Weakness, a common ED complaint, can reflect a vast array of pathology with varying degrees of severity. Patients may use to the term weakness to describe either focal or systemic complaints and often use the broader description of weakness to convey otherwise vague or subjective symptoms, such as fatigue, lethargy, or general malaise. As a result, weakness as chief or associated complaint can be quite challenging, both from a diagnostic and therapeutic perspective.

Up to 10% of ED visits are for generalized weakness, with a preponderance of the complaint among elders. Over half of these patients are identified as having a serious condition, and the diagnoses span cardiovascular, hematologic, neurologic, toxicologic, psychiatric, endocrine, pulmonary, metabolic, and infectious causes.

This chapter focuses on the initial evaluation of the generalized complaint of weakness and the specific evaluation of acute neuromuscular weakness. The latter may be focal or generalized and may originate in central or peripheral nerves, the neuromuscular junction (NMJ), or myofibers themselves. Other chapters in this text provide additional information regarding the diagnosis and management of specific neurologic causes of weakness including the brain and cranial nerves (CNs; see Chapter 91 ), spinal cord (see Chapter 92 ), and peripheral nerves (see Chapter 93 ), as well as neuromuscular disorders (see Chapter 94 ).

There are many diagnostic considerations for the patient presenting with diffuse weakness ( Box 9.1 ). While a singular cause of weakness may be identified, elders and patients with multiple medical problems may have numerous factors contributing to weakness. Alterations in plasma volume, electrolyte imbalance, anemia, decreased cardiac function, drop in systemic vascular resistance, increased metabolic demand (infection, toxin, endocrinopathy), and mitochondrial dysfunction (severe sepsis) can all produce non-localized weakness. A global depression in central nervous system (CNS) activity from sedative effects or stimulant withdrawal can also present as generalized weakness. Focal weakness confined to one area in the face or body (left, right, distal, or proximal) typically indicates a localized neurological issue corresponding to a specific area of the central or peripheral nervous systems (PNSs).

Lesions involving the motor areas of the cerebral hemispheres may cause unilateral weakness, and lesions in the cerebral cortex outside the motor area may cause receptive or expressive aphasias and complex cerebral motor deficits such as apraxia. Peripherally, the spinal nerves extend from the anterior horn of the spinal cord and represent the anatomic origins of the lower motor neuron (LMN). The neuroanatomic distinction between LMNs and upper motor neurons (UMNs) is essential in localizing lesions.

The differential diagnosis for generalized weakness is broad. Consideration of systemic causes such as infectious, neurological, toxicologic, metabolic, and physiological causes is important (see Box 9.1 ). The first step is to address potential life threats, major systemic conditions, and disorders requiring emergent intervention. A detailed history should elucidate the nature, onset, and progression of symptoms, exacerbating or alleviating factors, and fluctuations in severity that may help discern if weakness is a result of cardiovascular disease, pulmonary insufficiency, metabolic disturbance, concurrent infection, toxic ingestion, medication imbalance, or malignancy. Medication reactions or interactions are an important consideration in patients taking multiple medications. A thorough review of systems should also be performed to identify associated signs or symptoms that may help to form a unifying diagnosis. For example, a review of systems might reveal orthopnea and symptoms of congestive heart failure in the fatigued patient with significant cardiac disease, chronic blood loss in the anemic patient, or incontinence in an older adult with a urinary tract infection. Elders often present with less localizing symptoms of infection, such as dysuria or frequency in the case of a possible urinary tract infection, and require a broad diagnostic approach, including laboratory and radiological studies.

Vital sign abnormalities, including bradycardia, tachycardia, tachypnea, fever, hypothermia, or hypotension should prompt immediate intervention and a search for a systemic cause of the weakness. A general detailed physical examination, including evaluation of the skin and mucous membranes, may provide evidence of systemic disease. A cardiovascular examination can give the clinician a sense of the adequacy of circulation. A carefully performed neurologic examination is important to determine the occasionally subtle presentations of focal central or PNS lesions.

If history, physical examination, and ancillary testing do not identify a systemic cause of weakness, the investigation should broaden to include consideration of neural or primary muscular causes for weakness. Focal causes of weakness include central and peripheral neurological disease. Conditions involving UMNs tend to produce signs that include spasticity to extension in the upper extremities, spasticity to flexion in the lower extremities, hyperreflexia, pronator drift, and Hoffmann and Babinski signs. UMN signs signify a lesion within the cerebral cortex or corticospinal tract (CST) of the brainstem or spinal cord. Although these findings are not always detectable in the acute period, the presence of even one of them suggests pathology within the CNS. Weakness caused by LMN dysfunction is often accompanied by flaccidity, decreased reflexes, fasciculations, or muscle cramps. Lesions in the anterior horn of the spinal cord and its axonal extensions at the nerve root and peripheral nerve produce these findings.