What are the recommended steps for assessing and managing peripheral neuropathy?

Assessment of Peripheral Neuropathy

All patients with type 2 diabetes should be screened for peripheral neuropathy at diagnosis, and type 1 diabetes patients should be screened 5 years after diagnosis, then annually thereafter using a structured clinical examination that includes 10-g monofilament testing plus at least one additional neurological test. 1, 2

Initial Clinical Assessment

History Taking

• Document specific symptoms: numbness, tingling, burning sensations, or pain in a distal symmetric "stocking and glove" distribution 1, 3
• Assess pain severity using a simple numeric rating scale (0-10 Likert scale) 1, 3
• Note nocturnal exacerbation of symptoms, which is characteristic of diabetic neuropathy 1
• Screen for autonomic symptoms: orthostatic dizziness, syncope, constipation, diarrhea, urinary retention, erectile dysfunction, and abnormal sweating 1, 2
• Identify risk factors: diabetes duration, glycemic control, smoking, alcohol use, chemotherapy exposure, and family history 4, 5

Physical Examination Components

The examination must assess both small-fiber and large-fiber function using multiple modalities 1:

Small-fiber function:

• Pinprick sensation testing 1
• Temperature perception (hot/cold discrimination) 1

Large-fiber function:

• Vibration perception using a 128-Hz tuning fork 1
• Lower-extremity reflexes (ankle reflexes) 1, 4

Protective sensation:

• 10-g monofilament testing at multiple sites on each foot—this is the single most sensitive test for identifying ulceration risk and must not be skipped 2, 4

Loss of protective sensation (LOPS) is confirmed when 10-g monofilament sensation is absent plus one other abnormal neurological test 2

Vascular Assessment

• Palpate lower extremity pulses (dorsalis pedis, posterior tibial) 4
• Auscultate for femoral bruits 4
• Assess capillary refill time 4
• Inspect feet for ulcers, wounds, deformities, and calluses 2, 4

Laboratory Evaluation

Initial Testing Panel

Order these tests for all patients with suspected peripheral neuropathy 3, 5, 6:

• Fasting blood glucose and hemoglobin A1c 3, 4
• Complete blood count 4, 5
• Comprehensive metabolic profile 5, 6
• Vitamin B12 level 3, 5, 6
• Thyroid-stimulating hormone (TSH) and free T4 3, 4, 6
• Erythrocyte sedimentation rate 5
• Serum protein electrophoresis with immunofixation 6

Additional Testing When Clinically Indicated

• Hepatitis B, C, and HIV testing if risk factors present 3, 4
• Anti-ganglioside antibodies if Guillain-Barré syndrome suspected 3
• Anti-MAG antibodies if demyelinating neuropathy suspected 3

Electrodiagnostic Studies

Nerve conduction studies and electromyography are rarely needed for typical diabetic neuropathy but should be ordered when clinical features are atypical, the diagnosis is unclear, or asymmetric symptoms are present 1, 7, 8

These studies help differentiate:

• Axonal versus demyelinating neuropathy 5, 7, 8
• Entrapment syndromes from generalized neuropathy 1
• Severity and distribution of nerve involvement 8

Management Approach

Glycemic Optimization

• Optimize glucose control as the foundational disease-modifying intervention—this effectively delays or prevents neuropathy development in type 1 diabetes and slows progression in type 2 diabetes 1, 3
• Target individualized HbA1c goals based on patient factors 3

Cardiovascular Risk Factor Management

• Optimize blood pressure control 1
• Manage dyslipidemia aggressively 1, 3
• Address weight management 1

Pharmacologic Pain Management

First-line medications for neuropathic pain 1, 3:

• Duloxetine 60 mg once daily (can increase to 120 mg if needed) 3
• Pregabalin 3
• Gabapentin 3
• Tricyclic antidepressants (amitriptyline 25-75 mg/day), though anticholinergic side effects limit use 3

Opioids, including tramadol and tapentadol, should not be used for neuropathic pain treatment given the potential for adverse events 1

Non-Pharmacologic Interventions

• Regular physical activity 3
• Acupuncture 3
• Cognitive behavioral therapy 3
• Concurrent treatment of sleep and mood disorders 1

Critical Pitfalls to Avoid

• Up to 50% of diabetic peripheral neuropathy is asymptomatic—never rely on symptoms alone for diagnosis 1, 2
• Diabetic neuropathy is a diagnosis of exclusion—always evaluate for other treatable causes 1
• Asymmetric symptoms should prompt evaluation for alternative etiologies, not diabetic neuropathy 1
• Annual screening is mandatory even in asymptomatic patients to prevent ulceration and amputation 1, 2
• The 10-g monofilament test identifies feet at highest risk for ulceration and must be performed annually 1, 2

Referral Indications

• Endocrinology for diabetes optimization 4
• Neurology if electrodiagnostic studies needed or diagnosis unclear 1, 6
• Podiatry for patients with LOPS, foot deformities, or ulceration risk 4
• Vascular surgery if significant peripheral arterial disease identified 4