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Cramps, Muscle
Cramps, Muscle MB Bromberg, University of Utah, Salt Lake City, UT, USA r 2014 Elsevier Inc. All rights reserved.
Introduction
Clinical Characteristics
Focal muscle pain is a frequent medical complaint. The word ‘cramp’ is a commonly used term, but true muscle cramps should be distinguished from other causes of focal muscle pain. A cramp is an involuntary, painful focal muscle contraction that develops rapidly and subsides over minutes. Cramps may occur at rest or with muscle contraction, and they are always associated with electromyographic (EMG) activity. Muscle cramps occur frequently in the normal population, but they can be associated with diseases. This article focuses on true muscle cramps but mentions other types of focal muscle pain. The demographic features and frequency of cramps in healthy individuals and those with medical conditions are presented. Whether cramps originate in motor neurons or peripheral nerves is uncertain, but relevant features of the pathogenesis are discussed.
Muscle cramps occurring at rest are common, being reported in more than one-third of respondents in a population survey. They affect feet, legs, and thigh muscles but rarely upper extremity muscles. They occur more frequently with age. Cramps are associated with muscle shortening. Nocturnal cramps in the calf and toe muscles are presumably due to activation of shortened muscles with change of body position. Exerciseinduced cramps may occur more frequently with vigorous exercise but also with trivial activity. Some individuals appear to be more prone to cramps. Cramps can occur with greater frequency in muscles that are fatigued from exercise. Changes in the chemical milieu of muscle, such as electrolyte loss from dehydration, have been proposed, but there are few specific data that are supportive. Mild cramps can be relieved by stretching the affected muscle. This is an instinctual response when the sleeping individual jumps out of bed and walks around or when the athlete stops the causative activity. Muscle cramp pain can be severe, with muscle soreness remaining for several days, and there may be an elevation in serum creatine kinase levels, indicating muscle fiber damage. Muscle cramps occur more frequently in neuropathic diseases that include motor nerves, such as peripheral neuropathy and radiculopathy. The most ominous is amyotrophic lateral sclerosis (ALS). Although cramps may be common in healthy individuals, patients with ALS describe new-onset cramps or a greater frequency of cramps, both rest cramps and exercise-induced cramps. In ALS, cramps occur outside of the usual distribution, including the arms and hands, the trunk, and the platysma muscle. Cramps in a new area may precede the onset of clinical weakness. Muscle cramps occur with greater frequency in certain metabolic diseases. Cramps are frequent during the final period of hemodialysis. They are more common in patients who have liver failure. Cramps occur commonly during the last trimester of pregnancy. Certain drugs are prone to causing cramps, including terbutaline, salbutamol, and nifedipine.
Definitions As stated in the introduction, true muscle cramps are acute, involuntary, and painful muscle contractions that resolve over minutes. A common term used by patients for a cramp is ‘Charley Horse.’ Interestingly, the derivation of this term is obscure but likely comes from baseball in the mid-nineteenth century to describe a player who runs slowly due to painful muscles. The analogy appears to be with a horse named Charley who failed to perform in a race. The early baseball examples suggest muscle injury from overuse and less from true cramps. Medical dictionaries define a Charley Horse as resulting from injury of thigh muscles. However, the term Charley Horse in common usage now seems to denote a true muscle cramp, at least in the elderly, who more frequently watch than play baseball. Another term used by patients to denote a muscle pain is a spasm. They may mean a true cramp or a more diffuse pain, as in low back pain. Greater clinical detail is necessary to determine whether a patient is describing true cramps versus other painful muscle conditions. Muscle contractures are to be distinguished from cramps for several reasons. Sudden, painful contractures originate from muscle and are electrically silent. They are due to abnormalities of muscle energy metabolism (glycogen storage diseases such as McArdles’ disease) and occur with muscle activity and not at rest. Severe muscle contractures may cause myoglobinuria. In patients with myotonic dystrophy or myotonia congenita, myotonia following a vigorous contraction can occasionally be painful. Writer’s cramp represents a focal dystonia associated with particular repetitive activities, and the dystonic muscle groups can be painful. Focal dystonias have a central nervous system origin.
Encyclopedia of the Neurological Sciences, Volume 1
Physiological Features Cramps can only be induced in a shortened muscle. They can be initiated by a forceful contraction of a shortened muscle or by electrical stimulation of peripheral nerves innervating the muscle. Pain from an induced cramp is similar to that of a spontaneous cramp. Cramps begin locally within the muscle and are associated with focal hardness of the muscle to palpation. Fasciculations may be observed as the cramp develops. True muscle cramps consist of trains of motor unit action potentials (MUAPs). Needle EMG recordings during induced cramps show trains of MUAPs that are similar to those
doi:10.1016/B978-0-12-385157-4.00611-4
885
886
Cramps, Muscle
recorded from the same muscle during noncramping voluntary contractions. The MUAP discharge frequency during a cramp may be very rapid, and it decreases as the cramp pain wanes. Multiple motor units may be activated, and there is a correlation between the number and pain intensity. Recordings indicate that different portions of a muscle may become active during a cramp. Determining the origin of cramps has been a challenge for more than 100 years. Initial theories focused on fluid and electrolyte imbalances to explain cramps observed in workers performing in hot and humid environments, but in controlled trials no gross disturbances of electrolytes or degree of hydration has been found. True cramps do not originate in muscle because they cannot be induced in a muscle paralyzed by neuromuscular blockade. The current debate focuses on whether cramps arise from peripheral nerve (axons) or from motor neuron cell bodies. In support of a peripheral nerve origin, cramps can be induced by electrical stimulation of a motor nerve distal to peripheral nerve blockade. The initiation site for electrical activity could be along the motor axon or at presynaptic terminals. Other observations support a contribution from spinal reflexes and changes of excitability within the motor neuron. In support of central factors, cramps can be initiated by activation of muscle spindle afferent fibers (group Ia) by electrical stimulation, vibration stimuli, or a tap to the homonymous tendon that monosynaptically activates motor neurons innervating the cramping muscle. Furthermore, cramps may be relieved by electrical stimulation of cutaneous nerves that inhibit motor neurons innervating the cramping muscle. A hypothesis has emerged from these data on central factors that states that motor neurons can exist in two excitability states – a normal state and a heightened state in which the motor neuron discharges spontaneously and regularly, leading to a cramp. It is unlikely that a single theory will serve to explain all types of cramps in healthy individuals with factors of age, pregnancy, level of exercise, level of conditioning, predilection for certain muscle groups, and so forth. Associated factors for some are that certain individuals are more prone to cramps than others, and in a few families there is a hereditary crampfasciculation syndrome. It is unclear why cramps occur more frequently in diseases involving motor nerves. The explanation may be different for diseases affecting the motor neurons (such as in ALS) or the axon (such as radiculopathies and peripheral neuropathies).
Treatment Although only one-third of patients reporting cramps seek medical attention, cramps are a troublesome symptom. Many different therapies have been attempted, ranging from physical changes to the bed and bed covers to muscle stretching exercises based on the fact that stretching relieves a cramp and prophylactic stretching may be preventative. Formal assessments of symptomatic treatment for muscle cramps
based on evidence-based criteria by the American Academy of Neurology and a Cochrane Review concluded that there is class I evidence for a modest benefit from quinine sulfate, but warned against its use due to nonfatal hypersensitivity reactions that can occur immediately or after chronic use and include hemolytic uremic syndrome–thrombotic thrombocytopenia purpura syndrome and disseminated intravascular coagulation. The Food and Drug Administration restricted the approval of quinine sulfate to malaria based on the abovementioned side effects in 2007. Other drugs with class II evidence include naftidrofuryl (not available in USA), vitamin B complex, and diltiazem, whereas gabapentin is probably not effective. There is anecdotal evidence for reduced cramps with cessation of coffee.
Conclusion True muscle cramps are common in normal individuals. However, patients may use a variety of terms to describe painful muscle phenomena, and it is appropriate to clearly determine to which phenomena the patient is referring. Muscle cramps can occur in specific disease states and may be a clue in the diagnostic evaluation. Whatever the cause, muscle cramps are challenging to treat. Although formal clinical trials of treatment and clinical experience support quinine sulfate, its use in the USA and other countries is restricted due to potential side effects. Other pharmacological treatments are unproven. Perhaps stretching of leg muscles before bedtime is the most reasonable alternative.
See also: Fasciculations. Muscle Contraction; Overview. Muscle Tone. Myopathy, Endocrine. Neuromuscular Disorders; Overview. Writer’s Cramp/Tremor
Further Reading Baldissera F, Cavallari P, and Dworzak F (1994) Motor neuron ‘bistability.’ A pathogenetic mechanism for cramps and myokymia. Brain 117: 929–939. El-Tawi S, Al Musa T, Valli H, et al. (2010) Quinine for muscle cramps (Review). Cochrane Database Systematic Reviews 12, CD005044. Katzberg HD, Khan AH, and So YT (2010) Assessment: Symptomatic treatment for muscle cramps (an evidence-based review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 74: 691–696. Layzer R (1980) Motor unit hyperactivity states. In: Vinken P and Bruyn G (eds.) Diseases of Muscle, vol. 41, pp. 295–314. Amsterdam: North-Holland. McGee S (1990) Muscle cramps. Archives of Internal Medicine 150: 511–518. Naylor J and Young J (1994) A general population survey of rest cramps. Age and Ageing 23: 418–420. Norris F, Gasteiger E, and Chatfield P (1957) An electromyographic study of induced and spontaneous muscle cramps. Electroencephalography and Clinical Neurophysiology 9: 139–147. Schwellnus M, Derman E, and Noakes T (1997) Aetiology of skeletal muscle ‘cramps’ during exercise: A novel hypothesis. Journal of Sports Science 15: 277–285. Shulman D (1949) Whence ‘‘Charley Horse’’? American Speech 24: 100–104.
Introduction
Clinical Characteristics
Focal muscle pain is a frequent medical complaint. The word ‘cramp’ is a commonly used term, but true muscle cramps should be distinguished from other causes of focal muscle pain. A cramp is an involuntary, painful focal muscle contraction that develops rapidly and subsides over minutes. Cramps may occur at rest or with muscle contraction, and they are always associated with electromyographic (EMG) activity. Muscle cramps occur frequently in the normal population, but they can be associated with diseases. This article focuses on true muscle cramps but mentions other types of focal muscle pain. The demographic features and frequency of cramps in healthy individuals and those with medical conditions are presented. Whether cramps originate in motor neurons or peripheral nerves is uncertain, but relevant features of the pathogenesis are discussed.
Muscle cramps occurring at rest are common, being reported in more than one-third of respondents in a population survey. They affect feet, legs, and thigh muscles but rarely upper extremity muscles. They occur more frequently with age. Cramps are associated with muscle shortening. Nocturnal cramps in the calf and toe muscles are presumably due to activation of shortened muscles with change of body position. Exerciseinduced cramps may occur more frequently with vigorous exercise but also with trivial activity. Some individuals appear to be more prone to cramps. Cramps can occur with greater frequency in muscles that are fatigued from exercise. Changes in the chemical milieu of muscle, such as electrolyte loss from dehydration, have been proposed, but there are few specific data that are supportive. Mild cramps can be relieved by stretching the affected muscle. This is an instinctual response when the sleeping individual jumps out of bed and walks around or when the athlete stops the causative activity. Muscle cramp pain can be severe, with muscle soreness remaining for several days, and there may be an elevation in serum creatine kinase levels, indicating muscle fiber damage. Muscle cramps occur more frequently in neuropathic diseases that include motor nerves, such as peripheral neuropathy and radiculopathy. The most ominous is amyotrophic lateral sclerosis (ALS). Although cramps may be common in healthy individuals, patients with ALS describe new-onset cramps or a greater frequency of cramps, both rest cramps and exercise-induced cramps. In ALS, cramps occur outside of the usual distribution, including the arms and hands, the trunk, and the platysma muscle. Cramps in a new area may precede the onset of clinical weakness. Muscle cramps occur with greater frequency in certain metabolic diseases. Cramps are frequent during the final period of hemodialysis. They are more common in patients who have liver failure. Cramps occur commonly during the last trimester of pregnancy. Certain drugs are prone to causing cramps, including terbutaline, salbutamol, and nifedipine.
Definitions As stated in the introduction, true muscle cramps are acute, involuntary, and painful muscle contractions that resolve over minutes. A common term used by patients for a cramp is ‘Charley Horse.’ Interestingly, the derivation of this term is obscure but likely comes from baseball in the mid-nineteenth century to describe a player who runs slowly due to painful muscles. The analogy appears to be with a horse named Charley who failed to perform in a race. The early baseball examples suggest muscle injury from overuse and less from true cramps. Medical dictionaries define a Charley Horse as resulting from injury of thigh muscles. However, the term Charley Horse in common usage now seems to denote a true muscle cramp, at least in the elderly, who more frequently watch than play baseball. Another term used by patients to denote a muscle pain is a spasm. They may mean a true cramp or a more diffuse pain, as in low back pain. Greater clinical detail is necessary to determine whether a patient is describing true cramps versus other painful muscle conditions. Muscle contractures are to be distinguished from cramps for several reasons. Sudden, painful contractures originate from muscle and are electrically silent. They are due to abnormalities of muscle energy metabolism (glycogen storage diseases such as McArdles’ disease) and occur with muscle activity and not at rest. Severe muscle contractures may cause myoglobinuria. In patients with myotonic dystrophy or myotonia congenita, myotonia following a vigorous contraction can occasionally be painful. Writer’s cramp represents a focal dystonia associated with particular repetitive activities, and the dystonic muscle groups can be painful. Focal dystonias have a central nervous system origin.
Encyclopedia of the Neurological Sciences, Volume 1
Physiological Features Cramps can only be induced in a shortened muscle. They can be initiated by a forceful contraction of a shortened muscle or by electrical stimulation of peripheral nerves innervating the muscle. Pain from an induced cramp is similar to that of a spontaneous cramp. Cramps begin locally within the muscle and are associated with focal hardness of the muscle to palpation. Fasciculations may be observed as the cramp develops. True muscle cramps consist of trains of motor unit action potentials (MUAPs). Needle EMG recordings during induced cramps show trains of MUAPs that are similar to those
doi:10.1016/B978-0-12-385157-4.00611-4
885
886
Cramps, Muscle
recorded from the same muscle during noncramping voluntary contractions. The MUAP discharge frequency during a cramp may be very rapid, and it decreases as the cramp pain wanes. Multiple motor units may be activated, and there is a correlation between the number and pain intensity. Recordings indicate that different portions of a muscle may become active during a cramp. Determining the origin of cramps has been a challenge for more than 100 years. Initial theories focused on fluid and electrolyte imbalances to explain cramps observed in workers performing in hot and humid environments, but in controlled trials no gross disturbances of electrolytes or degree of hydration has been found. True cramps do not originate in muscle because they cannot be induced in a muscle paralyzed by neuromuscular blockade. The current debate focuses on whether cramps arise from peripheral nerve (axons) or from motor neuron cell bodies. In support of a peripheral nerve origin, cramps can be induced by electrical stimulation of a motor nerve distal to peripheral nerve blockade. The initiation site for electrical activity could be along the motor axon or at presynaptic terminals. Other observations support a contribution from spinal reflexes and changes of excitability within the motor neuron. In support of central factors, cramps can be initiated by activation of muscle spindle afferent fibers (group Ia) by electrical stimulation, vibration stimuli, or a tap to the homonymous tendon that monosynaptically activates motor neurons innervating the cramping muscle. Furthermore, cramps may be relieved by electrical stimulation of cutaneous nerves that inhibit motor neurons innervating the cramping muscle. A hypothesis has emerged from these data on central factors that states that motor neurons can exist in two excitability states – a normal state and a heightened state in which the motor neuron discharges spontaneously and regularly, leading to a cramp. It is unlikely that a single theory will serve to explain all types of cramps in healthy individuals with factors of age, pregnancy, level of exercise, level of conditioning, predilection for certain muscle groups, and so forth. Associated factors for some are that certain individuals are more prone to cramps than others, and in a few families there is a hereditary crampfasciculation syndrome. It is unclear why cramps occur more frequently in diseases involving motor nerves. The explanation may be different for diseases affecting the motor neurons (such as in ALS) or the axon (such as radiculopathies and peripheral neuropathies).
Treatment Although only one-third of patients reporting cramps seek medical attention, cramps are a troublesome symptom. Many different therapies have been attempted, ranging from physical changes to the bed and bed covers to muscle stretching exercises based on the fact that stretching relieves a cramp and prophylactic stretching may be preventative. Formal assessments of symptomatic treatment for muscle cramps
based on evidence-based criteria by the American Academy of Neurology and a Cochrane Review concluded that there is class I evidence for a modest benefit from quinine sulfate, but warned against its use due to nonfatal hypersensitivity reactions that can occur immediately or after chronic use and include hemolytic uremic syndrome–thrombotic thrombocytopenia purpura syndrome and disseminated intravascular coagulation. The Food and Drug Administration restricted the approval of quinine sulfate to malaria based on the abovementioned side effects in 2007. Other drugs with class II evidence include naftidrofuryl (not available in USA), vitamin B complex, and diltiazem, whereas gabapentin is probably not effective. There is anecdotal evidence for reduced cramps with cessation of coffee.
Conclusion True muscle cramps are common in normal individuals. However, patients may use a variety of terms to describe painful muscle phenomena, and it is appropriate to clearly determine to which phenomena the patient is referring. Muscle cramps can occur in specific disease states and may be a clue in the diagnostic evaluation. Whatever the cause, muscle cramps are challenging to treat. Although formal clinical trials of treatment and clinical experience support quinine sulfate, its use in the USA and other countries is restricted due to potential side effects. Other pharmacological treatments are unproven. Perhaps stretching of leg muscles before bedtime is the most reasonable alternative.
See also: Fasciculations. Muscle Contraction; Overview. Muscle Tone. Myopathy, Endocrine. Neuromuscular Disorders; Overview. Writer’s Cramp/Tremor
Further Reading Baldissera F, Cavallari P, and Dworzak F (1994) Motor neuron ‘bistability.’ A pathogenetic mechanism for cramps and myokymia. Brain 117: 929–939. El-Tawi S, Al Musa T, Valli H, et al. (2010) Quinine for muscle cramps (Review). Cochrane Database Systematic Reviews 12, CD005044. Katzberg HD, Khan AH, and So YT (2010) Assessment: Symptomatic treatment for muscle cramps (an evidence-based review): Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 74: 691–696. Layzer R (1980) Motor unit hyperactivity states. In: Vinken P and Bruyn G (eds.) Diseases of Muscle, vol. 41, pp. 295–314. Amsterdam: North-Holland. McGee S (1990) Muscle cramps. Archives of Internal Medicine 150: 511–518. Naylor J and Young J (1994) A general population survey of rest cramps. Age and Ageing 23: 418–420. Norris F, Gasteiger E, and Chatfield P (1957) An electromyographic study of induced and spontaneous muscle cramps. Electroencephalography and Clinical Neurophysiology 9: 139–147. Schwellnus M, Derman E, and Noakes T (1997) Aetiology of skeletal muscle ‘cramps’ during exercise: A novel hypothesis. Journal of Sports Science 15: 277–285. Shulman D (1949) Whence ‘‘Charley Horse’’? American Speech 24: 100–104.