Malignant neuroleptic syndrome: what is it, symptoms, treatment, prognosis

What is neuroleptic malignant syndrome?

Malignant neuroleptic syndrome (ZNS) Is a rare but potentially life-threatening reaction to the use of virtually any of the antipsychotic drugs or major tranquilizers (neuroleptics). These drugs are usually prescribed to treat schizophrenia and other neurological, mental, or emotional disorders. Some of the most commonly prescribed antipsychotics include thioridazine, haloperidol, chlorpromazine, fluphenazine, and perphenazine.

ZNS is characterized by high fever, muscle stiffness, altered mental status (paranoid behavior), and autonomic dysfunction. Autonomic dysfunction is associated with a malfunction of the components of the involuntary (autonomic) nervous system, which leads to sharp fluctuations in blood pressure, excessive sweating and excessive secretion of saliva.

Suspected, but not proven, the genetic basis of the disease. It is clear that a defect in dopamine receptors (dopamine D2 receptor antagonism) is an important factor in causing neuroleptic malignant syndrome.

Signs and symptoms

Symptoms of neuroleptic malignant syndrome usually include a very high temperature (39 to 40 degrees Celsius), an irregular heartbeat, a rapid heartbeat (tachycardia), rapid breathing (tachypnea), muscle stiffness, changes in mental status, dysfunction of the autonomic nervous system leading to high or low blood pressure, profuse and increased sweating.

Other symptoms may include hepatic or renal failure, abnormally high levels of potassium (hyperkalemia), severe destruction of skeletal muscle tissue (rhabdomyolysis), or blood clots in veins and arteries.

Causes

Neuroleptic malignant syndrome is most likely due to "dopamine D2 receptor antagonism." Dopamine is a chemical (neurotransmitter) found in the brain and other parts of the central nervous system that carries messages from one cell to another. In a sense, the use of a certain drug blocks the dopamine receptor in the brain cell.

When dopamine receptors in the hypothalamus or other bundle of nerve fibers (nigrostrial pathways) and / or spinal cord are blocked, the result is increased muscle stiffness. Interaction with dopamine receptors in the hypothalamus is also likely to be responsible for high body temperature as well as fluctuations in blood pressure.

Some doctors believe that neuroleptic malignant syndrome may be associated with malignant hyperthermia, a genetic disorder characterized by an abnormal response to anesthetic drugs.

Affected populations

Neuroleptic malignant syndrome (NMS) can affect anyone taking antipsychotic drugs. Men are at higher risk than women. Some clinicians believe that stronger antipsychotics are more likely to trigger an attack of NMS.

Although two-thirds of cases are thought to occur within the first week after starting treatment, the syndrome can start at any time during treatment.

Recurrence of attacks of NNS is not uncommon. The risk of relapse is closely related to the time elapsed between the end of the initial episode of neuroleptic malignant syndrome and the start of a new antipsychotic drug. If the waiting period is two weeks or less, about 63% will repeat. If the waiting period is more than two weeks, the percentage of patients experiencing a relapse drops to about 30.

Symptomatic disorders

Symptoms of the following diseases may be similar to those of neuroleptic malignant syndrome. Comparisons can be useful for differential diagnosis:

• Anaphylaxis Is abnormally severe allergic reaction on any substance. Major symptoms may include severe itching, hives, redness, edema, vomiting, diarrhea, labored breathing (shortness of breath) and loss of consciousness (syncope). A high fever is not a sign of anaphylaxis.
• Deadly catatonia - a condition similar to NNS, and is often confused with it. A detailed history may indicate that the patient has experienced catatonic states without taking antipsychotics. If so, it is highly likely that the present syndrome is NNS. A patient with fatal catatonia will respond to antipsychotic drugs. However, it is nearly impossible to predict whether a patient's symptoms will worsen or improve. Patients with fatal catatonia almost always endure a period of excitement and excitement prior to catatonia. This is in contrast to a patient with NMS, whose first symptom is usually muscle stiffness.
• Heatstroke Is a very serious disease characterized by a sharp and rapid rise in body temperature, which can reach 40-41 degrees Celsius. Heatstroke usually occurs as a result of exposure to extremely hot environments. The skin may become hot, reddened, and dry. The rapid loss of fluid can lead to perspiration. Sweating is essential for cooling the body. There may also be an increase in heart rate and respiration. The victim may become disoriented and eventually experience seizures or pass out. Measures such as wrapping a person in cold, damp sheets should be taken immediately to lower their body temperature. A person suffering from heatstroke should be hospitalized as soon as possible.
• Malignant hyperthermia Is a genetic disorder characterized by an abnormal response to muscle relaxants and general anesthetic drugs. Symptoms of malignant hyperthermia appear only after the patient has been placed under general anesthesia. Along with a rapid increase in body temperature, which can reach 43 degrees, muscle rigidity and / or muscle twitching occurs. The patient may also have a very fast and irregular heartbeat, abnormally low blood pressure, painful sweet breath, headache, nausea, and vomiting. It is not known if neuroleptic malignant hyperthermia is a form of malignant hyperthermia, but some researchers have suggested that these disorders may be related.
• Serotonin Syndrome imitates malignant neuroleptic hyperthermia. If the use of selective serotonin reuptake inhibitors (SSRIs) results in symptoms such as altered mental state, autonomic dysfunction and neuromuscular defects, then this is most likely serotonin syndrome. As SSRIs are used in increasing amounts, there is reason to expect that the incidence of serotonin syndrome will also increase. Serotonin syndrome can in most cases be distinguished from NNS by a detailed history, which clarifies any changes in treatment and / or dosage. In addition, serotonin syndrome is usually not accompanied by severe muscle stiffness.

The following disorder may be associated with long-term use of antipsychotics. Differential diagnosis does not require:

• Tardive dyskinesia Is a disease that occurs as a result of prolonged use of antipsychotics and is characterized by involuntary and abnormal movements of the jaw, lips and tongue. Typical symptoms include a grimace on the face, protruding tongue, sucking or fishy mouth movements. A large percentage of schizophrenics who have been in psychiatric hospitals for a long time and took antipsychotics have a high risk of developing tardive dyskinesia.

Diagnostics

The diagnosis of neuroleptic malignant syndrome is based on the presence of signs that include treatment antipsychotic drugs during the last 1-4 weeks, high body temperature (above 38 degrees Celsius); muscle stiffness; and at least five of the following symptoms:

• change in mental status;
• cardiopalmus (tachycardia);
• low or high blood pressure (hypo- or hypertension);
• excessive sweating (hyperhidrosis);
• excessive production of saliva (sialorrhea)
• tremor;
• urinary incontinence;
• increased creatine phosphokinase or increased myoglobin in the urine;
• an increased number of leukocytes (leukocytosis);
• increased concentration of metabolic acids in the blood and urine.

It is also necessary to exclude other mental or systemic diseases caused by taking medication.

Standard treatments

Treatment of neuroleptic malignant syndrome consists in the abolition of neuroleptic drugs under the supervision of a physician, immediate measures to restore adequate water and nutrient levels, as well as measures to reduce body temperature person. Medications prescribed as treatment may include skeletal muscle relaxants such as dantrolene; dopamine production and activity stimulants such as bromocriptine; and / or continuous perfusion of central nervous system depressants such as diazepam.

Complications that can result from neuroleptic malignant syndrome, such as renal failure, lack of oxygen entering the tissues (hypoxia) and / or decreased blood alkalinity, and fabrics (acidosis) can be extremely serious and require immediate treatment. After patients recover from neuroleptic malignant syndrome, about 87% will be able to tolerate antipsychotic drugs at some point in the future. Doctors usually switch to a different class of antipsychotics and to atypical antipsychotics. Such patients should be closely monitored, since relapses of neuroleptic malignant syndrome are not uncommon.

Forecast

Initial reports of mortality from ANS were over 30%, but the increased awareness of physicians and the introduction of new antipsychotics over the past few decades has helped reduce them to almost 10%.

With early detection and aggressive treatment, NMS is usually non-lethal, and most patients recover completely within 2–14 days. But if diagnosis and treatment are delayed, resolution may take weeks or longer, and in surviving patients there may be residual catatonia or parkinsonism or significant morbidity secondary to renal or cardiopulmonary complications.

When death does occur, it is usually associated with arrhythmias, DIC syndrome or cardiovascular, respiratory, or renal failure. Thus, early recognition and initiation of therapeutic interventions by physicians are still of paramount importance in reducing the number of severe cases of NMS and the limitation of this significant source of morbidity and mortality among patients receiving antipsychotics.