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Peripheral nerves consist of two principal cellular structures – motor or sensory cell with its axon and the myeline sheath covering it. Myelin sheath is produced by Schwann cells between each node of Ranvier. Blood supply is via vasa nervorum.


Six principal mechanisms, some coexisting, cause nerve malfunction.

  1. Demyelination: When the Schwann cell is damaged, the myelin sheath is disrupted. This causes marked slowing of conduction, seen for example in Guillain-Barre syndrome, post diphtheritic neuropathy and many hereditary sensorimotor neuropathies.
  1. Axonal degeneration: The primary damage is in the axon, which dies back from the periphery. Conduction velocity tends to remain normal (cf. demyelination) because axonal continuity is maintained in surviving fibers. Axonal degeneration occurs typically in toxic neuropathies.
  1. Wallerian degeneration: This describes the changes following nerve section. Both the distal axon and the distal myelin sheath degenerate over several weeks.
  1. Compression: Focal demyelination at the point of compression. The myelin sheath is disrupted. This occurs typically in entrapment neuropathies e.g. carpal tunnel syndrome.
  1. Infarction: Micro infarction of vasa nervorum occurs in arteritis, e.g. polyarteritis nodosa, Churg Strauss syndrome and in diabetes mellitus. Wallerian degeneration occurs distal to the ischemic zone.


  1. Infiltration: Peripheral nerves are infiltrated by inflammatory cells in leprosy, by malignant cells in cancers, or granulomas in sarcoidosis.


Important definitions required to understand neuropathies of any type:


  • Neuropathy simply means a pathological process affecting a peripheral nerve or nerves.


  • Mononeuropathy means a process affecting a single nerve. [From the web: damage to a single peripheral nerve.]
  • Mononeuritis multiplex (multiple mononeuropathy and or multifocal neuropathy) affects several or multiple nerves. [From the web: is the simultaneous malfunction of two or more peripheral nerves in separate areas of the body. It causes abnormal sensations and weakness.]
  • Polyneuropathy describes diffuse, symmetrical disease, usually commencing peripherally. The course may be acute, chronic, static, progressive, relapsing or towards recovery. Polyneuropathies are motor, sensory, sensorimotor and autonomic. They are classified broadly into demyelinating and axonal types, depending upon which principal pathological process predominates. It is often impossible to separate these clinically. Many systemic diseases cause neuropathies. Widespread loss of tendon reflexes is typical, with distal weakness and distal sensory loss. [From the web: is the simultaneous malfunction of many peripheral nerves throughout the body.]
  • Radiculopathy means disease affecting nerve roots
  • Plexopathy pathology of the brachial or lumbosacral plexus.


  • Myelopathy means disease of the cord.


List of the causative categories of peripheral neuropathy and some examples of each:


  • Metabolic/endocrine: diabetes mellitus (autonomic and sensory neuropathy), uremia, and hypothyroidism.
    • Diabetes causes the damage by microvascular injury (vasa nervorum are damaged.) Capillary basement membrane thickening and endothelial hyperplasia causes narrowing of the lumen. This in turn leads to ischemic damage to the nerve.
    • Uremic neuropathy occurs in the advanced renal failure. Usually peripheral axons are damaged resulting in the segmental demyelination. Exact cause is not known, it is theorized that reduced thiamin, zinc, and biotin or reduced activity of transketolase can cause the axonal damage.
    • Hypothyroidism can cause water retention. This in turn causes swollen tissue compressing and damaging the nerves.


  • Nutritional: deficiencies of vitamin B12, vitamin B6 (look for history of isoniazid use), thiamine (“dry” beriberi), and vitamin E


  • Toxins/medications: lead poisoning (the classic symptom is wrist or foot drop; look for coexisting CNS or abdominal symptoms) or other heavy metals, isoniazid, vincristine, ethambutol (optic neuritis), and aminoglycosides (especially CN VIII)


  • Lead poisoning and heavy metal poisoning is due increased reactive oxygen specie production. Lead can also mimic other metals and act as a false cofactor with the enzymes. This results in the enzyme malfunction. Issues with heme synthesis are an example.


  • Immunization and autoimmune disorders: Guillain-Barré syndrome, SLE, polyarteritis nodosa, scleroderma, sarcoidosis, and amyloidosis
    • Guillain-Barre syndrome, usually after the GIT or upper respiratory tract infections. Immune system incorrectly attacks the myeline sheath cells.


  • Trauma: Carpal tunnel syndrome (entrapment of the median nerve at the wrist; usually due to repetitive physical activity but may be a presentation of acromegaly or hypothyroidism; look for positive Tinel and Phalen signs), pressure paralysis (radial nerve palsy in alcoholics), and fractures (causing nerve compression)
    • Tinel sign is tested by tapping on the median nerve.
    • Phalen sign is tested with the arms at 90 degrees and wrist joints opposed at 90 degrees. If in 30 seconds or so the tingling and numbness appear then the sign is positive.


  • Infectious: Lyme disease, diphtheria, HIV, and leprosy
    • In diphtheria for example, the exotoxin binds to a cell with the B subunit and then the A subunit is phagocytozed. These subunits are released in the cytoplasm. A subunit binds with the elongation factor 2 and ADP-ribosylates it. This results in reduction in protein synthesis and the cell dies.


Question: What test can be used to prove the presence of a peripheral neuropathy, regardless of cause?


Answer: Nerve conduction velocity is slowed with a peripheral neuropathy.

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