JOURNAL CLUB JOURNAL CLUB
Journal Club: Real-Time Magnetic Resonance–Guided Stereotactic Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy Ying Meng, MD*‡ Suganth Suppiah, MD*‡ Alireza Mansouri, MD*‡§ *Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; ‡Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; §Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada Correspondence: Ying Meng, MD, 399 Bathurst St., WW 4-427, Toronto, Ontario M5T 2S8, Canada. E-mail: [email protected]
Copyright © 2015 by the Congress of Neurological Surgeons.
Subject Article: Willie JT, Laxpati NG, Drane DL, et al. Real-time magnetic resonanceguided stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy. Neurosurgery. 2014;74(6):569-584.
SIGNIFICANCE/CONTEXT AND IMPORTANCE OF THE STUDY
T
he article by Willie et al is a novel contribution to the literature regarding minimally invasive approaches to the management of patients with medically refractory mesial temporal lobe epilepsy (mTLE). The evidence in favor of surgery has been strengthened ever since the randomized, controlled trial by Wiebe et al.1 However, concerns regarding long-term neuropsychiatric and cognitive sequelae have led to the development of alternative minimally invasive approaches such as stereotactic radiosurgery and radiofrequency ablation.2 Willie et al describe a novel technique of using laser thermal ablation guided by intraoperative magnetic resonance imaging to induce highly specific tissue ablation of the hippocampus and amygdala with minimal effect on surrounding tissue. This study, which has been eloquently designed and reported, is certainly a significant improvement on the current evidence, which has thus far been based on smaller sample sizes and less rigorous design.3 Additionally, it is an important preliminary step toward larger trials designed to further establish the long-term safety and efficacy of this approach.
ORIGINALITY OF THE WORK The application of stereotactic laser ablation has been recently evolving. This spectrum includes the treatment of primary and metastatic brain tumors and various epileptogenic foci in the pediatric population such as tubers, cortical dysplasias, and hamartomas. This is the first reported series of stereotactic laser ablation
NEUROSURGERY
applied to treat mTLE. Additionally, the authors have combined stereotactic-guided laser ablation with intraoperative magnetic resonance visualization, which nicely provides immediate feedback and ensures additional patient safety. A detailed outline of their surgical technique can enable other centers to replicate the same procedure, thereby making this article a seminal paper in the field of minimally invasive, laserbased ablative procedures.
APPROPRIATENESS OF THE STUDY DESIGN OR EXPERIMENTAL APPROACH This study is based on a consecutive, prospective case series of 13 patients with mTLE who had been identified as surgical candidates through standard workup. The objective of this study was to enroll a patient population that was representative of patients seen in a typical neurosurgical epilepsy unit. They took an ethical approach of allowing the patient to choose between the standard of care and stereotactic laser amygdalohippocampotomy (SLAH). Outcome measures appropriately included seizure control, as well as proportions of structures ablated and surgical complications. However, the methodology of this study could have been refined through the following strategies. Study Design Given the concerns regarding bias, the inclusion of a parallel intervention arm via a randomized, blinded process could significantly increase the validity of their results. For example, radiofrequency (RF)–based ablation follows a similar principle as SLAH and has been more systematically studied for mTLE.3 Therefore, randomizing patients to a parallel RF arm would enable an assessment of the true effect of SLAH. Furthermore, randomization would help ensure that known and unknown baseline prognostic
VOLUME 77 | NUMBER 2 | AUGUST 2015 | 307
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
MENG ET AL
parameters are balanced across patients, whereas blinding and allocation concealment would minimize performance and detection bias. Such bias is particularly concerning given that the study was industry sponsored, and some of the authors are consultants, employees, or stakeholders in Visualase. On the other hand, the pilot nature of this trial as well as potential technical and resource constraints can affect the feasibility of this proposed approach.
all patients were subjected to the same preoperative evaluation criteria. Finally, because a major advantage of this technique is to provide highly selective anatomic ablation while sparing other neocortical structures in the temporal lobe, the neuropsychological outcome measures would be key results of interest. These variables were measured, as per the methods section, but the results were, unfortunately, not presented or discussed.
Outcome Assessment Although the rate of seizure freedom observed in this study is similar to others reported for the surgical treatment of mTLE,1 the large variability in the length of follow-up limits the strength of their conclusions. Moreover, there are inherent flaws stemming from the scheme of self-reported seizure outcomes. The Engel classification is a common outcome measure for seizure freedom in the literature, but it has been criticized for its subjectivity (eg, “disabling seizures” vs “worthwhile seizure reduction”). Additionally, qualifiers of the Engel classification require a minimum 2 years of follow-up to make direct comparisons between patients. A more robust and objective strategy would be documentation of patient seizures before and after intervention in the setting of a video-electroencephalography unit.
RELEVANCE OF DISCUSSION
ADEQUACY OF EXPERIMENTAL TECHNIQUES The authors have provided a thorough description of their surgical technique and method of analysis, which enables replication by future studies. However, certain steps in their experimental technique could benefit from further standardization and objectivity. For instance, the authors manually segment the magnetic resonance images to calculate the proportion of structures ablated, where independent duplicate assessment would have alleviated concerns regarding measurement error. Also, 2 patients were considered as having an “insufficient” amount of tissue ablated; the criteria for this classification were not clearly outlined.
SOUNDNESS OF CONCLUSIONS AND INTERPRETATION Willie et al have appropriately offered their conclusions based on the available data while also cautioning against overinterpretation, given the relatively small sample size and short-term followup. Overall, SLAH appears to be a feasible alternative to open surgical resection for mTLE. Conclusions regarding the effectiveness of SLAH compared with the standard procedure may be better supported by improvements in the methodology, as mentioned previously. In terms of effectiveness, they noted that seizure freedom achieved in patients undergoing SLAH (54%) is similar to that observed in the literature with open surgical resection (67%).1 However, when compared with the authors’ standard anterior temporal lobectomy cohort, the SLAH arm did not fare as well (Figure 6). This is concerning given that, as noted by the authors,
308 | VOLUME 77 | NUMBER 2 | AUGUST 2015
A thoughtful discussion about the clinical significance of SLAH for mTLE was provided. One of the authors’ suggestions was that a reasonable approach for patients could be an initial trial of SLAH with subsequent open resection if seizure freedom was not achieved. This is a reasonable option with several caveats. First, in settings where there are already long wait times for a neurosurgical consultation, this would potentially be further burdened by this approach in patients who do not achieve seizure freedom with SLAH.1 Second, the cumulative morbidity of multiple surgeries on patients must also be taken into consideration. Furthermore, from a health economic perspective, this approach should be weighed against the impact on upfront and future costs along with anticipated patient utilities. Various centers have shown open resection to be a cost-effective treatment for medically intractable epilepsy.4 Therefore, it would be prudent to conduct cost-utility analyses in the setting of future multicenter trials comparing upfront SLAH (followed by open surgery for failures) with the currently accepted upfront open resection. Such analyses should incorporate utilities that are specific to patients with medically refractory epilepsy and should ideally examine all direct and indirect costs. Moreover, given that epilepsy is a chronic condition, long-term follow-up would be imperative to truly delineate seizure outcomes and derived utilities. Thus, appropriate time horizons and discounting of costs and effects must be considered. The discussion overall was comprehensive, but areas of potential relevance to the application of a novel technique merit further elaboration. For instance, 1 patient experienced postoperative hemianopsia due to a poor trajectory of the intraparenchymal device. This complication was attributed to technical challenges. Also, only 1 of the first 6 patients achieved Engel class I seizure freedom, whereas 6 of the next 7 patients did. Therefore, the potential relevance of the learning curve could have been explored further. Moreover, an important factor contributing to the safety of the SLAH was pointed out as the ability of pial margins to limit thermal spread and damage to surrounding tissues. This phenomenon would be a clear advantage to laser ablation, and it would be enlightening to understand its underlying physiology. Finally, the viability of the SLAH is based on the premise that it minimizes neuropsychological impairments and improves patient quality of life compared with standard surgery. Although the authors have recently published the results of neurocognitive testing in a separate publication,5 a brief description of those findings would be worthwhile. Likewise, the patients’ perspective
www.neurosurgery-online.com
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
JOURNAL CLUB
would be important to determine, especially as it relates to possible increases in wait time and the impact of a continued lack of seizure freedom on biopsychosocial functioning.
underwent open surgery. This figure could have been presented more upfront to demonstrate the flow of patient recruitment through the study.
CLARITY OF WRITING, STRENGTH, AND ORGANIZATION OF THE PAPER
FUTURE/NEXT STEPS
This article had a clear and comprehensive description of their surgical technique and method of analysis, which would be amenable to replication and sets the groundwork for meta-analysis in the future. It would benefit from a greater degree of conciseness in the results and discussion sections.
ECONOMY OF WORDS The style of writing was technical and served the purpose of the article for illustrating the surgical technique. The clarity and length of the methods and results sections could perhaps be improved with use of flow diagrams.
RELEVANCE, ACCURACY, AND COMPLETENESS OF BIBLIOGRAPHY The bibliography was comprehensive in including seminal papers that established the effectiveness of surgical treatment for epilepsy such as the study by Wiebe et al and the ERSET trial. The relevant meta-analysis on the superiority of surgery for mTLE was also included. Moreover, it was thorough in providing the literature behind stereotactic laser ablation for neurosurgical conditions, such as the study by Curry et al on treatment of medically refractory epilepsy in children.
NUMBER AND QUALITY OF FIGURES, TABLES, AND ILLUSTRATIONS The authors provided several figures to illustrate their equipment, technique, and ablation planning. Tables are used to highlight their patient demographic characteristics and clinical outcomes, which are easy to read and helpful. In our opinion, Tables 1 and 2 could have been merged with more individualized presentation of data. Also, making Figures 1 and 3 supplementary may help the organization of the article. The figure demonstrating the histology of the ablated tissue is interesting but detracts from the clinical thrust of the article and its conclusions; this could have perhaps been included as a supplementary figure. Finally, Figure 6 illustrates the institutional patient outcomes for those who
NEUROSURGERY
Willie et al have set the groundwork for potentially fruitful randomized, controlled trials and health economic analyses based on less invasive procedures for mTLE. Furthermore, their preliminary results comparing naming and recognition functions in patients who underwent open resection vs SLAH were recently published elsewhere.5 It would be interesting to evaluate these 2 treatment arms in terms of postoperative outcomes such as seizure freedom, quality of life measures, and neuropsychological testing through a study that assesses long-term outcomes. Future work can also aim to establish patient prognostic indicators that predict the likelihood of seizure freedom after SLAH. This information would help clinicians select the patient population most suitable for stereotactic treatment, thereby maximizing benefit and minimizing risk. The authors note that a larger multicenter trial is currently under way to investigate the effectiveness of SLAH, and we eagerly await the results of that study. We believe that the addition of SLAH and a good understanding of how it fits in the management of mTLE will lead to improved patient care. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
REFERENCES 1. Wiebe S. Effectiveness and safety of epilepsy surgery: what is the evidence? CNS Spectr. 2004;9(2):120-122. 2. Vojtech Z, Krámská L, Malíková H, et al. Cognitive outcome after stereotactic amygdalohippocampectomy. Seizure. 2012;21(5):327-333. 3. Quigg M, Harden C. Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies. J Neurosurg. 2014;121(suppl): 232-240. 4. King JT Jr, Sperling MR, Justice AC, O’Connor MJ. A cost-effectiveness analysis of anterior temporal lobectomy for intractable temporal lobe epilepsy. J Neurosurg. 1997;87(1):20-28. 5. Drane DL, Loring DW, Voets NL, et al. Better object recognition and naming outcome with MRI-guided stereotactic laser amygdalohippocampotomy for temporal lobe epilepsy. Epilepsia. 2015;56(1):101-113.
Acknowledgment The authors thank Abhaya Kulkarni, MD, PhD, FRCSC, for trusting them with this endeavor and providing insightful feedback.
VOLUME 77 | NUMBER 2 | AUGUST 2015 | 309
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
Journal Club: Real-Time Magnetic Resonance–Guided Stereotactic Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy Ying Meng, MD*‡ Suganth Suppiah, MD*‡ Alireza Mansouri, MD*‡§ *Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada; ‡Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada; §Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada Correspondence: Ying Meng, MD, 399 Bathurst St., WW 4-427, Toronto, Ontario M5T 2S8, Canada. E-mail: [email protected]
Copyright © 2015 by the Congress of Neurological Surgeons.
Subject Article: Willie JT, Laxpati NG, Drane DL, et al. Real-time magnetic resonanceguided stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy. Neurosurgery. 2014;74(6):569-584.
SIGNIFICANCE/CONTEXT AND IMPORTANCE OF THE STUDY
T
he article by Willie et al is a novel contribution to the literature regarding minimally invasive approaches to the management of patients with medically refractory mesial temporal lobe epilepsy (mTLE). The evidence in favor of surgery has been strengthened ever since the randomized, controlled trial by Wiebe et al.1 However, concerns regarding long-term neuropsychiatric and cognitive sequelae have led to the development of alternative minimally invasive approaches such as stereotactic radiosurgery and radiofrequency ablation.2 Willie et al describe a novel technique of using laser thermal ablation guided by intraoperative magnetic resonance imaging to induce highly specific tissue ablation of the hippocampus and amygdala with minimal effect on surrounding tissue. This study, which has been eloquently designed and reported, is certainly a significant improvement on the current evidence, which has thus far been based on smaller sample sizes and less rigorous design.3 Additionally, it is an important preliminary step toward larger trials designed to further establish the long-term safety and efficacy of this approach.
ORIGINALITY OF THE WORK The application of stereotactic laser ablation has been recently evolving. This spectrum includes the treatment of primary and metastatic brain tumors and various epileptogenic foci in the pediatric population such as tubers, cortical dysplasias, and hamartomas. This is the first reported series of stereotactic laser ablation
NEUROSURGERY
applied to treat mTLE. Additionally, the authors have combined stereotactic-guided laser ablation with intraoperative magnetic resonance visualization, which nicely provides immediate feedback and ensures additional patient safety. A detailed outline of their surgical technique can enable other centers to replicate the same procedure, thereby making this article a seminal paper in the field of minimally invasive, laserbased ablative procedures.
APPROPRIATENESS OF THE STUDY DESIGN OR EXPERIMENTAL APPROACH This study is based on a consecutive, prospective case series of 13 patients with mTLE who had been identified as surgical candidates through standard workup. The objective of this study was to enroll a patient population that was representative of patients seen in a typical neurosurgical epilepsy unit. They took an ethical approach of allowing the patient to choose between the standard of care and stereotactic laser amygdalohippocampotomy (SLAH). Outcome measures appropriately included seizure control, as well as proportions of structures ablated and surgical complications. However, the methodology of this study could have been refined through the following strategies. Study Design Given the concerns regarding bias, the inclusion of a parallel intervention arm via a randomized, blinded process could significantly increase the validity of their results. For example, radiofrequency (RF)–based ablation follows a similar principle as SLAH and has been more systematically studied for mTLE.3 Therefore, randomizing patients to a parallel RF arm would enable an assessment of the true effect of SLAH. Furthermore, randomization would help ensure that known and unknown baseline prognostic
VOLUME 77 | NUMBER 2 | AUGUST 2015 | 307
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
MENG ET AL
parameters are balanced across patients, whereas blinding and allocation concealment would minimize performance and detection bias. Such bias is particularly concerning given that the study was industry sponsored, and some of the authors are consultants, employees, or stakeholders in Visualase. On the other hand, the pilot nature of this trial as well as potential technical and resource constraints can affect the feasibility of this proposed approach.
all patients were subjected to the same preoperative evaluation criteria. Finally, because a major advantage of this technique is to provide highly selective anatomic ablation while sparing other neocortical structures in the temporal lobe, the neuropsychological outcome measures would be key results of interest. These variables were measured, as per the methods section, but the results were, unfortunately, not presented or discussed.
Outcome Assessment Although the rate of seizure freedom observed in this study is similar to others reported for the surgical treatment of mTLE,1 the large variability in the length of follow-up limits the strength of their conclusions. Moreover, there are inherent flaws stemming from the scheme of self-reported seizure outcomes. The Engel classification is a common outcome measure for seizure freedom in the literature, but it has been criticized for its subjectivity (eg, “disabling seizures” vs “worthwhile seizure reduction”). Additionally, qualifiers of the Engel classification require a minimum 2 years of follow-up to make direct comparisons between patients. A more robust and objective strategy would be documentation of patient seizures before and after intervention in the setting of a video-electroencephalography unit.
RELEVANCE OF DISCUSSION
ADEQUACY OF EXPERIMENTAL TECHNIQUES The authors have provided a thorough description of their surgical technique and method of analysis, which enables replication by future studies. However, certain steps in their experimental technique could benefit from further standardization and objectivity. For instance, the authors manually segment the magnetic resonance images to calculate the proportion of structures ablated, where independent duplicate assessment would have alleviated concerns regarding measurement error. Also, 2 patients were considered as having an “insufficient” amount of tissue ablated; the criteria for this classification were not clearly outlined.
SOUNDNESS OF CONCLUSIONS AND INTERPRETATION Willie et al have appropriately offered their conclusions based on the available data while also cautioning against overinterpretation, given the relatively small sample size and short-term followup. Overall, SLAH appears to be a feasible alternative to open surgical resection for mTLE. Conclusions regarding the effectiveness of SLAH compared with the standard procedure may be better supported by improvements in the methodology, as mentioned previously. In terms of effectiveness, they noted that seizure freedom achieved in patients undergoing SLAH (54%) is similar to that observed in the literature with open surgical resection (67%).1 However, when compared with the authors’ standard anterior temporal lobectomy cohort, the SLAH arm did not fare as well (Figure 6). This is concerning given that, as noted by the authors,
308 | VOLUME 77 | NUMBER 2 | AUGUST 2015
A thoughtful discussion about the clinical significance of SLAH for mTLE was provided. One of the authors’ suggestions was that a reasonable approach for patients could be an initial trial of SLAH with subsequent open resection if seizure freedom was not achieved. This is a reasonable option with several caveats. First, in settings where there are already long wait times for a neurosurgical consultation, this would potentially be further burdened by this approach in patients who do not achieve seizure freedom with SLAH.1 Second, the cumulative morbidity of multiple surgeries on patients must also be taken into consideration. Furthermore, from a health economic perspective, this approach should be weighed against the impact on upfront and future costs along with anticipated patient utilities. Various centers have shown open resection to be a cost-effective treatment for medically intractable epilepsy.4 Therefore, it would be prudent to conduct cost-utility analyses in the setting of future multicenter trials comparing upfront SLAH (followed by open surgery for failures) with the currently accepted upfront open resection. Such analyses should incorporate utilities that are specific to patients with medically refractory epilepsy and should ideally examine all direct and indirect costs. Moreover, given that epilepsy is a chronic condition, long-term follow-up would be imperative to truly delineate seizure outcomes and derived utilities. Thus, appropriate time horizons and discounting of costs and effects must be considered. The discussion overall was comprehensive, but areas of potential relevance to the application of a novel technique merit further elaboration. For instance, 1 patient experienced postoperative hemianopsia due to a poor trajectory of the intraparenchymal device. This complication was attributed to technical challenges. Also, only 1 of the first 6 patients achieved Engel class I seizure freedom, whereas 6 of the next 7 patients did. Therefore, the potential relevance of the learning curve could have been explored further. Moreover, an important factor contributing to the safety of the SLAH was pointed out as the ability of pial margins to limit thermal spread and damage to surrounding tissues. This phenomenon would be a clear advantage to laser ablation, and it would be enlightening to understand its underlying physiology. Finally, the viability of the SLAH is based on the premise that it minimizes neuropsychological impairments and improves patient quality of life compared with standard surgery. Although the authors have recently published the results of neurocognitive testing in a separate publication,5 a brief description of those findings would be worthwhile. Likewise, the patients’ perspective
www.neurosurgery-online.com
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
JOURNAL CLUB
would be important to determine, especially as it relates to possible increases in wait time and the impact of a continued lack of seizure freedom on biopsychosocial functioning.
underwent open surgery. This figure could have been presented more upfront to demonstrate the flow of patient recruitment through the study.
CLARITY OF WRITING, STRENGTH, AND ORGANIZATION OF THE PAPER
FUTURE/NEXT STEPS
This article had a clear and comprehensive description of their surgical technique and method of analysis, which would be amenable to replication and sets the groundwork for meta-analysis in the future. It would benefit from a greater degree of conciseness in the results and discussion sections.
ECONOMY OF WORDS The style of writing was technical and served the purpose of the article for illustrating the surgical technique. The clarity and length of the methods and results sections could perhaps be improved with use of flow diagrams.
RELEVANCE, ACCURACY, AND COMPLETENESS OF BIBLIOGRAPHY The bibliography was comprehensive in including seminal papers that established the effectiveness of surgical treatment for epilepsy such as the study by Wiebe et al and the ERSET trial. The relevant meta-analysis on the superiority of surgery for mTLE was also included. Moreover, it was thorough in providing the literature behind stereotactic laser ablation for neurosurgical conditions, such as the study by Curry et al on treatment of medically refractory epilepsy in children.
NUMBER AND QUALITY OF FIGURES, TABLES, AND ILLUSTRATIONS The authors provided several figures to illustrate their equipment, technique, and ablation planning. Tables are used to highlight their patient demographic characteristics and clinical outcomes, which are easy to read and helpful. In our opinion, Tables 1 and 2 could have been merged with more individualized presentation of data. Also, making Figures 1 and 3 supplementary may help the organization of the article. The figure demonstrating the histology of the ablated tissue is interesting but detracts from the clinical thrust of the article and its conclusions; this could have perhaps been included as a supplementary figure. Finally, Figure 6 illustrates the institutional patient outcomes for those who
NEUROSURGERY
Willie et al have set the groundwork for potentially fruitful randomized, controlled trials and health economic analyses based on less invasive procedures for mTLE. Furthermore, their preliminary results comparing naming and recognition functions in patients who underwent open resection vs SLAH were recently published elsewhere.5 It would be interesting to evaluate these 2 treatment arms in terms of postoperative outcomes such as seizure freedom, quality of life measures, and neuropsychological testing through a study that assesses long-term outcomes. Future work can also aim to establish patient prognostic indicators that predict the likelihood of seizure freedom after SLAH. This information would help clinicians select the patient population most suitable for stereotactic treatment, thereby maximizing benefit and minimizing risk. The authors note that a larger multicenter trial is currently under way to investigate the effectiveness of SLAH, and we eagerly await the results of that study. We believe that the addition of SLAH and a good understanding of how it fits in the management of mTLE will lead to improved patient care. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
REFERENCES 1. Wiebe S. Effectiveness and safety of epilepsy surgery: what is the evidence? CNS Spectr. 2004;9(2):120-122. 2. Vojtech Z, Krámská L, Malíková H, et al. Cognitive outcome after stereotactic amygdalohippocampectomy. Seizure. 2012;21(5):327-333. 3. Quigg M, Harden C. Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies. J Neurosurg. 2014;121(suppl): 232-240. 4. King JT Jr, Sperling MR, Justice AC, O’Connor MJ. A cost-effectiveness analysis of anterior temporal lobectomy for intractable temporal lobe epilepsy. J Neurosurg. 1997;87(1):20-28. 5. Drane DL, Loring DW, Voets NL, et al. Better object recognition and naming outcome with MRI-guided stereotactic laser amygdalohippocampotomy for temporal lobe epilepsy. Epilepsia. 2015;56(1):101-113.
Acknowledgment The authors thank Abhaya Kulkarni, MD, PhD, FRCSC, for trusting them with this endeavor and providing insightful feedback.
VOLUME 77 | NUMBER 2 | AUGUST 2015 | 309
Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
