Guillain-Barre syndrome

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Diagnosis and reasoning

To the uninitiated, clinical neurology is perhaps the difficult branch of medicine, encompassing a diverse range of complex disorders. A structured and systematic approach is key in arriving at a diagnosis; this patient is an excellent example in point. The differential diagnosis of acute lower limb weakness is extremely broad, encompassing lesions from the brainstem, to the spinal cord, peripheral nerves, neuromuscular junction (NMJ), and muscles. However, examination shows the weakness to be flaccid in nature - this signifies a lower motor neuron (LMN) lesion, and localizes it to the neuromuscular arc (i.e. from the anterior horn cells to the nerves, NMJ and muscles). In addition, the history of numbness (i.e. a sensory disturbance) excludes pure diseases of the anterior horn cells (such as motor neurone disease or poliomyelitis), of the NMJ (such as myasthenia gravis) and of the muscle (such as polymyositis or channelopathies). However, note the lack of objective sensory findings; this allows us to 'short-circuit' the diagnostic process, as the combination of sensory symptoms without corresponding signs is almost characteristic of Guillain–Barré syndrome (GBS). This prospective diagnosis is further supported by the symmetric and progressive nature of the weakness, and absence of a clear-cut motor level; the history of a preceding respiratory tract infection lends further credence. It is important to keep in mind that a few other diseases can present in this manner - most particularly hypokalemia, toxic neuropathies (i.e. due to alcohol, lead or mercury), acute porphyria and tick paralysis. However, there is no evidence of electrolyte disturbances; the remaining conditions are comparatively rare, and should probably be considered only if GBS is definitively excluded. Cerebrospinal fluid (CSF) analysis and nerve conduction studies (NCS) should be performed, as these may demonstrate changes characteristic of GBS. However, the negative results here do not exclude the disease, as these investigations are often normal or equivocal in the first week. This emphasizes the importance of being astute enough to clinically diagnose GBS, as the outcome is directly proportionate to the timeliness of diagnosis and treatment. GBS is a life threatening condition; she needs immediate treatment with IV Immunoglobulins; close observation and management in an intensive care setting should be considered. There is no role for corticosteroids or IV antibiotics in her current management. Stool cultures are not indicated here (but would have been considered if poliomyelitis were suspected).


Discussion

Guillain–Barré syndrome (GBS) is the most common cause of non-trauma-related acute flaccid paralysis, with an estimated incidence of 1 to 2 per 100,000 individuals annually. All age groups are affected, although the highest incidence is between 20 to 40 years of age. There is substantial evidence of suggest that GBS has an autoimmune mediated basis; the underlying mechanism is believed to be an immune response triggered by the molecular mimicry between an infecting organism and the host nerve tissue. The immune attack primarily targets the gangliosides in myelin sheath of peripheral nerve and to a lesser extent, the axons. While GBS is most often (primarily) demyelinating in nature (hence the alternative name "Acute Inflammatory Demyelinating Polyradiculoneuropathy" - AIDP), it should be noted that several other subtypes exist. These include acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), acute pan-autonomic neuropathy (APN) and more rarely Miller-Fisher syndrome (MFS), a proximal variant with ataxia, areflexia and ophthalmoplegia. In approximately two-thirds of patients, GBS is preceded by an unremarkable infection such as an upper respiratory tract infection or acute gastroenteritis. A wide variety of microorganisms have been implicated, including C. jejuni, M. pneumoniae, Cytomegalovirus, Epstein–Barr virus, and Influenza virus. Cases have also been reported following surgery, immunization and parturition. Most patients initially develop paresthesia (i.e. numbness, tingling, or a burning sensation) in the lower limb. This is followed by symmetric muscle weakness, which progressively ascends from the lower limbs to the upper limbs, trunk, and head and neck, typically over a period of 2 to 4 weeks. The severity may range from relatively mild weakness to a total tetraplegia eventually needing mechanical ventilation due to respiratory muscle paralysis. Occasionally facial, ocular and oropharyngeal weakness are also observed. Disturbances of the autonomic nervous system are common, but usually do not persist longer than one to two weeks; however, very rarely, severe complications such as life threatening arrhythmias and severe hypo-or-hypertension may occur. Sphincter function is usually preserved. Around half of patients may be bothered by neuropathic lower back pain or leg pain. Note that GBS is mainly a motor neuropathy; overt sensory dysfunction is not always present (but is more likely to be encountered in the demyelinating subtype). The diagnosis of GBS is mainly clinical, and based on the observation of progressive symmetrical muscle weakness in more than one limb within 4 to 8 weeks, along with areflexia. Investigations may be performed to support the clinical diagnosis; these include CSF analysis and electrodiagnostic studies. CSF analysis characteristically shows albuminocytologic dissociation (elevated protein levels with normal cell counts). Nerve conduction studies may show features suggestive of demyelination and/or axonal degeneration. An important point to keep in mind is that in the first week, only half of patients show albuminocytologic dissociation, while NCS studies may be normal or equivocal. As prompt treatment is essential for a good outcome, the importance of clinical diagnosis cannot be underemphasized. Antibody assays may be of use in patients with an atypical presentation (for example, Antiganglioside antibodies in MFS); however, these have limited clinical utility. There are two key aspects to the management of GBS: immunotherapy to halt disease progression, and monitoring and supportive care to prevent and treat associated complications. Both plasmapheresis and IV immunoglobulin (IVIg) are equally effective immunomodulatory therapies; however, plasma exchange is both more complex to administer and associated with more complications, making IVIg preferable in most cases. Note that combining the two techniques does not provide any additional benefit. Treatment should be commenced as soon as the diagnosis is made; it is essential to start treatment within 2 to 4 weeks from the onset of symptoms to hope for motor recovery. Meticulous monitoring is essential to detect life threatening complications due to respiratory muscle paralysis and autonomic disturbance; supportive care should be given accordingly. All patients should receive deep venous thrombosis (DVT) prophylaxis, while measures should be taken to prevent bed sores. Good nutrition (i.e. a high energy, high protein diet) is also essential. GBS is typically a monophasic disease, although approximately 7% of patients experience a recurrence. While most individuals will experience a complete recovery with no or minimal residual effects, this is slow and may take upto 2 years. Approximately 20% of patients will experience long term residual effects. This is more common in individuals who had severe disease with widespread nerve damage, with advanced age and in patients who required prolonged mechanical ventilation. Severe fatigue is also a recognized sequel of GBS in adults. The mortality rate is approximately 5% to 7%; causes include respiratory failure, aspiration pneumonia, pulmonary embolism, cardiac arrhythmias, and/or hospital sepsis.


Take home messages

  1. GBS is a neurological emergency with potentially life-threatening consequences.
  2. Investigations may be normal or equivocal in the early stages; a high index of clinical suspicion is essential.
  3. The ultimate outcome is directly related to how soon appropriate treatment is started.
  4. Most individuals recover completely, although this may take months to years.

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  1. AAN Offers New Guidelines for Treatment of Guillain-Barre Syndrome. Laurie Barclay, MD. 2003
  2. Guillain-Barré Syndrome. DANA L. NEWSWANGER,CHARLES R. WARREN,Am Fam Physician. 2004
  3. Guillain–Barré Syndrome. Nobuhiro Yuki, M.D., Ph.D., and Hans-Peter Hartung, M.D. N Engl J Med 2012; 366:2294-2304
  4. Motor conduction studies in Guillain-Barré syndrome: description and prognostic value. Cornblath DR, Mellits ED, Griffin JW, McKhann GM, Albers JW, Miller RG, Feasby TE, Quaskey SA.1988
  5. Plasma exchange for Guillain-Barré syndrome. Raphaël JC, Chevret S, Hughes RA, Annane D,2012
  6. Treatment guidelines for Guillain–Barré Syndrome. A. K. Meena, S. V. Khadilkar and J. M. K. Murthy,Ann Indian Acad Neurol. 2011