The role of systemic therapy in advanced skull base chordomas: overview of the current state and the MD Anderson protocol.

The role of systemic therapy in primary or advanced and metastatic chordoma has been traditionally limited because of the inherent resistance to cytotoxic therapies and lack of specific or effective therapeutic targets. Despite resection and adjuvant radiation therapy, local recurrence rates in clival chordoma remain high and the risk of systemic metastases is not trivial, leading to significant morbidity and mortality. Recently, molecular targeted therapies (MTTs) and immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic avenues in chordoma. In recent years, preclinical studies have identified potential targets based on intrinsic genetic dependencies, epigenetic modulators, or newly identified tumor-associated cell populations driving treatment resistance and recurrence. Nonetheless, the role of systemic therapies in the neoadjuvant or adjuvant setting for primary, locally progressive, and distant metastatic chordomas is still being investigated. Herein, an overview of current and emerging systemic treatment strategies in advanced clival chordoma is provided. Furthermore, several molecular biomarkers have been recently uncovered as potential predictors of the response to specific molecular therapeutics. The authors describe the recently discovered role of 1p36 and 9p21 deletions as biomarkers capable of guiding drug selection. Then they discuss completed and ongoing clinical trials of MTTs, including several tyrosine kinase inhibitors used as monotherapy or in combination, such as imatinib, sorafenib, dasatinib, and lapatinib, among others, as well as mammalian target of rapamycin inhibitors such as everolimus and rapamycin. They present their experience and other recent studies demonstrating vast benefits in advanced chordoma from ICIs. Additionally, they provide a brief overview of novel systemic strategies such as adoptive cell transfer (CAR-T and NK cells), oncolytic viruses, epigenetic targeting (KDM6, HDAC, and EZH2 inhibitors), and several promising preclinical studies with high translational potential. Finally, the authors present their institutional multidisciplinary protocol for the incorporation of systemic therapy for both newly diagnosed and recurrent chordomas based on molecular studies including upfront enrollment in MTT trials in patients with epidermal growth factor receptor upregulation or INI-1 deficiency or enrollment in ICI clinical trials for patients with high tumor mutational burden or high PD-L1 expression on tumor cells or in the tumor microenvironment.

Clinical Outcomes and Complication Profile of Spine Surgery in Septuagenarians and Octogenarians: Case Series.

OBJECTIVE: The aging global population presents an increasing challenge for spine surgeons. Advancements in spine surgery, including minimally invasive techniques, have broadened treatment options, potentially benefiting older patients. This study aims to explore the clinical outcomes of spine surgery in septuagenarians and octogenarians. METHODS: This retrospective analysis, conducted at a US tertiary center, included patients aged 70 and older who underwent elective spine surgery for degenerative conditions. Data included the Charlson Comorbidity Index (CCI), ASA classification, surgical procedures, intraoperative and postoperative complications, and reoperation rates. The objective of this study was to describe the outcomes of our cohort of older patients and discern whether differences existed between septuagenarians and octogenarians. RESULTS: Among the 120 patients meeting the inclusion criteria, there were no significant differences in preoperative factors between the age groups (P > 0.05). Notably, the septuagenarian group had a higher average number of fused levels (2.36 vs. 0.38, P = 0.001), while the octogenarian group underwent a higher proportion of minimally invasive procedures (P = 0.012), resulting in lower overall bleeding in the oldest group(P < 0.001). Mobility outcomes were more favorable in septuagenarians, whereas octogenarians tended to maintain or experience a decline in mobility(P = 0.012). A total of 6 (5%) intraoperative complications and 12 (10%) postoperative complications were documented, with no statistically significant differences observed between the groups. CONCLUSIONS: This case series demonstrates that septuagenarians and octogenarians can achieve favorable clinical outcomes with elective spine surgery. Spine surgeons should be well-versed in the clinical and surgical care of older adults, providing optimal management that considers their increased comorbidity burden and heightened fragility.

Oral Treprostinil is Associated with Improved Survival in FREEDOM-EV and its Open-Label Extension.

INTRODUCTION: In the event-driven FREEDOM-EV trial, oral treprostinil delayed clinical worsening in patients with pulmonary arterial hypertension (PAH). Open-label extension studies offer additional data about tolerability, efficacy, and survival, especially for those initially assigned placebo. The aim of the current study was to determine if oral treprostinil changed survival when considering the parent and extension study, if treprostinil provides functional benefits for participants initially assigned to placebo, and if the benefits observed for those treated with treprostinil were durable. METHODS: Both active and placebo participants from FREEDOM-EV could enroll in the FREEDOM-EV open-label extension (OLE) study after experiencing an investigator-assessed clinical worsening event or after parent study closure. All participants in the OLE were offered open-label oral treprostinil. Previously assigned placebo participants titrated to maximally tolerated doses; previously assigned treprostinil participants continued dose titration. We repeated assessments including functional class and 6-min walk distance (6MWD) at 12-week intervals and measured N-terminal pro-brain natriuretic peptide (NT-proBNP) at week 48. Survival was estimated by Kaplan-Meier analysis, and we estimated hazard ratio (HR) using Cox proportional hazards. RESULTS: Of 690 FREEDOM-EV participants, 470 enrolled in the OLE; vital status was available for 89% of initial Freedom-EV participants. When considering the combined parent and open-label data, initial assignment to oral treprostinil reduced mortality (HR 0.64, 95% confidence interval 0.46-0.91, p = 0.013); absolute risk reduction was 9%. Participants randomized to placebo who initiated oral treprostinil after clinical worsening and tolerated treatment through week 48 demonstrated favorable shifts in functional class (p < 0.0001), 6MWD improvements of + 84 m (p < 0.0001), and a reduction in NT-proBNP of - 778 pg/mL (p = 0.02), compared to OLE baseline. Modest trends toward benefit were measured for those initially assigned placebo who did not have clinical worsening, and 132/144 (92%) of treprostinil assigned participants without clinical worsening remained on drug at week 48 in the OLE study. Adverse events were consistent with FREEDOM-EV. CONCLUSION: Initial treprostinil assignment improved survival in the entire data set; those who began treprostinil after a clinical worsening in the placebo arm and tolerated drug to week 48 enjoyed substantial functional gains. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01560637.

Parenteral treprostinil induction for rapid attainment of therapeutic doses of oral treprostinil.

RATIONALE: Oral treprostinil slows disease progression and improves exercise capacity in pulmonary arterial hypertension; however, titration can be prolonged. Published data suggests prostacyclin-naïve patients achieve total daily oral treprostinil doses of about 6 mg by Week 16, while those on prior parenteral treprostinil reach higher doses at the same timepoint. OBJECTIVES: EXPEDITE (NCT03497689), a single-arm, multicenter study, assessed the efficacy of rapid parenteral treprostinil induction to quickly reach higher doses of oral treprostinil for the treatment of pulmonary arterial hypertension. METHODS: Parenteral treprostinil was titrated for 2-8 weeks, followed by cross-titration of oral treprostinil. The primary endpoint was percentage of patients reaching ≥12 mg daily of oral treprostinil at Week 16. Secondary endpoints included clinical changes from baseline to Week 16. RESULTS: Twenty-nine prostacyclin-naïve patients were included in efficacy analyses. At Week 16, the mean daily oral treprostinil dose was 16.4 mg; 79% of patients met the primary endpoint. From baseline to Week 16, median REVEAL Lite 2 score improved (decreased) from 6 to 3.5 (p = 0.0006). Statistically significant improvements were also seen in World Health Organization Functional Class, N-terminal-pro brain natriuretic peptide levels, 6-minute walk distance, right atrial area, Borg Dyspnea Score, and emPHasis-10 score. Favorable trends were seen in risk stratification, echocardiography parameters, disease symptoms, and treatment satisfaction. CONCLUSION: Short-course parenteral treprostinil induction resulted in oral treprostinil doses over twice those reported in de novo initiations and may be a useful approach to quickly achieve the therapeutic benefits of oral treprostinil.

Implementing the EXPEDITE parenteral induction protocol: Rapid parenteral treprostinil titration and transition to oral treprostinil.

Treprostinil is a prostacyclin analogue that targets multiple cellular receptors to treat pulmonary arterial hypertension (PAH). In certain scenarios, patients may require aggressive treprostinil titration. Several studies have demonstrated that higher doses of treprostinil lead to greater clinical benefit. Data supports successful transitions from parenteral to oral treprostinil; however, administration routes, transition duration, and transition setting vary in the real-world. The EXPEDITE clinical trial (NCT03497689) prospectively studied whether rapid parenteral treprostinil induction can be used to achieve high doses of oral treprostinil (total daily dose: ≥12 mg) in prostacyclin naïve PAH patients. Parenteral prostacyclin induction may be more appropriate for patients who need to reach therapeutic dosing more urgently than longer titration durations reported with conventional de novo oral treprostinil initiation. This summary provides strategies utilized in EXPEDITE. Parenteral treprostinil was initiated at 2 ng/kg/min intravenously or subcutaneously; clinicians determined the frequency and dose increment of up-titration. Two distinct transition schedules from parenteral to oral treprostinil were employed: rapid cross-titration in an inpatient setting (median: 2 days) or gradual cross-titration in an outpatient setting (median: 5 days). Patient status was closely monitored after transition; oral treprostinil dose was titrated to clinical effect and tolerability. Factors considered when individualizing dosing strategies included parenteral and oral treprostinil target doses, nursing support, patient education, medication counseling and adverse events management. EXPEDITE demonstrated the time to a therapeutic dose of oral treprostinil is significantly shorter when utilizing a short-term parenteral induction strategy and may be suitable for patients requiring aggressive titration of oral treprostinil.

The Adjustable Cranial Plate: A Novel Implant Designed to Eliminate the Need for Cranioplasty Surgery Following a Hemicraniectomy Operation.

BACKGROUND: Decompressive hemicraniectomy (DHC) is performed to relieve life-threatening intracranial pressure elevations. After swelling abates, a cranioplasty is performed for mechanical integrity and cosmesis. Cranioplasty is costly with high complication rates. Prior attempts to obviate second-stage cranioplasty have been unsuccessful. The Adjustable Cranial Plate (ACP) is designed for implantation during DHC to afford maximal volumetric expansion with later repositioning without requiring a second major operation. METHODS: The ACP has a mobile section held by a tripod fixation mechanism. Centrally located gears adjust the implant between the up and down positions. Cadaveric ACP implantation was performed. Virtual DHC and ACP placement were done using imaging data from 94 patients who had previously undergone DHC to corroborate our cadaveric results. Imaging analysis methods were used to calculate volumes of cranial expansion. RESULTS: The ACP implantation and adjustment procedures are feasible in cadaveric testing without wound closure difficulties. Results of the cadaveric study showed total volumetric expansion achieved was 222 cm3. Results of the virtual DHC procedure showed the volume of cranial expansion achieved by removing a standardized bone flap was 132 cm3 (range, 89-171 cm3). Applied to virtual craniectomy patients, the total volume of expansion achieved with the ACP implantation operation was 222 cm3 (range, 181-263 cm3). CONCLUSIONS: ACP implantation during DHC is technically feasible. It achieves a volume of cranial expansion that will accommodate that observed following survivable hemicraniectomy operations. Moving the implant from the up to the down position can easily be performed as a simple outpatient or inpatient bedside procedure, thus potentially eliminating second-stage cranioplasty procedures.

Human Brainstem and Cerebellum Atlas: Chemoarchitecture and Cytoarchitecture Paired to MRI.

Lesion localization is the basis for understanding neurologic disease, which is predicated on neuroanatomical knowledge carefully cataloged from histology and imaging atlases. However, it is often difficult to correlate clinical images of brainstem injury obtained by MRI scans with the details of human brainstem neuroanatomy represented in atlases, which are mostly based on cytoarchitecture using Nissl stain or a single histochemical stain, and usually do not include the cerebellum. Here, we report a high-resolution (200 µm) 7T MRI of a cadaveric male human brainstem and cerebellum paired with detailed, coregistered histology (at 2 µm single-cell resolution) of the immunohistochemically stained cholinergic, serotonergic, and catecholaminergic (dopaminergic, noradrenergic, and adrenergic) neurons, in relationship to each other and to the cerebellum. These immunohistochemical findings provide novel insights into the spatial relationships of brainstem cell types and nuclei, including subpopulations of melanin and TH+ neurons, and allows for more informed structural annotation of cell groups. Moreover, the coregistered MRI-paired histology helps validate imaging findings. This is useful for interpreting both scans and histology, and to understand the cell types affected by lesions. Our detailed chemoarchitecture and cytoarchitecture with corresponding high-resolution MRI builds on previous atlases of the human brainstem and cerebellum, and makes precise identification of brainstem and cerebellar cell groups involved in clinical lesions accessible for both laboratory scientists and clinicians alike.SIGNIFICANCE STATEMENT Clinicians and neuroscientists frequently use cross-sectional anatomy of the human brainstem from MRI scans for both clinical and laboratory investigations, but they must rely on brain atlases to neuroanatomical structures. Such atlases generally lack both detail of brainstem chemical cell types, and the cerebellum, which provides an important spatial reference. Our current atlas maps the distribution of key brainstem cell types (cholinergic, serotonergic, and catecholaminergic neurons) in relationship to each other and the cerebellum, and pairs this histology with 7T MR images from the identical brain. This atlas allows correlation of the chemoarchitecture with corresponding MRI, and makes the identification of cell groups that are often discussed, but rarely identifiable on MRI scan, accessible to clinicians and clinical researchers.

Endoscopic Reconstruction of the Anterior Skull Base Following Tumor Resection: Application of a Novel Bioabsorbable Plate.

OBJECTIVE: Endoscopic repair of skull base defects is required following resection of intracranial pathology via the endoscopic endonasal approach (EEA). Many closure techniques have been described, but choosing between techniques remains controversial. We report outcomes of 560 EEA procedures of skull base reconstruction performed on 508 patients over a 15-year-period. Halfway through this period, we adopted the use of a rigid, bioabsorbable extrasellar plate for reconstruction, enabling a comparison between this technique and those used previously. METHODS: All patients undergoing EEA from 2005 to 2019 at our institution were retrospectively reviewed. Demographic information, surgical pathology, tumor dimensions and radiographic features, reconstructive technique, and patient-related outcomes were collected and analyzed with univariate and multivariate statistical modeling. RESULTS: Five-hundred sixty procedures were performed on 508 patients. The series complication rate was 8.2%. Overall, cerebrospinal fluid (CSF) leak rate was 5.0% but varied significantly across closure techniques (p < 0.001). Critically, the CSF leak rate in the 272 cases prior to our 2013 adoption of the Resorb-X Plate (RXP) was 8.5%, whereas leak rate in the subsequent 288 cases was 1.7%. RXP was protective against CSF leak (p = 0.001), whereas gross total resection (GTR) correlated with increased leak rate (p = 0.001). Patient BMI was significantly associated with risk of leak (p = 0.047). Other variables did not impact leak risk. CONCLUSION: Reconstructive technique, extent of resection, and patient BMI significantly contributed to CSF leak rate. GTR was associated with increased leak risk while the RXP was protective. The bioabsorbable RXP is an effective option for rigid skull base repair with comparatively few complications. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1092-1098, 2023.

Evaluation of Sagittal Spinopelvic Balance in Spinal Cord Stimulator Patients.

OBJECTIVE: Spinal cord stimulation (SCS) has become a popular nonopioid pain intervention. However, the treatment failure rate for SCS remains significantly high and many of these patients have poor sagittal spinopelvic balance, which has been found to correlate with increased pain and decreased quality of life. The purpose of this study was to determine if poor sagittal alignment is correlated with SCS treatment failure. MATERIALS AND METHODS: Comparative retrospective analysis was performed between two cohorts of patients who had undergone SCS placement, those who had either subsequent removal of their SCS system (representing a treatment failure cohort) and those that underwent generator replacement (representing a successful treatment cohort). The electronic medical record was used to collect demographic and surgical characteristics, which included radiographic measurements of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Also included were data on pain medication usage including opioid and nonopioid therapies. RESULTS: Eighty-one patients met inclusion criteria, 31 had complete removal, and 50 had generator replacements. Measurement of sagittal balance parameters demonstrated that many patients had poor alignment, with 34 outside normal range for LL (10 vs 24 in removal and replacement cohorts, respectively), 30 for PI (12 [38.7%] vs 18 [36.0%]), 46 for PT (18 [58.1%] vs 28 [56.0%]), 38 for SS (18 [58.1%] vs 20 [40.0%]), and 39 for PI-LL mismatch (14 [45.2%] vs 25 [50.0%]). There were no significant differences in sagittal alignment parameters between the two cohorts. CONCLUSIONS: This retrospective cohort analysis of SCS patients did not demonstrate any relationship between poor sagittal alignment and failure of SCS therapy. Further studies of larger databases should be performed to determine how many patients ultimately go on to have additional structural spinal surgery after failure of SCS and whether or not those patients go on to have positive outcomes.

Minimally Invasive Approaches to Anterior Skull Base Meningiomas.

Objective Anterior skull base meningiomas include olfactory groove, planum sphenoidale, and tuberculum sellae lesions. Traditionally, standard craniotomy approaches have been used to access meningiomas in these locations. More recently, minimally invasive techniques including supraorbital and endonasal endoscopic approaches have gained favor; however there are limited published series comparing the use of these two techniques for these meningiomas. Using our patent database, we identified patients who underwent these two approaches, and conducted a retrospective chart review to compare outcomes between these two techniques. Methods A total of 32 patients who underwent minimally invasive approaches were identified: 20 supraorbital and 11 endoscopic endonasal. Radiographic images, presenting complaints and outcomes, were analyzed retrospectively. The safety of each approach was evaluated. Results The mean extent of resection through a supraorbital approach was significantly greater than that of the endoscopic endonasal approach, 88.1 vs. 57.9%, respectively ( p = 0.016). Overall, preoperative visual acuity and anopsia deficits were more frequent in the endonasal group that persisted postoperatively (visual acuity: p = 0.004; anopsia: p = 0.011). No major complications including cerebrospinal fluid (CSF) leaks or wound-related complications were identified in the supraorbital craniotomy group, while the endonasal group had two CSF leaks requiring lumbar drain placement. Length of stay was shorter in the supraorbital group (3.4 vs. 6.1 days, p < 0.001). Conclusion Anterior skull base meningiomas can be successfully managed by both supraorbital and endoscopic endonasal approaches. Both approaches provide excellent direct access to tumor in carefully selected patients and are safe and efficient, but patient factors and symptoms should dictate the approach selected.

Cervical alignment in the obese population following posterior cervical fusion for cervical myelopathy.

STUDY DESIGN: Retrospective cohort study OBJECTIVE: The aim of this study was to investigate the effect of body mass index (BMI) on the reoperation rate and cervical sagittal alignment of patients who underwent posterior cervical decompression and fusion for cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Cervical sagittal balance has been correlated with postoperative clinical outcomes. Previous studies have shown worse postoperative sagittal alignment and higher reoperation rates in patients with high BMI undergoing anterior decompression and fusion. Similar evidence for the impact of obesity in postoperative sagittal alignment for patients with (CSM) undergoing posterior cervical decompression and fusion (PCF) is lacking. METHODS: A retrospective analysis of 198 patients who underwent PCF for cervical myelopathy due to degenerative spine disease was performed. Demographics, need for reoperation, and perioperative radiographic parameters were collected. Cervical lordosis (CL), C2-7 sagittal vertical axis (SVA), and T1 slope (T1S) was measured on standing lateral radiographs. Comparative analysis of the patient cohort was performed by stratifying the sample population into three BMI categories (<25, 25-30, ≥30). RESULT: Of the 198 patients that met inclusion criteria, 53 had BMI normal (<25), 65 were overweight (25-30), and 80 were obese (≥30). Mean SVA increased postoperatively in all groups, 4 mm in the normal group, 13 mm in the overweight group, and 13 mm in the obese group (p = 0.003). There was no significant difference in the postoperative change of cervical lordosis or T1 slope between the groups. Multivariate analysis demonstrated fusions involving the cervicothoracic junction and those involving 5 or more levels significantly affected alignment parameters. There were 27 complications requiring reoperation (14%) with no significant differences among the groups stratified by BMI (p = 0.386). CONCLUSIONS: Overweight patients (BMI>25) with CSM undergoing PCF had a greater increase in SVA than normal weight patients while reoperation rates were similar. In addition, preoperative CL increased with increasing BMI, although this trend was not Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation significant and there was not found to be a significant difference between the change in CL from baseline to post-fusion between BMI cohorts. This study further highlights the importance of considering BMI when attempting to optimize sagittal alignment in patients undergoing PCF.

Cognitive and Psychological Functioning in Chiari Malformation Type I Before and After Surgical Decompression - A Prospective Cohort Study.

BACKGROUND: Chiari Malformation Type I (CM-I) is defined as cerebellar tonsil displacement more than 5 mm below the foramen magnum. This displacement can alter cerebrospinal fluid flow at the cervicomedullary junction resulting in Valsalva-induced headaches and syringomyelia and compress the brainstem resulting in bulbar symptoms. However, little is known about cognitive and psychological changes in CM-I. OBJECTIVE: To prospectively assess cognitive and psychological performance in CM-I and determine whether changes occur after surgical decompression. METHODS: Blinded evaluators assessed symptomatic CM-I patients ages ≥18 with a battery of neuropsychological and psychological tests. Testing was conducted preoperatively and 6 to 18 mo postoperatively. Data were converted to Z-scores based on normative data, and t-tests were used to analyze pre-post changes. RESULTS: A total of 26 patients were included, with 19 completing both pre- and post-op cognitive assessments. All patients had resolution of Valsalva-induced headaches and there was improvement in swallowing dysfunction (P < .0001), ataxia (P = .008), and sleep apnea (P = .021). Baseline performances in visual perception and construction (z = -1.11, P = .001) and visuospatial memory (z = -0.93, P = .002) were below average. Pre-post comparisons showed that CM-I patients had stable cognitive and psychological functioning after surgery, without significant changes from preoperative levels. CONCLUSION: CM-I patients had below average performance in visuospatial and visuoconstructional abilities preoperatively. Prospective longitudinal data following surgery demonstrated improved neurologic status without any decline in cognition or psychological functioning. Routine pre- and postoperative formal neuropsychological assessment in CM-I patients help quantify cognitive and behavioral changes associated with surgical decompression.

Bone flap management strategies for postcraniotomy surgical site infection.

BACKGROUND: Surgical site infection (SSI) after a craniotomy is traditionally treated with wound debridement and disposal of the bone flap, followed by intravenous antibiotics. The goal of this study is to evaluate the safety of replacing the bone flap or performing immediate titanium cranioplasty. METHODS: All craniotomies at single center between 2008 and 2020 were examined to identify 35 patients with postoperative SSI. Patients were grouped by bone flap management: craniectomy (22 patients), bone flap replacement (seven patients), and titanium cranioplasty (six patients). Retrospective chart review was performed to identify patient age, gender, index surgery indication and duration, diffusion restriction on MRI, presence of gross purulence, bacteria cultured, sinus involvement, implants used during surgery, and antibiotic prophylaxis/ treatment. These variables were compared to future infection recurrence and wound breakdown. RESULTS: There was no significant difference in infection recurrence or future wound breakdown among the three bone flap management groups (P = 0.21, P = 0.25). None of the variables investigated had any significant relation to infection recurrence when all patients were included in the analysis. However, when only the bone flap replacement group was analyzed, there was significantly higher infection recurrence when there was frank purulence present (P = 0.048). CONCLUSION: Replacing the bone flap or performing an immediate titanium cranioplasty is safe alternatives to discarding the bone flap after postoperative craniotomy SSI. When there is gross purulence present, caution should be used in replacing the bone flap, as infection recurrence is significantly higher in this subgroup of patients.

Metastatic Renal Cell Carcinoma to the Spine: Outcomes and Morbidity: Single-Center Experience.

BACKGROUND: Renal cell carcinoma with metastases to the spine (RCCMS) requires a multidisciplinary approach. We reviewed our institutional experience with RCCMS patients undergoing spinal surgery in order to identify factors that may affect clinical outcomes, survival, and complications. METHODS: Patients with RCCMS who underwent operative intervention from 2007 to 2020 were reviewed retrospectively. RESULTS: Forty-four patients with the diagnosis of RCCMS were identified. Pain was the most common symptom, and neurologic dysfunction was present in one third of cases. Thoracic spine was the most common location (N = 27), followed by the lumbar (N = 12) and cervical (N = 5) regions. The overall survival from diagnosis of renal cell carcinoma was 25 (2 - 194) months and 8 (0.3 - 92) months after spinal surgery. Gender, age, spinal level, postoperative radiation, and nephrectomy had no bearing on survival. Survival for patients with a Tokuhashi score of 0 - 8, 9 - 11, and 12 - 15 was 6.5 (1.5 - 23.5), 8.9 (0.3 - 91.6), and 23.4 (2.5 - 66) months, respectively (P = 0.03). The postoperative American Spinal Cord Injury Association score of E (hazard ratio 0.109 [95% confidence interval 0.022 - 0.534, P = 0.006) also bore a significant influence on survival. There was a total of 10 complications in 7 of 44 (16%) patients. CONCLUSIONS: Median postoperative survival of patients with RCCMS was 8 (0.3 - 92) months. Higher Tokuhashi score and ASIA E score at follow-up correlated with improved overall survival. Complication rate was 16%. Spinal surgery in RCCMS is indicated for the preservation of function and prevention of neurologic deterioration. Multimodality therapy with improved chemotherapy and stereotactic spinal radiation is expected to impact quality and length of survival positively.

Fourth ventricle roof angle as a measure of fourth ventricle bowing and a radiographic predictor of brainstem dysfunction in Chiari malformation type I.

OBJECTIVE: Chiari malformation type I (CM-I) is a congenital and developmental abnormality that results in tonsillar descent 5 mm below the foramen magnum. However, this cutoff value has poor specificity as a predictor of clinical severity. Therefore, the authors sought to identify a novel radiographic marker predictive of clinical severity to assist in the management of patients with CM-I. METHODS: The authors retrospectively reviewed 102 symptomatic CM-I (sCM-I) patients and compared them to 60 age-matched normal healthy controls and 30 asymptomatic CM-I (aCM-I) patients. The authors used the fourth ventricle roof angle (FVRA) to identify fourth ventricle "bowing," a configuration change suggestive of fourth ventricle outlet obstruction, and compared these results across all three cohorts. A receiver operating characteristic (ROC) curve was used to identify a predictive cutoff for brainstem dysfunction. Binary logistic regression was used to determine whether bowing of the fourth ventricle was more predictive of brainstem dysfunction than tonsillar descent, clival canal angle, or obex position in aCM-I and sCM-I patients. RESULTS: The FVRA had excellent interrater reliability (intraclass correlation 0.930, 95% CI 0.905-0.949, Spearman r2 = 0.766, p < 0.0001). The FVRA was significantly greater in the sCM-I group than the aCM-I and healthy control groups (59.3° vs 41.8° vs 45.2°, p < 0.0001). No difference was observed between aCM-I patients and healthy controls (p = 0.347). ROC analysis indicated that an FVRA of 65° had a specificity of 93% and a sensitivity of 50%, with a positive predictive value of 76% for brainstem dysfunction. FVRA > 65° was more predictive of brainstem dysfunction (OR 5.058, 95% CI 1.845-13.865, p = 0.002) than tonsillar herniation > 10 mm (OR 2.564, 95% CI 1.050-6.258, p = 0.039), although increasing age was also associated with brainstem dysfunction (OR 1.045, 95% CI 1.011-1.080, p = 0.009). A clival canal angle < 140° (p = 0.793) and obex below the foramen magnum (p = 0.563) had no association with brainstem dysfunction. CONCLUSIONS: The authors identified a novel radiographic measure, the FVRA, that can be used to assess fourth ventricular bowing in CM-I and is more predictive of brainstem dysfunction than tonsillar herniation. The FVRA is easy to measure, has excellent interrater variability, and can be a reliable universal radiographic measure. The FVRA will be useful in further describing CM-I radiographically and clinically by identifying patients more likely to be symptomatic as a result of brainstem dysfunction.

Relationship between odontoid fracture angle and cervical sagittal balance.

BACKGROUND: Fractures can occur in various locations within the odontoid process with differing orientations. However, little is known about what factors contribute to the anterior versus posterior angles/orientation of these fractures. METHODS: We evaluated 74 patients with odontoid fractures (2013-2018) from a single-institution. Patients' fracture angles/orientations were measured on computed tomography studies, and were grouped into oblique posterior (OP) or oblique anterior (OA) groups. We also took into account cervical sagittal balance utilizing upright x-rays. Other variables studied included patients' ages, sagittal balance measurements, and the mechanisms of injury. RESULTS: Fracture angles were significantly steeper in the OP group. OP fractures had larger C2-C7 sagittal vertical axis, occiput-C2 angles, and occiput-C7 angles versus anteriorly oriented fractures. In our linear regression model, advanced age and large occiput-C2 angles were predictive of the odontoid fracture angle. Patients who sustained ground-level falls also had significantly steeper fracture angles versus those involved in motor vehicle accidents. CONCLUSION: The odontoid tends to fracture at a steep, posterior angle in elderly patients who demonstrate a large positive sagittal balance when the head is extended following a ground-level falls.

Case series of sphenoid wing meningioma - What is a maximal safe resection?

BACKGROUND: Sphenoid wing meningiomas are a challenging surgical disease with relatively high perioperative morbidity. Most studies to date have focused on resection strategies as it relates to disease recurrence. Few have examined the optimal strategy as it relates to overall patient survival. We retrospectively reviewed our case series and evaluated extent of resection and perioperative stroke as it relates to all cause and disease-specific survival. PATIENTS/METHODS: Ninety-four patients were included in the study. Demographics, clinical features, operative features and clinical course, and time to mortality evaluation were collected. Extent of resection (EOR) was defined as gross total (GTR, 100%), near total (NTR, ≥ 95%), and subtotal (STR,<95%). RESULTS: The overall mean EOR was 94.5% with 70.2% of cases achieving GTR, 12.8% achieved NTR, and 17% achieved STR. Postoperative stroke only occurred with GTR or NTR (p=0.041). Age alone was significant on Cox regression analysis for all cause mortality (p=0.042, HR 1.054 [95% CI 1.002 - 1.109]). Postoperative stroke was associated with worse disease-specific mortality (p=0.046, HR 23.337 [95% CI 1.052 - 517.782) with no impact from extent of resection (p=0.258). CONCLUSIONS: Although maximizing resection and minimizing recurrence is ideal, GTR or NTR confer a significantly higher stroke risk. Most patients do not die from their meningioma, as all cause mortality was associated only with age. However, perioperative stroke conferred decreased survival throughout follow up. This series demonstrates that an overly aggressive surgical philosophy negatively impacted disease specific survival.

Tethered spinal cord syndrome in adults in the MRI era: recognition, pathology, and long-term objective outcomes.

OBJECTIVE: Tethered cord syndrome (TCS) has been well described in pediatric patients. Many recent reports of TCS in adult patients have grouped retethering patients with newly diagnosed ones without separately analyzing each entity and outcome. The authors reviewed their experience of newly diagnosed adult TCS patients to identify and explore TCS misdiagnosis, recognition, subtype pathology, and individual objective outcomes. METHODS: This study included 24 adult patients (20 female and 4 male) who fit the criteria of being newly diagnosed and aged 20 years and older (age range 20-77 years). Preexisting dermal sinus was present in 6 patients, hypertrichosis in 5, skin tag/cleft/dimple and fatty subcutaneous masses in 5, scoliosis in 2, and neurological abnormalities in 4 patients. The pathology consisted of TCS with taut filum in 8 patients, conus lipoma with TCS in 7, diastematomyelia in 7, and cervical cord tethering in 2 patients. Of the 24 study patients, nondermatomal low-back or perineal pain occurred in 19 patients, bladder dysfunction in 21, and motor, sensory, and reflex abnormalities in 21 patients. Aggravating factors were repeated stretching, multiple pregnancies, heavy lifting, and repeated bending. Urological evaluation included bladder capacity, emptying, postvoid residuals, detrusor function, pelvic floor electromyography (EMG), bladder sensitivity, and sphincter EMG, which were repeated at 6 months and 1 year postoperatively. The follow-up was 1 to 30 years. Detailed postoperative neurological findings and separate patient outcome evaluations were recorded. Four of the 24 patients did not have an operation. RESULTS: Resolution of pain occurred in 16 of the 19 patients reporting low-back or perineal pain. Motor and sensory complaints resolved in 17 of 20 patients. Regarding bladder dysfunction, in the 20 patients with available data, bladder function returned to normal in 12 patients, improved in 3 patients, and was unchanged in 5 patients. If the symptom duration was less than 6-8 months, there was recovery of all parameters of pain, bladder dysfunction, and neurological deficit, and recovery from hyperreflexia matched that from neurological deficit. Fifteen patients were employed preoperatively and returned to work, and an additional 3 others who were unable to work preoperatively were able to do so postoperatively. CONCLUSIONS: Most adults with newly diagnosed TCS have unrecognized neurocutaneous abnormalities and neurological deficits. The triad of nondermatomal sacral or perineal pain, bladder dysfunction, and neurological deficit should not be confused with hip or degenerative lumbosacral disease. Addressing the primary pathology often leads to successful results.