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{{Guillain-Barré syndrome}}
{{Guillain-Barré syndrome}}


{{CMG}}; '''Associate Editors-In-Chief:''' [[Priyamvada Singh|Priyamvada Singh, MBBS]] [mailto:psingh@perfuse.org]
{{CMG}}; {{AE}} {{Fs}}


==Overview==
==Overview==
'''Guillain-Barré syndrome''' ('''GBS''') is an acute, autoimmune, [[neuropathy|polyradiculoneuropathy]] affecting the [[peripheral nervous system]], usually triggered by an acute infectious process. It involves an auto-immune mechanism in which the antibodies formed against the lipopolysaccharides of bacteria or certain vaccines cross reacts with the [[gangliosides]] present in myelin of peripheral nerves. As a result of which, myelin degeneration occurs leading to conduction defects that manifests as [[flaccid paralysis]].
The exact pathogenesis of Guillain Barre syndrome is not completely understood but in 2/3 of cases there is a history of an infectious disease in the past month.The most common pathogens responsible for these antecedent infections are: [[Campylobacter jejuni]], [[Cytomegalo virus infection|cytomegalo virus]] and [[Hemophilus influenzae]]. It is believed that the main underlying etiology of GBS is an [[Autoimmunity|autoimmune]] reaction due to molecular mimicry. On microscopic histopathological analysis: [[Lymphocyte]] and [[macrophage]] infiltration, [[demyelination]] in AIDP, [[Macrophage]] infiltration and [[axolemma]] disruption in [[Motor fiber|motor fibers]] in AMAN, disruption of both motor and sensory fibers. Little [[lymphocyte]] infiltration in AMSAN and [[Oculomotor nerve]] [[demyelination]] in Miller Fisher type.


==Pathophysiology==
==Pathophysiology==


* GBS is often associated with an antecedent infection with agents such as [[Campylobacter jejuni]] or exposure to some vaccines (influenza vaccine).
=== Physiology ===
* [[Soma]] is the neuronal cell body which is a closed area with [[cell membrane]].


* These causative agents have certain [[lipopolysaccharides]] [[antigens]] in their capsules that are similar to  [[gangliosides]] and  [[glycolipids]], such as GM1 and GD1b found in [[myelin]] tissues of the [[peripheral nerve]].
* [[Dendrite|Dendrites]] are branched processes which lead the impulse into the neuronal cell body.


* The immune responses directed against these bacterial capsular lipopolysaccharides also targets the similar GM1 ganglioside which are complex glycosphingolipids present in large quantities on human nerve tissues, especially in the [[nodes of Ranvier]]. An example is the GM1 ganglioside, which can be affected in as many as 20-50% of cases, especially in those preceded by ''[[Campylobacter jejuni]]'' infections. Another example is the GQ1b ganglioside, which is the target in the [[Miller Fisher syndrome]] variant.
* [[Axon|Axons]] in a single process which lead the impulse away from the neuronal cell body.


* Cellular and humoral immune mechanisms play an important role in the development of disease. Pathologic findings in GBS include lymphocytic infiltration of peripheral nerves, followed by macrophage-mediated, multifocal attack of myelin.
* [[Myelin sheath]] is the [[oligodendrocyte]] membrane which wraps around the [[Axon|axons]].  
* [[Myelin sheath]] is insulated against electrical impulses and is separated by [[nodes of Ranvier]] which can transfer the electrical impulse.


* These type of immune response that are primarily for foreign antigens (such as infectious agents or vaccines) but are mis-targeted to host nerve tissues instead are called [[antigenic mimicry]] or [[molecular mimicry]].
* This structure leads to fast traveling of electrical impulses.<ref name=":0">{{cite book | last = Mattle | first = Heinrich | title = Fundamentals of neurology : an illustrated guide | publisher = Thieme | location = Stuttgart New York | year = 2017 | isbn = 9783131364524 }}</ref>


* The end result of such [[autoimmune]] attack on the peripheral nerves is inflammation of [[myelin]], defects in the propagation of electrical nerve impulses and conduction block, leading to a muscle [[paralysis]] that may be accompanied by sensory or [[autonomic]] disturbances.  
=== Pathogenesis ===
* The exact pathogenesis of Guillain Barre syndrome is not completely understood but in 2/3 of cases there is a history of an infectious disease in the past month.<ref name="pmid3404161">{{cite journal |vauthors=Winer JB, Hughes RA, Anderson MJ, Jones DM, Kangro H, Watkins RP |title=A prospective study of acute idiopathic neuropathy. II. Antecedent events |journal=J. Neurol. Neurosurg. Psychiatry |volume=51 |issue=5 |pages=613–8 |date=May 1988 |pmid=3404161 |pmc=1033063 |doi= |url=}}</ref>
* The most common pathogens responsible for these antecedent infections are:<ref name="pmid9781538">{{cite journal |vauthors=Jacobs BC, Rothbarth PH, van der Meché FG, Herbrink P, Schmitz PI, de Klerk MA, van Doorn PA |title=The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study |journal=Neurology |volume=51 |issue=4 |pages=1110–5 |date=October 1998 |pmid=9781538 |doi= |url=}}</ref><ref name="pmid11026446">{{cite journal |vauthors=Ogawara K, Kuwabara S, Mori M, Hattori T, Koga M, Yuki N |title=Axonal Guillain-Barré syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan |journal=Ann. Neurol. |volume=48 |issue=4 |pages=624–31 |date=October 2000 |pmid=11026446 |doi= |url=}}</ref>
** [[Campylobacter jejuni]]
** [[Cytomegalo virus infection|Cytomegalo virus]]
** [[Hemophilus influenzae]]
* It is believed that the main underlying etiology of GBS is an [[Autoimmunity|autoimmune]] reaction.
* The main theory explaining the relation between these infections and GBS is molecular mimicry.
* There are many antigens on the surface of these pathogens which are similar to [[myelin sheath]] or [[Axon|axonal]] proteins.
* [[Campylobacter jejuni]] [[Lipopolysaccharide|LPS]] contains antigens resembling [[GM1]] and GQ1b.
* In the serum of GBS patients with [[campylobacter jejuni]] as the antecedent infection, we may see [[antibodies]] against [[GM1 gangliosidoses|GM1]] and GQ1b which can cause [[Acute motor axonal neuropathy|AMAN]] and [[Miller Fisher Syndrome|Miller Fisher]] respectively.<ref name="pmid8228822">{{cite journal |vauthors=Yuki N, Taki T, Inagaki F, Kasama T, Takahashi M, Saito K, Handa S, Miyatake T |title=A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure |journal=J. Exp. Med. |volume=178 |issue=5 |pages=1771–5 |date=November 1993 |pmid=8228822 |pmc=2191246 |doi= |url=}}</ref><ref name="pmid8413947">{{cite journal |vauthors=Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I |title=Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies |journal=Neurology |volume=43 |issue=10 |pages=1911–7 |date=October 1993 |pmid=8413947 |doi= |url=}}</ref>
* In the serum of GBS patients with [[Cytomegalovirus infection|CMV]] as the antecedent infection, we may see [[antibodies]] against [[GM2 gangliosidoses|GM2]].<ref name="pmid8784256">{{cite journal |vauthors=Irie S, Saito T, Nakamura K, Kanazawa N, Ogino M, Nukazawa T, Ito H, Tamai Y, Kowa H |title=Association of anti-GM2 antibodies in Guillain-Barré syndrome with acute cytomegalovirus infection |journal=J. Neuroimmunol. |volume=68 |issue=1-2 |pages=19–26 |date=August 1996 |pmid=8784256 |doi= |url=}}</ref>
* [[Haemophilus influenzae]] have [[GM1]] like structure on its surface and in the serum of patients with [[haemophilus influenzae]] related GBS we may see [[antibodies]] against [[GM1 gangliosidoses|GM1]].<ref name="pmid10214761">{{cite journal |vauthors=Mori M, Kuwabara S, Miyake M, Dezawa M, Adachi-Usami E, Kuroki H, Noda M, Hattori T |title=Haemophilus influenzae has a GM1 ganglioside-like structure and elicits Guillain-Barré syndrome |journal=Neurology |volume=52 |issue=6 |pages=1282–4 |date=April 1999 |pmid=10214761 |doi= |url=}}</ref>
* although [[antibody]] formation and [[humoral immunity]] said to be the underlying pathophysiology mechanism, sometimes pathologic findings underscore the importance of circulating [[antibodies]] in the pathogenesis of GBS.
* there are 4 types of GBS with different pathological sequences of events:
** AIDP:<ref name="pmid8619548">{{cite journal |vauthors=Hafer-Macko CE, Sheikh KA, Li CY, Ho TW, Cornblath DR, McKhann GM, Asbury AK, Griffin JW |title=Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy |journal=Ann. Neurol. |volume=39 |issue=5 |pages=625–35 |date=May 1996 |pmid=8619548 |doi=10.1002/ana.410390512 |url=}}</ref>
*** [[Lymphocyte|Lymphocytes]] will infiltrate in peripheral nerves and [[Nerve root|nerves root]] of [[spinal cord]].
*** [[Complement]] components will deposit in the outer surface of [[schwann cell]] membrane and starts the process of [[myelin]] disruption.
*** [[Macrophage|Macrophages]] will infiltrate and complete the [[demyelination]].
** [[Acute motor axonal neuropathy|AMAN]]:<ref name="pmid8871584">{{cite journal |vauthors=Hafer-Macko C, Hsieh ST, Li CY, Ho TW, Sheikh K, Cornblath DR, McKhann GM, Asbury AK, Griffin JW |title=Acute motor axonal neuropathy: an antibody-mediated attack on axolemma |journal=Ann. Neurol. |volume=40 |issue=4 |pages=635–44 |date=October 1996 |pmid=8871584 |doi=10.1002/ana.410400414 |url=}}</ref><ref name="pmid6502752">{{cite journal |vauthors=Ganser AL, Kirschner DA |title=Differential expression of gangliosides on the surfaces of myelinated nerve fibers |journal=J. Neurosci. Res. |volume=12 |issue=2-3 |pages=245–55 |date=1984 |pmid=6502752 |doi=10.1002/jnr.490120212 |url=}}</ref>
*** [[Immunoglobulin G|IgG]] and activated [[complement]] attack to the [[axolemma]] of motor fibers in [[Nodes of Ranvier|Ranvier nodes]].
*** [[Macrophage|Macrophages]] will migrate to these nodes and separate the [[axon]] from overlying [[schwann cells]] and destroy the [[axolemma]].
** AMSAN:<ref name="pmid8336165">{{cite journal |vauthors=Feasby TE, Hahn AF, Brown WF, Bolton CF, Gilbert JJ, Koopman WJ |title=Severe axonal degeneration in acute Guillain-Barré syndrome: evidence of two different mechanisms? |journal=J. Neurol. Sci. |volume=116 |issue=2 |pages=185–92 |date=June 1993 |pmid=8336165 |doi= |url=}}</ref><ref name="pmid3790970">{{cite journal |vauthors=Feasby TE, Gilbert JJ, Brown WF, Bolton CF, Hahn AF, Koopman WF, Zochodne DW |title=An acute axonal form of Guillain-Barré polyneuropathy |journal=Brain |volume=109 ( Pt 6) |issue= |pages=1115–26 |date=December 1986 |pmid=3790970 |doi= |url=}}</ref>
*** Very little [[lymphocyte]] infiltration
*** direct attack to the [[axon]] of motor and sensory neurons.
** Miller Fisher:<ref name="pmid84139472">{{cite journal |vauthors=Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I |title=Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies |journal=Neurology |volume=43 |issue=10 |pages=1911–7 |date=October 1993 |pmid=8413947 |doi= |url=}}</ref>
*** [[Immunoglobulin G|IgG antibody]] against GQ1b [[ganglioside]] which is present in the [[oculomotor nerve]], [[cerebellar]] [[Neuron|neurons]] and [[dorsal root ganglion]] cells.
**It seems that antibody-mediated mechanism is more prominent in [[Acute motor axonal neuropathy|AMAN]], whereas cellular mechanisms are more important in AIDP.
***
== Genetics ==
* There is no characteristic genetic association with GBS.


* However, in mild cases, axonal function remains intact and recovery can be rapid if remyelination occurs.
== Microscopic Pathology ==
 
* On microscopic histopathological analysis:<ref name="pmid3790970" /><ref name="pmid8336165" /><ref name="pmid6502752" /><ref name="pmid8871584" /><ref name="pmid8619548" />
* In severe cases, such as in the AMAN or AMSAN variants, axonal degeneration occurs, and recovery depends on axonal regeneration. Recovery becomes much slower, and there is a greater degree of residual damage.
** AIDP: [[Lymphocyte]] and [[macrophage]] infiltration, [[demyelination]]
 
** AMAN: [[Macrophage]] infiltration and [[axolemma]] disruption in [[Motor fiber|motor fibers]]
* Recent studies on the disease have demonstrated that approximately 80% of the patients have [[myelin]] loss, whereas, in the remaining 20%, the pathologic hallmark of the disease is indeed [[axon]] loss.
** AMSAN: Disruption of both motor and sensory fibers. Little [[lymphocyte]] infiltration
 
** Miller Fisher: [[Oculomotor nerve]] [[demyelination]]<ref name="pmid6736980">{{cite journal |vauthors=Phillips MS, Stewart S, Anderson JR |title=Neuropathological findings in Miller Fisher syndrome |journal=J. Neurol. Neurosurg. Psychiatry |volume=47 |issue=5 |pages=492–5 |date=May 1984 |pmid=6736980 |pmc=1027825 |doi= |url=}}</ref>
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==References==
==References==
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[[Category:Autoimmune diseases]]
[[Category:Neurological disorders]]
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[[Category:Immunology]]
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[[Category:Emergency medicine]]

Latest revision as of 16:04, 27 December 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.

Overview

The exact pathogenesis of Guillain Barre syndrome is not completely understood but in 2/3 of cases there is a history of an infectious disease in the past month.The most common pathogens responsible for these antecedent infections are: Campylobacter jejuni, cytomegalo virus and Hemophilus influenzae. It is believed that the main underlying etiology of GBS is an autoimmune reaction due to molecular mimicry. On microscopic histopathological analysis: Lymphocyte and macrophage infiltration, demyelination in AIDP, Macrophage infiltration and axolemma disruption in motor fibers in AMAN, disruption of both motor and sensory fibers. Little lymphocyte infiltration in AMSAN and Oculomotor nerve demyelination in Miller Fisher type.

Pathophysiology

Physiology

  • Dendrites are branched processes which lead the impulse into the neuronal cell body.
  • Axons in a single process which lead the impulse away from the neuronal cell body.
  • This structure leads to fast traveling of electrical impulses.[1]

Pathogenesis

Genetics

  • There is no characteristic genetic association with GBS.

Microscopic Pathology

References

  1. ↑ Mattle, Heinrich (2017). Fundamentals of neurology : an illustrated guide. Stuttgart New York: Thieme. ISBN 9783131364524.
  2. ↑ Winer JB, Hughes RA, Anderson MJ, Jones DM, Kangro H, Watkins RP (May 1988). "A prospective study of acute idiopathic neuropathy. II. Antecedent events". J. Neurol. Neurosurg. Psychiatry. 51 (5): 613–8. PMC 1033063. PMID 3404161.
  3. ↑ Jacobs BC, Rothbarth PH, van der Meché FG, Herbrink P, Schmitz PI, de Klerk MA, van Doorn PA (October 1998). "The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study". Neurology. 51 (4): 1110–5. PMID 9781538.
  4. ↑ Ogawara K, Kuwabara S, Mori M, Hattori T, Koga M, Yuki N (October 2000). "Axonal Guillain-Barré syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan". Ann. Neurol. 48 (4): 624–31. PMID 11026446.
  5. ↑ Yuki N, Taki T, Inagaki F, Kasama T, Takahashi M, Saito K, Handa S, Miyatake T (November 1993). "A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure". J. Exp. Med. 178 (5): 1771–5. PMC 2191246. PMID 8228822.
  6. ↑ Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I (October 1993). "Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies". Neurology. 43 (10): 1911–7. PMID 8413947.
  7. ↑ Irie S, Saito T, Nakamura K, Kanazawa N, Ogino M, Nukazawa T, Ito H, Tamai Y, Kowa H (August 1996). "Association of anti-GM2 antibodies in Guillain-Barré syndrome with acute cytomegalovirus infection". J. Neuroimmunol. 68 (1–2): 19–26. PMID 8784256.
  8. ↑ Mori M, Kuwabara S, Miyake M, Dezawa M, Adachi-Usami E, Kuroki H, Noda M, Hattori T (April 1999). "Haemophilus influenzae has a GM1 ganglioside-like structure and elicits Guillain-Barré syndrome". Neurology. 52 (6): 1282–4. PMID 10214761.
  9. ↑ 9.0 9.1 Hafer-Macko CE, Sheikh KA, Li CY, Ho TW, Cornblath DR, McKhann GM, Asbury AK, Griffin JW (May 1996). "Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy". Ann. Neurol. 39 (5): 625–35. doi:10.1002/ana.410390512. PMID 8619548.
  10. ↑ 10.0 10.1 Hafer-Macko C, Hsieh ST, Li CY, Ho TW, Sheikh K, Cornblath DR, McKhann GM, Asbury AK, Griffin JW (October 1996). "Acute motor axonal neuropathy: an antibody-mediated attack on axolemma". Ann. Neurol. 40 (4): 635–44. doi:10.1002/ana.410400414. PMID 8871584.
  11. ↑ 11.0 11.1 Ganser AL, Kirschner DA (1984). "Differential expression of gangliosides on the surfaces of myelinated nerve fibers". J. Neurosci. Res. 12 (2–3): 245–55. doi:10.1002/jnr.490120212. PMID 6502752.
  12. ↑ 12.0 12.1 Feasby TE, Hahn AF, Brown WF, Bolton CF, Gilbert JJ, Koopman WJ (June 1993). "Severe axonal degeneration in acute Guillain-Barré syndrome: evidence of two different mechanisms?". J. Neurol. Sci. 116 (2): 185–92. PMID 8336165.
  13. ↑ 13.0 13.1 Feasby TE, Gilbert JJ, Brown WF, Bolton CF, Hahn AF, Koopman WF, Zochodne DW (December 1986). "An acute axonal form of Guillain-Barré polyneuropathy". Brain. 109 ( Pt 6): 1115–26. PMID 3790970.
  14. ↑ Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I (October 1993). "Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies". Neurology. 43 (10): 1911–7. PMID 8413947.
  15. ↑ Phillips MS, Stewart S, Anderson JR (May 1984). "Neuropathological findings in Miller Fisher syndrome". J. Neurol. Neurosurg. Psychiatry. 47 (5): 492–5. PMC 1027825. PMID 6736980.

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