A. Introduction

1. Requirements for Consciousness
   1. Brainstem Intact - critical areas in Pons and Rostral Medulla
   2. Critical brainstem region is the Reticular Activating System (RAS)
   3. One Cerebral Hemisphere must ALSO be intact
   4. Therefore, disruption of both cerebral hemispheres OR RAS causes loss of consciousness
2. Coma
   1. Continuous unarousable state
   2. Closed eyes
   3. No response to verbal stimulation or appropriate resistance to motor stimulation
   4. Loss of oculocephalic response ("doll's eyes")
   5. Loss of caloric responses
   6. Decerebrate responses
   7. Caused by structural, toxic, or metabolic disturbances of reticular system or thalamic projections
3. Vegetative State (VS) [1,2]
   1. Condition of patients with severe brain damage
   2. Vegetative functions persist: sleep-wake cycles, autonomic control, breathing
   3. Awareness is abolished - including all cognitive function and emotion
   4. Incapable of interaction with others
   5. No purposful, sustained or reproducible voluntary behavioral response to visual, auditory, tactile or noxious stimuli
   6. no language comprehension or expression
   7. Bowel and bladder incontinence
   8. Preserved cranial nerve reflexes
   9. In USA, ~15,000 patients exist in persistent VS each year
4. Coma and VS therefore differ
   1. Eyes open in "awake cycle" of VS
   2. Spontaneous respiration in VS
5. Minimally Conscious State (Panel 3, Ref [1])
   1. Global impaired responsiveness
   2. Limited but discernable evidence of awareness of self and environment by at least one of:
   3. Following simply commands
   4. Gestural or verbal repsonses to yes/no questions
   5. Intelligible verbalization
   6. Purposeful behavior: movements or affective behaviors that occur in response to relevant environmental stimuli (not simply reflexes)
6. Locked-In Syndrome
   1. Awareness is intact, communication difficult
   2. Intact wakefulness
   3. Intact breathing, often with brain stem signs
   4. Quadraplegia and pseudobulbar palsy
   5. Electroencephalogram (EEG) usually normal
   6. Normal or nearly normal PET/functional MRI (fMRI)
7. Brain Death
   1. Absent awareness, wakefulness, brain stem, respiratory function
   2. EEG silent
   3. Absent cortical metabolism on PET or fMRI
   4. Legally dead in most jurisdictions

B. Causes of Coma

1. Anoxia - Most Common Cause
   1. Global Hypoperfusion -myocardial infarction, aortic dissection, hemorrhage, cardiac arrest, severe congestive heart failure
   2. Focal Hypoperfusion of Reticular Activating System
   3. Very Severe Pneumonia / Respiratory Failure
2. Trauma
   1. Subdural and subarachnoid Hemorrhage
   2. Parenchymal Intracranial Bleed
   3. About half of patients with trauma who enter VS recover within 1 year
3. Herniation Syndromes
4. Metabolic
   1. Hypoxia
   2. Diabetic Ketoacidosis, Nonketotic Coma
   3. Hypoglycemia
   4. Hypercalcemia
5. Endocrine - hypothyroidism, hypopituitarism, adrenal insufficiency (Addison Syndrome)
6. Organ Dysfunction - Hepatic Failure, Renal Failure with Uremia
7. Toxins - hypnotics, tranquilizers, EtOH, opiates, anti-cholinergics, carbon monoxide
8. Infectious - Meningitis and Encephalitis
9. Hydrocephalus
10. Patients in a coma may:
    1. Remain in a coma
    2. Enter a VS, either persistent or temporary
    3. Recover with minimal brain damage

C. Assessment

1. Glasgow Coma Scale (GCS): Each of three categories graded:
   1. Eye Response (1-4)
   2. Verbal Response (1-5)
   3. Motor Response (1-6)
2. Cold Calorics (Brainstem vestibulo-ocular response, CN VIII, III and VI)
3. Corneal Blink Reflex (CN V, VII, and III)
4. Electroencephalography (EEG)
5. Cerebral MRI Analysis [2]
   1. Superior to CT for detection of brainstem and corpus callosal lesions
   2. May be superior to CT for prognosis
   3. Definitely superior to EEG
   4. Functional MRI (fMRI) or PET scan now considered standard of care for evaluation

D. Disturbances of Respiratory Pattern

1. Abnormal respiratory patterns are common in unconscious patients
   1. Kussmaul Breathing
   2. Cheyne-Stokes Respiration
   3. Central neurogenic hyperventilation associated with midbrain damage
   4. Ataxic breathing (agonal gasps) commonly associated with pontine-medullary junction
   5. Hypoventilation or apnea commonly associated with medullary dysfunction
2. Kussmaul Breathing
   1. Rapid, deep breathing in unconscious patients
   2. Associated with metabolic encephalopathy (acidosis)
   3. Diabetic ketoacidosis frequently produces this pattern
   4. Also found with pontomesencephalic lesions
3. Cheyne-Stokes Respiration
   1. Periodic (cyclical) breathing pattern usually found in severe disease
   2. Apenas or hypopneas alternate with hyperventilation in cresecendo-decrescendo pattern
   3. Bilateral cortical dysfunction including coma
   4. Sedative drug intoxication
   5. Heart Failure
   6. Sleep Apena
   7. Direct vascular lesions
   8. Theophylline has been shown to effectively alleviate this condition [3]
   9. Oxygen or carbon dioxide may also be effective
4. Brain dead patients may have shallow respiratory-like movements with back arching

D. Prognosis

1. Criterion: Coma >6 hours
   1. 76% dead within 1 month
   2. 88% dead within 1 year
2. Vegetative State (VS)
   1. About 50% of patients in persistent VS from trauma recover in 1 year
   2. MRI scans performed 6-8 weeks after traumatic injury predict outcome very well [2]
   3. Presence of lesions in corpus callosum or dorsolateral brainstem predict poor outcome
   4. Auditory or visual stimulations do not appear to alter outcomes

References

1. Bernat JL. 2006. Lancet. 367(9517):1181
2. Kampfl A, Schmutzhard E, Franz G, et al. 1998. Lancet. 351(9118):1763
3. Pesek CA, Cooley R, Narkiewicz K, et al. 1999. Ann Intern Med. 130(5):427