Studies On Clinical Features, Treatment And Prognosis Of Human Guillain-barré Syndrome

Part 1 Clinical features of Guillain-Barré syndrome associated with exogenous ganglioside administrationBackground and objective: Guillain-Barré syndrome(GBS) following intravenous ganglioside treatment was reported in Europe several decades ago. However, ganglioside as a nutritional agent has been hitherto widely used in China and ganglioside-associated GBS cases have been rarely documented. In addition, it remains unknown whether the clinical course and the outcome of gangliosideassociated GBS are distinguishable from non-ganglioside-associated sporadic GBS.Methods: We identified 7 patients who developed GBS after intravenous use of gangliosides(ganglioside+ group). Their clinical data were compared with those of 77 non-ganglioside-associated GBS patients(ganglioside- group) in 2013, aiming at gaining the distinct features of ganglioside-associated GBS.Results: Although the mean age, protein levels in cerebrospinal fluid(CSF) and frequency of cranial nerve involvement were similar between the two groups, the Hughes Functional Grading Scale(HFGS) score and the Medical Research Council(MRC) sum score at nadir significantly differed(4.9 ± 0.4 vs 3.6 ± 1.0; 7.7 ± 5.5 vs 36.9 ± 14.5, both p < 0.001), indicating more severe disease severity of gangliosideassociated GBS. A higher ratio of patients in the ganglioside-associated GBS group required mechanical ventilation(85.7% vs 15.6%, p < 0.01). The short-term prognosis of ganglioside-associated GBS, as measured by the HFGS score and the MRC sum score at discharge, was poorer(4.3 ± 0.5 vs 2.8 ± 1.1; 17.3 ± 12.9 vs 46.0 ± 13.9, both p < 0.001). All the patients in the ganglioside+ group presented an axonal form of GBS. When compared with the axonal form of GBS in the ganglioside- group, more severe functional deficits at nadir and poorer recovery after standard treatment were still prominent in ganglioside-associated GBS. Anti-GM1 and anti-GT1 a antibodies were detectable in patients with AMAN. The concentrations of these antibodies in patientswith AMAN were insignificantly different between the ganglioside+ and gangliosidegroups.Conclusions: The subtype of ganglioside-associated GBS is predominately AMAN, which usually manifests a more severe clinical course and poorer outcome.Part 2 Comparative study on clinical characteristics of GuillainBarré syndrome between adults and childrenBackground and objective: Guillain-Barré syndrome(GBS) is an acute inflammatory disorder of the peripheral nervous system, and it is an important cause of acute neuromuscular paralysis. Patients with GBS usually presented as rapidly progressive, symmetric flaccid weakness of the extremities. GBS could develop at any age, and the clinical characteristics of pediatric GBS have been extensively studied and well-characterized in a number of different countries. However, the clinical characteristics of childhood GBS have been scarcely compared with that in adults.Methods: We investigated the clinical data of 750 patients(541 adults and 209 children) with GBS from 2003 to 2014, and clinical characteristics of pediatric patients were compared with adult ones.Results: Pain was a more frequent complaint in children(17.2% vs 9.6%, p < 0.01), who were also found shorter interval from onset to nadir(6.3d vs 7.3d, p < 0.01) and higher incidence of bulbar dysfunction(14.8% vs 22.0%, p < 0.05). The disease severity in children was comparable with adults. In addition, a higher incidence of pediatric GBS was found in summer, especially in July and August, when compared with adults(both p < 0.01). The clinical features of acute motor axonal neuropathy(AMAN) and acute inflammatory demyelinating polyneuropathy(AIDP) in children were comparable with adult ones. Similar to adults, bulbar dysfunction(odds ratio [OR]: 4.621, 95% confidence interval [CI]: 1.240-17.218, p < 0.05) and lower nadir MRC(OR: 0.897, 95% CI: 0.855-0.941, p < 0.01) were also risk factors for mechanical ventilator in children. Autonomic dysfunction, which was significantly higher in mechanically ventilated children(39.1% vs 8.8%, p < 0.01), served as apredictor for mechanical ventilator in pediatric GBS(OR: 70.415, 95% CI: 9.265-535.158, p < 0.01). As to the efficacy of intravenous immunoglobulin(IVIg) to GBS, there was insignificantly different between children and adults.Conclusions: The clinical characteristics of pediatric GBS differ from those of adults. Unlike adults, autonomic dysfunction was an independent risk factor for mechanical ventilation in pediatric patients.Part 3 Investigation on the efficacy of intravenous corticosteroids to patients with Guillain-Barré syndromeBackground and objective: Intravenous immunoglobulin(IVIg) has been proven most effective in treating Guillain-Barré syndrome(GBS). Corticosteroids as an addon therapy when used combined with IVIg have been proven more effective in treating GBS. However, some authors believed that the efficacy of intravenous corticosteroids combined with IVIg did not superior to IVIg therapy. Herein we explored the therapeutic effects of intravenous corticosteroids to GBS patients.Methods: We analyzed the clinical data of 527 adult patients with GBS who were prescribed to different treatments from 2003 to 2014. According to the treatment modality, the enrolled patients were divided into four groups. The therapeutic effect of a treatment was evaluated by the improvement of Hughes Functional Grading Scale(HFGS) and Medical Research Council(MRC) sum score.Results: With comparable incidence of infectious complications(p > 0.05), more mechanically ventilated patients were found improvement after IVIg treatment than combination IVIg with intravenous corticosteroids(MRC: 97% vs 72.4%, p < 0.05; HFGS: 97% vs 72.4%, p < 0.05). As to bedridden patients without mechanical ventilation, incidence of infectious complications(p > 0.05) and ratio of patients who were improved after IVIg were insignificantly different from the combination therapy(MRC: 89.6% vs 86.5%; HFGS: 69.6% vs 61.5%; both p > 0.05), even if the intravenous corticosteroids were initiated within 7 days after onset(p > 0.05). In addition, supportive treatment was sufficient for patients who were able to walk withhelp(HFGS = 3) and mildly affected(HFGS < 3) when compared with IVIg and intravenous corticosteroids.Conclusions: IVIg is sufficient to GBS patients who are unable to walk(HFGS > 3), while corticosteroids are detrimental for short-term prognosis in mechanically ventilated patients when used in combination with IVIg. As to patients who were able to walk with or without help, intravenous corticosteroids therapy does not superior to supportive treatment and IVIg.Part 4 Fasting glucose level correlates with disease severity and short-term prognosis in adult patients with Guillain-Barré syndromeBackground and objective: Hyperglycemia has been found to be associated with the occurrence and clinical severity of many diseases. A potential association between diabetes and Guillain-Barré syndrome(GBS) has been indicated by a few case studies. We retrospectively analyzed the clinical features of a large cohort of GBS patients during acute phase to explore the relationship between the fasting plasma glucose(FPG) level obtained at admission and the severity of GBS, as well that between FPG level and the short-term prognosis.Methods: A total of 371 adult patients with available FPG at admission were enrolled in the study. According to the level of FPG at admission, they were divided into two groups, i.e. the normal FPG group and high FPG group. Then the correlation of FPG level with disease severity of adult GBS, as well as short-term prognosis was investigated.Results: In total, 127 patients fell into the high FPG group while the remaining 244 patients were in the normal FPG group. The mean age of the high FPG group was 46.6 years old while it was 37.8 years old in the normal FPG group(p < 0.01). The proportion of aged patient(older than 60-year-old) was higher in the high FPG group than the normal FPG group(18.1% vs 9.0%, p < 0.05). Regards to the ratio of male, incidence of antecedent infections, hyporeflexia or areflexia, cranial nerve deficits,sensory disturbance, and hyponatremia, they were all comparable between the two groups(all p > 0.05). In addition, the interval from onset to admission, as well the interval from onset to nadir in the high FPG group was insignificantly different from that in the normal FPG group(both p > 0.05). However, the ratio of HFGS > 3 point GBS patients was higher in the high FPG group(69.3% vs 58.6%, p < 0.01). Importantly, the MRC at admission and at nadir were both lower while the HFGS at admission and at nadir were both higher in high FPG group(all p < 0.01), indicating the clinical severity was more severe in the high FPG group. Similarly, we found that the MRC was lower while HFGS was higher in the high FPG group when the patients discharged(both p < 0.01), accompanied with longer duration(p < 0.01), implying the short-term prognosis was worse in the high FPG group. Then we further explored the correlation between FPG and clinical severity, as well as that between FPG and shortterm prognosis. We found that FPG was negatively correlated with MRC at admission, at nadir and at discharge(p < 0.01); while it was positively correlated with the duration of hospitalization and HFGS at admission, at nadir and at discharge(p < 0.01).Conclusions: High FPG correlates with more severe clinical severity and poorer shortterm prognosis of adult GBS.Part 5 Predictors for mechanical ventilation and short-term prognosis in patients with Guillain-Barré syndromeBackground and objective: Guillain-Barré syndrome(GBS) is an immune-mediated disorder of the peripheral nervous system. Respiratory failure requiring mechanical ventilation(MV) is a serious complication of GBS. Identification of modifiable risk factors for MV and poor short-term prognosis in mechanically ventilated patients with GBS may contribute to the individualized management and improve the outcome of the GBS patients.Methods: We analyzed the clinical data of 541 patients who were diagnosed as GBS from 2003 to 2014. Independent predictors for MV and short-term prognosis inmechanically ventilated patients were identified on multivariate logistic regression analysis.Results: The mean age was 41.6 year-old with a male predilection(61.2%). Eighty patients(14.8%) required MV. Multivariate analysis revealed that shorter interval from onset to admission(p < 0.05), facial nerve palsy(p < 0.01), bulbar dysfunction(p < 0.01) and lower Medical Research Council(MRC) sum score at nadir(p < 0.01) were risk factors for MV; while disease occurrence in summer(p < 0.01) was a protective factor. As to prognostic factors, absence of antecedent infections(p < 0.01) and lower MRC at nadir(p < 0.01) were predictors of poor short-term prognosis in mechanically ventilated patients regardless of treatment modality. We further investigated the predictors of poor short-term prognosis in patients requiring MV with different nadir MRC sum score. Combined use of intravenous corticosteroids with intravenous immunoglobulin(odds ratio(OR): 10.200, 95% confidence interval(CI): 1.068-97.407, p < 0.05) was an independent predictor of poor short-term prognosis in mechanically ventilated patients with a nadir MRC sum score from 0 to 12 points, regardless of existence of antecedent infection.Conclusions: Clinical predictors of MV and poor short-term prognosis in mechanically ventilated GBS patients were distinct. Add-on use of intravenous corticosteroids was a risk factor for poor short-term prognosis in mechanically ventilated patients with a nadir MRC sum score from 0 to 12 points.