Dr. Kirkby is a family medicine physician in private practice in Pietermaritzburg, KwaZulu-Natal, South Africa, and an editor for DynaMed. Dr. Alper is medical director of clinical reference products for EBSCO Publishing, in Ipswich, Mass., and editor-in-chief of DynaMed (www.dynamicmedical.com), a database of comprehensive updated summaries covering nearly 2,000 clinical topics.

• Involuntary nighttime painful leg muscle contraction that does not relax
• Also called muscle cramps, nocturnal muscle cramps, age-related cramps

ICD-9 codes
• 728.85 spasm of muscle
• 729.82 cramp of limb

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• >95% of people sometime in their lives
• Especially common in women and elderly

Most commonly affected muscle groups
• Calf and foot

• Most commonly no cause found
• Possible causes (or associated conditions) include
— Fluid and electrolyte imbalance: hypocalcemia, hyponatremia, hypomagnesemia, hypokalemia, hyperkalemia, chronic diarrhea, hemodialysis
— Endocrine disease: thyroid disease, diabetes mellitus, Addison’s disease
— Neuromuscular disease: nerve-root compression, motor-neuron disease, mononeuropathies, polyneuropathies, dystonias
— Drugs: calcium channel blockers (nifedipine), diuretics, phenothiazines, fibrates, selective estrogen receptor modulators (raloxifene), ethanol, morphine withdrawal
— Toxins: lead, strychnine, spider bites
— Congenital disease: McArdle’s disease, glycogen storage disease, autosomal dominant cramping disease
— Peripheral vascular disease
— Iron deficiency anemia
— Cirrhosis of the liver, chronic alcoholism, sarcoidosis
— HIV myelopathy
• Pathophysiology speculative, may include reduced blood flow and oxygen supply
Likely precipitating factors
• Activity excessive for condition of muscle
• Sleeping prone or supine with toes fully extended
• Pregnancy (insufficient calcium intake)
• Older age

• Insomnia
• Irritability
• Anxiety
• Depression

Clinical evaluation
• History of onset and clues to underlying condition
• Drug history crucial
• Local exam: arterial pulses, skin, nerves
— Pulses and capillary fill (rule out vascular compromise)
— Assess skin changes
— Sensation/vibration

Differential diagnoses
• Intermittent claudication
• Peripheral neuritis
• Restless legs syndrome
• HIV myelopathy
• Physiologic cramps due to heat, exercise, excessive activity
• Electrolyte abnormalities
• Polycythemia
• Endocrine disease: diabetes, thyroid disease, parathyroid disease, adrenal disease
• Muscle diseases: glycogen storage or mitochondrial

Testing (for recurrences or underlying disease)
• Electrolytes
• Glucose
• Blood urea nitrogen, creatinine• Calcium, magnesium, phosphate
• Hemoglobin, ferritin
• Zinc
• Liver function tests
• Thyroid function tests
• HIV if appropriate
• Doppler studies of arteries
• Electromyelography

Nonpharmacologic management
• Reassurance to exclude causes that might result in patient concern, e.g., vascular disease
• Major thrust is to avoid sleep disturbance
• Trial of omitting possible causative medication
• Other treatments to consider
— Local heat, massage
— Osteopathic manipulative therapy (OMT): myofascial release, facilitated positional release

Medications to consider
• Quinine sulfate 200-400 mg nightly
— Beware long-term use.
— Rare but serious side effects described (disseminated intravascular coagulopathy, thrombocytopenia, pancytopenia, hemolytic uremic syndrome)
— Consider monitoring complete blood count or platelets.
• Other drugs similar to quinine— Hydroquinine 300 mg
— Quinidine sulfate 400 mg
• Other drugs not similar to quinine
— Verapamil 120 mg nightly
— Gabapentin (Neurontin) may reduce frequency and severity of muscle cramps.
— Magnesium not clearly effective
• Benzodiazepines
(clonazepam, diazepam) or baclofen
— Not traditionally associated with nocturnal cramp therapy but helpful in other spastic muscle conditions, e.g., tetanus, status epilepticus, and back muscle spasm
— Address treatment goals of avoiding sleep disturbance.
• Gastrocnemius trigger point injection of 1% lidocaine
• Randomized n-of-1 trials alternating drug and placebo may determine efficacy of specific drugs for individual patients.

• Stretching exercises—e.g., nightly or twice daily
• 20-minute walk may enhance stretching exercises.

See www.dynamicmedical.com for references.