Encephalopathy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]

Encephalopathy is a clinical manifestation that can be caused by any pathology affecting brain function. The pathology can be intracranial or extra-cranial in origin. This brain malfunction can be due to systemic metabolic derangements in cardiopulmonary,mitochondrial[[3]], renal, hepatic or endocrine systems. In medical jargon it can refer to a wide variety of degenerative brain disorders with very different etiologies, prognoses and implications. For example, prion diseases, all of which cause transmissible spongiform encephalopathies, are nearly always fatal and have an infectious origin, but other encephalopathies are reversible and can be caused by deficiency, toxins, and several other causes.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]

Encephalopathy can be classified based upon the underlying pathophysiology.

There are many types of encephalopathy.

• Hepatic encephalopathy – Arising from advanced cirrhosis of the liver
• Hypoxic encephalopathy – Permanent or transitory encephalopathy arising from severely reduced oxygen delivery to the brain
• Wernicke’s encephalopathy – Arising from thiamine deficiency, usually in the setting of alcoholism
• Hashimoto’s encephalopathy – Arising from an auto-immune disorder
• Hypertensive encephalopathy – Arising from acutely increased blood pressure
• Metabolic encephalopathy
• Toxic Metabolic encephalopathy – A catch-all for brain dysfunction caused by infection, organ failure, or intoxication.
• Uremic encephalopathy – Arising from high levels of toxins normally cleared by the kidneys — rare where dialysis is readily available
• Mitochondrial encephalopathy – Metabolic disorder caused by dysfunction of mitochondrial DNA. It can affect many body systems, particularly the brain and nervous system.
• Glycine encephalopathy – A pediatric metabolic disorder
• Static encephalopathy – Unchanging, or permanent, brain damage
• Transmissible spongiform encephalopathy – A collection of diseases all caused by prions, and characterized by “spongy” brain tissue (riddled with holes), impaired locomotion or coordination, and a high fatality rate. It includes bovine spongiform encephalopathy (mad cow disease), scrapie, and kuru among others.
• HIV encephalopathy – Neurological manifestation of AIDS, seen in terminally ill patients

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]

Encephalopathy may be due to damage to blood brain barrier with accumulation of toxic substances (Hepatic encephalopathy), low oxygen (Hypoxic encephalopathy), low levels of vitamins such as vitamin B1 (Wernicke encephalopathy) and sepsis (Septic encephalopathy).

Encephalopathy is a broad term given to numerous condition’s which cause dysfunction of the brain. There are various underlying mechanisms:

• Hepatic encephalopathy

The brain is protected from the circulatory toxins by the blood brain barrier lined by astrocytes. In cases of hepatic failure due to any reason, the detoxifying capacity of liver is drastically reduced. This causes an increase in the concentration of circulatory toxins like ammonia, mercaptans, manganese. Circulatory toxins damage the barrier made by astrocytes and cause pathological changes in the cells. This alters blood brain barrier and toxins gain access into the brain tissues.

• Hypoxic encephalopathy

The brain needs a large oxygen supply owing to its high metabolic activity. When oxygen is deprived from the brain, energy stores of the neuronal cells is decreased rapidly resulting in neuronal injury and encephalopathy.

• Metabolic encephalopathy

Normal neuronal activity requires a balanced environment of electrolytes, water and lots of substrates. In case of dehydration and renal diseases causing electrolyte abnormalities this equilibrium is disturbed. This results in dysfunction of the brain.

• Wernicke encephalopathy

This is a disorder of diencephalic brain tissue around the third and fourth ventricle. It results of deficiency of vitamin B1, thiamine. It is the most under recognized cause of encephalopathy in intensive care units. Thiamine is an important co-factor for enzyme required for glucose utilization in brain. If this is deficient it automatically goes into a low energy state and performs suboptimally.

• Septic encephalopathy

Sepsis elicits a systemic inflammatory response which produces numerous cytokines and other micro circulatory abnormalities. These damage the blood brain barrier and damage the brain tissue.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]

Encephalopathy alters brain function and/or structure. It may be caused by an infectious agent (bacteria, virus, orprion), metabolic or mitochondrial dysfunction, brain tumor or increased intracranial pressure, prolonged exposure to toxins (including solvents, drugs, alcohol, paints, industrial chemicals, and certain metals), radiation, chronic progressive trauma, poor nutrition, or lack of oxygen or blood flow to the brain. It is also known that concomitant use of lithium with other neuroleptics may, in rare cases, cause encephalopathy.

• Infections
• Hypoxia
• Alcoholism
• Hepatic failure
• Renal failure
• Brain tumors
• Poisonings
• Malnutrition

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]

Encephalopathy can present in many ways mimicking many other brain conditions. Certain conditions like encephalitis, meningitis, brain tumors, epilepsy, and overdosing of certain medications may mimic encephalopathy.

The symptoms of encephalopathy may overlap with the symptoms of other diseases:

• Encephalitis which is differentiated from encephalopathy by the presence of fever and other signs and symptoms of a viral infection.
• Meningitis which is differentiated from encephalopathy by the presence of neck stiffness, headache, meningeal signs, fever

• Postictal state which would be differentiated by the presence of seizures

• Intracranial lesions like tumors, masses, granulomas which are differentiated by the presence of focal neurologic signs and symptoms

Encephalopathy must be differentiated from other causes of headache,seizures and loss of consciousness.

Toxic encephalopathy must also be differentiated from other diseases that cause personality changes, altered level of consciousness and hand tremors (asterixis). The differentials include the following:^{[12][13][14][15][16][17][18][19][20][21][22]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]

Elderly patients and patients with multisystem disease are at risk for the development of encephalopathy.

Most common cause of encephalopathy is metabolic cause. In this condition there will be increase in toxic substance to brain keeping the person at high risk of encephalopathy.

Common

• Liver diseases
• Renal diseases
• Diabetes
• Underlying brain condition’s like stroke ,epilepsy
• Electrolyte abnormalities – hypernatremia, hyponatremia, hypercalcemia
• Uncontrolled hypertension
• Massive trauma

Less common

• Nutritional deficiency
• Post surgical status

^{[1] [2]} “Metabolic encephalopathy secondary to diabetic ketoacidosis: a case report | BMC Endocrine Disorders | Full Text”. ^[3]Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2]

Encephalopathies of different types have different ways of progression of disease. Few conditions can lead to abrupt onset and few develop over a period of time. Some types are completely reversible where as few cause irreversible damage and dysfunction. Most encephalopathies have similar kind of progression with little variation.

Patients presenting with encephalopathy usually have past history of any chronic disease. In various conditions, some precipitating factors may contribute to the manifestation of encephalopathy such as constipation or infection in patients with liver disease. Symptoms are quite varied among the different types of encephalopathies. They can be ranging from sub-clinical presentation to coma. Encephalopathies are the presentation of severe disease which if untreated never resolves on its own. Prompt identification and treatment are warranted in these conditions, if delayed chances of residual neurological effects are more.

Complications related to encephalopathy are due to the underlying disease process such as electrolyte imbalances, drugs and poisons, sepsis and multiorgan failure and can include:

• Coma

• Death

Treating the underlying cause of the disorder may improve or reverse symptoms. However, in some cases, the encephalopathy may cause permanent structural changes and irreversible damage to the brain. Some encephalopathies can be fatal. Certain factors are of prognostic importance like:

• Age

• Rapidity of onset

• Delay in correcting the cause

• Most important is the underlying cause

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