In general, patients with altered mental status have suffered a diffuse insult to the brain. For patients with no history of trauma, the most common causes are metabolic abnormalities, poisonings, and infectious etiologies, such as meningitis and encephalitis. For coma to occur, the underlying abnormality must be either damage or dysfunction to both cerebral hemispheres or to the ascending reticular activating system, which transverses the brain stem through the upper pons, midbrain, and diencephalon, and plays a fundamental role in arousal. Coma can result from structural damage to tissue, infectious processes, metabolic derangements, poisonings, or inadequate cerebral perfusion. Metabolic, infectious, and toxic etiologies tend to produce diffuse but symmetric deficits, such as confusion, that precede other abnormalities, such as motor deficits. Structural lesions result in focal deficits that progress in a predictable pattern. Supratentorial lesions produce focal findings that progress in a rostral–caudal fashion, whereas subtentorial lesions result in brain stem dysfunction followed by a sudden onset of coma, cranial nerve palsies, and respiratory disturbances. The causes of coma are listed in Tables 5-2 and 5-3.6,7