Central nervous system


The central nervous system shows both multiple developmental and ischemic changes. The developmental defects include brain malformations suggestive of aberrant neuronal migration including heterotopia, irregular cortical thickness, incomplete gyral formation, poor definition of cortical layers, and hamartia. Additionally, adolescent and adult patients have very few neural progenitors (stem cells). Despite these malformations, most SIOD patients have normal social, language, motor, and cognitive development until the onset of symptoms from reduced brain blood supply (cerebral ischemia).

The cerebral ischemia can either temporarily or permanently disturb the blood supply of a given area of the brain and thereby cause temporary (47%, transient ischemic attacks) or permanent (44%, strokes) dysfunction. The cerebral ischemic attacks and strokes are often precipitated by acute changes in blood pressure, such as following the administration of high doses of steroids. Ischemic changes include loss of neurons and myelin, gliosis (scarring), brain atrophy, and degeneration of infarcted regions including atrophy of the cerebellum. Likely as a complication of the cerebral ischemia and atherosclerosis, a few of the patients have also manifest Moyamoya disease.

Another common neurological feature in SIOD patients is severe migraine-like headaches (60%). The cause of the headaches is still unknown but they tend to be more severe and refractory to anti-migraine medications that migraine-like headaches in the general population. In one patient a reversible cerebral vasoconstriction syndrome was suspected. 

-National Organization for Rare Disorders