What are the clinical presentations of polyneuropathy, including distal symmetric polyneuropathy, asymmetric/multifocal neuropathies, and autonomic neuropathy?

Clinical Presentations of Polyneuropathy

Polyneuropathy presents in three main clinical patterns: distal symmetric polyneuropathy, asymmetric/multifocal neuropathies, and autonomic neuropathy, each with distinct clinical features that guide diagnosis and management. 1

Distal Symmetric Polyneuropathy (DSP)

• Characterized by diffuse, symmetrical involvement of peripheral nerves in a length-dependent pattern, typically beginning distally and progressing proximally 1

• Symptoms usually begin symmetrically in the toes and feet, later progressing to fingertips as the condition advances 1, 2

• Common presentations include:

  • Sensory symptoms: numbness, paresthesia, burning pain, tingling, and dysesthesia 1, 2
  • Motor symptoms: distal muscle weakness and atrophy, particularly in advanced cases 1
  • Reduced or absent deep tendon reflexes, particularly at the ankles 1
  • Gait disturbances with wide-based, unsteady gait due to proprioceptive loss 1

• Physical examination typically reveals:

  • Distal sensory loss to multiple modalities (temperature, pinprick, vibration, position) 1, 2
  • Reduced or absent ankle reflexes 1
  • Distal muscle weakness and atrophy in more advanced cases 1

Asymmetric/Multifocal Neuropathies

• Present with asymmetric sensory and/or motor deficits affecting multiple individual nerves or nerve roots 3, 4

• Clinical features include:

  • Asymmetric onset, often with sequential or stepwise progression 4
  • Focal or multifocal deficits that may affect cranial nerves, causing facial weakness or visual disturbances 1
  • Pain is often a prominent feature, particularly in inflammatory or vasculitic causes 3, 4
  • Motor involvement may be more pronounced than in typical DSP 4

• Common presentations include:

  • Mononeuritis multiplex: involvement of multiple individual nerves in an asymmetric pattern 3, 4
  • Radiculopathies: involvement of nerve roots causing dermatomal sensory loss and myotomal weakness 3
  • Plexopathies: affecting brachial or lumbosacral plexus with regional sensory and motor deficits 3, 4

• Physical examination reveals:

  • Asymmetric sensory and motor deficits in the distribution of specific nerves or roots 4
  • Variable reflex changes depending on nerves affected 4
  • Possible cranial nerve involvement 1

Autonomic Neuropathy

• Occurs in several distinct phenotypes: as a component of generalized polyneuropathy, as a distinct autonomic neuropathy, or as part of small fiber sensory polyneuropathy 3, 5

• May occur in isolation with autonomic fiber involvement preceding somatic fiber involvement 3, 5

• Clinical presentations include:

  • Cardiovascular manifestations:

    • Orthostatic hypotension 3, 1
    • Fixed heart rate with loss of heart rate variability 3, 5
    • Exercise intolerance 3

  • Gastrointestinal manifestations:

    • Alternating diarrhea and constipation 1
    • Early satiety, nausea, vomiting 3
    • Gastroparesis 3

  • Genitourinary manifestations:

    • Urinary retention or incontinence 1
    • Sexual dysfunction (erectile dysfunction in males) 3, 1

  • Sudomotor dysfunction:

    • Abnormal sweating patterns (hyperhidrosis or anhidrosis) 3
    • Circulatory instability in the feet 3

• In distal symmetric polyneuropathy with autonomic involvement, the most common findings are abnormalities of sweating and circulatory instability in the feet 3

Small Fiber Polyneuropathy

• Often presents with prominent pain and autonomic symptoms with minimal or absent motor findings 3, 2
• Clinical features include:
  • Burning pain affecting the feet, often with allodynia 3
  • Erythromelalgia (red, hot, painful skin) 3
  • Concurrent involvement of autonomic and somatic C fibers 3
  • Normal strength and reflexes 2
  • Conventional nerve conduction studies may be normal 2

Diagnostic Considerations

• Nerve conduction studies show diffuse abnormalities in DSP but may be normal in small fiber neuropathy 1, 2
• Autonomic testing should be considered to document autonomic nervous system dysfunction, particularly for suspected autonomic neuropathy or small fiber sensory polyneuropathy 3, 5
• Heart rate variability testing is a simple and reliable test of cardiovagal function 3, 5
• Skin biopsy with intraepidermal nerve fiber density measurement is valuable for diagnosing small fiber neuropathy 3, 2
• Nerve biopsy may be useful in specific cases such as suspected amyloid neuropathy, vasculitic neuropathy, or atypical forms of chronic inflammatory demyelinating polyneuropathy 3, 6

Clinical Pearls and Pitfalls

• The distinction between polyneuropathy patterns is crucial as they often have different underlying causes requiring different treatment approaches 1
• Multifocal neuropathies may be mistaken for multiple mononeuropathies or radiculopathies; careful clinical and electrodiagnostic assessment is essential 4
• Autonomic symptoms may be overlooked or attributed to other conditions; systematic assessment of autonomic function is important 3, 5
• Small fiber neuropathy may be missed if only conventional nerve conduction studies are performed 2
• A battery of validated autonomic tests rather than a single test is recommended to achieve the highest diagnostic accuracy 3, 5