Encephalopathy Overview

Encephalopathy is a broad term used to describe abnormal brain function or brain structure. (Encephalo= brain + pathy= disorder). The abnormality may be transient, recurrent, or permanent. The loss of brain function may be reversible, static and stable, or progressive with increasing loss of brain activity over time.

Normal brain function

Brain cells are linked together with neurons, called axons and dendrites, covered in myelin sheaths. The electrical impulses work together with chemical receptors to allow brain activity to translate into thought and action. Different locations in the brain are associated with specialized function, for example, vision function is located in the occipital lobes, speech production in Broca's area in the lower part of the frontal lobe, speech recognition is located in Wernicke's area of the temporal lobe, and the motor strip in the parietal lobes of each hemisphere.

The brain also requires blood flow to provide oxygen and glucose to function. Other chemicals, nutrients, and vitamins are needed for normal function both immediately and in the long term.

Abnormalities and conditions that affect brain function

The brain develops quickly in the fetus as it grows in a mother's uterus; and any disruption in this growth and development may lead to encephalopathy.

Abnormalities in anatomic structure, electrical, and chemical function may lead to altered mental function and encephalopathy.

Poisoning  of brain tissue and cells may also affect function. This poison may be produced within the body, for example from liver or kidney failure, or it may be ingested intentionally or unintentionally. Examples of intentional ingestion include alcohol intoxication or drug abuse. Examples of unintentional ingestion include carbon monoxide poisoning, medications, or toxic substances such as lead paint.

Encephalopathy may be due to a birth defect (a genetic abnormality causing abnormal brain structure or chemical activity with symptoms being found at birth), or it may be evident towards the end of life due to disease, such asdementia or Alzheimer's disease.

Depending upon the cause, encephalopathy may occur at any age. Symptoms may present as a form of altered mental status including confusion and loss of memory because the impairment affects the thought process locations in the brain, or symptoms may present with a physical impairment like weakness or numbness of a body part, or uncoordinated movements because it affects the motor or sensory parts of the brain. Global involvement may present as seizure, or any combination of thought, motor, or sensory symptoms. The symptoms depend on what part of the brain is being affected and how much or how little it continues to function.

Encephalopathy Causes

Abnormal brain function may occur because of many different conditions; for example, lack of nutrients, poisoning, infection, structural changes, or anoxia (lack of oxygen delivery to the brain).

Alcoholic encephalopathy

Alcohol is a classic example of an acute and chronic ingestion that causes brain function changes. When a person drinks alcohol to excess, it alters brain activity. An acutely intoxicated person demonstrates lack of judgment and decreased reflexes and coordination. If enough alcohol is ingested, the parts of the brain that control wakefulness and breathing can be depressed to the point that the person can become comatose. These effects are short lived and transient as the liver metabolizes the alcohol and removes it from the body. When the alcohol is gone, the individual

returns to normal functioning. However, when alcohol is repeatedly abused, it can cause liver disease increasing ammonia levels and encephalopathy or there can be direct damage to the brain with loss of brain tissue.

Wernicke-Korsakoff syndrome is one type of alcoholic encephalopathy that is caused by thiamine (vitamin B1) deficiency due to malnutrition. The malnutrition occurs because most of the dietary calories are derived from alcohol, decreased appetite from a regular diet, and possibly malabsorption of nutrients from the intestine. There may be memory loss and confusion, loss of coordination and ataxia with a wobbling gait (walk), and confusion.

Non-alcohol related causes can include AIDS, cancer, renal (kidney) dialysis, andhyperthyroidism (thyrotoxicosis).

Anoxic/hypoxic encephalopathy

Anoxic (an= no + oxia= oxygen) or hypoxic (hypo=less + oxia=oxygen) encephalopathy is a condition where brain tissue is deprived of oxygen and there is global loss of brain function. The longer brain cells lack oxygen, the more damage occurs.

In pregnancy, the fetus may develop hypoxic encephalopathy if blood supply from the placenta is compromised. Placenta abruptio and placenta previa are two situations that occur in the third trimester leading to fetal distress. Difficulties during the delivery, for example when the umbilical cord is wrapped around the fetus' neck, may cause distress and compromise oxygen delivery to its brain.

Anoxic or hypoxic encephalopathy may occur at any time in life. In cardiac arrest, the heart stops and oxygen isn't pumped to the brain. The purpose of starting CPR (cardiopulmonary resuscitation) immediately is to try to continue blood flow and oxygen delivery. Delays in this process may result in brain cell damage and death.

Hypoxia can also occur because of prolonged seizures when the patient isn't breathing adequately or with prolonged asthma attacks or exacerbations of COPD.

Hypertensive encephalopathy

Hypertensive encephalopathy occurs when blood pressure rises to levels high enough to affect brain function. Headache, nausea and vomiting, changes in vision, and decreased level of consciousness may be due to markedly elevated pressure. This condition is also known as a hypertensive crisis (hypertensive emergency), where high blood pressure readings are associated with organ failure. In addition to encephalopathy, there can also be symptoms of chest pain, shortness of breath, and kidney failure. Hypotension (low blood pressure) due to many factors (for example, bleeding, major infection, or blood pressure medications) may result in encephalopathy with symptoms of fainting, weakness, and altered mental status.

Infectious encephalopathy

Infections are a cause of encephalopathy. Many types of bacteria, viruses, and fungi can cause encephalitis by infection and inflammation of the brain tissue or of the meninges (meningitis) that line the brain and spinal cord.

Prions are the cause of rare infections like Jacob-Creutzfeldt disease, which is related to bovine spongiform encephalopathy (BSE) or mad cow disease. The prions invade brain tissue and begin to form abnormal protein deposits between brain cells, disrupting tissue structure. The disease is progressive and untreatable leading ultimately to death. Kuru is another type of human prion brain infection.

Ischemic encephalopathy

Ischemic encephalopathy occurs because the small blood vessels that supply blood to brain tissue gradually narrow and cause a generalized decrease in blood flow to the brain. This causes progressive loss of brain tissue with associated loss of function. Risk factors for narrowing blood vessels in the brain are the same as forheart disease and peripheral vascular disease and include smoking, high blood pressure, high cholesterol, and diabetes

Metabolic encephalopathy

Metabolic encephalopathy (toxic metabolic encephalopathy) is a broad category that describes abnormalities of the water,electrolytes, vitamins, and other chemicals that adversely affect brain function. In addition to liver and kidney waste products, it may include abnormally high or low blood sugar (hyperglycemia, hypoglycemia), thyroid problems, and sodium levels in the blood (hyponatremia=low sodium, hypernatremia=high sodium).

Other causes of metabolic encephalopathy include carbon monoxide or cyanide poisoning, which prevents hemoglobin from carrying oxygen in the bloodstream and results in tissue anoxia.

Toxic metabolic encephalopathy can also include medication side effects or drug ingestions affecting the chemical transmitters in the brain. Called neurotransmitters,dopamine, GABA, serotonin, acetylcholine, andglutamine help nerve endings pass electrical signals between brain cells. Alterations in these transmitters can decrease brain function. Concentrations of neurotransmitters and abnormal function can be seen in seizure disorders and Alzheimer's disease.

Structural encephalopathy

Head trauma can cause brain damage due to bleeding in and around the brain. This can cause increased pressure within the skull that presses on brain tissue and cause abnormal brain function. Shear injuries to brain tissue can disrupt the neurons that connect brain cells together. Aside from the direct brain tissue injury, increased pressure buildup within the skull can decrease the amount of blood flow to the brain causing anoxic or hypoxic damage.

Blood supply to the brain may be compromised because of stroke, where one of the arteries to the brain becomes blocked and that part of the brain is replaced with scar tissue. If enough cells are injured, there can be permanent damage. Alternatively, hemorrhagic stroke occurs when bleeding occurs into the brain itself causing damage.

Chronic Traumatic Encephalopathy (CTE) describes a brain that has gradual degeneration in function because of repeated head injuries causing both concussions with symptoms and those that are asymptomatic. The symptoms ofconcussion usually fade, but months or years later, new symptoms can occur. CTE symptoms gradually progress. Initially, there may be concentration and memory issues with episodes of disorientation and confusion, dizziness, and headache. Emotions can be labile and the patient can develop aggressive and psychotic behavior. As CTE progresses, the behavior can become erratic and Parkinson's-like symptoms may be seen. Finally, thought processes decrease even further into dementia with more Parkinson's symptoms including speech and walking abnormalities. These symptoms are progressive and cannot be stopped.

The diagnosis of CTE is made clinically. Neither bleeding nor major abnormalities are seen on CT scan and it appears to act like other diseases that attack brain function. It can be confirmed in retrospect on autopsy and dissection of the brain. An abnormal protein called tau builds up in the brain and causes abnormal nerve fiber and cell tangles in the brain. At autopsy, the brain has a different appearance than that seen in Alzheimer's disease.

Uremic encephalopathy

Acute or chronic kidney failure can lead to uremic encephalopathy. When the kidneys fail to adequately cleanse the bloodstream, a variety of toxins can gradually build and cause brain function to decrease. If kidney function is not restored or if dialysis is not instituted, permanent brain tissue damage can occur, ultimately leading to death.

Encephalopathy Symptoms

Encephalopathy describes abnormal brain function due to problems with the brain tissue. Symptoms of encephalopathy can be generalized causing decreased level of consciousness from minimal lethargy to coma. Encephalopathy can cause abnormal thought processes including confusion, poor memory, hallucinations, and even psychotic thinking.

The symptoms may be evident because the parts of the body that the brain controls may not work appropriately. There may be incoordination and difficulty walking (ataxia) or there may be abnormalities with vision and eye movement. The encephalopathy may mimic stroke with weakness and numbness of one side of the body, including facial droop and speech problems. The abnormalities may not only affect motor function but also sensation. It all depends upon what part of the brain is not functioning.

In some patients, the encephalopathy is so profound that it affects basic brain functions that control wakefulness, breathing, heartbeat, and temperature.

The symptoms depend on the basic cause of encephalopathy and the potential for reversal of the cause. Symptoms may be present and remain constant or they may wax and wane. The symptoms may present once and never recur or they can be progressive and lead to death. For example, low blood glucose (hypoglycemia) may be easily reversed with no brain damage, while profound anoxia may be partially reversible or result in disability or death

Encephalopathy Diagnosis

The diagnosis of encephalopathy begins with the history provided by the patient, family, or friends. The health care professional will have a better understanding about potential causes of the encephalopathy based upon information regarding symptoms, for example, how quickly they appeared, how long they have been present, whether they wax and wane, or whether there is a progressive downward course. Past history of medical illness, intentional or unintentional ingestions, prescribed medications, chemical exposure, and infections may provide clues as to why the patient has encephalopathy.

Testing will depend upon the patient's history and physical examination that lead the health care professional to look for potential diagnoses. Routine blood tests such as acomplete blood count (CBC) may provide information about possible infection, anemia, or vitamin deficiency. Chemistry tests can evaluate electrolytes, glucose levels, kidney function, and liver function. Other tests may be ordered for different types of vitamin deficiencies. If appropriate, drug and alcohol screening may be suggested.

Imaging studies such as X-rays, computerized tomography (CT), and magnetic resonance imaging (MRI) may be useful depending upon the clinical situation.

Lumbar puncture (spinal tap) may be helpful to look for infection, bleeding, and inflammation. The cerebrospinal fluid can also be analyzed for abnormal proteins, chemicals, and cells.

Other testing may be appropriate depending upon the clinical situation and the suspicions of the health care practitioner.

Encephalopathy Treatment

Encephalopathy Self-Care at Home

As previously mentioned, patients who have known recurrent encephalopathy may have home treatment programs that may be attempted; however, any individual with unexplained confusion, altered mental function, coma, seizure, or weakness should access emergency care immediatel

Encephalopathy Medical Treatment

Treatment for encephalopathy varies according to the basic cause; for example, short-term anoxia may only require oxygen therapy, while uremic poisoning may require dialysis and akidney transplant. Consequently, specific medications and treatment programs will be prescribed based upon the underlying disease. The first episode of encephalopathy should be evaluated immediately by a physician to potentially diagnose and treat the basic cause; such action may reverse or limit the symptoms and affect the prognosis for encephalopathy.

Other treatment scenarios include:

When patients present for the first time with confusion, lethargy, or other symptoms suggestive of decreased brain function, an initial cocktail of naloxone (Narcan) and glucose may be injected intravenously to treat quickly reversible narcotic drug overdose and low blood sugar (hypoglycemia) -- if these are the causes of the patient's encephalopathy.

The ABCs of resuscitation are always evaluated (Airway, Breathing, Circulation). If the airway is compromised and the patient is unable to breathe adequately, endotracheal intubation may be considered. A tube is placed through the mouth into the trachea and a ventilator is used to breathe for the patient. The patient is usually unconscious or nearly so (obtunded) when this situation arises.

Encephalopathy Follow-up Aside from patients who present with an acute poisoning that requires short-term intervention, most patients

with encephalopathy will need life-long care and monitoring. Establishing a relationship with a primary care doctor will allow appropriate monitoring of specific disease states, regulation of medications and diet to help prevent acute flares of encephalopathy, and decrease the potential for gradual decline in mental function.

Encephalopathy Prevention

Some encephalopathies are preventable by positive lifestyle choices and others cannot be foreseen. For example, hepatic encephalopathy from liver failure due to alcoholism may be prevented with a patient's commitment to abstinence from alcohol and use of medical care and community support to prevent or minimize the risk of relapse. Liver failure from other illnesses and congenital or accidental trauma that results in encephalopathy may not be preventable

Encephalopathy Prognosis

Research continues to assist in understanding brain function and understanding the mechanisms that can cause encephalopathies. The National Institute of Neurological Disorders and Stroke helps coordinate ongoing clinical trials.

Some encephalopathies may be easily reversible, while others can progress and cause permanent structural changes in the brain and even death; the outlook depends on the underlying cause of encephalopathy and its potential for treatment.