The stereotactic approach for mapping epileptic networks


J Neurosurg 121:1239–1246, 2014

Stereoelectroencephalography (SEEG) is a methodology that permits accurate 3D in vivo electroclinical recordings of epileptiform activity. Among other general indications for invasive intracranial electroencephalography (EEG) monitoring, its advantages include access to deep cortical structures, its ability to localize the epileptogenic zone when subdural grids have failed to do so, and its utility in the context of possible multifocal seizure onsets with the need for bihemispheric explorations. In this context, the authors present a brief historical overview of the technique and report on their experience with 2 SEEG techniques (conventional Leksell frame-based stereotaxy and frameless stereotaxy under robotic guidance) for the purpose of invasively monitoring difficult-to-localize refractory focal epilepsy.

Methods. Over a period of 4 years, the authors prospectively identified 200 patients with refractory epilepsy who collectively underwent 2663 tailored SEEG electrode implantations for invasive intracranial EEG monitoring and extraoperative mapping. The first 122 patients underwent conventional Leksell frame-based SEEG electrode placement; the remaining 78 patients underwent frameless stereotaxy under robotic guidance, following acquisition of a stereotactic ROSA robotic device at the authors’ institution. Electrodes were placed according to a preimplantation hypothesis of the presumed epileptogenic zone, based on a standardized preoperative workup including video-EEG monitoring, MRI, PET, ictal SPECT, and neuropsychological assessment. Demographic features, seizure semiology, number and location of implanted SEEG electrodes, and location of the epileptogenic zone were recorded and analyzed for all patients. For patients undergoing subsequent craniotomy for resection, the type of resection and procedure-related complications were prospectively recorded. These results were analyzed and correlated with pathological diagnosis and postoperative seizure outcomes.

Results. The epileptogenic zone was confirmed by SEEG in 154 patients (77%), of which 134 (87%) underwent subsequent craniotomy for epileptogenic zone resection. Within this cohort, 90 patients had a minimum follow-up of at least 12 months; therein, 61 patients (67.8%) remained seizure free, with an average follow-up period of 2.4 years. The most common pathological diagnosis was focal cortical dysplasia Type I (55 patients, 61.1%). Per electrode, the surgical complications included wound infection (0.08%), hemorrhagic complications (0.08%), and a transient neurological deficit (0.04%) in a total of 5 patients (2.5%). One patient (0.5%) ultimately died due to intracerebral hematoma directly ensuing from SEEG electrode placement.

Conclusions. Based on these results, SEEG methodology is safe, reliable, and effective. It is associated with minimal morbidity and mortality, and serves as a practical, minimally invasive approach to extraoperative localization of the epileptogenic zone in patients with refractory epilepsy.

Anticonvulsant prophylaxis for brain tumor surgery

Seizures frequency

J Neurosurg 121:1139–1147, 2014

Patients who undergo craniotomy for brain tumor resection are prone to experiencing seizures, which can have debilitating medical, neurological, and psychosocial effects.

A controversial issue in neurosurgery is the common practice of administering perioperative anticonvulsant prophylaxis to these patients despite a paucity of supporting data in the literature. The foreseeable benefits of this strategy must be balanced against potential adverse effects and interactions with critical medications such as chemotherapeutic agents and corticosteroids. Multiple disparate metaanalyses have been published on this topic but have not been applied into clinical practice, and, instead, personal preference frequently determines practice patterns in this area of management.

Therefore, to select the current best available evidence to guide clinical decision making, the literature was evaluated to identify meta-analyses that investigated the efficacy and/or safety of anticonvulsant prophylaxis in this patient population. Six meta-analyses published between 1996 and 2011 were included in the present study.

The Quality of Reporting of Meta-analyses and Oxman-Guyatt methodological quality assessment tools were used to score these meta-analyses, and the Jadad decision algorithm was applied to determine the highest-quality meta-analysis. According to this analysis, 2 metaanalyses were deemed to be the current best available evidence, both of which conclude that prophylactic treatment does not improve seizure control in these patients.

Therefore, this management strategy should not be routinely used.

Tailored Unilobar and Multilobar Resections for Orbitofrontal-Plus Epilepsy

Tailored Unilobar and Multilobar Resections for Orbitofrontal-Plus Epilepsy

Neurosurgery 75:388–397, 2014

Surgery for frontal lobe epilepsy often has poor results, likely because of incomplete resection of the epileptogenic zone.

OBJECTIVE: To present our experience with a series of patients manifesting 2 different anatomo-electro-clinical patterns of refractory orbitofrontal epilepsy, necessitating different surgical approaches for resection in each group.

METHODS: Eleven patients with refractory epilepsy involving the orbitofrontal region were consecutively identified over 3 years in whom stereoelectroencephalography identified the epileptogenic zone. All patients underwent preoperative evaluation, stereoelectroencephalography, and postoperative magnetic resonance imaging. Demographic features, seizure semiology, imaging characteristics, location of the epileptogenic zone, surgical resection site, and pathological diagnosis were analyzed. Surgical outcome was correlated with type of resection.

RESULTS: Five patients exhibited orbitofrontal plus frontal epilepsy with the epileptogenic zone consistently residing in the frontal lobe; after surgery, 4 patients were free of disabling seizures (Engel I) and 1 patient improved (Engel II). The remaining 6 patients had multilobar epilepsy with the epileptogenic zone located in the orbitofrontal cortex associated with the temporal polar region (orbitofrontal plus temporal polar epilepsy). After surgery, all 6 patients were free of disabling seizures (Engel I). Pathology confirmed focal cortical dysplasia in all patients. We report no complications or mortalities in this series.

CONCLUSION: Our findings highlight the importance of differentiating between orbitofrontal plus frontal and orbitofrontal plus temporal polar epilepsy in patients afflicted with seizures involving the orbitofrontal cortex. For identified cases of orbitofrontal plus temporal polar epilepsy, a multilobar resection including the temporal pole may lead to improved postoperative outcomes with minimal morbidity or mortality.

Robot-Assisted Stereotactic Laser Ablation in Medically Intractable Epilepsy


Operative Neurosurgery 10:167–173, 2014

Stereotactic laser ablation offers an advantage over open surgical procedures for treatment of epileptic foci, tumors, and other brain pathology. Robotassisted stereotactic laser ablation could offer an accurate, efficient, minimally invasive, and safe method for placement of an ablation catheter into the target.

OBJECTIVE: To determine the feasibility of placement of a stereotactic laser ablation catheter into a brain lesion with the use of robotic assistance, via a safe, accurate, efficient, and minimally invasive manner.

METHODS: A laser ablation catheter (Visualase, Inc) was placed by using robotic guidance (ROSA, Medtech Surgical, Inc) under general anesthesia into a localized epileptogenic periventricular heterotopic lesion in a 19-year-old woman with 10-year refractory focal seizure history. The laser applicator (1.65 mm diameter) position was confirmed by using magnetic resonance imaging (MRI). Ablation using the Visualase system was performed under multiplanar imaging with real-time thermal imaging and treatment estimates in each plane. A postablation MRI sequence (T1 postgadolinium contrast injection) was used to immediately confirm the ablation. RESULTS: MRI showed accurate skin entry point and trajectory, with the applicator advanced to the lesion’s distal boundary. Ablation was accomplished in less than 3 minutes of heating. The overall procedure, from time of skin incision to end of last ablation, was approximately 90 minutes. After confirmation of proper lesioning by using a T1 contrast-enhanced MRI, the applicator was removed, and the incision was closed using a single stitch. No hemorrhage or other untoward complication was visualized. The patient awoke without any complication, was observed overnight after admitting to a regular floor bed, and was discharged to home the following day.

CONCLUSION: This technique, using a combination of Visualase laser ablation, ROSA robot, and intraoperative MRI, facilitated a safe, efficacious, efficient, and minimally invasive approach that could be used for placement of 1 or multiple electrodes in the future.

Fifty Consecutive Hemispherectomies

50 Hemispherectomies

Neurosurgery 74:182–195, 2014

Techniques for achieving hemispheric disconnection in patients with epilepsy continue to evolve.

OBJECTIVE: To review the outcomes of the first 50 hemispherectomy surgeries performed by a single surgeon with an emphasis on outcomes, complications, and how these results led to changes in practice.

METHODS: The first 50 hemispherectomy cases performed by the lead author were identified from a prospectively maintained database. Patient demographics, surgical details, clinical outcomes, and complications were critically reviewed.

RESULTS: From 2004 to 2012, 50 patients underwent hemispherectomy surgery (mean follow-up time, 3.5 years). Modified lateral hemispherotomy became the preferred technique and was performed on 44 patients. Forty patients (80%) achieved complete seizure freedom (Engel I). Presurgical and postsurgical neuropsychological evaluations demonstrated cognitive stability. Two cases were performed for palliation only. Previous hemispherectomy surgery was associated with worsened seizure outcome (2 of 6 seizure free; P .005). The use of Avitene was associated with a higher incidence of postoperative hydrocephalus (56% vs 18%; P = .03). In modified lateral hemispherotomy patients without the use of Avitene, the incidence of hydrocephalus was 13%. Complications included infection (n = 3), incomplete disconnection requiring reoperation (n = 1), reversible ischemic neurological deficit (n = 1), and craniosynostosis (n = 1). There were no (unanticipated) permanent neurological deficits or deaths. Minor technique modifications were made in response to specific complications.

CONCLUSION: The modified lateral hemispherotomy is effective and safe for both initial and revision hemispherectomy surgery. Avitene use appears to result in a greater incidence of postoperative hydrocephalus.

Surgery for low-grade glioma infiltrating the central cerebral region

Surgery for low-grade glioma infiltrating the central cerebral region

J Neurosurg 119:318–323, 2013

A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient’s functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life.

Methods. Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution.

Results. For the central cohort, the median extent of resection was 92% (range 80%–97%), and for the frontal cohort, the median extent of resection was 93% (range 83%–98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001).

Conclusions. Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.

Risk factor analysis of the development of new neurological deficits following supplementary motor area resection

Supplementary motor area

J Neurosurg 119:7–14, 2013

Supplementary motor area (SMA) resection often induces postoperative contralateral hemiparesis or speech disturbance. This study was performed to assess the neurological impairments that often follow SMA resection and to assess the risk factors associated with these postoperative deficits.

Methods. The records for patients who had undergone SMA resection for pharmacologically intractable epilepsy between 1994 and 2010 were gleaned from an epilepsy surgery database and retrospectively reviewed in this study.

Results. Forty-three patients with pharmacologically intractable epilepsy underwent SMA resection with intraoperative cortical stimulation and mapping while under awake anesthesia. The mean patient age was 31.7 years (range 15–63 years), and the mean duration and frequency of seizures were 10.4 years (range 0.1–30 years) and 14.6 per month (range 0.1–150 per month), respectively. Pathological examination of the brain revealed cortical dysplasia in 18 patients (41.9%), tumors in 16 patients (37.2%), and other lesions in 9 patients (20.9%). The mean duration of the follow-up period was 84.0 months (range 24–169 months). After SMA resection, 23 patients (53.5%) experienced neurological deficits. Three patients (7.0%) experienced permanent deficits, and 20 (46.5%) experienced symptoms that were transient. All permanent deficits involved contralateral weakness, whereas the transient symptoms patients experienced were varied, including contralateral weaknesses in 15, apraxia in 1, sensory disturbances in 1, and dysphasia in 6. Thirteen patients recovered completely within 1 month. Univariate analysis revealed that resection of the SMA proper, a shorter lifetime seizure history (< 10 years), and resection of the cingulate gyrus in addition to the SMA were associated with the development of neurological deficits (p = 0.078, 0.069, and 0.023, respectively). Cingulate gyrus resection was the only risk factor identified on multivariate analysis (p = 0.027, OR 6.530, 95% CI 1.234–34.562).

Conclusions. Resection of the cingulate gyrus in addition to the SMA was significantly associated with the development of postoperative neurological impairment.

Tissue localization during resective epilepsy surgery

Tissue localization

Neurosurg Focus 34 (6):E8, 2013

Imaging-guided surgery (IGS) systems are widely used in neurosurgical practice. During epilepsy surgery, the authors routinely use IGS landmarks to localize intracranial electrodes and/or specific brain regions. The authors have developed a technique to coregister these landmarks with pre- and postoperative scans and the Montreal Neurological Institute (MNI) standard space brain MRI to allow 1) localization and identification of tissue anatomy; and 2) identification of Brodmann areas (BAs) of the tissue resected during epilepsy surgery. Tracking tissue in this fashion allows for better correlation of patient outcome to clinical factors, functional neuroimaging findings, and pathological characteristics and molecular studies of resected tissue.

Methods. Tissue samples were collected in 21 patients. Coordinates from intraoperative tissue localization were downloaded from the IGS system and transformed into patient space, as defined by preoperative high-resolution T1-weighted MRI volume. Tissue landmarks in patient space were then transformed into MNI standard space for identification of the BAs of the tissue samples.

Results. Anatomical locations of resected tissue were identified from the intraoperative resection landmarks. The BAs were identified for 17 of the 21 patients. The remaining patients had abnormal brain anatomy that could not be meaningfully coregistered with the MNI standard brain without causing extensive distortion.

Conclusions. This coregistration and landmark tracking technique allows localization of tissue that is resected from patients with epilepsy and identification of the BAs for each resected region. The ability to perform tissue localization allows investigators to relate preoperative, intraoperative, and postoperative functional and anatomical brain imaging to better understand patient outcomes, improve patient safety, and aid in research.

Noninvasive Language Mapping in Patients With Epilepsy or Brain Tumors


Neurosurgery 72:555–565, 2013

Functional magnetic resonance imaging (fMRI) has become part of routine brain mapping in patients with epilepsy or tumor undergoing resective surgery. However, robust localization of crucial functional areas is required.

OBJECTIVE: To establish a simple, short fMRI task that reliably localizes crucial language areas in individual patients who undergo respective surgery.

METHODS: fMRI was measured during an 8-minute auditory semantic decision task in 28 healthy controls and 35 consecutive patients who had focal epilepsy or a brain tumor. Nineteen underwent resective surgery. Group and individual analyses were performed. Results in patients were compared with postsurgical language outcome and electrocortical stimulation when available.

RESULTS: fMRI activations concordant with the anterior and posterior language areas were found in 96% and 89% of the controls, respectively. The anterior and posterior language areas were both activated in 93% of the patients. These results were concordant with electrocortical stimulation results in 5 patients. Transient postsurgical language deficits were found in 2 patients in whom surgery was performed in the vicinity of the fMRI activations or who had postsurgical complications implicating areas of fMRI activations.

CONCLUSION: The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects. It appears to be a valuable complementary tool for surgical planning of epileptogenic foci and of brain tumors.

Higher incidence of epilepsy in meningiomas located on the premotor cortex: a voxel-wise statistical analysis

Acta Neurochir (2012) 154:2241–2249

A substantial number of patients with brain tumors develop recurrent seizures, known as tumorassociated epilepsy. It is important to identify specific subgroups of brain tumor patients with higher incidences of epilepsy because a meta-analysis failed to certify the effectiveness of prophylactic anti-epileptic drugs (AEDs) to abort tumor-associated epilepsy as a whole.

Methods To investigate the relationship between tumor location and incidence of epilepsy, we performed voxel-wise comparison between 3D MRI scans obtained from patients with meningioma-associated epilepsy and those from control patients using spatial normalization techniques on neuroimaging data. Variables such as age, tumor size, the degree of edema, and pathological diagnosis were also compared between the two groups.

Results Our results showed the highest incidence of epilepsy when the tumor was located on the premotor cortex in the frontal lobe (Z-scores >2.0, Liebermeister’s quasi-exact test). The stepwise multiple regression analysis on the clinical data revealed that the tumor diameter (p<0.001) and the patient’s age (p=0.024) were positive and negative predictors, respectively, for the onset of epilepsy.

Conclusions The incidence of epilepsy was higher in meningiomas located on the premotor cortex than on the other cortex. Larger volume also contributed to the onset of epilepsy. We suggest that variations of epilepsy incidence dependent on tumor characteristics can be considered when treating tumor-associated epilepsy.

Pediatric Epilepsy Surgery: Long-term 5-Year Seizure Remission and Medication Use

Neurosurgery 71:985–993, 2012

It is unclear whether long-term seizure outcomes in children are similar to those in adult epilepsy surgery patients.

OBJECTIVE: To determine 5-year outcomes and antiepilepsy drug (AED) use in pediatric epilepsy surgery patients from a single institution.

METHODS: The cohort consisted of children younger than 18 years of age whose 5-year outcome data would have been available by 2010. Comparisons were made between patients with and without 5-year data (n = 338), patients with 5-year data for seizure outcome (n = 257), and seizure-free patients on and off AEDs (n = 137).

RESULTS: Five-year data were available from 76% of patients. More seizure-free patients with focal resections for hippocampal sclerosis and tumors lacked 5-year data compared with other cases. Of those with 5-year data, 53% were continuously seizure free, 18% had late seizure recurrence, 3% became seizure free after initial failure, and 25% were never seizure free. Patients were more likely to be continuously seizure free if their surgery was performed during the period 2001 to 2005 (68%) compared with surgery performed from 1996 to 2000 (61%), 1991 to 1995 (36%), and 1986 to 1990 (46%). More patients had 1 or fewer seizures per month in the late seizure recurrence (47%) compared with the not seizure-free group (20%). Four late deaths occurred in the not seizure-free group compared with 1 in the seizure-free group. Of patients who were continuously seizure free, 55% were not taking AEDs, and more cortical dysplasia patients (74%) had stopped taking AEDs compared with hemimegalencephaly patients (18%).

CONCLUSION: In children, 5-year outcomes improved over 20 years of clinical experience. Our results are similar to those of adult epilepsy surgery patients despite mostly extratemporal and hemispheric operations for diverse developmental etiologies.

Predictors of seizure freedom in the surgical treatment of supratentorial cavernous malformations

J Neurosurg 115:1169–1174, 2011. DOI: 10.3171/2011.7.JNS11536

Seizures are the most common presenting symptom of supratentorial cerebral cavernous malformations (CCMs) and progress to medically refractory epilepsy in 40% of patients. Predictors of seizure freedom in the resection of CCMs are incompletely understood.

Methods. The authors systematically reviewed the published literature on seizure freedom following the resection of supratentorial CCMs in patients presenting with seizures. Seizure outcomes were stratified across 12 potential prognostic variables. A total of 1226 patients with supratentorial CCMs causing seizures were identified across 31 predominantly retrospective studies; 361 patients had medically refractory epilepsy.

Results. Seventy-five percent of the patients were seizure free after microsurgical lesion removal, whereas 25% continued to have seizures. All patients had had preoperative seizures and > 6 months of postoperative follow-up. Modifiable predictors of postoperative seizure freedom included gross-total resection (OR 36.6, 95% CI 8.5–157.5) and surgery within 1 year of symptom onset (OR 1.83, 95% CI 1.30–2.58). Additional prognostic indicators of a favorable outcome were a CCM size < 1.5 cm (OR 15.4, 95% CI 5.2–45.4), the absence of multiple CCMs (OR 2.02, 95% CI 1.13–3.60), medically controlled seizures (OR 2.38, 95% CI 1.29–4.39), and the lack of secondarily generalized seizures (OR 3.33, 95% CI 2.09–5.30). Other factors, including extended resection of the hemosiderin ring, were not significantly predictive.

Conclusions. In the surgical treatment of supratentorial CCMs, gross-total resection and early operative intervention may improve seizure outcome. While surgery should not be considered the first-line treatment for CCM-related epilepsy, it is important to understand the variables associated with seizure freedom in CCM resection given the considerable morbidity and diminished quality of life associated with epilepsy.

Surgical approaches to hypothalamic hamartomas

Neurosurg Focus 30 (2):E2, 2011.(DOI: 10.3171/2010.11.FOCUS10250)

Hypothalamic hamartomas (HHs) are devastating lesions causing refractory epilepsy, rage attacks, social ineptitude, and precocious puberty. Microsurgical and/or endoscopic resection offers an excellent risk/benefit profile for cure or improvement of epilepsy.

Methods. The authors reviewed a prospective database maintained during the first 7 years of the Barrow Hypothalamic Hamartoma program. They describe and illustrate their surgical methods, and they review data from several previous publications regarding surgical outcome.

Results. To date, the authors have performed surgery in 165 patients for symptomatic HHs. Patients underwent an endoscopic, transcallosal, or skull base approach, or multiple approaches. Twenty-six patients (15.8%) required more than 1 treatment for their HH.

Conclusions. Microsurgical and endoscopic resection of symptomatic HHs are technically demanding but can be performed safely with excellent results and an acceptable risk profile. Meticulous attention to the subtleties of surgical management helps optimize outcomes.

Epileptogenicity of Cavernomas Depends on (Archi-) Cortical Localization

Neurosurgery 67:918–924, 2010 DOI: 10.1227/NEU.0b013e3181eb5032

Patients with cerebral cavernomas have an estimated risk of the development of epilepsy of 1.5% to 2.4% per patient-year.

OBJECTIVE: To clarify the predictive value of different risk factors for epilepsy in patients with supratentorial cavernomas.

METHODS: We retrospectively analyzed data of 109 patients with supratentorial cavernomas. The correlation of epilepsy with the variables of single or multiple cavernomas, sex, age, side, cortical involvement, mesiotemporal archicortical vs neocortical involvement, lobar location of neocortical cavernomas, the presence of a hemosiderin rim and of edema, and the maximal diameters of cavernoma, hemosiderin rim, and edema, if present, were calculated using univariate and multivariate penalized likelihood logistic regression models.

RESULTS: Cortical involvement was the most relevant risk factor for epilepsy (P , .0001). No patient with a subcortical cavernoma presented with epilepsy. Epilepsy was more common in patients with mesiotemporal archicortical cavernomas than in patients with neocortical cavernomas (P = .02), whereas the lobar location of neocortical cavernomas was not significantly associated with the risk of the development of epilepsy. In the multivariate analysis, a greater diameter of the cavernoma, the absence of edema, and localization in the left hemisphere were also associated with the occurrence of epilepsy (P , .05).

CONCLUSION: The epileptogenicity of supratentorial cavernomas depends on cortical, especially mesiotemporal archicortical, involvement. Exclusively subcortical cavernomas are highly unlikely to cause epilepsy. This information is helpful in counseling patients with cavernomas regarding their risk of epileptic seizures and in patients with multiple cavernomas and epilepsy to generate a valid hypothesis of which cavernoma may cause epilepsy.