Encephalopathy is a condition characterized by altered brain function and structure. It is caused by diffuse brain disease.
Encephalopathy may be caused by advanced and severe disease states, infections, or as a result of taking certain medications. The three main causes of encephalopathy are liver disease, kidney disease, and lack of oxygen in the brain. The associated symptoms can include subtle personality changes, inability to concentrate, lethargy, progressive loss of memory and thinking abilities, progressive loss of consciousness, and abnormal involuntary movements. Symptoms vary with the severity and type of encephalopathy.
Encephalopathy may vary in severity from only subtle changes in mental state to a more advanced state that can lead to deep coma. Cerebral edema is a common manifestation of severe encephalopathy, which causes an increase in intracranial pressure. The major related causes of death include sepsis, circulatory collapse, and brain failure related to a syndrome encompassing cerebral edema, damaged blood-brain-barrier, increased intracranial pressure, brainstem herniation, and/or neurotoxins leaking into the brain and killing brain cells. Additionally, patients with severe encephalopathy usually develop intracranial hypertension, which can produce cerebral ischemia injury and cerebral herniation.
There is no statistical information available for encephalopathy per se. Encephalopathy can occur at any age and there seems to be no gender or racial predilection, because encephalopathy is a manifestation of a primary illness.
There is a wide variety of conditions that cause encephalopathy. Encephalopathy can be caused by infections (bacteria, viruses, or prions); lack of oxygen to the brain; liver failure; kidney failure; alcohol/drug overdose; prolonged exposure to toxic chemical (solvents, paints, industrial chemicals, drugs, radiation); metabolic diseases; brain tumor; increased intracranial pressure; and poor nutrition.
HYPOXIC ENCEPHALOPATHY Hypoxic encephalopathy refers to a lack of oxygen to the entire brain, which
Cardiac arrest is the most common condition that causes cerebral hypoxia. When the heart stops pumping, oxygen-rich blood cannot be delivered to vital organs such as the brain. Hypoxia to the brain causes irreversible brain damage after two minutes.
HEPATIC ENCEPHALOPATHY Hepatic encephalopathy refers to a condition of brain and nervous system damage caused by liver (hepatic) failure. Diseases that damage the liver causing impairment of the detoxification and functional capabilities of the liver can cause hepatic encephalopathy. Examples of disorders that decrease liver function are hepatitis or cirrhosis. Impairment in the detoxification capabilities of the liver causes accumulation of toxic chemicals in the blood such as ammonia, in addition to many other impurities that all collectively cause damage to the nervous system.
KIDNEY FAILURE The main function for the kidneys is to eliminate excess fluid and waste material from the blood. When the kidneys lose the ability to filter the blood, dangerous levels of waste products accumulate in the body. Chronic renal failure can be caused by diabetes, analgesic nephropathy (due to long-term use of aspirin or nonsteroidal anti-inflammatory drugs), kidney diseases (polycystic kidney disease, pyelonephritis, and glomerulonephritis), renal artery stenosis (a narrowing of the artery that supplies blood to the kidneys), and lead poisoning.
SEVERE INFECTIONS Severe infections, especially those that affect the brain, can cause encephalopathy. Infections that specifically target the brain are encephalitis, which is inflammation of the brain, typically caused by a virus, or meningitis, which is inflammation of the tissue that surrounds and protects the brain.
CHRONIC ALCOHOL USE Long-term use of alcohol not only causes destruction of brain cells but can cause cirrhosis of the liver or hepatitis, which results in the destruction of liver cells. Chronic alcoholism leads to progressive destruction of liver cells, which can cause end-stage liver failure. A subtype of hepatitis infection called hepatitis C typically causes progressive destruction to liver cells.
UREMIC ENCEPHALOPATHY Uremia describes the final stage of progressive renal insufficiency, which culminates in end-stage kidney failure with neurologic involvement. This is called uremic encephalopathy. The cause is unknown and no single metabolite or toxin is responsible for symptoms, but rather it is an accumulation of several chemicals/toxins in the blood that causes symptoms of encephalopathy.
The hallmark of encephalopathy is altered mental state. In mild cases, hypoxia can cause an altered mental state, which includes symptoms such as motor incoordination, poor judgment, and inattentiveness. Mild cases have no lasting effects. Patients who have severe hypoxia or anoxia (total lack of oxygen delivery, usually from cardiac arrest) lose consciousness within seconds. Other symptoms of encephalopathy include lethargy, nystagmus (rapid, involuntary eye movement), tremor, dementia, seizures, myoclonus (involuntary twitching of a muscle or group of muscles), muscle weakness and atrophy, and loss of ability to speak or swallow. An early and characteristic feature of hepatic encephalopathy is called constitutional apraxia, which is inability to reproduce simple designs such as a star. Patients with liver failure may exhibit a symptom called asterixis, an involuntary jerking tremor of the hands.
The diagnosis of encephalopathy depends on the presence of acute or chronic liver disease; altered mental state such as confusion, stupor, or coma; symptoms of central nervous system damage; and abnormal wave patterns on an encephalogram. Diagnostic tests that may be utilized to establish the diagnosis include, but are not to limited to: complete blood count; liver function tests; ammonia and glucose levels; lactate levels (often elevated due to impaired tissue perfusion and because of decreased clearance by the liver); arterial blood gases (may reveal hypoxemia); kidney function tests; blood cultures (to detect infectious agents); virology testing (for hepatitis); neuroimaging studies; and ultrasound studies.
The causes of encephalopathies are broad. Additionally, the symptoms are also broad, ranging from mild changes of consciousness to coma or death. Therefore, the treatment team can consist of a broad spectrum of specialists that can include, but is not limited to, an internist, oncologist, pulmonologist, critical care physician, radiologist, hepatologist (specialist in liver diseases), and surgeon. The disorder can also occur in the pediatric ages or even at birth. In these critical situations, specialists in pediatric critical care, a neonatologist, and a perinatologist (specialist in maternal-fetal health) would be involved.
Hypoxia or anoxic encephalopathy is an emergency, and immediate measures are necessary to prevent further damage to the brain and to restore breathing and circulation. It is necessary to treat hepatic encephalopathy early to prevent long-term damage. Specific treatment for hepatic encephalopathy is aimed at eliminating toxic substances and/or treatment of the primary illness that caused encephalopathy. Elimination of toxins such as ammonia can be accomplished by decreasing absorption of protein from the gut. By giving the patient a compound called lactulose, absorption of ammonia can be decreased. Persons with hepatic encephalopathy should not consume protein, and constipation should be avoided. Uremic encephalopathy caused by chronic renal failure is treated with transplantation or dialysis.
Recovery and rehabilitation
Recovery is an emergency for all patients with severe hypoxia or anoxia. Vital functions such as breathing, cardiac function, and delivery of oxygen-rich blood to the brain should be restored within two to five minutes. If anoxia persists for more than two minutes, there will be permanent and severe damage to the brain.
There are four active government-sponsored clinical trials that are recruiting patients. There is a phase III clinical trial concerning birth asphyxia (hypoxic-ischemic encephalopathy) in infants up to six hours old. A phase II clinical trial is investigating the neuroimaging findings associated with persistent encephalopathy caused by the tick-transmitted infection called Lyme's disease (persistent Lyme encephalopathy). A third study is investigating a genetic form of familial dementia that causes encephaolpathy due to neurodegeneration of brain tissue. A fourth study investigates a disorder called neuronal ceroid lipofuscinosis (NCLS), which is a common heritable form of encephaopathy that occurs in one of 12,500 children. Detailed information about each of these studies can be obtained online from the website <http://www.clinicaltrials.gov>.
The outcome for patients who present with symptoms of encephalopathy depends on the cause. If the cause can be corrected in time, the outcome can be favorable. However, if encephalopathy is a manifestation of more advanced chronic disease, or if it is part of a rapidly fulminating disorder, the outcome can be poor and death may ensue due to the primary cause.
Persons who present with encephalopathy have advanced disease or the beginning of an advanced disease process. Vigilance on the part of the primary care provider is necessary to take all precautions to prevent this process.
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National Institute of Neurological Disorders and Stroke NIH Neurological Institute. P.O. Box 5801, Bethesda, MD 20824. (301) 496-5751 or (800) 352-9424. <http://www.ninds.nih.gov>.
Laith Farid Gulli, MD
Alfredo Mori, MB, BS