What are the clinical diagnostic criteria for neuropathy?

Clinical Diagnostic Criteria for Neuropathy

The diagnosis of neuropathy is primarily clinical, based on a combination of characteristic symptoms, physical examination findings, and exclusion of other causes, with specific diagnostic tests used to confirm the diagnosis when needed.

Clinical Assessment for Peripheral Neuropathy

Symptoms to Evaluate

• Pain, dysesthesias (unpleasant abnormal sensations of burning and tingling), and numbness are the most common symptoms, particularly in small fiber involvement 1
• Symptoms typically follow a distal-to-proximal pattern, often beginning in the feet 1
• Nocturnal exacerbation of symptoms is characteristic of neuropathic pain 1
• Inquire about orthostatic intolerance, syncope, exercise intolerance, gastrointestinal symptoms, urinary symptoms, sexual dysfunction, and sweating abnormalities when autonomic involvement is suspected 2

Physical Examination Components

• Assessment should follow the typical distal symmetric polyneuropathy pattern, starting distally (dorsal aspect of the hallux) on both sides and moving proximally 1
• Clinical tests should include:
  • Pinprick sensation 1
  • Vibration threshold using a 128-Hz tuning fork 1
  • Light touch perception using a 10-g monofilament 1
  • Ankle reflexes 1
• Several clinical instruments that combine more than one test have >87% sensitivity in detecting diabetic peripheral neuropathy 1

Diagnostic Criteria for Specific Types of Neuropathy

Distal Symmetric Polyneuropathy (DSPN)

• Clinical diagnosis is based on:
  • Presence of typical symptoms (pain, dysesthesias, numbness) 1
  • Abnormal findings on at least one of the following: temperature sensation, pinprick sensation, vibration perception, pressure sensation, or ankle reflexes 1
• Diagnostic algorithm:
  1. Confirm diabetic status or other risk factors 1
  2. Exclude other causes of similar clinical symptoms 1
  3. Perform sensory testing (temperature, pinprick, vibration, pressure, ankle reflexes) 1
  4. If one or more tests are positive, diagnose as DSPN 1
  5. If tests are negative but symptoms persist, classify as "possible DSPN" 1
  6. Consider neuroelectrophysiological examination if diagnosis remains unclear 1

Autonomic Neuropathy

• Cardiovascular autonomic neuropathy diagnosis requires:
  • Heart rate variability testing 2
  • Baroreflex sensitivity testing 2
  • Orthostatic hypotension assessment 2
• Diagnostic criteria:
  • Early CAN: one abnormal heart rate test result 2
  • Definite CAN: two or more abnormal heart rate test results 2
  • Severe CAN: presence of orthostatic hypotension along with abnormal heart rate tests 2
• Gastrointestinal autonomic neuropathy:
  • Gastric emptying scintigraphy (4-hour test) is the gold standard for suspected gastroparesis 2
  • 13C octanoic acid breath test is an approved alternative 2

Painful Diabetic Peripheral Neuropathy

• Diagnosis is primarily clinical, relying on:
  • Patient's description of pain: distal, symmetrical, with nocturnal exacerbation 1
  • Commonly used descriptors such as burning, tingling, electric shock-like sensations 1
  • Usually accompanied by blunting of sensation on clinical examination 1

Additional Diagnostic Testing

When to Consider Additional Testing

• Atypical presentation (asymmetric symptoms, rapid progression, motor predominance) 1, 3
• Unclear diagnosis after clinical assessment 1
• Significant autonomic involvement 3
• Suspected small-fiber neuropathy 3

Recommended Tests

• Neuroelectrophysiological studies (nerve conduction studies and electromyography) to differentiate axonal from demyelinating neuropathy 1
• Skin biopsy for intraepidermal nerve fiber density assessment in suspected small-fiber neuropathy 3
• Laboratory tests to exclude other causes:
  • Complete blood count 1
  • Comprehensive metabolic profile 1
  • Fasting blood glucose 1
  • Vitamin B12 levels 1
  • Thyroid-stimulating hormone levels 1

Differential Diagnosis Considerations

Conditions to Exclude

• Neurotoxic medications 1
• Heavy metal poisoning 1
• Alcohol abuse 1
• Vitamin B12 deficiency 1
• Renal disease 1
• Chronic inflammatory demyelinating neuropathy 1
• Inherited neuropathies 1
• Vasculitis 1
• Cervical and lumbar disease (nerve root compression, spinal stenosis, cervical and lumbar degeneration) 1
• Cerebral infarction 1

Common Pitfalls to Avoid

• Relying on a single test rather than a battery of validated tests 2
• Failing to consider age-related changes in autonomic function 2
• Not controlling for medications that can affect autonomic function 2
• Testing during periods of glycemic instability 2
• Overlooking autonomic neuropathy in patients with small fiber neuropathy 2
• Failing to exclude other causes of neuropathy, as diabetic neuropathy is a diagnosis of exclusion 3