An Initial Cost-Effectiveness Analysis of Magnetic Resonance-Guided Laser Interstitial Thermal Therapy in Pediatric Epilepsy Surgery.

INTRODUCTION: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a new technology that provides a clinically efficacious and minimally invasive alternative to conventional microsurgical resection. However, little data exist on how costs compare to traditional open surgery. The goal of this paper is to investigate the cost-effectiveness of MRgLITT in the treatment of pediatric epilepsy. METHODS: We retrospectively analyzed the medical records of pediatric patients who underwent MRgLITT via the Visualase® thermal therapy system (Medtronic, Inc., Minneapolis, MN, USA) between December 2013 and September 2017. Direct costs associated with preoperative, operative, and follow-up care were extracted. Benefit was calculated in quality-adjusted life years (QALYs), and the cost-effectiveness was derived from the discounted total direct costs over QALY. Sensitivity analysis on 4 variables was utilized to assess the validity of our results. RESULTS: Twelve consecutive pediatric patients with medically refractory epilepsy underwent MRgLITT procedures. At the last postoperative follow-up, 8 patients were seizure free (Engel I, 66.7%), 2 demonstrated significant improvement (Engel II, 16.7%), and 2 patients showed worthwhile improvement (Engel III, 16.7%). The average cumulative discounted QALY was 2.11 over the lifetime of a patient. Adjusting for inflation, MRgLITT procedures had a cost-effectiveness of USD 22,211 per QALY. Our sensitivity analysis of cost variables is robust and supports the procedure to be cost--effective. CONCLUSION: Our data suggests that MRgLITT may be a cost-effective alternative to traditional surgical resection in pediatric epilepsy surgery.

Is the use of Stereotactic Electroencephalography Safe and Effective in Children? A Meta-Analysis of the use of Stereotactic Electroencephalography in Comparison to Subdural Grids for Invasive Epilepsy Monitoring in Pediatric Subjects.

BACKGROUND: Stereoelectroencephalography (SEEG) is an alternative addition to subdural grids (SDG) in invasive extra-operative monitoring for medically refractory epilepsy. Few studies exist on the clinical efficacy and safety of these techniques in pediatric populations. OBJECTIVE: To provide a comparative quantitative summary of surgical complications and postoperative seizure freedom associated with invasive extra-operative presurgical techniques in pediatric patients. METHODS: The systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A literature search was conducted utilizing Ovid Medline, Embase, Pubmed, and the Cochrane database. RESULTS: Fourteen papers with a total of 697 pediatric patients undergoing invasive SDG monitoring and 9 papers with a total of 277 pediatric patients undergoing SEEG monitoring were utilized in the systemic review. Cerebral spinal fluid (CSF) leaks were the most common adverse event in the SDG studies (pooled prevalence 11.9% 95% confidence interval [CI] 5.7-23.3). There was one case of CSF leak in the SEEG studies. Intracranial hemorrhages (SDG: 10.7%, 95% CI 5.3-20.3; SEEG: 2.9%, 95% CI -0.7 to 10.8) and infection (SDG: 10.8%, 95% CI 6.7-17) were more common in the SDG studies reviewed. At the time of the last postoperative visit, a greater percentage of pediatric patients achieved seizure freedom in the SEEG studies (SEEG: 66.5%, 95% CI 58.8-73.4; SDG: 52.1%, 95% CI 43.0-61.1). CONCLUSION: SEEG is a safe alternative to SDG and should be considered on an individual basis for selected pediatric patients.

MR-Guided Laser Interstitial Thermal Therapy for Medically Refractory Lesional Epilepsy in Pediatric Patients: Experience and Outcomes.

INTRODUCTION: MR-guided laser interstitial thermal therapy (MRgLITT) has emerged as a safe and effective treatment option for the ablation of epileptic foci. Its minimally invasive nature makes it attractive due to decreased morbidity and hospital stay. OBJECTIVE: To report the efficacy and safety of MRgLITT as a minimally invasive procedure for the ablation of epileptic foci in the pediatric population of medically refractory lesional epilepsy. METHODS: A retrospective review of patients who underwent MRgLITT via Visualase laser ablation at a single pediatric center was performed. Demographic and outcome data were compiled and analyzed. RESULTS: Twelve pediatric patients with a total 18 lesions underwent MRgLITT procedures between December 2013 and September 2017. Mean age at surgery was 11.1 years. Surgical substrates included 4 hypothalamic hamartomas, 3 periventricular heterotopias, 2 deep focal cortical dysplasias, 2 tuberous sclerosis, and 1 mesial temporal sclerosis. Methods of stereotaxis used included Leksell frame, BrainLab VarioGuide, ROSA robot guidance, and ClearPoint navigation. Mean procedure length was 250 min, and mean length of stay was 1.3 days. After treatment, 8 patients were seizure free (Engel I, 66.7%), 2 patients demonstrated significant improvement (Engel II, 16.7%), and 2 patients showed worthwhile improvement (Engel III, 16.7%). One patient developed a left superior quadrantanopsia postoperatively. Mean follow-up duration was 10 months. CONCLUSION: This study contributes to the sparse literature in this field by demonstrating the high efficacy and low morbidity of MRgLITT as a minimally invasive method of ablation of epileptic foci in the pediatric population of medically refractory lesional epilepsy.

An initial cost-effectiveness analysis of intraoperative magnetic resonance imaging (iMRI) in pediatric epilepsy surgery.

PURPOSE: Previous studies have illustrated the clinical utility of the addition of intraoperative magnetic resonance imaging (iMRI) to conventional microsurgical resection. While iMRI requires initial capital cost investment, long-term reduction in costly follow-up management and reoperation costs may prove economically efficacious. The objective of this study is to investigate the cost-effectiveness of the addition of iMRI utilization versus conventional microsurgical techniques in focal cortical dysplasia (FCD) resection in pediatric patients with medically refractory epilepsy. METHODS: We retrospectively reviewed the medical records of pediatric subjects who underwent surgical resection of FCD at the Children's National Health System between March 2005 and April 2015. Patients were assigned to one of three cohorts: iMRI-assisted resection, conventional resection with iMRI-assisted reoperation, or conventional resection. Direct costs included preoperative, operative, postoperative, long-term follow-up, and antiepileptic drug (AED) costs. The cost-effectiveness was calculated as the sum total of all direct medical costs over the quality-adjusted life years (QALYs). We also performed sensitivity analysis on numerous variables to assess the validity of our results. RESULTS: Fifty-six consecutive pediatric patients underwent resective surgery for medically intractable FCD. Ten patients underwent iMRI-assisted resection; 7 underwent conventional resection followed by iMRI-assisted reoperation; 39 patients underwent conventional microsurgical resection. Taken over the lifetime of the patient, the cumulative discounted QALY of patients in the iMRI-assisted resection cohort was about 2.91 years, versus 2.61 years in the conventional resection with iMRI-assisted reoperation cohort, and 1.76 years for the conventional resection cohort. Adjusting for inflation, iMRI-assisted surgeries have a cost-effectiveness ratio of $16,179 per QALY, versus $28,514 per QALY for the conventional resection with iMRI-assisted reoperation cohort, and $49,960 per QALY for the conventional resection cohort. Sensitivity analysis demonstrated that no one single variable significantly altered cost-effectiveness across all three cohorts compared to the baseline results. CONCLUSION: The addition of iMRI to conventional microsurgical techniques for resection of FCD in pediatric patients with intractable epilepsy resulted in increased seizure freedom and reduction in long-term direct medical costs compared to conventional surgeries. Our data suggests that iMRI may be a cost-effective addition to the surgical armamentarium for epilepsy surgery.

Repeat surgery for focal cortical dysplasias in children: indications and outcomes.

OBJECTIVE Focal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy that often may be treated by surgery. Following resection, many patients continue to experience seizures, necessitating a decision for further surgery to achieve the desired seizure outcomes. Few studies exist on the efficacy of reoperation for intractable epilepsy due to FCD in pediatric cohorts, including the definition of prognostic factors correlated with clinical benefit from further resection. METHODS The authors retrospectively analyzed the medical records and MR images of 22 consecutive pediatric patients who underwent repeat FCD resection after unsuccessful first surgery at the Children's National Health System between March 2005 and April 2015. RESULTS Accounting for all reoperations, 13 (59%) of the 22 patients achieved complete seizure freedom and another 5 patients (23%) achieved significant improvement in seizure control. Univariate analysis demonstrated that concordance in electrocorticography (ECoG) and MRI localization (p = 0.005), and completeness of resection (p = 0.0001), were associated with seizure freedom after the first reoperation. Patients with discordant ECoG and MRI findings ultimately benefited from aggressive multilobe lobectomy or hemispherectomy. Repeat lesionectomies utilizing intraoperative MRI (iMRI; n = 9) achieved complete resection and seizure freedom in all cases. CONCLUSIONS Reoperation may be clinically beneficial in patients with intractable epilepsy due to FCD. Patients with concordant intraoperative ECoG and MRI localization may benefit from extended resection of residual dysplasia at the margins of the previous lesional cavity, and iMRI may offer benefits as a quality control mechanism to ensure that a complete resection has been accomplished. Patients with discordant findings may benefit from more aggressive resections at earlier stages to achieve better seizure control and ensure functional plasticity.

Resective surgery for focal cortical dysplasia in children: a comparative analysis of the utility of intraoperative magnetic resonance imaging (iMRI).

PURPOSE: Seizure freedom following resection of focal cortical dysplasia (FCD) correlates with complete resection of the dysplastic cortical tissue. However, difficulty with intraoperative identification of the lesion may limit the ability to achieve the surgical objective of complete extirpation of these lesions. Intraoperative magnetic resonance imaging (iMRI) may aid in FCD resections. The objective of this study is to compare rates of postoperative seizure freedom, completeness of resection, and need for reoperation in patients undergoing iMRI-assisted FCD resection versus conventional surgical techniques. METHODS: We retrospectively reviewed the medical records of pediatric subjects who underwent surgical resection of FCD at Children's National Medical Center between March 2005 and April 2015. RESULTS: At the time of the last postoperative follow-up, 11 of the 12 patients (92 %) in the iMRI resection group were seizure free (Engel Class I), compared to 14 of the 42 patients (33 %) in the control resection group (p = 0.0005). All 12 of the iMRI patients (100 %) achieved complete resection, compared to 24 of 42 patients (57 %) in the control group (p = 0.01). One (8 %) patient from the iMRI-assisted resection group has required reoperation, compared to 17 (40 %) patients in the control resection group. CONCLUSION: Our results suggest that the utilization of iMRI during surgery for resection of FCD results in improved postoperative seizure freedom, completeness of lesion resection, and reduction in the need for reoperation.

The role of intraoperative MRI in resective epilepsy surgery for peri-eloquent cortex cortical dysplasias and heterotopias in pediatric patients.

OBJECTIVE: Previous studies have demonstrated that an important factor in seizure freedom following surgery for lesional epilepsy in the peri-eloquent cortex is completeness of resection. However, aggressive resection of epileptic tissue localized to this region must be balanced with the competing objective of retaining postoperative neurological functioning. The objective of this study was to investigate the role of intraoperative MRI (iMRI) as a complement to existing epilepsy protocol techniques and to compare rates of seizure freedom and neurological deficit in pediatric patients undergoing resection of perieloquent lesions. METHODS: The authors retrospectively reviewed the medical records of pediatric patients who underwent resection of focal cortical dysplasia (FCD) or heterotopia localized to eloquent cortex regions at the Children's National Health System between March 2005 and August 2015. Patients were grouped into two categories depending on whether they underwent conventional resection (n = 18) or iMRI-assisted resection (n = 11). Patient records were reviewed for factors including demographics, length of hospitalization, postoperative seizure freedom, postoperative neurological deficit, and need for reoperation. Postsurgical seizure outcome was assessed at the last postoperative follow-up evaluation using the Engel Epilepsy Surgery Outcome Scale. RESULTS: At the time of the last postoperative follow-up examination, 9 (82%) of the 11 patients in the iMRI resection group were seizure free (Engel Class I), compared with 7 (39%) of the 18 patients in the control resection group (p = 0.05). Ten (91%) of the 11 patients in the iMRI cohort achieved gross-total resection (GTR), compared with 8 (44%) of 18 patients in the conventional resection cohort (p = 0.02). One patient in the iMRI-assisted resection group underwent successful reoperation at a later date for residual dysplasia, compared with 7 patients in the conventional resection cohort (with 2/7 achieving complete resection). Four (36%) of the patients in the iMRI cohort developed postoperative neurological deficits, compared with 15 patients (83%) in the conventional resection cohort (p = 0.02). CONCLUSIONS: These results suggest that in comparison with a conventional surgical protocol and technique for resection of epileptic lesions in peri-eloquent cortex, the incorporation of iMRI led to elevated rates of GTR and postoperative seizure freedom. Furthermore, this study suggests that iMRI-assisted surgeries are associated with a reduction in neurological deficits due to intraoperative damage of eloquent cortex.

Intraoperative MRI-guided resection of focal cortical dysplasia in pediatric patients: technique and outcomes.

OBJECTIVE Previous meta-analysis has demonstrated that the most important factor in seizure freedom following surgery for focal cortical dysplasia (FCD) is completeness of resection. However, intraoperative detection of epileptogenic dysplastic cortical tissue remains a challenge, potentially leading to a partial resection and the need for reoperation. The objective of this study was to determine the role of intraoperative MRI (iMRI) in the intraoperative detection and localization of FCD as well as its impact on surgical decision making, completeness of resection, and seizure control outcomes. METHODS The authors retrospectively reviewed the medical records of pediatric patients who underwent iMRI-assisted resection of FCD at the Children's National Health System between January 2014 and April 2015. Data reviewed included demographics, length of surgery, details of iMRI acquisition, postoperative seizure freedom, and complications. Postsurgical seizure outcome was assessed utilizing the Engel Epilepsy Surgery Outcome Scale. RESULTS Twelve consecutive pediatric patients (8 females and 4 males) underwent iMRI-guided resection of FCD lesions. The mean age at the time of surgery was 8.8 years ± 1.6 years (range 0.7 to 18.8 years), and the mean duration of follow up was 3.5 months ± 1.0 month. The mean age at seizure onset was 2.8 years ± 1.0 year (range birth to 9.0 years). Two patients had Type 1 FCD, 5 patients had Type 2A FCD, 2 patients had Type 2B FCD, and 3 patients had FCD of undetermined classification. iMRI findings impacted intraoperative surgical decision making in 5 (42%) of the 12 patients, who then underwent further exploration of the resection cavity. At the time of the last postoperative follow-up, 11 (92%) of the 12 patients were seizure free (Engel Class I). No patients underwent reoperation following iMRI-guided surgery. CONCLUSIONS iMRI-guided resection of FCD in pediatric patients precluded the need for repeat surgery. Furthermore, it resulted in the achievement of complete resection in all the patients, leading to a high rate of postoperative seizure freedom.

Altered lysosomal positioning affects lysosomal functions in a cellular model of Huntington's disease.

Huntington's disease (HD) is a hereditary and devastating neurodegenerative disorder caused by a mutation in the huntingtin protein. Understanding the functions of normal and mutant huntingtin protein is the key to revealing the pathogenesis of HD and developing therapeutic targets. Huntingtin plays an important role in vesicular and organelle trafficking. Lysosomes are dynamic organelles that integrate several degradative pathways and regulate the activity of mammalian target of rapamycin complex 1 (mTORC1). In the present study, we found that the perinuclear accumulation of lysosomes was increased in a cellular model of HD derived from HD knock-in mice and primary fibroblasts from an HD patient. This perinuclear lysosomal accumulation could be reversed when normal huntingtin was overexpressed in HD cells. When we further investigated the functional significance of the increased perinuclear lysosomal accumulation in HD cells, we demonstrated that basal mTORC1 activity was increased in HD cells. In addition, autophagic influx was also increased in HD cells in response to serum deprivation, which leads to premature fusion of lysosomes with autophagosomes. Taken together, our data suggest that the increased perinuclear accumulation of lysosomes may play an important role in HD pathogenesis by altering lysosomal-dependent functions.