Postoperative Spinal Cerebrospinal Fluid-Venous Fistulas Associated With Dural Tears in Patients With Intracranial Hypotension or Superficial Siderosis-A Digital Subtraction Myelography Study.

BACKGROUND: Postoperative spinal cerebrospinal fluid (CSF) leaks are common but rarely cause extensive CSF collections that require specialized imaging to detect the site of the dural breach. OBJECTIVE: To investigate the use of digital subtraction myelography (DSM) for patients with extensive extradural CSF collections after spine surgery. METHODS: A retrospective review was performed to identify a consecutive group of patients with extensive postoperative spinal CSF leaks who underwent DSM. RESULTS: Twenty-one patients (9 men and 12 women) were identified. The mean age was 46.7 years (range, 17-75 years). The mean duration of the postoperative CSF leak was 3.3 years (range, 3 months to 21 years). MRI showed superficial siderosis in 6 patients. DSM showed the exact location of the CSF leak in 19 (90%) of the 21 patients. These 19 patients all underwent surgery to repair the CSF leak, and the location of the CSF leak could be confirmed intraoperatively in all 19 patients. In 4 (19%) of the 21 patients, DSM also showed a CSF-venous fistula at the same location as the postoperative dural tear. CONCLUSION: In this study, DSM had a 90% detection rate of visualizing the exact site of the dural breach in patients with extensive postoperative spinal CSF leaks. The coexistence of a CSF-venous fistula in addition to the primary dural tear was present in about one-fifth of patients. The presence of a CSF-venous fistula should be considered if CSF leak symptoms persist in spite of successful repair of a durotomy.

A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma.

PURPOSE: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line. PATIENTS AND METHODS: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, ≤ 4-mg dexamethasone daily dose, and Karnofsky score ≥70. Vaccine treatment consisted of two phases: an induction phase with vaccine given weekly for 4 weeks, and a maintenance phase with vaccines administered every 8 weeks until depletion of supply or disease progression. Patients with newly diagnosed GBM also received standard-of-care radiation and temozolomide. The primary objective for this open-label, single-institution trial was to assess the safety and tolerability of the autologous DC vaccine. RESULTS: For the 11 patients with newly diagnosed GBM, median progression-free survival (PFS) was 8.75 months, and median overall survival was 20.36 months. For the 25 patients with recurrent GBM, median PFS was 3.23 months, 6-month PFS was 24%, and median survival was 11.97 months. A subset of patients developed a cytotoxic T-cell response as determined by an IFNγ ELISpot assay. CONCLUSIONS: In this trial, treatment of newly diagnosed and recurrent GBM with autologous DC vaccine pulsed with lysate derived from an allogeneic stem-like cell line was safe and well tolerated. Clinical outcomes add to the body of evidence suggesting that immunotherapy plays a role in the treatment of GBM.

A Crowdsourced Consensus on Supratotal Resection Versus Gross Total Resection for Anatomically Distinct Primary Glioblastoma.

BACKGROUND: Gross total resection (GTR) of contrast-enhancing tumor is associated with increased survival in primary glioblastoma. Recently, there has been increasing interest in performing supratotal resections (SpTRs) for glioblastoma. OBJECTIVE: To address the published results, which have varied in part due to lack of consensus on the definition and appropriate use of SpTR. METHODS: A crowdsourcing approach was used to survey 21 neurosurgical oncologists representing 14 health systems nationwide. Participants were presented with 11 definitions of SpTR and asked to rate the appropriateness of each definition. Participants reviewed T1-weighed postcontrast and fluid-attenuated inversion-recovery magnetic resonance imaging for 22 anatomically distinct glioblastomas. Participants were asked to assess the tumor location's eloquence, the perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans. RESULTS: Most neurosurgeons surveyed (n = 18, 85.7%) agree that GTR plus resection of some noncontrast enhancement is an appropriate definition for SpTR. Overall, moderate inter-rater agreement existed regarding eloquence, equipoise, and personal treatment plans. The 4 neurosurgeons who had performed >10 SpTRs for glioblastomas in the past year were more likely to recommend it as their treatment plan (P < .005). Cases were divided into 3 anatomically distinct groups based upon perceived eloquence. Anterior temporal and right frontal glioblastomas were considered the best randomization candidates. CONCLUSION: We established a consensus definition for SpTR of glioblastoma and identified anatomically distinct locations deemed most amenable to SpTR. These results may be used to plan prospective trials investigating the potential clinical utility of SpTR for glioblastoma.

A phase I trial of surgical resection with Gliadel Wafer placement followed by vaccination with dendritic cells pulsed with tumor lysate for patients with malignant glioma.

High grade gliomas are associated with poor prognosis and high mortality. Conventional treatments and management of high grade gliomas have shown little improvement in 5-year overall survival. This phase I trial evaluated the safety, immunogenicity, and potential synergy of surgical resection with Gliadel Wafer implantation, followed by autologous tumor lysate-pulsed dendritic cell (DC) vaccine in patients with malignant glioma. Primary end points of this study were safety and surrogate markers of immunogenicity, overall survival, and progression free survival. Following surgical resection, Gliadel Wafers were placed along the resection cavity. Patients subsequently received intradermal injections of autologous tumor lysate-pulsed DC vaccines 3 times at 2 week intervals. Treatment response was evaluated clinically and through MRI at regular intervals. Twenty-eight patients received Gliadel Wafers and DC vaccination: 11 newly diagnosed (8 glioblastoma [GBM], 2 anaplastic astrocytoma [AA], and 1 anaplastic oligodendroglioma [AO]) and 17 recurrent (15 GBMs, 1 AA, and 1 AO) high grade gliomas. Immunogenicity data was collected for 20 of the 28 patients. Five of 20 patients showed elevated IFN-γ responses following vaccination. Median progression-free survival and overall survival for all GBM patients in the trial from the start of vaccination were 3.6 months and 16.9 months respectively. Comparisons between vaccine responders and non-vaccine responders were not statistically significant. Adjuvant autologous dendritic cells pulsed with tumor-lysate following resection and Gliadel Wafer placement is safe, elicits modest immunogenicity and shows similar clinical outcomes in patients who had DC vaccination in previous studies.

Exoscopic resection of atrial intraventricular meningiomas using a navigation-assisted channel-based trans-sulcal approach: Case series and literature review.

The surgical treatment of atrial meningiomas carries unique challenges. Recent advancements have aimed to optimize visualization and minimize insult to adjacent tissue. To investigate outcomes following resection of atrial meningiomas using an integrated tubular retraction system with neuro-navigated exoscope. A retrospective analysis of surgical outcomes in consecutive patients who underwent surgical resection of atrial meningiomas via an exoscopic tubular retraction system at three university hospital institutions. Four patients harboring intraventricular meningiomas in the atrium of the lateral ventricle were treated using an integrated navigation-assisted, channel-based trans-sulcal approach via a left temporal-occipital (1), right parieto-occipital (2), or left posterior-temporal (1) sulcal approach with exoscopic visualization. Indications for surgery included headaches (4/4, 100%), dizziness (1/4, 25%), or evidence of progression on imaging (3/4, 75%). Mean maximal tumor diameter was 25.5 mm (range 22-28 mm). No intraoperative complications were observed, and no conversion to a microscopic or open approach was required. Gross total resection (GTR) was obtained in all 4 cases. Median hospital length of stay was 3 days (range 3-4 days). Postoperative complications included homonymous hemianopsia (1) and transient bilateral lower extremity paresthesias (1). At 3-month follow up both complications had improved and all patients had returned to work. At last follow-up (3-24 months), 3 patients (75%) reported improvement of preoperative symptoms. Utilization of a channel-based, navigable retractor with the aid of an exoscope can be an excellent option for accessing the atrium of the lateral ventricles and for achieving complete surgical resection of atrial meningiomas.

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.

L5 Osteoid Osteoma Treated with Partial Laminectomy and Cement Augmentation.

Osteoid osteoma is a benign primary bone tumor of unknown etiology that occurs most commonly in males during adolescence and early adulthood. Osteoid osteoma affects the spine in 20% of cases, and may cause spinal deformity, stiffness, and pain that may sometimes be worst at night. We present a novel description of a partial laminectomy with cement augmentation after resection of an osteoid osteoma. A 22-year-old male with a past medical history of Hodgkin's lymphoma status post chemotherapy and radiation to the mediastinum, and right hip osteoblastoma treated with surgery and radiofrequency ablation presented with low back pain for five years with a recent onset of severe radicular symptoms. The pain was described as shooting and radiating laterally down the right leg to the mid-calf without bowel or bladder incontinence. He has a known right L5 laminar sclerotic lesion measuring 11 x 10 mm causing neuroforaminal narrowing and it kept increasing in size despite previous treatment with stereotactic radiosurgery and radiofrequency ablation. This lesion was metabolically active on positron emission tomography-computed tomography (PET-CT) imaging. His pain was worsening and was refractory to physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and radiation therapy. A right L5 partial laminectomy was performed to resect the abnormality in an en-bloc fashion. The lesion did not involve the inner cortex of the bone. Lamina reconstruction was achieved with bone cement augmentation for the preservation of vertebral column strength. Pathology was consistent with osteoid osteoma with marrow edema. Microscopic findings include bony trabeculae associated with prominent rimming and hypercellular fibroblastic stroma. No nuclear atypia, necrosis or appreciable mitotic activity was observed. The patient remains neurologically intact with significantly improved radicular symptoms and low back pain. Osteoid osteoma of the lamina may be resected using a partial laminectomy and cement augmentation done to preserve the integrity of the posterior ligamentous complex, prevent potential fracture of the pars interarticularis, and avoid the need for lumbar fusion in younger patients in whom this pathology is commonly found.

Isolated Extracranial Intraosseous Metastasis of an Intracranial Meningioma following Bevacizumab Therapy: Case Report and Review of the Literature.

Meningiomas account for a significant proportion of all primary intracranial tumors; distant metastasis is quite rare. We report a patient with resected, atypical meningioma. The patient's clinical course over 5 years included two craniotomies, a course of radiation, and a shortened course of bevacizumab. Only 5 months after starting bevacizumab, the patient developed an isolated left clavicular pathological fracture attributable to metastatic anaplastic meningioma. This constitutes the first report of meningioma with isolated extracranial intraosseous metastasis in the modern English literature and highlights concerns associated with the use of anti-angiogenic agents in promoting more invasive tumor phenotypes upon disease recurrence.

False localizing sign of cervico-thoracic CSF leak in spontaneous intracranial hypotension.

OBJECTIVE: Spontaneous spinal CSF leaks are an important cause of new-onset headaches. Such leaks are reported to be particularly common at the cervico-thoracic junction. The authors undertook a study to determine the significance of these cervico-thoracic CSF leaks. METHODS: The patient population consisted of a consecutive group of 13 patients who underwent surgery for CSF leak repair based on CT myelography showing CSF extravasation at the cervico-thoracic junction but without any evidence of an underlying structural lesion. RESULTS: The mean age of the 9 women and 4 men was 41.2 years. Extensive extrathecal longitudinal CSF collections were demonstrated in 11 patients. At surgery, small leaking arachnoid cysts were found in 2 patients. In the remaining 11 patients, no clear source of CSF leakage could be identified at surgery. Resolution of symptoms was achieved in both patients with leaking arachnoid cysts, but in only 3 of the 11 patients with negative intraoperative findings. Postoperative spinal imaging was performed in 9 of the 11 patients with negative intraoperative findings and showed persistence of the longitudinal intraspinal extradural CSF. Further imaging revealed the site of the CSF leak to be ventral to the thoracic spinal cord. Five of these patients underwent microsurgical repair of the ventral CSF leak with resolution of symptoms in all 5 patients. CONCLUSIONS: Cervico-thoracic extravasation of dye on myelography does not necessarily indicate the site of the CSF leak. Treatment directed at this site should not be expected to have a high probability of sustained improvement of symptoms.

Adult Brainstem Glioblastoma Multiforme: Long-term Survivor.

Adult, malignant brainstem gliomas are rare entities that often cause treatment conundrums due to the difficulty of surgical resection and, therefore, the absence of pathological diagnosis. This leads to a reliance on radiological imaging for diagnosis, which can often be unreliable. These shortcomings have made the treatment of brainstem gliomas challenging with unpredictable outcomes. The mainstay of treatment consists of chemotherapy and radiation; however, recurrence is inevitable. Predicting outcomes has been the major difficulty in treating these patients as adult malignant brainstem gliomas Grade II have a median survival between five to seven years while Grades III and IV are between 10-17 months (with some studies showing significantly longer survival in Grade III). Here, we present the case of a patient with the pathologic diagnosis of a right brachium pontis glioblastoma who had a remarkable survival of 73 months, whereas the expected median survival for these patients is 10-17 months.

Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma.

BACKGROUND: This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107). METHODS: TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma (GBM) were eligible. Mononuclear cells from leukapheresis were differentiated into dendritic cells, pulsed with TAA peptides, and administered intradermally three times at two-week intervals. RESULTS: Twenty-one patients were enrolled with 17 newly diagnosed (ND-GBM) and three recurrent GBM patients and one brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33 % responders. TAA expression by qRT-PCR from fresh-frozen tumor samples showed all patient tumors expressed at least three TAA, with 75 % expressing all six. Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM-2 were observed, and a trend for longer survival was observed with gp100 and HER2 antigens. Target antigens gp100, HER1, and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2+ patients. A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection. At a median follow-up of 40.1 months, six of 16 ND-GBM patients showed no evidence of tumor recurrence. Median PFS in newly diagnosed patients was 16.9 months, and median OS was 38.4 months. CONCLUSIONS: Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors.

Spinal manifestations of spontaneous intracranial hypotension.

OBJECT: The goal of the study was to elucidate the spinal manifestations of spontaneous intracranial hypotension. METHODS: The authors reviewed the medical records and imaging studies of 338 consecutive patients with spontaneous intracranial hypotension who were evaluated at their institution between 2001 and 2010. RESULTS: Twenty patients (6%; mean age 35.8 [range 16 to 60 years]; 5 males and 15 females) had convincing signs or symptoms referable to the spinal cord or spinal nerve roots. The spinal manifestations consisted of radiculopathy in 11 patients (unilateral in 8 and bilateral in 3), myelopathy in 8 patients, and bibrachial amyotrophy in 1 patient. The cervical spine was involved in 12 patients, the thoracic spine in 5, and the lumbosacral spine in 3. The spinal symptoms were positional in only 3 patients. The spinal manifestations occurred around the time of the headache onset in 16 patients, and months to years after the positional headache had resolved in 4 patients. A large extrathecal CSF collection causing compression of the spinal cord or nerve root was responsible for the spinal manifestations in the majority of patients. Treatment of the spinal CSF leak resulted in resolution of the spinal manifestations along with the headache, except for those in the patient with bibrachial amyotrophy. CONCLUSIONS: Spinal manifestations are uncommon in cases of spontaneous intracranial hypotension, occurring in about 6% of patients, but myelopathy and radiculopathy involving all spinal segments do occur. Unlike the headache, the spinal manifestations usually are not positional and are caused by mass effect from an extradural CSF collection.

Application of diffusion tensor imaging to magnetic-resonance-guided brain tumor resection.

Interventional magnetic resonance imaging (MRI) continues to make a profound impact on the practice of neurosurgery. We describe a new MRI modality, diffusion tensor imaging (DTI), which uses the diffusion energy of water to map white matter fibers. DTI has been established in other disorders such as metabolic, demyelinating and ischemic diseases. We describe the use of DTI in identifying white matter tracts such as optic radiations and avoiding them intraoperatively in 2 children with low-grade glial tumors.

Extracranial-intracranial bypass for symptomatic occlusive cerebrovascular disease not amenable to carotid endarterectomy.

OBJECT: The role of cerebral revascularization remains unclear in symptomatic occlusive cerebrovascular disease refractory to medical therapy. Despite the disappointing findings of the Cooperative Study on Extracranial-Intracranial Bypass, a subpopulation of patients with ischemic cerebrovascular disease and poor hemodynamic reserve may benefit from extracranial-intracranial (EC-IC) bypass. The authors reviewed the records of 65 patients who underwent 71 EC-IC bypass procedures at their institution over the past 6 years. METHODS: All patients except one presented with repeated transient ischemic attacks (TIAs) that were referable to the involved vascular region. Eight patients underwent EC-IC bypass urgently for "crescendo" TIAs refractory to antiplatelet and anticoagulation therapy. Indications for surgery included cervical internal carotid artery (ICA) occlusion in 28, supraclinoid ICA stenosis in two, middle cerebral artery stenosis or occlusion in 14, moyamoya disease in 18, and ICA dissection in three. Cerebral angiography demonstrated poor collateral flow to the involved region in each case. There were no postoperative strokes or deaths in this series. Following EC-IC bypass, the vast majority (95.4%) of patients experienced cessation of their ischemic events and stabilization of preexisting neurological dysfunction. Of the eight patients who underwent EC-IC bypass urgently for crescendo TIAs, two awoke with increased neurological deficits that improved rapidly within 24 hours of surgery. CONCLUSIONS: Although the Cooperative Study failed to show benefit from this treatment modality, the authors have continued to perform EC-IC bypass in certain cases. Carefully selected individuals with occlusive cerebrovascular disease and persistent ischemic symptoms refractory to maximal medical therapy appear to benefit from cerebral revascularization.