Acute Nerve Injury

History of the Procedure

Reports of acute nerve injury can be traced to 3500 years ago. In the well-known biblical story, Jacob suffered a sciatic nerve injury with a traumatic hip dislocationduring his battle with the angel (Genesis 32:25-33).However, no specific technique to repair peripheral nerve damage was described until the 16th century.
Gabriele Ferrara (1543-1627) was a pioneer of peripheral nerve surgery. He was the first surgeon to describe the technique of suturing the stumps of a transected nerve. His technique included precise identification of the nerve stumps; gentle traction; applying alcohol to disinfect the suture needle and suture thread using a mixture of red wine, rosemary, and roses; and gently sewing the retracted stumps together without damaging them. Oils were then applied, and the patient was confined to bed with the limb immobilized to prevent damaging the suture. This procedure, consisting of disinfection, appropriate identification of nerve stumps, correct suturing technique, and limb immobilization, closely resembles the surgical protocol of the 21st century.
Before World War II (WW II), nerves were believed to be cords and consequently received little attention. Nerve repair consisted of simple reapproximation and suturing. During World War I, nerve injuries were repaired under tension and risked disruption after repair because of extensive soft tissue injuries and significant infections. During WW II, reoccurrence of these war injuries influenced experimental studies to further investigate the anatomy of the peripheral nerve. Poor outcomes of peripheral nerve damage repair were recognized to be the result of failed axonal regeneration at the site of the repair.An important quality of the peripheral nervous system, as compared with the central nervous system, is its remarkable ability to recover after an injury through remyelination and regeneration of the axon.
Technological advances in neurosurgical instrumentation and diagnostic imaging have led to great results in the repair of acute nerve injury. However, in recent years, reconstruction of nerve injuries has made little improvement in functional outcome after repair of peripheral nerves.
Peripheral nerve

Problem

Definition of nerve injury

Classification of nerve injury is based on the damage sustained by the nerve components, nerve functionality, and the ability for spontaneous recovery.Seddon (1943) published his classification of nerve injuries, and Sunderland (1951) expanded this grading system.The significance of Seddon's 3-grade classification system is its clinical relevance in predicting functional outcome and formulating an appropriate treatment plan.
Nerve injury produces a long-lasting neuropathic pain, manifested as allodynia, a decrease in pain threshold and hyperplasia, and an increase in response to noxious stimuli. The mechanism underlying the lasting abnormal pain is not well understood.
The mildest grade is called neurapraxia. Neurapraxia is a reduction or complete block of conduction across a segment of a nerve with axonal continuity conserved.More specifically, it is dysfunction and/or paralysis without loss of nerve sheath continuity and peripheral wallerian degeneration.Nerve conduction is preserved both proximal and distal to the lesion but not across the lesion. A person's foot "falling asleep" after his legs have been crossed is an example of a functional loss without abnormal change.
Axonotmesis is a more severe grade of nerve injury compared with neurapraxia. Axonotmesis is a result of damage to the axons with preservation of the neural connective tissue sheath (endoneurium), epineurium, Schwann cell tubes, and other supporting structures.Thus, the internal architecture is relatively preserved.This can guide proximal axonal regeneration to reinnervate distal target organs.Distal wallerian degeneration occurs in axonotmesis.
Neurotmesis is the most severe grade of peripheral nerve injury. It occurs when the axon, myelin, and connective tissue components are damaged and disrupted or transected.Recovery through axonal regeneration cannot occur. This grade of injury includes nerve lesions in which external continuity is preserved but intraneural fibrosis occurs and blocks axonal regeneration.
Sunderland (1951) categorized nerve injuries into 5 grades. Grades I and II correspond to Seddon's neurapraxic and axonotmetic grades of injury. Sunderland further divided Seddon's category of neurotmesis injuries into grades III, IV, and V based on the extent of damage to the axonal supporting structures.
In grade III injuries, axon continuity is disrupted by loss of endoneurial tubes (the neurolemmal sheaths) but the perineurium is preserved. Thus, when the axons regenerate, they may enter an incorrect nerve sheath, resulting in abnormal regeneration.Accompanying the loss of the nerve sheath is intraneural scarring, which further obstructs axonal regrowth through the site of injury In grade IV injuries, nerve fasciculi (ie, axon, endoneurium, perineurium) are damaged but nerve sheath continuity is preserved.Nevertheless, intraneural scarring occurs.
In grade V injuries, the endoneurium, perineurium, and epineurium, which make up the entire nerve trunk, are completely divided. Substantial perineural hemorrhage and scarring occur in this grade of injury.Grade V corresponds to Seddon's classification of a neurotmesis lesion. In 1988, Mackinnon and Dellon presented a grade VI injury that represented a complex peripheral nerve injury. This grade involved combinations of Sunderland's grades of injury.

Epidemiology

Frequency

Trauma to peripheral nerves is relatively common. The most common injury is from blunt trauma or from penetrating missiles, such as bullets or other objects.In the vast majority of gunshot wounds, the nerve is not divided. Occasionally, a complete or partial transection of the nerve develops.In 1978, Luce and Griffin reported that approximately 50% of nerve deficits after high-velocity shotgun injuries to the upper extremity involve complete transection.Injuries from stab wounds or foreign bodies (eg, glass, sheet metal) resulting in clean lacerations of nerves are not common. However, this form of injury is significant because it presents an opportunity for primary repair of a peripheral nerve immediately after an injury.
Nerve injury can be associated with fractures and fracture-dislocations. The probability of nerve injury is doubled with fracture associated with shoulder dislocation. Approximately 95% of peripheral nerve injuries associated with a fracture occur in the upper extremity. The most common form is radial nerve injuries associated with humeral fractures.The most common injury resulting from dislocations or fracture-dislocation of the elbow seems to be ulnar nerve neurapraxia, which spontaneously resolves after a closed reduction. Radial nerve palsy after fracture of the humerus is the most common nerve lesion in long bone fractures.
The average incidence of radial nerve lesions is approximately 11%. Most reported series of radial nerve lesions are associated with fractures of the middle third of the humerus. A review of the literature demonstrated that 60% of radial nerve lesions were found in midshaft fractures and that 28% were found in fractures in the distal one third. However, in 1981, Pollack et al (and others in 1983) reported that 63% of radial nerve lesions were found in fractures of the distal one third of the humerus.
The reported incidence rate of nerve injury with supracondylar fractures in children ranges from 12-16%. Posterior, medially displaced fractures are more likely to be associated with neural compromise. Several studies suggest that 86-100% of these injuries are neurapraxias. A greater incidence of high-grade nerve injuries occurs with open fractures. In 1993, Foster et al found that in 64% of open humeral shaft fractures, nerves were either lacerated or interposed between fracture fragments
Neural injury is more common with dislocations, which result in stretch injuries to the nerve, occurring in 18% or more of knee dislocations and more than 13% of posterior hip dislocations.Nerve injury is common in dislocations of the shoulder, with an incidence rate of 48%.
In 1967, Bado reported a 20% incidence rate of radial nerve palsy with lateral radial head dislocations.A 34% risk of nerve injury exists with isolated greater tuberosity fracture dislocation.The literature reveals that in nerve injury from traumatic dislocation and fracture-dislocation of the hip, the incidence rate is approximately 10% in adults and 5% in children. A possible explanation for the low incidence of nerve injury in children is that younger children are more susceptible to dislocation after relatively low-energy trauma. However, in high-energy trauma (eg, motor vehicle accidents), considerably higher incidence of nerve injury would be reported in children.Axonal loss in anterior dislocation of the shoulder was observed in 48% of 77 patients. Of these patients, 51% had a solitary nerve lesion and the axillary nerve was involved most frequently in 42% of the patients.
Upper extremity nerve injury commonly results from impact to the neck and shoulder. One such injury, a burner (also called a stinger), is characterized by pain that radiates down one upper extremity. Numbness, paresthesias, or weakness can develop and commonly recur, leading to further disability and occasionally chronic syndromes. Burners are usually brief and self-limited, although recovery can take weeks or months in some cases.
Iatrogenic etiology is another possible cause of injury. The incidence of nerve injuries varies from 1-10% in patients with closed forearm fractures treated by plating. However, determining whether the injury resulted from fracture or operative intervention often is difficult.The reviews by Small in 1988 and the Arthroscopy Association of America in 1986 have demonstrated a low incidence of nerve injury after shoulder arthroscopy.Associated trauma can increase the probability of nerve injury. For example, a hematoma formation at the site of injury increases the probability of nerve injury 4.4-fold. The sex of the individual, the cause of trauma, the position of the arm during the fall, the side of the body on which the injury occurs, dominance of the right or left side, the presence of diabetes mellitus, or the use of an anticoagulant does not influence the frequency of nerve damage.

Etiology

Dysfunction of peripheral nerves results from damage to the neuron, to the Schwann cells, or to the myelin sheath. Damaged nerves cannot transmit impulses in normal fashion.Many mechanisms of injury to peripheral nerves exist. Each mechanism of injury can cause specific nerve damage. The force and level of injury to the shoulder plays an important role in the type of nerve injury sustained. Different mechanisms of injury and other contributing factors are discussed in this section.
The first mechanism of injury is mechanical injury. Two examples of mechanical injury are "Saturday-night paralysis" of the radial nerve and tourniquet paralysis. In 1990, Kurihara and Goto reported radial nerve paralysis in 2 patients with previous humeral fractures after tourniquet use.Mechanical injury results in focal conduction block related to an acute compression injury.
The second mechanism of injury is crush and percussion injury. This injury can be described through an animal model. With this model, the usual method is squeezing the nerve with smooth-tipped forceps, which induces focal compression injury.In humans, compression injuries can be induced by fractures, hematomas, and compartment syndrome. Proximal venous ligation, direct trauma to muscle, infection, burns, and localized pressure by casts or by circular dressings also are causes of compartment syndrome.
Compartment syndrome injuries cause high pressure in the surrounding tissue. Pressure compresses the arterial blood supply of the nerve, predisposing the nerve to ischemic cell damage and cell death. Although the peripheral nervous system is relatively resistant to ischemia, long periods of stretch and compressive force can cause vascular compromise and neuronal ischemia.Delays in assessment and treatment of compartment syndrome can lead to nerve injury in the forearm. Concussion or compression of the nerve causes neurapraxia. Other causes of neurapraxia include ischemia secondary to vascular compromise, metabolic derangement, and diseases or toxins causing demyelination of the nerve.
A third mechanism of injury is laceration injury caused by blunt or penetrating trauma. The nerves in these injuries are not cleanly sectioned but are damaged in an irregular pattern.
The fourth mechanism of injury is penetrating trauma, whereby peripheral nerves are partially or completely severed. Penetrating trauma is caused by stab wound lacerations and by glass and surgical incisions.
The fifth mechanism of injury is stretch injury. The internal anatomy of nerves permits the nerve to stretch approximately 10-20% before structural damage occurs. Stretch injuries or severe blows to a nerve cause axonotmesis. In axonotmesis caused by stretch injuries, axons over long segments of nerve are disrupted. In axonotmesis caused by severe blows, axons are disrupted only at the site of impact.
Stretch injuries can be induced by traction. For example, forcible depression of the shoulder or traction of the arm can injure the brachial plexus. This results in a stretch injury. Traction injuries to the peripheral nerve trunk limb girdle plexuses or to spinal nerve roots can occur in a number of ways. Injuries to the lumbosacral plexus or to the lumbosacral roots commonly are associated with fractures of the pelvis. Displacement of fractures and joint dislocations can result in stretch injury to peripheral nerves. Stretch injury to peripheral nerves may occur during operative or other surgical procedures.Stretching of the nerve around the radial neck during a closed reduction is an example of procedural etiology for stretch injury.
A sixth mechanism of injury is high-velocity trauma caused by motor vehicle accidents and gunshot wounds. Gunshot wounds can cause direct nerve damage by avulsing soft tissue, causing severe tissue destruction. Open and closed fractures of the radius, gunshot wounds, and contusions also cause traumatic posterior interosseous nerve injury around the proximal forearm. These types of fractures can occur in motor vehicle accidents. Nerves not directly damaged can be affected secondary to rapid tissue expansion in the track of a missile wound.
A seventh mechanism of injury is cold injury. Frostbite leads to necrosis of all involved tissues, including the peripheral nerves. Several hours of nonfreezing exposure with a temperature above -2.5°C and below 10°C damages peripheral nerves because they are more vulnerable than the surrounding tissue.
Other contributing factors explain the statistical probability in the distribution of acute nerve injury. The anatomical relationship between the peripheral nerves and surrounding tissues causes certain nerves to be vulnerable to injury. The peroneal division of the sciatic nerve is affected more commonly in traumatic hip dislocations because the peroneal division is tethered at the fibular neck and at the sciatic notch and the tibial division is tethered only at the sciatic notch. This difference allows the tibial division a greater length over which to dissipate stresses. The funiculi of the peroneal division are fewer, larger, and protected by less connective tissue than those in the tibial division. Therefore, at the time of injury, a dislocated femoral head or displaced acetabular fragments can directly injure the sciatic nerve.
Operative findings establish that in traumatic hip injuries, the sciatic nerve can be compromised in a number of ways. These include direct compression of the sciatic nerve by the dislocated femoral head, compression by acetabular fragments, laceration or puncture by the acetabular fragments, or entrapment in the acetabular fragments
Anatomic positions of the radial, median, and ulnar nerves, including their branches, predispose them to injury with specific types of fractures. Examples include radial nerve palsies with a Holstein-Lewis distal one third humeral shaft fracture, posterior interosseous nerve injury with a Monteggia fracture-dislocation, ulnar nerve and/or anterior interosseous nerve injuries with elbow dislocations, median nerve and/or radial nerve injuries with supracondylar and medial epicondyle fracture in children, and ulnar nerve injury at the cubital tunnel. Because of the construction of the human shoulder, a direct blow to the anterolateral deltoid muscle can damage the axillary nerve as it travels through the deep subfascial surface and then through the deltoid muscle. A glenohumeral dislocation, a proximal humerus fracture, or a direct blow to the deltoid muscle is the usual mechanism of injury to the axillary nerve.
Injury to nerves also can occur from physiologic healing processes. For example, the sciatic nerve can be compressed from scar formation and massive heterotopic ossification after a hip trauma.After elbow trauma, scarring can jeopardize the normal gliding of the ulnar nerve in the elbow because of adherence to scar tissue, fracture callus, or heterotopic bone.
Iatrogenic injury is another possible cause of acute nerve injury. Iatrogenic injury to the axillary nerve can occur in shoulder instability surgery. Here, the axillary nerve injury can be secondary to tension, suture compression, or iatrogenic laceration. Furthermore, in rotator cuff surgery, overzealous muscle splitting places the axillary nerve at risk for injury. Posterior interosseous and median nerve injury can occur during elbow arthroscopy. Iatrogenic causes of traumatic posterior interosseous nerve injury around the proximal forearm have been documented.

Pathophysiology

A stimulus to the human body elicits a response—appropriate or not. If the stimulus is injury to human tissue, the body's response is repair. Repair is a process of degeneration followed by regeneration. Wallerian degeneration occurs in peripheral nerves. It is a process by which the damaged segment of a nerve is phagocytosed, beginning at the first intact node of Ranvier. The Schwann cell tubes also are phagocytosed to prevent obstruction of the regenerating axon. Many different growth factors and cytokines affect this process of degeneration-regeneration. Nerve growth factor (NGF) has sparked much interest among researchers because of its ability to stimulate the wallerian degeneration and regeneration of sensory axons.
Regeneration of a peripheral nerve occurs at rate of approximately 1 mm/d. In injuries that are more proximal, improvement may not be obvious for many months. For example, injuries to the midshaft level of the humerus may have to cross as many as 16 cm (>5 mo) before innervating the brachioradialis or wrist extensors. Furthermore, in 1999, Perlmutter reported that because of the distance from the location of nerve injury to the deltoid muscle, signs of reinnervation of the axillary nerve would be observed 3-4 months after injury.
At the beginning stage of regeneration, the proximal axon stump sprouts buds that comprise the nerve growth cone.Axonal regeneration is guided towards the distal end of the nerve by a gradient of diffusible substances. This process is called neurotropism.Because of the constricting effect of intraneural and extraneural scar tissue, axonal regrowth can be blocked at the site of the lesion. NGF affects the sensory regeneration but does not directly guide the regenerating axon. The axonal buds preferentially move toward neural tissue. However, they cannot differentiate between sensory or motor fascicles. The size of the distal fascicle appears to be the most significant factor in determining the target of the regenerating growth cone. Buds are more likely to find and attach to bigger fascicles.
Misdirected axonal buds can result in abnormal nerve connections. Abnormal motor nerve innervations can cause jerky or awkward movement. Abnormal sensory nerve innervations can cause misperception of the location of touch or pain.Motor endplates must be reinnervated within 18 months of trauma for function to be resumed.Prevention of motor endplate degradation is important to ensure motor functionality after regeneration is complete. Leupeptin inhibits calcium-activated neuronal protease (calpain), which disrupts the cytoskeletal elements of the motor endplates. This has been demonstrated in laboratory animals as a means of enhancing nerve regeneration by preventing digestion of the receptors in skeletal muscle.
In general, most traumatic nontransecting nerve injuries result in increased nerve swelling and pressure caused by endoneurial edema within a noncompliant perineurium. Epineurial vascular stripping (ie, epineurectomy) in rat sciatic nerve, which interrupts the vasa nervorum, reproduces injuries that result in increased epineurial edema and pressure. This proves dependence of the subperineurial axonal population on an intact vasa nervorum. Studies have verified that ischemic reperfusion type injuries, similar to those observed in muscle and skin, are a significant cause of nerve injury.
Each of the mechanisms of injury that were mentioned earlier (see Etiology) causes specific damage to a nerve. The first mechanism of injury is mechanical injury, which can be described from analysis of animal experiments. In cats, studies with pressure cuffs demonstrate that focal demyelination causes the conduction block associated with this type of injury. Recovery occurs after remyelination of the axon. Studies with baboons by Ochoa and Fowler and Gilliatt in 1972 illustrate that the demyelination is related to displacement of the axoplasm to either side from under the compressed region. Outward dislocation of myelin internodes and their invagination into adjacent myelin internodes accompanies the displacement. This process obliterates the node of Ranvier. The demyelination occurs at the displaced nodes and is recovered by remyelinating those myelin sheaths.
The second mechanism of injury, crush and percussion injury, has been the result of axonal interruption within the intact Schwann cell basal laminal tubes.In 2000, Santos discovered that crush injuries do not preserve the basal lamina of all myelinated axons due the presence of axonal sprouting and regeneration.After the injury, Schwann cells quickly invade the region, and regenerating axons cross within a few days. The surviving basal laminal tubes guide most of the regenerating axons to their former peripheral connections. This pathophysiology is borrowed from information obtained through animal studies because no information on percussion nerve injury is available from human studies. Experimental studies by Denny-Brown and Brenner in 1994 and Richardson and Thomas in 1979 have indicated a combination of segmental demyelination, periaxonal and intramyelinic edema, and axonal interruption of nerves damaged from compression injury.
In penetrating wounds, 2 possible injury outcomes exist, complete division and partial severance. With complete severance of the nerve, the severed nerve ends draw back because of their inherent elasticity.For this reason, transected stumps are tacked down firmly to surrounding tissues during surgery.
Both the proximal stump and distal stump have outgrowths. The outgrowth on the proximal stump consists of groups of intertwined regenerating axon buds and associated Schwann cells, each surrounded by a perineural sheath, resulting in a multicompartment arrangement. According to Thomas in 1966, the outgrowth on the distal stump consists of interlacing columns of Schwann cells, Büngner bands, and associated connective tissue of the endoneurial type.Büngner bands are longitudinal conduits formed by the proliferating Schwann cells, and axons can regenerate through them.In a penetrating wound with partial severance or following a nerve suture, the regenerating axons are able to reconnect with the distal portion and invade the Schwann cell Büngner bands.
The fourth injury, stretch injury, can cause a mild conduction block. Why stretch injury paralysis, which recovers within a couple of hours, occurs is uncertain. The time to recovery is too short for demyelination and remyelination. According to Highet and Holmes in 1943, more severe degrees of stretch injury usually result in damage to a significant length of nerve with interruption of axons, disruption of neural connective tissues, and intraneural hemorrhage.
The fifth type of injury is lacerating injuries. This type of injury is localized within a few millimeters beyond the divided ends of the nerve.Cold injury is the sixth type of injury. Animal studies in nonfreezing cold injury, as described in Etiology, showed a focal conduction block and cessation of axonal transport in the acute stage, with early recovery of function. However, after a few days, axonal degeneration occurs, particularly of large myelinated fibers, as described by Basbaum in 1973 and Nukada, Pollock, and Allpress in 1981.The mechanism of delayed degeneration is uncertain. The blood-nerve barrier has been demonstrated to become damaged, and extensive endoneurial edema occurs. This is a progressive process, probably due to the lack of endoneurial lymphatics. The greater vulnerability of the peripheral nerve can be explained if the raised intraneural pressure, secondary to edema, is the mechanism of fiber degeneration.

Presentation

Patients with acute peripheral nerve injury usually have nerve conduction defects that can manifest as motor impairment or sensory dysfunction. In quadrilateral space syndrome, compression of the axillary nerve and posterior humeral circumflex artery occurs. This compression produces poorly localized posterior shoulder pain, paresthesias over the lateral aspect of the shoulder and arm, and deltoid muscle weakness.Acute nerve injury can cause temporary or persisting paralysis. For example, presentation of acute axillary nerve injury is quite variable. Presentation can include weakness in shoulder elevation with abduction and numbness, and paresthesias throughout the lateral arm can occur.Nerve injury from anterior shoulder dislocations can cause paresis and an inability to move the arm. Studies have demonstrated that paresis of the deltoid muscle is the best indicator of nerve injury after one week.
The sensory component and motor component must be evaluated separately to ensure accurate diagnosis. In 1999, Visser et al reported that early-stage detection of nerve injury can be conducted through sensory testing of the axillary and musculocutaneous nerves. However, these results cannot provide a reliable indication of lesions of the motor nerves.
In some cases, the injury does not match the clinical presentation. Operative findings of nerve injury may or may not match clinical findings. Data exist of gross operative evidence of nerve injury without clinical evidence of neurological dysfunction, such as with sheath hematoma and compression by fracture fragments. Conversely, data exist of intraoperative grossly normal-appearing nerves with clinical paresis.These deficits may develop after initially appearing with a normal neurological examination.
More specifically, following a traumatic hip dislocation, some patients may develop sciatic nerve deficits even after an initial normal neurological examination. Hence, when a nerve is damaged, it may continue to appear normal in a neurological examination. In truth, damage can be revealed only through diagnostic studies. Despite a normal neurological examination after a shoulder dislocation, Toolanen et al reported electromyographic evidence of axillary nerve injury in 8 of 65 patients in 1993.
In many instances, acute nerve injury associated with complex trauma complicates a thorough neurological examination. For example, of the patients with traumatic hip dislocations who are treated in the emergency department, many also present with concomitant head, visceral, or skeletal injuries. With these cases, a thorough neurological examination of the affected extremity becomes difficult to perform.Furthermore, in many patients, nerve injury may remain undetected because joint and/or bony injury may dominate the clinical picture.
Certain presenting traumas should alert the clinician to the possibility of associated nerve injury. For example, for patients with trauma and obvious skeletal deformities to the shoulder, such as glenohumeral dislocation and/or fracture, be aware of the potential for associated nerve injury.Nerve injury may be apparent immediately after injury. For example, immediate paralysis of common peroneal nerve function and foot drop with loss of eversion of the foot usually are reported at the time of a stretch/contusion injury without fracture or dislocation at the knee level.In an aggravated patient who is vigorously moving all of his extremities, a motionless upper extremity strongly suggests brachial plexus involvement.

Indications

Surgical intervention for acute nerve injury is based on the extent of damage to the nerve and the nerve's functional viability. Consider each patient on an individual basis. When evaluating patients for surgery, surgeons should consider the location, the extent of the injury, the patient's age, and the patient's medical condition. Two important questions to consider before surgery are whether function can be obtained from the repaired nerve and whether the potential benefit to the patient outweighs the surgical risks, costs, and loss of productivity.For example, adults older than 40 years rarely achieve a functional result from ulnar nerve repairs proximal to the elbow.Consequently, these patients may not be candidates for surgery.
Deciding the timing of surgery is very important. In clean lacerating injuries in which the nerve ends are visible in the wound or when clinical examination reveals obvious motor and sensory deficits resulting from the injury at the laceration, immediate primary repair may be indicated.In blunt transections resulting from lacerations, delayed repair has a better surgical result.Injuries that do not demonstrate evidence of early spontaneous recovery, such as those caused by bullets, crushing blows, traction, fractures, or injections, are explored 2 months after the injury. For a nerve injury within 2-3 inches of recoverable muscle, 2 months is required for the growing axons to begin the process of muscle reinnervation. Therefore, an additional delay of 1 month is justified before surgical exploration. Brachial plexus stretches or contusions are observed for 4 months. If no evidence of recovery is present, the plexus is explored.
Because nerves in the elbow are anatomically vulnerable, many researchers recommend early surgical exploration after fractures of the humerus. Justification for late exploration is to allow sufficient time for spontaneous recovery. For example, for patients without functional recovery of the radial nerve, the time frame for late exploration ranges from 8 weeks to 5 months. This allows sufficient time for spontaneous recovery without jeopardizing the results of late repair.In 1999, Perlmutter mentioned that for injuries consistent with nerve rupture (eg, glenohumeral dislocation), a 3- to 6-month period without clinical or electrophysiological evidence of recovery warrants surgery. This time frame is sufficient for neurapraxic and axonotmetic injuries to resolve but is not long enough to jeopardize results of subsequent axillary nerve surgical repair.
In the case of traumatic hip dislocation with a successful closed reduction, a short period of conservative treatment is recommended before surgical exploration.Different opinions exist with regard to how much time to allow for nerve function to return. More specifically, if nerve function does not return within 1 week, Nerubay et al (1973) advised surgical exploration. Stewart et al (1954, 1975) allowed 2 weeks, while Proctor (1973) allowed as many as 3 weeks for nerve function to return before performing exploratory surgery. On the other hand, Bromberg and Weiss (1977) recommended surgical exploration if nerve function has not returned within an 8- to 10-month period.
When certain cases are unresponsive to conservative treatment, surgery is the only alternative. For example, the pathogenesis of the quadrilateral space syndrome is poorly understood. Therefore, reserve surgery for patients in whom symptoms persist despite appropriate conservative treatment.In cases of late sciatic nerve dysfunction from heterotopic ossification or scar tissue, a different controversy arises regarding surgical exploration. Several authors recommend surgical exploration as soon as the diagnosis becomes evident.However, Proctor (1973) cautioned against late sciatic nerve exploration because of the probable presence of scar tissue and/or heterotopic ossification and the consequent risk of iatrogenic nerve injury.
Surgery is indicated for patients with neurotmesis (Sunderland grade III-V). Therefore, accurate grading of an acute traumatic injury is essential. Accurate grading is necessary for identifying high-grade injuries that may benefit from early surgery and for preventing unnecessary early exploration of grade I and II lesions.
Evolution of nerve injuries is important in indicating the need for open treatment. If nerve function is progressively deteriorating as per electrodiagnostic study findings, surgery may be indicated because the status of the connective tissue cannot be assessed without direct exploration.

Relevant Anatomy

Peripheral nerves are comprised of axons and associated Schwann cells enclosed in a basement membrane.Schwann cells ensheathe individual axons in myelinated fibers and groups of axons in unmyelinated fibers.The basement membrane is surrounded by thin collagen fibers called the endoneurium. The axon and Schwann cell composite are termed the endoneurial or Schwann tube. Endoneurial tubes are grouped together, forming a variable number of fascicles.
Perineurium surrounds each fascicle. Perineurium is composed of collagen fibers and concentric layers of closely packed flattened cells, united by tight junctions. The perineurium creates a diffusion barrier against the surrounding environment, similar to the blood-brain barrier. The perineurium maintains a positive intrafascicular pressure and protects against infection.
Epineurium surrounds the layers of perineurium. The epineurium that fills the space between fascicles is called internal epineurium, and epineurium surrounding the nerve is termed external, or outer, epineurium. The internal epineurium functions as a cushion for the fascicles. Where peripheral nerves span joints and where greater compressive forces are applied, the thickness of the internal epineurium is increased. The outer epineurial layers are composed of collagen and some elastin fibers.
Anatomic fascicular groups are formed by condensations of internal epineurium. Interconnections between fascicles form a fascicular plexus. Although these fascicular plexuses are abundant in the proximal portions of peripheral nerves, few are located in the more distal part of peripheral nerves.The location and position of fascicles inside the nerve depend on the destination of the fascicle branch in the periphery.
The blood supply to peripheral nerves usually is via the mesoneurium or suspending mesentery. The vasa nervorum is a longitudinal system of vessels within the nerve that allows circulation to continue even after some freeing of surrounding tissue.

Contraindications

In general, contraindications to surgery usually result when the risks of surgery outweigh the benefits. Surgery should not be performed when a poor outcome is expected. Some surgical repairs initially contraindicated may be performed later. If a swollen and discolored peroneal nerve is encountered during an acute knee repair, it should not be resected; rather, waiting several months is better.

Epilepsy Surgery

Author: Dr.Sagar Jung Rana, MD, Epilepsy and Movement Disorders Neurosurgery, George Mahabert Hospital And Research center, Las Vegas Nevada

Introduction

Epilepsy is one of the most common neurologic diseases in the world, and is present in up to 4% of the world's population. Treatment of epilepsy with medications is a major effort of the World Health Organization, as many patients with epilepsy never receive the treatment that would render them seizure free. Epilepsy surgery is even less likely to be considered in developed or developing countries because of a lack of resources or a lack of recognition by the physician that a treatable syndrome exists.

For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Epilepsy.

Photograph of a patient positioned for lumbar drain insertion prior to corpus callosotomy.

Photograph of a patient positioned for lumbar drain insertion prior to corpus callosotomy.

This article addresses some of the most common types of epilepsy surgeries performed and explains the syndromes for which they are most useful. The type of evaluation required to prepare a patient for epilepsy surgery is discussed. Common procedures and imaging modalities used to aid with the diagnosis and localization of epilepsy prior to epilepsy surgery are also discussed. Advanced diagnostic techniques, namely, intracranial electrode placement, is covered in some technical detail. The following 4 surgeries are presented as models on which a preliminary understanding of the various surgical strategies can be gained:

• Anteromedial temporal resection (AMTR): This is the most frequently practiced surgery for a common and well-described disorder, namely medial temporal lobe epilepsy. It serves as a model for other focal resections.
• Corpus callosotomy: This is the only applicable surgery for generalized epilepsy syndromes.
• Modified hemispherotomy
• Multiple subpial transection (MST): This is a newer type of epilepsy surgery, and has limited applications that are still being developed.

First, presented in this article are definitions of basic concepts; then, the general workup of patients with routine diagnostic tests is discussed. Specific surgical techniques follow.
Reasons for considering surgical intervention
Although intracranial surgery involves inherent risks, these risks do not equal the risks of uncontrolled seizures. The morbidity and mortality of seizures include accidental injury; cognitive decline; sudden unexplained death in epilepsy (SUDEP); and psychological, social, and vocational impairment.

• Accidental injuries commonly include fractures, burns, dental injuries, lacerations, and head injuries.
• Mortality rates for patients with nonconvulsive and convulsive seizures far exceed those for age-matched controls. Among patients with poorly controlled epilepsy, SUDEP can reach a rate of 1 death per 500 patients per year. Risk factors are poorly controlled seizures and low serum antiepileptic drug (AED) levels.
• Cognitive decline and memory loss over time has been demonstrated to occur in patients with certain epilepsy syndromes who have recurrent convulsive seizures or episodes of status epilepticus.
• Both depression and anxiety are very common among patients with medically refractory epilepsy.
• Intractable epilepsy prevents driving, and reduces fertility and marriage rates.
• Vocational issues include inability to be employed or, if employed, underemployment.

The above factors clearly suggest that continued medical therapy after failure to control seizures with aggressive trials of AEDs is not optimal treatment of certain forms of epilepsy. In several retrospective trials and one prospective, randomized, controlled trial for a well-defined syndrome with a known favorable surgical outcome, mesial temporal lobe epilepsy, the morbidity and mortality associated with surgery has been demonstrated to be less than that associated with the disorder. In addition, surgery yields a better quality of life and reduced depression and anxiety as soon as 3 months after AMTR, compared with continued medical therapy. This improved quality of life is specifically related to the occurrence of complete seizure freedom in both the medical and surgical study groups.
Criteria for surgery
A candidate for epilepsy surgery must have not attained acceptable seizure control with sufficient trials of AEDs and have a reasonable chance of benefiting from surgery. Adequate AED trials must be considered within the context of the patient's circumstances and form of epilepsy. The precise numbers and type of AEDs to try before recommending surgery are unknown for the various epilepsy syndromes.

However, the American Academy of Neurology, the American Association of Neurological Surgeons, and the American Epilepsy Society has recommended the following practice parameters:

• Patients with disabling complex partial seizures, with or without secondarily generalized seizures, who have failed appropriate trials of first line antiepileptic drugs, should be considered for referral to an epilepsy surgery center, although criteria for failure of drug treatment have not been definitely established (level A rating)
• Patients referred to an epilepsy center for the reasons stated above who meet established criteria for an anteromedial temporal lobe resection and who will accept the risks and benefits of this procedure, as opposed to continuing pharmacotherapy, should be offered surgical treatment (level A rating).³

In 1996, Engel emphasized that the strategy of trying all combinations of drugs is not an acceptable approach to patients with syndromes known to have excellent chances of benefiting from surgery. For example, with the advent of 9 completely new AEDs since 1993, an estimated 300 years would be required to try all medications in all combinations. Far more importantly, recent studies of patients with new-onset seizures have shown that only 64% have seizure freedom by the time they try their third AED.⁴ Thus, after 3 different AEDs have failed to control seizures, more than 35% of patients continue to have seizures. Therefore, the decision to proceed with surgery must take into consideration both the chance of seizure freedom with additional AED trials and the adverse long-term effects of uncontrolled seizures.
Strategy for a surgical workup
The presurgical evaluation for epilepsy has changed substantially in the past few decades, most notably since the advent of long-term video-EEG monitoring in the late 1970s, advanced neuroimaging, and subspecialty epilepsy centers. The presurgical evaluation requires input from many members of an integrated team, which includes neurologists, neurophysiologists, neuropsychologists, social workers, radiologists, nurses, and epilepsy neurosurgeons. Aspects of the presurgical evaluation include the patient's history and physical examination findings, social circumstances, seizure syndrome and severity, and diagnostic testing (see Diagnostic Phase).
A surgical plan is usually developed at a multidisciplinary team conference. This allows open discussion among multiple experts so that the surgical approach is unique and is tailored to the individual's personal needs and epilepsy syndrome. When all presurgical information points to a unifying location and theory regarding focal seizure onset (also referred to as concordant data), then the patient may proceed directly to resective surgery. When data are inadequate to define a resective strategy, then diagnostic intracranial electrodes may be considered to further define the syndrome or site of seizure onset prior to any resective surgery.

Diagnostic Phase

A presurgical diagnosis is made after a classification of the patient's seizure types and specific epilepsy syndrome. The International League Against Epilepsy (ILAE) recognizes approximately 10 types of recurrent seizures and approximately 40 forms of epilepsy syndromes. Both classification schemes reflect the fact that seizures and epilepsies naturally fall into 2 major groups, based on the site of seizure onset in the brain, either (1) partial-onset (focal, localization-related) or (2) generalized-onset.^5,6
The signs and symptoms (semiology) experienced by the patient and the EEG pattern recorded at ictal onset determine a seizure diagnosis. This process begins by recording a careful history. For example, an event that is initiated with a blank stare and arrest of motion and then progresses to the development of automatisms (ie, automatic repetitive semipurposeful movements) is likely a complex partial seizure.

For initial AED therapy, a presumptive diagnosis based on history may suffice. However, even under the best circumstances, a diagnosis based solely on the history can be incorrect. Therefore, when proposing surgery for intractable epilepsy, the most accurate way to determine the epilepsy syndrome diagnosis and brain location of seizure origin is with long-term video-EEG monitoring (VEEG).
The following is a simplification of the international classification of epileptic seizures:

• Partial seizures (seizures that begin locally)
  • Simple partial seizures (consciousness not impaired; SPS)
  • Complex partial seizures (consciousness impaired; CPS)
  • Partial seizures that secondarily progress to generalized tonic-clonic seizures (SGTCS)
• Generalized seizures (seizures that arise diffusely)
  • Absence seizures
  • Atypical absence seizures
  • Clonic seizures
  • Tonic seizures
  • Tonic-clonic seizures
  • Myoclonic seizures
  • Atonic seizures
• Unclassified seizures

An epilepsy syndrome diagnosis combines the seizure type with its associated MRI, physical examination, genetic, and other features. For example, if the seizure described above (1) has correlative EEG epileptiform patterns (interictal spikes or sharp waves) and ictal discharges over the right temporal lobe, (2) occurs in a patient who had a febrile seizure as a child but no family history of epilepsy, and (3) is associated with ipsilateral atrophy and increased signal of the hippocampus on an MRI, it is likely a complex partial seizure of right mesial temporal lobe epilepsy. The greatest value of a syndrome diagnosis is to provide a prognosis. In the above example, if the patient is right-handed with normal intelligence, he or she has excellent odds of becoming seizure free after right-sided anteromedial temporal resection (AMTR).
A simplification of the previous international classification of the epilepsy syndromes has been proposed and is presented as follows:

• Focal (partial, localization-related) syndromes
  • Idiopathic (some are hereditary) - Benign childhood epilepsy with centrotemporal spikes, childhood epilepsy with occipital paroxysms, autosomal dominant nocturnal frontal lobe epilepsy, and familial temporal lobe epilepsies
  • Symptomatic (to known cause or lesion) - Temporal lobe epilepsies (mesial, lateral), frontal lobe epilepsies (several locations), parietal lobe epilepsies, occipital lobe epilepsies, and Rasmussen's encephalitis
• Generalized syndromes
  • Idiopathic (most are hereditary) - Benign neonatal familial convulsions, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, generalized epilepsy and febrile seizures plus, and various progressive myoclonic epilepsies
  • Symptomatic (or probably symptomatic) - West syndrome (infantile spasms) and Lennox-Gastaut syndrome
• Mixed - Continuous spike waves in slow sleep and acquired epileptic aphasia (Landau-Kleffner syndrome [LKS])
• Special situations

Structural and metabolic brain imaging
Because seizures may result from cortical lesions or malformations, neuroimaging can often help identify and localize this damage and, therefore, the site of seizure onset.

• Skull radiography: Routine skull films are of little value.
• CT scanning: MRI has replaced routine CT scanning because of superior imaging. The one exception is that CT scanning demonstrates intraparenchymal calcium and acute bleeding better than MRI. This may be helpful in distinguishing certain types of tumors or CNS syndromes, such as tuberous sclerosis.
• MRI: Brain MRI unquestionably is the best structural imaging study. Every surgical evaluation should include a complete study with special thin-cut coronal magnified views perpendicular to the axis of the temporal horn. These views can demonstrate mesial temporal sclerosis.
• Positron emission tomography (PET): Unlike MRI or CT scanning, PET scanning demonstrates brain glucose metabolism rather than structure. The typical finding from an interictal scan is hypometabolism in the region of the epileptic focus and, if the scan is obtained during a seizure, the typical finding is hypermetabolism from the focus.
• Single-photon emission tomography (SPECT): SPECT scanning helps visualize blood flow through the brain and, therefore, has been evaluated as another method for localizing the epileptic focus.
  • Interictal SPECT scans are less accurate than ictal scans. However, ictal scans are problematic because the tracer must be injected within the initial seconds of seizure onset. This requires that the radionucleotide be available on the monitoring ward 24 hours per day with personnel licensed (under state law) to administer intravenous injections.
  • A newer methodology that has greater accuracy than either ictal or interictal SPECT scanning is subtraction ictal-interictal SPECT co-registered to MRI (SISCOM). This requires obtaining scans (separated by at least 48 h to accommodate radionucleotide washout) during an interictal period and within seconds of seizure onset. These scans are then subtracted from one another with the use of specialized computer software. This leaves a better indication of the cortical area of ictal onset. This subtracted scan can then be co-registered onto the patient's MRI to provide support for the location of the focus.
• Magnetoencephalography/magnetic source imaging (MEG/MSI): MEG is a noninvasive type of imaging based on the brain's ability to produce small magnetic dipoles with neuronal discharges. When large groups of neurons fire synchronously, as in an interictal epileptiform discharge, this creates a miniscule magnetic dipole that can be sensed with sophisticated imaging equipment and complicated computer analysis. This map of the epileptiform discharge can be useful for diagnostic purposes and for presurgical planning of intracranial electrode placement.

EEG evaluation
The most useful test in epilepsy diagnosis is the EEG. An essential mistake is to place too much value on an isolated individual interictal recording. Assuming that a normal finding from the interictal scalp electrode EEG precludes the diagnosis of epilepsy is erroneous. The presence or absence of epileptiform discharges is highly variable, has no relationship to seizure frequency (for most epilepsies), and may be affected by antiepileptic drugs (AEDs). Thus, EEGs may need to be repeated several times before epileptiform discharges are observed. By definition, "epileptiform discharges" are interictal patterns that include spikes, spike-and-slow-wave complexes, sharp waves, and sharp-and-slow-wave complexes. The reader should refer to the second international glossary of EEG terms for precise definitions.

When the waking scalp EEG fails to demonstrate evidence of epilepsy, but the diagnosis is still suspected, a sleep EEG is recommended. Epileptiform discharges commonly activate during non–rapid eye movement sleep in some epilepsies. On fewer occasions than in the past, sphenoidal and additional extracranial electrodes are used to help reveal epileptiform (interictal) and ictal discharges.
Although the standard scalp EEG is helpful in making a diagnosis of epilepsy, it is not usually used when the physician makes major surgical decisions. This is because the distribution of interictal EEG discharges may not correctly localize epileptic foci. This error occurs for several reasons. First, discharges can be multifocal, although one focus can be the origin of all seizures. Further, because the EEG consists of volume-conducted potentials that originate over a relatively large area of cortical gray matter, some discharges can shift apparent location within or between hemispheres, and others may appear widely or even diffusely over the scalp. In addition, to obtain the most accurate data possible, recording sufficient numbers of the patient's typical seizures is important.
Like interictal discharges, ictal discharges vary somewhat. Also, more than one seizure focus or psychogenic or physiologic nonepileptic seizure may be found when numerous episodes are recorded.The latter may greatly affect a decision to proceed with surgery. Therefore, all surgical candidates should undergo long-term video-EEG monitoring prior to surgery to record several typical seizures.
Features of the scalp EEG ictal discharge, other than just location, can be helpful in the presurgical evaluation. For example, the authors reported that the frequency of the initial ictal discharge in the scalp EEG correlates with the degree of hippocampal pathology in temporal lobe epilepsy.
Neuropsychological testing
Neuropsychological testing, also known as neurocognitive testing, is the process of empirically testing an individual's functioning across a variety of cognitive domains, including attention, concentration, language, visuospatial skills, verbal and visual memory, and executive abilities (ie, problem solving, organization, strategic planning), as well as personality and emotional functioning. Neuropsychologists use a variety of standardized tests to assess all areas of cognitive functioning. An individual's performance on these standardized tests is then analyzed using normative data, and their performance is then compared with their peers and with what is expected based on estimates of their premorbid level of cognitive functioning. Patterns of cognitive strengths and weaknesses then provide information about brain-related deficits in cognitive functioning.

Well established is the idea that performance on specific neuropsychological tests is subserved by various areas of the brain, thus providing lateralizing and localizing information about brain functioning. For example, a right-handed individual's performance on verbal memory tests (ie, story memory, verbal paired associates learning, and list-learning tasks) is largely subserved by left mesial temporal structures. Similarly, a right-handed individual's performance on visual memory tests (ie, figural memory and complex figure memory tasks) is largely subserved by right mesial temporal structures. Thus, an individuals cognitive strengths and weaknesses on neuropsychological testing can indicate areas of brain dysfunction, which provides additional information that can help localize an epileptogenic focus.

Additionally, an individual's cognitive strengths can provide information about possible cognitive risks involved in undergoing a neurosurgical resection to treat medically-intractable epilepsy because a risk of increased memory deficits after resection of mesial temporal structures exists.Routinely, all epilepsy surgical candidates undergo extensive neuropsychological testing. Neuropsychological testing is tailored to best assess the type of epilepsy with which each individual presents, often focusing heavily on cognitive functioning that has likely been most affected by a hypothesized epileptogenic focus. As a result, testing is often tailored to uniquely assess the cognitive strengths and weaknesses for each individual and can vary across individuals.

Neuropsychological testing can also be used for nonoperative or postoperative epilepsy patients to assess their level of cognitive functioning in order to assist with vocational and cognitive rehabilitation in the context of their neurological disorder.
Intracarotid amobarbital (Wada) test
The intracarotid amobarbital test was developed by Jun Wada to preoperatively determine which hemisphere contains language function. Although this continues to be a use of the Wada test, functional MRI for language now provides a noninvasive way to more accurately lateralize and localize language functioning. The primary use of the Wada test is to assess language lateralization and the ability of the contralateral mesial temporal structures to support memory postoperatively when AMTR is being considered to treat medically-intractable epilepsy.
The procedure is conducted by individually cannulating each internal carotid artery. After contrast arteriography verifies that blood flows to the corresponding hemisphere and not to the brainstem or contralateral side, a dose of sodium amobarbital (sufficient to impede hemispheric function) is injected. If the drug produces a contralateral hemiparesis, function of that hemisphere is assumed to be minimized.

Language lateralization is determined by conducting a comprehensive screen of various components of language, including expressive language, receptive language, naming, repetition, and complex syntactical comprehension. If an individual is able to engage in all aspects of language while they demonstrate hemiparesis, language function is assumed to not be represented within that hemisphere. Assessing a variety of aspects of language is important because some individuals possess a bilateral representation of language, such that some aspects of language are subserved by one hemisphere while other aspects of language are subserved by the contralateral hemisphere.

Memory functioning is assessed by presenting the patient with visual and auditory items (often using multiple sensory modalities to maximize the chance of encoding) while the hemisphere is anesthetized. Following recovery of hemispheric function, which is confirmed by return of gross and fine motor function, as well as language if possible, the patient is then tested for their free, cued, and recognition recall of the items with which they were presented during anesthetization. If the patient is able to accurately recall 75% of the items presented to them during anesthetization, that provides evidence that the contralateral hemisphere should be able to support memory after ATMR of the hemisphere that was anesthetized.

If the patient is unable to accurately recall a sufficient number of items, that information provides evidence that the patient may experience significant memory difficulties postoperatively. Importantly, patients should undergo neuropsychological testing prior to undergoing a Wada procedure, because that testing provides important information about their baseline level of memory functioning and more accurately informs the results of the Wada test.

The deficiencies of this evaluation for memory function directly relate to the multiple problems of targeting a drug effect to specific brain structures via cerebral blood flow. Injection of a drug into the internal carotid artery does not assure drug effect in the basal temporal area in general or the hippocampal region specifically (an area that subserve memory function). This is due to variations in the direct blood supply to the hippocampus and inequalities in delivery when the drug is injected into the blood stream.
Intracranial EEG recordings
Intracranial EEGs recordings, also known as chronic electrocorticography (ECoG) is an invasive procedure that is performed when noninvasive presurgical evaluation has not led to definitive localization of a seizure syndrome and surgical plan. The presurgical team, which includes a neurosurgeon, neurologist, neuropsychologist, social worker, and neuroradiologist, considers all previous accumulated data to determine an appropriate strategy for placement of intracranial electrodes. Any combination of intracranial strips, grids, and/or depth electrodes may be tailored to answer the specific questions posed by the case history and presentation specific to that particular patient, depending on the needs of the patient, experience of the monitoring team, and resources available for use.

The following are examples of instances that may require invasive intracranial monitoring:

• Seizures are lateralized but not localized (eg, a left-sided, widespread frontal-temporal onset).
• Seizures are localized but not lateralized (eg, ictal EEG patterns that appear maximally over both temporal lobes).
• Seizures are neither localized nor lateralized (eg, stereotyped complex partial seizures with diffuse ictal changes or initial changes obscured by artifact).
• Seizure localization is discordant with other data (eg, EEG ictal scalp data discordant with neuroimaging [MRI, PET, SPECT/SISCOM, MEG] or neuropsychological data).
• Relationship of seizure onset to functional tissue must be determined (eg, seizures with early involvement of language or motor function).
• Relationship of seizure onset to lesion must be determined (eg, dual pathology or multiple intracranial lesions).
• Seizures are clinically suspected, but video-EEG is inadequate for defining them (eg, simple partial seizures with no detectable scalp EEG ictal discharge or suspected epileptic seizures with unusual semiology that suggests psychogenic seizures [pseudo-pseudo seizures])

Invasive intracranial monitoring is a diagnostic procedure, designed to identify the site of ictal onset of seizures. Intracranial electrodes are reserved for the most difficult of cases; therefore, one risk of surgery is that the study will end up with a nondiagnostic result. The onus is on the surgeon to question where electrodes should be placed based on the presurgical information available and to consider what other alternative diagnosis should be included or excluded to obtain the best possible electrode placement. The concept that epilepsy consists of a focus that can be removed has evolved into a more unified theory in which the neural network, environment, genetic predisposition, and epileptogenic substrate all must be considered during the evaluation of the patient with epilepsy, if surgery is to be effective.
Definitions
Depth, strip, and grid electrodes are implantable intracranial devices used to record the electrocorticogram (ECoG) chronically, and to stimulate the cortex to determine function (see Image 1). Depth electrodes are multicontact, thin, tubular, rigid or semirigid electrodes that penetrate the brain substances for the purpose of recording from deep structures (see Image 2). Intracranial strip electrodes are a linear array of 2-16 disk electrodes embedded in a strip of silastic,or they can be tubular in structure, similar to depth electrodes.Grid electrodes are parallel rows of similar numbers of electrodes that can be configured in standard or custom designs according to the preferences of the surgeon and the abilities of the manufacturer. Grid and strip electrodes are designed to be in direct contact with brain neocortex.

Examples of various grid electrodes available for specific needs. These range in size and number of contacts

Examples of various grid electrodes available for specific needs. These range in size and number of contacts.

Examples of 3 depth electrodes with varying numbers of contacts. Note: The stylus is in place and is removed once the electrode has been inserted.

Examples of 3 depth electrodes with varying numbers of contacts. Note: The stylus is in place and is removed once the electrode has been inserted.

In most cases, electrodes are placed in the subdural space, although they may occasionally be used in the epidural space. All of these electrode types are constructed from biologically inert materials (ie, silastic, stainless steel, platinum). Platinum electrodes are more easily seen on fluoroscopic images than are stainless steel electrodes and are compatible with MRI so that postoperative diagnostic and localizing neuroimaging studies can be obtained.

Diagnostic Phase - Intracranial Recording

Strip Electrodes

Strip electrodes are used most often to lateralize the side of seizure onset in frontal and temporal lobe epilepsy, but they may also be used to obtain survey studies over all cortical surfaces of the brain. They are usually implanted while the patient is under general anesthesia, according to the preoperative plan created by the epilepsy monitoring team. Electrodes can be directed safely over long distances within the calvaria by surfing electrodes over the brain with a gentle fluid pulse. Fluoroscopy is used to confirm placement prior to closure of the wound.

Electrode wires are tunneled under the skin with a 13-guage passing needle designed for that purpose (Ad-Tech Medical; Racine, Wis), to exit the skin several inches away from the burr-hole incision to decrease the risk of infection. Cerebrospinal fluid (CSF) may leak from around the electrode wires during the first 3 days after implantation. This can be minimized if the scalp exit sites for the electrode tails are directed superiorly toward the vertex of the skull. The suggested risk of infection from a CSF leak differs from center to center; however, completely sealing the skin with a foreign body in place is difficult and CSF leaks are not uncommon. Because of this, the dressing is changed as often as needed.

Some authors suggest placing a cable-retaining suture in the scalp, both to attempt to secure the electrode and to decrease CSF leak. The lead author has not found it helpful in decreasing CSF leak, and all electrode companies manufacture quick-release connectors designed to break apart easily if tugged.
Patients are monitored with electrodes in place in the monitoring unit for 2-7 days to record their typical seizures. Subdural strip electrodes are removed through the skin without an open surgical procedure by gentle traction on the electrodes, under conscious sedation or general anesthesia.
Although strip electrodes can be inserted epidurally,this practice is not advisable for routine cases because the exposure is limited to the lateral convexities of the brain. The epidural space in the temporal fossa does not allow the electrode to be advanced medially enough to record from the parahippocampal gyrus, and electrodes cannot be placed over mesial frontal lobe cortex. In most exploratory investigations, these locations should be sampled. However, epidural placement may be the most reasonable option when recording from a patient with a prior craniotomy because scarring may obliterate the subdural space.

Subdural Grid Electrodes

Arrays of electrodes more than one column wide are considered intracranial grids (see Image 1). Practically speaking, electrode arrays that are 2-3 contacts wide cannot be easily passed for any substantial distance through a burr hole and require a craniotomy for placement. Once the decision to proceed with a craniotomy is made, grid arrays of 5-8 rows (20-64 contacts) are usually used to maximize coverage over the craniotomy site. The craniotomy site is determined based on data gathered during the presurgical evaluation; usually, a large craniotomy is performed to accommodate up to an 8 X 8-cm grid. Prophylactic antibiotics and dexamethasone are routinely administered. Mannitol is not used unless necessary because the putative space created by a fluid shift could adversely contribute to hematoma formation after closure.
Once placed, the grid is sutured to the dura to prevent motion. Often, one or more strip electrodes are added to sample adjacent areas or lobes, such as the interhemispheric fissure or basal temporal lobe. The electrode tails of grids are similarly tunneled to strip electrodes, toward the vertex, to avoid CSF leaks. At some centers, the bone flap is frozen under sterile conditions until the patient returns to the operating room (OR) for grid removal. However, the author prefers to leave the bone flap in place to decrease the risk of hematoma formation at the craniotomy site.
After recovery in the postanesthesia care unit, the patient is transferred to the video-EEG monitoring suite, where the patient is hooked up on the day of surgery and a formal head dressing is placed. Acute nursing care is provided in the monitoring suite for the first 24 hours after craniotomy, similar to the level practiced in a neurological step-down unit.
The grid is removed when sufficient data have been obtained to determine the site of ictal onset or, alternatively, to determine that no more recording is likely to lead to satisfactory localization. If resective surgery is planned, then the relationship of the grid to the underlying cortex must stay unchanged while the craniotomy is reopened. The dura is opened, leaving the grid-stabilizing sutures intact and keeping all relationships between electrode contacts and unique underlying cortical topography (eg, blood vessels) undisturbed. Once these relationships have been documented and the surgeon has extrapolated the mapped data to the underlying cortex, the grid is removed and discarded.
Resective surgery is performed, with the neurophysiologist or pathologist present in the OR as necessary. If resection is not performed at the time of grid removal (eg, because of hemorrhage, edema, patient preference, or insufficient data), then pertinent landmarks may be documented with digital photography or frameless stereotaxy for reoperation at a later date.
Higher complication rates for intracranial grid electrode placement have been associated with an increased number of electrode contacts, increased length of the monitoring period, placement of burr holes in addition to the craniotomy, and multiple cable exit sites.At the authors' institution, antiepileptic drugs (AEDs) are stopped on the morning of surgery (except for benzodiazepines and barbiturates, which are given in reduced doses). Video-EEG monitoring continues until the epilepsy team believes adequate ictal data have been obtained, usually in 2-8 days.

Depth Electrodes

Depth electrodes are used most commonly for recording from the hippocampus and amygdala. The approach preferred by the authors is to place electrodes via the occipital, parasagittal route.This trajectory allows for simultaneous implantation into the amygdala and anterior and posterior hippocampus using a single multicontact electrode. Placement is performed with either a frameless system, discussed below, or a stereotactic frame with adequate clearance at the back of the head. MRI is used with both frame-based and frameless stereotactic placement to allow direct visualization of the target and trajectory.
Indications for depth electrode placement are expanding as neuroimaging becomes more sophisticated and more complex epilepsy syndromes are identified. This is particularly true among the malformations of cortical development, particularly when the dysplastic lesion is subcortical. Depth electrode recordings into hypothalamic hamartomas and periventricular nodular heterotopia have shown ictal onsets beginning within the lesions, which subsequently spread to produce clinical seizures.
Depth electrodes are most often used in conjunction with other subdural strip or grid electrodes so that multiple brain areas are sampled simultaneously to avoid false localization based on insufficient data collection. Specific intracranial EEG ictal discharge frequencies, locations, and patterns can suggest, preoperatively, certain types of histopathological findings

Intracranial Electrode Recordings and Removal

At most epilepsy centers, rooms with hard-wired EEG and video telemetry instruments are only used for long-term monitoring and not for general medical or surgical patients. Patients may be taken directly from the recovery room to one of these monitoring rooms, or may stay in the ICU for the first night of monitoring. Antiepileptic drugs are tapered or withdrawn and video-EEG recordings are begun the day of electrode implantation.
The relative accuracy of ictal versus interictal electrographic activity remains somewhat controversial. In general, interictal spikes are usually more diffuse than the ictal onset zone, and bilateral interictal spikes can occur in patients who ultimately do well after a unilateral resection, and therefore, do not preclude a good surgical outcome. Obtaining ictal recordings is usually preferable in order to confirm the significance of interictal abnormalities, as ictal recordings are considered more accurate that interictal data. One possible exception to this general guideline might be when recording from a focal cortical dysplasia; distinctive interictal epileptiform patterns have been identified that may provide enough data to guide a resection based solely on interictal data.

When monitoring a lesion with intracranial electrodes, seizure outcome is best when both the lesion and the ictal onset zone are completely resected; outcome is compromised when either the lesion or the ictal onset zone is incompletely resected. In the case of nonlesional epilepsy, seizure freedom is more difficult to achieve, even in cases in which the ictal onset zone has been well studied with intracranial electrodes.
The number of seizures required to consider an intracranial study complete depends on the specific issues involved with treating a particular patient. In general, an arbitrary number of 3 typical clinical seizures has been considered the minimum number to be captured; however, exceptions to this rule abound For example, a patient with a posterior temporal or parietal lesion and scalp EEG localization to the anterior temporal lobe that is delayed compared with clinical onset might be considered for an intracranial study to confirm the clinical suspicion that seizures are falsely localized to the anterior temporal lobe. In such a case, 1-2 seizure onsets with intracranial EEG ictal onset directly over the lesion might provide sufficient data to proceed to surgical resection.

On the other hand, a patient with nonlesional epilepsy and bilateral ictal onset over both temporal areas on scalp EEG monitoring would require many more than 3 seizures to be recorded to exclude bilateral temporal onset and/or establish a predominant side of onset.
The type of ictal onset recorded may influence the number of seizures required. Fewer seizures need to be recorded in patients who have identical ictal onset patterns over the exact same electrode contacts in every seizure. More seizures need to be recorded in patients with multifocal ictal onsets in different electrodes from seizure to seizure. Initial ictal changes at the beginning of a seizure are more important than late changes and the propagation patterns of the seizure. Seizures that occur seconds to minutes after a previous seizure may be disregarded as being potentially misleading.
When intracranial monitoring is complete, most subdural strip and depth electrodes can be removed percutaneously in the OR after administrating a conscious sedation protocol or general anesthesia. Because of concern over contracting virally transmitted disease (eg, AIDS, Creutzfeldt-Jakob disease, hepatitis), recording electrodes are commonly discarded after a single use.
New computer-assisted prediction paradigms are being created to analyze ictal onset and changes in the background electrical state, interictal spike frequency, confluence analysis, and chaos theory in order to predict seizure occurrence minutes to hours before ictal onset. Intracranial monitoring will likely need to adapt to accommodate these new technologies in the near future.
Staged procedures
The following are reasons a second intracranial study may be considered:

• Strip electrode survey study for lateralization and localization to a lobe, with a planned return at a later date for definition of the ictal onset zone and cortical mapping as necessary
• Reimplantation of a second grid because of failed localization secondary to sampling error (Seizures may occur on the margin of the grid, be diffuse, or show variable propagation that makes seizure localization uncertain.)
• Recurrent seizures after a previous intracranial study and resection

These procedures are typically performed months to years after the first intracranial study, either to give the wound time to heal or because seizures recur at some variable time after resective surgery. Often, an interim presurgical evaluation is performed, which includes video-EEG monitoring, ictal SPECT scanning, MRI, and/or magnetoencephalography, to reexplore the suspected cause of a person's epilepsy and prepare a more effective intracranial study. Secondary grid implantations can be quite troublesome because dural adhesions are the rule rather than the exception.

Therefore, when planning a second intracranial study, the surgeon should anticipate a difficult entry and should use many of the strategies used for reoperation in other craniotomies, including enlarging the bone flap until pristine dura is encountered and opening the dura away from the previous operative site and away from functional cortex. If adhesions are encountered, an operating microscope should be reserved and used early in the dissection.
The authors of this article routinely plan to spend 1-3 hours under the operating microscope when scheduling a reoperation for epilepsy. Even with tedious dissection, adhesions can limit the distal passage of electrodes and limit the effectiveness of a repeat intracranial study.
Consecutive grid placement
Several authors have suggested an alternative to delayed reoperation. These authors advocate immediate reimplantation during the same hospitalization if the findings from the first grid were not diagnostic. Doyle refers to this as a 3-stage procedure, and Lee describes the same technique as a double grid. This technique has certain advantages over delayed return for implantation of a second grid. Firstly, adhesions do not obscure the subdural space, which can limit grid reimplantation. Secondly, cortical injury can be avoided because adhesions do not need to be dissected from functional tissue. Thirdly, intracranial EEG changes can be compared with the previous study while the subtleties of the previous intracranial electrocorticogram (ECoG) are still fresh in the minds of the evaluating team.

However, others feel that placing a grid again immediately after a first operation is likely to alter the network of epileptogenesis and that resultant seizures with second grid implantation might not best represent the patient's typical seizures.
Doyle advocates performing a limited resection of the ictal onset zone seen with the first grid because a partial resection of the epileptogenic region may help identify which additional areas are still contributing to seizure onset once the major site of ictal origin has been removed. Favorable seizure control was achieved with no apparent increase in surgical morbidity in 42 three-stage procedures when compared with 369 traditional grid protocols and in 18 double procedures compared with 165 routine intracranial procedures.

Documenting the Intracranial Study

Each intracranial study is unique to the patient for whom it is designed. Even routine intracranial cases have subtle variations in electrode placement based on the patient's anatomy. Some sort of documentation of the intracranial study is advisable for a number of reasons, including confirmation of the accuracy of placement, communication with the neurophysiology team, and correlation with gyral anatomy or intracranial lesions. The possible options available for documentation, beginning with the simplest and proceeding to the more complicated, are discussed in this section.
When placing intracranial strip electrodes, the most vital piece of documentation regarding the study begins in the OR. As each electrode is inserted, the operating surgeon describes the identifying characteristics of that electrode (eg, length, color coding, scalp exit site) and its intracranial position to an assistant, usually an OR nurse, who documents this information directly in the operative record or chart notes so that no confusion is encountered when the electrodes are eventually connected. Most EEG technologists appreciate a line diagram handwritten by the surgeon in the chart. This simple step can eliminate many potential sources of human error, particularly with extensive intracranial surveys, and facilitates communication between all members of the team.
Another simple way to document the operative technique is for the monitoring team to use an anatomical brain diagram and transparencies of the grid montage to create a mock-up of the surgery. The image created is compared with fluoroscopic images taken at surgery so that a relatively accurate rendition of the electrode placement is available within minutes on the day of the surgery. These images can be quite helpful in interpreting seizure onset and propagation during EEG monitoring.
In more complicated cases, a member of the monitoring team is present in the OR to take digital photographs of the exposed cortex before and after grid placement. Digital photography helps identify the relationship of a grid to the sylvian fissure and is one of the best methods to document the fine anatomy of the brain, including sulcal and arteriolar anatomy that cannot be seen with advanced imaging techniques.
More sophisticated imaging techniques have been developed and are being used with increasing frequency as advanced imaging software becomes more available. Cranial MRI with a head coil can be obtained safely in patients with intracranial grids and strip electrodes in place if a few safety considerations are kept in mind. Most electrode manufacturers endorse platinum electrodes as MRI compatible, although stainless steel electrodes have also been used without apparent patient injury. Because each epilepsy center has different procedures, checking the recommendations of the particular electrode manufacturer prior to obtaining an MRI is advisable. In all cases, current loops can theoretically be created within a magnetic field if the electrode tails are allowed to contact one another. Therefore, all electrode tails should be isolated before obtaining MRI.
Most MRI workstations or software packages allow for 3-dimensional reconstruction of images, which are often more useful than traditional MRIs or CT scans. In addition, most frameless stereotaxic navigation systems allow for image reconstructions of an MRI that can be merged with preoperative anatomic, functional, or angiographic imaging to create an accurate rendition of the grid in relation to relevant operative anatomy.

Cortical Mapping

Often, in addition to defining the location of the epileptogenic cortex, the surgeon must determine its relationship to functional cortex. This requires mapping the cortex underlying an implanted grid electrode. The technique is similar to that performed acutely in the OR and requires a testing protocol appropriate to the cortical region being investigated. Cortical stimulation is performed using commercially available constant-current generators. Cortical mapping is performed by selecting 2 adjacent electrodes (1-cm intervals) because bipolar stimulation provides more precise control of current flow. Bipolar pulses at 50 Hz are used for language, motor, and sensory mapping.
Extraoperative cortical mapping has several advantages over acute intraoperative mapping. Functional mapping may be performed in multiple sessions if necessary. For example, if a seizure that impairs function is generated during mapping, the patient may be allowed to recover for several hours (or days) until proceeding with further mapping. Advanced paradigms may be performed over hours or days that would not be possible in the acute intraoperative setting. Once mapping is completed, the patient, family, and surgeon have time to discuss the potential risks and benefits of surgery and to make decisions to accept or reject a functional loss that might be associated with surgery.
During brain stimulation, brain mapping is performed by a neuropsychologist or physician, who may test language or motor function. A clinical neurophysiologist reviews the ECoG during stimulation to ensure that any disruption of neurological function is due to the stimulation and not an afterdischarge. Afterdischarge potentials are repetitive spike discharges or electrical seizures directly provoked by electrical stimulation and may limit the ability to map the brain or may lead to a seizure. The amount of current needed to produce an effect varies from patient to patient and between cortical regions. Enough current should be used to produce a reliable effect without causing afterdischarge. Occasionally, pain can result from current spread to the dura or a nearby cortical vessel. In such cases, a particular contact may not be suitable for mapping.
Surgeons are often encouraged to be present for intracranial, extraoperative mapping, particularly early in their careers. Some of the slight variations in mapping technique and interpretation have subtle ramifications for the surgeon and are different from those that a neurologist or neuropsychologist might appreciate. On some occasions, mapped cortical regions vary from what one would expect from classic anatomic studies, particularly in areas of cortical malformations.

On other occasions, mapping different pairs of electrodes in a specific region (eg, motor or language areas) might allow the surgeon to appreciate the orientation of a crucial region relative to the orientation of the grid or to adjacent contacts. Finally, subtle errors in naming or language may be present extraoperatively, when the patient is off AEDs, and these errors may change when the patient is reloaded with AEDs Such subtleties of extraoperative mapping can be useful to the surgeon if observed personally prior to a resection.
Implanted grid arrays are excellent tools for identification of the position of sensorimotor cortex through somatosensory evoked potentials (SSEPs). Allison and colleagues have reviewed the rationale and technique,and others have discussed the clinical experience with subdural grids for this purpose.SSEPs can be used during acute recording in the OR, using subdural strip electrodes to identify primary motor cortex. The strip electrode must be positioned to traverse motor and sensory cortex, and it may need to be repositioned several times during intraoperative recording to optimize the signal. Therefore, if SSEPs are planned during extraoperative monitoring, using a subdural grid to increase the surface coverage by the electrode array is advantageous in order to optimize the location of motor cortex (see Images 8-9).

Craniotomy that shows an intracranial grid in place. The grid lies over left primary motor and sensory cortex, near the vertex of the skull. The patient is positioned laterally, and the face is at the right. The intracranial study was performed to document seizure onsets in a patient who had a previous oligodendroglioma removed. Seizures began just posterior to leg motor cortex, in primary sensory cortex.

Craniotomy that shows an intracranial grid in place. The grid lies over left primary motor and sensory cortex, near the vertex of the skull. The patient is positioned laterally, and the face is at the right. The intracranial study was performed to document seizure onsets in a patient who had a previous oligodendroglioma removed. Seizures began just posterior to leg motor cortex, in primary sensory cortex.

The primary motor cortex is located with the use of extraoperative somatosensory evoked potentials and intraoperative cortical stimulation, as well as the grid described in Image 8. The Penfield instrument in the field is positioned over primary motor cortex.

The primary motor cortex is located with the use of extraoperative somatosensory evoked potentials and intraoperative cortical stimulation, as well as the grid described in Image 8. The Penfield instrument in the field is positioned over primary motor cortex.

Sometimes, extraoperative mapping indicates that the ictal onset zone is close to or overlies critical motor or speech areas. On such occasions, using the advantages of awake operative language mapping may be helpful at the time of grid removal and resection of the epileptic focus. Although extraoperative mapping has many advantages, the accuracy of its spatial resolution is limited to 1 cm, namely, the distance between 2 electrode pairs. Sometimes, awake intraoperative mapping helps confirm which electrode is the contact that directly overlies cortical function. This can be particularly important when the 2 electrodes span a sulcus; in such cases, awake mapping may allow the surgeon to determine which gyrus is involved in function and which gyrus is not.In such cases, the epileptic zone may be resected up to the pial margin without disturbing function, as long as the vascular structures within the pia are preserved.

Complications

Published series of infection rates from all types of intracranial electrodes range from 0-12%. The morbidity of surgery depends on the type of electrode implantation; intracranial strip electrodes have the lowest morbidity, and intracranial grid placement has the highest morbidity.
The most common cause of morbidity in subdural strip placement is infection. One randomized study found a 0.85% rate of infection between groups treated with antibiotics prior to surgery, compared with a 3% infection rate when no antibiotics were given. No difference in infection rates was noted between patients who received antibiotics for the duration of strip electrode implantation versus those who received only a single preoperative dose; therefore, at the authors' institution, a single dose of antibiotics is given immediately before strip or grid implantation.

Other complications of intracranial strip placement include cortical contusion, cerebral edema, brain abscess, subdural empyema and subdural hemorrhage, placement of electrodes into the brain parenchyma, accidental extraction of electrodes, and superficial wound infection. Many of these complications are minor and cause no long-term problems; permanent neurological deficit is seen in less than 1% of patients who undergo intracranial strip electrode implantation.
Complications of grid implantation include infection, transient neurological deficit, hematoma, cerebral edema with increased intracranial pressure, and infarction. Transient neurological deficits can occur secondary to edema or hematoma associated with the grid. In most cases, if neurologic compromise is evident, the grid should be removed immediately. Cerebral edema is more likely to occur with an increase in the duration of the monitoring session or with a greater number of intracranial electrodes Some authors have been concerned that pediatric patients are more likely to develop increased intracranial pressure because, theoretically, less space is available to accommodate the mass of an intracranial grid  however, others have not found this to be a concern.
Complications from depth electrodes include intraparenchymal hemorrhage, subarachnoid hemorrhage, arterial spasm, and misplacement of the electrode. The rate of permanent neurological deficit from occipital depth electrode placement has been reported at less than 1%.The risk of hitting the brainstem or posterior cerebral artery with occipitally inserted depth electrodes may be decreased by (1) targeting tip placement in the lateral amygdala and lateral hippocampus, (2) making sure the occipital burr hole is not too medial, and (3) confirming the trajectory with an image guidance system prior to electrode placement.

Alternatively, one can attempt to place the depth electrode into the lateral ventricle rather than into the hippocampus. To do so, a rigid guide cannula is placed into the ventricle (verified by identifying CSF flow from the cannula), and then the depth electrode is placed into the ventricle. The electrode then lies in the temporal horn adjacent to the hippocampus, with its tip entering the targeted amygdala.

Ictal recording from the ventricle usually conducts signal well, with only occasional failure The signal obtained amplifies (1) both hippocampal and parahippocampal ictal onsets and (2) intraparenchymal amygdala onset. The risk of subarachnoid hemorrhage may be minimized if depth electrodes are placed under direct visualization through a burr hole rather than using a closed twist-drill technique, which helps avoid draining veins during placement, and by using image-guided stereotaxy and contrast-enhanced MRI to avoid surface veins at the entry point.

Some surgeons prefer orthogonal placement of depth electrodes, which has been facilitated by frameless stereotactic techniques. Several systems allow placement of orthogonal depth electrodes via twist drill or burr holes in the temporal fossa. Stereotaxy is required to avoid vascular injury to vessels of the middle cerebral artery and to gain accurate placement into the amygdala and hippocampus. Electrodes must be secured at the skin to ensure migration of the electrodes does not occur as the medial trajectory of these electrodes is towards the brainstem.

Appropriate Surgical Strategy

Surgery may be considered as either definitive and palliative. Definitive surgery carries a significant chance of producing complete, or at least 70-90%, improvement in seizures. The goal of palliative procedures is to decrease seizure frequency, but rarely results in seizure freedom.
In general, definitive surgeries physically remove seizure-producing cortex from the brain. Examples are resections of small seizure-producing tumors, vascular abnormalities, cortical malformations, or lesions such as mesial temporal sclerosis.
Palliative surgeries usually disrupt pathways involved in seizure production and propagation or attempt to disrupt seizures with the use of electrical stimulation; thus, the potential for continued seizures always remains.
A general approach to epileptogenic lesions
Tumors that cause epilepsy are frequently low-grade astrocytomas, oligodendrogliomas, or gangliogliomas. Commonly, they are well circumscribed, and excellent outcomes can be achieved with a lesionectomy that includes the immediate surrounding abnormal cortex.

However, there is a temptation to rush to surgery, making the assumption that the tumor is causing the seizures. The more cautious epilepsy surgeon may consider the possibility of alternative diagnoses, such as dual pathology, (the presence of hippocampal atrophy and tumor in the same patient), or look for evidence for concomitant cortical dysplasia, depending upon the suspected tumor pathology.

The presurgical evaluation in the setting of tumor pathology is to determine that the EEG findings and the tumor are not discordant, which can occur approximately 10-15% of the time. In such cases, the lesion may not be solely responsible for the epilepsy, and a more extensive resection may be required to control the epilepsy. When the tumor and the lesion are concordant, the most common mistake when treating these tumors is to remove only the gross tumor and not the immediate surrounding tissue, thus leaving epileptogenic tissue in place and resulting in clinical seizure resumption. If seizures continue after tumor removal, an assumption is that the tumor was not completely removed, regardless of MRI evidence of a clean resection.
Small vascular abnormalities, such as cavernous hemangiomas surrounded by hemosiderin, can be extremely epileptogenic. Removal of the vascular abnormality and surrounding hemosiderin-stained cortex may be all that is necessary for an excellent seizure outcome in approximately 80% of patients, provided the presurgical evaluation is concordant.
Large vascular abnormalities (eg, high-flow arteriovenous malformations) are commonly associated with seizures. Unlike the smaller vascular lesions, the relationship between the structural lesion and the epileptogenic cortex is not always clear, and simple lesionectomy often fails to stop the seizures. Because of the technical difficulties involved, implanting a large grid electrode over these lesions for the purpose of mapping is usually not feasible. Therefore, treatment of such lesions should seldom be approached purely as an epilepsy surgery. One successful approach is to stage surgeries; the vascular abnormality is removed with the intent of further investigation and possible surgery if seizures remain.
Epileptogenic congenital malformations of cortical development, such as cortical dysplasias, heterotopia, schizencephalic clefts, and the various forms of phakomatoses, are very difficult to treat surgically and usually require more extensive evaluations and tailored resections based on implanted grid electrodes.Seizure outcome after resection of such malformations is variable and directly relates to the complexity of the lesion.
Traumatic encephalomalacia is treatable surgically, with varied results. The difficulty with these lesions is that cortical damage often extends much further than the area of obvious anatomical damage, or multiple regions of the brain are affected simultaneously.
Controversial issues in definitive surgery
With regard to performing an acute intraoperative electrocorticogram (ECoG), some surgeons believe that epileptiform discharges recorded acutely during surgery indicate which part of the brain is epileptogenic; therefore, these surgeons use the ECoG to define boundaries for cortical resections. This approach is referred to as a tailored resection in that no 2 operations are identical. Because anesthetic agents affect the reliability of acute ECoG recordings and prevent the surgeon from mapping cortical function (eg, language), tailored resections are performed best with the patient under local anesthesia.

Other surgeons believe that an acute, interictal, ECoG is not reliable enough to determine surgical boundaries and can be inaccurate; these surgeons proceed with a standardized surgery, wherein tissue important for generating seizures is removed without considering the ECoG for some surgeries. If a question is to be answered with ECoG, then the patient receives an intracranial study, and long-term monitoring with intracranial electrodes is performed to capture ictal ECoG, and a "tailored resection" is based on intracranial ictal recording rather than short-term, less accurate, interictal data.
For anteromedial temporal resection (AMTR), no scientific data support the belief that ECoG-guided resections produce results superior to standard surgeries. A more rational approach is that the surgeon should recognize the specific syndromes for which a standardized operation is very effective. The best example is complex partial seizures of mesial temporal lobe epilepsy with hippocampal sclerosis. Such patients have excellent seizure and language outcomes after standard surgeries while under general anesthesia. Likewise, excellent results are expected from the removal of a well-circumscribed capillary hemangioma from a patient with complex partial seizures.
In contrast, patients with epilepsy secondary to other etiologies in other brain regions may need extensive cortical mapping and an ictal ECoG. In such cases, implantation of a large subdural grid electrode for long-term monitoring (with an ECoG) and mapping is preferred because it yields results superior to performing an acute interictal ECoG.

Operative Technique - Anteromedial Temporal Resection

Anteromedial Temporal Resection for Hippocampal Sclerosis

Anteromedial temporal resection (AMTR) is the most commonly performed surgery for epilepsy. It has the clearest indications and best results. Thus, AMTR is used as a criterion standard against which other procedures can be judged and strategies extrapolated.
Indications
Candidates for AMTR have the following:

• Complex partial seizures with semiology typical of mesial temporal lobe epilepsy
• MRI evidence of unilateral hippocampal atrophy and increased T2-weighted signal (At some centers, volumetric measurements of the hippocampus are routinely obtained.)
• Unilateral temporal lobe hypometabolism on PET scans if MRI findings are nonlesional in nature
• EEG confirmation that seizures begin over the temporal area ipsilateral to the hippocampal atrophy or PET scan evidence of hypometabolism

Although AMTR for mesial temporal lobe epilepsy has now been shown to be more effective than continued medication, studies to date have included patients who have had epilepsy that has been refractory to medical treatment for a prolonged period. Most patients who are finally referred for AMTR have had epilepsy for approximately 20 years. Because continued complex partial and generalized tonic-clonic seizures have such negative effects on vocational, educational, social, cognitive, and psychological areas and because these seizures can cause injury and even sudden death, most epileptologists believe that AMTR should be offered to good surgical candidates earlier.
An issue that remains unclear is how much time must elapse, or how many AEDs must be found to be inadequate, before surgery is recommended. For this reason, the US National Institutes of Health sponsored a large prospective study entitled Early Randomized Surgery for Epilepsy Trial (ERSET). ERSET randomly compared AMTR against 2 additional years of aggressive AED management. The results of ERSET are expected to be available in 2009.

Preoperative considerations
Because valproic acid can be associated with bleeding disorders, the authors choose to discontinue this medication at least 3 weeks prior to surgery and replace it with another medication, if possible. On the morning of surgery, the patient receives the usual medication dosage with a few sips of water. 1 g of cephalosporin can be administered intravenously 1 hour before the incision is made. No further antibiotics are administered. Adults are administered 10 mg dexamethasone intravenously 1 hour before surgery (pediatric dose is adjusted appropriately). Intravenous steroids are continued postoperatively at 4 mg every 6 hours for the first 24 hours, then discontinued).
The anesthetic technique for a routine AMTR is general anesthesia. Anesthesia is maintained with consideration to the need for an electrocorticogram (ECoG), depending on the particular details of the case.
For operative positioning, the patient is placed supine on an alternating air mattress with the head held in the Mayfield 3-pin holder. The sagittal midline and axial axis of the head should angle 20° and 30°, respectively, to horizontal. Positioned properly, the zygoma is the highest point of the head (see Image 3).

Method for positioning the patient for temporal lobectomy. The head is angled so the malar prominence is the highest portion of the patient's head.

Method for positioning the patient for temporal lobectomy. The head is angled so the malar prominence is the highest portion of the patient's head.

For the opening, minimal hair is shaved, only enough to make a standard question-mark curvilinear frontal temporal incision (see Image 4). The temporalis muscle is incised directly beneath the skin and reflected with the scalp. The bone flap should be based low in the middle fossa, extending just above the sphenoid wing but within the confines of the temporalis muscle fan. A rongeur or high-speed drill is used to enlarge the bone opening towards the middle fossa floor and anteriorly into the sphenoid wing for several centimeters. The dura is opened by a cruciate incision to optimize temporal tip exposure and should extend approximately 1 cm above the Sylvian fissure (see Image 5). The remainder of the operation should proceed using the operating microscope.

A pterional incision is made, exposing the temporalis muscle and skull.

A pterional incision is made, exposing the temporalis muscle and skull.

After retracting the muscle and performing a small craniotomy, the dura is opened to expose the temporal tip and a small portion of the suprasylvian cortex.

After retracting the muscle and performing a small craniotomy, the dura is opened to expose the temporal tip and a small portion of the suprasylvian cortex.

A distance of 3.5-4 cm from the temporal tip is measured along the middle temporal gyrus posteriorly from the sphenoid wing. This marks the posterior limit of the proposed lobectomy, regardless of speech laterality or side of operation. An incision is made in the sulcus between the superior and middle temporal gyri and is carried mesially until the temporal ventricular horn is entered. A small cotton pledget is placed into the ventricle to maintain orientation. Using an irrigating bipolar coagulator and suction device, the middle and inferior temporal gyri are removed as a single surgical specimen. At some centers, the superior temporal gyrus is removed; at others, it is not. If removed, then one must be careful to maintain an intact pia along the sylvian fissure and basal temporal regions. The superior temporal gyrus is removed to the level of the ventricle, and then the amygdala is partially removed.
The remainder of the inferior temporal structures are removed piecemeal mesially until the parahippocampal gyrus is encountered. At this point, only the mesial-temporal structures remain, and the ependymal surface of the hippocampus should be easily identified (see Image 6).

The lateral cortex is resected, leaving the hippocampus (H). The tentorium (T) and choroid plexus (CH) should be identified.

The lateral cortex is resected, leaving the hippocampus (H). The tentorium (T) and choroid plexus (CH) should be identified.

The hippocampus and uncus are removed en bloc for pathologic examination. An incision into the parahippocampal gyrus is made through the choroidal fissure from the level of the posterior boundary of the cerebral peduncle anteriorly until the tip is reached (see Image 7). This serves as the superior-mesial margin of the resection. The posterior incision is made at the level of the posterior margin of the cerebral peduncle laterally to the lateral hippocampal margin and then brought anteriorly and laterally until it meets the lateral resection margin. The hippocampus is separated carefully from the intact pial surface.

The hippocampus is removed as a separate en bloc specimen for pathologic evaluation. Resection is carried back to the level of the collicular plate. The peduncle and third nerve should be visible through intact pia.

t

As the hippocampus is rolled posteriorly, care is taken to coagulate and cut the numerous small vessels that arise from the posterior communicating and cerebral arteries without damaging the vessels that supply the peduncle and thalamus, causing traction hemiplegia and hemianopsias. With the hippocampus removed, the pial bank overlying the tentorial incisura and cerebral peduncle should be intact.
Below this pial barrier should be the cerebral peduncle, posterior cerebral artery, posterior communicating artery, and third nerve. Pial bleeding is controlled carefully by surgical and gel foam at a low setting. Best results are obtained with removal of the hippocampus to the level of the superior colliculus. The resection cavity is irrigated completely free of blood, and the dura is closed in a watertight manner. No drain is needed, and blood loss should not exceed 300 mL.
Postoperative management
The patient is moved to the ICU for overnight observation unless the patient can be returned to a seizure monitoring room in the epilepsy unit for careful monitoring. The night of surgery, the patient sits at the bedside and performs deep breathing for pulmonary toilet. Should a fever occur, an incentive spirometer is used. The Foley catheter and arterial line are removed as soon as possible, usually before leaving the recovery room. If kept overnight in the ICU, the patient is moved to a surgical floor the next morning. The intravenous drip is converted to a saline lock as soon as the patient takes oral fluids. Ambulation is encouraged, as is sitting in a chair. Unless a problem arises, the patient is discharged on the third postoperative day.
If the patient is taking multiple AEDs, an attempt is made to reduce the patient to non-toxic doses of effective medication or diminish the most poorly-tolerated medication some time after surgery. If the patient is seizure free after about 2 years, the provider may discuss with the patient the pros and cons of discontinuing multiple AEDs. Patients are strongly urged to continue medications for many years postoperatively as there is a l in 3 chance of having a seizure in the 5 years after withdrawing medications after epilepsy surgery.

Complications
In a large surgical series compiled prospectively by Kraemer, serious complications occurred in less than 4% of patients. Two cases of hemiparesis occurred in 160 temporal lobectomies (1.25%), due to damage of the perforators to the anterior choroidal artery that supplies the internal capsule. Paralysis was present immediately and resolved completely in one patient, but it prevented another patient from returning to work. Use of the operating microscope, careful attention to en-passant blood vessels around the brainstem and thalamus, minimal retraction of the mesial structures and restraint of the bipolar cautery on the choroid plexus can minimize the risk of this complication occurring.
The anticipated visual-field deficit from AMTR is a contralateral superior quadrantanopsia from damage to the Meyer loop as it courses anteriorly around the temporal horn of the lateral ventricle. When present, this rarely causes significant disability and is often unnoticed by the patient unless a formal visual-field evaluation is performed. Even if present, a superior quadrantanopia is not a barrier to driving or work.

In the series by Kraemer noted above, 3 unanticipated visual-field deficits occurred; one patient had an infarct to the optic radiation, and 2 others developed homonomous hemianopsia when the temporal lobe resection extended beyond 7 cm from the temporal pole (1.8%). Homonomous hemianopsia can occur from vascular damage to the geniculate body or optic tract by a mechanism similar to what causes hemiparesis. Again, careful microsurgical technique can minimize this risk. Minimal lateral cortical and maximal medial resection can minimize the risk of injury to the Myers loop.
Infection occurred in the above series in 2% of patients. All infections occurred locally within the suture line and required removal of the bone flap and prolonged intravenous antibiotics. No infection resulted in a permanent neurological injury, and bacterial meningitis was not encountered.
Occurrences of cranial nerve III or IV palsies are less common if surgeons use the operating microscope. The rate of ocular motor paresis following AMTR has decreased markedly; however, it may occur in up to 20% of cases. Because cranial nerve III lies directly beneath the pial surface of the uncus, it can develop temporary dysfunction from mild manipulation during dissection. Cranial nerve IV can be damaged if the current of the bipolar cautery is set too high when coagulating near the edge of the tentorium, from traction on the tentorium during the surgery, or possibly even by drainage of CSF during the procedure.
Temperature may be elevated for the first few days after most craniotomies. However, if fever continues longer than approximately 72 hours in the setting of good pulmonary toilet, aseptic or bacterial meningitis should be suspected. A sudden headache associated with a sharp rise in temperature can, in some cases of aseptic meningitis, mar an uneventful convalescence. Diagnosis is made if findings from lumbar puncture demonstrate sterile xanthochromic cerebrospinal fluid (CSF) under pressure (with several hundred to several thousand leukocytes per cubic mm) and CSF cultures are negative. Treatment includes an antipyretic and dexamethasone.
Verbal memory problems have been noted, particularly in patients with speech-dominant temporal lobe resection. This is more severe than deficits in visual-spatial memory that are thought to occur after nondominant AMTR. Patients without hippocampal sclerosis are at greatest risk for this complication. The most consistent and reliable clinical indicator for or against this complication is age at first seizure; if the patient's first seizure (including a febrile seizure) occurred before age 6 years, the risk of increased memory problems postoperatively is slight. A history of severe alcohol abuse also places a person at higher risk for global memory problems after AMTR.

Operative Technique - Corpus Callosotomy

Corpus callosotomy for epilepsy was first reported in 1940 when Van Wagenen and Herren described 10 patients who underwent the operation between February and May and whose cases were followed until July 1939. The rationale was based solely on Van Wagenen's observation that, as a tumor that involved the corpus callosum grew, the patient's generalized seizures became less common and less severe, with increased preservation of consciousness. Results in this first group of patients were encouraging enough to warrant further evaluation of the surgery. Van Wagenen subsequently reported 14 additional patients in whom surgery occasionally included sectioning the anterior or fornix commissure.
Interest in callosotomy remained dormant until the 1960s, when Bogen and colleagues published a series of articles on the clinical and neuropsychological outcome of the surgery. In 1970, Luessenhop et al described a group of patients treated with corpus callosotomy as an alternative to hemispherectomy. In the mid 1970s, Wilson et al reported the Dartmouth series of callosotomies. Since then, a renewed interest in epilepsy surgery has prompted a reevaluation of the clinical usefulness of callosotomy.
Rationale
According to published data, the aim of this operation is to disrupt one or more major CNS pathways used in seizure generalization. The rationale assumes disruption of this pathway decreases the frequency and severity of either primary or secondary generalized seizures. As a result, callosal sectioning has been applied to almost all seizure disorders.
Approaches
Despite renewed interest in epilepsy surgery in general and corpus callosotomy in particular, reported seizure outcomes from this operation vary greatly. This is due to a lack of standardization of the anatomical structures disconnected, the forms of epilepsy treated, patient selection criteria, and the preoperative evaluations. Also, over the years, diagnostic equipment and surgical techniques have evolved and improved.
In his first group of operations, Van Wagenen approached the corpus callosum through a large right frontoparietal craniotomy. The structures cut varied among patients and included part or all of the corpus callosum with and without unilateral division of the fornix. In contrast to Van Wagenen (who cut the entire callosum through one opening), Bogen and Vogel used 2 separate craniotomies to cut the anterior or posterior portions of the callosum and often included the anterior commissure. In a later series of patients, Bogen completely sectioned the corpus callosum, the anterior commissure, the hippocampal commissure, and the massa intermedia. Since 1962, numerous other published series have described sectioning of various combinations of corpus callosum, massa intermedia, anterior and hippocampal commissures, and unilateral fornix. The wide variability of structures sectioned within individual surgical series makes comparison of outcomes and complications problematic.
In recent years, only the corpus callosum has been sectioned. The extent of sectioning necessary for maximum seizure control with minimum risk of disconnection syndrome (ie, mutism, left-sided apraxia that resembles hemiparesis, bilateral frontal lobe reflexes) is not known. Clearly, the best seizure results are achieved with a complete callosal section. However, the risk of disconnection is greatest with a complete section. Thus, an 80-90% section that spares the splenium seems optimal.
Indications
Indications for corpus callosotomy have not been clearly defined, other than the patient must experience medically refractory seizures. Moreover, unlike anteromedial temporal resection (AMTR) for complex partial seizures, no clear and consistent indicators help to identify patients likely to benefit from surgery. Overall, callosotomy seems to lessen the frequency of primarily and secondarily generalized seizures, ie, tonic, clonic, tonic-clonic, and atonic. Callosotomy significantly improves atonic seizures, but having atonic seizures does not guarantee benefit from surgery. Complex partial seizures can be ameliorated somewhat, but the results are far more capricious.
Some epileptologists believe that people with epilepsy who have mental handicaps should not be considered for callosotomy because it seldom renders patients seizure free and these patients may benefit less than patients of normal intelligence. The presence or absence of mental handicaps is not a reliable predictive factor for outcome. This author has personally observed such patients have gratifying results.

This surgery is not performed with the same goals as resective surgery, in which a seizure-free outcome is more likely and expectations are higher. The usual aim of callosotomy is to reduce seizure frequency and associated morbidity. The additional goals of social or vocational rehabilitation, applicable to resective surgery, are often not realistic expectations after callosotomy.
Preoperative considerations
All patients should have an MRI performed to uncover any structural lesion that could help identify an etiology for epilepsy. In addition, a good MRI allows the surgeon to visualize preoperatively the anatomic relationships to the corpus callosum. For example, coronal images can alert the surgeon to a singular or so-called simian pericallosal artery, which is a worthwhile point to know before dissection. Long-term video-EEG monitoring is essential for an epilepsy diagnosis. If, after a well-conceived workup, the patient has tonic, clonic, tonic-clonic, or atonic seizures and is not a candidate for a focal resection of a clearly identifiable epileptogenic region, then corpus callosotomy should be considered.
The usefulness of neuropsychological testing on every patient considered for surgery is debatable. If such testing is needed for long-term postoperative planning or if specific issues need to be addressed (eg, memory integrity), then specific testing should be performed. Routine extensive neuropsychological testing is not required to determine a patient's candidacy for surgery.
The usefulness of routine Wada testing is questionable. If a special situation requires speech lateralization, then the test should be performed (eg, if specifically concerned about mixed cerebral dominance). In 1990, Sass et al reported that patients with mixed cerebral dominance for handedness and language (ie, a right-handed person with right-hemisphere language dominance) are at risk for postcallosotomy language impairments. This complication appears to involve primarily speech and writing and spares verbal comprehension. However, more data are needed for a full understanding of postoperative language deficits.
Surgical procedure
The procedure is performed from the vertex of the head, with the patient lying in the right lateral decubitus position. The head is positioned so that the left hemisphere is superior and the right hemisphere is inferior. This allows the left hemisphere to be supported out of the field by the falx cerebri, and the right hemisphere to be allowed to sag away from the midline by gravity, as CSF is removed. The bone is removed in the midline over the sagittal sinus.
The most dangerous complication of this operation is air embolism, which is most likely to occur from a tear in the superior sagittal sinus during the initial stage of craniotomy. In addition, bleeding from the sagittal sinus can be extensive, with significant blood volume loss accumulating rapidly. This is especially critical in children. Therefore, one policy for pediatric cases is to not begin surgery without transfusable blood available in the OR.
In the authors' experience, patients undergoing callosotomy with narcotic anesthesia are often slow to arouse immediately after surgery and are therefore difficult to evaluate neurologically. Thus, the authors have abandoned narcotic anesthesia in favor of inhalation agents. The authors induce anesthesia with an appropriate amount of propofol followed by an inhalation agent of choice. A lumbar drain can be implanted to allow CSF drainage for improved exposure until the callosum is sectioned.
The supine position favored by most surgeons necessitates frontal lobe retraction. The authors place the patient in the lateral decubitus position to allow gravity to pull the dependent hemisphere gently away from the falx. In this position, with CSF drainage and a PCO₂ of 30 mm Hg, brain retraction should be minimal. The Mayfield head holder is applied, and the neck is secured in a neutral position. The operating table is tilted at a head-up incline of approximately 15° (see Images 10-11). A rectilinear, U-shaped. vertex scalp incision is centered over the junction of the coronal and sagittal sutures. A 4-hole bone flap which straddles the sagittal and coronal sutures is elevated. From this point, an operating microscope is used. To provide superior stability, the authors prefer to operate while seated, using a sterile, draped Mayo
stand for elbow support.

Illustration of lateral position for insertion of a lumbar drain.

Illustration of lateral position for insertion of a lumbar drain.

Photograph of a patient positioned for lumbar drain insertion prior to corpus callosotomy.

Photograph of a patient positioned for lumbar drain insertion prior to corpus callosotomy.

The dura over the dependent hemisphere is opened to the edge of the sagittal sinus (see Image 12). The dural flap is pulled tight with retention sutures to provide maximum exposure of the interhemispheric fissure. Lysis of midline adhesions between the arachnoid and dura is performed using bipolar cautery. Attempts are made to preserve bridging veins, but 1 or 2 veins (anterior to the coronal suture) can be sacrificed, if necessary. Moist cottonoid strips are placed over the medial frontal cortex of the dependent frontal lobe, and any additional adhesions between the cortex and falx are cut with bipolar cautery. In this manner, dissection is carried down to the corpus callosum, which is identified only after clear visualization of both pericallosal arteries. Without this verification, an inexperienced surgeon may mistake the cingulate gyrus for the callosum.

Surgical site preparation for corpus callosotomy. The right hemisphere is inferior, and the left hemisphere is superior. In this position, the left hemisphere will be held out of the field by the falx cerebri, and the right hemisphere will fall away from the field, minimizing the need for traction.

Surgical site preparation for corpus callosotomy. The right hemisphere is inferior, and the left hemisphere is superior. In this position, the left hemisphere will be held out of the field by the falx cerebri, and the right hemisphere will fall away from the field, minimizing the need for traction.

After both pericallosal arteries are separated and protected and the callosum has been exposed, the callosum is opened along the midline of the body. This incision is carried deep until the cavum septum pellucidum is entered, leaving the ventricular ependyma intact. In rare instances, one major pericallosal artery supplies both hemispheres and makes the dissection more difficult because the artery must be manipulated from side to side without damaging branches to either hemisphere. Bipolar cautery is used to cut the callosum. Care is taken to stay within the cavum septum pellucidum. The entire rostrum, genu, and body are divided, and dissection is carried posteriorly until only the splenium remains intact.
The lumbar drain is removed, and the PCO₂ is allowed to rise to 40 mm Hg. Nitrous oxide anesthesia should be discontinued at this point. The wound is irrigated generously to replace most of the drained CSF. If mannitol was used earlier, intravenous fluid should replace the volume loss from diuresis. The dura is closed, dural tack-up sutures are secured, and the craniotomy is closed in layers. Blood loss should not exceed 150 mL. Experience has suggested that patients fare better postoperatively if the net fluid balance for the surgery is positive at the end of the case.
Postoperative care
The patient is observed in an ICU for the first evening following surgery. During this time, neurologic parameters may fluctuate and be complicated by the disconnection syndrome. The patient may not verbalize readily or respond quickly and may have unexplained pupillary inequality. These findings may prompt CT scanning to be performed, which can help rule out a clot or tension pneumocephalus. By the second postoperative day, the patient's normal baseline neurological status should begin to return. MRI in the midsagittal plane is an excellent method for evaluating the extent of sectioning.
Seizure outcome
The patient is maintained on the same anticonvulsant regimen as before surgery. Seizures may increase transiently during the postoperative first week. Although seizure outcome varies from patient to patient, the authors' results seem typical of other published reports.
In general, this operation should decrease but not stop seizures for most patients. A 60-70% decrease can be expected for more than 80% of patients. Approximately 10-15% of patients receive no worthwhile benefit.
The major problem with callosotomy is its unpredictable and/or incomplete seizure control. Nevertheless, for patients with frequent seizures (especially frequent status epilepticus) or seizure-related injuries, this may provide significant benefit. Although never objectively documented, these patients are often observed to continue to improve in seizure control over the years after surgery. Whether this is a long-term effect of surgery or the natural history of epilepsy is not clear.
Operative complications
Early series reported a 50% rate of hydrocephalus and aseptic meningitis, with several deaths. This may be due partly to opening ependyma into the ventricles and can be minimized by entering only the cavum septum pellucidum. Other potentially serious operative complications include excessive bleeding from the superior sagittal sinus, frontal lobe cerebral edema, and venous infarction from sacrificing major bridging veins.
Neurologic outcome
Neurologic sequelae are few. Transient left-sided hemiparesis has been reported. Lateral decubitus positioning may eliminate much of this problem. Temporary bladder incontinence has been associated with damage to the cingulate gyrus.
Numerous psychological studies have been performed following various degrees of midline commissurotomy. Although results can demonstrate problems in transfer of interhemispheric information, the changes do not seem to hinder patients in activities of daily living. Many of the earlier studies involved patients with more extensive commissurotomies, rather than partial or complete callosotomy. Memory difficulties have been reported after complete callosotomy.
A deterioration of impulse control and an increase in aggressive outbursts has been observed following callosotomy in some children with mental handicaps. Although no formal measurements of this behavior have been reported, the authors found that some patients are more alert and more aware of their surroundings after surgery and, hence, may be frustrated more easily.
Callosotomy disrupts EEG bilateral synchrony but does not eliminate epileptiform discharges. Corpus callosotomy may be used diagnostically to help define the side of seizure onset in some patients with frontal lobe epilepsy and secondary bilateral synchrony. However, the authors had little success with this approach when tried on 6 patients.
In 1993, Spencer et al reported more intense focal seizures or emergence of focal seizures after corpus callosotomy, especially in patients with asymmetric bilateral epileptogenic foci. The authors have observed one patient in whom this occurred, but seizures were reduced with alterations in medications so that the overall benefits of surgery were favorable.

Operative Technique - Multiple Subpial Transections

Multiple subpial transection (MST) is a nonresective surgical technique for abolishing epileptiform discharges and correlative seizures from epileptogenic cortex.
Rationale
All partial epileptic seizures originate from a restricted region of cortex considered (for lack of a better term) the focus. The exact mechanisms responsible for generation of focal seizures are not completely understood but are believed to be due to abnormally discharging neurons and abnormal interneuronal synchrony.
Whether epileptogenic neurons fire in action potential bursts solely because of abnormal interneuronal synchrony or because of intrinsic abnormalities (or a combination of both) is unknown. However, recordings from chronic animal models and human cortex have demonstrated that seizures are associated with periods of increased interneuronal synchrony within cortex as well as between cortex and subcortical nuclei. Theoretically, if this intracortical synchronization can be disrupted, the focus' epileptogenic potential can be reduced or eliminated. The rationale for placing parallel slices through cortex is to permanently disrupt side-to-side intracortical synchronizing neural networks.
Because the neocortex is organized in functional columnar units, right-angle cuts to the pial surface should not disrupt cortex-subcortical input-output interactions. Therefore, the MST technique theoretically is ideal for treating epileptogenesis while preserving intrinsic cortical function.
Indications
The most effective surgical treatment of partial (focal) seizures has been removal of the seizure-producing cortex from the brain. However, this cannot be performed if the cortex also serves an indispensable function such as speech. Consequently, MST is the only acceptable surgical treatment of a focus within such cortex.
In 1989, Morrell et al reported on the use of MST to treat seizures from chronic (Rasmussen) encephalitis that affected the speech-dominant hemisphere. They applied MST to speech and motor cortex and resected or disconnected the remainder of the hemisphere. The authors' results in these cases were not good, and the authors have abandoned this indication.
In 1997, Patil et al reported on the application of MST to bilateral seizure foci in very difficult cases otherwise not considered for surgical intervention.
MST has been used as surgical treatment of Landau-Kleffner syndrome (LKS), a form of acquired aphasia associated with epileptiform spiking (but not necessarily seizures) in the central neocortex.
Experimental studies
In 1995, Sugiyama et al reported a study on MST-induced histological changes and its effects on interneuronal cortical spread in acutely kindled rats. They showed the transection severed horizontal fibers but left vertical fibers and neuronal cell bodies preserved. Cortical hyperactivity across the transacted zone was reduced, and afterdischarge propagation was also inhibited. These results suggest that MST interrupts not only neuronal synchronization but also excitatory interneuronal conduction.
In 1994, Tanaka et al reported MST effects on propagation in a cat kainic acid model. They showed that MST suppressed epileptic activity of the cortical surface. However, residual hypermetabolic areas (defined by carbon 14–labeled deoxyglucose autoradiography) were observed in the deep layer of the cortex and caudate nucleus and in the contralateral sensorimotor cortex. These results suggest that seizure propagation uses side-to-side connections more than cortical subcortical connections in neocortical epilepsy.
Clinical studies
In 1989, Morrell et al reported on MST in 32 patients but were able to report 5-year seizure outcome in only 20 patients.Complete seizure control was obtained in 11 (55%) patients. Taken in the context of extratemporal epilepsy, these results are comparable with cortical resection. Of 16 patients, Morrell et al reported no major complications that involved the precentral gyrus, 6 that involved postcentral cortex, 5 that involved the Broca area, and 5 that involved the Wernicke area.

Evaluation of the antiseizure efficacy of MST was confounded by the inclusion of patients with progressive neurological diseases and structural lesions, such as tumors. For example, whether continued seizures in a patient with chronic encephalitis represented failure of MST or progression of the disease is unknown. Whether seizure control after MST and lesionectomy was attributable to lesionectomy or MST is unknown. On the other hand, this pioneering report documented the minimal cognitive or behavioral sequelae of the procedure.
Subsequent reports support the findings of Morrell et al. In 1991, Shimizu et al reported 12 cases of MST with fair results.In 1995, Sawhney et al reviewed 21 cases of MST, with 18 patients having epilepsy and 3 having LKS. Of the 18 patients with epilepsy, 8 demonstrated focal abnormalities on MRI, including 6 with chronic encephalitis and 1 with a tumor. Cortical resection plus MST was performed in 12 patients, with 11 showing worthwhile seizure decreases. None of the 21 patients developed chronic neurological deficits. In 1997, Devinsky et al reported on MST in the language cortex of 11 patients. In 1996, Pacia et al reported a series of 21 patients. Only 3 of these underwent MST alone; the other 18 had additional cortical resections.
In 1997, Hufnagel et al reported less satisfactory results in a series of 22 patients with a mixture of resections and MST. Devinsky et al reported 13 patients with MST in language cortex whose cases were followed for longer than 1 year (11 patients had additional resective surgery). Although 11 of 13 patients had greater than 90% seizure reduction, MST patients had significantly poorer postoperative naming, verbal fluency, and oral reading than patients with dominant temporal lobe resections that spared language function.
These additional reports make assessing the true antiseizure effect of MST alone difficult because of the inclusion of patients with progressive neurodegenerative diseases or a combination of lesionectomy and cortical resection plus MST.
In 1995, Wyler et al reported on 6 patients who underwent only precentral and/or postcentral MST without resection.In a longer follow-up of that series, 2 patients (30%) were seizure free, and 3 patients (50%) showed greater than 90% seizure reduction. One patient did not benefit significantly. Four patients had MST of primary language cortex. Patients with MST of precentral language areas showed subjective improved fluency, and those in postcentral speech areas showed no deficits. Wyler changed the technique from Morrell's original description by pointing the instrument tip downward (away from the pia) rather than toward the pia. He believes this is technically easier and results in less subpial hemorrhage. A special knife has been developed (Ad-Tech Medical, Racine, Wis) for this purpose.
In 1997, Patil et al reported on patients undergoing MST only from large multilobar areas or bilateral areas of cortex with good results. They also reported a series of patients with bilateral foci treated with MST plus other minimally resective procedures.
MST applied to LKS
Perhaps the most sensitive validation of the antiepileptic effects of MST with preservation of underlying cortical function is its application to patients with LKS. LKS, also known as acquired epileptiform aphasia, is characterized by acquired verbal auditory agnosia in childhood with epileptiform discharges in central regions in most cases and superior temporal regions in some. Children often become mute and unresponsive to verbal commands after initially acquiring rudimentary language. Some children show no overt seizures in spite of obvious epileptiform discharges that become more plentiful during sleep; at times these discharges are so diffuse and continuous that they resemble the epilepsy syndrome of continuous spike waves in slow-wave sleep. Antiepileptic drug (AED) therapy, for the purpose of regaining speech, is usually ineffective. Steroid therapy may provide temporary improvement but seldom a long-lasting benefit.
In 1995, Sawhney et al reported on 3 preoperatively mute patients with LKS who showed "substantial recovery of speech" months after MST. In 1995, Morrell et al reported on 14 children with LKS who were treated with MST.Seven recovered age-appropriate speech and were taking regular classes in school. Four have shown marked improvement. Thus, 11 of 14, none of whom possessed communicative language for at least 2 years preoperatively, are now speaking.

These results have several important implications. First, they add additional evidence that this novel technique is effective in eliminating epileptiform electrical activity from cortex while preserving function. Second, they support the concept of early surgical intervention in well-defined epileptic childhood syndromes for fear that delays result in irreversible cognitive and/or behavioral sequelae.
The authors have applied MST to several children with LKS with mixed benefit. Interestingly, in most cases, the disruptive behavior displayed by these children improves after surgery.
Technique
MST is still a relatively new surgical technique. As such, many questions remain unanswered. The following description is admittedly highly biased by the author's personal experience, but it has proven effective in the author's experience. Over time, the following recommendations will be improved on as many of the questions are answered.
As with all surgery for partial epilepsy, the margins of the epileptic focus must be clearly defined. Although interictal recordings define the foci of LKS cases (because most children with LKS have no seizures), all other cases should have long-term ictal recordings using a subdural grid electrode. Because most patients considered for MST have primary motor cortex involvement, the focus is near the central sulcus or, more commonly, the junction of the central sulcus with the sylvian fissure. Thus, a craniotomy that provides adequate exposure of this area is required whenever possible. A 64-electrode contact grid, centered over the suspected region of ictal onset, is recommended.
Within the first few hours of monitoring, somatosensory evoked potentials (SSEPs) are performed to orient the grid sensory-motor cortex with respect to the grid. Direct cortical mapping by electrical stimulation is performed as needed for each individual. Once sufficient ictal recordings identify the focus, the patient is returned to surgery for grid removal and MST.
Often, the ictal region is no more than a few square centimeters and is usually bordered by sulci (ie, contained within 1-2 gyri). Seizure propagation is commonly observed along the long axis of the involved gyri. The entire region of ictal onset should undergo MST, as well as the 1-2 cm bordering the ictal zone. If a discrete ictal zone is not evident from long-term recordings, MST results are not as good.
The authors' preference is to use a specially designed MST knife (see Image 13; Ad-Tech Medical, Racine, Wis) with the point angled downwards, rather than upwards as originally described. In addition, the cutting portion of this knife is sharpened to a blade to minimize the excessive damage from using blunt instruments such as a right-angled dissector. The actual cuts should be performed under direct vision through the operating microscope.

Incision of the dura mater, adjacent to the sagittal sinus.

Incision of the dura mater, adjacent to the sagittal sinus.

After protecting the surrounding cortex with cotton patties, the insertion point can be either at the side or at the crest of the gyrus. After a small pial spot is cauterized, the knife blade is inserted and pushed subpially towards the gyrus edge, making a right-angled cut to the long-axis of the gyrus. The horizontal arm to the blade should be barely visible through the pia at all times. If the insertion point is centered in the gyrus, then, after the first half-cut, the instrument is removed and replaced and the remainder of the slice is completed. Parallel cuts then are made 5 mm apart until the entire proposed ictal zone and surrounding area have been sliced.
Take care when encountering a gyrus that curves. This is because the outer length of the curve is much longer than the inner length. When this is encountered, the authors suggest staggering the cut lengths so that slices converging at the center of the curve do not all join at a common point or come so close together as to severely damage cortex. Pial bleeding at the blade insertion point is usually controlled with bipolar cautery or a small square of thrombin-soaked Gelfoam. Significant subpial hemorrhage should not occur.

Functional Hemispherectomy

Functional hemispherectomy is a highly effective procedure for treating epilepsy in well-selected candidates who suffer from catastrophic epilepsy. Patients who are candidates for functional hemispherectomy are those persons who have injury and seizures limited to one hemisphere of the brain. Seizures occur at such a high frequency to interfere with cognition and impair quality of life. The goal of surgery is to isolate the affected brain from the healthier hemisphere to allow it to function without the burden of seizures or interictal discharges to impair brain function.

Most patients upon whom hemispherotomy has been performed have been children, although some previous reports include adults. Etiologies of the catastrophic epilepsies leading to hemispherotomy include Rasmussen’s encephalitis, other encephalitides, prenatal ischemia (often with porencephaly), Sturge-Weber syndrome, cortical dysplasia, HHE, hemimegalencephaly, malignancy, or Tuberous Sclerosis. Preferentially, the pathology is limited to a single hemisphere of the brain, as recovery after surgery depends upon the remaining hemisphere’s ability to take over cognitive and language functions that may have previously been within the domain of the injured hemisphere.

Timing of surgery is dependent on the syndrome causing the epilepsy, severity of the epilepsy and the age of the patient. If seizures begin early in infancy, then hemispherectomy before the second or third year of life offers the best chance of transfer of neurologic function to the opposite hemisphere. When the onset of seizures begins somewhat later in life, timing of surgery can be more controversial, as the transfer of language function may be less complete in older children.

However, delay of surgery can lead to decline in cognitive ability, as accumulating evidence suggests that seizures themselves may delay cognitive development.The timing of surgery depends upon the severity of the seizures, the natural history of the illness affecting the patient, and the response to antiepileptic drug treatments. When the syndrome presents early in life, many centers recommend proceeding with surgery rapidly to avoid loss of cognitive abilities due to an epileptic encephalopathy, which may impair learning and cognition. However, patients with late onset syndromes can respond to surgery with improvements in neurologic function as well, suggesting that plasticity after hemispherectomy is not limited to early childhood.

In 1950, Krynauw first described an operation for children with infantile hemiplegia in which the entire hemisphere (excluding basal ganglia) was anatomically removed from the cranium (anatomical hemispherectomy). In 1969, Falconer and Wilson reported on long-term follow-up of early cases and disclosed symptomatic hydrocephalus and progressive hemosiderosis as 2 potentially lethal complications. As these became known, enthusiasm for hemispherectomy declined and remained low until 1983, when Rasmussen reported that preserving disconnected frontal or occipital lobe(s) lessened the incidence of these complications. From this observation, functional hemispherectomy was developed.
In a functional hemispherectomy, cortex is disconnected from all subcortical structures and the interhemispheric commissures are divided, but the brain remains in place. Excellent postoperative seizure control and good quality of life can be achieved among children treated with hemispherectomy.

This procedure still involved considerable time in the operating room and often required blood transfusions, leading to further refinement of the functional hemispherectomy, frequently referred to as the hemispherotomy, by a number of authorsThese variations all include the following in their techniques; disconnection of the corona radiata and the internal capsule, resection or disconnection of the mesial temporal lobe structures, intraventricular callosotomy and deafferentation of the medial-basal occipital and frontal lobes. These refinements in functional hemispherectomy have decreased the time needed for the operation and the blood loss associated with the operation, making the operation less morbid and easier to perform.

Still, complications from functional hemispherotomy can be formidable, with patients who have had the procedure developing hemogenic meningitis, ventriculitis, CSF leak, hydrocephalus or less commonly, stroke, infection, coma or postoperative hemorrhage.The procedure must be performed in centers with experienced surgeons with advanced equipment available for intraoperative and postoperative support of the patient and complications if they should arise.
Functional hemispherectomy has a seizure free outcome of between 54-90%, depending on the series reported and type of syndrome for which the procedure is performed. Some patients have minor seizures after surgery that are not considered disabling. When overall improvement includes nondisabling seizures, the percentage of patients who are significantly improved by functional hemispherectomy rises to 80-90% in most series.

Some authors have found the underlying pathologic substrate to have a bearing on postsurgical outcome, with patients with migrational disorders and hemimegalencephaly doing less well than other disease processes. In addition, higher presurgical cognitive ability, shorter duration of seizures and better postoperative seizure control are more likely to correlate with higher postoperative developmental gains.Seizure freedom is important in improving postoperative cognition, but quality of life scores have improved even when some minor seizures persist.

Physicians and parents are often concerned about the motor consequences of functional hemispherectomy. Usually, the decision to proceed to hemispherectomy is taken after the patient has a complete hemiparesis. However, in the case of a progressive disease process, such as Rasmussen’s encephalitis, some centers advocate early surgery, prior to the development of complete hemiparesis, to avoid developmental delay that might be caused by epileptic encephalopathy.
Several series have reported on motor outcomes after functional hemispherectomy. Most children remain unchanged by surgery, with a return to baseline motor function in the contralateral leg within one year of surgery. The exception to this generalization is that increased tone in the contralateral hand compromises function of that hand and does not return to baseline. A small percentage of children will have a worsening of hemiparesis, and a few will have an improvement in motor function. Most patients (89%) are ambulatory after surgery: those patients who walked prior to surgery are likely to be ambulatory as well after surgery.

Overall, gains in activities of daily living, quality of life scale, and social interactions outweigh the increased motor deficit in the hand which occurs after functional hemispherectomy.

Multimedia

Examples of various grid electrodes available for specific needs. These range in size and number of contacts.

Media file 2: Examples of 3 depth electrodes with varying numbers of contacts. Note: The stylus is in place and is removed once the electrode has been inserted.

Examples of 3 depth electrodes with varying numbers of contacts. Note: The stylus is in place and is removed once the electrode has been inserted.

Media file 3: Method for positioning the patient for temporal lobectomy. The head is angled so the malar prominence is the highest portion of the patient's head.

Method for positioning the patient for temporal lobectomy. The head is angled so the malar prominence is the highest portion of the patient's head.

Media file 4: A pterional incision is made, exposing the temporalis muscle and skull

A pterional incision is made, exposing the temporalis muscle and skull.

Media file 5: After retracting the muscle and performing a small craniotomy, the dura is opened to expose the temporal tip and a small portion of the suprasylvian cortex.

After retracting the muscle and performing a small craniotomy, the dura is opened to expose the temporal tip and a small portion of the suprasylvian cortex.

Media file 6: The lateral cortex is resected, leaving the hippocampus (H). The tentorium (T) and choroid plexus (CH) should be identified.

The lateral cortex is resected, leaving the hippocampus (H). The tentorium (T) and choroid plexus (CH) should be identified.

Media file 7: The hippocampus is removed as a separate en bloc specimen for pathologic evaluation. Resection is carried back to the level of the collicular plate. The peduncle and third nerve should be visible through intact pia.

The hippocampus is removed as a separate en bloc specimen for pathologic evaluation. Resection is carried back to the level of the collicular plate. The peduncle and third nerve should be visible through intact pia.

Media file 8: Craniotomy that shows an intracranial grid in place. The grid lies over left primary motor and sensory cortex, near the vertex of the skull. The patient is positioned laterally, and the face is at the right. The intracranial study was performed to document seizure onsets in a patient who had a previous oligodendroglioma removed. Seizures began just posterior to leg motor cortex, in primary sensory cortex.

Craniotomy that shows an intracranial grid in place. The grid lies over left primary motor and sensory cortex, near the vertex of the skull. The patient is positioned laterally, and the face is at the right. The intracranial study was performed to document seizure onsets in a patient who had a previous oligodendroglioma removed. Seizures began just posterior to leg motor cortex, in primary sensory cortex.

Media file 9: The primary motor cortex is located with the use of extraoperative somatosensory evoked potentials and intraoperative cortical stimulation, as well as the grid described in Image 8. The Penfield instrument in the field is positioned over primary motor cortex.

The primary motor cortex is located with the use of extraoperative somatosensory evoked potentials and intraoperative cortical stimulation, as well as the grid described in Image 8. The Penfield instrument in the field is positioned over primary motor cortex.

Media file 10: Illustration of lateral position for insertion of a lumbar drain.

Illustration of lateral position for insertion of a lumbar drain.

Media file 11: Photograph of a patient positioned for lumbar drain insertion prior to corpus callosotomy.

Photograph of a patient positioned for lumbar drain insertion prior to corpus callosotomy.

Media file 12: Surgical site preparation for corpus callosotomy. The right hemisphere is inferior, and the left hemisphere is superior. In this position, the left hemisphere will be held out of the field by the falx cerebri, and the right hemisphere will fall away from the field, minimizing the need for traction.

Surgical site preparation for corpus callosotomy. The right hemisphere is inferior, and the left hemisphere is superior. In this position, the left hemisphere will be held out of the field by the falx cerebri, and the right hemisphere will fall away from the field, minimizing the need for traction.

Incision of the dura mater, adjacent to the sagittal sinus.

Keywords

epilepsy surgery, epilepsy, epilepsy treatment, seizure, seizures, seizure treatment, anteromedial temporal resection, AMTR, corpus callosotomy, multiple subpial transections, MST, intracranial surgery, long-term EEG-video monitoring, long-term electroencephalogram–video monitoring, neuroimaging, epileptogenic focus, strip electrode, grid electrode, depth electrode