| BackgroundGuillain-Barre Syndrome (GBS) is an autoimmune disease, peripheral nervous system (PNS) involved, characterized by acute flaccid paralysis of limbs, demyelinating or axonal injuries in nerve conduction studies and albumino-cytological dissociation in cerebrospinal fluid (CSF). The incidence of GBS worldwide is 0.6 to 4 per 100,000 person-years, with the male/female ratio about 1.5.The main subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), Miller-Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE).The main immunotherapies are intravenous immunoglobulin (IVIG) and plasma exchange. Nonetheless, about 3% to 5% patients die from this disease under current treatment. Death can occur in all phases of the disease. The most common causes of death are respiratory insufficiency, pulmonary infection, pulmonary embolism, autonomic dysfunction, and cardiac arrest, etc.The pathogenesis of GBS is not entirely illuminated now. According to reports, the common causes are as follows:1. Infection:Infection is the well accepted risk factor of GBS. In 1958, Campbell, through reviewing literatures and studying of cases he encountered, proposed that infection was related to GBS. Now it is believed that two-thirds GBS patients had infections before the onset of GBS, especially respiratory infection and diarrhea. In 1982, the first case was reported with confirmed Campylobacter jejuni infection before the onset of GBS. From then on, C. jejuni had been considered to be one of the most common bacteria which trigger GBS. About 30% of GBS patients suffered from diarrhea caused by C. jejuni before GBS. However, not all patients developed GBS after this kind of bacteria infection, and the incidence of GBS among people infected C. jejuni is 1/1000-5000. The latency time between diarrhea and the onset of GBS is 3 days to 6 weeks, with the median time of 10 days.C. jejuni infection is thought to be associated with AMAN. Some studies showed that GBS after C. jejuni infection are all AMAN subtype, while some other studies showed that only half GBS after C. jejuni infection could be classified into AMAN type. The possible pathogenesis is molecular mimicry of antigenic determinant on the C. jejuni react with gangliosides on the peripheral nerves which triggers the onset of AMAN.In addition, there are many other pathogens related to GBS, such as Haemophilus influenzae, Epstein-Barr virus, cytomegalovirus, Mycoplasma pneumoniae, Salmonella species, Herpes viruses.2. Vaccination:Influenza vaccine and rabies vaccine may trigger GBS. In 1976, the incidence of GBS among people who had influenza A (H1N1) vaccination was four to eight times higher than that in population without such vaccination.Early rabies vaccine originated from sheep caused GBS, which may be due to the nervous tissue ingredients in the vaccine. A few cases of GBS were reported after receiving human papillomavirus recombinant vaccine, but whether the occurrence of GBS was associated with this kind of vaccination is not clear yet. More recent population studies suggest that the risk of developing GBS following newer formulations of the influenza vaccine is very low.3. Surgery:Many reports showed the occurrence of GBS in patients after surgery, such as cardiac surgery, gastrointestinal surgery, neurosurgery and so on. In a retrospective study, Gensicke showed that the risk of GBS in patients after surgery was 13.1 times of that in people without surgery. And in a similar study carried out in Finland, the risk was 6 times of that in the general population.4. Trauma:Some cases of GBS after trauma were also reported, and the trauma often involved damages to brain, spinal cord or peripheral nerve.5. Ganglioside:In 1993, several cases of GBS after administration of gangliosides were reported, which finally led to the withdrawl of gangliosides in Italy in December 1993. But the relationship between ganglioside and the incidence of GBS is still controversial. Some studies showed that there was no correlation between intravenous ganglioside and occurrence of GBS. There are also studies showed that the incidence of GBS did not significantly decline after the withdrawl of ganglioside. Although ganglioside is widely used, very few people developed GBS after the administration of the drug. Matias-Guiu believed that gangliosides would not affect the incidence rate of GBS. Yuki, etc. established axonal type of GBS models by immunizing Japanese rabbits with mixed gangliosides.6. Other drugs:There are reports proposed that immunosuppressive drugs and antitumor drugs may trigger GBS, especially tumor necrosis factor-a (TNF-a) and cytosine arabinoside.7. Other autoimmune diseases:Systemic lupus erythematosus (SLE) patients may have peripheral neuropathies, and in some cases, peripheral neuropathies were the initial clinical symptoms. However, it is difficult to discriminate between GBS and SLE-related peripheral neuropathy.8. Immune suppression:Immunosuppressive state may be related to the pathogenesis of GBS, such as Hodgkin’s diseases, non-Hodgkin’s lymphoma, bone marrow transplant, organ transplant. Pregnancy may also be a trigger of GBS.9. The unknown risk factors:In addition to the possible triggers mentioned above, there are still cases of GBS with no clear causes. Some may have asymptomatic infection before the onset of symptoms. For example, about half people infected with C. jejuni have no signs of diarrhea.We have noticed cases of GBS following surgery, trauma, administration of ganglioside in our clinical work. Therefore, we performed a retrospective analysis of possible triggers of GBS.PurposeIt has been accepted that infection is the most common trigger of GBS. Surgery and trauma might be the risk factors. We analyzed GBS patients admitted to Shandong Provincial Qianfoshan hospital in the last 4 years to explore the risk factors. Risk factors in our study were compared with that in Sipila’s study. We compared the proportion of subtype, intubation and hospital stay of GBS patients after surgery/trauma with patients without these factors.Methods1. Case collectionWe searched all patients (age≥16 years old) hospitalized in Shandong Provincial Qianfoshan Hospital from June 2011 to May 2015 via electronic medical records management system with the keyword "Guillain-Barre Syndrome", "Miller-Fisher syndrome", and "Bickerstaff Brainstem Encephalitis". After reviewing medical histories and the laboratory examinations, patients met the diagnostic criteria of Chinese Guillain-Barre syndrome treatment guidelines (2010) were included. The possible risk factors, clinical features (age, gender, mean days to onset, electromyography, and cerebrospinal fluid findings, length of stay, etc.) were also collected.2. Ethical ConsiderationsThis retrospective study was done with all clinical and patient data collected in a confidential way. This study received local ethical approval from the medical ethics committee of Shandong Provincial Qianfoshan Hospital with the following reference number:2015(006).3. Statistical methodsMean age, gender ratio and mean days to onset were calculated. We calculated the proportion of infection, surgery or vaccination in our cohort and compared with that in Siplia’s study. We calculated and compared the proportions of different subtype, intubation and mean duration of hospitalization in both non-surgical/trauma GBS group and surgical/trauma GBS group. Pearson’s Chi-square test was used to compare the proportion of potential triggers in study population and those reported previously in literature. For quantitative data, comparison between two groups was undertaken using the Student’s t-test. Statistical analyses were performed using the SPSS software, version 19.0. A significant level was set at P< 0.05.ResultsThirty-six patients were included in this study. The average age was 50.7 years and male/female ratio 28:8.Twenty-six patients had lumbar puncture, in which 21 patients showed albumino-cytological dissociation in CSF. Seventeen patients had infections (7 were respiratory tract infection,6 were digestive tract infection, the other 4 were post-surgery/trauma group); 9 had surgery/trauma prior to GBS (8 received ganglioside treatment before the onset of symptoms,4 combined with infection,2 combined with tumor); 14 patients were found with no clear risk factors. No patient had vaccination before the onset of GBS. No patients who were given ganglioside because of acute cerebral infarction, Parkinson’s disease and peripheral neuropathy developed GBS.Compared our study with Siplia’s research, there was no significant difference in the average age, sex ratio and the proportion of GBS after vaccination. However, the proportion of GBS after infection (47.2%) in our study was lower than that in Siplia’s research (P< 0.05). And the proportion of post-surgical GBS in present study was 19.4%, which was greater than that of the study led by Sipila and colleagues (P< 0.05).Thirty-two patients had electrophysiological examination. These patients were classified into AIDP (17 patients), AMAN (4 patients), AMSAN (5 patients), MFS (2 patients) and unclassified subtype (4 patients) based on clinical manifestations and the electromyography results. Among the 27 GBS patients without surgery/trauma,4 didn’t have electrophysiological examination,4 were unclassified,14 were demyelinating subtype,3 were axonal subtype, and 2 were MFS. Among the 9 GBS patients following surgery/trauma,3 were demyelinating subtype, and 6 were axonal subtype. The proportion of axonal subtype in the surgery/trauma group (66.7%) was significant higher than that in the non-surgery/trauma group (15.3%) (P= 0.013). The average hospital stay was 19.8 days in all GBS patients, and 33.7 days in the surgery/trauma group, which was significantly higher than that in the non-surgery/trauma group (P< 0.05).Conclusion1. Infection is the most common trigger of GBS. The main infection sites are respiratory tract and digestive tract.2. In our study, surgery, trauma and ganglioside treatment may be risk factors of GBS. Eight in 9 (88.9%) patients following surgery/trauma were treated with ganglioside before the onset of GBS, and 4 (44.5%) had infections. Ganglioside, infection and surgery/trauma may play a synergistic effect in development of GBS. Compared with previous study, the proportion of post-surgical GBS was higher.3. Axonal type (66.7%) was more common in post-surgical/traumatic GBS patients. Post-surgical/traumatic GBS patients stayed longer (33.7 days) in hospital. |
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