Guillain-Barré Syndrome (GBS) is an immune-mediated disorder of the peripheral nervous system. The immune system attacks spinal nerve roots, peripheral nerves, and cranial nerves, resulting in focal inflammation, with variable damage to myelin sheaths and axon fibers. GBS is the most common acute neuropathy of adults, and occurs worldwide at an incidence of 1 to 2 cases per 100,000 annually (El-sabrout et al, 2001). It is slightly more common in men, by a ratio of 1.3 to 1. GBS affects all ages, with peaks among young adults and the elderly. The classic clinical picture is that of an acute ascending paralysis, with depressed/lost deep tendon reflexes, facial weakness, and minimal sensory loss (Asbuy, 1981). Involvement of autonomic nerves can result in life-threatening fluctuations in blood pressure and heart rate, and severe cases can develop respiratory failure requiring artificial ventilation. GBS can develop very rapidly, over hours to days, but always reaches its worst stage within 4 weeks. Although the vast majority of patients recover, 10% are left severely disabled. Worse prognosis is associated with more severe disease, older age, and very abnormal electrodiagnostic studies. The mortality rate of 3% to 8% reflects autonomic and respiratory problems, and indicates that all but the mildest cases should be monitored in an intensive care setting. For patients on a respirator, the mortality rate is even higher (15% to 30%). GBS is typically monophasic, but 3% of cases experience relapses. Laboratory hallmarks of GBS involve cerebrospinal changes (elevated protein, normal cell count) which reflect damage to the blood-cerebrospinal fluid barrier, and a series of electrodiagnostic peripheral nerve abnormalities (slowed or blocked nerve conduction, prolonged latency, delayed or absent F and H responses, abnormal temporal dispersal rates). GBS is associated with preceding infection in some 70% of cases. Other associations are with vaccination, pregnancy, malignancy (especially Hodgkin's and non-Hodgkin's lymphomas), and bone marrow transplantation. Treatment of GBS involves plasma exchange (generally at least four) or intravenous immunoglobulin, supportive .care, and careful monitoring.

In the last few years, research studies have shed new light on a number of disease aspects that have enhanced understanding of GBS. First, there is a better appreciation of the link between inferior and GBS. The most commonly identified triggering agents are Campylobacter jejuna (in 13% to 39%), followed by cytomegalovirus (5%to 22%), Epstein Barr virus (1% to 13%), and mycoplasma pneumoniae (5%) (Hadden et al, 2001). Campylobacter is even more common as an antecedent infection in Japanese and Chinese cases. These pathogens share protein sequences (antigens) in common with peripheral nerve tissue. It is believed that this ''molecular mimicry'' results in a cross-reactive immune attack by host anti-bodies and T cells which are dirtied against the pathogen, but also recognize and attack nerve components. Second, GBS is now appreciated as a heterogeneous spectrum of disorders which encompasses a number of distinct subtypes. Most patients have acute inflammatory demyelinating polyradiculoneuropathy, characterized by loss of myelin from otherwise relatively intact nerves. However, there are other forms of GBS that involve predominantly axon damage. Involvement can be limited to motor nerves (acute motor axonal neuropathy), or both sensory and motor nerves (acute sensory motor axonal neuropathy). These axonal forms are more common in China. Predominantly axonal forms of GBS tend to be more severe, with greater likelihood of permanent damage. The primary target of attack is the node of Ranvier (Asbury & McKhann, 1997). Another subtype, the Miller Fisher syndrome, involves acute onset of ataxia, areflexia, and ophthalmoplegia (paralysis of eye movements). Some patients progress to classic GBS (Yuki, 20003. Other subtypes are sensory GBS, which involves acute sensory loss with areflexia; acute autonomic neuropathy, with involvement limited to autonomic nerves; pharyngeal-cervical-paraparetic brachial GBS (associated with anti-GT1a IgG antibodies (Ariga et at, 2001). and ptosis without ophthalmoplegia variants (Ob et at, 2001). Third, there appear to be immunologic differences among GBS patients based on the triggering infection and the clinical subtype. GBS following Campylobacter infection is associated with IgG auto-antibodies to GM1 ganglioside. Gangliosides are highly expressed in nerve tissues (Yuki, et al, 2001). These patients are more likely to have pure motor involvement, axonal damage, lower cerebrospinal fluid protein, and a worse outcome (Hadden et al, 2001). GBS following cytomegalovirus typically shows prominent sensory involvement, has higher levels of immune activation markers, and takes a more severe course. The Miller Fisher syndrome is associated with IgG antibodies to a distinct ganglioside, GQ1b. Finally, immune factors (T cell activation, certain higher proinflammatory cytosine production, anti-ganglioside levels) are associated with worse prognosis (Hadden et al, 2001). The blood-nerve barrier is leakier than the blood-brain barrier. It would allow greater penetration of cells and antibodies to injure nerve roots and terminals (Yuki et at, 2001). Antibodies to glycolipids appear to play an im1 portent role in GBS (Ariga et al 2001). 60% to 70% of GBS patients have antiglycolipid antibodies (Kusunokis et al 2000). Future studies, as they refine the different subtypes of GBS, and their infection and immune links, will lead to more effective therapies. Ultimately GBS may be preventable using immunoprophylaxis and immunomodulation strategies.