Peripheral neuropathy pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]
Overview
The pathophysiologic processes that can adversely affect peripheral nerves is very extensive. Processes which can damage the peripheral nerves at multiple levels via many molecular pathways include: Immunologic, metabolic, genetic, infectious, toxic and traumatic processes. Any pathologic process affecting the cell body will result in downstream degeneration of the cell's axon. Primary motor neuron diseases, such as ALS or SMA, demonstrate axonal pathology peripherally when central neurons degenerate. Similarly, metabolic conditions, such as diabetes, the metabolic syndrome, nutritional deficiencies, or chronic renal failure, affect DRG cell bodies by mechanisms involving insulin resistance, oxidative stress, and apoptosis. Pathologic damage may also be considered to take place directly at the axon, independent of the cell body. Schwann cells and the myelin sheath are often selectively targeted in immune-mediated processes such as GBS, CIDP, paraproteinemias, and their variants. It is theorized that a phenomenon of molecular mimicry occurs in these diseases, wherein glycoprotein epitopes found in myelin bear structural similarity to those found in other infectious agents. Immune recognition of these pathogens then spreads to include normal epitopes on the myelin sheath. Pathologic studies reveal both humoral and cellular immune activation and lymphocytic infiltration with patchy demyelination and remyelination. A number of GBS variants which are more prevalent in Asia and Central/South America also damage axons along with myelin, and are commonly associated with Campylobacter jejuni infection. Hereditary neuropathies can also affect both axons and/or their myelin sheaths. The most common type, hereditary motor sensory neuropathy (HMSN or Charcot-Marie-Tooth disease), is classified into many clinical subtypes. Many other genetic syndromes also produce varying disruption of Schwann cell, axon and/or neuronal function. Both the Schwann cells and axons of the peripheral nerve depend upon delicate vasa nervorum for perfusion and metabolic support. Many metabolic and inflammatory processes, while directly affecting peripheral nerves and neuronal cell bodies, can also result in damage to nerve vasculature and indirectly produce ischemic damage, particularly to axons. Primary vasculitides as well as other rheumatologic disorders (systemic lupus erythematosus, Sjögren's syndrome, nonsystemic vasculitis of the peripheral nerves, etc.)
Pathophysiology
- The pathophysiologic processes that can adversely affect peripheral nerves is very extensive.[1]
- Processes which can damage the peripheral nerves at multiple levels via many molecular pathways include:[1]
- Any pathologic process affecting the cell body will result in downstream degeneration of the cell's axon. Primary motor neuron diseases, such as ALS or SMA, demonstrate axonal pathology peripherally when central neurons degenerate. Similarly, metabolic conditions, such as diabetes, the metabolic syndrome, nutritional deficiencies, or chronic renal failure, affect DRG cell bodies by mechanisms involving insulin resistance, oxidative stress, and apoptosis. Pathologic damage may also be considered to take place directly at the axon, independent of the cell body.[1][2][3][1]
- Schwann cells and the myelin sheath are often selectively targeted in immune-mediated processes such as GBS, CIDP, paraproteinemias, and their variants. It is theorized that a phenomenon of molecular mimicry occurs in these diseases, wherein glycoprotein epitopes found in myelin bear structural similarity to those found in other infectious agents. Immune recognition of these pathogens then spreads to include normal epitopes on the myelin sheath. Pathologic studies reveal both humoral and cellular immune activation and lymphocytic infiltration with patchy demyelination and remyelination. A number of GBS variants which are more prevalent in Asia and Central/South America also damage axons along with myelin, and are commonly associated with Campylobacter jejuni infection.[4][5]
- Hereditary neuropathies can also affect both axons and/or their myelin sheaths. The most common type, hereditary motor sensory neuropathy (HMSN or Charcot-Marie-Tooth disease), is classified into many clinical subtypes. Many other genetic syndromes also produce varying disruption of Schwann cell, axon and/or neuronal function. Both the Schwann cells and axons of the peripheral nerve depend upon delicate vasa nervorum for perfusion and metabolic support. Many metabolic and inflammatory processes, while directly affecting peripheral nerves and neuronal cell bodies, can also result in damage to nerve vasculature and indirectly produce ischemic damage, particularly to axons. Primary vasculitides as well as other rheumatologic disorders (systemic lupus erythematosus, Sjögren's syndrome, nonsystemic vasculitis of the peripheral nerves, etc.)[1][6][7][8]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Callaghan BC, Price RS, Chen KS, Feldman EL (2015). "The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral Neuropathy: A Review". JAMA Neurol. 72 (12): 1510–8. doi:10.1001/jamaneurol.2015.2347. PMC 5087804. PMID 26437251.
- ↑ Fischer-Hayes LR, Brotherton T, Glass JD (2013). "Axonal degeneration in the peripheral nervous system: implications for the pathogenesis of amyotrophic lateral sclerosis". Exp Neurol. 246: 6–13. doi:10.1016/j.expneurol.2013.05.001. PMID 23664960.
- ↑ Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL (2012). "Diabetic neuropathy: clinical manifestations and current treatments". Lancet Neurol. 11 (6): 521–34. doi:10.1016/S1474-4422(12)70065-0. PMC 4254767. PMID 22608666.
- ↑ Joint Task Force of the EFNS and the PNS (2010). "European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision". J Peripher Nerv Syst. 15 (3): 185–95. doi:10.1111/j.1529-8027.2010.00278.x. PMID 21040140.
- ↑ Dimachkie MM, Barohn RJ, Katz J (2013). "Multifocal motor neuropathy, multifocal acquired demyelinating sensory and motor neuropathy, and other chronic acquired demyelinating polyneuropathy variants". Neurol Clin. 31 (2): 533–55. doi:10.1016/j.ncl.2013.01.001. PMC 4098937. PMID 23642723.
- ↑ Saporta MA, Shy ME (2013). "Inherited peripheral neuropathies". Neurol Clin. 31 (2): 597–619. doi:10.1016/j.ncl.2013.01.009. PMC 3646296. PMID 23642725.
- ↑ Collins MP, Arnold WD, Kissel JT (2013). "The neuropathies of vasculitis". Neurol Clin. 31 (2): 557–95. doi:10.1016/j.ncl.2013.01.007. PMID 23642724.
- ↑ Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F; et al. (2013). "2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides". Arthritis Rheum. 65 (1): 1–11. doi:10.1002/art.37715. PMID 23045170.