1. Aetna considers temporal lobectomy, corpus callosotomy, and cerebral hemispherectomy medically necessary when all of the following selection criteria are met:
   
   
   1. Non-epileptic attacks such as cardiogenic syncope and psychogenic seizures have been ruled out.
   2. The diagnosis of epilepsy has been documented, and the epileptic seizure type and syndrome has been clearly defined. In general, appropriate candidates for epilepsy surgery are members who are incapacitated by their frequent seizures as well as the toxicity of antiepileptic drugs. The general characteristics of individuals for each type of surgical procedure for epilepsy are as follows:
      
      
      1. temporal lobectomy: members with complex partial seizures of temporal or extratemporal origin;
      2. corpus callosotomy: members with secondarily generalized seizures;
      3. cerebral hemispherectomy: members with unilateral multifocal epilepsy associated with infantile hemiplegia (especially in hemimegalencephaly and Sturge-Weber disease).
         
         
   3. There must have been an adequate period of drug therapy, namely, the correct drugs used in the correct dosage, carefully monitored for treatment effects and members' compliance.
   4. Seizures occur at a frequency that interferes with members' daily living and threatens their well being.
   5. Members' quality of life may significantly improve with surgery. 

   Aetna considers temporal lobectomy, corpus callosotomy, and cerebral hemispherectomy experimental and investigational when selection criteria are not met.

2. Aetna considers deep brain stimulation, or cerebellar stimulation for members with intractable seizures experimental and investigational because their effectiveness for this indication has not been established.
3. Aetna considers localized neocortical resections experimental and investigational for uncontrolled complex partial seizures because its effectiveness has not been established.
4. Aetna considers hippocampal electrical stimulation for the treatment of mesial temporal lobe epilepsy experimental and investigational because its effectiveness has not been established.

5. Aetna considers responsive cortical stimulation (e.g., the NeuroPace RNS System) experimental and investigational for the treatment of refractory epilepsy because its effectiveness has not been established.

Note: The Wada test (intra-carotid amobarbital procedure), part of the pre-surgical evaluation of members who may undergo temporal lobectomy, is considered a medically necessary service.

See also: CPB 191 - Vagus Nerve Stimulation, CPB 208 - Deep Brain Stimulation, CPB 425 - Ambulatory Electroencephalography, CPB 221 - Quantitative EEG (Brain Mapping), CPB 322 - Electroencephalographic (EEG) Video Monitoring and CPB 469 - Transcranial Magnetic Stimulation and Cranial Electrical Stimulation.

For patients who have intractable seizures despite adequate treatment with appropriate antiepileptic drugs, surgery is their last hope. The goal of epilepsy surgery is not only to decrease the frequency of seizures, but also to improve quality of life.

Temporal lobectomy has been found to be safe and effective for treating patients with complex partial seizures of temporal or extratemporal origin. Patients who have a single identifiable focus in a restricted cortical area that can be safely excised without producing additional disability can be considered as candidates for temporal lobectomy.

Corpus callosotomy has been found to be safe and effective for treating patients with partial and secondarily generalized seizures.

There is only limited evidence that cerebral hemispherectomy is effective in managing unilateral multifocal epilepsy associated with infantile hemiplegia (especially in hemimegalencephaly and Sturge-Weber disease). However, it is the last hope for these patients to eliminate/alleviate their disabling epileptic seizures, and to avoid adverse irreversible psychosocial consequences that may lead to lifelong disability.

Since the advent of deep brain stimulation (DBS) for the treatment of a variety of movement disorders, studies have been performed to ascertain whether this method can reduce seizure frequency. Evidence from experimental animal studies suggests the existence of a nigral control of the epilepsy system. The results of animal studies are promising, but work on humans is preliminary.

In a pilot study, Boon et al (2007) assessed the effectiveness of long-term DBS in medial temporal lobe (MTL) structures in patients with MTL epilepsy. A total of 12 consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. Ten of 12 patients underwent long-term MTL DBS; 2 of 12 patients underwent selective amygdalo-hippocampectomy. After mean follow-up of 31 months (range of 12 to 52 months), 1 of 10 stimulated patients was seizure free (more than 1 year), 1 of 10 patients had a  greater than 90 % reduction in seizure frequency; 5 of 10 patients had a seizure-frequency reduction of greater than equal to 50 %; 2 of 10 patients had a seizure-frequency reduction of 30 to 49 %; and 1 of 10 patients was a non-responder. None of the patients reported side effects. In 1 patient, MRI showed asymptomatic intra-cranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalo-hippocampectomy are seizure-free (more than 1 year), anti-epileptic drugs are unchanged, and no side effects have occurred. The authors concluded that this open pilot study demonstrated the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multi-center randomized controlled trials.

The Wada test (intra-carotid amytal procedure) is commonly used as a predictor of memory dysfunction following temporal lobectomy for intractable epilepsy. Asymmetry in memory scores can provide focus lateralizing information.

The Agency for Healthcare Research and Quality's technology assessment on the management of treatment-resistant epilepsy stated that the data are inconsistent across studies and do not allow for firm evidence-based conclusions as to the exact proportion of patients who will become seizure-free or who will not benefit from multiple subpial transection. In addition, too few studies were available to allow for an evidence-based evaluation of parietal or occipital lobe surgery (Chapell, et al., 2003). The American Academy of Neurology's practice parameter on temporal lobe and localized neocortical resections for epilepsy stated that there remains no Class I or II evidence regarding the safety and efficacy of localized neocortical resections. Further studies are needed to determine if neocortical seizures benefit from surgery (Engel, et al., 2003).

Candidates for epilepsy surgery and their family, if applicable, should receive detailed information regarding the specific surgical procedures and their possible benefits and side effects. Candidates for epilepsy surgery should not have co-existent progressive neurological disease or major psychological or medical disorder. Persons with progressive neurological diseases or major medical or psychological disorders are generally unsuitable candidates for epilepsy surgery because of the possibility that surgery could worsen the course of these other conditions.

In a pilot study (n = 5), Velasco and colleagues (2005) examined the safety and effectiveness of cerebellar stimulation (CS) on patients with medically refractory motor seizures, and especially generalized tonic-clonic seizures. Bilateral modified 4-contact plate electrodes were placed on the cerebellar superomedial surface through 2 sub-occipital burr holes. The implanted programmable, battery-operated stimulator was adjusted to 2.0 microC/cm2/phase with the stimulator case as the anode; at this level, no patient experienced the stimulation. Patients served as their own controls, comparing their seizure frequency in pre-implant basal phase (BL) of 3 months with the post-implant phases from 10 months to 4 years (average, 8 epochs of 3 months each). During the month after implantation, the stimulators were not activated. The patient and the evaluator were blinded as to the next 3-month epoch, as to whether stimulation was used. The patients were randomized into 2 groups: (i) 3 with the stimulator ON, and (ii) 2 with the stimulator OFF. After a 4-month post-implantation period, all patients had their stimulator ON until the end of the study and beyond. Medication was maintained unchanged throughout the study. EEG paroxysmal discharges also were measured. Generalized tonic-clonic seizures: in the initial 3-month double-blind phase, 2 patients were monitored with the stimulation OFF; no change was found in the mean seizure rate (patient 1, 100%, and patient 5, 85%; mean, 93%), whereas the 3 patients with the stimulation initially ON had a reduction of seizures to 33 % (patient 2, 21%; patient 3, 46%; patient 4, 32%) with a statistically significant difference between OFF and ON phase of p = 0.023. All 5 patients then were stimulated and monitored. At the end of the next 6 months of stimulation, the 5 patients had a mean seizure rate of 41% (14 -75%) of the BL. The second patient developed an infection in the implanted system, which had to be removed after 11 months of stimulation; the seizures were being reduced with stimulation to a mean of 1 per month from a mean of 4.7 per month (BL level) before stimulation. At the end of 24 months, 3 patients were monitored with stimulation, resulting in a further reduction of seizures to 24% (11 - 38%). Tonic seizures: 4 patients had these seizures, which at 24 months were reduced to 43% (10 - 76%). Follow-up surgery was necessary in 4 patients because of infection in 1 patient and lead/electrode displacement needing repositioning in 3 patients. The statistical analysis showed a significant reduction in tonic-clonic seizures (p < 0.001) and tonic seizures (p < 0.05). These investigators concluded that the superomedial cerebellar cortex appears to be a safe and effective target for electrical stimulation for decreasing motor seizures over the long term. The effect shows generalized tonic-clonic seizure reduction after 1 - 2 months and continues to decrease over the first 6 months and then maintains this effectiveness over the study period of 2 years and beyond. The results of this pilot study needed to be validated by additional trials with larger patient populations.

Electrical stimulation of the hippocampus has been proposed as a possible treatment for mesial temporal lobe epilepsy (MTLE). Tellez-Zenteno et al (2006) reported their findings of 4 patients with refractory MTLE (whose risk to memory contraindicated temporal lobe resection) who underwent implantation of a chronic stimulating depth electrode along the axis of the left hippocampus. These investigators used continuous, sub-threshold electrical stimulation (90 microsec, 190 Hz) and a double-blind, multiple cross-over, randomized controlled design, consisting of 3 treatment pairs, each containing two 1-month treatment periods. During each treatment pair, the stimulator was randomly turned ON 1 month and OFF 1 month. Outcomes were assessed at monthly intervals in a double-blind manner, using standardized instruments and accounting for a washout period. These researchers compared outcomes between ON, OFF, and baseline periods. Hippocampal stimulation produced a median reduction in seizures of 15 %. All but 1 patient's seizures improved; however, the results did not reach significance. Effects seemed to carry over into the OFF period, and an implantation effect cannot be ruled out. These researchers found no significant differences in other outcomes. There were no adverse effects. One patient has been treated for 4 years and continued to experience substantial long-term seizure improvement. The authors demonstrated important beneficial trends, some long-term benefits, and absence of adverse effects of hippocampal electrical stimulation in MTLE. However, the effect sizes observed were smaller than those reported in non-randomized, unblinded studies. They stated that large scale, double-blind randomized controlled studies are needed to ascertain the effectiveness of hippocampal electrical stimulation in patients with MTLE.

Velasco and colleagues (2007) evaluated the safety and effectiveness of electrical stimulation of the hippocampus in a long-term follow-up study, as well as its impact on memory performance in the treatment of patients with refractory MTLE. A total of 9 patients were included. All had refractory partial complex seizures, some with secondary generalizations. All patients had a 3-month-baseline-seizure count, after which they underwent bilateral hippocampal diagnostic electrode implantation to establish focus laterality and location -- 3 patients had bilateral; 6 had unilateral foci. Diagnostic electrodes were explanted and definitive Medtronic electrodes were implanted directed into the hippocampal foci. Position was confirmed with MRI and afterwards, the DBS system internalized. Patients attended a medical appointment every 3 months for seizure diary collection, DBS system checkup, and neuropsychological testing. Follow-up ranged from 18 months to 7 years. Patients were divided in 2 groups: (i) 5 had normal MRIs and seizure reduction of greater than 95 %, and (ii) 4 had hippocampal sclerosis and seizure reduction of 50 to 70 %. No patient had neuropsychological deterioration, nor did any patient show side effects. Three patients were explanted after 2 years due to skin erosion in the trajectory of the system. The authors concluded that electrical stimulation of the hippocampus provides a non-lesional method that improves seizure outcome without memory deterioration in patients with hippocampal epileptic foci. This is a small study; its findings need to be validated by studies with larger patient populations.

Sun and associates (2008) stated that with the success of DBS for treatment of movement disorders, brain stimulation has received renewed attention as a potential treatment option for epilepsy. Responsive stimulation aims to suppress epileptiform activity by delivering stimulation directly in response to electrographic activity. Animal and human data support the concept that responsive stimulation can abort epileptiform activity, and this modality may be a safe and effective treatment option for epilepsy. Responsive stimulation has the advantage of specificity. In contrast to the typically systemic administration of pharmacotherapy, with the concomitant possibility of side effects, electrical stimulation can be targeted to the specific brain regions involved in the seizure. In addition, responsive stimulation provides temporal specificity. Treatment is provided as needed, potentially reducing the likelihood of functional disruption or habituation due to continuous treatment. The authors reviewed current animal and human research in responsive brain stimulation for epilepsy and discussed the NeuroPace RNS System, an investigational implantable responsive neurostimulator system that is being evaluated in a multi-center, randomized, double-blinded trial to assess the safety and efficacy of responsive stimulation for the treatment of medically refractory epilepsy.