| Objective:Anti-N-methyl-D-aspartic acid(NMDA)receptor encephalitis is an immune disease characterized by neuropsychiatric symptoms mediated by autoimmune antibodies against the Glu NI subunit of NMDA receptor.Cognitive impairment is a common symptom of anti-NMDA receptor encephalitis,but it is easy to be ignored due to the severe mental symptoms of most patients in the acute phase and it is difficult to evaluate cognitive function during acute phase of disease.About 50% of the patients showed no specific abnormalities in routine head magnetic resonance imaging(MRI),and routine MRI of patients with anti-NMDA receptor encephalitis lacked specificity due to the diversity of brain regions involved,so its significance in the diagnosis of anti-NMDA receptor encephalitis was limited.The purpose of this study was to explore the changes of cognitive function in the acute phase of patients with anti-NMDA receptor encephalitis and their recovery with the course of disease,as well as the changes in structural and functional MRI and cognitive function between patients with favorable outcome and healthy controls,as well as the relationship between these changes and the severity of the disease in the acute stage.Materials and Methods:The first chapter of this study included patients with anti-NMDA receptor encephalitis and those admitted into west China hospital of Sichuan university’s during the acute phase from November 2017 to May 2019.Verbal fluency test,Boston naming test,rey auditory verbal learning test(RAVLT)immediate and delayed recall,digit span forward and backward,Visual-paired associates immediate and delayed recall,Verbal-paired associates immediate and delayed recall,symbol digit modalities test,and Trail Marking Test were evaluated in subjects.Follow-up was performed 6 and 12 months after the onset of disease,and scales were re-evaluated.At the same time,healthy controls matched with age,sex and education level were included.The cognitive function of patients in the acute phase was compared with that of healthy controls.For patients who completed the follow-up at three time points,repeated measure analysis of variance was used to compare the differences in scores of each scale at three time points.The experimental group in the second chapter of this study was anti-NMDA receptor encephalitis patients who were admitted to West China Hospital of Sichuan University from June 2012 to December 2018 and those had a score of less than 2 on the Modified Rankin Scale(m RS),and had 3 months after the onset of disease,and did not have obvious intracranial abnormal signals in general head MRI.The control group were healthy individuals matched with the experimental group in age,sex and education level.resting-state functional MRI,diffusion tensor imaging,and high resolution 3D-T1 scanning were performed on all subjects,and scale assessment was performed.Comparisons of amplitude of low-frequency(ALFF),degree centrality(DC),regional homogeneity(Re Ho),fractional anisotropy(FA),gray matter volume(GMV)and scores of each scale were conducted between patients with anti-NMDA receptor encephalitis and healthy control.Some regions with significant differences in ALFF and DC analysis were extracted as regions of interest,and their functional connectivity(FC)to the whole brain was analyzed.According to the severity of the disease in the acute phase,namely the maximum MRS score in the acute phase(Max＿m RS＿A),patients in the experimental group were divided into severe group(MAX＿MRS＿A=5 points)and relatively mild group(MAX＿MRS＿A<5 points),and was further divided into subgroups for analysis.The regions with significant differences in MRI analysis and the scales with significant differences in cognitive scale evaluation were analyzed by Pearson correlation.Results:In this study,21 patients during the acute phase of anti-NMDA receptor encephalitis were enrolled in the first chapter of this study,of whom 18 patients completed follow-up at 6 months after onset,13 patients completed follow-up at 12 months after onset,and 12 patients completed three follow-up.Forty-nine patients during the recovery phase of anti-NMDA receptor encephalitis were included in the second chapter of this study.Compared with healthy controls,patients with anti-NMDA receptor encephalitis in the acute phase showed significant differences in Verbal fluency test,Boston naming test,RAVLT immediate and delayed recall,digit span forward and backward,Visual-paired associates immediate and delayed recall,Verbal-paired associates immediate and delayed recall,symbol digit modalities test,and Trail Marking Test.There were statistically significant differences in verbal fluency,Boston naming,RAVLT immediate and delayed recall,digit span forward and backward,Visual-paired associates immediate recall,Verbal-paired associates immediate recall,and symbol digit modalities test among repeated measurement analysis(P<0.05).The Visual-paired associates delayed recall,word pairing delay test and connection test had no statistical difference(P>0.05).Post hoc analysis showed that the tests of number width,visual pairing immediacy,Verbal-paired associates delayed recall,and symbol digit modalities test improved significantly at 6 months and 12 months after onset compared with the acute phase,but there was no significant difference between at 6 months and 12 months after onset.Significant improvements in verbal fluency,RAVLT immediate and delayed recall were observed at 12 months after onset compared with the acute phase.In recovery phase of patients with anti-NMDA receptor encephalitis,ALFF was decreased in the frontal＿sup＿orb＿R and increased in the postcentral gyrus,precuneus,and rolandic＿oper＿R compared to controls.DC was decreased in the frontal＿mid＿orb,cingulum＿ant,caudate,insula＿L,and pallidm＿L,and increased in temporal＿mid＿R,occipital＿mid＿R,angular＿R,and postcentral＿L.Re Ho was increased in the postcentral gyrus,fusiform＿L,occipital＿inf＿L and cerebelum＿6＿R(P<0.005).According to the severity of the disease in the acute stage,the subgroup analysis showed that ALFF had significant differences in the paracental lobule and the precentral gyrus and poscentral gyrus.DC had significant differences in the anterior cingulate and medial prefrontal cortex,and Re Ho had significant differences in the paracentals lobule,frontal＿mid and parietal＿inf(P<0.005).In the post hoc analysis,the ALFF values of the postcentral＿L in both the severe group and the relatively mild group were significantly higher than in the healthy control group.In addition,the ALFF values of the frontal＿inf＿tri＿R,pre C＿L,paracentral louble and the supplementary motor area were also significantly different between the groups with different severity of the disease.Compared with healthy controls,DC values in the anterior cingulate gyrus region were significantly decreased in both severe and relatively mild patients.The Re Ho values in the fusiform＿L,paracentral louble and postcentral＿L in the severe group were significantly higher than those in the healthy control group,while the Re Ho values in the frontal＿mid＿R and parietal＿inf＿L were significantly lower than those in the healthy control group.And the Re Ho values in the fron＿inf＿tri＿R in the relatively mild group was higher than those in the healthy control group.FC analysis showed that the functional connections between the anterior cingulate area and the temporal＿inf＿R,fusiform＿R,lingual＿R,and the medial prefrontal cortex were decreased in the patients with anti-NMDA receptor encephalitis compared with the healthy controls,while the functional connections between the posterior central gyrus,the paracentral lobule and the precentral gyrus,the postcentral gyrus,and the supplementary motor area were increased.The average FA value of Max＿m RS＿A=5 group in the corpus callosum,fornix,internal capsule,anterior corona radiata,posterior corona radiata and superior corona radiata regions were significantly lower than that in the Max＿m RS＿A<5group.In addition,the FA value of Max＿m RS＿A=5 group in fornix was lower than that in healthy control group.Patients with anti-NMDA receptor encephalitis in recovery phase had reduced GMV in anterior cingulate cortex.In further subgroup analysis,the GMV in the anterior cingulate cortex decreased in both the MAX＿MRS＿A =5 group and the MAX＿MRS＿A <5 group compared with the healthy control group.However,there was no significant difference in the GMV between the two groups with different severity in the acute phase.Except digit span forward,symbol digit modalities test,and Trail Marking Test,in other cognitive function assessment,patients with anti-NMDA receptor encephalitis in the recovery phase scored significantly lower than controls.According to the illness severity in the acute phase,patients were divided into subgroup for analysis,and there are still significant differences among the scales,and relatively lower mild group scores higher.After the post hoc analysis,it was found that all scales with statistical differences in the analysis of variance showed statistical differences between the Max-MRS-A=5 group and the control group after correction.There were statistical differences in RAVLT immediate and delayed recall and Verbal-paired associates delayed recall between the Max-MRS-A<5group and the Max-MRS-A=5 group,while only significant differences were found between the Max-MRS-A<5 group and the control group after correction in digit span backward and RAVLT immediate recall.The correlation analysis between MRI and cognitive scale showed that the Visual-paired associates immediate and delayed recall was negatively correlated with the Re Ho value of the occipital＿inf＿L and the RAVLT immediate and delayed recall was negatively correlated with the Re Ho value of the cerebelum＿6＿R.The Visual-paired associates delayed recall was positively correlated with the volume of the anterior cingulate cortex.Verbal fluency test,Visual-paired associates immediate recall,RAVLT immediate and delayed recall were positively correlated with FA value of fornix.Conclusion:The cognitive function of patients with anti-NMDA receptor encephalitis is obviously impaired in the acute stage,but part of these function can be gradually improved with the course of the disease.The patients with anti-NMDA receptor encephalitis with good prognosis at the convalescence stage and no obvious intracranial abnormal signals in general head MRI showed significant differences in their resting state f MRI and cognitive function compared with healthy controls,which were mainly manifested as activation of sense-motor areas and suppression of default network,and impairment of cognitive functions such as memory and language ability.There were significant differences in the structure,functional magnetic resonance and cognitive function among patients with different severity of the disease in the acute phase,and the impairment of the white matter structure around the corpus callosum and cognitive function was more obvious in patients with severe disease in the acute phase.FA value of fornix,gray matter volume of the anterior cingulate cortex,and Re Ho value of theoccipital＿inf＿L were associated with Visual-paired associates test.FA value of fornix was also associated with Verbal fluency test and RAVLT. |
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