Neuropsychiatric Sequelae In Acute Carbon Monoxide Poisoning:A Structural MRI Study

Background and ObjectivesAcute carbon monoxide poisoning（ACOP）is a type of poisoning with a fairly high incidence and mortality rate.Some patients die after ACOP,and survivors may suffer from neuropsychiatric sequelae even after treatment.Neuropsychiatric sequelae can be defined as persistent neuropsychiatric sequelae（PNS）and delayed neuropsychiatric sequelae（DNS）.Previous studies have focused on the incidence,clinical presentation,typical imaging findings,prognosis,and outcome of patients with DNS.At present,studies have found that DWI can predict the occurrence of DNS and the prognosis of DNS,while there are few studies on the clinical manifestations and imaging characteristics and prognosis of PNS.Cerebral gray matter lesions,especially pallidum were the most common lesions after ACOP,and cerebral white matter lesions were related to the occurrence and prognosis of DNS.Diffusion kurtosis imaging（DKI）can quantify the diffusion distribution of non-Gaussian,and can more objectively reflect the subtle structural changes in the whole brain tissue.Compared with DWI,DKI can more accurately assess the complexity of the micro-environment of the tissue structure.Previous animal experiments and clinical studies have confirmed that the damage of cerebral cortex gray matter is also closely related to the occurrence of DNS.The relationship between the pattern of cortical injury and early complex clinical symptoms in CO poisoning patients remains unclear.Surface-based morphometry（SBM）is a structural MRI data analysis method,which can analyze various characteristics of cortical structure,such as gyrification index（GI）,sulcus depth（SD）,and cortical thickness（CT）.Movement disorders and cognitive impairment are the most important symptoms affecting the quality of life of patients with DNS.Movement disorders are due to extrapyramidal symptoms of impaired basal ganglia.Parkinson’s syndrome occurs in approximately 10%of patients with CO poisoning.Gray matter and cerebral cortex are involved in the neural pathway network in Parkinson’s syndrome（COP-P）.Previous studies have shown that cerebral cortex hypoperfusion,demyelination of the central white matter and of the corpus callosum are associated with cognitive decline after CO poisoning.There are also studies using voxel-based morphology（VBM）to investigate the characteristics of cognitive impairment in the chronic phase of CO poisoning.However,there are few studies on the early gray and white matter structural changes in patients with cognitive impairment（COP-CI）after CO poisoning.Thus,the main objectives of this study include:1.To evaluate the clinical features,laboratory results,acute brain lesions（ABLs）on diffusion-weighted imaging（DWI）at presentation,and long-term outcomes and explored the differences between patients with PNS and DNS.2.To investigate the value of quantitative evaluation of white matter damage caused by delayed encephalopathy（DNS）with carbon monoxide poisoning（CO）with diffuse kurtosis imaging（DKI）.3.To explore the characteristics of cortical thickness and shape indices in patient with carbon monoxide poisoning,and to investigate correlations between these cortical abnormalities and neuropsychological scores.4.To apply voxel-and surface-based morphology（VBM and SBM）to measure the gray matter volume,white matter volume,cortical thickness,and shape indices in carbon monoxide poisoning-induced parkinsonism（COP-P）and carbon monoxide poisoning-related cognitive impairment（COP-CI）,and to investigate the association between abnormal brain structure and the severity of motor dysfunction,cognitive impairment,and neuropsychiatric disorders.Methods1.The study included 443 patients who had suffered from carbon monoide poisoning,underwent DWI and completed 1-year follow-up.The demographics, symptomatology,laboratory results,ABLs on DWI at presentation,and long-term outcomes were compared between patients with PNS and those with DNS.2.A prospective study was conducted in 28 patients diagnosed with delayed encephalopathy followed by CO poisoning.DKI scans were performed within 7 days after onset and DKI-derived parameters including axial kurtosis（AK）,mean kurtosis（MK）and radial kurtosis（RK）were obtained.The DKI-derived parameters of the 9regions of interest（ROIs）of the white matter were measured.Neuropsychology tests were performed on both subjects using the Mini Mental State Examination Scale（MMSE）,Barthel Index,Verbal Fluency Test（VFT）,and Digital Breadth Test（DST）.3.Using surface-based morphometry,we investigated the differences in cortical thickness and shape indices between a COP group（n=44）vs healthy controls（HCs,n=36）,and between the DNS（n=21）vs non-DNS（n=23）subgroups.Additionally,the influence of cortical damage on neurological disorders was explored.4.Eighteen patients with COP-P,22 patients with COP-CI（14 patients with dementia,8 patients with no-dementia）,and 22 matched healthy controls（HCs）were included in the study.MRI scans were performed within 3 months after COP,and whole-brain structures were analyzed in conjunction with VBM and SBM in all subjects.Partial correlation analysis was performed to analyze the relationship between differences in brain volume and cortical thickness measures,structural changes,and clinical scores.Results1.The 42（9.5%）and 96（21.7%）patients with PNS and DNS,respectively,showed no significant differences in demographics,duration of CO exposure,initial conscious level,symptomatology,and laboratory results.ABLs on DWI were observed in 33 patients（33/42）with PNS and 62 patients（62/96）with DNS.The most common region of ABLs was the globus pallidus（60.6%and 56.6%in PNS and DNS,respectively）.The proportion of ABLs present and lesion distribution did not differ significantly between the two groups.At 1 year,a significantly higher proportion of patients in the PNS group showed a good outcome（modified Rankin Scale[m RS]scores of 0-2,81%）compared with the DNS group（81%vs.56.3%,p=0.047）.2.Compared with the control group,the MK,AK and RK values in all of ROIs showed an trend of increasing in DNS group.Among which,the anterior semioval center（ACS）,posterior semioval center（PCS）and frontal（FL）increased obviously（P<0.05）.In the genu of corpus callosum（CCG）,body of corpus callosum（CCB）and parietal lobe（PL）,the AK value of DNS group was higher than controls（P<0.05）.Except for temporal lobe（TL）and occipital lobe（OL）,The AK value of other ROIs had better performance than RK and MK to diagnosis DNS,of which ACS（0.802,P=0.000）>PCS（0.785,P=0.000）>FL（0.749,P=0.001）>CCG（0.730,P=0.003）>PL（0.699,P=0.009）>CCB（0.654,P=0.045）.AK value was negatively correlated with the neuropsychiatric psychology score,and the AK value of ACS had the best correlation with the VFT-backward（r=-0.603,P=0.000）.3.The COP group exhibited significant cortical thinning mainly in the bilateral fronto-parietal lobes（P<0.05,family-wise error corrected）.When cortical thinning in the bilateral parietal lobes,bilateral primary motor areas,left primary sensory areas,and bilateral paracentral lobules was explored in the DNS subgroups compared to the non-DNS subgroup（P<0.05,FWE corrected）,no differences in shape indices between the two subgroups were noted.In the COP group,there were significant positive correlations between the Mini-Mental State Examination（MMSE）score and cortical thickness in the right superior frontal gyrus（SFG）and bilateral rostral middle frontal gyrus（r MFG）（P<0.05,false discovery rate corrected）.There was no any significant correlation between cortical thickness and Neuropsychiatric inventory（NPI）,UPDRS III scores（P>0.05,FDR-corrected）.4.In patients with COP-P,VBM analysis showed reduced GM volumes in the bilateral frontal and temporal lobes,anterior cingulate cortex（ACC）,amygdala,striatum,thalamus,and cerebellum（FDR-corrected P<0.001）and a trend towards WM atrophy in the anterior cerebral and medial mesencephalon but swelling in the posterior cerebral and motor cortical areas（uncorrected P<0.001）in the patients.SBM analysis showed widespread cortical thinning that extended beyond the frontotemporal regions and involved the occipitoparietal areas and regional shallow sulcal depth in the left supramarginal gyrus in the patients（FWE-corrected P<0.05）.The severity of motor disorders was correlated with GM atrophy in the medial orbital superior frontal gyrus（SFG）,ACC,caudate,thalamus,and caudal middle frontal gyrus,while nonmotor disorders were correlated with atrophy in the SFG,ACC,thalamus,amygdala,and cerebellum crus I（P<0.05）.In patients with COP-CI,Compared to HCs,the patients exhibited significantly reduced GM volume in the bilateral medial orbital superior frontal gyrus（SFG）,bilateral gyrus rectus,bilateral anterior cingulate cortex（ACC）,left olfactory cortex（OLF）,right Parahippocampal,bilateral thalamus,bilateral temporal lobes,right angular gyrus,and bilateral posterior cerebellar lobes（FDR-corrected P<0.005）.But there was no significant differences in regional white matter（WM）volume between the COP-D and COP-non D subgroups（uncorrected P<0.001）.SBM analysis showed widespread cortical thinning in the bilateral hemisphere,among which,the regions of vertices>500 were the bilateral rostral middle frontal gyri,superior frontal gyri,precentral,and superior parietal lobes（FWE-corrected P<0.05）.There was no significant differences in regional GM volume,WM volume,and cortical thickness between the two groups（FDR-corrected P<0.005）.The reduced GM volume in the bilateral medial orbital SFG,bilateral ACC,left OLF,right Parahippocampal,bilateral thalamus,right angular gyrus,and bilateral posterior cerebellar lobes were positive correlation with the MMSE and Mo CA,while the left rectus,right Parahippocampal,bilateral thalamus,right fusiform,and left inferior temporal gyrus were negative correlation with the Time _COP-MRI（P<0.05）.Conclusion1.Demographics,laboratory results,clinical features and symptoms,and acute brain lesions on MRI at presentation did not differ between the PNS and DNS groups.The presence of ABLs on DWI was significantly associated with the development of PNS and DNS.DWI in acute CO poisoning may be useful for the early identification of patients at risk of developing neurological sequelae.However,the long-term outcome of PNS was better than that of DNS.2.DKI can quantitatively evaluate the microstructural damage of white matter from DNS,and the increase of AKwas related to the decrease of neurological function in patients with DNS.3.Cortical thickness is a more sensitive index than shape for measuring cortical damage in patients with COP exposure,as cortical thinning in the right SFG and bilateral r MFG is related to cognitive impairment.4.COP-P is characterized by reduced local gray matter volume,shallow groove depth,and thinning of the cortex.Gray matter atrophy is the main feature of brain atrophy in the early stage in COP-CI.Structural analysis of the brain in combination with VBM and SBM helps to reveal the pathological features of early imaging changes in patients with COP-P and COP-CI.