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In this chapter we consider the clinically related phenomena of lassitude, fatigue, nervousness, irritability, anxiety, and depression. These complaints form the core of a group of “symptom-based” disorders that are a large part of medical practice. Although more abstruse than paralysis, sensory loss, seizures, or aphasia, they are no less important, if for no other reason than their frequency. In an audit of one neurologic outpatient department, anxiety and depressive reactions were the main diagnosis in 20 percent of patients, second only to the symptom of headache (Digon et al). Similarly, in two primary care clinics in Boston and Houston, fatigue was the prominent complaint in 21 and 24 percent of patients, respectively. Some of these symptoms, acting through the autonomic nervous system, represent only slight aberrations of function or a heightening or exaggeration of normal reactions to all manner of environmental stress or medical and neurologic diseases; others are integral features of the diseases themselves; and still others represent disturbances of neuropsychiatric function that are components of the diseases described in the section on psychiatry. It is because of their frequency and clinical significance that we have accorded them a chapter of their own among the cardinal manifestations of neurologic disease.

Of the symptoms to be considered in this chapter, lassitude and fatigue are the most frequent, and often the most vague. Fatigue refers to the universally familiar state of weariness or exhaustion resulting from physical or mental exertion. Lassitude has much the same meaning, although more strictly it connotes an inability or disinclination to be active, physically or mentally. More than half of all patients entering a general hospital register a complaint of fatigability or admit to it when questioned. During World War I, fatigue was such a prominent symptom in combat personnel as to be given a separate place in medical nosology, namely combat fatigue, a term that came to be applied to practically all acute psychiatric disorders occurring on the battlefield. In subsequent wars, it has become a key element of the posttraumatic stress disorders related to exposure to highly stressful circumstances. The common clinical antecedents and accompaniments of fatigue, its significance, and its physiologic and psychologic bases will be better understood if we first consider the effects of fatigue on the normal individual.

Effects of Fatigue on the Normal Person

Fatigue has both explicit and implicit effects, grouped under (1) a series of biochemical and physiologic changes in muscles and a reduced capacity to generate force manifest as weakness, or asthenia; (2) an overt disorder in behavior, taking the form of a reduced output of work (work decrement) or a lack of endurance; and (3) a subjective feeling of tiredness and discomfort.

As to the biochemical and physiologic changes, continuous muscular work leads to depletion of muscle adenosine triphosphate (ATP), the supply of which is derived from creatine phosphate via phosphorylation of adenosine ...

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