✓ In vitro binding of 3H-nimodipine to human brain membranes is demonstrated in this study. This binding was specific and saturable, and had an apparent affinity constant (KD) of 0.27 nM. The maximal number of binding sites for 3H-nimodipine was 5.8 pmoles/gm wet weight of human frontal cortex. The binding was shown to be dependent on calcium, with half-maximal stimulation obtained at 3 × 10−5 M CaCl2. Other 1,4-dihyropyridine calcium antagonists were shown to be competitive antagonists of 3H-nimodipine binding. In contrast, the calcium antagonists, verapamil and diltiazem, had complex interactions with 3H-nimodipine binding. These results represent the first identification of 3H-calcium antagonist binding sites in human brain, and they confirm that various calcium antagonist drugs may differ with respect to both their potency and their molecular site of action.
Stephen J. Peroutka and George S. Allen
George T. Tindall, John Kapp, Guy L. Odom and Stephen C. Robinson
✓ Thirty-one patients with aneurysms of the anterior communicating artery that filled from both sides during carotid arteriography were treated by a combined operative procedure consisting of clip-ligation of one proximal anterior cerebral artery followed by gradual occlusion of the opposite common carotid artery with a Crutchfield clamp. In 14 patients, intravascular pressure recordings in the carotid vessels in the neck were obtained both before and immediately after ligation of the anterior cerebral artery. Before ligation the average intravascular pressure reduction was 55%, while after ligation the average reduction was 71%. Of the 31 patients, 22 have had good results and no recurrent hemorrhage. Nine patients died, four from recurrent hemorrhage. Follow-up carotid arteriography in nine patients showed the aneurysm obliterated in six, smaller in one, and unchanged in two. The results of this study indicate that treatment of certain anterior communicating aneurysms by the combined operative approach described is useful.
Stephen L. Ondra, Henry Troupp, Eugene D. George and Karen Schwab
✓ The authors have updated a series of 166 prospectively followed unoperated symptomatic patients with arteriovenous malformations (AVM's) of the brain. Follow-up data were obtained for 160 (96%) of the original population, with a mean follow-up period of 23.7 years. The rate of major rebleeding was 4.0% per year, and the mortality rate was 1.0% per year. At follow-up review, 23% of the series were dead from AVM hemorrhage. The combined rate of major morbidity and mortality was 2.7% per year. These annual rates remained essentially constant over the entire period of the study. There was no difference in the incidence of rebleeding or death regardless of presentation with or without evidence of hemorrhage. The mean interval between initial presentation and subsequent hemorrhage was 7.7 years.
Stephen R. Parker, Peggy Harris, Thomas J. Cummings, Timothy George, Herbert Fuchs and Gerald Grant
Posterior fossa decompression with duraplasty for Chiari malformation Type I (CM-I) is a common pediatric neurosurgery procedure. Published series report a complication rate ranging from 3% to 40% for this procedure. Historically, many dural substitutes have been used, including bovine grafts, human cadaveric pericardium, synthetic dura, and autologous pericranium. The authors hypothesized that a recently observed increase in complications was dependent on the graft used.
Between January 2004 and January 2008, 114 consecutive patients ≤ 18 years old underwent primary CM-I decompression using duraplasty. Records were retrospectively reviewed for short- and intermediate-term complications and operative technique, focusing on the choice of duraplasty graft with or without application of a tissue sealant.
The average age of the patients was 8.6 years. The dural graft used was variable: 15 were treated with cadaveric pericardium, 12 with Durepair, and 87 with EnDura. Tisseel was used in 75 patients, DuraSeal in 12, and no tissue sealant was used in 27 patients. The overall complication rate was 21.1%. The most common complications included aseptic meningitis, symptomatic pseudomeningocele, or a CSF leak requiring reoperation. The overall complication rates were as follows: cadaveric pericardium 26.7%, Durepair 41.7%, and EnDura 17.2%; reoperation rates were 13%, 25%, and 8.1%, respectively. Prior to adopting a different graft product, the overall complication rate was 18.1%; following the change the rate increased to 35%. Complication rates for tissue sealants were 14.8% for no sealant, 18.7% for Tisseel, and 50% for DuraSeal. Nine patients were treated with the combination of Durepair and DuraSeal and this subgroup had a 56% complication rate.
Complication rates after CM-I decompression may be dependent on the dural graft with or without the addition of tissue sealant. The complication rate at the authors' institution approximately doubled following the adoption of a different graft product. Tissue sealants used in combination with a dural substitute to augment a duraplasty may increase the risk of aseptic meningitis and/or CSF leak. The mechanism of the apparent increased inflammation with this combination remains under investigation.
Nestor G. Rodriguez-Martinez, Amey Savardekar, Eric W. Nottmeier, Stephen Pirris, Phillip M. Reyes, Anna G. U. S. Newcomb, George A. C. Mendes, Samuel Kalb, Nicholas Theodore and Neil R. Crawford
Transvertebral screws provide stability in thoracic spinal fixation surgeries, with their use mainly limited to patients who require a pedicle screw salvage technique. However, the biomechanical impact of transvertebral screws alone, when they are inserted across 2 vertebral bodies, has not been studied. In this study, the authors assessed the stability offered by a transvertebral screw construct for posterior instrumentation and compared its biomechanical performance to that of standard bilateral pedicle screw and rod (PSR) fixation.
Fourteen fresh human cadaveric thoracic spine segments from T-6 to T-11 were divided into 2 groups with similar ages and bone quality. Group 1 received transvertebral screws across 2 levels without rods and subsequently with interconnecting bilateral rods at 3 levels (T8–10). Group 2 received bilateral PSR fixation and were sequentially tested with interconnecting rods at T7–8 and T9–10, at T8–9, and at T8–10. Flexibility tests were performed on intact and instrumented specimens in both groups. Presurgical and postsurgical O-arm 3D images were obtained to verify screw placement.
The mean range of motion (ROM) per motion segment with transvertebral screws spanning 2 levels compared with the intact condition was 66% of the mean intact ROM during flexion-extension (p = 0.013), 69% during lateral bending (p = 0.015), and 47% during axial rotation (p < 0.001). The mean ROM per motion segment with PSR spanning 2 levels compared with the intact condition was 38% of the mean intact ROM during flexion-extension (p < 0.001), 57% during lateral bending (p = 0.007), and 27% during axial rotation (p < 0.001). Adding bilateral rods to the 3 levels with transvertebral screws decreased the mean ROM per motion segment to 28% of intact ROM during flexion-extension (p < 0.001), 37% during lateral bending (p < 0.001), and 30% during axial rotation (p < 0.001). The mean ROM per motion segment for PSR spanning 3 levels was 21% of intact ROM during flexion-extension (p < 0.001), 33% during lateral bending (p < 0.001), and 22% during axial rotation (p < 0.001).
Biomechanically, fixation with a novel technique in the thoracic spine involving transvertebral screws showed restoration of stability to well within the stability provided by PSR fixation.
John E. Ziewacz, Matthew C. Davis, Darryl Lau, Abdulrahman M. El-Sayed, Scott E. Regenbogen, Stephen E. Sullivan and George A. Mashour
The surgical Apgar score (SAS) reliably predicts postoperative death and complications and has been validated in a large cohort of general and vascular surgery patients. However, there has been limited study of the utility of the score in the neurosurgical population. The authors tested the hypothesis that the SAS would predict postoperative complications and length of stay after neurosurgical procedures.
A cohort of 918 intracranial and spine surgery patients treated over a 3-year period were retrospectively evaluated. The 10-point SAS was calculated and postoperative 30-day mortality and complications rates, intensive care unit (ICU) stay, and hospital stay were assessed by 2 independent raters. Univariate analysis and multivariate logistic regression were performed.
There were 145 patients (15.8%) with at least 1 complication and 24 patients (2.6%) who died within 30 days of surgery. Surgical Apgar scores were significantly associated with the likelihood of postoperative complications (p < 0.001) and death (p = 0.002); scores varied inversely with postoperative complication and mortality risk in a multivariate analysis. Low SASs also predicted prolonged ICU and hospital stay. Patients with scores of 0–2 stayed a mean of 18.9 days (p < 0.001) and patients with scores of 3–4 stayed an average of 14.3 days (p < 0.001) compared with 4.1 days in patients with scores of 9–10.
The application of the surgical Apgar score to a neurosurgical cohort predicted 30-day postoperative mortality and complication rates as well as extended ICU and hospital stay. This readily calculated score may help neurosurgical teams efficiently direct postoperative care to those at highest risk of death and complications.
Michael A. Mooney, Joseph Georges, Mohammedhassan Izady Yazdanabadi, Katherine Y. Goehring, William L. White, Andrew S. Little, Mark C. Preul, Stephen W. Coons, Peter Nakaji and Jennifer M. Eschbacher
The objective of this study was to evaluate the feasibility of using confocal reflectance microscopy (CRM) ex vivo to differentiate adenoma from normal pituitary gland in surgical biopsy specimens. CRM allows for rapid, label-free evaluation of biopsy specimens with cellular resolution while avoiding some limitations of frozen section analysis.
Biopsy specimens from 11 patients with suspected pituitary adenomas were transported directly to the pathology department. Samples were immediately positioned and visualized with CRM using a confocal microscope located in the same area of the pathology department where frozen sections are prepared. An H & E–stained slide was subsequently prepared from imaged tissue. A neuropathologist compared the histopathological characteristics of the H & E–stained slide and the matched CRM images. A second neuropathologist reviewed images in a blinded fashion and assigned diagnoses of adenoma or normal gland.
For all specimens, CRM contrasted cellularity, tissue architecture, nuclear pleomorphism, vascularity, and stroma. Pituitary adenomas demonstrated sheets and large lobules of cells, similar to the matched H & E–stained slides. CRM images of normal tissue showed scattered small lobules of pituitary epithelial cells, consistent with matched H & E–stained images of normal gland. Blinded review by a neuropathologist confirmed the diagnosis in 15 (94%) of 16 images of adenoma versus normal gland.
CRM is a simple, reliable approach for rapidly evaluating pituitary adenoma specimens ex vivo. This technique can be used to accurately differentiate between pituitary adenoma and normal gland while preserving biopsy tissue for future permanent analysis, immunohistochemical studies, and molecular studies.