The current practice under which patients with refractory epilepsy are surgically treated is based mainly on the identification of specific cortical areas, mainly the epileptogenic zone, which is believed to be responsible for generation of seizures. A better understanding of the whole epileptic network and its components and properties is required before more effective and less invasive therapies can be developed.
Despite significant underutilization of surgical treatment for drug-resistant epilepsy, no studies have quantified patient desire for surgery within a representative population.
An online survey was administered to all clients connected with a core epilepsy community access center. It obtained information about demographics, clinical characteristics, knowledge of epilepsy surgery, and interest in receiving surgery before and after receiving risk/benefit information about it.
Of 118 potential respondents, 48 (41%) completed the questionnaire, of which 67% had failed more than two AEDs and 78% experienced seizures in the past year. Eleven ( 26%) were uninterested in receiving surgery at baseline, and this decreased significantly to 7 (16%) following knowledge translation regarding the benefits (p = 0.001). Significance was lost with subsequent complication rate information despite fewer respondents still being uninterested compared to baseline (20% vs. 26%). Having experienced seizures within the past month was correlated with being interested in or undecided regarding surgery at baseline and following all steps of knowledge translation. Subjects had conservative views regarding the benefits of surgery and largely overestimated the risks.
A significant portion of those with active epilepsy in the community do not desire surgical treatment. Passive knowledge translation regarding the risks and benefits enhanced optimistic attitudes and mobilized interest within a subset of participants. Preexisting views regarding the risks of surgery were exaggerated, and analysis suggests that these views can be modified with information about the benefits of surgery. However, exaggerated risk perceptions return following crude descriptions of the risks, underlying the importance of sensitive counseling from primary care physicians 1).
In Epilepsy surgery where resective surgery is not indicated, deep brain stimulation (DBS) may be an effective alternative. The majority of available literature targets the thalamic nuclei (anterior; centromedian), subthalamic nucleus, hippocampus, and cerebellum.
Data show DBS may be a safe and effective treatment option for refractory epilepsy 2).
Surgery is a safe and effective option for some patients, however the opportunity exists to develop less invasive and more effective surgical options. To this end, multiple minimally invasive, image-guided techniques have been applied to the treatment of epilepsy. These techniques can be divided into thermoablative and disconnective techniques. Each has been described in the treatment of epilepsy only in small case series. Larger series and longer follow up periods will determine each option's place in the surgical armamentarium for the treatment of refractory epilepsy but early results are promising 3).
The goal is to eliminate seizures or significantly reduce seizure burden.
In most state-of-the-art epilepsy units, resective epilepsy surgery is currently the standard treatment for intractable epilepsy. Generally, the success rate, defined as a seizure-free status or Engel class I, is between 62% and 71%, as compared to 14% in non-operated cases 4) 5).
Generally, surgery is considered in patients whose seizures cannot be controlled by adequate trials of two different medications. Epilepsy surgery has been performed for more than a century, but its use dramatically increased in the 1980s and '90s, reflecting its efficacy in selected patients.
Patients with comorbid psychosis and temporal lobe drug-resistant epilepsy may benefit from epilepsy surgery under close psychiatric supervision 6).
Epilepsy surgery is an effective and safe therapeutic modality in childhood. In children with extratemporal epilepsy, more careful interpretation of clinical and investigative data is needed to achieve favorable seizure outcome 7).
Several palliative neuromodulation treatment modalities are currently available for adjunctive use in the treatment of medically intractable epilepsy. Over the past decades, a variety of different central and peripheral nervous system sites have been identified, clinically and experimentally, as potential targets for chronic, nonresponsive therapeutic neurostimulation. Currently, the main modalities in clinical use, from most invasive to least invasive, are anterior thalamus deep brain stimulation, vagus nerve stimulation, and trigeminal nerve stimulation. Significant reductions in seizure frequency have been demonstrated in clinical trials using each of these neuromodulation therapies 8).
Engel J Jr, Van Ness PC, Rasmussen T, Ojemann LM: Outcome with respect to epileptic seizures, in Engle J Jr (ed): Surgical Treatment of the Epilepsies, ed 2. New York: Raven Press, 1993, pp 609–621
Giulioni et al. conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. They compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis.
Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (p < 0.001). A statistically significant association was observed between FCD diagnosis and the following variables: tailored surgery (p < 0.001), temporal resection (p = 0.001), and surgical center (p = 0.012).
The nationwide LEATs study gives important insights on factors predicting seizure outcome in refractory epilepsy and determining variability in FCD detection. Timely surgery, regardless of pharmacoresistance and oriented to optimize epileptologic, neuropsychological, and oncologic outcomes should be warranted 9).
Three hundred fifty-two patients underwent surgical resection and there was one death. Forty-two percent had invasive monitoring. Thirty patients (9%) had microscopic infarct. Univariable analyses showed that microscopic infarct was higher among patients with invasive monitoring relative to no invasive monitoring (20% vs. 0.5%, respectively, p < 0.001). Eighteen patients (5%) had macroscopic infarct on CT or MRI. Univariable analysis showed no significant difference in macroscopic infarct between invasive monitoring and no invasive monitoring (8% vs. 3%, respectively, p = 0.085). One patient with microscopic infarct had transient right hemiparesis, and two with both macroscopic and microscopic infarct had unexpected persistent neurologic deficits. Thirty-two major complications (9.1%) were reported, with no difference in major complications between invasive monitoring and no invasive monitoring (10% vs. 7%, p = 0.446). In the multivariable analysis, invasive monitoring increased the odds of microscopic infarct (odds ratio [OR] 15.87, p = 0.009), but not macroscopic infarct (OR 2.6, p = 0.173) or major complications (OR 1.4, p = 0.500), after adjusting for age at surgery, sex, age at seizure onset, operative type, and operative location.
Microscopic infarct was associated with invasive monitoring, and none of the patients had permanent neurologic deficits. Macroscopic infarct was not associated with invasive monitoring, and two patients with macroscopic infarct had persistent neurologic deficits 10).
A total of 3060 patients were presurgically studied, and resective surgery was performed in 66.8% (n=2044) of them: medial temporal sclerosis (MTS): n=675, 33.0%; benign tumour (BT): n=408, 20.0%; and focal cortical dysplasia (FCD): n=284, 13.9%. Of these, 1929 patients (94.4%) had a follow-up of 2 years, and 50.8% were completely seizure free (Engel IA). Seizure freedom rate slightly improved over time. Presurgical evaluations continuously increased, whereas surgical interventions did not. Numbers for MTS, BT and temporal lobe resections decreased since 2009. The number of non-lesional patients and the need for intracranial recordings increased. More evaluated patients did not undergo surgery (more than 50% in 2010-2013) because patients were not suitable (mainly due to missing hypothesis: 4.5% in 1990-1993 up to 21.1% in 2010-2013, total 13.4%) or declined from surgery (maximum 21.0% in 2010-2013, total 10.9%). One potential reason may be that increasingly detailed information on chances and risks were given over time.
The increasing volume of the presurgical programme largely compensates for decreasing numbers of surgically remediable syndromes and a growing rate of informed choice against epilepsy surgery. Although comprehensive diagnostic evaluation is offered to a larger group of epilepsy patients, surgical numbers remain stable 11).
Despite its potential to offer seizure freedom, resective epilepsy surgery (RES) is seldom performed in patients 60 years of age or older. Demonstrating successful outcomes including an improved quality of life may raise awareness about the advantages of referring this underrepresented population for specialized evaluation. Accordingly, Dewar et al investigated outcomes and life fulfillment in patients with an age ≥ 60 years who had undergone RES.
All patients who, at the age of 60 years or older, had undergone RES for medically refractory focal onset seizures at the authors' center were evaluated. A modified Liverpool Life Fulfillment (LLF) tool was administered postoperatively (maximum score 32). Seizure outcomes were classified according to the Engel classification system.
Twelve patients underwent RES. The majority of patients (9 [75%] of 12) had at least 1 medical comorbidity in addition to seizures. The mean follow-up was 3.1 ± 2.1 years. At the time of the final follow-up, 11 (91.7%) of 12 patients were documented as having a good postsurgical outcome (Engel Class I-II). Half (6 of 12 patients) were completely seizure free (Engel Class IA). Liverpool Life Fulfillment (LLF) data were available for 11 patients. Following surgery, the mean LLF score was 26.7 ± 6. Eight patients (72.7%) noted excellent satisfaction with their RES, with 5 (45.5%) noting postoperative improvements in overall health. CONCLUSIONS Resective epilepsy surgery is safe and effective in patients with an age ≥ 60 years. Over 90% had a good surgical outcome, with 50% becoming completely seizure free despite 1 or more medical comorbidities in the majority. The study data indicated that an advancing age should not negatively influence consideration for RES 12).
Loddenkemper et al identified 50 infants among 251 consecutive pediatric patients (<18 years old) undergoing epilepsy surgery. Charts were reviewed for clinical data and neurodevelopmental testing with the Bayley Scales of Infant Development. A developmental quotient was calculated to compare scores of children at different ages.
Complete data were available on 24 of 50 infants. Surgeries included 14 hemispherectomies and 10 focal resections. Seventeen patients became seizure free; 5 patients had >90% seizure reduction, 1 had >50% seizure reduction, and 1 had no change. The developmental quotient indicated modest postoperative improvement of mental age. The preoperative and postoperative development quotients correlated well. Younger infants had a higher increase in developmental quotient after surgery. Patients with epileptic spasms were younger and had a lower developmental quotient at presentation, but increase in developmental quotient was higher in this subgroup.
After surgery, seizure frequency and developmental quotient improved. Developmental status before surgery predicted developmental function after surgery. Patients who were operated on at younger age and with epileptic spasms showed the largest increase in developmental quotient after surgery 13).