| Part One Effect of glucocorticoid on patients with different subtypes of Guillain-Barré syndrome in southern ChinaObjectives:Guillain-Barré syndrome（GBS）is an immune-mediated polyradiculoneuropathy,which is an important cause of acute neuromuscular paralysis.Clinical treatment mainly adopts intravenous immunoglobulin（IVIg）and plasma exchange.However,the effect of glucocorticoids（GCs）in the treatment of GBS has been controversial,and there is a lack of in-depth research on the difference of GCs in the efficacy of different subtypes of GBS.Based on this,the purpose of this study was to investigate the efficacy of GCs on two different GBS subtypes of acute inflammatory demyelinating polyradiculoneuropathy（AIDP）and acute motor axonal neuropathy（AMAN）,and to analyze the effects of different dosage on clinical outcomes.Methods:The clinical data of GBS patients treated with GCs alone in 31 Class A tertiary hospitals in 14 provinces south of Huaihe River from January 1,2013 to September30,2016 were collected and analyzed retrospectively.The main analysis indexes included neurological symptoms,complications,electrophysiological typing and Hughes disability score at admission,nadir illness,discharge and 3 months after onset and length of hospital stay.According to the treatment plan,the patients were divided into high dosage group--methylprednisolone 250~1000 mg/d,which is gradually reduced after 3~5days;and low dosage group--methylprednisolone 40~120 mg/d（3~5 days）,or dexamethasone 10~20 mg/d（5~7 days）,or oral prednisolone 1 mg/kg/d（1 week）,gradually reduced later.The therapeutic effects of different dosage of GCs in patients with different subtypes of GBS were compared and analyzed.Results:（1）General data: A total of 251 GBS patients were included,including 189（75.3%）AIDP and 62（24.7%）AMAN.（2）Neurological symptoms: Compared with the patients of AMAN,AIDP had a higher proportion of facial paralysis（45.5% vs 16.1%,P = 0.000）and paresthesia（49.2% vs 32.3%,P = 0.027）,but a lower proportion of hyperreflex（5.8% vs 19.3%,P = 0.004）.（3）Complications: Among patients of AIDP,the proportion of pulmonary infection was higher in those treated with low-dosage of GCs（9.2% vs 20.9%,P =0.026）.（4）Hughes score: After treatment with GCs,the Hughes score of patients with AIDP was significantly lower than that of AMAN at discharge（2.51 ± 0.98 vs 2.84 ±0.73,P = 0.005）and 3 months after onset（2.06 ± 1.14 vs 2.50 ± 0.80,P = 0.000）.The Hughes score in patients of AIDP treating with high dosage GCs was lower at nadir（3.28 ± 0.88 vs 3.74 ± 0.74,P = 0.000）,even lower at discharge（2.36 ± 1.03 vs 2.68 ±0.88,P = 0.005）and 3 months after onset（1.83 ± 1.30 vs 2.30 ± 0.89,P = 0.000）compared with low dosage GCs.There was no difference in Hughes score at nadir（P= 0.262）,discharge（P = 0.591）and 3 months after onset（P = 0.386）in patients of AMAN with different dosage of GCs treatment.（5）Length of hospital stay: The days of hospital stay（13.27 ± 8.47 vs 15.16 ±7.62,P = 0.023）was significantly shorter in AIDP patients with high dosage of GCs treatment,compared with low dosage of GCs.Among patients with AMAN,there was no significant difference（P = 0.943）in hospital stay between different dose dosage of GCs treatment.Conclusion:In patients of AIDP,treatment with high dosage GCs may be more favorable in terms of their hospital stay and short-term outcome;however,in patients of AMAN,there was no difference in the efficacy with different dosages of GCs.Different dosages of GCs have different effects in the treatment of different subtypes of GBS,which suggest the status of GCs in the treatment of GBS cannot be completely denied.Part Two Efficacy of glucocorticoid combined with immunoglobulin and immunoglobulin alone in different subtypes of Guillain-Barrésyndrome in southern ChinaObjectives:Guillain-Barré syndrome（GBS）includes two major subtypes: acute inflammatory demyelinating polyradiculoneuropathy（AIDP）and acute motor axonal neuropathy（AMAN）.Intravenous immunoglobulin（IVIg）is the most widely used and proven effective method for the treatment of GBS.Clinical randomized controlled trials show that IVIg combined with glucocorticoids（GCs）has no additional benefit in the treatment of GBS.However,the pathophysiological mechanisms of AIDP and AMAN are different,and most of the clinical studies of IVIs and GCs in the treatment of GBS are not classified by subtype.In view of this,the purpose of this study was to investigate the efficacy of IVIg alone and GCs combined with IVIg in patients with different subtypes of GBS.Methods:The data of GBS patients treating using IVIg alone and GCs combined with IVIg in 69 tertiary hospitals in 14 provinces south of Huaihe River from January 1,2013 to September 30,2016 were collected and analyzed retrospectively.According to the treatment plan for the patients,two groups were divided: 1)IVIg alone--0.4 g/kg/d for 5 days;2)combination of GCs and IVIg--IVIg（0.4g/kg/d for 5 days）,methylprednisolone 40~1000 mg/d for 3~5 days,or dexamethasone 10~20 mg/d for 5~7 days,and then gradually reduced to oral prednisone tablets.The main analysis indexes included electrophysiological typing,Hughes score and length of hospital stay.The main analysis indexes included Hughes scores at admission,nadir,discharge and illness onset after three months and length of stay;and the efficacy differences of GBS and its subtypes（AIDP and AMAN）for different treatment schemes were compared and analyzed.Results:（1）General data: 1)A total of 447 GBS patients were enrolled,including 292 cases treated with IVIg alone and 155 GCs combined with IVIg.2)Among 226 AIDP patients,153 cases were treated with IVIg alone and 73 GCs combined with IVIg.Among 94 AMAN patients,59 cases were treated with IVIg alone and 35 GCs combined with IVIg.（2）Hughes scores: 1)In GBS patients,those with combination of GCs and IVIg had lower Hughes scores at discharge（2.28 ± 1.18 vs 1.94 ± 1.29,P = 0.003）and illness onset after three months（1.51 ± 1.13 vs 1.11 ± 0.96,P = 0.000）compared to IVIg alone.2)In AIDP patients,those with combination of GCs and IVIg had lower Hughes scores at discharge（2.25 ± 1.14 vs 1.90 ± 1.31,P = 0.041）and illness onset after three months（1.38 ± 1.12 vs 1.04 ± 0.98,P = 0.025）compared to IVIg alone.3)In AMAN patients,there was no difference in Hughes scores between IVIg alone and combination of GCs and IVIg at discharge（P = 0.871）and illness onset after three months（P = 0.449）.（3）Length of hospital stay: Compared with IVIg alone,GBS patients treated with combination of GCs and IVIg had longer hospital days（17.59 ± 10.58 vs 18.01 ±8.44,P = 0.023）;AIDP patients had shorter hospital days（18.00 ± 11.13 vs 17.75 ±5.67,P = 0.045）and AMAN patients had significantly longer hospital days（16.83 ±10.02 vs.21.60 ± 12.24,P = 0.009）.Conclusion:Compared with IVIg alone,combination of GCs and IVIg is of remarkable efficiency in AIDP patients.In contrast,there was no significant improvement applying combination therapy for AMAN patients.Part Three Dynamic expression of unfolded protein response pathway of endoplasmic reticulum stress in macrophages under different concentrations of methylprednisolone in rats with experimental autoimmune neuritisObjectives:At present,the pathogenesis and immunologic action of Guillain-Barré syndrome are still unclear.Previous clinical researches have speculated that the difference in the efficacy of glucocorticoids（GCs）in the treatment of different subtypes of GBS may be due to the different mechanism of inflammatory response in macrophages,and the regulation of hormone on macrophages is mainly realized through endoplasmic reticulum stress（ERS）.Based on this,this study aims to detect the expression of related molecules of unfolded protein response（UPR）signal pathway in macrophage ERS when treated with different doses of methylprednisolone（MPS）,explore the mechanism of different doses of GCs on experimental autoimmune neuritis（EAN）,so as to provide a new direction for the treatment of GBS patients,and provide possible evidence for the clinical standardized application of GCs in GBS patients.Methods:Twenty-four male Lewis rats weighing 170 ± 10 g were randomly divided into control,EAN,EAN + MPS（50 mg/kg）and EAN + MPS（10 mg/kg）groups,with 6rats in each group.The EAN model was immunized with P257-81 peptide;the control group was treated with PBS.The rats were weighed daily and the neurological score was recorded.The rats in the control group were killed at the end of the observation,and the rats in the three experimental groups were killed when the neurological function score was the highest after immunization.The inflammatory cell infiltration of sciatic nerve was observed under light microscope using HE staining.The dynamic expression of molecules on UPR pathway in the macrophages of spleen was detected by RT-PCR and Western blot.Results:（1）Body weight changes: The body weight of rats increased steadily on the 1st ~10th day of immunization in groups of EAN + MPS（50 mg / kg）and ENA + MPS（10 mg / kg）,with no difference from the control group.The body weight in MPS（10mg / kg）group decreased from the 10 th day,reached the lowest point on the 18 th day,and then gradually recovered,which was consistent with the change of the control group.The body weight of rats in MPS（50 mg / kg）group continued to increase,began to decline slowly on the 14 th day,and was the lowest on the 22 nd day,but was always higher than that in the groups of control and MPs（10 mg / kg）.（2）Neurological function score: In groups of EAN and MPS（10 mg / kg）,the rats began to reduce activity on the 10 th day,progressive hindlimb paralysis on the13 th day,and reached the peak of the disease on the 16 th day;with the highest score of was 6 points in the two groups.In MPS（50 mg / kg）group,the rats had neurological symptoms on the 13 th day,tail weakness on the 16 th day,reached the peak of the disease on the 18 th 20 th day,and the highest score was 3 points.No rats had quadriplegia and death.（3）Histopathology of sciatic nerve: HE staining showed that the inflammatory cell infiltration of sciatic nerve in groups of EAN and low-dose MPS（10 mg / kg）was significantly higher than that in high-dose MPS（50 mg / kg）group.（4）UPR related protein level: The expression of UPR related protein of in macrophages of spleen in EAN group was consistent with that in low-dose MPS（10mg / kg）group,which was significantly higher than that in high-dose MPS（50 mg /kg）group（P < 0.01）.Conclusion:UPR pathway of macrophage ERS is involved in the pathogenesis of EAN.Among them,high concentration GCs slows down the progress of EAN by inhibiting macrophage UPR signaling pathway,which has a therapeutic effect on EAN rats,while low concentration GCs has no obvious effect on macrophage ERS. |
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