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V./4.8.: Treatment
V./4.8.1.: Specific treatment of acute ischemic stroke
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Thrombolytic therapy with recombinant tissue plasminogen activator agent (rt-PA) is the only effective therapeutic method in acute ischemic stroke. The dose of the intravenous rt-PA is 0.9 mg/kg (max 90 mg), 10% of which have to be given as a shot followed by continuous infusion of the rest in 60 minutes. The treatment has to be started in 3 hours after stroke onset. It can be effective beyond 3 hours, recently (2012) is 4.5 hours time window is recommended. Multimodal neuroimaging (perfusion CT scan and diffusion MRI) can also help in selecting these patients. One study analysing consecutive data on rt-PA found that prognosis depends on the early begin of thrombolysis even in the 3 hour time window. This study also proved the advantage of rt-PA treatment in 4.5 hours after stroke onset.
Blood pressure have to be controlled and below 185/110 mmHg before the start of thrombolysis. Intravenous rt-PA can be used in patients with epileptic seizure and stroke, if neurological deficit is clearly caused by acute ischemic lesion. Treating patients below 18 years or above 80 years of age is currently off-label, but in some cases, intravenous rt-PA may be used in these groups. Intraarterial thrombolysis can be executed in 6 hours in cases of acute MCA or basilar artery strokes. Acut basilar artery occlusion is treated by intraarterial thrombolysis or alternatively intravenous thrombolysis beyond 3 hours.
In 48 hours after stroke onset aspirin have to be given (dose needed to saturation: 160-325mg). In case of rt-PA treatment, any kind of aspirin or antithrombotic agent is prohibited for 24 hours. In acute ischemic stroke, no other antithrombotic agent (single or combination) is recommended than aspirin. Heparin, low molecular weight heparin (LMWH) or heparinoid given early is not recommended in acute ischemic stroke. There are no therapeutic guidelines recommend the use of neuroprotective agents in acute ischemic stroke.
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Formerly used streptokinase is prohibited since the marked increase in the risk of bleeding and death. Recent investigations are conducted with intravenous desmoteplaze in patients with diffusion-perfusion mismatch in 3-9 hours after stroke onset. Pro-urokinase for Acute Ischemic Stroke study, a randomized clinical trial showed significantly better results using pro-urokinase (pUK) in proximal MCA occlusion with 6 hours time window, compared with placebo treatment. Apart from that, there are only observational or non-randomized studies using rt-PA or other agents in this indication. Intraarterial urokinase or rt-PA got good results in acute basilar artery occlusion. Embolectomy, mechanical remove of the embolus is a new therapeutic choice.
In case of large hemispheric infarction, space occupying brain swelling is the leader cause of early progression and death. It is called malignant media syndrome or malignant MCA infarction, and usually caused by ICA or MCA occlusion. Usually starts in 2-5 days of the stroke onset, but in 1/3 of the patients it could progress even in the first 24 hours. In that case, if the patient is below 60 years of age surgical decompressive craniectomy (hemicraniectomy) have to be done in 48 hours. Osmotherapeutic agents can be used to decrease intracranial pressure before operation.
V./4.8.2.: General treatment of acute ischemic stroke
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Patients with persistent and severe neurological deficit should be monitored for at least 72 hours: neurological symptoms, heart rate, blood pressure, temperature and oxygen saturation have to be observed. Electrolyte- and fluid balance have to be regularly monitored as well. Treatment of high blood pressure is not always recommended in acute stroke, only in case of extreme high values above 220/120 mmHg. Decreased blood pressure is preferable in severe heart failure, dissection of the aorta or in hypertensive encephalopathy. A sudden drop in blood pressure values should be avoided. Blood glucose is also necessary to check. Insulin treatment is adjusted if blood glucose level is above 10 mmol/l (180 mg/dl). Severe hypoglycaemia (blood glucose below 2.8 mmol/l or 50 mg/dl) also has to be corrected. Fever- temperature above 37.5 C) and infections should be treated.
Antithrombotic therapy is needed after the acute stage. Platelet aggregation inhibitors should be given to the patients does not need anticoagulant therapy. Aspirin and dipirydamol combination or clopidogrel treatment is recommended if possible. Aspirin monotherapy or triflusal is an alternative. Aspirin and clopidogrel combination is not routinely recommended in acute stroke, but in some specific condition such as unstable angina, non-Q myocardial infarction or recent stenting. Indication of anticoagulant therapy discussed in the chapter on secondary prevention.
V./4.8.3.: Treatment methods of carotid stenosis
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Carotid artery stenosis can be treated either conservatively or invasively. Invasive treatment methods are the carotid endarterectomy (CEA) and the endovascular intervention (percutaneous transluminar angioplasty with/without stenting- CAS). Occluded carotid vessel cannot be treated this way.
According to current guidelines, operating asymptomatic carotid stenosis is only recommended in patients with significant stenosis and high stroke risk. The severity of the stenosis should be above 80% and have to be operated in a specialized institution.
In case of 70-99% symptomatic carotid stenosis (e.g. after TIA or stroke with slight residual symptoms), CEA is recommended. If the patient has severe residual symptoms, operation is not recommended. Recent guidelines state, that vascular surgical treatment should be done the earliest possible after stabilization of symptoms, which ideally take place in two weeks. Thrombocyte aggregation inhibitors have to be taken before and after surgery. Concomitant contralateral occlusion of the ICA does not contraindicate CEA operation, but carries higher perioperative risk.
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CAS treatment is recommended in some patients with one of the following conditions: co-morbidity and contraindication of surgery, stenosis cannot be reached by surgical methods, tandem stenosis exist, restenosis after CEA operation or post irradiation stenosis. Endovascular treatment should be considered in case of symptomatic intracranial stenosis. Aspirin and clopidogrel combination pharmacotherapy should be followed right before the intervention and min 1 month, generally 3-6 months after.
Bilateral significant carotid stenosis or simultaneous occlusion and stenosis carry increased stroke risk. In these cases examination of the condition of the dominant hemisphere is outmost important. Examination of the cerebrovascular reserve capacity is also recommended with SPECT or TCD). Carotid artery surgery has to be done as soon as possible on the side, where reserve capacity is below 10%, if no other indication exists.
Surgical anastomosis between the temporal superficial artery and the MCA in case of MCA stenosis or occlusion is not effective in prevention of stroke.
Conservative treatment means, that the risk factors of atherosclerosis have to be surveyed and treated according to guidelines properly, until therapeutic goal is reached. Low dose aspirin is needed for patients with asymptomatic carotid stenosis of >50% to lower vascular risk.
V./4.8.4.: Secondary prevention
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Stroke or TIA patients have to be treated with thrombocyte aggregation inhibitors (platelet antiaggregants) if anticoagulant therapy is not needed. The chosen therapy is considered by a neurologist. Medications currently available are aspirin, clopidogrel, aspirin combined with dipirydamol, triflusal and ticlopidin.
Anticoagulant treatment is recommended in stroke patients with underlying atrial fibrillation (AF). In case cardioembolic stroke is proved without AF and risk of recurrent stroke is high, anticoagulation is recommended again. Anticoagulants have to be given in case of atheroma of the aorta, fusiform aneurysm on the BA, cervical artery dissection atrial septum aneurysm, patent foramen ovale and proved deep vein thrombosis even if stroke is not cardioembolic origin.
Anticoagulants have no indication in carotid atherosclerosis. K-vitamin antagonist acenocumarol or warfarin is used, which therapeutic effect can be checked with INR (goal INR: 2-3). With the use of the new drugs, such as dabigatran (direct thrombin inhibitor), rivaroxaban and apixaban (activated factor X inhibitors) INR control is not needed nor special (low on vitamin K) diet followed. It is contraindicated severe renal insufficiency, since eliminated with the kidney.
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Blood pressure and glucose have to be monitored regularly. Antihypertensive therapy has to be given even to patients with normal values. Pharmacotherapy of diabetes has to be individualized and integrated with life-style changes. Statin therapy is recommended due to high cardiovascular risk. Smoking cessation and decrease excessive alcohol intake is also advisable. Regular physical activity to reach normal body mass index is recommended. Special diet with lessened salt and saturated fat intake, more vegetables, fruits and fibres is advised. Sleep respiratory disorders such as obstructive sleep apnoea should be treated with continuous positive pressure ventilation.
V./4.8.5.: Rehabilitation
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Multidisciplinary rehabilitation is recommended in acute stroke, started as early as possible. Patients with slight or moderate and stable symptoms can be discharged from stroke unit, but rehabilitation should be continued ambulatory. Rehabilitation can be continued for one year after stroke. Long-term results are better with increased length and intensity of the rehabilitation treatment.
Depression have to always be checked inpatient and in follow-up period. Pharmacotherapy along with other non-pharmacotherapeutical interventions should be used. Antidepressant and anticoagulant treatment is recommended in post-stroke neuropathic pain. In case of post-stroke spasticity, botulinum toxin treatment should be considered; but it has to be mentioned that functional effect is multifactorial.
V./4.8.6.: Follow-up
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Follow-up is needed in a stroke patient, since 17% of strokes are recurrent. Symptoms of the second or third cerebrovascular attack are usually more severe then at first. Probability of recurrent stroke is 10-12% in the first year, 5-8% in the 2-5 years and 30-40% beyond 5 years. Every tenth patients suffer re-stroke in three months.
General condition of the patient and his risk factors are followed, therapeutic goals are checked. In case of carotid stenosis above >50%, regular carotid ultrasonography control is needed in every 6 months or in selected cases (soft plaque or rough surface) before. Cooperation is needed e.g. with vascular surgeons, cardiologists and diabetologists.
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