Dissections within the carotid arteries or vertebral arteries may compromise blood flow to the brain due to thrombosis, and dissections increase the risk of vessel rupture. Idiopathic
Idiopathic diseases are those that occur spontaneously without a known cause. Moyamoya is an example of an idiopathic cerebrovascular disorder that results in narrowing and occlusion of intracranial blood vessels. The most common presentation is stroke or transient ischemic attack, but cognitive decline within children may also be a presenting symptom. The disease may begin to show symptoms beginning in adolescence, but some may not have symptoms until adulthood. Pathophysiology
Mechanism of brain cell death
When a reduction in blood flow lasting seconds occurs, the brain tissue suffers ischemia, or inadequate blood supply. If the interruption of blood flow is not restored in minutes, the tissue suffers infarction followed by tissue death. When the low cerebral blood flow persists for a longer duration, this may develop into an infarction in the border zones (areas of poor blood flow between the major cerebral artery distributions). In more severe instances, global hypoxia-ischemia causes widespread brain injury leading to a severe cognitive sequelae called hypoxic-ischemic encephalopathy.An ischemic cascade occurs where an energetic molecular problem arises due to lack of oxygen and nutrients. The cascade results in decreased production of adenosine triphosphate (ATP), which is a high-energy molecule needed for cells in the brain to function. Consumption of ATP continues in spite of insufficient production, this causes total levels of ATP to decrease and lactate acidosis to become established (ionic homeostasis in neurons is lost).
Each represents a distinct molecular point of failure in a subunit that is required for activation of the enzyme. Tay–Sachs disease
Tay–Sachs disease is a rare autosomal recessive genetic disorder that causes a progressive deterioration of nerve cells and of mental and physical abilities that begins around six months of age and usually results in death by the age of four. It is the most common of the GM2 gangliosidoses. The disease occurs when harmful quantities of cell membrane gangliosides accumulate in the brains nerve cells, eventually leading to the premature death of the cells. Sandhoff disease
Sandhoff disease is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. The disease results from mutations on chromosome 5 in the HEXB gene, critical for the lysosomal enzymes beta-N-acetylhexosaminidase A and B. Sandhoff disease is clinically indistinguishable from Tay–Sachs disease. The most common form, infantile Sandhoff disease, is usually fatal by early childhood. AB variant
GM2-gangliosidosis, AB variant is a rare, autosomal recessive metabolic disorder that causes progressive destruction of nerve cells in the brain and spinal cord. Mutations in the GM2A gene cause AB variant. The GM2A gene provides instructions for making a protein called the GM2 activator. This protein is a cofactor that is required for the normal function of beta-hexosaminidase A. The disease is usually fatal by early childhood. Treatment
There are no authorized therapies for the treatment of the GM2 Gangliosidosis (Tay-Sachs and Sandhoff disease).