative addiction.

Main drug interactions

Voriconazole, nifedipine, some antiretrovirals, imatinib, irinotecan, hydromorphone, quetiapine, naproxen, ketorolac, zolpidem.

Main side effects

Somnolence, syncope, erythroderma, megaloblastic anemia, immune hypersensitivity reaction, liver damage, hallucinations.

Pregnancy category

D.

Special points

Monitor serum drug level, complete blood count, creatinine, liver function tests.

Cost/cost-effectiveness

Inexpensive generic available.

Carbamazepine (oral)

Standard dosage

800 to 1,200 mg/d.

Contraindications

Bone marrow depression, recent or active use of monoamine oxidase inhibitor (MAOI), use with nefazodone or rilpivirine, hypersensitivity to carbamazepine or tricyclic compounds.

Main drug interactions

Oral contraceptives, ezogabine, vigabatrin, rufinamide, levetiracetam, lamotrigine, topiramate, phenytoin, valproic acid, primidone, felbamate, midazolam, ketorolac, naproxen, fentanyl, grapefruit juice, tricyclics, haloperidol, selegiline, fluoxetine, clozapine, nifedipine, diltiazem, omeprazole, phenelzine, rilpivirine, nefazodone, praziquantel, ranolazine, voriconazole, procarbazine, irinotecan, some antiretrovirals.

Main side effects

Black box warnings: serious dermatologic reactions, associated with Asian race and HLA-B*1502, aplastic anemia, agranulocytosis; other side effects include atrioventricular block, cardiac dysrhythmia, congestive heart failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, hypocalcemia, hyponatremia (4 %–21.7 %), pancreatitis, hepatitis, acute intermittent porphyria, renal failure, angioedema, blood pressure changes, gastrointestinal symptoms, dizziness, nystagmus, somnolence, blurred vision, suicidal ideation.

Pregnancy category

D.

Special points

Monitor serum sodium, creatinine, complete cell count, liver function tests.

Cost/cost-effectiveness

Inexpensive generic available.

Oxcarbazepine (oral)

Standard dosage

1,200 to 2,400 mg/d.

Contraindications

Hypersensitivity to oxcarbazepine.

Main drug interactions

Oral contraceptives, phenytoin, valproic acid, phenobarbital, lamotrigine, carbamazepine, clopidogrel, naproxen, ketorolac, selegiline, verapamil, simvastatin, some antivirals, tolvaptan, cyclosporine, gingko.

Main side effects

Stevens-Johnson syndrome, toxic epidermal necrolysis, hyponatremia, pancreatitis, agranulocytosis, suicidal thoughts, angioedema, ataxia, dizziness, headache, nystagmus, somnolence, tremor, gastrointestinal symptoms, diplopia, suicidal ideation.

Pregnancy category

C.

Special points

Monitor creatinine and serum sodium.

Cost/cost-effectiveness

Inexpensive generic available.

Zonisamide (oral)

Standard dosage

100 to 600 mg/d.

Contraindications

Hypersensitivity to zonisamide or sulfonamides.

Main drug interactions

Ketorolac, naproxen, metformin, ginkgo.

Main side effects

Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, aplastic anemia, schizophreniform disorder, ataxia, confusion, dizziness, memory impairment, somnolence, gastrointestinal symptoms.

Pregnancy category

C.

Special points

Monitor serum bicarbonate, complete cell count, creatinine, blood urea nitrogen.

Cost/cost effectiveness

Inexpensive generic available.

Felbamate (oral)

Standard dosage

2,400 to 3,600 mg/d.

Contraindications

Blood dyscrasias, hepatic dysfunction, hypersensitivity to felbamate or carbamates.

Main drug interactions

Oral contraceptives, clopidogrel, naproxen, ketorolac, valproic acid, clobazam, carbamazepine, phenytoin, phenobarbital, warfarin, citalopram, methsuximide.

Main side effects

Black box warnings: aplastic anemia, hepatic failure; other side effects include agranulocytosis, Stevens-Johnson syndrome, acute hepatic failure, anaphylactoid reaction, seizure, photosensitivity, weight loss, gastrointestinal symptoms, dizziness, headache, insomnia.

Pregnancy category

C.

Special points

Monitor creatinine, complete cell count, platelets, reticulocyte count, liver function tests.

Cost/cost-effectiveness

Expensive.

Pregabalin (oral)

Standard dosage

150 to 600 mg/d.

Contraindications

Hypersensitivity to pregabalin.

Main side effects

Jaundice, angioedema, peripheral edema, weight gain, constipation, asthenia, ataxia, dizziness, headache, incoordination, somnolence, tremor, diplopia, thought disturbance, euphoria.

Pregnancy category

C.

Special points

A baseline creatinine should be obtained before initiating.

Cost/cost-effectiveness

Expensive (same retail price for all dosage form, 25–300 mg).

Gabapentin (oral)

Standard dosage

900 to 3,600 mg/d.

Contraindications

Hypersensitivity to gabapentin.

Main drug interactions

Naproxen, ketorolac, hydrocodone, morphine, antacids, gingko.

Main side effects

Viral infections, Stevens-Johnson syndrome, drug-induced coma, seizures, suicidality, peripheral edema, gastrointestinal symptoms, ataxia, dizziness, nystagmus, somnolence, hostile behavior, fever.

Pregnancy category

C.

Special points

Monitor creatinine at initiation.

Cost/cost-effectiveness

Inexpensive generic available.

Lacosamide (oral)

Standard dosage

200 to 400 mg/d.

Contraindications

None specifically made, although prolonged PR cardiac interval has been reported.

Main drug interactions

Naproxen, ketorolac.

Main side effects

Nausea, vomiting, ataxia, diplopia, dizziness, headache, fatigue, atrial fibrillation or flutter, first-degree atrioventricular block, suicidal ideation.

Pregnancy category

C.

Special points

Obtain baseline EKG if history of cardiac abnormalities; monitor creatinine at initiation.

Cost/cost-effectiveness

Expensive.

Ezogabine (retigabine) (oral)

Standard dosage

1,200 mg/d in three divided doses.

Contraindications

None known currently.

Main drug interactions

Phenytoin, carbamazepine, lamotrigine, digoxin.

Main side effects

Confusion, incoordination, memory impairment, somnolence, tremor, vertigo, diplopia, urinary retention, prolonged QT interval, transient abnormal liver function tests.

Pregnancy category

C.

Special points

This medication was recently approved by the US Food and Drug Administration in December 2011 for the indication of adjunctive treatment for refractory partial-onset seizures.

Cost/cost-effectiveness

To be determined.

Folic acid (oral)

Standard dose

0.4 mg/d for women of childbearing age [28, Class III].

Contraindications

Allergy to folic acid.

Main drug interactions

May reduce levels of phenytoin, phenobarbital, primidone, barbiturate, pyrimethamine.

Main side effects

Loss of appetite, confusion, irritability, sleep pattern disturbance.

Pregnancy category

A.

Special points

Folic acid levels decrease in patients taking phenytoin, phenobarbital, and valproic acid. Low folic acid levels can result in neural tube defects in newborns.

Cost/cost-effectiveness

Inexpensive.

Calcium supplementation (oral)

Standard dose

1,000 to 1,500 mg/d over two or three divided doses.

Contraindications

Concurrent use with intramuscular or subcutaneous injection of calcium chloride or calcium gluconate.

Main drug interactions

Digoxin, eltrombopag, dasatinib, ciprofloxacin, zalcitabine, tetracyclines, chlorothiazide.

Main side effects

Constipation, metallic taste, nausea, vomiting, bradyarrhythmia, cardiac arrest, hypercalciuria.

Pregnancy category

C.

Special points

Osteopenia and osteoporosis can occur with prolonged valproic acid, carbamazepine, and phenobarbital, making supplementation important.

Cost/cost-effectiveness

Inexpensive.

Surgery

  • Surgical options are often considered when the patient demonstrates medication refractory seizures.

Vagus nerve stimulator (VNS)

Standard procedure

VNS implantation.

Contraindications

Bilateral or left vagotomy, cardiac conduction abnormalities.

Relative contraindications

Swallowing difficulties, dyspnea, obstructive sleep apnea.

Side effects

Voice alteration, cough, dyspnea, dysphagia, nausea, paresthesias.

Complications

Pain, wound infections, transient vocal cord palsy, cardiac arrhythmia during test stimulation, electrode malfunction or fracture, post-traumatic dysfunction of the device [29].

Special points

VNS were approved in 1997 for the treatment of partial-onset epilepsy. This applies to the majority of patients with PTE. In analysis of a subset of data, 28 patients with PTE and implanted with VNS for a mean of 5 years, Elliot et al. [30, Class IV for TBI] found a statistically significant mean reduction of seizures by 68.4 %. This suggests that VNS may be a good option for patients with PTE. In 2005, VNS received approval for refractory depression. Depression has a high comorbidity in patients with TBI and epilepsy, and this adjunctive indication may also be beneficial.

Cost/cost-effectiveness

Expensive up front, also requires maintenance such as clinic visit for reprogramming and surgical procedures for battery change.

Epilepsy surgery

Standard procedure

Resection of seizure focus.

Contraindications

High risk for neurological impairment due to surgical procedure.

Complications

Neurological impairment.

Special points

Surgical resection requires rigorous identification of the seizure focus followed by precise mapping of function related to the seizure focus. This may include intracranial EEG monitoring, WADA testing, functional MRI, neuropsychiatric testing, SPECT, MEG, and electrocorticography. Based on the work-up, if a seizure focus is identified and there is little to no risk of neurological and neuropsychological impairment postoperatively, then surgical resection could potentially provide seizure reduction or resolution. In a retrospective review of 30 patients with PTE who underwent medial temporal lobe resection, no significant differences was found in their postoperative outcomes when compared with matched nontraumatic medial temporal lobe epilepsy surgery outcomes [31, Class IV]. This suggests that patients with PTE may be surgical candidates.

Cost/cost-effectiveness

This treatment modality carries a high cost up front but is cost-effective in the long term if successful.

Assistive devices

  • The following may protect the patient from injury or death.

Nocturnal event monitor: device or human

Usage

Prevention of sudden unexplained death in epilepsy patients (SUDEP).

Special points

There are various kinds of electronic monitoring devices that can be placed on the bed or on the patient to timely alert the patient or a third party about an adverse event, such as unusual motor activity or compromised vital signs. There are other anecdotal events of patients successfully using baby monitors with family members at night to monitor nocturnal seizure activity. Patients with siblings, bed partners, or roommates are also anecdotally said to have increased protection against SUDEP (Class IV).

Cost/cost-effectiveness

Variable.

Seizure alert or seizure response dogs

Usage

For seizure alerting or for response during and after a seizure.

Special points

Seizure alert dogs may detect and warn of an impending seizure seconds to 45 min prior to a seizure. Seizure response dogs perform specific behaviors such as protective behavior or calling for help measures during and immediately after a seizure. The studies examining the effectiveness of seizure dogs were retrospective or observational with very small numbers of subjects. The majority of the studies concluded that some dogs could be trained for seizure alerting or response [32, 33]. One study suggests that seizure dogs may reduce seizure frequency in patients with tonic clonic seizures and without history of psychogenic nonepileptic seizures. In that study, 90 % of subjects showed a 34 % or greater reduction of seizures, and only one patient showed no improvement [34, Class IV].

Cost/cost-effectiveness

The cost of training a seizure dog is estimated to be $10,000 to $25,000.

Exercise

  • In a Norwegian survey-based study, 36 % of patients with epilepsy reported improvement of their seizures with exercise. Ten percent reported worsening of their seizures [35, Class IV].

  • Patients with epilepsy may be at risk of sedentary lifestyles and obesity. This may be compounded by sedating or weight gain side effects of antiepileptics. A survey-based study found that epilepsy patients were 50 % more sedentary and had decreased aerobic capacity [36]. Another survey-based study compared patients with epilepsy with their nonepileptic siblings and found that patients with epilepsy tended to be more overweight and less active [37].

  • Animal studies of TBI preliminarily show that exercise during specific time points may produce an immunomodulatory effect, and this effect may apply to humans [38].

Exercise and sports

Usage

Exercise and sports can be done with some safety planning.

Special points

Water sports, height sports, and motor sports are of higher risk and should receive special consideration.

Cost/cost-effectiveness

Variable.

Diet

  • The ketogenic diet is an established treatment option for refractory seizures in humans, especially in children. There is ongoing research at the animal model stage toward the hypothesis that the ketogenic diet initiated in the early period after TBI may be neuroprotective against brain damage and PTE [39]. There is no published literature specifically addressing the role of the ketogenic diet and PTE in humans.

Ketogenic diet

Usage

A dietician typically assists with implementing the diet.

Special points

The diet is often difficult for adults to tolerate.

Cost/cost-effectiveness

Variable.

Preventive measures

Sleep

  • Sleep deprivation is a known trigger for seizures and would presumably be so for patients with PTE. Counseling on a regular sleep schedule should be included in clinical care.

Caffeine, alcohol, drugs of abuse

  • These substances are known triggers for seizures and would presumably be so for patients with PTE. Counseling and, where appropriate, substance abuse referrals, should be included in clinical care.

Driving

  • Patients with uncontrolled epilepsy are at risk of motor vehicle accidents. Evaluation for driving safety should be addressed with all patients. In some states in the United States, reporting patients with uncontrolled episodes of altered awareness or motor function is mandatory. Physicians are advised to review local state laws regarding their patients and driving.

Safety

  • Safety counseling should be included in clinical care. The patient’s lifestyle should be addressed, including occupational risks, cooking, bathing, swimming, and climbing to heights.

Pregnancy

  • Some antiepileptics are known to lower oral contraceptive protection levels. Special attention and collaboration with the patient’s gynecologist should be practiced. All women of childbearing age should be placed on an antiepileptic with low teratogenicity when possible. The American Academy of Neurology recommends folic acid supplementation for women on antiepileptic medications. Women on phenytoin, phenobarbital, carbamazepine, and valproic acid and women taking more than one antiepileptic are at higher risk of birth defects [28].

Emerging therapies

  • Moderate to severe TBI has the highest risk of PTE, partly due to damage from inflammation, ischemia, hemorrhage, and cerebral edema. A growing trend for the acute management of TBI is neuromonitoring in the intensive care unit. Multiple critical parameters are simultaneously monitored using intracranial probes recording intracranial pressure, cerebral perfusion pressure, cerebral microdialysis, and brain tissue oxygenation level. These parameters help guide timely interventions to protect brain parenchyma [40, Class IV].

  • Continuous and/or quantitative EEG is increasingly utilized for monitoring critically ill TBI patients. In addition to recording epileptiform abnormalities, EEG registers CBF decreases below 25 to 30 mL/100 g/min within minutes [41, Class IV]. Hemorrhagic lesions can also be appreciated on EEG. This allows timely diagnosis and treatment. Quantitative EEG analyzes large time periods of EEG and allows rapid interpretation of the record.

Multimodal neuromonitoring

Standard procedure

Intracranial pressure, cerebral microdialysis, brain tissue oxygenation level.

Contraindications

Non-candidate for intracranial probe placement.

Complications

Pain, infection, intracranial hemorrhage.

Special points

The relationship between collected data from neuromonitoring and their clinical significance is still under investigation.

Cost/cost-effectiveness

Expensive.

Continuous or quantitative electroencephalogram

Standard procedure

Electrode is placed on patient’s head, and data are recorded and interpreted.

Contraindications

Electrodes cannot be placed on patient’s head.

Complications

None.

Special points

Timely review of the record needs to be assured.

Cost/cost-effectiveness

Expensive.

Notes

Disclosure

No potential conflicts of interest relevant to this article were reported.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2012

Authors and Affiliations

  1. 1.Department of Neurology, Department of Veterans Affairs (VA)Greater Los Angeles Healthcare SystemLos AngelesUSA
  2. 2.Department of NeurologyUniversity of CaliforniaLos AngelesUSA

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