References

Hypoxia and related conditions. In Graham DI, Lantos PL, eds. Greenfield's Neuropathology. Vol. 1. 7th ed. Arnold London, 2002 233-280. 2. Saito N, Kawai K, Nowak TS Jr. Reexpression of developmentally regulated MAP2c mRNA after ischemia colocalization with hsp72 mRNA in vulnerable neurons. J Cereb Blood Flow Metab 1995 15 205-215. 3. Petito C, Feldmann E, Pulsinelli W, et al. Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology 1987 37...

Radiographic Indicators Of Progressing Stroke

CT and MRI performed early during the evaluation of the stroke patient have become useful in the identification of risk factors for progressing stroke. In a series of 152 consecutive patients with acute ischemic stroke who were hospitalized within 5 hr of stroke onset, extended focal hypodensity on CT involving cortical or corticosubcortical areas increased the risk of neurologic worsening by a factor of 8.9 and predicted subsequent deterioration with a probability of 60 (7). The same...

Mouse Models

Mouse models of vasospasm are similar to rat models and have been recently developed to take advantage of transgenic technology. The first model used endovascular perforation of the ACA (122). In this model, a 5-0 monofilament suture with a blunt end is advanced through the ICA up to the ACA until resistance is felt. The suture is advanced 5 mm further to perforate the ACA and then withdrawn. Acute mortality with this model is 28 . To determine vasospasm, animals are perfused with 10 formalin,...

Other Applications of Extracranial Duplex Screening

Duplex technology can determine if stroke patients have carotid lesions other than atherosclerosis. Examples include carotid thromboembolism, dissection, fibromuscular dysplasia, and radiation injury. These lesions have distinctively different appearances on B-mode ultrasound, Figure 1 High-risk plaque types and artery-to-artery embolization. (Upper left and middle panels) Hypoechoic plaque on B-mode is marked by arrows 1, shadows produced by calcified aspects of the predominantly echolu-cent...

Excitotoxicity Intracellular Calcium And Ischemic Brain Injury

Energy failure due to cessation of blood flow can result in calcium accumulation in brain cells via diffusion along electrochemical gradients, depolarization and opening of voltage-dependent calcium channels (VDCC), internal release from organelles the endoplasmic reticulum (ER) and mitochondria , and via excessive stimulation of glutamate receptors. Ischemia also results in the accumulation and release of excitatory amino acids (EAAs), such as glutamate and aspartate, which contribute to...

Role Of Cerebral Blood Flow Changes

The association of cerebral ischemia and edema formation has been well studied. Although, based on experimental animal models, ischemia was initially thought to contribute to edema in ICH (44-48). This theory is currently controversial, and it is becoming more and more evident that ischemia does not play a role in edema formation in ICH. No good test exists by which to measure the cerebral response at the cellular level in ICH, but emergent technology, such as MRI, single-photon emission...

European Cooperative Acute Stroke Study II

In the wake of the NINDS rtPA Stroke Study, ECASS II was undertaken to determine if rtPA could be effective even when administered more than 3 hr after the onset of stroke symptoms. ECASS II is the largest randomized trial of thrombolytic therapy that has been conducted in acute stroke to date, enrolling 800 patients in 108 centers throughout Europe, Australia, and New Zealand, randomly assigning them to rtPA, using the NINDS Stroke Study dosing regimen versus placebo (43). To prevent the large...

Anesthetic Considerations

The anesthetic management of patients with ICH can be complex, depending on the patient's neurologic status, the size of the ICH, and its systemic manifestations, as well as the preexisting comorbidities. Decrease in level of consciousness might indicate elevated ICP, which can lead to nausea and vomiting, resulting in pneumonitis. The high ICP might invoke Cushing's reflex, with increased systemic blood pressure and bradycardia, possibly accompanied by systemic hypo-volemia. Induction of...

Increased Intracranial Pressure And Cerebral Edema

Intracranial hypertension is operationally defined as sustained ICP > 20 mmHg. A patient with suspected elevated ICP and a deteriorating level of consciousness requires invasive ICP monitoring (44). IVCs are considered the gold standard ICP monitor. This form of external ventricular drainage is also useful in treatment of elevated ICP because IVCs allow cerebro-spinal fluid drainage. Recommendations to use antibiotic prophylaxis and to periodically exchange IVCs are largely the result of...

Epidemiology And Risk Factors

In that no prospective, population-based, epidemiologic studies have been conducted to specifically examine CVT, the current incidence in the general population is not known. Most studies are from autopsy series (7-13). However, in the last decade an increase in diagnosis and survival of patients with CVT can be attributed to improved knowledge of hypercoagu-lable states, better detection via magnetic resonance imaging (MRI), which includes magnetic resonance venography (MRV), (Fig. 1) and...

Alteplase Thrombolysis for Acute Noninterventional Therapy in Stroke Study

The alteplase thrombolysis for acute noninterventional therapy in stroke (ATLANTIS) study was double-blinded, randomized, multicentered, and placebo controlled (17). It initially began in August 1991, with a goal to test the efficacy and safety of IV administration of rtPA in patients with acute ischemic stroke within a 0- to 6-hr window. This company-sponsored trial was to run concurrently with the NINDS trial. However, in December 1993, safety concerns arose concerning the 5- to 6-hr time...

Identification Of Patients For Hemicraniectomy

Early identification of patients susceptible to malignant MCA infarction is crucial. Neuroimaging is an invaluable tool for identifying patients at risk for developing ischemic brain edema. Neurologic deterioration correlates with horizontal displacement of the anterior septum and pineal gland (as seen on CT scan), rather than with ICP elevation. The presence of low-density infarction and edema that occupies more than 50 of MCA territory on CT scan is a reliable predictor of subsequent edema...

Histopathology Of Global Ischemia

The spectrum of brain pathology observed following global ischemic insults has been extensively studied in a range of clinical and experimental conditions (1). Neuron populations throughout the brain represent the major cell type at risk, illustrated in Figure 1 by the distribution of stress response gene induction in a rat model of cardiac arrest (2). A comparatively small subset of these neurons exhibits histopathologic evidence of vulnerability under the experimental conditions of commonly...

Right to Left Shunts and Emboli Detection

Ultrasound can detect, quantify, and localize embolization in real time, and this methodology has been utilized in cerebral vessels with TCD (48-51). Detection of emboli with TCD is based on the definition of microembolic signals (MES) provided by the International Cerebral Hemodynamics Society Consensus Statement (52). MES (Fig. 3) have the following characteristics on spectral Doppler analysis (i) random occurrence during the cardiac cycle, (ii) brief duration (usually < 0.1 second), (iii)...

Membrane Stabilization Citicoline

Citicoline (Interneuron Pharmaceuticals) is an exogenous form of cytidine-5'-diphosphocholine (CDP-choline), used in membrane biosynthesis. Citicoline appears to reduce ischemic injury, both by stabilizing membranes and by decreasing free radical formation. Citicoline is an approved stroke treatment medication in several countries. A Phase 2 United States trial found improved outcome in stroke patients treated with 500 mg of citicoline (32). A Phase 3 trial was then conducted to confirm...

Carotid Artery Occlusion

Unilateral carotid artery occlusion in most animals does not lead to ischemic changes unless combined with severe hypotension (19) or asphyxia (20). The same procedure, however, leads to even fatal strokes in gerbils, as the gerbil lacks a functioning Circle of Willis (21,22) and, therefore, gerbil cerebrovascular anatomy is different from human anatomy. Furthermore, the gerbil focal brain ischemia models present several other disadvantages (i) not all animals develop an infarction (22), (ii)...

Sequence Of Events During Complete And Incomplete Cerebral Ischemia

Complete global cerebral ischemia refers to situations in which cerebral blood flow (CBF) falls to zero, such as in the case of cardiac arrest. Incomplete global cerebral ischemia refers to situations in which CBF does not completely cease but falls sufficiently to impair cellular processes, metabolism, and function. Incomplete ischemia arises from various causes of arterial hypotension, shock, and intracranial hypertension. The brain requires a continuous supply of oxygen and glucose for...

Conclusion

The recent history of neuroprotective clinical trials in stroke reveals multiple agents that demonstrated efficacy in preclinical studies failed to achieve expected results in clinical trials. Although the exact reasons for this are unknown, possibilities include longer time window in clinical trials than in animal studies, lower tolerated drug levels, a more heterogeneous variety of strokes compared to pure middle cerebral artery (MCA) stroke animal studies, the majority of clinical strokes...

Grading And Prognosis Of aSAH

The single most important predictor of outcome after an aSAH is the presenting level of consciousness. The mental status and consciousness level seen during triage are routinely quantified by health care personnel using the Glasgow Coma Scale (GCS) (Table 2). The assessments of eye opening, verbal responses, and motor commands contribute to the initial assessment and reflect the sum of the other prognostic factors associated with SAH, such as extent of hemorrhage, injury to the brain, size of...

Prognosis And Clinical Predictors

The neurologic examination is the first step in assessing the prognosis of a comatose patient after CA (17). Coma can be defined as a state of unarousable unresponsiveness characterized by the eyes being closed (as in sleep) and the absence of purposeful movements to stimulation (18). Stupor refers to a state of deep sleep, with arousal only to vigorous stimulation. In contrast, patients in vegetative states do not appear asleep but open their eyes to stimulation (although diurnal sleep-wake...

Anticoagulant Therapy

Trials have also been conducted to evaluate the efficacy of enoxaparin, a low-molecular-weight heparin, in the prevention of DINDs. The first trial was a double-blinded, randomized trial of 170 patients who were treated with either placebo or enoxaparin for 10 days after aneurysm occlusion. The authors found no difference in neurologic outcomes between the two groups at three months (35). A subsequent double-blinded, randomized trial was conducted in 120 consecutive patients who received a...

Vertebral Dissecting Aneurysms

The natural history of dissecting vertebral artery aneurysms (DVAA) is not well described however, once the artery is ruptured with SAH, high morbidity and mortality rates have been reported (68). DVAA are often caused by a shearing injury at the origin of the meningeal branch of the VA. Indeed, one study reported that 69 of patients rebled before they reached therapy of these, 57 rebled within 24 hr, with a mortality rate of 46.7 (69). Other investigators have shown SAH with isolated...

Shivering and Pharmacologic Paralysis

Shivering can cause a significant disruption of therapeutic hypothermia by generation of heat, leading to increased core body temperature and oxygen consumption (10,55). The European and Australian studies used vecuronium infusion as a paralytic, with IV midazolam as an accompanying sedative (8,9) . The initiation of pharmacologic paralysis with sedation will require full mechanical respiratory support. Total paralysis will also make clinical neurologic assessment very limited. Therefore, a...

Middle Cerebral Artery Occlusion Models

Intraluminal Suture (Monofilament) Middle CerebralArteryOcclusion Model The intraluminal suture (monofilament) MCAO model is the most commonly used in focal brain ischemia studies, probably because it is relatively easy to perform and less invasive than other models. Because a craniectomy is not required, damage from brain retraction, vessel manipulation, temperature loss, and desiccation of exposed brain are all avoided. In this model, the MCA is occluded by inserting a monofilament suture...

Familial Aneurysmal Formation

At least some role for congenital factors in the development of aneurysms is evidenced by studies that show a higher prevalence of cerebral aneurysms among family members of affected cohorts. Some studies suggest that the prevalence of familial cerebral aneurysms (defined as at least 2 affected first-degree relatives in the same family) ranges from 6 to 10 (73-78). One study found a 20 prevalence rate, and this was true for Caucasian, African American, and Hispanic patients (73). Another study...

Transcranial Ultrasonography

Currently, no standard, rapid method is available to functionally image the cerebral vasculature for recanalization after thrombolysis administration in suspected large vessel ischemic strokes. Taking the patient outside of the emergency room or ICU setting to undergo a CT scan, MRI, or angiography is potentially dangerous. With the advancement of ultrasound technology, the use of transcranial-Doppler ultrasonography (TCD) is being researched. The advantage of TCD is that it is a rapid, bedside...

Info

International Standard Book Number-10 0-8493-9870-3 (Hardcover) International Standard Book Number-13 978-0-8493-9870-4 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all...