Poliomyelitis has disappeared from most of the world except for Afghanistan and the bordering country of Pakistan because of on going internal war and terrorism which prevented the completion of the vaccination program which has again been reinstated in Pakistan. In fact prevention of vaccination has been part of the terrorists’ acts of war. However flaccid paralysis is still seen in young people which leaves 20% disabled and 5% dead despite plasmapheresis. This Guillain–Barré syndrome, is characterized by acute areflexic paralysis with albuminocytologic dissociation (i.e., high levels of protein in the cerebrospinal fluid and normal cell counts), was described in1916. This discrepancy in the CSF is the basis of diagnosis. This is also seen in the Miller Fisher variant which can, in a small number of patients, develop into a full blown GB syndrome.
Various studies of the immuno-pathogenesis of the Guillain–Barré syndrome suggest that the disease actually encompasses a group of peripheral-nerve disorders,
each distinguished by the distribution of weakness in the limbs or cranial-nerve–
innervated muscles and underlying pathophysiology (Fig. 1).5-7 There is substantial
evidence to support an autoimmune cause of this syndrome, and the autoantibody
profile has been helpful in confirming the clinical and electrophysiological relationship of the typical Guillain–Barré syndrome to certain other peripheral-nerve conditions.
What infections may be responsible for setting off the GB syndrome?
Two thirds of cases are preceded by symptoms of upper respiratory tract infection
or diarrhea. The most frequently identified infectious agent associated with subsequent development of the Guillain–Barré syndrome is Campylobacter jejuni, and 30% of infections were attributed to C. jejuni in one meta-analysis, whereas cytomegalovirus has been identified in up to 10%. The incidence of the Guillain–Barré syndrome is estimated to be 0.25 to 0.65 per 1000 cases of C. jejuni infection, and 0.6 to 2.2 per 1000 cases of primary cytomegalovirus infection. Other infectious
agents with a well-defined relationship to the Guillain–Barré syndrome are Epstein–
Barr virus, varicella–zoster virus, and Mycoplasma pneumoniae. The immune response can be directed towards the myelin or the axon of peripheral nerve, resulting in demyelinating and axonal forms of GBS. Because of the immune response it is also known as the AIDP or acute inflammatory demyelinating polyneuropathy. The Zika virus can also be a trigger. A small percentage of patients develop GBS after another triggering event such as immunization, surgery, trauma, and bone-marrow transplantation.
The cardinal clinical features of Guillain-Barré syndrome (GBS) are progressive, fairly symmetric muscle weakness accompanied by absent or depressed deep tendon reflexes. Patients usually present a few days to a week after onset of symptoms. The weakness can vary from mild difficulty with walking to nearly complete paralysis of all extremity, facial, respiratory, and bulbar muscles.
GBS is associated with the following clinical features:
- The weakness usually starts in the legs, but it begins in the arms or facial muscles in about 10 percent of patients.
- Severe respiratory muscle weakness necessitating ventilatory support develops in 10 to 30 percent.
- Facial nerve palsies occur in more than 50 percent, and oropharyngeal weakness eventually occurs in 50 percent.
- Oculomotor weakness occurs in about 15 percent of patients.
- Decreased or absent reflexes in affected arms or legs are found in approximately 90 percent of patients at presentation and in all patients with disease progression.
- Paresthesias in the hands and feet accompany the weakness in more than 80 percent of patients, but sensory abnormalities on examination are frequently mild.
- Pain due to nerve root inflammation, typically located in the back and extremities, can be a presenting feature and is reported during the acute phase by two-thirds of patients with all forms of GBS.
- Dysautonomia occurs in approximately 70 percent of patients included diarrhea/constipation, hyponatremia, bradycardia, urinary retention, tachycardia (3 versus, reversible cardiomyopathy, and Horner syndrome. Severe autonomic dysfunction is important to recognize since this is occasionally associated with sudden death.
- The syndrome of inappropriate antidiuretic hormone secretion (SIADH), which may be due to autonomic involvement, is another complication of GBS.
- Unusual features of GBS include papilledema, facial myokymia, hearing loss, meningeal signs, vocal cord paralysis, and mental status changes. In addition, posterior reversible encephalopathy syndrome, also known as reversible posterior leukoencephalopathy syndrome (see “Reversible posterior leukoencephalopathy syndrome”), has been associated with GBS in adults and children, likely related to acute hypertension from dysautonomia.
A detailed neurologic assessment will help localizes the disease to the peripheral nerves rather than to the brain stem, spinal cord, cauda equina, neuromuscular junction, or muscles. The presence of distal paresthesia increases the likelihood that the correct diagnosis is the Guillain–Barré syndrome. If sensory involvement is absent, disorders such as poliomyelitis, myasthenia gravis, electrolyte disturbance, botulism, or acute myopathy should be considered. Hypokalemia shares some features with the Guillain–Barré syndrome but is commonly overlooked in the differential diagnosis. In patient with acute myopathy, tendon jerks are preserved and serum creatine kinase levels are increased. If paralysis develops abruptly and urinary retention is prominent, magnetic resonance imaging
of the spine should be considered, to rule out a compressive lesion.
Nerve-conduction studies help to confirm the presence, pattern, and severity of neuropathy. Consider alternative causes, such as vasculitis, beriberi, porphyria, toxic neuropathy, Lyme disease, and diphtheria.
Historically, the Guillain-Barré syndrome (GBS) was considered a single disorder. It now is recognized as a heterogeneous syndrome with several variant forms. Each form of GBS has distinguishing clinical, pathophysiologic, and pathologic features.
- Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is the most common form representing approximately 85 to 90 percent of cases.
- The clinical variant Miller Fisher syndrome (MFS), characterized by ophthalmoplegia, ataxia, and areflexia, occurs in approximately 10 percent of cases. There may be incomplete forms and Bickerstaff’s brain stem encephalitis. The presence of distal paresthesia is associated with the Miller Fisher syndrome. Careful clinical assessment and focused investigations such as brain imaging and electrophysiological examinations can rule out other conditions, such as brain-stem stroke, Wernicke’s encephalopathy, myasthenia gravis, and botulism. The disease peaks at a median of 1 week, and improvement often starts at a median of 2 weeks.4 Recovery from ataxia and recovery from ophthalmoplegia take a median of 1 and 3 months, respectively. By 6 months after the onset of neurologic symptoms, most patients have recovered from ataxia and ophthalmoplegia.
- Acute motor axonal neuropathy (AMAN).
- Acute motor and sensory axonal neuropathy (AMSAN) are primary axonal forms of GBS.
A lumbar puncture is usually performed in patients with suspected Guillain–Barré syndrome, primarily to rule out infectious diseases, such as Lyme disease, or malignant conditions, such as lymphoma. A common misconception holds that
there should always be albumino-cytologic dissociation. However, albumino-cytologic dissociation is present in no more than 50% of patients with
the Guillain–Barré syndrome during the first week of illness, although this percentage increases to 75% in the third week. Some patients with human immunodeficiency virus infection and the Guillain–Barré syndrome have pleocytosis.
Only 7% of cases recur and tend to recur after many years. Although hyporeflexia or areflexia is a hallmark of the Guillain–Barré syndrome, 10% of patients have normal or brisk reflexes during the course of the illness. Thus, the possibility of the Guillain–Barré syndrome should not be excluded in a patient with normal or brisk reflexes if all other features are supportive of the diagnosis. Clinical deterioration after initial improvement or stabilization with immunotherapy suggests that the treatment had
a transient effect or that chronic inflammatory demyelinating polyneuropathy (CIDP)is present.
The variations in the rate and extent of recovery in the Guillain–Barré syndrome make prognostication difficult. One clinical scoring system that has been developed uses the patient’s age, the presence or absence of antecedent diarrhea, and disease severity to predict whether a patient will be able to walk independently at 1, 3, or 6 months. Another prognostic scale uses the number of days between the onset of weakness and hospital admission, the presence or absence of facial or bulbar
weakness, and the severity of the limb weakness to predict the likelihood that respiratory insufficiency will develop. Both scales, validated in their respective patient populations, can be useful in the care of patients with the Guillain–Barré syndrome.
DEMYELINATING AND AXONAL SUBTYPES
The histologic features of the Guillain–Barré syndrome support a classification that includes demyelinating and axonal subtypes — acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. The classification is based on nerve-conduction studies.
There are localized forms of the Guillain–Barré syndrome that are distinguished by involvement of certain muscle groups or nerves. Facial diplegia with paresthesia is a localized form of the demyelinating Guillain–Barré syndrome, where a pharyngeal–cervical–brachial weakness, which is characterized by acute weakness of the oropharyngeal, neck, and shoulder muscles, represents a localized form of the axonal Guillain–Barré syndrome.
Plasma exchange was the first treatment that was found to be effective in hastening recovery in patients with the Guillain–Barré syndrome, and it appeared to be most effective when it was started within the first 2 weeks after disease onset in
patients who were unable to walk. An electrophysiological examination is not always required for the initiation of immunotherapy. Plasma exchange nonspecifically removes antibodies and complement and appears to be associated with
reduced nerve damage and faster clinical improvement, as compared with supportive therapy alone. The usual empirical regimen is five exchanges over a period of 2 weeks, with a total exchange of 5 plasma volumes. One trial showed
that patients who could walk with or without aid but could not run benefited from two exchanges of 1.5 plasma volumes, but more severely affected patients required at least four exchanges. Treatment with intravenous immune globulin, initiated within 2 weeks after disease onset, is reported to be about as effective as plasma
exchange in patients with the Guillain–Barré syndrome who cannot walk independently. It is thought that immune globulin may act by neutralizing pathogenic antibodies and inhibiting autoantibody-mediated complement activation, resulting in reduced nerve injury and faster clinical improvement, as compared with no treatment, although no comparative studies have been performed. In general, intravenous immune globulin has replaced plasma exchange as the treatment of choice in many medical centers because of its greater convenience and availability.
According to the standard treatment regimen, immune globulin is given at a total dose of 2 g per kilogram of body weight over a period of 5 days. The pharmacokinetics of immune globulin varies among patients, and some patients have a smaller rise in serum IgG after the administration of immune globulin. These
patients are likely to have a poorer outcome, with fewer able to walk unaided at 6 months. A second course of immune globulin in severely unresponsive patients was reported to be beneficial in one study.
The combination of plasma exchange followed by a course of intravenous immune globulin is not significantly better than plasma exchange or immune globulin alone. Neither prednisolone nor methylprednisolone can significantly accelerate recovery or affect the long-term outcome in patients with the Guillain–Barré syndrome. Eculizumab, erythropoietin, and fasudil, which have been used in the treatment
of other, unrelated medical conditions, have shown promise in animal models of the Guillain–Barré syndrome, but clinical studies are lacking.
One of the differential diagnoses of AIDP is CIDP or chronic inflammatory demyelinating polyneuropathy. Typical CIDP is a fairly symmetric sensorimotor polyneuropathy with proximal and distal motor involvement that exceeds sensory involvement. The presentation is usually one of gradually progressive symptoms over the course of several months or longer. Some patients present with more rapidly progressive symptoms, resembling acute inflammatory demyelinating polyneuropathy (AIDP) and which have been termed “acute-onset CIDP”.
One variant is:
Asymmetric sensorimotor (multifocal) — The Lewis-Sumner syndrome, also known as multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), is a well-described atypical variant of CIDP that accounts for 5 to 10 percent of CIDP cases. Patients present with a strikingly asymmetric, multifocal picture, indistinguishable from other forms of mononeuropathy multiplex, resulting in sensory and/or motor signs and symptoms in individual nerve distributions. Symptoms may start in any nerve distribution. Some patients may have autonomic symptoms, neuropathic pain, and cranial nerve involvement. Some patients present with focal CIDP with symptoms restricted to a single limb or nerve.
Sensory-predominant — The sensory-predominant form of CIDP is characterized clinically by symptoms and signs consistent with large fiber sensory dysfunction, including balance problems, pain, paresthesias, and dysesthesias.
Distal and sensory-predominant — Distal acquired demyelinating symmetric neuropathy (DADS) refers to a distal and sensory-predominant variant of CIDP, which is usually more slowly progressive than typical CIDP. Patients typically present with length-dependent, symmetric sensory or sensorimotor dysfunction in the lower extremities with sparing of proximal limbs, trunk, and face
Pure motor — A pure motor variant of CIDP has been reported in a small number of cases. Involvement of motor nerves and sparing of sensory fibers is present on clinical and electrodiagnostic evaluations. Weakness tends to be relatively symmetric and may involve any part of the body, including motor cranial nerves,
Neurofascin antibody-mediated — Patients with autoantibodies to neurofascin (NF) 155 appear to be younger and more likely to have sensory ataxia and prominent tremor compared with those with antibody-negative CIDP
Contactin 1 antibody-mediated — Autoantibodies of the IgG4 class to contactin 1 (CNTN1) or contactin-associated protein 1 (CASPR1) are found in a small subset of patients with CIDP
Lumbar puncture — Cerebrospinal fluid (CSF) analysis is recommended in most patients with suspected CIDP and particularly for patients in whom the clinical and electrophysiologic findings are inconclusive. Albuminocytologic dissociation is a hallmark of CIDP and represents supportive evidence in the EFNS/PNS diagnostic criteria
Neuroimaging — Magnetic resonance imaging (MRI) with gadolinium of the spine (including spinal roots, cauda equina), brachial plexus, lumbosacral plexus, and other nerve regions can be used to look for enlarged or enhancing nerves.
Nerve ultrasound — When appropriate expertise is available, neuromuscular ultrasound can also be used to detect nerve hypertrophy in patients with acquired and hereditary forms of chronic demyelinating neuropathies.
Nerve biopsy — The diagnostic utility of nerve biopsy (typically of the sural nerve) for suspected CIDP is controversial [68-70], and nerve biopsy is unnecessary for most patients with suspected CIDP, especially those with typical electroclinical findings.
There is general agreement that the following criteria support the diagnosis of the classic form of CIDP:
- Progression over at least two months
- Weakness more than sensory symptoms
- Symmetric involvement of arms and legs
- Proximal muscles involved along with distal muscles
- Widespread reduction or loss of deep tendon reflexes
- Increased cerebrospinal fluid (CSF) protein without pleocytosis
- Nerve conduction evidence of a demyelinating neuropathy
- Nerve biopsy evidence of segmental demyelination with or without inflammation
- Gait ataxia secondary to large fiber sensory loss
Two sets of criteria, the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) criteria (see ‘EFNS/PNS criteria’ below) and the Koski criteria (see ‘Koski criteria’ below), deserve special mention. Please look them up in Uptodate in the CIDP section.
Both clinical experience and data from retrospective studies suggest that the over-diagnosis of CIDP is common, involving one-third to nearly one-half of patients so labeled. Furthermore, many of those with an erroneous diagnosis of CIDP are exposed to the potential toxicities and costs of long-term treatment with intravenous immune globulin (IVIG) and glucocorticoids.
(This article (10.1056/NEJMra1114525) was
updated on June 14, 2012, at NEJM.org.
N Engl J Med 2012;366:2294-304)