Ischaemic stroke
Stroke is the third leading cause of death after myocardial infarction and cancer, and the leading cause of permanent disability and of disability-adjusted loss of independent life years in western countries. Aside from the tragic consequences for patients and their families, the socio-economic impact is enormous, as stroke patients with permanent deficits such as hemi-paresis and aphasia are frequently unable to live independently or pursue an occupation. he direct and indirect cost estimates of a survived stroke episode vary between US$35,000 and US$50,000 per year. In the face of an ageing population, the incidence and prevalence of stroke is expected to rise, and an effective and widely applicable treatment of this devastating disease is desperately needed.
General management and diagnosis
It is essential to evaluate and stabilize vital signs and other physiological variables before initiating specific stroke therapy. he patient’s neurological status should be assessed urgently using standard stroke scales such as the National Institutes of Health Stroke Scale, and the time point of stroke onset identified. Close monitoring of neurological status, heart rate and rhythm, blood pressure, oxygen saturation (SpO2 ), body temperature and laboratory variables, such as blood glucose, is crucial. Oxygen should be administered if SpO2 falls below 95% and serum glucose levels >18.0 mmol l-1 (180 mg dl-1) treated with insulin infusion.
Up to 70% of ischaemic stroke patients present with elevated blood pressure, but this usually normalizes within the first hours and days after stroke onset. Normal autoregulation of cerebral blood flow (CBF) can be impaired in the acute phase after stroke, and perfusion of ischaemic brain is likely to depend primarily on systemic blood pressure. As vessel occlusion or stenosis may be (partly) compensated by collaterals and acute elevation of blood pressure, substantial reductions in blood pressure should be avoided early after stroke onset. Guidelines from the American Heart Association and the European Stroke Organisation recommend that blood pressure should be lowered only if systolic blood pressure (SBP) exceeds 220 mmHg and diastolic blood pressure (DBP) exceeds 120 mmHg. Early initiation of co-therapies including speech, physical and occupational therapies minimize complications such as aspiration pneumonia, thrombosis and limb contractures. Secondary prophylaxis with antiplatelet agents, statins and antihypertensives is recommended to avoid early recurrent strokes. Optimal management of vascular risk factors also requires that smoking be discouraged and patients who are overweight managed with regular physical activity and a weight-reducing diet.
Imaging
There are several imaging modalities that can be used to identify patients who may benefit from acute reca-nalization therapy after ischaemic stroke. Options include non-contrast CT and advanced CT techniques using CT angiography (CTA) and CT perfusion. Multiparametric MRI stroke protocols, including diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), gradient-recalled echo (GRE) and MR angiography (MRA), provide additional information (Fig. 25.1). A simple non-contrast CT to exclude intracranial haemorrhage is sufficient within the early 3-4.5 h time window, whereas advanced imaging techniques are able to identify patients who are likely to benefit from therapy delivered in extended time windows (see below).
Fig. 25.1. Imaging of a 76-year-old man with occlusion of the proximal left middle cerebral artery (MCA). (a-d) Pre-treatment MRI scans (a, diffusion-weighted imaging (DWI); b, fluid-attenuated inversion recovery; c, perfusion-weighted imaging (PWI); d, magnetic resonance angiography) showing a large PWI/DWI mismatch in the MCA territory. (e) Post-treatment (intravenous thrombolysis) CT scan showing only minor infarction in the left MCA territory.
Acute specific therapy
Intravenous thrombolysis
Occlusion of a brain vessel leads to an immediate reduction in cerebral perfusion and to ischaemic infarction in a central core of irreversible damaged brain tissue within minutes. Surrounding this is an area of hypo-perfused but still vital brain tissue (the ischaemic penumbra), which can potentially be salvaged by rapid restoration of blood flow. he underlying rationale for the application of thrombolytic agents is the lysis of occluding thrombus and subsequent re-establishment of tissue reperfusion.
Currently, the only approved reperfusion therapy is CT-guided intravenous recombinant tissue plasminogen activator (rtPA) administered according to recognized inclusion and exclusion criteria within 3 h of stroke onset. he standard regimen is rtPA 0.9 mg (kg body weight)-1 (maximum dose 90 mg) with 10% of the dose given as an initial bolus and the remaining dose over the following hour. Findings from the European Cooperative Acute Stroke Study (ECASS) III suggest some benefit of rtPA up to 4.5 h from stroke onset. However, pooled analysis of data from rtPA trials confirms that, even within a 3 h window, earlier treatment results in better outcome.
Several large observational studies as well as smaller randomized trials have successfully utilized MRI sequences to select patients for intravenous thromb-olysis (IVT) in time windows extended up to 9 h after stroke onset. MRI-guided treatment appears to be safer than standard CT-guided treatment and is at least as effective. However, such extended time windows for IVT are not yet incorporated into routine clinical practice, and MRI is logistically more difficult to perform than CT in the acute phase.
Intra-arterial thrombolysis and interventional therapy
Another strategy in thrombolytic therapy is an intra-ar-terial, interventional approach. Compared with IVT, it has the advantage of providing a higher concentration of the thrombolytic agent at the target site, while minimizing systemic concentration and therefore complications. he technique requires cerebral angiography to localize the occluding clot, navigation of a microcatheter to the side of the clot and administration of the lytic agent at the level of, or inside, the clot. he higher technical demands and specialist equipment usually cause a considerable time delay compared with IVT and the limiting factor is often the availability of an interventional neuroradiologist. Intra-arterial thrombolysis (IAT) may be combined with mechanical recanalization devices, such as the Mechanical Embolus Removal in Cerebral Embolism retriever (MERCI retriever) or the Penumbra device, and with remodelling techniques including percutaneous transluminal angioplasty (PTA) and/ or stent-ing. Although the Intra-arterial Prourokinase for Acute Ischemic Stroke (PROACT) II study demonstrated an outcome benefit of IAT in proximal middle cerebral artery (MCA) occlusion with pro-urokinase within 6 h of stroke onset, this was not sufficient for this therapy to be approved by the US Food and Drug Administration. Prourokinase is no longer available and, although there are no randomized controlled data on IAT using other agents, rtPA is of en used as an individual treatment option for patients with proximal MCA or acute basi-lar artery occlusion (see below). Common intra-arterial doses of rtPA should not exceed 40 mg.
Combined intravenous/intra-arterial thrombolysis
The combination of IVT and IAT allows early IVT to ‘buy time’ until IAT can be undertaken and is often referred to as the ‘bridging approach. As with IAT alone, there is no formal approval for this combination, but it is being used in some centres for patients with proximal MCA or acute basilar occlusion. he Emergency Management of Stroke (EMS) and the Interventional Management of Stroke (IMS) I and II trials suggest that a reduced dose of intravenous rtPA (0.6 mg (kg body weight)-1, maximum dose 60 mg) should be administered immediately after exclusion of ICH, with overall and intra-arterial rtPA doses not exceeding 90 and 40 mg, respectively. Bridging lysis may also be combined with mechanical clot removal devices or PTA.
Fig. 25.2. Digital subtraction angiography (DSA) of an 80-year-old male with acute basilar artery occlusion. (a) Pre-treatment DSA showing complete basilar artery occlusion. (b) Post-treatment DSA. After combined intravenous/intra-arterial thrombolysis and mechanical intervention, there is complete recanlization of the basilar artery.
Acute basilar artery occlusion
Although basilar artery occlusion (BAO) is rare, it is the most severe type of ischaemic stroke, with a case fatality rate of up to 90%. In younger patients, it is usually related to embolism from cardiac sources or, less commonly, vertebral artery dissection, whereas local atherothrombosis is more common in the elderly.
Basilar artery occlusion and other ischaemic infarctions in the vertebrobasilar territory are associated with variable symptoms but often present with progressive or hyperacute brainstem symptoms, tetraplegia and alterations in consciousness ranging from somnolence to coma. Typical cerebellar symptoms may occur with or without visual deficits and loss of cranial nerve functions. Specific symptoms depend on the affected vessel and exact localization of the abnormality within the vessel. Different patterns include caudal vertebrobasilar, mid-basilar and top-of-the-basilar thrombosis syndromes, the first being mostly of atherothrombotic causes and the last of embolic origin. Top-of-the-basilar syndrome is defined by bilateral thalamic, mesenceph-alic, superior cerebellar artery and posterior cerebral artery infarctions with coma, vertical ocular paresis and skew deviation. Extensive basilar artery thrombosis may result in a ‘locked-in’ syndrome.
Due to the poor prognosis of untreated acute BAO, diagnostic vessel imaging using either non-invasive methods (CT/CTA or MRI/MRA) or digital subtraction angiography (DSA) should be initiated as early as possible (Fig. 25.2). MRI is superior to CT at identifying ischaemic lesions within the brainstem and will confirm the extent of the infarction. Differential diagnoses of acute BAO range from intoxication to a post-seizure reduction of consciousness. herefore, other aetiologies should be considered and additional diagnostic procedures, such as lumbar puncture and EEG, may be useful in clarifying the diagnosis.
Treatment of basilar artery occlusion
Patients with persistent BAO face an almost inevitably grim prognosis, and those with suspected BAO need immediate referral to a specialist centre for further imaging and possible rescue therapy. In the case of proven BAO, IVT, IAT or both, in combination with mechanical recanalization, is usually recommended, although the lack of randomized studies means that the optimal treatment remains unclear. However, most national guidelines favour endovascular thromboly-sis in combination with mechanical removal of the thrombus. Regardless of the treatment modality, acute recanalization is the single most important predictor of improved outcome. Multiple case series have been published in the last 25 years, but most include small numbers with only a few studies recruiting even 40 or 50 patients. In observational studies, survival rates range from 30 to 73%, although a recent meta-analysis showed that, notwithstanding improved recanaliza-tion rates after IAT, survival rates were comparable to IVT. herefore, in centres without interventional neu-roradiologists, IVT is a viable alternative for patients withBAO.
A multicentre observational study demonstrated that the ‘bridging approach’, using combined treatment with intravenous platelet glycoprotein IIb/IIIa receptor inhibitors and IAT with rtPA, combined with PTA or stenting in cases of severe residual stenosis af er IAT, might improve neurological outcome compared with IAT alone. Recently, bridging therapy with intravenous platelet glycoprotein IIb/IIIa inhibitors plus IAT with rt-PA has been shown to be associated with a significant increase in recanalization rates without an increased risk of bleeding complications compared with IAT alone.
Intensive care management of acute ischaemic stroke
Although most ischaemic stroke patients can be treated in high-dependency or dedicated stroke units, some require admission to a (neurological) intensive care unit (ICU). Indications for ICU admission may be related to general medical issues or specific to the acute ischaemic stroke (Table 25.1). he focus of ICU management therefore includes general medical measures, such as airway management, mechanical ventilation and cardiovascular support, as well as disease-specific interventions such as treatment of space-occupying brain oedema and other stroke-related complications.
Prevention and management of general complications
Up to 50% of patients with a hemiplegic stroke are initially dysphagic, and early evaluation of swallowing function is essential to prevent aspiration pneumonia, the most common stroke-related complication on the ICU. he prevalence of dysphagia declines to approximately 15% within 3 months after stroke onset. It is associated with a higher incidence of medical complications and a higher rate of malnutrition, which is itself a predictor of poor functional outcome and increased mortality. Early feeding via a nasogastric tube is essential, and a percutaneous gastrostomy should be considered in patients in whom dysphagia might be prolonged. Early feeding also prevents bacterial aspiration pneumonia, although diminished cough and immobilization increase its risk.
Table 25.1 Indications for ICU admission after acute ischaemic stroke
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Stroke related |
Large MCA territory stroke |
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Brainstem stroke |
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Significant brain oedema causing |
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raised ICP and midline shift |
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Decreased consciousness |
|
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Dysphagia, pulmonary aspiration |
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Respiratory insufficiency, mechanical |
|
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ventilation |
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Severe cardiac arrhythmia |
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Circulatory shock |
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Recurrent epileptic seizures |
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Extended monitoring after: |
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• Thrombolysis |
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• Neurosurgical intervention |
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(e.g. hemicraniectomy) |
|
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• Neuroradiological |
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interventions |
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|
General medical conditions |
Pneumonia |
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Sepsis, other infections |
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(Multi)organ failure |
|
|
Pre-existing comorbidities |
ICP, intracranial pressure; MCA, middle cerebral artery.
Another feared complication of stroke is the development of deep vein thrombosis (DVT) and pulmonary embolism (PE). Up to 50% of patients develop DVT, and PE occurs in 3-39%. Pulmonary embolism accounts for around 2% of early deaths after acute stroke. Early rehydration and graduated compression stockings are recommended to reduce the risk of venous thromboembolism (VTE). Several large trials have demonstrated that low-molecular-weight heparin is safe in stroke patients and significantly reduces the incidence of DVT and PE. he PREvention of VTE after Acute Ischemic Stroke with LMWH Enoxparin (PREVAIL) study showed a 43% relative risk reduction in VTE events in patients receiving enoxaparin compared with unfractionated heparin for the development of symptomatic or asymptomatic DVT and symptomatic and/or fatal PE during the treatment period. Deep vein thrombosis prophylaxis using low-molecular-weight heparin should therefore be administered to all stroke patients showing persisting motor deficits.
Fig. 25.3. Cranial CT scan of a 58-year-old male with left-sided middle cerebral artery (MCA) infarction. (a) Subtotal left-sided MCA infarction with oedema and early midline shift. (b) Post-treatment scan showing decompressive hemicraniectomyand ventriculostomy.
Other common complications in stroke patients include urinary tract infection, focal or secondary generalized epileptic seizures, pressure ulcers, gastric ulcers and critical illness polyneuropathy. Treatment of these complications is identical to that in non-stroke patients.
