Metabolic encephalopathy is a transient or permanent impairment of brain function resulting from physiological insufficiency or aberrant metabolic processes accompanying certain systemic illness such as diabetes or liver disease. Timely recognition and treatment of the predisposing condition can reverse the potential damage to the brain.
Metabolic encephalopathies generally present as impairment of brain function, including loss of consciousness. The latter is presumed to be due to failure of the neocortex , to coordinate with other forebrain structures involved in cognition to stimulate the ascending reticular activating system (ARAS). Ascend from the ARAS via thalamic synaptic relays to the neocortex is mediated by specific brainstem nuclei and associated fibers. Thus, metabolic encephalopathies result from biochemical aberrations at both neocortex and ARAS centers. Initially, respiration rate decreases and the pupils are small but reactive. Asterixis, also termed “flapping tremor” observed in sedative intoxication, uremia and hepatic disease. Asterixis is caused by the loss in voluntary muscle postural tone of the head, tongue, limbs or trunk. In advanced stages seizures occur as in acute liver failure and hypoglycemia. Concomitant loss of brainstem respiratory control result in Cheyne-Stokes breathing. Lack of movement control and coordination due to focal metabolic changes in basal ganglia and the cerebellum are seen in metabolic encephalopathies such as those associated with avitaminosis and ingestion of toxic substances.
The symptoms of metabolic encephalopathy are:
Early recognition of these manifestations and immediate treatment may serve to reverse the encephalopathy, prevent death or at least diminish the subsequent damage to the brain.
Metabolic Encephalopathy is one of many conditions manifested by aberrant brain function, with diverse etiology ranging from infection, structural damage, systemic diseases, and poisoning. Differential diagnosis entails recognition of this multifarious causes and the importance of prompt intervention to minimize or prevent permanent damage to the brain. Acute encephalopathy in a child may be due instead to sepsis, meningitis or structural abnormalities as in intracranial hemorrhage or brain tumor. One should be aware of the possibility of shaken baby syndrome. Inborn errors of metabolism should be ruled out in neonates.
On the basis of clinical findings, blood and urine test should be done for inborn errors of metabolism.
Incase of new born patients metabolic screening studies result should re-examine and repeated if necessary.
Delirium should be treated as a medical emergency. Monitoring of respiratory and circulatory functions is first priority, with neurological, laboratory and neuroimaging evaluations. Early recognition of the predisposing factor is essential. The patient should be allowed to recuperate in a placid, stress-free environment and encouraged to engage in cognitive activities.
Analgesic may be given for pain control. Antipsychotics, such as haloperidol in low, frequent doses (1-5 mg IV q 4-6 hours) with monitoring of the electrocardiographic QTc interval and normal magnesium levels, quetiapine (25-100 mg/day po) or olanzapine (2.5-7.5 mg/day po) have been used although without FDA approval. Recent studies suggest increased mortality with this treatment in the elderly . Other deleterious effects of these drugs are extrapyramidal movement disorders and neuroleptic malignant syndrome. Benzodiazepines are used in cases of alcoholism and cocaine withdrawal. Trials with dexmedetomidine versus midazolam or lorazepam decreased the occurrence and shortened the episodes of delirium .
Prognosis of encephalopathy open link depends on the underlying cause and the potential for reversing or eliminating this cause. Thus, recovery varies among patients and poor prognosis could lead to complete loss of brain function or death. Prompt diagnosis and intervention is important as exemplified in the management of hypoglycemic patients. Patients given glucose at the onset of symptoms recover completely. Delayed treatment may lead to seizures or coma which may be reversed within hours or days with partial recovery. However, long or multiple delays can be fatal.
The causes of metabolic encephalopathies are diverse ranging from pathophysiologic states, peripheral organ dysfunctions, infection, systemic diseases and poisoning. The most common toxic agent is alcohol .
Major causes of metabolic encephalopathies:
Hypoxia occurs when the brain is deprived of oxygen. In anemia, red blood cells are not able to deliver sufficient oxygen to the brain. In pulmonary disease and alveolar hypoventilation diminished blood flow likewise compromise the oxygen requirement for normal brain function.
Ischemia is the result of narrowing of small blood vessels, thus, decreasing blood flow in the brain. This condition is linked to hypo/hypertension; hyperviscosity syndrome; cardiovascular disease (including cardiac arrest); microvascular diseases; Stokes-Adams syndrome, cardiac arrhythmias; and hypersensitive carotid sinus.
Systemic diseases are subject to derangement of their normal functions and the body's metabolic processes, thus, predisposing to oxygen deficit in the brain. These disease are: acid-base, electrolytes and fluid imbalances; vitamin deficiency; hepatic disease; renal failure; paraneoplastic syndromes; pancreatic disease; endocrine dysfunction (hypo/hyperglycemia, hyperosmolarity); vasculitis; infections; and sepsis.
Toxic agents poison brain tissues and cells in various ways, even taken unintentionally, like drugs and alcohol, or accidentally like insecticides. These are: alcohol; sedatives; narcotics; antibiotics and other drugs for chemotherapeutic purposes; psychiatric medications; heavy metals; and solvents.
Toxic metabolic encephalopathy can also include medication drug ingestions side effects or affecting the chemical transmitters in the brain called neurotransmitters; dopamine, serotonin, acetylcholine, GABA and glutamine 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.
The diverse nature of metabolic encephalopathy makes it difficult to obtain population-based studies for epidemiological assessment. One study report that patients with an eGFR of less than 10 mL/min manifested some degree of encephalopathy although the patients were not clearly symptomatic. In one pediatric study, 40% of the children with a BUN level greater than 90 mg/dL were considered positive for encephalopathy. These children were more likely to develop convulsions as BUN levels increased .
Research aims to understand brain function and the underlying mechanisms that cause metabolic encephalopathies. As in other encephalopathies loss of brain function is basically attributed to a disturbance of blood brain barrier and changes in the amino acid and neurotransmitter conduits. Researchers have identified vascular factors, infection and endotoxins in the pathophysiology of the disorder. Histopathologic findings in hepatic and vascular encephalopathies include tissue edema, hypoxia, and necrosis. Astrocytes have been found to undergo hyperplasia and morphologic changes resembling Alzheimer type II cells  .
To help avoid the risk of coma:
Metabolic encephalopathy is an impairment of brain function resulting from the pathophysiological processes which occur in peripheral organ dysfunction such as diabetes, cardiovascular disorder, liver disease, and renal failure. The damage to the brain may be transient or permanent and reversible if the predisposing condition is treated or eliminated. Timely medical intervention is essential to prevent secondary structural abnormalities in the brain.
The two major types of metabolic encephalopathy are:
Encephalopathy due to abnormalities in brain chemistry and coma can occur. A variety of concomitant conditions such as vitamin deficiencies, hereditary disease, neuroendocrine disorders may cause brain dysfunction. Toxic encephalopathy can be traced to exposure to heavy metals and organic solvents. Ethanol can damage the brain permanently in the presence of avitaminosis and protein-calorie malnutrition. Hepatic encephalopathy has been linked to brain damage secondary to alcoholic cirrhosis.
Metabolic encephalopathy is a temporary loss of brain function which may develop in intensive care unit patients being treated for some other systemic disease. As such, it serves to predict deterioration of the patient's condition or progression of organ dysfunction that could lead to hypoxia or accumulation of toxins in the bloodstream. Early recognition and prompt medical intervention could reverse the condition or at least prevent permanent damage to the brain. The most common predisposing factor in metabolic encephalopathy is liver failure.
Causes and Risk factors
The risk of metabolic encephalopathy is increased with concomitant systemic diseases (e.g., liver cirrhosis, hepatitis, cardiovascular disease, diabetes, renal failure); vitamin B1 deficiency; Hashimoto's thyroiditis; infections; trauma; major surgery; effect of sedatives and narcotics; alcohol intoxication; poisoning (from lead, carbon monoxide, insecticide); sepsis; intestinal bleeding; hypothermia/hyperthermia; electrolyte imbalance (hypo/hypernatremia, hypercalcemia); hypoglycemia; hyperosmolar hyperglycemic crisis; metabolic acidosis; meningitis, encephalitis; and persistent vomiting or diarrhea that lowers blood potassium levels.
Symptoms of metabolic encephalopthy include:
The symptoms of metabolic encephalopathy are readily recognized by the physician. However, it is also necessary to confirm if other underlying conditions are responsible for the disorder.
Laboratory examinations include complete blood count; blood chemistry; assessment of cerebrospinal fluid (CSF) and blood oxygen concentration. Other confirmatory tests may be prescribed e.g., X-rays, CT scan, MRI, and encephalogram (EEG).
Successful treatment of metabolic encephalopathy depends on early recognition of the symptoms and prompt intervention to reverse the conditions that could lead to hypoxia or accumulation of toxins in the bloodstream. Delayed treatment could result in permanent or residual damage to the brain.
Patients are maintained on a low-protein diet to lower blood ammonia levels since ammonia is a by-product of protein metabolism. Comatose patients may required special tube feedings and life support systems.
Liver transplantation may be considered in patients with chronic liver cirrhosis.