Faculty Bibliography

Advances in stereotactic navigation technology have helped to improve the ease, reliability, and workflow of neurosurgical intraoperative navigation. These advances have also allowed novel, minimally invasive neurosurgical techniques to emerge. Minimally invasive techniques for intracerebral hemorrhage (ICH) evacuation, including endoscopic evacuation and passive catheter drainage, are notable examples, and as these gain support in the literature and their use expands, stereotactic navigation will take on an increasingly important and central role. Each neurosurgical navigation system has unique characteristics. Operators may find that certain aspects are more important than others, depending on the environment in which the evacuation is performed and operator preferences. This review will describe the characteristics of three popular stereotactic neuronavigation systems and compare their advantages and disadvantages as they relate to minimally invasive ICH evacuation.

We report a 50-year-old woman with a chondromyxoid fibroma of the occipital bone, who presented with a cerebellar hemorrhage due to invasion of the adjacent sinus. Chondromyxoid fibromas are benign cartilaginous tumors. However, this case represents the first example, to our knowledge, of a chondromyxoid fibroma invading the transverse-sigmoid junction, resulting in intracranial hemorrhage. Our report highlights that the location of an intracranial chondromyxoid fibroma is an important factor in guiding surgical management.

BACKGROUND:No conventional surgical intervention has been shown to improve outcomes for patients with spontaneous intracerebral hemorrhage (ICH) compared with medical management. OBJECTIVE:We report the initial multicenter experience with a novel technique for the minimally invasive evacuation of ICH using the Penumbra Apollo system (Penumbra Inc, Alameda, California). METHODS:Institutional databases were queried to perform a retrospective analysis of all patients who underwent ICH evacuation with the Apollo system from May 2014 to September 2014 at 4 centers (Medical University of South Carolina, Stony Brook University, University of California at San Diego, and Semmes-Murphy Clinic). Cases were performed either in the neurointerventional suite, operating room, or in a hybrid operating room/angiography suite. RESULTS:Twenty-nine patients (15 female; mean age, 62 ± 12.6 years) underwent the minimally invasive evacuation of ICH. Six of these parenchymal hemorrhages had an additional intraventricular hemorrhage component. The mean volume of ICH was 45.4 ± 30.8 mL, which decreased to 21.8 ± 23.6 mL after evacuation (mean, 54.1 ± 39.1% reduction; P < .001). Two complications directly attributed to the evacuation attempt were encountered (6.9%). The mortality rate was 13.8% (n = 4). CONCLUSION/CONCLUSIONS:Minimally invasive evacuation of ICH and intraventricular hemorrhage can be achieved with the Apollo system. Future work will be required to determine which subset of patients are most likely to benefit from this promising technology.

PURPOSE/OBJECTIVE:Glioblastoma is the most common adult primary malignant intracranial cancer. It is associated with poor outcomes because of its invasiveness and resistance to multimodal therapies. Human adipose-derived mesenchymal stem cells (hAMSC) are a potential treatment because of their tumor tropism, ease of isolation, and ability to be engineered. In addition, bone morphogenetic protein 4 (BMP4) has tumor-suppressive effects on glioblastoma and glioblastoma brain tumor-initiating cells (BTIC), but is difficult to deliver to brain tumors. We sought to engineer BMP4-secreting hAMSCs (hAMSCs-BMP4) and evaluate their therapeutic potential on glioblastoma. EXPERIMENTAL DESIGN/METHODS:The reciprocal effects of hAMSCs on primary human BTIC proliferation, differentiation, and migration were evaluated in vitro. The safety of hAMSC use was evaluated in vivo by intracranial coinjections of hAMSCs and BTICs in nude mice. The therapeutic effects of hAMSCs and hAMSCs-BMP4 on the proliferation and migration of glioblastoma cells as well as the differentiation of BTICs, and survival of glioblastoma-bearing mice were evaluated by intracardiac injection of these cells into an in vivo intracranial glioblastoma murine model. RESULTS:hAMSCs-BMP4 targeted both the glioblastoma tumor bulk and migratory glioblastoma cells, as well as induced differentiation of BTICs, decreased proliferation, and reduced the migratory capacity of glioblastomas in vitro and in vivo. In addition, hAMSCs-BMP4 significantly prolonged survival in a murine model of glioblastoma. We also demonstrate that the use of hAMSCs in vivo is safe. CONCLUSIONS:Both unmodified and engineered hAMSCs are nononcogenic and effective against glioblastoma, and hAMSCs-BMP4 are a promising cell-based treatment option for glioblastoma.

INTRODUCTION/BACKGROUND:Glioblastoma is the most common primary malignant brain tumor, and is refractory to surgical resection, radiation, and chemotherapy. Human mesenchymal stem cells (hMSC) may be harvested from bone marrow (BMSC) and adipose (AMSC) tissue. These cells are a promising avenue of investigation for the delivery of adjuvant therapies. Despite extensive research into putative mechanisms for the tumor tropism of MSCs, there remains no direct comparison of the efficacy and specificity of AMSC and BMSC tropism towards glioma. METHODS:Under an IRB-approved protocol, intraoperative human Adipose MSCs (hAMSCs) were established and characterized for cell surface markers of mesenchymal stem cell origin in conjunction with the potential for tri-lineage differentiation (adipogenic, chondrogenic, and osteogenic). Validated experimental hAMSCs were compared to commercially derived hBMSCs (Lonza) and hAMSCs (Invitrogen) for growth responsiveness and glioma tropism in response to glioma conditioned media obtained from primary glioma neurosphere cultures. RESULTS:Commercial and primary culture AMSCs and commercial BMSCs demonstrated no statistically significant difference in their migration towards glioma conditioned media in vitro. There was statistically significant difference in the proliferation rate of both commercial AMSCs and BMSCs as compared to primary culture AMSCs, suggesting primary cultures have a slower growth rate than commercially available cell lines. CONCLUSIONS:Adipose- and bone marrow-derived mesenchymal stem cells have similar in vitro glioma tropism. Given the well-documented ability to harvest larger numbers of AMSCs under local anesthesia, adipose tissue may provide a more efficient source of MSCs for research and clinical applications, while minimizing patient morbidity during cell harvesting.

PURPOSE/OBJECTIVE:Throughout his early career, Cushing proposed a variety of methods for temporary and permanent drainage and diversion of CSF in his patients, and acknowledged that certain techniques were more suited to particular subsets of hydrocephalus. METHODS:Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital, from 1896 to 1912, were reviewed. Patients operated upon by Harvey Cushing were selected for further analysis. Within this cohort, we recovered all available records for a single patient with hydrocephalus and spina bifida, who was treated with a ventriculosubgaleal shunt prior to repair of the spina bifida. RESULTS:A 3 month-old infant presented with hydrocephalus associated with spina bifida. Cushing performed serial lumbar and ventricular punctures. Following this, Cushing took the patient to the operating room for placement of a ventriculosubgaleal shunt. The patient subsequently underwent excision of the myelomeningocele sac, with post-operative mortality due to unspecified causes. CONCLUSIONS:Cushing's publications document a preference for translumbar-peritoneal drainage in patients with congenital hydrocephalus, particularly those with spina bifida. Although the placement of ventriculosubgaleal shunts has become an accepted practice for contemporary neurosurgeons, this case illustrates the challenges that early neurosurgeons faced in developing operative approaches for the treatment of congenital hydrocephalus.

Despite intensive clinical and laboratory research and effort, Glioblastoma remains the most common and invariably lethal primary cancer of the central nervous system. The identification of stem cell and lineage-restricted progenitor cell populations within the adult human brain in conjunction with the discovery of stem-like cells derived from gliomas which are themselves tumorigenic and have been shown to have properties of self-renewal and multipotency, has led to the hypothesis that this population of cells may represent glioma initiating cells. Extensive research characterizing the anatomic distribution and phenotype of neural stem cells in the adult brain, and the genetic underpinnings needed for malignant transformation may ultimately lead to the identification of the cellular origin for glioblastoma. Defining the cellular origin of this lethal disease may ultimately provide new therapeutic targets and modalities finally altering an otherwise bleak outcome for patients with glioblastoma.

BACKGROUND:In 1908, Anton and von Bramann proposed the Balkenstich method, a corpus callosum puncture which created a communication between the ventricle and subarachnoid space. This method offered the benefit of providing continuous CSF diversion without the implantation of cannula or other shunting devices, yet it received only slight reference in the literature of the time. It remained a novel and perhaps underutilized approach at the time Cushing began expanding his neurosurgical practice at the Johns Hopkins Hospital. MATERIALS AND METHODS/METHODS:Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital for the period 1896-1912 were reviewed. Patients operated upon by Harvey Cushing were selected. RESULTS:7 patients underwent puncture of the corpus callosum for treatment of hydrocephalus. 6 patients were treated for obstructive hydrocephalus secondary to presumed intracranial lesions. 1 patient was treated for congenital hydrocephalus. CONCLUSION/CONCLUSIONS:The series reported here documents Cushing's early use of the corpus callosum puncture to divert CSF in patients with obstructive hydrocephalus secondary to intracranial tumors, as well as an attempt to use the procedure in a pediatric patient with congenital hydrocephalus. Notably, 3 patients developed new onset left-sided weakness post-operatively, possibly due to retraction injury upon the supplementary motor intra-operative manipulations.

OBJECT/OBJECTIVE:This retrospective comparative cohort study was aimed at discovering the risk factors associated with subdural hygroma (SDG) following decompressive craniectomy (DC) to relieve intracranial hypertension in severe head injury. METHODS:Sixty-eight of 104 patients who had undergone DC during a 48-month period and survived > 30 days were eligible for this study. To assess the dynamics of subdural fluid collections, the authors compared CT scanning data from and the characteristics of 39 patients who had SDGs with the data in 29 patients who did not have hygromas. Variables significant in the appearance, evolution, and resolution of this complication were analyzed in a 36-week longitudinal study. RESULTS:The earliest imaging evidence of SDG was seen during the 1st week after DC. The SDG volume peaked between Weeks 3 and 4 post-DC and was gradually resolved by the 17th week. Among the mechanisms of injury, motor vehicle accidents were most often linked to the development of an SDG after DC (p < 0.0007), and falls were least often associated (p < 0.005). Moreover, patients with diffuse brain injury were more prone to this complication (p < 0.0299) than those with an evacuated mass (p < 0.0001). There were no statistically significant differences between patients with and without hygromas in terms of age, sex, Glasgow Coma Scale score, intraventricular and subarachnoid hemorrhage, levels of intracranial pressure and cerebral perfusion pressure, timing of decompression, and the need for CSF diversion. More than 90% of the SDGs were ipsilateral to the side of the craniectomy, and 3 (8%) of 39 SDGs showed evidence of internal bleeding at approximately 8 weeks postinjury. Surgical evacuation was needed in 4 patients with SDGs. CONCLUSIONS:High dynamic accidents and patients with diffuse injury were more prone to SDGs. Close to 8% of SDGs converted themselves into subdural hematomas at approximately 2 months postinjury. Although SDGs developed in 39 (approximately 60%) of 68 post-DC patients, surgical evacuation was needed in only 4.