Lower Limb Pain Neurogenic and Referred Differential Diagnoses

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 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)