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Peter F. Morgenstern and Jared Knopman
Iryna Ivasyk, Peter F. Morgenstern, Eva Wembacher-Schroeder, and Mark M. Souweidane
Convection-enhanced delivery (CED) uses positive pressure to induce convective flow of molecules and maximize drug distribution. Concerns have been raised about the effect of cystic structures on uniform drug distribution with CED. The authors describe the case of a patient with a diffuse intrinsic pontine glioma (DIPG) with a large cyst and examine its effect on drug distribution after CED with a radiolabeled antibody. The patient was treated according to protocol with CED of 124I-8H9 to the pons for nonprogressive DIPG after radiation therapy as part of a Phase I trial (clinical trial registration no. NCT01502917, clinicaltrials.gov). Care was taken to avoid the cystic cavity in the planned catheter track and target point. Co-infusion with Gd-DTPA was performed to assess drug distribution. Infusate distribution was examined by MRI immediately following infusion and analyzed using iPlan Flow software. Analysis of postinfusion MR images demonstrated convective distribution around the catheter tip and an elongated configuration of drug distribution, consistent with the superoinferior corticospinal fiber orientation in the brainstem. This indicates that the catheter was functioning and a pressure gradient was established. No infusate entry into the cystic region could be identified on T2-weighted FLAIR or T1-weighted images. The effects of ependymal and pial surfaces on drug delivery using CED in brainstem tumors remain controversial. Drug distribution is a critical component of effective application of CED to neurosurgical lesions. This case suggests that cyst cavities may not always behave as fluid “sinks” for drug distribution. The authors observed that infusate was not lost into the cyst cavity, suggesting that lesions with cystic components can be treated by CED without significant alterations to target and infusion planning.
Lessons learned in the evolution of endoscopic skull base surgery
JNSPG 75th Anniversary Invited Review Article
Theodore H. Schwartz, Peter F. Morgenstern, and Vijay K. Anand
OBJECTIVE
Endoscopic skull base surgery (ESBS) is a relatively recent addition to the neurosurgical armamentarium. As with many new approaches, there has been significant controversy regarding its value compared with more traditional approaches to ventral skull base pathology. Although early enthusiasm for new approaches that appear less invasive is usually high, these new techniques require rigorous study to ensure that widespread implementation is in the best interest of patients.
METHODS
The authors compared surgical results for ESBS with transcranial surgery (TCS) for several different pathologies over two different time periods (prior to 2012 and 2012–2017) to see how results have evolved over time. Pathologies examined were craniopharyngioma, anterior skull base meningioma, esthesioneuroblastoma, chordoma, and chondrosarcoma.
RESULTS
ESBS offers clear advantages over TCS for most craniopharyngiomas and chordomas. For well-selected cases of planum sphenoidale and tuberculum sellae meningiomas, ESBS has similar rates of resection with higher rates of visual improvement, and more recent results with lower CSF leaks make the complication rates similar between the two approaches. TCS offers a higher rate of resection with fewer complications for olfactory groove meningiomas. ESBS is preferred for lower-grade esthesioneuroblastomas, but higher-grade tumors often still require a craniofacial approach. There are few data on chondrosarcomas, but early results show that ESBS appears to offer clear advantages for minimizing morbidity with similar rates of resection, as long as surgeons are familiar with more complex inferolateral approaches.
CONCLUSIONS
ESBS is maturing into a well-established approach that is clearly in the patients’ best interest when applied by experienced surgeons for appropriate pathology. Ongoing critical reevaluation of outcomes is essential for ensuring optimal results.
Peter F. Morgenstern, Caitlin E. Hoffman, Gary Kocharian, Ranjodh Singh, Philip E. Stieg, and Mark M. Souweidane
OBJECT
The optimal method for detecting recurrent arteriovenous malformations (AVMs) in children is unknown. An inherent preference exists for MR angiography (MRA) surveillance rather than arteriography. The validity of this strategy is uncertain.
METHODS
A retrospective chart review was performed on pediatric patients treated for cerebral AVMs at a single institution from 1998 to 2012. Patients with complete obliteration of the AVM nidus after treatment and more than 12 months of follow-up were included in the analysis. Data collection focused on recurrence rates, associated risk factors, and surveillance methods.
RESULTS
A total of 45 patients with a mean age of 11.7 years (range 0.5–18 years) were treated for AVMs via surgical, endovascular, radiosurgical, or combined approaches. Total AVM obliteration on posttreatment digital subtraction angiography (DSA) was confirmed in 27 patients, of whom the 20 with more than 12 months of follow-up were included in subsequent analysis. The mean follow-up duration in this cohort was 5.75 years (median 5.53 years, range 1.11–10.64 years). Recurrence occurred in 3 of 20 patients (15%). Two recurrences were detected by surveillance DSA and 1 at the time of rehemorrhage. No recurrences were detected by MRA. Median time to recurrence was 33.6 months (range 19–71 months). Two patients (10%) underwent follow-up DSA, 5 (25%) had DSA and MRI/MRA, 9 (45%) had MRI/MRA only, 1 (5%) had CT angiography only, and 3 (15%) had no imaging within the first 3 years of follow-up. After 5 years posttreatment, 2 patients (10%) were followed with MRI/MRA only, 2 (10%) with DSA only, and 10 (50%) with continued DSA and MRI/MRA.
CONCLUSIONS
AVM recurrence in children occurred at a median of 33.6 months, when MRA was more commonly used for surveillance, but failed to detect any recurrences. A recurrence rate of 15% may be an underestimate given the reliance on surveillance MRA over angiography. A new surveillance strategy is proposed, taking into account exposure to diagnostic radiation and the potential for catastrophic rehemorrhage.
Mark M. Souweidane, Peter F. Morgenstern, Sungkwon Kang, Apostolos John Tsiouris, and Jonathan Roth
Object
Fenestration of the floor of the third ventricle is vital to the success of endoscopic third ventriculostomy (ETV) in treating patients with noncommunicating hydrocephalus. A generous prepontine interval (PPI) is generally accepted as one anatomical feature that may affect the safety and functionality of ETV. Whether a diminished PPI influences the safety or success of ETV, however, has not been adequately assessed.
Methods
A review was conducted on the last 100 ETV procedures performed by the first author (M.M.S.). From archived preoperative MR imaging studies, the PPI was measured between the dorsum sellae and the basilar artery. For any patient with an interval of ≤1 mm, the technical and functional success of the procedure was recorded. Technical success was defined when a surgically created fenestration was accomplished without patient morbidity. Functional success was defined as the patient not needing any additional CSF diversionary procedure within 3 months after ETV.
Results
In the entire cohort, the PPI ranged from 0 to 9.5 mm (mean 3.2 mm). There were 15 procedures performed in patients with a PPI of ≤1 mm. In all 15 procedures, a fenestration of the tuber cinereum was accomplished without vascular injury or patient morbidity. The ETV was successful in 11 patients (73.3%). All 4 failures occurred in children who had surgery during infancy (mean age 11 months).
Conclusions
Patients with an obliterated or reduced PPI can safely undergo ETV. The functional success rate appears equivalent to historical controls. Most failures in this series may be attributed to other patient characteristics, namely young age at the time of ETV.
Peter F. Morgenstern, Zhiping Zhou, Eva Wembacher-Schröder, Vincent Cina, Apostolos John Tsiouris, and Mark M. Souweidane
OBJECTIVE
Convection-enhanced delivery (CED) has been explored as a therapeutic strategy for diffuse intrinsic pontine glioma (DIPG). Variables that may affect tolerance include infusate volume, infusion rate, catheter trajectory, and target position. Supratentorial approaches for catheter placement and infusate distribution patterns may conflict with corticospinal tracts (CSTs). The clinical relevance of these anatomical constraints has not been described. The authors report their experience using CED in the brainstem as it relates to anatomical CST conflict and association with clinical tolerance.
METHODS
In a phase I clinical trial of CED for DIPG (clinical trial registration no. NCT01502917, clinicaltrials.gov), a flexible infusion catheter was placed with MRI guidance for infusion of 124I-8H9, a radioimmunotherapeutic agent. Intra- and postprocedural MR images were analyzed to identify catheter trajectories and changes in T2-weighted signal intensity to approximate volume of distribution (Vd). Intersection of CST by the catheter and overlap between Vd and CST were recorded and their correlation with motor deficits was evaluated.
RESULTS
Thirty-one patients with a mean age of 7.6 years (range 3.2–18 years) underwent 39 catheter insertions for CED between 2012 and 2017. Thirty catheter insertions had tractography data available for analysis. The mean trajectory length was 105.5 mm (range 92.7–121.6 mm). The mean number of intersections of CST by catheter was 2.2 (range 0–3) and the mean intersecting length was 18.9 mm (range 0–44.2 mm). The first 9 infusions in the highest dose level (range 3.84–4.54 ml infusate) were analyzed for Vd overlap with CST. In this group, the mean age was 7.6 years (range 5.8–10.3 years), the mean trajectory length was 109.5 mm (range 102.6–122.3 mm), and the mean overlap between Vd and CST was 5.5 cm3. For catheter placement–related adverse events, 1 patient (3%) had worsening of a contralateral facial nerve palsy following the procedure with two CST intersections, an intersecting distance of 31.7 mm, and an overlap between Vd and CST of 3.64 cm3. For infusion-related adverse events, transient postinfusion deficits were noted in 3 patients in the highest dose level, with a mean number of 2 intersections of CST by catheter, mean intersecting length of 12.9 mm, and mean overlap between Vd and CST of 6.3 cm3.
CONCLUSIONS
A supratentorial approach to the brainstem crossing the CST resulted in one worsened neurological deficit. There does not appear to be a significant risk requiring avoidance of dominant motor fiber tracts with catheter trajectory planning. There was no correlation between Vd–CST overlap and neurological adverse events in this cohort.
Clinical trial registration no.: NCT01502917 (clinicaltrials.gov)
Erwin M. J. Cornips, Mariel Ter Laak-Poort, Alida A. Postma, Joost Nicolai, and Johan S. H. Vles
Peter F. Morgenstern, Nathan Osbun, Theodore H. Schwartz, Jeffrey P. Greenfield, Apostolos John Tsiouris, and Mark M. Souweidane
Object
Simultaneous endoscopic third ventriculostomy (ETV) and tumor biopsy is a widely accepted therapeutic and diagnostic procedure for patients with noncommunicating hydrocephalus secondary to a pineal region tumor. Multiple approaches have been advocated, including the use of a steerable fiberoptic or rigid lens endoscope via 1 or 2 trajectories. However, the optimal approach has not been established based on the individual anatomical characteristics of the patient.
Methods
A retrospective review of patients undergoing simultaneous ETV and tumor biopsy was undertaken. Preoperative MR images were examined to measure the width of the anterior third ventricle and maximal diameters of the tumor, Monro foramen (right), and massa intermedia. The distances between the tumor and massa intermedia, tumor and anterior commissure, midbrain and massa intermedia, and the dorsum sella and anterior commissure were also recorded. Single and dual trajectory approaches were compared using paired t-tests for each parameter.
Results
Over an 8-year interval, 15 patients underwent simultaneous ETV and tumor management. These patients ranged from 6 to 71 years of age (mean 36.7 years); 5 were younger than 18 years of age. Seven were treated using a dual trajectory approach, and 8 were treated using a single trajectory approach. All cases were completed without complications or the need for an additional CSF diversionary procedure within 6 months. The diagnostic yield at biopsy was 86.7%. There were no statistically significant differences between the single and dual trajectory groups for the measured parameters. However, the dual trajectory group demonstrated a larger anterior third ventricular diameter (1.43 vs 1.21 cm, p = 0.29). The single trajectory group trended toward a smaller tumor–anterior commissure interval (2.23 vs 2.51 cm, p = 0.24) and a larger dorsum sella–anterior commissure distance (1.67 vs 1.49 cm, p = 0.28).
Conclusions
These data confirm the safety and diagnostic efficacy of simultaneous ETV and biopsy for tumors of the pineal region. Although no statistically significant differences were seen in the authors' recorded measurements, several trends suggest a role for a tailored approach to selecting a single or dual trajectory approach when using a rigid endoscope.
Evan D. Bander, Alexander D. Ramos, Eva Wembacher-Schroeder, Iryna Ivasyk, Rowena Thomson, Peter F. Morgenstern, and Mark M. Souweidane
OBJECTIVE
While the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single-dose drug infusions, agents for oncological therapy may require repeated or chronic infusions to maintain therapeutic drug concentrations. Repeat and chronic CED infusions have rarely been described for oncological purposes. Currently available CED devices are not approved for extended indwelling use, and the only potential at this time is for sequential treatments through multiple procedures. The authors report on the safety and experience in a group of pediatric patients who received sequential CED into the brainstem for the treatment of diffuse intrinsic pontine glioma.
METHODS
Patients in this study were enrolled in a phase I single-center clinical trial using 124I-8H9 monoclonal antibody (124I-omburtamab) administered by CED (clinicaltrials.gov identifier NCT01502917). A retrospective chart and imaging review were used to assess demographic data, CED infusion data, and postoperative neurological and surgical outcomes. MRI scans were analyzed using iPlan Flow software for volumetric measurements. Target and catheter coordinates as well as radial, depth, and absolute error in MRI space were calculated with the ClearPoint imaging software.
RESULTS
Seven patients underwent 2 or more sequential CED infusions. No patients experienced Clinical Terminology Criteria for Adverse Events grade 3 or greater deficits. One patient had a persistent grade 2 cranial nerve deficit after a second infusion. No patient experienced hemorrhage or stroke postoperatively. There was a statistically significant decrease in radial error (p = 0.005) and absolute tip error (p = 0.008) for the second infusion compared with the initial infusion. Sequential infusions did not result in significantly different distribution capacities between the first and second infusions (volume of distribution determined by the PET signal/volume of infusion ratio [mean ± SD]: 2.66 ± 0.35 vs 2.42 ± 0.75; p = 0.45).
CONCLUSIONS
This series demonstrates the ability to safely perform sequential CED infusions into the pediatric brainstem. Past treatments did not negatively influence the procedural workflow, technical application of the targeting interface, or distribution capacity. This limited experience provides a foundation for using repeat CED for oncological purposes.
Edgar G. Ordóñez-Rubiano, Jonathan A. Forbes, Peter F. Morgenstern, Leopold Arko, Georgiana A. Dobri, Jeffrey P. Greenfield, Mark M. Souweidane, Apostolos John Tsiouris, Vijay K. Anand, Ashutosh Kacker, and Theodore H. Schwartz
OBJECTIVE
Gross-total resection (GTR) of craniopharyngiomas (CPs) is potentially curative and is often the goal of surgery, but endocrinopathy generally results if the stalk is sacrificed. In some cases, GTR can be attempted while still preserving the stalk; however, stalk manipulation or devascularization may cause endocrinopathy and this strategy risks leaving behind small tumor remnants that can recur.
METHODS
A retrospective review of a prospective cohort of patients who underwent initial resection of CP using the endoscopic endonasal approach over a period of 12 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, was performed. Postresection integrity of the stalk was retrospectively assessed using operative notes, videos, and postoperative MRI. Tumors were classified based on location into type I (sellar), type II (sellar-suprasellar), and type III (purely suprasellar). Pre- and postoperative endocrine function, tumor location, body mass index, rate of GTR, radiation therapy, and complications were reviewed.
RESULTS
A total of 54 patients who had undergone endoscopic endonasal procedures for first-time resection of CP were identified. The stalk was preserved in 33 (61%) and sacrificed in 21 (39%) patients. GTR was achieved in 24 patients (73%) with stalk preservation and 21 patients (100%) with stalk sacrifice (p = 0.007). Stalk-preservation surgery achieved GTR and maintained completely normal pituitary function in only 4 (12%) of 33 patients. Permanent postoperative diabetes insipidus was present in 16 patients (49%) with stalk preservation and in 20 patients (95%) following stalk sacrifice (p = 0.002). In the stalk-preservation group, rates of progression and radiation were higher with intentional subtotal resection or near-total resection compared to GTR (67% vs 0%, p < 0.001, and 100% vs 12.5%, p < 0.001, respectively). However, for the subgroup of patients in whom GTR was achieved, stalk preservation did not lead to significantly higher rates of recurrence (12.5%) compared with those in whom it was sacrificed (5%, p = 0.61), and stalk preservation prevented anterior pituitary insufficiency in 33% and diabetes insipidus in 50%.
CONCLUSIONS
While the decision to preserve the stalk reduces the rate of postoperative endocrinopathy by roughly 50%, nevertheless significant dysfunction of the anterior and posterior pituitary often ensues. The decision to preserve the stalk does not guarantee preserved endocrine function and comes with a higher risk of progression and need for adjuvant therapy. Nevertheless, to reduce postoperative endocrinopathy attempts should be made to preserve the stalk if GTR can be achieved.
