Andrew J. Baker, Richard J. Moulton, Vernon H. MacMillan and Peter M. Shedden
✓ Evidence from models of traumatic brain injury implicates excitotoxicity as an integral process in the ultimate neuronal damage that follows. Concentrations of the excitatory amino acid glutamate were serially measured in the cerebrospinal fluid (CSF) of patients with traumatic brain injuries and in control patients for comparison. The purpose of the study was to determine whether glutamate concentrations were significantly elevated following traumatic brain injury and, if so, whether they were elevated in a time frame that would allow the use of antagonist therapy. Cerebrospinal fluid was sampled fresh from ventricular drains every 12 hours and analyzed using high-performance liquid chromatography for the excitatory amino acids. The peak concentrations of glutamate in the CSF of the 12 brain-injured patients ranged from 14 to 474 µM and were significantly higher than those in the three control patients, 4.9 to 17 µM (Mann-Whitney U-test, p < 0.02). Glutamate concentrations in five of the eight patients who were still being sampled on Day 3 were beyond the control group range. The implication of this study is that severely head-injured patients are exposed to high concentrations of a neurotoxic amino acid for days following injury and thus may benefit from antagonist intervention.
Christen M. O’Neal, Cordell M. Baker, Chad A. Glenn, Andrew K. Conner and Michael E. Sughrue
The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath’s work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.
Michael G. Fehlings and Andrew Baker
Robert A. Morantz, John S. Neuberger, Larry H. Baker, Gary B. Beringer, Andrew B. Kaufman and Tom D. Y. Chin
✓ A cluster of seven primary brain neoplasms was identified in a town of 3000 population during the 10-year period from 1973 to 1982. With six deaths, this represents an age-adjusted mortality rate 4.1 times greater than expected. No other neoplasms were found to be in excess of the anticipated incidence in this town. When brain-tumor mortality rates in 36 other towns of approximately the same population were calculated, only one other town was found to have an excessive rate. All seven tumors in this study were histologically verified: six were diagnosed as glioblastoma multiforme. Interviews were conducted with patients or next-of-kin to obtain the exposure histories of the patients. A number of respondents reported occupational or residential exposure either to a shoe factory or to one of the several chicken hatcheries in the town. Many of the patients ate fish from local ponds that had previously been used as coal mining strip pits. Two patients were siblings. None of the patients had a history of significant head trauma. This unique situation may provide an opportunity to learn more about environmental risk factors for brain neoplasia. Further epidemiological studies are planned.
Joshua D. Bell, Theresa Currier Thomas, Elliot Lass, Jinglu Ai, Hoyee Wan, Jonathan Lifshitz, Andrew J. Baker and R. Loch Macdonald
Glutamate is important in the pathogenesis of brain damage after cerebral ischemia and traumatic brain injury. Notably, brain extracellular and cerebrospinal fluid as well as blood glutamate concentrations increase after experimental and clinical trauma. While neurons are one potential source of glutamate, platelets also release glutamate as part of their recruitment and might mediate neuronal damage. This study investigates the hypothesis that platelet microthrombi release glutamate that mediates excitotoxic brain injury and neuron dysfunction after subarachnoid hemorrhage (SAH).
The authors used two models, primary neuronal cultures exposed to activated platelets, as well as a whole-animal SAH preparation. Propidium iodide was used to evaluate neuronal viability, and surface glutamate receptor staining was used to evaluate the phenotype of platelet-exposed neurons.
The authors demonstrate that thrombin-activated platelet-rich plasma releases glutamate, at concentrations that can exceed 300 μM. When applied to neuronal cultures, this activated plasma is neurotoxic, and the toxicity is attenuated in part by glutamate receptor antagonists. The authors also demonstrate that exposure to thrombin-activated platelets induces marked downregulation of the surface glutamate receptor glutamate receptor 2, a marker of excitotoxicity exposure and a possible mechanism of neuronal dysfunction. Linear regression demonstrated that 7 days after SAH in rats there was a strong correlation between proximity to microthrombi and reduction of surface glutamate receptors.
The authors conclude that platelet-mediated microthrombosis contributes to neuronal glutamate receptor dysfunction and might mediate brain injury after SAH.
Andrew K. Conner, Joshua D. Burks, Cordell M. Baker, Adam D. Smitherman, Dillon P. Pryor, Chad A. Glenn, Robert G. Briggs, Phillip A. Bonney and Michael E. Sughrue
The purpose of this study was to describe a method of resecting temporal gliomas through a keyhole lobectomy and to share the results of using this technique.
The authors performed a retrospective review of data obtained in all patients in whom the senior author performed resection of temporal gliomas between 2012 and 2015. The authors describe their technique for resecting dominant and nondominant gliomas, using both awake and asleep keyhole craniotomy techniques.
Fifty-two patients were included in the study. Twenty-six patients (50%) had not received prior surgery. Seventeen patients (33%) were diagnosed with WHO Grade II/III tumors, and 35 patients (67%) were diagnosed with a glioblastoma. Thirty tumors were left sided (58%). Thirty procedures (58%) were performed while the patient was awake. The median extent of resection was 95%, and at least 90% of the tumor was resected in 35 cases (67%). Five of 49 patients (10%) with clinical follow-up experienced permanent deficits, including 3 patients (6%) with hydrocephalus requiring placement of a ventriculoperitoneal shunt and 2 patients (4%) with weakness. Three patients experienced early postoperative anomia, but no patients had a new speech deficit at clinical follow-up.
The authors provide their experience using a keyhole lobectomy for resecting temporal gliomas. Their data demonstrate the feasibility of using less invasive techniques to safely and aggressively treat these tumors.
Joshua D. Burks, Andrew K. Conner, Phillip A. Bonney, Chad A. Glenn, Cordell M. Baker, Lillian B. Boettcher, Robert G. Briggs, Daniel L. O’Donoghue, Dee H. Wu and Michael E. Sughrue
The orbitofrontal cortex (OFC) is understood to have a role in outcome evaluation and risk assessment and is commonly involved with infiltrative tumors. A detailed understanding of the exact location and nature of associated white matter tracts could significantly improve postoperative morbidity related to declining capacity. Through diffusion tensor imaging–based fiber tracking validated by gross anatomical dissection as ground truth, the authors have characterized these connections based on relationships to other well-known structures.
Diffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. The OFC was evaluated as a whole based on connectivity with other regions. All OFC tracts were mapped in both hemispheres, and a lateralization index was calculated with resultant tract volumes. Ten postmortem dissections were then performed using a modified Klingler technique to demonstrate the location of major tracts.
The authors identified 3 major connections of the OFC: a bundle to the thalamus and anterior cingulate gyrus, passing inferior to the caudate and medial to the vertical fibers of the thalamic projections; a bundle to the brainstem, traveling lateral to the caudate and medial to the internal capsule; and radiations to the parietal and occipital lobes traveling with the inferior fronto-occipital fasciculus.
The OFC is an important center for processing visual, spatial, and emotional information. Subtle differences in executive functioning following surgery for frontal lobe tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study.
Joshua D. Burks, Andrew K. Conner, Robert G. Briggs, Phillip A. Bonney, Adam D. Smitherman, Cordell M. Baker, Chad A. Glenn, Cameron A. Ghafil, Dillon P. Pryor, Kyle P. O’Connor and Bradley N. Bohnstedt
A shifting emphasis on efficient utilization of hospital resources has been seen in recent years. However, reduced screening for blunt vertebral artery injury (BVAI) may result in missed diagnoses if risk factors are not fully understood. The authors examined the records of blunt trauma patients with fractures near the craniocervical junction who underwent CTA at a single institution to better understand the risk of BVAI imposed by occipital condyle fractures (OCFs).
The authors began with a query of their prospectively collected trauma registry to identify patients who had been screened for BVAI using ICD-9-CM diagnostic codes. Grade and segment were recorded in instances of BVAI. Locations of fractures were classified into 3 groups: 1) OCFs, 2) C1 (atlas) fractures, and 3) fractures of the C2–6 vertebrae. Univariate and multivariate analyses were performed to identify any fracture types associated with BVAI.
During a 6-year period, 719 patients underwent head and neck CTA following blunt trauma. Of these patients, 147 (20%) had OCF. BVAI occurred in 2 of 43 patients with type I OCF, 1 of 42 with type II OCF, and in 9 of 62 with type III OCF (p = 0.12). Type III OCF was an independent risk factor for BVAI in multivariate modeling (OR 2.29 [95% CI 1.04–5.04]), as were fractures of C1–6 (OR 5.51 [95% CI 2.57–11.83]). Injury to the V4 segment was associated with type III OCF (p < 0.01).
In this study, the authors found an association between type III OCF and BVAI. While further study may be necessary to elucidate the mechanism of injury in these cases, this association suggests that thorough cerebrovascular evaluation is warranted in patients with type III OCF.