intractable epilepsy in children

Epilepsia, 37(Suppl 3): 14-27, 1996 Lippincott-Raven Publishers, Philadelphia 0 International League Against Epilepsy

Special Lecture

Intractable Epilepsy in Children

Gregory L. Holmes

Department of Neurology, Hurvard Medical School, Children’s Hospital, Boston, Massachusetts, U.S.A.

Summary: Although most children with epilepsy have a good prognosis, a small but significant minority have seizures that either do not respond to conventional antiepileptic drugs (AEDs) or have significant adverse reactions to AEDs. Many children may benefit from epilepsy surgery. Surgical treatment of epilepsy is becoming a well- established therapy for infants and young children with severe, medically intractable seizures. As in older children and adults, the presurgical evaluations of possible surgical candidates typically consist of a detailed history, neurologic and neuropsychologic examination, and anatomic and functional neuroimaging. The “gold standard” test, however, is the recording of ictal events by using simulta-

neous EEG and videomonitoring. Although temporal lobe resection is the most commonly performed surgery in older children and adults, nontemporal lobe resection, corpus callosotomy , and hemispherectomy are commonly performed in younger children. Efficacy of surgery in children compares favorably with results from adult patients. In addition, because the immature brain is more plastic than the mature brain, recovery offunction is often greater after surgery in children than in adults. Early surgery in children with intractable epilepsy is recommended. Key Words: Epilepsy-Seizures-Temporal lobectomy-Corpus callosotomy-Hemispherectomy.

Most children with epilepsy have a good prognosis for eventual remission. Of children with idiopathic epilepsy, -80% can be expected to become totally seizure free for 2 5 years (1). The majority of children enter this seizure-free state within l year of treatment onset (2). Children with symptomatic epilepsy have a lower likelihood of remission; neverthe- less, even children with epilepsy associated with a neurologic deficit present at birth have a 40% chance of achieving total seizure control (2).

Most children destined to do well in terms of seizure control can be identified in the first year after diagnosis (2). Only a small percentage of children not controlled by 2 years after diagnosis can be expected to achieve seizure freedom. Children with recurrent seizures are at risk for injury, social ostracism, and possible progressive cognitive impair- ment. In disorders such as infantile spasms or Sturge-Weber syndrome, the clinician is often faced with frequent, medically intractable seizures and a “plateauing” or even decline in development. If the child’s seizures are not controlled ‘by antiepileptic drugs (AEDs) within 2 years of therapy onset, alter- native forms of therapy should be considered.

Address correspondence and reprint requests to Dr. G . L. Holrnes at Clinical Neurophysiology Laboratory, Hunnewell 2, The Children’s Hospital, 300 Longwood Ave., Boston, MA 021 15. U.S.A.

Epilepsy surgery provides great hope to children with medically intractable epilepsy. The rationale for early surgical intervention is to stop the seizures and to prevent further brain injury from either the underlying abnormality causing the seizures, the seizures themselves, or the AEDs. Removing the focal brain abnormality theoretically will allow the re- mainder of the brain to develop free of the undesir- able influences of the abnormal epileptic tissue and AED therapy.

EPILEPSY SURGERY

There has been a phenomenal growth of interest in surgery in infants and early childhood during the past several years. Although AED therapy clearly is the treatment of choice for the majority of children with epilepsy, a significant number of patients with seizures respond to surgical treatment (3-7).

Epilepsy surgery in children presents a number of unique challenges and some differences from that in adults (8). It is critically important to identify those children who have epileptic syndromes in which remission is likely because surgery in these patients would be inappropriate. Epilepsy surgery offers hope to a number of children with severe epilepsy, but surgery is not free of risks. The risks of creating a permanent deficit must be balanced with the likelihood that the surgery will eliminate or

14

INTRACTABLE CHILDHOOD EPILEPSY 15

significantly reduce the seizure frequency. Once it is likely that the child will not go into remission the clinician must decide when to perform surgery. Plasticity is greatest during infancy and early childhood (9- 13). If surgery is to be done, from a recovery standpoint, the earlier the better. However, rushing into surgery without adequate trials of AEDs is also inappropriate.

Presurgical evaluation The goal in the evaluation of patients with partial

epilepsies is to identify the epileptic focus. The focus is identified through a close examination of the history, neurologic examination, neuropsychologic evaluation, EEG, and neuroimaging (both anatomic and functional). Each epilepsy center has its own surgical protocol, but there is general agreement that surgery should be performed only when there is a preponderance of evidence pointing to a single epileptic focus.

An accurate description of the clinical manifestations of spontaneous seizures is probably the most important piece of clinical information derived from the history. Parents usually concentrate on the most dramatic portion of the seizure, so it is important to question the observer closely about the initial phases of the seizure. For example, in infantile spasms, eye deviation or focal clonic activity before the spasm provides information that the seizure began focally. A history of asymmetries of strength postictally, even if subtle, may provide important localizing findings for seizure onset.

With the widespread use of computerized tomography (CT) and magnetic resonance imaging (MRI), the value of the neurologic examination has been reduced. However, asymmetries of strength or re- flexes may provide evidence of focal pathologic conditions even in the face of normal neuroimaging.

Neuroimaging The MRI is essential for all patients undergoing

a possible surgical evaluation (14). MRI has been demonstrated to be the most sensitive and specific neuroimaging procedure in patients with partial or localization-related epilepsy. Even in the patient with a normal CT scan, the MRI may be abnormal (15-17). The MRI is particularly valuable in detect- ing hippocampal sclerosis (1 8-20). Computer-as- sisted volume analysis of the temporal lobes may detect asymmetries that are not readily apparent on visual scan analysis (21-24).

Functional neuroimaging, single-photon-emission computed tomographic (SPECT), and positron emission tomography (PET) are increasingly used in the evaluation of children with epilepsy (25-28). The

SPECT, which measures blood flow, demonstrates hyperperfusion at the site of the epileptic focus when done during an actual seizure (29). The interictal scan may show hypoperfusion at the epileptic focus. The ictal scan is superior to the interictal scan in the localization of the epileptic focus. In a series of 119 primarily adult patients with unilateral temporal lobe epilepsy, Berkovic et al. (30) performed interictal SPECT scans in 119, postictal scans in 77, and ictal scans in 51 patients. Interictal scans had temporal hypoperfusion on the correct side in 48%, hypoperfusion on the incorrect side in lo%, and was inconclusive in 42%. Postictal scans correctly lateralized the focus in 71%, whereas ictal scans were correct in 97%. Whereas SPECT studies in children have been more limited, results in children appear to be similar to those in adults (25,28,31,32). Hwang et al. (25), in an evaluation of 20 infants and children who underwent surgical excision of the epileptogenic foci, found a good correlation between blood- flow abnormalities on the interictal SPECT and the epileptic focus in 15 patients. The ictal SPECT was positive in four of four cases.

PET scanning, like SPECT, is a noninvasive functional imaging test that has been used to evaluate cerebral metabolic rates (33-35). Although many agents have been labeled with positron-emitters, 2- deoxy-2('*F)fluoro-~-g1ucose (FDG) is the agent most commonly used in epilepsy (5,6,34,36). The interictal scan typically demonstrates hypometabo- lism, whereas scans obtained during a seizure dem- onstrate hypermetabolism (33,37,38). PET scanning has been found to be a useful adjunctive test in the evaluation of both children and adults with epilepsy. Chugani et al. (34) claim that PET is superior to CT and MRI in localizing focal areas of cortical dysplasia and other structural abnormalities corresponding to surface electrographic localization of epileptogenic regions. In the hands of experienced investigators, PET may eliminate or reduce the need for invasive monitoring (34). Unfortunately, PET scans are available in only a few centers.

Neuropsychologic evaluation A developmental assessment in the toddler and

neuropsychologic battery in older children also should be used to screen for focal or global brain dysfunction (39-43). For example, in older children, deficits in verbal memory or language acquisition suggest dominant temporal lobe abnormality, whereas deficits in visuospatial memory suggest nondominant temporal lobe dysfunction. Significant deficits in both suggest bilateral temporal lobe dam- age. The neuropsychologic battery also provides

Epilcpsia, Vol. 37, Suppl. 3 , 1996

16 G. L. HOLMES

baseline data for comparison with postoperative data (42).

Electroencephalography EEG investigation remains the cornerstone for

localization of the epileptic foci (44). Both interictal and ictal epileptiform activity are used in localization of the epileptic zone (45-47). Interictal abnormalities include spikes, sharp waves, focal slowing, or asymmetries of beta activity. Figure 1 is from a patient with temporal lobe epilepsy. Although no spikes or sharp waves are present, there is polymor- phic slowing over the left temporal lobe.

Sphenoidal electrodes are often used in the evaluation of patients with suspected temporal lobe epilepsy. Sphenoidal electrodes may be inserted inside a 22-gauge lumbar-puncture needle into the muscles of the cheek, through the space between the zygo- matic process and the angle of the mandible. When properly placed, the sphenoidal electrode lies near the region of the foramen ovale and provides increased sensitivity to discharges from mesiobasal temporal regions (Fig. 2). Maximum amplitude of epileptiform discharges at sphenoidal or anterior temporal scalp electrodes suggests that the origin of the seizures is the anteromesial temporal area (48,49).

Insertion of sphenoidal electrodes in children may

be accomplished more comfortably with intravenous premedication (50). In one series, children were pre- medicated with intravenous meperidine and midazolam in small aliquots over an - 10-min period. Doses were titrated to a level of relaxation in which the patients either showed no signs of discomfort or just winced slightly but were not asleep. An added benefit of the midazolam was amnesia, so that none of the children remembered the procedure. This was especially helpful to prevent later anxiety when children returned for repeated EEG evaluations.

When EEG results are congruent with clinical, neuroimaging, and PET findings, it may be appro- priate to proceed directly to surgery. When the noninvasive EEG evaluation does not show that all the epileptiform discharges are localized to the anterior temporal lobe on one side, or when clinical, EEG, and neuroimaging findings are not convergent, then further evaluation with invasive neurophysiologic techniques may be necessary.

However, because interictal discharges on scalp recording are absent in some patients, poorly localized or bilaterally independent in others, and occa- sionally falsely localizing, more attention is typically paid to ictal recordings. The onset of an EEG seizure is considered the most reliable of the localizing signs.

In instances in which seizures cannot be well localized with surface electrodes or if the SPECT, PET, MRI, or neuropsychologic data are not concor- dant with the EEG findings, use of intracranial elec-

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FIG. 2. Left anterior temporal lobe spikes in patient with temporal lobe epilepsy. Note phase reversal of spike at F7 and Spl .


FIG. 3. lnterictal EEG from patient with depth electrodes placed in the right amygdala, hippocampus, and mesial frontal region. Paper speed 30 mmls.

trodes is indicated. A variety of intracranial electrodes have been used, most commonly depth, subdural, or epidural (51,52). Depth electrodes consist of thin wires with multiple EEG recording contacts. Depth electrodes are implanted stereotaxically and can be implanted into a variety of cerebral structures; subdural electrodes are placed over the surface of the brain. Depth electrodes allow accurate recording from structures located at a distance from the surface and are particularly valuable when the clinician suspects the seizures are arising from the amygdala or hippocampus (Fig. 3).

Subdural or epidural electrodes consist of strips or grids placed in a thin sheet of plastic. Both ictal and interictal epileptiform discharges are often better delineated by using subdural electrodes. These electrodes may be helpful in planning a safe, effective resection for patients with an epileptogenic region near functional cortex, because the clinician can electrically stimulate the electrodes to map functional cortex (53-57). For example, we evaluated an 8-year-old boy with seizures characterized by sudden onset of head pain followed by agitation, crying, and altered responsiveness. Surface EEGs did not accurately localize seizure onset, although there was a suggestion that the seizures were coming from the left parietal or temporal region. For that reason, subdural electrodes were placed over the left parietal and temporal lobes (Fig. 4). A focal seizure was recorded involving parietal electrodes 37,38, and 39 (Fig. 5) . Unfortunately electrical stimulation of this area consistently resulted in move- ments of the right hand. Median nerve evoked potentials demonstrated a phase reversal at electrode 39, demonstrating that the seizure focus involved primary sensory cortex (Fig. 6). For that reason, the patient underwent a subpial transection instead of

a focal res’ection. The child continues to have seizures, but there has been a 90% reduction in seizure frequency.

Subdural electrode grids may be slipped under the edges of the open craniotomy, including under the temporal or frontal lobe or in the interhemispheric fissure. Because of the higher incidence of nontemporal epileptic foci in children, subdural or epidural electrodes are used more frequently in many centers than are depth electrodes.

Epidural peg electrodes may be useful when there is a desire to sample EEGs from two or more neocortical areas (58-60). The electrode is placed through a cranial small-twist drill hole, so that the recording element lies on the dura. The advantage of epidural peg electrodes compared with epidural or subdural electrode arrays is that they can be placed over more widespread or distant areas. These electrodes cannot be used to record from areas other than the cerebral convexities, such as interhemispheric, mesial temporal, or orbital frontal regions. Stimulation with epidural electrodes may cause pain because of stimulation of meningeal nerve fibers and are therefore not useful in cortical mapping.

As electrodes become more invasive, they tend to provide more detailed and precisely localized information, at the expense of more limited sampling (60). The most invasive techniques, such as depth electrodes and epidural or subdural grids, are very helpful to answer specific neurophysiologic ques- tions about a very restricted cortical area but are less helpful in exploring more widespread localization problems between large cortical areas (60). There- fore these techniques should be reserved for cases in which basic regional localization problems have already been resolved by scalp EEG and other diag- nostic studies. Although all invasive electrodes are

18 G. L. HOLMES

FIG. 4. A: Lateral skull film from 8-year-old boy with seizures arising from the parietal lobe. A subdural electrode grid was placed over the left parietal and temporal lobes. Surface electrodes were placed over the frontal region. B: Anterior-posterior skull film from the same patient.

associated with risks, such as infection and bleeding, they are remarkably well tolerated by children (41).

Surgical procedures Surgical procedures are summaried in Table 1.

Temporal lobe resection Simple or complex partial seizures of temporal

lobe origin usually begin in the early school-age years, but in one series, 16% had onset of seizures before age 2 years (61). Because infants with partial seizures often have more subtle ictal signs (45,62- 64) and fewer focal epileptiform discharges on rou- tine interictal EEG (65,66), the diagnosis may be delayed. Patients with early-onset temporal lobe epilepsy may have an increased incidence of structural lesions on CT or MRI (60,61), sometimes bringing the child to attention for earlier epilepsy surgery because of the concern about possible neoplasm (60).

The rate of spontaneous remission appears low in childhood temporal lobe epilepsy. In one series, 10% of children eventually had spontaneous seizure remission (61), and another 18% achieved good control with AEDs (67). As noted by Wyllie (60), other series

with higher remission rates either intentionally included patients with benign partial epilepsy of childhood or were based on clinical diagnosis only and did not rigorously exclude children with benign partial epilepsy of childhood, childhood absence epilepsy, or psychogenic seizures. Long-term prospective studies are needed, but available data suggest that remission rates in temporal lobe epilepsy are low (60).

Temporal lobe seizures The majority of children undergoing temporal lo-

bectomy have mesial temporal sclerosis, a neoplasm, chronic infection, or a dysplastic lesion.

Brain neoplasms account for only 0.2-1.4% of all children with seizure disorders (68), but seizures occur in 25-76% of children with supratentorial astrocytic tumors (69). In a series from our hospital, 98 children younger than 18 years with supratentorial astroglial neoplasms were reviewed. Of 25 patients with temporal lobe tumors, 20 (80%) had seizures. Nine of 14 children aged between 16 months and 12 years who were seizure free after temporal lobectomy at the Cleveland Clinic had low-grade temporal neoplasms (70).

Epilepsia, Vol. 37, Suppl. 3 , 1996

INTRACTABLE CHILDHOOD EPILEPS Y 19

58

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FIG. 5. A-C: EEG from patient with subdural electrodes placed over the parietal and temporal region, as shown in Fig. 4. Note onset of seizure involving electrodes 37, 38, and 39. The alarm was activated by the mother when the child complained of head pain. The three EEG segments are continuous. Paper speed 30 mm/s.

20 G. L. HOLMES

FIG. 5.

Temporal lobe gangliogliomas are a common cause of intractable temporal lobe epilepsy. These tumors resemble a mixed glial abnormality with giant nerve cells that resemble ganglion cells, although in some cases, a mixed astrocytic component can be seen. These tumors have been attributed to malfor- mation, ectopic sympathetic tissue, or a form of tuberous sclerosis or neurofibromatosis. The tumors typically have a paucity of glial cells with a predomi- nance of ganglion cells. Gangliogliomas tend to spare the lateral temporal neocortex, with primary involvement of the mesial structures.(71). Compared with children with other supratentorial tumors, children with gangliogliomas seem to be particularly prone to seizures. Shady et al. (69) found that 88% of children with gangliogliomas had seizures. In gen-

FIG. 6. Median nerve evoked potentials from patient with subdural electrodes, as shown in Fig. 4. Note phase reversal at electrode 39, corresponding to the child’s primary sensory cortex.

Continued.

eral, seizure control after excision of these tumors is excellent.

Dysembryoplastic neuroepithelial tumors (DNTs) are also a common cause of temporal lobe epilepsy (72). Daumas-Duport et al. (72) reported 24 (62%) of 39 cases with the lesion in the temporal lobe. Seizures typically begin in early childhood and are not associated with neurologic deficits. The lesion is composed of astrocytes, oligodendrocytes, and neurons. DNTs are differentiated from gangliogliomas by the prominent amount of oligodendroglial components, the multinodular configuration, and the absence of ganglion-like cells and lymphocytes.

Mixed glial tumors, such as oligoastrocytomas, and primary glial tumors, astrocytomas, or oligoden- drogliomas, can lead to temporal lobe epilepsy. Mixed glial tumors are similar in clinical presenta- tion to gangliogliomas, whereas primary glial tumors behave in a more aggressive fashion (73,74).

Mesial temporal sclerosis (MTS) refers to the pathologic entity of hippocampal sclerosis and atrophy with loss of neurons in the CA1 region and endfolium (CA3/CA4) but with relative sparing of the CA2 region (74). Loss of dentate hilar neurons (endfolium sclerosis) is a common feature and in some patients may be the only apparent hippocampal lesion. Although it is clear, based on MRI (75-78) and pathologic examination (77), that MTS can occur in children, the incidence of MTS in children

Epilepsiu, Vol. 37, Suppl. 3 , 1996


TABLE 1. Summury of surgical procedures for children with medically intractable seizures

Procedure Seizure types EEG Pathologic conditions Risks

Temporal lobectomy

Nontemporal re sections

Corpus callosotomy

Hemispherectomy

Simple or complex partial 2 secondarily generalized

Partial 2 secondarily generalized

Partial +- secondarily generalized; tonic, atonic, “drop” attacks

Unilateral partial ? secondarily generalized seizure; hemiparesis

Interictal: Temporal or frontal spikes, sharp waves.

Ictal: Initially unilateral discharges (spikes, sharp waves, beta, or rhythmic slowing) from temporal lobe, may then spread

Interictal: Focal spikes/ sharp waves, occasional generalized spike-wave.

Ictal: Focal spikes, beta activity, rapid spikes, spike-wave, polyspike- wave

spikesisharp waves, generalized spike-wave, polyspikes, polyspike- wave

Ictal: Rapid spikes, spike- wave, polyspike-wave

Interictal: Preponderance of lateralized EEG discharges over involved hemisphere; may have bilateral spikes

Ictal: Lateralized onset to seizure over involved hemisphere

Interictal: Multifocal

Neoplasm Mesial temporal sclerosis Dysplasia Chronic encephalitis

Neoplasm Dysplasia Chronic encephalitis

Hypoxic-ischemic disease Traumatic brain injury Encephalitis

Rasmussen’s encephalitis Sturge-Weber syndrome Cerebral infarction

Quadrantanopic field deficit; cerebrovascular acci- dent; 3rd nerve palsy

Dependent on surgical site; weakness: visual field cut

Disconnection syndrome; speech deficits; increased frequency or intensity of partial seizures

Hemiparesis; hemosider- osis; hydrocephalus

with temporal lobe epilepsy is not known. In a study of 16 children younger than 12 years with temporal lobe epilepsy, Duchowny et al. reported only two children who had MTS ( 3 ) . Kuzniecky et al. (77) reported MTS in 10 of 20 children with temporal lobe resection; however, only two of 10 children were younger than 12 years. Duchowny et al. (79) found only one patient who had MTS in 14 patients between the ages of 3 and 22 years who were first seen with posterior temporal seizures. It appears that MTS is not as common in children as in adults.

Rasmussen’s encephalitis is a rare, progressive, catastrophic disorder in which children have partial seizures and slowly develop a hemiparesis (80,81). Epilepsia partialis continua (EPC), which is synony- mous with focal status epilepticus, is common in this disorder and is characterized by regular or irregular focal clonic muscular twitching repeated at fairly regular short intervals for a period of days to years (82). The EEG typically shows diffuse slowing over the hemisphere involved. Interictal and ictal spikes may have a widespread distribution, even outside the rolandic area. Multifocal independent foci of epileptic discharges over both hemispheres occur in approximately a third of patients, and bilaterally synchronous epileptiform discharges are found in half (83).

In a review of 160 patients with partial seizures

who underwent a focal cortical resection of epileptogenic tissue, Laxer (84) reported eight patients with pathologic features suggesting focal encephalitis. Two had a progressive course with clinical and pathologic features consistent with chronic focal encephalitis; the other six did not have evidence of a deteriorating course. However, only one of these six became seizure free after the resection. We have seen three children initially with typical temporal lobe epilepsy and normal neurologic examinations who, to our dismay, had evidence for a chronic encephalitis at the time of temporal resection. Unfortu- nately, all three children continued to have severe seizures and eventually underwent a hemispherectomy in spite of the lack of apresurgical hemiparesis.

With improving MRI technology, there has been a growing appreciation of the role of cerebral dysgenesis in chronic epilepsy (85-87). In a series of 16 children younger than 12 years who underwent temporal lobectomy for intractable epilepsy, Du- chowny et al. ( 3 ) found abnormalities of neurogen- esis to be the most common pathologic lesion, occur- ring in seven. Several different types of developmental abnormality can cause these lesions; abnormalities of radial migration, neural cell fate determination, neuronal differentiation, and normal regressive processes such as neural cell death.

Hamartomas and focal cortical dysplasia of the

22 G. L. HOLMES

temporal lobe are the most common development malformations (71). Hamartomas consist of an abnormal proliferation of neuronal, meningeal, glial, or a combination of these cell types without evidence of neoplastic changes. They are usually detected as a hyperintense signal on T, MRI images and, in the temporal lobe, primarily involve the medial structures (71).

Pathologically, focal cortical dysplasia is characterized by abnormal cortical formation and organiza- tion (71 38). Macroscopically, the lesions may mani- fest by a thickened cortical ribbon and an indistinct cortex-white matter junction. In many cases, the lesions are not apparent on gross inspection of the brain and are detected only on microscopic examination. Histologic examination of the tissue reveals a disruption of cortical lamination, large and bizarre- appearing neurons scattered throughout all cortical layers except the first, and astrocytic proliferation (71,87-90). Gliosis is not typically striking, and mild myelin loss may be present. Some children with tuberous sclerosis have a solitary tuber, the so- called forme fruste of tuberous sclerosis. Histologi- cally, the tuber resembles focal cortical dysplasia with abnormal large cells in the cortex, but gener- ally, fewer cells are present (71). Some authors do not consider this lesion to be a distinct pathologic entity (71 $37).

Why patients with focal cortical dysplasia have seizures is not clear. However, abnormalities in the morphology and distribution of local-circuit inhibi- tory neurons may account for the enhanced tissue excitability (91).

Surgical techniques Temporal lobe resection is an effective procedure

in selected children and adults with uncontrolled complex partial seizures (3,92-97). The surgical ap- proach varies from center to center. Some centers advocate tailored resection in which the amount of tissue removed is determined by intraoperative cor- ticography and stimulation studies. The resection may be quite limited, consisting only of an amygdalohippocampectomy (98). Other centers use an en bloc resection in which the anterior temporal lobe is removed in one piece (94,99,100). There are no studies convincingly demonstrating better results of one method over the other.

Outcome In 1975, Davidson and Falconer (101) reported the

outcome after temporal lobectomy in 40 children younger than 16 years with medically intractable seizures. Of the 40 patients, 31 (78%) were either seizure free or had only rare seizures. Subsequent

childhood temporal lobectomy series confirmed these early results. In one of the largest series from one center, Adams et al. (102) reported that of 44 children younger than 16 years who underwent temporal lobectomy in Oxford, England, 66% became seizure free, and another 16% had a 90% reduction in seizure frequency. Although remission rates vary from center to center, 50-90% of patients will have total freedom from seizures or have only rare seizures (103,104). These results should be contrasted with the outcome of 100 children with temporal epilepsy prospectively monitored into adulthood by Lindsay et al. (105,106); fewer than half experienced seizure remissions, and one third were physically dependent with major handicaps. Behavioral disturbances were frequent, and social ostracism was common in patients with persistent seizures.

In most series of pediatric temporal lobectomies, the majority of patients are adolescents. Duchowny et al. (3) reported their experience with temporal lobectomy in 16 children younger than 12 years. In all patients, the standard anterior temporal lobectomy was tailored according to the extent of the lesion and epileptogenic field. At follow-up, 1 I children were seizure free, and three were 90% im- proved.

Nontemporal lobe resections Temporal lobectomy is the most frequent type of

epilepsy surgery among patients overall, but extratemporal resection is more common among the youngest children (57). Tumors and dysplastic lesions are the most common causes of seizures arising outside the temporal lobes.

Unfortunately, locating a seizure focus in nontemporal lobe structures is one of the more challenging tasks for the clinical neurophysiologist. This is particularly difficult when the seizures are suspected to arise from the frontal lobe. The large surface area of the frontal lobe, as well as anatomic structures like the mesial and orbital regions that are far removed from the recording electrodes, makes it very difficult to localize either interictal or ictal EEG abnormalities (107-109). Focal EEG seizures may also arise in a “silent” region of the frontal lobe, produc- ing clinical symptoms only after seizure spread to neighboring frontal lobe structures or to the temporal lobe.

The task is even more complicated by the exis- tence of a functional network of pathways permitting spread of discharges within and outside the frontal lobes (107). The bidirectional spread of epileptic discharges through the uncinate fasciculus and the cin- gulate gyrus seizures arising from the frontal lobe may be falsely localized to the temporal lobe and


vice versa. Because of this difficulty in localizing abnormalities, there is a poorer electroclinical correlation of ictal events in the frontal lobe than else- where (1 10,11 I ) . Most children with frontal lobe seizures who do not have structural lesions on MRI require invasive electrode monitoring.

The incidence of excellent outcome with patients seizure free or with auras only after extratemporal resection was only 17% in a series including children and adults (1 12). However, the frequency of significant clinical improvement after extratemporal resection, with worthwhile reduction of seizure frequency, was 70%. With daily partial seizures in spite of adequate serum levels of AEDs, it may be appro- priate to consider extratemporal cortical resection. With increasing sophistication of PET and SPECT scanning, it is likely that results of extratemporal resections will improve in the future.

Hemispherectomy The removal of all or most of one hemisphere is

one of the most drastic yet effective means of treat- ing seizures ( 1 13-1 19). The procedure is typically used in patients with severe unilateral motor seizures who already have a hemiparesis and nonfunc- tional hand. Patients with Rasmussen’s encephalitis and Sturge-Weber syndrome are frequently candidates for this type of surgery. In addition, patients with hemimegalencephaly (1 14) and other disorders of cerebral dysgenesis, cerebral infarction, and trauma may also benefit from the surgery.

The presurgical evaluation must establish that the patient is not a candidate for a more restricted surgical resection. Bilateral interictal spikes are common in patients with unilateral hemisphere pathologic conditions, but determination that the seizures begin unilaterally is essential. However, this may be difficult to establish in patients with severe atrophy of the hemisphere, when only surface EEG monitoring is performed, because the ictal discharges may not propagate well to the surface of the head. In these cases, the clinical features of the seizures and functional neuroimaging can be useful in lateralizing the epileptic focus.

The response to the procedure is gratifying with more than three quarters of the patients having a favorable outcome after the procedure. Because of late complications, including superficial hemosider- osis with obstructive hydrocephalus, bleeding into the hemispherectomy cavity, or fatal brainstem shift (1 18), surgeons have been performing modified hemispherectomies that isolate but do not remove the frontal and occipital poles (1 17) or hemicortec- tomy (120).

Corpus callosotomy In some patients, in spite of extensive evaluations,

a focus cannot be identified. In others, presurgical evaluation will detect more than one focus. These patients may benefit from a corpus callosotomy. In this procedure, epileptic tissue is not removed, but the spread of the seizure is altered.

Few large series of children undergoing corpus callosotomy have been published. All of the reports of corpus callosotomy have been marred by their retrospective nature, lack of a control group, short duration of follow-up, and failure to quantify seizure frequency and duration before and after the surgery. The reported success of the surgery is therefore open to question. In series including both adult and pediatric patients, there have been no notable differences between children and adults in either seizure control or sequelae. Wilson et al. (121), in a consecutive series of patients who underwent “central” complete commissurotomy in two stages, reported that eight (66.7%) of 12 patients had surgery before age 21 years. The outcome in seven (87.5%) of eight children was good or excellent. Spencer et al. (122) performed surgery before age 21 years in almost 60% of their patients. Outcome after either anterior corpus callosotomy or complete corpus callosotomy was not related to age at the time of surgery. Nord- gren et al. (123) reported that of 18 children between the ages of 7 and 16 years undergoing complete corpus callosotomy, one child became seizure free, 12 had a S O % reduction in seizures, and three had a 50-80% reduction in seizure frequency. However, Makari et al. (124) found that only eight (40%) of 20 children undergoing anterior two thirds corpus callosotomy had worthwhile outcomes.

No firm criteria now can be used to predict which patients will benefit from surgery. Factors that have been associated with favorable outcome by some but not all investigators have included normal in- telligence (121,125,126), focal EEG abnormality (121,126,127), focal CT scan abnormality (126), the presence of generalized tonic-clonic, tonic, or atonic seizures (123- 125), and hemiparesis (126- 128). The procedure is usually reserved for patients with very frequent seizures, particularly “drop” attacks (atonic and tonic seizures).

Although complications from the corpus callosotomy are relatively few, the procedure is not without risk. A disconnection syndrome has been described after the callosotomy (126). Patients may have difficulties with speech and motor functioning for days to weeks after surgery. There may be decreased spontaneity of speech, which may be as severe as complete mutism or as mild as a slowness in initiat- ing speech. In addition, variable degrees of paresis

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24 G. L. HOLMES

of the nondominant leg, forced grasping of the nondominant hand, and incontinence are present. These deficits usually improve with speech and physical therapy. However, there have been reports of permanent language disturbances after isolated anterior, posterior, or complete callosotomy, but only in patients with mixed cerebral dominance (126,129). When the hemisphere of language dominance is not the hemisphere controlling handedness, language deficits are more likely to develop. In these patients a prior injury to the dominant hemisphere may cause transfer of some expressive language to the contra- lateral hemisphere without changing the preferred hand.

A small number of patients have had persistent antagonism between the two hemispheres, reflected in difficulties with motor function (126). In these patients, the nondominant hand may no longer respond correctly to verbal commands, and further, may function in an antagonistic manner toward the activity of the dominant hand.

Acknowledgment: This study was supported by an NIH N I N D S grant NS27984 t o G.L.H.

REFERENCES

I . Annegers JF, Hauser WA, Elveback LR. Remission of seizures and relapse in patients with epilepsy. Epilepsia I979;20:129-37.

2. Hauser WA. Epidemiology of epilepsy in children. Neuro- surg Clin North Am 1995;6:419-29.

3. Duchowny M, Levin B, Jayakar P, et al. Temporal lobectomy in early childhood. Epilepsia 1992;33:298-303.

4. Luders H, Wyllie E, Rothner DA, Bourgeois B, Kotagal P. Surgery of localization related epilepsies in children. Brain Deu 1989;11:98-101.

5 . Chugani HT, Shields WD, Shewmon DA, Olson DM, Phelps ME, Peacock WJ. Infantile spasms: I. PET identifies focal cortical dysgenesis in cryptogenic cases for surgical treatment. Ann Neurol 1990;27:406-13.

6. Chugani HT, Shewmon DA, Peacock WJ, Shields WD. Mazziotta JC, Phelps ME. Surgical treatment of intractable neonatal onset seizures: the role of positron emission tomography. Neurology l988;38: 1178-88.

7. Ribaric 11, Nagulic M, Djurovic B. Surgical treatment of epilepsy: our experiences with 34 children. Childs Neru Syst 1991 ;7993:402-4.

8. Shewmon DA, Shields WD, Chugani HT, Peacock WJ. Contrasts between pediatric and adult epilepsy surgery: rationale and strategy for focal resection. J Epilepsy I990;3(suppl): 1 -15.

9. Bower AJ. Plasticity in the adult and neonatal central nervous system. Br J Neurosurg 1990;4:253-64.

10. Huttenlocher PR. Morphometric study of human cerebral cortex development. Neuropsychologia 1990;28:5 17-27.

11. Farmer SF, Harrison LM, Ingram DA, Stephens JA. Plastic- ity of central motor pathways in children with hemiplegic cerebral palsy. Neurology 1991;41:1505-10.

12. Lassonde M, Sauerwein H , Chicoine AJ, Geoffroy G. Absence of disconnection syndrome in callosal agenesis and early callosotomy: brain reorganization or lack of structural specificity during ontogeny? Neuropsychologia I99 1 ;29:48 1-95.

13. Lassonde M, Sauerwein H , McCabe N , Lauerencelle L , Geoffroy G. Extent and limits of cerebral adjustment to early section of congenital absence of the corpus callosum. Behau Brain Res 1988;30:165-81.

14. Cascino GD. Structural neuroimaging in partial epilepsy. Neurosurg Clin North A m 1995;6:455-64.

15. Heinz ER, Heinz TR, Radtke R, et al. Efficacy of MR vs CT in epilepsy. AJR A m J Roentgenol 1989;152:347-52.

16. Convers P, Bierme T, Ryvlin P, et al. Contribution of magnetic resonance imaging in 100 cases of refractory partial epilepsy with normal CT scans. Reu Neurol1990;146:330-7.

17. Francheschi M, Triulzi F , Ferini-Strambi L, et al. Focal cerebral lesions found by magnetic resonance imaging in cryptogenic nonrefractory temporal lobe epilepsy patients. Epilepsia 1989;30:540-6.

18. Berkovic SF, Andermann F , Olivier A, et al. Hippocampal sclerosis in temporal lobe epilepsy demonstrated by magnetic resonance imaging. Ann Neurol 1991 ;29: 175-82.

19. Jackson GD, Berkovic SF, Tress BM, Kalnins RM, Fabinys GCA, Bladin PF. Hippocarnapal sclerosis can be reliably detected by magnetic resonance imaging. Neurology 1990;40: 1869-75.

20. Kuzniecky R, De La Sayette U , Ethier R, et al. Magnetic resonance imaging in temporal lobe epilepsy: pathological correlations. Ann Neurol 1987;22:341-7.

.21. Jack CR Jr, Sharbrough FW, Cascino GD, Hirschorn KA, O’Brien PC, Marsh WR. Magnetic resonance image-based hippocampal volumetry: correlation with outcome after temporal lobectomy. Ann Neurol l992;3 I : 138-46.

22. Kuzniecky RI, Cascino GD, Palmini A, et al. Structural neuroimaging. In: Engel J. ed. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press, 1993: 197-209.

23. Cascino GD, Jack CR Jr, Parisi JE , et al. MR1-based volume studies in temporal lobe epilepsy: pathological correlations. Ann Neurol 1991;30:31-6.

24. Lencz T, McCarthy G, Bronen RA, et al. Quantitative magnetic resonance in temporal lobe epilepsy: relationship to neuropathology and neuropsychological function. Ann Ner4- rol 1992;3 1:629-37.

25. Hwang PA, Gilday DL, Adams C, Chuang S, Becker LE, Hoffman HJ. SPECT studies in epilepsy: application to epilepsy surgery in children. J Epilepsy 1990;3(suppl I ):83-92.

26. Rowe CC, Berkovic SF, Austin MC, McKay WJ, Bladin PF. Patterns of postictal cerebral blood flow in temporal lobe epilepsy: qualitative and quantitative analysis. Neurology I99 I ;4 1 : 1096- 103.

27. Harvey AS, Berkovic SF. SPECT imaging of regional cerebral blood flow in children with partial epilepsy. Acta Ner4- ropediatr 1994; 1 :9-27.

28. Jabbari B, Van Nostrand D, Gunderson CH, et al. EEG and neuroimaging localization in partial epilepsy. Elec- troencephalogr Clin Neurophysiol 1991 ;79: 108-13.

29. Treves ST, Connolly LP. Single-photon emission computed tomography (SPECT) in pediatric epilepsy. Neurosurg Clin North Am 1995;6:473-80.

30. Berkovic SF, Newton MR, Chiron C, Dulac 0. Single photon emission tomography. In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press, 1993 : 23 3-43.

31. Adams C, Hwang PA, Gilday DL, Armstrong DC, Becker LE, Hoffman HJ. Comparison of SPECT, EEG, CT, MRI, and pathology in partial epilepsy. Pediatr Neurol 1992;s: 97- 103.

32. Gelfand MJ, Stowens DW. I 123 Iofetamine SPECT in school-age children with difficult to control seizures. Clin Nucl Med 1989;14:675-80.

33. Olson DM, Chugani H , Shewmon A, Phelps M, Peacock W. Electrocorticographic confirmation of focal positron emission tomographic abnormalities in children with intractable epilepsy. Epilepsia 1990;3 1:731-9.

34. Chugani HT, Shewmon A, Shields WD, Peacock WJ, Phelps ME. Pediatric epilepsy surgery: pre- and postoperative evaluation with PET. J Epilepsy 1990;3(suppl 1):75-82.


INTRACTABLE CHILDHOOD EPILEPS Y 25

35. Cummings TJ, Chugani DC, Chugani HT. Positron emission tomography in pediatric epilepsy. Neurosurg Clin North A m 1995;6:465-72.

36. Chugani HT, Shewmon DA, Sankar R, Chen BJ, Phelps ME. lnfantile spasms: 11. Lenticular nuclei and brainstem activation on positron emission tomography. Ann Neurol 1992;3 I :2 12-9.

37. Ochs RF, Gloor P, Tyler JL, et al. Effect of generalized spike-and-wave discharge on glucose metabolism measured by positron emission tomography. Ann Neurol l987;21:

38. Theodore WH, Brooks R, Margolin R, et al. Positron emission tomography in generalizied seizures. Neurology

39. Jones-Gotman M, Smith ML, Zatorre RJ. Neuropsychologi- cal testing for localizing and lateralizing the epileptogenic region. In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press, 1993:245-61.

40. Jones-Gotman M. Presurgical psychological assessment in children: special tests. J Epilepsy 1990;3(suppl):93-102.

41. Riviello JJ Jr, Kramer U, Holmes G, et al. Safety of invasive electroencephalographic monitoring: a comparison of adults and children. Neurology 1993 ;43(suppl): A288.

42. Dodrill CB, Hermann BP, Rausch R, Chelune GJ, Oxbury S. Neuropsychological testing for assessing prognosis fol- lowing surgery for epilepsy. In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press, 1993:263-71.

43. Holmes Bernstein J , Prather PA, Rey-Casserly C. Neuro- psychological assessment in preoperative and postoperative evaluation. Neurosurg Clin North A m 1995;6:443-54.

44. Engel J Jr. A practical guide for roufine EEG studies in epilepsy. J Clin Neurophysiol 1984;l: 109-42.

45. Holmes GL. Partial complex seizures in children: an analysis of 69 seizures in 24 patients using EEG FM radioteleme- try and videotape recording. Electroencephalogr Clin Neu- rophysiol 1984;57: 13-20,

46. Jasper H , Pertuisset B. Flanigin H. EEG and cortical elec- trograms in patients with temporal lobe seizures. Arch Neurol Psychiatry 1951 ;65:272-90.

47. Klass DW. Electroencephalographic manifestations of complex partial seizures. In: Penry JK, Daly DD, eds. Complex partial seizures and their treatment. New York: Raven Press, 1975:113-40. (Advances in Neurology, Vol 1 1 )

48. Morris HH 111, Kanner A, Luders H , et al. Can sharp waves localized at the sphenoidal electrode accurately identify a mesio-temporal epileptogenic focus? Epilepsia 1989;30: 532-9.

49. Morris HH 111, Liiders H. Electrodes. In: Gotman J, Ives JR. Gloor P, eds. Long-term monitoring in epilepsy. Amster- dam: Elsevier, 1985:3-26.

50. Wyllie E, Wyllie R, Kotagal P, Luders H, Kanner A. Com- fortable insertion of sphenoidal electrodes in children. Epi- lepsiu l990;3 I :52 1-3.

51. Delgado-Escueta AV, Walsh GO. The selection process for surgery of intractable complex partial seizures: surface EEG and depth electrocorticography. In: Ward AA Jr, Penry JK, Purpura DP, eds. Epilepsy: Proceedings of the Association .for Research in Nervous and Mental Diseases. Vol61. New York: Raven Press, 1983:295-326.

52. Blom S, Flink R, Hetta J, et al. Interictal and ictal activity recorded with subdural electrodes during preoperative evaluation for surgical treatment of epilepsy. J Epilepsy 1989;2: 9-20.

53. Goldring S , Gregorie EM. Surgical management using epidural recordings to localize the seizure focus: review of 100 cases. Neurosurgery 1984;60:457-66.

54. Luders H, Lesser RP, Dinner DS, et al. Chronic intracranial recording and stimulation with subdural electrodes. In: En- gel J Jr, ed. Surgical treatment of the epilepsies. New York: Raven Press, 1987:297-321.

55. Wyllie E, Luders H , Morris H H 111, et al. Clinical outcome

458-64.

1985;35:684-90.

after complete or partial cortical resection for intractable epilepsy. Neurology 1987;37: 1634-41.

56. Wyllie E , Luders H , Morris HH, et al. Subdural electrodes in the evaluation for epilepsy surgery in children and adults. Neuropediatrics 1988 ; 19: 80-6.

57. Nespeca M, Wyllie E, Luders H, et al. EEG recording and functional localization studies with subdural electrodes in infants and young children. J Epilepsy 1990;3(suppl): 107-24.

58. Awad I , Assirati JA, Burgess R, Barnett G, Luders H. A new class of electrodes of “intermediate invasiveness”: preliminary experience with epidural pegs and foramen ovale electrodes in the mapping of seizure foci. Neurol Res 199 1 ; 13: 177-83.

59. Wyllie E, Burgess R, Awad I , Barnett G, Luders H. Flexible epidural peg electrodes for chronic EEG recording. Ann Neurol 1989:26:471.

60. Wyllie E . EEG in the evaluation for epilepsy surgery in children. In: Holmes GL, Moshe SL, eds. Pediatric clinical neurophysiology. Norwalk, CT: Appleton & Lange (in press).

61. Harbord MG, Manson JI. Temporal lobe epilepsy in childhood: reappraisal of etiology and outcome. Pediatr Neurol 1987;3:263-8.

62. Holmes GL. Partial seizures in children. Pediatrics 1986; 77:725-3 1.

63. Wyllie E , Luders H. Complex partial seizures in children: clinical manifestations, and identification of surgical candidates. Cleve Clin J Med 1989;56:S43-52.

64. Wyllie E, Rothner AD, Luders H. Partial seizures in children: clinical features, medical treatment, and surgical con- siderations. Pediatr Clin North A m 1989;36:343-64.

65. Duchowny MS. Complex partial seizures of infancy. Arch Neurol 1987;44:911-4.

66. Yamamoto N, Watanabe K , Negoro T, et al. Complex partial seizures in children: ictal manifestations and their rela- tion to clinical course. Neurology 1987;37: 1379-82.

67. Kotagal P, Rothner AD, Erenberg G, Cruse RP, Wyllie E . Complex partial seizures of childhood onset: a five-year follow-up study. Arch Neurol 1987;44: 1177-80.

68. Page LK, Lombroso T, Matson D. Childhood epilepsy with late detection of cerebral glioma. J Neurosurg 1969;31:

69. Shady JA, Black PM, Kupsky WJ, et al. Seizures in children with supratentorialastroglial neoplasms. Pediutr Neurosurg 1994;21:23-30.

70. Wyllie E , Chee M, Granstrom M-L, et al. Temporal lobe epilepsy in early childhood. Epilepsia 1993;34:859-68.

71. Vigevano F, Fusco L , Ricci S, GranataT, Viani F. Dyspla- sias. In: Dulac 0, Chugani H , Dalla Bernardina B, eds. Infantile spasms and West syndrome. London: WB Saun- ders, 1994:178-91.

72. Daumas-Duport C, Scheithauer BW, Chodkiewicz J-P, Laws ER, Jr, Vedrenne C. Dysembryoplastic neuroepithelial tumor: a surgically curable tumor of young patients with intractable partial seizures: report of thirty-nine cases. Neu- rosurgery 1988;23:545-56.

73. Bruton CJ. The neuropathology of temporal lobe epilepsy. New York: Oxford University Press, 1988.

74. Armstrong DD. The neuropathology of temporal lobe epilepsy. J Neuropathol Exp Neurol 1993;52:433-43.

75. Cendes F, Amdermann F , Dubeau F, et al. Early childhood prolonged febrile convulsions, atrophy, and sclerosis of mesial structures, and temporal lobe epilepsy: an MRI vol- umetric study. Neurology 1993;43: 1083-7.

76. Cross JH, Jackson GD, Neville BGR, et al. Early detection of abnormalities in partial epilepsy using magnetic resonance. Arch Dis Child 1993;69: 104-9.

77. Kuzniecky R, Murro A, King D, et al. Magnetic resonance imaging in childhood intractable partial epilepsies: pathologic correlations. Neurology 1993;43:68 1-7.

78. Grattan-Smith JD, Harvey AS, Desrnond PM, Chow CW. Hippocampal sclerosis in children with intractable temporal

253-61.

Epilepsia, Vol. 37, Suppl. 3 , 1996

G. L. HOLMES 26

79.

80.

81.

82.

83.

84.

us.

86.

87.

88.

89.

90.

91.

92.

93.

94.

95.

96.

97.

98.

99.

I 00.

101.

lobe epilepsy: detection with MR imaging. AJR Atn J Roentgen01 1993;161: 1045-8. Duchowny M, Jayakar P, Resnick T, Levin B, Alvarez L. Posterior temporal epilepsy: electroclinical features. Ann Nrrirol 1994;34:427-3 I . Aguilar MJ, Rasmussen T. Role of encephalitis in pathogenesis of epilepsy. Arch Neurol 1960;2:663-76. Andermann FA, Freeman JM, Vigevano F , Hwang PALS. Surgically remediable diffuse hemispheric syndromes. In: Engel J Jr, ed. Surgical treattnent o f t h e epilepsies. 2nd ed. New York: Raven Press, 1993:87-101. Juul-Jensen P, Denny-Brown D. Epilepsia partialis continua. Arch Neurol 1966; 15:563-78. So N, Gloor P. Electroencephalographic and electrocorticographic findings in chronic encephalitis of the Rasmussen type. In: Andermann E. ed. Chronic encephalitis und epilepsy: Rasmussen’s syndrome. Boston: Butterworth- Heinemann, 1991 :37-45. Laxer KD. Temporal lobe epilepsy with inflammatory pathologic changes. In: Andermann F, ed. Chronic, encephu- l i / i s and epilepsy: Rasmrissc~n’s syndrome. Boston: Butter- worth-Heinemann, 199 1 : 135-40. Vinters HV, Fischer RW, Cornfield ME, et al. Morphologi- cal substrates of infantile spasms: studies based on surgically resected cerebral tissue. Childs Neru Syst I9923 :8- 17. Vinters HV, De Rosa MJ, Farrell MA. Neuropathologic study of resected cerebral tissue from patients with infantile spasms. Epilepsia 1993:34:772-9. Palmini A, Andermann F, Olivier A, et al. Focal neuronal migration disorders and intractable partial epilepsy: a study of 30 patients. Ann Nenrol 1991;30:741-9. Taylor DC, Falconer MA, Bruton CJ, Corsellis JAN. Focal dysplasia of the cerebral cortex in epilepsy. J Neurol Nerrrosirrg P.sychiatrv 1971 ;34:369-87. Kuzniecky R, Garcia J , Faught E, Morawetz R. Cortical dsyplasia in TLE: MRI correlations. Ann Neurol I991 ; 29:293-8. Hardiman 0, Burke T . Phillips J. et al. Microdysgenesis in resected temporal neocortex: incidence and clinical signifi- cance in focal epilepsy. Neurology 1988;38: 1041-7. Ferrer I , Pineda M, Tallada M, et al. Abnormal local-circuit neurons in epilepsia partialis continua associated with focal cortical dysplasia. Actu Neuropathol 1992;83:647-52. Engel JJ, Driver MV, Falconer MA. Electrophysiological correlates of pathology and surgical results in temporal lobe epilepsy. Brain 1975;98: 129-56. Jensen I , Vacernet K. Temporal lobe epilepsy: follow-up investigation of 74 temporal lobe resected patients. Ac,ta Neurochir 1977;37: 173-200. Falconer MA. Place of surgery for temporal lobe epilepsy during childhood. Br Med J 1972;2:631-5. King DW, Flanigin HF, Gallagher BB, et al. Temporal lobectomy for partial complex seizures: evaluation, results, and I-year follow-up. Neurology 1986;36:334-9. Penfield W, Flanigin H. Surgical therapy of temporal lobe seizures. Arch Neurol Psychiatry 1950;64:491-500. Mizrahi EM, Kellaway P, Grossman RG, et al. Anterior temporal lobectomy and medically refractory temporal lobe epilepsy of childhood. Epilepsia 1990;31:302-12. Siege1 AM, Wieser HG. Comparative pre- and postoperative interictal scalp electroencephalographic examinations in patients with selective amygdalohippocampectomy. J Epi- lepsy 1989;2:65-72. Falconer MA, Serafetinides EA, Corsellis JAN. Etiology and pathogenesis of temporal lobe epilepsy. Arch Nrurol 1964;10:233-48. Falconer MA. Mesial temporal (Ammon’s horn) sclerosis in epilepsy: etiology, treatment, and prevention. Lancet I974;2:767-70. Davidson S, Falconer MA. Outcome of surgery in 40 children with temporal-lobe epilepsy. Lancet 1975; I : 1260-3.

102.

103.

104.

105.

106.

107.

108.

109.

110.

1 1 1 .

112.

113.

114.

115.

116.

117.

118.

119.

120.

121.

122.

123.

A d a m CBT, Beardsworth ED, Oxbury SM, Fenwick PBC. Temporal lobectomy in 44 children: outcome and neuropsychological follow-up. J Epilepsy 199O;(suppl 1): 157-68. Duchowny MS. Surgery for intractable epilepsy: issues and outcome. Pediatrics 1989;84:886-94. Shields WD, Duchowny MS, Holmes GL. Surgically remediable syndromes of infancy and early childhood. In: Engel J Jr, ed. Surgical treatment of the epilepsies. 2nd ed. New York: Raven Press, 1993:35-48. Lindsay J , Ounsted C, Richards P. Longterm outcome in children with temporal lobe seizures. I: Social outcome and childhood factors. Deu M e d Child Neurol 1979;21: 285-98. Lindsay J , Ounsted C, Richards P. Longterm outcome in children with temporal lobe seizures. 111. Psychiatric as- pects in childhood and adult life. Deu M e d Child Neurol

Quesney LF. Seizures of frontal lobe origin. In: Pedley TA, Meldrum BS, eds. Recent uduances in epilepsy. 3rd ed. New York: Churchill Livingstone, 1986:81-110. Quesney LF, Krieger C, Leitner C, Gloor P, Olivier A. Frontal lobe epilepsy: clinical and electrographic presenta- tion. In: Porter RJ, Mattson RH, Ward AA Jr. Dam M, eds. Advances in Epileptology: XVth Epilepsy International Sywzposium. New York: Raven Press, 1984:503-8. Quesney LF, Gloor P. Localization of epileptic foci. Electroencephalogr Clin Neurophysiol 1985;(suppl 37): 165-200. Geier S, Bancaud J , Talairach J , Bonk A, SziklaG, Enjelvin M. The seizures of frontal lobe epilepsy: a study of clinical manifestations. Neurology 1977;27:95 1-8. Bossi L, Munari C , Stoffels C, et al. Somatomotor manifestations in temporal lobe epilepsy. Epilepsiu 1984;25: 70-6. Van Ness P, Estes ML. Salanova V, Morris HH, Luders H. Seizure reduction and pathologic findings in 37 operated patients with suspected neocortical epilepsy. Epilepsiu 1989;30:728. Cairns H, Davidson MA. Hemispherectomy in the treatment of infantile hemiplegia. Lancet 1951 ;2:411-5. Vigenvano F, Bertini E , Boldrini R. et al. Hemimegal- encephaly and intractable epilepsy: benefits of hemispherectomy. Epilepsiu 1989;30:833-43. Tinuper P, Andermann F, Villemure J-G, Rasmussen TB. Quesney LF. Functional hemispherectomy for treatment of epilepsy associated with hemiplegia: rationale, indication, results, and comparison with callosotomy. Ann Neirrol 1988;24:27-34. Rasmussen T. Hemispherectomy for seizures revisited. Can J Neurol Sci 1983;10:71-8. Rasmussen T, Villemure J-G. Cerebral hemispherectomy for seizures with hemiplegia. Cleue Clin J M e d 1988; 56:S62-8. Verity CM, Strauss EH, Moyes PD, Wada JA, Dunn HG, Lapointe JS. Long-term monitoring follow-up after cerebral hemispherectomy: neurophysiologic, radiologic, and psychological findings. Neurology 1982;32:629-39. Smith SJ, Andermann F, Villemure JG, Rasmussen TB, Quesney LF. Functional hemispherectomy: EEG findings, spiking from isolated brain postoperatively, and prediction of outcome. Neurology 1991;41:1790-4. Winston KR, Welch K , Adler JR, Erba G. Cerebral hemicor- ticetomy for epilepsy. J Neurosurg 1992;77:889-95. Wilson DH, Reeves AG, Gazzaniga MS. “Central” commissurotomy for control of intractable generalized epilepsy: series two. Neurology 1982;32:687-97. Spencer SS, Spencer DD, Williamson PD, Sass KJ, Novelly RA, Mattson RH. Corpus callosotomy for epilepsy. 1. Sei- zure effects. Neurology 1988;38: 19-24. Nordgren RE, Reeves AG, Viguera AC, Roberts DW. Cor- pus callosotomy for intractable seizures in the pediatric age group. Arch Neurol 1991 ;48:364-72.

1979;21:630-6.

Epdepsici. V o l . 37, Suppl. 3 , 1996

INTRACTABLE CHILDHOOD EPILEPS Y

124. Makari GS, Holmes GL, Murro AM, et al. Corpus callosotomy for the treatment of intractable epilepsy in children. J Epilepsy 1989;2:1-7.

125. Murro AM, Flanigin HF, Gallagher BB, King DW, Smith JR. Corpus callosotomy for the treatment of intractable epilepsy. Epilepsy Res 1988;2:44-50.

126. Spencer SS. Corpus callosum section and other disconnection procedures for medically intractable epilepsy. Epilepsia 1988;29(suppl 2):S85-99.

127. Luessenhop AJ, de la Cruz TC, Fenichel GM. Surgical

27

disconnection of the cerebral hemispheres for intractable seizures: results in infancy and childhood. JAMA 1970; 2 13: 1630-6.

128. Wilson DH, Reeves A, Gazzaniga M, Culver C. Cerebral commissurotomy for control of intractable seizures. Neurol- ogy 1977;27:649-53.

129. Sass KJ, Spencer DD, Spencer SS, Novelly RA, Williamson PD, Mattson RH. Corpus callosotomy for epilepsy. 11. Neurologic and neuropsychological outcome. Neurology 1988;38:24-8.


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