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Biomedical subjects

Marc R Mayberg

Publications and source records attributed to Marc R Mayberg.

At least 19 recordsLinked to original sources
PubMed2006

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.

Adenoma↗
PubMed2006

Loss of shear stress induces leukocyte-mediated cytokine release and blood-brain barrier failure in dynamic in vitro blood-brain barrier model.

Brain ischemia is associated with an acute release of pro-inflammatory cytokines, notably TNF-alpha and IL-6 and failure of the blood-brain barrier. Shear stress, hypoxia-hypoglycemia, and blood leukocytes play a significant role in blood-brain barrier failure during transient or permanent ischemia. However, these mechanisms have not been studied as independent variables for in vitro ischemia. The present study, using a dynamic in vitro blood-brain barrier model, showed that flow cessation/reperfusion under normoxia-normoglycemia or hypoxia-hypoglycemia without blood leukocytes in the luminal perfusate had a modest, transient effect on cytokine release and blood-brain barrier permeability. By contrast, exposure to normoxic-normoglycemic flow cessation/reperfusion with blood leukocytes in the luminal perfusate led to a significant increase in TNF-alpha and IL-6, accompanied by biphasic blood-brain barrier opening. Enhanced permeability was partially prevented with an anti-TNF-alpha antibody. In leukocyte-free cartridges, the same levels of IL-6 had no effect, while TNF-alpha caused a moderate increase in blood-brain barrier permeability, suggesting that blood leukocytes are the prerequisite for cytokine release and blood-brain barrier failure during reduction or cessation of flow. These cells induce release of TNF-alpha early after ischemia/reperfusion; TNF-alpha triggers release of IL-6, since blockade of TNF-alpha prevents IL-6 release, whereas blockade of IL-6 induces TNF-alpha release. Pre-treatment of blood leukocytes with the cyclooxygenase (COX) inhibitor, ibuprofen, inhibited cytokine release and completely preserved blood-brain barrier permeability during the reperfusion period. In conclusion, loss of flow (flow cessation/reperfusion) independent of hypoxia-hypoglycemia plays a significant role in blood-brain barrier failure by stimulating leukocyte-mediated inflammatory mechanisms.

Animals↗
PubMed2006

Cystic dilation of the conus ventriculus terminalis presenting as an acute cauda equina syndrome relieved by decompression and cyst drainage: case report.

OBJECTIVE AND IMPORTANCE: The ventriculus terminalis of the conus, or "fifth ventricle" refers to the ependymal-lined space in the middle of the conus that is present in childhood and whose persistence into adulthood is rare. A number of cases of cystic dilatation of the ventriculus terminalis have been described in adulthood. Patients tend to present with either pain alone or gradually progressive conus or cauda equina syndromes with varying degrees of recovery after cyst drainage. Presentation with an acute cauda equina syndrome and its successful surgical management has not been previously reported. CLINICAL PRESENTATION: A 57-year-old woman experienced back pain and bilateral sciatica ascribed to diabetic neuropathy for 2 years. Over a 24-hour period she developed bilateral lower extremity weakness, saddle anesthesia, and bowel and bladder incontinence. Lumbosacral magnetic resonance imaging demonstrated a large cystic dilatation of the ventriculus terminalis. INTERVENTION: She was taken for emergency surgical decompression and cyst drainage. Immediately after surgery, she experienced significant increase in lower extremity strength and has since regained continence. CONCLUSION: Cystic dilation of the ventriculus terminalis should be part of the differential diagnosis for a cauda equina syndrome; surgical decompression with simple cyst drainage can result in excellent clinical results.

Decompression, Surgical↗
PubMed2005

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.

Bone Diseases↗
PubMed2005

Awake craniotomy for microsurgical obliteration of mycotic aneurysms: technical report of three cases.

OBJECTIVE AND IMPORTANCE: Infectious (mycotic) aneurysms that do not resolve with medical treatment require surgical obliteration, usually requiring sacrifice of the parent artery. In addition, patients with mycotic aneurysms frequently need subsequent cardiac valve repair, which often necessitates anticoagulation. Three cases of awake craniotomy for microsurgical clipping of mycotic aneurysms are presented. Awake minimally invasive craniotomy using frameless stereotactic guidance on the basis of computed tomographic angiography enables temporary occlusion of the parent artery with neurological assessment before obliteration of the aneurysm. CLINICAL PRESENTATION: A 56-year-old woman presented with progressively worsening mitral valve disease and a history of subacute bacterial endocarditis and subarachnoid hemorrhage 30 years previously. A cerebral angiogram revealed a 4-mm left middle cerebral artery (MCA) angular branch aneurysm, which required obliteration before mitral valve replacement. The second patient, a 64-year-old woman with a history of rheumatic fever, had an 8-mm right distal MCA aneurysm diagnosed in the setting of pulmonary abscess and worsening cardiac function as a result of mitral valve disease. The third patient, a 57-year-old man with a history of fevers, night sweats, and progressive mitral valve disease, had an enlarging left MCA angular branch aneurysm despite the administration of antibiotics. Because of their location on distal MCA branches, none of the aneurysms were amenable to preoperative test balloon occlusion. INTERVENTION: After undergoing stereotactic computed tomographic angiography with fiducial markers, the patients underwent a minimally invasive awake craniotomy with frameless stereotactic navigation. In all cases, the results of the neurological examination were unchanged during temporary parent artery occlusion and the aneurysms were successfully obliterated. CONCLUSION: Awake minimally invasive craniotomy for an infectious aneurysm located in eloquent brain enables awake testing before permanent clipping or vessel sacrifice. Combining frameless stereotactic navigation with computed tomographic angiography allowed us to perform the operation quickly through a small craniotomy with minimal exploration.

Aneurysm, Infected↗
PubMed2005

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.

Angioplasty↗
PubMed2004

Pituicytoma.

Pituicytoma is a rare, low-grade neoplasm that originates in the neurohypophysis of the pituitary gland. We report the clinicopathologic features of a pituicytoma arising in a 52-year-old man who presented with a mass and panhypopituitarism, clinically suggestive of a pituitary adenoma. The tumor was marked by a proliferation of elongated cells arranged in bundles and interlacing fascicles. The tumor demonstrated positive staining with S-100 protein and glial fibrillary acid protein antibodies. The tumor did not stain with antibodies to cytokeratin, synaptophysin, chromogranin, anterior pituitary hormones, or p53. An MIB-1 labeling index of 1.1% was observed. The tumor was subtotally resected and recurred 11 months after the initial surgery. The literature on this rare tumor will be reviewed and differential diagnosis discussed.

Biomarkers, Tumor↗
PubMed2004

The cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in vascular homeostatis and pathophysiology.

It is widely accepted that vascular mechanisms are involved in the genesis of many neurological disorders. In particular, blood-brain barrier (BBB) dysfunction has been related to the severity of Alzheimer's disease, encephalopathy due to meningitis, multiple sclerosis, HIV-associated encephalopathy, epilepsy, gliomas and metastatic brain tumors. The BBB may constitute an important therapeutic target to protect neurons after CNS diseases. Both in vivo and in vitro, the functional phenotype of vascular endothelium is dynamically responsive to circulating cytokines, growth factors and puslatile blood flow (shear stress). Shear stress can play a critical role in vascular homeostasis and pathophysiology; it is a major regulator of remodeling in developed blood vessels and in blood vessels affected by atherosclerotic lesions. The physiological fluid mechanic stimulus, shear stress, could be considered to be an important 'differentiative' stimulus capable of modulating endothelial phenotype in vivo. Endothelial cells undergo cell cycle arrest after exposure to physiological levels of shear stress. As for mature endothelial cells, in which flow mediated shear stress may play a role in the induction, progression and/or prevention of atherosclerosis by changing their function, stress may play a role in endothelial cell differentiation from hemopoietic stem cells and/or from embryonic stem cells. Stem cells may be used to repair vascular damage, including loss of EC, due to a variety of diseases (e.g. myocardial neovascularization by adult bone marrow derived angioblasts). In the brain, it was proposed that neuron-producing stem cells may be used to treat Alzheimer's disease, paralysis, etc. Surprisingly, very few investigators are exploring the use of endothelial precursors to revert or prevent cerebrovascular disease. This review summarizes the most recent data related to cerebral vasculature as a therapeutic target for neurological disorders and the role of shear stress in blood-brain barrier homeostasis and pathophysiology.

Animals↗
PubMed2004

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.

Adult↗
PubMed2004

W. James Gardner: pioneer neurosurgeon and inventor.

W. James Gardner, a skillful neurosurgeon and inventor, is best remembered for his cervical tongs and hydrodynamic theory of syringomyelia. A pioneer of modern neurosurgery, Gardner trained under Charles Frazier in Philadelphia, and in 1929 he moved to Ohio where he became chief of neurosurgery at the Cleveland Clinic, a position he was to hold for the next 33 years. A large surgical practice made it imperative for Gardner to develop surgical methods that were quick, effective, and advantageous for patient and surgeon. He was an early proponent of the sitting position for patients undergoing cranial surgery, which led to the development of a neurosurgical chair with a head fixation device. To reduce the risks of hypotension and air embolism when the patient is in the sitting position, Gardner invented the clinical G suit. He was the first to advocate and use induced arterial hypotension for intracranial surgery and the first neurosurgeon in the US to publish his experiences performing lumbar discography. He converted an operating table so that he could induce hypothermia during aneurysm surgery and then applied pneumatic cuffs to occlude the major arterial supply to the brain. His pioneering work has been documented in many other areas such as hemifacial spasm and trigeminal neuralgia, for which he performed the first vascular decompression, in cervical sympathectomy for treatment of various ailments, and in the use of intrathecally delivered steroid drugs for sciatica. During his career, he authored 256 publications and one book on the dysraphic states. Many of his contributions to the discipline of neurosurgery are now taken for granted.

Craniotomy↗
PubMed2004

Risk of persistent cranial nerve injury after carotid endarterectomy.

OBJECT: Cranial nerve injuries, particularly motor nerve injuries, following carotid endarterectomy (CEA) can be disabling and therefore patients should be given reliable information about the risks of sustaining such injuries. The reported frequency of cranial nerve injury in the published literature ranges from 3 to 23%, and there have been few series in which patients were routinely examined before and after surgery by a neurologist. METHODS: The authors investigated the risk of cranial nerve injuries in patients who underwent CEA in the European Carotid Surgery Trial (ECST), the largest series of patients undergoing CEA in which neurological assessment was performed before and after surgery. Cranial nerve injury was assessed and recorded in every patient and persisting deficits were identified on follow-up examination at 4 months and 1 year after randomization. Risk factors for cranial nerve injury were examined by performing univariate and multivariate analyses. There were 88 motor cranial nerve injuries among the 1739 patients undergoing CEA (5.1% of patients; 95% confidence interval [CI] 4.1-6.2). In 23 patients, the deficit had resolved by hospital discharge, leaving 3.7% of patients (95% CI 2.9-4.7) with a residual cranial nerve injury: 27 hypoglossal, 17 marginal mandibular, 17 recurrent laryngeal, one accessory nerve, and three Homer syndrome. In only nine patients (0.5%; 95% CI 0.24-0.98) the deficit was still present at the 4-month follow-up examination; however, none of the persisting deficits resolved during the subsequent follow up. Only duration of operation longer than 2 hours was independently associated with an increased risk of cranial nerve injury (hazard ratio 1.56, p < 0.0001). CONCLUSIONS: The risk of motor cranial nerve injury persisting beyond hospital discharge after CEA is approximately 4%. The vast majority of neurological deficits resolve over the next few months, however, and permanent deficits are rare. Nevertheless, the risk of cranial nerve injury should be communicated to patients before they undergo surgery.

Aged↗
PubMed2003

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.

Animals↗
PubMed2003

Serum S100beta: a noninvasive marker of blood-brain barrier function and brain lesions.

BACKGROUND: S100beta protein is expressed constitutively by brain astrocytes. Elevated S100beta levels in cerebrospinal fluid and serum reported after head trauma, subarachnoid hemorrhage, and stroke were correlated with the extent of brain damage. Because elevated serum S100beta also was shown to indicate blood-brain barrier (BBB) dysfunction in the absence of apparent brain injury, it remains unclear whether elevation of serum levels of S100beta reflect BBB dysfunction, parenchymal damage, or both. METHODS: The authors conducted a prospective study of serum S100beta levels in six patients who underwent hyperosmotic BBB disruption (BBBD) with intraarterial chemotherapy for primary central nervous system lymphoma. In addition, 53 serum S100beta samples were measured in 51 patients who had a variety of primary or metastatic brain lesions at the time of neuroimaging. RESULTS: S100beta was correlated directly with the degree of clinical and radiologic signs of BBBD in patients who were enrolled in the hyperosmotic study. In patients with neoplastic brain lesions, gadolinium enhancement on a magnetic resonance image was correlated with elevated S100beta levels (n = 45 patients; 0.16 +/- 0.1 microg/L; mean +/- standard error of the mean) versus nonenhancing scans (n = 8 patients; 0.069 +/- 0.04 microg/L). Primary brain tumors (n = 8 patients; 0.12 +/- 0.08) or central nervous system metastases also presented with elevated serum S100beta levels (n = 27 patients; 0.14 +/- 0.34). Tumor volume was correlated with serum S100beta levels only in patients with vestibular schwannoma (n = 6 patients; 0.13 +/- 0.10 microg/L) but not in patients with other brain lesions. CONCLUSIONS: S100beta was correlated directly with the extent and temporal sequence of hyperosmotic BBBD, further suggesting that S100beta is a marker of BBB function. Elevated S100beta levels may indicate the presence of radiologically detectable BBB leakage. Larger prospective studies may better determine the true specificity of S100beta as a marker for BBB function and as an early detection or follow-up marker of brain tumors.

Adult↗
PubMed2003

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.

Biomarkers↗