Elevation of monocyte chemoattractant protein-1 in patients experiencing neurocognitive decline following carotid endarterectomy.

BACKGROUND: Previous studies have demonstrated that elevated pre-operative monocyte count is an independent predictor of acute neurocognitive decline following carotid endarterectomy (CEA). Monocyte chemoattractant protein-1 (MCP-1), secreted by human endothelial and monocyte-like cells, is a potent mediator of inflammation and mononuclear cell trafficking. This study examines the relationship between peri-operative serum MCP-1 elevation and post-operative neurocognitive injury following CEA. METHODS: Fifty-two patients undergoing CEA and 67 lumbar laminectomy (LL) controls were administered a battery of five neuropsychological tests pre-operatively and on post-operative day 1 (POD 1). Change in individual test scores from baseline to POD 1 were converted into Z-score and used to develop a point system quantifying the degree of neurocognitive dysfunction relative to change within the LL group. Neurocognitive injury following CEA was defined as a score greater than 2 standard deviations above mean total deficit scores of LL controls. Serum MCP-1 levels were measured pre-operatively and on POD 1 by enzyme-linked immunosorbent assay. FINDINGS: Mean percent MCP-1 elevation was higher for the 13 injured CEA patients (147.7 +/- 32.4%) in our cohort compared to 39 age- and sex-matched uninjured CEA patients (76.0 +/- 16.5%). In unconditional multivariate logistic regression analysis, percent elevation in serum MCP-1 level was associated with neurocognitive injury one day after CEA (OR = 2.19, 95% CI = 1.13-4.26, P = 0.021, for a 100% elevation from pre-operative levels). CONCLUSIONS: Peri-operative elevations in serum MCP-1 levels correlate with acute neurocognitive dysfunction following CEA. These data implicate an inflammatory mechanism in the pathogenesis of Ischaemic neurocognitive decline.

Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke.

Acute neutrophil (PMN) recruitment to postischemic cardiac or pulmonary tissue has deleterious effects in the early reperfusion period, but the mechanisms and effects of neutrophil influx in the pathogenesis of evolving stroke remain controversial. To investigate whether PMNs contribute to adverse neurologic sequelae and mortality after stroke, and to study the potential role of the leukocyte adhesion molecule intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of stroke, we used a murine model of transient focal cerebral ischemia consisting of intraluminal middle cerebral artery occlusion for 45 min followed by 22 h of reperfusion. PMN accumulation, monitored by deposition of 111In-labeled PMNs in postischemic cerebral tissue, was increased 2.5-fold in the ipsilateral (infarcted) hemisphere compared with the contralateral (noninfarcted) hemisphere (P < 0.01). Mice immunodepleted of neutrophils before surgery demonstrated a 3.0-fold reduction in infarct volumes (P < 0.001), based on triphenyltetrazolium chloride staining of serial cerebral sections, improved ipsilateral cortical cerebral blood flow (measured by laser Doppler), and reduced neurological deficit compared with controls. In wild-type mice subjected to 45 min of ischemia followed by 22 h of reperfusion, ICAM-1 mRNA was increased in the ipsilateral hemisphere, with immunohistochemistry localizing increased ICAM-1 expression on cerebral microvascular endothelium. The role of ICAM-1 expression in stroke was investigated in homozygous null ICAM-1 mice (ICAM-1 -/-) in comparison with wild-type controls (ICAM-1 +/+). ICAM-1 -/- mice demonstrated a 3.7-fold reduction in infarct volume (P < 0.005), a 35% increase in survival (P < 0.05), and reduced neurologic deficit compared with ICAM-1 +/+ controls. Cerebral blood flow to the infarcted hemisphere was 3.1-fold greater in ICAM-1 -/- mice compared with ICAM-1 +/+ controls (P < 0.01), suggesting an important role for ICAM-1 in the genesis of postischemic cerebral no-reflow. Because PMN-depleted and ICAM-1-deficient mice are relatively resistant to cerebral ischemia-reperfusion injury, these studies suggest an important role for ICAM-1-mediated PMN adhesion in the pathophysiology of evolving stroke.

Three psychological treatments for bulimia nervosa. A comparative trial.

The specificity and magnitude of the effects of cognitive behavior therapy in the treatment of bulimia nervosa were evaluated. Seventy-five patients who met strict diagnostic criteria were treated with either cognitive behavior therapy, a simplified behavioral version of this treatment, or interpersonal psychotherapy. Assessment was by interview and self-report questionnaire, and many aspects of functioning were evaluated. All three treatments resulted in an improvement in the measures of the psychopathology. Cognitive behavior therapy was more effective than interpersonal psychotherapy in modifying the disturbed attitudes to shape and weight, extreme attempts to diet, and self-induced vomiting. Cognitive behavior therapy was more effective than behavior therapy in modifying the disturbed attitudes to shape and weight and extreme dieting, but it was equivalent in other respects. The findings suggest that cognitive behavior therapy, when applied to patients with bulimia nervosa, operates through mechanisms specific to this treatment and is more effective than both interpersonal psychotherapy and a simplified behavioral version of cognitive behavior therapy.

Regional cerebral metabolic activity in the rat following experimental subarachnoid hemorrhage.

A new experimental model was employed to investigate alterations of cerebral metabolic activity in rats subjected to extensive subarachnoid hemorrhage (SAH). The hemorrhages were produced in anesthetized animals by inserting 0.37 ml fresh autologous arterial blood into the subarachnoid space. Rats that underwent sham operations received subarachnoid injections of mock CSF to study the effects of sudden raised intracranial pressure (ICP). Forty-eight hours after subarachnoid injection, the unanesthetized rats were given intravenous injections of [14C]2-deoxyglucose. Experiments were terminated 45 min later by decapitation, and the brains were removed and frozen. Regional brain metabolic activity was studied employing quantitative autoradiography. In comparison with control animals, cerebral metabolic activity was diffusely decreased following SAH. Statistically significant decreases in metabolic activity of less than 34% were observed in 17 of 30 brain regions studied. The largest percentage reductions were in regions displaying the highest basal metabolic rates. Subarachnoid injections of mock CSF also produced depression of cerebral metabolic activity, but quantitatively these changes were not as pronounced as in the hemorrhage group. These studies demonstrate regional changes in brain function following SAH. The data relate these changes to both the presence of blood in the subarachnoid space and sudden raised ICP.

Current strategies for the management of aneurysmal subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm represents a major health issue. Although most people who experience an aneurysmal SAH survive to be admitted to a hospital, less than one third of these patients ever return to their premorbid status. Clearly, morbidity of this magnitude demands reevaluation of the clinical approach to this problem. This article reviews the natural history of aneurysmal SAH, and examines the current therapeutic strategies that have been suggested to improve the outcome. Careful evaluation of the existing data suggests that early aneurysm surgery and aggressive postoperative volume expansion therapy constitute the best presently available approach to patients with ruptured intracranial aneurysms.

Prophylactic volume expansion therapy for the prevention of delayed cerebral ischemia after early aneurysm surgery. Results of a preliminary trial.

From June 1986 to June 1987, 47 consecutive patients with ruptured intracranial aneurysms were treated with immediate aneurysm surgery and prophylactic volume expansion therapy for ten to 14 days after subarachnoid hemorrhage (SAH). Twenty-four patients were admitted within three days of SAH. Twenty-three of these patients had an excellent result, and one patient died. There were no cases of delayed cerebral infarction. In 18 of 23 patients admitted more than three days after SAH, there was an excellent result. The other five patients had permanent morbidity related to the original SAH. These preliminary data suggest that immediate aneurysm surgery and aggressive postoperative prophylactic volume expansion in all patients can substantially reduce rebleeding and delayed cerebral ischemia, potential causes of morbidity, after aneurysmal subarachnoid hemorrhage. A more extensive prospective trial of this approach will be required to test this hypothesis.

The clinical spectrum of unruptured intracranial aneurysms.

OBJECTIVE: A retrospective study was performed to delineate the clinical characteristics of symptomatic unruptured aneurysms. DESIGN: Patient histories, operative reports, and angiograms in 111 patients with 132 unruptured aneurysms were reviewed. SETTING: Tertiary care university hospital. PATIENTS: One hundred eleven patients with 132 unruptured intracranial aneurysms were studied. There were 85 women and 26 men, with a mean age of 51.2 years (age range, 11 to 77 years). Many patients were referred by community neurologists and neurosurgeons for further evaluation and neurosurgical management. RESULTS: Fifty-four symptomatic patients were identified. Group 1 (n = 19; mean aneurysm diameter, 2.1 cm) had acute symptoms: ischemia (n = 7), headache (n = 7), seizure (n = 3), and cranial neuropathy (n = 2). Group 2 (n = 35; mean aneurysm diameter, 2.2 cm) had chronic symptoms attributed to mass effect: headache (n = 18), visual loss (n = 10), pyramidal tract dysfunction (n = 4), and facial pain (n = 3). Group 3 (n = 57; mean aneurysm diameter, 1.1 cm) had asymptomatic aneurysms. CONCLUSIONS: Acute severe headache, comparable to subarachnoid hemorrhage headache, but without nuchal rigidity, was associated with the following mechanisms: aneurysm thrombosis, localized meningeal inflammation, and unexplained. Unruptured aneurysms may be misdiagnosed as optic neuritis or migraine, or serve as a nidus for cerebral thromboembolic events. Internal carotid artery and posterior circulation aneurysms were more likely to cause focal symptoms from mass effect than were anterior cerebral artery and middle cerebral artery aneurysms. Weeks to years may elapse before their diagnosis. The absence of subarachnoid blood does not exclude an aneurysm as a cause for acute or chronic neurologic symptoms.

Developmental deficits in adult patients with arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are congenital masses of arteries and veins that appear to undergo an unclear "maturation" for many years. Using structured interviews, we compared developmental history of adult patients with AVM with a comparison group of patients with cerebral tumor or aneurysm. OBJECTIVE: To determine whether a remote history of developmental abnormality in adult patients with AVM might be an early marker of cerebral status. DESIGN: Adult patients with AVM and a comparison group of patients with cerebral aneurysm or low-grade tumor participated in a survey. SETTING: Urban medical school-based tertiary care center. PATIENTS: Forty-four randomly selected patients with AVM from the Columbia-Presbyterian AVM Database. There were 32 comparison patients:15 randomly chosen patients from the institution's Cerebral Aneurysm Database and all 17 patients who underwent a biopsy from 1990 to 1995 with a diagnosis of low-grade tumor and who could be contacted. MAIN OUTCOME MEASURES: A brief, structured interview adapted from the Centers for Disease Control and Prevention for its 1994 study of the prevalence of learning disabilities in American children. We defined the positive occurrence of a condition as an affirmative answer to the question, " Did have (condition) during his/her school-age years?" Each patient was also asked if there had been any problems in the following skill areas: reading, writing, listening, speaking, attention, impulsivity, organization, mathematics, or drawing. The AVM size was calculated on the angiographic film by measuring its longest diameter in any dimension. RESULTS: Patients with AVM were significantly more likely to report a positive occurrence to any survey question (P<.05). Two thirds of all patients with AVM (66%) reported at least 1 skill difficulty during their school years, significantly more than the comparison group (P<.001). Neither the maximum AVM diameter nor the occurrence of hemorrhage as an adult differed between patients with AVM with and without early skill difficulty. CONCLUSIONS: Patients with AVM are more likely to report a developmental learning disorder than patients with tumor or aneurysm despite the absence of other neurologic symptoms of diseases not diagnosed for another 20 years. These data support the notion that disorders of behavioral and intellectual function are sensitive markers of early cerebral status.

Cardiac injury associated with neurogenic pulmonary edema following subarachnoid hemorrhage.

OBJECTIVE: To describe the clinical features of cardiac injury associated with neurogenic pulmonary edema (NPE) in patients with acute subarachnoid hemorrhage (SAH). BACKGROUND: NPE is generally viewed as a form of noncardiogenic pulmonary edema related to massive sympathetic discharge. METHODS: Case series. RESULTS: We found echocardiographic evidence of reduced global and segmental left ventricular (LV) systolic function in five women (mean age, 44; range, 36 to 57) with SAH and NPE. None had a history of heart disease. Four patients were Hunt/Hess grade III and one was grade IV. All five patients experienced (1) sudden hypotension (systolic blood pressure < 110 mm Hg) following initially elevated blood pressures, (2) transient lactic acidosis, (3) borderline (2 to 4%) creatine kinase MB elevations, and (4) varied acute (< 24 hours) electrocardiographic changes followed by widespread and persistent T wave inversions. Pulmonary artery wedge pressures were normal in 3/3 patients at the onset of pulmonary edema but reached high levels (> 16 mm Hg) in all four patients studied beyond this period. Reduced cardiac output and LV stroke volume were identified in three patients; the fourth patient demonstrated normal values on high doses of intravenous pressors. Cerebral infarction due to vasospasm occurred in four patients and resulted in two deaths. Follow-up echocardiography performed 2 to 6 weeks after SAH revealed normal LV function in all three survivors. CONCLUSIONS: A reversible form of cardiac injury may occur in patients with NPE following SAH and is associated with characteristic clinical findings. Impaired LV hemodynamic performance in this setting may contribute to cardiovascular instability, pulmonary edema formation, and complications from cerebral ischemia.

Sleep stability with home sleep recording and automatic sleep stage analysis.

Three home sleep recordings were conducted in 12 normal subjects using the Oxford Medilog 9000 system with automatic sleep stage analysis (SS90III). Each night was separated by 1 week. No significant differences were noted for any sleep parameter, with the mean intraindividual variation less than 20% for most parameters. This indicates that sleep patterns are stable over time.

Evaluation of first night effect using ambulatory monitoring and automatic sleep stage analysis.

Home sleep recordings were conducted over three consecutive nights in 12 normal subjects using the Oxford Medilog 9000 system and automatic sleep stage analysis. The equipment was well tolerated and adequate sleep recordings were obtained on each test evening. The results showed that there was no significant differences over the three nights for any of the sleep parameters measured.

Lithium increases slow wave sleep: possible mediation by brain 5-HT2 receptors?

The effect of lithium on slow wave sleep (SWS) was studied in ten normal male volunteers using home based cassette sleep recording and automatic sleep stage analysis. Lithium increased SWS, an effect consistent with a reduction in brain 5-HT2 receptor function.

Dose-related effects of selective 5-HT2 receptor antagonists on slow wave sleep in humans.

The effects of the selective 5-HT2 receptor antagonists, ritanserin (1, 5 and 10 mg) and ICI 169.369 (50 and 100 mg), were studied on the sleep EEG of healthy volunteers using home-based Medilog 9000 cassette monitoring. Ritanserin (5 and 10 mg) produced a significant increase in slow wave sleep (SWS) while ICI 169,369 also increased SWS but only at a dose of 100 mg. These findings are consistent with the proposal that selective 5-HT2 receptor blockade increases SWS in humans; however, the data cannot exclude involvement of the closely related 5-HT1c receptor in this effect.

Reduction of postoperative pain and narcotic use by transcutaneous electrical nerve stimulation.

Transcutaneous electrical nerve stimulation (TENS) was evaluated as a postoperative analgesic. Patients undergoing lumbar spine operations, hip surgery, and gynecological laparotomies were studied. Sterile electrodes, placed near the incision immediately after operation, were connected to a continuously operating stimulator for 48 hours after operation. Results from 46 experimental patients demonstrated that TENS could reduce the demand for postoperative narcotics in a group of patients who had not used narcotic analgesics before operation. No significant benefit was observed for patients who had used narcotics prior to operation.

The effects of norepinephrine depletion on cerebral blood flow in the rat.

Cerebral blood flow (CBF) was measured by [14C]butanol indicator fractionation in 10 rats given intraventricular injections of 6-hydroxydopamine (6-OHDA) compared to 8 saline-injected controls. Rats treated with 6-OHDA displayed an 83% reduction in cortical norepinephrine (NE) levels. CBF was significantly increased in 6-OHDA-treated rats compared to controls (average whole brain blood flow of 126.0 +/- 8.3 and 97.1 +/- 10.6 ml.min-1.10(-2)g-1 respectively, P less than 0.05). These studies suggest that noradrenergic innervation of the brain and cerebral microvasculature exerts a moderating effect on resting CBF.

Increased norepinephrine synthesis in the cerebral hemispheres of rats following subarachnoid hemorrhage.

Norepinephrine (NE) was assayed in rat brains 72 h after the creation of an experimental subarachnoid hemorrhage (SAH). NE in the cerebral hemispheres was found to increase by 64% when compared to controls. NE in the brainstem and cerebellum was unchanged. The kinetics of hemispheric NE metabolism were then studied in control and SAH rats. SAH caused a 3-fold increase in NE synthesis and a 44% reduction in turnover time when compared to controls. These results may reflect increased activity of central noradrenergic neuronal pathways in SAH.

Defective cerebrovascular autoregulation in regions proximal to arteriovenous malformations of the brain: a case report and topic review.

We report the case of a patient with a large left subfrontal arteriovenous malformation (AVM) that was supplied by the right internal carotid artery. The anomalous blood supply developed because of complete occlusion of the left internal carotid artery. When the AVM was removed, the patient experienced a hemorrhage into the right basal ganglia. The possibility that this hemorrhage was related to a defect of autoregulation in blood vessels that lie proximal to a large AVM is discussed. Even though this is a unique case, the pathophysiological events that are documented are relevant to the preoperative preparation and surgical management of all patients with AVMs.

New aneurysm clip appliers for "key-hole" neurosurgery.

A new set of aneurysm clip appliers has been developed to overcome many of the obstacles to safe clipping of complex intracranial aneurysms. The applier set consists of six units, each one delivering clips at a different specified angle to the applier shaft. These appliers have been independently tested on over 250 aneurysm operations and found to be of great utility.

Perimesencephalic nonaneurysmal subarachnoid hemorrhage: review of the literature.

OBJECTIVE: A critical review of the literature on the incidence, presentation, diagnosis, and prognosis of perimesencephalic nonaneurysmal subarachnoid hemorrhage. METHODS: Review of the relevant literature. CONCLUSION: The importance of early computed tomography (< 3 d), anatomy of the perimesencephalic and neighboring cisterns, and adequate four-vessel angiography are discussed. Treatment strategies, including the avoidance of repeated angiographic studies and surgical exploration, are presented.

Surgical management of arteriovenous malformations that follow the tentorial ring.

In a series of 200 intracranial arteriovenous malformations (AVMs) treated surgically, 33 malformations were situated very close to the tentorial incisura. All but one of these AVMs were totally removed. Four operative approaches were utilized in this group of patients: an interhemispheric approach for lesions of the medial hemispheres, splenium of the corpus callosum, and posterior 3rd ventricle; a subtemporal approach to the inferior and medial temporal lobe; a supracerebellar-infratentorial approach to anterodorsal cerebellum and quadrigeminal regions; and a subtemporal transtentorial exposure to the dorsolateral mesencephalon. There were no surgical deaths. Three patients had unsatisfactory outcomes. Our experience with this series indicates that deep cerebral AVMs in the region of the tentorial incisura may be safely removed if there is proper selection of operative approach and attention to surgical technique.