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Saturday, April 14, 2012

Muscle Cramping

Author: Dr Martin Schwellnus University of Cape Town South Africa 2008-07-28

What is a muscle cramp?

The word “cramp” is probably derived from the old High German and Norse root word “cram” which means an uncomfortable squeezing, pressing or pinching 1. Muscle cramping is a common symptom that is likely to affect most people at some stage during life. It has been reported that 35-60% of elderly persons suffer from cramping 1, and in one study it has been documented that 37% of the adult population will experience muscle cramping in a year 2.

Generally, cramping is experienced as a sudden feeling of a painful “pulling” in the muscle without any specific provocation or injury to the muscle. It can also be experienced mainly as “tightness,” but is always associated with a contracted and taut muscle. This results in the inability to move the joints around the muscle. In the medical literature, a muscle cramp is defined as a sudden, painful, involuntary contraction of the skeletal muscles 3. This distinguishes muscle cramping from muscle spasms (which are sometimes not painful) 3 and muscle contractures, of which there are various forms 3, the most common of which is known as an antalgic (painful) contracture. An anatlagic contracture refers to a muscle contraction in response to an injury that is experienced, for example, when a lumbar disc causes lower back pain. There are other forms of muscle contracture that may be painless. 

Are there different forms of muscle cramping?

There are many different forms of muscle cramping, and there are complicated and extensive classifications and numerous lists of causes of muscle cramping 1-4. The severity of cramping can vary and it can range from a relatively benign, infrequent occurrence to a symptom which is part of a serious underlying medical disease 1. Therefore, in general, muscle cramping can be classified into two main groups: 1) a more benign form of muscle cramping that in most cases poses no risk to a person’s long-term health, or 2) muscle cramping that is part of a disease process or a side effect of drugs or medications. Muscle cramping that occurs as a result of an underlying medical illness, toxins or use of drugs is often only one component of the symptom complex of the disease (one of many other symptoms). Cramping under these circumstances is often not the predominant symptom of the medical condition. Medical conditions and drugs or medications that can cause cramping will not be discussed in detail but are listed in this knol.
The most common forms of cramping in the general population are the more benign forms of cramping. The three most common forms of benign cramping are pregnancy associated cramping, night cramps, and exercise associated muscle cramping. These are the forms of cramping that will be discussed in detail in this knol.

Pregnancy associated muscle cramping

Muscle cramping during pregnancy is very common and has been reported in up to 50% of pregnant women. Typically, muscle cramping occurs in the latter stages of pregnancy (in the second and third trimesters), and mainly affects the lower leg (calf) muscles. In some reports, this form of cramping has also been referred to as “restless leg syndrome in pregnancy 5.”

What causes muscle cramping in pregnancy?

The precise cause or causes of muscle cramping in pregnancy is not known. It has been suggested that the possible mechanisms responsible for cramping in pregnancy are related to 1) changes in the circulation, 2) pressure on the nerves to the legs, 3) metabolic abnormalities 1, 4) fluid retention 1, 5) deficiencies in electrolytes such as calcium and magnesium 6;7, or 6) deficiencies in Vitamin B1 and B6 8;9.

Who is at risk of developing cramps in pregnancy?

Cramping in pregnancy typically occurs in the second and third trimester 1, but specific risk factors for cramps in pregnancy have not been studied well. One study identified risk factors for restless leg syndrome in pregnancy 5. Of the 146 women in the study, 38 suffered from restless leg syndrome, which allowed the researchers to identify the following risk factors: additional medical conditions such as excessive daytime sleepiness, lower blood hemoglobin levels, slightly higher blood progresterone levels, and less frequent use of iron and vitamin supplements 5.  

How is the diagnosis of cramps during pregnancy made?

The diagnosis of cramps during pregnancy is made by the attending medical practitioner through a comprehensive clinical history, a thorough physical examination, and special investigations that may be requested to confirm the diagnosis.
The classic clinical history is that of cramps starting in the second or mainly the third trimester of pregnancy. The main complaint is usually that of episodic, painful, involuntary contractions, usually in the lower leg (calf) muscles. Frequently these occur at night, and at the time of resting the muscle. They may be precipitated by positions in which the muscles are kept in a shortened position; for example, lying in bed with the toes pointed (plantar flexed).
The medical practitioner will perform a full physical examination that is mainly aimed at identifying any underlying medical conditions that may present as cramping during pregnancy. Special investigations, including blood tests for electrolyte or hormone levels may be requested.

What are the treatment options for cramps during pregnancy?

Immediate treatment of an acute cramp during pregnancy
The treatment of an acute sudden severe cramp is to stretch the muscle gently. This first aid treatment is effective for cramps during pregnancy, and practical step-wise suggestions for stretching are listed in Table 1. The mechanism by which stretching relieves cramping is based on a reflex inhibition of the muscle. Stretching stimulates the discharge of nerve endings in the tendons (Golgi tendon organ), and this results in inhibiting muscle contraction. 

Table 1: Steps in the immediate treatment of a muscle cramp (static stretching)
1.    Identify the affected muscle
2.    Using a towel/ band or your hand, apply a gentle stretch to the muscle. The actual technique that is used differs in each muscle group. In the case of cramping the back thigh (hamstring) muscle, this is performed as follows (see Figure 1 below):
·      Lie flat on your back then bend the leg at the hips and the knee
·      Loop the towel (band) over the front part of the foot, hold both ends of the towel in each hand
·      Gently pull on the towel to stretch the leg so that the hip bends and the knee straightens
·      A stretch should be felt at the back of the thigh, the calf and in the foot muscles.
3.    It is important to note that in the first 10-20 seconds of stretching, the severity of the cramp may increase slightly (as a result of an initial reflex contraction of the muscle)
4.    After 20-30 seconds the muscle will slowly start to relax (activation of the inhibitory tendon reflex)
5.    Hold the stretch for 30-60 seconds
6.    Keep the muscle in a lengthened (stretched) position for a few minutes

Figure 1: Technique to effectively stretch the hamstring muscle 

Longer term treatment options for cramps during pregnancy
A number of treatment options to reduce the frequency and severity of cramps during pregnancy have been suggested over the last 40-50 years. In most instances, the scientific evidence to confirm the efficacy of these treatment options is lacking. However, in recent years, studies have shown that some treatment options are beneficial, and these are listed (together with the strength of scientific support) in Table 2. It appears that magnesium supplementation, is the preferred supplement to prevent cramps during pregnancy. 

Table 2: Treatment options for cramps during pregnancy 6-10
Evidence that the treatment option is effective
Treatment option
Good evidence that the treatment option is likely to be beneficial for cramps during pregnancy
·  Magnesium supplements

Treatment options that have been used but their use is not based on strong evidence
·  Calcium supplements
·  Multivitamins and mineral supplements
·  Vitamin B supplements
·  Iron supplements
·  Sodium chloride

Other options to prevent cramping in pregnancy, which have not been well-studied, are:
·   Regular stretching of the affected muscles (three stretches that are held for about 30 seconds, two to three times a day)
·   Performing regular exercise (as recommended by the attending medical practitioner)
·   Lying on the side in bed rather than on the back (to avoid compression of blood vessels and nerves)

Night cramps

Night cramps are also known as nocturnal leg cramps. This form of benign cramping usually occurs in the calf muscles or the small muscles of the foot 11. Night cramps are more frequent in older people, typically over the age of 50 years 12. In one study, 30% of people over the age of 60 years reported night cramps during the preceding two months, while this increased to 50% in persons over the age of 80 years 11.

What causes night cramps?

The cause of night cramping is not completely understood. First and foremost, any person suffering from night cramps needs to realise that night cramping may be related to underlying medical conditions, or the use of certain drugs or medicines 12. Therefore, any person suffering from night cramps requires a full medical assessment to exclude the possibility of underlying medical disease. Only once medical conditions and medicines (and drugs) are excluded as a cause, can the cramping be termed benign night cramps.

Who is at risk of developing night cramps?

Although not systematically studied, the following risk factors have been associated with development of night cramps: 11-14
·   Increased age
·   Poor calf muscle flexibility
·   Presence of underlying medical disease (typically vascular disease, cancer, renal disease, neurological disease, metabolic disease, and endocrine disease)
·   Use of medications or drugs

How is the diagnosis of night cramps made?

The diagnosis of night cramps is made by the medical practitioner on the basis of a comprehensive medical history, a thorough physical, and selected special investigations 13. Elements in the medical history that are important include: 1) the frequency and intensity of muscle cramping, 2) the muscle groups affected, 3) factors that precipitate or aggravate cramping, 4) factors that may relieve cramping, 5) evidence that there may be symptoms of an underlying medical condition by taking a systematic medical history, and 6) a history of use of medications or drugs.
The physical examination should include a comprehensive examination of all the systems, with the main focus on the neurological and vascular systems. Even if no abnormality to indicate an underlying medical condition is detected during the physical examination, some routine special investigations should be performed. These will include some blood tests for endocrine (glandular) disease, renal (kidney) function, and cancer screening. Other specialized investigations such as electromyography (a test that examines the muscles), nerve conduction studies, muscle biopsies, or muscle enzyme analyses may be performed. 

What are the treatment options for night cramps?

Immediate treatment of an acute night cramp
The treatment of an acute sudden severe night cramp is to stretch the muscle gently. This first aid treatment is effective for night cramps and other forms of benign cramping (Table 1).
Longer term treatment options for night cramps
Many options for the prevention and longer term treatment of night cramps have been suggested. This is probably a reflection on the fact that there are many possible causes for night cramp. If an underlying disease that manifested as night cramp has been identified, that should be treated. If no underlying disease or medicine/drug has been identified, this is often termed idiopathic night cramp. The options for preventing idiopathic night cramp are listed in Table 3.

Table 3: Treatment options for night cramp 4;10;11;14-19
Evidence that the treatment option is effective
Treatment option
Good evidence that the treatment option reduces the frequency of night cramp
·   Quinine

Evidence that the treatment option is likely to reduce the frequency of night cramp
·   Quinine and theophylline

Treatment options that have been used but their use is not based on strong evidence
·   Regular calf muscle stretching
·   Vitamin E
·   Magnesium supplements
·   Analgesic (pain relief) medication
·   Compression stockings

It appears from most research studies that quinine is effective in the treatment of night cramping 10;11;18. In an evidence based review of the benefits of quinine for leg cramps, it was concluded that there is strong evidence that quinine reduces the frequency of leg cramps 10. However, it is very important to point out that quinine is associated with significant symptoms including bitter taste in the mouth, headache, ringing or buzzing in the ears (tinnitus), fever, blurred vision, dizziness, itchy skin, and muscle pain 10;18. Furthermore, quinine treatment can also negatively affect the white cell and platelet counts in the blood 18. Quinine may also interfere with other medications such as warfarin 1.
Other medications that have been used for cramping include the anti-convulsant gabapentin 1, botulinum toxin (Botox), the vasodilator naftidrofuryl oxalate 11, the calcium channel blocker verapamil 11, orphenadrine citrate (an antihistamine), and more recently pycnogenol (an antioxidant derived from pine bark) 20. However, there is no sufficient scientific evidence to suggest that any of these medications are effective or safe in the long term management of night cramps. 
Although regular calf stretching has not been shown to be of benefit in the treatment of night cramps in one study 17, there is anecdotal evidence that some patients benefit. Therefore, as this is a safe intervention, a therapeutic trial of stretching in patients suffering from night cramps is suggested.

Exercise Associated Muscle Cramps (EAMC)

About 30-50% of all endurance athletes will experience cramping at some stage in their running careers 21. The causes, diagnosis, and treatment of exercise associated muscle cramping are still not well understood. Muscle cramps can be a manifestation of some underlying medical disease, but the majority of these medical diseases are rare and most athletes with cramping suffer from Exercise-Associated Muscle Cramping (EAMC). EAMC is defined as a "painful, spasmodic, involuntary contraction of skeletal muscle that occurs during or immediately after muscular exercise.”

What causes exercise associated muscle cramps?

Early observations have led to the belief that cramps in athletes are caused by shortages of electrolytes (sodium, chloride, and magnesium), dehydration, or heat. Despite a lack of scientific support for these theories the term “heat cramps,” which was first used in 1935, is still in use today. However, there is increasing evidence that EAMC is caused by muscle fatigue which results in a disturbance in the normal control of the nerves that cause muscle contraction. A number of researchers who have reviewed the medical literature now conclude that this “altered neuromuscular control” mechanism is probably responsible for the majority of EAMC in athletes 21-23.  As with other forms of cramping, a small proportion of EAMC may also be as a result of underlying medical disease or drugs 21;23. 

Who is at risk of developing exercise associated muscle cramps?

Risk factors for EAMC have recently been reviewed 21 and can be divided into intrinsic risk factors (inherent to the athlete), or extrinsic risk factors (external factors to the athlete). In this review the most important risk factors for cramping are listed in Table 4.

Table 4: Intrinsic and extrinsic risk factors for EAMC 21
Evidence to indicate if risk factors are associated with EAMC
Risk factor
Intrinsic risk factors
Strong evidence
Past history of EAMC
Increased exercise intensity (race pace or subjective assessment)
Weak evidence
Muscle fatiguing exercise
Increased exercise duration (time, in the later stages of an event)
Increased age
Longer history of running
Shorter daily stretching time
Irregular stretching habits
Positive family history of cramping
Extrinsic risk factors
Limited evidence
Increased environmental temperature and humidity

In this analysis, evidence that commonly proposed  risk factors such as dehydration, disturbances in blood electrolyte concentrations, and the more recently proposed risk factor of  “salty sweating” (increased sweat sodium concentration) 24-27 were also analyzed. It was concluded that there is strong evidence that these risk factors are not associated with EAMC 21. 
It has also been observed, though not proven that muscles most prone to cramping are those that span across two joints (hamstring muscles, one of the front thigh muscles, some of the calf muscles and foot muscles). These are also the muscles that are often contracted in a shortened position during exercise. 

How is the diagnosis of exercise associated muscle cramps made?

The clinical features of EAMC are skeletal muscle fatigue followed by twitching of the muscle (“cramp prone state”). A typical history of an athlete presenting with acute EAMC will include the following features 21:
·    EAMC is more common when intense prolonged exercise is performed.
·    EAMC is more common when exercise is performed in a competitive environment. The onset of EAMC is usually preceded by the development of skeletal muscle fatigue.
·    EAMC is more common in athletes that are not well conditioned for the event.
·    Hot and humid environmental conditions predispose to EAMC by causing premature fatigue.
·    Cramping is usually preceded by a noticeable twitching of the muscle and is then followed by spasmodic spontaneous contractions and obvious muscle cramping if the activity is continued.
·    The pain associated with EAMC usually develops gradually over a few minutes during intense or prolonged exercise,
·    Passive stretching of the affected muscle and stopping the activity provide the most effective relief from the cramp prone state.
·    During the cramp prone state, cramping can be precipitated by contraction of the muscle in a shortened position (inner range).
·    In the majority of cases, muscle cramping is confined to muscle groups that are very active during the athletic event; most commonly these are the calf muscle groups, hamstring muscles, and the quadriceps muscles.
·    EAMC usually lasts for a few minutes to a few hours once activity is ceased.

The clinical examination of an athlete with EAMC typically shows obvious distress, pain, a hard contracted muscle, and visible fasciculation (twitching) over the muscle belly 21. In most instances the athlete is conscious, responds normally to stimuli, and is able to conduct a conversation. Vital signs and a general examination usually reveal no abnormalities. In particular, most athletes with acute cramping are not dehydrated or do not have an excessively high body temperature.
An athlete who has generalised severe cramping or is confused, semi-comatosed, or comatosed should be treated as an emergency and requires immediate hospitalisation where full investigation is required.

What are the treatment options for exercise associated muscle cramps?

Immediate treatment of an acute exercise associated muscle cramp
The immediate treatment for acute cramping is passive stretching of the affected muscle groups and then holding the muscle in stretched position until fasciculation (twitching) ceases (Table 1), followed by a period of rest 21. Supportive treatment is by keeping the athlete at a comfortable temperature and by providing oral fluids if required 28.  Athletes with recurrent, acute EAMC should be investigated fully to exclude other medical conditions.
Longer term prevention and treatment options for exercise associated muscle cramps
The strategies to prevent EAMC have also recently been reviewed 21 and include the following:
·   The key to avoid EAMC is to prevent the development of premature muscle fatigue, by being well conditioned for an event, and ensuring that exercise is performed at an intensity and duration to which the athlete is accustomed to
·   Athletes that perform exercise at a high intensity or prolonged duration, should be aware of the early sign of EAMC, which is muscle twitching. It twitching is experienced, exercise intensity should be decreased (running at a slower speed) so that the muscle can recover before EAMC develops.
·   Prevention of premature muscle fatigue is particularly important in events that are conducted in hot and humid environmental conditions.
·   Regular stretching of the muscle groups that are prone to cramping may be of benefit to prevent EAMC.
·   Other strategies to prevent premature muscle fatigue include giving attention to adequate nutritional intake (particularly carbohydrate). Athletes may need to consult a sports dietician.

Muscle cramping associated with diseases and drugs

There are many diseases in many of the body systems that can be associated with muscle cramps. A list of these is provided in Table 5.

Table 5: Diseases in various body systems that may be associated with muscle cramping 21
Diseases of the muscles
1.        Metabolic myopathy ( deficiency of myophosphorilase, phosfophruttokinase, phosfogliceromutase, phosfoglicerokinase, lactate dehydrogenase (LDH), adenylate deaminase, G6PDH, phosforylase b-kinase)
2.        Mitochondrial myopathy (Carnitine deficiency, CPT1 and 2 deficiency)
3.        Endocrine myopathy (Hoffman’s syndrome)
4.        Dystrophinopathies (Duchenne, Becker, and others)
5.        Myotonia (Becker, rippling syndrome)
6.        Inflammatory myopathies (Myositis, myopathy with tubular aggregates, rheumathic polymyagia)
7.        Others (rare) (Lambert-Brody’s diseases, Swartz-Jampel syndrome, eosinophilia-myalgia syndrome type 2 muscle fibre myopathy
Diseases of the nervous system
1.        Motoneuron disease
2.        Occupational dystonias
3.        Parkinson’s disease
4.        Tetanus
5.        Multiple sclerosis
6.        Radiculopathies
7.        Plexopathies
8.        Peripheral neuropathies ( inherited, endocrin-metabolic, infectious, toxic, inflammatory, demyelinizing)
9.        Others (rare) (neurolathyrism, familial paroxysmal dystonic choreoathetosis)
Diseases of the heart and blood vessels
1.        Venous diseases
2.        Arterial diseases
3.        Heart diseases
4.        Hypertension
Diseases of the glandular system
1.        Hypo-hyperthyroidism
2.        Hypo- hyperparathyroidism
3.        Isolated deficiency of ACTH accompanied by generalised painful muscle cramp 
4.        Bartter’s syndrome
5.        Gitelman’s syndrome
6.        Conn’s disease
7.        Addison’s disease
Diseases of the kidney and other diseases affecting water and electrolyte balance
1.        Uremia and dialysis
2.        Dehydration with or without electrolytes imbalance (diarrhoea and vomiting, etc)
3.        Hypo-hypernatremia
4.        Hypo-hypercalcemia
5.        Hypo-hyperkalemia
6.        Hypomagnesemia
Medicines, drugs, and toxins
1.        Drugs
2.        Pesticides
3.        Black widow spider bite
4.        Toxic oil syndrome
5.        Malignant hyperthermia
Other diseases
1.        Cirrhosis of the liver
2.        Various cancers
3.        Psychiatric disorders




    











































Most of these conditions are rare, but any person presenting with muscle cramping must consult with their medical practitioner so that investigations can be performed to exclude any of these conditions. Similarly, medications, other drugs, and toxins can also cause cramping (Table 6). These also need to be considered before the cause of cramping is regarded as one of the more benign forms.

Table 6: Medicines or drugs that may be associated with muscle cramping 1;3;4;11;13;14;17;19
Medications
Diuretics
Statin drugs
Clofibrate
β-agonists (salbutamol, terbutaline)
Phenothiazines
Morphine
Nifedipine
Cimetidine
Penicillamine
Lithium
Estrogen receptor modulators
Nicotinic acid
Drugs
Etnanol
Toxins
Black-widow spider bite
Strychnine
Lead
Tetanus
Pesticides
 

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