CD133 mRNA-Loaded Dendritic Cell Vaccination Abrogates Glioma Stem Cell Propagation in Humanized Glioblastoma Mouse Model.

Cancer stem cells are initiating cells of cancer and propagate its growth through self-renewal and differentiation of its daughter cells. CD133 is a cell surface antigen that is present on glioma stem cells and has been used to prospectively isolate glioma stem cells. We hypothesized that a major histocompatibility complex (MHC)-independent and long-lasting immune response against CD133 could be generated by transfecting CD133 mRNA into dendritic cells and vaccinating animals with experimental gliomas. To test this hypothesis, we developed a novel humanized mouse model using CD34-positive hematopoietic stem cells. We confirmed the robust simultaneous activation of CD8- and CD4-positive T cells by dendritic cell vaccination with modified CD133 mRNA leading to a potent and long-lived immune response, with subsequent abrogation of CD133-positive glioma stem cell propagation and tumor growth. This study for the first time demonstrates in both a humanized mouse model and in a syngeneic mouse model of glioblastoma that targeting a glioma stem cell-associated antigen is an effective strategy to target and kill glioma stem cells. This novel and simple humanized mouse model for immunotherapy is a significant advance in our ability to test human-specific immunotherapies for glioblastoma.

Resection of Cervical Juxtacortical Chondroma and Circumferential Spinal Stabilization for Kyphotic Deformity.

Chondromas are rare, benign tumors composed of cartilaginous tissue that mainly affect the metaphases of long tubular bones. Juxtacortical (periosteal) chondromas arise from the surface of periosteum and rarely affect the cervical spine. We present a patient with a spinal juxtacortical chondroma causing spinal cord compression and a cervical deformity treated with surgical resection and circumferential spinal fixation and stabilization. A 55-year-old female with past medical history of Crohn's disease with years of neck pain, balance issues, and left upper extremity radicular symptoms. Cervical spine x-rays show kyphosis with an apex at C5, degenerative changes of the endplates and facet joints, and grade 2 anterolisthesis C4 on C5 with no abnormal motion with flexion/extension. MRI showed a left sided C5-6 extramedullary mass measuring 11 x 11 x 15 mm causing spinal cord compression and neural foraminal narrowing. Her pain is worsening and refractory to physical therapy, gabapentin and methocarbamol. A C4-5 & C5-6 anterior cervical discectomy and fusion, C4-5 & C5-6 laminectomy for tumor resection, and C4-5 & C5-6 posterior fusion with instrumentation was performed. The tumor was completely removed in piecemeal fashion. Microscopic findings showed bland well differentiated cartilaginous neoplasm consistent with juxtacortical chondroma. Postoperative X-rays show partial reduction of C4-5 anterolisthesis and partial reversal of cervical kyphosis. The patient's radicular pain resolved and neck pain improved postoperatively but she still has some left sided neck pain and hand dysesthesias that are controlled with oral medication one year following surgery. Cervical chondromas are rare, benign cartilaginous tumors that may present with spinal cord or nerve root compression. They are more complex when they present in patients with co-existing spinal deformities. Maximal safe resection followed by spinal re-alignment and fixation without adjuvant chemotherapy or radiation is recommended in most cases. Close follow-up is recommended to monitor for recurrence.

Unusual Exophytic Appearance of Spinal Cord Subependymoma.

BACKGROUND: Subependymomas are rare in the spinal cord. They are typically expansile, intramedullary spinal cord masses, eccentrically located with minimal gadolinium enhancement. CASE DESCRIPTION: We present a case of subependymoma originating from the cervical cord with an unusual exophytic appearance. Hallmarks of subependymoma and treatment are reviewed. CONCLUSIONS: This is the first case, to our knowledge, where imaging revealed a mass appearing to be completely extramedullary with a primary exophytic component. Therefore, subependymomas should remain on the differential for masses in the spinal cord that appear extramedullary and exophytic.

The Long and Winding Road: Thoracic Myelopathy Associated With Occipitocervical Dural Arteriovenous Fistula.

OBJECTIVES: Spinal dural arteriovenous fistulas (DAVFs) have diverse presentations. Magnetic resonance imaging (MRI) reveals spinal cord swelling in only 45% to 74% of cases. We present an unusual case of a 57-year old man with a craniocervical junction DAVF in which the edema appeared in the thoracolumbar region, skipping the cervical spinal cord. METHODS: A case report and literature review from a tertiary referral center are provided. RESULTS: In our patient, symptoms progressed over 3 months from low back and radicular pain to weakness, saddle anesthesia, and urinary retention. MRI showed T2 hyperintensity from T3-4 to the conus medullaris. The results from initial brain and spine angiograms were negative. Repeated angiography with the patient under anesthesia revealed a DAVF in the craniocervical junction composed of a cervical branch arising from the right vertebral artery and entering the nidus at the foramen magnum. A prominent intradural draining vein extended inferiorly along the posterior aspect of the cervical spinal cord. The patient was taken to the operating room, where the extradural vertebral artery was dissected and a suboccipital craniectomy was performed. After the dura was opened, the arterialized vein was visualized and clipped. Somatosensory evoked potentials and motor evoked potentials remained at baseline throughout the occlusion. The dura and fistula were removed en bloc, and the draining vein was confirmed to lose flow on indocyanine green. Postoperatively, the patient's symptoms completely resolved, and he experienced full strength in the lower extremities and perineal sensation. A review of 19 cases of DAVF at the craniocervical junction with cord edema shows that >90% involve the brainstem or cervical cord. Only 1 other patient had a similar "skip lesion," in which the cord edema first appeared in the thoracic cord. CONCLUSIONS: This rare presentation highlights the importance of diagnostic persistence when unexplained cord findings are seen on MRI. Repeated angiography and the inclusion of proximal vascular lesions may be considered in the evaluation of isolated thoracic edema.

Risk of Aneurysm Residual Regrowth, Recurrence, and de Novo Aneurysm Formation After Microsurgical Clip Occlusion Based on Follow-up with Catheter Angiography.

INTRODUCTION: Established guidelines for radiologic surveillance after microsurgical treatment of intracranial aneurysms are lacking in the literature because of small sample sizes, poor definitions, and heterogeneous use of imaging modalities. We aimed to propose clinically meaningful definitions for postoperative aneurysm residual, recurrence, and de novo aneurysm formation and to analyze our long-term follow-up catheter angiography results in patients with microsurgically treated intracranial aneurysms. METHODS: A retrospective review of all aneurysms treated microsurgically in a consecutive, single-surgeon series from 1997 to present identified patients with long-term follow-up catheter angiography (>1 year after surgery). Clinical and radiologic data were collected for analysis. RESULTS: We identified 240 patients harboring 380 aneurysms (mean follow-up time, 6.0 ± 3.3 years per patient; range, 1.0-16.8 years). Postoperative residuals were present in 16 out of 346 clipped aneurysms (4.6%), of which only 3 were left unintentionally. Two out of 16 residual aneurysms (12.5%) demonstrated regrowth, with a regrowth risk of 2.1% per year from 93.6 patient-years of angiographic follow-up. Of 326 aneurysms with no postoperative residual, 5 (1.5%) demonstrated aneurysm recurrence, with a recurrence risk of 0.26% per year from 1931.9 patient-years of angiographic follow-up. Eight de novo aneurysms were identified in 240 patients (3.3%), with a risk of 0.6% per year from 1441.9 patient-years of angiographic follow-up. CONCLUSIONS: Microsurgically treated aneurysms have a very low risk of postoperative residuals and aneurysm recurrence. Growth of residuals and de novo aneurysm formation justify following up with catheter angiography 3 to 5 years after microsurgical clipping.

Primary spinal intradural extramedullary lymphoma: A novel management strategy.

Primary spinal intradural extramedullary lymphoma remains a very rare entity in spinal oncology. In this case report, we present the first treatment of a PSIEL diagnosed by cytopathologic analysis alone followed by urgent radio- and chemotherapy in the literature. At 18-month follow-up, our patient was ambulatory with near total imaging resolution of the lesion. In conclusion, surgical excision or biopsy may not be necessary when suspicion for PSIEL exists, and may delay prompt medical and radiation treatment due to necessity for wound healing. Further research into the management of extramedullary lymphoma treatment strategies is warranted.

Relationship of urinary endothelin-1 with estimated glomerular filtration rate in autosomal dominant polycystic kidney disease: a pilot cross-sectional analysis.

BACKGROUND: The pathogenesis of progressive renal insufficiency in autosomal dominant polycystic kidney disease (ADPKD) is unclear. Evidence from experimental models of ADPKD suggests that elevated endothelin-1 (ET-1) drives cyst growth, renal fibrosis and loss of renal function, but whether ET-1 is elevated in humans with ADPKD is uncertain. METHODS: In a cross-sectional study of ADPKD we measured urinary ET-1, a surrogate for ET-1 in kidney cortex, in spot collections corrected for creatinine. The volume of each kidney was measured using MRI-based stereology. The relationship of urine ET-1 with MDRD eGFR and kidney volume was modeled by multiple linear regression with adjustment for clinical covariates. RESULTS: Patients with ADPKD were ages 18 to 53 with eGFRs (median, interquartile range) of 63.2 (43.5-80.2) ml/min/1.73 m(2) and albumin/creatinine ratios (ACR) of 115.0 (7.5-58.5) µg/mg. Urine ET-1 was inversely associated with eGFR (r = -0.480, P < 0.05) and positively (r = 0.407, P = 0.066) with ACR independent of age and female sex (P < 0.01). ET-1 appeared to be positively associated with total kidney volume (r = 0.426, P = 0.100), with a test for trend across urine ET-1 quartiles yielding z = 1.83, P = 0.068. ET-1 strongly correlated with NAGase (r = 0. 687, P = 0.001), a marker of tubular damage and a surrogate marker of renal disease progression in ADPKD. Of note, ET-1 levels in urine were not correlated with hypertension. CONCLUSIONS: In a translational study of patients with ADPKD, urinary ET-1 was inversely associated with eGFR and positively correlated with total kidney volume. Taken together with results from experimental models, these findings suggest that the role of ET-1 in ADPKD warrants further investigation.