Peripheral Neuropathy

• Responsible for one-third of all neuropathies (most common cause).
• Can present as a small fiber polyneuropathy, large fiber peripheral polyneuropathy, multifocal neuropathy, mononeuropathy, and/or lumbosacral plexopathy.
  • Commonly manifests as a distal symmetric polyneuropathy, typically in a “stocking-glove” distribution.
• EMG testing will show axonal pathology.
• Pathology: Thickened blood vessels with basement membrane reduplication.
• Patients should be screened with a hemoglobin A1c level, fasting glucose, or a 2-hour glucose tolerance test.

• Presents with distal axonal sensorimotor polyneuropathy which leads to limb weakness or difficulty weaning off of artificial ventilation.
• Sepsis, SIRS, and multiorgan failure are risk factors.
  • Patients with critical illness neuropathy may also have concurrent critical illness myopathy.
• Diagnostic studies may include EMG showing spontaneous activity (i.e. fibrillations) and nerve conduction studies (NCS) showing normal velocity and amplitude reduction.
• Symptoms can take months to years to recover and one-third of patients never walk independently again.

• Seen in patients with poor diets: Chronic alcoholism, post-gastric bypass, and nitrous oxide abuse.
  • Strict vegan diets may also lead to this deficiency, but this would take years to develop.
  • Other causes include atrophic gastritis, Crohn’s disease, celiac disease, and enteritis.
• Symptoms are generally symmetrical and may present as peripheral neuropathy, subacute combined degeneration, or even neuropsychiatric conditions.
• If B12 levels are borderline abnormal, you should check methylmalonic acid and homocysteine levels if the concern is high.
• See the Toxicology chapter for more details.

• Presents similarly to B12 deficiency.
• Seen in patients with a malabsorption disorder or from excessive zinc intake.
• May also be seen in genetic diseases such as Menke’s disease.

• Peripheral neuropathy can be seen in patients with polyarteritis nodosa, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, giant cell arteritis, lupus, and Wegener’s granulomatosis.

• HIV-related distal symmetric polyneuropathy is the most common neurological complication of HIV, affecting 50% of patients. 
• Concurrent treatment with nucleoside reverse-transcriptase inhibitors (NRTIs) like didanosine, zalcitabine, and stavudine increases the risk of HIV-related neuropathy.

• Chronic hypothyroidism can present with mono- or polyneuropathy due to compression of nerves.

• Presents as a chronic demyelinating disorder that can be similar phenotypically to those with CIDP.

• Seen in about 28-50% of hepatitis C patients.

• POEMS is an acronym for Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes.
• Occurs due to high levels of serum vascular endothelial growth factor (VEGF) and low levels of erythropoietin.
• Patients develop a progressive symmetric, length-dependent sensorimotor polyneuropathy.
• Organomegaly presents as hepatomegaly and/or splenomegaly.
• Possible endocrinopathies are diabetes mellitus, hypogonadism, and hypothyroidism.
• “M protein” represents the production of monoclonal proteins. This can be secondary to MGUS, plasmacytoma, osteolytic myeloma, and osteosclerotic myeloma.
  • Osteosclerotic and osteolytic myelomas can usually be detected on a bone survey.
• “Skin changes” represent focal or generalized hyperpigmentation and/or skin thickening.
• Serum levels of VEGF normalize in response to therapy.

Can be sporadic or hereditary (see familial amyloid polyneuropathy below)