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.

JA Louw. The differential diagnosis of neurogenic and referred leg pain

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 Sjögren 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
    • Parkinson’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</br>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)