Abstract
Epilepsy is a neurologic disease with a yearly incidence of 0.5% to 2.3%, with up to 40% of patients developing intractable disease. Seizures can manifest as either partial seizures (simple, complex, or partial leading to general) or generalized seizures (absence, myoclonic, tonic-clonic, or atonic). Although the exact etiology of epilepsy is unknown, there are several congenital and acquired diseases associated with it. The disease management goal is to optimize the patient’s ability to function. This includes a complete workup of the disease and the patient’s comorbidities. Treatment can range from expectant to pharmacological to interventional. Anticonvulsant therapy can complicate induction and maintenance of and emergence from anesthesia. The anesthesiologist involved in a patient having an active seizure should be prepared to stop the seizure, secure the airway, and manage any physiologic sequelae of the seizure.
Keywords
epilepsy, anticonvulsants, simple partial seizures, complex partial seizures, tonic-clonic seizures, interventional treatment of seizure disorder
Case Synopsis
A 33-year-old woman presents for a partial mastectomy and axillary lymph node biopsy. She has a history of seizure disorder well controlled on levetiracetam and mild asthma requiring occasional rescue with an albuterol inhaler. Her physical examination is normal.
Problem Analysis
Definition
Epilepsy is a type of neurologic disease that is caused by abnormal electrical activity in one (focal) or more (general) loci in the cerebral cortex. Its presentation depends on the location and severity of the seizure activity. The yearly incidence is estimated to be 0.5% to 2.3%, with up to 40% of patients developing intractable seizures (greater than one per month). Approximately 400,000 people in the United States have medically uncontrolled epilepsy. Two cases per 1000 patients per year result in sudden death. Various neurologic diseases are associated with epilepsy or the use of anticonvulsant drugs, such as migraines, depression, psychosis, mood or behavioral disorders, and chronic pain. The use of anticonvulsants for these conditions can influence how anesthesiologists treat these patients.
The type of seizures that a patient experiences (as well as the patient’s allergies) can determine which treatment regimen is prescribed. Seizures can be classified as partial or general. Partial seizures occur in one hemisphere and can be subdivided as follows:
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Simple partial seizures: no change in mental status
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Complex partial seizures: change in mental status
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Partial seizure leading to generalized seizure
Generalized seizures occur globally in the cortexes that affect both hemispheres. They are associated with changes in mental status and can be subdivided as follows:
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Absence seizures
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Myoclonic seizures
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Tonic-clonic seizures
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Atonic seizures
Complex partial seizures are the most common form of epilepsy, accounting for approximately 25% of adult and 40% of pediatric epileptics. Tonic-clonic seizures, the second most common, account for about 25% of adult and 19% of pediatric epileptics.
The exact etiology of epilepsy is not completely understood. Seizures are associated with congenital diseases such as tuberous sclerosis, neurofibromatosis, multiple endocrine adenomatosis, and Jervell-Lange-Neilson syndrome. Pathologies associated with traumatic brain injury, stroke, brain tumor, and Alzheimer’s disease are also associated with epilepsy.
Absence seizures are often triggered by stimuli such as bright or flashing lights and are thought to be caused by changes in communication between the thalamus and the frontal, visual, auditory, and somatosensory cortexes. This can lead to a dissociated state similar to non–rapid eye movement sleep in an otherwise awake patient. The success of treatment with valproic acid and ethosuximide suggests that γ-aminobutyric acid (GABA) receptors (valproic acid, benzodiazepines) and T-type calcium channels (ethosuximide) may be involved.
Other generalized seizures involve intense muscular activity (myoclonic, tonic-clonic) that are thought to be caused by frequent depolarization of sodium channels. Subsequently, a decrease in the number of voltage-stabilizing potassium channels has also been studied.
Partial seizures (simple and complex) may be caused by dysfunction of the GABA receptor leading to an increase of excitability and decreased inhibition of neurons affected.
Because of the limited contact with the patient in the perioperative arena, the anesthesiologist should consult with the medical providers managing the patient with epilepsy. The patient’s evaluation should include the following:
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History of the diagnosis of the seizure disorder
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Possible etiologies of the seizure disorder
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Current and past managements of the seizure disorder
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Effectiveness of current pharmacologic regimen
The goal of the patient’s management is to optimize the patient’s ability to function. This includes the following:
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Minimizing the frequency and severity of epileptic attacks
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Surgical management of cerebral causes (masses, hydrocephalus, traumatic brain injury, stroke, bleeding, seizure foci)
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Balancing treatment regimens with side effects
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Compliance with therapeutic plan
In the absence of family history, a clear medical causality, and a negative electroencephalogram (EEG), a single epileptic episode (which may be a misdiagnosis) can lead to only expectant management. The chance of a recurrent seizure is about 25%; however, subsequent episodes increase the risk to 80%, and pharmacologic management is recommended. If an organic cause is diagnosed, the patient should be started on medication and invasive interventions may be indicated.
Parturients with epilepsy have an increased risk of the following:
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Passing on congenital abnormalities secondary to hereditary or pharmacologic causes
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Changes in pharmacokinetic effects of existing therapies due to physiologic changes of pregnancy
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Changes in therapy that may lead to subtherapeutic efficacy because of possible teratogenic effects of prepartum drug regimens
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Risk of preterm labor, preeclampsia, abruption, and intrauterine death
The pharmacologic regimen is determined by the patient’s primary medical provider. The goals are as follows:
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Expectant management
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One medication
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Combination therapy (two or more medications)
The primary management should balance efficacy with side effects, optimizing the patient’s ability to function, as well as ability to maintain compliance. If one regimen fails because of lack of efficacy or unacceptable side effects (including allergic reactions and pregnancy), the provider should look at one or more medications that work at alternative mechanisms of action.
If pharmacologic therapy fails to control epilepsy, interventional therapy may be considered. Vagal nerve stimulation (VNS), deep brain stimulation (DBS), or even a partial or total temporal lobectomy may be indicated, depending on the etiologies of the seizure disorder. VNS is referred to as a “pacemaker for the brain” according to the Epilepsy Foundation. DBS, originally advocated for treating Parkinson’s disease, has shown promise in treating epilepsy in patients failing pharmacologic and VNS therapy. Ultimately, if seizure foci can be identified with functional magnetic resonance imaging (fMRI) or EEG mapping, partial or total temporal lobectomy may be considered.
A new therapy, MRI-guided laser interstitial thermal therapy, is being evaluated. The procedure involves stereotactic placement of fiberoptic fibers into the defined foci. Under MRI guidance the foci are ablated by heat generated by a laser. It is considerably less invasive than a craniotomy for lobectomy.
Recognition
Anesthesiologists caring for a patient with epilepsy should take into account the following:
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Frequency and sequelae of seizure activity
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Effectiveness of current treatment regimens
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Compliance with prescribed treatment regimens
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Triggers
Triggers include bright or flashing lights, noise, hunger, hypoglycemia, thirst, caffeine withdrawal, drug and substance intoxication or withdrawal, sleepiness, fatigue, stress, and anxiety. These triggers should be addressed in the perioperative period.
Risk Assessment
Patients with seizure disorders have a 20-fold increase in mortality risk, and this does not include other comorbidities that the patient may have. There are neurologic, cardiac, and pulmonary sequelae to epilepsy that can affect medical perioperative management of the patient. Nonperioperative effects such as impaired cognitive function from recurrent seizures, associated diseases (e.g., cerebral palsy), social isolation, stigma from the disease, and infantilization of a pediatric/adolescent patient can complicate the ability to obtain informed consent, obtain intravenous access, and ensure postoperative support. Patients on anticonvulsants often suffer from polypharmacy, including antidepressants, central-acting muscle relaxants, benzodiazepines, and pain medications.
Anticonvulsants can be sedating, which can effect induction of, maintenance of, and emergence from anesthesia. Many anticonvulsants induce cytochromes in hepatic metabolism, increasing the metabolism of aminosteroid nondepolarizing muscle relaxants (vecuronium, rocuronium). The binding drug sugammadex has decreased the incidence of overrelaxation to compensate, but its use is cautioned in women of childbearing age and patients with an allergy to sugammadex.