Persistent Vegetative State

Overview

Definition

Persistent vegetative state, also called unresponsive wakefulness, describes the condition of individuals with severe anoxic brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification injury who have progressed to a state of wakefulness without any meaningful response to their environment.

• The definition requires permanence of vegetative state, which is established:
  • 3 months after a hypoxic brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification injury
  • 1 year after a traumatic brain injury Traumatic brain injury A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain. Le Fort Fractures
• The persistent vegetative state represents a transition between coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma and recovery or between coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma and death.
• The following criteria need to be present for the diagnosis:
  • No evidence of awareness of self or environment and an inability to interact with others
  • No evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli
  • No evidence of language comprehension or expression
  • Intermittent wakefulness manifested by the presence of sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep–wake cycles
  • Sufficiently preserved hypothalamic and brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem autonomic function to permit survival with medical and nursing care
  • Bowel and bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess incontinence
  • Variably preserved cranial nerve reflexes and spinal reflexes

Epidemiology

• In the United States, there are 15,000–40,000 individuals in a persistent vegetative state.
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency varies widely: estimated at 0.2–6.1 individuals per 100,000

Etiology

• Anything that causes extensive damage to the cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex: Anatomy and spares the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem
• Traumatic brain injury Traumatic brain injury A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain. Le Fort Fractures (most common)
• Nontraumatic brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification injury
  • Hypoxic–ischemic injury ( hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, cardiac arrest Cardiac arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest, arrhythmia, near-drowning)
  • Hemorrhagic or thrombotic cerebrovascular event
  • Toxins:
    • Uremia Uremia A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of renal insufficiency. Most uremic toxins are end products of protein or nitrogen catabolism, such as urea or creatinine. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms. Acute Kidney Injury
    • Ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism
    • Opiates Opiates Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
    • Lead
  • Bacterial, viral, or fungal infection
  • Increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension (e.g., tumor Tumor Inflammation or abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease)
  • Electrolyte imbalance:
    • Hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia or hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia
    • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia or hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus
    • Hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia or hypercalcemia Hypercalcemia Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Hypercalcemia
  • Endocrine disorders:
    • Adrenal insufficiency Adrenal Insufficiency Conditions in which the production of adrenal corticosteroids falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the adrenal glands, the pituitary gland, or the hypothalamus. Adrenal Insufficiency and Addison Disease 
    • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy disorders
  • Degenerative and metabolic diseases:
    • Urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle cycle disorders
    • Reye syndrome Reye syndrome A form of encephalopathy with fatty infiltration of the liver, characterized by brain edema and vomiting that may rapidly progress to seizures; coma; and death. It is caused by a generalized loss of mitochondrial function leading to disturbances in fatty acid and carnitine metabolism. Varicella-Zoster Virus/Chickenpox
    • Mitochondrial diseases Mitochondrial diseases Diseases caused by abnormal function of the mitochondria. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes. Mitochondrial Myopathies
  • Hepatic encephalopathy Encephalopathy Hyper-IgM Syndrome

Pathophysiology

Arousal and wakefulness are supported by neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology that project to both thalamic and cortical neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology.

• In persistent vegetative state:
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem function is mostly spared → maintains arousal and autonomic functions
  • Gray and white matter White Matter The region of central nervous system that appears lighter in color than the other type, gray matter. It mainly consists of myelinated nerve fibers and contains few neuronal cell bodies or dendrites. Brown-Séquard Syndrome of both cerebral hemispheres are severely damaged.
  • Cortical metabolism of individuals in a vegetative state is 30%–40% of the normal range of values → may be irreversible structural neuronal loss or potentially reversible damage
• In a coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma, the individual:
  • Does not open the eyes, even with vigorous stimulation
  • Displays no evidence of awareness of their surroundings, even after the discontinuation of sedative drugs 
  • In the transition from a coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma to persistent vegetative state → eyes are open intermittently (wakefulness), but there is no evidence of awareness of consciousness 

Clinical Presentation

Individuals may present with persistent vegetative state several months after a traumatic or anoxic brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification injury.

Clinical features

• Compatible with persistent vegetative state: 
  • Generally able to breathe without mechanical support
  • Cardiovascular, GI, and renal function may be normal.
  • Stool and urine incontinence are present.
  • The individual appears to be asleep with their eyes closed at times and awake but unaware with their eyes open at other times.
  • Individuals in a persistent vegetative state may:
    • Make a range of spontaneous movements, including chewing, teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth: Anatomy grinding, and swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility
    • Grimace or move their extremities in response to external stimuli
    • Have emotional responses (smile, shed tears, scream) with no discernible reason
    • Turn their head and eyes fleetingly to follow a moving object or loud sound 
    • Have spontaneous roving movements of the eyes
  • Neurologic exam:
    • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem reflexes (pupillary, oculocephalic, corneal, and gag) are usually intact. 
    • Painful stimulation may provoke an extensor or flexor response of the extremities.
    • Grasp reflexes may be present.
• Incompatible with persistent vegetative state:
  • Any unambiguous sign of conscious perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment or deliberate action 
  • Any evidence of purposeful movement, communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence, or consistent response to a command:
    • Can easily be missed, especially in individuals whose motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology capacities are limited
    • Fluctuating arousal or motivation may prevent this evidence from being detected during a single examination.
    • Repeated exams are necessary before concluding that an individual’s wakefulness is unaccompanied by awareness.
    • The rate of misdiagnosis of persistent vegetative state has been estimated at 37%–43%.

Testing

• Labs: To rule out other conditions causing decreased responsiveness (e.g., profound electrolyte disturbances, toxic substances, infection): 
  • Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes
  • CBC
  • Arterial or venous blood gas analysis
  • Toxicologic tests
  • CSF analysis CSF analysis Meningitis
• Imaging: 
  • MRI: shows generalized reduction of cerebral blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure
  • Fluorodeoxyglucose–positron emission tomography (FDG– PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging) scan → generalized and markedly reduced cerebral metabolism of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
• Other testing:
  • Quantitative EEG EEG Seizures: to assess sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep architecture
  • Event-related potentials: records small changes in EEG EEG Seizures signals in response to external stimuli

Management and Ethical Considerations

Individuals in a persistent vegetative state require ongoing supportive care for the prevention of complications as well as treatment of seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures if they occur.

Supportive care

• Nutrition via nasogastric or gastrostomy tube
• Adequate hydration
• Establishment of secure airway Airway ABCDE Assessment and tracheostomy Tracheostomy Surgical formation of an opening into the trachea through the neck, or the opening so created. Laryngomalacia and Tracheomalacia if needed
• Pressure ulcer prophylaxis Prophylaxis Cephalosporins
• Deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus ( DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis) prophylaxis Prophylaxis Cephalosporins
• Physical therapy Physical Therapy Becker Muscular Dystrophy 
• Treatment of seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures if needed

Ethical considerations

• Decision-making capacity Decision-making capacity Decision-making capacity describes a patient’s ability to make autonomous decisions regarding their care, as determined by a physician. Decision-making Capacity and Legal Competence or power of attorney is transferred to the family, who may choose to:
  • Continue life-supporting measures 
  • Discontinue life-supporting measures: considered ethical by the American Academy of Neurology
• If the individual has an advance directive, this should be honored.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Potential for recovery:
  • Spectrum of regaining consciousness to functional living:
    • Some individuals have regained consciousness after years of being in a persistent vegetative state, but with major, persistent physical impairment.
    • Determination of what constitutes “worthwhile” recovery is highly subjective and variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables.
  • In 15% of nontraumatic injury cases and 50% of traumatic injury cases, the individual will recover consciousness by 12 months.
  • Persistent vegetative state of traumatic origin has a better prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas in general than one of nontraumatic origin.
• Younger individuals have a more favorable prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
• 80% mortality Mortality All deaths reported in a given population. Measures of Health Status after 5 years

Differential Diagnosis

• Minimally conscious state: This term is used to describe individuals who are not in a vegetative state but are unable to communicate consistently. They can reproducibly demonstrate ≥ 1 of the following behaviors: visually tracking, following simple commands, gestural or verbal yes/no response to questions, intelligible speech, purposeful behavior. Further improvement is more likely than in individuals in a persistent vegetative state; however, some people remain in a minimally conscious state permanently. 
• Locked-in syndrome: This is a state of quadriplegia (inability to move the limbs) and anarthria (inability to articulate speech) resulting from brain stem injury. Locked-in syndrome is defined by sustained eye opening, awareness of the environment, aphonia or hypophonia, quadriplegia or quadriparesis, and vertical or lateral eye movement or blinking of the upper eyelid to signal yes/no responses. Eye or eyelid movements are the only method of communication. These individuals characteristically retain alertness and cognitive ability.
• Brain death: “Brain death” is a legal and clinical term that describes the irreversible cessation of all cerebral and brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem functions, including the ability of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stem to regulate vegetative and respiratory activities. In addition to the bedside neurologic exam, additional ancillary studies may occasionally be needed to support the diagnosis. A diagnosis of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification death must be established prior to considering organ donation Organ Donation Brain Death.