Epilepsy, Epilepsy Surgery

I. Epilepsy

Definitions
Epileptic seizures are the clinical manifestations (signs and symptoms) of excessive and/or hypersynchronous abnormal activity of neurons in the cerebral cortex. This activity is usually self-limited. The features of the seizure reflect the functions of the cortical areas from which the abnormal activity originates and to which it spreads. Epileptic seizures have electrophysiologic correlates that are recorded on a scalp electroencephalogram (EEG).
Epilepsy is a chronic disorder caused by a variety of pathologic processes in the brain and is characterized by epileptic seizures. The incidence of epilepsy ranges from 0.5% to 2% of the total population; 25% to 30% of persons who have epilepsy experience more than one seizure a month.
Classification of epileptic seizures
Partial seizures have an onset that is localized or focal within the brain.
1. Simple partial. Alteration in consciousness does not occur during these seizures. They are classified according to symptoms: motor, sensory, autonomic, and psychic. Auras are the sensory, autonomic, or psychic symptoms that precede a progression to impaired consciousness or motor seizure.
2. Complex partial. These seizures spread into multiple areas of the brain and alter consciousness; they are also called psychomotor or temporal lobe seizures. A simple partial seizure can progress to become complex.
3. Convulsive. These seizures have a partial onset but then spread to involve most areas of the brain and brain stem. They are not easily distinguishable from generalized seizures.
Generalized seizures when the EEG shows simultaneous involvement of both cerebral hemispheres and consciousness is impaired. These seizures are the following:
1. Inhibitory or nonconvulsive, such as atonic or absence seizures (petit mal)
2. Excitatory or convulsive, which produce myoclonic, tonic, or clonic seizures
Unclassified seizures
Mechanisms of epilepsy are diverse and include abnormalities in the regulation of neural circuits and the balance of neural excitation and inhibition. Factors that influence the appearance of epilepsy can be genetic, environmental, or physiologic.
Associated medical problems include the following:
Psychiatric disorders
Rare syndromes: tuberous sclerosis, neurofibromatosis, multiple endocrine adenomatosis
History of trauma
Sleep deprivation
Treatment of epilepsy
Medical therapy involves the following:
1. Various antiepileptic drugs are used: phenytoin, phenobarbital, primidone, carbamazepine, clonazepam, valproic acid, and diazepam. Some of the newer drugs are gabapentin, lamotrigine, and topiramate.
2. Treatment consists of either a single medication or multiple drug therapy.
3. The choice depends on considerations of the pharmacokinetics, clinical toxicity, efficacy, and type of epilepsy.
Adverse effects of antiepileptic drugs are dose dependent and are usually associated with long-term therapy. Newer drugs claim to have fewer side effects.
1. Many drugs have neurologic side effects including sedation, confusion, learning impairment, and ataxia as well as gastrointestinal problems such as nausea and vomiting.
2. Most anticonvulsants are metabolized by the liver. Therefore, long-term usage may cause induction of liver enzymes, which increases the rate of metabolism of other drugs, particularly anesthetics.
3, Long-term therapy with phenytoin causes gingival hyperplasia with poor dentition and, potentially, difficulties with airway management.
4. Carbamazepine can depress the hemopoietic system and, in rare cases, causes cardiac toxicity.
5. Valproic acid may occasionally lead to thrombocytopenia and platelet dysfunction.
Surgical treatment. Epilepsy is deemed refractory if unacceptable side effects associated with antiepileptic drugs preclude adequate seizure control. This occurs in 5% to 30% of patients. Approximately 15% to 20% of patients who have intractable epilepsy are candidates for surgical resection of the epileptogenic focus.
Status epilepticus
Status epilepticus is defined as epileptic seizures that are so frequently repeated or so long in duration that they create a fixed and lasting epileptic condition, either convulsive or nonconvulsive. This is considered a neurologic emergency.
Treatment. To prevent brain damage, seizures must be stopped as quickly as possible. Approaches for treatment are as follows:
1. Secure the airway, provide oxygen, and maintain circulation.
2. Protect the patient from traumatic injury secondary to involuntary motor movements.
3. If hypoglycemia is present or cannot be ruled out, 50% glucose, 50 mL intravenously (i.v.), and thiamine, 100 mg i.v., should be given.
4. There are different approaches, but the initial drug choices usually include phenobarbital, phenytoin, and benzodiazepines; an example is diazepam, 0.2 mg/kg i.v., or lorazepam, 0.1 mg/kg i.v., followed by phenytoin, 15 to 20 mg/kg, given slowly at a rate of no >50 mg/minute.
5. Seizures that continue to be refractory might require barbiturate coma titrated to EEG effect.
6. Other anesthetic drugs that have been used include etomidate, ketamine, propofol, halothane, enflurane, isoflurane, and desflurane.
Pro- and anticonvulsant effects of anesthetic drugs. Numerous reports describe how anesthetic agents can paradoxically exhibit convulsant and anticonvulsant properties with different doses, under different physiologic situations, and with different species.
The inhalation drugs isoflurane and desflurane are effective anticonvulsants. Although controversial, sevoflurane has also been shown to produce epileptiform activity. Nitrous oxide (N₂O) does not have any anticonvulsant properties, nor does it produce seizure activity on EEG.
Barbiturates are anticonvulsants, but when given in small doses, thiopental and methohexital activate the epileptiform activity from a seizure focus, as indicated by EEG monitoring. Etomidate and ketamine can activate the epileptogenic focus and have also been used to treat status epilepticus. Benzodiazepines are effective anticonvulsants. Propofol is an anticonvulsant but there have been controversial reports of seizure and seizure-like activity after its use in patients who have and do not have epilepsy.
Opioids (e.g., fentanyl, alfentanil, and remifentanil) can activate the epileptiform activity from a seizure focus in patients who have epilepsy.
Local anesthetic drugs are anticonvulsant in low doses but, at higher serum concentrations, can produce central nervous system excitation.
Interaction between anesthetic and antiepileptic drugs
The requirements for muscle relaxants, opioids, and barbiturates increase in patients taking most anticonvulsants, particularly phenytoin and phenobarbital, on a long-term basis owing to the enhanced activity of hepatic microsomal enzymes, which accelerates hepatic biotransformation.
Interactions with endogenous neurotransmitters and changes in the number of receptors, including opioid, may occur.
Anesthetic management of an epileptic patient for nonepilepsy surgery
Preoperative assessment focuses on the following:
a. General assessment and preparation
b. Specific concerns with an epileptic patient
(1) Medical problems including psychiatric disorders associated with epilepsy
(2) Complications from anticonvulsant therapy
(3) Continuation of anticonvulsant therapy
Anesthetic management and monitoring depend on the needs of the patient and the procedure.
1. Drugs that potentiate seizure activity should not be used.
2. The requirement for anesthetic drugs may increase.
3. Consideration should be given to the administration of additional doses of antiepileptic drugs during prolonged procedures.
4. Hyperventilation might potentiate seizure activity and should be avoided unless necessary for surgery.
5. Seizures can occur postoperatively because anesthetic drugs and changes in body physiology during the operation can significantly affect blood levels of anticonvulsants.

II. Epilepsy surgery

Procedure
Surgery for partial seizure disorders involves the resection of a specific epileptogenic focus that may show either sclerosis or gliosis. This is frequently accomplished by some form of a temporal lobectomy.
Generalized seizures are treated by interrupting the seizure circuits by a corpus callosotomy or a hemispherectomy.
A patient who either remains seizure free or has a significant reduction in seizure frequency is considered a surgical cure. This occurs in 50% to 80% of patients.
Cognitive improvement also results because the doses of anticonvulsive drugs are either reduced or eliminated.
Patient suitability for epilepsy surgery. A complete multidisciplinary evaluation is needed to assess whether the patient is a candidate for epilepsy surgery. Invasive and noninvasive investigations are needed to identify the origin of seizure activity and to evaluate the feasibility of performing surgery safely with minimal risk of neurologic and cognitive injury. Advances in neuroimaging techniques have reduced the need for invasive evaluation.
Noninvasive evaluation includes medical history; assessment of the frequency, severity, and type of seizures; physical examination; and psychosocial and neuropsychiatric testing. Surface-electrode monitoring of EEG activity may also be combined with video-camera monitoring of the seizures.
Radiologic imaging can supplement EEG data. Computed tomographic (CT) scanning and magnetic resonance imaging (MRI) can help identify areas of sclerosis and low-grade intracranial neoplasms.
Functional imaging is accomplished with positron emission tomography, single-photon emission CT scan, and functional MRI and spectroscopy to assess brain activity, cerebral blood flow, and the metabolic effects of resection of the seizure focus.
Thiopental testing may be performed to assist in EEG localization of the seizure focus. The technique is accomplished by producing a gradual increase in the blood level of thiopental during EEG recording. This causes an increase in beta activity in normally functioning neural tissue but not in the seizure focus.
Intracarotid sodium amytal injection (Wada test) is used to test for lateralization of language and memory.
Invasive evaluation is accomplished by the insertion of intracranial electrodes. Epidural electrodes are inserted through multiple burr holes; subdural grids or strip electrodes are inserted through a full craniotomy. Stereotactic techniques can also be used. These electrodes are inserted several weeks before the definitive operation to monitor the patient for an adequate period of time. The patient's behavior and EEG are continuously recorded and displayed on a television monitor in specialized units.
Placement of intracranial electrodes or grids is usually performed under general anesthesia. The anesthetic plan should consider the concerns of a patient who has epilepsy and the precautions that apply to any craniotomy. Routine noninvasive monitoring is required with the addition of intra-arterial blood pressure measurement as indicated. The anesthetic drugs used are not specific because there is no EEG recording. Electrode plates and large grids are quite bulky and might require brain shrinkage through the use of mannitol and hyperventilation. These patients may develop postoperative problems with brain edema and require urgent removal of the grid because of the development of intracranial hypertension.
Intraoperative localization of epileptogenic focus
Electrocorticography (ECoG) is performed during surgery after opening of the dura by placing electrodes directly on the cortex over the area predetermined to be epileptogenic as well as on adjacent cortex. Additional recordings can be obtained from microelectrodes inserted into the cortex or depth electrodes into the amygdala and hippocampal gyrus.
Stimulation of epileptogenic focus is possible pharmacologically, if insufficient information is obtained to define the seizure focus adequately during routine ECoG. Drugs used in adults include a small dose of methohexital, 10 to 50 mg; thiopental, 25 to 50 mg; propofol, 10 to 20 mg; or etomidate, 2 to 4 mg. If the patient is under general anesthesia, other drugs such as alfentanil, 20 to 50 mcg/kg, and enflurane can be used with or without hypocarbia.
Direct electrical stimulation of the cortex delineates eloquent areas of brain function, such as speech, memory, and sensory and motor function. This allows these areas to be preserved during resection of the seizure focus. Only motor testing can be done when the patient is under general anesthesia.
Preoperative preparation for epilepsy surgery. Communication among all members of the team, including the neurologist, neurosurgeon, and anesthesiologist, is vital to the successful management of the patient throughout the perioperative period.
Routine and specific epilepsy assessment is carried out.
Appropriate preparation of the patient for the anesthetic technique selected is carried out.
Anticonvulsant agents are administered before surgery in consultation with the neurologist and surgeon.
Premedication for the purpose of sedation is rarely required because these patients are usually well informed; all drugs that might influence EEG, such as benzodiazepines, should be avoided.
Techniques of anesthesia. Historically, epilepsy surgery was performed with the patient awake for at least some part of the procedure. These procedures are now performed with the use of either conscious sedation (neuroleptanesthesia) or general anesthesia. The neurosurgeon usually makes the decision, which depends on the location of the seizure focus, the need for testing of eloquent function, and the patient's ability to withstand an awake procedure.
Conscious sedation/neuroleptanesthesia
A. The reasons for having an awake patient are as follows:
(1) Better ECoG localization of the seizure focus without the influence of general anesthetic drugs
(2) Availability of immediate responses from the patient to direct electrical stimulation of the cerebral cortex to delineate eloquent areas of brain function to preserve them during surgical resection
(3) Continuous clinical neurologic monitoring of the patient throughout the procedure
B. The challenge is to have the patient comfortable enough to remain immobile through a long procedure but sufficiently alert and cooperative to comply with testing. The analgesic and sedative drugs employed must have minimal interference with ECoG and stimulation testing.
C. Specific preoperative preparation
(1) The patient is prepared psychologically and informed about the complexities and demands of an awake craniotomy.
(2) The establishment of good rapport between the anesthesiologist and the patient is absolutely essential.
(3) The anesthesiologist should be aware of the signs and symptoms that may indicate that the patient is experiencing the onset of a seizure.
D. Preparation of the operating room. An awake craniotomy adds additional stress to the patient and the entire team. All preparations should be complete before the patient arrives in the room so that the patient can receive the full attention of all team members.
(1) Anesthetic drugs and equipment for conscious sedation, induction of general anesthesia, and the treatment of complications are available.
(2) Routine monitoring equipment is ready to connect to the patient.
(3) Extra pillows, soft mattress, and soft headrest or fixed head frame are available for positioning the patient.
(4) Room environment is at normal room temperature with a quiet, reassuring atmosphere. It is essential to prevent unnecessary traffic by placing a sign on the door advising people of the procedure within.
E. Patient management
(1) Positioning is usually in the lateral decubitus, which is most comfortable for the patient and allows better access to the patient.
(a) Pillows are placed behind patient's back, between the legs, and under the arms.
(b) Extra blankets may be needed at the beginning.
(c) Patients should be positioned in such a way as to have some freedom of movement of the extremities.
(d) The patient's head is positioned on a pillow of appropriate size and shape. However, neuronavigation for imaging is now frequently used, which necessitates the placement of the patient's head in a rigid skull pin-fixation system. Pins are inserted with the use of local anesthesia under conscious sedation.
(e) The placement of the surgical drapes should allow for maximum visibility of the patient's face by the anesthesiologist and for the patient to see the anesthesiologist continuously.
(2) The neurosurgeon usually performs scalp block.
(a) Long-acting local anesthetic agents, such as bupivacaine with the addition of epinephrine, are used.
(b) Lidocaine, which has a fast onset, may be added and used to infiltrate areas that are still painful during the procedure, such as dura.
(c) The maximum dose for bupivacaine is 3 mg/kg and for lidocaine, 5 to 7 mg/kg.
(d) The scalp block is painful. The patient might need analgesia and sedation.
(3) Monitors
(a) Electrocardiogram (ECG), noninvasive blood pressure cuff, pulse oximeter, and end-tidal carbon dioxide (CO₂) via nasal prongs used to deliver supplemental oxygen.
Invasive monitoring is not routinely required for all patients.
(b) The intravenous catheter should be inserted in the arm not involved in seizure activity.
(c) Fluids should be kept to a minimum; therefore, a urinary catheter is not routinely needed.
(d) Dextrose-containing fluids should be avoided.
(4) Anesthetic drugs
(a) The techniques of drug administration and dosage requirements vary greatly and need to be titrated to each patient.
(b) The drugs may be administered by intermittent bolus, continuous infusion, target-controlled infusion, patient-controlled analgesia, or a combination.
(c) Short-acting anesthetic drugs provide good conditions and ensure that the patient is alert for assessments.
(d) Traditionally, intermittent boluses of fentanyl and droperidol were used. Now the most common combination is an infusion of propofol (25 to 100 mcg/kg/minute) with either intermittent boluses of fentanyl (0.5 to 1 mcg/kg) or an infusion of remifentanil (starting at 0.0125 mcg/kg/minute). Other opioids (e.g., sufentanil and alfentanil) have also been used.
(e) The infusion of propofol has to be discontinued at least 20 minutes before the start of ECoG recording.
(f) Dexmedetomidine, a new alpha2-adrenoreceptor agonist, has been used as an adjunct for sedation and analgesia with minimal risk of respiratory depression.
(g) Antiemetic drugs including dimenhydrinate, prochlorperazine, metoclopramide, odansetron, dolasetron, and granisetron, may also be needed and do not affect the ECoG.
(5) Nonpharmacologic measures are very useful to help the patient through the procedure. These include frequent reassurance, allowing the patient to move intermittently, warning the patient in advance about loud noises (drilling and rongeuring bone) and painful interventions, providing ice chips and a cold cloth to the face, and just holding the patient's hand.
Intraoperative complications
(1) Pain/discomfort. At certain times, patients might feel either pain or discomfort and should be warned about this (e.g., the scalp block) in advance. Patients may also experience pain during the bone work if dural vessels come in contact with instruments and during the manipulation of the dura mater and major vessels within brain tissue. The loud noises of drills and rongeurs can be frightening if not actually painful.
(2) Nausea/vomiting. Many factors may be responsible for the high incidence of nausea and vomiting including anxiety, medications, and surgical stimulation, especially the stripping of the dura and manipulation of the temporal lobe and meningeal vessels.
(3) Seizures can occur at any time.
(a) Short, mild seizures may not require any treatment. Convulsive or generalized seizures need to be treated immediately.
(b) The patient should be protected from injury.
(c) A patent airway, adequate oxygenation, and circulatory stability must be ensured.
(d) Before ECoG recording, seizures can be treated with a small dose of either thiopental, 25 to 50 mg, or propofol, 10 to 20 mg.
(e) After all recordings have been completed, benzodiazepines may be used.
(f) If repeated treatments are required, the patient may become very drowsy and need airway support.
(4) Respiratory. Oxygen desaturation and airway obstruction may result from oversedation, seizures, mechanical obstruction, or loss of consciousness from an intracranial event. Treatment needs to be immediate and includes decreasing sedation and jaw thrust, or the insertion of an oral airway, laryngeal mask, or endotracheal tube.
(5) Induction of anesthesia. If a patient either becomes uncooperative or complications such as hemorrhage or continuous seizures develop, the induction of general anesthesia may be required. To do this safely a plan of action is necessary. Airway assessment determines the best approach.
(a) The laryngeal mask airway may be used temporarily or for completion of the procedure.
(b) Occasionally, endotracheal intubation will be required. This can be accomplished with the patient either on his or her side or supine. With adequate assistance, the anesthesiologist comes to the patient's head while the surgeon protects the sterile brain field. After preoxygenation, anesthesia can be induced if necessary with a small dose of propofol (with or without opioids and muscle relaxant). Intubation may be accomplished with any airway device with which the anesthesiologist is comfortable, such as direct or fiberoptic laryngoscopy or the intubating laryngeal mask.
(c) If any difficulty in securing the airway is anticipated, an awake intubation with local anesthesia should be performed.
(6) Other less common complications include excessive blood loss and a tight brain.
Closure. During closure of the wound, the patient may be sedated with other drugs, such as benzodiazepines, that were not used up to this point.
Recovery of the patient takes place in an intensive care or specialized observation unit.
Postoperative complications are the same as for any patient after a craniotomy. Seizures might still occur and may require treatment.

Asleep-awake-asleep is a modified technique of conscious sedation that may also be used.
General anesthesia is used for the craniotomy and closure. Either inhalation or intravenous anesthetic drugs with or without controlled ventilation may be used.
Appropriate airway devices include endotracheal tube, special oral airway, or, most commonly, the laryngeal mask airway.
The advantages of the laryngeal mask airway are easier placement and decreased coughing and laryngospasm.
The patient is awakened completely and the airway device removed for the period of intraoperative neurologic evaluation.
For resection of the lesion and for closure, general anesthesia is again induced with reinsertion of the airway device.
This technique requires complex intraoperative airway manipulation after neurologic testing while the head is fixed.
Advantages include increased patient comfort and tolerance during craniotomy and a secured airway with ability to control ventilation and prevent hypercapnia.

General anesthesia
The reason for choosing general anesthesia depends on the preference of the neurosurgeon, or the patient's inability to tolerate an awake craniotomy, or both.
The advances in preoperative neuroimaging, functional testing, and the use of frameless stereotactic surgery for localization of the epileptic focus have lessened the need for the patient to be awake during the procedure.
The challenge to general anesthesia, if intraoperative localization is needed, is to provide good conditions for EEG, ECoG, and motor testing. The influence of the anesthetic drugs needs to be kept at a minimum while avoiding long periods of potential awareness on the part of the patient.
Specific preoperative preparation involves informing patients of the possibility that awareness might occur at the time of ECoG recording and testing but reassuring them that it will be brief and painless.
Preparation of the operating room, anesthetic equipment and drugs, and positioning supplies are as for any craniotomy. In addition to routine monitors, intra-arterial and urinary catheters are frequently used.
Anesthetic management
(1) Specific concerns include the increased dosage requirements for opioids and neuromuscular blocking drugs effected by long-term anticonvulsant therapy.
(2) N₂O. If the patient has had a recent craniotomy or burr holes for electrode placement, intracranial air might still be present. N₂O should be avoided to prevent complications from an expanding pneumocephalus.
(3) Anesthetic drugs
(a) Drugs should be short acting with minimal influence on EEG and ECoG and nonseizure-producing activity.
(b) A balanced technique may be used with opioids, muscle relaxant, N₂O, and low concentrations of inhalation drugs.
(c) Total intravenous anesthesia with propofol may also be used.
(d) Inhalation drugs and propofol must be eliminated at least 20 minutes before ECoG recording. N2O may also have to be eliminated.
(4) Motor testing is possible during general anesthesia by discontinuing all inhalation drugs and propofol and either reversing or allowing the muscle paralysis to wear off. This testing demands very careful planning and care of the patient. Either additional opioids or lidocaine might decrease the chance of the patient's coughing.
Complications
(1) Craniotomy-related complications
(2) The possibility of awareness
(3) Movement from seizures, especially during any stimulation testing
Recovery is the same as for awake patients

Pediatric surgery. The considerations for epilepsy surgery in pediatric patients are similar to those for adults, except that most children are not able to tolerate an awake craniotomy.
General anesthesia is used for most procedures.
Awake craniotomy may be tolerated by an older child.
Asleep-awake-asleep technique with the use of a laryngeal mask airway is an alternative.
Coexisting conditions with multiple organ system involvement and significant psychological and behavior problems may be present.
Parents may be very actively involved in the patient's management and also require consideration and education.
Cerebral hemispherectomy and corpus callosotomy. Treatment of diffuse generalized seizures might require either resection of substantial portions of the entire cerebral hemisphere or section of the corpus callosum. These procedures are usually performed under general anesthesia because they involve a large craniotomy and most of the patients are children. The major concern with these lengthy procedures is the possibility of extensive blood loss and air emboli because the surgical site is close to major vessels and sinuses.