Table 2.
Common causes of distal symmetric polyneuropathy
| Disease | Comment |
|---|---|
| Metabolic | |
| Diabetes | Most common cause, accounting for 32–53% of cases |
| Pre-diabetes | Glucose tolerance test has highest sensitivity |
| Chronic kidney disease (CKD) | Neuropathy particularly severe when CKD caused by diabetes |
| Chronic liver disease | Neuropathy typically mild |
| Idiopathic | 24–27% of all cases |
| Toxin | |
| Alcohol | Second most common cause (requires in depth questioning) |
| Inherited |
Detailed family history required, ask about hammer toes, high arches |
| CMT1 | Inherited demyelinating sensory motor neuropathy |
| CMT2 | Inherited axonal sensory motor neuropathy |
| Familial amyloidosis | Transthyretin mutation most common |
| Nutritional |
Methylmalonic acid level important when B12 level 200–400 pg/mL |
| Vitamin B12 deficiency | Can cause cerebellar ataxia |
| Vitamin E deficiency | Can cause neuropathy when level too high or too low |
| Vitamin B6 deficiency | Can present with ataxia, ophthalmoparesis, and confusion |
| Thiamine deficiency | Often presents with a myeloneuropathy |
| Copper deficiency | Often difficult to determine which factor responsible |
| Gastric bypass surgery | Often difficult to determine which factor responsible |
| Malabsorption syndromes | |
| Medication | |
| Chemotherapy (vincristine, cisplatin, taxol, bortezomib) |
Known dose limiting side effect of many agents |
| Amiodarone | Can cause a demyelinating neuropathy |
| Phenytoin | Typically after many years of use |
| Nucleosides | Can be hard to distinguish cause of neuropathy (HIV vs. medication) |
| Nitrofurantoin | Worse in the setting of renal failure |
| Metronidazole | Usually after high, prolonged IV doses |
| Hydralazine | Avoid by concomitant use of B6 |
| Isoniazid | Avoid by concomitant use of B6 |
| Colchicine | Can also cause myopathy |
| Autoimmune | |
| Rheumatoid arthritis | Can also cause mononeuritis multiplex |
| Lupus | Can also cause mononeuritis multiplex |
| Sjogren’s syndrome | Can also cause a sensory neuronopathy or mononeuritis multiplex |
| Sarcoidosis | Can present with several neurologic manifestations |
| Secondary amyloidosis | Diagnosis aided by fat pad biopsy or sural nerve biopsy |
| Infectious | |
| HIV | Medications used to treat can also cause neuropathy |
| Hepatitis B/C | Can also cause mononeuritis multiplex associated with polyarteritis nodosa and cryoglobulinemia |
| Neoplastic | |
| MGUS | Immunofixation increases sensitivity of paraprotein detection |
| Multiple myeloma | Associated with IgG or IgA paraproteinemia |
| Primary amyloidosis | Diagnosis aided by fat pad biopsy or sural nerve biopsy |
Bold statements indicate most important take home points
CMT=Charcot Marie Tooth disease, HIV=human immunodeficiency virus, MGUS=monoclonal gammopathy of unclear clinical significance