Prospective, randomized controlled multicenter study of posterior lumbar facet arthroplasty for the treatment of spondylolisthesis.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of a posterior facet replacement device, the Total Posterior Spine (TOPS) System, for the treatment of one-level symptomatic lumbar stenosis with grade I degenerative spondylolisthesis. Posterior lumbar arthroplasty with facet replacement is a motion-preserving alternative to lumbar decompression and fusion. The authors report the preliminary results from the TOPS FDA investigational device exemption (IDE) trial. METHODS: The study was a prospective, randomized controlled FDA IDE trial comparing the investigational TOPS device with transforaminal lumbar interbody fusion (TLIF) and pedicle screw fixation. The minimum follow-up duration was 24 months. Validated patient-reported outcome measures included the Oswestry Disability Index (ODI) and visual analog scale (VAS) for back and leg pain. The primary outcome was a composite measure of clinical success: 1) no reoperations, 2) no device breakage, 3) ODI reduction of ≥ 15 points, and 4) no new or worsening neurological deficit. Patients were considered a clinical success only if they met all four measures. Radiographic assessments were made by an independent core laboratory. RESULTS: A total of 249 patients were evaluated (n = 170 in the TOPS group and n = 79 in the TLIF group). There were no statistically significant differences between implanted levels (L4-5: TOPS, 95% and TLIF, 95%) or blood loss. The overall composite measure for clinical success was statistically significantly higher in the TOPS group (85%) compared with the TLIF group (64%) (p = 0.0138). The percentage of patients reporting a minimum 15-point improvement in ODI showed a statistically significant difference (p = 0.037) favoring TOPS (93%) over TLIF (81%). There was no statistically significant difference between groups in the percentage of patients reporting a minimum 20-point improvement on VAS back pain (TOPS, 87%; TLIF, 64%) and leg pain (TOPS, 90%; TLIF, 88%) scores. The rate of surgical reintervention for facet replacement in the TOPS group (5.9%) was lower than the TLIF group (8.8%). The TOPS cohort demonstrated maintenance of flexion/extension range of motion from preoperatively (3.85°) to 24 months (3.86°). CONCLUSIONS: This study demonstrates that posterior lumbar decompression and dynamic stabilization with the TOPS device is safe and efficacious in the treatment of lumbar stenosis with degenerative spondylolisthesis. Additionally, decompression and dynamic stabilization with the TOPS device maintains segmental motion.

A Prospective Study of Lumbar Facet Arthroplasty in the Treatment of Degenerative Spondylolisthesis and Stenosis: Results from the Total Posterior Spine System (TOPS) IDE Study.

STUDY DESIGN: Prospective randomized Food and Drug Administration investigational device exemption clinical trial. OBJECTIVE: The purpose of the present study is to report the 1-year clinical and radiographic outcomes and safety profile of patients who underwent lumbar facet arthroplasty through implantation of the Total Posterior Spine System (TOPS) device. SUMMARY OF BACKGROUND DATA: Lumbar facet arthroplasty is one proposed method of dynamic stabilization to treat grade-1 spondylolisthesis with stenosis; however, there are currently no Food and Drug Administration-approved devices for facet arthroplasty. METHODS: Standard demographic information was collected for each patient. Radiographic parameters and patient-reported outcome measures were assessed preoperatively and at regular postoperative intervals. Complication and reoperation data were also collected for each patient. RESULTS: At the time of this study, 153 patients had undergone implantation of the TOPS device. The mean surgical time was 187.8 minutes and the mean estimated blood loss was 205.7cc. The mean length of hospital stay was 3.0 days. Mean Oswestry Disability Index, Visual Analog Score leg and back, and Zurich Claudication Questionnaire scores improved significantly at all postoperative time points ( P >0.001). There were no clinically significant changes in radiographic parameters, and all operative segments remained mobile at 1-year follow-up. Postoperative complications occurred in 11 patients out of the 153 patients (7.2%) who underwent implantation of the TOPS device. Nine patients (5.9%) underwent a total of 13 reoperations, 1 (0.6%) of which was for device-related failure owing to bilateral L5 pedicle screw loosening. CONCLUSIONS: Lumbar facet arthroplasty with the TOPS device demonstrated a statistically significant improvement in all patient-reported outcome measures and the ability to maintain motion at the index level while limiting sagittal translation with a low complication rate.

Intradural intramedullary dermoid cyst in a 42-year-old man at the L1-L2 region.

Background: Intramedullary dermoid cysts within the spine are a rare benign tumor. We present this case, which has atypical presenting symptoms, in order to increase awareness of intradural dermoid cysts. Clinical presentation: We present here a case of a 42 year old man with a 12-month history of lumbar spinal pain as well progressive left lower extremity loss of strength, as well as numbness and paresthesia radiating into the left foot. Magnetic resonance imaging scan revealed a 4 × 1 × 1.3cm intradural mass at the cauda equina L1-L2 region and was hyperintense in both T1 and T2 causing cord compression. L1-L2 laminectomy and intradural micro resection were performed with successful excision of the suspicious mass. Histopathological review revealed keratinaceous debris and adnexal structures consistent with a dermoid cyst. Conclusions: Our case is unusual with the other reported cases of dermoid cysts due to superior involvement in the lumbar region compared to other case reports with predominantly lumbosacral involvement. This location of the cyst lead to radicular symptoms, rather than lumbosacral pain and sphincter incompetence that is more commonly represented in the literature.

GBM Derived Gangliosides Induce T Cell Apoptosis through Activation of the Caspase Cascade Involving Both the Extrinsic and the Intrinsic Pathway.

Previously we demonstrated that human glioblastoma cell lines induce apoptosis in peripheral blood T cells through partial involvement of secreted gangliosides. Here we show that GBM-derived gangliosides induce apoptosis through involvement of the TNF receptor and activation of the caspase cascade. Culturing T lymphocytes with GBM cell line derived gangliosides (10-20 µg/ml) demonstrated increased ROS production as early as 18 hrs as indicated by increased uptake of the dye H2DCFDA while western blotting demonstrated mitochondrial damage as evident by cleavage of Bid to t-Bid and by the release of cytochrome-c into the cytosol. Within 48-72 hrs apoptosis was evident by nuclear blebbing, trypan blue positivity and annexinV/7AAD staining. GBM-ganglioside induced activation of the effector caspase-3 along with both initiator caspases (-9 and -8) in T cells while both the caspase-8 and -9 inhibitors were equally effective in blocking apoptosis (60% protection) confirming the role of caspases in the apoptotic process. Ganglioside-induced T cell apoptosis did not involve production of TNF-α since anti-human TNFα antibody was unable to protect T cells from nuclear blebbing and subsequent cell death. However, confocal microscopy demonstrated co-localization of GM2 ganglioside with the TNF receptor and co-immunoprecipitation experiments showed recruitment of death domains FADD and TRADD with the TNF receptor post ganglioside treatment, suggesting direct interaction of gangliosides with the TNF receptor. Further confirmation of the interaction between GM2 and TNFR1 was obtained from confocal microscopy data with wild type and TNFR1 KO (TALEN mediated) Jurkat cells, which clearly demonstrated co-localization of GM2 and TNFR1 in the wild type cells but not in the TNFR1 KO clones. Thus, GBM-ganglioside can mediate T cell apoptosis by interacting with the TNF receptor followed by activation of both the extrinsic and the intrinsic pathway of caspases.

TSGA10 is Specifically Expressed in Astrocyte and Over-expressed in Brain Tumors.

In this study TSGA10 has been demonstrated as a testis-specific human gene that encodes a protein localized in sperm-tail and conserved in ciliary structure. Further investigations showed TSGA10 signalling and expression during embryogenesis, brain development and some malignancies including brain tumors. Given the role of this protein in neuronal development and in certain tumors, it could potentially serve as a diagnostic marker and therapeutic target in brain tumors. Therefore, using immunohistochemistry, we evaluated the localization of TSGA10 in different regions of brain, and its pattern/level of expression in tissue microarray (Cybrdi) containing human brain tumors and normal brain. In rat specimens, TSGA10 was mainly expressed in subventricular zone, hippocampus and granular layer of cerebellum of the brain. The antibody also stained the diverse and different types of human brain cancers. The TSGA10 was strongly over-expressed in glioblastoma and astrocytoma when compared to normal human brain. The expression of TSGA10 was also confirmed in astrocyte derived from a human astroctyoma cell line by immunocytochemistry. This study indicates that TSGA10 can be used as an immunohistochemical marker for human neuroglia and astrocyte cells and is over-expressed in brain tumors.

World Health Organization Grades II and III meningiomas are rare in the cranial base and spine.

OBJECTIVE: This study was undertaken to assess a possible relationship between the tumor location and the incidence of World Health Organization (WHO) Grades II and III meningiomas. METHODS: A retrospective review of 794 consecutive patients who underwent meningioma resection between January 1991 and March 2004 was conducted. Among these, 47 patients (5.9%) with WHO Grade II meningiomas and 16 patients (2%) with Grade III meningiomas were further analyzed. Tumor location was assessed using preoperative magnetic resonance imaging scans and/or operative reports. Histological grading was done according to the WHO 2000 Classification scheme. RESULTS: WHO Grade II tumors were found in eight out of 289 (2.8%) cranial base meningiomas and in zero spinal meningiomas, compared with 39 out of 429 (9.1%) non-cranial base meningiomas. Grade III histology was encountered in two (0.7%) cranial base tumors and in one out of 76 (1.3%) spinal tumors, compared with 13 (3%) non-cranial base tumors. The combined incidence of Grades II and III meningiomas was significantly lower in the cranial base (3.5%) and spinal (1.3%) locations compared with non-cranial base locations (12.1%) (P < 0.001). CONCLUSION: WHO Grades II and III meningiomas occur far less frequently in the cranial base and spinal locations. Tumors arising from these locations may have different mechanisms of tumorigenesis and/or progression compared with meningiomas arising from other (non-cranial base) regions.

GM2 expression in renal cell carcinoma: potential role in tumor-induced T-cell dysfunction.

Multiple mechanisms have been proposed to account for immune escape by tumors. Although gangliosides have long been known to suppress T-cell immunity, few studies have examined the effect of human tumor-derived gangliosides on immune responses. Here, we show that gangliosides isolated from renal cell carcinoma (RCC) cell lines and clear cell tumor tissue can induce apoptosis in peripheral blood T cells. The RCC tissue-derived gangliosides also suppressed IFN-gamma and, in many cases, interleukin-4 production by CD4+ T cells at concentrations (1 ng/mL-100 pg/mL) well below those that induce any detectable T-cell death (4-20 microg/mL). Additional findings show that GM2 expressed by RCC plays a significant role in promoting T-cell dysfunction. This is supported by the demonstration that all RCC cell lines examined (n = 5) expressed GM2 as did the majority of tumors (15 of 18) derived from patients with clear cell RCC. Furthermore, an antibody specific for GM2 (DMF10.167.4) partially blocked (50-60%) T-cell apoptosis induced by coculturing lymphocytes with RCC cell lines or with RCC tissue-derived gangliosides. DMF10.167.4 also partially blocked the suppression of IFN-gamma production induced by RCC tissue-derived gangliosides, suggesting that GM2 plays a role in down-regulating cytokine production by CD4+ T cells.

A feasibility study of optical coherence tomography for guiding deep brain probes.

Deep brain simulation (DBS) is effective for the treatment of various diseases including Parkinson's disease and essential tremor. However, anatomical targeting combined with microelectrode mapping of the region requires significant surgical time. Also, the fine-tipped microelectrode imposes a risk of hemorrhage in the event that the trajectory intersects subcortical vessels. To reduce the operation time and the risk of hemorrhage, we propose to use optical coherence tomography (OCT) to guide the insertion of the DBS probe. We conducted in vitro experiments in the rat brain to study the feasibility of this application. The result shows that OCT is able to differentiate structures in the rat brain. White matter tends to have higher peak reflectivity and steeper attenuation rate compared to gray matter. This structural information may help guide DBS probe advance and electrical measurements.

Intracranial collision tumor mimicking an octreotide-SPECT positive and FDG-PET negative meningioma.

UNLABELLED: OBJECTIVE/IMPORTANCE: Cancer metastasis to a pre-existing intracranial tumor is rare, but several cases have been reported. We report an unusual case of a "collision tumor" consisting of a renal cell carcinoma metastasis to an intracranial meningioma. CLINICAL PRESENTATION: A 67-year old male with renal cell carcinoma had an asymptomatic right posterior frontal dural-based lesion identified on a screening CT scan. MRI characteristics of the tumor were consistent with meningioma. On octreotide-SPECT and F-18 fluorodeoxyglucose (FDG)-PET scans, the lesion showed octreotide uptake but did not accumulate FDG, both of which are consistent with a diagnosis of benign meningioma. One week later, he presented with a 1-day history of progressive left-sided weakness. The intracranial tumor was resected, and subacute subdural blood was found overlying a soft, reddish tumor. Microscopic examination was consistent with renal cell carcinoma with a minor portion consisting of meningioma. The meningothelial component was strongly immunoreactive to vimentin and weakly reactive to epithelial membrane antigens. Neither area reacted with glucose transporter-1 (GLUT-1), correlating with low FDG-PET uptake. CONCLUSION: Collision tumor involving metastatic renal cell carcinoma to an intracranial meningioma is a rare occurrence. Diagnosis by non-invasive means, with use of a combination of octreotide-SPECT and FDG-PET may not accurately reflect the malignant component of such a collision tumor. In this case, the collision tumor also demonstrated a propensity to undergo spontaneous hemorrhage. A high degree of suspicion of intracranial metastasis should be maintained for patients who have known systemic cancer and are found incidentally to have a dural-based mass lesion.

Glioblastomas induce T-lymphocyte death by two distinct pathways involving gangliosides and CD70.

Here we report that glioblastoma multiforme (GBM) mediates immunosuppression by promoting T-cell death via tumor-associated CD70 and gangliosides that act through receptor-dependent and receptor-independent pathways, respectively. GBM lines cocultured with T cells induced lymphocyte death. The GBM lines were characterized for their expression of CD70, Fas ligand (FasL), and tumor necrosis factor-alpha (TNF-alpha), and the possible participation of those molecules in T-cell killing was assessed by doing GBM/T cell cocultures in the presence of anti-CD70 antibodies, Fas fusion proteins, or anti-TNF-alpha antibodies. CD70 but not TNF-alpha or FasL is responsible for initiating T-cell death via the receptor-dependent pathway. Of the four GBM cell lines that induced T-cell death, three highly expressed CD70. Two nonapoptogenic GBM lines (CCF3 and U138), on the other hand, had only minimally detectable CD70 expression. Blocking experiments with the anti-CD70 antibody confirmed that elevated CD70 levels were involved in the apoptogenicity of the three GBM lines expressing that molecule. Gangliosides were found to participate in the induction of T-cell apoptosis, because the glucosylceramide synthase inhibitor (PPPP) significantly reduced the abilities of all four apoptogenic lines to kill the lymphocytes. High-performance liquid chromatography (HPLC) and mass spectroscopy revealed that GM2, GM2-like gangliosides, and GD1a were synthesized in abundance by all four apoptogenic GBM lines but not by the two GBMs lacking activity. Furthermore, gangliosides isolated from GBM lines as well as HPLC fractions containing GM2 and GD1a were directly apoptogenic for T cells. Our results indicate that CD70 and gangliosides are both products synthesized by GBMs that may be key mediators of T-cell apoptosis and likely contribute to the T-cell dysfunction observed within the tumor microenvironment.

A transcranial approach for direct mechanical thrombectomy of dural sinus thrombosis. Report of two cases.

Cerebral venous sinus thrombosis is often difficult to manage. Treatment options include systemically delivered anticoagulation therapy or chemical thrombolysis. Targeted endovascular delivery of thrombolytic agents is currently a popular option, but it carries an increased risk of hemorrhage. These strategies require significant time to produce thrombolysis, often in a patient with a rapidly deteriorating neurological condition. Rapid mechanical recanalization with thrombectomy is therefore very attractive; this procedure provides rapid recanalization with no increased risk of hemorrhage from use of thrombolytic agents. Nevertheless, the rheolytic catheter is large and stiff and may not be able to navigate tortuous intracranial vascular anatomy. The authors present their experience with direct dural sinus mechanical thrombectomy performed using the rheolytic catheter via a transcranial route. Two patients with dural sinus thrombosis and rapidly deteriorating levels of consciousness underwent unsuccessful attempts at mechanical thrombolysis via the usual transfemoral route. Through a burr hole over the dural sinus, mechanical thrombectomy was subsequently performed using the thrombectomy catheter. Sinus patency was restored following treatment and both patients demonstrated neurological recovery. Hemorrhage or a rapidly deteriorating neurological condition may preclude the use of systemic or locally delivered thrombolytic agents for the treatment of cerebral venous sinus thrombosis. Mechanical thrombectomy may be the treatment of choice in these circumstances. In patients with limited transfemoral access, a transcranial approach may be used to access the cerebral dural sinuses and thrombectomy may be safely and effectively performed. Further evaluation of this therapy is warranted.

Cerebellar paraganglioma.

Paragangliomas arising as primary neoplasms in the intracranial portion of the central nervous system are relatively uncommon and only have been rarely reported. We report a case of apparent primary paraganglioma arising in the left cerebellar hemisphere in an 11-year-old girl who presented with a 6-month history of headaches. The tumor was marked by a nested architectural pattern (zellballen), delimited by S-100-positive sustentacular cells. Morphologic and immunohistochemical features of the neoplasm are discussed and literature is reviewed regarding involvement of the central nervous system by paraganglioma.

Laparoscopic revision of a ventriculoperitoneal shunt.

Ventriculoperitoneal (VP) shunts are the most common treatment modality for hydrocephalus. Distal catheter malfunction represents a surgical emergency and a significant cause of procedural morbidity. We report the case of a patient with acute abdominal pain following VP shunt insertion. On examination she had a tender, irreducible bulge at the abdominal laparotomy site. Exploratory laparoscopy of the abdomen yielded no abdominal wall abnormalities. At the same time, the distal catheter was noted to be absent. The abdominal bulge was incised along the laparotomy scar and clear cerebrospinal fluid was encountered. The incision was explored and the distal catheter was coiled and knotted within the preperitoneal space. The catheter was laparoscopically returned to the peritoneal cavity. This case exemplifies the utility of laparoscopy for VP shunt revision and we present a review of laparoscopic shunt revision.

Successful surgical management of a case of spontaneous epidural hematoma of the spine during pregnancy.

BACKGROUND CONTEXT: A spontaneous epidural hematoma of the spine occurring during pregnancy is extremely rare. The development of a significant neurologic deficit may be rapid. Therefore, the neurosurgeon should be aware of the presentation, diagnosis and treatment options available. PURPOSE: The authors report a case of a spontaneous epidural hematoma of the spine during the third trimester of pregnancy, which was successfully managed with surgical evacuation. The case is unique in that the patient demonstrated a subacute presentation. STUDY DESIGN: The authors report a case of a 27-year-old primagravada presented with the subacute onset of progressive paraparesis. She became nonambulatory before admission. A magnetic resonance imaging study (MRI) demonstrated ventral epidural compression in the upper thoracic region. METHODS: A retrospective review of a case of spontaneous epidural hematoma of the spine during pregnancy was performed. The inpatient and outpatient charts were used to gather clinical information of the case, and the pertinent radiographs and images were reviewed. RESULTS: An urgent cesarean section was performed followed by evacuation of the epidural hematoma. The decompression was performed by means of a thoracic laminectomy with partial facetectomy. The patient had a prompt return of neurologic function. CONCLUSION: Spontaneous epidural hematoma of the spine should be suspected in the setting of acute back or neck pain with or without an associated progressive neurologic deficit. Spine surgeons and obstetricians should also recognize that a spinal epidural hematoma during pregnancy may also present subacutely, as illustrated in our case. Prompt diagnosis may be made with MRI, and evacuation of the hematoma should be performed, ideally before the onset of neurologic signs or symptoms. The prognosis for return of neurologic function is good after urgent evacuation.

Impact of chromosome 1p status in response of oligodendroglioma to temozolomide: preliminary results.

In this IRB-approved retrospective study, we analyzed the efficacy of temozolomide on World Health Organization Grade II and III oligodendrogliomas, as well as mixed oligoastrocytomas, to determine if a correlation exists between the tumors' 1p status and control of growth by this new oral agent. We assessed six patients with oligodendrogliomas with 1p intact (38%) and 10 patients with 1p loss (62%), who received temozolomide. Chromosome 1p status was significantly associated with response to treatment using temozolomide. While nine of 10 patients (90%) with 1p loss responded to temozolomide, only two of six patients (33%) with 1p intact benefited from this treatment (p = 0.04). Although the number of patients evaluated was small, there was no association between 1p status and gender, age, and tumor grade. Gender, age, and tumor grade were similarly not correlated with response to chemotherapy. This report is the first to find that patients harboring oligodendrogliomas with 1p loss are more likely to be sensitive to treatment with temozolomide than those that retain this chromosomal element. Larger prospective trials are needed to confirm these findings; however, temozolomide should be considered in the management of these tumors.

Metastatic epithelioid sarcoma to the brain: palisaded necrosis mimicking glioblastoma multiforme.

Epithelioid sarcomas are rare, morphologically distinct tumors that have a propensity to arise in the extremities. Brain metastasis from epithelioid sarcoma are a relatively rare occurrence. We report a case of brain metastasis in a 50-year-old man who was previously diagnosed with an epithelioid sarcoma arising in the elbow. Before the diagnosis of brain metastasis, he had developed an axillary lymph node metastasis. He presented with neurologic symptoms of progressively worsening headache and loss of vision on the right side. He underwent gross total resection of an occipital lobe mass. Histologically, the tumor was focally characterized by prominent perinecrotic pseudopalisading and demonstrated immunoreactivity with antibodies to cytokeratin AE1/3 and CAM5.2; the tumor did not stain with glial fibrillary acidic protein antibody. The literature is reviewed and the morphologic distinction between metastatic epithelioid sarcoma and other central nervous system neoplasms is discussed.