Epilepsy surgery assessment and testing Flashcards
Refractory (Drug Resistant, Intractable, Pharmacoresistant) Epilepsy
The latest definition by the international league against epilepsy (ILAE) task force defines refractory epilepsy as failure of “adequate” trials of two antiseizure medications (ASMs) either as monotherapy or as combination (poly-) therapy, to control seizures [1]. In order to meet this cri- terion, it is critical to make sure that the ASMs have been given enough chance (“adequate trial”)—i.e., they must have been used at the maximum tolerated dose (with no severe side effects)—and given enough time (determine sei- zure reduction after a follow-up period 3 times the longest interseizure interval, or one year, whichever longer). Therefore, with proper man- agement, in most cases the diagnosis of refrac- tory epilepsy should be possible to make within 1–2 years of the start of the seizures.
Treatment Options for Refractory Partial Epilepsy
Besides trying different combinations of ASMs, a variety of treatment options are available, including established methods of surgical resec- tion of the seizure focus, or surgical “non-resection” options such as vagus nerve stimulation (VNS), responsive neurostimulation (RNS), or multiple subpial transections (MST). Currently there are also several investigational surgical treatments available such as deep brain stimulation (DBS, which has been approved as a treatment in Europe), transcranial magnetic stimulation (TMS), trigeminal nerve stimulation (TGNS), external VNS, or transcranial direct current stimulation (tDCS).
In particular circumstances, other non-surgical methods, e.g., ketogenic diet in young children, can be of therapeutic value. Currently, research for newer ASMs as well as novel potential therapies such as gene therapy, cell transplanta- tion, or vaccination is underway.
Presurgical evaluation summary
The purpose of presurgical evaluation is to char- acterize the seizure type and to lateralize and localize the seizure onset focus in patients with refractory partial epilepsy. Therefore, patients should be admitted to a properly equipped epi- lepsy monitoring unit (EMU) for continuous video-EEG monitoring. The ASMs are usually tapered down in order to record electrographic and clinical seizures for the above purposes. Patients also need appropriate neuroimaging studies including high-resolution epilepsy proto- col MRI and other available imaging technologies as indicted or available such as MR spectroscopy (MRS), positron emission tomography (PET), single-photon emission computed tomography (SPECT), or magneto-encephalography (MEG).
In case the scalp recording is of limited value, patients who are considered potential candidates for surgical treatment may need invasive recordings using strips, grids, or depth electrodes and possibly cortical mapping before an appro- priate surgical procedure could be planned. After lateralization and localization of the seizure onset focus, potential surgical candidates should undergo a series of tests for further evaluation to define their final candidacy for an appropriate surgical treatment including neuropsychological testing and functional MRI or intracarotid amo- barbital procedure (IAP, Wada test)
Neuropsychology
The main questions that are addressed by a neu- ropsychological test include determining parts of the brain that are impaired. In particular, higher cognitive functions such as verbal and visual memory and language are studied. The test also helps establish a baseline for future comparison. This helps predict potential postsurgical deficits. Studies have shown that the best predictor of postoperative adequacy is the preoperative cog- nitive and psychosocial status; i.e., the lower the preoperative cognitive and psychosocial status, the lower the risk for further decline [2, 3].
Intracarotid Amobarbital Procedure (Wada Test)
This test “imitates” the prospective temporal lobectomy by temporarily inhibiting unilateral brain functions using a drug. Therefore, it helps lateralizing language dominance and memory function. The Wada test evaluates memory function of each temporal lobe separately to determine whether the nonepileptic side would be capable of handling memory function by itself after the affected temporal lobe is surgically removed. The test also can assist with seizure onset side since there is typically concordance between the seizure onset side and poor memory function on that side (upon contralateral injection).
Epilepsy surgery - efficacy and safety RCTs
Randomized, controlled trials (RCT) to assess the efficacy and safety of epilepsy surgery were missing till 2001. In the first such study [4], 80 patients with temporal lobe epilepsy (TLE) were randomly assigned to surgery (n = 40) or treat- ment with ASMs for one year (n = 40). The primary outcome was seizure freedom and sec- ondary outcome included seizure frequency and severity, quality of life (QOL), disability, and death.
At 1 year, the cumulative proportion of patients who were seizure free was 58% in the surgical group versus 8% in the medical group (P < 0.001). Patients in the surgical group had fewer complex-partial seizures (CPS) and sig- nificantly better quality of life (P < 0.001 for both comparisons) than the patients in the med- ical group. Four patients (10%) had adverse effects of surgery (mainly the expected mild language and memory-related problems such as word finding and short-term memory difficulties) while one patient in the medical group died. This study confirmed that in TLE, surgery is superior to prolonged medical therapy. This RCT also showed that randomized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects.
Early Randomized Surgical Epilepsy Trial (ERSET)
It has been well established that years of active epilepsy predict cognitive impairment in children and adolescents [5, 6]. Therefore, in order to investigate the effects of early surgery, i.e., whether it would be superior to continued med- ical management, Engel et al., conducted a multicenter, parallel-group RCT soon after the failure of 2 ASM trials in patients with temporal lobe epilepsy [7]. Thirty-eight patients (18 M/20 F; age 12 years) with MTS and refractory MTLE who were within 2 consecutive years of adequate trials of 2 ASMs were randomized (1) continued ASM (n = 23), or (2) anterior mesial temporal lobectomy (AMTR) plus ASM treatment (n = 15) and were followed for two years. The primary outcome was seizure freedom during the second year of follow-up, and the secondary outcome was health-related quality of life (QOL), cognitive function, and social adaptation.
Seizure freedom during the second year of follow-up was reported in 11 of 15 patients in the surgical group versus none of the 23 in the medical group (P < 0.001). Also, improvement of QOL was higher in the surgical group (P = 0.01). Memory decline occurred in 4 patients (36%) after surgery. Adverse events included one stroke in a surgical case versus 3 cases of status epilepticus in the medical group. It was concluded that resective surgery plus ASM in patients with new refractory MTLE results in lower probability of seizures during second year of follow-up than continued ASM treatment alone.
Epilepsy surgical methods
There are different surgical methods depending on the patient and seizure type and other char- acteristics including:
Temporal lobe surgery
Lobectomy
Resection of the epileptogenic zone Lesionectomy
Corpus Callosotomy Hemispherectomy
Multiple subpial transections (MST)
Types of temporal lobectomies
There are different methods to remove the seizure focus in the temporal lobe. Anterior temporal lobectomy is the classic and most commonly used type of surgery, but it may be done using different approaches including:
– Standard (en bloc) anterior temporal lobec- tomy (ATL) including 3–6 cm of anterior temporal neocortex and 1–3 cm of mesial structures (amygdala and hippocampus)
– Modified (Yale group) and limited neocorti- cal resection (3.5 cm from temporal pole) sparing superior temporal gyrus, to address language deficits
– Selective amygdalohippocampectomy
– Stereotactic radiosurgery [8, 9]
Selective Amygdalohippocampectomy (SAH)
This method was introduced by Niemeyer in 1958 in an attempt to preserve the lateral tem- poral cortex out of concern for language deficits. The technique includes accessing temporal horn to selectively resecting mesial temporal struc- tures through a small incision in the middle temporal gyrus while preserving the neocortical area. Other approaches to selective amygdalo- hippocampectomy include:
– Transsylvian approach [10, 11].
– Subtemporal approach [12].
– Other variants of the transcortical approach
[13].
Long-term outcomes following surgery - MTLE, MTS
Temporal lobectomy provides continued long-term seizure control but risk of seizure recurrence >= 2 years after surgery is present. In one report, 50 consecutive post-temporal lobec- tomy patients with MTS (mean follow-up 5.8 years, range 2–9.2) seizure-free rates were 82% at 12 months, 76% at 24 months, and 64% at 63 months [14]. Complete, or better, seizure outcome was associated with significantly better long-term QOL, and risk factor for seizure recurrence was the reduction in ASM intake—or absorption—in 5 of 17 patients (29%), including 3 of 5 with a first seizure recurrence within 24 months.
Outcomes after standard ATL
In another study, 116 patients with MTS, MTLE, and post-anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) were studied (follow-up period: 6.7 years) [15]. Complete seizure freedom was seen in 103 patients (89%) and Engel Class I or II outcome in 109 patients (94%). The highest concordance (i.e., test consistent with the side of eventual surgery) was seen with video-EEG (100%), PET (100%), MRI (99.0%), and Wada test (90.4%). The lowest concordance was seen with SPECT (84.6%) and neuropsychological testing (82.5%). A strong Wada memory lateralization appearedto be the predictor of excellent long-term seizure control, while less disparity in the memory score between the sides was the predictor of persistent seizures.
Temporal Lobectomy—Inferior Temporal Approach
Inferior temporal gyrus approach to mesial tem- poral lobe resection is safe and effective with low morbidity and mortality. One study reviewed 483 patients with AMTL resection via inferior tem- poral gyrus approach for TLE [16]. Thirteen complications (2.7%) (3 months post-op) were reported including eight delayed SDH (1.6%), two superficial wound infections (0.4%), one delayed ICH (0.2%), one small lacunar stroke (0.2%), and one transient frontalis nerve palsy (0.2%). There were no deaths or severe neuro- logical impairments. Complications were more common among older patients.
Selective Amygdalohippocampectomy
SAH in TLE patients with MTS results in seizure-free outcomes comparable to procedures with more extensive temporal neocortical resec- tions [17]. Although this method was introduced to minimize the neurocognitive side effects of temporal lobectomy, interestingly, at this point there is more controversy regarding postopera- tive neuropsychological outcomes, rather than seizure-free outcome, when compared to stan- dard ATL. Some studies have suggested that SAH results in better cognitive function com- pared to ATL [10], while others have shown no evidence of a clear neurocognitive benefit and in fact SAH might cause significant verbal memory deficits in dominant temporal lobe resection [18, 19].
In another study, 76 adult patients with SAH for MTLE via the trans-middle temporal gyrus approach reported 92% Engel Class I or II with very low surgical morbidity and no mortality. Postoperative neuropsychological testing showed verbal memory decline in the left SAH group, but no memory decline in the right SAH group was seen while some even showed improvement [20].
Neurocognitive Deficits and Risk Factors Following ATL
Cognitive impairment is very common in epilepsy patients and may be negatively or pos- itively affected by surgery. Larger temporal lobe resections are associated with better seizure control, but at the same time resecting more functional tissues carries higher risk of cognitive outcome [21].
Comparison of the changes in cognitive per- formance in relation to the extent of resection of mesial and lateral temporal structures (1–2 cm and >2 cm for mesial, and 4 or 4 cm for neocortical) in 47 right-handed patients with left temporal lobectomy for MTLE showed no dif- ference in cognitive outcome between the groups. However, there was a negative correla- tion with patient age at seizure onset [22].