Safety and efficacy of low-dose rhBMP-2 use for anterior cervical fusion.

OBJECTIVE: The use of recombinant human bone morphogenetic protein 2 (rhBMP-2) in routine anterior cervical fusion (ACF) is controversial. Early reports described high complication rates. A variety of dosing regimens ranging from 0.6 to 2.1 mg per level fused have been reported. The authors hypothesized that the high amounts of rhBMP-2 used in these studies led to the high complication rates observed; therefore, they set out to evaluate the safety and efficacy of low-dose rhBMP-2 for use in ACFs. METHODS: Patient inclusion criteria were 1) age 18 to 70 years; 2) initial stand-alone ACF construct; 3) fusion augmentation with rhBMP-2; and 4) at least 1 year of radiographic follow-up. A successful fusion was defined by either 1) lateral flexion-extension radiographs with less than 1 mm of movement across the fused spinous processes, or 2) bone bridging at least half of the fusion area originally achieved by surgery on fine-cut CT. Patient demographics, perioperative data, and postoperative complications were recorded. RESULTS: A total of 198 patients met the inclusion criteria and were included for analysis. Sixty-two patients (31%) were smokers. The median number of levels fused was 2 (IQR 1.25). The mean dose of rhBMP-2 was 0.50 ± 0.09 mg per level. Twenty-two (11%) patients experienced dysphagia. Eleven (6%) patients experienced cervical swelling. Two (1%) patients returned to the operating room (OR) for postoperative hematoma. One (0.5%) patient returned to the OR for seroma. Two (1%) patients experienced pseudarthrosis requiring a posterior fusion. Three (2%) patients experienced a new postoperative neurological deficit that had recovered by last the follow-up. Overall, 190 (96%) patients experienced solid arthrodesis over an average of 15 months of follow-up. There was no difference in fusion rates between patients who were either smokers or nonsmokers (p = 0.7073). CONCLUSIONS: The use of low-dose rhBMP-2 safely and effectively augmented anterior cervical arthrodesis. The low-dose protocol assessed in this study appeared to significantly reduce complications associated with rhBMP-2 use in ACF compared with the literature. The authors have determined that using low-dose rhBMP-2 in patients who are smokers, those with multilevel ACFs, or others at high risk of developing pseudarthrosis is recommended.

Standardization of cerebrospinal fluid shunt valves in pediatric hydrocephalus: an analysis of cost, operative time, length of stay, and shunt failure.

OBJECTIVE: CSF shunts are the most common procedures performed in the pediatric neurosurgical population. Despite attempts in multiple studies, a superior shunt valve has never been shown. Because of this, the authors aim was to examine the impact of shunt valve standardization at their institution to determine if there is a difference in surgical cost, operative time, or short-term postoperative shunt failure. METHODS: A retrospective analysis at the authors' institution was performed for all new CSF diversion shunts, as well as shunt revisions requiring a new valve, or a new valve and at least a new proximal or distal catheter over a 1-year period (January 1, 2016, to December 31, 2016). After a period of transition, neurosurgeons were encouraged to use only one type of fixed-differential-pressure valve and one type of programmable valve when performing shunt surgeries. These patients who underwent "standardized" shunt surgery over a 1-year period (January 1, 2018, to December 31, 2018) were then compared to patients in the prestandardization epoch. All patients were followed for a 12-month period after surgery. Demographic information, surgical cost, operative time, and postoperative shunt failure data were collected in all patients in the study. RESULTS: The authors analyzed 87 shunt surgeries in patients prior to standardization and 94 shunt surgeries in patients after standardization. The rate of violation of the standardized shunt valve policy after implementation was 5.3% (5 of 94 procedures). When comparing the prestandardization group to those who received the standardized valve, operative costs were less ($1821.04 vs $1333.75, p = 0.0034). There was no difference in operative times between groups (78 minutes vs 81 minutes, p = 0.5501). There was no difference in total number of shunt failures between the two groups at 12 months after surgery (p = 0.0859). The rate of postoperative infection was consistent with the literature at 8%. CONCLUSIONS: In accordance with quality improvement principles, the reduction of unexplained clinical variance invariably leads to a decrease in cost and, more importantly, increased value. In this study, the implementation of a standardized shunt valve decreased operative cost. There were no differences in postoperative shunt failures at 12 months after surgery and no differences in length of surgery. Standardizing shunt valves in the treatment of pediatric hydrocephalus seems to be cost-effective and safe.

Institutional review of the management of type II odontoid fractures: associations and outcomes with fibrous union.

OBJECTIVE: Type II odontoid fractures may be managed operatively or nonoperatively. If managed with bracing, bony union may never occur despite stability. This phenomenon is termed fibrous union. The authors aimed to determine associations with stable fibrous union and compare the morbidity of patients managed operatively and nonoperatively. METHODS: The authors performed a retrospective review of their spine trauma database for adults with type II odontoid fractures between 2015 and 2019. Two-sample t-tests and Fisher's exact tests identified associations with follow-up stability and were used to compare operative and nonoperative outcomes. Sensitivity, specificity, and predictive values were calculated to validate initial stable upright cervical radiographs related to follow-up stability. RESULTS: Among 88 patients, 10% received upfront surgical fixation, and 90% were managed nonoperatively, of whom 22% had fracture instability on follow-up. Associations with instability after nonoperative management include myelopathy (OR 0.04, 95% CI 0.0-0.92), cerebrovascular disease (OR 0.23, 95% CI 0.06-1.0), and dens displacement ≥ 2 mm (OR 0.29, 95% CI 0.07-1.0). Advanced age was not associated with follow-up instability. Initial stability on upright radiographs was associated with stability on follow-up (OR 4.29, 95% CI 1.0-18) with excellent sensitivity and positive predictive value (sensitivity 89%, specificity 35%, positive predictive value 83%, and negative predictive value 46%). The overall complication rate and respiratory failure requiring ventilation on individual complication analysis were more common in operatively managed patients (33% vs 3%, respectively; p = 0.007), even though they were generally younger and healthier than those managed nonoperatively. Operative or nonoperative management conferred no difference in length of hospital or ICU stay, discharge disposition, or mortality. CONCLUSIONS: The authors delineate the validity of upright cervical radiographs on presentation in association with follow-up stability in type II odontoid fractures. In their experience, factors associated with instability included cervical myelopathy, cerebrovascular disease, and fracture displacement but not increased age. Operatively managed patients had higher complication rates than those managed without surgery. Fibrous union, which can occur with nonoperative management, provided adequate stability.

Improving Function in Cavernous Sinus Meningiomas: A Modern Treatment Algorithm.

Background: The efficacy and safety of radiosurgery led to paradigm shift in the management of cavernous sinus meningiomas. Nevertheless, patients are still significantly affected by cranial nerve deficits related to the mass effect of these tumors. Our management strategy involves the combination of a functional surgical decompression followed by radiation therapy. Methods: We reviewed a single institution's cohort of patients who underwent endoscopic endonasal decompression (EED) for symptomatic meningiomas primarily involving the cavernous sinus (CS) from 2010 to 2016. The preoperative neuro-ophthalmological exam was compared to the 1- and 6-month postoperative exams. The patient's length of hospital stay, complications, and radiological and clinical follow-up were noted. Results: A total of 17 patients underwent EED for CS meningiomas that fit our radiological criteria. The final outcome at the 6-month visit showed five patients (62.5%) with normalization of deficit and three patients (37.5%) with partial improvement of the CNII deficit. Out of the 12 patients who had cavernous sinus cranial nerves (CSCN) deficits, the final outcome at the 6-month visit showed four patients (33.33%) with normalization of deficit, seven patients (58.3%) with partial improvement, and one patient (8.33%) with no improvement. There were no intraoperative complications. Conclusion: The EED for CS meningiomas is a valuable technique when addressing acute/subacute CNII and CSCN deficits. This conservative surgical approach showed good functional outcomes, low morbidity, and low complication rates. However, it does not exempt the need for radiosurgery/radiation therapy for control of tumor growth.

Extended Supraorbital Approach with Modified Eyebrow Incision: Technical Note.

BACKGROUND: The extended supraorbital approach through a modified eyebrow incision is a minimally invasive variant of the frontotemporal or pterional approach that enriches a neurosurgeon's armamentarium for the treatment of pathologies lateral to the anterior clinoid process, by advancing laterally with frontal facial nerve branches monitoring. To demonstrate the steps of the approach, we studied 2 formalin-fixed and artery/vein silicone-injected adult cadaveric heads, and reviewed 1 of the 3 clinical cases operated on to illustrate the applicability of the approach. CLINICAL PRESENTATION: A 56-year-old woman presented with a history of seizures and a complaint of headache that started 2 months ago. She underwent an examination with brain magnetic resonance imaging that showed a dural-based lesion at the medial third of the lesser wing of sphenoid (which is consistent with meningioma). The patient underwent craniotomy with an extended supraorbital approach through a modified eyebrow incision that allowed Simpson grade II removal to be performed and good aesthetic outcome to be achieved. CONCLUSIONS: The extended supraorbital approach through a modified eyebrow incision is a minimally invasive approach that can add to a neurosurgeon's armamentarium and be used with microscopy, assisted by endoscope, or both to reach the anterior and middle cranial fossae.

Infradentate Approach to the Fourth Ventricle.

BACKGROUND: The use of minimally invasive transcranial ports for the resection of deep-seated lesions has been shown to be safe and effective for supratentorial lesions. The routine use of this surgical modality for posterior fossa masses has not been well established in the literature. In particular, fourth ventricular tumors are not the typical target for neuro-port surgery because of potential injury to the dentate nucleus. OBJECTIVE: To describe the use of a tubular retractor system to reach the fourth ventricle while sparing the cerebellar vermis and the dentate nucleus. Three cases illustrations are presented. METHODS: Surgical access to the fourth ventricle was developed sparing the cerebellar vermis and the dentate nucleus. The authors reviewed 3 cases to illustrate the feasibility of minimal access transcerebellar port surgery for the resection of these lesions using an infradentate access. RESULTS: None of the patients developed new neurological deficits and the pathology was successfully resected in all cases. There were no major complications related to surgery and no mortalities. CONCLUSION: The infradentate approach obviates the need for traditional approaches to the fourth ventricle, thus making this challenging target in the posterior fossa more accessible to neurosurgeons. The authors observed successful removal of lesions involving the fourth ventricle while avoiding any associated morbidity or mortality.

Management of Skull Base Tumors in the Obstetric Population: A Case Series.

BACKGROUND: Neoplasms rarely present during pregnancy; however, increases in plasma volume, hormone release-induced growth, and tumor hypervascularity can cause rapidly progressive symptoms of varying severity, ranging from those not requiring intervention to those necessitating emergent operations. Here we describe an algorithm for the management of symptomatic neoplasms in the obstetric population and provide recommendations for surgical indications and timing. METHODS: Patients who presented to the skull base clinic at a large tertiary care hospital between 2010 and 2016 were reviewed to identify those who presented with a skull base tumor during pregnancy. RESULTS: Our study cohort comprised 9 women with a skull base tumor during pregnancy. Four patients presented with symptoms that necessitated emergent skull base surgery, and 5 underwent surgery after delivery or were followed with continued surveillance. All operated patients had a World Health Organization grade I or II meningioma or schwannoma. There were no maternal complications. Based on our experience with this cohort, we have created a management algorithm. CONCLUSIONS: Management of a symptomatic tumor during pregnancy requires balancing the potential for curing the mother and the risk of harming the fetus. Trimester of pregnancy is the most critical factor in evaluating the need for urgent management. The second trimester is the optimal time for surgery, associated with the lowest risk for spontaneous abortion or preterm birth. The first and third trimesters are associated with increased risk of miscarriage and preterm labor, respectively. Induction of labor for preterm delivery, followed by surgery, may be appropriate in the early third trimester. Regardless of the perceived risk, however, all pregnant women with an emergent presentation should be offered surgery, regardless of trimester.

Cerebrospinal Fluid Leak Rhinorrhea after Systemic Erlotinib Chemotherapy for Metastatic Lung Cancer: A Familiar Problem from an Unfamiliar Culprit.

BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhea after medical therapy for pituitary prolactinoma is a rare but well-described phenomenon. To our knowledge, no CSF leaks have been reported after targeted medical treatment of pituitary or anterior skull base metastases. We report this unusual case to raise awareness of spontaneous CSF leaks in the setting of skull base metastatic disease. CASE PRESENTATION: A 66-year-old woman presented with epidermal growth factor receptor-mutant stage IV adenocarcinoma of the lung. Headache workup revealed a large sellar and clival lesion consistent with metastatic disease. Systemic erlotinib chemotherapy was initiated with a robust positive response. Approximately 1 week after chemotherapy initiation, the patient noted clear discharge from the right nostril. Her oncologist first diagnosed her with allergic rhinitis, but she presented with meningitis 4 days after diagnosis of CSF leak and was admitted for intravenous antibiotics and definitive repair of a CSF leak via an endoscopic endonasal approach. An erosion of bone and dura was found at the dorsum sellae where tumor had regressed due to the chemotherapy. A multilayer skull base repair was made uneventfully, and she recovered fully with no leakage seen at 2-month follow-up. CONCLUSIONS: All members of the treatment team should be aware of this possibility of CSF leak after initiation of systemic chemotherapy and tumor regression and urgently refer patients for repair if a leak should develop before the development of meningitis.

A Side Door to Meckel's Cave: Anatomic Feasibility Study for the Lateral Transorbital Approach.

BACKGROUND: In the last decade, endoscopic skull base surgery has significantly developed and generated a plethora of techniques and approaches for access to the cranial ventral floor. However, the exploration for the least-aggressive, maximally efficient approach continues. OBJECTIVE: To describe in detail an anatomical study, along with the technical nuances of a novel endoscopic approach to Meckel's Cave (MC) using a lateral transorbital (LTO) route. METHODS: Eighteen orbits of injected cadaveric specimens were operated on, using an endoscopic LTO approach to MC, middle cranial fossa, and paramedian skull base preserving the orbital rim. Surgical navigation and an after-the-fact infratemporal craniectomy were utilized to identify the limits of the approach. RESULTS: Following a transorbital approach opening a trapezoid window at the superolateral aspect (average 166.7 mm 2 ), a middle fossa "peeling" and full visualization of MC was accomplished with no difficulties in all specimens. The entire approach was performed extradurally without the need to expose the temporal lobe. CONCLUSION: In a cadaveric model, the endoscopic LTO approach affords a direct route to access MC. Its main advantage is that it is minimally disruptive in nature, less brain retraction is required, and it reaches the middle fossa in an anterolateral perspective. It also requires no manipulation of the temporalis muscle, limited cosmetic incision, and rapid recovery. It seems a viable alternative to traditional approaches for lesions lateral to the cranial nerves at the cavernous sinus and MC, that is, schwannomas. Clinical utilization of this approach will challenge its efficacy and identify limitations.

Pipeline embolization device for recurrence of previously treated aneurysms.

OBJECTIVE The utilization of the Pipeline embolization device (PED) has increased significantly since its inception and original approval for use in large, broad-necked aneurysms of the internal carotid artery. While microsurgical clipping and advances in endovascular techniques have improved overall efficacy in achieving complete occlusion, recurrences still occur, and the best modality for retreatment remains controversial. Despite its efficacy in this setting, the role of PED utilization in the setting of recurrent aneurysms has not yet been well defined. This study was designed to assess the safety and efficacy of PED in the recurrence of previously treated aneurysms. METHODS The authors reviewed a total of 13 cases in which patients underwent secondary placement of a PED for aneurysm recurrence following prior treatment with another modality. The PEDs were used to treat aneurysm recurrence or residual following endovascular coiling in 7 cases, flow diversion in 2, and microsurgical clipping in 4. The mean time between initial treatment and retreatment with a PED was 28.1 months, 12 months, and 88.7 months, respectively. Clinical outcomes, including complications and modified Rankin Scale (mRS) scores, and angiographic evidence of complete occlusion were tabulated for each treatment group. RESULTS All PEDs were successfully placed without periprocedural complications. The rate of complete occlusion was 80% at 6 months after PED placement and 100% at 12 months in these patients who underwent PED placement following failed endovascular coiling; there were no adverse clinical sequelae at a mean follow-up of 26.1 months. In the 2 cases in which PEDs were placed for treatment of residual aneurysms following prior flow diversion, 1 patient demonstrated asymptomatic vessel occlusion at 6 months, and the other exhibited complete aneurysm occlusion at 12 months. In patients with aneurysm recurrence following prior microsurgical clipping, the rate of complete occlusion was 100% at 6 and 12 months, with no adverse sequelae noted at a mean clinical follow-up of 27.7 months. CONCLUSIONS The treatment of recurrent aneurysms with the PED following previous endovascular coiling, flow diversion, or microsurgical clipping is associated with a high rate of complete occlusion and minimal morbidity.

Viral vectors encoding endomorphins and serine histogranin attenuate neuropathic pain symptoms after spinal cord injury in rats.

BACKGROUND: The treatment of spinal cord injury (SCI)-induced neuropathic pain presents a challenging healthcare problem. The lack of available robust pharmacological treatments underscores the need for novel therapeutic methods and approaches. Due to the complex character of neuropathic pain following SCI, therapies targeting multiple mechanisms may be a better choice for obtaining sufficient long-term pain relief. Previous studies in our lab showed analgesic effects using combinations of an NMDA antagonist peptide [Ser1]histogranin (SHG), and the mu-opioid peptides endomorphins (EMs), in several pain models. As an alternative to drug therapy, this study evaluated the analgesic potential of these peptides when delivered via gene therapy. RESULTS: Lentiviruses encoding SHG and EM-1 and EM-2 were intraspinally injected, either singly or in combination, into rats with clip compression SCI 2 weeks following injury. Treated animals showed significant reduction in mechanical and thermal hypersensitivity, compared to control groups injected with GFP vector only. The antinociceptive effects of individually injected components were modest, but the combination of EMs and SHG produced robust and sustained antinociception. The onset of the analgesic effects was observed between 1-5 weeks post-injection and sustained without decrement for at least 7 weeks. No adverse effects on locomotor function were observed. The involvement of SHG and EMs in the observed antinociception was confirmed by pharmacologic inhibition using intrathecal injection of either the opioid antagonist naloxone or an anti-SHG antibody. Immunohistochemical analysis showed the presence of SHG and EMs in the spinal cord of treated animals, and immunodot-blot analysis of CSF confirmed the presence of these peptides in injected animals. In a separate group of rats, delayed injection of viral vectors was performed in order to mimic a more likely clinical scenario. Comparable and sustained antinociceptive effects were observed in these animals using the SHG-EMs combination vectors compared to the group with early intervention. CONCLUSIONS: Findings from this study support the potential for direct gene therapy to provide a robust and sustained alleviation of chronic neuropathic pain following SCI. The combination strategy utilizing potent mu-opioid peptides with a naturally-derived NMDA antagonist may produce additive or synergistic analgesic effects without the tolerance development for long-term management of persistent pain.