Stroke acute treatment

Hacke W. The results of the joint analysis of two phase II trials on desmoteplase in acute ischemic stroke with treatment 3 to 9 hours after stroke onset. 14th European Stroke Conference. Bologna, Italy, May 2005. 

Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage a phase II randomized placebo-controlled trial. Stroke 2005 36 1627-1632. 

Aleksic M, Rueger MA, Lehnhardt EG, Sobesky J, Matoussevitch V, Neveling M, Heiss WD, Bmnkwall J, Jacobs AH. Primary stroke unit treatment followed by very early carotid endarterectomy for carotid artery stenosis after acute stroke. Cerebrovasc Dis 2006 22 276-281. 

The Heparin in Acute Embolic Stroke Trial (HAEST) was a multicenter, randomized trial of the effect of LMWH (dalteparin 100 lU/kg sc twice daily) or aspirin (160 mg once daily) for the acute treatment of 449 patients with ischemic stroke and atrial fibrillation (AF). The primary outcome was the rate of recurrent stroke within 14 days. No difference in rates of early recurrence (8.5% dalteparin treated vs. 7.5% aspirin treated) or good 3-month functional outcome was found. The frequency of early slCH was 2.7% on dalteparin versus 1.8% on aspirin. 

Middle cerebral artery embolectomy remains controversial in the acute treatment of stroke. Patients who may benefit from this procedure are those who have good collateral circulation and can be operated on within the first few hours after the onset of symptoms. 

Alteplase (rt-PA Activase) is an IV thrombolytic (fibrinolytic) that was approved for acute stroke treatment in 1996 based on the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial.10 The current American Stroke Association guidelines include alteplase as the only Food and Drug Administration (FDA) approved acute treatment for ischemic stroke and strongly encourage early diagnosis and treatment of appropriate patients.11... 

Streptokinase is not indicated for use in acute ischemic stroke treatment. Three large randomized controlled trials evaluating streptokinase were stopped early due to a high incidence of hemorrhage in the streptokinase-treated patients.14-16 At the present time, there is no indication for the use of streptokinase or thrombolytics other than alteplase in the acute treatment of ischemic stroke. 

Acute neurologic events, such as stroke, will require hospitalization and close monitoring. Patients should have physical and neurologic examinations every 2 hours.27 Acute treatment may include exchange transfusion or simple transfusion to maintain hemoglobin at around 10 g/dL (100 g/L or 6.2 mmol/L) and HbS concentration at less than 30%. Patients with a history of seizure may need anticonvulsants, and interventions for increased intracranial pressure should be initiated if necessary. Children with a history of stroke should be initiated on chronic transfusion therapy. Adults presenting with ischemic stroke should be considered for thrombolytic therapy if it has been less than 3 hours since the onset of symptoms.6,27... 

Aspirin has gained additional importance in the last few years due to its inhibition of platelet aggregation. Low dose treatment with aspirin leads to irreversible acetylation of COX-1 in platelets and is used in the acute treatment and chronic prevention of myocardial infarction and stroke (Higgs et al., 1987). 

Clinical use Acetylsalicylic acid is the prototype of a nonsteroidal anti-inflammatory drug and is used in a large number of inflammatory and pain indications including musculoskeletal, soft tissue and joint disorders, headache, dysmenorrhoea and fever (Symposium on new perspectives on aspirin therapy 1983, various authors). Furthermore, acetylsalicylic acid is used as an antiplatelet drug in the acute treatment of myocardial infarction in combination with thrombolytics and for the prevention of myocardial infarction and stroke (Patrono, 1994). 

Preventing misdiagnosis of stroke is increasingly important in the acute stage of the disease when thrombolytic or interventional therapies with potential adverse effects are considered. Misdiagnosis may have serious consequences A misdiagnosed patient may be subject to unjustified thrombolytic therapy and encounter an elevated bleeding risk. Or, another serious nonvascular disorder maybe misclassified as stroke and treatment options maybe missed. 

Knowledge of the anatomy of the blood supply of the brain is often helpful in understanding the etiology and mechanisms of TIA and stroke, which enable accurate targeting of acute treatment and secondary prevention. An awareness of the mechanisms underpinning the regulation of cerebral blood flow allows the clinician to identify patients at risk of stroke and assess the possible effects of treatments. 

Wintermark M, Meuli R, Browaeys P et al. (2007). Comparison of CT perfusion and angiography and MRI in selecting stroke patients for acute treatment. Neurology 68 694-697... 

I Acute treatment of transient ischemic attack and minor stroke... 

This chapter will summarize the aspects of acute treatment that are specific to TIA and minor stroke. 

Acute treatment of major stroke general principles... 

Kwiatkowski TG, Libman RB, Frankel M (1999). Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group. New England Journal of Medicine 340 1781-1787 Lees KR, Zivin JA, Ashwood T et al. (2006). Stroke-Acute Ischemic NXY Treatment (SAINT I) Trial Investigators. NXY-059 for acute ischemic stroke. New England Journal of Medicine 354 588-600... 

Patients with acnte neurologic events must be hospitalized and monitored closely. Physical and neurologic examination should be performed every 2 hours. Acute treatment for children should include exchange transfusion or simple transfusion to maintain Hgb at approximately 10 g/dL and HbS less than 30%, anticonvulsants for patients with a history of seizure, and therapy for increased intracranial pressure if needed. Chronic transfusion therapy should be initiated for children with ischemic stroke as discussed above. In adults presenting with ischemic stroke, thrombolytic therapy should be considered if less than 3 hours since onset of symptoms. " ... 

The results of the 2008 European Cooperative Acute Stroke Study (ECASS 111) expanded the 3-h time window for IV thrombolysis and revealed that although safe and effective up to 4.5 h after stroke onset, treatment benefits roughly one-half as many patients as those treated within 3 h [2, 158, 159]. Hence, the ratio between the hemorrhagic risk of treatment and the potential clinical benefit of treatment becomes a more critical consideration as the time window for therapy is expanded with newer IV and lA techniques. It is the mismatch between the size of the infarct core (proportional to hemorrhagic risk) and the size of the ischemic penumbra (proportional to potentially salvageable tissue), as determined by CTP, that provides an imaging measure of this risk-to-benefit ratio. Evidence suggests that core/penumbra mismatch may persist up to 24 h in some patients [160,161]. 

Hacke, W. The Results of the Joint Analysis of Two Phase II Trials on Desmoteplase in Acute Ischemic Stroke with Treatment 3 to 9 Hours after Stroke Onset, in 14th European Stroke Conference. May, 2005. Bologna, Italy. 

Ticlopidine and clopidogrel are thienopyridines, which through inhibition of platelet aggregation prolong bleeding time and delay clot retraction. The thienopyridines are prescribed for reduction of myocardial infarction and stroke, for treatment of peripheral arterial disease, and in combination with aspirin for acute coronary syndromes. This latter utility appears to result from the fact that both aspirin and the thienopyridines block major amplification pathways, leading to platelet aggregation... 

A study in 14 treatment-resistant depressed patients aged between 61 and 82 found that 7 showed eomplete improvement and 3 showed partial improvement, 3 to 21 days after lithium was added to treatment with the tricyclic or related antidepressants. Lithium adverse effects occurred in 6 patients 4 of whom stopped lithium as a result. One of them was successfully restarted at a lower dose. Tremor was the most frequent adverse effect, and reversible neurotoxicity with a stroke-like syndrome was the most severe. The antidepressants used were amitriptyline, doxepin, maprotiline and trazodone. A meta-analysis of 9 studies on the acute treatment of unipolar or bipolar depression indicated that the combined use of a mood stabiliser (lithium in 6 studies) and a tricyclic antidepressant was associated with an increased risk of switches into (hypo)mania, when compared with a mood stabiliser alone. It was suggested that monotherapy with a mood stabiliser should be tried to see if it is effective, before adding an antidepressant. Tricyclics were considered to be second-line antidepressants, with SSRIs the preferred choice. ... 

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