Comparative Analysis of Bone Structural Parameters Reveals Subchondral Cortical Plate Resorption and Increased Trabecular Bone Remodeling in Human Facet Joint Osteoarthritis.

Facet joint osteoarthritis is a prominent feature of degenerative spine disorders, highly prevalent in ageing populations, and considered a major cause for chronic lower back pain. Since there is no targeted pharmacological therapy, clinical management of disease includes analgesic or surgical treatment. The specific cellular, molecular, and structural changes underpinning facet joint osteoarthritis remain largely elusive. The aim of this study was to determine osteoarthritis-related structural alterations in cortical and trabecular subchondral bone compartments. To this end, we conducted comparative micro computed tomography analysis in healthy (n = 15) and osteoarthritic (n = 22) lumbar facet joints. In osteoarthritic joints, subchondral cortical plate thickness and porosity were significantly reduced. The trabecular compartment displayed a 42 percent increase in bone volume fraction due to an increase in trabecular number, but not trabecular thickness. Bone structural alterations were associated with radiological osteoarthritis severity, mildly age-dependent but not gender-dependent. There was a lack of association between structural parameters of cortical and trabecular compartments in healthy and osteoarthritic specimens. The specific structural alterations suggest elevated subchondral bone resorption and turnover as a potential treatment target in facet joint osteoarthritis.

Bow hunter's syndrome revisited: 2 new cases and literature review of 124 cases.

Rotational occlusion of the vertebral artery (VA), or bow hunter's syndrome, is a rare yet surgically treatable cause of vertebrobasilar insufficiency. The underlying pathology is dynamic stenosis of the VA by osteophytes, fibrous bands, or lateral disc herniation with neck rotation or extension. The authors present 2 previously unreported cases of bow hunter's syndrome and summarize 124 cases identified in a literature review. Both patients in the new cases were treated by VA decompression and fusion of the subaxial spine. Each had > 50% occlusion of the left VA at the point of entry into the transverse foramen with a contralateral VA that ended in the posterior inferior cerebellar artery. Analyzing data from 126 cases (the 2 new cases in addition to the previously published 124), the authors report that stenosis was noted within V1 in 4% of cases, in V2 in 58%, in V3 in 36%, and distal to C-1 in 2%. Patients presented in the 5th to 7th decade of life and were more often male than female. The stenotic area was decompressed in 85 (73%) of the 116 patients for whom the type of treatment was reported (V1, 4 [80%] of 5; V2, 52 [83%] of 63; V3/V4, 29 [60%] of 48). Less commonly, fusion or combined decompression and fusion was used (V2, 7 [11%] of 63; V3/V4, 14 [29%] of 48). Most patients reported complete resolution of symptoms. The authors conclude that patients with bow hunter's syndrome classically have an impaired collateral blood flow to the brainstem. This condition carries an excellent prognosis with decompression, fusion, or combined surgery, and individual patient characteristics should guide the choice of therapy.

Cost effectiveness of subaxial fusion--lateral mass screws versus transarticular facet screws.

As health care reform continues to evolve, demonstrating the cost effectiveness of spinal fusion procedures will be of critical value. Posterior subaxial cervical fusion with lateral mass screw and rod instrumentation is a well-established fixation technique. Subaxial transarticular facet fixation is a lesser known fusion technique that has been shown to be biomechanically equivalent to lateral mass screws for short constructs. Although there has not been a widespread adoption of transarticular facet screws, the screws potentially represent a cost-effective alternative to lateral mass rod and screw constructs. In this review, the authors describe an institutional experience with the use of lateral mass screws and provide a theoretical cost comparison with the use of transarticular facet screws.

Management of cerebrospinal fluid leaks after anterior decompression for ossification of the posterior longitudinal ligament: a review of the literature.

OBJECT: Anterior decompression is an effective way to treat cervical myelopathy associated with ossification of the posterior longitudinal ligament (OPLL); however, this approach is associated with an increased risk of a dural tear and resultant CSF leak because fusion of the dura with the ossified PLL is common in these cases. The authors review the literature and present an algorithm for treatment of CSF leaks in these patients. METHODS: A MEDLINE review was performed to identify papers related to CSF leak after anterior decompression for OPLL, and data were summarized to identify treatment options for various situations. A treatment algorithm was identified based on these findings and the experience of the authors. RESULTS: Eleven studies were identified that presented data on intra- and postoperative management of a CSF leak during ventral surgery for OPLL. The incidence of cervical dural tears and CSF leaks after anterior decompression procedures for OPLL ranged from 4.3% to 32%. Techniques including preventative measures, intraoperative dural repair with various materials, and postoperative drainage or shunt placement have all been used. CONCLUSIONS: Although direct dural repair is the preferred treatment for CSF leak, this technique is not always technically possible. In these cases, intraoperative adjuncts in combination with postoperative measures can be used to decrease the pressure gradient across the dural tear.

Thoracoscopic discectomy and instrumented fusion using a minimally invasive plate system: surgical technique and early clinical outcome.

OBJECT: The use of minimally invasive noninstrumented fusions has increased as thoracoscopic approaches to the spine have evolved. The addition of instrumentation is infrequent, in part because of the lack of a minimally invasive implant system. The authors describe a technique for thoracoscopic plating after discectomy and report early clinical outcomes. METHODS: After a standard endoscopic discectomy and partial corpectomy and before exposure of the ventral thecal sac, the authors implanted a polyaxial screw and clamping element under fluoroscopic guidance. Reconstruction involves placement of autograft in the defect and subsequent placement of the remainder of the screw/plate construct with 2 screws per vertebral level. RESULTS: Twenty-five patients underwent thoracoscopic and thoracoscopy-assisted discectomies and fusion in which the aforementioned plate system was used. Of 19 patients presenting with pain, 10 had 6-month clinical follow-up with a greater than 50% reduction in visual analog scale score, which continued to improve up to 2 years postoperatively. There were 3 cases of pneumonia, 3 CSF leaks, 1 chyle leak, and 1 death due to a massive pulmonary embolus on the 1st postoperative day. CONCLUSIONS: The authors conclude that thoracoscopic discectomy and plate-instrumented fusion can be achieved with acceptable results and morbidity. Further studies should evaluate the role of instrumented fusions after thoracoscopic discectomy in larger groups of patients and during a longer follow-up period.

Force quantification and simulation of pedicle screw tract palpation using direct visuo-haptic volume rendering.

PURPOSE: We present a feasibility study for the visuo-haptic simulation of pedicle screw tract palpation in virtual reality, using an approach that requires no manual processing or segmentation of the volumetric medical data set. METHODS: In a first experiment, we quantified the forces and torques present during the palpation of a pedicle screw tract in a real boar vertebra. We equipped a ball-tipped pedicle probe with a 6-axis force/torque sensor and a motion capture marker cluster. We simultaneously recorded the pose of the probe relative to the vertebra and measured the generated forces and torques during palpation. This allowed us replaying the recorded palpation movements in our simulator and to fine-tune the haptic rendering to approximate the measured forces and torques. In a second experiment, we asked two neurosurgeons to palpate a virtual version of the same vertebra in our simulator, while we logged the forces and torques sent to the haptic device. RESULTS: In the experiments with the real vertebra, the maximum measured force along the longitudinal axis of the probe was 7.78 N and the maximum measured bending torque was 0.13 Nm. In an offline simulation of the motion of the pedicle probe recorded during the palpation of a real pedicle screw tract, our approach generated forces and torques that were similar in magnitude and progression to the measured ones. When surgeons tested our simulator, the distributions of the computed forces and torques were similar to the measured ones; however, higher forces and torques occurred more frequently. CONCLUSIONS: We demonstrated the suitability of direct visual and haptic volume rendering to simulate a specific surgical procedure. Our approach of fine-tuning the simulation by measuring the forces and torques that are prevalent while palpating a real vertebra produced promising results.

Intradural spinal metastasis of renal cell cancer. Report of a case and review of 26 published cases.

Metastatic disease in the intradural compartment of the spine is a rare manifestation of cancer. We report the case of an 82-year-old patient with an intradural, extramedullary metastasis of renal cell carcinoma in the cervical spine. A literature search for intradural spinal metastases of renal cell carcinoma yielded a total of 26 further cases. 18 patients had sporadic renal cell carcinoma, and 9 patients had von Hippel-Lindau disease (VHL) in which the metastases of the renal cell carcinoma were embedded within spinal haemangioblastomas. Patients presented with paresis, back pain, altered sensation or, less frequently, bladder dysfunction. Intradural spinal metastases were diagnosed at an earlier age in VHL patients than in sporadic cases (mean 43 +/- 5 years vs. 60 +/- 14.5 years). The metastasis was surgically removed in 81% of patients. Pain improved in all patients, paresis in 90%, hypaesthesia in 38% and bladder dysfunction in 50%. Death occurred as a result of systemic cancer progression. 93% of patients in the sporadic renal cell cancer group died within 1.5 years, whereas two thirds of the VHL patients were alive after 2 years.

Inertial Measurement Unit-Assisted Implantation of Pedicle Screws in Combination With an Intraoperative 3-Dimensional/2-Dimensional Visualization of the Spine.

BACKGROUND: Inertial measurement units (IMUs) are microelectromechanical systems used to track orientation and motion. OBJECTIVE: To use instruments mounted with IMUs in combination with a 3- and 2-dimensional (3D/2D) rendering of the computed-tomography scan (CT) to guide implantation of pedicle screws. METHODS: Pedicle screws were implanted from T1 to S1 in 2 human cadavers. A software application enabled the surgeon to select the starting points and trajectories on a 3D/2D image of the spine, then locate these starting points on the exposed spine and apply the IMU-mounted instruments to reproduce the trajectories. The position of the screws was evaluated on the postoperative CT scan. RESULTS: A total of 72 pedicle screws were implanted. Thirty-seven (77%) of the thoracic screws were within the pedicle (Heary I), 7 (15%) showed a lateral breach of the pedicle, and 4 (8%) violated the anterior or lateral vertebral body (Heary III). In the lumbar spine and S1, 21 screws (88%) were within the pedicle (Gertzbein 0), 2 (8%) screws had a pedicle wall breach < 2 mm (Gertzbein 1), and 1 > 2 to < 4 mm (Gertzbein 2). In the second cadaver, the position was compared to the intraoperatively shown virtual position. The median offset was 3°(mean 3° ± 2°, variance 5, range 0°-9°) in the sagittal plane and 3° (mean 4° ± 3°, variance 9, range 0°-12°) in the axial plane. CONCLUSION: IMU-assisted implantation of pedicle screws combined with an intraoperative 3D/2D visualization of the spine enabled the surgeon to precisely implant pedicle screws on the exposed spine.

Outcome of Spinal Surgery in Patients Older Than Age 90 Years.

BACKGROUND: Increased life expectancy has led to indications for spine surgery in patients older than 90 years, but data on associated risks and outcome are lacking. METHODS: Indication, type of surgery, complications, functional outcome, and mortality were retrospectively collected from all patients aged 90 years or older operated between 2006 and 2016 at the University Hospital Basel, Switzerland. RESULTS: Sixty-nine patients were included, of which 55% had degenerative, 36% traumatic, and 9% other pathologies. Most surgeries (84%) were performed electively and 16% as emergencies. More than a third (36%) of elective and 58% of emergency surgeries required stabilization. The complication rate was 54% in the elective surgery group (ELSG) and 125% in the emergency surgery group (EMSG). Stabilization (P = 0.006) and emergency surgeries (P = 0.032) were significant risk factors for experiencing complications. Six weeks after surgery, 80% of the patients reported symptomatic improvement. More than half (58%) of the patients in the ELSG reached their specific median life expectancy, compared with 38% in the EMSG. Seventeen percent of patients in the EMSG versus 0% in the ELSG died in the first 3 months after surgery. In the nonstabilized group, 67% of the patients reached their median life expectancy, compared with 38% of the stabilized group. CONCLUSIONS: Elective spinal surgery in patients older than 90 years of age does not reduce life expectancy and has a good functional outcome for well-selected patients, whereas emergency surgery and stabilization surgery in this age group are associated with a high rate of complications and higher mortality.

Inertial Measurement Unit-Assisted Implantation of Thoracic, Lumbar, and Sacral Pedicle Screws Improves Precision of a Freehand Technique.

OBJECTIVE: A method applying inertial measurement units (IMUs) was developed to implant pedicle screws in the thoracic and lumbosacral spine. This was compared with a freehand technique. METHODS: The study was done on 9 human cadavers. For each cadaver, a preoperative computed tomography (CT) scan was performed to measure the axial and sagittal tilt angles of the screw trajectories from T1 to S1. After the entry points were defined on the exposed spine, the IMU-equipped pedicle finder and screwdriver were used to reproduce these tilt angles and implant half of the screws. The other half was implanted with a freehand technique. Fluoroscopy was not used. The screw trajectories were analyzed on postoperative CTs. RESULTS: A hundred and sixty-two screws were placed with use of the IMUs and 162 screws were implanted by freehand. The IMU-guided technique matched the planned trajectories significantly better than the freehand technique (axial tilt P < 0.001, sagittal tilt P < 0.001). With IMU assistance, the mean offsets between the planned and postoperatively measured tilt angles of the screws were 3.3 degrees ± 3.5 degrees for the axial plane (median 2 degrees, range 0-23 degrees) and 3.4 degrees ± 3 degrees for the sagittal plane (median 3 degrees, range 0-13 degrees). For the freehand technique, the mean offsets between the planned and postoperatively measured tilt angles of the screws were 5.6 degrees ± 4.5 degrees for the axial plane (median 5 degrees, range 0-31 degrees) and 6.7 degrees ± 5.4 degrees for the sagittal plane (median 6 degrees, range 0-33 degrees). CONCLUSIONS: IMU-assisted implantation of pedicle screws may enhance the performance of a freehand technique in the thoracic and lumbosacral spine.

Thalidomide Embryopathy as Possible Cause of Anterior Sacral Meningocele: A Case Report.

A 54-year-old male presented with a sudden burning sensation during urination and left flank pain. Apart from having congenital facial palsy and malformation of the inner right ear that was linked to thalidomide embryopathy, the patient has always been in good health. Urine examination showed the presence of a urinary tract infection. An abdominal ultrasound revealed a large cyst in the lower abdomen, which on MRI corresponded to a large anterior sacral meningocele (ASM) with sacral agenesis at S1/S2. After antibiotic treatment and the spontaneous passage of a kidney stone, the symptoms resolved. This suggests that the patient's acute symptoms were caused by the urolithiasis and not the ASM. Thalidomide is teratogenic between days 17 and 30 after conception. The neural tube closes between days 20 and 36, therefore, thalidomide embryopathy was the possible cause of ASM in this patient. Birth Defects Research 109:1390-1392, 2017.© 2017 Wiley Periodicals, Inc.

A novel approach to navigated implantation of S-2 alar iliac screws using inertial measurement units.

OBJECT: The authors report on a novel method of intraoperative navigation with inertial measurement units (IMUs) for implantation of S-2 alar iliac (S2AI) screws in sacropelvic fixation of the human spine and its application in cadaveric specimens. METHODS: Screw trajectories were planned on a multiplanar reconstruction of the preoperative CT scan. The pedicle finder and screwdriver were equipped with IMUs to guide the axial and sagittal tilt angles of the planned trajectory, and navigation software was developed. The entry points were chosen according to anatomical landmarks on the exposed spine. After referencing, the sagittal and axial orientation of the pedicle finder and screwdriver were wirelessly monitored on a computer screen and aligned with the preoperatively planned tilt angles to implant the S2AI screws. The technique was performed without any intraoperative imaging. Screw positions were analyzed on postoperative CT scans. RESULTS: Seventeen of 18 screws showed a good S2AI screw trajectory. Compared with the postoperatively measured tilt angles of the S2AI screws, the IMU readings on the screwdriver were within an axial plane deviation of 0° to 5° in 15 (83%) and 6° to 10° in 2 (11%) of the screws and within a sagittal plane deviation of 0° to 5° in 15 (83%) and 6° to 10° in 3 (17%) of the screws. CONCLUSIONS: IMU-based intraoperative navigation may facilitate accurate placement of S2AI screws.

Sonication of catheter tips for improved detection of microorganisms on external ventricular drains and ventriculo-peritoneal shunts.

The diagnosis of infections involving internal or external neurosurgical drainage devices is challenging, and to our knowledge no single reliable microbiological test exists. We used sonication to study bacterial colonization in 14 explanted external ventricular drains (EVD) and 13 ventriculo-peritoneal shunt (VPS) devices. This technique dislodges biofilm bacteria from the surface of implanted materials before culture. Removed devices were sonicated in saline (40 kHz, 1 minute, 0.25 W/cm(2)), the resulting fluid was cultured aerobically and anaerobically at 37°C, and bacterial growth was counted. Ventricular cerebrospinal fluid (CSF) was cultured separately. In the EVD group, sonication cultures grew significantly more bacteria (64%, 9/14) than cultures of aspirated ventricular CSF (14%, 2/14). In the VPS group the difference was not significant. Positive sonication cultures of EVD catheters yielded a median of >100 colony forming units (CFU) (range, 60-800). For positive sonication cultures of VPS, the median was 1000 CFU (range, 20-100,000). All patients with bacteria in their CSF also had positive sonication cultures from the removed device. Of the five patients with sterile or presumably contaminated CSF cultures but positive sonication cultures of removed shunts, one became afebrile after removal of the EVD, two developed meningitis and two remained asymptomatic. Sonication culture of EVD appears to improve the microbiological assessment of device-related infection and it corroborates with CSF cultures of revision surgery for VPS. Sonication of the removed EVD tip may raise awareness for the onset of meningitis.

iPod touch-assisted instrumentation of the spine: a technical report.

BACKGROUND: Instrumentation of the spine depends on choosing the correct insertion angles to implant screws. Although modern image guidance facilitates precise instrumentation of the spine, the equipment is costly and availability is limited. Although most surgeons use lateral fluoroscopy to guide instrumentation in the sagittal plane, the lateromedial angulation is often chosen by estimation. To overcome the associated uncertainty, iPod touch-based applications for measuring angles can be used to assist with screw implantation. OBJECTIVE: To evaluate the use of the iPod touch to adjust instruments to the optimal axial insertion angle for placement of pedicle screws in the lumbar spine. METHODS: Twenty lumbar pedicle screws in 5 consecutive patients were implanted using the iPod touch. The lateromedial angulation was measured on preoperative images and reproduced in the operative field with the iPod touch. The instruments to implant the screws were aligned with the side of the iPod for screw insertion. Actual screw angles were remeasured on postoperative imaging. We collected demographic, clinical, and operative data for each patient. RESULTS: In 16 of 20 screws, the accuracy of implantation was within 3 degrees of the ideal trajectory. The 4 screws with an angle mismatch of 7 to 13 degrees were all implanted at the caudal end of the exposure, where maintaining the planned angulation was impeded by strong muscles pushing medially. CONCLUSION: iPod touch-assisted instrumentation of the spine is a very simple technique, which, in combination with a lateral fluoroscopy, may guide placement of pedicle screws in the lumbar spine.

Characteristics of infections associated with external ventricular drains of cerebrospinal fluid.

OBJECTIVES: Manifestations of external ventricular drain (EVD) - associated infections overlap with those of the underlying neurosurgical conditions. We analyzed characteristics of EVD-associated infections. METHODS: We included patients aged ≥18 years with EVD-associated infections from 1997 to 2008, using modified CDC criteria for nosocomial infections. Hospital charts were reviewed retrospectively and the in-hospital outcome was evaluated. RESULTS: Forty-eight patients with EVD-associated infections were included (median age, 52 years, range 20-74 years). The median EVD-indwelling time was 7 days (range, 1-39 days) and EVD-associated infection occurred 6 days after insertion (range, 1-17 days). In 23% of patients, meningitis occurred 1-10 days after EVD removal. Fever >38 °C was present in 79% of patients, but Glasgow Coma Scale (GCS) scores were reduced in only 29%, and headache, vomiting and/or neck stiffness were present in only 31%. The median cerebrospinal fluid (CSF) leukocyte count was higher at onset of EVD-associated infection than at EVD insertion (175 × 10(6)/l versus 46 × 10(6)/l, p = 0.021), but other CSF parameters did not differ significantly. The most commonly implicated organisms were coagulase-negative staphylococci (63%) and Propionibacterium acnes (15%). CONCLUSIONS: Fever and increased CSF leukocytes should raise the suspicion of EVD-associated infection, which may occur up to 10 days after removal of EVD.

An odontoid fracture causing apnea, cardiac instability, and quadriplegia.

Odontoid fractures are typically associated with low rates of acute neurologic deficit and morbidity/mortality in nonelderly patients. In the patient in this case, traumatic injury triggered by a syncopal event led to a combined C1-C2 fracture and a fatal spinal cord injury with apnea, quadriplegia, and cardiovascular instability. We briefly review the anatomical basis for the pathophysiology of cardiac dysfunction following high-cervical spine injury and present an example of a worst-case scenario.

A Nonenhancing World Health Organization Grade II Intramedullary Spinal Ependymoma in the Conus: Case Illustration and Review of Imaging Characteristics.

Spinal ependymomas comprise ~60% of all intramedullary tumors in adults. Ependymomas demonstrate distinct imaging features, such as central location within the spinal cord, symmetrical expansion, intra- and extratumoral cysts, hemosiderin caps, and strong enhancement on contrast-injected, T1-weighted magnetic resonance (MR) imaging. In adults, most ependymomas are myxopapillary, and in children, most are nonmyxopapillary. In general, nonmyxopapillary or classic ependymomas are hyperintense on T2- and hypointense on T1-weighted MR imaging, but whereas the signal intensity on T1 and T2 is variable, homogeneous contrast enhancement is usually a characteristic finding. Here, the authors provide an overview on spinal ependymomas with an emphasis on imaging characteristics and morphological background and present the case of a World Health Organization grade II ependymoma in the conus that did not enhance. Interestingly, the tumor contained a large hemorrhagic cyst. Just as hemorrhagic metastatic tumors may not enhance, a hemorrhagic ependymoma may likewise not enhance after administration of contrast agent. Thus, the differential diagnosis of a nonenhancing intramedullary lesion in the conus should include ependymoma, particularly if there is concomitant hemorrhage.

Computed tomography-based determination of a safe trajectory for placement of transarticular facet screws in the subaxial cervical spine.

OBJECT: Placement of transarticular facet screws is one option for stabilization of the subaxial cervical spine. Small clinical series and biomechanical data support their role as a substitute for other posterior stabilization techniques; however, the application of transarticular facet screws in the subaxial cervical spine has not been widely adopted, possibly because of surgeon unfamiliarity with the trajectory. In this study, the authors' objective is to define insertion points and angles of safe trajectory for transarticular facet screw placement in the subaxial cervical spine. METHODS: Thirty fine-cut CT scans of cervical spines were reconstructed in the multiplanar mode and evaluated for safe transarticular screw placement in the subaxial cervical spine (C2-3, C3-4, C4-5, C5-6, C6-7). As in placement of lateral mass screws, the vertebral artery and exiting nerve root were bypassed posterolaterally. The entry point was set 1 mm medial and 1 mm caudal to the center of the lateral mass. From this entry point, the sagittal angulation was set to traverse the facet joint plane approximately perpendicularly. For the axial angulation, the exit point was set posterolaterally to the transverse process. After ideal insertion angles and screw lengths were identified, the trajectory was simulated on CT scans of 20 different cervical spines to confirm safe screw placement. RESULTS: The mean optimal mediolateral insertion angles (± SD) were as follows: 23° ± 5° at C2-3; 24° ± 4° at C3-4; 25° ± 5° at C4-5; 25° ± 4° at C5-6; and 33° ± 6° at C6-7. The mean sagittal insertion angles measured to the sagittal projection of the facet joint space were as follows: 77° ± 10° at C2-3; 77° ± 10° at C3-4; 80° ± 11° at C4-5; 81°± 8° at C5-6; and 100° ± 11° at C6-7. The mean trajectory lengths were 15 ± 2 mm at C2-3; 14 ± 1 mm at C3-4; 15 ± 1 mm at C4-5; 16 ± 2 mm at C5-6; and 23 ± 4 mm at C6-7. Simulation of these insertion angles on 20 different cervical spine CTs yielded a safe trajectory in 85%-95% of spines for C2-3, C3-4, C4-5, C5-6, and C6-7. CONCLUSIONS: The calculated optimal insertion angles and lengths for each level may guide the safe placement of subaxial cervical transfacet screws.

An epidural neuroblastoma causing spinal cord compression in a 67-year-old woman.

We report a case of disseminated neuroblastoma (NB) causing epidural spinal cord compression in a 67-year-old woman. Because NB is primarily a tumor of infancy and childhood, less is known about its clinical course and optimal treatment in adults. This patient was treated with a thoracic laminectomy and tumor resection; polychemotherapy with one cycle of vindesine, cisplatin, and etoposide; one cycle of vincristine, dacarbazine, ifosfamide, and doxorubicin; and radiotherapy to the spine. She remained able to walk but died 8.5 months later of diffuse systemic tumor progression.