What is the diagnosis and treatment for a patient who awakens from sleep with severe calf pain, suggestive of nocturnal leg cramps, that improves with walking?

Nocturnal Leg Cramps: Diagnosis and Management

This patient has nocturnal leg cramps, and the first priority is to rule out restless legs syndrome (RLS) and identify any reversible secondary causes through targeted history, medication review, and selective laboratory testing. 1, 2

Confirming the Diagnosis

Your clinical suspicion is correct—the severe calf pain awakening her from sleep that improves with walking is classic for nocturnal leg cramps. However, you must differentiate this from RLS using specific questions 3, 1, 2:

• Ask: "What does it feel like?" - True cramps are painful muscle contractions; RLS causes uncomfortable sensations or urge to move 3, 2
• Ask: "Is it worse later in the day/evening?" - RLS symptoms worsen in evening; cramps occur randomly at night 3, 1
• Ask: "Does it come back again a few minutes after you sit or lie back down?" - This suggests RLS, not cramps 3, 1
• Ask: "Does your bed partner complain that you have twitchy legs or kicking movements in your sleep?" - This indicates periodic limb movements, not cramps 3, 1

The key distinction: RLS involves dysesthesias and urge to move; nocturnal leg cramps are sudden, painful muscle contractions 2, 4

Essential Initial Workup

Perform these baseline investigations to identify treatable secondary causes 1, 2:

• Blood tests: Electrolytes (especially magnesium and potassium), renal function, calcium, HbA1c, thyroid function 1, 2
• Physical examination: Check for peripheral edema, lower limb weakness, gait abnormalities, tremor, and signs of peripheral neuropathy 1, 2
• Blood pressure measurement 1

If hypomagnesemia is found, treat with magnesium oxide 12-24 mmol daily given at night 1

Critical Medication Review

Review all medications, as several drug classes cause or worsen nocturnal leg cramps 1, 2:

• Diuretics (most common culprit) 1, 2, 5
• Calcium channel blockers 1, 2
• Lipid-lowering agents 1
• Beta-agonists 1
• NSAIDs 1, 2
• Lithium 1, 2
• Intravenous iron sucrose, conjugated estrogens, raloxifene, naproxen, teriparatide 5

Consider discontinuing or modifying these medications if clinically feasible 2

Screen for Associated Conditions

Nocturnal leg cramps are associated with specific medical conditions that require evaluation 1, 2, 5:

• Vascular disease: Ask about ankle swelling, shortness of breath on walking, claudication symptoms 1, 2
• Peripheral neuropathy: Check for numbness, weakness, sensory changes (especially if diabetic) 1, 2
• Neurological conditions: Screen for early parkinsonism (tremor, slowness of movement, problems controlling legs) 1
• Cardiovascular disease: Assess for heart failure, hypertension 1
• Renal disease: Check creatinine and urinalysis 1

If peripheral neuropathy is suspected, direct neurology referral is warranted 1

Treatment Approach

First-Line: Non-Pharmacologic Measures

Start with conservative management 2, 5:

• Stretching exercises before bed (though evidence is limited) 5, 6
• Adequate hydration before bedtime 2
• Massage and ice application during acute episodes 1

Important caveat: A randomized controlled trial found calf-stretching exercises were NOT effective in reducing frequency or severity of night cramps 6, so set realistic expectations.

Pharmacologic Options

If conservative measures fail and symptoms are severe 1, 5, 7:

• Baclofen: Start at 10 mg/day with weekly increases up to 30 mg/day for severe cramps 1
• Calcium channel blockers: Supported by guidelines for treatment 2
• Magnesium supplementation: If deficiency documented or suspected 1, 5

Quinine is no longer recommended due to rare but serious immune-mediated reactions and modest benefit that doesn't justify the risks, especially in older patients 5, 7. If patients are already on quinine, advising them to stop will result in no major problems, and 26.5% will successfully discontinue without worsening symptoms 6, 7.

Clinical Pitfalls to Avoid

• Don't miss RLS: The treatment is completely different (dopamine agonists, iron supplementation if ferritin <75 ng/mL) 1, 2
• Don't overlook medication causes: This is the most reversible etiology 1, 2
• Don't order extensive testing routinely: History and physical examination are usually sufficient 5
• Don't prescribe quinine: The risks outweigh benefits 5, 7
• Don't assume electrolyte abnormalities: Most patients have normal electrolytes; cramps are likely due to muscle fatigue and nerve dysfunction 5