INTRODUCTION — Stroke is a common and potentially devastating manifestation of sickle cell disease (SCD) that can affect children and adults. Challenges in management include distinguishing acute stroke from other central nervous system complications of the disease such as seizures, meningitis, complicated migraine and cerebral malaria (in endemic areas); and distinguishing acute ischemic stroke from hemorrhagic stroke. Care of the patient with an acute stroke requires specialized expertise in exchange transfusion practices.
This topic discusses an approach to the acute assessment and treatment of stroke in children and adults with SCD.
Risk stratification and primary stroke prevention, as well as secondary prevention for individuals with SCD who have had an acute stroke or transient ischemic attack (TIA) are presented in detail separately. (See "Prevention of stroke (initial or recurrent) in sickle cell disease".)
DIAGNOSIS AND IMMEDIATE MANAGEMENT — Individuals with SCD are at risk of ischemic and hemorrhagic stroke, especially those with HbSS or HbS-beta0 thalassemia. It has been estimated that without stroke-risk screening and primary stroke prevention, 11 percent of patients with SCD will have a clinically apparent stroke by age 20 years, and one-fourth of patients with SCD will have a stroke by age 45. Stroke risk factors and epidemiology in patients with SCD are presented separately. (See "Prevention of stroke (initial or recurrent) in sickle cell disease".)
The diagnosis of suspected stroke involves a rapid initial clinical assessment accompanied by neuroimaging to differentiate ischemia from hemorrhage and to exclude stroke mimics.
Central nervous system ischemia is defined as brain, spinal cord, or retinal cell death attributable to ischemia; ischemic stroke is specifically defined as brain infarction accompanied by sudden onset of overt stroke symptoms. Diagnosis is based on clinical, neuroimaging, and/or neuropathologic evidence of permanent injury.
Hemorrhagic stroke includes intracerebral hemorrhage (ICH), which involves bleeding directly into the brain parenchyma and formation of hematoma, intraventricular hemorrhage (IVH) excluding preterm infants, and subarachnoid hemorrhage (SAH), in which bleeding occurs directly into the subarachnoid space under arterial pressure. The blood spreads quickly within the cerebrospinal fluid (CSF), leading to a rapid increase in intracranial pressure. Death or deep coma may ensue if the bleeding continues.
A reasonable approach to patients presenting with ischemic or hemorrhagic stroke is as follows:
●Initial stabilization and simple transfusion as necessary to correct worsened anemia. (See 'Immediate management (all patients)' below.)
●Clinical and radiologic assessment to confirm the diagnosis and distinguish between ischemic and hemorrhagic stroke. (See 'Clinical assessment' below and 'Neuroimaging' below.)
●For individuals with ischemic stroke, exchange transfusion to lower the percentage of hemoglobin S. (See 'Transfusion' below.)
Clinical assessment — Acute ischemic stroke due to vaso-occlusion in cerebral vessels is the first consideration in a patient known to have SCD who presents with new neurologic findings or severe headache. However, it is also important not to overlook other potential causes of neurologic deterioration.
Clinical assessment of the patient with SCD who presents with a potential stroke based on a new neurologic defect (focal or nonfocal) or altered level of consciousness includes consideration of the following diagnoses [1]:
●Acute ischemic stroke
●Acute hemorrhagic stroke
●Transient ischemic attack (TIA)
●Cerebral venous sinus thrombosis
●Infection, including acute meningitis, brain abscess, meningoencephalitis, or cerebral malaria (in endemic areas)
●Seizure, particularly when associated with prolonged postictal paralysis (Todd's)
●Migraine
If clinical suspicion for an acute stroke is high and the patient has a hemoglobin concentration significantly below baseline (eg, at least 2 g/dL below baseline), a simple transfusion should be given rapidly, without waiting for neuroimaging confirmation. (See 'Immediate management (all patients)' below.)
Additional nonvascular conditions that can mimic stroke include tumors and other structural brain lesions; familial alternating hemiplegia; reversible posterior leukoencephalopathy syndrome; metabolic derangements; intracranial infection; demyelinating conditions such as acute disseminated encephalomyelitis, idiopathic intracranial hypertension, drug toxicity, postinfectious cerebellitis; musculoskeletal conditions; and psychogenic conditions. One consideration in particular for patients on chronic opioid therapy is the possibility of opioid overdose. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'Differential diagnosis'.)
The most common locations for an acute ischemic stroke in patients with SCD include large vessel territories and borderzone regions (figure 1). Hemorrhagic transformation of infarcts can also occur in these sites [1]. Age may be somewhat helpful for predicting the ultimate diagnosis. Ischemic stroke is more common than hemorrhagic stroke in children and adolescents with SCD. Hemorrhagic stroke is more common than ischemic stroke in adults with SCD [1]. However, individuals of all ages with SCD may have any of these diagnoses. The epidemiology of stroke in SCD, which may differ according to the age of the patient, is discussed separately. (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Incidence'.)
The clinical features may suggest certain stroke subtypes, though no clinical features are pathognomonic for distinguishing different types of stroke:
●Ischemic stroke – Infants with stroke may present with focal weakness but are more likely than older children to present with seizures and altered mental status. Older children usually have hemiparesis or other focal neurologic signs such as aphasia, visual disturbance, or cerebellar signs, although seizures, headache, and lethargy are not uncommon. (See "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors" and "Overview of the evaluation of stroke".)
●Transient ischemic attack – Historically, stroke symptoms or signs that last <24 hours have been defined as a transient ischemic attack (TIA). However, with modern brain imaging, up 33 percent of patients with stroke symptoms lasting <24 hours are found to have an infarct when appropriate neuroimaging is completed [2]. This has led to a new, tissue-based definition of TIA, which is a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction seen on neuroimaging [3]. (See "Definition, etiology, and clinical manifestations of transient ischemic attack".)
●Intracerebral hemorrhage – The presentation of intracerebral hemorrhage depends primarily on the size of the hematoma, anatomical location, and whether there is extension of the hemorrhage into the ventricles. Typically, rapid onset of neurologic dysfunction and signs of increased intracranial pressure such as headache, vomiting, and decreased level of consciousness are seen. For patients with large volume hemorrhage, stupor or coma is typical. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis".)
●Subarachnoid hemorrhage – The primary symptom of aneurysmal SAH is a sudden, severe headache, which may or may not be associated with a brief loss of consciousness, nausea or vomiting, and meningismus. Restricted subarachnoid hemorrhage may manifest with transient motor or sensory symptoms that suggest epileptic phenomena and/or frank seizures. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis" and "Nonaneurysmal subarachnoid hemorrhage".)
●Cerebral venous thrombosis – The clinical presentation of cerebral venous thrombosis (CVT; also called cerebral sinovenous thrombosis [CSVT]) is highly variable because there may be associated brain swelling, edema, venous infarction, or hemorrhagic venous infarction caused by venous occlusion. The onset can be acute, subacute, or chronic. Headache (of gradual, acute, or thunderclap onset) is the most frequent symptom, and may occur as part of an isolated intracranial hypertension syndrome, with or without vomiting, papilledema, and visual problems. In other cases, headache may be accompanied by focal neurologic deficits, focal or generalized seizures, papilledema, and encephalopathy with altered mental status or coma. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)
The major management implication of the distinction between an acute ischemic versus hemorrhagic event is in helping to decide whether urgent exchange transfusion is appropriate. Urgent exchange transfusion is indicated for patients with acute ischemic stroke or TIA (and patients with hemorrhagic transformation of an acute ischemic stroke). The role of exchange transfusion in the management of hemorrhagic stroke is less clear. Patients with TIA should be treated with urgent exchange transfusion, because TIA tends to be a warning sign of impending stroke. While reports of TIA are rare in children, a high percentage of adults with TIA have an ischemic stroke within seven days [4]. In one small study in children with TIA, 16 percent had infarcts on follow up MRI [5]. Exchange transfusion is protective.
Individuals with TIA should then undergo further evaluation for stroke risk and strong consideration of regular prophylactic transfusions [6]. (See 'Transfusion' below.)
We also perform a repeat MRI of the brain two to four weeks after the initial presentation, since diffusion weighted images of the brain, an indication of acute neurologic injury, may be negative upon presentation and with subsequent imaging demonstrating ischemic injury [7].
Determining a true baseline image of cerebral infarcts is critical because of the need to determine progression or recurrence of infarcts. Further, during a TIA or acute ischemic infarct, the use of blood transfusion therapy may hasten recovery to baseline. Thus, the importance of the duration of an acute neurologic event that lasts less than 24 hours must be interpreted in the context of active treatment with blood transfusion. For this reason and others, the traditional threshold for distinguishing a stroke from a TIA is somewhat arbitrary.
TIAs and acute ischemic strokes are treated in the same acute fashion with exchange blood transfusion therapy.
Exchange transfusion for subarachnoid or parenchymal hemorrhage without ischemia is less clear and should be addressed on a case-by-case basis; however, simple transfusion as described for acute stroke is typically recommended, as this increases oxygen carrying capacity and will reduce the risk of complications from anesthesia that may be needed for diagnostic procedures such as cerebral angiography.
The distinction between a primary cerebrovascular cause of stroke symptoms and an infectious cause of acute symptoms is also essential. Prompt institution of broad spectrum antibiotics may be lifesaving for those with acute meningitis or sepsis, as individuals with SCD are functionally asplenic and at risk for overwhelming infection with encapsulated and other organisms. Fever and/or leukocytosis and altered neurologic function may be a sign of meningitis or another infection such as acute chest syndrome (ACS) with pneumonia. Fever may also be seen with stroke in the absence of infection; however, all patients with SCD who present with fever and acute neurologic findings should be treated presumptively for a bacterial infection until this possibility is eliminated, unless there is a good rationale not to do so. (See "Evaluation and management of fever in children and adults with sickle cell disease".)
As noted above, other rare stroke mimics must be considered if the initial evaluation and imaging do not reveal a cause for the patient's symptoms. A discussion of other causes of focal neurologic findings in the differential diagnosis of stroke is presented separately. (See "Differential diagnosis of transient ischemic attack and acute stroke".)
Immediate management (all patients) — All patients with SCD and possible stroke should have the following [1]:
●Immediate assessment by clinicians with expertise in stroke and SCD management
●In most cases, intensive monitoring and/or care in a dedicated stroke unit
●Airway protection from aspiration
●An imaging study, if not already performed (see 'Neuroimaging' below)
●Baseline laboratory testing, if not already performed (see 'Laboratory and other testing' below)
●Monitoring of oxygen saturation and administration of supplemental oxygen to maintain a saturation above 95 percent
●Precautions to minimize crying and hyperventilation, both of which can lower PaCO2 and thereby induce or worsen cerebral ischemia by causing vasoconstriction
●Avoidance of hypotension, hypovolemia, hyperthermia, hyperglycemia, and hypocarbia
●Intravenous access and hydration with isotonic fluids, typically at 1.25 to 1.5 times the normal maintenance rate
●Simple transfusion to raise the hemoglobin concentration to approximately 10 g/dL (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques")
●Attention to blood pressure control (see "Initial assessment and management of acute stroke", section on 'Blood pressure management')
●Attention to identification and treatment of concurrent infection; including antipyretics if needed
●Management of seizures if present
Attention to oxygenation and possible infection is especially important in SCD for reducing sickling, which could further worsen cerebral ischemia and other vaso-occlusive complications, and for preventing serious complications of infection due to functional asplenia. Use of additional management strategies to maximize cerebral perfusion, ventilation, and maintenance of a normoglycemic state are also critical. Hydration with normal saline rather than hypotonic saline will avoid the potential worsening of cytotoxic cerebral edema that may occur with infusion of hypotonic fluid; excessive fluids should be avoided, however. (See "Initial assessment and management of acute stroke" and "Ischemic stroke in children: Management and prognosis", section on 'Initial management'.)
For those with moyamoya syndrome (bilateral or unilateral internal carotid artery stenosis with prominent collateral vessels) and acute stroke, acute treatment is mainly symptomatic and directed towards improving cerebral blood flow, and controlling seizures. Additional management issues related to moyamoya syndrome are presented separately. (See "Moyamoya disease and moyamoya syndrome: Treatment and prognosis".)
Neuroimaging — Neuroimaging is critical for all patients with suspected stroke. In children, a head computed tomography (CT) is generally considered inadequate to diagnose ischemic stroke, and magnetic resonance imaging (MRI) may be required to reliably exclude stroke mimics. As noted above (see 'Clinical assessment' above), patients with a high suspicion of acute stroke should receive a simple transfusion prior to neuroimaging. Transfusion may also reduce the risk of complications from sedation should sedation for the imaging procedure be required.
Brain MRI is more sensitive for acute ischemia than CT, particularly with use of diffusion-weighted imaging in the hyperacute time period. In addition, brain MRI provides better visualization of the posterior fossa, and is able to detect intracerebral hemorrhage with good sensitivity using high susceptibility sequences. Head CT should be substituted if the patient is not stable for MRI, MRI is not tolerated, or will not be rapidly available after arrival to the medical facility. In adults with SCD, either CT or MRI may be used as the initial study. Brain MRI with diffusion-weighted imaging is typically preferred if available because it is more sensitive for the diagnosis of acute ischemic stroke than CT. However, for older adults with SCD who have risk factors for embolic stroke, CT with CT angiography of the head and neck will diagnose a large vessel occlusion. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis", section on 'Brain imaging' and "Neuroimaging of acute stroke".)
Limitations of MRI include a requirement for patient cooperation (which may not be possible for very young children), MRI availability, and cost. For young children who cannot cooperate, MRI may require sedation, which carries additional risks and costs. In comparison, CT may be easier to obtain, and unenhanced CT can reveal an area of hemorrhage. However, CT is a source of radiation exposure.
Given these considerations, the imaging approach and local institutional practices may vary. When an MRI can be obtained rapidly this is the preferable imaging study. An alternative approach if MRI is not rapidly available is to perform an initial CT scan to evaluate the possibility of acute hemorrhage, and if this is normal, to obtain an MRI once the patient is stabilized [1].
Neurovascular imaging with magnetic resonance angiography (MRA) or CT angiography should be obtained in all adults and children with acute stroke to look for large vessel arteriopathy (eg, dissection, moyamoya, atherosclerosis) and to exclude aneurysm. When cerebral venous sinus thrombosis is a consideration, brain MRI in combination with magnetic resonance venography (MRV) is the most sensitive technique for demonstrating the thrombus and the occluded dural sinus or vein. A more extensive discussion of neuroimaging in the diagnosis of acute stroke is presented separately. (See "Neuroimaging of acute stroke" and "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis", section on 'Neuroimaging'.)
As discussed elsewhere, a large portion of the world's SCD population may not have access to neuroimaging, especially in the acute setting. For these individuals, it may be necessary to make a presumptive diagnosis of stroke based on clinical features alone. (See "Sickle cell disease in sub-Saharan Africa", section on 'Stroke'.)
Laboratory and other testing — Patients with SCD who have a suspected or confirmed stroke should have a complete blood count (CBC), reticulocyte count, percent hemoglobin S, and type and crossmatch for red blood cell (RBC) transfusion. The CBC and other hematologic studies are critical to management because RBC transfusion is the cornerstone of treatment, and it must be titrated to percent hemoglobin S and total hemoglobin, in order to lower the sickle hemoglobin sufficiently without precipitating hyperviscosity syndrome. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Risk of hyperviscosity syndrome from simple transfusion'.)
Coagulation studies (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) and basic metabolic profile with electrolytes, urea nitrogen, creatinine, and glucose should also be obtained as a baseline and to eliminate stroke mimics such as hypoglycemia [1].
Other testing includes oxygen saturation, echocardiography, and electrocardiography. The role of these studies is discussed in more detail separately. (See "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis".)
ISCHEMIC STROKE AND TIA: ADDITIONAL MANAGEMENT
Transfusion — For patients with SCD who have a clinically and/or radiologically confirmed acute ischemic stroke, we suggest transfusion therapy.
The goals of transfusion in ischemic stroke are to lower the percentage of sickle hemoglobin to <30 percent of total hemoglobin (typically 15 to 20 percent) and to aim for a total hemoglobin level of approximately 10 g/dL. This is best achieved using exchange transfusion. However, it takes time to mobilize resources for exchange transfusion, which may also require transfer to another facility. Thus, when exchange transfusion is not available within two hours of presentation for medical care and the hemoglobin is ≤8.5 g/dL, simple transfusion can be performed to avoid delays in treatment, often while awaiting the results of the clinical assessment and neuroimaging and possibly the placement of an apheresis catheter. Subsequently, after ischemic stroke is confirmed, exchange transfusion is used. (See 'Immediate management (all patients)' above.)
If the hemoglobin is less than 5 g/dL, we would consider raising the hemoglobin level to 10 g/dL with a simple transfusion and then obtaining a percent hemoglobin S concentration to make an informed decision regarding the requirement for red blood cell exchange lower the hemoglobin S level to less than 30 percent.
Patients with transient ischemic attacks (TIA) should be treated with urgent exchange transfusion and should undergo further evaluation for stroke risk and consideration of regular prophylactic transfusions. (See "Prevention of stroke (initial or recurrent) in sickle cell disease".)
Evidence for the benefit of transfusion in patients with SCD and acute stroke includes our clinical experience, and is supported by basic studies of the physiology of the disease, in which sickling and hypoxemia interact to worsen vaso-occlusion (see "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Mechanisms'), and the expectation of significant morbidity and mortality if no intervention is made. There are no randomized trials comparing transfusion with other interventions in the setting of acute stroke in patients with SCD.
Simple transfusion for all patients — The potential benefits of providing simple transfusion initially include the following:
●Less delay in starting therapy
●Possible mitigation of the risks of the placement of an exchange catheter
●Rapid improvement in hemoglobin level
●Allowance of time to prepare for exchange transfusion, which may include transfer to another facility with blood bank support for the procedure
Exchange transfusion for those with confirmed ischemic stroke or TIA — The rationale for our use of exchange transfusion rather than continuing simple transfusions includes our clinical experience in this setting and the general observation that simple transfusion cannot lower the percentage of hemoglobin S sufficiently without causing hyperviscosity or transfusional volume overload. Randomized trials comparing exchange transfusion with simple transfusion for acute stroke in SCD are lacking.
Exchange transfusion typically requires placement of an apheresis catheter. A single exchange transfusion is usually sufficient to lower the hemoglobin S concentration to the desired level. The usual post-transfusion targets are a hemoglobin concentration of approximately 10 g/dL and a hemoglobin S concentration of 15 to 20 percent of total hemoglobin. These parameters permit an interval of two to four weeks before further transfusion becomes necessary. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Exchange blood transfusion'.)
Exchange transfusion may also reduce the risk of stroke recurrence. This was suggested by a retrospective study of 137 children with SCD who had an acute stroke [8]. For the 52 patients who presented within 24 hours of onset of initial stroke symptom for whom treatment information was available, second strokes were more likely in those who received simple transfusions (8 of 14 patients [57 percent]) compared with those who were treated with exchange transfusions (8 of 38 patients [21 percent]; RR 5.0, 95% CI 1.3-18.6), despite similar baseline risk factors.
Our approach is consistent with a 2014 consensus report on SCD management from the National Heart, Lung, and Blood Institute (NHLBI) in the United States [9,10].
Additional information about the differences between simple and exchange transfusion, an overview of transfusion practices in SCD, and a discussion of transfusion risks, are presented separately. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques".)
Thrombolytics/antithrombotics — Thrombolytic or antithrombotic agents for acute ischemic stroke associated with SCD are controversial. For patients with a high likelihood of non-SCD-related cause of ischemic stroke such as embolism in the setting of atrial fibrillation, it is logical to offer treatments similar to the general population for acute stroke and stroke prevention unless there is a strong reason not to do so. Therapies specific to SCD are also important.
Thrombolytic therapy — There is a concern that the use of thrombolytic agent could precipitate intracranial hemorrhage at a higher rate in individuals with SCD. However, the risk of intracranial hemorrhage in SCD seems to be due to an increased prevalence of aneurysm rather than evidence of bleed risk specific to SCD. SCD is not an exclusion criterion for tissue plasminogen activator (tPA). One observational study used administrative data to compare 832 adults with stroke and SCD and 3328 adults with stroke who did not have SCD and found no difference in the fraction receiving thrombolytic therapy (8.2 versus 9.4 percent) or in the incidence of symptomatic intracranial hemorrhage complicating thrombolytic therapy (4.9 versus 3.2 percent) [11]. Thrombolysis was felt to be safe; however, the effect of thrombolytic therapy on functional outcomes was not reported.
For children <18 years of age with SCD, intravenous tPA is not recommended; tPA is not FDA-approved for individuals <18 years of age.
Adults with SCD presenting with symptoms of acute ischemic stroke should be considered for intravenous tPA. They should meet typical criteria:
●Age ≥ 18 years
●No hemorrhage on CT scan
●Within 4.5 hours of onset of stroke symptoms
●No contraindications for thrombolysis
Only one study has assessed the use of tPA for adults with SCD using administrative data [11]; thus, administration of tPA should not replace or delay typical SCD-related acute stroke care, specifically simple blood transfusion therapy, which improves oxygen carrying capacity. Older patients with typical adult stroke risk factors such as atrial fibrillation, diabetes, hypertension, and hyperlipidemia may be viewed as more likely to benefit from tPA than younger adults without these risk factors
Patients and their families must be made aware of the limited data regarding the use of thrombolytic agents in patients with SCD [12]. We also suggest that these therapies be attempted only in centers with significant experience and in consultation with the appropriate specialists to help manage the risk of hemorrhage. (See "Approach to reperfusion therapy for acute ischemic stroke" and "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use" and "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack" and "Ischemic stroke in children: Clinical presentation, evaluation, and diagnosis".)
Anticoagulation — We generally do not use anticoagulation as a component of ischemic stroke management in patients with SCD. However, SCD is associated with a hypercoagulable state, and prophylactic dose anticoagulation may be appropriate for venous thromboembolism prophylaxis in those admitted with an acute medical illness, especially adults and those with decreased mobility. An anticoagulant may also be appropriate in specific situations, such as cerebral sinovenous thrombosis or increased probability of thromboembolic disease, once the immediate risk of hemorrhagic conversion has receded. (See "Overview of the management and prognosis of sickle cell disease", section on 'Thromboembolism prophylaxis'.)
Testing for hypercoagulable conditions is appropriate when a CSVT is found. (See "Overview of the causes of venous thrombosis" and "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors".)
Antiplatelet agents — Antiplatelet therapy with aspirin is a mainstay of treatment of acute ischemic stroke in the general population; however, the cause of the majority of ischemic strokes in the general population is not the same in children and adults with sickle cell disease. In the general population, ischemic strokes are primarily caused as a result of small vessel disease, large artery atherosclerosis or cardioembolism [13]. Cerebral infarctions due to hemodynamic changes (eg, hypoperfusion) are far less common [14] In contrast, in SCD, altered cerebral hemodynamics due to chronic hemolysis, low hemoglobin levels, and the abnormal sickle red blood cells are the main causes of cerebral ischemic injury. (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Pathophysiology and risk factors'.)
Aspirin has not been specifically studied for prevention of recurrent ischemic stroke in children and adults with SCD. Thus, aspirin is variably applied for stroke prevention in children and adults with SCD with no evidence of clinical utility [15].
In individuals with SCD and strokes, antiplatelet prophylaxis may be appropriate for stroke prevention when ischemic strokes are associated with traditional stroke risk factors, similar to the general population [6]. Some providers may consider starting antiplatelet therapy for children and adults with moyamoya syndrome; however, no evidence is available that this approach prevents infarct recurrence. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack" and "Ischemic stroke in children: Management and prognosis", section on 'Treatment for specific causes'.)
Post-diagnosis evaluation — Additional evaluation is appropriate for other causes of ischemic stroke. These may include cardioembolic sources such as atrial fibrillation or patent foramen ovale (PFO), vasospasm in association with drug use (eg, from cocaine or amphetamines), and vascular disease associated with hypercholesterolemia or diabetes. (See "Overview of the evaluation of stroke" and "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors" and "Stroke in the newborn: Classification, manifestations, and diagnosis" and "Stroke in patients with atrial fibrillation" and "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse".)
In principle, any of these conditions could affect patients of any age. However, their likelihood is age dependent. Additional information about the possible etiologies according to patient age is presented separately.
●Newborns – (See "Stroke in the newborn: Classification, manifestations, and diagnosis".)
●Children – (See "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors".)
●Adults – (See "Overview of the evaluation of stroke".)
INTRACRANIAL HEMORRHAGE - ADDITIONAL MANAGEMENT — Intracranial hemorrhage, also called hemorrhagic stroke in this setting, accounts for approximately one-third of cerebrovascular events in patients with SCD [16]. In patients with SCD, hemorrhagic stroke is more common in older individuals. (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Incidence' and "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Risk factors: Hemorrhagic stroke'.)
Treat bleeding — The site of bleeding may be subarachnoid, intraparenchymal, intraventricular, or a combination of these locations. The peak incidence of hemorrhagic stroke in SCD is between the ages of 20 and 29. Approximately 3 percent of children with SCD will have a hemorrhagic stroke by 20 years of age, and 25 to 50 percent will die within two weeks of the event [16,17]. (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Incidence' and "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Pathophysiology and risk factors'.)
In addition to acute stabilization of the patient as described above (see 'Immediate management (all patients)' above), the following should be done immediately for the patient with SCD who has a hemorrhagic stroke:
●Discontinue all anticoagulants and antiplatelet agents, unless their benefits are thought to outweigh their risks for that patient.
●For patients receiving an anticoagulant, decide whether a reversal agent is needed.
●For patients with thrombocytopenia, administer platelet transfusions as necessary to maintain the platelet count over 100,000/microL.
●Obtain neurosurgical consultation if an intervention may be required (eg, to reduce intracranial pressure or to treat a bleeding aneurysm).
●Obtain angiography if appropriate to guide further therapy.
The management of intracerebral hemorrhage and subarachnoid hemorrhage in the general population is discussed in greater detail separately. (See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis" and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Nonaneurysmal subarachnoid hemorrhage".)
Additional therapy according to type of lesion — Certain types of lesions may require additional interventions. Angiography to identify the vascular defect and guide further therapy is used in most cases.
●Hemorrhagic transformation of an ischemic lesion – Hemorrhagic transformation of an ischemic lesion should be managed as with other causes of hemorrhagic stroke, including stopping and reversing any anticoagulation, correcting any coagulopathy, and transfusing platelets as needed. As noted above, transfusion is also appropriate in this setting. (See 'Immediate management (all patients)' above and 'Transfusion' above.)
●Subarachnoid hemorrhage from aneurysmal bleeding – Initial treatment of subarachnoid hemorrhage includes intensive care monitoring, analgesia, and close attention to blood pressure control; as well as ventriculostomy for those with increased intracranial pressure. For patients with aneurysmal bleeding, surgical repair should be attempted if possible. Specific information about the optimal therapy of hypertension and choice of approach (eg, surgery, endovascular therapy) is presented separately. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Treatment of cerebral aneurysms" and "Nonaneurysmal subarachnoid hemorrhage".)
Patients with subarachnoid hemorrhage who are undergoing surgery should have exchange transfusion if possible prior to surgery, to reduce the concentration of sickle hemoglobin below 30 percent; ideally surgery is performed within a week of exchange transfusion. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Prophylactic preoperative transfusion'.)
●Intraventricular hemorrhage – Intraventricular hemorrhage (IVH) may occur when subarachnoid hemorrhage extends into the ventricles or via direct extension of intraparenchymal hemorrhage into the ventricles [18]. Patients with a prior ischemic stroke may be at risk for intraventricular and intraparenchymal hemorrhage as a late event, months to years later [19]. Hemorrhage into the third ventricle or cerebral aqueduct places patients at high risk for late deterioration. Such patients may be awake and alert immediately following the bleed and then become comatose over the ensuing 48 hours because of obstructive hydrocephalus and ventricular dilation. Emergent ventricular drainage may be necessary [20]. Additional management issues are discussed separately. (See "Intraventricular hemorrhage".)
Despite these interventions, the mortality rate in patients with SCD and central nervous system hemorrhagic lesions is as high as 24 to 50 percent [16,21-23]. Deaths generally occur within the first two weeks of the event, many on the first day [16]. In addition, some survivors are left with moderate to severe residual disability [21].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sickle cell disease and thalassemias" and "Society guideline links: Stroke in children".)
SUMMARY AND RECOMMENDATIONS
●Individuals with sickle cell disease (SCD) are at risk of ischemic and hemorrhagic stroke, especially those with HbSS or HbS-beta0 thalassemia. Without intervention, up to 11 percent of patients with SCD will have a clinically apparent stroke by 20 years of age, and one-fourth will have a stroke by age 45. (See "Prevention of stroke (initial or recurrent) in sickle cell disease".)
●Clinical assessment of the patient with SCD who presents with a new neurologic defect or altered level of consciousness includes consideration of the possibility of acute ischemic stroke, acute hemorrhagic stroke, transient ischemic attack, cerebral venous sinus thrombosis, seizure, and a number of less common stroke mimics. Neuroimaging is critical. Appropriate imaging modalities and additional laboratory testing are discussed above. (See 'Diagnosis and immediate management' above.)
●Patients with SCD and possible stroke should have assessment by clinicians with expertise in stroke and SCD management as rapidly as possible. Transfer to another facility may be required, especially if needed to provide access to exchange transfusion. In addition to standard acute stroke management and stabilization of the patient, SCD-specific interventions include attention to concurrent infection and immediate simple transfusion (prior to neuroimaging) to correct worsened anemia if the clinical suspicion for acute stroke is high. (See 'Immediate management (all patients)' above.)
●For patients with SCD who have a clinically and/or radiologically confirmed acute ischemic stroke, we suggest transfusion (Grade 2C). The goal of transfusion is to lower the percentage of sickle hemoglobin to <30 percent of total hemoglobin (typically 15 to 20 percent) and to aim for a total hemoglobin level of approximately, but not greater than, 10 g/dL. For most patients receiving transfusion, we suggest exchange transfusion rather than simple transfusion (Grade 2C). It is appropriate to provide simple transfusion while assembling resources for exchange transfusion. (See 'Transfusion' above.)
●We suggest not using anticoagulants for ischemic stroke in most individuals with SCD (Grade 2C). Exceptions are listed above. In contrast, aspirin is appropriate for acute ischemic stroke in SCD, similar to the general population, and thrombolytic therapy may be appropriate in qualifying patients. (See 'Thrombolytics/antithrombotics' above.)
●Intracranial hemorrhage (hemorrhagic stroke) accounts for approximately one-third of cerebrovascular events in patients with SCD. In addition to immediate assessment, stabilization, and other standard acute stroke management, patients with SCD and acute hemorrhagic stroke should have neurosurgical evaluation and angiography to guide therapy. Additional interventions for specific types of hemorrhagic stroke are discussed above. (See 'Intracranial hemorrhage - additional management' above.)
●Information about transfusion in SCD, including simple versus exchange transfusion, transfusion practices, and complications, is presented separately. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques".)
●Stroke prevention in individuals with SCD at risk of stroke and in those who have had an acute stroke is discussed in detail separately. (See "Prevention of stroke (initial or recurrent) in sickle cell disease".)
●Management of other acute vaso-occlusive complications of SCD is discussed in separate topic reviews. (See "Acute vaso-occlusive pain management in sickle cell disease" and "Acute chest syndrome (ACS) in sickle cell disease (adults and children)".)
ACKNOWLEDGMENT — UpToDate acknowledges ZoAnn Dreyer, MD, who contributed to earlier versions of this topic review.
The UpToDate editorial staff also acknowledge the extensive contributions of Donald H Mahoney, Jr, MD to earlier versions of this topic review.
