Lower Limb Pain Neurogenic and Referred Differential Diagnoses

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There are at least 300 conditions that can cause lower limb neurogenic and referred pain. See the article below for a summary.

Differential Diagnoses

  • Systemic Conditions
    • Metabolic Neuropathy
      • Diabetes Mellitus with distal symmetrical polyneuropathy
      • Diabetes Mellitus of other subtypes - proximal diabetes, truncal, cranial, median and ulnar neuropathies
      • Diabetes Mellitus with autonomic neuropathy
      • Diabetic amyotrophy - Probably a vasculitis aetiology with ischaemia followed by axonal degeneration and demyelination. Characterised by unilateral weakness, wasting, and pain, commonly in the quadriceps, then spreading later to the contralateral side asymmetrically.
    • Vasculitic Neuropathy - vasculitis of the small and medium-sized vessels in the peripheral nervous system.
      • Primary vasculitides: Churg-Strauss syndrome, microscopic polyangiitis, classic polyarteritis nodosa and Wegener granulomatosis
      • Secondary vasculitides: A complication of connective tissue disease (systemic lupus erythematosus, rheumatoid arthritis and Sjรถgren syndrome), infection (hepatitis B and C, human immunodeficiency virus, Lyme disease, cytomegalovirus, Herpes zoster virus and various bacterial infections), medication (sulphonamides, other antibiotics and anti-viral agents) and paraneoplastic vasculitis
    • Paraneoplastic peripheral neuropathy - In addition to local effects and paraneoplastic vasculitis, can also get sensorimotor paraneoplastic neuropathy. May have anti-neuronal antibodies and EMG findings.
  • Brain
    • Multiple sclerosis
    • Parkinsonโ€™s disease
    • Motor neurone disease
    • Post-stroke pain in lenticulo-capsular haemorrhages
    • Space-occupying lesions.
  • Spinal Cord
    • Multiple sclerosis
    • Motor neurone disease
    • Syringomyelia
    • Transverse myelitis
    • Posterior or anterolateral situated space-occupying lesion (e.g. disc herniation, tumour, abscess, haematoma)
  • Cervical and Thoracic Spinal Canal
    • Any posterior or anterolateral space-occupying lesion (e.g. abscess, tumour, haematoma)
  • Conus Medullaris
    • Disc pathology - parasagittal, as nerve roots are lateral to spinal cord
    • Tumours (soft tissue, intradural, extradural, bone, metastases)
  • Lumbar Spine Canal
    • Interspinous bursa (kissing spines, Baastrup's disease)
    • Facet joint (OA, hypertrophy, cyst, rotational instability)
    • Degenerative spondylolisthesis - the vertebral body and inferior facet joints displace anteriorly, compressing the dural sac and nerve roots against the posterior aspect of the caudal vertebral body - May only be appreciated on flexion/extension radiographs
    • Space-occupying lesion (disc pathology, haematoma, tumours)
  • Lumbar Nerve Root Canal
    • Intervertebral disc herniation
    • Facet joint - superior articular process moves upwards and forwards impinging nerve root against pedicle or posterior vertebral body in presence of loss of disc height.
    • Osteophytes from superior facet joint or posterior inferior vertebral endplate impinging nerve root
    • Anterior subluxation of vertebra in degenerative spondylolisthesis with hypertrophy of superior facet joint extending into canal.
    • Any nerve root lesion (e.g. cyst, tumour)
    • Isthmic spondylolisthesis, with nerve root narrowing due to combination of disc bulging and pars interarticularis hypertrophy
    • Pedicle moving down compressing nerve root in complete loss of disc height in combination with spondylolisthesis and degenerative scoliosis.
  • Lumbar Extraforaminal Area
    • Far lateral disc herniation compression of exiting nerve root
    • Corporotransverse ligament nerve entrapment in rotatory subluxation with complete disc space narrowing - The corporotransverse ligament extends from the vertebral body to the transverse process of the same vertebra.
    • Psoas pathology (abscess, haematoma, tumour)
    • Spondylolisthesis with severe disc space narrowing causing impingement of the L5 nerve root between the L5 transverse process and the ala of the sacrum
    • Degenerative scoliosis with tilting of L5 and depression of the concave L5 transverse process causing impingement of the L5 nerve root
  • Pelvis
    • Pelvic malalignment
    • L5 transitional vertebra pseudoarthrosis with a large osteophyte compressing L5 nerve root
    • Lumbosacral ligament ossification in combination with inferior L5 vertebral body osteophytes impinging L5 nerve root
    • Stress fracture of sacrum or pubic rami
    • Degenerative sacroiliitis with an osteophyte extending anteriorly compressing a nerve root
    • Sacroiliitis of any type
    • Tumours of bone and soft tissue
    • Lumbosacral radiculoplexus neuropathy - presents with asymmetrical lower limb pain, weakness, atrophy and paraesthesia. It can be caused by diabetic lumbosacral radiculoplexus neuropathy, non-diabetic lumbosacral radiculoplexus neuropathy, chronic inflammatory demyelinating polyneuropathy, connective tissue disease, Lyme disease, sarcoidosis, HIV and cytomegalovirusrelated polyradiculopathy.
    • Piriformis muscle syndrome with compression of sciatic nerve
    • Superior gluteal nerve entrapment syndrome - The clinical diagnosis triad of buttock pain, weakness of hip, abduction and marked tenderness on deep palpation in the region just lateral to the greater schiadic notch
  • Lower Extremity
    • Greater trochanteric pain syndrome (Greater trochanteric bursitis and gluteus medius tendinopathy)
    • Stress fracture of femoral neck, intertrochanteric area, and proximal femur
    • Iliopsoas and iliopectineal bursitis and synovitis
    • Non-traumatic focal mononeuropathies
    • Myositis and myopathy
    • Sports related leg pain
      • Medial tibial stress syndrome
      • Chronic exertional compartment syndrome
      • Tendinopathies
      • Nerve entrapment syndromes
      • Vascular syndromes
      • Myopathies
    • CRPS
    • Restless legs syndrome
    • Painful legs and moving toes syndrome
    • Nerve entrapment syndromes
      • Iliohypogastric (T12, L1), Ilioinguinal (T12, L1), Genitofemoral (L1, L2) - Usually after lower abdominal surgery
      • Lateral femoral cutaneous nerve (L2-4)
      • Femoral nerve (L2-4) entrapment below the inguinal ligament
      • Pelvic procedures with acutely flexed, abducted, and externally rotated positioning
      • Saphenous nerve (L3-4) entrapment as it pierces the roof of the adductor canal, by femoral vessels, pes anserine bursitis, varicose vein operations, and medial knee surgery
      • Common peroneal neuropathy
      • Deep peroneal nerve
      • Superficial peroneal nerve
      • Proximal tibial entrapment neuropathy
      • Distal tibial entrapment
      • Sural nerve
      • Medial plantar nerve neuropathy
      • Inferior calcaneal nerve
      • Interdigital neuropathy
      • Medial plantar proper digital neuropathy (Joplin's neuroma)