Table of Contents
Patients, Families and Friends
Health Care Providers
|MANAGEMENT AND THERAPY OF SICKLE CELL DISEASE|
NIH Publication No. 95-2117, Revised December 1995 (Third Edition) National Institutes of Health, National Heart, Lung, and Blood Institute
Clinically evident stroke is a devastating complication of SS disease that affects from 6 to 12 percent of patients. Strokes are very rare in persons with Hb SC disease. In children under age 10 years, the most common cause of stroke is cerebral infarction. Ischemic stroke typically presents with signs and symptoms of hemiparesis or monoparesis, hemianesthesia, visual field deficits, aphasia, cranial nerve palsies, or acute change in behavior. Although recovery occasionally is complete, intellectual, motor, and sensory impairments are typical sequelae. Intracranial hemorrhage becomes increasingly more common with advancing age. In hemorrhagic stroke, more generalized phenomena such as coma, headache, and seizures occur. Recurrent stroke causes progressively greater impairment and increased likelihood of mortality. A "completed stroke" signifies a fixed neurologic deficit, whereas "stroke in progression" implies worsening of the neurologic deficit or appearance of new focal abnormalities while the patient is under observation. Nonfocal complaints such as dizziness, headache, or fainting are not in themselves representative of cerebral vascular disease but should be investigated carefully.
A transient ischemic attack (TIA) is a focal neurologic deficit persisting for less than 48 hours (24 hours for internal carotid, anterior, or middle cerebral arteries and 48 hours for vertebral or basilar arteries) that follows a vascular distribution. Typically, there is no clinically apparent residual deficit from a TIA, though newer imaging modalities such as MRI and positron emission tomography (PET) have identified ischemic brain lesions in both the gray and white matter in some patients. TIA often is a harbinger of subsequent stroke.
Infarction usually occurs in a segmental pattern that suggests damage to the large cerebral arteries. The most common abnormalities found on arteriography or magnetic resonance angiography (MRA) are marked narrowing or complete occlusion of the anterior cerebral arteries (ACA) and/or middle cerebral arteries (MCA). Multiple, bilateral vessel involvement is usual, even in patients who have unilateral neurologic signs. Vessel narrowing is the consequence of intimal and medial proliferation that is thought to be caused by endothelial damage from sickled red blood cells. The damaged, irregular endothelium can serve as a nidus for the adhesion of platelets and sickle cells, thereby resulting in thrombus formation. The stroke event occurs when narrowing is severe enough to compromise distal flow or the thrombus dislodges and causes distal embolization. Transient neurologic symptoms can result from vessel spasm. Intracranial hemorrhage can be intracerebral or subarachnoid and can result from rupture of an aneurysm of the circle of Willis. Intracerebral hemorrhage may also occur years later in patients who had prior cerebral infarction as a result of a rupture of fragile collateral vessels (moyamoya). DIAGNOSIS A high-resolution, computerized tomographic (CT) scan performed as an emergency diagnostic procedure without contrast may be normal at the onset in cerebral infarction but is helpful in ruling out bleeding, abscess, tumor, or other abnormalities. The CT scan 2 to 7 days later typically is able to demonstrate the area of infarction. MRI is a sensitive technique for detecting intracranial hemorrhage or infarction. MRA permits visualization of major intracerebral vessels without the potential hazards of hypertonic contrast materials. However, MRI/MRA scanning requires more time at the imaging center than CT scanning, and high-resolution equipment (1.5 tesla or more) is required. Lumbar puncture, which should be done only if a CT scan or MRI reveals no evidence of increased intracranial pressure, is occasionally necessary to eliminate infection or subarachnoid hemorrhage as the cause of the stroke. Arteriography is not necessary to confirm cerebral infarction demonstrated by CT scan, MRI, or MRA, but it can be helpful in clarifying the diagnosis in the rare symptomatic (hemiparesis) patient with normal CT or MRI scans. Use of hyperosmolar contrast material makes arteriography potentially hazardous in patients with sickle cell disease. Adequate hydration, reduction of the Hb S level to less than 30 percent by transfusion, and close supervision decrease the risk. In emergency situations, partial or total exchange transfusion can be used to lower the level of Hb S rapidly (see Chapter 10, Transfusion). It is uncertain whether CT scanning with intravenous infusion of the new contrast agents with reduced osmolarity is less hazardous in untransfused patients. CT scan or MRI/MRA should be performed on patients who experience a TIA. Patients with persistent or severe headaches, syncopal episodes, or seizures deserve thorough evaluations, often by a neurologist, and may need neurologic imaging. Transcranial Doppler studies or ultrasonography of the large cerebral vessels may reliably predict the patient who is at risk for stroke when narrowing of the MCA or ACA is identified. The prognostic value of newer techniques such as PET or metabolic MRI are under intensive investigation. Data suggest that abnormalities on metabolic MRI scans or PET scans in SS patients, who do not have overt neurologic deficits, may be useful in identifying patients at risk for progression of the cerebral vasculopathy and future strokes. A schema for evaluating neurological events is displayed in figures 1 and 2.
TREATMENT OF ACUTE VASO-OCCLUSIVE STROKE
For the patient with acute occlusive stroke, rapid evaluation and careful monitoring are essential. Patients should be admitted to an intensive care unit. Raised intracranial pressure should be treated promptly with pharmacological agents. Assisted ventilation may be necessary. Hyperventilation therapy, however, should be avoided. The involvement of a neurologist and/or neurosurgeon is essential. Seizures are common during acute infarction and hemorrhage and require anticonvulsant therapy. Exchange transfusion to decrease the level of Hb S to less than 30 percent may help to prevent progression of the acute stroke. Figure 1 (Figure omitted) Algorithm for evaluating clinical stroke. Figure 2 (Figure omitted) Algorithm for evaluating transcient ischemic attacks and repeat afebrile seizures. In addition to transfusions, it is important to provide rehabilitation services to the patient. Although many children may exhibit remarkable recovery from a stroke, a detailed assessment of intellectual function should be done to determine if the child would benefit from special assistance with academic work because acquired learning difficulties may be the consequence of the stroke.
PREVENTION OF RECURRENT OCCLUSIVE STROKE
Vaso-occlusive strokes will recur in at least two-thirds of patients, unless they are placed on a chronic program. Transfusions of packed red blood cells given at regular intervals to keep the level of Hb S below 30 percent are effective in minimizing a recurrence of cerebral infarction in children. A transfusion program should be maintained for a minimum of 5 years. Should neurologic symptoms develop in adequately transfused patients, repeat imaging studies are warranted. The optimal duration of transfusion therapy is not known. The risk of recurrence in untransfused children is greatest in the first 3 years after the initial event. Many centers transfuse patients for years but modify the intensity of transfusions to reduce the rate of iron accumulation. Centers that transfuse patients for long periods use iron-chelating agents (deferoxamine mesylate) to decrease iron overload.
Prognosis for long-term neurologic function and independent self-sufficient adult life is guarded. The role of bone marrow transplantation as an alternative therapy for these patients is unclear at - present. Inadequate transfusion therapy, as defined by a failure to suppress Hb S below 30 percent, may be due to inadequate frequency of transfusions, poor compliance, development of alloimmune or autoimmune antibodies, or blood loss. Although aspirin or coumadin therapy has been effective in decreasing the risk of recurrent stroke in adult patients with normal hemoglobin (AA), or in those who have had prior TIA, the efficacy of such therapy in central nervous system disease in patients with sickle cell disease has not been established.
Patients with intracranial hemorrhage (IH) may present with focal neurological deficits, severe headache, increased intracranial pressure, or coma. Immediate mortality is as high as 50 percent. This is a frequent cause of sudden unexpected death at home. In patients with end-stage renal failure from sickle cell disease, IH is a common cause of death. Immediate CT or MRI scanning should demonstrate the hemorrhage. Lumbar puncture may be necessary to demonstrate the subarachnoid hemorrhage (blood in cerebrospinal fluid) in some patients. Because vasospasm in the area of hemorrhage can produce secondary cerebral infarction, immediate exchange transfusion is recommended. There are no data regarding the efficacy of long-term transfusion therapy for patients with IH. In those patients who are not uremic, arteriography is necessary to determine if a surgically correctable lesion (aneurysm) is present.
IDENTIFICATION OF PATIENTS AT RISK FOR STROKE
Abnormal cerebral blood flow assessed by transcranial Doppler ultrasonography has been shown to be predictive of stroke in patients with sickle cell disease. Increased flow rates in the intracerebral arteries is secondary to stenosis and is associated with an increased risk for infarctive stroke.
This syndrome must be treated rapidly and aggressively. Complete exchange transfusion is thought to be useful. Aggressive treatment of hypoxia, including the use of positive end-expiratory pressure (PEEP) or oscillating ventilatory devices if necessary, is essential as well as management in an intensive care unit.
Adams R, McKie V, Nichols FT, et al. The use of transcranial ultrasonography to predict stroke in sickle cell disease. N Engl J Med 1992;326:605-10.
Anson JA, Koshy M, Ferguson L, Crowell RM. Subarachnoid hemorrhage in sickle cell disease. J Neurosurg 1991;75:522- 88.
Craft S, Schatz J, Glauser TA, Lee B, DeBaun MR. Neuropsychological effects of stroke in children with sickle cell anemia. Pediatrics 1993;123:712-7.
Koshy M, Thomas C, Goodwin J. Vascular lesions in the central nervous system in sickle cell disease (neuropathology). J Assoc Acad Minor Phys 1990;1:71-8.
Pavlakis SG, Prohovnik I, Piomelli S, DeVivo DC. Neurologic complications in sickle cell disease. Adv Pediatr 1989;36:247-76.
Powars D, Wilson B, Imbus C, Pegelow C, Allen J. The natural history of stroke in sickle cell disease. Am J Med 1978;65:461.
Russel MO, Goldberg HI, Hodson A, et al. Effect of transfusion therapy on arteriographic abnormalities on the recurrence of stroke in sickle cell disease. Blood 1984;63:162.
Wang WC, Kavnar EH, Tonkin IL, et al. High risk of recurrent stroke after discontinuance of five to twelve years of transfusion in patients with sickle cell disease. J Pediatr 1991;118:377.
Wiznitzer M, Ruggieri PM, Masaryk TJ, Ross JS, Modic MT, Berman B. Diagnosis of cerebrovascular disease in sickle cell anemia by magnetic resonance angiography. J Pediatr 1990;117:551-5.