Subthalamic Gamma Knife Radiosurgery in Parkinson's Disease: A Cautionary Tale.

INTRODUCTION: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has been shown to reliably improve several symptoms of Parkinson's disease (PD) in appropriately selected patients. Various factors may preclude patients from undergoing DBS and for them, non-invasive lesion-based therapies such as focused ultrasound and Gamma Knife (GK) radiosurgery may present a safer alternative. MATERIALS AND METHODS: Based on preliminary positive reports of STN GK for PD, we conducted a prospective, open-label, single-center, pilot study in PD patients deemed potential candidates for unilateral DBS based on their disease characteristics, but contraindicated due to age >74, an irreversible bleeding diathesis, or significant comorbid medical disease. Stereotactic MRI-guided GK radiosurgery was performed using a single 110- or 120-Gy dose targeting the STN contralateral to the more symptomatic extremity. Clinical follow-up and imaging assessed the safety and efficacy of the procedure over a 12-month period. RESULTS: Four PD patients with medication-refractory tremors and disabling dyskinesias underwent unilateral STN GK radiosurgery. Contraindications to DBS included high-risk comorbid cardiovas-cular disease in 3 patients and an irreversible bleeding diathesis in 1. There were no immediate post-procedural adverse events. One patient who underwent left STN GK radiosurgery developed right hemiparesis and dysarthria 7 months post-procedure followed by hospitalization at 9 months for bacterial endocarditis and liver failure from which he died. The remaining 3 patients were free of adverse events up to 12 months post-procedure and experienced a reduction in contralateral rigidity, bradykinesia, and tremor. Upon extended follow-up, 2 patients developed subacute worsening of gait. One died at 16 months due to complications of a fall whereas the other saw no change in gait up to 42 months post-procedure. All 3 patients with adverse events demonstrated a hyper-response in the targeted area on follow-up neuroimaging. DISCUSSION/CONCLUSION: Despite the potential for clinical improvement, our results suggest that unilateral STN GK radiosurgery should be approached cautiously in medically frail PD patients who may be at higher risk of GK hyper-response and neurologic complications.

Intermediate-grade meningeal melanocytoma associated with nevus of Ota: a case report and review of the literature.

Meningeal melanocytomas are rare melanin-producing tumors that are often found to be benign. However, a small subset of these tumors can present as intermediate-grade melanocytomas (IGMs) that have histopathological features that are between those of benign melanocytomas and malignant melanomas. IGMs have the potential to recur and metastasize or progress to a more histologically high grade melanoma. Melanocytomas appear to differ from primary and metastatic melanoma by their prolonged clinical course and they appear to have different driver mutations (i.e. mutation of GNAQ gene). The association of a meningeal melanocytoma with nevus of Ota is extremely rare. To our knowledge, there have been only 10 reported cases of synchronous occurrence and only one of the cases involved an IGM. We report the second case of intermediate-grade meningeal melanocytoma that is associated with congenital nevus of Ota. Histopathological work-up confirmed the intermediate grade of the lesion and a driver GNAQ mutation was identified consistent with previous reports.

Technical modifications and decision-making to reduce morbidity in thoracic disc surgery: An institutional experience and treatment algorithm.

BACKGROUND: Symptomatic thoracic disc herniation (TDH) is an uncommon condition with significant treatment risks. OBJECTIVE: To evaluate strategies to avoid and manage complications from thoracic disc surgery. METHODS: All TDH cases by the senior author were retrospectively reviewed from 2000 to 2012. Complications were recorded, together with avoidance and management strategies. To reduce access-related morbidity, a thoracoscopic-tubular retractor approach was developed later in the series. RESULTS: 64 patients were treated for TDH, the majority undergoing an anterior minimally-invasive approach. Complications occurred in 15 patients (23%). Three patients with intercostal neuralgia persisting for >3 months had pain resolution after intercostal nerve blocks and radiofrequency lesioning. Five of the six patients with dural tears during anterior surgery had no further events following dural repair, lumbar drain insertion, and placement of chest tube to water seal. One case of persistent CSF leakage was successfully treated with a laparoscopically-mobilized omental flap. Preoperative metallic marker placement was effective at guiding correct-level surgery. For anterior operations, no pneumothorax occurred with routine chest tube placement. Our approach and techniques evolved based on early experience, allowing us to reduce surgical morbidity. The thoracoscopic-tubular retractor approach was associated with low morbidity (no complications among 13 cases other than temporary intercostal neuralgia). CONCLUSIONS: Several strategies may reduce morbidity from thoracic disc surgery: careful approach selection, preoperative level marking, use a tubular retractor with thoracoscopic guidance, rib resection at the mini-thoracotomy site, routine chest tube placement for anterior operations, and routine lumbar drain insertion in the event of a dural tear. Prospective comparative studies are needed to assess the efficacy of these techniques.

Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas.

BACKGROUND: The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts. METHODS: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. RESULTS AND DISCUSSION: In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN)-gamma Enzyme-Linked Immuno-SPOT (ELISPOT) assay in another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA) epitope EphA2883-891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-gamma post-vaccine responses or prolonged progression-free survival in these participants. CONCLUSION: Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines.

Optimizing intracranial metastasis detection for stereotactic radiosurgery.

BACKGROUND AND PURPOSE: The authors characterize the detection of additional intracranial metastases in cancer patients at the time of stereotactic radiosurgery (SRS) using a specialized high-resolution magnetic resonance imaging (MRI) protocol. METHODS: A retrospective review of 150 consecutive radiosurgical procedures for patients with < or =5 known metastatic intracranial tumors diagnosed using MRI was undertaken at a single center. On the day of SRS, all patients underwent rigid head fixation in a stereotactic frame followed by a specialized MRI using a 3-dimensional fast spoiled-gradient sequence on a 1.5-tesla magnet with double-dose gadolinium. Axial imaging was performed using 2-mm cuts and no gap. RESULTS: Additional metastases were detected in 29.3% of patients. The number of known tumors before SRS was predictive of additional metastases being found (p = 0.014). In multivariate analysis, we more frequently found additional metastases at radiosurgery in patients with 3-5 previously known metastases (p = 0.005), in patients with non-small cell lung cancer (p = 0.012) and in patients with a longer time interval between their diagnostic MRI and their stereotactic MRI (p = 0.030). Age, sex and prior fractionated radiation therapy were not predictive factors. CONCLUSION: Our specialized protocol of high-resolution, double-dose contrast-enhanced MRI is a reliable method to evaluate the extent of intracranial disease in patients with known brain metastasis. Treatment planning for radiosurgery, radiation therapy and open surgical therapy are all impacted by improved metastasis detection.

When the bone flap hits the floor.

OBJECTIVE: There is no published data in the neurosurgical literature describing the incidence, treatment, or outcome of contaminating a bone flap. We reviewed our departmental experience to determine methods of prevention and assess our treatment strategies. METHODS: We retrospectively reviewed all incidents of dropped bone flaps during a craniotomy at a single medical center during a 16-year period. In addition, a questionnaire was mailed to neurosurgeons in the United States and abroad asking their own experience and method of management. RESULTS: Fourteen incidents of dropped bone flaps occurred during a 16-year period. Follow-up varied from 2 to 176 months. The bone flap was dropped while elevating the bone (n = 4), when handing the bone off the field (n = 4), and during plating (n = 4). The context was unknown in two cases. Management included soaking the flap in betadine and/or antibiotic solution (n = 8), autoclaving (n = 2), or discarding the bone flap and replacing with a mesh cranioplasty (n = 3). The treatment remains unknown in one case. No instances of infection were noted in follow-up. In response to the survey, 66% (33 out of 50) of the polled neurosurgeons had experienced this complication during their practice, and 83% would replace the bone flap after disinfection. CONCLUSION: Dropping a bone flap during neurosurgery remains an uncommon but preventable complication. Treatment options include discarding the bone followed by cranioplasty versus replacing the bone after treatment with antibiotic irrigation, betadine, and/or autoclaving. Replacement after disinfection is an appropriate option for contaminated bone flaps that avoids the expense and time of cranioplasty.

Improving the informed consent process for surgery.

OBJECTIVE: Obtaining and documenting informed consent is of vital importance to physicians. We developed a procedure-based consent form that facilitates patient discussion and validated this process by surveying the patient regarding elements of the consent process, using an independent evaluator. METHODS: One hundred and twenty consecutive outpatients were evaluated before different neurosurgery procedures. The consent form listed specific diagnoses, procedures, alternatives (eight listed), and risks (22 listed), and each point discussed was checked off by the surgeon. Between 10 and 20 minutes later, each element was questioned by one lay-member of the office staff. A group of patients not at risk for cognitive decline were resurveyed months later. RESULTS: One hundred and twenty (100%) of 120 of patients answered correctly regarding their diagnosis and the planned procedure. Four hundred and twenty-eight alternative treatments were discussed, and 420 (98.1%) of the 428 were recalled correctly. Of 1207 risks that were discussed, 1176 (97.4%) were recalled correctly. When a subset of the patients were reevaluated at a mean of 4.5 months later, all 20 patients correctly recalled their procedure and diagnosis. Of 79 alternatives discussed with patients before surgery, 73 (92.4%) were subsequently recalled. Of 217 risks discussed before surgery, 199 (91.7%) were recalled. Although the immediate or delayed recall rates were high (> 90%), there was a reduction in the recall rate over time (alternatives, P = .007; risks, P < 0.0001). CONCLUSION: A consent process designed for an individual surgeon's practice was validated and showed high rates of patient recall in the postprocedural period. We think that this method to obtain and document informed consent should be considered for use by physicians.