What are the differential diagnoses for a patient presenting with a new involuntary movement in the leg causing instability?

Differential Diagnoses for New Involuntary Leg Movement Causing Instability

The most critical first step is to determine the temporal pattern and triggers of the involuntary movement: sudden onset with voluntary action suggests paroxysmal kinesigenic dyskinesia, rest-predominant urge to move with circadian worsening indicates restless legs syndrome, and acute onset with neurological deficits requires immediate stroke evaluation. 1, 2

Immediate Life/Limb-Threatening Causes (Rule Out First)

Acute Stroke or TIA

• Sudden onset involuntary movements with associated neurological deficits (facial droop, dysarthria, sensory loss, weakness, visual field defects) require immediate CT or MRI. 2
• Acute cerebral infarction involving the contralateral hemisphere, basal ganglia, thalamus, or corpus callosum can present with involuntary movements. 2

Acute Limb Ischemia (ALI)

• Presents with sudden onset (<2 weeks) of the "6 Ps": pain, pallor, pulselessness, poikilothermia (coolness), paresthesias, and paralysis. 3
• Examine bilateral lower extremity pulses, capillary refill time, check for rubor on dependency, pallor on elevation, and venous filling time. 3
• Obtain ankle-brachial index (ABI) if vascular disease suspected; ABI <0.90 confirms peripheral artery disease. 3

Focal Motor Seizures

• Characterized by rhythmic, synchronous, numerous (20-100) involuntary movements that may progress to other body parts. 2
• May be followed by post-ictal confusion or Todd's paralysis. 2
• Requires EEG and neurology consultation if suspected. 2

Movement Disorder Causes

Paroxysmal Kinesigenic Dyskinesia (PKD)

• PKD should be strongly considered if involuntary movements are triggered by sudden voluntary actions (sudden standing, starting to run, getting on/off a car) and last <1 minute in over 98% of cases. 4, 2
• Manifests as unilateral or bilateral dystonia, chorea, ballism, or a mixture; dystonia is most common. 4
• Approximately 78-82% of patients experience aura (numbness, tingling, muscle weakness) prior to the attack. 4
• Episodes worsen with emotional stress, sound/image stimulation, or hyperventilation. 4
• Age of onset typically ranges from several months to 20 years, with peak incidence in 7-15 year-olds; males affected 2:1 to 4:1. 4
• Obtain full spinal column MRI if secondary PKD suspected (prolonged duration >1 minute, atypical features). 4

Restless Legs Syndrome (RLS)

• Characterized by four essential criteria: (1) urge to move legs with uncomfortable sensations, (2) symptoms begin/worsen during rest/inactivity, (3) partial/total relief with movement, (4) symptoms worse evening/night than daytime. 4, 1
• Sensations described as creepy-crawly, burning, itching, or painful feeling in lower extremities. 4
• Check serum ferritin—values <50 ng/mL are consistent with RLS and indicate need for iron supplementation. 4, 1
• Perform thorough neurological examination to exclude peripheral neuropathy or radiculopathy, which lack the characteristic urge to move, circadian pattern, and relief with movement. 4, 1

Chorea (Including Sydenham Chorea)

• Purposeless, involuntary, non-stereotypical movements of trunk or extremities. 4, 2
• Often associated with muscle weakness and emotional lability. 4
• Can be predominantly unilateral and requires careful neurological examination. 4
• Exclude Huntington chorea, systemic lupus erythematosus, Wilson disease, and drug reactions. 4

Drug-Induced Movement Disorders

• Toxic/metabolic-caused movement disorders are the most frequent diagnostic category (35%) in hospitalized patients with involuntary movements, particularly related to medications. 5
• Tricyclic antidepressants, SSRIs, lithium, and dopamine antagonists (antipsychotics) can exacerbate or cause involuntary movements. 4
• Levodopa can cause involuntary movements and neuroleptic malignant syndrome (NMS) with dose reduction or withdrawal, characterized by fever, muscle rigidity, involuntary movements, and altered consciousness. 6

Vascular Causes

Peripheral Artery Disease (PAD)

• Presents with leg fatigue, claudication (pain, aching, cramping, tired/fatigued feeling in buttocks, thigh, calf, or foot during walking), and rest pain relieved with dependency. 4, 1
• Leg symptoms include tingling, numbness, burning, throbbing, or shooting sensations that worsen with exertion. 4, 3
• Obtain ABI as initial test; ABI <0.90 confirms PAD diagnosis. 1, 3
• Critical limb-threatening ischemia (CLTI) manifests as ischemic rest pain affecting forefoot, worsened by limb elevation, relieved by dependency, with symptoms >2 weeks. 3

Neurological Causes

Peripheral Neuropathy

• Perform 10-g monofilament testing plus one additional test (pinprick, temperature, ankle reflexes, or 128-Hz tuning fork vibration) to diagnose peripheral neuropathy. 1, 3
• Lacks the characteristic urge to move, circadian pattern, and relief with movement seen in RLS. 1
• Thorough neurological examination essential to identify sensory deficits, diminished reflexes, or radiculopathy. 3

Spinal Cord Lesions

• Spinal cord lesions can generate periodic leg movements identical to sleep-related periodic leg movements. 7
• Complete spinal cord transection can produce rhythmic involuntary leg movements that alternate from one side to the other. 7
• New severe back/neck pain, radiating pain, decreased leg strength, difficulty controlling legs, wobbly gait, numbness/tingling radiating from chest/stomach/groin/legs, or inability to walk are alarm symptoms requiring urgent MRI within 12 hours. 4

Diagnostic Algorithm

Step 1: Characterize Temporal Pattern and Triggers

• Sudden onset with voluntary action + duration <1 minute → Consider PKD. 4, 2
• Rest-predominant + urge to move + circadian worsening (evening/night) + relief with movement → Consider RLS. 4, 1
• Sudden onset with neurological deficits → Immediate stroke evaluation. 2
• Exertional symptoms + absent pulses + skin changes → Consider PAD. 1, 3

Step 2: Targeted Physical Examination

• Assess bilateral lower extremity pulses, capillary refill, rubor on dependency, pallor on elevation. 3
• Perform thorough neurological examination including 10-g monofilament plus one additional sensory test. 1, 3
• Observe for signs of leg discomfort (rubbing, kneading, groaning) and excessive motor activity in cognitively impaired patients. 4

Step 3: Laboratory and Diagnostic Testing

• Serum ferritin if RLS suspected (target >50 ng/mL). 4, 1
• ABI testing if vascular disease suspected (ABI <0.90 confirms PAD). 1, 3
• 10-g monofilament plus one additional sensory test if neuropathy suspected. 1, 3
• Immediate CT/MRI if stroke suspected. 2
• EEG and neurology consultation if seizure suspected. 2
• Urgent MRI within 12 hours if alarm symptoms for spinal cord compression present. 4

Critical Pitfalls to Avoid

• Do not assume all leg shaking is RLS—the differential is broad and requires systematic evaluation of timing, triggers, and relief patterns. 1
• Do not skip ferritin testing in suspected RLS—iron deficiency is a treatable secondary cause. 1
• Do not assume all intermittent leg symptoms are benign—PAD carries 25-35% one-year mortality with CLTI, and ABI testing should not be skipped in patients with atherosclerosis risk factors. 3
• Do not diagnose RLS without confirming all five essential criteria—16% of subjects without RLS will be misclassified if you only ask about symptoms. 3
• Do not diagnose RLS in cognitively impaired patients without observing signs of leg discomfort (rubbing, kneading, groaning) and excessive motor activity that worsens with inactivity and improves with activity. 4, 1
• Do not exclude secondary PKD if duration >1 minute—secondary factors must be ruled out. 4
• Do not miss spinal cord compression—new severe back pain with neurological symptoms requires urgent MRI within 12 hours. 4