Cerebral reorganization of language and motor control secondary to chronic hemispheric vasculopathy in a patient with homozygous sickle‐cell disease

Abstract

A 43-year-old man with homozygous sickle-cell disease (SCD) had a first ischemic stroke in the left middle cerebral artery territory at the age of 15 years, with a minor persistent neurological deficit of right limbs due to occlusion of the left middle cerebral artery with a Moya-Moya-like lenticular-striatal collateral network. At 32 years, he had a second left hemisphere stroke, involving the whole territory of the middle and posterior cerebral arteries, sparing only prefrontal areas. This second major infarct produced only limited clinical symptoms: incomplete right hemiparesis and hypoesthesia, right lateral hemianopia, and reduced verbal fluency without overt aphasia. Morphological magnetic resonance imaging (MRI) showed atrophy of the left cerebral hemisphere and peduncle associated with Wallerian degeneration. Single-photon-emission computed tomography (SPECT) showed hypoperfusion of the entire left cerebral hemisphere. In contrast, no vasculopathy was revealed by magnetic resonance angiography (MRA), SPECT, or transcranial doppler ultrasonography of the right cerebral hemisphere. Functional mapping of the motor cortex was obtained with trans-cranial magnetic stimulation (TMS) with MRI-guided navigation 1. Navigated TMS showed that all motor-evoked potentials recorded on the right side of the body had their origin in the right precentral cortex. In addition, functional MRI showed that language functions had been lateralized in the right hemisphere (Image 1). This unusual lateralization of motor and language functions in the right hemisphere suggests successful adaptive neuroplasticity from the damaged left hemisphere to the right hemisphere. As no sign of cerebral vasculopathy was found in this hemisphere, chronic blood-exchange transfusions (BET) could be stopped and replaced by oral hydroxyurea. BET is the treatment of choice for reducing the risk of stroke in children with SCD and abnormal cerebral blood flow on trans-cranial doppler or MRA 2. Despite its recognized benefits, BET is associated with various complications, for example, infections, alloimmunization, hemolytic transfusion reactions, and iron overload. Functional MRI and TMS provide simultaneous analyses of brain-function localization and could thus represent a complementary tool for therapy management: if specific functional areas are identified in brain regions at risk of hypoperfusion, treatment should be reinforced, including BET, whereas affected nonfunctional areas are not therapeutic targets. This case illustrates the importance of functional and neurocognitive rehabilitation of SCD patients who have had a stroke, particularly during childhood when the vasculopathy appears. Even though very few studies have evaluated the impact of rehabilitation of SCD patients 3, our observations support that functional reorganization can occur in this particular population.