What causes bilateral lower limb cramps occurring mainly at night?

Causes of Bilateral Lower Limb Cramps Mainly at Night

Bilateral nocturnal leg cramps are most commonly idiopathic in older adults, but you must systematically rule out restless legs syndrome (RLS), peripheral neuropathy, vascular disease, medication effects, and metabolic abnormalities before settling on this diagnosis.

Primary Differential Diagnosis

The critical first step is distinguishing true muscle cramps from RLS, as they require completely different management approaches:

Nocturnal Leg Cramps

• Painful, involuntary muscle contractions typically in the calf muscles with no urge to move the legs 1
• Relief comes specifically from stretching the affected muscle, not general movement 1, 2
• The pain is a tightening sensation rather than dysesthesias 1

Restless Legs Syndrome (Mimicker)

• Uncomfortable urge to move the legs with dysesthesias (crawling, tingling sensations) 3, 1
• Symptoms worsen with rest/inactivity and are relieved by any movement (walking, stretching) but return when movement stops 3, 1
• Symptoms worsen in the evening or at night 3
• Up to 90% have associated periodic limb movements during sleep 1

Underlying Etiologies to Investigate

Neurological Causes

• Peripheral neuropathy is strongly associated with nocturnal cramps 3, 4
• Foot dorsiflexion weakness (OR 1.02 per unit decrease in strength) and other lower limb weakness markers 4
• Radiculopathy can present with cramping 3
• Muscle twitching (fasciculations) is independently associated with night cramps (OR 4.6) 4
• Lower limb tingling is independently associated (OR 4.1) 4

Metabolic and Systemic Causes

• Iron deficiency (ferritin <50 ng/mL) is associated with RLS and secondary cramping 3
• Endocrinologic disorders including thyroid dysfunction, diabetes 5
• Electrolyte imbalances (though evidence for this as a primary cause is weak) 6

Vascular Causes

• Intermittent claudication from peripheral arterial disease 3
• Venous varicosities 3

Medication-Induced

• Diuretics are a common culprit 5
• Statins can cause muscle-related symptoms 5
• For RLS specifically: tricyclic antidepressants, SSRIs, lithium, and dopamine antagonists can exacerbate symptoms 7

Idiopathic

• A significant portion of cases have no identifiable cause despite thorough evaluation 5

Essential Clinical Evaluation

History Questions

Ask these specific questions to differentiate cramps from RLS 1:

• "What does it feel like?" (painful tightening vs. urge to move with dysesthesias)
• "Is it relieved by movement?" (stretching the specific muscle vs. any movement)
• "When does it occur?" (during sleep vs. at rest while awake in evening)

Physical Examination

• Thorough neurological exam looking for signs of peripheral neuropathy or radiculopathy 3
• Vascular assessment including pulses and signs of arterial insufficiency 3
• Lower limb strength testing, particularly foot dorsiflexion 4
• Examine for muscle fasciculations 4

Laboratory Testing

• Serum ferritin (values <50 ng/mL suggest iron deficiency and need for supplementation) 3
• Consider metabolic panel, thyroid function, glucose, and renal function based on clinical suspicion 5
• No specific laboratory test confirms muscle cramps 3

Common Pitfalls to Avoid

• Do not assume electrolyte depletion is the cause without evidence—this theory is poorly supported, as systemic abnormalities don't explain localized cramping 6
• Do not order polysomnography for simple nocturnal leg cramps; reserve this for suspected periodic limb movement disorder or RLS when diagnosis is unclear 1, 2
• Do not miss medication review—many commonly prescribed drugs cause or worsen cramping 5
• Do not confuse cramps with RLS—this leads to inappropriate dopaminergic therapy when stretching would suffice 1

Mechanistic Understanding

The strongest evidence supports altered neuromuscular control as the primary mechanism 6:

• Muscle fatigue disrupts the balance between excitatory drive from muscle spindles and inhibitory drive from Golgi tendon organs 6
• This results in localized muscle cramp in overworked muscle groups 6
• Neurological dysfunction markers (weakness, twitching, tingling) are the strongest independent predictors 4
• Mechanical disruption, ephaptic transmission, and persistent inward currents in motor neurons have been implicated in neurogenic cramps 8