Epilepsy, Epilepsy Surgery, Awake Craniotomy for Tumor Surgery, and Intraoperative Magnetic Resonance Imaging

Epileptic seizures

Classification

Status epilepticus

Medical treatment of epilepsy

Anesthesia for non-epilepsy surgery

Pro- and anticonvulsant effects of anesthetic drugs

Epilepsy surgery

Preoperative evaluation, localization of epileptogenic focus, and preparation for surgery

Techniques of anesthesia: Conscious sedation, asleep–awake–asleep, general anesthesia

Awake craniotomy for tumor

Anesthesia for intraoperative MRI

SUMMARY

1. Management of patients who have epilepsy for any operation requires an understanding of the disease, its treatment, and possible drug interactions during anesthesia.

2. Operation for intractable epilepsy involves extensive assessments and preparation. Various techniques of anesthesia are used depending on the nature and requirements of the operation.

3. Awake craniotomy for tumor surgery is used to protect areas of eloquent brain function during tumor resection.

4. Providing anesthesia in an intraoperative MRI suite requires preparation and knowledge of the effects of MRI on anesthesia equipment.

I. EPILEPSY

A. Definitions

1. 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 can be recorded on a scalp EEG.

2. 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.

B. Classification of epileptic seizures

1. Partial seizures have an onset that is localized or focal within the brain.

a. Simple partial. Alteration in consciousness does not occur during these seizures. They are classified according to signs and symptoms: motor, sensory, autonomic, and psychic. Auras are the sensory, autonomic, or psychic symptoms that precede a progression to impaired consciousness or motor seizure.

b. 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.

c. 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.

2. We speak of generalized seizures when the EEG shows simultaneous involvement of both cerebral hemispheres and consciousness is impaired. These seizures can be

a. Inhibitory or non-convulsive, such as atonic or absence seizures (petit mal)

b. Excitatory or convulsive, which produce myoclonic, tonic, or clonic seizures

3. Unclassified seizures

C. 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.

D. Associated medical problems include (1) psychiatric disorders; (2) rare syndromes: tuberous sclerosis, neurofibromatosis, and multiple endocrine adenomatosis; (3) history of trauma; and (4) sleep deprivation.

E. Treatment of epilepsy

1. Medical therapy involves various antiepileptic drugs:

a. First generation: phenytoin, phenobarbital, primidone, carbamazepine, clonazepam, valproic acid, and benzodiazepines. These have more adverse effects and drug interactions.

b. Second generation: gabapentin, lamotrigine, topiramate, felbamate, vigabatrin, oxcarbamazepine, zonisamide and pregabalin. These have a safer profile and fewer drug interactions.

c. Treatment consists of either a single medication or multiple-drug therapy.

d. The choice depends on considerations of the pharmacokinetics, clinical toxicity, efficacy, and type of epilepsy.

2. Adverse effects of antiepileptic drugs are dose dependent and are usually associated with long-term therapy:

a. Many drugs have neurologic side effects including sedation, confusion, learning impairment, and ataxia as well as gastrointestinal problems such as nausea and vomiting.

b. 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.

c. Long-term therapy with phenytoin causes gingival hyperplasia with poor dentition and, potentially, difficulties with airway management.

d. Carbamazepine can depress the hemopoietic system and, in rare cases, causes cardiac toxicity.

e. Valproic acid may occasionally lead to thrombocytopenia and platelet dysfunction.

3. Surgical treatment

a. Epilepsy is deemed refractory in up to 30% of patients when there is a failure to obtain adequate seizure control or there are unacceptable side effects associated with antiepileptic drugs. Approximately 15% to 20% of these patients are candidates for surgical treatment.

b. There should be reasonable evidence that the treatment will benefit the patient. A surgical cure occurs in 50% to 80% of patients who either remain seizure free or have a significant reduction in the frequency of their seizures.

c. Cognitive improvement also results because the dose of anticonvulsant drugs is either reduced or eliminated.

F. Status epilepticus

1. 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 non-convulsive. This is considered a neurologic emergency.

2. Treatment. To prevent brain damage, seizures must be stopped as quickly as possible. Emergent treatment includes the following:

a. Secure the airway, provide oxygen, and maintain circulation.

b. Protect the patient from traumatic injury from involuntary motor movements.

c. If hypoglycemia is present or cannot be ruled out, administer 50% glucose, 50 mL intravenously, and thiamine, 100 mg intravenously.

d. There are different approaches, but the initial drugs of choice usually include phenobarbital, phenytoin, and benzodiazepines. One regimen is diazepam, 0.2 mg/kg intravenously, or lorazepam, 0.1 mg/kg intravenously, followed by phenytoin, 15 to 20 mg/kg intravenously, given slowly at a rate of no > 50 mg/minute.

e. Seizures that continue to be refractory to drug therapy might require barbiturate coma titrated to EEG effect.

f. Other anesthetic drugs that have been used include etomidate, ketamine, propofol, halothane, enflurane, isoflurane, and desflurane.

G. Pro- and anticonvulsant effects of anesthetic drugs. Numerous reports describe how anesthetic drugs can paradoxically exhibit proconvulsant and anticonvulsant properties with different doses, under different physiologic situations, and in different species.

1. The inhalation drugs isoflurane and desflurane are effective anticonvulsants. Although controversial, sevoflurane has been shown to produce epileptiform activity. Nitrous oxide (N₂O) does not have any anticonvulsant properties and tends to inhibit seizure spikes on EEG.

2. 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.

3. Opioids (e.g., fentanyl, alfentanil, and remifentanil) can activate the epileptiform activity from a seizure focus in patients who have epilepsy.

4. Local anesthetic drugs are anticonvulsant in low doses but, at higher serum concentrations, can produce central nervous system (CNS) excitation.

H. Interaction between anesthetic and antiepileptic drugs

1. 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.

2. Interactions with endogenous neurotransmitters and changes in the number of receptors, including opioid, may occur.

I. Anesthetic management of an epileptic patient for non-epilepsy surgery

1. Preoperative assessment focuses on general assessment and preparation. Specific concerns with an epileptic patient include:

a. Medical problems including psychiatric disorders associated with epilepsy

b. Complications from anticonvulsant therapy

c. Continuation of anticonvulsant therapy

2. Anesthetic management and monitoring depend on the needs of the patient and the procedure.

a. Drugs that potentiate seizure activity should be avoided.

b. The requirement for anesthetic drugs may increase.

c. Seizures can occur postoperatively because anesthetic drugs and changes in body physiology during the operation can significantly affect blood levels of anticonvulsants.

d. Consideration should be given to the administration of additional doses of antiepileptic drugs during prolonged procedures.

e. Hyperventilation might potentiate seizure activity and should be avoided unless necessary for the operation itself.

II. SURGERY FOR EPILEPSY

A. Procedures

1. Craniotomy for surgical resection of the epileptogenic focus is used mostly for patients who have partial epilepsy disorders with discrete structural lesions showing sclerosis or gliosis and with specific syndromes such as mesial temporal lobe epilepsy.

2. Other surgical treatment modalities include insertion of a vagus-nerve stimulator or a deep-brain stimulator. Both have been shown to improve frequency and duration of seizures and/or severity. Vagus-nerve stimulator insertion is usually performed under general anesthesia. Deep-brain stimulators are usually inserted under monitored anesthesia care/ conscious sedation but general anesthesia may also be used.

3. Generalized seizures are treated by interrupting the seizure circuits by means of a corpus callosotomy or a hemispherectomy.

B. Patient suitability for epilepsy surgery. A complete multidisciplinary evaluation is needed to assess whether the patient is a candidate for epilepsy surgery. Invasive and non-invasive investigations identify the origin of seizure activity and 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.

1. Non-invasive evaluations

a. This includes medical history; assessment of the frequency, severity, and type of seizures; physical examination; and psychosocial and neuropsychiatric testing.

b. Surface-electrode monitoring of EEG activity may also be combined with video-camera monitoring of the seizures.

c. Radiologic imaging can supplement EEG data. Computed tomographic (CT) scanning and MRI help identify areas of sclerosis and the presence of low-grade intracranial neoplasms.

d. Functional imaging facilitates assessment of brain activity, cerebral blood flow (CBF), and the metabolic effects of resection of the seizure focus. Modalities include positron-emission tomography, single-photon emission CT scan, functional MRI, subtraction ictal single-photon emission CT scan, and spectroscopy.

2. Invasive evaluations

a. 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.

b. Intracarotid sodium amytal injection (WADA test) is used to test for lateralization of language and memory.

c. Insertion of intracranial electrodes. Epidural electrodes are inserted through multiple burr holes. Subdural grids, depth electrodes, 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 recorded continuously and displayed on a television monitor in specialized units.

d. 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 non-invasive monitoring is required with the addition of intra-arterial blood pressure measurement as indicated. The choice of anesthetic drugs is not limited as the EEG is not recorded. Electrode plates and large grids are quite bulky, however, so that brain shrinkage might be required through the use of mannitol, hyperventilation, and intravenous anesthetics. These patients may develop brain edema postoperatively and require urgent removal of the grid because of the development of intracranial hypertension.

e. Removal of electrodes may be performed in the operating room under sedation or general anesthesia either separately or in conjunction with the surgical resection.

C. Intraoperative localization of epileptogenic focus

1. 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 and on the adjacent cortex. Additional recordings can be obtained from microelectrodes inserted into the cortex or depth electrodes inserted into the amygdala and the hippocampal gyrus.

2. Pharmacologic stimulation of the epileptogenic focus is possible if insufficient information is obtained to define the seizure focus adequately during routine ECoG. Drugs used in adults include 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.

3. 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.

D. 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.

1. Routine and specific epilepsy assessment is carried out.

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