Introduction
Cardiac diseases can be relevant to stroke in different respects:
In embolic stroke, cardiac diseases may be the cause of embolism, such as atrial fibrillation (AF), endocarditis, left ventricular aneurysm, or cardiomyopathies like left ventricular hypertrabeculation/non-compaction (LVHT).
Brady- and tachyarrhythmias may compromise cerebral blood flow.
Cardiac diseases may coexist, and influence the clinical course and rehabilitation, such as coronary heart disease or dilated cardiomyopathy (dCMP).
In some instances, cardiac diseases may be the consequence of the stroke, such as stroke-induced transient left ventricular dysfunction, also referred to as Takotsubo cardiomyopathy (TTC).
Congenital abnormalities such as patent foramen ovale (PFO) or atrial septal aneurysm (ASA) may implicate paradoxical embolism.
Several diseases may coexist in a single patient, such as coronary heart disease and AF. Thus, from a pragmatic point of view, this chapter aims to focus on the most frequent and controversially discussed cardiac abnormalities in stroke patients.
Atrial Fibrillation
Prevalence of Atrial Fibrillation
AF is a cardiac arrhythmia, defined by the absence of P waves and varying RR distances in the electrocardiogram. AF is a common arrhythmia and its prevalence increases with age. According to the community-based Rotterdam study, the prevalence of AF is 24% in men and 16% in women for those >85 years. Approximately 95% of the individuals with AF are older than 65 years [1]. It is estimated that in the European Union, 8.8 million adults over 55 years of age had AF in 2010. It is projected that this number will double by 2060 to 17.9 million if the age- and sex-specific prevalence remains stable [1].
Apart from hemodynamic consequences due to the loss of atrial contraction and symptoms such as palpitations, AF may lead to embolic stroke or peripheral or mesenteric embolism. Compared to patients with sinus rhythm, patients with AF due to rheumatic heart disease, particularly mitral stenosis, have a 17-fold increased risk of stroke, whereas patients with non-rheumatic AF have a 5-fold increased risk of stroke. Among all ischemic strokes, up to 31% occur because of embolic complications of AF [2].
Diagnosing Paroxysmal Atrial Fibrillation
Whereas diagnosis of permanent AF is easily feasible from the 12-lead electrocardiogram, identifying paroxysmal AF in stroke patients is still a challenge. Various cardiac monitoring methods are available starting with admission electrocardiogram, serial inpatient electrocardiograms, continuous inpatient electrocardiographic monitoring, continuous inpatient cardiac telemetry, in-hospital Holter monitoring, ambulatory Holter, mobile cardiac outpatient telemetry, external loop recording, and implantable loop recording (Figure 8.1). A review of 50 studies (comprising 11 658 patients) stratified cardiac monitoring methods into four sequential phases of screening: phase 1 (emergency room) consisted of admission electrocardiogram (ECG); phase 2 (in hospital) comprised serial ECG, continuous inpatient ECG monitoring, continuous inpatient cardiac telemetry, and in-hospital Holter monitoring; phase 3 (first ambulatory period) consisted of ambulatory Holter; and phase 4 (second ambulatory period) consisted of mobile cardiac outpatient telemetry, external loop recording, and implantable loop recording [3]. The summary proportion of patients diagnosed with post-stroke AF was 7.7% in phase 1, 5.1% in phase 2, 10.7% in phase 3, and 16.9% in phase 4. The overall AF detection yield after all phases of sequential cardiac monitoring was 23.7% [3]. The results of this review suggest that by sequentially combining cardiac monitoring methods, AF might be newly detected in nearly a quarter of patients with stroke or transient ischemic attack, and that the overall proportion of patients with stroke who are known to have AF seems to be higher than previously estimated.
Figure 8.1 The Reveal Linq (Medtronic Inc.) is an implantable device recording the cardiac rhythm for up to 3 years. Ongoing studies are evaluating these implantable loop recorders for the diagnosis of paroxysmal atrial fibrillation in patients with stroke.
Problems in Assessing the Clinical Relevance of Detection of Paroxysmal Atrial Fibrillation
AF may be the consequence and not the cause of the stroke:
AF can occur in the setting of an acute stressor, such as medical illness or surgery. It is uncertain if AF detected in these settings (AFOTS: atrial fibrillation occurring transiently with stress) is secondary to a reversible trigger or is simply paroxysmal AF. Published studies report incidences of AFOTS ranging from 1% to 44% in patients with acute medical illness [4]. The highest estimates have been reported in critically ill patients and in those undergoing continuous monitoring. A small number of studies have reported the recurrence of AF after AFOTS to be 55–68% within 5 years of medical illness. These studies are limited by retrospective design and low-sensitivity ascertainment [4]. Prospective post-discharge studies using sensitive AF detection strategies are needed to define the relationship between AFOTS and clinical AF.
Neurogenic mechanisms are discussed as potential triggers for AF after stroke. In a study of 275 acute ischemic stroke patients, 23 with newly diagnosed AF, 64 with known AF, and 188 with sinus rhythm, those with newly diagnosed AF had a higher frequency of insular involvement (30.4% vs. 9.5%, p = 0.017) than participants with known AF. Compared with patients in sinus rhythm, those with newly diagnosed AF had a higher proportion of brain infarcts of 15 mm or more (601% vs. 37%) and a higher frequency of insular involvement (30% vs. 7%) [5].
AF may be an “innocent bystander”:
Clinically silent AF is frequently detected by continuous electrocardiographic monitoring in older patients without a history of AF. Clinically silent AF lasting longer than 5 minutes was detected by implanted subcutaneous electrocardiographic monitors in 34.4% of 256 patients ≥65 years of age attending cardiovascular or neurology outpatient clinics with no history of atrial fibrillation, but any of the following: CHA2DS2-VASc score of ≥2 (Table 8.1), sleep apnea, or body mass index >30 kg/m2 [6]. In that study, baseline predictors of AF were increased age, left atrial dimension, and blood pressure, but not prior stroke. The rate of occurrence of AF in those with a history of stroke, systemic embolism, or transient ischemic attack was 39.4%/y versus 30.3%/y without (p = 0.32) [6].
The clinical consequences of these uncertainties are:
It is unknown whether AF detected after acute ischemic stroke is caused by neurogenic or cardiogenic mechanisms. The role of AF detected after stroke and its associated risk of stroke recurrence has not yet been investigated; therefore, it is uncertain whether patients in whom AF is only detected after stroke should be treated with oral anti-coagulants [7].
Table 8.1 The CHA2DS2-VASc score for atrial fibrillation risk estimation
| Characteristics | Point | |
|---|---|---|
| C | Congestive heart failure | 1 |
| H | Hypertension | 1 |
| A2 | Age ≥75 years | 2 |
| D | Diabetes mellitus | 1 |
| S2 | Stroke, arterial embolism, or transient ischemic attack | 2 |
| V | Vascular disease like myocardial infarction or peripheric arterial occlusive disease | 1 |
| A | Age 65–75 years | 1 |
| Sc | Sex category (female) | 1 |
Primary and Secondary Stroke Prevention in Atrial Fibrillation
Oral Anti-Coagulant Therapy
In AF patients, the risk for stroke and embolism can be quantified by the CHA2DS2-VASc score. Primary stroke prevention by oral anti-coagulants (OACs) is recommended if the CHA2DS2-VASc score is ≥2. Secondary prophylaxis by OACs is recommended after stroke in all patients with AF. For decades, vitamin K antagonists (VKAs) were the only available drugs for OAC. In the last years, non-vitamin K antagonist oral anti-coagulants (NOACs) like dabigatran, rivaroxaban, apixaban, and edoxaban have been introduced as OACs, based on large randomized trials, and their use is recommended by various guidelines [8]. NOACs are assumed to overcome some of the limitations of VKAs due to fewer food and drug interactions and a more predictable anti-coagulant effect, thus allowing fixed dosing without the need for laboratory monitoring.
The use of NOACs, however, deserves diligent observation of the patients because of:
Drug–drug interactions: Intestinal absorption and renal elimination of NOACs are dependent on the intestinal and renal permeability glycoprotein (P-gp) efflux transporter protein system. Furthermore, NOACs are substrates of the hepatic cytochrome P 450 3A4 and 2J9 enzymes. Thus, pharmacodynamic drug interactions may occur when NOACs are administered concomitantly with drugs affecting the activity of P-gp, CYP3A4, or CYP2J9 systems. Pharmacokinetic drug interactions mediated by P-gp alone (dabigatran etexilate) or in combination with CYP3A4 or 2J9 enzymes (rivaroxaban, apixaban, or edoxaban) have been reported. Induction of P-gp or CYP3A4 or 2J9 might decrease serum NOAC levels, reduce anti-coagulant effects, and lead to an increase in embolic risk. Inhibition of P-gp or CYP3A4 or 2J9 might increase serum NOAC levels, increase anti-coagulant effects, and lead to an increased bleeding tendency [9].
Bleeding and thromboembolic risk dependent on renal function: Since all NOACs are partially eliminated by the kidneys, monitoring of the creatinine clearance is necessary, preferentially by the Cockcroft-Gault formula. The NOAC dose has to be modified if the creatinine clearance is 30–50 ml/min und NOACs are contraindicated if the creatinine clearance is <30 ml/min. Since edoxaban has been shown to have a reduced preventive effect against thromboembolism in patients with excellent renal function (creatinine clearance >95 ml/min), it should be avoided.
Lack of data in elderly patients: Frail elderly people were not represented in NOAC-investigating trials due to various exclusion criteria, and only a third of patients were >75 years [8]. The maximum age of included patients is not listed in any of the available NOAC investigating trials and registries, thus it is unclear if nonagenarians were included [10].
Lack of easily available tests for laboratory monitoring: This problem becomes relevant in emergency situations like bleeding events, when acute surgery is necessary or in acute stroke when thrombolysis is considered. Furthermore, the lack of a laboratory test renders the situation more difficult in patients with questionable medication adherence or in suspected cases of drug–drug interactions.
The decision to prescribe VKA or NOAC for stroke prevention in AF has to be individualized, considering many factors like comorbidities, comedication, adherence, renal function, and frailty.
Left Atrial Appendage Occlusion for Stroke Prevention
Surgical or percutaneous closure of the left atrial appendage (LAA) is considered an alternative to OAC to prevent strokes in AF [11]. However, there are several concerns about the rationale and safety of LAA occlusion.
There is no evidence that embolism in AF exclusively derives from LAA thrombi. When prospectively investigating clinically stable outpatients with AF and with no recent embolism by transesophageal echocardiography, the prevalence of LAA thrombi was only 2.5%, and during a follow-up of 58 months LAA thrombus did not predict stroke or embolism [12].
The LAA has properties which may impede the completion of the occlusion. The LAA myocardium has a higher distensibility than the left atrial myocardium. Progressive dilatation of the LAA occurs in AF, possibly leading to leakage of a primarily completely closed LAA. Incomplete LAA closure creates a pouch with stagnant blood flow, which enhances thrombus formation (Figure 8.2).
Even if technical improvements might lead to a more effective LAA occlusion, potential further side-effects have to be considered. The LAA plays an important role in hemodynamic and body fluid regulation. LAA elimination may impede physiological regulation of heart failure and thirst-perception. The LAA is a place of secretion of atrial natriuretic peptide (ANP). ANP contributes to physiological control of lipid mobilization in humans, so LAA elimination might promote development of obesity. In view of global warming and the obesity epidemic, LAA elimination is a highly questionable procedure for stroke prevention [13].
Although LAA occlusion is carried out as a procedure to obviate the need for OAC, patients need at first dual, followed by indefinite single, therapy with anti-platelet drugs. Anti-platelet drugs, however, increase the bleeding risk, especially in elderly patients [14].
Considering these uncertainties and concerns, LAA occlusion should only be carried out within well-designed randomized clinical trials, preferentially independent from manufacturers of the devices or pharmaceutical companies [13].
Figure 8.2 Transesophageal echocardiographic picture of the left atrium and left atrial appendage with a percutaneously implanted left atrial appendage occluder (PLAATO device) showing a small jet by color Doppler sonography (arrow) between the PLAATO device and the left atrial appendage wall. This jet was not visible at PLAATO implantation, but was only detected after 24 months.
Ablation of Atrial Fibrillation for Stroke Prevention
Catheter ablation of AF (CFA) by radiofrequency or cryoballoon techniques is an increasingly performed interventional method to cure AF. There are concerns, however, whether CFA is a safe and effective therapy to prevent strokes.
The targets of CFA are myocardial sleeves near the junction of the pulmonary veins with the left atrium and autonomic ganglia in the left atrial posterior wall, all located epicardially. The CFA catheter, however, is introduced into the left atrium and thus energy is delivered from the endocardial surface with the aim of creating transmural lesions. Thus, CFA can only be performed successfully when affecting the epicardial side of the left atrial wall. Therefore, the rate of procedural complications, including pericardial tamponade and life-threatening atrio-esophageal fistula, is considerably high [15, 16].
Since AF is not only an electrical problem, the targets of CFA are not well defined. AF results from long-standing arterial hypertension, and ischemic and valvular heart disease leading to structural abnormalities such as atrial myocardial fibrosis. Since CFA does not abolish myocardial fibrosis, it can be expected that ectopic activity may arise from other non-ablated regions and that AF may recur. These considerations are supported by the low long-term efficacy of CFA, especially in patients with permanent AF and structural heart disease [16, 17].
The mean age of patients in whom CFA has been performed so far is 59–62 years [16, 17]. The success rate of CFA is low when the patients are older than 65 years [17]. The prevalence of AF, however, increases with advancing age [1]. Thus, the proportion of AF patients who might profit from CFA is much lower than the proportion of those who might not.
Possible candidates for CFA tend to have a low risk of embolic stroke since they are younger than 65 years and mostly have AF without cardiovascular diseases [16]. The procedure of CFA, however, increases the risk of stroke periprocedurally due to endocardial lesions. Thus, OAC for at least 3 months is recommended to prevent thrombus formation on the ablation lines. It has also been emphasized that recurrent AF is more frequently clinically silent after than before CFA [18]. As a consequence, it is uncertain whether OAC can be stopped at all after CFA. Furthermore, the transseptal puncture during CFA creates persisting interatrial shunts in up to 26% of the patients [19]. It is at present unknown whether these shunts are clinically relevant as sources for paradoxical embolism. Thus, CFA may create new potential sources of arterial embolism.
We doubt that CFA prevents stroke in AF for the following reasons:
The majority of AF patients are too old for CFA.
Candidates for CFA belong to a subgroup with a low risk of embolism.
The CFA procedure itself may increase the embolic risk.
It is uncertain how long the embolic risk persists after the procedure.
Atrial fibrillation (AF) may lead to embolic stroke. It is uncertain whether patients in whom AF is only detected after stroke should be treated with oral anti-coagulants. Catheter ablation of AF and closure of the left atrial appendage are cardiac interventions with questionable value for stroke prevention.
Bradycardia and Tachycardia
If brady- or tachycardia is observed in a stroke patient, the initial diagnostic steps are very similar and aim to assess the clinical severity and to differentiate between cardiac and non-cardiac causes. A practical approach to stroke patients with brady- or tachycardia is given in Box 8.1.
Box 8.1 Practical Approach to Stroke Patients with Brady- or Tachycardia
Assessment of vital signs
Measurement of blood pressure
Registration of a 12-lead electrocardiogram
Measurement of the QT interval according to Bazett’s formula: QTc = QT/√RR
Registration of the body temperature
Blood tests (electrolytes, blood cell count, D-dimer, C-reactive protein, thyroid function tests)
Assessment of current and previous medication
Brady- or tachycardias cause symptoms such as dizziness, light-headedness, or fainting spells. These symptoms may erroneously be interpreted as epileptic seizures. Thus, telemetric or Holter monitoring to detect recurrent episodes of brady- or tachycardia may be useful in patients with suggestive symptoms. The electroencephalogram is usually normal in these patients.
Bradycardia
Bradycardia is defined as a heart rate <50 beats per minute, and becomes symptomatic only when the rate drops significantly. Bradycardia may be due to cardiac and non-cardiac causes. Non-cardiac causes comprise side-effects of drugs, and disorders such as hypothyroidism, hypothermia, electrolyte disturbances, and increased parasympathetic tone. Furthermore, the brain may be involved in cardiovascular regulation, and the insular cortex is assumed to play a role in rhythm control. Cardiac causes of bradycardia include acute or chronic coronary heart disease, valvular heart disease, and degenerative primary electrical disease. Performing a standard electrocardiogram enables one to diagnose more precisely the type of bradycardia as sinus bradycardia, atrioventricular block, sinus arrest, or AF, and to look for signs of acute myocardial ischemia and to assess whether QT prolongation is present, which is a potentially life-threatening situation (see below, “QT Prolongation”).
Tachycardia
Tachycardia is defined as a heart rate >100 beats per minute. Like bradycardia, tachycardia may be caused by non-cardiac and cardiac causes. Non-cardiac causes of tachycardia in stroke patients comprise fever, hypovolemia, anemia, hyperthyroidism, pulmonary embolism, pain, alcohol withdrawal, bronchospasm, side-effects of drugs, and rebound in patients previously treated with beta-blocking agents. Cardiac causes of tachycardia are the same as for bradycardia, and the clinical consequences range from palpitations to sudden cardiac death.
QT Prolongation
Prolongation of ventricular repolarization manifests as a prolongation of the QT interval on the electrocardiogram. QT prolongation may be associated with torsades de pointes tachycardia. Torsades de pointes are often self-limited and are associated with palpitations, dizziness, or syncope. Degeneration into ventricular fibrillation and sudden cardiac death can occur. In addition to the congenital long QT syndrome many drugs, such as anti-arrhythmic drugs class IA and III, antibiotics, anti-histamines, neuroleptics, and anti-depressants, are known to prolong the QT interval. Information about QT-prolonging drugs can be obtained from the internet. Most of these drugs block a specific potassium channel substantially involved in ventricular repolarization. Cardiovascular diseases induce a higher susceptibility to drug-induced prolongation of the QT interval. Correctable factors of QT prolongation include hypokalemia, concomitant administration of different QT-prolonging drugs, and bradycardia.
QT prolongation in stroke may be due to cardiovascular comorbidity, concomitant drug intake, and metabolic disturbances, but may also originate from ischemic cerebral region, especially the insular region. If QT prolongation is observed in a stroke patient, triggering factors should be screened and, if possible, corrected. Special care should be taken with patients with QT prolongation associated with bradycardia because it entails the risk of torsades de pointes. In these patients the heart rate should be raised to >80 beats per minute and implantation of a pacemaker should be strongly considered. QT prolongation in patients with acute ischemic stroke is a dynamic parameter and may regress after several days. Prolonged QTc after 48 hours, but not baseline QTc, correlated with poor neurological outcome and 1-year mortality [20].
QT prolongation persisting 48 hours after stroke is an indicator for poor neurological outcome and mortality.
Coronary Heart Disease
Coexistence of Coronary Heart Disease and Stroke
There is a frequent coexistence of coronary heart disease and stroke, most probably due to common atherosclerotic risk factors such as arterial hypertension, diabetes mellitus, smoking, and hypercholesterolemia. A history of symptomatic coronary heart disease, either myocardial infarction or angina pectoris, is found in up to 33% of patients with ischemic stroke. Coronary heart disease influences the prognosis of patients surviving a stroke. Vascular disease is the major cause of death among long-term survivors of stroke [21]. These results stress the importance for the neurologist to be aware of cardiac symptoms of stroke patients and for the cardiologist to develop cardioprotective measures for stroke patients.
There is a frequent coexistence of coronary heart disease and stroke, most probably due to common atherosclerotic risk factors.
Diagnosis of Coronary Heart Disease in Stroke Patients
When caring for stroke patients in the acute or rehabilitation phase, it is necessary to be aware of clinical symptoms of myocardial ischemia such as chest pain or exertional dyspnea, or electrocardiographic abnormalities such as ST-depression, T-wave abnormalities, or newly developing Q-waves.
The detection of myocardial injury can be improved by measuring serum levels of troponin T or troponin I, biomarkers which are found to be highly specific for myocardial necrosis. Elevated troponin levels in stroke patients with signs or symptoms of myocardial ischemia should entail rhythm monitoring and cardiological consultation regarding further therapeutic and diagnostic measures, including coronary angiography and percutaneous coronary intervention. In acute stroke patients without a history or signs of coronary heart disease, however, elevated troponin levels are not indicators of silent coronary heart disease, but rather of a bad prognosis due to heart and renal failure [22]. Troponin positivity may also indicate myocardial involvement in neuromuscular disease [23].
Stroke patients with normal troponin levels but signs and symptoms suggestive of myocardial ischemia should also be referred to the cardiologist, because stress testing might be indicated.
Myocardial Infarction as a Cause of Embolism
Cardiogenic embolism from a left ventricular thrombus may occur as a complication of acute or subacute myocardial infarction or due to a ventricular aneurysm in the chronic phase of a large, mainly anterior wall infarction. The incidence of left ventricular thrombi early after myocardial infarction has declined in recent years, most probably due to changes in the acute therapy of myocardial infarction, which now comprises intensive anti-coagulant therapy and percutaneous coronary interventions [24]. However, left ventricular thrombi may still be detected in patients after myocardial infarction, especially if revascularization in the acute phase has not been performed or was unsuccessful or if the myocardial infarction affected large parts of the left ventricle (Figure 8.3). Thus, imaging studies to look for left ventricular thrombi, preferentially transthoracic echocardiography, should be performed in all stroke patients with a history or electrocardiographic signs of previous myocardial infarction. In cases with questionable echocardiographic results or poor acoustic window, cardiac magnetic resonance imaging should be carried out [24].
Figure 8.3 Transthoracic echocardiographic apical five-chamber view showing an apical thrombus in a patient with a subacute myocardial infarction.
Acute or subacute myocardial infarction and ventricular aneurysms can be a cause of embolic stroke.
Valvular Heart Disease
Infective Endocarditis and Stroke
Cerebrovascular complications of endocarditis occur in 25–70% of patients with infective endocarditis. They cluster during the period of untreated infection [25]. Among patients with endocarditis and stroke, the mitral valve seems to be more frequently affected than the aortic valve. Native valves as well as prosthetic valves may be affected by endocarditis, leading to stroke. Stroke patients with prosthetic valves have a worse prognosis than patients with native valves.
Diagnosis of Infective Endocarditis
Despite the availability of echocardiography, laboratory, and microbiological investigations, considerable delay occurs until infective endocarditis is diagnosed. Between onset of the symptoms and diagnosis a mean interval of 1 month has been reported [26]. This is due to the unspecific symptoms of endocarditis, such as prolonged flu-like disease, generalized weakness, and fatigue. Embolic events such as stroke are frequently the cause of hospital admission in these patients. Thus, endocarditis has to be considered as a differential diagnosis in all stroke patients, and symptoms suggestive of endocarditis should be asked for at admission. The suspicion of endocarditis should increase if laboratory signs such as elevated blood sedimentation rate, leukocytosis, or elevated C-reactive protein are found or if the patient is febrile. Blood cultures should be taken in these patients before initiation of antibiotic therapy. In most of the cases with stroke and suspected endocarditis transesophageal echocardiography is necessary because of its better visualization of the valves, valve prosthesis, and vegetation to confirm or exclude the diagnosis (Figure 8.4).
Figure 8.4 Transesophageal echocardiographic picture (left) and autopsy specimen (right) of a patient with embolic stroke and aortic valve endocarditis.
LA – left atrium, MV – mitral valve, LV – left ventricle, VE – vegetation, AO – aortic valve.
Therapy of Infective Endocarditis
Antibiotic therapy is the main measure in therapy for infective endocarditis. The risk of stroke in infective endocarditis has been shown to decrease rapidly within 1 week after the initiation of antibiotic therapy [25]. However, if there are large vegetations or destruction of the valves leading to heart failure, cardiac surgery may be necessary. In the past, cardiac surgeons have frequently been reluctant to operate on infective endocarditis patients with acute stroke because of concerns about cerebral bleeding complications due to anti-coagulation during the cardio-pulmonary bypass. However, delay in surgical intervention can lead to the death of patients who might have benefited from surgery. Although no prospective data are available, recent data suggest that the risk of neurological exacerbation may be lower than previously believed. Current guidelines reflect a shift towards early surgery for such patients, but there continue to be important areas of clinical equipoise [27]. For clinical decision-making, an endocarditis team is recommended, including cardiac surgeons, cardiologists, infectious diseases specialists, neurologists, neurosurgeons, and interventional neuroradiologists. The therapy should be planned with consideration of the clinical course, the echocardiographic findings, the microorganism involved, the response to antibiotic therapy, and the neurological condition.
Strokes occur in up to 70% of patients with endocarditis. Endocarditis must be considered as a differential diagnosis in all stroke patients if laboratory signs of inflammation are present.
Related posts:
Chapter 4 – Imaging for Prediction of Functional Outcome and for Assessment of Recovery
Chapter 7 – Common Risk Factors and Prevention
Chapter 16 – Stroke and Dementia
Chapter 19 – Acute Therapies for Stroke
Chapter 22 – Management of Acute Ischemic Stroke and its Late Complications
Chapter 21 – Intensive Care of Stroke
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