Desmond A. Brown

Anterior nuclear deep brain stimulation guided by concordant hippocampal recording

OBJECT Anterior nuclear (AN) stimulation has been reported to reduce the frequency of seizures, in some cases dramatically; however, it has not been approved by the US Food and Drug Administration. The anterior nucleus is difficult to target because of its sequestered location, partially surrounded by the ventricle. It has traditionally been targeted by using transventricular or lateral transcortical routes. Here, the authors report a novel approach to targeting the anterior nucleus and neurophysiologically confirming effective stimulation of the target, namely evoked potentials in the hippocampus. METHODS Bilateral AN 3389 electrodes were placed in a novel trajectory followed by bilateral hippocampal 3391 electrodes from a posterior trajectory. Each patient was implanted bilaterally with a Medtronic Activa PC+S device under an investigational device exemption approval. Placement was confirmed with CT. AN stimulation-induced hippocampal evoked potentials were measured to functionally confirm placement in the anterior nucleus. RESULTS Two patients had implantations by way of a novel AN trajectory with concomitant hippocampal electrodes. There were no lead misplacements. Postoperative stimulation of the anterior nucleus with a PC+S device elicited evoked potentials in the hippocampus. Thus far, both patients have reported a > 50% improvement in seizure frequency. CONCLUSIONS Placing AN electrodes posteriorly may provide a safer trajectory than that used for traditionally placed AN electrodes. In addition, with a novel battery that is capable of electroencephalographic recording, evoked potentials can be used to functionally assess the Papez circuit. This treatment paradigm may offer increased AN stimulation efficacy for medically intractable epilepsy by assessing functional placement more effectively and thus far has proven safe.

Diagnostic Dilemma in Primary Blastomyces dermatitidis Meningitis: Role of Neurosurgical Biopsy.

A 52-year-old male on chronic prednisone for polymyalgia rheumatica presented with a subacute history of headaches, nausea, phonophobia, intermittent diplopia and gait instability. He was hospitalized 2 weeks prior to presentation with extensive evaluations only notable for leptomeningeal inflammation on MRI. His symptoms progressively worsened and he developed aphasia. He was transferred to our facility where extensive spinal fluid examinations were repeated and were again nondiagnostic. Ultimately, a diagnostic skull-based biopsy was performed which demonstrated Blastomyces dermatitidis fungal meningitis. Despite extensive sampling and cultures, only 1 of the intraoperative samples yielded diagnostic results. This underscores the low sensitivity of current methods to diagnose CNS blastomycosis. This case suggests that a neurosurgical biopsy may be necessary and should be considered early in the diagnostic process, especially if a definitive diagnosis is elusive. If a biopsy is performed, sampling should be ample and from multiple areas. Following the diagnosis, our patient was treated with liposomal amphotericin B and then voriconazole with a good clinical response.

A cost-effective method for femoral head allograft procurement for spinal arthrodesis: An alternative to commercially available allograft

Study Design. A cost-effective procurement process for harvesting, storing, and using femoral head allografts is described. A brief review of the literature on the use of these allografts and a discussion of costs are provided. Objective. To describe a cost-effective method for the harvesting, storage, and use of femoral heads from patients undergoing total hip arthroplasty at our institution as a source of allograft bone. Summary of Background Data. Spine fusion surgery uses a large proportion of commercially available bone grafts and bone substitutes. As the number of such surgical procedures performed in the United States continues to rise, these materials are at a historically high level of demand, which is projected to continue. Iliac crest bone autograft has historically been the standard of care, although this may be losing favor due to potential donor site morbidity. Although many substitutes are effective in promoting arthrodesis, their use is limited because of cost. Methods. Femoral heads are harvested under sterile conditions during total hip arthroplasty. The patient is tested per Food and Drug Administration regulations, and the tissue sample is cultured. The tissue is frozen and quarantined for a 6-month minimum pending repeat testing of donors and subsequently released for use. The relative cost-effectiveness of this tissue as a source of allograft bone is discussed. Results. The average femoral head allograft is 54 to 56 mm in diameter and yields 50 cm3 of bone graft, with an average cost of US

Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center

435 for processing of the tissue resulting in a cost of US

Insurance correlates with improved access to care and outcome among glioblastoma patients

8.70 per cm3 of allograft produced. Average production costs are significantly lower than those for other commonly available commercial bone grafts and substitutes. Conclusion. Femoral head allograft is a cost-effective alternative to commercially available allografts and bone substitutes. The method of procurement, storage, and use described could be adopted by other institutions in an effort to mitigate cost and increase supply. Level of Evidence: N/A

Synchronous Epstein-Barr virus–associated skull base and adrenal smooth-muscle tumors in an 8-year-old girl with recent Epstein-Barr virus infection

Objective: To determine adverse event rates for adult cranial neuro‐oncologic surgeries performed at a high‐volume quaternary academic center and assess the impact of resident participation on perioperative complication rates. Patients and Methods: All adult patients undergoing neurosurgical intervention for an intracranial neoplastic lesion between January 1, 2009, and December 31, 2013, were included. Cases were categorized as biopsy, extra‐axial/skull base, intra‐axial, or transsphenoidal. Complications were categorized as neurologic, medical, wound, mortality, or none and compared for patients managed by a chief resident vs a consultant neurosurgeon. Results: A total of 6277 neurosurgical procedures for intracranial neoplasms were performed. After excluding radiosurgical procedures and pediatric patients, 4151 adult patients who underwent 4423 procedures were available for analysis. Complications were infrequent, with overall rates of 9.8% (435 of 4423 procedures), 1.7% (73 of 4423), and 1.4% (63 of 4423) for neurologic, medical, and wound complications, respectively. The rate of perioperative mortality was 0.3% (14 of 4423 procedures). Case performance and management by a chief resident did not negatively impact outcome. Conclusion: In our large‐volume brain tumor practice, rates of complications were low, and management of cases by chief residents in a semiautonomous manner did not negatively impact surgical outcomes.

Swollen Middle Cerebral Artery Stroke in the Elderly

Background The current standard of care for glioblastoma (GBM) constitutes maximal safe surgical resection, followed by fractionated radiation and temozolomide. This treatment regimen is logistically burdensome, and in a health care system in which access to care is variable, there may be patients with worsened outcomes due to inadequate access to optimal treatment. Methods The National Cancer Database was queried for patients with diagnoses of GBM in 2006-2014. Patients were grouped according to insurance status: private insurance, Medicare, Medicaid, or uninsured. Treatments provided (surgery, radiation, and chemotherapy) were compared between groups in univariate and multivariable logistic regression analysis. Results A total of 61614 patients were analyzed. Compared with private insurance, the odds of surgery for Medicaid and uninsured patients were 0.72 (95% CI: 0.66-0.79) and 0.77 (95% CI: 0.69-0.87), respectively (P < 0.001). The multivariable odds of receiving radiotherapy were 0.91 (95% CI: 0.86-0.96), 0.62 (95% CI: 0.57-0.68), and 0.47 (95% CI: 0.43-0.52) for Medicare, Medicaid, and uninsured patients, respectively (all P < 0.001). In addition, the odds of receiving chemotherapy were 0.94 (95% CI: 0.89-0.99), 0.53 (95% CI: 0.49-0.57), and 0.41 (95% CI: 0.38-0.46) for Medicare, Medicaid, and uninsured patients, respectively (all P < 0.001). Conclusion Insurance status and type of insurance coverage appear to impact treatments rendered for GBM, independently of other variables. Furthermore, we find that such differential access to care significantly impacts survival. Ensuring adequate access to care for all patients with diagnoses of glioblastoma is critical to optimize survival, especially as therapies continue to advance.

DIPG-14. EVALUATING THERAPEUTIC VULNERABILITIES IN DIPG TUMORS USING HIGH-THROUGHPUT SCREENING

Epstein-Barr virus-associated smooth-muscle tumors are rare tumors seen in immunocompromised patients. Most cases occur in the context of AIDS and organ transplantation, and very rarely in the setting of congenital immunodeficiency, with only 5 case reports of the latter published so far in the literature. The authors report the case of a previously healthy 8-year-old girl with headaches and precocious puberty who was found to have a large skull base lesion. There was a synchronous left adrenal lesion. She underwent resection of the skull base lesion and a left adrenalectomy. Thorough evaluation for immunodeficiency was negative for a known congenital immunodeficiency syndrome. She had a short course of intravenous immunoglobulin and has had no recurrence of disease or new lesions in the 17 months since presentation. Continued surveillance for the development of opportunistic infections and new or recurrent lesions is warranted in this case. Repeat surgery for surgically accessible tumors or chemoradiation would be recommended for any additional lesions.

Headache, TIA and subarachnoid haemorrhage: dissecting an unusual cause for stroke-like symptoms

Large territorial infarctions of the brain involving virtually an entire hemisphere may swell, cause tissue shift, and become symptomatic. When associated with clinical signs of brain tissue shift, the affix “malignant” has been used but neither all swelling is “malignant” nor clinically recognizable. This term was coined to describe the rapidity and relentlessness of neurological deterioration which occurs as a consequence of space-occupying cerebral edema in the context of large MCA ischemic infarctions [1–3] although the syndrome had long been described [4, 5]. Deterioration may occur within the first 24 h or may be more protracted over several days following the initial ischemic insult. The incidence is approximately 10–20 per 100,000 person-years often affecting patients that are approximately a full decade younger (56 ± 9.4 years) than the average age of patients presenting with ischemic strokes in general [1].

Outcomes following cerebrospinal fluid shunting in high-grade glioma patients

Abstract Pediatric high-grade gliomas including Diffuse Intrinsic Pontine Gliomas (DIPGs) are among the most lethal cancers known with no effective cure. Recently, somatic mutations in the H3F3A or HIST1H3B genes have been detected in the majority of midline high-grade pediatric glioma cases which leads to an amino acid change at lysine 27 of H3 to methionine. In an effort to identify drugs for rapid clinical translation, we performed a rigorous high-throughput in vitro drug screen of FDA approved chemotherapeutics and epigenetic regulators. Over 200 drugs were tested including FDA approved cancer drugs and a comprehensive library of epigenetic regulators in 6 H3K27M tumors lines and 3 wild type (WT) cell lines using a HTS platform. We identified several major classes of drugs that potently reduce cell viability of DIPG tumors with the H3K27M mutation. Based on these results we uncovered a major signaling pathway that has not been previously reported as a therapeutic target for DIPG. We found proteins in this pathway that were overexpressed in H3K27M tumors compared to WT tumors and normal brain. Furthermore, depletion or inhibition of this pathway selectively inhibit the proliferation of H3K27M mutant DIPG cells, decreases cell colony formation, increases apoptosis compared to WT expressing tumors and restores H3K27 trimethylation patterns. These findings were validated in orthotopic xenografts. Malignant gliomas including DIPG, are one of the most aggressive primary malignant brain tumors with no effective therapies at this time. Using a HTS we identified a class of drugs that utilize a specific signaling pathway that is critical for H3K27M tumors. These studies pave the way for developing molecularly targeted therapies as our understanding how these mutations lead to tumorigenesis unfold.