Case Report Stereotact Funct Neurosurg DOI: 10.1159/000495414 Received: June 25, 2018 Accepted after revision: November 13, 2018 Published online: January 16, 2019 Anterior Corpus Callosotomy Using Laser Interstitial Thermal Therapy for Refractory Epilepsy Tyler Ball a Mayur Sharma a Andrew C. White b Joseph S. Neimat a a Department of Neurosurgery, University of Louisville School of Medicine, Louisville, KY, USA; b Department of Radiology, University of Louisville School of Medicine, Louisville, KY, USA Abstract Corpus callosotomy is a viable treatment for patients with refractory generalized or multifocal epilepsy, particularly those who have drop attacks. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical option for various intracranial lesions. In this report, we present a 2-trajectory thermal ablation using the NeuroBlate® system (Monteris Medical, MN, USA) for an anterior two-thirds callosotomy in a patient with refractory epilepsy and frequent drop attacks. Adequate ablation of the corpus callosum was confirmed by MRI during the procedure. At the 1-month follow-up, the frequency had decreased from multiple seizures per day to only 3 over the course of 1 month. In addition, he had not suffered any drop attacks or tonic-clonic movements since the procedure. Five months after surgery, seizures had decreased to 1 per month with no drop attacks or loss of consciousness, consistent with an Engel class II outcome. In conclusion, LITT ablation of the corpus callosum is a safe, feasible, and minimally invasive treatment option for patients with refractory epilepsy, and it may be an attractive alternative for patients unwilling or unable to undergo open surgery. © 2019 S. Karger AG, Basel © 2019 S. Karger AG, Basel E-Mail karger@karger.com www.karger.com/sfn Introduction Epilepsy causes a significant health care burden and affects approximately 3.4 million people in the USA (around 1.2% of the population) [1]. Approximately 40% of epilepsy patients are refractory to antiepileptic drugs (AEDs), a condition referred to as drug-resistant epilepsy (DRE) [2]. Patients with DRE benefit from surgery rather than prolonged medical therapy, especially those with temporal lobe epilepsy [3]. However, according to the National Association of Epilepsy Centers, fewer than 2,000 patients undergo surgery annually [4]. While there are many reasons for this, our experience indicates that many patients and families are resistant to the idea of open brain surgery and the risks it entails [2]. Corpus callosotomy has been shown to improve outcomes in patients with generalized epilepsy, absence, atonic or myoclonic seizures, or drop attacks [5, 6]. Laser interstitial thermal therapy (LITT) is a minimally invasive, stereotactic-guided surgical technique, which has shown favorable outcomes in patients with a variety of brain lesions including those with brain tumors [7–9] and epilepsy [10, 11]. The minimally invasive nature of LITT offers significant advantages over open surgical procedures in terms of length of hospital stay, blood loss, and size of surgical incision. We present a case of an anterior two-thirds corpus callosotomy using LITT in a patient with refractory epilepsy and frequent drop attacks. Joseph S. Neimat, MD University of Louisville, Department of Neurosurgery, Frazier Rehabilitation Institute 220 Abraham Flexner Way, 15th Floor Louisville, KY 40202 (USA) E-Mail joseph.neimat @ ulp.org Downloaded by: Auckland University of Technology 156.62.3.11 - 1/29/2019 10:12:09 AM Keywords Corpus callosotomy · Laser interstitial thermal therapy · Minimally invasive callosotomy · Epilepsy · Drop attacks Operative Details We used the NeuroBlate® system (Monteris Medical, MN, USA) to achieve thermal ablation in our patient. Prior to the LITT procedure, 6 WayPointTM bone marker anchors were placed in the skull and a stereotactic CT scan was obtained. This scan was fused with the preoperative MRI scan, and FHC WayPoint planning software (v3.0) was used to plan the 2 trajectories (Fig. 1). The anterior (right frontal) trajectory was designed to ablate the rostrum and genu of the corpus callosum, while the posterior (right parietal) trajectory was designed to ablate the anterior two-thirds of the body of the corpus callosum. Two StarFix platforms were designed based on the planned trajectories. On the day of surgery, after general anesthesia had been induced, the StarFix frame for the parietal trajectory was attached to the posterior 4 anchors. Next, the scalp was opened in the normal fashion and the 4.5-mm twist-drill was used to make a small hole. Next, we opened the dura with a flexible cautery. We then inserted the Monteris bolt along the posterior trajectory. When that was secured, we inserted the titanium mandrel to depth along the trajectory to create a path for the probe. We then removed the mandrel, plugged the opening with the sterile plug, and placed a TegadermTM over the attachment. We then removed the posterior frame and attached the anterior frame to the anterior 4 screws. The same process was repeated for the second trajectory. The skull anchors were removed and the incisions closed prior to leaving the operation room. The patient was then transported to the MRI suite. Here, we inserted the parietal trajectory probe through the posterior bolt. The first MRI sequence showed that the ablation probe had been deflected superiorly as it contacted the corpus callosum. This put the probe closer than planned to the pericallosal arteries. We repositioned the probe by reinserting the sterile titanium mandrel to recreate the tract, and then followed it immediately with the laser 2 Stereotact Funct Neurosurg DOI: 10.1159/000495414 Fig. 1. Frontal and parietal trajectories shown for ablation of the rostrum/genu and anterior two-thirds of the body of the corpus callosum, respectively. Fig. 2. T2-FLAIR sequence showing trajectory of posterior probe and the anterior two-thirds of the body of corpus callosum ablated. probe. This produced a correct trajectory through the callosum and provided a safer distance to the pericallosal arteries. We then performed lesions starting near the genu, and sequentially retracted the probe in a posterior direction 4 cm to ablate the anterior two-thirds of the body of the corpus callosum (Fig. 2, 3). Ablations were carried out until the margin of ablation reached the inferior Ball/Sharma/White/Neimat Downloaded by: Auckland University of Technology 156.62.3.11 - 1/29/2019 10:12:09 AM Case History The patient was a 21-year-old male with a history of developmental delay and intractable generalized seizures. Preoperatively, he had multiple seizures daily with frequent drop attacks. Seizures were described as behavioral arrest with tensing of the neck and arms, often progressing to drop attacks. He had also had multiple prior hospitalizations due to injuries sustained from falls during seizures. His EEG showed interictal left and right temporal epileptiform discharges, interictal generalized epileptiform discharges, and interictal focal right central discharges. His stay in the epilepsy-monitoring unit showed varied EEG correlates, but most typically generalized spike wave discharges. An MRI scan did not reveal any lesional cause of the epilepsy. The patient’s antiepileptics included clobazam, clonazepam, topiramate, levetiracetam, phenytoin, and diazepam. He also tried and failed oxcarbazepine. He had had a vagal nerve stimulator implanted 18 months previously with no significant reduction in seizures. Despite all of these treatment modalities, his seizures were significantly impacting his quality of life (QOL), as well as that of his parents who were constantly occupied in attending to him to prevent injury from his seizures. The option of an open callosotomy was discussed with the family, but they expressed significant concern about open surgery. We offered the possibility of performing the procedure through stereotactic laser ablation, and they elected to proceed with the LITT procedure. Color version available online Case Report Fig. 3. a, b Sagittal oblique 8-mm multipla- nar volume reconstruction reformats of T1-weighted 3D fast spoiled gradient echo MR images through the corpus callosum demonstrate the ablation zone covering most of the genu and anterior portion of the body. a b 4 5 Fig. 4. T2-FLAIR sequence showing the an- terior extent of ablation of the genu. Fig. 5. Coronal T2 showing sequential abla- tions covering both sides of the midline. surface of the corpus callosum at the edge of the ventricle. The posterior probe was then removed, and the bolt was temporarily covered with a sterile dressing. For the anterior trajectory, we utilized the larger directional laser probe. We placed the 3.3-mm laser probe through the anterior bolt. MRI confirmed an acceptable location, and ablation of the rostrum and genu of the corpus callosum was performed under real-time MR thermography. We retracted the probe after each ablation from deep to superficial, creating an oblique lesion. The directional lead was used to bias each of the adjacent lesions toward the center of the corpus callosum, producing a broad lesion that was more conformal. Postablation MRI showed satisfactory coverage of the rostrum and genu (Fig. 4, 5). The anterior laser probe was then removed. A postoperative MRI demonstrated what appeared to be effective lesions of the body, genu, and rostrum of the corpus callosum (Fig. 2–6). In addition, a diffusion-weighted imaging sequence demonstrated no areas of diffusion restriction or concern for ischemia in the distribution of the anterior cerebral arteries. Notably, the volume of ablation conformed to the corpus callosum relatively well, likely due to the heat sink effect of the ventricles inferi- orly, and the pericallosal arteries and cerebrospinal fluid (CSF) of the interhemispheric sulcus superiorly. However, some degree of T2 hyperintensity and enhancement could be appreciated in the adjacent cingulate cortex (Fig. 5, 6). Following satisfactory ablation, the bolts were removed. The skin was closed using the 4–0 purse-string Monocryl that was originally placed in the operating room. Anterior Corpus Callosotomy Using LITT for Refractory Epilepsy Stereotact Funct Neurosurg DOI: 10.1159/000495414 3 Downloaded by: Auckland University of Technology 156.62.3.11 - 1/29/2019 10:12:09 AM Outcome At the 1-month follow up, the patient had experienced only 3 seizures and had not suffered any falls or tonic-clonic movements. His family also did not notice any cognitive or behavioral changes postoperatively. He had experienced mild difficulty with balance (an occasional tendency to lean to the right side) in the immediate postoperative period, but this had gradually returned to baseline. Our typical practice is to get an MRI at around 1 month postoperatively to assess the extent of the callosotomy; however, given that the patient would require general anesthesia for an MRI and was doing so well clinically, we did not proceed with this as it would not have altered our treatment plan. Five months postop- a b c Fig. 6. a, b T2 sequences show that there seems to be a preserved, nonablated zone around the pericallosal arteries and the ventricles. However, there is some spread of the hyperintensity into the adjacent cingulate cortex. c Axial T1 postcontrast sequence shows enhancement that appears to involve the cingulate gyrus anteriorly on the left and posteriorly on the right. Discussion Traditional open corpus callosotomy has demonstrated significant efficacy in reducing the spread of seizures from one hemisphere to another [5, 6]. This can aid in the reduction of drop attacks and reduce the severity of seizures in patients who are not candidates for lesional resection. While corpus callosotomy does not typically eliminate seizures in the way that focal temporal or extratemporal resections can in the setting of focal-onset seizures, the reduction in severity can lead to dramatic improvements in QOL for patients and their families. Despite the effectiveness of open callosotomy in reducing drop attacks, patients and their families are often reluctant to consent to such an invasive intervention. While LITT for ablation of the corpus callosum is a much newer technology with more unknowns than open callosotomy, the fact that patients have only a small twist-drill burr hole and a shorter hospital stay may make the procedure an attractive option to families. Falowski and Byrne [12] first described the use of a carbon dioxide laser in place of bipolar electrocautery to lesion the corpus callosum in open surgery in 2 patients 4 Stereotact Funct Neurosurg DOI: 10.1159/000495414 with generalized epilepsy. In 2015, Choudhri et al. [13] described a similar technique to complete 8 callosotomies in 6 pediatric patients, resulting in either complete resolution or an improvement in the frequency of drop attacks in all patients; no complications were noted in this study. Regarding minimally invasive LITT for corpus callosotomy, there have been 3 published reports of 5 cases using MRI thermography for real-time visualization of the lesion. Pruitt et al. [14] reported a series of 49 patients that included 3 corpus callosotomies and reported a complication of catheter malposition in 1 patient. There was no clinical follow-up available in this series. In 2016, Ho et al. [15] reported a case of minimally invasive laser ablation of the splenium of the corpus callosum for a patient with DRE and persistent drop attacks despite prior open surgery for anterior two-thirds callosotomy. They achieved an adequate ablation of the splenial remnant without any associated neurological impairment. This patient had no further episodes of atonic seizures and a > 50% reduction in overall seizure frequency at the 4-month follow-up. In 2018, Karsy et al. [10] described an anterior two-thirds callosotomy using minimally invasive laser ablation, with an immediate and significant reduction in the number and severity of symptoms, fewer emergency room visits, and no surgical complications at the 9-month follow-up. These cases and ours suggest that laser callosotomy may be a safe and effective alternative to open corpus callosotomy, and also provides greater comfort and a faster recovery without compromising efficacy. Ball/Sharma/White/Neimat Downloaded by: Auckland University of Technology 156.62.3.11 - 1/29/2019 10:12:09 AM eratively, the mother reported that the patient had experienced only 1 seizure per month, and that these were much milder than prior to the procedure, consistent with an Engel class II outcome. Additionally, he had not experienced any drop attacks, and had not required hospitalization since the procedure. Regarding the technical aspects of the surgery, we learned a few lessons that we would like to share. First, we feel that targeting accuracy can be maximized by minimizing the interval from when the titanium mandrel is removed from the brain and the ablating probe is reinserted. The best way to do this would be to insert the probes in the operating room directly after the titanium mandrel is removed. However, this would make transport and positioning the patient in MRI examination more difficult. Also, because this technology uses cooling of the probe to control the extent of ablation, damage of the probe could lead to insufficient cooling and damage to the surrounding brain. Pruitt et al. [14] describe a case where the probe was bent by movement of the patient during the procedure, which caused it to overheat. Presumably, this caused charred tissue in the region of the choroid to adhere to the probe, leading to intraventricular hemorrhage upon probe removal. Next, it would be ideal to enter denser white-matter tracts (i.e., the corpus callosum) in a more perpendicular fashion, as trying to pass a relatively blunt probe into a denser substrate at a shallow angle carries a higher chance of deflection. However, given anatomical constraints, this is often not possible. Given this risk of deflection, extra care should be taken to ensure the probe is in the desired location (via MRI confirmation) prior to ablating. We used 2 trajectories to achieve an anterior corpus callosotomy. Karsy et al. [10] described using 3 trajectories to achieve anterior corpus callosotomy in a patient with Lennox-Gastaut syndrome and drug-resistant drop seizures. Another study described using a single trajectory for an anterior two-thirds corpus callosotomy and 2 trajectories for complete callosotomy [20]. It is notable that the variable curvature of the corpus callosum in each individual patient may require slightly different approaches and numbers of trajectories in each patient. Finally, as can be seen in Figure 6, the patient presented here had a generous amount of CSF surrounding his pericallosal arteries. While the arteries themselves can serve as a heat sink, it is unknown to what degree the surrounding CSF shields the arteries from damage. Nevertheless, our report provides insight into the utility of LITT in a patient with DRE. Our review of the postoperative imaging suggests that the lesions are likely less complete/confluent than what can be achieved with traditional open surgical techniques. For this reason, it would be desirable to have a delayed postoperative scan and, specifically, examine diffusion tensor imaging sequences of the callosum. Be- Anterior Corpus Callosotomy Using LITT for Refractory Epilepsy Stereotact Funct Neurosurg DOI: 10.1159/000495414 5 Downloaded by: Auckland University of Technology 156.62.3.11 - 1/29/2019 10:12:09 AM Although our patient did not suffer any clinically apparent neurologic deficits, it must be noted that the T2 hyperintensity and enhancement from the lesion did spread into the adjacent cingulate cortex (Fig. 2, 5, 6a–c). While there was some bilateral involvement of the cingulate cortex, the left cingulate gyrus was predominately involved anteriorly, while the right cingulate gyrus was predominately more posteriorly involved. This is consistent with the path of the probe. Other reports of LITT for corpus callosotomy do not comment on cingulate cortex involvement. Additionally, the paucity of published images following the procedure makes it difficult to discern the frequency of radiographic involvement of adjacent structures. Multiple studies have addressed the clinical sequalae of cingulate cortex damage. In 1994, Cohen et al. [16] described side effects of bilateral anterior cingulate gyrus damage including disrupted habituation of the orienting response. Notably, the patients in their study had normal IQs. The effects of cingulate gyrus damage may be less apparent in a patient with developmental delay, as in this case report. Five years later, Cohen et al. [17] showed that a group of patients treated with bilateral cingulotomies for chronic intractable pain had focused and sustained attention deficits, as well as mild executive dysfunction. Self-initiated responses, including spontaneous verbal utterances and unstructured design fluency, were found to be most impaired. In 2001, the emotional and personality changes following cingulotomy for chronic, intractable pain were described [18]. At the 1-year follow-up, patients had the greatest impairments, evident when performing tasks involving intention and spontaneous response production. Regarding the positive effects of cingulotomy, the greatest impacts were on the aspects of mood and affect that related to the level of emotional tension and agitation. The authors concluded that since the anterior cingulate cortex (ACC) appears to have an effect on maintaining arousal and effort, and subsequent emotional or physical tension, ACC activation might result in perceived emotional tension. The reduction in this perceived tension following cingulotomy might explain some of its efficacy in treating chronic pain and obsessivecompulsive disorder. In addition to the cognitive and emotional side effects, Wilkinson [19] reported transient or well-controlled seizures in 39% of patients (in a series of 28 cingulotomies). Notably, this series of patients underwent callosotomy between 1979 and 1996, and air ventriculography was used for some patients. Therefore, the rate of postoperative seizures in this group may not be comparable to a group undergoing callosotomy using modern techniques. cause attaining such a scan would have required general anesthesia and inconvenience for the patient (without personal benefit), we did not obtain this scan. It is notable that there can be a relatively successful outcome simply due to the substantial reduction of callosal fibers, even if the lesion is incomplete. Conclusion Statement of Ethics The authors have no ethical conflicts to disclose. Disclosure Statement The authors have no relevant disclosures. Funding Sources LITT ablation of the corpus callosum is a safe, feasible, and minimally invasive treatment option for patients with refractory epilepsy, and it may be a particularly attractive alternative for patients unwilling or unable to undergo an open procedure. There was no funding. Author Contributions Tyler Ball and Mayur Sharma prepared the manuscript. Andrew White helped with radiologic analysis and reformatting of images for publication. Joseph Neimat assisted in manuscript preparation and revision and was the senior neurosurgeon responsible for the care of the patient in this case report. References 6 7 Sharma M, Balasubramanian S, Silva D, Barnett GH, Mohammadi AM. Laser interstitial thermal therapy in the management of brain metastasis and radiation necrosis after radiosurgery: an overview. Expert Rev Neurother. 2016;16(2):223–32. 8 Sharma M, Krivosheya D, Borghei-Razavi H, Barnett GH, Mohammadi AM. 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