What are the primary causes of lower limb weakness in a young adult male?

Primary Causes of Lower Limb Weakness in Young Adult Males

Vascular Causes

In young adults presenting with lower limb weakness, popliteal artery entrapment syndrome (PAES) is the most common surgically correctable vascular cause and should be prioritized in the differential diagnosis. 1

• PAES presents with calf claudication, paresthesia, and swelling during exercise, occurring primarily in endurance athletes and young active males 1
• External iliac artery endofibrosis (EIAE) causes performance-limiting claudication in elite endurance athletes, particularly cyclists, with lower-extremity weakness and thigh pain that resolves after stopping exercise 1
• Buerger disease affects small- and medium-sized distal arteries in heavy tobacco smokers aged 25-45 years, presenting with progressive claudication, paresthesias, rest pain, and ulceration 1
• Acute limb ischemia requires immediate exclusion if weakness developed suddenly with the "6 Ps": pain, pallor, pulselessness, poikilothermia, paresthesias, and paralysis 2

Neurological Causes

Spinal Cord Pathology

• Tethered cord syndrome causes progressive sensorimotor disturbances of lower limbs, pain, muscle weakness, gait disturbances, and bladder/bowel dysfunction, often triggered by sudden back stretching events 1
• Degenerative cervical myelopathy can present as subjective lower limb weakness without conventional upper motor neuron signs, potentially leading to misdiagnosis if cervical pathology is not considered 3
• Spinal cord compression from tumors (e.g., meningioma) presents with progressive lower limb weakness and upper motor neuron signs 4

Peripheral Nerve/Neuromuscular

• Guillain-Barré syndrome causes acute ascending weakness and should be considered in acute presentations 2, 5
• Myasthenia gravis presents with fatigable weakness, though typically affects ocular and bulbar muscles before limbs 5

Myopathic Causes

Idiopathic inflammatory myopathies present with objective symmetric proximal lower extremity weakness that is progressive over time, with elevated creatine kinase being a key diagnostic feature. 2, 6

• Inflammatory myopathy characteristics include neck flexors weaker than extensors, proximal muscles weaker than distal, and elevated CK, LDH, AST, or ALT 2
• Anti-Jo-1 antibody positivity adds significant diagnostic certainty for inflammatory myopathy 2
• Overlap syndromes (SLE-myositis) are rare but present with proximal muscle weakness and positive autoantibodies 7
• Late-onset Pompe disease (GSD II) causes primarily truncal and proximal weakness affecting lower more than upper limbs, with diaphragm involvement but without hepatomegaly or hypoglycemia 1
• Glycogen storage disease type III causes both proximal and distal weakness accompanied by hypoglycemia and hepatomegaly in children, with elevated CK 1

Metabolic/Endocrine Causes

• Thyroid disease (both hyper- and hypothyroidism) commonly causes proximal myopathy 6
• Osteomalacia from vitamin D deficiency presents with proximal weakness 6
• Drug-induced myopathy from statins, corticosteroids, or alcohol should be excluded 6

Critical Diagnostic Pitfalls

• Do not assume lumbar pathology when patients present with subjective lower limb weakness; cervical myelopathy must be excluded 3
• Distinguish true weakness from fatigue by performing careful functional muscle testing—weakness is defined as loss of power resulting in reduction of motor function 5
• Asymmetric presentation mandates vascular examination including pulse palpation, skin temperature, color assessment, and ankle-brachial index 2
• Bilateral symmetric proximal weakness points toward myopathy or metabolic causes rather than vascular or focal neurological lesions 2, 6