Kirkham, F; (2020) Sickle Cell Disease. In: Rosenberg, R and Pascual, J, (eds.) Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease. (pp. 595-609). Elsevier

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Abstract

Sickle cell disease, a chronic hemolytic anemia secondary to a single-gene mutation leading to a hemoglobin which polymerizes on hypoxic exposure, leads to a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, anterior and posterior territory transient ischemic attacks, “soft neurological signs,” seizures, headache, coma, visual loss, and altered mental status. There is a peak for ischemic stroke in childhood, typically associated with stenosis or occlusion of the distal internal carotid and proximal middle cerebral arteries diagnosable using magnetic resonance angiography (MRA) or transcranial Doppler ultrasound (TCD). For hemorrhagic stroke the peak age is early adulthood, when aneurysms are common. Silent infarction is detected on magnetic resonance imaging in up to 50% by middle age. Cognitive difficulties, characteristically affecting attention, executive function, memory, arithmetic, and processing speed, are also common. Indefinite transfusion is standard care for secondary prevention. For primary prevention in those with TCD velocities >200 cm/s, transfusion is recommended for a year; switching to hydroxyurea thereafter is noninferior if MRA is normal. l-Glutamine is FDA-approved for prevention of pain but data on CNS endpoints are lacking. New management strategies include voxelator, which decreases polymerization, monoclonal antibodies against inflammatory targets, genome editing to increase HbF and gene therapy using a lentiviral vector, as well as transplantation; trials with CNS endpoints are currently in progress.

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