Influence of focused ultrasound on locoregional drug delivery to the brain: Potential implications for brain tumor therapy.

INTRODUCTION: Efficient delivery of therapeutics across the blood-brain barrier (BBB) for the treatment of central nervous system (CNS) tumors is a major challenge to the development of safe and efficacious therapies. Locoregional drug delivery platforms offer an improved therapeutic index by achieving high drug concentrations in the target tissue with negligible systemic exposure. Intrathecal (intraventricular) [IT] and convection-enhanced delivery [CED] are two clinically relevant methods being employed for various CNS malignancies. Both of these standalone platforms suffer from passive post-administration distribution forces, sometimes limiting the desired distribution for tumor therapy. Focused ultrasound and microbubble-mediated blood-brain barrier opening (FUS-BBBO) is a recent modality used for enhanced drug delivery. It is postulated that coupling of FUS with these alternative delivery routes may provide benefits. Multimodality FUS may provide the desired ability to increase the depth of parenchymal delivery following IT administration and provide a means for contour directionality with CED. Further, the transient enhanced permeability achieved with FUS-BBBO is well established, but drug residence and transit times, important to clinical dose scheduling, have not yet been defined. The present investigation comprises two discrete studies: 1. Conduct a comprehensive quantitative evaluation to elucidate the effect of FUS-BBBO as it relates to varying routes of administration (IT and IV) in its capacity to facilitate drug penetration within the striatal-thalamic region. 2. Investigate the impact of combining FUS-BBBO with CED on drug distribution, with a specific focus on the temporal dynamics of drug retention within the target region. METHODS: Firstly, we quantitatively assessed how FUS-BBBO coupled with IT and IV altered fluorescent dye (Dextran 2000 kDa and 70 kDa) distribution and concentration in a predetermined striatal-thalamic region in naïve mice. Secondly, we analyzed the pharmacokinetic effects of using FUS mediated BBB disruption coupled with CED by measuring the volume of distribution and time-dependent concentration of the dye. RESULTS: Our results indicate that IV administration coupled with FUS-BBBO successfully enhances delivery of dye into the pre-defined sonication targets. Conversely, measurable dye in the sonication target was consistently less after IT administration. FUS enhances the distribution volume of dye after CED. Furthermore, a shorter time of residence was observed when CED was coupled with FUS-BBBO application when compared to CED alone. CONCLUSION: 1. Based on our findings, IV delivery coupled with FUS-BBBO is a more efficient means for delivery to deep targets (i.e. striatal-thalamic region) within a predefined spatial conformation compared to IT administration. 2. FUS-BBBO increases the volume of distribution (Vd) of dye after CED administration, but results in a shorter time of residence. Whether this finding is reproducible with other classes of agents (e.g., cytotoxic agents, antibodies, viral particles, cellular therapies) needs to be studied.

Innovations in the Diagnosis and Surgical Management of Low-Grade Gliomas.

Low-grade gliomas are a broad category of tumors that can manifest at different stages of life. As a group, their prognosis has historically been considered to be favorable, and surgery is a mainstay of treatment. Advances in the molecular characterization of individual lesions has led to newer classification systems, a better understanding of the biological behavior of different neoplasms, and the identification of previously unrecognized entities. New prospective genetic and molecular data will help delineate better treatment paradigms and will continue to change the taxonomy of central nervous system tumors in the coming years. Advances in the field of radiomics will help predict the molecular profile of a particular tumor through noninvasive testing. Similarly, more precise methods of intraoperative tumor tissue analysis will aid surgical planning. Improved surgical outcomes propelled by novel surgical techniques and intraoperative adjuncts and emerging forms of medical treatment in the field of immunotherapy have enriched the management of these lesions. We review the contemporary management and innovations in the treatment of low-grade gliomas.

Weighing the Risk Profile of Cervical Spine MRI in Evaluating Pediatric Cervical Spine Injuries.

OBJECTIVE: Screening for cervical spine injury after blunt trauma is common, but there remains varied practice patterns and clinical uncertainty regarding adequate radiographic evaluation. An oft-cited downside of MRI is the added risk compared to CT in the pediatric population; however, these specific risks have not yet been reported. This study examines the risks of cervical spine MRI in pediatric trauma patients in the context of what value MRI adds. METHODS: This was a retrospective observational study of all pediatric blunt trauma patients who were evaluated with a cervical spine MRI over a 4-year period at a level 1 pediatric trauma center. Clinical and radiographic data were abstracted, as well as anesthesia requirements and MRI-related major adverse events. CT and MRI results were compared for their ability to detect clinically unstable injuries - those requiring halo or surgery. RESULTS: There was one major adverse event related to MRI among the 269 patients who underwent cervical spine MRI - a rate of 0.37%. While 55% of children had an airway and anesthesia for MRI, only 57% of these airways were newly placed for the MRI. None of the 85 patients newly intubated for MRI developed aspiration pneumonitis or ventilator-associated pneumonia, and no patients had a significant neurologic event while at MRI. Another area of the body was imaged concurrently with the cervical spine MRI in 64% of patients and 83% of MRIs were performed within 48 h. CT and MRI were both 100% sensitive for injuries requiring halo or operative intervention. Eighty-three patients had an MRI performed after a negative CT, 11% (9/83) of these patients had a clinically stable injury detected on subsequent MRI, and none of these patients presented for delayed cervical spine complications. CONCLUSIONS: Overall, the safety profile of MRI in this setting is excellent and less than one-third of patients need new airway and anesthesia solely for MRI. In this clinical scenario, MRIs can happen relatively quickly and many patients require another body part to be imaged concurrently anyway. MRI and CT were both 100% sensitive for clinically unstable injuries. In the appropriate patients, MRI remains a safe and radiation-free alternative to CT.

Acromegaly: Medical and Surgical Considerations.

Acromegaly results from excessive secretion of insulinlike growth factor-1 and growth hormone, which most commonly occurs because of pituitary somatotrophinoma. Diagnostic features of acromegaly include elevated insulinlike growth factor-1 and growth hormone; lesion on brain MRI; and clinically dysmorphic features, such as soft tissue swelling, jaw prognathism, and acral overgrowth. Transsphenoidal resection is the primary therapy for individuals with acromegaly, even in the cases where gross total resection is not possible because of parasellar extension and cavernous sinus involvement. For recurrent or persistent disease after resection, systemic medications and stereotactic radiosurgery are used.

Transseptal interforniceal endoscopic removal of superiorly recessed colloid cysts.

OBJECTIVE: Transforaminal endoscopic colloid cyst resection is well described. However, some anatomical colloid cyst variants may warrant a modified approach. Rarely, colloid cysts separate the forniceal columns and grow superiorly within the leaflets of the septum pellucidum. Thus, the authors' goal was to characterize the imaging features, clinical presentation, surgical strategy, and outcomes of patients with this superiorly recessed colloid cyst variant. METHODS: A retrospective evaluation of patients who underwent endoscopic resection of colloid cysts from 1999 to 2020 was performed. The patients were dichotomized depending on whether the cyst was located predominately below the forniceal columns or was superiorly recessed (forniceal column separation with variable intraseptal extension). This comparative cohort study focused on clinical presentation, imaging features, operative technique, and patient outcome. RESULTS: In total, 182 patients were identified. Seventeen patients had colloid cysts that were defined as superiorly recessed and underwent transseptal interforniceal removal, and 165 patients underwent a standard transforaminal approach. Patients had similar demographic characteristics. However, transseptal cysts were on average larger (17.8 mm vs 11.4 mm, p < 0.0001), and these patients had a greater frontal-occipital horn ratio (0.45 vs 0.41, p = 0.012). They were also more likely to have undergone a previous resection (p = 0.02). The two cohorts had similar surgical outcomes, with no differences in extent of resection, recurrence, or complications. CONCLUSIONS: Superiorly recessed intraseptal colloid cysts are larger and tend to splay the bodies of the fornix, thus requiring a parasagittal transseptal interforniceal endoscopic approach. This achieves complete removal with comparatively negligible morbidity or rare recurrence (5.9%).

Arachnoid cysts: using prenatal imaging and need for pediatric neurosurgical intervention to better understand their natural history and prognosis.

OBJECTIVES: Intracranial arachnoid cysts are commonly characterized as congenital. Evidence to support a congenital origin is scant and documented evolution during infancy also calls into question the genesis of these lesions. To improve our understanding of the natural history and the clinical significance of arachnoid cysts on prenatal ultrasound, we conducted a study to describe the fate of these cysts after initial diagnosis. METHODS: We conducted a retrospective descriptive review of all prenatal ultrasounds with reported intracranial arachnoid cysts at a tertiary care center from 2010 to 2016 and cohort study comparing patients with additional ultrasound abnormalities to those with an isolated finding of arachnoid cyst. Data collected included gestational age at cyst diagnosis, cyst evolution on follow-up imaging, cyst size and cyst location, postnatal imaging and neurosurgical consultation and intervention. Statistical analysis including Chi-square and Fisher's exact tests and univariate logistic regressions were performed using Stata v. 13 (StataCorp 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP). Confidence intervals were reported at 95% and a p-value < .05 was considered significant. RESULTS: A total of 33,621 anatomical ultrasound scans were performed from 2010 to 2016. Seventy patients (0.2%) had prenatal findings of arachnoid cyst, of which the mean gestational age was 21.46 weeks. Ventriculomegaly was observed in one patient (1.4%) at the time of diagnosis and other abnormalities were found in twelve patients (17%). Complete sonographic follow-up prior to delivery was obtained in 53 (75.7%) patients with 5(9.4%) progression, 5(9.4%) regression, and 43(81.1%) no longer visualized. Forty-three cysts (81.1%) were no longer visualized on follow-up imaging, all of which were interhemispheric in location. All of the cysts that progressed in size on prenatal ultrasounds were > 2 cm in size on initial diagnosis. Cyst fenestration was performed in two patients (2.9%) that had arachnoid cysts measuring at least 3 cm in each dimension on prenatal imaging, one at eight months and one at six months of age. Patients with and without additional sonographic abnormalities had similar rates of AMA (23.1% vs 26.3%, p = .56), nulliparity (61.5% vs 70.2%, p = .38), obesity (0.0% vs 12.3%, p = .221), major medical comorbidities (38.5% vs 33.3%, p = .48) and pregnancy achieved via Assisted Reproductive Technology (38.5% vs 24.6%, p = .25), respectively. Patients with additional sonographic abnormalities were significantly more likely to have prenatal Magnetic Resonance Imaging (OR: 8.28, CI: 1.84-40.4, p = .07), prenatal neurosurgery consultation (OR: 8.25, CI: 1.23-69.05, p = .04) and invasive diagnostic genetic testing (OR: 11.25, CI: 2.33-64.35, p = .003). CONCLUSIONS: Arachnoid cysts are infrequently found on prenatal screening. Size greater than 2 cm on second trimester ultrasound and location outside of the interhemispheric fissure may indicate the need for further evaluation and eventual fenestration. Prenatally diagnosed arachnoid cysts are not typically associated with other anatomic or genetic abnormalities, although the presence of additional abnormalities usually leads to more intensive prenatal and postnatal investigations.

A critical analysis of surgery for occult tethered cord syndrome.

INTRODUCTION: Tethered cord syndrome (TCS) is an amalgamation of neurological, urological, orthopedic, and dermatologic signs and symptoms with radiographic evidence of a thickened filum and low-lying conus. Surgical sectioning of the filum and disconnection of any tethering entities such as dermal sinus tracts or lipomas has been shown to improve outcomes. The manifestation of TCS symptoms in the absence of a low-lying conus has been referred to as occult tethered cord syndrome (OTCS) and is much less well reviewed in the literature. To date, there has only been one randomized controlled trial examining the effect of intervention in OTCS; therefore, contemporary data is often elicited from limited cohorts. OBJECTIVE: To perform a comprehensive literature review of management in OTCS and evaluate treatment response rates to sectioning of the filum terminale. RESULTS: Seventeen papers met inclusion criteria for our review. Sample sizes ranged from 8 to 60 children, and results were mixed, often dependent on study design, definition of typical OTCS symptoms, and follow-up intervals. Symptomatic improvement was observed in > 50% of patients for all but one study; however, the recurrence rates were highly variable. CONCLUSION: The data regarding the efficacy of surgical treatment in OTCS is mixed and merits more rigorous scientific examination with strict and clear parameters regarding symptomatic operationalization and follow-up time points to monitor for TCS recurrence.

Closed-loop vagal nerve stimulation for intractable epilepsy: A single-center experience.

PURPOSE: A new class of heart-rate sensing, closed-loop vagal nerve stimulator (VNS) devices for refractory epilepsy may improve seizure control by using pre-ictal autonomic changes as an indicator for stimulation. We compared our experience with closed- versus open-loop stimulator implantation at a single institution. METHODS: We conducted a retrospective chart review of consecutive VNS implantations performed from 2004 to 2018. Bivariate and multivariable analyses were performed to compare changes in seizure frequency and clinical outcomes (Engel score) with closed- versus open-loop devices. Covariates included age, duration of seizure history, prior epilepsy surgery, depression, Lennox Gastaut Syndrome (LGS), tonic seizures, multiple seizure types, genetic etiology, and VNS settings. We examined early (9-month) and late (24-month) outcomes. RESULTS: Seventy subjects received open-loop devices, and thirty-one received closed-loop devices. At a median of 8.5 months, there was a greater reduction of seizure frequency after use of closed-loop devices (median 75% [IQR 10-89%]) versus open-loop (50% [0-78%], p < 0.05), confirmed in multivariable analysis (odds ratio 2.72 [95% CI 1.02 - 7.4]). Similarly, Engel outcomes were better after closed-loop compared to open-loop confirmed in the multivariable analysis at the early timepoint (OR 0.26 [95% CI 0.09 - 0.69]). These differences did not persist at a median of 24.5 months. CONCLUSIONS: This retrospective single-center study suggests the use of closed-loop VNS devices is associated with greater seizure reduction and more favorable clinical outcomes than open-loop devices at 9-months though not at 24-months. Expansion of this study to other centers is warranted to increase the generalizability of our study.

Utility of invasive electroencephalography in children 3 years old and younger with refractory epilepsy.

OBJECTIVE: Early surgical intervention for pediatric refractory epilepsy is increasingly advocated as surgery has become safer and data have demonstrated improved outcomes with early seizure control. There is concern that the risks associated with staged invasive electroencephalography (EEG) in very young children outweigh the potential benefits. Here, the authors present a cohort of children with refractory epilepsy who were referred for invasive monitoring, and they evaluate the role and safety of staged invasive EEG in those 3 years old and younger. METHODS: The authors conducted a retrospective review of children 3 years and younger with epilepsy, who had been managed surgically at two institutions between 2001 and 2015. A cohort of pediatric patients older than 3 years of age was used for comparison. Demographics, seizure etiology, surgical management, surgical complications, and adverse events were recorded. Statistical analysis was completed using Stata version 13. A p < 0.05 was considered statistically significant. Fisher's exact test was used to compare proportions. RESULTS: Ninety-four patients (45 patients aged ≤ 3 [47.9%]) and 208 procedures were included for analysis. Eighty-six procedures (41.3%) were performed in children younger than 3 years versus 122 in the older cohort (58.7%). Forty-two patients underwent grid placement (14 patients aged ≤ 3 [33.3%]); 3 of them developed complications associated with the implant (3/42 [7.14%]), none of whom were among the younger cohort. Across all procedures, 11 complications occurred in the younger cohort versus 5 in the older patients (11/86 [12.8%] vs 5/122 [4.1%], p = 0.032). Two adverse events occurred in the younger group versus 1 in the older group (2/86 [2.32%] vs 1/122 [0.82%], p = 0.571). Following grid placement, 13/14 younger patients underwent guided resections compared to 20/28 older patients (92.9% vs 71.4%, p = 0.23). CONCLUSIONS: While overall complication rates were higher in the younger cohort, subdural grid placement was not associated with an increased risk of surgical complications in that population. Invasive electrocorticography informs management in very young children with refractory, localization-related epilepsy and should therefore be used when clinically indicated.

Syringomyelia Resolution Following Chiari Surgery: A Novel Scale for Communication and Research.

BACKGROUND: The pathophysiological connection between Chiari malformation and syringomyelia is accepted. Debate remains, however, how can we best define changes in syringomyelia following surgery. OBJECTIVE: To introduce a grading system focusing on syrinx reduction based on routinely and reproducible radiological information, and provide a suggestion of the application of this scale for prediction of patient's prognoses. METHODS: Data from 48 patients with Chiari malformation and syringomyelia were compiled. We calculated syrinx cross-sectional area by approximating an ellipse in the largest axial plane. We compared the percentage of reduction or enlargement following surgery. The percentage change was grouped into four grades: Grade 0 = Increasing size, grade I ≤ 50% reduction, grade II = 50% to 90% reduction, grade III ≥ 90% reduction. RESULTS: A total of 89.6% of patients had syrinx improvement after surgery. A total of 5 patients were grade 0, 14 were grade I, 20 patients were grade II, and 9 patients met criteria for grade III. The mean postoperative syrinx area was 24.1 mm2 (0-169 mm2) with a mean syrinx reduction of 62.7%. CONCLUSION: Radiological improvement of syringomyelia can be mathematically defined and standardized to assist in communication in outcome-based trials. Radiological resolution is expected most patients.

The slope of the learning curve in 600 consecutive endoscopic transsphenoidal pituitary surgeries.

BACKGROUND: Endonasal endoscopic transsphenoidal surgery (EETS) for pituitary adenoma has become a mainstay of treatment over the last two decades and it is generally accepted that once this learning curve is achieved, a plateau is reached with little incremental improvement. OBJECTIVE: The objective of this study was to assess the slope of the learning curve over a long period of time for a variety of outcomes measures. METHODS: We examined outcomes and complications in a consecutive series of 600 EETS for pituitary adenoma grouped into quartiles based on date of surgery. RESULTS: GTR significantly increased across quartiles from 55 to 79% in the last quartile (p < 0.005). The rate of intraoperative CSF leak significantly decreased from 60% in the first quartile to 33% in the last quartile and the rate of lumbar drain placement from 28% in the first quartile to 6% in the last quartile (p < 0.005). Hormonal remission for secreting adenomas increased from 68% in the first quartile to 90% in the last quartile (p < 0.05). The rate of post-operative CSF leak trended lower (3% in first quartile to 0.7% in last two quartiles). The greatest improvement in outcome occurred between the first and second quartiles (19.9%), but persistent improvement occurred between the second and third (6.7%) and third and fourth quartiles (8.0%). CONCLUSION: Although the slope of the learning curve is steeper earlier in a surgeon's experience, the slope does not plateau and continues to increase even over more than a decade.

Ventrolateral Tonsillar Position Defines Novel Chiari 0.5 Classification.

BACKGROUND: Cervicomedullary compression in young children has been described in the context of Chiari type 1 malformation, with symptoms associated with the extent of tonsillar herniation below McRae line. Historically, Chiari type 1 malformation has been defined by tonsillar herniation of at least 5 mm. However, in certain populations, including very young children, Chiari symptoms may be present without this finding. A new Chiari classification is thus necessary. METHODS: Cases involving patients up to 5 years of age evaluated for possible posterior fossa decompression were retrospectively reviewed. Preoperative symptoms, magnetic resonance imaging findings, surgical management, and short- and long-term outcome and follow-up were recorded. Tonsillar descent and presence of ventral herniation (VH) were recorded. We define VH as the tonsils crossing a line that bisects the caudal medulla at the level of the foramen magnum, thus creating a novel entity, Chiari type 0.5 malformation. Patients with ventrally herniated tonsils were compared with patients exhibiting more typical Chiari morphology. RESULTS: Of 41 cases retrospectively reviewed, 20 met criteria for VH. These differed from cases without VH because of the predominance of medullary symptoms. In the VH cohort, 11 patients underwent surgical decompression with symptom resolution; 9 were initially managed conservatively, but 3 subsequently required surgery. CONCLUSIONS: We define a novel Chiari entity, Chiari type 0.5 malformation, characterized by ventral tonsillar wrapping around the medulla in young children in the absence of classic Chiari type 1 malformation imaging findings. These patients are more likely to present with medullary symptoms than patients without VH. They are also more likely to require surgical decompression and respond favorably to intervention.

How long is the tail end of the learning curve? Results from 1000 consecutive endoscopic endonasal skull base cases following the initial 200 cases.

OBJECTIVE: Endoscopic endonasal approaches (EEAs) to the skull base have evolved over the last 20 years to become an essential component of a comprehensive skull base practice. Many case series show a learning curve from the earliest cases, in which the authors were inexperienced or were not using advanced closure techniques. It is generally accepted that once this learning curve is achieved, a plateau is reached with little incremental improvement. Cases performed during the early steep learning curve were eliminated to examine whether the continued improvement exists over the "tail end" of the curve. METHODS: A prospectively acquired database of all EEA cases performed by the senior authors at Weill Cornell Medicine/NewYork-Presbyterian Hospital was reviewed. The first 200 cases were eliminated and the next 1000 consecutive cases were examined to avoid the bias created by the early learning curve. RESULTS: Of the 1000 cases, the most common pathologies included pituitary adenoma (51%), meningoencephalocele or CSF leak repair (8.6%), meningioma (8.4%), craniopharyngioma (7.3%), basilar invagination (3.1%), Rathke's cleft cyst (2.8%), and chordoma (2.4%). Use of lumbar drains decreased from the first half to the second half of our series (p <0.05) as did the authors' use of fat alone (p <0.005) or gasket alone (p <0.005) for dural closure, while the use of a nasoseptal flap increased (p <0.005). Although mean tumor diameter was constant (on average), gross-total resection (GTR) increased from 60% in the first half to 73% in the second half (p <0.005). GTR increased for all pathologies but most significantly for chordoma (56% vs 100%, p <0.05), craniopharyngioma (47% vs 0.71%, p <0.05) and pituitary adenoma (67% vs 75%, p <0.05). Hormonal cure for secreting adenomas also increased from 83% in the first half to 89% in the second half (p <0.05). The rate of any complication was unchanged at 6.4% in the first half and 6.2% in the latter half of cases, and vascular injury occurred in only 0.6% of cases. Postoperative CSF leak occurred in 2% of cases and was unchanged between the first and second half of the series. CONCLUSIONS: This study demonstrates that contrary to popular belief, the surgical learning curve does not plateau but can continue for several years depending on the complexity of the endpoints considered. These findings may have implications for clinical trial design, surgical education, and patient safety measures.

Incidence and risk factors associated with reoperation for sellar hematoma following endoscopic transsphenoidal pituitary surgery.

OBJECTIVE: Postoperative sellar hematoma is an uncommon complication of endonasal endoscopic transsphenoidal surgery (EETS) for pituitary adenoma that often requires emergency surgical evacuation. Sellar hematomas can cause mass effect and compress parasellar structures, leading to clinically significant symptoms such as visual impairment and severe headache. The objective of this study was to determine the incidence and risk factors associated with reoperation for postoperative hematoma after EETS for pituitary adenoma. METHODS: The authors reviewed a prospectively acquired database of EETS for pituitary adenoma over 13 years at Weill Cornell Medicine, NewYork-Presbyterian Hospital and identified cases that required reoperation for confirmed hematoma. They also reviewed clinical and radiographic data of a consecutive series of patients undergoing EETS for pituitary adenoma who did not have postoperative hematoma, which served as the control group. Demographic data and risk factors were compared between the groups using univariate and multivariate analyses via binary logistic regression. RESULTS: Among a cohort of 583 patients undergoing EETS for pituitary adenoma, 9 patients (1.5%) required operation for sellar hematoma evacuation. All 9 patients with reoperation for sellar hematoma presented with worsening in their vision, and severe headache was present in 67%. New postoperative endocrine dysfunction developed in 78%. Clot evacuation improved vision in 88%. The mean time to hematoma evacuation was 4.5 days. The median length of stay for patients with sellar hematoma was 8 days (range 4-210 days) compared with a median length of stay of 3 days (range 1-32 days) for the control patients (p < 0.005). Significant risk factors in univariate analysis were tumor diameter ≥ 30 mm (p < 0.005), suprasellar extension (p < 0.005), tumor volume (p < 0.005), cavernous sinus invasion (p < 0.05), gonadotroph histology (p < 0.05), antiplatelet use (p < 0.05), and elevated BMI (p < 0.05). On multivariate analysis, tumor diameter ≥ 30 mm (OR 4.555, CI 1.30-28.90; p < 0.05) and suprasellar extension (OR 1.048, CI 1.01-1.10; p < 0.05) were found to be the only independent predictors of sellar hematoma. The incidence of hematoma in tumors ≥ 30 mm was 5% (7/139). CONCLUSIONS: Postoperative sellar hematoma requiring reoperation is a rare phenomenon after transsphenoidal surgery, often presenting with visual loss and headache. Clot evacuation results in improvement in vision, but long-term endocrinopathy often ensues. Tumor diameter ≥ 30 mm and suprasellar extent are the most reliable risk factors. Close postoperative scrutiny should be given to patients at high risk.

Magnetic resonance-guided focused ultrasound for ablation of mesial temporal epilepsy circuits: modeling and theoretical feasibility of a novel noninvasive approach.

OBJECTIVE: The authors tested the feasibility of magnetic resonance-guided focused ultrasound (MRgFUS) ablation of mesial temporal lobe epilepsy (MTLE) seizure circuits. Up to one-third of patients with mesial temporal sclerosis (MTS) suffer from medically refractory epilepsy requiring surgery. Because current options such as open resection, laser ablation, and Gamma Knife radiosurgery pose potential risks, such as infection, hemorrhage, and ionizing radiation, and because they often produce visual or neuropsychological deficits, the authors developed a noninvasive MRgFUS ablation strategy for mesial temporal disconnection to mitigate these risks. METHODS: The authors retrospectively reviewed 3-T MRI scans obtained with diffusion tensor imaging (DTI). The study group included 10 patients with essential tremor (ET) who underwent pretreatment CT and MRI prior to MRgFUS, and 2 patients with MTS who underwent MRI. Fiber tracking of the fornix-fimbria pathway and inferior optic radiations was performed, ablation sites mimicking targets of open posterior hippocampal disconnection were modeled, and theoretical MRgFUS surgical plans were devised. Distances between the targets and optic radiations were measured, helmet angulations were prescribed, and the numbers of available MRgFUS array elements were calculated. RESULTS: Tractograms of fornix-fimbria and optic radiations were generated in all ET and MTS patients successfully. Of the 10 patients with both the CT and MRI data necessary for the analysis, 8 patients had adequate elements available to target the ablation site. A margin (mean 8.5 mm, range 6.5-9.8 mm) of separation was maintained between the target lesion and optic radiations. CONCLUSIONS: MRgFUS offers a noninvasive option for seizure tract disruption. DTI identifies fornix-fimbria and optic radiations to localize optimal ablation targets and critical surrounding structures, minimizing risk of postoperative visual field deficits. This theoretical modeling study provides the necessary groundwork for future clinical trials to apply this novel neurosurgical technique to patients with refractory MTLE and surgical contraindications, multiple prior surgeries, or other factors favoring noninvasive treatment.

A Dual Approach for the Management of Complex Craniovertebral Junction Abnormalities: Endoscopic Endonasal Odontoidectomy and Posterior Decompression with Fusion.

BACKGROUND: Ventral brainstem compression secondary to complex craniovertebral junction abnormality is an infrequent cause of neurologic deterioration in pediatric patients. However, in cases of symptomatic, irreducible ventral compression, 360° decompression of the brainstem supported by posterior stabilization may provide the best opportunity for improvement in symptoms. More recently, the endoscopic endonasal corridor has been proposed as an alternative method of odontoidectomy associated with less morbidity. We report the largest single case series of pediatric patients using this dual-intervention surgical technique. The purpose of this study was to evaluate the surgical outcomes of pediatric patients who underwent posterior occipitocervical decompression and instrumentation followed by endoscopic endonasal odontoidectomy performed to relieve neurologic impingement involving the ventral brainstem and craniocervical junction. METHODS: Between January 2011 and February 2017, 7 patients underwent posterior instrumented fusion followed by endonasal endoscopic odontoidectomy at our unit. Standardized clinical and radiological parameters were assessed before and after surgery. A univariate analysis was performed to assess clinical and radiologic improvement after surgery. RESULTS: A total of 14 operations were performed on 7 pediatric patients. One patient had Ehlers-Danlos syndrome, 1 patient had a Chiari 1 malformation, and the remaining 5 patients had Chiari 1.5 malformations. Average extubation day was postoperative day 0.9. Average day of initiation of postoperative feeds was postoperative day 1.0. CONCLUSIONS: The combined endoscopic endonasal odontoidectomy and posterior decompression and fusion for complex craniovertebral compression is a safe and effective procedure that appears to be well tolerated in the pediatric population.

Endoscopic removal of recurrent colloid cysts.

OBJECTIVE: Removal of colloid cysts of the third ventricle using a purely endoscopic method has been established as a safe and advantageous technique. It is hypothesized that endoscopic removal in recurrent cases might pose more technical challenges and result in less success. The objective of this study was to assess the feasibility and outcomes of using a purely endoscopic approach for the management of recurrent colloid cysts compared to primary cysts. METHODS: A retrospective cohort study was performed on patients who underwent purely endoscopic removal of their colloid cyst. Descriptive statistics were compared for patients undergoing surgery for a recurrent cyst and those for a control cohort undergoing surgery for a primary cyst. Bivariate analysis was conducted using a Fisher's exact test for categorical variables and Mann-Whitney U-test for continuous variables. RESULTS: In total, 121 patients had a primary colloid cyst endoscopically removed and 10 patients had a total of 11 recurrent cysts removed. Recurrence or progression after surgery occurred in 3 (2.5%) cases in the primary cyst group and 2 (18.2%) cases in the recurrent cyst group. Symptomatic presentation during the follow-up period occurred in 6 (54.5%) cases in the recurrent cyst group versus 75 (62%) cases in the primary cyst group (p = 0.749). Two patients (20%) in the recurrent group had a second recurrence in a mean period of 30 months (1 patient at 15 and 1 patient at 45 months). One of these patients required a tertiary endoscopic removal 8 years after the second resection. No immediate postoperative complications or new morbidities were observed after repeat endoscopic surgery. The authors' findings indicated a nonsignificant trend toward a higher recurrence rate (18.2% vs 2.5%, p = 0.055) and a decreased proportion of complete removal (90.9% vs 81.8%, p = 0.296) in the recurrent cyst group compared to the primary cyst group. However, a significantly higher rate of preoperative hydrocephalus was observed in the primary cyst group compared with the recurrent cyst group (63.6% vs 18.2%, p = 0.007). CONCLUSIONS: Purely endoscopic approaches for the removal of recurrent colloid cysts of the third ventricle are feasible and equally safe compared with endoscopic removal of primary cysts. The study's findings did not show a statistically significant difference in the rate of recurrence between the 2 groups. The proportion of patients with symptomatic cysts on presentation was lower in patients with recurrent cysts than in patients with primary cysts. Due to the high rate of complete removal with negligible morbidity, the authors continue to advocate for an endoscopic removal at the time of cyst recurrence.