Effect of cerebral ischaemia on the cerebrovascular and cardiovascular response to haemorrhage

Reports studying the combination of low blood pressure and cerebral ischaemia are few, and it remains to be determined how cerebral circulatory insufficiency modifies the cerebral perfusion and the central haemodynamic response to blood loss. We hypothesised that occlusion of arteries to the brain modifies the cerebrovascular and cardiovascular responses to blood loss. Continuous measurements of the cerebral microcirculation with laser Doppler microprobes in the cerebral cortex were performed in anaesthetised pigs during cerebral ischaemia and haemorrhagic hypotension. The response to rapid bleeding (25% of the blood volume) was recorded during normal conditions and during cerebral ischaemia induced by bilateral occlusion of the common carotid arteries. During normal conditions haemorrhage caused insignificant decreases in cerebral microcirculation. Haemorrhage during bilateral carotid artery occlusion, however, caused significantly greater changes in cerebral microcirculation and a greater posthaemorrhagic increase in cerebrovascular resistance shortly after the blood loss. Haemorrhage during bilateral carotid artery occlusion also caused greater reductions in cardiac output and arterial pressure than similar blood loss caused during normal conditions. This study showed a disproportionate decrease in cerebral blood flow with haemorrhage during bilateral carotid occlusion, caused by an immediate increase in cerebrovascular resistance. The results suggest that even a moderate blood loss in patients with impaired cerebral circulation could be dangerous, because normal compensatory mechanisms to haemorrhage are impaired.     

Amaurosis fugax and carotid artery disease: indications for angiography

A prospective study of 80 patients presenting with amaurosis fugax was performed in an attempt to relate clinical features to angiographic findings in the internal carotid artery. Carotid bruit, transient cerebral ischaemic attacks, hypertension, and claudication were associated with a high prevalence of angiographic abnormality. Every patient who showed all these features had an operable lesion, as did 88% of those who had three features. In patients over 50 years of age carotid stenosis and atheromatous ulceration were occasionally found in the absence of bruit and transient cerebral ischaemia, but only one patient aged under 50 had an operable lesion and no associated features. Clinical features were therefore valuable in predicting the outcome of angiography, but it seems prudent to restrict angiography to patients aged over 50, who are most likely to benefit from surgery on the carotid artery.     

Ischaemic stroke from cerebral embolism in cephalic fibromuscular dysplasia

Fibromuscular dysplasia (FMD) of the internal carotid arteries and its relationship with focal cerebral ischaemia is unproven. This vasculopathy is often detected incidentally during a cerebral angiogram for non-ischaemic cerebral events. FMD affects the proximal one-third of the internal carotid artery in almost all cases and is bilateral in 60% to 85%, with middle-aged women affected in 85% of the cases. Ischaemic stroke has been postulated to result from severe stenosis or thrombotic occlusion at the FMD site. Cerebral embolism from FMD has rarely been reported. We report 3 young patients with acute ischaemic stroke who had FMD on cerebral angiography. They presented with a focal hemispheric stroke where the probable pathophysiology is embolism to the distal internal carotid artery from thrombus formed at the proximal FMD site. The patients were all males, with unilateral proximal internal carotid artery FMD lesions and occlusion of the internal carotid artery distally on the same side. All were extensively investigated and no other causes for stroke were found.     

Dissociative experiences and eating disorders in a female college sample

OBJECTIVES: Perioperative ischaemic stroke is the leading cause of morbidity and mortality associated with carotid endarterectomy (CEA). The aim was to test the hypotheses that the detection of microembolic ultrasonic signals (MES) with transcranial Doppler ultrasound (TCD) during and after the operation may be of value in identifying patients at increased perioperative stroke risk. DESIGN: Open prospective case series. PATIENTS AND METHODS: Eighty-one consecutive patients undergoing CEA with TCD monitoring. Preoperative, intraoperative and interval postoperative TCD monitoring of the middle cerebral artery (MCA) ipsilateral to the operated carotid artery. On-line pre- and intraoperative MES counting and blinded off-line analysis of postoperative MES counts. End-points were any focal neurological deficit and death at 30 days postoperatively. RESULTS: MES were detected in 94% of patients intraoperatively and 71% of cases during the first postoperative hour. MES counts ranged from 0 to 25 per operative phase (range of median counts 0-8) and from 0 to 212 per hour postoperatively (range of median counts 0-4). Eight cases (10%) developed postoperative MES counts greater than 50/h. Five of these eight cases evolved ischaemic neurological deficits in the territory of the insonated MCA, indicating a strong association between frequent postoperative microembolism and the development of early cerebral ischaemia (chi 2 = 34.2, p < 0.0001). Intraoperative MES were not associated with clinical outcome measures. CONCLUSIONS: MES counts of greater than 50/h in the early postoperative phase of carotid endarterectomy are predictive of the development of ipsilateral focal cerebral ischaemia.     

Evaluation of cerebral blood flow and hemodynamic reserve in symptomatic moyamoya disease using stable Xenon-CT blood flow

Moyamoya disease is a vascular abnormality seen in children and adults characterized by progressive narrowing of the internal carotid, middle, anterior, and posterior cerebral arteries and the development of leptomeningeal and proximal internal carotid artery collaterals, which appear diaphanous on angiogram. Although adults tend to present with subarachnoid hemorrhage and children with ischemic events, the clinical sequelae in these two populations overlap. Expanding upon work done at this institution using stable xenon computer tomographic blood flow determinations with acetazolamide and carbon dioxide challenge to predict which population of patients with severe carotid disease and hemodynamic compromise would benefit from surgical intervention, we used similar rationale to determine which patients with moyamoya disease would likely benefit from revascularization. Data and outcome concerning four such patients make up the body of this report.     

Cerebral blood flow response pattern during balloon test occlusion of the internal carotid artery

PURPOSE: To evaluate the risk of temporary or permanent internal carotid artery occlusion. METHODS: In 156 patients intraarterial balloon test occlusion in combination with a stable xenon-enhanced CT cerebral blood flow study was performed before radiologic or surgical treatment. All 156 patients passed the clinical balloon test occlusion and underwent a xenon study in combination with a second balloon test. Quantitative flow data were analyzed for absolute changes as well as changes in symmetry. RESULTS: Fourteen patients exhibited reduced flow values between 20 and 30 mL/100 g per minute, an absolute decrease in flow, and significant asymmetry in the middle cerebral artery territory during balloon test occlusion. These patients would be considered at high risk for cerebral infarction if internal carotid artery occlusion were to be performed. With one exception they belonged to a group (class I) of 61 patients who showed bilateral or ipsilateral flow decrease and significant asymmetry with lower flow on the side of occlusion. The other 95 patients, who showed a variety of cerebral blood flow response patterns including ipsilateral or bilateral flow increase, were at moderate (class II) or low (class III) stroke risk. In contrast to these findings, exclusively qualitative flow analysis failed to identify the patients at high risk: a threshold with an asymmetry index of 10% revealed only 16% specificity whereas an asymmetry index of 45% showed only 61% sensitivity for detection of low flow areas (< 30 mL/100 g per minute). CONCLUSION: For achieving a minimal hemodynamic related-stroke rate associated with permanent clinical internal carotid artery occlusion we suggest integration of a thorough analysis of quantitative cerebral blood flow data before and during balloon test occlusion.     

Gut intraepithelial T lymphocytes

One of the most prominent features of the early phase of cerebral ischaemia is the immunohistochemical collapse of cytoskeletal proteins. Among these proteins, microtubule-associated protein 2 (MtP2) has been shown to be vulnerable to ischaemic injuries. In order to identify a suitable volatile anaesthetic on the basis of cytoskeletal protein breakdown during cerebral ischaemia, we have compared the effects of isoflurane and halothane on MtP2 degradation in rats. Under equipotent isoflurane or halothane anaesthesia, forebrain ischaemia was induced by occlusion of the bilateral common carotid artery, combined with a decrease in mean arterial pressure to 50 mm Hg. After 20 min of ischaemia, the frontoparietal cortex, brainstem, hippocampus and cerebellum were removed separately and homogenized. MtP2 from each region was measured using an enzyme-linked immunosorbent assay. MtP2 degradation in the frontoparietal cortex and hippocampus was significantly (P < 0.05 and P < 0.01) less with isoflurane anaesthesia (75.6 (SD 10.7)% and 72.3 (12.8)%, respectively) than with halothane (65.0 (13.1)% and 54.7 (13.9)%, respectively).     

Reversible dementia due to dural arteriovenous fistula: a simple surgical option

Dural AVMs can produce a wide variety of symptoms related to raised intracranial pressure, venous congestion, and cerebral ischaemia. We present a unique case of reversible dementia, due to venous hypertension. The cerebral ischaemia was caused by extensive bilateral arteriovenous malformations of the external carotid system, which drained into the superior sagittal and transverse sinuses and resulted in venous hypertension. Although partial occlusion by endovascular embolization and ligation procedures had some effect, only 'scalping and silastic implantation' gave satisfactory amelioration of symptoms.     

Clinical and angiographic predictors of stroke and death from carotid endarterectomy: systematic review

OBJECTIVE: To identify risk factors for operative stroke and death from carotid endarterectomy. DESIGN: Systematic review of all studies published since 1980 which related risk of stroke and death to various preoperative clinical and angiographic characteristics, including unpublished data on 1729 patients from the European carotid surgery trial. MAIN OUTCOME MEASURE: Operative risk of stroke and death. RESULTS: Thirty six published studies fulfilled our criteria. The effect of 14 potential risk factors was examined. The odds of stroke and death were decreased in patients with ocular ischaemia alone (amaurosis fugax or retinal artery occlusion) compared with those with cerebral transient ischaemic attack or stroke (seven studies; odds ratio 0.49; 95% confidence interval 0.37 to 0.66; P < 0.00001). The odds were increased in women (seven studies; 1.44; 1.14 to 1.83; P < 0.005), subjects aged > or = 75 years (10 studies: 1.36; 1.09 to 1.71; P < 0.01), and with systolic blood pressure > 180 mm Hg (four studies; 1.82; 1.37 to 2.41; P < 0.0001), peripheral vascular disease (one study; 2.19; 1.40 to 3.60; P < 0.0005), occlusion of the contralateral internal carotid artery (14 studies; 1.91; 1.35 to 2.69; P < 0.0001), stenosis of the ipsilateral internal carotid siphon (five studies; 1.56; 1.03 to 2.36; P = 0.02), and stenosis of the ipsilateral external carotid artery (one study; 1.61; 1.05 to 2.47; P = 0.03). Operative risk was not significantly related to presentation with cerebral transient ischaemic attack versus stroke, diabetes, angina, recent myocardial infarction, current cigarette smoking, or plaque surface irregularity at angiography. Multiple regression analysis of data from the European carotid surgery trial identified cerebral versus ocular events at presentation, female sex, systolic hypertension, and peripheral vascular disease as independent risk factors. CONCLUSIONS: The risk of stroke and death from carotid endarterectomy is related to several clinical and angiographic characteristics. These observations may help clinicians to estimate operative risks for individual patients and will also facilitate more meaningful comparison of the operative risks of different surgeons or at different institutions by allowing some adjustment for differences in case mix.     

Trends and future developments in the pharmacological treatment of acute ischaemic stroke

Stroke stands as the third leading cause of death. It makes great demands on patients, who must not only survive the complications of the acute stages, but must cope then with the great physical and economic costs of long-term disabilities. Therefore, there is urgent need to establish generally useful regimens for the acute treatment of ischaemic stroke. Three treatment approaches are based upon pathophysiologic concepts derived from experimental work with focal cerebral ischaemia. These include pharmacologic strategies for arterial recanalisation, inhibition of inflammatory processes and neural protection. Focal cerebral ischaemia secondary to occlusion of a brain-supplying artery initiates neuronal and microvascular events, and the simultaneous processes of inflammation which further injure tissue. The use of plasminogen activators to mediate thrombus and lysis in the acute setting has been shown to be clinically beneficial. Further work with arterial reperfusion strategies is under way. Early clinical studies with polymorphonuclear leukocyte-dependent endothelial adhesion receptor antagonists are being completed, but a strategy has yet to emerge. A large effort examining the potential efficacy of agents which may stabilise or protect neurons from ischaemic injury has shown promise in experimental models, and has been translated into clinical trials. Experimental work, and limited clinical experience, have indicated that: (a) the time window for intervention is important in limiting ischaemic and inflammatory injury, and for reducing the risk of haemorrhagic transformation; (b) putative neuroprotective strategies may potentially elongate the time interval for treatment; and (c) limitations from the adverse effects of plasminogen activators and of agents which beneficially affect neuronal dysfunction during ischaemia must yet be overcome. This review surveys pharmacological approaches currently undergoing evaluation which provide the goal of establishing effective strategies for the treatment of patients with acute cerebral ischaemia.     

Is impaired cerebral vasomotor reactivity a predictive factor of stroke in asymptomatic patients?

BACKGROUND AND PURPOSE: Identification of the subgroup of asymptomatic patients with severe internal carotid artery stenosis and high risk of stroke has important clinical implications. Cerebral vasomotor reactivity provides information regarding intracranial hemodynamic features and might have a prognostic value in predicting cerebrovascular ischemic events, especially in patients with carotid stenosis. The aim of our study was to assess the cerebral vasomotor reactivity in asymptomatic patients with carotid stenosis and evaluate its role in stroke occurrence. METHODS: Cerebral vasomotor reactivity was assessed using transcranial Doppler ultrasonology and the Diamox test (intravenous administration of 1.0 g acetazolamide) in 44 asymptomatic patients with severe (> 70%) internal carotid artery stenosis. Patients were followed up prospectively (mean, 2 years). RESULTS: Cerebral vasomotor reactivity was estimated as good (> 40% increase of blood flow velocity in the middle cerebral artery ipsilateral to the carotid stenosis after undergoing the Diamox test) in 23 patients; it was impaired in the other 21. During the follow-up period, the overall annual rate for ipsilateral stokes was 2.3%; it was 7.9% for all ischemic cerebral events. No strokes or transient ischemic attacks occurred in the former group, but there were 7 cerebral ischemic events (2 strokes [1 fatal] and 5 transient ischemic attacks) in the latter group. There was a statistically significant correlation between cerebral ischemic events and impaired cerebral vasomotor reactivity (P = .009). CONCLUSIONS: The data of this preliminary study suggest an important role of impaired cerebral vasomotor reactivity in predicting ischemic cerebral events. Preventive vascular surgery might be considered in this high-risk subgroup of asymptomatic patients with severe carotid stenosis.     

Can acute stroke be treated with hypothermia?

In animal stroke models, treatment with mild hypothermia (30-34 degrees C) for 3-4 hours may reduce the size of cerebral infarction if started within three hours of the initiation of cerebral ischaemia. The mechanism by which hypothermia exerts its neuroprotective effect is unknown, but experimental studies have shown the release of neurotoxic excitatory amino acids and free oxygen radicals to be reduced during hypothermic ischaemia. In patients with acute stroke, body temperature above 37.5 degrees C are associated with poor outcome, and temperatures below 36.5 degrees C with improved outcome, compared to normothermic patients. Due to the unpleasantness of cooling and side effects as shivering, hypothermia may not be tolerated by stroke patients without sedation of light anaesthesia which may increase the risk of hypotension and respiratory complications. However, lowering body temperature by 1-2 degrees C may suffice to improve functional outcome in acute stroke patients, and such mild hypothermia should be tested in randomized controlled clinical trials.     

Time-dependent changes in CT-based dosimetry of I-125 prostate brachytherapy

OBJECTIVE: To determine if overnight hospital stay after carotid endarterectomy (CEA) is feasible and safe in the Australian setting. DESIGN: Case series with follow-up of 4-11 months (mean, 7 months). PATIENTS AND SETTING: All patients undergoing primary CEA performed by a vascular surgeon (BMB) between 30 May and 11 November 1996. Surgery was performed in one of four hospitals (a district general public hospital with about 400 beds and three private hospitals) in the Gosford area of New South Wales. INTERVENTIONS: CEA using regional anaesthesia and sedation, after diagnosis by duplex ultrasound scan, avoiding cerebral angiography and intensive care; planned discharge after overnight hospital stay; review at one month and duplex ultrasound scan at four months. OUTCOME MEASURES: Length of hospital stay and complications. RESULTS: 65 patients were admitted for CEA during the study period and 59 were scheduled for overnight stay (one had "re-do" surgery, two remained longer for reasons unrelated to carotid artery disease, and three had been scheduled before the change to overnight stay). 54 (92%) were discharged on the first postoperative day, and only three required readmission within 30 days (for urinary retention, angina and reperfusion syndrome). There were no deaths, no myocardial infarctions and no recognised instances of cerebral ischaemia during follow-up. CONCLUSION: CEA can be performed safely without cerebral angiography or intensive care, with over 90% expectation of a single night's stay in hospital.     

Dopplerographic assessment of the autoregulation of the blood supply to the brain in neurosurgical pathology

The development of an informative, noninvasive technique for evaluating the reserve of the cerebral circulatory system is a topical task of clinical angioneurology. The authors developed methods of Doppler evaluation of an autoregulatory response from hyperemic changes after short-term regional hypotension caused by digital compression of the cervical carotid. They calculated the indices acceptable in routine clinical practice, defined the range of their values in health and in typical variants of cerebral circulatory insufficiency in patients with disseminated neurosurgical pathology. The carotid compression test by recording linear blood flow velocity in the cerebral arteries is a safe, valid, and reproducible method of semiquantitative assessment of the autoregulation reserve which may be used to determine the tension of resistive vessels in the middle cerebral arterial bed as an important index of the functional status of the cerebral circulatory system.     

Magnetic resonance spectroscopy of high-energy phosphates and lactate immediately after coronary artery bypass surgery

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 +/- 0.86 vs after: 2.57 +/- 1.31; mean +/- 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 +/- 0.04 vs 7.16 +/- 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 +/- 0.37 vs 6.39 +/- 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.     

Microemboli during carotid angiography. Association with stroke risk factors or subsequent magnetic resonance imaging changes?

BACKGROUND AND PURPOSE: Carotid angiography is associated with a 1% risk of major stroke. Recently, transcranial Doppler ultrasonography (TCD) has shown cerebral microemboli during carotid angiography. To determine their significance, we correlated the number of microemboli during angiography with clinical characteristics, angiography findings, and preangiography and postangiography cerebral magnetic resonance imaging (MRI). METHODS: One middle cerebral artery was monitored with TCD in 24 patients during angiography for carotid territory ischemia. The number of microemboli was correlated with angiographic and clinical characteristics. T2-weighted cerebral MRI was performed before and < or = 48 hours after angiography, and the number of new ischemic lesions was determined in a blinded review. RESULTS: Microemboli were seen in all patients, with an average of 51 per procedure (range, 12 to 154). The majority of microemboli had signal characteristics typical of air. Sixteen of the 24 patients had both preangiography and postangiography MRI. One of 24 patients had an angiographic stroke, with a single new thalamic lesion on MRI. No other patient had a new lesion. The microembolus count correlated with the angiographic contrast volume (P < .001) but not with any other radiological or clinical characteristic. CONCLUSIONS: This study confirmed the presence of numerous cerebral microemboli during carotid angiography. The microembolic signal characteristics and the correlation with contrast volume indicate that introduced air is the cause. These microemboli are usually clinically silent and do not lead to new changes on cerebral MRI.     

Endoscopic removal of a dental instrument from the stomach: case report

The records of 628 patients admitted to the Joint Study of Extracranial Arterial Occlusion with transient symptoms of carotid system ischemic disease were examined to determine the accuracy of predicting disease of the extracranial internal carotid artery on the basis of clinical information alone. A patient with a history of episodes of amaurosis fugax is more likely to have a lesion of the internal carotid artery on the same side than if he were having only transient cerebral ischemic attacks. In patients with transient symptoms and a carotid bruit on the appropriate side, the incidence of an angiographically normal carotid artery was 15%. In those patients with transient symptoms and no palpable pulsation in the cervical region on the appropirate side, the incidence of an angiographically normal carotid artery was zero.     

Smoking, transient ischaemic attacks and stroke: A temporal association

Two patients are described, both of whom demonstrate a temporal association between the clinical manifestations of cerebral ischaemia and smoking. A number of mechanisms through which smoking may influence cerebral blood flow and platelet function are discussed, and their relevance to the present cases is considered.     

Cerebral hyperperfusion syndrome following carotid endarterectomy

Three patients with a severe symptomatic carotid stenosis developed headache, epileptic seizures and focal neurologic deficits several days after carotid endarterectomy. CT of the brain revealed hypodensities, indicative of cerebral oedema with haemorrhagic components. This is caused by cerebral hyperperfusion, a complication after carotid endarterectomy as a result of increased cerebral perfusion on the side of the operated carotid stenosis. Dysfunction of the cerebral autoregulation believed to be the cause of this hyperperfusion. Sometimes these complications are incorrectly attributed to one of the better known types of stroke.     

Angioplasty of the occluded internal carotid artery

PURPOSE: To review patients who have presented with acute strokes from a middle cerebral artery occlusion in whom in addition to the middle cerebral artery thromboembolus, an internal carotid artery occlusion has been present, and in whom angioplasty of these totally occluded internal carotid arteries has bee n successful. METHODS: We reviewed retrospectively our experience in treating a cute stroke patients with intracranial, intraarterial urokinase. Six of 27 patients had internal carotid artery occlusions in addition to middle cerebral artery occlusions. Two patients presented with spontaneous carotid dissections for wh ich no further intervention from the ipsilateral internal carotid artery was attempted. In the remaining four internal carotid artery occlusions secondary to atherosclerotic disease, standard guide wires and catheters were negotiated across the level of the internal carotid artery occlusion, which expedited intracranial catheterization for thrombolysis. Subsequently, angioplasty of the internal carotid artery was performed. RESULTS: All four occluded internal carotid arteries could be traversed. No new neurologic deficits occurred. No vascular injuries occurred. No deaths occurred. Four- to 6-month follow-up showed all four internal carotid arteries remained patent. CONCLUSION: In acute occlusions of the internal carotid artery from atherosclerosis, the occluded vessel can sometimes be recanalized with low morbidity. In addition, endovascular access to the intracranial circulation can be expedited by using the recanalized internal carotid artery.