Neuromuscular Notes: A Practical Approach to the Diagnosis and Management of Muscle Cramps

A cramp is a sudden, involuntary, painful contraction of muscle that typically lasts from seconds to minutes.¹ During a cramp, the muscle is often taut if palpated and may generate enough force to cause abnormal posturing of a joint. Muscle cramps are common in the general population, with reported prevalences ranging from 37% to 95%.² They can occur across all age groups, but are more frequently seen in older individuals, athletes, pregnant women, and individuals with underlying neuromuscular disorders. When frequent or severe, muscle cramps can cause prolonged postcramp soreness and can diminish quality of life by disrupting sleep, limiting physical activity, and provoking anxiety about symptom recurrence.³

Classification
The term “cramps” is often used nonspecifically to describe various neurologic phenomena. However, strictly speaking, true muscle cramps are associated with characteristic cramp discharges on EMG, and are thought to be neurogenic in origin. In this review, we use a broader, clinically based definition for cramps (ie, sudden involuntary painful contraction of muscle) rather than the stricter definition. This is mainly for practical reasons. In some cases, it is simply not known whether cramping sensations (eg, due to medication side effects) are true cramps or not. In addition, some phenomena are clinically indistinguishable from true cramps, and it may not always be practical to try to differentiate them with an EMG. As one example, painful contractures can be seen in glycogen storage diseases, such as McArdle disease (type 5). These contractures are characterized by painful shortening of muscle triggered by physical activity, but are different from true cramps in that they are electrically silent on EMG. 

Although we are using a broader definition for cramps, there are other defined neurologic phenomena from which cramps should be distinguished because the etiologies differ from each other. Usually these phenomena can be elucidated on the basis of the clinical history and neurologic examination. Table 1 shows examples of other neurologic phenomena that may mimic cramps. 

Based on the etiology, muscle cramps can be classified as physiologic, secondary to disease or exposures, or idiopathic.⁴ Physiologic cramps are those that occur in healthy individuals, and are often provoked by strenuous or unaccustomed exercise, dehydration, electrolyte imbalance, or excessive heat. In addition, women in the third trimester of pregnancy or peripartum period are at a heightened risk for muscle cramps, particularly in their lower extremities.⁵ Muscle cramps can also occur as a side effect of medications or due to toxic exposures, underlying metabolic conditions and peripheral nervous system disorders.⁴ Idiopathic muscle cramps are those that do not have an identifiable cause and typically occur in older individuals, especially in the lower extremities at night. Figure 1 summarizes the classification of muscle cramps and highlights important causes. 

Figure 1. Classification of muscle cramps and common causes.
The figure was generated using AI tools.

Differential Diagnosis
The differential diagnosis for muscle cramps is broad and includes benign etiologies as well as various neurologic and systemic conditions. Muscle cramps are associated with several endocrinopathies, including hypothyroidism, diabetes, and adrenal insufficiency.⁴ Individuals with cirrhosis or chronic renal failure also frequently report muscle cramps, likely secondary to nerve damage, changes in plasma volume, or electrolyte imbalance.⁶ Furthermore, individuals undergoing dialysis often experience muscle cramps as part of dialysis disequilibrium syndrome due to fluid shifts and acute changes in osmolality.⁷ Electrolyte disturbances, including abnormal levels of sodium, potassium, magnesium, and calcium, are also common causes of cramps.⁸ Cramps are frequently reported as a side effect of various medications, including diuretics, cholesterol-lowering drugs, β-adrenergic agonists, corticosteroids, H2 receptor blockers, nifedipine, cholinesterase inhibitors, and chemotherapy agents (particularly platinum-based drugs, vinca-alkaloid drugs, and hormonal therapies).⁸ Moreover, several toxins are associated with cramps, such as heavy metals (eg, lead, mercury, arsenic), organophosphates, alcohol, illicit drugs (eg, amphetamines, cocaine, heroin), and snake or spider venom. 

Table 2 highlights neurologic diseases associated with muscle cramps and provides a structured overview of key features of clinical history, physical examination findings, and diagnostic investigations that may aid in determining the underlying etiology. Figure 2 presents a diagnostic algorithm for muscle cramps.

Figure 2. Diagnostic algorithm for muscle cramps.
Abbreviation: CK, creatine kinase.

Diagnostic Workup
The first step in evaluating an individual with muscle cramps is obtaining a history that includes details on the duration, frequency, distribution, and triggers of the cramps, as well as associated symptoms.⁸ Muscle cramps are often benign, but certain red flags may suggest an underlying neurologic or systemic condition that warrants further investigation. Concerning features include cramps that are widespread, frequent, severe, and progressive, and those that occur without an identifiable cause, such as exercise or dehydration. Cramps associated with weakness, muscle atrophy, sensory disturbances, or gait impairment should prompt further evaluation for disorders of the muscle or the central or peripheral nervous system. Finally, the presence of systemic symptoms, such as unexplained weight loss or fatigue, should trigger assessment for underlying systemic disease. Table 3 summarizes questions that may help elucidate the underlying cause of cramps and highlights red flag symptoms that suggest the need for further investigation.

The second step is to perform a comprehensive neurologic examination to assess for the presence of fasciculations, muscle atrophy or hypertrophy, weakness, abnormal reflexes, sensory dysfunction, and gait impairment. Examination findings can help differentiate benign cramps from those associated with neuromuscular pathology. Table 2 highlights examination findings that can be seen in various neuromuscular conditions that can cause muscle cramps.

Initial laboratory workup is guided by the frequency and severity of muscle cramps as well as the presence of other systemic or neurologic symptoms. In most cases, muscle cramps are benign and self-limiting and do not require further laboratory investigation. If there are any concerning features based on patient history or examination, basic serologic workup for cramps should include complete metabolic panel (ie, electrolytes, kidney function, liver function), magnesium, thyroid-stimulating hormone, and hemoglobin A1c (HbA1c). Elevated creatine kinase (CK) levels can be due to myopathy or denervation, but cramps can also cause mild elevations in CK (usually <1,000 U/L) depending on the severity and frequency of cramps. Therefore, a mildly elevated CK level does not necessarily imply an underlying neuromuscular condition as the cause of cramps. Additional and more detailed testing for muscle cramps should be guided by the neurologic examination results and may include additional serologic studies, EMG tests, or genetic testing (Table 2). 

Electromyography
Nerve conduction studies and EMG tests are typically not used to diagnose cramps but can be useful to look for evidence of peripheral nerve injury or hyperexcitability.⁹ Afterdischarges (ie, repetitive or sustained firing of motor units after stimulus) following compound muscle action potentials or on testing F-waves on nerve conduction studies suggest peripheral nerve hyperexcitability, as do fasciculation potentials, myokymic discharges, and neuromyotonic discharges on EMG. In addition, there is a protocol that can be used to assess for peripheral nerve hyperexcitability. Repetitive nerve stimulation is applied to the tibial nerve at 1-Hz, 3-Hz, and 5-Hz frequencies with recording over the abductor hallucis muscle.¹⁰ After stimulation, the presence of afterdischarges, repetitive motor unit firing, or clinical cramping may indicate peripheral nerve hyperexcitability. Figure 3 illustrates afterdischarges and cramps in an individual with cramp fasciculation syndrome after varying frequencies of repetitive nerve stimulation. 

Figure 3. Cramp-fasciculation protocol stimulating the tibial nerve and recording over the left abductor hallucis muscle. Repetitive nerve stimulation at 1-Hz (top panel), 3-Hz (middle panel), and 5-Hz (bottom panel) with electrodiagnostic evidence of afterdischarges (top and middle panel) and cramp (bottom panel).

Treatment
Treatment of muscle cramps can be broadly categorized into nonpharmacologic and pharmacologic strategies. Individuals presenting with benign cramps often do not require treatment but benefit from reassurance regarding the self-limiting nature of this symptom. It is important to review an individual’s medication list to identify any pharmacologic agents known to induce cramps. If a culprit medication is identified, modifying the dose or substituting it with an alternative agent may help alleviate symptoms. Individuals should also be counseled on limiting caffeine and alcohol intake as well as recreational drug use, all of which can exacerbate cramp frequency and severity. Although the evidence is variable, it is reasonable to recommend hydration, electrolyte replacement, stretching, and activity modification for cramp management.¹¹ Individuals at higher risk of dehydration may benefit from consuming electrolyte-containing solutions rather than water alone due to the risk of diluting electrolyte concentrations in the body.¹² In individuals with documented deficiencies, replenishing electrolytes is recommended for the management of cramps; however, routine supplementation in individuals with a normal metabolic profile has demonstrated inconsistent results. Bedtime stretching, especially of the calf and hamstring muscles, has demonstrated favorable results in terms of reducing the frequency and severity of nocturnal leg cramps.^13,14

Pharmacologic management of muscle cramps (Table 4) is typically reserved for individuals with frequent or severe symptoms that do not respond to nonpharmacologic measures. Treatment is often individualized on the basis of symptom severity, individual comorbidities, and tolerance to therapy. Although quinine has the most robust evidence for efficacy, the Food and Drug Administration has issued a warning against using it to treat muscle cramps due to the increased risk of thrombocytopenia and cardiac arrhythmias.¹⁵ Alternatives such as mexiletine and levetiracetam have demonstrated success at reducing cramp frequency and severity in individuals with amyotrophic lateral sclerosis and are generally well-tolerated.^16,17 Other agents, such as a vitamin B complex, baclofen, oxcarbazepine, carbamazepine, and diltiazem, have been evaluated in select populations, and have generally shown benefit in reducing muscle cramp frequency or intensity.^18-23 Although magnesium is frequently prescribed to individuals with cramps, the results of a Cochrane review suggest that it is not superior to placebo at reducing cramp frequency, intensity, or duration.²⁴ The data on magnesium are mixed for pregnancy-associated cramps, but magnesium may be a reasonable option to try when other options are limited due to concern for risks to the fetus. Botulinum toxin injections have shown favorable results in individuals with cramps secondary to diabetic neuropathy, cramp-fasciculation syndrome, or lumbar spinal stenosis; however, cost and logistics likely limit its utility in clinical practice.^25-27