Etiology, Diagnosis, and Screening of Peripheral Neuropathy

Metabolic Causes

Renal disease can produce peripheral neuropathy through accumulation of metabolic toxins, highlighting the need to assess renal function in patients with unexplained neuropathy. 1
Renal disease is also recognized as a metabolic contributor to neuropathy in diabetes‑focused research, reinforcing its role across diverse patient groups. 2

Platinum‑based agents (cisplatin, oxaliplatin), taxanes (paclitaxel), vinca alkaloids (vincristine), proteasome inhibitors (bortezomib), and immunomodulatory drugs (thalidomide) are major iatrogenic causes of peripheral neuropathy. 3
The risk of chemotherapy‑induced neuropathy varies with the specific agent, cumulative dose, treatment duration, and pre‑existing metabolic conditions such as diabetes. 4

Chronic alcohol consumption is a frequent toxic etiology of peripheral neuropathy and should be excluded during evaluation. 6

A comprehensive review of neurotoxic medications is essential, as many drugs can contribute to neuropathic symptoms. 2

Human immunodeficiency virus (HIV) infection can cause peripheral neuropathy independent of antiretroviral therapy, necessitating HIV testing when other causes are not evident. 7

Plasma‑cell dyscrasias such as multiple myeloma, especially when associated with POEMS syndrome, are linked to peripheral neuropathy. 3
Solid tumors, including bronchogenic carcinoma, may present with neuropathic manifestations, underscoring the importance of malignancy screening in unexplained cases. 7
Light‑chain amyloidosis can lead to widespread peripheral neuropathy through deposition of amyloid fibrils. 1

Chronic inflammatory demyelinating polyneuropathy (CIDP) is recognized as a distinct immune‑mediated peripheral neuropathy that should be considered in chronic, progressive cases. 6

The American Diabetes Association recommends initial laboratory evaluation that includes fasting blood glucose to screen for diabetes as a potential cause of neuropathy. 6

Diabetic neuropathy is a diagnosis of exclusion; clinicians must systematically rule out alternative etiologies even when diabetes is present. 8

Cervical or lumbar spine disease (e.g., nerve root compression, spinal stenosis) can produce symptoms indistinguishable from peripheral neuropathy. 1
Cerebral infarction may present with peripheral‑type sensory deficits, requiring neuroimaging for differentiation. 1
Severe arteriovenous disease (e.g., venous embolism, abnormal lymphangiogenesis) can mimic neuropathic pain. 1
Peripheral nerve entrapments and fascial inflammation are common mimickers and should be evaluated with targeted physical examination. 10
Vascular claudication due to peripheral arterial disease can be confused with neuropathic pain, highlighting the need for vascular assessment. 6

For individuals diagnosed with type 2 diabetes, peripheral neuropathy screening should commence at the time of diabetes diagnosis. 11
For individuals with type 1 diabetes, screening should begin five years after diagnosis. 11
After initial screening, annual reassessment is recommended for all diabetic patients to detect early neuropathic changes. 11

Patients receiving neurotoxic chemotherapy agents (e.g., oxaliplatin, paclitaxel, cisplatin, vincristine, bortezomib, thalidomide) should be proactively monitored for the development of peripheral neuropathy throughout treatment. 5