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Overview Guillain-Barre syndrome (GBS) is an inflammatory disorder of the peripheral nerves. The peripheral nerves convey sensory information (e.g., pain, temperature) from the body to the brain and motor (i.e., movement) signals from the brain to the body. GBS is characterized by weakness and numbness or tingling in the legs and arms, and possible loss of movement and feeling in the legs, arms, upper body, and face. Chronic inflammatory demyelinating polyradicalneuropathy (CIDP), is considered to be a related form of Guillain-Barre syndrome. It is much less common than GBS, and evolves much more slowly and usually is longer lasting. Some CIDP patients experience periods of worsening and improvement, and individual relapses are often confused with GBS. Incidence Guillain-Barre syndrome is a rare disorder; its frequency is about 1 to 2 cases in every 100,000 people per year in the United States. Men and women, young and old, are equally prone to contracting GBS. Causes Guillain-Barre syndrome is not hereditary or contagious. What causes GBS is not known; however, in about half of all cases the onset of the syndrome follows a viral or bacterial infection, such as the following: flu, common cold gastrointestinal viral infection infectious mononucleosis viral hepatitis campylobacteriosis (usually from eating undercooked poultry) porphyria (rare disease of red blood cells)

A small number of cases have been known to occur after a medical procedure, such as minor surgery. Guillain-Barre syndrome may be an autoimmune disorder in which the body produces antibodies that damage the myelin sheath that surrounds peripheral nerves. The myelin sheath is a fatty substance that surrounds axons. It increases the speed at which signals travel along the nerves. Signs and Symptoms The first symptoms of GBS are usually numbness or tingling (paresthesia) in the toes and fingers, with progressive weakness in the arms and legs over the next few days.

Some patients experience paresthesia only in their toes and legs; others only experience symptoms on one side of the body. The symptoms may stay in this phase, causing only mild difficulty in walking, requiring crutches or a walking stick. However, sometimes the illness progresses, leading to complete paralysis of the arms and legs. About one quarter of the time, the paralysis continues up the chest and freezes the breathing muscles, leaving the patient dependant on a ventilator. If the swallowing muscles are also affected, a feeding tube may be needed. In CIDP, the course of illness is longer and respiratory failure is much more unlikely. Diagnosis Because its symptoms vary and its cause is unknown, GBS can be difficult to diagnose. If the symptoms occur uniformly across the body and progress rapidly, the diagnosis is easier. Observation of the patient's symptoms and an evaluation of the medical history provide the basis for diagnosis of Guillain-Barre syndrome, although no single observation is suitable to make the diagnosis. Tests Three tests can confirm a diagnosis of Guillain-Barre syndrome. Lumbar puncture (spinal tap) The patient is given local anesthetic. Once the anesthetic has taken effect, a needle is inserted between two lower (lumbar) vertebrae and a sample of cerebrospinal fluid is drawn. An elevated level of protein in the fluid is characteristic of GBS. Electromyogram (EMG) This is an effective diagnostic tool because it records muscle activity and can show the loss of reflexes due to the disease's characteristic slowing of nerve responses. Nerve conduction velocity (NCV) This test is performed with EMG, and together, they are often referred to as EMG/NCV studies. NCV records the speed at which signals travel along the nerves. Treatment GBS is considered a medical emergency and most patients are admitted to intensive care soon after diagnosis. Though GBS can improve spontaneously, there are a number of treatments that facilitate recovery. Like GBS, CIDP can improve spontaneously. However, recovery may be very slow and the illness can either get progressively better or worse, or can follow a relapsing/remitting course. Most patients with GBS and CIDP are treated with plasmapheresis or immunoglobulin. Corticosteroids may be used to treat CIDP but are not used to treat GBS, as it worsens rather than improves the condition.

Plasmapheresis Patients diagnosed early in the course of the disease and those who are acutely ill often respond well to blood plasma exchange (plasmapheresis). In this procedure, blood is withdrawn and passed through a series of filters that separate the different types of blood cells. The blood cells are then suspended in donor or synthetic plasma and returned to the patient's body. Plasmapheresis is thought to remove the substances that damage myelin. It can shorten the course of GBS, alleviate symptoms, and prevent paralysis. Immunoglobulin Large doses of immunoglobin given intravenously can help shorten the duration of symptoms. This treatment is recommended when plasmapheresis is not available, when patients do not respond to it, and when patients are not good candidates. Medications Muscle and joint pain can be treated with over-the-counter analgesics such as aspirin. If necessary, stronger pain medication (e.g., acetaminophen with codeine) may be prescribed. Muscle spasms can be controlled with relaxants such as diazepam (Valium). In the later stages of rehabilitation, lingering sensation problems can be treated with tricyclic antidepressants or anticonvulsants such as gabapentin (Neurontin). Corticosteroids, which often effectively treat the symptoms of autoimmune disorders, actually worsen Guillain-Barre syndrome and should not be used. They are sometimes used to treat CIDP. Physical therapy Before recovery begins, caregivers move the patient's arms and legs to prevent stiffness. After symptoms subside, the rehabilitation team will prescribe an active exercise routine to help regain muscle strength and independence. Training with adaptive devices, such as a wheelchair or braces, give the patient mobility. Hydrotherapy Whirlpool therapy (hydrotherapy) may help relieve pain and be useful in retraining the movement of affected limbs. Counseling Counseling often is suggested to reassure patients diagnosed with GBS or CIDP and to help them feel positive about their treatment and recovery. Prognosis Patients may remain in the hospital for several months and recovery may take a year or more. Most patients recover completely, but some have residual weakness, numbness, and occasional pain. A small number are unable to resume their normal occupation. Fewer than 5% of GBS patients die. Those fatalities usually result from cardiovascular or respiratory complications. Death resulting from CIDP is rare.

What is Guillain-Barr Syndrome (GBS)? http://www.gbsfi.com/overview.html Guillain-Barr (Ghee-yan Bah-ray) Syndrome, also called acute inflammatory demyelinating polyneuropathy and Landry's ascending paralysis, is an inflammatory disorder of the peripheral nerves - those outside the brain and spinal cord. It is characterized by the rapid onset of weakness and, often, paralysis of the legs, arms, breathing muscles and face. GBS is the most common cause of rapidly acquired paralysis in the United States today, affecting one to two people in every 100,000. The disorder came to public attention briefly when it struck a number of people who received the 1976 Swine Flu vaccine. It continues to claim thousands of new victims each year, striking any person, at any age, regardless of gender or ethnic background. It typically begins with weakness and/or abnormal sensations of the legs and arms. It can also affect muscles of the chest, face and eyes. Although many cases are mild, some patients are virtually paralyzed. Breathing muscles may be so weakened that a machine is required to keep the patient alive. Many patients require an intensive care unit during the early course of their illness, especially if support of breathing with a machine is required. Although most people recover, the length of the illness is unpredictable and often months of hospital care are required. The majority of patients eventually return to a normal or near normal lifestyle, but many endure a protracted recovery and some remain wheelchair-bound indefinitely. The cause of GBS is not known and there is no effective treatment.

How is GBS Diagnosed? Quite often, the patient's symptoms and physical exam are sufficient to indicate the diagnosis. The rapid onset of (ascending) weakness, frequently accompanied by abnormal sensations that affect both sides of the body similarly, is a common presenting picture. Loss of reflexes, such as the knee jerk, are usually found. To confirm the diagnosis, a lumbar puncture to find elevated fluid protein and electrical test of nerve and muscle function may be performed.

How is GBS Treated? Because progression of the disease in its early stages is unpredictable, most newly diagnosed patients are hospitalized and usually placed in an intensive care unit to monitor breathing and other body functions. Care involves use of general supportive measures for the paralyzed patient, and also methods specifically designed to speed recovery, especially for those patients with major problems, such as the inability to walk. Plasma exchange (a blood "cleansing" procedure) and high dose intravenous immune globulins are often helpful to shorten the course of

GBS. Most patients, after their early hospital stay and when medically stable, are candidates for a rehabilitation program to help learn optimal use of muscles as nerve supply returns.

What Causes GBS? The cause is not known. Perhaps 50% of cases occur shortly after a microbial (viral or bacterial) infection such as a sore throat or diarrhea. Some theories suggest an autoimmune mechanism, in which the patient's defense system of antibodies and white blood cells are triggered into damaging the nerve covering or insulation, leading to weakness and abnormal sensation.

Guillain-Barr Syndrome
Last Updated: February 20, 2006

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Synonyms and related keywords: Guillain-Barr syndrome, GBS, acute inflammatory demyelinating polyneuropathy, AIDP, acute motor axonal neuropathy, AMAN, acute motor-sensory axonal neuropathy, AMSAN, Miller-Fisher syndrome, MFS, acute panautonomic neuropathy, pharyngeal-brachial-cervical variant, pure sensory variant

INTRODUCTION

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Background: In 1859, Landry published a report on 10 patients with an ascending paralysis. This was followed by a report in 1916 written by 3 French physicians working in the Sixth Army camp during the First World War; they described 2 French soldiers with motor weakness, areflexia, and albuniocytological dissociation in the cerebrospinal fluid. In this report Guillain, Barr, and Strohl carefully recorded and interpreted the tendon reflexes of their patients and became the first to recognize the peripheral nature of the illness. Further cases were recognized, and the identified syndrome was later named Guillain-Barr syndrome (GBS). Historically, GBS was a single disorder; however, current practice divides the syndrome into several variant forms.

GBS is a heterogeneous grouping of immune-mediated processes generally characterized by motor, sensory, and autonomic dysfunction. In its classic form, GBS is an acute inflammatory demyelinating polyneuropathy characterized by progressive symmetric ascending muscle weakness, paralysis, and hyporeflexia with or without sensory or autonomic symptoms; however, variants involving the cranial nerves or pure motor involvement are not uncommon. In severe cases, muscle weakness may lead to respiratory failure, and labile autonomic dysfunction may complicate the use of vasoactive and sedative drugs. Pathophysiology: Although the clinical syndrome classically presents as a rapidly progressive acute polyneuropathy, several pathologic and etiologically subtypes exist. Most patients with GBS exhibit absent or profoundly delayed conduction in action nerve fibers. This aberrant conduction results from demyelination of nerve cell axons. Peripheral nerves and spinal roots are the major sites of demyelination, but cranial nerves also may be involved. GBS is believed to result from an autoimmune response, both humoral and cell mediated, to a recent infection or any of a long list of medical problems. Its relation to antecedent infections and the identification of various antiganglioside antibodies suggest that molecular mimicry may serve as a possible mechanism for the disease. The antibodies formed against gangliosidelike epitopes in the lipopolysaccharide layer of some infectious agents have been shown in both necropsy and animal models to cross-react with the ganglioside surface molecules of peripheral nerves. Symptoms generally coincide pathologically with various patterns of lymphocytic infiltration and macrophage-mediated demyelination, depending on the subtype in question. Recovery is typically associated with remyelination. In a subset of patients, GBS is associated primarily with myelin-sparing axonal damage resulting from a direct cellular immune attack on the axon itself. The acute inflammatory demyelinating polyneuropathy (AIDP) subtype of GBS is by far the most commonly identified form in the United States. It is generally preceded by an antecedent bacterial or viral infection. Nearly 40% of patients are seropositive for Campylobacter jejuni. Lymphocytic infiltration and macrophage-mediated demyelination of the peripheral nerves are present. Symptoms generally resolve with remyelination. The acute motor axonal neuropathy (AMAN) subtype is a purely motor subtype, which is more prevalent amongst pediatric age groups. Nearly 70-75% of patients are seropositive for Campylobacter. One third of these cases may actually be hyperreflexic. AMAN is generally characterized by a rapidly progressive weakness, ensuing respiratory failure, and good recovery. Acute motor-sensory axonal neuropathy (AMSAN) is an acute severe illness similar to AMAN except that AMSAN also affects sensory nerves and roots. Patients are typically adults with both motor and sensory dysfunction, marked muscle wasting, and poor recovery.

Miller-Fisher syndrome (MFS) is a rare variant that typically presents with the classic triad of ataxia, areflexia, and ophthalmoplegia. The ataxia tends to be out of proportion to the degree of sensory loss. Patients may also have mild limb weakness, ptosis, facial palsy, or bulbar palsy. Anti-GQ1b antibodies are prominent in this variant, and patients have reduced or absent sensory nerve action potentials and absent tibial H reflex. Recovery generally occurs within 1-3 months. Acute panautonomic neuropathy is among the rarest of all variants and involves both the sympathetic and parasympathetic nervous systems. Cardiovascular involvement is common, and dysrhythmias are a significant source of mortality in this form of the disease. The patient may also experience sensory symptoms. Recovery is gradual and often incomplete. Frequency:

In the US: The incidence is 1-3 per 100,000 inhabitants, making GBS the most common cause of acute flaccid paralysis in the United States. Internationally: AMAN is a purely motor form that occurs mainly in northern China but is also more common in developing nations. AIDP accounts for up to 90% of cases in Europe, North America, and the developed world. Epidemiologic studies from Japan indicate that in this region a greater percentage of GBS cases are associated with antecedent C jejuni infections and a lesser number are related to antecedent cytomegalovirus infections when compared with their North American and European counterparts.

Mortality/Morbidity: Most patients (up to 85%) with GBS achieve a full and functional recovery within 6-12 months. Recovery is maximal by 18 months past onset.

Patients may have persistent weakness, areflexia, imbalance, or sensory loss. Approximately 7-15% of patients have permanent neurologic sequelae including bilateral footdrop, intrinsic hand muscle wasting, sensory ataxia, and dysesthesia. The mortality rate varies but may be less than 5% in tertiary care centers with a team of medical professionals who are familiar with GBS management. Causes of death include adult respiratory distress syndrome, sepsis, pneumonia, pulmonary emboli, and cardiac arrest. Despite intensive care, 3-8% of patients die.

Race: No racial preponderance exists.

Sex: The male-to-female ratio is 1.5:1. A Swedish epidemiologic study indicated that the incidence of GBS is lower during pregnancy and increases in the months immediately following delivery. Age: GBS occurs at all ages, but a bimodal distribution with peaks in young adulthood (15-35 y) and elderly persons (50-75 y) appears to exist. Rare cases have been noted in infants.

CLINICAL

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History: The typical GBS patient (likely AIDP) presents 2-4 weeks after a relatively benign respiratory or gastrointestinal illness complaining of dysesthesias of the fingers and lower extremity proximal muscle weakness. The weakness may progress over hours to days to involve the arms, truncal muscles, cranial nerves, and the muscles of respiration. The illness progresses from days to weeks, with the mean time to the nadir of clinical function being 12 days and 98% of patients reaching a nadir by 4 weeks. A plateau phase of persistent, unchanging symptoms then ensues followed days later by gradual symptom improvement. The mean time to improvement and clinical recovery are 28 and 200 days, respectively.

Up to one third of patients require mechanical ventilation during the course of their illness. Causes for this include cranial nerve involvement affecting airway maintenance and respiratory muscle paralysis. Motor dysfunction
o

Symmetric limb weakness typically begins as proximal lower extremity weakness and ascends to involve the upper extremities, truncal muscles, and the head. Inability to stand or walk despite reasonable strength, especially when ophthalmoparesis or impaired proprioception is present. Respiratory muscle weakness with shortness of breath may be present. Cranial nerve palsies (III-VII, IX-XII) may be present. Patients may present with facial weakness mimicking Bell palsy, dysphagia, dysarthria, ophthalmoplegia, and pupillary disturbances. The Miller-Fisher variant is unique in that this subtype begins with cranial nerve deficits. Lack of deep tendon reflexes is a hallmark sign.

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Sensory dysfunction
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Paresthesia generally begins in the toes and fingertips and progresses upward but generally not extending beyond the wrists or ankles. Pain is most severe in the shoulder girdle, back, buttocks, and thighs and may occur with even the slightest movements. Loss of vibration, proprioception, touch, and pain distally may be present.

Autonomic dysfunction
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Cardiovascular signs may include tachycardia, bradycardia, dysrhythmias, wide fluctuations in blood pressure, and postural hypotension. Urinary retention due to urinary sphincter disturbances may be noted. Constipation due to bowel paresis and gastric dysmotility may be present. Facial flushing and venous pooling secondary to abnormal vasomotor tone may be present. Hypersalivation Anhydrosis Tonic pupils

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Papilledema secondary to elevated intracranial pressure is present in rare cases.

Physical:

Vital signs
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Patient may have tachycardia or bradycardia, hypertension or hypotension, or hyperthermia or hypothermia. Low oxygen saturation may be present with advanced respiratory muscle involvement.

Cranial nerves: Patients may present with facial weakness mimicking Bell palsy, dysphagia, dysarthria, ophthalmoplegia, and pupillary disturbances. Dysreflexia

Patients with manifest weakness are invariably hyporeflexic or areflexic in the involved areas. Respiratory Poor inspiratory effort or diminished breath sounds

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Motor
o

Symmetric limb weakness typically begins as proximal lower extremity weakness and ascends to involve the upper extremities, truncal muscles, and the head. Inability to stand or walk despite reasonable strength, especially when ophthalmoparesis or impaired proprioception is present. Hypotonia Wasting of limb muscles is not an acute finding.

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Abdominal
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Paucity or absence of bowel sounds suggests paralytic ileus. Suprapubic tenderness or fullness may be suggestive of urinary retention.

Sensory: Patients may experience numbness, paresthesias, impaired proprioception, and pain. Papilledema secondary to elevated intracranial pressure is present in rare cases.

Causes: GBS has been associated with antecedent bacterial and viral infections, administration of certain vaccinations, and other systemic illnesses. Case reports exist regarding numerous medications and procedures; however, whether any causal link exists is unclear.

Bacterial infections include C jejuni, Haemophilus influenzae, Mycoplasma pneumoniae, and Borrelia burgdorferi. Viral infections include cytomegalovirus, Ebstein-Barr virus, and during seroconversion with the human immunodeficiency virus (HIV). Vaccines

A study reviewing the cases of GBS during the 1992-1993 and 1993-1994 influenza seasons found an adjusted relative risk of 1.7 cases per 1 million influenza vaccinations. Epidemiologic studies from Finland, southern California, and Latin America failed to validate an earlier retrospective study from Finland suggesting a cause-effect relationship between oral polio vaccination and GBS. Data from 2 large-scale epidemiologic studies found that fewer cases of GBS occurred following administration of tetanus toxoid containing vaccinations than occurred in the baseline population. Two epidemiologic studies failed to show any conclusive epidemiologic association between GBS and the hepatitis B vaccine. A large Latin American study of more than 2000 children with GBS following a mass measles vaccination program in 1992 and 1993 failed to establish a statistically significant causal relationship between administration of the measles vaccine and GBS. A recent report from the Centers for Disease Control and Prevention (CDC) suggests that an increased incidence of GBS may exist amongst recipients of the Menactra meningococcal conjugate vaccine. Case reports exist regarding group A streptococci vaccines, the rabies vaccine, and the swine flu vaccine; however, conclusive statistically significant evidence is lacking.

Medications
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A case-controlled study showed that patients with GBS had used antimotility drugs and penicillins more often, and oral contraceptives less often. No definite cause-effect relationship has been established. Case reports exist regarding streptokinase, isotretinoin, danazol, captopril, gold, heroin, and epidural anesthesia among others.

Anecdotal associations include systemic lupus erythematosus, sarcoidosis, lymphoma, surgery, renal transplantation, and snake bites.
Section 4 of 10

DIFFERENTIALS

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CBRNE - Botulism Cauda Equina Syndrome Diphtheria Encephalitis Hyperkalemia Hypokalemia Hypophosphatemia Meningitis Myasthenia Gravis Polymyositis Spinal Cord Infections Spinal Cord Injuries Systemic Lupus Erythematosus Tick-Borne Diseases, Lyme Toxicity, Alcohols Toxicity, Heavy Metals Toxicity, Organophosphate and Carbamate Other Problems to be Considered: Basilar artery occlusion Chronic inflammatory demyelinating polyneuropathy Folate deficiency Hereditary neuropathies Neoplasia Neurotoxic fish poisoning Poliomyelitis Porphyria Sarcoid meningitis Spinal cord compression Spinal cord syndromes, particularly postinfection Tick paralysis Transverse myelitis Vitamin B-12 deficiency

WORKUP

Section 5 of 10

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Lab Studies:

Diagnosis usually is made on clinical grounds. Laboratory studies are useful to rule out other diagnoses and to better assess functional status and prognosis. Lumbar puncture and spinal fluid analysis

Elevated or rising protein levels on serial lumbar punctures and 10 or fewer mononuclear cells/mm2 strongly support the diagnosis. Most, but not all, patients have an elevated level of CSF protein (>400 mg/L), with no elevation in CSF cell counts. Normal CSF protein does not rule out GBS because the level of CSF protein remains normal in 10% of cases and because any rise in the CSF protein may not be observed until 1-2 weeks after the onset of weakness. CSF pleocytosis is well recognized in HIV-associated GBS.

Biochemical screening
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Biochemical screening includes electrolytes levels; liver function tests (LFTs); CPK level; erythrocyte sedimentation rate (ESR); antiganglioside antibodies; and antibodies to C jejuni, cytomegalovirus, Ebstein-Barr virus, herpes simplex virus (HSV), HIV, and M pneumoniae. Syndrome of inappropriate antidiuretic hormone (SIADH) occurs in some patients with GBS. LFTs results are elevated in up to one third of patients. CPK and ESR may be elevated with myopathies or systemic inflammatory conditions. Patients with the Miller-Fisher variant may have anti-GQ1b antibodies. Patients who have antibody subtype GM1 may have poorer prognoses.

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Stool culture for C jejuni Pregnancy test

Imaging Studies:

MRI
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MRI is a sensitive but nonspecific test. Spinal nerve root enhancement with gadolinium is a nonspecific feature seen in inflammatory conditions and caused by disruption of the bloodnerve barrier.

Selective anterior nerve root enhancement appears to be strongly suggestive of GBS. The cauda equine nerve roots are enhanced in 83% of patients.

Other Tests:

Forced vital capacity

o

Forced vital capacity (FVC) is very helpful in guiding disposition and therapy. Patients with an FVC less than 15-20 mL/kg, maximum inspiratory pressure less than 30 cm H2O, or a maximum expiratory pressure less than 40 cm H2O generally progress to require prophylactic intubation and mechanical ventilation.

Nerve conduction studies

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A delay in F waves is present, implying nerve root demyelination. Nerve motor action potentials may be decreased. This is technically difficult to determine until the abnormality is severe. Compound muscle action potential (CMAP) amplitude may be decreased. Frequently patients show evidence of conduction block or dispersion of responses at sites of natural nerve compression. The extent of decreased action potentials correlates with prognosis. Prolonged distal latencies Rarely neurophysiologic testing is normal in patients with GBS. This is believed to be due to the location of demyelinating lesions in proximal sites not amenable to study.

o o

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Muscle biopsy may help to distinguish GBS from a primary myopathy in unclear cases. Many different abnormalities may be seen on ECG, including second-degree and third-degree atrioventricular (AV) block, T-wave abnormalities, ST depression, QRS widening, and a variety of rhythm disturbances.

Procedures:

Lumbar puncture and spinal fluid analysis

TREATMENT

Section 6 of 10

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Prehospital Care:

ABCs, IV, oxygen, and assisted ventilation may be indicated. Monitor for cardiac arrhythmias. Transport expeditiously.

Emergency Department Care:

ABCs, IV, oxygen, and assisted ventilation may be indicated. Intubation should be performed on patients who develop any degree of respiratory failure. Clinical indicators of the need for intubation include hypoxia, rapidly declining respiratory function, poor or weak cough, and suspected aspiration. Typically, intubation is indicated whenever the FVC is less than 15 mL/kg. Patients who have, or are suspected of having, GBS should be monitored closely for changes in blood pressure, heart rate, and other arrhythmias.
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Treatment rarely is needed for tachycardia. Atropine is recommended for symptomatic bradycardia. Because of the lability of dysautonomia, hypertension is best treated with short-acting agents, such as a short-acting beta-blocker or nitroprusside. Hypotension of dysautonomia usually responds to intravenous fluids and supine positioning. Temporary pacing may be required for patients with second-degree and third-degree heart block.

Consultations:

A neurologist should be consulted if any uncertainty exists as to the diagnosis. The ICU team should be consulted for evaluation of need for admission to the unit.

MEDICATION

Section 7 of 10

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Only plasma exchange therapy and IV immune serum globulin have proven effective. Both therapies have been shown to shorten recovery time by as much as 50%. The cost, difficulty, and efficacy of the 2 treatments are comparable. Corticosteroids are ineffective as monotherapy. Evidence suggests that no benefit exists in giving steroids in combination with IV immunoglobulins or in combination with plasma exchange. Immunoadsorption is an alternative that is still in the early stages of evaluation. A small prospective study showed no difference in outcome between patients treated with immunoadsorption and those treated with plasma exchange. Interferon beta was not associated with significant clinical improvement compared with controls in a small randomized control trial. Deep vein thrombosis (DVT) prophylaxis with gradient compression hose and subcutaneous low molecular weight heparin (LMWH) may cause a dramatic reduction in the incidence of venous thromboembolism, one of the major sequela of extremity paralysis. True gradient compression stockings (30-40 mm Hg or higher) are highly elastic, providing a gradient of compression that is highest at the toes and gradually decreases to the level of the thigh. This reduces capacity venous volume by approximately 70% and increases the measured velocity of blood flow in the deep veins by a factor of 5 or more. The ubiquitous white stockings known as antiembolic stockings or thromboembolic disease (TED) hose produce a maximum compression of 18 mm Hg and rarely are fitted in such a way as to provide adequate gradient compression. They have not been shown effective as prophylaxis against thromboembolism.

Drug Category: Blood product derivatives -- Are used to improve the clinical and
immunologic aspects of the disease. They may decrease autoantibody production and increase solubilization and removal of immune complexes. Intravenous immune globulin (IVIG, Gammagard S/D) -May neutralize circulating myelin antibodies through antiidiotypic antibodies and down-regulate proinflammatory cytokines, including interferon-gamma (INF-gamma). In addition, may block the complement cascade and promote remyelination. 0.4 g/kg/d IV for 5 d Administer as in adults

Drug Name

Adult Dose Pediatric Dose

Contraindications Interactions Pregnancy

Documented hypersensitivity; IgA deficiency and antiIgE/IgG antibodies None reported C - Safety for use during pregnancy has not been established. Check serum IgA before IVIG (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion) Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease; lab result changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia Albumin -- Used in plasma exchange when the patient's plasma is exchanged with a plasma substitute. May remove autoantibodies and immune complexes from serum. Plasma exchange is carried out with albumin (50 mL/kg) over a 10d period. Has been shown to decrease recovery time by 50%. May aid in removing cytotoxic constituents from serum. Remove 3-4 L of the patient's plasma and substitute with albumin; administered IV <16 years: Not established >16 years: Administer as in adults Pulmonary edema; renal insufficiency None reported C - Safety for use during pregnancy has not been established. While theoretically attractive, no proven benefit of colloid resuscitation over isotonic crystalloids exists

Precautions

Drug Name

Adult Dose Pediatric Dose Contraindications Interactions Pregnancy Precautions

Drug Category: Fractionated low molecular weight heparins -- These are used in
the prophylaxis of DVT. Fractionated LMWH first became available in the United States as enoxaparin (Lovenox). LMWH has been used widely in pregnancy, although clinical trials are not yet available to demonstrate that it is as safe as unfractionated heparin. Reversible elevation of hepatic transaminases occurs occasionally. Heparin-associated thrombocytopenia has been observed with fractionated low molecular weight heparin.

Drug Name

Enoxaparin (Lovenox) -- Enhances the inhibition of factor Xa and thrombin by increasing antithrombin III activity. Also slightly affects thrombin and clotting time and preferentially increases the inhibition of factor Xa. Has a wide therapeutic window; the prophylactic dose is not adjusted based upon the patient's weight. Enoxaparin is safer and more effective than unfractionated heparin for the prophylaxis of venous thromboembolism. The average duration of treatment is 7-14 d. 30 mg SC bid Not established The following doses have been suggested: <2 months: 0.75 mg/kg/dose bid >2 months to 18 years: 0.5 mg/kg/dose bid Documented hypersensitivity; major bleeding and thrombocytopenia Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding B - Usually safe but benefits must outweigh the risks. If thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminases may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated LMWH; 1 mg of protamine sulfate will reverse effect of approximately 1 mg of enoxaparin if significant bleeding complications develop
Section 8 of 10

Adult Dose Pediatric Dose

Contraindications Interactions Pregnancy

Precautions

FOLLOW-UP

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Further Inpatient Care:

Admission to the ICU should be considered for all patients with labile dysautonomia, an FVC of less than 20 mL/kg, or severe bulbar palsy. Any patients exhibiting clinical signs of respiratory compromise, in any degree, also should be admitted to an ICU. The risk of sepsis and infection can be decreased by use of minimal sedation, frequent physiotherapy, and mechanical ventilation with positive end expiratory pressure where appropriate.

The risk of DVT and pulmonary embolus may be minimized by administration of heparin or a low molecular weight heparin and intermittent pneumatic compression devices. The use of cardiac telemetry and pacing in the case of severe bradycardia may help to reduce the risk of cardiac morbidity and mortality. Pain may be symptomatically improved by frequent passive limb movements, gentle massage, frequent position changes, and the use of carbamazepine and gabapentin. Narcotics should be used judiciously because patients may already be at risk for ileus.

Further Outpatient Care:

Physical therapy and occupational therapy may be beneficial in helping patients to regain their baseline functional status.

Transfer:

Transfer may be appropriate if a facility does not have the proper resources to care for patients who may require prolonged intubation or prolonged intensive care.

Complications:

With modern methods of respiratory management, most complications result from long-term paralysis. Possible complications include the following:
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Persistent paralysis Respiratory failure, mechanical ventilation Hypotension or hypertension Thromboembolism, pneumonia, skin breakdown Cardiac arrhythmia Ileus Aspiration Urinary retention

Psychiatric problems such as depression and anxiety

Prognosis:

Poor prognosis is associated with rapid progression of symptoms, advanced age, prolonged ventilation (>1 mo), and severe reduction of action potentials on neuromuscular testing. Published reports indicate full recovery may be expected in 50-95% of cases. Neurologic sequelae
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Reported incidence of permanent neurologic sequelae ranges from 1040%. The worst-case scenario is tetraplegia within 24 hours with incomplete recovery after 18 months or longer. The best-case scenario is mild difficulty walking, with recovery within weeks. The usual scenario is peak weakness in 10-14 days with recovery in weeks to months. Average time on a ventilator (without treatment) is 50 days.

Mortality
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Most is due to severe autonomic instability or from the complications of prolonged intubation and paralysis. Mortality rates range from 5-10%.

Patient Education:

For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Guillain-Barr Syndrome.
Section 9 of 10

MISCELLANEOUS

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Medical/Legal Pitfalls:

Failure to anticipate dysrhythmias and autonomic instability Failure to anticipate progressive respiratory failure

Failure to correctly diagnose GBS in patients with a variant form of the disease or in those with a normal CSF protein Failure to provide adequate DVT prophylaxis in a patient that develops a DVT and/or pulmonary embolism.

Special Concerns:

The leading cause of death in elderly patients with GBS is arrhythmia. Recurrence is rare but has been reported in 2-5% of patients. Variants may present with pure motor dysfunction or acute dysautonomia. The Miller-Fisher syndrome is a variant of GBS in which the initial symptoms include ataxia, ophthalmoplegia, and areflexia.

SINDROMA GUILLAIN-BARRE http://library.usu.ac.id/download/fk/bedah-iskandar%20japardi46.pdf Dr ISKANDAR JAPARDI Fakultas Kedokteran Bagian Bedah Universitas Sumatera Utara Pendahuluan Sindroma Guillain-Barre (SGB) merupakan penyebab kelumpuhan yang cukup sering dijumpai pada usia dewasa muda. SGB ini seringkali mencemaskan penderita dan keluarganya karena terjadi pada usia produktif, apalagi pada beberapa keadaan dapat menimbulkan kematian, meskipun pada umumnya mempunyai prognosa yang baik. Beberapa nama disebut oleh beberapa ahli untuk penyakit ini, yaitu Idiopathic polyneuritis, Acute Febrile Polyneuritis, Infective Polyneuritis, Post Infectious Polyneuritis, Acute Inflammatory Demyelinating Polyradiculoneuropathy, Guillain Barre Strohl Syndrome, Landry Ascending paralysis, dan Landry Guillain Barre Syndrome. Definisi Parry mengatakan bahwa, SGB adalah suatu polineuropati yang bersifat ascending dan akut yang sering terjadi setelah 1 sampai 3 minggu setelah infeksi akut. Menurut Bosch, SGB merupakan suatu sindroma klinis yang ditandai adanya paralisis flasid yang terjadi secara akut berhubungan dengan proses autoimun dimana targetnya adalah saraf perifer, radiks, dan nervus kranialis. Sejarah Pada tahun 1859, seorang neurolog Perancis, Jean-Baptiste Landry pertama kali menulis tentang penyakit ini, sedangkan istilah landry ascending paralysis diperkenalkan oleh Westphal. Osler menyatakan terdapatnya hubungan SGB dengan kejadian infeksi akut. Pada tahun 1916, Guillain, Barre dan Strohl menjelaskan tentang adanya perubahan khas berupa peninggian protein cairan serebrospinal (CSS) tanpa disertai peninggian jumlah sel. Keadaan ini disebut sebagai disosiasi sitoalbuminik. Nama SGB dipopulerkan oleh Draganescu dan Claudian. Menurut

Lambert dan Murder mengatakan bahwa untuk menegakkan diagnosa SGB selain berdasarkan gejala klinis,pemeriksaan CSS, juga adanya kelainan pada pemeriksaan EMG dapat membantu menegakkan diagnosa. Terdapat perlambatan kecepatan hantar saraf pada EMG. Epidemiologi Penyakit ini terjadi di seluruh dunia, kejadiannya pada semua musim. Dowling dkk mendapatkan frekwensi tersering pada akhir musism panas dan musim gugur dimana terjadi peningkatan kasus influenza. Pada penelitian Zhao Baoxun didapatkan bahwa penyakit ini hampir terjadi pada setiap saat dari setiap bulan 2002 digitized by USU digital library 2 dalam setahun, sekalipun demikian tampak bahwa 60% kasus terjadi antara bulan Juli s/d Oktober yaitu pada akhir musim panas dan musim gugur. Insidensi sindroma Guillain-Barre bervariasi antara 0.6 sampai 1.9 kasus per 100.000 orang pertahun. Selama periode 42 tahun Central Medical Mayo Clinic melakukan penelitian mendapatkan insidensi rate 1.7 per 100.000 orang. Terjadi puncak insidensi antara usia 15-35 tahun dan antara 50-74 tahun. Jarang mengenai usia dibawah 2 tahun. Usia termuda yang pernah dilaporkan adalah 3 bulan dan paling tua usia 95 tahun. Laki-laki dan wanita sama jumlahnya. Dari pengelompokan ras didapatkan bahwa 83% penderita adalah kulit putih, 7% kulit hitam, 5% Hispanic, 1% Asia dan 4% pada kelompok ras yang tidak spesifik. Data di Indonesia mengenai gambaran epidemiologi belum banyak. Penelitian Chandra menyebutkan bahwa insidensi terbanyak di Indonesia adalah dekade I, II, III (dibawah usia 35 tahun) dengan jumlah penderita laki-laki dan wanita hampir sama. Sedangkan penelitian di Bandung menyebutkan bahwa perbandingan laki-laki dan wanita 3 : 1 dengan usia rata-rata 23,5 tahun. Insiden tertinggi pada bulan April s/d Mei dimana terjadi pergantian musim hujan dan kemarau. Etiologi Etiologi SGB sampai saat ini masih belum dapat diketahui dengan pasti penyebabnya dan masih menjadi bahan perdebatan. Beberapa keadaan/penyakit yang mendahului dan mungkin ada hubungannya dengan terjadinya SGB, antara lain: Infeksi Vaksinasi Pembedahan Penyakit sistematik: o keganasan o systemic lupus erythematosus o tiroiditis o penyakit Addison Kehamilan atau dalam masa nifas SGB sering sekali berhubungan dengan infeksi akut non spesifik. Insidensi kasus SGB yang berkaitan dengan infeksi ini sekitar antara 56% - 80%, yaitu 1 sampai 4 minggu sebelum gejala neurologi timbul seperti infeksi saluran pernafasan atas atau infeksi gastrointestinal Infeksi akut yang berhubungan dengan SGB Infeksi Definite Probable Possible Virus CMV EBV HIV Varicella-zoster Vaccinia/smallpox Influenza

Measles Mumps Rubella Hepatitis Coxsackie Echo Bakteri Campylobacter Jejeni Mycoplasma Pneumonia Typhoid Borrelia B Paratyphoid Brucellosis Chlamydia Legionella Listeria 2002 digitized by USU digital library 3 Patogenesa Mekanisme bagaimana infeksi, vaksinasi, trauma, atau faktor lain yang mempresipitasi terjadinya demielinisasi akut pada SGB masih belum diketahui dengan pasti. Banyak ahli membuat kesimpulan bahwa kerusakan saraf yang terjadi pada sindroma ini adalah melalui mekanisme imunlogi. Bukti-bukti bahwa imunopatogenesa merupakan mekanisme yang menimbulkan jejas saraf tepi pada sindroma ini adalah: 1. didapatkannya antibodi atau adanya respon kekebalan seluler (celi mediated immunity) terhadap agen infeksious pada saraf tepi. 2. adanya auto antibodi terhadap sistem saraf tepi 3. didapatkannya penimbunan kompleks antigen antibodi dari peredaran pada pembuluh darah saraf tepi yang menimbulkan proses demyelinisasi saraf tepi. Proses demyelinisasi saraf tepi pada SGB dipengaruhi oleh respon imunitas seluler dan imunitas humoral yang dipicu oleh berbagai peristiwa sebelumnya, yang paling sering adalah infeksi virus. Peran imunitas seluler Dalam sistem kekebalan seluler, sel limposit T memegang peranan penting disamping peran makrofag. Prekursor sel limposit berasal dari sumsum tulang (bone marrow) steam cell yang mengalami pendewasaan sebelum dilepaskan kedalam jaringan limfoid danperedaran. Sebelum respon imunitas seluler ini terjadi pada saraf tepi antigen harus dikenalkan pada limposit T (CD4) melalui makrofag. Makrofag yang telah menelan (fagositosis) antigen/terangsang oleh virus, allergen atau bahan imunogen lain akan memproses antigen tersebut oleh penyaji antigen (antigen presenting cell = APC). Kemudian antigen tersebut akan dikenalkan pada limposit T (CD4). Setelah itu limposit T tersebut menjadi aktif karena aktivasi marker dan pelepasan substansi interlekuin (IL2), gamma interferon serta alfa TNF. Kelarutan E selectin dan adesi molekul (ICAM) yang dihasilkan oleh aktifasi sel endothelial akan berperan dalam membuka sawar darah saraf, untuk mengaktifkan sel limfosit T dan pengambilan makrofag . Makrofag akan mensekresikan protease yang dapat merusak protein myelin disamping menghasilkan TNF dan komplemen. Patologi Pada pemeriksaan makroskopis tidak tampak jelas gambaran pembengkakan saraf tepi. Dengan mikroskop sinar tampak perubahan pada saraf tepi. Perubahan pertama berupa edema yang terjadi pada hari ke tiga atau ke empat, kemudian

timbul pembengkakan dan iregularitas selubung myelin pada hari ke lima, terlihat beberapa limfosit pada hari ke sembilan dan makrofag pada hari ke sebelas, poliferasi sel schwan pada hari ke tigabelas. Perubahan pada myelin, akson, dan selubung schwan berjalan secara progresif, sehingga pada hari ke enampuluh enam, sebagian radiks dan saraf tepi telah hancur. Asbury dkk mengemukakan bahwa perubahan pertama yang terjadi adalah infiltrasi sel limfosit yang ekstravasasi dari pembuluh darah kecil pada endo dan epineural. Keadaan ini segera diikuti demyelinisasi segmental. Bila peradangannya berat akan berkembang menjadi degenerasi Wallerian. Kerusakan myelin disebabkan 2002 digitized by USU digital library 4 makrofag yang menembus membran basalis dan melepaskan selubung myelin dari sel schwan dan akson. Klasifikasi Beberapa varian dari sindroma Guillan-Barre dapat diklasifikasikan, yaitu: 1. Acute inflammatory demyelinating polyradiculoneuropathy 2. Subacute inflammatory demyelinating polyradiculoneuropathy 3. Acute motor axonal neuropathy 4. Acute motor sensory axonal neuropathy 5. Fishers syndrome 6. Acute pandysautonomia Gejala klinis dan kriteria diagnosa Diagnosa SGB terutama ditegakkan secara klinis. SBG ditandai dengan timbulnya suatu kelumpuhan akut yang disertai hilangnya refleks-refleks tendon dan didahului parestesi dua atau tiga minggu setelah mengalami demam disertai disosiasi sitoalbumin pada likuor dan gangguan sensorik dan motorik perifer. Kriteria diagnosa yang umum dipakai adalah criteria dari National Institute of Neurological and Communicative Disorder and Stroke (NINCDS), yaitu: I. Ciri-ciri yang perlu untuk diagnosis: Terjadinya kelemahan yang progresif Hiporefleksi II. Ciri-ciri yang secara kuat menyokong diagnosis SGB: a. Ciri-ciri klinis: Progresifitas: gejala kelemahan motorik berlangsung cepat, maksimal dalam 4 minggu, 50% mencapai puncak dalam 2 minggu, 80% dalam 3 minggu, dan 90% dalam 4 minggu. Relatif simetris Gejala gangguan sensibilitas ringan Gejala saraf kranial ?50% terjadi parese N VII dan sering bilateral. Saraf otak lain dapat terkena khususnya yang mempersarafi lidah dan otot-otot menelan, kadang < 5% kasus neuropati dimulai dari otot ekstraokuler atau saraf otak lain Pemulihan: dimulai 2-4 minggu setelah progresifitas berhenti, dapat memanjang sampai beberapa bulan. Disfungsi otonom. Takikardi dan aritmia, hipotensi postural, hipertensi dangejala vasomotor. Tidak ada demam saat onset gejala neurologis b. Ciri-ciri kelainan cairan serebrospinal yang kuat menyokong diagnosa: Protein CSS. Meningkat setekah gejala 1 minggu atau terjadi peningkatan pada LP serial Jumlah sel CSS < 10 MN/mm3 Varian:

o Tidak ada peningkatan protein CSS setelah 1 minggu gejala o Jumlah sel CSS: 11-50 MN/mm3 2002 digitized by USU digital library 5 c. Gambaran elektrodiagnostik yang mendukung diagnosa: Perlambatan konduksi saraf bahkan blok pada 80% kasus. Biasanya kecepatan hantar kurang 60% dari normal Diagnosa Banding Gejala klinis SGB biasanya jelas dan mudah dikenal sesuai dengan kriteria diagnostik dari NINCDS, tetapi pada stadium awal kadang-kadang harus dibedakan dengan keadaan lain, seperti: Mielitis akuta Poliomyelitis anterior akuta Porphyria intermitten akuta Polineuropati post difteri Terapi Pada sebagian besar penderita dapat sembuh sendir. Pengobatan secara umum bersifat simtomik. Meskipun dikatakan bahwa penyakit ini dapat sembuh sendiri, perlu dipikirkan waktu perawatan yang cukup lama dan angka kecacatan (gejala sisa) cukup tinggi sehingga pengobatan tetap harus diberikan. Tujuan terapi khusus adalah mengurangi beratnya penyakit dan mempercepat penyembuhan melalui sistem imunitas (imunoterapi). Kortikosteroid Kebanyakan penelitian mengatakan bahwa penggunaan preparat steroid tidak mempunyai nilai/tidak bermanfaat untuk terapi SGB. Plasmaparesis Plasmaparesis atau plasma exchange bertujuan untuk mengeluarkan faktor autoantibodi yang beredar. Pemakain plasmaparesis pada SGB memperlihatkan hasil yang baik, berupa perbaikan klinis yang lebih cepat, penggunaan alat bantu nafas yang lebih sedikit, dan lama perawatan yang lebih pendek. Pengobatan dilakukan dengan mengganti 200-250 ml plasma/kg BB dalam 7-14 hari. Plasmaparesis lebih bermanfaat bila diberikan saat awal onset gejala (minggu pertama). Pengobatan imunosupresan: 1. Imunoglobulin IV Pengobatan dengan gamma globulin intervena lebih menguntungkan dibandingkan plasmaparesis karena efek samping/komplikasi lebih ringan. Dosis maintenance 0.4 gr/kg BB/hari selama 3 hari dilanjutkan dengan dosis maintenance 0.4 gr/kg BB/hari tiap 15 hari sampai sembuh. 2. Obat sitotoksik Pemberian obat sitoksik yang dianjurkan adalah: 6 merkaptopurin (6-MP) azathioprine cyclophosphamid Efek samping dari obat-obat ini adalah: alopecia, muntah, mual dan sakit kepala. 2002 digitized by USU digital library 6 Prognosa Pada umumnya penderita mempunyai prognosa yang baik tetapi pada sebagian kecil penderita dapat meninggal atau mempunyai gejala sisa. 95% terjadi penyembuhan tanpa gejala sisa dalam waktu 3 bulan bila dengankeadaan antara lian: pada pemeriksaan NCV-EMG relatif normal

mendapat terapi plasmaparesis dalam 4 minggu mulai saat onset progresifitas penyakit lambat dan pendek pada penderita berusia 30-60 tahun