William S Anderson, M.A., M.D., Ph.D.

• Associate Professor of Neurosurgery

https://www.hopkinsmedicine.org/profiles/results/directory/profile/5467950/william-anderson

Most case series report that the risk of hemorrhagic stroke due to amphetamines is twice that of cocaine use [4] erectile dysfunction doctor las vegas purchase line priligy. The pharmacokinetics of amphetamines differ among children and adults erectile dysfunction pills in india purchase priligy with mastercard, posing a cardiovascular risk in adults with prolonged amphetamine use [24] erectile dysfunction bp meds order priligy 60 mg fast delivery. It is suspected that as vasospasm resolves and perfusion is restored erectile dysfunction 23 years old quality 60 mg priligy, arterial rupture can occur [30] erectile dysfunction rap 90 mg priligy sale. Amphetamines and Ischemic Stroke Cocaine and amphetamines have the strongest association with ischemic stroke [4] impotence nhs purchase priligy discount. Compared to nonusers, amphetamines increase the odds of suffering a stroke by 4 times [4]. Ischemic events occur due to a rise in catecholamine levels, vasoconstriction of extra- and intracerebral vasculature, and formation of oxygen-free radicals. Histological evidence demonstrates amphetamines produce vessel wall necrosis, atherosclerosis, and occlusion leading to infarcts [4]. Cerebral vasculitis reducing vessel caliber with resulting infarction has also been postulated as a possible mechanism of amphetamine-related ischemic stroke. One case series revealed the presence of fibrinoid necrosis, luminal thrombosis, and mixed inflammatory cells in smalland medium-sized arteries, identical to a necrotizing angiitis as seen with polyarteritis nodosa [26,31]. Other histopathological studies have countered these findings, showing no evidence of inflammation and varying extent of vessel wall medial necrosis [26]. Some have postulated that atherosclerosis occurs with time as methamphetamines cause repeated episodes of hypertension with resulting microinfarction in the vaso vasorum and atherosclerosis [26]. The annual prevalence of cocaine use among adults in 2011 in Western and Central Europe was 1. Abuse has increased especially among African-Americans from low socioeconomic status in urban areas [34]. The illicit forms of cocaine are cocaine hydrochloride and cocaine alkaloid also known as crack cocaine. Crack cocaine or "crack" is the cocaine alkaloid "free base" which is a crystalline chemical that is heat stable and can be smoked and absorbed by the lungs. It is often the form smoked by addicts from low socioeconomic status and is very addictive [34]. Acute and chronic adverse effects include anxiety, intense high followed by dysphoria, sleeplessness, hypertension, addiction, loss of appetite, nasal septal perforation, ciliary madarosis, long pinky nail (cake nail), lung damage, and death from overdose [11]. The majority of patients with cocaine intoxication present with ischemic rather than hemorrhagic stroke [35]. Larger studies are needed to quantify the risk and assess stroke type, concomitant amphetamine use, duration and frequency of cocaine use, and hypertension variation. The relationship between stroke and cocaine is influenced by other factors including demographics, lifestyle, patterns of cocaine use, and concomitant use of other drugs or medical problems. Multiple, bilateral, deep, and convexity cerebral hemorrhages are rare but have been associated with smoking crack cocaine and consuming large quantities of ethanol. In the absence of a vascular lesion, etiologies still include acute hypertension as well as hemorrhagic conversion following ischemia. No pathological evidence exists demonstrating an association between cocaine and cerebral vasculitis unlike the sympathomimetics [36]. The association of cocaine use and delayed cerebral ischemia was not significant nor was the impact on functional outcome [37]. Cocaine and Ischemic Stroke the pathophysiological mechanisms of cocainerelated ischemic stroke include vasospasm, microischemia, endothelial dysfunction with thrombus formation, and vasculitis [35]. Autopsies have also shown plateletrich arterial thrombi suggesting platelet activation as the underlying pathophysiological mechanism [38]. Crack cocaine induces more rapid blood levels and a more rapid high hydrochloride compared to cocaine hydrochloride, which is snorted or administered intravenously. Regardless of route of administration, strokes occur shortly after use with a predilection for the brain stem. Concomitant ethanol use carries a synergistic action with cocaine, likely potentiating its effects. In the presence of ethanol, cocaine is metabolized to cocaethylene which binds more powerfully to the monoamine transport proteins [41]. A double-blind randomized controlled trial of 24 healthy and neurologically normal men with mean age of 29 years and mean lifetime cocaine use of eight exposures studied the effect of low-dose intravenous cocaine administration on the cerebral vasculature. In the absence of other stroke risk factors, cocaine administration induced dose-related cerebral vasoconstriction. Prior cocaine use revealed a statistically significant dose-related effect, suggesting greater lifetime use predisposed users to a higher likelihood of cerebral vasoconstriction [39]. There was a significant difference in velocities and pulsatility between cocaine abusers and the control group, with increased cerebrovascular resistance that persisted despite abstinence of 1 month. Further studies are needed to assess if pharmacological intervention would impact cocaine-related cerebrovascular resistance and outcome [20,40]. Despite small retrospective studies showing no increased risk of hemorrhage with thrombolysis in patients presenting with acute ischemic strokes in the setting of cocaine use, the actual risk of hemorrhagic conversion remains uncertain and mandates further research [35]. Systemic symptoms of heroin include eosinophilia, elevated immune and gamma globulins, hemolysis with positive Coombs test, and lymph node hypertrophy [41]. Heroin is often injected intravenously, though smoking or inhaling heroin is also increasingly popular [2]. Other neurological complications reported with heroin include transverse myelopathy, septic embolism with abscess formation, and bilateral basal ganglia necrosis [43]. Heroin and Ischemic Stroke Mechanisms of heroin-associated stroke include cardioembolism secondary to infective endocarditis, anoxic injury secondary to hypoxemia and hypotension due to heroin-induced shock, and infective vasculitis secondary to heroin adulterants [2]. Heroin is often adulterated with quinine, lactose, and other diluents triggering angiitis secondary to a hyperimmune response with eosinophilia that can play a role in stroke [41,42]. Common neurological manifestations include mono- or poly-neuropathies, stroke, and psychiatric disorders. Other mechanisms include deposition of eosinophilic proteins in the endothelium, causing damage in the small and larger arterioles. A component of the eosinophilic granule, the eosinophilic cationic protein, also increases blood viscosity, and with an elevated eosinophil count results in hypercoagulability and higher risk of stroke [44]. Standard-sized portions of wine, liquor, or beer contain about the same amount of alcohol [49]. Alcohol and Ischemic Stroke Observational studies have demonstrated an association between light to moderate alcohol intake and decreased risk of ischemic stroke, thought to be due to atherosclerosis prevention, although no clear explanation has been found. A cross-sectional analysis has indicated light to moderate alcohol intake is associated with decreased atherosclerotic burden in the proximal aortic arch which could explain the lower incidence of ischemic stroke. Protective effects of alcohol on the vasculature include regulation of lipids and fibrinolysis, decreased platelet aggregation, coagulation factors, inflammation, and insulin resistance [50]. An increased risk of cardioembolism is expected in heavy drinkers with underlying risk factors such as atrial fibrillation or cardiomyopathy. Increased blood flow during early intoxication may cause artery-to-artery emboli in atherosclerotic vessels. Despite the decreased risk of ischemic stroke with mild to moderate alcohol consumption, this risk is modified in the setting of other concomitant risk factors that include apolipoprotein E (apoE) genotype. ApoE4 positivity with moderate alcohol consumption is associated with an increased risk of ischemic stroke [51]. Mechanisms of heroin-associated myelopathy include hypotension, vasculitis, hypersensitivity, or a direct toxic effect of heroin. Hypotension is an unlikely cause and no patterns have correlated with spinal cord watershed zones. With a hypersensitivity reaction, heroin undergoes haptenation with an in vivo protein. This may be a protein specific to the spinal cord with resulting local inflammation, ischemia, and tissue injury [45]. It remains unclear if reducing alcohol intake will also reduce the incidence of stroke. A multivariate regression analysis was performed in 1714 patients with hemorrhagic stroke. The economic cost of smoking on society has totaled nearly $193 billion per year [55]. Tobacco smoke contains over 4000 different chemicals including heavy metals and toxins that result in free radical formation and vascular endothelial injury leading to accelerated atherosclerosis. Cigarette smoking also causes a procoagulant state induced by a change in concentrations of hemostatic and inflammatory markers. Smoking also promotes fibrinogen formation, a decrease in fibrinolytic therapy, an increase in platelet aggregation, and polycythemia. Cigarettes and Ischemic Stroke the Framingham study demonstrated that cigarette smoking increases risk of all types of stroke due to arterial thromboembolism, is dose related, and independent of history of hypertension [56,57]. This study reported no significant differences in the smoking status of all subjects with various stroke subtypes including atherosclerotic, vasculopathic, cardioembolic, or cryptogenic [56]. A causal relationship between secondhand smoking and stroke has been suggested even at low levels of exposure. Exposure to secondhand smoke causes platelet aggregation, thrombosis, endothelial dysfunction, and inflammation [59]. Two-thirds of young patients continue to smoke despite the effectiveness of smoking cessation in reducing the risk of recurrent stroke [58]. After 1 year, the risk of heart disease is reduced to half and by 15 years, the risk of heart disease is that of a nonsmoker [55]. They nonetheless had a higher risk of stroke compared to nonusers of tobacco [60]. There is some exposure of nicotine, organic compounds, and fine particles with e-cigarettes, but there is insufficient evidence that the exhaled aerosol is dangerous to the public. Some argue that e-cigarette use promotes nicotine addiction and "renormalizes smoking behavior" [61]. Cigarettes also reduce the activity of -1-antitrypsin which is a proteolytic enzyme that prevents breakdown of collagen and elastin [33]. A healthy lifestyle consisting of abstinence of smoking, healthy diet including low to moderate alcohol intake, exercise, and maintaining optimal body weight are effective in lowering risk of coronary artery disease, diabetes, and cancer than any other single factor. A healthy lifestyle has also been shown to significantly lower risk of ischemic stroke [64]. A healthy lifestyle also embodies avoidance of illicit drug use, specifically cocaine, heroin, and amphetamines, though profound use continues to rise and has become a major source of stroke-related morbidity and mortality in the younger population. Given the perception that cannabis is harmless and legalization continues to be debated, health care professionals and the general public need to be made aware of the increased risk of cardio- and cerebrovascular disorders. Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard. Heavy cannabis users at elevated risk of stroke: evidence from a general population survey. Acute temporal lobe infarction in a young patient associated with marijuana abuse: an unusual cause of stroke. Cannabis, cannabinoids, and cerebral metabolism: potential applications in stroke and disorders of the central nervous system. Is intimal hyperplasia associated with cranial arterial stenosis in cannabis-associated cerebral infarction Both hemorrhagic and ischemic stroke following high doses of cannabis consumption. Cerebrovascular perfusion in marijuana users during a month of monitored abstinence. Potential adverse effects of amphetamine treatment on brain and behavior: a review. Subarachnoid hemorrhage from a thoracic radicular artery pseudoaneurysm after methamphetamine and synthetic cannabinoid abuse: case report. Brain hemorrhage and cerebral vasospasm associated with chronic use of cannabis and buprenorphine. Cocaine use and the likelihood of nonfatal myocardial infarction and stroke: data from the Third National Health and Nutrition Examination Survey. A case-control study of stroke risk factors and outcomes in African American stroke patients with and without crack-cocaine abuse. Immediate hemorrhagic transformation after intravenous tissue-type plasminogen activator injection in 2 cocaine users. Cocaine-induced cerebral vasoconstriction detected in humans with magnetic resonance angiography.

Syndromes

• REM sleep-behavior disorder (a person moves during REM sleep and may act out dreams)
• Modified plants or animals may have genetic changes that are unexpected and harmful.
• Femoral nerve dysfunction
• Incorrect positioning of the baby (fetal malposition)
• Hematoma (blood accumulating under the skin)
• Liver failure
• This procedure delivers very focused radiation directly to the area of the AVM to cause scarring and shrinkinge.
• Complete blood count (CBC)
• There is loss of hearing.
• Tumors

As demonstrated in the Nordic twin cohort erectile dysfunction best pills order priligy 90mg without prescription, most aneurysms in practice are only modestly influenced by genetic predisposition when compared to environmental risk factors [8] erectile dysfunction and diabetic neuropathy purchase priligy 90mg online. Further risk stratification to determine the need for prophylactic surgical or endovascular obliteration is performed based on other known modifiers such as aneurysm size erectile dysfunction doctor discount priligy 90 mg amex, interval growth of an aneurysm erectile dysfunction drugs causing order priligy toronto, aneurysm location erectile dysfunction causes symptoms and treatment cheap priligy american express, and irregular morphology [10 erectile dysfunction blue pill cheap priligy 60 mg fast delivery,12]. The sudden and severe headache may also be accompanied by some degree of altered mental status, nausea or vomiting, and meningismus. Although seizures are less common, they have been shown to portend a poor prognosis [15]. Although it may be absent within the first hours of the ictus, the presence of xanthochromia in the delayed setting has a specificity for cerebral aneurysm that reaches approximately 95% [19]. Appropriate clinical suspicion and diagnosis are essential for appropriate treatment and patient outcome, as ruptured aneurysms not treated within 24 h of presentation are associated with an almost 15% risk of rerupture [16,17,21]. Physiologically, clot formation around the dome of a ruptured aneurysm prevents continuous hemorrhage of arterial blood into the subarachnoid space. Initial medical management focuses on the prevention of increase in arterial pressure and maintenance of that clot. Clinically, rerupture manifests as a worsened headache, seizure, or decreased level of consciousness. It is often associated with an acute spike in blood pressure and intracranial pressure. Maintenance of the clot integrity is optimized with reversal of antiplatelet and anticoagulant therapy. Those on aspirin or clopidogrel (Plavix) will receive platelets with an overall platelet goal of > 100,000. Intraparenchymal, subarachnoid, and intraventricular blood manifests both intracranially and systemically. The most concerning feature of intracranial blood is the increase in intracranial pressure and local mass effect in the case of intraparenchymal clot. Clinically, the elevation in intracranial pressure and the cortical and meningeal irritation by blood products lead to the "worst headache of life," nuchal pain/rigidity, nausea or vomiting, confusion/agitation, decreased level of consciousness, and seizures. Analgesia with acetaminophen and administration of opiates are initiated to minimize pain and the associated blood pressure elevation, while maintaining the level of consciousness for neurologic examinations. Mass effect from intraparenchymal clot can represent an especially grave circumstance necessitating emergent decompression to prevent uncal herniation and death. These lesions are more often associated with middle cerebral artery aneurysms and manifest with decrease in consciousness and, at extreme stages, third-nerve compression with pupillary dilatation. Radiographically, an acute hemorrhage in the middle fossa measuring greater than 15 cc may require emergent embolization/clipping and decompression. Both open surgical evacuation of the hemorrhage and clipping of the lesion or endovascular embolization with subsequent decompression are the current treatment options, with neither treatment showing significant difference in outcomes. Communicating, or noncommunicating, hydrocephalus may occur as a result of subarachnoid blood. Hydrocephalus is managed with an external ventricular drain placed into the lateral ventricle. Although cerebral vasospasm may be asymptomatic at first, it has the potential to lead to symptomatic delayed cerebral ischemia, often involving watershed territories or other vascular areas distal to the aneurysm [30]. As such, several measures may be taken to reduce the incidence of vasospasm and its downstream effects. Such measures include the prophylactic use of nimodipine, which has been shown to improve outcomes [31]. Additionally, many clinicians use the "Triple-H" (hypertension, hemodilution, hypervolemia) therapy to treat and minimize the risk of vasospasm; however, there is equivocal clinical evidence supporting its use [32,33]. In case of failure of medical therapy, endovascular strategies such as intra-arterial pharmacotherapy with verapamil may be used [34]. Subarachnoid hemorrhage incidence among Whites, Blacks and Caribbean Hispanics: the Northern Manhattan Study. Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification. Worst headache and subarachnoid hemorrhage: prospective, modern computed tomography and spinal fluid analysis. Treatment of these lesions is not without risks; hence, several prospective trials have evaluated aneurysmal characteristics associated with an increased risk of rupture and the need for prophylactic treatment. A multidisciplinary expert discussion ultimately continues to play a central role in determining the most appropriate treatment for any given lesion. Lesions are typically addressed on a case-by-case basis, with anatomic and morphologic variables combined with patient characteristics to dictate an optimal care plan. Determining the sensitivity of computed tomography scanning in early detection of subarachnoid hemorrhage. Results of routine ventriculostomy with external ventricular drainage for acute hydrocephalus following subarachnoid haemorrhage. Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience. Effectiveness of neurosurgical clip application in patients with aneurysmal subarachnoid hemorrhage. This chapter focuses on intracerebral Primer on Cerebrovascular Diseases, Second Edition dx. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. Recent trends in the treatment of cerebral aneurysms: analysis of a nationwide inpatient database. A comparison of nicardipine and labetalol for acute hypertension management following stroke. Occurrence and implications of seizures in subarachnoid hemorrhage due to ruptured intracranial aneurysms. The relationship between ruptured aneurysm location, subarachnoid hemorrhage clot thickness, and incidence of radiographic or symptomatic vasospasm in patients enrolled in a prospective randomized controlled trial. In ischemic stroke, diminished blood flow leads to inadequate oxygenation of brain parenchyma and neuronal infarction. Hemorrhagic stroke occurs most often due to vascular injury resulting in hematoma formation and local mass effect on surrounding neural tissue. Hypertensive hemorrhage occurs most often in the deep regions of the brain such as the basal ganglia, thalamus, pons, and cerebellum. Hyaline, collagen, protein, and fat replace arterial smooth muscle, thin the adventitia, and eventually form atheromas. The stiffened and narrowed lumen results in small areas of brain ischemia followed by encephalomalacia known as lacunes. This term is derived from the Latin word "lacunae," which appropriately means "lake. However, it has since been shown by electron microscopy that these "microaneurysms" are actually miniature hematomas located in the subadventitial or extravascular spaces. These proteins exhibit "apple-green birefringence," upon exposure to Congo red stain under polarized light. Cerebral amyloid deposition occurs over time and has been found in about half of all patients over 70 years of age [3]. Over time, the amyloid proteins replace the smooth muscle cells found in arteries leading to decreased compliance and an increased bleeding risk. Cavernous malformations have a lower propensity for bleeding with annual rates of <1% for incidentally found lesions, 2% for symptomatic lesions not related to hemorrhage, and 4. Anticoagulation is often used to reduce venous and arterial thromboembolic risk in patients with certain cardiac, stroke, or malignancy histories. Common conditions include atrial fibrillation, implanted vascular stents, prior strokes, deep vein thrombosis, pulmonary embolism, and inherited or acquired coagulopathic states. Novel oral anticoagulants appear to have a more favorable profile of reduced hemorrhagic risk [9,10], but have yet to be as frequently prescribed as traditional vitamin K antagonists. Contralateral hemisensory loss, can extend to hemiparesis when internal capsule is involved. Vertical gaze palsy, retraction nystagmus, skew deviation, loss of convergence, ptosis + miosis + fixed and dilated pupils if spreads to midbrain. Hypertension + bradycardia + irregular respirations due to compression of fourth ventricle or cerebral aqueduct/intraventricular involvement. Severe headache, photophobia, nausea, vomiting, neck stiffness, hydrocephalus (lethargy, altered mental status, bradycardia, respiratory failure). As with all patients with neurological disease, the location of the injury is often the most important factor in determining presentation (Table 92. This is in contrast to an acute ischemic stroke with symptoms that present as both sudden and maximum at onset due to vessel occlusion. It is both fast and ideal for showing acute hemorrhage as a hyperdense mass relative to brain parenchyma. This allows the clinician to immediately differentiate hemorrhage from ischemic stroke. We follow the same imaging protocol for patients with traumatic cerebral contusions as well, although data by Anandalwar et al. Unfortunately, given the fascicular organization of the brain, the highly condensed "information highways" that carry the majority of information are located in these deep structures, making hemorrhage in these areas particularly devastating. Mycotic aneurysms are typically located in the distal arterial branches, rather than the proximal vessels seen most often in classic cerebral aneurysms. There is also demonstration of prominent ventricles and atrophy within the left hemisphere. He has a history of intravenous drug use complicated by endocarditis involving a mechanical aortic valve replacement and indefinite Coumadin anticoagulation for his mechanical valve. One must gather as much information as possible from the patient, close contacts, neurological examination, laboratory data, and imaging findings when deciding upon management. In 2015 the American Heart Association and the American Stroke published an up-to-date treatment guideline [15] for clinicians. The initial goal of treatment is to reduce the risk of acute re-bleed and treat any pathology leading to immediate mortality. Blood pressure control and reversal of coagulopathy are priorities in acute hemorrhage. A bedside external ventricular drain may be necessary in patients with acute hydrocephalus. Decompressive operations are an option in select patients who are acutely decompensating, and can sometimes be combined with clot evacuation. To reduce the risk of re-bleeding, strict blood pressure parameters are maintained with attention to premorbid perfusion dependency. Maximizing hemostatic ability including optimization of coagulation factors, and platelet count and function are equally important. In patients with thrombocytopenia, or using antiplatelet medications, platelet transfusion helps to form the initial platelet plug that acts as a scaffold for clot formation. Following formation of a platelet plug, coagulation factors have a major role in clot stability. Patients with coagulopathies such as those with liver disease or on anticoagulation may be given exogenous factors through transfusions of fresh frozen plasma, prothrombin concentrate complex, or even fast-acting antibodies that disable the latest generation of anticoagulants. Vitamin K should be given to those with functional livers to maintain coagulation factor production over a sustained time period. Untreated seizures can lead to increased intracranial pressure, re-rupture of vascular pathologies, or accelerated herniation in mass-occupying lesions. During workup of a stable patient, if an underlying lesion such as a vascular malformation or tumor is noted in the region of hemorrhage, the patient may elect to undergo surgery, with the goal being to removal to reduce risk of future hemorrhage. Aneurysmal sources represent the lesions with greatest incidence of acute re-hemorrhage. Emergent surgery is indicated as a lifesaving measure in cases of significant mass effect leading to herniation. Cerebellar hemorrhage >3 cm in diameter with brain stem compression or evolving hydrocephalus should be considered for emergent surgery due to the small volume of the posterior fossa and high risk of tonsillar and/or upward cerebellar herniation with hematoma expansion. Patients with large volume supratentorial hemorrhage causing shift and subsequent herniation at the level of the falx, tentorium, or foramen magnum should also be considered for emergent clot evacuation. Another group of patients who require surgery are those with accessible lesions who develop delayed neurological deterioration due to hematoma growth. For example, a middle-aged patient with putamenal hemorrhage and progressive weakness due to an enlarging hematoma compressing the internal capsule would benefit from decompression. This 5-year trial showed no benefit from early surgery when compared to conservative management. However, there was a trend toward better outcomes in those with superficial hemorrhage. There were also a high percentage of participant crossovers from the medical to the surgical arm upon rapid neurological decline.

Epidemiology impotence groups priligy 60 mg free shipping, pathophysiology erectile dysfunction shakes menu buy cheap priligy, diagnosis erectile dysfunction doctor patient uk order 30 mg priligy overnight delivery, and management of intracranial artery dissection doctor for erectile dysfunction philippines purchase on line priligy. Outcomes and prognostic factors of intracranial unruptured vertebrobasilar artery dissection impotence tumblr order cheap priligy on-line. The natural history of radiographically defined vertebrobasilar nonsaccular intracranial aneurysms protein shake erectile dysfunction order priligy without prescription. Non-saccular vertebrobasilar aneurysms and dolichoectasia: a systematic literature review. Cardiogenic stroke occurs when (1) clots embolize from the heart and reach the brain via the arterial circulation, or (2) as a result of severe heart failure and cerebral hypoperfusion. Medications as well as certain cardiac procedures performed to treat heart disease can lead to adverse neurological complications such as ischemic stroke. For example, there is a strong correlation between cardiac disease and cerebral atherosclerosis, which escalates the risk of thrombotic stroke. Cardiac sources of embolism include blood clots, tumor fragments, infected and noninfected vegetations, calcified particles, and atherosclerotic debris [2]. As more advanced diagnostic techniques have been developed, more causative cardiac abnormalities and their association with stroke have been recognized [1]. Conditions that are known to lead to systemic embolization may be subdivided into a high-risk and a low-risk groups based on their embolic potential (Table 85. Undetermined (cryptogenic) cause (no cause identified, more than one cause, or incomplete investigation). The risk of embolism also varies within individual cardiac abnormalities depending on many factors. Additionally, it is important to remember that the presence of a potential cardiac source of embolism does not definitely indicate that the stroke was caused by an embolus from the heart. In the Lausanne Stroke Registry, among patients with potential cardiac embolic sources, 11% of patients had severe cervicocranial vascular occlusive disease (>75% stenosis) and 40% had mild to moderate stenosis proximal to brain infarcts [4]. Ventricular thrombi can also occur in patients with chronic ventricular dysfunction caused by coronary artery disease, hypertension, and dilated cardiomyopathy. Congestive Heart Failure: Current data indicates that congestive heart failure affects an estimated 5. Patients with ischemic and nonischemic dilated cardiomyopathy have a similarly increased stroke risk by a factor of 2 to 3, accounting for an estimated 10% of ischemic strokes [1,5,7]. The 5-year recurrent stroke rate in patients with cardiac failure has been reported to be as high as 45% [1,5,8]. Prosthetic Valves and Devices: the magnitude of risk for brain embolism from a diseased heart valve depends on the nature and severity of the disease, as well as the surgical procedure performed. Intracardiac Vegetation Emboli, including ischemic strokes, are common in patients with infective endocarditis [1]. Specific vegetation characteristics, such as large size, mobility, and location on the mitral valve, as well as vegetations related to a Staphylococcus aureus infection, are associated with an increased risk of symptomatic embolism [9,10]. An infected embolus can also cause a hemorrhagic infarction with massive bleeding in patients who are on anticoagulation at the time of the event [1,9,10]. Warfarin does not prevent embolization and is contraindicated in patients with endocarditis and known cerebral embolism, unless indicated in patients with prosthetic valves or pulmonary embolism [1]. Intracardiac Tumors Primary cardiac tumors, which can be associated with cerebral embolism and stroke, are extremely rare with atrial myxomas constituting over half of the cases. Papillary fibroelastoma is another histologically benign tumor associated with embolism. Embolic events have long been thought to occur in patients with cardiac tumors secondary to embolization of tumor fragments [1,11]. Aortic valve and left atrial tumors pose the greatest anatomical risk for embolism. Furthermore, patients with smaller tumors, minimal symptomatology, and no evidence of mitral regurgitation also have a high risk of embolism. Cardiac tumors can be resected with low early mortality, and late survival after operation in the context of an embolic stroke is similar to patients with cardiac tumors who undergo resection for other indications [1,11]. Ulcerated atheromatous plaques are often found at necropsy in patients with ischemic strokes, particularly in patient with cryptogenic stroke [1,12]. In the setting of nonmobile protruding aortic arch atheroma, antiplatelet agents are the treatment regimen of choice for stroke prevention in patients with aortic arch disease [1,14]. Bilateral border-zone distribution strokes are traditionally attributed to systemic hypoperfusion. The weight of data suggests that most instances of hypoperfusion caused by cardiac pump failure cause either no symptoms or attacks of transient brain ischemia without resulting in major brain infarction. Brain perfusion during cardiac surgery is an important factor in predicting the presence and severity of ischemic brain damage after surgery. The clinical picture of watershed infarctions is often progressive or fluctuating. One characteristic feature is the occurrence of early-onset partial seizures, which occur more often with cortical watershed infarcts than in other forms of stroke [16,20]. Patients may become acutely comatose after receiving very large doses of intravenous lidocaine, with adverse reactions of sedation, irritability, twitching, and seizures. Amiodarone can cause ataxia, weakness, tremors, paresthesias, visual symptoms, a parkinsonian-like syndrome, and occasionally delirium, even at normal dosages [1]. Cerebral watershed or border zone infarcts involve the junction of the distal fields of two nonanastomosing arterial systems, which are hemodynamic risk zones, and account for up to 10% of all strokes [16,19]. Cortical: occurring at the junction between cortical territories of the anterior, middle, and posterior cerebral arteries. Subcortical: occurring in the white matter between the deep and superficial perfusion systems of the middle cerebral artery [16,17]. Potential mechanisms for ischemic cerebrovascular events during cardiac angiography include cerebral embolism from a local clot, catheter tip thromboembolism, atherosclerotic plaque or cholesterol embolism, air emboli, arterial vasospasm, and/or hypotension [1,21]. Mechanism of intracranial hemorrhage is suspected to be related to intraprocedural anticoagulation. In severely affected patients, reduction of cardiac output may elevate the risk of vasospasm-induced cerebral ischemia [1,26]. Electrophysiologic Procedures and Electrical Cardioversion Thromboembolic stroke can be a complication of cardiac electrophysiologic procedures, including radiofrequency catheter ablation of arrhythmia. Anticoagulation before and after cardioversion lowers the risk of embolism [1,21]. Arrhythmias Various cardiac arrhythmias have been found in stroke patients, most frequently sinus bradycardia, sinus tachycardia, and premature ventricular contractions [1,22]. Some arrhythmias are manifestations of primary cardiac problems, but others are undoubtedly secondary to brain lesions. The incidence of sinus tachycardia and bradycardia is maximal on the first day after intracerebral hemorrhage [27]. Arrhythmias are more common in patients who have primary brainstem lesions or brainstem compression [1]. The name takotsubo cardiomyopathy was initially coined because the shape of the end-systolic left ventriculogram was thought to resemble an octopus catcher used in Japan [29]. In ischemic stroke patients, takotsubo cardiomyopathy occurs soon after stroke onset, is commonly asymptomatic, and is associated with insular damage [30]. In some patients with excessive surgical risks, anticoagulation may represent an alternative treatment. Clearly, optimal medical therapy should be instituted preoperatively and continued after surgery [1]. Systemic Arterial Hypertension Acute and chronic high blood pressure damages deep, penetrating small intracranial arteries, accelerates the development of atherosclerosis in the extracranial and large intracranial arteries, and results in ischemic syndromes of lacunar infarction, diffuse white matter ischemic changes, and intracerebral hemorrhage. The most relevant imaging method is the chest X-ray, where diffuse hyperintensive infiltrates in both lungs are apparent. Disorders of consciousness, syncope, and seizures frequently occur at the onset of aortic dissection. Aortic dissections can affect the outflow of supra-aortal, spinal, as well as extremity arteries, leading to a variety of neurological symptoms including disturbances of brain, spinal cord, or peripheral nervous system. Symptoms of acute ischemic stroke are the most common initial neurological finding. Spinal cord ischemia on the basis of aortic dissection is a much rarer syndrome and more common with distal aortic dissections. Involvement of the peripheral nerves can occur as ischemic neuropathy, ischemic plexopathy, or due to the direct compression of a nerve by the enlarging false arterial lumen. It is important to recognize aortic dissection in ischemic stroke patients in particular. Thrombolysis as an emergency stroke therapy may be life threatening for these patients, because of the high risk of fatal rupture of the ascending aorta or the aortic arch or of dissection into the pericardium. Routine chest X-ray and being alert to physical examination findings such as hypotension, asymmetrical pulses, or cardiac murmur may reduce the risk of delayed diagnosis or misdiagnosis. However, it has been observed that patients with lateral medullary and pontine infarcts die unexpectedly and also have a high incidence of autonomic dysregulation. Postmortem analysis of stroke patients who died suddenly without any evidence of coronary disease often shows myocytolysis and myofibrillar degeneration [33]. The most frequent cause of death in stroke patients is coronary artery disease, and extra- and intracranial arterial atherosclerosis is common in patients with coronary artery disease [1]. Guidelines for the use of echocardiography in the evaluation of a cardiac source of embolism. Cardiac sources of embolism and cerebral infarction: clinical consequences and vascular concomitants. Heart disease and stroke statistics-2013 update: a report from the American Heart Association. Predictors of mortality and recurrence after hospitalized cerebral infarction in an urban community. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. Atherosclerosis of the thoracic aorta and systemic emboli: efficacy of anticoagulation and influence of plaque morphology on recurrent stroke. The pathophysiology of watershed infarction in internal carotid artery disease (review of cerebral perfusion studies). Improvement of outcomes after coronary artery bypass: a randomized trial comparing intraoperative high vs. Watershed infarctions are more prone than other cortical infarcts to cause early-onset seizures. Cardiac and cardiovascular findings in patients with nervous system disease: strokes. Correlation of cardiac arrhythmias with brainstem compression in patients with intracerebral hemorrhage. Transient left ventricular dysfunction under severe stress: brain-heart relationship revisited. Aortic arch disease has been a subject of study for many years as a potential source of embolic stroke and is common in individuals over 60 years of age. Complex, ulcerated plaques are common, and mural thrombi can superimpose upon ulcers. Mural thrombi can occasionally be loosely adherent and mobile, increasing the risk of embolization to the brain, retina, or peripheral organs. Large plaques, defined as those 4 mm in size, have been shown to further increase the risk of stroke [1,2] and have been linked to a 2. The presence of complex features such as ulceration has also been suggested to further increase the risk of stroke in individuals with aortic arch disease [4]. Atherosclerotic disease of the aortic arch has thus been considered a potential source of cerebral ischemia in patients with cryptogenic stroke. Varying degrees of aortic arch disease are found in about 1 in 4 patients with an embolic event [5]. Atherosclerosis burden of the thoracic aorta, particularly in lesions with complex characteristics and size of >4 mm, has been considered a major risk factor for both cerebral ischemia and peripheral embolization [6]. Interestingly, lesions in the descending thoracic aorta, located distal to the anatomical branch points of the great vessels, have been considered a potential source of cerebral embolism through retrograde aortic flow [7,8]. Retrograde flow-related emboli have been suggested as a potential cause of retinal or cerebral infarcts in 24% of patients with cryptogenic stroke [9]. Stroke prevention in patients with atherosclerotic burden of the aortic arch has been controversial, and there is no known optimal stroke prevention strategy. In this chapter, we will summarize some seminal studies along with some of the most recent studies investigating aortic arch disease as a source of ischemic stroke. Aortic Arch Plaques as a Risk Factor for Ischemic Stroke Aortic arch plaques >4 mm in thickness are found in one-third of patients with stroke of an unknown source, which accounts for about one-third of the total ischemic stroke population over the age of 60 years [10]. It has also been reported that the association between aortic arch atheroma and stroke is stronger when the size of plaque is 4 mm [10]. Caplan [13] reports that large protruding plaques in the ascending aorta and transverse arch are a major source of aortoembolic stroke, and the risk increases with mobile plaques.

This can impede the normal flow of interstitial fluid through the brain erectile dysfunction frequency age priligy 90 mg on line, contributing to the buildup of edema and also delaying the resolution of that edema erectile dysfunction pills at cvs priligy 30mg with visa. Mixed Edema It should be noted that cerebral ischemia and intracerebral hemorrhage have mixed forms of edema erectile dysfunction protocol amazon order cheap priligy online, with both vasogenic and cytotoxic components erectile dysfunction pump manufacturers order 30 mg priligy with amex. The relative importance of these components to brain edema formation varies with time and the nature of the stroke erectile dysfunction adderall 60mg priligy fast delivery. In addition causes of erectile dysfunction in 40 year old discount 30mg priligy fast delivery, these changes will enhance fluid outflow from the brain by reducing compression of the extracellular and perivascular spaces. Diffusion-weighted imaging and apparent diffusion coefficient sequences can aid in distinguishing cytotoxic edema, with restricted diffusion, from vasogenic edema, with normal or increased diffusion [9]. The only current clinically effective therapy for cerebral ischemia is early reperfusion with either tissue plasminogen activator or thrombectomy. Early reperfusion can limit parenchymal cell injury and, thereby, cytotoxic edema. As noted earlier, brain edema formation is associated with ion shifts between blood and brain and between the brain extracellular and intracellular spaces. A number of approaches have been tried to modulate those changes preclinically [7]. Edema can result from events at the cerebrovasculature and/ or in parenchymal cells. Although treatments have not changed substantially in decades, a greater understanding of the underlying pathology suggests several new promising targets. Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence. In otherwise normal brain, all transmembrane ion and water balances are restored within less than a minute, which is even more metabolically costly than seizures. Disruption of ion homeostasis in the neurogliovascular unit underlies the pathogenesis of ischemic cerebral edema. The depolarization and ion fluxes create a characteristic 20- to 30-mV extracellular negative slow potential shift. Nevertheless, the term spreading depression has historical significance, and is well recognized and widely used by the scientific and clinical Primer on Cerebrovascular Diseases, Second Edition dx. Spreading depression: from serendipity to targeted therapy in migraine prophylaxis. Note the terminal depolarization at the end of the recording in both electrodes sequentially (arrowhead). They have been shown to stimulate neurogenesis, and may even promote angiogenesis. In moderately ischemic penumbra (c), the response is mainly a monophasic hypoperfusion. This is in part because, unlike in human brain, animal models of other brain injury states. Once triggered, they propagate through and beyond the ischemic penumbra in virtually all species studied to date, including human. Hence, they can only be detected reliably using intracortical or subdural electrodes. There is considerable interest in noninvasive detection methods using surface electrophysiology with data processing, or optical tools such as near-infrared or diffuse correlation spectroscopy. Recurrent spreading depolarizations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex. Inverse neurovascular coupling to cortical spreading depolarizations in severe brain trauma. Of the known risk factors for cerebrovascular disease, hypertension is associated with some of the most profound effects. However, efforts for clinical translation have gained momentum thanks to technological advances in the field of neurocritical care. Radial, spiral and reverberating waves of spreading depolarization occur in the gyrencephalic brain. Supply-demand mismatch transients in susceptible peri-infarct hot zones explain the origins of spreading injury depolarizations. Chronic hypertension is very common in adults and is currently the number one risk factor for overall disease burden and health loss worldwide. In this chapter, we briefly highlight the effects of acute and chronic hypertension on large and small vessels in Primer on Cerebrovascular Diseases, Second Edition dx. The box in the lower portion of the figure lists examples of key vascular changes that occur in hypertension. As noted by others, the term small vessels refer to small arteries and arterioles within the pial circulation on the brain surface, along with arterioles, capillaries, and venules within the parenchyma [1,3]. This collective process normally occurs in a controlled spatial and temporal manner to match delivery of glucose, oxygen, and other nutrients with variations in cellular activity. In addition, levels and progression of hypertension are modified by sex-dependent mechanisms, genetics and epigenetics, diet, metabolism, the environment, and aging. In addition to insight obtained clinically, experimental models are being commonly used in an effort to better define these relationships and include various genetic, renal, and pharmacological models of hypertension. Endothelium affects vessel diameter through its influence on underlying smooth muscle via several endothelium-dependent mechanisms. In this role, endothelial cells are critical mediators of vasodilator responses to physical forces (shear stress), neurotransmitters, metabolic factors, and therapeutic agents. In addition, endothelial cells control vascular permeability (see later discussion) and play a fundamental role in thromboresistance through antiplatelet, antithrombotic, and fibrinolytic mechanisms [6]. The loss of normal endothelium-dependent mechanisms is a key (often initiating) event in the pathogenesis of vascular disease [4,7]. The phrase endothelial dysfunction describes collective endothelial-based abnormalities that promote oxidative stress, low-grade inflammation, increased vascular tone and permeability, atherosclerosis, and thrombosis. It is particularly noteworthy that in addition to regulating local perfusion, changes in the endothelial control of vascular tone in disease are predictive of clinical events including stroke [4,7]. Hypertension affects each element of endothelial function in large arteries and microvessels. In relation to vascular function, chronic hypertension is associated with impairment of both basal and agonist-induced endothelium-dependent vasodilation [4]. Both low-grade inflammation and oxidative stress within the vessel wall are commonly seen in animal models and humans with hypertension. The progression of atherosclerosis is accelerated in both cerebral and peripheral blood vessels. Acute hypertension (or hypertension emergencies) presents additional cerebrovascular and neurological challenges. The presence of preexisting chronic hypertension is a key risk factor for acute hypertension. In addition, both normotensive and chronically hypertensive persons may exhibit periods of acute hypertension as a result of myocardial infarction, aortic dissection, drug abuse or misuse, head injury, and hypertensive disorders of pregnancy, among other causes. Acute hypertension also affects endothelial integrity, vascular tone, and vascular permeability. Injury to endothelium following rapid increases in arterial pressure occurs throughout the cerebral circulation including in arterioles, capillaries, and venules. Such a sequence of events is seen in hypertensive encephalopathy and posterior reversible encephalopathy syndrome. Neurovascular Coupling Neurovascular coupling is the term used to describe alterations in local perfusion that occur in response to changes in neuronal activity. Also known as functional hyperemia, neurovascular coupling involves the integration of multiple signaling molecules (or events) and cell types. Intact neurovascular coupling requires an integrated multicellular response to provide the perfusion needs that result from acute and often changing focal neuronal activation. In addition to local perfusion changes driven by neurons and astrocytes, dilation of arterioles and arteries upstream from the site of activation also occurs via endothelium-dependent mechanisms [8]. Thus the endothelial dysfunction noted earlier may also contribute to diminished neurovascular coupling. The identity and relative importance of various cell types and signaling molecules and their contribution to neurovascular coupling are subjects of debate, particularly in regions like the somatosensory cortex (where most studies have focused). Mechanisms that underlie neurovascular coupling also vary regionally and may be better defined in the cerebellum, basal forebrain, and hippocampus. Regardless of the underlying mechanism(s), a common experimental finding is impairment of neurovascular coupling in both experimental models (genetic and pharmacological) and humans with chronic hypertension. Along with endothelial dysfunction and hypoperfusion, impaired neurovascular coupling is thought to contribute to tissue injury, loss of function, and cellular degeneration over time. In relation to the fundamental vascular changes described earlier, some common underlying mechanisms may be involved [4,9]. Lastly, the immune system has emerged as a key contributor to mechanisms that produce hypertension. Myogenic tone (tone generated by a vessel when pressurized) and myogenic responses (changes in tone that occur with changes in transmural pressure) are seen through a large portion of the brain circulation: cerebral arteries, and pial and parenchymal arterioles. Myogenic mechanisms contribute to autoregulation in that these vessels constrict with increases in pressure and dilate with reductions in transmural pressure [10]. Size-dependent responses to pressure have been described both in vivo and in vitro, with greater levels of myogenic tone being seen in pial and parenchymal arterioles than in large cerebral arteries [5]. Myogenic mechanisms have been studied widely using isolated vessels and it is well established that the cellular basis for the response resides in vascular muscle [10]. For example, what actually senses changes in pressure to then activate downstream pathways that alter vessel diameter remains unsettled. Key intermediates may include integrins, G-proteins, ion channels and other regulators of membrane potential, kinase-mediated events, and ultimately contractile proteins. Myogenic tone is increased in isolated arteries and arterioles from hypertensive models. This is a welldescribed clinical problem in patients with essential or primary hypertension. The underlying causes for the shift are not entirely clear, but are thought to result collectively from both functional and structural changes that occur in the vasculature. First, increases in the cross-sectional area of the vessel wall (or hypertrophy), are commonly seen and represent an adaptive response that reduces wall stress during hypertension. Depending on specific features, hypertrophy may also encroach on the vessel lumen and thus increase vascular resistance. Increases in the cross-sectional area of the vessel wall occur in many models of hypertension and are present in hypertensive humans. In contrast, hypertension can also promote degeneration and thinning of the vessel wall over time contributing to leakage of molecules from the circulation along with microbleeds and intracerebral hemorrhage. Key events that underlie these changes include oxidative stress along with changes in activity of matrix metalloproteinases and endogenous tissue inhibitors of metalloproteinases in vascular cells and the extracellular matrix. Second, a three-dimensional rearrangement of the vessel wall occurs known as inward remodeling. Although endothelial cells are the site of the barrier, its properties and function are influenced by other cell types including astrocytes and pericytes, additional cells in what is often referred to as the neurovascular unit. Inward vascular remodeling is commonly seen in arterioles and small arteries in some, but not all forms of hypertension. There is evidence that similar remodeling occurs in small cerebral arteries in humans. The two changes in vascular structure outlined earlier are both adaptive and maladaptive. However, the reduction in lumen diameter also increases minimal vascular resistance, thus limiting vasodilator responses and collateral-dependent perfusion during ischemia. Third, rarefaction has been described in arterioles and capillaries in experimental models and humans with hypertension. Reductions in both collateral number and diameter have been described in models of hypertension [13]. Resistance of cerebral vessels is increased during chronic hypertension, including when the vasculature is maximally dilated. As vascular disease progresses, the process impacts other cell types in the brain including gray and white matter. It is through such effects that hypertension is believed to promote dementias and other forms of neurological dysfunction. Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury. Vascular resistance is elevated so vasodilator reserve is reduced including in collateral vessels. In the cerebrovasculature, accelerated atherosclerosis of the large vessels is believed to contribute to complications, such as stroke and transient ischemic attacks. There is growing body of evidence that microvascular disease also contributes to stroke and other neurological diseases including Alzheimer disease and vascular cognitive impairment [1]. This chapter will summarize the epidemiological data on diabetes and cerebrovascular diseases with a focus on stroke and cognitive impairment and discuss the impact of diabetes-mediated pathological changes in cerebrovascular function and structure on stroke and cognitive impairment in preclinical models. As reviewed in 2012, determining the effect of glycemic control on stroke prevention has been challenging but evidence from multiple trials suggests that tight glycemic control reduces the risk of cerebrovascular disease and it takes many years of follow-up to demonstrate this benefit in patients [1]. In addition to a higher risk, acute and long-term outcomes of stroke are also worse in patients with diabetes.

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