neurologic disorders
Overview of Coma and Impaired Consciousness
Pathophysiology
Maintaining alertness requires intact function of the cerebral hemispheres and preservation of arousal mechanisms in the reticular activating system (RAS—also known as the ascending arousal system)—an extensive network of nuclei and interconnecting fibers in the upper pons, midbrain, and posterior diencephalon. Therefore, the mechanism of impaired consciousness must involve both cerebral hemispheres or dysfunction of the RAS. To impair consciousness, cerebral dysfunction must be bilateral; unilateral cerebral hemisphere disorders are not sufficient, although they may cause severe neurologic deficits. However, rarely, a unilateral massive hemispheric focal lesion (eg, left middle cerebral artery stroke) impairs consciousness if the contralateral hemisphere is already compromised or if it results in compression of the contralateral hemisphere (eg, by causing edema). RAS dysfunction can result from a condition that has diffuse effects, such as toxic or metabolic disturbances (eg, hypoglycemia, hypoxia, uremia, drug overdose). RAS dysfunction can also be caused by focal ischemia (eg, certain upper brain stem infarcts), hemorrhage, or direct, mechanical disruption. Any condition that increases intracranial pressure (ICP) may decrease cerebral perfusion pressure, resulting in secondary brain ischemia. Secondary brain ischemia may affect the RAS or both cerebral hemispheres, impairing consciousness. When brain damage is extensive, Brain Herniation (see also figure Directly compresses brain tissue Blocks the blood supply to areas of the brain Increases ICP May lead to hydrocephalus by obstructing the cerebral ventricular system Results in neuronal and vascular cell dysfunction May shift brain structures from one side of the brain to the other side In addition to the direct effects of increased ICP on neuronal and vascular cells, cellular pathways of apoptosis and autophagy (which are forms of programmed cell death or destruction) can become activated. Apoptosis has early and late phases that ultimately lead to the destruction of deoxyribonucleic acid (DNA) in cells. In autophagy, components of cell cytoplasm are recycled in an attempt to remove nonfunctional organelles and can sometimes lead to neuronal and vascular cell injury ( Pathophysiology references ). Additional pathways that are tied to apoptosis and autophagy have been newly discovered; these pathways involve circadian clock genes that can oversee daily cellular function ( Impaired consciousness may progress to coma and ultimately to Brain Death . 1.Maiese K, Chong ZZ, Shang YC, Wang S: Targeting disease through novel pathways of apoptosis and autophagy.Expert Opin Ther Targets16 (12):1203–1214, 2012. doi: 10.1517/14728222.2012.719499 Epub 2012 Aug 27. 2.Maiese K: Cognitive impairment and dementia: Gaining insight through circadian clock gene pathways.Biomolecules11 (7):1002, 2021. doi: 10.3390/biom11071002 