Non-Diabetic Causes of Polyneuropathy
Diabetic neuropathy is a diagnosis of exclusion, and numerous non-diabetic causes of polyneuropathy must be considered when evaluating patients with peripheral nerve symptoms. 1
Common Non-Diabetic Causes of Polyneuropathy
Toxic/Metabolic Causes
- Alcohol abuse (prevalence 22-66% among chronic alcoholics) 2
- Vitamin deficiencies:
- Medications and chemotherapy:
- Uremia/renal disease 1, 3, 4
- Hypothyroidism 1, 3
Inflammatory/Immune-Mediated Causes
- Guillain-Barré syndrome (most common cause of acute generalized weakness) 5
- Chronic inflammatory demyelinating polyneuropathy (CIDP) 5, 6
- Vasculitis 1
- Connective tissue diseases 6
- HIV-associated neuropathy 6
- Neuroborreliosis (Lyme disease) 4
- Neuralgic amyotrophy 4
Malignancy-Related Causes
- Multiple myeloma 1
- Bronchogenic carcinoma 1
- Monoclonal gammopathy of undetermined significance (MGUS) 6
Hereditary/Genetic Causes
Clinical Patterns to Aid in Differential Diagnosis
Pattern of Involvement
- Symmetrical sensory pattern: Typical of toxic neuropathies, uremic and early metabolic neuropathies 4
- Symmetrical motor pattern: Seen in Guillain-Barré syndrome or as progression of sensory neuropathies 4
- Asymmetric pattern: Suggests vascular neuropathies, inflammatory causes like neuroborreliosis 4
- Length-dependent (stocking-glove) pattern: Suggests metabolic causes 3
- Multifocal pattern: Suggests inflammatory or compression causes 3
Diagnostic Approach
Key Diagnostic Tests
- Complete blood count
- Comprehensive metabolic profile
- Vitamin B12 levels
- Thyroid-stimulating hormone levels 3
- Electromyography and nerve conduction studies 2, 4
- CSF analysis (particularly for inflammatory causes) 4
Management Considerations
For non-diabetic polyneuropathies, treatment depends on identifying the underlying cause:
- Toxic neuropathies: Remove offending agent (alcohol, medications)
- Nutritional neuropathies: Replace deficient vitamins
- Inflammatory neuropathies: Immunomodulatory therapies
- Hereditary neuropathies: Supportive care, genetic counseling
For neuropathic pain, regardless of cause:
- First-line medications: pregabalin (300-600 mg/day), duloxetine (60-120 mg/day), gabapentin (900-3600 mg/day) 3
- Second-line: tricyclic antidepressants (amitriptyline, imipramine) 3
- Third-line: venlafaxine, valproate, carbamazepine, tramadol 3
Important Clinical Pitfalls
Failure to recognize non-diabetic causes in diabetic patients: Diabetic patients can develop neuropathies from other causes that may be treatable 1
Overlooking treatable causes: Up to 50% of polyneuropathies have potentially treatable causes 2
Delayed diagnosis: Patients with severe neuropathy of unidentified cause should be referred to specialized centers for thorough evaluation 2
Missing multisystem involvement: Some polyneuropathies are part of systemic disorders requiring comprehensive management 6