Guillain-Barré syndrome

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

Guillain-Barré syndrome (GBS) is an acute, autoimmune, polyradiculoneuropathy affecting the peripheral nervous system, usually triggered by an acute infectious process. It is included in the wider group of peripheral neuropathies.

The disease was first described by the French physician Jean Landry in 1859. In 1916, Georges Guillain, Jean Alexandre Barré and Andre Strohl diagnosed two soldiers with motor weakness, areflexia and a the key diagnostic abnormality of increased spinal fluid protein production, but normal cell count. Later, it was called Guillain-Barré syndrome after them. GBS is also known as acute inflammatory demyelinating polyneuropathy, acute idiopathic polyradiculoneuritis, acute idiopathic polyneuritis, French Polio and Landry’s ascending paralysis.

Guillain Barre syndrome may be classified according to the underlying pathophysiology into four groups: Acute motor axonal neuropathy (AMAN), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy and Miller Fisher syndrome.

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.

Guillain Barre syndrome may be caused by Campylobacter jejuni, Cytomegalovirus, haemophilus influenza, epstein-Barr virus, Varicella zoster virus and HIV-1.

Guillain Barre syndrome must be differentiated from: Acute Flaccid Myelitis, adult botulism, infant botulism, Eaton-Lambert syndrome, myasthenia gravis, electrolyte disturbance, organophosphate toxicity, tick paralysis, tetrodotoxin poisoning, stroke, poliomyelitis, transverse myelitis, neurosyphilis, muscular dystrophy, multiple sclerosis exacerbation, amyotrophic lateral sclerosis and inflammatory myopathy.

Incidence vary from 0.4 to 4.0 cases per population of 100 000. In previous studies, Guillain-Barre syndrome mortality rate was 2.58%. It can happen in any age group but it’s more common in late adolescence. The reason behind this is that immune suppressor mechanisms will decrease with age. It was demonstrated in one study that the incidence rate for whites were 0.44 and for blacks were 0.28 per 100,000, but it seems that despite all of these, the incidence is similar across different races. It is more common among males compared to females. Male to female ratio 1.5:1.

Risk factors in the development of Guillain Barre syndrome include: Rabies vaccine and swine-flu influenza vaccine.

There is insufficient evidence to recommend routine screening for Guillain Barre syndrome.

The symptoms of Guillain Barre syndrome typically develop 1 to 3 weeks after the Antecedent Infection. If left untreated, 65% of patients with Guillain Barre syndrome will recover with no permanent disability. 35% of them will not fully recover. 8% of these 35% will die from complication and others will have permanent disabilities.

Common complications of GBS include: respiratory failure, autonomic failure, bulbar pulsy, Deep vein thrombosis, Cardiac arrhythmia, Pain, Urinary retention, Ileus and persistent fatigue

There is no single diagnostic study of choice for Guillain Barre syndrome, though GBS may be diagnosed based on NINDS criteria established by National Institute of Neurological Disorders and Stroke: Progressive ascending weakness or paralysis usually starting from legs, involving are 4 limbs, the trunk, bulbar and facial muscles, and external ocular muscles and Areflexia or decreased reflexes in affected limbs.

Patients with Guillain Barre syndrome may have a positive history of: Prior infection with Campylobacter jejuni, Cytomegalovirus, Haemophilus influenzae, Epstein-Barr virus, Varicella zoster virus and HIV-1, recent vaccination with influenzae or rabies vaccine, limb tingling and paresthesia, lower extremity weakness and muscle pain.

Common symptoms of Guillain Barre syndrome include: Symmetrical ascending weakness and paralysis, tingling and paresthesia and pain.

Physical examination of patients with Guillain Barre syndrome is usually remarkable for abnormal gait, heart rate and blood pressure disturbance, ophthalmoplegia, papilledema, facial myokymia, vocal cord paralysis, urinary retention, hyperreflexia or areflexia, bilateral distal and proximal muscle weakness and unilateral or bilateral sensory abnormality.

Laboratory findings consistent with the diagnosis of Guillain Barre syndrome include: Elevated CSF protein level, normal CSF WBC count, normal CSF cell count (in some cases there is mildly elevated cell count) and serum IgG antibody to GQ1b in Miller Fisher syndrome.

The dysautonomia seen in Guillian Barre syndrome may lead to some conduction and rhythm disturbances. Findings on an ECG suggestive of Guillain Barre syndrome include: ST segment depresion, T wave inversion, QT prolongation and Ttachycardia.

There are no characteristic x-Ray findings associated with Guillain Barre disease.

There are no characteristic echocardiography/ultrasound findings associated with Guillain Barre syndrome.

There are no characteristic CT scan findings associated with Guillain Barre syndrome but we can perform CT scan to exclude other etiologies.

Findings on MRI suggestive of Guillain Barre syndrome include: Anterior and posterior nerve root and cauda equina enhancement.

There are no other imaging findings associated with Guillain Barre sydnrome.

Nerve conduction studies and needle electromyography may be helpful in the diagnosis of Guillain Barre syndrome and differentiating various sub types. Findings diagnostic of demyelinating forms of Guillain Barre syndrome include: Reduced conduction velocity of motor nerves, increased distal motor latency, increased latency of F wave, conduction block and Temporal scattering. Findings diagnostic of axonal forms of Guillain Barre syndrome include: Reduced amplitude of distal motor and/or sensory nerve impulses and conduction block of motor nerves.

Supportive therapy for Guillain Barre syndrome include: Respiratory assistance, Heart rate and blood pressure monitoring, prevention of thromboembolic complications by heparin, minimal sedation in intensive care units, pain control and early passive movements. Immunomodulating therapy for Guillain Barre syndrome include: Plasma exchange, High dose immunoglobulin and Corticosteroids.

Surgical intervention is not recommended for the management of Guillain Barre syndrome.

There are no established measures for the primary prevention of Guillain Barre syndrome.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Priyamvada Singh, MBBS [2]

The disease was first described by the French physician Jean Landry in 1859. In 1916, Georges Guillain, Jean Alexandre Barré and Andre Strohl diagnosed two soldiers with motor weakness, areflexia and a the key diagnostic abnormality of increased spinal fluid protein production, but normal cell count. Later, it was called Guillain-Barré syndrome after them. GBS is also known as acute inflammatory demyelinating polyneuropathy, acute idiopathic polyradiculoneuritis, acute idiopathic polyneuritis, French Polio and Landry’s ascending paralysis.

• The disease was first described by the French physician Jean Landry in 1859.
• In 1916, Georges Guillain, Jean Alexandre Barré and Andre Strohl diagnosed two soldiers with motor weakness, areflexia and a the key diagnostic abnormality of increased spinal fluid protein production, but normal cell count.^[1]. Later, it was called Guillain-Barré syndrome after them.
• GBS is also known as acute inflammatory demyelinating polyneuropathy, acute idiopathic polyradiculoneuritis, acute idiopathic polyneuritis, French Polio and Landry’s ascending paralysis.

File:Griffith, Andy (Whitehouse).jpg

• Markus Babbel, former international footballer.^[2]
• Tony Benn, British politician.^[3]
• Rachel Chagall, actress.^[4]
• Samuel Goldstein, American athlete and Paralympian.^[5]
• Andy Griffith, American actor.^[6]
• Joseph Heller, author.^[7]
• Luci Baines Johnson, daughter of President Lyndon Johnson and Lady Bird Johnson.^[8]
• Hugh McElhenny, American football player.^[9]
• Lucky Oceans, Grammy Award-winning musician.^[10]
• Len Pasquarelli, sports writer and analyst for ESPN and resident of the Pro Football Writers of America.^[11]
• Serge Payer, Canadian-born professional hockey player.^[12]
• William “The Refrigerator” Perry, former professional American football player.^[13]
• Franklin D. Roosevelt, U.S. president.^[14]
• Norton Simon, American industrialist and philanthropist.^[15]
• Hans Vonk, Dutch conductor.^[16]
• Danny Wuerffel, 1996 Heisman Trophy winner.^[17]

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

Guillain Barre syndrome may be classified according to the underlying pathophysiology into four groups: Acute motor axonal neuropathy (AMAN), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy and Miller Fisher syndrome.

Guillain Barre syndrome may be classified according to the underlying pathophysiology into four groups:^{[1][2][3][4][5][6][7][8][9]}

Subtypes	Explanation
Acute Motor Axonal Neuropathy (AMAN)	The most common type (85-90%). Prior infection can trigger it. Autoimmune disorder. The target is schwann cell surface membrane or the myelin. Causes demyelination. In electrodiagnostic tests we can see slowing of nerve conduction. In pathology we can see lymphocytic infiltration of peripheral nerves and macrophage invasion of myelin sheath and schwann cells.
Acute Motor Axonal Neuropathy (AMAN)	It’s common among Chinese and Japanese people. It can be triggered by C. jejuni. It is associated with antiganglioside antibodies. Autoimmune disorder. Target is axonal membrane. Causes axonal degeneration in motor neurons. In electrodiagnostic study we can see reduction of compound muscle action potential.
Acute motor and sensory axonal neuropathy	The incidence rate is under 10%. Causes axonal degeneration. It is similar with AMAN but involves both motor and sensory axons.
Miller Fisher syndrome	Causes a clinical triad: ophthalmoplegia, ataxia and areflexia. Associated with ganglioside GQ1b antibody.

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

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.

• Soma is the neuronal cell body which is a closed area with cell membrane.

• 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.

• Myelin sheath is the oligodendrocyte membrane which wraps around the axons.
• Myelin sheath is insulated against electrical impulses and is separated by nodes of Ranvier which can transfer the electrical impulse.

• This structure leads to fast traveling of electrical impulses.^[1]

• 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.^[2]
• The most common pathogens responsible for these antecedent infections are:^[3][4]
  • Campylobacter jejuni
  • Cytomegalo virus
  • Hemophilus influenzae
• It is believed that the main underlying etiology of GBS is an 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 axonal proteins.
• Campylobacter jejuni 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 and GQ1b which can cause AMAN and Miller Fisher respectively.^[5][6]
• In the serum of GBS patients with CMV as the antecedent infection, we may see antibodies against GM2.^[7]
• 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.^[8]
• 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:^[9]
    • Lymphocytes will infiltrate in peripheral nerves and nerves root of spinal cord.
    • Complement components will deposit in the outer surface of schwann cell membrane and starts the process of myelin disruption.
    • Macrophages will infiltrate and complete the demyelination.
  • AMAN:^[10][11]
    • IgG and activated complement attack to the axolemma of motor fibers in Ranvier nodes.
    • Macrophages will migrate to these nodes and separate the axon from overlying schwann cells and destroy the axolemma.
  • AMSAN:^[12][13]
    • Very little lymphocyte infiltration
    • direct attack to the axon of motor and sensory neurons.
  • Miller Fisher:^[14]
    • IgG antibody against GQ1b ganglioside which is present in the oculomotor nerve, cerebellar neurons and dorsal root ganglion cells.
  • It seems that antibody-mediated mechanism is more prominent in AMAN, whereas cellular mechanisms are more important in AIDP.

• There is no characteristic genetic association with GBS.

• On microscopic histopathological analysis:^{[13][12][11][10][9]}
  • AIDP: Lymphocyte and macrophage infiltration, demyelination
  • AMAN: Macrophage infiltration and axolemma disruption in motor fibers
  • AMSAN: Disruption of both motor and sensory fibers. Little lymphocyte infiltration
  • Miller Fisher: Oculomotor nerve demyelination^[15]

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

Guillain Barre syndrome may be caused by Campylobacter jejuni, Cytomegalovirus, haemophilus influenza, epstein-Barr virus, Varicella zoster virus and HIV-1.

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. GBS has a different natural history in every patient based on age and the speed of symptoms occurrence, so it can lead to death or patients may fully recover no matter what the etiology is.^[1][2]

• Campylobacter jejuni^[3][4][5][6]
  • Most common cause of gastroenteritis
  • Most common infection associated with GBS
  • There is a strong association between C. jejuni and AMAN type of GBS.
  • The C. jejuni LPS contains a tetrasaccharide which is similar to GM1.
  • C. jejuni can also cause MFS
  • It has antigens similar to GQ1b which is found in ocular motor nerves so it can cause ophthalmoplegia.

• Cytomegalovirus^[7][8][9]
  • This virus can cause respiratory infection, mononucleosis and flu-like symptoms.
  • The most common virus associated with GBS.
  • It will mostly cause AIDP in young females.
  • In some of the patients’ serum we can detect antibodies against GM2.

• Haemophilus influenza^[10]
  • It is mostly associated with AMAN type of GBS.
  • There is a molecular similarity with ganglioside GM1.

• Epstein-Barr virus
• Varicella zoster virus^[8]
• HIV-1^[11]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Priyamvada Singh, MBBS [2]

Guillain-Barré syndrome is an acute, autoimmune, polyradiculoneuropathy affecting the peripheral nervous system, usually triggered by an acute infectious process. It is included in the wider group of peripheral neuropathies.

Template:WH Template:WS

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

Incidence vary from 0.4 to 4.0 cases per population of 100 000. In previous studies, Guillain-Barre syndrome mortality rate was 2.58%. It can happen in any age group but it’s more common in late adolescence. The reason behind this is that immune suppressor mechanisms will decrease with age. It was demonstrated in one study that the incidence rate for whites were 0.44 and for blacks were 0.28 per 100,000, but it seems that despite all of these, the incidence is similar across different races. It is more common among males compared to females. Male to female ratio 1.5:1.

• Incidence vary from 0.4 to 4.0 cases per population of 100 000.^[1]

• In previous studies, Guillain-Barre syndrome mortality rate was 2.58%.^[2]

• It can happen in any age group but it’s more common in late adolescence.
• The reason behind this is that immune suppressor mechanisms will decrease with age.^[1]

• It was demonstrated in one study that the incidence rate for whites were 0.44 and for blacks were 0.28 per 100,000, but it seems that despite all of these, the incidence is similar across different races.^[3]

• It is more common among males compared to females. Male to female ratio 1.5:1.^[1]

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

Risk factors in the development of Guillain Barre syndrome include: Rabies vaccine and swine-flu influenza vaccine.

• Risk factors in the development of Guillain Barre syndrome include:
  • There are some evidence demonstrating that there might be a connection between vaccination and Guillain Barre syndrome.
    • These vaccines include:^[1][2]
      • Rabies vaccine
      • Swine-flu influenza vaccine

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

The symptoms of Guillain Barre syndrome typically develop 1 to 3 weeks after the Antecedent Infection. If left untreated, 65% of patients with Guillain Barre syndrome will recover with no permanent disability. 35% of them will not fully recover. 8% of these 35% will die from complication and others will have permanent disabilities.

Common complications of GBS include: respiratory failure, autonomic failure, bulbar pulsy, Deep vein thrombosis, Cardiac arrhythmia, Pain, Urinary retention, Ileus and persistent fatigue

• The symptoms of Guillain Barre syndrome typically develop 1 to 3 weeks after the Antecedent Infection.
• If left untreated, 65% of patients with Guillain Barre syndrome will recover with no permanent disability.
• 35% of them will not fully recover. 8% of these 35% will die from complication and others will have permanent disabilities.
• Treatment will just reduce the recovery period and has no effect on natural history of the disease.
• The first symptoms are lower extremities weakness and paresthesia.^[1][2][3]

• Common complications of GBS include:^[4][5]
  • respiratory failure
  • Autonomic failure
  • Bulbar pulsy
  • Deep vein thrombosis
  • Cardiac arrhythmia
  • Pain
  • Urinary retention
  • Ileus
  • Persistent fatigue

• About 65% of patients with GBS will fully recover with no permanent disability.
• 35% of them do not fully recover. 8% of this group will die from GBS complication and others will have permanent disabilities.
• Treatment of GBS just reduce the recovery time and doesn’t affect prognosis.^[6]
• Overally, older patients will have worst prognosis in comparison to children who discover very fast.^[1][2]

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