Sickle cell disease is an inherited disorder caused by the abnormal properties of red blood cells containing mutant sickle cell hemoglobin. The disorder is autosomal recessive and is seen in blacks of African descent. The prevalence of sickle cell trait is 8–10% among black newborns in the United States and as high as 25–30% in western Africa. In the United States, there are 4,000 to 5,000 pregnancies at risk for sickle cell disease each year. About 50,000 to 60,000 patients with sickle cell disease live in the United States.

Acute and chronic organ dysfunction, chronic hemolytic anemia, and recurrent painful episodes are the main features of sickle cell disease. In the deoxygenated condition, the hemoglobin tetramer polarizes and the cell shape becomes distorted, resulting in rigid red blood cells. Cell damage leads to hemolytic anemia and to occlusion of vessels in multiple organs, including the brain.

The different sickle cell syndromes that result from distinct inheritance patterns of the sickle cell gene (beta S gene) are divided into sickle cell disease and sickle cell trait. Sickle cell disease is associated with chronic anemia and recurrent pain. The sickle cell trait is largely asymptomatic.9,10

Clinical presentation

The typical patient is anemic but asymptomatic, except during painful episodes. Most organ systems are subject to vascular occlusion, resulting in the characteristic acute and chronic multisystem failure.

Neurologic complications include stroke, which is the second leading cause of death after infection and occurs in 5.5–15.0% of homozygous children. The risk of stroke in children with sickle cell disease is 250 to 400 times that of the general population, with the probability of stroke by age 40 years approximately 32%. The mean age of development of cerebral infarcts is 8 years. Hemorrhage is usually seen in older patients, at a mean age of 25 years.10

Evaluation of seizures

The incidence of focal or generalized seizures among patients in the United States with sickle cell disease varies from 6% to 12%.9,10 In these patients, seizures may

  • accompany ischemic or hemorrhagic acute strokes
  • result from a previous stroke (e.g., focal gliotic parenchymal lesion)
  • accompany CNS infections, such as meningitis or meningoencephalitis
  • accompany a systemic infection with high fever, sepsis, or disseminated intravascular coagulation
  • accompany any metabolic abnormality due to systemic malfunction, such as acidemia or uremia due to renal insufficiency
  • be precipitated by dehydration, which is a risk factor for sickling
  • be precipitated by medications commonly used for sickle cell disease, such as meperidine (Demerol)

Magnetic resonance imaging (MRI) and transcranial Doppler (TCD) flow studies are useful in detecting subclinical cerebral infarction. The ability to predict strokes by detecting arterial stenosis with TCD and to prevent the occurrence of such strokes with chronic transfusion has led to the recommendation that TCD be used for routine screening and that transfusion be instituted on detection of arterial stenosis.12–17

Patients with sickle cell anemia may be at particular risk of ischemic cerebral injury in situations associated with hyperventilation, which produces cerebral artery constriction and cerebral hypoxia.18 Therefore, if the assessment includesEEG, these patients should probably not be hyperventilated.

Treatment of seizures

Therapeutic interventions for sickle cell disease are directed at specific complications. When seizures occur, their treatment may interfere with some aspects of sickle cell disease or its management:

  • Exacerbation of folate deficiency: Repeated episodes of hemolytic anemia may lead to folic acid deficiency, which is exacerbated by some antiepileptic drugs (AEDs) (see Folate deficiency). Patients with this condition take 1 mg per day of folic acid, regardless of any AEDs they are taking. Folate deficiency is a special concern for women of childbearing age.
  • Drug interactions: Warfarin and minidose heparin have been advocated in sickle cell disease, and methylprednisolone has been reported to provide pain relief. Hepatic enzyme–inducing AEDs increase the metabolism of anticoagulants and steroids (see Anticoagulation and antiplatelet therapy in epilepsy). Another sickle-cell treatment is bone marrow transplantation. Carbamazepine may decrease blood levels of cyclosporine, the main immunosuppressive agent after transplants.11

If it can be used effectively as monotherapy, gabapentin may be a good choice for the chronic treatment of seizures in sickle cell disease, since it is less likely to interfere with other drugs or medical conditions than many other AEDs. Other choices include lamotrigine or topiramate, based on their side effect profiles and the likelihood of interactions with other drugs commonly administered for this condition.

For acute seizure management, diazepam and lorazepam are reasonable choices. If needed, phenytoin can be administered for a short time and later changed to one of the chronic AEDs mentioned.

Adapted from: Sepkuty JP and Kaplan PW. Hematologic and pulmonary disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;209–228. 
With permission from Elsevier (www.elsevier.com). 

Reviewed by: Steven C. Schachter, MD
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