Neurology Assignment

On

Guillain

Barre Syndrome

Submitted By:

Amit Kochhar

B.O.T.-4th year

18th Batch

Roll No. 1

Introduction

The term Guillain–Barré syndrome (GBS) tends to be used interchangeably with acute idiopathic demyelinating polyneuropathy. Other names used for the condition have included: acute post-infective polyradiculoneuropathy, acute infectious polyneuritis, Landry–Guillain–Barré–Strohl syndrome, and post-infective polyneuritis. These conditions produce acute and diffuse demyelination or conduction block, or less frequently axonal degeneration affecting the spinal roots and peripheral nerves, and occasionally the cranial nerves. They are usually post-infective and recover spontaneously.

Guillain-Barré syndrome is a disorder in which the body's immune system attacks part of the peripheral nervous system. The first symptoms of this disorder include varying degrees of weakness or tingling sensations in the legs. In many instances the weakness and abnormal sensations spread to the arms and upper body. These symptoms can increase in intensity until certain muscles cannot be used at all and, when severe, the patient is almost totally paralyzed. In these cases the disorder is life threatening - potentially interfering with breathing and, at times, with blood pressure or heart rate and is considered a medical emergency. Such a patient is often put on a respirator to assist with breathing and is watched closely for problems such as an abnormal heart beat, infections, blood clots, and high or low blood pressure. Most patients, however, recover from even the most severe cases of Guillain-Barré syndrome, although some continue to have a certain degree of weakness.

Guillain-Barré syndrome can affect anybody. It can strike at any age and both sexes are equally prone to the disorder. The syndrome is rare, however, afflicting only about one person in 100,000. Usually Guillain-Barré occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal viral infection. Occasionally surgery or vaccinations will trigger the syndrome.

After the first clinical manifestations of the disease, the symptoms can progress over the course of hours, days, or weeks. Most people reach the stage of greatest weakness within the first 2 weeks after symptoms appear, and by the third week of the illness 90 percent of all patients are at their weakest.

Antecedent infections

Over half of Guillain–Barré syndrome patients experience symptoms of viral respiratory or gastrointestinal infections during the 1–3 weeks prior to the onset of neurological symptoms. Serological studies have implicated a wide range of infective agents. Cytomegalovirus (13 per cent) and Campylobacter jejuni (in approximately 30 per cent) are the most common. Epstein–Barr virus (10 per cent), Mycoplasma pneumoniae (5 per cent), human immunodeficiency virus (HIV), and childhood exanthems are also reported. The Guillain–Barré syndrome may accompany primary infection with HIV at a stage before viral antibodies are detectable in the serum; measurement of the p24 capsid antigen proving the underlying infection.Cytomegalovirus and campylobacter infections precipitate differing forms of Guillain–Barré syndrome. That associated with cytomegalovirus tends to occur in younger patients, with a high occurrence of respiratory muscle weakness, cranial nerve involvement, and significant sensory involvement. By contrast, Campylobacter jejuni infection is associated with preceding diarrhoeal illness in 70 per cent, a pure motor disorder (AMAN) is common, the electrophysiology often points to axonal dysfunction rather than demyelination, and recovery can be markedly slow. Forms of Guillain–Barré syndrome precipitated by both campylobacter and cytomegalovirus show delayed recovery compared to cases unassociated with these two infections.When Campylobacter jejuni enteritis has precipitated Guillain–Barré syndrome, stool culture may be positive and serum IgM antibodies detected. Preceding Campylobacter jejuni infections can evoke Guillain–Barré syndrome even if there has been prompt treatment with antibiotics. Unusual forms of acute polyneuritis may occur following campylobacter infection, including variants with ophthalmoplegia.

Occasionally the Guillain–Barré syndrome may be associated with underlying lymphoma, usually Hodgkin's disease. It can appear in patients already being treated with substantial doses of steroids, and is occasionally seen after renal transplantation from a cytomegalovirus-positive donor, and after bone-marrow or hepatic engraftment.

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 and manifests as a descending paralysis, proceeding in the reverse order of the more common form of GBS. It usually affects the eye muscles first and presents with the triad of ophthalmoplegia, ataxia, and areflexia.Anti-GQ1b antibodies are present in 90% of cases.

Acute motor axonal neuropathy (AMAN), 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 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.

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, obstipation, 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 specially in the Pons, Midbrain and Medulla. BE 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.

Pathology

An autoimmune basis for the Guillain–Barré syndrome seems likely but remains unproven. Although antibodies to various gangliosides are described in Guillain–Barré syndrome, particularly following campylobacter infection, it is unclear whether these antibodies are pathogenic. Certainly no single antibody is ubiquitous for Guillain–Barré syndrome. Guillain–Barré syndrome bears a strong histological resemblance to experimental allergic neuritis, an acute monophasic disorder induced by immunization of experimental animals with peripheral-nerve myelin proteins, particularly P2 and galactocerebroside. It is likely that diverse immunopathogenic mechanisms occur, including both antibody- and cell-mediated immune mechanisms. Prominent neural inflammatory infiltrates can occur in both Guillain–Barré syndrome and experimental allergic neuritis.

The peripheral nerves in acute Guillain–Barré syndrome often show inflammatory cell infiltrate, with associated areas of demyelination, resembling experimental allergic neuritis. This inflammatory infiltrate is mainly perivascular and comprised of lymphocytes and macrophages. Electron microscopy shows that macrophages cause the myelin damage, and penetrate the basement membrane around nerve fibres before stripping myelin sheaths off axons. Spinal nerve roots may be particularly affected, but changes are found at all levels of the peripheral nervous system. Teased peripheral sensory nerve fibre preparations may show marked segmental demyelination. Some Wallerian degeneration may occur. Biopsy of the sural nerve may show surprisingly few abnormalities in comparison to the marked clinical severity of the neuropathy; this may reflect the distal and purely sensory nature of the sural nerve.

Predisposing Factors

• Age (extreme ages)

• Sex (men)

Precipitating Factors• Post infection of Campylobacter Jejuni• Herpes simplex• AIDS/HIV• Hodgkin’s disease• Surgery• Epstein Barr Virus• Mononucleosis• Rarely, rabies/influenza immunizations• Poor hygiene• Stress• Diet

Etiologic AgentCampylobacter Jejuni

Enters the body by the use of multifenestratedcells or other mechanisms

Innate immune response results in theuptake of the pathogens by immature

antigen presenting cells.

Migration to lymph nodes, a mature, differentiated antigen presenting cell can

present in major histocompatibility complex molecules and activate CD4 T cells that

recognize antigens from the infectious pathogen

Pathogen and host cell have homologous/identical amino acid

sequences, antigens in its capsule are shared with nerves.

B cells can be activated as well by newly activated Th2 cells. This produces a cell mediated and humoral response against the pathogen.

Autoimmunity/auto immune disease is the consequence of an immune response against self antigens that results in the damage and eventual dysfunction of target organs

MOLECULAR MIMICRY -a mechanism wherein immune response is

triggered against autoantigens

DEMYELINATION

Auto antigens attack and damages GBS target organ---the PNS (peripheral nervous system)

Guillain–Barré syndrome

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 (CSF)

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 criteriaRequired: 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 EMG

Differential diagnosis:

The Guillain–Barré syndrome usually presents a distinctive clinical picture. The potential range of differential diagnosis of acutely evolving paralysis is enormous: spinal cord disease; neuromuscular transmission disorders; myopathy; vasculitic neuropathy; porphyria; malignant meningitis; infective neuropathies such as diphtheria, borreliosis, or poliomyelitis; biological toxins such as tick paralysis or botulism; drug and chemical toxins; metabolic abnormalities; critical illness polyneuropathy; and psychologically determined weakness.

Acute spinal-cord lesions pose the most common diagnostic difficulty, and spinal MRI needs to be undertaken in cases of doubt. However, the distinction is usually simple because of the extensor plantar responses, sensory level, prominent sphincter involvement, and the cellular spinal fluid encountered in acute ascending or transverse myelitis. It is rare for acute inflammatory myopathies to be confused with the Guillain–Barré syndrome. Pointers to primary muscle disease include the absence of

sensory symptoms, preserved reflexes, normal spinal-fluid protein, abnormal electromyogram, and raised serum creatine kinase levels.

Three rare acute neuropathies should be distinguished from the Guillain–Barré syndrome because they require different approaches to therapy. Borrelia infection causing Lyme disease or Bannwarth's syndrome is suggested by prominent unilateral or bilateral facial paralysis, radicular pain, and a cellular CSF. Porphyric polyneuropathy is associated with early neuropsychiatric abnormalities, abdominal pain, a purely motor syndrome, and preservation of the ankle jerks despite loss of the knee jerks.

Clinical Features

“Typical” GBS is an acute, predominantly motor neuropathy involving distal limb paresthesias, relatively symmetric leg weakness, and frequent gait ataxia. Most cases will have subsequent arm weakness, and possibly

weakness of facial, ocular, and oropharyngeal muscles. Weakness is always bilateral, although some asymmetry in onset

and severity is common. Proximal muscles weakness very frequent, especially initially, with

subsequent distal arm and leg weakness. GBS with a descending pattern of weakness seen in 14% cases;

onset initially with cranial nerve or arm muscle weakness, followed by leg weakness.

In 1/3 of cases, the degree of weakness in the arms and legs is roughly equal.

Reduced or absent reflexes characterize GBS. Early loss of reflexes may be due to desynchronization of afferent

impulses in reflex arc due to non-uniform demyelination. About 70% of patients present with loss of reflexes; less than 5%

retained all reflexes during the illness; The presence of intact reflexes should suggest an alternative

diagnosis other than GBS. Sensory disturbance

>50% will present with symmetric distal limb paresthesias, before clinically evident limb weakness. Early finger paresthesias suggest a patchy process, unlike the pattern seen with distal axonopathies.i. Paresthesias of trunk or face unusual, but sensory loss over

the trunk frequent and a psuedolevel may be evident

beware if definite sensory level present as this may suggest structural cord disease

ii. large diameter afferent modalities (JPS, vibration) are most severely affected.

iii. an early sensory ataxia may not be obscured by concurrent limb weakness

Pain Some discomfort reported in 2/3 of patients which may take one

of the following forms:i. deep muscle aching in back, hips or proximal legs,

ii. sharp radicular pain into the legs,iii. severe burning dyesthetic pain in feet or hands.

Radicular pain can occasionally be a presenting complaint obscuring the true diagnosis.

Cranial nerve involvement 1/2 of GBS patients have some degree of cranial nerve

dysfunction during their illness. Facial weakness most common, especially if substantial limb

weakness present.i. normal facial strength in the presence of marked

quadriparesis very unusual in typical GBS.ii. facial weakness usually bilateral but may be unequal in

severity; only rarely truly unilateral. Ophthalmoparesis see in 10-20% of patients.

i. abducens palsy most common; usually bilateral. Oropharyngeal weakness present in almost 1/2 of cases

increasing the risk of aspiration.i. Rarely, patients with GBS may appear locked-in, due to

paralysis of all cranial muscles, ventilatory failure, and flaccid paralysis.

Respiratory dysfunction due to diaphragmatic weakness occurs in about 1/3 of patients.

Diaphragmatic weakness common in patients with severe quadriparesis; may also occur early on in patients with bibrachial weakness.

Patients with weakness of neck muscles, tongue and palate often have concommitant diaphragmatic and respiratory muscle involvement.

Pathogenesis of respiratory failure:i. atelectasis results from reduced vital capacity, inspiratory

force and tidal volume due to diaphragmatic weakness.ii. atelectasis worsened by impair cough; result is arteriovenous

shunting and hypoxia.iii. the resultant tachypnea and increased work of breathingiv. if diaphragmatic and respiratory muscle weakness has not

occurred by 2 weeks into illness then assisted ventilation usually unnecessary.

v. patients requiring ventilator support have less favorable prognosis for neurologic recovery, have longer hospitalizations, and higher mortality.

Dysautonomia occurs in about 65% of cases more frequent in patients with severe paralysis and ventilator

difficulties but may develop in mild cases. Most common manifestations include cardiac dysfunction such as

sinus tachycardia, sinus bradycardia, sinus arrest and other supraventricular arrhythmias, paroxysmal hypertension, and hypotension (especially postural),

ICU monitoring necessary because of possible cardiac complications.

Other features: ileus, urinary retention (1/4 cases), inappropriate ADH, altered sweating, mild orthostatic hypotension.

Management

Survival in the Guillain–Barré syndrome depends primarily upon meticulous attention to intensive care during the acute paralytic phase. Feeding by nasogastric tube should be instituted in those with bulbar dysfunction. Subcutaneous heparin (5000 units four times daily) and elastic stockings provide prophylaxis against deep venous thrombosis and pulmonary embolism. Vigilant electrocardiographic monitoring allows prompt recognition and treatment of cardiac arrhythmias which may be provoked by endotracheal suctioning or suxamethonium administration. β-Blockers may be required for those with hypertensive crises. Patients with Guillain–Barré syndrome are particularly susceptible to hypotensive side-effects of drugs, including thiopentone (thiopental), frusemide (furosemide), and morphine. Nursing care will prevent decubitus ulcers. Regular Occupational therapy, physiotherapy and careful limb positioning will prevent muscle contractions in patients with prolonged paralysis. The gastrocnemius and soleus muscles are particularly prone to such contractures, which may lead to permanent walking disability even if muscle power returns.

VentilationEndotracheal intubation and ventilation should be instituted without delay either if respiratory muscle failure is imminent or if paralysis of bulbar and laryngeal muscles places the patient at risk of choking. Assisted ventilation is usually required when the vital capacity has fallen to 15 ml/kg body weight; that is, a vital capacity of approximately 1 litre for a 65 kg adult. Nasal endotracheal tubes are well tolerated by conscious patients and should be replaced by temporary tracheostomy if, as is usually the case, the period of ventilation is likely to exceed 1 week. Pulmonary atelectasis and infection are common in intubated patients and should be treated promptly with antibiotics and Occupational therapy/physiotherapy.Plasma exchange

Plasma exchange shortens the time taken for patients with Guillain–Barré syndrome to start to improve, to regain functional abilities such as walking, and reduces their requirement for assisted ventilation. Plasma exchange enabled the median patient to walk independently at 53 days compared to 85 days for controls, and allowed 82 per cent to walk independently at 6 months compared to 71 per cent of controls. It is unclear whether plasma exchange improves survival or reduces the number of patients unable to walk at 1 year. To be maximally effective, plasma exchange needs to be started within the first week of neurological symptoms. Plasma exchange is recommended for those patients approaching inability to walk or with impairment of bulbar or respiratory function. Plasma-exchange schedules vary, but four or five 4-litre exchanges using a continuous-flow technique, given on sequential days, are recommended. About 10 per cent of patients treated by plasma exchange will subsequently undergo a mild relapse between 5 and 42 days later, which may be treated by a further course of plasma exchange.

Intravenous immunoglobulin

Intravenous immunoglobulin (IvIg), given at 0.4 g/kg body weight/day for 5 days, is at least equally effective as plasma exchange. has become the treatment of choice because it is immediately available, does not require cannulation of a major vessel, has fewer side-effects than plasma exchange, and doesn't carry the same risks of exacerbating circulatory disturbances due to autonomic neuropathy. Also, IvIg may be more effective than plasma exchange for the motor axonal subgroup resulting from diarrhoeal campylobacter infections.

Prognosis

Most patients with the Guillain–Barré syndrome will make a good spontaneous recovery if they receive competent supportive treatment. Even when general intensive care facilities are available, up to 10 per cent of patients may die in the acute phase of the disease. These patients are usually elderly and generally succumb to cardiac disease, pulmonary embolism, or chest infections. The mortality is 4–5 per cent even for patients treated in specialist neurological units with plasma exchange or IvIg. Of the survivors, nearly 60 per cent make a full recovery but the other 40 per cent show some permanent residual symptoms and signs, usually weakness of distal leg muscles, absent ankle jerks, or distal sensory loss. Even after IvIg or plasma exchange therapy, 16.5 per cent are unable to walk at 48 weeks.

The factors predictive of poor outcome with slow recovery or permanent disability, include age over 60 years, a preceding diarrhoeal illness, development of severe paralysis within 5 days of the onset, respiratory failure requiring ventilation, and mean distal compound muscle action potentials of less than 20 per cent of normal.

Bibliography:

NEUROLOGY AND NEUROSURGERY ILLUSTRATED- Lindsay

Neurology-Brain's Diseases of the Nervous System

Wikipedia

Guillain Barre Syndrome and Its Variants- Alan R. Berger, M.D.

Guillain Barré Syndrome- Jacqueline Lim RN

Guillain-Barré syndrome- Angelika F Hahn