Toward robot-assisted neurosurgical lasers.

Despite the potential increase in precision and accuracy, laser technology is not widely used in neurological surgery. This in part relates to challenges associated with the early introduction of lasers into neurosurgery. Considerable advances in laser technology have occurred, which together with robotic technology could create an ideal platform for neurosurgical application. In this study, a 980-nm contact diode laser was integrated with neuroArm. Preclinical evaluation involved partial hepatectomy, bilateral nephrectomy, splenectomy, and bilateral submandibular gland excision in a Sprague-Dawley rat model (n = 50). Total surgical time, blood loss as weight of surgical gauze before and after the procedure, and the incidence of thermal, vascular, or lethal injury were recorded and converted to an overall performance score. Thermal damage was evaluated in the liver using tissue samples stained with hematoxylin and eosin. Clinical studies involved step-wise integration of the 980-nm laser system into four neurosurgical cases. Results demonstrate the successful integration of contact laser technology into microsurgery, with and without robotic assistance. In preclinical studies, the laser improved microsurgical performance and reduced thermal damage, while neuroArm decreased intra- and intersurgeon variability. Clinical studies demonstrate dutility in meningioma resection (n = 4). Together, laser and robotic technology offered a more consistent, expedient, and precise tool for microsurgery.

A prospective qualitative study on patients' perceptions of endoscopic endonasal transsphenoidal surgery.

BACKGROUND: Endoscopic transsphenoidal surgery has been shown to be a safe and effective treatment option for patients with pituitary tumours, but no study has explored patients' perceptions before and after this surgery. OBJECTIVE: The authors in this study aim to explore patients' perceptions on endoscopic transsphenoidal surgery. METHODS: Using qualitative research methodology, two semi-structured interviews were conducted with 30 participants who were adults aged > 18 undergoing endoscopic transsphenoidal surgery for the resection of a pituitary tumour between December 2008 and June 2011. The interviews were audiotaped and transcribed. The resulting data was analyzed using a modified thematic analysis. RESULTS: Seven overarching themes were identified: (1) Patients had a positive surgical experience; (2) patients were satisfied with the results of the procedure; (3) patients were initially surprised that neurosurgery could be performed endonasally; (4) patients expected a cure and to feel better after the surgery; (5) many patients feared that something might go wrong during the surgery; (6) patients were psychologically prepared for the surgery; (7) most patients reported receiving adequate pre-op and post-op information. CONCLUSIONS: This is the first qualitative study reporting on patients' perceptions before and after an endoscopic endonasal transsphenoidal pituitary surgery, which is increasingly used as a standard surgical approach for patients with pituitary tumours. Patients report a positive perception and general satisfaction with the endoscopic transsphenoidal surgical experience. However, there is still room for improvement in post-surgical care. Overall, patients' perceptions can help improve the delivery of comprehensive care to future patients undergoing pituitary tumour surgery.

Gamma knife radiosurgery for the treatment of cystic cerebral metastases.

PURPOSE: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. METHODS: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. RESULTS: A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. CONCLUSIONS: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.

Stereotactic radiosurgery for the treatment of melanoma and renal cell carcinoma brain metastases.

Renal cell carcinoma (RCC) and melanoma brain metastases have traditionally been considered radioresistant lesions when treated with conventional radiotherapeutic modalities. Radiosurgery provides high-dose radiation to a defined target volume with steep fall off in dose at lesion margins. Recent evidence suggests that stereotactic radiosurgery (SRS) is effective in improving local control and overall survival for a number of tumor subtypes including RCC and melanoma brain metastases. The purpose of this study was to compare the response rate to SRS between RCC and melanoma patients and to identify predictors of response to SRS for these 2 specific subtypes of brain metastases. We retrospectively reviewed a prospectively maintained database of all brain metastases treated with Gamma Knife SRS at the University Health Network (Toronto, Ontario) between October 2007 and June 2010, studying RCC and melanoma patients. Demographics, treatment history and dosimetry data were collected; and MRIs were reviewed for treatment response. Log rank, Cox proportional hazard ratio and Kaplan-Meier survival analysis using SPSS were performed. A total of 103 brain metastases patients (41 RCC; 62 melanoma) were included in the study. The median age, Karnofsky performance status score and Eastern Cooperative Oncology Group performance score was 52 years (range 27-81), 90 (range 70-100) and 1 (range 0-2), respectively. Thirty-four lesions received adjuvant chemotherapy and 56 received pre-SRS whole brain radiation therapy. The median follow-up, prescription dose, Radiation Therapy Oncology Group conformity index, target volume and number of shots was 6 months (range 1-41 months), 21 Gy (range 15-25 Gy), 1.93 (range 1.04-9.76), 0.4 cm3 (range 0.005-13.36 cm3) and 2 (range 1-22), respectively. Smaller tumor volume (P=0.007) and RCC pathology (P=0.04) were found to be positive predictors of response. Actuarial local control rate for RCC and melanoma combined was 89% at 6 months, 84% at 12 months, 76% at 18 months and 61% at 24 months. Local control at 12 months was 91 and 75% for RCC and melanoma, respectively. SRS is a valuable treatment option for local control of RCC and melanoma brain metastases. Smaller tumor volume and RCC pathology, predictors of response, suggest distinct differences in tumor biology and the extent of radioresponse between RCC and melanoma.

Proteins involved in regulating bone invasion in skull base meningiomas.

BACKGROUND: Bone invasive skull base meningiomas are a subset of meningiomas that present a unique clinical challenge due to brain and neural structure involvement and limitations in complete surgical resection, resulting in higher recurrence and need for repeat surgery. To date, the pathogenesis of meningioma bone invasion has not been investigated. We investigated immunoexpression of proteins implicated in bone invasion in other tumor types to establish their involvement in meningioma bone invasion. METHODS: Retrospective review of our database identified bone invasive meningiomas operated on at our institution over the past 20 years. Using high-throughput tissue microarray (TMA), we established the expression profile of osteopontin (OPN), matrix metalloproteinase-2 (MMP2), and integrin beta-1 (ITGB1). Differential expression in tumor cell and vasculature was evaluated and comparisons were made between meningioma anatomical locations. RESULTS: MMP2, OPN, and ITGB1 immunoreactivity was cytoplasmic in tumor and/or endothelial cells. Noninvasive transbasal meningiomas exhibited higher vascular endothelial cell MMP2 immunoexpression compared to invasive meningiomas. We found higher expression levels of OPN and ITGB1 in bone invasive transbasal compared to noninvasive meningiomas. Strong vascular ITGB1 expression extending from the endothelium through the media and into the adventitia was found in a subset of meningiomas. CONCLUSIONS: We have demonstrated that key proteins are differentially expressed in bone invasive meningiomas and that the anatomical location of bone invasion is a key determinant of expression pattern of MMP1, OPN, and ITGB1. This data provides initial insights into the pathophysiology of bone invasion in meningiomas and identifies factors that can be pursued as potential therapeutic targets.

Quality of life after transsphenoidal pituitary surgery: a qualitative study.

BACKGROUND: Microscopic and endoscopic approaches are both utilized for transsphenoidal resection of sellar/parasellar lesions. The endoscopic approach has been gaining popularity over the past decade; however, quality-of-life studies comparing the microscopic and endoscopic approaches are lacking. We aimed to compare the patients' perceptions of their postoperative recovery periods following microscopic and endoscopic procedures. METHODS: Qualitative research methodology was used for this study. Each participant underwent a single semi-structured, open-ended interview based on an interview guide. Each participant had undergone at least one microscopic and one endoscopic transsphenoidal procedure for resection of a sellar/parasellar lesion. The interviews were audiotaped and transcribed. The transcripts were then analyzed for overarching themes. Demographic information was also collected. RESULTS: The following five overarching themes emerged from the data: (1) the endoscopic procedure was better tolerated than the microscopic procedure and was the preferred approach by 22 out of 27 patients should they require another surgery in the future; (2) most patients did not know that they had undergone two different surgical approaches; (3) other than an unpleasant malodorous smell, rhinologic complications (including drainage, crusting, and alterations in smell) following the endoscopic procedures were comparable to those following the microscopic procedures; (4) the patient's postoperative experience after the microscopic procedure had an impact on his/her expectations of the endoscopic procedure; (5) any significant pain or discomfort experienced from either procedure was mainly related to the nasal packing or fascia lata graft donor site. CONCLUSIONS: The endoscopic procedure was the preferred approach over the microscopic approach by the majority of patients because of its better tolerability, despite comparable rhinologic complications.

A scoring system for elective triage of referrals: Spine Severity Score.

BACKGROUND CONTEXT: The Spine Severity Score (SSS) is a 15-point scoring system devised for the purpose of triaging elective surgical spine referrals. From the referral letter and the accompanying radiology report, a total score is calculated based on clinical, pathological, and radiological criteria; a maximum score of 5 can be obtained within each category. A higher total score represents a referral that should be seen more urgently. PURPOSE: To report interrater and intrarater reliability for the SSS and compare the scoring system against the traditional system for triage, that is, the surgeon's clinical experience. STUDY DESIGN: A prospective cross-comparison design was used to evaluate the reliability and convergent validity of the SSS using spine case referrals. METHODS: Four spine surgeons (experts) and three administrative assistants (nonexperts) at the University of Calgary scored 25 referrals. A second iteration of scoring was performed with a minimum time interval elapsed of 6 weeks. Raters were instructed to choose the most concerning (the one with the highest associated score) descriptor in each category that was thought relevant to the individual referral. No further instructions were given on how to interpret the referral letter or the radiology report. The surgeons also scored the referrals using their own preexisting four-point scoring systems. The results were analyzed with independent and dependent t tests, Pearson product moment correlation coefficient, and generalizability and decision analysis. RESULTS: An independent-measures t test (p>.05) revealed no statistical differences between experts and nonexperts (ie, interrater reliability) for both Iterations 1 and 2 on total scores of the SSS and a moderately strong relationship between their ratings across iterations (r=0.79, p<.001). Similarly, a paired-samples t test (p>.05) indicated a nonsignificant mean difference between Total SSS ratings at Time 1 and Time 2 (ie, intrarater reliability) and a high degree of agreement (r=0.96, p<.001) between the two iterations. These results were confirmed with correlational analyses. Pearson product moment correlation coefficients between the gold standard and the mean score were calculated from expert ratings on Total SSS at Time 1 (r=0.71, p<.001) and at Time 2 (r=0.69, p<.001). CONCLUSIONS: The SSS is a reliable scoring system for triage of elective spine referrals, even among nonexperts. We have been able to demonstrate strong interrater and intrarater reliability for the SSS and moderately strong correlation with the traditional triage system.

Anaplastic meningioma arising from a radiologically diagnosed arachnoid cyst: case report.

OBJECTIVE AND IMPORTANCE: We report the first example of an anaplastic meningioma arising from an intracranial arachnoid cyst and discuss the diagnostic challenges of this case, including the useful role of genetic markers. CLINICAL PRESENTATION: A 72-year-old man presented with transient episodes of expressive dysphasia and focal motor seizures, superimposed on a 6-month history of worsening headaches and dizziness. His past history was significant for a previously drained left-sided chronic subdural hematoma and a radiologically diagnosed left middle fossa arachnoid cyst. Magnetic resonance imaging on admission showed variable wall thickening of the arachnoid cyst with mild mass effect on the left frontotemporal lobes. INTERVENTION: The patient underwent decompression of the arachnoid cyst and biopsy of the cyst wall. Histologic and immunohistochemical studies of the thickened portion initially suggested a metastatic carcinosarcoma, but fluorescence in situ hybridization (FISH) studies confirmed the diagnosis of anaplastic meningioma based on characteristic chromosomal deletions. The patient returned 2 months later with progressive disease, leading to his death 6 weeks later despite repeat surgery for tumor debulking. CONCLUSION: Malignant transformation of meningothelial elements in arachnoid cysts is an exceptionally rare complication that poses considerable diagnostic challenges. Genetic markers may be particularly helpful in such cases.

Use of peri-operative anti-epileptic drugs in patients with newly diagnosed high grade malignant glioma: a single center experience.

An American Academy of Neurology practice parameter recommends that long-term prophylactic anti-epileptic drugs (AED) should not be routine in patients with newly diagnosed brain tumors. However, prospective multi-center North American data shows that most newly diagnosed glioma patients receive prophylactic AED. We examined our own peri-operative AED practice patterns in newly-diagnosed patients with malignant glioma to determine if we deviate from published guidelines. A retrospective chart review was performed in adult patients with newly diagnosed malignant gliomas undergoing surgery in southern Alberta between January 2003 and December 2005. Demographic information, AED use, seizure incidence, adverse effects, tumor size, and tumor location were recorded. Of 164 eligible patients, 54 (33%) presented with seizures and all received AED. Prophylactic AED were given to 44 patients (27%). Peri-operative seizures (within 1 week) occurred in two patients without (3%) and no patients with seizure prophylaxis. Adverse AED reactions and adverse effects attributable to seizures were both rare. Prophylactic AED were continued >1 week post-op in 30 patients (18%). Patients receiving prophylactic AED were more likely to have had tumors involving the temporal lobe than those who did not (50 vs. 20%; P < 0.01). Patients receiving peri-operative AED prophylaxis were common, had a trend to reduced peri-operative seizures, and had few adverse effects. However, most of these patients were maintained on prophylactic AED continued beyond the first peri-operative week, contradicting published guidelines. Increased awareness of practice guidelines may help modify AED prescription patterns in malignant glioma patients.

Clinical examination of brachial and pelvic plexus tumors.

A thorough history and physical examination are fundamental to the assessment of patients with brachial and pelvic plexus tumors. Typical of most peripheral nerve tumors, the presenting symptoms and signs are few, and if present, can be subtle. Presenting complaints may include a palpable mass lesion, either symptomatic or asymptomatic; sensory alterations; pain; motor deficits; visceral symptoms; or autonomic dysfunction. Motor deficits are usually a late feature in the pathogenesis of this lesion, and a progressive course of pain and significant sensory and motor deficits suggests a malignant pathological process. A detailed family history may reveal familial syndromes and neurocutaneous disorders that predispose the patient to neoplasia, such as neurofibromatosis. The physical examination should be conducted in a systematic fashion, looking for any cutaneous features and motor and sensory deficits. The mass should also be examined for form, consistency, and mobility. An irregular, firm, and immobile mass suggests a malignant lesion. Complete and accurate clinical information must be gathered to pinpoint the anatomical localization of the lesion and formulate a differential diagnosis.

Inhibition of Wilms tumor 1 transactivation by bone marrow zinc finger 2, a novel transcriptional repressor.

The Wilms tumor suppressor gene, wt1, encodes a zinc finger transcription factor that has been implicated in the regulation of a number of genes. Protein-protein interactions are known to modulate the transcription regulatory functions of Wilms tumor (WT1) and have also implicated WT1 in splicing. In this report, we identify a novel WT1-interacting protein, bone marrow zinc finger 2 (BMZF2), by affinity chromatography utilizing immobilized WT1 protein. BMZF2 is a potential transcription factor with 18 zinc fingers. The BMZF2 mRNA is mainly expressed in fetal tissues, and the protein is predominantly nuclear. Co-immunoprecipitation experiments are consistent with an in vivo association between WT1 and BMZF2. Glutathione S-transferase pulldown assays and far Western blots revealed that zinc fingers VI-X (amino acids 231-370) are required for interaction with the zinc finger region of WT1. Functionally, BMZF2 inhibits transcriptional activation by WT1. Moreover, a chimeric protein generated by fusion of BMZF2 to the GAL4 DNA-binding domain significantly decreases promoter activity of a reporter containing GAL4 DNA-binding sites, suggesting the presence of an active repressor domain within BMZF2. Our results suggest that BMZF2 interferes with the transactivation potential of WT1.