This article describes the pathophysiology of fever. Fever is a symptom of some neurologic disorders as well as some systemic disorders that affect the nervous system. Neurologic complications of fever, such as febrile seizures and brain damage, are also considered. Fever is also associated with poor prognosis in patients with stroke and brain injury. Management of a patient with fever requires both the investigation of the cause as well as lowering of the temperature; various measures are described.
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• Fever is probably the most common symptom observed by physicians.
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• Thermoregulatory centers and pathways in the brain are involved in the control of body temperature.
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• Several neurologic disorders, both infectious and noninfectious, have fever as a manifestation.
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• Management of the patient with high fever depends on the cause.
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• High fever may need to be lowered by use of antipyretics and cooling devices.
Historical note and terminology
Fever is probably the most common symptom observed by neurologists and other physicians involved in patient care. Fever is defined as elevation of body temperature above normal limits of the central regulatory processes originating in the hypothalamus. The normal temperature is 37°C (98.6°F) based on Wunderlich's original observation (43). However, temperature readings are higher in healthy young individuals and lower in the elderly. There are circadian variations with lower temperatures in the morning and higher in the afternoon so that fever can be defined as morning temperature of greater than 37.2°C (98.9°F) and afternoon temperature greater than 37.7°C (99.9°F). Rectal temperatures are usually 0.6°C higher than those recorded from the skin. Elevations of 0.8°C (1.5°F) may occur during physical exercise. Measuring body temperature remains 1 of the basic procedures for assessing general health. A current study in the United States has determined that mean body temperature in men and women, after adjusting for age, height, and weight, has decreased monotonically by 0.03°C per birth decade during the past 150 years (32). An explanation of this is the development of treatments for infectious diseases over the last century, which has enabled marked reduction in inflammatory conditions that people had -- tuberculosis, syphilis, periodontal disease, nonhealing wounds, and dysentery -- with antibiotics and vaccines. Nonsteroidal antiinflammatory drugs enable us to live almost inflammation-free, which might have contributed to a steady decline in average body temperature as the body no longer needs to heat up to fight off disease.
Conditions other than fever may also cause rise of body temperature. For example, hyperthermia is due to excessive internal heat production or impairment of heat dissipation, such as in heat stroke, which results in a body temperature rise to above that set by the central regulatory processes. Although 2 different terms are used to describe rise of body temperature, the single term "hypothermia" is used for drop in body temperature, whether due to disturbance of central regulation, exposure to cold environment, or both acting simultaneously.
Along with pain, fever is 1 of the earliest symptoms recorded in medical antiquity. Historical aspects of fever are reviewed elsewhere (01; 07). Fever as a manifestation of infectious diseases was recognized before the discovery of microorganisms as causes of infections. Ancient physicians assessed fever merely by touch of the hand; measurement of the degree of fever was not possible until the discovery of the thermometer in the early 1800s. Prior to the discovery of antibiotics, high fever due to severe infections was associated with high mortality. Sir William Osler called it the most terrible enemy of mankind. Fever is now recognized to be a symptom of noninfectious inflammatory conditions as well. Several substances were recognized as exogenous pyrogens (in Greek, pyro means fire) or fever producing. Immune challenges result in the production of endogenous pyrogens that act at the hypothalamic level.
Progress in neuroscience has enabled a better understanding of the neurobiological basis of fever. Fever associated with neurologic disorders is also referred to as neurogenic fever. Apart from being a symptom of neurologic disorders, high fever can also produce neurologic complications.
Fever was also induced for therapeutic purposes, due to the belief that fever is a protective reaction of the body and high temperatures can destroy pathogenic organisms. In the earlier part of the 20th century fever was induced by inoculation with tertian malaria to cure general paresis, a form of neurosyphilis. This approach became obsolete after the introduction of penicillin.
Management of a feverish patient in the pre-pharmacological era included use of herbs and application of cooling, such as by baths. Aspirin, introduced in 1897, was recognized to reduce pain and fever, but its mechanism of action was not known at that time. The action is now believed to be mediated at the CNS level.