Guillain–Barré syndrome

Guillain-Barré syndrome
Classification and external resources
ICD-10	G61.0
ICD-9	357.0
OMIM	139393
DiseasesDB	5465
MedlinePlus	000684
eMedicine	emerg/222 neuro/7 pmr/48 neuro/598
MeSH	D020275

Guillain–Barré syndrome (GBS) (French pronunciation: [ɡiˈlɛ̃ baˈʁe], English pronunciation: /ˈɡiːlænˈbɑreɪ/), sometimes called Landry's paralysis, is an acute polyneuropathy, a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom, and some subtypes cause change in sensation or pain as well as dysfunction of the autonomic nervous system. It can cause life-threatening complications, in particular if the breathing muscles are affected or if there is with autonomic nervous system involvement. The disease is usually triggered by an infection.

The diagnosis is usually made by nerve conduction studies. With prompt treatment by intravenous immunoglobulins or plasmapheresis, together with supportive care, the majority will recover completely. Guillain–Barré syndrome is rare, at 1–2 cases per 100,000 people annually, but is the most common cause of acute non-trauma-related paralysis in the world. The syndrome is named after the French physicians Georges Guillain and Jean Alexandre Barré, who described it in 1916.

Contents 1 Classification 2 Signs and symptoms 3 Cause 4 Diagnosis 4.1 Diagnostic criteria 5 Treatment 6 Prognosis 7 Epidemiology 8 History 9 Notable cases 10 References 11 External links

Classification

Six different subtypes of Guillain–Barré syndrome exist:

• Acute inflammatory demyelinating polyneuropathy (AIDP) is the most common form of GBS, and the term is often used synonymously with GBS. It is caused by an auto-immune response directed against Schwann cell membranes.
• Miller Fisher syndrome (MFS) is a rare variant of GBS. Accounting for approximately 5% of GBS cases, it manifests as a descending paralysis, proceeding in the reverse order of the more common form of GBS..^[1] It usually affects the eye muscles first and presents with the triad of ophthalmoplegia, ataxia, and areflexia. The ataxia predominantly affects the gait and trunk, with the limbs relatively spared. Anti-GQ1b antibodies are present in 90% of cases.
• Acute motor axonal neuropathy (AMAN),^[2] also known as Chinese paralytic syndrome, attacks motor nodes of Ranvier and is prevalent in China and Mexico. It is probably due to an auto-immune response directed against the axoplasm of peripheral nerves. The disease may be seasonal and recovery can be rapid. Anti-GD1a antibodies^[3] are present. Anti-GD3 antibodies are found more frequently in AMAN.
• Acute motor sensory axonal neuropathy (AMSAN) is similar to AMAN but also affects sensory nerves with severe axonal damage. Like AMAN, it is probably due to an auto-immune response directed against the axoplasm of peripheral nerves. Recovery is slow and often incomplete.^[4]
• Acute panautonomic neuropathy is the most rare variant of GBS, sometimes accompanied by encephalopathy. It is associated with a high mortality rate, owing to cardiovascular involvement, and associated dysrhythmias. Impaired sweating, lack of tear formation, photophobia, dryness of nasal and oral mucosa, itching and peeling of skin, nausea, dysphagia, constipation unrelieved by laxatives or alternating with diarrhea occur frequently in this patient group. Initial nonspecific symptoms of lethargy, fatigue, headache, and decreased initiative are followed by autonomic symptoms including orthostatic lightheadedness, blurring of vision, abdominal pain, diarrhea, dryness of eyes, and disturbed micturition. The most common symptoms at onset are related to orthostatic intolerance, as well as gastrointestinal and sudomotor dysfunction (Suarez et al. 1994). Parasympathetic impairment (abdominal pain, vomiting, constipation, ileus, urinary retention, dilated unreactive pupils, loss of accommodation) may also be observed.
• Bickerstaff's brainstem encephalitis (BBE), is a further variant of Guillain–Barré syndrome. It is characterized by acute onset of ophthalmoplegia, ataxia, disturbance of consciousness, hyperreflexia or Babinski's sign. The course of the disease can be monophasic or remitting-relapsing. Large, irregular hyperintense lesions located mainly in the brainstem, especially in the pons, midbrain and medulla are described in the literature. BBE despite severe initial presentation usually has a good prognosis. Magnetic resonance imaging (MRI) plays a critical role in the diagnosis of BBE. A considerable number of BBE patients have associated axonal Guillain–Barré syndrome, indicative that the two disorders are closely related and form a continuous spectrum.

Signs and symptoms

The disorder is characterized by symmetrical weakness that usually affects the lower limbs first, and rapidly progresses in an ascending fashion. Patients generally notice weakness in their legs, manifesting as "rubbery legs" or legs that tend to buckle, with or without dysesthesias (numbness or tingling). As the weakness progresses upward, usually over periods of hours to days, the arms and facial muscles also become affected. Frequently, the lower cranial nerves may be affected, leading to bulbar weakness, oropharyngeal dysphagia (drooling, or difficulty swallowing and/or maintaining an open airway) and respiratory difficulties. Most patients require hospitalization and about 30% require ventilatory assistance for treatment of Type II respiratory failure.^[5] Facial weakness is also commonly a feature, but eye movement abnormalities are not commonly seen in ascending GBS, but are a prominent feature in the Miller-Fisher variant.

Sensory loss, if present, usually takes the form of loss of proprioception (position sense) and areflexia (complete loss of deep tendon reflexes), an important feature of GBS. Loss of pain and temperature sensation is usually mild. In fact, pain is a common symptom in GBS, presenting as deep aching pain, usually in the weakened muscles, which patients compare to the pain from overexercising. These pains are self-limited and may be treated with standard analgesics. Bladder dysfunction may occur in severe cases but is usually transient.

In severe cases of GBS, loss of autonomic function is common, manifesting as wide fluctuations in blood pressure, orthostatic hypotension (a fall in blood pressure on standing, leading to an increased risk of collapse), and cardiac arrhythmias.

Acute paralysis in Guillain–Barré syndrome may be related to sodium channel blocking factor in the cerebrospinal fluid (CSF). Significant issues involving intravenous salt and water administration may occur unpredictably in this patient group, resulting in SIADH, a cause of low sodium levels in the blood.

Cause

Structure of a typical neuron

Neuron
Dendrite Soma Axon Nucleus Node of Ranvier Axon terminal Schwann cell Myelin sheath

All forms of Guillain–Barré syndrome are due to an immune response to foreign antigens (such as infectious agents) that is mistargeted at host nerve tissues instead. The targets of such immune attack are thought to be gangliosides, compounds naturally present in large quantities in human nerve tissues. The most common antecedent infection is the bacterium Campylobacter jejuni^[6][7], followed by cytomegalovirus (CMV). ^[8] However, 60% of cases do not have a known cause. Some cases may be triggered by the influenza virus, or by an immune reaction to the influenza virus.^[9] There was increased incidence of Guillain-Barré syndrome following influenza immunization during the 1976-1977 swine flu pandemic, ^[10] however epidemiologic studies since then have demonstrated either an extremely small increased risk following immunization, under 1 additional case per million vaccinations, or no increased risk. ^{[11] [12]}

The end result of such autoimmune attack on the peripheral nerves is damage to the myelin, the fatty insulating layer of the nerve, and a nerve conduction block, leading to a muscle paralysis that may be accompanied by sensory or autonomic disturbances.

However, in mild cases, nerve axon (the long slender conducting portion of a nerve) function remains intact and recovery can be rapid if remyelination occurs. In severe cases, axonal damage occurs, and recovery depends on the regeneration of this important tissue. Recent studies on the disorder have demonstrated that approximately 80% of the patients have myelin loss, whereas, in the remaining 20%, the pathologic hallmark of the disorder is indeed axon loss.

Guillain-Barré, unlike disorders such as multiple sclerosis (MS) and Lou Gehrig's disease (ALS), is a peripheral nerve disorder and does not in general cause nerve damage to the brain or spinal cord.

Diagnosis

The diagnosis of GBS usually depends on findings such as rapid development of muscle paralysis, areflexia, absence of fever, and a likely inciting event. Cerebrospinal fluid analysis (through a lumbar spinal puncture) and electrodiagnostic tests of nerves and muscles (such as nerve conduction studies) are common tests ordered in the diagnosis of GBS.

• cerebrospinal fluid

Typical CSF findings include albumino-cytological dissociation. As opposed to infectious causes, this is an elevated protein level (100–1000 mg/dL), without an accompanying increased cell count pleocytosis. A sustained increased white blood cell count may indicate an alternative diagnosis such as infection.

• Electrodiagnostics

Electromyography (EMG) and nerve conduction study (NCS) may show prolonged distal latencies, conduction slowing, conduction block, and temporal dispersion of compound action potential in demyelinating cases. In primary axonal damage, the findings include reduced amplitude of the action potentials without conduction slowing.

Diagnostic criteria

Required:

• Progressive, relatively symmetrical weakness of two or more limbs due to neuropathy
• Areflexia
• Disorder course < 4 weeks
• Exclusion of other causes (see below)

Supportive:

• relatively symmetric weakness accompanied by numbness and/or tingling
• mild sensory involvement
• facial nerve or other cranial nerve involvement
• absence of fever
• typical CSF findings obtained from lumbar puncture
• electrophysiologic evidence of demyelination from electromyogram

Treatment

Supportive care is the cornerstone of successful management in the acute patient. Of greatest concern is respiratory failure due to paralysis of the diaphragm, the muscle most important for breathing. Intubation may be needed when there is evidence of impending failure of the muscles of breathing - when the vital capacity (VC) is less than 20 ml/kg, the negative inspiratory force (NIF) is less negative (i.e., closer to zero) than -25 cmH₂O, more than 30% decrease in either VC or NIF within 24 hours, rapid progression of disorder, or autonomic instability.

Subsequent treatment consists of attempting to reduce the body's attack on the nervous system, either by plasmapheresis, filtering antibodies out of the blood stream, or by administering intravenous immunoglobulins (IVIg), to neutralize harmful antibodies and inflammation causing disease. These two treatments are equally effective and a combination of the two is not significantly better than either alone. Glucocorticoids have not been found to be effective in GBS. ^[13][14] Treatment is usually begun as soon as the diagnosis is made. Plasmapheresis hastens recovery when used within 4 weeks of the onset of symptoms. ^[14] IVIg has equivalent efficacy to plasmapheresis when started within 2 weeks of the onset of symptoms, and has fewer complications. ^[14] IVIg is usually used first because of its ease of administration and safety profile. The use of intravenous immunoglobulins is not without risk, occasionally causing hepatitis, or in rare cases, renal failure if used for longer than five days.

Following the acute phase, treatment often consists of rehabilitation with the help of a multidisciplinary team to focus on improving activities of daily living (ADLs). Occupational therapists may offer equipment (such as wheelchair and special cutlery) to help the patient achieve ADL independence. Physiotherapists assist to correct functional movement, avoiding harmful compensations that might have a negative effect in the long run. There is also some evidence supporting physiotherapy in helping patients with Guillain–Barré syndrome regain strength, endurance, and gait quality,^[15] as well as helping them prevent contractures, bedsores, and cardiopulmonary difficulties.^[16] Speech and language therapists help regain speaking and swallowing ability, especially if the patient was intubated or received a tracheostomy.

Prognosis

Recovery usually starts after the fourth week from the onset of the disorder. Approximately 80% of patients have a complete recovery within a few months to a year, although minor findings may persist, such as areflexia. About 5–10% recover with severe disability, with most of such cases involving severe proximal motor and sensory axonal damage with inability of axonal regeneration. Despite all improvements in treatment and supportive care, the death rate is still about 2–3% even in the best intensive care units. Worldwide, the death rate runs slightly higher (4%), mostly from a lack of availability of life support equipment during the lengthy plateau lasting four to six weeks, and in some cases up to one year, when a ventilator is needed in the worst cases. About 5–10% of patients have one or more late relapses, in which case they are then classified as having chronic inflammatory demyelinating polyneuropathy (CIDP).

Poor prognostic factors include: 1) age, over 40 years, 2) history of preceding diarrheal illness, 3) requiring ventilator support, 4) high anti-GM1 titre and 5) poor upper limb muscle strength.

Epidemiology

The incidence of GBS during pregnancy is 1.7 cases per 100,000 of the population.^[17] In general, the mother will improve with treatment, but death of the fetus is a risk. The risk of Guillain–Barré syndrome increases after delivery, in particular during the first two weeks postpartum. There is evidence of Campylobacter jejuni as an antecedent infection in approximately 26% of disease cases, requiring special care in the preparation and handling of food. Congenital and neonatal Guillain–Barré syndrome have also been reported.^[18]

History

The disorder was first described by the French physician Jean Landry in 1859. In 1916, Georges Guillain, Jean Alexandre Barré, and André Strohl diagnosed two soldiers with the illness and discovered the key diagnostic abnormality of increased spinal fluid protein production, but normal cell count.^[19]

GBS is also known as acute idiopathic polyradiculoneuritis, acute idiopathic polyneuritis, French polio, Landry's ascending paralysis and Landry Guillain Barré syndrome.

Canadian neurologist C. Miller Fisher described the variant that bears his name in 1956.^[20]

Notable cases

• Markus Babbel, former international footballer, contracted GBS in 2001, following a period suffering from the Epstein–Barr virus. He lost almost an entire year of his footballing career between the two illnesses and never again demonstrated the same level of ability that won him over 50 caps for Germany.^[21]
• Tony Benn, British politician.^[22]
• Rachel Chagall, actress, contracted GBS in 1982. In 1987 she portrayed Gabriela Brimmer, a notable disabilities activist.^[23]
• Samuel Goldstein, American athlete and Paralympian^[24]
• Andy Griffith, American actor on Andy Griffith Show, and Matlock. He developed Guillain–Barré in 1983.^[25]
• Joseph Heller, author, contracted GBS in 1981. This episode in his life is recounted in the autobiographical No Laughing Matter, which contains alternating chapters by Heller and his good friend Speed Vogel.^[26]
• Luci Baines Johnson, daughter of President Lyndon Johnson and Lady Bird Johnson. Diagnosed and under treatment for Guillain–Barré in April 2010.^[27]
• Hugh McElhenny, former Hall-of-Fame, professional American football player with the San Francisco 49ers.^[28]
• Lucky Oceans, Grammy Award winning musician with Asleep at the Wheel was diagnosed with GBS in 2008.^[29]
• Len Pasquarelli, sports writer and analyst for ESPN and resident of the Pro Football Writers of America, diagnosed in 2008.^[30]
• Serge Payer, Canadian-born professional hockey player. After battling and overcoming the syndrome, he set up the Serge Payer Foundation, which is dedicated to raising money for research into new treatments and cures for Guillain–Barré syndrome.^[31]
• William “The Refrigerator” Perry, former professional American football player with the Chicago Bears, Super Bowl XX champion, and former Clemson University consensus 1st team All-American was diagnosed with GBS in 2008.^[32]
• Franklin D. Roosevelt, U.S. president. In 2003, a peer-reviewed study^[33] found that Roosevelt's paralysis — long attributed to poliomyelitis—was more likely caused by Guillain–Barré syndrome.
• Norton Simon, American industrialist and philanthropist.^[34]
• Hans Vonk, Dutch conductor.^[35]
• Danny Wuerffel, 1996 Heisman Trophy winner from the University of Florida.^[36]

References

External links

• Guillain–Barré syndrome at the Open Directory Project

Nervous system pathology, PNS, somatic (G50–G64, 350–357)   Nerve, nerve root, plexus Cranial nerve disease V (Trigeminal neuralgia, Anesthesia dolorosa) · VII (Facial nerve paralysis, Bell's palsy, Melkersson–Rosenthal syndrome, Parry–Romberg syndrome, Central seven) · XI (Accessory nerve disorder) Radiculopathy, plexopathy brachial plexus (Brachial plexus lesion, Thoracic outlet syndrome) · Phantom limb Mono- neuropathy Upper limb median nerve (Carpal tunnel syndrome, Ape hand deformity) ulnar nerve (Ulnar nerve entrapment, Froment's sign, Guyon's canal syndrome, Ulnar claw) radial nerve (Radial neuropathy, Wrist drop, Cheiralgia paresthetica) long thoracic nerve (Winged scapula) Lower limb lateral cutaneous nerve of thigh (Meralgia paraesthetica) tibial nerve (Tarsal tunnel syndrome) plantar nerve (Morton's neuroma) superior gluteal nerve (Trendelenburg's sign) sciatic nerve (Piriformis syndrome) General Causalgia · Mononeuritis multiplex · Neuropathy (Neuralgia/Neuritis) · Nerve compression syndrome   Polyneuropathies/Polyradiculoneuropathy HMSN Charcot–Marie–Tooth disease · Dejerine–Sottas disease · Refsum's disease · Hereditary spastic paraplegia Autoimmune/demyelinating Guillain–Barré syndrome · Chronic inflammatory demyelinating polyneuropathy Other Alcoholic polyneuropathy M: PNS anat(h/r/t/c/b/l/s/a)/phys(r)/devp/prot/nttr/nttm/ntrp noco/auto/cong/tumr, sysi/epon, injr proc, drug(N1B)

Immune disorders: hypersensitivity and autoimmune diseases (279.5–6) Type I/allergy/atopy (IgE) Foreign Atopic dermatitis · Allergic urticaria · Hay fever · Allergic asthma · Anaphylaxis · Food allergy (Milk, Egg, Peanut, Tree nut, Seafood, Soy, Wheat), Penicillin allergy Autoimmune none Type II/ADCC (IgM, IgG) Foreign Pernicious anemia · Hemolytic disease of the newborn Autoimmune Cytotoxic Autoimmune hemolytic anemia · Idiopathic thrombocytopenic purpura  · Bullous pemphigoid  · Pemphigus vulgaris · Rheumatic fever · Goodpasture's syndrome "Type 5"/receptor Graves' disease · Myasthenia gravis Type III (Immune complex) Foreign Henoch–Schönlein purpura · Hypersensitivity vasculitis · Reactive arthritis · Farmer's lung · Post-streptococcal glomerulonephritis · Serum sickness · Arthus reaction Autoimmune Systemic lupus erythematosus · Subacute bacterial endocarditis · Rheumatoid arthritis Type IV/cell-mediated (T-cells) Foreign Allergic contact dermatitis · Mantoux test Autoimmune Diabetes mellitus type 1 · Hashimoto's thyroiditis · Guillain–Barré syndrome  · Multiple sclerosis  · Coeliac disease · Giant-cell arteritis GVHD Transfusion-associated graft versus host disease Unknown/ multiple Foreign Hypersensitivity pneumonitis (Allergic bronchopulmonary aspergillosis) · Transplant rejection · Latex allergy (I+IV) Autoimmune Sjögren's syndrome · Autoimmune hepatitis · Autoimmune polyendocrine syndrome (APS1, APS2) · Autoimmune adrenalitis · Systemic autoimmune disease M: LMC cell/phys/auag/auab/comp, igrc imdf/ipig/hyps/tumr proc, drug(L3/4)