AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

Since the late 19th century, surgery has been accepted as a treatment for medically refractory epilepsy. Although a multicenter randomized trial has not been performed, published data from individual centers and pooled data from the University of California Los Angeles (UCLA) Palm Desert Conference held in 1992 show that surgery for seizures results in seizure-free outcome in a majority of patients with hippocampal sclerosis or a well-defined lesion.

Seizure-based outcome classification systems

When looking at the efficacy of epilepsy surgery, a patient's postsurgical seizure frequency is compared to his or her preoperative seizure frequency. Usually, these assessments are performed at individual centers where the number of patients is small, and patients serve as their own controls. In doing so, the assumption is made, based on the natural history of intractable epilepsy, that spontaneous remissions without surgery are infrequent. We now know from through the work of Berg et al that prolonged remissions can occur before eventual intractability becomes evident.

Numerous classification systems are used by epilepsy centers. The Engel classification system, devised in 1987, is the most commonly used scale. All seizure-outcome scales now in use contain subjective components such as "worthwhile improvement" or "significant reduction." The Engel classification, for example, requires these subjective assessments to distinguish a class 3 outcome from a class 4 outcome. Class 1 includes patients with residual auras. Usually, auras do not bother the patient if they are infrequent. However, depending on the frequency and the nature of the auras (eg, intense fear), they can affect postoperative quality of life even though they do not affect driving ability or independence. In fact, Vickrey et al found that, of patients who undergo surgery, those with residual auras have less improvement in quality-of-life outcomes than those who do not have residual auras. Furthermore, in some patients, residual auras can be associated with unrecognized loss of awareness.

A seizure-outcome scale should reflect dynamic changes in seizure outcome. It must differentiate between freedom from seizures and quality of life. For example, a useful scale must be able to assess whether a patient who is not seizure free after surgery but has had prolonged periods of remission or a reduction of seizure frequency since surgery has had an improvement in quality of life.

Vickrey et al demonstrated the variability in seizure classification systems in 1995. They compared 7 previously published seizure-based classification systems to an external standard, a self-reported, health-related quality-of-life (HRQL) inventory specifically designed for patients with epilepsy. They found that these different seizure classification systems varied in their degree of correlation to this external standard. Since the ultimate goal of epilepsy surgery is improvement in HRQL and functioning, seizure-outcome scales need to be objective and reflect dynamic changes in seizure outcome. This will help us to determine whether certain degrees of postoperative seizure control correlate with HRQL measures.

OUTCOME FOR SURGERY FOR TEMPORAL LOBE EPILEPSY

Section 3 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

Outcome for temporal lobe epilepsy surgery

Only one class I randomized controlled intent to treat trial comparing epilepsy surgery to medical treatment has been performed. In 2001, Wiebe and colleagues from Canada published a landmark study in the New England Journal of Medicine in which 80 patients with suspected temporal lobe epilepsy were assigned to medical or surgical groups before presurgical evaluation.

• Those assigned to the surgical group received temporal lobe epilepsy surgery immediately if the presurgical evaluation revealed that they were surgical candidates.
• Those assigned to the medical group were placed on the usual 1-year waiting list for epilepsy surgery.
• At the end of 1 year, 58% of patients in the surgical group were free of disabling seizures, and 10-15% had little or no improvement compared with only 8% free of disabling seizures in the medical group (p <.001).
• This study also showed that quality of life (QOL) at 1 year was significantly improved in the surgical group compared with the medical group.
• Morbidity was minimal and similar in both groups. However, one patient died in the medical arm, and no mortality occurred in the surgical group.

A recent American Academy of Neurology Practice Parameter published in 2004 reviewed data from published studies from January 1, 1990 to September 2001.

• With the exception of the Wiebe study described above, only class IV studies were identified defined as uncontrolled studies from single centers.
• Twenty-four papers were identified that described seizure outcome for anteromedial temporal resection that met their criteria for analysis: (1) series with pure anteromedial temporal resections, pure localized neocortical temporal resections or both for medically intractable complex partial seizures with or without secondary generalization; (2) description of frequency of epileptic seizures other than auras (simple partial motor seizures without a motor component; and (3) quantitatively measured health-related QOL.
• All studies were retrospective with the exception of Sperling's study (1996).
• No study offered a quantitative number of preoperative seizure frequency. However, all patients were described as having disabling seizures.
• A total of 1,952 patients were identified and 1,285 (67%) were reported to be free of disabling seizures.
• Twenty-one of the centers subdivided outcome into 3 categories for 1,769 patients; 1150 (65%) were free of disabling seizures, 372 (21%) were improved, and 247 (14%) were not improved.
• All studies had at least 1 year of follow-up, and 17 studies had 2-5 years of follow-up.
• The results were consistent across studies and were nearly identical to the results of the class I study by Wiebe et al (2001).
• Seizure outcome for localized neocortical resections identified 8 papers. Many papers were excluded because they only evaluated patients with specific neocortical lesions. Overall, 50% were seizure free. Six of 8 centers subdivided outcome into 3 categories, with 49% free of disabling seizures, 30% improved, and 21% improved. The selected papers included nonlesional cases. In 131 lesional cases, 63% became seizure free.

A study from the Yale Multicenter Study of Epilepsy Surgery, which is a 7 center observational prospective study, reported its findings. Inclusion requirements included age 12 years or older, at least 1 seizure each month, failure of at least 2 standard AEDs, and a standard presurgical evaluation (see Presurgical Evaluation of Epilepsy) consistent with unilateral TLE.

• A total of 396 patients were selected for surgery, 339 of which had at least 2-year postoperative follow-up.
• At 2 years, overall 66% patients achieved a 2-year remission defined as an absence of seizures without auras.
• Sixty-eight percent had medial temporal resections and 50% had neocortical resections.
• Multivariate analysis showed that only the absence of generalized tonic-clonic seizures and the presence of hippocampal atrophy were independently associated with remission in the medial temporal resection group only.
• Duration of epilepsy, age of onset, and age at study entry were not predictors of outcome.
• The cumulative probability of attaining remission increased over time from years 2 to age 5 years from date of surgery.
• They also studied relapse rate in patients who initially attained a 2-year remission. Approximately 25% of the medial temporal group and 19% of the temporal neocortical resection group relapsed after a 2-year remission. The only factor that predicted relapse was delay to remission (ie, early seizure than subsequent remission vs seizure free from the time of hospital discharge). The study did not state whether the seizure frequency in those who relapsed was significantly less than their preoperative seizure frequency or whether the QOL of those who relapsed was improved compared with their presurgery baseline or different than those who remained seizure free. They also did not mention if those who relapsed had complex partial or generalized tonic-clonic seizures, whether their seizure(s) were exclusively nocturnal or whether they had sustained remission after an initial relapse. The study did note that relapse was not associated with AED reduction or withdrawal.

Predictors of seizure-free outcome at 1-2 years

The presence of hippocampal sclerosis is not an independent predictor of seizure-free surgical outcome in that only 50% of patients with hippocampal sclerosis become seizure free when noninvasive data such as interictal video-EEG recording and neuropsychological testing are not considered. In a Mayo Clinic series, 90% of patients with unilateral temporal interictal spikes, concordant ictal onsets, and unilateral hippocampal atrophy became seizure free after surgery. Patients with bilaterally independent, temporal, interictal epileptiform abnormalities, on the other hand, did not have as good a seizure-free outcome rate (ie, 70%). The factors predictive of freedom from seizures at 1 year after surgery in that series were MRI-detectable unilateral hippocampal formation atrophy and concordant interictal epileptiform discharges (IEDs).

In patients with an MRI showing hippocampal atrophy and IEDs discordant with ictal onset, only 60% had a seizure-free outcome. In patients with normal MRI findings, surgical outcome was similar, regardless of whether IEDs were concordant with ictal onsets. More recently, Jeong et al studied 93 patients with mesial temporal lobe epilepsy (TLE) who had anterior temporal resections. On multivariate analysis, the only factors predictive of seizure-free outcome were age at surgery and the presence of hippocampal sclerosis.

Long-term outcome

The length of postsurgical follow-up is important in determining both seizure-free outcome and HRQL outcome. For example, we need to know if epilepsy surgery produces a long-term outcome that is better than the natural history of the disease. Many studies have variable follow-up ranging from only 6 months to 2 years. During the 1990s, a few long-term single center long-term outcome studies were published that include reports of 5-year outcome, but some of these studies do not distinguish outcome for the different types of resective surgeries.

Rougier et al (1992) reported seizure outcome in 100 patients with 66% seizure free at 1 year and 51% seizure free at 5 years. Berkovic and colleagues (1995) found that 50% of MTS patients, 69% of foreign tissue lesion patients, and only 21% of nonlesional patients were seizure free for 5 continuous years. Similarly, Sperling et al (1996) showed that seizure-free outcome at 2 years predicted long-term outcome. They found that 55% of seizure recurrences occurred within 6 months of surgery, and 93% occurred within 2 years after surgery. Five years after temporal lobectomy, 70% had a class 1 outcome, and 11% had a greater than 80% reduction in seizures.

Rausch et al (1995) reported 10-year outcome in 27 patients who underwent ATL who at 1 year were seizure free or had auras only were likely to remain seizure free. She found that seizure-free outcome at 10 years was approximately 56%. Interestingly, some patients who were initially not seizure free at 2 years became seizure free at 10 years ("running down phenomenon").

Spencer (1996) reported 2- to 10-year outcome in 226 epilepsy surgery patients. They divided the seizure-free outcome (%) into pathological subgroups: glioma (70%), developmental (58%), vascular (60%), and mesial temporal sclerosis (67%). In the Mayo study of 245 patients (Wass, 1996) treated with epilepsy surgery (all types) between 1972 and 1985, 41% were seizure free since surgery, and 58% were seizure free for 5 or more years. The problems with these older long-term outcome studies is that they do not reflect the current state of epilepsy surgery in that most patients were identified prior to the routine use of high resolution dedicated epilepsy protocol MRI, and a significant number required invasive monitoring.

More recent long-term outcome studies by Berkovic et al (2005), Wiebe et al (2005) meta-analysis, and the multicenter epilepsy surgery study group found that long-term seizure-free outcome was approximately 57%.

EXTRATEMPORAL NEOCORTICAL EPILEPSY

Section 4 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

In patients with extratemporal epilepsy and a well-circumscribed lesion, such as a neoplasm or a cavernous malformation, seizure-free outcome rates are in the range of 70-80%. Usually, seizure-free outcome is related to complete lesion resection. The location of a well-circumscribed lesion (ie, temporal, parietal) does not affect the probability of having a seizure-free outcome, unless functional constraints limit the extent of the resection. Data from the study by Sisodiya of the Montreal Neurologic Institute show that for patients with less well-circumscribed lesions, such as malformations of cortical development (MCDs), seizure-free outcome rate is approximately 47%. In a small series of 14 patients from the Mayo Clinic, more than 70% of patients with frontal lobe encephalomalacia became seizure free.

A recent study by Janszky et al assessed predictors of outcome in lesional frontal lobe epilepsy and found that a generalized spike-and-wave EEG pattern adversely affected outcome. Mosewich et al analyzed predictors of outcome in frontal lobe epilepsy and found that the presence of a lesion, the absence of febrile convulsions, and postsurgical seizure control at 1 year were associated with an excellent outcome. A recent study of occipital lobe epilepsy by Aykut-Bingol et al at Yale found that the type of lesion can predict outcome; 85% of patients with tumors had an excellent/good outcome, while only 45% of patients with developmental lesions had an excellent/good outcome. Within the group with developmental lesions, cortical dysplasia was associated with a better outcome than heterotopia and hamartomas.

Of patients without a visible MRI lesion, only 20-25% have a seizure-free outcome, with an additional 25% of patients having worthwhile improvement.

DUAL PATHOLOGY

Section 5 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

Levesque et al defined dual pathology as a temporal or extratemporal lesion with coexisting hippocampal atrophy on MRI. Li et al reported that hippocampal atrophy is present more frequently with certain types of lesions, such as MCDs, developmental tumors (ie, gangliogliomas, dysembryoplastic neuroepithelial tumors), and perinatal lesions (eg, porencephaly), than with cavernous angiomas and low-grade gliomas. In patients with gliomas or cavernous angiomas, hippocampal atrophy is present more frequently when the lesion is medial (ie, medial to the collateral sulcus) than when it is lateral. In patients with temporal lobe lesions and coexisting hippocampal atrophy, freedom from seizures is not obtained unless both the lesion and the atrophic hippocampus are included in the resection.

Li et al (1999) found that seizure freedom was attained in 73% of patients with a lesionectomy and a medial temporal resection (resection of hippocampus, amygdala, and parahippocampal gyrus), whereas seizure-free outcome was only 20% in patients with medial temporal resection alone and only 12.5% with lesionectomy alone.

In patients with nontumoral occipitotemporal epilepsy, Aykut-Bingol et al (1999) found that patients who only had a hippocampal resection did poorly, whereas most patients with a combined occipital and temporal resection and some patients with an occipital lobe resection had a favorable surgical outcome. Malformations of cortical developmental were the most common pathologic substrate in their study. In patients with an occipital lobe lesion with semiologic features and/or EEG features of medial temporal lobe propagation, a lesionectomy without hippocampectomy is reasonable. In some cases where noninvasive data are equivocal, invasive EEG is required to determine whether independent ictal onsets occur in the temporal and the occipital lobe. In patients with occipital lobe epilepsy and ipsilateral hippocampal atrophy, a combined resection is likely to yield a greater chance for a seizure-free outcome.

EPILEPSY SURGERY OUTCOME IN CHILDREN

Section 6 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

Temporal and extratemporal resections

Surgical outcome in children with focal resections is similar to that in adults, with seizure-free rates in the range of 75-80%. However, the pathologic substrate of surgically treated epilepsy is different in children than in adults. For example, hippocampal sclerosis, the most common pathologic substrate in medically intractable TLE of adulthood, usually does not result in refractory seizures until adolescence or early adulthood. MCD and low-grade tumors, on the other hand, are the most frequent causes of intractable epilepsy in childhood. As in adults, outcome after resection of MCDs is less favorable, with only 50% attaining freedom from seizures, than outcome after resection of well-circumscribed lesions such as low-grade gliomas and cavernous angiomas.

Both Wyllie et al and Mathern et al reported rates of seizure-free outcome after multilobar resection in children of approximately 52%. Thus, in children, the best outcome is observed in those with focal cortical temporal resections with a non-MCD pathologic substrate, and a less favorable outcome is observed in those with extratemporal unilobar or multilobar MCDs. This difference in outcome likely represents the diffuse nature of MCDs, which limits complete resection of the epileptogenic region.

Hemispherectomy/functional hemispherectomy

Usually, this procedure is reserved for infants and children with catastrophic epilepsy, developmental regression, and a unilateral useless hand. The Cleveland Clinic, Johns Hopkins Hospital, and Miami Children's Hospital report seizure-free outcome rates in the range of 53-67%. Overall, their seizure surgery outcomes were better in patients with non-MCD pathologies (ie, perinatal infarction, Sturge-Weber syndrome) than in those with MCD. In the large UCLA series, the overall rate of seizure-free outcome with hemispherectomy was 64% at 2 years after surgery. No differences were reported in 2-year outcomes between the group with cortical dysplasia group and the group without cortical dysplasia. However, in a follow-up interval of 2-5 years, 25% of patients with cortical dysplasia (hemispherectomy, multilobar and lobar cases) had recurrent seizures.

Corpus callosotomy

This form of surgical treatment is recommended for children and adults with symptomatic generalized epilepsies, such as Lennox-Gastaut syndrome, who have disabling atonic and/or tonic seizures. These children usually have clusters of tonic seizures, which result in sudden falls causing head injury. These seizures severely limit the daily activities of these developmentally disabled patients. Corpus callosotomy is a palliative procedure to limit or modify tonic/atonic seizures; it rarely makes patients seizure free. It can limit seizures in 70% of patients, with 30% having significant improvement. The seizures still occur as partial seizures, but they do not result in falls.

After corpus callosotomy, most patients have significant improvement in cognitive function, activities of daily living, and behavior. Outcome is better with a complete callosotomy than with an anterior two-thirds callosotomy; however, the risk of a disconnection syndrome is greater.

With the recent introduction of new drugs (eg, lamotrigine, topiramate, zonisamide) and the vagal nerve stimulator, the number of patients requiring corpus callosotomy has been reduced.

NEUROPSYCHOLOGICAL OUTCOME

Section 7 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

Memory outcome

Since the hippocampus is important in memory and learning, anterior temporal resections have a potential risk of producing a memory deficit. Bilateral injury to the hippocampi is known to produce long-lasting profound anterograde amnesia. Unilateral anterior temporal lobectomy (ATL) does not produce a severe loss of memory unless the contralateral hippocampus is unable to sustain memory. In this regard, the intracarotid amobarbital test is essential prior to surgery to evaluate the ability of the contralateral hippocampus to sustain memory after unilateral ATL.

Material-specific memory impairment may occur after ATL. Significant impairment of verbal memory is a potential complication of dominant ATL. Individuals with average or above average memory function prior to surgery are at greatest risk of postoperative memory decline. After right ATL, most patients have an overall improvement or no change in memory function. Certain studies suggest, however, that some patients who undergo right ATL with high preoperative memory scores may experience a modest decline in memory after surgery.

Language outcome

Dominant-hemisphere ATL has a selective risk of postoperative decline in visual confrontation naming. The standard ATL includes resection of the middle temporal gyrus (MTG) and the inferior temporal gyrus (ITG) to approximately 4.5 cm and the superior temporal gyrus (STG) to 2 cm. The classic studies of Ojemann et al showed that few language sites are observed in the anterior 5 cm of the MTG and ITG; however, language sites may be observed in the first 2 cm of the STG. Numerous studies have demonstrated that patients with a high preoperative score on the Boston Naming Test (BNT) and a later age of onset (> 10 y) are at greatest risk of a postoperative decline in naming. (See article Presurgical Evaluation of Medically Refractory Epilepsy for the definition of the different types of temporal resections.)

Many centers perform an anteromedial temporal type resection (ie, Spencer type), which, unlike standard ATL, spares the STG and involves a less-extensive lateral resection of the MTG and the ITG. A few centers perform intraoperative language mapping (IOLM) with tailored resection. However, recent studies have shown that language outcomes at 1 year in patients treated with anteromedial type resection are no different than the outcomes of patients who underwent tailored resection with IOLM. Patients with a late age of onset and high BNT scores should be counseled that they are likely to have a significant reduction in their postoperative naming ability after dominant ATL.

HEALTH-RELATED QUALITY OF LIFE

Section 8 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

Patients with epilepsy hope to have an improvement in their HRQL, employment, education, and social activities. Improvement in these domains may be more difficult to achieve the longer the epilepsy has remained uncontrolled. Vickrey et al from UCLA showed that the degree of seizure control strongly correlates with scores on the Epilepsy Surgery Inventory-55 (ESI-55), a self-reported measure of quality of life. In 1995, Vickrey et al studied quality-of-life outcomes in 248 patients who had a diagnostic evaluation for epilepsy surgery. They found that patients who underwent surgery scored higher on 5 of 11 scales at follow-up than patients who did not undergo surgery for epilepsy. Vickrey et al found an improvement in HRQL in 170 patients who were seizure free after surgery. Patients with residual auras had improved HRQL, but less so than those who were completely seizure free.

SUMMARY AND CONCLUSIONS

Section 9 of 10  

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

In patients with unilateral medial TLE or a well-circumscribed lesion and concordant interictal and ictal EEG data, seizure-free outcome rates range from 80-90%. In patients with MCDs and interictal/ictal EEG data that are discordant with the MRI lesion, rate of seizure-free outcome is still favorable but is reduced to 50%. In patients with nonlesional neocortical epilepsy, on the other hand, seizure-free outcome rate was only 20%, with an additional 25% having a reduction in seizure frequency of at least 80%.

The most common sequela of dominant ATL, postoperative decline in naming, is related to later age of onset of epilepsy and high preoperative BNT score. Patients with early age of onset and low preoperative BNT score are at low risk of a postoperative decline in naming ability.

The ultimate goal of epilepsy surgery is to improve quality of life and improve social and occupational function. In the future, randomized controlled multicenter studies should address whether early surgical intervention yields a better HRQL outcome than medical treatment. Knowing whether the gains achieved by early intervention are reduced the longer the epilepsy remains uncontrolled is also important. Furthermore, both seizure and HRQL outcomes need to be determined for the type of pathologic substrate and the location. For example, some pathologies are localized (eg, gliomas), others may be bilateral (eg, MTS), and some may be multilobar (eg, MCDs), with implications for seizure control and cognitive outcome.

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

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Outcome For Surgery For Temporal Lobe Epilepsy
• Extratemporal Neocortical Epilepsy
• Dual Pathology
• Epilepsy Surgery Outcome In Children
• Neuropsychological Outcome
• Health-related Quality Of Life
• Summary And Conclusions
• References

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Article Last Updated: Jul 18, 2006