Recent Advances in Studies on Guillain-Barre Syndrome: Correlation Between Microorganisms and New Treatment Perspectives

The Guillain-BarrA© Syndrome (GBS) is a postinfectious and autoimmuneâ€ induced peripheroneural disorder characterized by being an acquired acute inflammatory demyelinating polyradiculoneuropathy which often follows gastrointestinal or respiratory infections...

and are some of the most widespread human pathogens, may also precede GBS as well as the Human Immunodeficiency Virus (HIV) which progressively leads to an immune deficiency that manifests with the appearance of life-threatening opportunistic infections [9,[14][15][16].
Dengue, Zika and Chikungunya are viruses that cause similar diseases which symptoms are nonspecific and overlap, [17] and all of them can be transmitted by mosquito bites: Dengue is characterized by high fever, arthralgia, myalgia, anorexia, petechiae/rash, and retro-orbital pain [9,17]. Zika virus infections are usually asymptomatic (60-80% of cases), although when the clinical symptoms appear they may include low fever, arthralgia, conjunctivitis and maculopapular rash [9,18,19]. Symptomatic Chikungunya infections present the clinical conditions of acute fever-arthralgia syndrome, which may progress to chronic and debilitating inflammatory rheumatism [9,20].
Like the previously mentioned pathogens, these viruses can be found in different countries; however, they are very prominent in Brazil, not only for the diseases they cause, but also for their association with GBS.

Guillain-Barre Syndrome in Brazil
In Brazil, the high rate of GBS diagnosed in recent years may be related to Dengue, Chikungunya and Zika virus (DCZ). The prevalence of these arboviruses is due to the favorable conditions for the development of vectors that can transmit them, and consequently spread these diseases [21]. The correlation between GBS and arbovirus diseases prevalent in Brazil has been associated as a sequel after manifestations of these viruses in patients. 6 In this country, Dengue cases have been prevalent for many years, but until 2014 there was no significant increase in reports of GBS.
However, after this period, there was the introduction of Zika virus in Brazil, and there was a significant increase in GBS cases, worrying the Health Departments of the country [22,23]. Given the above, detailed studies were performed, the information was collected from suspected, probable, confirmed and discarded cases, and later, they collected data from the patients analyzing whether they had acquired previous infections with DCZ. Data from several surveys showed that Brazil would need a national protocol for investigating GBS following infections caused by DCZ. The results showed a possible correlation between GBS and Zika vírus, since there were no outbreaks of the disease before the circulation of this virus was registered [23].
This correlation is reported in several studies, patients diagnosed with GBS had Zika virus-neutralizing antibodies, thus confirming this specific relationship between cases [23][24][25]. In addition to Brazil, outbreaks of GBS associated with Zika virus infections were diagnosed in French Poland in 2013 [26]. Despite many reports involving Zika virus, there are publications of neurological manifestations which were also caused by Dengue [27]. The etiopathogenesis of GBS after Dengue is still rare and poorly described [1]. Even though this correlation is an uncommon sequel, there are reports in the clinical literature and this association should be further investigated [1][2][3][4][5][6].
Chikungunya virus can also cause infections and evolve into severe neurological conditions, up to 60% of cases of severe atypical neurological complications of Chikungunya infection have been reported [28]. However, according to the literature most cases of GBS are associated with cases of infections caused by Zika virus.6 In Brazil and other tropical countries, DCZ certainly play an important role in GBS [29]. With the increasing incidence of GBS in Brazil and worldwide, it is extremely important to investigate new treatment alternatives, thus avoiding irreversible or fatal cases.

New Perspectives of Treatment
The conventional effective treatments for GBS are intravenous immunoglobulin and plasma exchange, the former being the first treatment choice due to easy application, availability and minor side effects [7,[30][31] Although these treatments are the most used, many patients may not respond well to them and have limited mobility, pain and fatigue, and in some cases even pass away, so these treatments should be administered as soon as possible for them to be more effective and prevent further nerve damage [32,33]. Currently, the development of new treatment alternatives is still very scarce. Given the above, there is a need for studies that can investigate more modern treatments.
A new treatment alternative, called the Zipper Method, can reduce mortality, accelerate weaning from mechanical ventilation, and decrease length of stay. This method consists of a combined administration of the two conventional methods, administering plasma exchange and subsequently intravenous infusion of immunoglobulin, than repeating the process around five times. This method may be promising, but it needs further clinical studies to prove its efficacy [7]. Some therapeutic biological agents have also attracted the attention of researchers [8]. These agents are protein drugs that mediate their effects by modulating the immune system [34]. These biological drugs have been reported to be effective for treating GBS, but more clinical studies are needed.
Advances in medicine are essential for a better understanding of the immunopathology of the disease in order to identify new therapeutic targets [8].

Conclusion
The increase in GBS cases in Brazil and worldwide has led to several studies to better understand the correlation between