Stroke clinical presentation

The NINDS rt-PA smdy was divided into two parts. NINDS part I included 291 patients and NINDS part II included 333 patients. In both parts, acute ischemic stroke patients presenting within 3 hours of symptom onset were randomized to placebo versus treatment with the human rt-PA Alteplase (Activase). The dose was 0.9 mg/kg (maximum dose 90 mg), with 10% of the total dose given as a bolus and the remaining 90% infused over 60 minutes. Inclusion and exclusion criteria for both parts are listed in Table 3.2. These criteria are now the standard clinical criteria used to determine IV rt-PA eligibility in acute stroke patients. 

For some of these diseases, such as hypertension and heart disease, drugs such as ACE inhibitors and beta-blockers are available for treatment. For some other diseases, such as Alzheimer s disease, more effective drugs have yet to be discovered. For stroke, two late stage (Phase III) trials of NXY-059 and desmoteplase failed to meet the trial criteria. Other clinical trials in progress for ischemic stroke are presented in Table 11.1. 

TIA-related infarctions on DWI can be predicted on the basis of certain clinical TIA features. Transient motor symptoms, preceding non-stereotypic attacks, the presence of an established cause of stroke, and presentation with aphasia are independent predictors of infarction on DWI (Ay et al. 2002 Crisostomo et al. 2003). In contrast, limb paresthesias, slurred speech, and brief attacks of dizziness or imbalance are not associated with occurrence of infarction. Of note, most symptoms that are not associated with infarction on DWI are based on patients subjective feelings and sensations in contrast to motor deficit or aphasia, it is not possible to objectively assess such symptoms and mark the brain as their origin. Of particular relevance to this point is that, according to a recent study, the independent predictors of infarction on DWI such as motor deficit and speech impairment are also independently associated with increased risk of stroke after TIA (Johnston et al. 2003), suggesting a potential role for DWI in the risk stratification for stroke following TIA. 

A 70-year-old man developed lithium intoxication after a transient ischemic attack (174). He had a bradycardia (35-40/minute) and episodes of sinoatrial block. The clinical presentation was suggestive of a stroke. 

Among the clinical indications for aspirin, the dose for prevention of stroke in patients following a transient ischemic attack or initial minor stroke is presently disputed, hi this respect, direct con iaiisons reveal no diiforences in efficacy between 300 mg and 1200 mg daily or between doses of 30 and 283 mg daily, though a small sample size was involved (60,61). h should also be noted that studies in which patients on larger aspirin doses were seen to do better also received another antiplatelet diug (62). 

Antithrombotic therapy is used in myriad CV diseases such as atrial fibrillation, heart failure, valve replacement, peripheral vascular disease, and stroke. This presents an ideal setting for a pharmacist-managed antithrombosis clinic. Today, many institutions have antithrombosis clinics managed by clinical pharmacists this trend continues to grow. 

Atrial myxoma is a rare atrial tumor that causes multiple emboli of either thrombus or myxomatous tissue. When myxomatous material is embolized from the left atrium into the brain arteries, they may cause the formation of multiple distal cerebral aneurysms with risk of hemorrhage [46]. Papillary fibroelastomas are rare benign cardiac tumors usually involving a heart valve. They are small vascular growths with marked papillary projections. They usually grow on the aortic or mitral valves. The tumor consists of fibrous tissue surrounded by an elastic membrane, which in turn is covered by endothelium. One of the most conunon clinical presentations is of transient ischemic attack or stroke [47,48]. 

Subarachnoid hemorrhage (SAH) is most commonly caused by rupture of an intracranial aneurysm. It can produce vasospasm that may cause ischemia and infarction. Currently, vasospasm has surpassed rebleeding as the most important complication after rupture of an aneurysm. Vasospasm due to SAH is thought to occur in the majority of cases of SAH (angiographic vasospasm is detectable in perhaps as many as 60-70% of patients after subarachnoid hemorrhage), but is symptomatic only in about a third of this population [81]. Symptomatic vasospasm carries a 15% to 20% risk of stroke or death. Vasospasm peaks around 1 week after SAH, but it can be seen as early as 3 days or as late as 3 weeks after the initial event [82], The underlying mechanisms are not understood, but vasospasm is clearly related to the amount of blood and its location in the subarachnoid space. Clinical symptoms generally develop slowly over a period of several hours to 1 or 2 days however, clinical evolution can be rapid in the onset with a stroke-like presentation [81, 82]. 

Identifies patients with symptoms of acute stroke based on clinical presentation or entry notification from prehospital EMS personnel... 

Mast H, Mohr JP, Osipov A et al. (1995) Steal is an unestablished mechanism for the clinical presentation of cerebral arteriovenous malformations. Stroke 26 1215-1220... 

The toxicity of ephedrine is closely related to adverse cardiovascular events, since the clinical presentation of toxicity reflects the sympathomimetic activity of these agents. The adrenergic effects can shorten cardiac refractory periods, permitting the development of reentrant cardiac arrhythmias. The worst complication related to the use of ephedrine is thrombotic stroke, presumably resulting from vasoconstriction of large cerebral arteries that in turn leads to local thrombosis [71]. Other adverse effects include hypertension, diaphoresis, hypothermia, and agitation. The best treatment in an overdose is the rapid identification of the symptoms followed by supportive management. 

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

This section will review the phase III clinical trials of IV thrombolytic agents for acute ischemic stroke, organized by the type of agent and the time window from stroke onset to study drug delivery (Table 3.1). The 1995 National Institute of Neurological Disorders and Stroke (NINDS) rt-PA trial is presented first because it showed that IV rt-PA, given within 3 hours of stroke onset, reduced stroke-related disability. This trial was the basis for the United States Food and Drug Administration (FDA) approval for rt-PA for use in acute ischemic stroke. 

Internal Carotid Artery Occlusion Acute stroke due to a distal ICA T (T = terminus) occlusion carry a much worse prognosis than MCA occlusions. In a recent analysis of 24 consecutive patients (median NIHSS 19) presenting with T occlusions of the ICA who were treated by lAT using urokinase at an average of 237 minutes from symptom onset, only four patients (16.6%) had a favorable outcome at 3 months. Partial recanalization of the intracranial ICA was achieved in 15 (63%), of the MCA in 4 (17%), and of the ACA in 8 patients (33%). Complete recanalization did not occur. The presence of good leptomeningeal collaterals and age <60 years were the only predictors of a favorable clinical outcome. New treatment strategies, such as the combination of IV rt-PA and lAT, or the use of new mechanical devices may improve the outcome in these patients. 

MN is a 48-year-old man with a history of hypertension and smoking who presents to the clinic for evaluation of his cholesterol. He denies having chest pain or history of myocardial infarction, stroke, or peripheral artery disease. He has no siblings and both parents are alive with no history of CHD. MN says that he smokes about 1 pack of cigarettes per day. He does not exercise on a regular basis. He has been fasting for approximately 11 hours. 

At present, a multitude of novel sodium channel blockers are in preclinical and clinical development. However, most compounds have been applied to many indications, especially epilepsy and stroke. This review includes only those substances for which activities in pain models have been reported. 

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