In general, the longer the coma lasts, the more likely it is to be a structural brain injury rather than a functional change. Structural brain injury causing coma is usually a large destructive or occupying lesion (e.g., hemorrhage, infarction, trauma, tumor, infection, etc.) that directly or indirectly (e.g., secondary to displacement of brain structures leading to cerebral herniation) involves a nonspecific ascending reticular system; metabolic lesions are usually caused by affecting energy metabolism (e.g., ischemia-hypoxia, hypoglycemia, hypothermia/hyperthermia, severe vitamin deficiencies, infections, etc.) that result in coma by affecting energy metabolism (e.g., ischemia-hypoxia, hypothermia/hyperthermia, severe vitamin deficiencies, infections, etc.), resulting in blockage of neuronal membrane excitability (e.g., electrolyte disorders, acid-base imbalances, hypertonic or hypotonic states, hyperglycemia, generalized epileptic seizures, cerebral contusions, overdose of drugs, and poisonings), or synaptic transmission (e.g., failure of the liver, kidneys, lungs, and pancreas, the occurrence of hepatic coma, azotemia, hypercarbia, acidosis, etc., and the buildup of toxic metabolites, and pseudo-neurotransmitter production). Careful history taking and observation of the patient’s response to stimuli, respiratory pattern, pupil and eye movements, and brainstem reflexes usually identify the gross anatomic site and etiology of the coma. Depending on the sequential changes in the loss or return of neurologic reflexes during coma, as well as the degree and rate of reversibility of coma, it is helpful to determine whether the nature of the coma is a structural lesion or a metabolic disorder. In primary structural brain lesions, pathological changes are consistent with neurological deficits, and even when consciousness is restored, severe disability often remains.Levy et al. found that, if a non-traumatic coma remains without pupillary light reflexes for 24 h, without motor responses to painful stimuli for 72 h, and without eye movements for 7 d, the patient is unlikely to survive.Edgren et al. concluded that the absence of motor responses to painful stimuli after 72 h is a poor prognosis for the patient’s survival. Hamel et al. used a prospective cohort study to observe death (69%) and severe disability (20%) at 2 months in 596 patients with nontraumatic coma (mean age 67 years, with cardiac arrest in 31% and stroke in 36%). He found that 5 clinical variables tested on day 3 of patient enrollment were independently associated with 2-month mortality from nontraumatic coma, including abnormal brainstem reflexes, nonavoidance of painful stimuli, absence of verbal response, increased blood creatinine level ≥132.6 umol/L, and age ≥70 years, with corrected odds ratios (ORs) of 3.2, 4.3, 4.6, 4.5, and 5.1, respectively ; the mortality rate at 2 months was 97% for those containing 4-5 variables. Abnormal brainstem reflexes or lack of motor response to pain both more accurately predicted the rate of death and severe disability in patients at 2 months (96%). In systemic dysmetabolic lesions, coma occurs gradually, usually without focal neurologic signs, and is characterized by preserved pupillary reflexes to light. Occasionally, in certain drug toxicities (e.g., opioids, anticholinergic overdose), a diminished or absent pupillary light reflex may be found, but it is usually symmetrical. Once the primary cause is controlled, the neurologic deficit improves rapidly or even dramatically, unless irreversible structural brain damage has been combined late in the course of the disease.