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Seizures and Epilepsy Valproic acid, phenobarbital, and phenytoin are associ- Seizures and Epilepsy in ated with MCMs and lower IQ in offspring; these drugs should Specific Populations be avoided if possible. Topiramate, carbamazepine, and AED Older Adults polypharmacy also should also be avoided because of increased Incidence of new-onset epilepsy is highest in older adults (age MCM risk. Valproic acid is associated with neural tube defects, >60 years). Because recurrence after a new-onset seizure in and topiramate with cleft lip and palate. Topiramate is of spe- this age group is more likely (50% to 60%) than in younger cial concern given its ability to induce metabolism of estrogen- adults (40%), treatment after one seizure is sometimes consid- containing contraceptive agents, leading to unexpected ered. Major risk factors for seizure recurrence include stroke pregnancy with teratogenicity. and dementia. Older adults usually require lower AED doses Serum levels of lamotrigine, oxcarbazepine, and leveti- and are at increased risk of drug interactions and decreased racetam are known to decrease significantly during pregnancy. drug clearance. Data suggest that levetiracetam, lamotrigine, For lamotrigine, a dose escalation of approximately 50% is and gabapentin are better tolerated and no less effective when needed to maintain therapeutic levels and prevent seizures; compared with older AEDs (see Table 20). Valproic acid should levels should be followed at least monthly during pregnancy. be used with caution because it can cause (reversible) parkin- Once delivery occurs, the lamotrigine dose should be rapidly sonism and cognitive dysfunction. decreased to avoid a sudden increase in serum levels and tox- icity risk. Breastfeeding is recommended in most women with epi- e In older patients, levetiracetam, lamotrigine, and lepsy who take AEDs, as benefits generally outweigh risks. gabapentin are better tolerated and no less effective Infant sedation is a concern, but AED exposure through breast when compared with older antiepileptic drugs. milk is probably less than that in utero.

Valproic acid, phenobarbital, and phenytoin are associ- Seizures and Epilepsy in ated with MCMs and lower IQ in offspring; these drugs should Specific Populations be avoided if possible. Topiramate, carbamazepine, and AED Older Adults polypharmacy also should also be avoided because of increased Incidence of new-onset epilepsy is highest in older adults (age MCM risk. Valproic acid is associated with neural tube defects, >60 years). Because recurrence after a new-onset seizure in and topiramate with cleft lip and palate. Topiramate is of spe- this age group is more likely (50% to 60%) than in younger cial concern given its ability to induce metabolism of estrogen- adults (40%), treatment after one seizure is sometimes consid- containing contraceptive agents, leading to unexpected ered. Major risk factors for seizure recurrence include stroke pregnancy with teratogenicity. and dementia. Older adults usually require lower AED doses Serum levels of lamotrigine, oxcarbazepine, and leveti- and are at increased risk of drug interactions and decreased racetam are known to decrease significantly during pregnancy. drug clearance. Data suggest that levetiracetam, lamotrigine, For lamotrigine, a dose escalation of approximately 50% is and gabapentin are better tolerated and no less effective when needed to maintain therapeutic levels and prevent seizures; compared with older AEDs (see Table 20). Valproic acid should levels should be followed at least monthly during pregnancy. be used with caution because it can cause (reversible) parkin- Once delivery occurs, the lamotrigine dose should be rapidly sonism and cognitive dysfunction. decreased to avoid a sudden increase in serum levels and tox- icity risk. Breastfeeding is recommended in most women with epi- e In older patients, levetiracetam, lamotrigine, and lepsy who take AEDs, as benefits generally outweigh risks. gabapentin are better tolerated and no less effective Infant sedation is a concern, but AED exposure through breast when compared with older antiepileptic drugs. milk is probably less than that in utero. Women with Epilepsy Contraception Women with epilepsy (WWE) may experience seizures around Enzyme-inducing AEDs (see Table 22) increase oral contracep- menstruation or ovulation. Some studies suggest adding pro- tive metabolism, which increases chances of pregnancy. gestin-containing oral contraceptives or acetazolamide to the Alternate methods of contraception, such as intrauterine AED regimen, but oophorectomy is not recommended to devices or barrier methods, are recommended. improve seizure control.

Women with Epilepsy Contraception Women with epilepsy (WWE) may experience seizures around Enzyme-inducing AEDs (see Table 22) increase oral contracep- menstruation or ovulation. Some studies suggest adding pro- tive metabolism, which increases chances of pregnancy. gestin-containing oral contraceptives or acetazolamide to the Alternate methods of contraception, such as intrauterine AED regimen, but oophorectomy is not recommended to devices or barrier methods, are recommended. improve seizure control. Reproductive Issues e In women with epilepsy who are of child-bearing Evidence is contradictory about WWE having decreased fertil- potential, levetiracetam and lamotrigine have minimal ity rates. Valproic acid, however, is associated with anovula- evidence of teratogenicity and are the preferred treat- tion and polycystic ovary syndrome. ment options.

Evidence is contradictory about WWE having decreased fertil- potential, levetiracetam and lamotrigine have minimal ity rates. Valproic acid, however, is associated with anovula- evidence of teratogenicity and are the preferred treat- tion and polycystic ovary syndrome. ment options. e Discovery of pregnancy alone is not reason enough to Pregnancy and Nursing stop antiepileptic drugs in women with epilepsy whose Most WWE have normal, healthy children. The rate of disease is well controlled; women with epilepsy must major congenital malformations (MCMs) in untreated WWE balance risk of teratogenicity with risk of uncontrolled mirrors that of the general population. All WWE of child- seizures, particularly generalized tonic-clonic seizures, bearing potential should receive preconception counseling which can result in fetal anoxia and death. and folate supplementation. WWE who take AEDs are e Valproic acid, phenobarbital, phenytoin, topiramate, unlikely to have an increased risk of cesarean section, late- carbamazepine, and antiepileptic drug polypharmacy pregnancy bleeding, or premature delivery, unless they are associated with major congenital malformations smoke; however, they may be at risk of having a small-for- and, if possible, should be avoided in pregnant women gestational age child. The best predictor of seizure control with epilepsy. during pregnancy is seizure frequency in the previous 9 to 12 months. Levetiracetam and lamotrigine are the preferred treat- Status Epilepticus ment options because of the lower risk of teratogenicity. Not all seizures require emergent treatment. Most GTCS will Patients with difficult to control seizures, however, may need cease spontaneously within 2 to 3 minutes. Treatment also dif- to continue teratogenic medications such as valproic acid. fers depending on the type of status epilepticus. Convulsive Discovery of pregnancy alone is not reason enough to stop or status epilepticus (CSE) is analogous to ventricular fibrillation change AEDs if epilepsy is well controlled. Physicians must (true emergency). Nonconvulsive status epilepticus (NCSE) is balance risk of teratogenicity with risk of uncontrolled sei- analogous to atrial fibrillation with or without rapid ventricular zures, particularly GTCS, which can result in fetal anoxia and response (management varies with symptom severity). Seizure death. etiology most often determines outcome; thus, evaluation for

e Discovery of pregnancy alone is not reason enough to Pregnancy and Nursing stop antiepileptic drugs in women with epilepsy whose Most WWE have normal, healthy children. The rate of disease is well controlled; women with epilepsy must major congenital malformations (MCMs) in untreated WWE balance risk of teratogenicity with risk of uncontrolled mirrors that of the general population. All WWE of child- seizures, particularly generalized tonic-clonic seizures, bearing potential should receive preconception counseling which can result in fetal anoxia and death. and folate supplementation. WWE who take AEDs are e Valproic acid, phenobarbital, phenytoin, topiramate, unlikely to have an increased risk of cesarean section, late- carbamazepine, and antiepileptic drug polypharmacy pregnancy bleeding, or premature delivery, unless they are associated with major congenital malformations smoke; however, they may be at risk of having a small-for- and, if possible, should be avoided in pregnant women gestational age child. The best predictor of seizure control with epilepsy. during pregnancy is seizure frequency in the previous 9 to 12 months. Levetiracetam and lamotrigine are the preferred treat- Status Epilepticus ment options because of the lower risk of teratogenicity. Not all seizures require emergent treatment. Most GTCS will Patients with difficult to control seizures, however, may need cease spontaneously within 2 to 3 minutes. Treatment also dif- to continue teratogenic medications such as valproic acid. fers depending on the type of status epilepticus. Convulsive Discovery of pregnancy alone is not reason enough to stop or status epilepticus (CSE) is analogous to ventricular fibrillation change AEDs if epilepsy is well controlled. Physicians must (true emergency). Nonconvulsive status epilepticus (NCSE) is balance risk of teratogenicity with risk of uncontrolled sei- analogous to atrial fibrillation with or without rapid ventricular zures, particularly GTCS, which can result in fetal anoxia and response (management varies with symptom severity). Seizure death. etiology most often determines outcome; thus, evaluation for 24

Seizures and Epilepsy Acute Stabilization Airway and vital sign monitoring (oxygen, ECG, fingerstick glucose) Obtain IV access Give thiamine and glucose Obtain CBC, BMP, and (if appropriate) toxicology/alcohol/antiepileptic drug levels | If seizure does not cease within 5 min of onset First Line: Benzodiazepine Lorazepam 0.1 mg/kg/dose IV (max 4 mg/dose, may repeat once), or Diazepam 0.15-0.2 mg/kg/dose IV (max 10 mg/dose, may repeat once), or If seizure ceases Midazolam 10 mg IM (single dose) If seizure does not cease within 20 min of onset Y Second Line: IV Antiepileptic Drug Fosphenytoin, 20 mg PE/kg (max, 1500 mg/dose), or Valproic acid, 40 mg/kg (max, 3000 mg/dose), or Levetiracetam, 60 mg/kg (max, 4500 mg/dose) Obtain head CT | If seizure does not cease within 40 min of onset If patient does not recover to | baseline within 30 minutes Third Line: IV Anesthetic? Intubation Immediate continuous Vv Avoid long-acting paralytic agents to facilitate examination EEG monitoring Choose propofol, midazolam, pentobarbital, or thiopental FIGURE 10. Management guidelines for convulsive status epilepticus. BMP = basic metabolic panel; CBC = complete blood count; EEG = electroencephalographic; IM = intramuscular; IV = intravenous; max = maximum; PE = phenytoin equivalents. °Or choose an appropriate second-line agent.

Intubation Immediate continuous Vv Avoid long-acting paralytic agents to facilitate examination EEG monitoring Choose propofol, midazolam, pentobarbital, or thiopental FIGURE 10. Management guidelines for convulsive status epilepticus. BMP = basic metabolic panel; CBC = complete blood count; EEG = electroencephalographic; IM = intramuscular; IV = intravenous; max = maximum; PE = phenytoin equivalents. °Or choose an appropriate second-line agent. serious causes (meningitis, intracranial hemorrhage) must in valproic acid or IV levetiracetam. There is insufficient evidence parallel with treatment. If meningitis is suspected, head CT is to support the use of lacosamide as a standard treatment in usually indicated before lumbar puncture, but no test should CSE. delay antibiotic administration. If convulsions stop, but the patient does not either improve within 10 minutes or return to baseline within 30 Convulsive Status Epilepticus minutes, immediate continuous EEG is required to diagnose CSE is defined as a generalized tonic-clonic seizure lasting NCSE. NCSE after CSE is still a medical emergency and should more than 5 minutes, or two within 5 minutes without return be treated aggressively. If convulsive seizure activity does not to baseline in between. CSE is diagnosed clinically and pre- cease, intubation is typically required, and patients are typi-

CSE is defined as a generalized tonic-clonic seizure lasting NCSE. NCSE after CSE is still a medical emergency and should more than 5 minutes, or two within 5 minutes without return be treated aggressively. If convulsive seizure activity does not to baseline in between. CSE is diagnosed clinically and pre- cease, intubation is typically required, and patients are typi- sents as continuous generalized clonic jerking of the entire cally placed in an anesthetically induced coma for 24 to 48 hours using propofol, midazolam, or pentobarbital. IV body. Unless PNES is strongly suspected, empiric therapy is anesthesia carries considerable risk, including prolonged ICU indicated without awaiting results of EEG, imaging, serum hospitalization and associated morbidity (e.g., infection, deep studies, or lumbar puncture because a longer duration of CSE is strongly linked to worse outcomes. venous thrombosis). Continuous EEG monitoring is manda- tory. Hypotension is most common with pentobarbital, which Securing the airway and obtaining intravenous (IV) access may accumulate in tissues and require many days for clear- are the first steps in management (Figure 10). If point-of-care ance. Midazolam is less morbid but often leads to tolerance glucose testing is not available, thiamine should be given, followed by IV glucose. First-line treatment is an intravenous and tachyphylaxis.

sents as continuous generalized clonic jerking of the entire cally placed in an anesthetically induced coma for 24 to 48 hours using propofol, midazolam, or pentobarbital. IV body. Unless PNES is strongly suspected, empiric therapy is anesthesia carries considerable risk, including prolonged ICU indicated without awaiting results of EEG, imaging, serum hospitalization and associated morbidity (e.g., infection, deep studies, or lumbar puncture because a longer duration of CSE is strongly linked to worse outcomes. venous thrombosis). Continuous EEG monitoring is manda- tory. Hypotension is most common with pentobarbital, which Securing the airway and obtaining intravenous (IV) access may accumulate in tissues and require many days for clear- are the first steps in management (Figure 10). If point-of-care ance. Midazolam is less morbid but often leads to tolerance glucose testing is not available, thiamine should be given, followed by IV glucose. First-line treatment is an intravenous and tachyphylaxis. benzodiazepine. If IV access is not available, diazepam may be given rectally or intramuscularly, although absorption is ¢ In patients with likely convulsive status epilepticus erratic. Fear of respiratory depression should not limit treat- (CSE), empiric therapy is indicated without awaiting ment; there is clear evidence that intubation rates are lower results of electroencephalography, imaging, serum stud- when CSE is treated with benzodiazepines. ies, or lumbar puncture because a longer duration of Typically, benzodiazepines should be followed by an IV CSE is strongly linked to worse outcomes. AED to avoid seizure recurrence. Fosphenytoin is preferred ¢ First-line treatment of convulsive status epilepticus is over phenytoin because it can be infused more rapidly and has an intravenous benzodiazepine typically followed by a lower incidence of skin necrosis (due to drug extravasation). an intravenous antiepileptic drug to avoid seizure Both fosphenytoin and phenytoin can cause acute bradycardia recurrence. and hypotension. Alternative second-line therapies include IV

benzodiazepine. If IV access is not available, diazepam may be given rectally or intramuscularly, although absorption is ¢ In patients with likely convulsive status epilepticus erratic. Fear of respiratory depression should not limit treat- (CSE), empiric therapy is indicated without awaiting ment; there is clear evidence that intubation rates are lower results of electroencephalography, imaging, serum stud- when CSE is treated with benzodiazepines. ies, or lumbar puncture because a longer duration of Typically, benzodiazepines should be followed by an IV CSE is strongly linked to worse outcomes. AED to avoid seizure recurrence. Fosphenytoin is preferred ¢ First-line treatment of convulsive status epilepticus is over phenytoin because it can be infused more rapidly and has an intravenous benzodiazepine typically followed by a lower incidence of skin necrosis (due to drug extravasation). an intravenous antiepileptic drug to avoid seizure Both fosphenytoin and phenytoin can cause acute bradycardia recurrence. and hypotension. Alternative second-line therapies include IV 25