DESCRIPTION
Guillain–Barré syndrome (GBS) is an acute polyneuropathy affecting the peripheral nervous system. GBS is also known as acute idiopathic polyradiculoneuritis, acute idiopathic polyneuritis, French polio, Landry's ascending paralysis and Landry–Guillain–Barré syndrome.
The most typical symptom is ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, and it is due to an autoimmune mechanism against the myelin sheath. Some subtypes cause change in sensation or pain and dysfunction of the autonomic nervous system. It can cause life-threatening complications, in particular involving the respiratory muscles and the autonomic nervous system. The disease is usually triggered by an infection.
EPIDEMIOLOGY
Guillain–Barré syndrome is rare, 1-2 cases per 100,000 people annually, but is the most common cause of acute non-trauma-related paralysis. Men are 1,5 times more likely to be affected than women and the incidence increases with age (1 case per 100,000 people < 30years old and about 4 cases per 100,000 people over 75 years old).
Worldwide, the annual incidence is about 0.6-4.0 occurrences per 100,000 people. The incidence of GBS during pregnancy is 1.7 cases per 100,000 and congenital and neonatal cases have also been reported.
SIGNS AND SYMPTOMS
The disorder is characterized by symmetrical weakness that usually affects the lower limbs first, and rapidly progresses migrating towards the trunk. Patients generally notice weakness in their legs ("rubbery legs") or legs that tend to buckle, with or without dysesthesias. The weakness progresses upward to the arms and facial muscles over periods of hours to days. The lower cranial nerves may be involved, leading to bulbar weakness, oropharyngeal dysphagia (drooling, difficulty swallowing and/or maintaining an open airway) and respiratory difficulties. For these reasons most patients require hospitalization and about 30% require ventilatory assistance for treatment of respiratory failure. Facial weakness is also common.
Sensory loss usually takes the form of loss of proprioception (position sense) and areflexia (complete loss of deep tendon reflexes), but it is not always present. A slight loss of pain and temperature sensation can be present, but pain is a common symptom in GBS, presenting as deep pain in the weakened muscles similar to the pain from overexercising. These pains are self-limited and may be treated with standard analgesics.
In severe cases, loss of autonomic function is common, manifesting as wide fluctuations in blood pressure, orthostatic hypotension (leading to an increased risk of collapse), and sinus tachycardia among other cardiac arrhythmias. Bladder dysfunction may occur.
Acute paralysis in Guillain–Barré syndrome may be related to sodium channel blocking factor in the cerebrospinal fluid.
SUBTYPES AND CLASSIFICATION
Six different subtypes of Guillain–Barré syndrome exist:
- Acute inflammatory demyelinating polyneuropathy (AIDP) is the most common form of GBS, often used synonymously with GBS. It is caused by an autoimmune response directed against Schwann cell membranes;
- Miller Fisher syndrome (MFS) is a rare variant of GBS (5% of GBS cases). It manifests as a descending paralysis, proceeding in the reverse order and usually affecting the eye muscles first (ophthalmoplegia). It also presents ataxia and areflexia;
- 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;
- Acute motor sensory axonal neuropathy (AMSAN) is similar to AMAN, but also affects sensory nerves with severe axonal damage. Recovery is slow and often incomplete;
- Acute panautonomic neuropathy is the rarest variant of GBS, involving the sympathetic and parasympathetic nervous system (abdominal pain, vomiting, constipation, urinary retention, dilated unreactive pupils, loss of accommodation). The patients have postural hypotension, anhidrosis, gastrointestinal and sudomotor dysfunction, decreased salivation and lacrimation, and pupillary abnormalities. Cardiovascular symptoms are common and can cause arrhythmias resulting in death. Recovery is gradual and sometimes not complete;
- Bickerstaff's brainstem encephalitis (BBE) is characterized by acute onset of ophthalmoplegia, areflexia and sensory loss. BBE usually has a good prognosis. A considerable number of BBE patients have associated axonal Guillain-Barré syndrome, indicative that the two disorders are closely related.
PATHOGENESIS
All forms of Guillain–Barré syndrome are autoimmune diseases, due to an immune response to antigens (such as infectious agents - bacterium Campylobacter Jejuni, Cytomegalovirus, Influenza virus) that unintentionally mistargets host nerve tissues (mechanism of molecular mimicry). The targets of such immune attack are thought to be gangliosides, present in large quantities in human peripheral nerve tissues.
MECHANISM OF ACTION: A bacterial cross-reactive antigen is recognized by macrophages and T cells that help B cells to produce antiganglioside antibodies, which penetrate blood-nerve barrier (BNB) and activate complement. Various cytokines may assist in the disruption of the BNB through which immune cells (T-Cells and Macrophages) can infiltrate and obtain direct access to the myelin and Schwann cells; anatomically, the BNB is deficient in the distal nerve terminals and nerve roots, and these regions are preferentially affected by an immune attack. Furthermore, Schwann cells can potentially modulate multiple aspects of inflammatory cascade by producing cytokines and toxic substances .
As a result:
- the antiganglioside antibodies bind with specific nerve gangliosides (and C. Jejuni antigen as well ). The type of ganglioside mimicry in C. jejuni seems to determine the specificity of the antiganglioside antibodies and the associated variant of GBS. The most common antibodies are GM1 antibodies. Some anti-GM1 may be monospecific whereas others may cross react with other gangliosides; related gangliosides epitopes may exist in both myelin and axolemma membranes in varying concentrations and configurations that can lead to preferential binding of antibody under different circumstances. Furthermore, this may change during the course of the disease. For instance, at the nodes of Ranvier axolemma, GM1 may be veiled during the early course of the disease but may become exposed for antibody binding due to paranodal demyelination induced by anti-GM1 or other antibody binding to GM1. Thus, an illness as AIDP could then evolve into AMAN or AIDP with secondary axonal damage;
- Activated endoneural macrophages release cytokine and free radicals (nitric oxide), invade compact myelin, periaxonal space, and sometimes block nerve conduction or cause axonal degeneration;
- Activated T-cells release proinflammatory cytokines (IFN-γ, IL-1β, TNF-α, and IL-6), fix complement, damage Schwann cell, and ultimately produce dissolution of myelin, leading to muscle paralysis accompanied by sensory or autonomic disturbances.
In mild cases, nerve axon 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. About 80% of patients have myelin loss; in the remaining 20%, the pathological hallmark is axon loss.
Guillain–Barré is a purely peripheral nerve disorder and does not in general cause nerve damage to the brain or spinal cord.
DIAGNOSIS
Clinical features required for diagnosis are progressive weakness in legs and often arms, and areflexia. Features that strongly support diagnosis are progression of symptoms over days to four weeks, relative symmetry of symptoms, sensory symptoms or signs, cranial nerve involvement (bilateral weakness of facial muscles), autonomic dysfunction, pain, high concentration of protein in CSF, and typical electrodiagnostic features.
Common tests ordered in the diagnosis of GBS are Cerebrospinal fluid analysis (through a lumbar spinal puncture) and electrodiagnostic tests of nerves and muscles (EMG and nerve conduction studies):
- Characteristic findings in cerebrospinal fluid include albumino-cytological dissociation, an elevated protein level (100–1000 mg/dl) without an accompanying increased cell count (absence of pleocytosis).
- Electromyography (EMG) and nerve conduction studies may show prolonged distal latencies, conduction slowing, conduction block, and temporal dispersion of compound action potential in demyelinating cases.
At histological examination of the peripheral nerves and especially in the motor fibers, there may be inflammatory infiltrate composed of lymphocytes, monocytes and macrophages, that may be responsible for the demyelination.
TREATMENT
Supportive care is essential for the successful management in the acute patient. The treatment of respiratory failure (due to paralysis of the diaphragm) is very important and intubation may be needed. Subsequent treatment consists in reducing the antibody 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 but a combination of the two is not significantly better than either alone. Plasmapheresis accelerates recovery when used within 4 weeks of the onset of symptoms, but IVIg has equivalent efficacy if started within 2 weeks and has fewer complications (IVIg is usually used first), even if occasionally it causes 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 (Occupational therapists, Physiotherapists, Speech and language therapists) to focus on improving activities of daily living (ADLs).
PROGNOSIS
Recovery usually starts after the fourth week from the onset of the disorder. About 80% of patients have a complete recovery within a few months to a year, even if areflexia may persist. About 5-10% recover with severe disability, involving severe proximal motor and sensory axonal damage with inability of axonal regeneration. About 5–10% of patients have one or more late relapses (chronic inflammatory demyelinating polyneuropathy).
The death rate is still about 2-3%. Worldwide, the death rate is about 4%, because of a lack of availability of life-support equipment during the critical phase, when a ventilator is needed in the worst cases. Various unfavorable factors (age over 40 years, previous gastrointestinal infection, required ventilator support, ICU admission, poor rehabilitation therapy) can aggravate the prognosis.
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