You are in: eMedicine Specialties > Neurology > Seizures and Epilepsy Posttraumatic EpilepsyArticle Last Updated: Oct 11, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Ewa Posner, MD, Consultant Paediatrician, Department of Paediatrics, University Hospital of North Durham, UK Ewa Posner is a member of the following medical societies: European Paediatric Neurology Society and Royal College of Paediatrics and Child Health Coauthor(s): Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Editors: Joseph F Hulihan, MD, Vice President, Medical Affairs, Ortho-McNeil Janssen Scientific Affairs, LLC; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Jose E Cavazos, MD, PhD, Assistant Professor, Departments of Medicine (Neurology), Pharmacology, and Physiology, University of Texas Health Science Center at San Antonio; Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital; Helmi L Lutsep, MD, Associate Professor, Department of Neurology, Oregon Health and Science University; Associate Director, Oregon Stroke Center Author and Editor Disclosure Synonyms and related keywords: PTE, head injury, head trauma, posttraumatic seizure, PTS, traumatic brain injury, TBI INTRODUCTIONSection 2 of 10
  BackgroundPosttraumatic epilepsy (PTE) refers to a recurrent seizure disorder, the cause of which is believed to be injury to the brain. This injury can be a result of head trauma or a sequel to an operation on the brain. The term PTE must be differentiated from the term posttraumatic seizure (PTS), which signifies any seizure that occurs as a sequel to brain injury. If the seizures occur within 24 hours of the injury, they are called immediate PTSs. A PTS that occurs within 1 week of injury is termed early PTS, and a seizure that occurs more than 1 week after injury is termed late PTS. About 20% of people who have 1 late PTS never have any more, and these people should not be described as having PTE. PathophysiologyThe mechanism by which trauma to the brain tissue leads to recurrent seizures is unknown. Cortical lesions seem important in the genesis of the epileptic activity. Early seizures are likely to have a different pathogenesis than late seizures; early PTS are thought to be a nonspecific response to the physical insult. In the pathophysiology of the PTE kindling model of epilepsy, damage by free radicals caused by iron deposition from extravasated blood and damage by excitotoxicity due to accumulation of glutamate have been postulated. Some natural antioxidants, such as alpha-tocopherol and condensed tannins, have been demonstrated to be prophylactic for the occurrence of epileptic discharge in the iron-injected animal brain. These studies suggest that the natural antioxidants may be useful alternative medications for preventing PTE. FrequencyUnited StatesAlthough the incidence of epilepsy in the general population is estimated at 0.5-2%, the incidence of PTS for all types of head injuries is 2-2.5% in civilian populations. This incidence increases to 5% in hospitalized neurosurgical patients. When only severe head injuries (usually Glasgow Coma Scale score <9) are considered, the incidence is 10-15% for adults and 30-35% for children. The incidence of PTS is as high as 50% in military series, as these studies include many patients with penetrating head injuries. The incidence of seizures (excluding early seizures) after uncomplicated mild head injury is the same in the military population as in the general population. InternationalThe data above are based on studies from the United States and Europe. In Japan, the occurrence of PTE is approximately 150,000 annually; this equals 10% of all hospitalized patients with head injury and 1% of all outpatients with head injury. Mortality/MorbidityApproximately 80% of first PTS occur within 2 years of the injury. AgeIn the United States, the incidence of brain injury is highest among young adults; this is reflected in the incidence of PTE in the relevant age group. Early PTS are more common in children, while late PTS are more common in adults. CLINICALSection 3 of 10
HistoryThe seizures are usually partial (focal) or generalized tonic-clonic. Often, both types coexist. Most early PTS are partial seizures, whereas most late PTS, especially when part of PTE, are generalized and either primary or secondary. PhysicalNo specific findings are noted on physical examination. CausesBy definition, PTE is a result of injury to the brain. Recent data suggest that neuroimaging and genomic information (eg, haptoglobin genotypes, apolipoprotein E levels) may be helpful in predicting an individual's risk for PTE. Early PTSs are more common in children younger than 5 years, in patients with focal neurologic deficits, and in patients with a linear or depressed skull fracture than in others. Factors that increase the risk of PTE are as follows:
DIFFERENTIALSSection 4 of 10
Absence Seizures Benign Childhood Epilepsy Benign Neonatal Convulsions Complex Partial Seizures Confusional States and Acute Memory Disorders Dizziness, Vertigo, and Imbalance Febrile Seizures First Seizure in Adulthood: Diagnosis and Treatment First Seizure: Pediatric Perspective Frontal Lobe Epilepsy Head Injury Neonatal Seizures Psychogenic Nonepileptic Seizures Temporal Lobe Epilepsy Tonic-Clonic Seizures
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| Drug Name | Sodium valproate (Depakote, Depakene, Depacon |
|---|---|
| Description | Chemically unrelated to other antiseizure drugs. Mechanism of action not established; may be related to increased brain levels of GABA or to enhanced GABA action. May potentiate postsynaptic GABA responses, affect potassium channel, or have direct membrane-stabilizing effect. For conversion to monotherapy, concomitant AED dose ordinarily reduced by about 25% q2wk. Reduction may start with therapy or delayed 1-2 wk if seizures possible with reduction; closely monitor patients during this time for increased seizure frequency. As adjunctive therapy, may be added to regimen at 10-15 mg/kg/d. May increase by 5-10 mg/kg/wk for optimal clinical response. Optimal clinical response usually achieved at <60 mg/kg/d. |
| Adult Dose | 600 mg/d PO divided bid, preferably after food; increase by 200 mg/d at 3-d intervals; not to exceed 2.5 g/d (20-30 mg/kg/d) |
| Pediatric Dose | <2 years: Not recommended; risk of fatal hepatotoxicity >2 years: 20 mg/kg/d PO initially in divided doses; can be increased, not to exceed 35 mg/kg/d |
| Contraindications | Documented hypersensitivity; active liver disease; porphyria; family history of hepatic dysfunction |
| Interactions | Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may reduce levels significantly; in children, salicylates decrease protein binding and metabolism; may result in variable changes of carbamazepine concentrations, with loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels, and either may decrease levels; may displace warfarin from protein-binding sites (perform coagulation tests); may increase zidovudine levels in HIV-positive patients |
| Pregnancy | D - Unsafe in pregnancy |
| Precautions | Thrombocytopenia and abnormal coagulation reported; risk of thrombocytopenia increases significantly at total trough plasma concentrations >110 (women) or >135 (men) mcg/mL; before therapy, periodically, and before surgery, determine platelet counts and bleeding time; reduce dose or discontinue if hemorrhage, bruising, or hemostasis or coagulation disorder occur. Monitor for hepatotoxicity (perform LFTs periodically); hyperammonemia may occur, resulting in hepatotoxicity; monitor closely for malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness |
| Drug Name | Carbamazepine (Tegretol) |
|---|---|
| Description | Indicated for complex partial seizures. May block posttetanic potentiation by reducing summation of temporal stimulation. After therapeutic response, may reduce dose to minimum effective level or discontinue at least once q3mo. |
| Adult Dose | 100-200 mg PO qd/bid; slowly increase to usual dose of 0.8-1.2 g/d in divided doses; not to exceed 1.6-2 g/d |
| Pediatric Dose | <1 year: 100-200 mg/d PO in divided doses 1-5 years: 200-400 mg/d PO in divided doses 10-15 years: 0.6-1g/d PO in divided doses |
| Contraindications | Documented hypersensitivity; AV conduction abnormalities (unless paced); porphyria; history of bone marrow depression; concurrent MAOIs |
| Interactions | Danazol may increase serum levels significantly (avoid within 30 d if possible); cimetidine may increase toxicity, especially if taken in first 4 wk; may decrease primidone, lamotrigine (via hepatic enzyme induction), and phenobarbital levels (coadministration may increase levels); lamotrigine may increase levels of active metabolites, leading to symptoms of cerebellar dysfunction |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | In first trimester, risk of teratogenesis, including neural tube defects, may be increased; in third trimester, manufacturer advises prophylactic vitamin K-1 for mother before delivery (and for neonate) because of risk of neonatal bleeding; counseling, screening, and folate supplements advised. Initiation should be gradual; caution with increased IOP; obtain CBC counts and serum iron level before treatment, during first 2 mo and then yearly or biyearly; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness |
| Drug Name | Phenytoin (Dilantin) |
|---|---|
| Description | May act in motor cortex, inhibiting spread of seizure activity; may inhibit activity of brainstem centers responsible for tonic phase of grand mal seizures. Individualize dose. Administer larger dose before sleep if cannot be divided equally. To minimize GI irritation, administer with or immediately pc. Rapid injection or direct IV injection may cause severe hypotension or CNS depression. |
| Adult Dose | IV loading dose for patients who have not received phenytoin in preceding 7 days: 10-15 mg/kg; rate not to exceed 50 mg/min (25 mg/min in elderly) Maintenance dose: 4-7 mg/kg/d PO/IV |
| Pediatric Dose | IV loading dose: 15-18 mg/kg; rate not to exceed 0.5-1 mg/kg/min or 50 mg/min; in infants, do not give via scalp vein Maintenance dose: 5 mg/kg/d PO/IV divided bid, adjust on basis of clinical signs and serum concentrations |
| Contraindications | May aggravate typical absence seizures; reduce dose in hepatic impairment; sinoatrial block; Adams-Stokes syndrome; second- or third-degree AV block |
| Interactions | Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity; barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects; may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Rapid IV infusion may cause death from cardiac arrest marked by QRS widening; narrow therapeutic index, and relationship between dose and plasma concentration nonlinear (must monitor plasma levels); avoid abrupt withdrawal; perform CBC counts and urinalyses at start and monthly for several months to monitor for blood dyscrasias; discontinue if skin rash occurs and do not resume if exfoliative, bullous, or purpuric; caution in acute intermittent porphyria and diabetes (may elevate blood glucose level); discontinue if hepatic dysfunction occurs |
Posttraumatic Epilepsy excerpt
Article Last Updated: Oct 11, 2006
