Therapy Insight: Stroke Risk and Its Management in Patients With Sickle Cell Disease

Fenella J. Kirkham

Disclosures

Nat Clin Pract Neurol. 2007;3(5):264-278. 

In This Article

Clinical Presentation of Stroke in Sickle Cell Disease

There is a broad spectrum of acute presentation with CVA and other neurological complications in patients with SCD ( Table 1 ). Clinical stroke, with focal signs lasting more than 24 hours (Figure 1A),[4] is 250 times more common in children with SCD than in the general pediatric population,[5] and commonly presents 'out of the blue' in an apparently well child.[1] Patients with SCD also have transient ischemic attacks with symptoms and signs resolving within 24 hours,[3] although many of these individuals are found to have had recent cerebral infarction or atrophy on imaging (Figure 1B).[4] The insidious onset of 'soft neurological signs', such as difficulty in tapping quickly, is usually associated with cerebral infarction.[6,7] In addition, seizures[8] (Figure 1C), coma[9] (Figure 1D) and headache[10] (Figure 1E) are common presentations of stroke and cerebrovascular disease in children with SCD. Hyperventilation, for example during an electroencephalogram, occasionally provokes transient or permanent neurological deficits, usually involving the posterior circulation territory.[11] Altered mental status—with or without reduced level of consciousness, headache, seizures, visual loss or focal signs—can occur in numerous contexts, including infection (Figure 1D), shunted hydrocephalus[12] (Figure 1E), acute chest syndrome (ACS)[13,14,15] (Figure 1F), aplastic anemia secondary to parvovirus,[16,17] after surgery,[10,18,19] transfusion[20] or immunosuppression[21,22] (Figure 1G), and apparently spontaneously[23] (Figure 1H). In one large series of patients with ACS, 3% of children had neurological symptoms at presentation, and such symptoms developed in a further 7-10% as a complication of ACS.[13] These patients are classified clinically as having had a CVA,[2,3] although there is a wide differential of focal and generalized vascular and nonvascular pathologies—often distinguished using acute magnetic resonance techniques[23] (Figure 1)—with important management implications.[11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27]

Axial T2-weighted MRI (unless otherwise stated). (A) Large middle cerebral territory infarct in a previously asymptomatic girl with sickle cell anemia (SCA). (B) Left occipital infarct with moderate lobar atrophy (arrow) in a boy with HbSβ0-thalassemia who presented with two episodes of reversible ischemic neurological deficit (left and right hemiparesis). (C) Covert ('silent') infarctions (arrow) in a child with SCA and focal tonic seizures. (D) Infarction in both anterior and posterior arterial border zones in an 8-year-old boy with previously uncomplicated SCA who developed seizures and coma after surgery to drain a painful swelling of his left cheek, which was sustained after a fall and was associated with fever. (E) CT scan of a child with hemoglobin sickle cell disease who had a shunt placed in infancy. The scan was performed 10 days after presentation with headache, and shows definite cerebral edema; the dense appearance of the straight sinus (arrow) raises the possibility of venous sinus thrombosis, but is not diagnostic. (F) Signal change in the left posterior occipital (arrow) and bilateral high parietal regions ('reversible posterior leukoencephalopathy') with hippocampal involvement in a woman with previously uncomplicated SCA who presented aged 18 years with acute chest syndrome. (G) Signal change in the grey and white matter ('reversible posterior leukoencephalopathy'; arrows) in a 9-year-old boy with SCA who had been treated with ciclosporin for nephrotic syndrome. (H) Intracerebral hemorrhage (arrow) in a previously well child with SCA who presented with acute headache.

In addition to those who have had obvious acute neurological events, by adolescence up to 25% of children with homozygous sickle cell anemia have covert or 'silent' infarction on MRI, characteristically in the anterior or posterior border zones[28,29,30,31] (Figure 1C), without having had a clinical stroke. Voxel-based morphometry (Figure 2) shows that, compared with controls, there is evidence of damage in the white matter of the border zones, even in patients with sickle cell anemia who have normal T2-weighted MRI.[31] Neurological examination is usually normal,[6,7] although these patients might have had subtle transient ischemic attacks, headaches or seizures.[32] Cognitive difficulties,[33,34] which commonly affect attention[33] and executive function,[35] are common in SCD, sometimes from infancy;[36] they can be progressive,[37,38] and are associated with covert brain damage.[31,33,37,39]

Voxel-based morphometry comparison of white matter density between controls and patients with sickle cell anemia and covert infarction. Regions of reduced white matter density in patients with sickle cell anemia and covert infarction are displayed on the mean white matter segment. The white matter abnormality distribution is similar to that in the patient with overt stroke shown in Figure 1D.

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