Non-lesional epilepsy does not necessarily convey poor outcomes after invasive monitoring followed by resection or thermal ablation.

OBJECTIVE: We aimed to compare outcomes including seizure-free status at the last follow-up in adult patients with medically refractory focal epilepsy identified as lesional vs. non-lesional based on their magnetic resonance imaging (MRI) findings who underwent invasive evaluation followed by subsequent resection or thermal ablation (LiTT). METHODS: We identified 88 adult patients who underwent intracranial monitoring between 2014 and 2021. Of those, 40 received resection or LiTT, and they were dichotomized based on MRI findings, as lesional (N = 28) and non-lesional (N = 12). Patient demographics, seizure characteristics, non-invasive interventions, intracranial monitoring, and surgical variables were compared between the groups. Postsurgical seizure outcome at the last follow-up was rated according to the Engel classification, and postoperative seizure freedom was determined by Kaplan-Meyer survival analysis. Statistical analyses employed Fisher's exact test to compare categorical variables, while a t-test was used for continuous variables. RESULTS: There were no differences in baseline characteristics between groups except for more often noted PET abnormality in the lesional group (p = 0.0003). 64% of the lesional group and 57% of the non-lesional group received surgical resection or LiTT (p = 0.78). At the last follow-up, 78.5% of the patients with lesional MRI findings achieved Engel I outcomes compared to 66.7% of non-lesional patients (p = 0.45). Kaplan-Meier curves did not show a significant difference in seizure-free duration between both groups after surgical intervention (p = 0.49). SIGNIFICANCE: In our sample, the absence of lesion on brain MRI was not associated with worse seizure outcomes in adult patients who underwent invasive intracranial monitoring followed by resection or thermal ablation.

Postoperative Cerebrospinal Fluid-Related Complications After Posterior Fossa and Posterolateral Skull Base Surgeries: Development of a Predictive Model and Clinical Risk Score.

BACKGROUND: Postoperative pseudomeningocele (PMC) and cerebrospinal fluid (CSF) leak are common complications following posterior fossa and posterolateral skull base surgeries. We sought to 1) determine the rate of CSF-related complications and 2) develop a perioperative model and risk score to identify the highest risk patients for these events. METHODS: We performed a retrospective cohort of 450 patients undergoing posterior fossa and posterolateral skull base procedures from 2016 to 2020. Logistic regressions were performed for predictor selection for 3 prespecified models: 1) a priori variables, 2) predictors selected by large effect sizes, and 3) predictors with P ≤ 0.100 on univariable analysis. A final model was created by elimination of nonsignificant predictors, and the integer-based postoperative CSF-related complications (POCC) clinical risk score was derived. Internal validation was done using 10-fold cross-validation and bootstrapping with uniform shrinkage. RESULTS: A total of 115 patients (25.6%) developed PMC and/or CSF leakage. Age >55 years (odds ratio [OR], 0.560; 95% confidence interval [CI], 0.328-0.954), body mass index >30 kg/m2 (OR, 1.88; 95% CI, 1.14-3.10), and postoperative CSF diversion (OR, 2.85; 95% CI, 1.64-5.00) were associated with CSF leak and PMC. Model 2 was the most predictive (cross-validated area under the receiver operating characteristic curve, 0.690). The final risk score was devised using age, body mass index class, dural repair technique, use of bone substitute, and duration of postoperative CSF diversion. The POCC score performed well (cross-validated area under the receiver operating characteristic curve, 0.761) and was highly specific (96.1%). CONCLUSIONS: We created the first generalizable and predictive risk score to identify patients at risk of CSF-related complications. The POCC score could improve surveillance, inform doctor-patient discussions regarding the risks of surgery, and assist in perioperative management.

Understanding the Effect of Prescription Isodose in Single-Fraction Stereotactic Radiosurgery on Plan Quality and Clinical Outcomes for Solid Brain Metastases.

BACKGROUND AND OBJECTIVES: There is wide variation in treatment planning strategy for central nervous system (CNS) stereotactic radiosurgery. We sought to understand what relationships exist between intratumor maximum dose and local control (LC) or CNS toxicity, and dosimetric effects of constraining hotspots on plan quality of multiple metastases volumetric modulated arc therapy radiosurgery plans. METHODS: We captured brain metastases from 2015 to 2017 treated with single-isocenter volumetric modulated arc therapy radiosurgery. Included tumors received single-fraction stereotactic radiosurgery, had no previous surgery or radiation, and available follow-up imaging. Our criterion for local failure was 25% increase in tumor diameter on follow-up MRI or pathologic confirmation of tumor recurrence. We defined significant CNS toxicity as Radiation Therapy Oncology Group irreversible Grade 3 or higher. We performed univariate and multivariate analyses evaluating factors affecting LC. We examined 10 stereotactic radiosurgery plans with prescriptions of 18 Gy to all targets originally planned without constraints on the maximum dose within the tumor. We replanned each with a constraint of Dmax 120%. We compared V50%, mean brain dose, and Dmax between plans. RESULTS: Five hundred and thirty tumors in 116 patients were available for analysis. Median prescription dose was 18 Gy, and median prescription isodose line (IDL) was 73%. Kaplan-Meier estimate of 12-month LC only tumor volume (HR 1.43 [1.22-1.68] P < .001) was predictive of local failure on univariate analysis; prescription IDL and histology were not. In multivariate analysis, tumor volume impacted local failure (HR 1.43 [1.22-1.69] P < .001) but prescription IDL did not (HR 0.95 [0.86-1.05] P = .288). Only a single grade 3 and 2 grade 4 toxicities were observed; tumor volume was predictive of CNS toxicity (HR 1.58 [1.25-2.00]; P < .001), whereas prescription IDL was not (HR 1.01 [0.87-1.17] P = .940). CONCLUSION: The prescription isodose line had no impact on local tumor control or CNS toxicity. Penalizing radiosurgery hotspots resulted in worse radiosurgery plans with poorer gradient. Limiting maximum dose in gross tumor causes increased collateral exposure to surrounding tissue and should be avoided.

Commissioning and clinical evaluation of the IDENTIFYTM surface imaging system for frameless stereotactic radiosurgery.

PURPOSE: To commission and assess the clinical performance of a new commercial surface imaging (SI) system by analyzing intra-fraction motion from the initial cohort of patients treated with frameless stereotactic radiosurgery (fSRS). METHODS: The IDENTIFYTM SI system was commissioned for clinical use on an Edge (Varian Medical Systems, Palo Alto, CA) linear accelerator. All patients who received intracranial radiotherapy with HyperArcTM (Varian Medical Systems, Palo Alto, CA) were immobilized with the EncompassTM (Qfix, Avondale, PA) thermoplastic mask and monitored for intra-fraction motion with SI. IDENTIFYTM log files were correlated with trajectory log files to correlate treatment parameters with SI-reported offsets. IDENTIFYTM reported offsets were correlated with gantry and couch angles to assess system performance for obstructed and clear camera field of view. Data were stratified by race to evaluate performance differences due to skin tone. RESULTS: All commissioning data were found to meet recommended tolerances. IDENTIFYTM was used to monitor intra-fraction motion on 1164 fractions from 386 patients. The median magnitude of translational SI reported offsets at the end of treatment was 0.27 mm. SI reported offsets were shown to increase when camera pods are blocked by the gantry with larger increases seen at non-zero couch angles. With camera obstruction, the median magnitude of the SI reported offset was 0.50 and 0.80 mm for White and Black patients, respectively. CONCLUSIONS: IDENTIFYTM performance during fSRS is comparable to other commercially available SI systems where offsets are shown to increase at non-zero couch angles and during camera pod blockage.

Pro-Ictal State in Human Temporal Lobe Epilepsy.

Pro-Ictal State in Human Temporal Lobe EpilepsyThe presence of pathologic pro-ictal states among a plethora of otherwise physiologic (e.g., sleep-wake cycle) states has not been established. In this series of 15 temporal lobe epilepsy patients, 1800 patient-hours of continuous thalamocortical electroencephalography data were analyzed. Distinct pro-ictal states were detected in each participant.

Forecasting seizure clusters from chronic ambulatory electrocorticography.

Seizure clusters are seizures that occur in rapid succession during periods of heightened seizure risk and are associated with substantial morbidity and sudden unexpected death in epilepsy. The objective of this feasibility study was to evaluate the performance of a novel seizure cluster forecasting algorithm. Chronic ambulatory electrocorticography recorded over an average of 38 months in 10 subjects with drug-resistant epilepsies was analyzed pseudoprospectively by dividing data into training (first 85%) and validation periods. For each subject, the probability of seizure clustering, derived from the Kolmogorov-Smirnov statistic using a novel algorithm, was forecasted in the validation period using individualized autoregressive models that were optimized from training data. The primary outcome of this study was the mean absolute scaled error (MASE) of 1-day horizon forecasts. From 10 subjects, 394 ± 142 (mean ± SD) electrocorticography-based seizure events were extracted for analysis, representing a span of 38 ± 27 months of recording. MASE across all subjects was .74 ± .09, .78 ± .09, and .83 ± .07 at .5-, 1-, and 2-day horizons. The feasibility study demonstrates that seizure clusters are quasiperiodic and can be forecasted to clinically meaningful horizons. Pending validation in larger cohorts, the forecasting approach described herein may herald chronotherapy during imminent heightened seizure vulnerability.

An unusual cause of shunt failure requiring multidisciplinary treatment.

Rarer etiologies of shunt malfunction may be difficult to detect, can present insidiously, and often require a multidisciplinary approach to safely and effectively address.

Control and Toxicity in Melanoma Versus Other Brain Metastases in Response to Combined Radiosurgery and PD-(L)1 Immune Checkpoint Inhibition.

PURPOSE: Prior studies have mixed conclusions about the efficacy and central nervous system (CNS) toxicity profile of combining radiosurgery with anti-programed cell death 1 (PD-1) immune checkpoint inhibition (ICI) for brain metastases. This study evaluates the safety and efficacy of combined radiosurgery and anti-PD-1 ICI for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) brain metastases (BM). METHODS AND MATERIALS: Forty-one patients with 153 radiation naïve melanoma BM and 33 patients with 118 BM of NSCLC and RCC origin from 2014 through 2019 received radiosurgery and either anti PD-1 receptor inhibition or anti PD-L1 inhibition targeting the PD-1 ligand with less than 4 months separating either therapy. Similar to Radiation Therapy Oncology Group 9005, high-grade CNS toxicity was defined as irreversible grade 3 or any grade 4/5 neurologic event. Salvage resection revealing necrosis and viable tumor was considered grade 4 toxicity and local failure. An increase in greatest cross-sectional diameter of 25% on contrasted magnetic resonance imaging was designated as a local failure. RESULTS: Median follow-up was 10 months (range, 1-41 months). Local control was estimated to be 90.3% at 1 year. Distant control was 38.8% at 1 year, and neither local nor distant control were significantly influenced by limiting steroids to the day of treatment (P = .55, .52 respectively). One-year freedom from high-grade toxicity was 90.4% for patients and 94.6% for tumors. Though melanoma accounted for 41 (55%) patients and 153 (56%) tumors, it accounted for all high-grade toxicities (P = .03). These patients had some combination of high tumor burden, aggressive steroid taper, and treatment with ipilimumab. CONCLUSIONS: Stereotactic radiosurgery combined with anti-PD-1 ICI appears to result in a high rate of local tumor control and a low rate of high-grade CNS toxicity, comparable to historical series with radiosurgery alone. High-grade toxicity is more likely in melanoma than RCC and NSCLC. Coming prospective studies will shed light on further questions about treatment timing, steroids, and response.

Transition From Manual to Automated Planning and Delivery of Volumetric Modulated Arc Therapy Stereotactic Radiosurgery: Clinical, Dosimetric, and Quality Assurance Results.

PURPOSE: Properly planned single isocenter volumetric modulated arc therapy (VMAT) radiosurgery plans exhibit high quality and efficiency. We report here the largest clinical experience to date, to our knowledge, comparing manual planning with a new automated platform designed to standardize and simplify radiosurgery planning and delivery processes. METHODS: We treated 693 patients with single isocenter VMAT radiosurgical plans generated by either our conventional manual (mVMAT) or a recently implemented automated (HyperArcTM) technique. All plans targeted the gross tumor volume without margin. Radiochromic film was used for patient-specific quality assurance (PSQA). We evaluated local control and toxicity data for a subgroup of 107 patients having 377 metastatic tumors that were treated with HyperArc. RESULTS: The median Radiation Therapy Oncology Group (RTOG) conformity index was 1.14 and was not different between the 2 techniques. The median Paddick gradient index was 5.42 for HyperArc versus 7.09 for mVMAT (P < .001). The median mean brain doses were 4.6% and 5.1% for HyperArc and mVMAT, respectively (P = .04). The PSQA for both techniques met clinical criteria, but 97% of the HyperArc plans satisfied the gamma tolerance limit recommended by the American Association of Physicists in Medicine Task Group No. 218, compared with 94% of the mVMAT plans (P = .02). The median treatment-planning times were not significantly different. The median treatment times were 10.5 and 11.4 minutes for HyperArc and mVMAT, respectively (P < .001). The Kaplan-Meier estimate of local control was 90.1% at 1 year. CONCLUSIONS: HyperArc produces high-quality radiosurgical plans that are at least as good as mVMAT plans created by an expert manual planner with easier planning and more efficient delivery workflow. A less experienced planner can produce very high-quality radiosurgical plans even for patients with more than 10 targets. The use of a single-isocenter technique for multiple targets with no PTV margin did not compromise clinical outcomes, and 1-year local control for treated targets remained congruent with historical series.

An Expedited Intracranial Pressure Monitoring Protocol Following Spontaneous CSF Leak Repair.

OBJECTIVE: Spontaneous cerebrospinal fluid (CSF) leaks represent a unique subset of skull base pathology and require distinctive management. Perioperative evaluation and management of intracranial hypertension are essential in preventing further erosion of the skull base and development of recurrent leak. The objective of this study is to evaluate the safety and utility of an expedited protocol for recording and managing intracranial hypertension following endoscopic repair of spontaneous CSF leaks. METHODS: Prospectively collected data was reviewed in patients undergoing endoscopic repair of spontaneous CSF leaks between January 2017 and March 2020. A standard intracranial pressure monitoring protocol was compared to an expedited protocol (EP), and data regarding the two groups was compared for leak location, short-term success of skull base repair, complications, hospital length of stay, and cost-based analysis. RESULTS: Fifty-five patients (standard protocol, n = 28 vs. EP, n = 27) were included in the study. Leak location was similar between cohorts, with the lateral recess being the most common locations in both groups (37.9% vs. 40.6%; P = .90). Postoperative complications (3.6% vs. 7.4%; P = .53) and ventriculoperitoneal shunt rate (32.1% vs. 22.2%; P = .41) were similar among cohorts. There was no difference in lumbar drain complications (0% vs. 7.4%; P = .14) or recurrent leak (7.1% vs. 0%; P = .16). Length of stay was shorter in the EP group [median(interquartile range): 3(1) vs. 2 (1); P < .01]. Total hospital charges were similar between groups (median (USD/$1,000): 83.57 ± 49.58 vs. 83.93 ± 46.11; P = .18). CONCLUSION: An expedited monitoring protocol shortened hospital stay without increased risk of complications. LEVEL OF EVIDENCE: III Laryngoscope, 131:E408-E412, 2021.

THE NOVEL USE OF STEREOTACTIC RADIOTHERAPY FOR REMNANT ADRENAL TISSUE IN NELSON SYNDROME.

OBJECTIVE: Recurrent Cushing disease (CD) is a rare complication that occurs in patients who have undergone bilateral adrenalectomy (BLA). We report a case of recurrent CD in a patient with Nelson syndrome and adrenalectomy due to remnant adrenal tissue, and a novel treatment strategy using stereotactic body radiation therapy (SBRT) to the adrenal glands. METHODS: We report a case of recurrent CD in a woman with Nelson syndrome and adrenalectomy and describe her clinical course and management. We also include a literature review of CD management and adrenal radiation. RESULTS: The patient had persistent pituitary CD despite pituitary surgery and radiosurgery and underwent BLA. She developed recurrent CD due to a remnant adrenal gland post adrenalectomy. She then underwent SBRT to both adrenal beds to treat the remnant adrenal tissue. Her serum cortisol dropped rapidly after adrenal radiation and she experienced minimal side effects. She has been in remission for over 2 years. CONCLUSION: This is the first reported case of recurrent CD in a patient post adrenalectomy that was successfully treated with SBRT to the remnant adrenal tissue.

Surface guided imaging during stereotactic radiosurgery with automated delivery.

PURPOSE: To report on the use of surface guided imaging during frameless intracranial stereotactic radiotherapy with automated delivery via HyperArcTM (Varian Medical Systems, Palo Alto, CA). METHODS: All patients received intracranial radiotherapy with HyperArcTM and were monitored for intrafraction motion by the AlignRT® (VisionRT, London, UK) surface imaging (SI) system. Immobilization was with the EncompassTM (Qfix, Avondale, PA) aquaplast mask device. AlignRT® log files were correlated with trajectory log files to correlate treatment parameters with SI reported offsets. SI reported offsets were correlated with gantry angle and analyzed for performance issues at non-zero couch angles and during camera-pod blockage during gantry motion. Demographics in the treatment management system were used to identify race and determine if differences in SI reported offsets are due to skin tone settings. RESULTS: A total of 981 fractions were monitored over 14 months and 819 were analyzed. The median AlignRT® reported motion from beginning to the end of treatment was 0.24 mm. The median offset before beam on at non-zero couch angles was 0.55 mm. During gantry motion when camera pods are blocked, the median magnitude was below 1 mm. Median magnitude of offsets at non-zero couch angles was not found to be significantly different for patients stratified by race. CONCLUSIONS: Surface image guidance is a viable alternative to scheduled mid-treatment imaging for monitoring intrafraction motion during stereotactic radiosurgery with automated delivery.

Systematic review of anterior congenital cephaloceles: open vs endoscopic repair.

BACKGROUND: Anterior cephaloceles are rare congenital malformations that have historically been corrected via open approaches. Although the advent of endoscopic endonasal surgery has provided a minimally invasive and theoretically less morbid approach to the anterior skull base, whether endoscopic approaches provide superior treatment outcomes to open techniques has yet to be elucidated. The objective of this study was to systematically review the available literature regarding presentation and outcomes of open vs endoscopic repair of congenital anterior cephaloceles. METHODS: A systematic review of the PubMed, Embase, CINAHL, and Cochrane databases was performed on January 15, 2020, to identify studies from the past 50 years reporting cases of congenital anterior cephaloceles. Data on gender, age at operation, imaging modality, cephalocele location, operative approach, and intra- and postoperative complications were collected. RESULTS: Nonduplicated data (153 articles) consisted of 781 patients with congenital anterior encephaloceles. Surgical outcomes were reported in 349 patients (222 open approaches, 127 endoscopic approaches), with an average age of 4.6 years. There was a 1.3:1 male-to-female ratio. Clinical presentation included nasal obstruction (n = 154), hypertelorism (n = 106), and cleft lip/palate (n = 100). Defects were classified as sincipital (n = 479) or basal (n = 257), with 45 patients broadly classified as anterior. The number of complications experienced per operation was 0.13 for endoscopic and 0.44 for open approaches (p < 0.0001). Mortality was significantly lower for the endoscopic group compared with patients treated with open surgery (0.008 vs 0.05, p < 0.05). CONCLUSION: Endoscopic repair of congenital anterior cephaloceles resulted in decreased postoperative complications and mortality compared with open approaches. ©2020 ARSAAOA, LLC.

Anticoagulant Medications and Operative Subdural Hematomas: A Retrospective Cohort Study Evaluating Reoperation Rates.

BACKGROUND: Anticoagulant therapy is common and complicates the operative management of acute and mixed-density subdural hematomas (SDHs). The risk of reoperation inferred by anticoagulant (AC) medication and the ability of reversal agents to reduce hemorrhagic complications in patients presenting with AC-associated SDHs are not fully understood. METHODS: Data were collected for 288 consecutive patients treated with craniotomy or craniectomy for evacuation of an acute or mixed-density SDH between 2012 and 2017 at 2 academic institutions. Primary end points were reoperation within 30 days and functional outcome at discharge. Groups were compared based on AC use. Logistic regression models were used to identify predictors of reoperation and functional outcome at discharge. RESULTS: Forty-six patients on ACs and 242 with no AC history were analyzed. All patients on AC underwent AC reversal before hematoma evacuation. Reoperation rates between groups were not significantly different (10.9% vs. 12.4%; P = 1.00); however, time to reoperation was significantly shorter in those on ACs (0.8 ± 1.1 days vs. 6.8 ± 10.4 days; P = 0.04). Aspirin use was independently associated with the need for reoperation (odds ratio, 3.05; confidence interval, 1.30-7.19; P = 0.01). Patients taking ACs were significantly older, had more medical comorbidities and were more likely to have a higher modified Rankin Scale score at discharge. CONCLUSIONS: Anticoagulant use was not associated with an increased reoperation rate, suggesting that reversal of AC may have eliminated the hemorrhagic risk conferred by these medications. Patients on ACs were significantly older, harbored more medical comorbidities, and had a worse functional outcome at discharge.

Preoperative radiographic and clinical factors associated with the visualization of intraoperative cerebrospinal fluid during endoscopic transsphenoidal resection of pituitary adenomas.

BACKGROUND: Intraoperative visualization of cerebrospinal fluid (CSF) during endoscopic endonasal resection of skull base tumors is the most common factor contributing to the development of postoperative CSF leaks. No previous studies have solely evaluated preoperative factors contributing to intraoperative CSF visualization. The purpose of this study was to identify preoperative factors predictive of intraoperative CSF visualization. METHODS: Retrospective review of patients who underwent transsphenoidal resection of pituitary adenomas was conducted. Clinical and radiographic variables were compared for those who had CSF visualized to those who did not. Nominal logistic regression models were built to determine predictive variables. RESULTS: Two hundred and sixty patients were included in the study. All significant demographic and radiographic variables on univariate analysis were included in multivariate analysis. Two multivariate models were built, as tumor height and supraclinoid extension were collinear. The first model, which considered tumor height, found that extension into the third ventricle carried a 4.60-fold greater risk of CSF visualization (P = 0.005). Increasing tumor height showed a stepwise, linear increase in risk; tumors >3 cm carried a 19.02-fold greater risk of CSF visualization (P = 0.003). The second model, which considered supraclinoid tumor extension, demonstrated that extension into the third ventricle carried a 4.38-fold increase in risk for CSF visualization (P = 0.010). Supraclinoid extension showed a stepwise, linear increase in intraoperative CSF risk; tumors with >2 cm of extension carried a 9.26-fold increase in risk (P = 0.017). CONCLUSION: Our findings demonstrate that tumor height, extension into the third ventricle, and extension above the clinoids are predictive of intraoperative CSF visualization.

Robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy: implantation technique and complications in the first 24 patients.

OBJECTIVE: Despite numerous imaging studies highlighting the importance of the thalamus in a patient's surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE). METHODS: After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study. The trajectory of one electrode planned for clinical sampling of the operculoinsular cortex was modified to extend it to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior nucleus of the thalamus (ANT) (n = 13) and the medial group of thalamic nuclei (MED) (n = 11), including the mediodorsal and centromedian nuclei, were targeted. The postimplantation CT scan was coregistered to the preoperative MR image, and Morel's thalamic atlas was used to confirm the accuracy of implantation. RESULTS: Ten (77%) of 13 patients in the ANT group and 10 (91%) of 11 patients in the MED group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical-level entry site were noted in 20.8% of patients, who did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from those of the MED group at the entry point-i.e., the precentral gyrus in the former and the postcentral gyrus in the latter. CONCLUSIONS: Using judiciously planned robot-assisted SEEG, the authors demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes or compromising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

Focal Management of Large Brain Metastases and Risk of Leptomeningeal Disease.

PURPOSE: Surgery is often used for large or symptomatic brain metastases but is associated with risk of developing leptomeningeal dissemination. Emerging data suggest that fractionated stereotactic radiation therapy (FSRT) is an effective management strategy in large brain metastases. We sought to retrospectively compare leptomeningeal disease (LMD) and local control (LC) rates for patients treated with surgical resection followed by radiosurgery (S + SRS) versus FSRT alone. METHODS AND MATERIALS: We identified all patients with a brain metastasis ≥3 cm in diameter treated from 2004 to 2017 with S + SRS or FSRT alone (25 or 30 Gy in 5 fractions) who had follow-up imaging. LMD was defined as focal or diffuse leptomeningeal enhancement that was >5 mm from the index metastasis. Categorical baseline characteristics were compared with the χ2 test. LMD and LC rates were evaluated by the Kaplan-Meier (KM) method, with the log-rank test used to compare subgroups. RESULTS: A total of 125 patients were identified, including 82 and 43 in the S + SRS and FSRT alone groups, respectively. Median pretreatment Graded Prognostic Assessment in the S + SRS and FSRT groups was 2.5 and 1.5, respectively (P < .001). Median follow-up was 7 months. The KM estimate of 12-month LMD rate in the S + SRS and FSRT groups was 45% and 19%, respectively (P = .048). The KM estimate of 12-month local control in the S + SRS and FSRT groups was 70% and 69%, respectively (P = .753). The 12-month KM estimate of grade ≥3 toxicity was 1.4% in S + SRS group versus 6.3% in the FSRT alone group (P = .248). After adjusting for graded prognostic assessment (GPA), no overall survival difference was observed between groups (P = .257). CONCLUSIONS: Surgery is appropriate for certain brain metastases, but S + SRS may increase LMD risk compared with FSRT alone. Because S + SRS and FSRT seem to have similar LC, FSRT may be a viable alternative to S + SRS in select patients with large brain metastases.

Optimizing therapies for neurobehavioral comorbidities of epilepsy using chronic ambulatory electrocorticography.

There is an unmet need to improve therapy for neuropsychiatric comorbidities that are highly prevalent in persons with epilepsy (PWE). However, diagnosing and monitoring the neurobehavioral symptoms is challenging as their presentation can overlap with seizures. In this retrospective study, we report the advantage of chronic ambulatory electrocorticography (ECoG) from implanted Responsive Neurostimulator System (RNS®) in characterizing these psychosomatic paroxysms as a possible ictal, postictal, or interictal phenomenon and how the diagnosis guided the therapy choices. Five out of 21 patients with RNS had neuropsychiatric symptoms (panic attack, psychosis, conversion, and somatization disorders) that overlapped with their seizure semiology and were found to benefit from the use of RNS ECoG data by timely diagnosing and titrating targeted therapies. The cases illustrate the use of RNS ECoG data in diagnosing and improving the management of comorbidities in PWE. The ability to access RNS ECoG data and correlate it with patient symptoms is unique among available therapeutic options for PWE.