Study On Thyroid Function And Anti-thyroid Antibody In Patients With Anti-N-methyl-N-aspartate Receptor Encephalitis

Background:Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a recently recognized autoimmune disorder.In 2010,Pruss et al first described the presence of anti-thyroid antibodies in non-tumor–associated anti-NMDAR encephalitis.Subsequently,relevant reports appeared one after another.Several reports have revealed the intertwining relationships between abnormal thyroid function and immune-mediated neurological disorders,such as multiple sclerosis and neuromyelitis optica spectrum disorder.However,the association between thyroid function/autoimmunity and anti-NMDAR encephalitis has not been discussed.In 2018,two case-control studies found abnormal thyroid function and anti-thyroid antibodies were presented in patients with anti-NMDAR encephalitis and which were related closely to clinical symptoms and imaging manifestations of patients with antiNMDAR encephalitis.But the number of cases included in the two studies was less,and the conclusions were different.Objective:1.Case-control studies were conducted to compare the differences in thyroid function(thyroid-stimulating hormone TSH,free triiodothyronine FT3,free thyroxine FT4)and anti-thyroid antibodies(anti-thyroid peroxidase antibodies TPOAb,antithyroglobulin antibodies TGAb)between patients with anti-NMDAR encephalitis and healthy people.2.To investigate the difference of clinical features about the patients with antiN-methyl-D-aspartate receptor while which serum thyroid function was in different levels and anti-thyroid antibodies was in different states(positive/negative).Methods:In this multi-institutional observational study,the patients with anti-NMDAR encephalitis diagnosed by the First Affiliated Hospital of Henan University of Science and Technology,the first affiliated Hospital of Zhengzhou University and the people's Hospital of Henan Province from January 2012 to December 2018 were collected as the case group.Same period,the healthy individuals whose gender and age matched with the case group were randomly selected from those who came to the hospital for a physical examination were the control group.Collected the following data for each case group including gender,age,hospitalization time,History of thyroid disease,clinical manifestations(Referring to the diagnostic criteria for anti-NMDAR encephalitis of the expert consensus on diagnosis and treatment of autoimmune Encephalitis in China: mental behavior abnormalities or Memory disorder,speech disorder,seizures,dyskinesia/involuntary movement,declination of consciousness,autonomic dysfunction and central hypoventilation),auxiliary examination(on admission,TSH,FT3,FT4,anti-TPOAb and anti-TGAb of serum,leukocyte count,protein,chloride and glucose of cerebrospinal fluid,serum/cerebrospinal fluid antiNMDAR antibody and brain MRI,etc.),Therapeutic regimen(methylprednisolone,immunoglobulins,methylprednisolone combined with immunoglobulins),With or without tumor,modified Rankin Scale(mRS)at admission and discharge.The following data were collected for each healthy control group: gender,age,history of thyroid disease,TSH,FT3,FT4,anti-TPOAb and anti-TGAb of serum.A case-control study was conducted to compare the differences of the thyroid function and antithyroid antibodies between the case group and the healthy control group.According to different levels of TSH,FT3 and FT4,the case group were divided into low TSH group,normal TSH group and high TSH group,low FT3 group,normal FT3 group and high FT3 group,low FT4 group and normal FT4 group and high FT4 group,and the differences in hospitalization days,clinical manifestations,laboratory tests,and imaging features of patients with anti-NMDAR encephalitis were compared between different TSH,FT3 and FT4 levels.According to the results of anti-thyroid antibodies test,the case group were divided into TPOAb(+)group,TPOAb(-)group and TGAb(+)group,TGAb(-)group.The differences were compared in hospitalization days,clinical manifestations,laboratory tests,and imaging features between the TPOAb(+)group and the TPOAb(-)group,between the TGAb(+)group and the TGAb(-)group.Results:1.Compared with the healthy control group,the level of TSH,FT3 and FT4 in patients with anti-NMDAR encephalitis was lower(P<0.01),and the positive rate of anti-TPOAb and anti-TGAb was significantly higher(P<0.01).2.Compared with the anti-thyroid antibodies(-)group,anti-thyroid antibodies(+)group of patients with anti-NMDAR encephalitis had longer average hospitalization time,higher prevalences of clinical symptoms such as seizures,decreased consciousness,autonomic dysfunction,and central hypoventilation were more frequent,a higher frequency of abnormal MRI,and a higher mRS score at discharge,and the difference was statistically significant(P<0.05).But there was no significant difference in clinical characteristics of anti-nmdar meningitis patients with different levels of serum TSH,FT3,FT4(P > 0.05).Conclusions:1.The patients with anti-NMDAR encephalitis have abnormal thyroid function and anti-thyroid antibodies.2.Anti-NMDAR encephalitis patients with anti-thyroid antibodies(+)had longer average hospitalization,higher prevalences of clinical symptoms such as seizures,decreased consciousness,autonomic dysfunction,and central hypoventilation were more frequent,a higher frequency of abnormal MRI,and a higher mRS score at discharge.