A case series of atypical features of patients with biopsy-proven isolated IgG4-related hypophysitis and normal serum IgG4 levels.

BACKGROUND: IgG4-related hypophysitis is a rare clinical entity that forms part of an emerging group of multi-organ IgG4-related fibrosclerotic systemic diseases. The rare prevalence of the disease, presenting features that overlap with other sellar pathologies, and variable imaging features can make preoperative identification challenging. PURPOSE AND METHODS: We report three cases of isolated IgG4-related hypophysitis with atypical clinical and imaging features that mimicked those of pituitary apoplexy and other sellar lesions. Additionally, we review the literature of IgG4-related hypophysitis to provide context for individual patient data described herein. RESULTS: All patients presented with symptoms that mimicked those of pituitary apoplexy and visual disturbance, and MRI findings suggestive of pituitary macroadenoma, Rathke's cleft cyst and craniopharyngioma. The clinical presentation warranted surgical decompression, resulting in rapid symptomatic improvement. Preoperative high-dose followed by postoperative low-dose glucocorticoid replacement therapy was administered in all cases. Histopathology showed dense infiltrate of IgG4 cells. Post-operative follow-up monitoring for 12-26 months revealed normal serum IgG4 levels with no other organ involvement, while endocrinological testing revealed persistent pituitary hormone deficiencies. CONCLUSIONS: Our cases highlight the importance of considering IgG4-related hypophysitis in the differential diagnosis of solid and cystic sellar lesions presenting acutely with pituitary apoplexy symptoms. Existing diagnostic criteria may not be sufficiently precise to permit rapid and reliable identification, or avoidance of surgery in the acute setting. In contrast to other reports of the natural history of this condition, despite the severity of presenting features, the disease in our cases was pituitary-restricted with normal serum IgG4 levels.

Evaluation of Surgical Resection Goal and Its Relationship to Extent of Resection and Patient Outcomes in a Multicenter Prospective Study of Patients With Surgically Treated, Nonfunctioning Pituitary Adenomas: A Case Series.

BACKGROUND: The influence of the surgeon's preoperative goal regarding the extent of tumor resection on patient outcomes has not been carefully studied among patients with nonfunctioning pituitary adenomas. OBJECTIVE: To analyze the relationship between surgical tumor removal goal and patient outcomes in a prospective multicenter study. METHODS: Centrally adjudicated extent of tumor resection (gross total resection [GTR] and subtotal resection [STR]) data were analyzed using standard univariate and multivariable analyses. RESULTS: GTR was accomplished in 148 of 171 (86.5%) patients with planned GTR and 32 of 50 (64.0%) patients with planned STR (P = .001). Sensitivity, specificity, positive predictive value, and negative predictive value of GTR goal were 82.2, 43.9, 86.5, and 36.0%, respectively. Knosp grade 0-2, first surgery, and being an experienced surgeon were associated with surgeons choosing GTR as the goal (P < .01). There was no association between surgical goal and presence of pituitary deficiency at 6 mo (P = .31). Tumor Knosp grade (P = .004) and size (P = .001) were stronger predictors of GTR than was surgical goal (P = .014). The most common site of residual tumor was the cavernous sinus (29 of 41 patients; 70.1%). CONCLUSION: This is the first pituitary surgery study to examine surgical goal regarding extent of tumor resection and associated patient outcomes. Surgical goal is a poor predictor of actual tumor resection. A more aggressive surgical goal does not correlate with pituitary gland dysfunction. A better understanding of the ability of surgeons to meet their expectations and of the factors associated with surgical result should improve prognostication and preoperative counseling.

Use of morning serum cortisol level after transsphenoidal resection of pituitary adenoma to predict the need for long-term glucocorticoid supplementation.

OBJECT: Accurate assessment of the hypothalamic-pituitary-adrenal (HPA) axis is critical for appropriate management of the disease in patients with pituitary adenoma after transsphenoidal resection. The authors examine the role of the morning total serum cortisol level in the early postoperative period as a predictor of long-term HPA function. METHODS: Morning total serum cortisol was measured in 83 patients on postoperative Day 1 (or Day 2 if the patient received glucocorticoids during surgery) after transsphenoidal surgery for pituitary adenoma. These results were compared with those of definitive assays of HPA function performed at 1-3 months postoperatively, including cortrosyn/synacthen stimulation test (CST), insulin tolerance test (ITT), and metyrapone test (MTT). The ability of the early-postoperative morning cortisol level to predict HPA function was determined using standard confusion matrix calculations and receiver-operator control curve analysis. RESULTS: The authors found that an early postoperative morning total cortisol level>or=15 microg/dl is a sensitive and accurate predictor of normal HPA function in the postoperative period (sensitivity 80.5%, specificity 66.7%, positive predictive value 96.9%). CONCLUSIONS: A morning total cortisol level>or=15 microg/dl in the early postoperative period after transsphenoidal surgery for pituitary adenomas is a good predictor of normal HPA function. This test has good sensitivity and accuracy and correlates well with the results of additional, definitive assays of HPA function (CST, ITT, and MTT) performed at 1-3 months postoperatively. Accordingly, it is the authors' practice to avoid exogenous perioperative glucocorticoid supplementation in patients with normal preoperative HPA function and postoperative morning total cortisol levels>or=15 microg/dl 1-2 days after transsphenoidal pituitary adenomectomy.

Results of a prospective multicenter controlled study comparing surgical outcomes of microscopic versus fully endoscopic transsphenoidal surgery for nonfunctioning pituitary adenomas: the Transsphenoidal Extent of Resection (TRANSSPHER) Study.

OBJECTIVE: Many surgeons have adopted fully endoscopic over microscopic transsphenoidal surgery for nonfunctioning pituitary tumors, although no high-quality evidence demonstrates superior patient outcomes with endoscopic surgery. The goal of this analysis was to compare these techniques in a prospective multicenter controlled study. METHODS: Extent of tumor resection was compared after endoscopic or microscopic transsphenoidal surgery in adults with nonfunctioning adenomas. The primary end point was gross-total tumor resection determined by postoperative MRI. Secondary end points included volumetric extent of tumor resection, pituitary hormone outcomes, and standard quality measures. RESULTS: Seven pituitary centers and 15 surgeons participated in the study. Of the 530 patients screened, 260 were enrolled (82 who underwent microscopic procedures, 177 who underwent endoscopic procedures, and 1 who cancelled surgery) between February 2015 and June 2017. Surgeons who used the microscopic technique were more experienced than the surgeons who used the endoscopic technique in terms of years in practice and number of transsphenoidal surgeries performed (p < 0.001). Gross-total resection was achieved in 80.0% (60/75) of microscopic surgery patients and 83.7% (139/166) of endoscopic surgery patients (p = 0.47, OR 0.8, 95% CI 0.4-1.6). Volumetric extent of resection, length of stay, surgery-related deaths, and unplanned readmission rates were similar between groups (p > 0.2). New hormone deficiency was present at 6 months in 28.4% (19/67) of the microscopic surgery patients and 9.7% (14/145) of the endoscopic surgery patients (p < 0.001, OR 3.7, 95% CI 1.7-7.7). Microscopic surgery cases were significantly shorter in duration than endoscopic surgery cases (p < 0.001). CONCLUSIONS: Experienced surgeons who performed microscopic surgery and less experienced surgeons who performed endoscopic surgery achieved similar extents of tumor resection and quality outcomes in patients with nonfunctioning pituitary adenomas. The endoscopic technique may be associated with lower rates of postoperative pituitary gland dysfunction. This study generally supports the transition to endoscopic pituitary surgery when the procedure is performed by proficient surgeons, although both techniques yield overall acceptable surgical outcomes.■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: prospective cohort trial; evidence: class III.Clinical trial registration no.: NCT02357498 (clinicaltrials.gov).

Proposal and Validation of a Simple Grading Scale (TRANSSPHER Grade) for Predicting Gross Total Resection of Nonfunctioning Pituitary Macroadenomas After Transsphenoidal Surgery.

BACKGROUND: A simple, reliable grading scale to better characterize nonfunctioning pituitary adenomas (NFPAs) preoperatively has potential for research and clinical applications. OBJECTIVE: To develop a grading scale from a prospective multicenter cohort of patients that accurately and reliably predicts the likelihood of gross total resection (GTR) after transsphenoidal NFPA surgery. METHODS: Extent-of-resection (EOR) data from a prospective multicenter study in transsphenoidal NFPA surgery were analyzed (TRANSSPHER study; ClinicalTrials.gov NCT02357498). Sixteen preoperative radiographic magnetic resonance imaging (MRI) tumor characteristics (eg, tumor size, invasion measures, tumor signal characteristics, and parameters impacting surgical access) were evaluated to determine EOR predictors, to calculate receiver-operating characteristic curves, and to develop a grading scale. A separate validation cohort (n = 165) was examined to assess the scale's performance and inter-rater reliability. RESULTS: Data for 222 patients from 7 centers treated by 15 surgeons were analyzed. Approximately one-fifth of patients (18.5%; 41 of 222) underwent subtotal resection (STR). Maximum tumor diameter > 40 mm; nodular tumor extension through the diaphragma into the frontal lobe, temporal lobe, posterior fossa, or ventricle; and Knosp grades 3 to 4 were identified as independent STR predictors. A grading scale (TRANSSPHER grade) based on a combination of these 3 features outperformed individual variables in predicting GTR (AUC, 0.732). In a validation cohort, the scale exhibited high sensitivity and specificity (AUC, 0.779) and strong inter-rater reliability (kappa coefficient, 0.617). CONCLUSION: This simple, reliable grading scale based on preoperative MRI characteristics can be used to better characterize NFPAs for clinical and research purposes and to predict the likelihood of achieving GTR.

Shunt scissors: technical note.

OBJECTIVEWhen performing ventriculoperitoneal shunt surgery it is necessary to create a subgaleal pocket that is of sufficient size to accommodate a shunt valve. In most cases the valve is placed over the posterior skull where the galea begins to transition to suboccipital neck fascia. Dense fibrous attachments in this region of the skull make it technically awkward to develop the subgaleal valve pocket using standard scissors and a blunt dissection technique. In this report the authors describe a new device that enables surgeons to create the shunt valve pocket by using a simple semi-sharp dissection technique.METHODSThe authors analyzed the deficiencies of the standard valve pocket dissection technique and designed shunt scissors that address the identified shortcomings. These new scissors allow the surgeon to sharply dissect the subgaleal space by using an efficient hand-closing maneuver.RESULTSStandard surgical scissors were modified to create shunt scissors that were tested on the benchtop and used in the operating room. In all cases the shunt scissors proved easy to use and allowed the efficient and reliable creation of a subgaleal valve pocket in a technically pleasing manner.CONCLUSIONSShunt scissors represent an incremental technical advance in the field of neurosurgical shunt operations.

Visual Field Outcome Reporting in Neurosurgery: Lessons Learned from a Prospective, Multicenter Study of Transsphenoidal Pituitary Surgery.

OBJECTIVE: Visual field (VF) outcomes are commonly reported in neurosurgical case series; however, substantial variability can exist in VF testing and outcome reporting. We aimed to evaluate the challenges of VF testing and to develop detailed recommendations for VF outcome reporting by analyzing results from an ongoing, multicenter study of transsphenoidal pituitary surgery. METHODS: VF testing results were collected during a prospective, multicenter clinical trial evaluating patient outcomes after transsphenoidal surgery for nonfunctioning pituitary adenomas (TRANSSPHER). Two independent ophthalmologists reviewed reliability and outcomes of all VF studies. Preoperative and postoperative VF studies were evaluated individually and as preoperative/postoperative pairs. RESULTS: Suboptimal perimetry field settings were reported in 37% of VF studies. Automated reliability criteria flagged 25%-29% of VF studies as unreliable, whereas evaluation by 2 independent ophthalmologists flagged 16%-28%. Agreement between automated criteria and raters for VF reliability was inconsistent (κ coefficients = 0.55-0.83), whereas agreement between the 2 raters was substantial to almost perfect (κ coefficients = 0.78-0.83). Most patients demonstrated improvement after surgery (rater 1, 67%; rater 2, 60%), with substantial rater agreement on outcomes for paired examinations (κ coefficient = 0.62). CONCLUSIONS: VF outcome studies demonstrated significant variability of test parameters and patient performance. Perimetry field settings varied among patients and for some patients varied preoperatively versus postoperatively. Reliance on automated criteria alone could not substitute for independent ophthalmologist review of test reliability. Standardized guidelines for VF data collection and reporting could increase reliability of results and allow better comparisons of outcomes in future studies.

Intensity-modulated radiotherapy for pituitary adenomas: the preliminary report of the Cleveland Clinic experience.

PURPOSE: Intensity-modulated radiotherapy (IMRT) is being increasingly used for the treatment of pituitary adenomas. However, there have been few published data on the short- and long-term outcomes of this treatment. This is the initial report of the Cleveland Clinic's experience. METHODS AND MATERIALS: Between February 1998 and December 2003, 34 patients with pituitary adenomas were treated with IMRT. A retrospective chart review was conducted for data analysis. RESULTS: With a median follow-up of 42.5 months, the treatment has proven to be well tolerated, with performance status remaining stable in 90% of patients. Radiographic local control was 89%, and among patients with secretory tumors, 100% had a biochemical response. Only 1 patient required salvage surgery for progressive disease, giving a clinical progression free survival of 97%. The only patient who received more than 46 Gy experienced optic neuropathy 8 months after radiation. Smaller tumor volume significantly correlated with subjective improvements in nonvisual neurologic complaints (p = 0.03), and larger tumor volume significantly correlated with subjective worsening of visual symptoms (p = 0.05). New hormonal supplementation was required for 40% of patients. Younger patients were significantly more likely to require hormonal supplementation (p = 0.03). CONCLUSIONS: Intensity-modulated radiation therapy is a safe and effective treatment for pituitary adenomas over the short term. Longer follow-up is necessary to determine if IMRT confers any advantage with respect to either tumor control or toxicity over conventional radiation modalities.

Cyclic Cushing syndrome: definitions and treatment implications.

Endogenous Cushing syndrome (CS) results from hypercortisolemia caused by excess adrenocorticotropic hormone production in a pituitary adenoma or ectopic tumor, or by an adrenal tumor that directly produces excess cortisol. The diagnosis can usually be ascertained with a reasonable degree of certainty based on clinical and laboratory findings of hypercortisolism. There are patients, however, in whom the production of excess cortisol exhibits a cyclic or intermittent pattern, and, as a result, the clinical symptoms may be quite complex and varied. In these patients the hypothalamic-pituitary-adrenal axis may be normal between cycles, and dexamethasone suppression testing may produce a paradoxical response. In the present article, the authors provide a definition of cyclic Cushing syndrome, review the causes and its potential pathophysiological mechanisms, and discuss the treatment options based on a review of the available literature.

Serum transthyretin monomer as a possible marker of blood-to-CSF barrier disruption.

The CNS is shielded from systemic influences by two separate barriers, the blood-brain barrier (BBB) and the blood-to-CSF barrier. Failure of either barrier bears profound significance in the etiology and diagnosis of several neurological diseases. Furthermore, selective opening of BBB tight junctions provides an opportunity for delivery of otherwise BBB impermeant drugs. Peripheral assessment of BBB opening can be achieved by detection in blood of brain-specific proteins that extravasate when these endothelial junctions are breached. We developed a proteomic approach to discover clusters of CNS-specific proteins with extravasation into serum that correlates with BBB openings. Protein profiles from blood samples obtained from patients undergoing iatrogenic BBB disruption (BBBD) with intra-arterial hyperosmotic mannitol were compared with pre-BBB opening serum. A low molecular weight protein (14 kDa) identified by mass spectroscopy as transthyretin (TTR) consistently correlated with BBBD. Protein gel electrophoresis and immunodetection confirmed that TTR was indeed extravasated in its monomeric form when CNS barriers were breached. The time course of TTR extravasation was compared with release from the brain of another BBB integrity marker, S-100beta (11 kDa). Kinetic analysis revealed that the appearance of S-100beta, presumably originating from perivascular astrocytic end feet, preceded extravasation of TTR by several minutes. Because TTR is localized primarily in choroid plexus and, as a soluble monomer, in CSF, we concluded that although S-100beta is a marker of BBB integrity, TTR instead may be a peripheral tracer of blood-to-cerebrospinal barrier.

Stent-assisted angioplasty of intracranial vertebrobasilar atherosclerosis: midterm analysis of clinical and radiologic predictors of neurological morbidity and mortality.

BACKGROUND AND PURPOSE: Initial reports of stent-assisted angioplasty for intracranial vertebrobasilar atherosclerosis suggest this is a feasible treatment, but there have been little data regarding predictors of success or failure. We analyzed a series of patients for independent predictors of neurologic morbidity and mortality. METHODS: Patient charts and angiograms from 39 patients who underwent intracranial angioplasty and stent placement of vertebrobasilar stenoses were retrospectively reviewed to obtain clinical and detailed angiographic data on potential predictors of neurologic morbidity and mortality. Univariate analyses of these predictors were performed with either Fisher's exact test or simple logistic regression. Multivariate analysis was subsequently performed on the statistically significant predictors. RESULTS: Complete clinical data were obtained for 39 patients, and angiographic review was possible for 35 of them. Angiography revealed severe intracranial vertebral (n = 18), basilar (n = 15), or basilar and vertebral (n = 2) stenoses. Two patients (5.1%) died in the periprocedural period, nine patients (23.1%) had neurologic complications, and one patient (2.6%) had transient neurologic symptoms. Univariate analysis revealed female sex, diabetes, and failure of coumadin or heparin therapy were associated with neurologic morbidity, whereas female sex, Mori B lesion, and length-to-stenosis ratio were associated with mortality. The presence of diabetes was the only independent predictor of neurologic morbidity and mortality. CONCLUSION: Because of the limited number of patients available for analysis, the only independent predictor of neurologic morbidity and mortality was diabetes, but several other predictors showed trends that deserve further review in future series.

Image-guided endoscopy: description of technique and potential applications.

OBJECT: Neuroendoscopic approaches to lesions of the central nervous system and spine are limited by the loss of stereoscopic vision and high-fidelity image quality inherent in the operating microscope. Image-guided endoscopy (IGE) and image-guided surgery (IGS) have the potential to overcome these limitations. The goal of this study was to evaluate IGE for its potential applications in neurosurgery. METHODS: To determine the feasibility of IGE, a rigid endoscope was tracked using an IGS system that provided navigational data for the endoscope tip and trajectory as well as a computer-generated, three-dimensional, virtual representation of the image provided by the endoscope. The IGE procedure was successfully completed in 14 patients (nine with pituitary adenomas, one with a temporal cavernous malformation, and four with unruptured aneurysms). No complications could be attributed to the procedure. Compared with direct microscopy performed using anatomical landmarks, registration of the endoscope, and virtual image were highly accurate. CONCLUSIONS: This procedure offers many potential advantages for central nervous system and spinal endoscopy. Advances in IGE may enable its application to regions outside the central nervous system as well.

Mechanisms of endothelial survival under shear stress.

Endothelial cells (ECs) are exposed to cytotoxic reactive oxygen species and oxidation products of NO, yet they are characterized by low apoptotic rates and have an average life span of many years. EC exposure to flow has been shown to downregulate cell cycle-related genes and cause cytoskeletal rearrangement. We hypothesized that exposure to flow also causes molecular and physiological changes that induce antioxidant properties in ECs. We used cDNA array expression profiling and protein analysis to study the responses of human ECs exposed to flow in a hollow fiber apparatus or the same ECs grown under static conditions. Our results show that shear-induced synchronized expression of processes control oxidant production; these changes included upregulation of NADH-producing enzymes (Krebs cycle dehydrogenases and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) accompanied by simultaneous decrease in NADH-depleting pathways (e.g., lactate dehydrogenase [LDH]) and diminished production of lactate. Exposure to flow upregulated cytoskeletal genes. Our results suggest that, in addition to inhibition of cell cycle, exposure to flow influences ECs by controlling expression of enzymes involved in the generation of antioxidant intermediates and in adaptive control of cell shape. These changes may explain longevity and antioxidant efficiency of ECs and may provide insight in mechanisms leading to pathological conditions such as arteriosclerosis.

Peripheral markers of brain damage and blood-brain barrier dysfunction.

PURPOSE: Occurrence of brain damage is frequently associated with abnormal blood-brain barrier (BBB) function. Two brain-specific proteins, S100beta and neuron-specific enolase (NSE) are released systemically in a variety of neurological diseases, but S100beta levels sometimes rise in the absence of neuronal damage, suggesting that S100beta is a marker of BBB rather than neuronal damage. METHODS: We measured both proteins in the serum of patients undergoing iatrogenic BBB disruption with intrarterial mannitol, followed by chemotherapy. RESULTS: Serum S100beta increased significantly after mannitol infusion (p<0.05) while NSE did not. Furthermore, in a model of intracerebral hemorrhage, S100beta increases in CSF did not lead to serum changes at a time when the BBB was intact. Modeling of S100beta release from the CNS suggested that low (<0.34 ng/ml) serum levels of S100beta are consistent with BBB opening without CNS damage, while larger increases imply synthesis and release from presumable damaged glia. CONCLUSIONS: Thus, S100beta in serum is an early marker of BBB openings that may precede neuronal damage and may influence therapeutic strategies. Secondary, massive elevations in S100beta are indicators of prior brain damage and bear clinical significance as predictors of poor outcome or diagnostic means to differentiate extensive damage from minor, transient impairment.

Effects of transient loss of shear stress on blood-brain barrier endothelium: role of nitric oxide and IL-6.

Loss of blood-brain barrier (BBB) function may contribute to post-ischemic cerebral injury by yet unknown mechanisms. Ischemia is associated with anoxia, aglycemia and loss of flow (i.e. shearing forces). We tested the hypothesis that loss of shear stress alone does not acutely affect BBB function due to a protective cascade of mechanisms involving cytokines and nitric oxide (NO). To determine the relative contribution of shear stress on BBB integrity we used a dynamic in vitro BBB model based on co-culture of rat brain microvascular endothelial cells (RBMEC) and astrocytes. Trans-endothelial electrical resistance (TEER), IL-6 release and NO levels were measured from the lumenal and ablumenal compartments throughout the experiment. Flow-exposed RBMEC were challenged with 1 h of normoxic-normoglycemic flow cessation (NNFC) followed by reperfusion for 2 to 24 h. NNFC caused a progressive drop in nitric oxide production during flow cessation followed by a time-dependent increase in ablumenal IL-6 associated with a prolonged NO increase during reperfusion. The nitric oxide synthetase (NOS) inhibitor L-NAME (10 microM) abrogated all effects of NNFC, including changes in NO and cytokine production. BBB permeability did not increase during or after NNFC/reperfusion, but was increased by treatment with L-NAME or when the effects of IL-6 were blocked. Flow adapted RBMEC and astrocytes respond to NNFC/reperfusion by overproduction of IL-6, possibly secondary to increased production of NO during the reperfusion. Maintenance of BBB function during and following NNFC appears to depend on intact NO signaling and IL-6 release.

A new dynamic in vitro model for the multidimensional study of astrocyte-endothelial cell interactions at the blood-brain barrier.

Blood-brain barrier endothelial cells are characterized by the presence of tight intercellular junctions, the absence of fenestrations, and a paucity of pinocytotic vesicles. The in vitro study of the BBB has progressed rapidly over the past several years as new cell culture techniques and improved technologies to monitor BBB function became available. Studies carried out on viable in vitro models are set to accelerate the design of drugs that selectively and aggressively can target the CNS. Several systems in vitro attempt to reproduce the physical and biochemical behavior of intact BBB, but most fail to reproduce the three-dimensional nature of the in vivo barrier and do not allow concomitant exposure of endothelial cells to abluminal (glia) and lumenal (flow) influences. For this purpose, we have developed a new dynamic in vitro BBB model (NDIV-BBB) designed to allow for extensive pharmacological, morphological and physiological studies. Bovine aortic endothelial cells (BAEC) developed robust growth and differentiation when co-cultured alone. In the presence of glial cells, BAEC developed elevated Trans-Endothelial Electrical Resistance (TEER). Excision of individual capillaries proportionally decreased TEER; the remaining bundles were populated with healthy cells. Flow played an essential role in EC differentiation by decreasing cell division. In conclusion, this new dynamic model of the BBB allows for longitudinal studies of the effects of flow and co-culture in a controlled and fully recyclable environment that also permits visual inspection of the abluminal compartment and manipulation of individual capillaries.

Sustained arterial narrowing after prolonged exposure to perivascular endothelin.

OBJECTIVE: The vasoconstrictor peptide endothelin-1 (ET-1) produces narrowing of cerebral arteries and has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. Little is known, however, regarding the physiological consequences of prolonged exposure of arterial wall to ET-1. METHODS: In 30 rats, normal saline or 10(-8) mol/h of ET-1 was continuously applied for 3 or 5 days to the adventitial surface of the femoral artery in a Silastic cuff via an osmotic infusion pump. Vessels were examined for histopathological changes and luminal narrowing during ET-1 infusion (3 or 5 d) or at intervals from 2 to 9 days after infusion was stopped. RESULTS: Marked arterial constriction (30-40% arterial diameter reduction) was present during continuous ET-1 infusion for 3 or 5 days. For both 3- and 5-day ET-1 infusions, significant reduction in arterial cross sectional area persisted up to 4 days after cessation of infusion, after which normal caliber returned. In arteries with persistent luminal narrowing after cessation of ET-1 infusion, light microscopic findings revealed morphological changes in the vessel wall similar to those observed in cerebral vasospasm after subarachnoid hemorrhage, with apparent increased collagen deposition in media and adventitia. CONCLUSION: Continuous infusion of ET-1 produces reversible arterial narrowing that persists beyond the usual interval of physiological effect for this agent. Prolonged arterial constriction may produce physiological changes in arterial wall that act to maintain a narrowed lumen.

Outcome after the treatment of spinal dural arteriovenous fistulae: a contemporary single-institution series and meta-analysis.

OBJECTIVE: Spinal dural arteriovenous fistulae (Type I spinal AVMs) are the most common type of spinal vascular malformations. The optimal treatment strategy has yet to be defined, and endovascular embolization is being offered with increasing frequency. A 7-year single-institution retrospective review of outcome with surgical management of Type I spinal AVMs is presented along with a meta-analysis of existing literature. METHODS: For the institutional analysis, a retrospective review of all patients who underwent treatment at our institution for Type I spinal AVMs was performed. Between 1995 and the present (the time frame during which endovascular treatments were available), 19 consecutive patients were treated. Follow-up was performed by clinical examination or telephone interview, and functional status was measured by use of the Aminoff-Logue score. For the meta-analysis, a MEDLINE search between 1966 and the present was performed for surgical, endovascular, or combined treatment of spinal dural arteriovenous fistula. These series were included in a meta-analysis to evaluate success and failure rates, complications, and functional outcome. Specifically, embolization and microsurgery were compared. RESULTS: For the institutional analysis, 18 of 19 patients were available for long-term follow-up after surgery. There were no surgical failures, but one complication was seen. Patients demonstrated a statistically significant improvement in gait and bladder function after surgery. For the meta-analysis, 98% of those patients treated with microsurgery had their dural arteriovenous fistulae successfully obliterated after the initial treatment, compared with only 46% with embolization, as judged by radiographic or clinical follow-up. 89% percent of patients demonstrated improvement or stabilization in neurological symptoms after surgical treatment. Few complications were demonstrated with either surgery or embolization. CONCLUSION: At this point, surgery seems to be superior to embolization for the management of spinal dural arteriovenous fistula. The fistula is usually obliterated after the initial treatment, with few clinical or radiographic recurrences. The majority of patients either improve or stabilize after treatment. Few worsen, and the morbidity is minimal. It is reasonable to attempt initial embolization, especially at the time of the initial diagnostic spinal angiogram. The treating physicians and patients should be aware of the high chance of recurrence, and patients may ultimately require surgery or repeat embolization. After endovascular therapy, patients are committed to repeat angiography and probably embolization. For these reasons, it is the authors' opinion that surgery should be used as the first-line therapy for spinal dural arteriovenous fistulae.