Acute cerebral blood flow and its connectivity in patients with anti-LGI1 encephalitis: an arterial spin labeling study

Acute cerebral blood flow and its connectivity in patients with anti-LGI1 encephalitis: an arterial spin labeling study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Acute cerebral blood flow and its connectivity in patients with anti-LGI1 encephalitis: an arterial spin labeling study yongwei shi, chuanyong yu, zonghong li, yun ma, yulei sun, ailiang miao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4432471/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Pseudocontinuous arterial spin labeling (PCASL) is an innovative technique for measuring cerebral blood flow (CBF). The aim of this study was to identify diagnostic CBF connectivity in patients with anti-leucine-rich glioma inactivated 1 autoimmune encephalitis (anti-LGI1 AE) . Methods A total of 46 patients with anti-LGI1 AE including 27 patients with CBF during the acute stage were recruited from May 2017 to Jan 2023. The CBF in 27 patients with anti-LGI1 AE during the acute stage and 65 healthy subjects was analyzed using arterial spin labeling. Regions with CBF alterations were identified and designated as regions of interest (ROIs). Subsequently, the CBF connectivity of the ROIs was also compared between the groups. Result Patients in the acute stage of disease exhibited increased CBF in the bilateral putamen, bilateral amygdala (Amygdala_Bi), bilateral hippocampus (Hippocampus_Bi), bilateral parahippocampus and right insula (Insula_R) (P=0.001, cluster-level familywise error [FWE] corrected). Decreased CBF connectivity was observed between the right hippocampus and the right superior temporal gyrus (STG_R), right rolandic operculum (RO_R), right caudate (Caudate_R), right superior temporal pole (STP_R), right middle cingulate gyrus (MCG_R), and right anterior cingulate gyrus; between the right amygdala and the STG_R, RO_R, STP_R, right putamen, Caudate_R, MCG_R, and right supplementary motor area; and between the Insula_R and the right middle temporal gyrus (MTG_R) and STG_R (P=0.001, cluster-level FWE corrected). Furthermore, the patients also showed decreased CBF connectivity between the right parahippocampus and the STP_R, RO_R, Insula_R, MCG_R and left MTG; between the left hippocampus and the left STG, and left insula; and between the left parahippocampus and the left lingual gyrus, and left precuneus. Increased CBF connectivity was observed between Amygdala_Bi and Hippocampus_Bi (P=0.001, cluster-level FWE corrected). Conclusion The PCASL technique demonstrated high sensitivity in identifying anti-LGI1 AE patients, who in which patients exhibited decreased CBF connectivity originating from subcortical regions with increased CBF. Biological sciences/Immunology Biological sciences/Neuroscience Health sciences/Neurology anti-LGI1 autoimmune encephalitis pseudocontinuous arterial spin labeling cerebral blood flow cerebral blood flow pattern cerebral blood flow connectivity Figures Figure 1 Figure 2 Figure 3 Introduction Anti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis is a subtype of autoimmune encephalitis (AE), that manifests as behavioral changes, memory impairment, epileptic seizures, and involuntary movements, including facial brachial dystonic seizures (FBDSs) 1, 2 . Early diagnosis of anti-LGI1 AE is necessary to improve the clinical prognosis of patients 3 . In China, the diagnosis of anti-LGI1 AE is achieved through antibody detection in serum and cerebrospinal fluid (CSF) lasting at least 3 days in China, which might delay treatment and contribute to worse outcomes. The clinical criteria formulated by experts aim to assist in promptly identifying AE and expediting the initiation of immunotherapy [4]. In addition to the assessment of antibodies in CSF, brain magnetic resonance imaging (MRI) is the commonly used as a preferred radiographic technique for the diagnosis of anti-LGI1 AE 4 . Although 74% of the patients with anti-LGI1 AE have abnormal MRI findings 2 , many other immune etiologies can mimic these MRI manifestations of patients with anti-LGI1 encephalitis 5 . Compared to MRI, 18 F-fluoro-2-deoxy- d -glucose positron emission tomography ( 18 F-FDG-PET) has greater sensitivity in AE diagnosis 6, 7 . In the previous studies, 18 F-FDG-PET examination of patients with anti-LGI1 encephalitis revealed increased metabolic activity in the basal ganglia (BG) or medial temporal lobe (MTL) 8–11 . The BG and MTL consist of numerous distinct brain structures, each serving a unique function, and the structures within the BG and MTL that exhibited hypermetabolism were not identified. The metabolic connectivity pattern between brain regions with hypermetabolism in patients with anti-LGI1 AE has not been well characterized or established. Notably, the cost of 18 F-FDG-PET is prohibitive for its widespread clinical utilization, and pseudocontinuous arterial spin labeling (PCASL) is being increasingly utilized as an innovative functional method. This noninvasive MRI technique utilizes magnetically labeled arterial blood water as a natural tracer to measure cerebral blood flow (CBF) 12–17 . The clinical implementation of ASL has been further refined since the release of a consensus by the Perfusion Study Group of the International Society for Magnetic Resonance in Medicine (ISMRM) and the European Consortium for ASL in Dementia in 2015, facilitating its transition to broader clinical application 16 . As opposed to the lack of disease-specific guidance in the 2015 consensus paper 16 , the 2023 ASL guidance offers comprehensive recommendations for utilizing ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative diseases, seizures/epilepsy, and pediatric neuroradiology applications 17 . The guidelines focus on disease-specific factors in sequence optimization and interpretation 17 . We have previously reported that PCASL revealed increased CBF in the putamen and temporal lobe and decreased CBF in the precuneus and occipital lobe in patients with anti-N-methyl-d-aspartate receptor AE (NMDAR) AE 18 . The main aim of the current study was to elucidate the specific brain regions with CBF alterations in patients with anti-LGI1 AE. Additionally, we aimed to assess the connectivity of CBF between these brain regions with altered CBF in patients with anti-LGI1 AE. Materials and methods Participants A total of 46 patients were admitted to the Department of Affiliated Brain Hospital of Nanjing Medical University from May 2017 to Jan 2023. The acute phase (within 3 months) and chronic phase (over 3 months) were defined according to the clinical consensus criteria 4 . The included patients had a definitive diagnosis of anti-LGI1 AE, and their serum and/or CSF were positive for anti-LGI1 antibodies. The data collected included demographic information, neurological symptoms, MRI findings, electroencephalography (EEG) results, laboratory test results, lumbar puncture results, therapeutic interventions and assessments of their efficacy, Mini-Mental State Examination scores assessing global cognitive function, and prognosis evaluation outcomes obtained through routine outpatient consultations or telephone surveys. The ASL data of 27 patients were successfully recorded during the acute phase (within 3 months) prior to receiving immunotherapy, and the ASL data from 81 healthy subjects were also recorded. The study was approved by the ethical boards of the Affiliated Brain Hospital of Nanjing Medical University, and all steps were performed in accordance with relevant guidelines. The patients/guardians provided informed consent to participate in this study. MRI data MRI data were acquired using a 3.0-T MR system manufactured by General Electric in the United States. Resting-state perfusion imaging was performed using a PCASL sequence with a 3D fast spin‒echo acquisition and background suppression (repetition time = 4886 ms, echo time = 10.5 ms, post-label delay = 2025 ms, spiral in readout of eight arms with 512 sample points; flip angle = 111°; field of view = 240 mm*240 mm; reconstruction matrix = 128*128; slice thickness = 4 mm, no gap; 36 axial slices; number of excitations = 3; and 1.9 mm*1.9 mm in-plane resolution).The total acquisition time for the resting state ASL scan was 4 min and 41 s. During MRI scans, all participants were instructed to close their eyes, remain physically relaxed, minimize movement, and avoid falling asleep. CBF calculation Label maps were subtracted from control maps to generate ASL difference maps 18, 19, 20 . CBF images were generated by averaging the three ASL difference images in conjunction with the proton-density-weighted reference images. CBF maps were obtained from the ASL difference maps as follows: ( 1 ) The CBF maps were registered to a PET-perfusion template in Montreal Neurological Institute space using Statistical Parametric Mapping (SPM, version 12, https://www.fil.ion.ucl.ac.uk/spm ) based on MATLAB R2018b software (MathWorks Inc., Natick, MA, USA) to generate the purpose of generating standardized CBF maps, thereby facilitating group-level statistical analysis. ( 2 ) Normalized CBF images were generated by dividing the standardized CBF maps of each voxel by the mean CBF of the entire brain. This step was implemented to mitigate potential variations in labeling efficiency and individual hemodynamic disparities. ( 3 ) The standardized CBF maps were smoothed with a Gaussian kernel of 8 mm × 8 mm × 8 mm full-width at half maximum (FWHM). Normalized CBF analyses The CSF antibody tiers and sex were used as grouping criteria. The differences in CBF between groups were compared using two-sample t tests of SPM12. Age and sex were considered covariates. To control for multiple comparisons (MCs), the cluster-level familywise error (FWE) method was employed with an adjusted significance threshold of P = 0.001. Clusters exhibiting a significant disparity among groups were utilized for illustration. CBF connectivity analyses CBF connectivity among specific brain regions was assessed by analyzing the correlation coefficient of concurrent changes in CBF in these regions using SPM12. The specific procedures were as follows: ( 1 ) Brain regions with CBF alterations in all patients were selected as the seed region of interest (ROI). ( 2 ) The DPABI software was used to measure the CBF measurement of each ROI for each subject from their respective CBF maps. The connectivity of the CBF between each ROI and all other global voxels across individuals was computed using a single-sample t test for each group, while controlling for confounding variables such as sex and age. Statistical analyses were performed to identify the voxels exhibiting positive or negative correlations with the CBF value of each seed ROI within each group. ( 3 ) For each seed ROI, a spatial mask was created using the CBF connectivity images of the two groups, where the CBF values of each voxel were associated with those of the ROI in either group. ( 4 ) CBF connectivity exhibited distinct slopes between the two groups for any given pair of voxels, indicating variations in CBF connectivity of CBF across the groups. The voxels expressing a meaningfully different CBF connectivity for each ROI between healthy subjects and patients with anti-LGI1 AE were mapped by performing a specific two-sample t test within the connectivity spatial mask generated in the previous step, while controlling for age and sex. The MCs were adjusted for using the cluster-level FWE method (P = 0.001). ( 5 ) DPABI software was used to measure the CBF measurement of each seed ROI from an individual CBF image. The correlation between ROIs was determined using the Pearson correlation (P < 0.05) 18, 21, 22 . Results A total of 46 patients diagnosed with anti-LGI1 AE (23 men; 23 women) were identified. The features of the patients diagnosed with anti-LGI1 AE are displayed in Table 1. CBF images during the acute stage of disease were recorded for 27 patients with anti-LGI1 AE. Cognitive impairment was observed in 32 (69.6%) patients, and 25 (53.4%) patients exhibited epileptic seizures. The primary types of epileptic seizures were focal seizures with awareness or impaired awareness and focal to bilateral tonic‒clonic seizures, as identified based on EEG recordings. Fifteen (32.6%) patients demonstrated involuntary movement. Only 1 patient exhibited increased CSF pleocytosis. Fifteen patients had an increased protein concentration (71±34 mg/dL). Gastrointestinal tumors were observed in only one patient. 3.1 CBF alterations in patients with anti-LGI1 AE In contrast to healthy subjects, the patients with anti-LGI1 AE demonstrated increased CBF in the bilateral putamen (Putamen_Bi), bilateral amygdala (Amygdala_Bi), bilateral hippocampus (Hippocampus_Bi), bilateral parahippocampus (Parahippocampus_Bi) , and right insula (Insula_R) (Fig. 1 and Table 2). 3.2 Changes in CBF connectivity between ROIs In contrast to the healthy subjects, the patients with anti-LGI1 AE displayed decreased CBF connectivity between the right hippocampus (Hippocampus_R) and the right superior temporal gyrus (STG_R), right rolandic operculum (RO_R), right caudate (Caudate_R), right superior temporal pole (STP_R), right middle cingulate gyrus (MCG_R), and right anterior cingulate gyrus (ACG_R) (Fig. 2 and Table 3); between the right amygdala (Amygdala_R) and the STG_R, RO_R, STP_R, right putamen (Putamen_R), Caudate_R, MCG_R, and right supplementary motor area (SMA_R); and between the Insula_R and the right middle temporal gyrus (MTG_R) and STG_R (Fig. 3 and Table 3). Decreased CBF connectivity was also observed between the right parahippocampus (Parahippocampus_R) and the STP_R, RO_R, Insula_R, MCG_R and left MCG (MCG_L); between the left hippocampus (Hippocampus_L) and STG_L, and left insula (Insula_L); and between the left parahippocampus (Parahippocampus_L) and the left lingual gyrus (Lingual_L), and left precuneus (Precuneus_L). Furthermore, increased CBF connectivity was observed between and the Amygdala_Bi and Hippocampus_Bi (Fig. 3 and Table 3). Discussion The present study demonstrated that the patients with anti-LGI1 AE displayed increased CBF and decreased CBF connectivity associated with the Putamen_Bi, Amygdala_Bi, Hippocampus_Bi, Parahippocampus_Bi, and Insula_R and these changes might contribute to the diagnosis of anti-LGI1 AE (Fig. 1 and Table 2 ). Both intentional and unintentional movements rely on coordinated muscle contractions, which are initiated and controlled by various structures within the central nervous system according to specific spatial and temporal patterns. Prior to the transmission of signals from the cerebral motor cortex to the brainstem or spinal motor neurons that control muscle movement, the BG affects both the motor and premotor cortex through the intermediary involvement of the thalamus 23–27 . The putamen and caudate are vital components of the BG 25 . Neurons associated with active or passive lower limb movements are situated in a lengthy rostrocaudal extension of the dorsolateral putamen. Orofacial movement-related neurons can be found ventromedially, while those related to upper limb movements occupy an intermediate position 27 . The putamen is associated with various involuntary and stereotyped movements 27 . Increased CBF in the Putamen_Bi was observed in patients with anti-LGI1 AE (Fig. 1 and Table 2 ). The SMA plays a role in maintaining posture, coordinating movements involving both hands, internally generating motion, and constructing movements sequences 28–31 . The SMA projects more in a caudally direction, mainly toward the putamen 25 . The putamen transmits outputs to the outer section of the globus pallidus, which subsequently extends toward the subthalamic nucleus. Finally, the circuit is completed by projections that are sent back to the motor area 23 . Interestingly, the patients with Parkinson’s disease exhibited abnormal connectivity between the putamen and the SMA 32 . Notably, the anterior cingulate cortex is linked to the amygdala and orbitofrontal cortex (OFC), both of which play a role in processing emotions and learning from action outcomes. This process involves acquiring knowledge about actions that lead to specific goals based on the reward or punishment received for different behaviors 33, 34 . The region in the MCG, known as the motor cingulate area, receives information from the ACG and is involved in controlling skeletal muscles during the process of learning action–outcome associations. This region also sends signals to motor areas 35–37 . Increased CBF in the Putamen_Bi might have resulted in involuntary movements in the patients in this study (Fig. 1 ; Table 2 ). The amygdala, a significant component of the limbic system, is responsible for encoding emotions in response to external stimuli. This information is then transmitted to the ventral caudate and putamen, which are involved in regulating emotional responses 25, 38, 39 . The involvement of the anterior and midcingulate cortical regions in emotion is evident, as they facilitate goal-oriented behaviors that act as stimuli for emotional responses 33, 40, 41 . Emerging evidence has indicated that the SMA might play a crucial role in human volition, executive function, and the amalgamation of affective, behavioral, and cognitive operations 43–44 . Many mental diseases are associated with SMA functions 45, 46 . Increased CBF in the Amygdala_Bi contributed to abnormal emotions (Fig. 1 ; Table 2 ). Decreased CBF connectivity between the Amygdala_R and the Putamen_R, Caudate_R, MCG_R, and SMA_R was observed in patients with anti-LGI1 AE, which might have resulted in involuntary movements in response to abnormal emotion (Fig. 3; Table 3 ). The STP plays an important role in social and emotional processing [47, 48], the STG is associated with auditory activity 49 , and the MTG plays a crucial role in integrating the auditory and visual processing streams 50, 51 . The cortical areas of the primate temporal lobe provide inputs to the amygdala, which is highly developed 52–55 . The insular cortex exhibits connections with the STG, temporal pole, amygdala, ACG, OFC, primary and association auditory cortices, visual association cortex, hippocampus, and entorhinal cortex. It plays a crucial role in processing attentional, emotional, verbal, and motor information as well as visual and auditory data. Decreased CBF connectivity between the Amygdala_R and the STG_R, RO_R, and STP_R and between the Insular_R and MTG_R, and STG_R might contribute to mental symptoms (auditory and visual hallucinations) in patients with anti-LGI1 AE (Fig. 3; Table 3 ). The formation and retrieval of episodic memories rely heavily on the pivotal function of the hippocampus. The ACG obtains reward-related data from the OFC and amygdala and transmits this information to the hippocampal memory system via the perirhinal and entorhinal cortex for processing 56, 57 . Along with the entorhinal cortex, the parahippocampal gyrus, particularly the lateral and medial regions, functions as a conduit for spatial information transmission to the hippocampal memory system 56, 57 . The OFC is also known to have a direct connection with the posterior cingulate cortex (PCC) 49, 56, 57 . The midcingulate motor area receives reward or outcome information from the ACG and action information from the PCC and subsequently transmits signals to premotor cortex area 6 and the SMA 49 . Decreased CBF connectivity between the Hippocampus_R and the Caudate_R, MCG_R, and ACG_R and between the Parahippocampus_R and the MCG_R and MCG_L might not allow the preservation of the memory of learned reward actions (Fig. 3 and Table 3 ). Connecting bridges were observed between the temporal lobes and hippocampus 49 . Patients with LGI1 encephalitis displayed decreased CBF connectivity between the Hippocampus_R and the STG_R, RO_R and STP_R; between the Hippocampus_L and the Insula_L and STG_L; between the Parahippocampus_R and the STP_R, RO_R, and Insula_R; and between the Parahippocampus_L and the Lingual_L and Precuneus_L (Fig. 3 and Table 3 ). Abnormal CBF connectivity between the hippocampus and temporal lobe might prevent auditory and visual information from being integrated with reward actions, i.e., “what” and “where” information, which contributes to memory impairment. Epileptic seizures were observed in 25 patients. Fifteen patients with increased CBF in the MTL showed epileptic seizures. The remaining 10 patients only exhibited increased CBF in the MTL without epileptic seizures. Abnormal structures of the hippocampus and amygdala play a crucial role in the initiation and spread of epileptic seizures in patients diagnosed with temporal lobe epilepsy 58, 59 . Increased CBF in the Amygdala_Bi, Hippocampus_Bi, Parahippocampus_Bi and Insula_R also contributed to epileptic seizures, similar to CBF changes during the ictal state of seizures 60 . The present study had several limitations. First, the patient population was small. Second, patients were not classified based on faciobrachial dystonic seizures (FBDSs) for further analysis. In addition to FBDSs, patients with anti-LGI1 AE exhibited other involuntary movements. Only 6 patients with anti-LGI1 AE displayed definite FBDSs. However, significant increases in CBF and connectivity were observed in patients with anti-LGI1 AE. Conclusion Significantly increased CBF in the Putamen_Bi, Amygdala_Bi, Hippocampus_Bi, and Parahippocampus_Bi was observed in patients with anti-LGI1 AE. Furthermore, patients also exhibited decreased CBF connectivity originating from the Putamen_R, Amygdala_Bi, Hippocampus_Bi, and Parahippocampus_R. Decreased CBF connectivity associated with subcortical hypertransfusion might be a pattern in patients with anti-LGI1 AE. Declarations Acknowledgements We would like to acknowledge the physicians and nurses at Department of Neurology, Nanjing Brain Hospital. Contributions Ailiang Miao: design and study supervision; Yunlei Sun: draft/revise the manuscript. Yongwei Shi: collect clinical data. Yun Ma and Chuanyong Yu: clinical work. Zonghong Li: acquire imaging data. All authors contributed to the article and approved the submitted version. Corresponding author: Correspondence to Yulei Sun and Ailiang Miao Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work was supported by Training Project for Young Talents of Nanjing Brain Hospital, and General project of Nanjing Municipal Health Commission (No.YKK21110), General project of Jiangsu Provincial Health Commission (M2022065), Supported by Suqian Sci&Tech Program (S202007). Ethics declarations Ethics approval and consent to participate Our study was reviewed and approved by the ethical boards of the Affiliated Brain Hospital of Nanjing Medical University, and written informed consent was obtained from the family of all participants. All steps were performed in accordance with relevant guidelines. Data availability The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author. 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Persistent antidepressant effect of low-dose ketamine and activation in the supplementary motor area and anterior cingulate cortex in treatment-resistant depression: A randomized control study. J Affect Disord. 225:709-714. https://doi:10.1016/j.jad.2017.09.008 (2018). Wang F. et al. Aberrant Brain Dynamics in Schizophrenia During Working Memory Task: Evidence From a Replication Functional MRI Study. Schizophr Bull. 5:sbad032. https://doi:10.1093/schbul/sbad032 (2023). Olson IR. et al. The Enigmatic temporal pole: a review of findings on social and emotional processing. Brain. 130(Pt7):1718-31. https://doi: 10.1093/brain/awm052 (2007). Nagai M. et al. Insular cortex and neuropsychiatric disorders: a review of recent literature. Eur Psychiatry. 22(6):387-94. https://doi: 10.1016/j.eurpsy.2007.02.006 (2007). Rolls ET. The cingulate cortex and limbic systems for action, emotion, and memory. Handb Clin Neurol. 166:23-37. https://doi:10.1016/B978-0-444-64196-0.00002-9 (2019c). 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Oxford: Oxford University Press (2011). Rolls ET. Invariant Visual Object and Face Recognition: Neural and Computational Bases, and a Model, VisNet. Front Comput Neurosci. 6:35. https://doi: 10.3389/fncom.2012.00035 (2012). Rolls ET. The storage and recall of memories in the hippocampo-cortical system. Cell Tissue Res. 373(3):577-604. https://doi:10.1007/s00441-017-2744-3 (2018b). Rolls ET. et al. Spatial representations in the primate hippocampus, and their functions in memory and navigation. Prog Neurobiol. 171:90-113. https://doi: 10.1016/j.pneurobio.2018.09.004 (2018). Chakravarty K. et al. Temporal lobe epilepsy with amygdala enlargement: A systematic review. Acta Neurol Scand . 144(3):236-250. https://doi: 10.1111/ane.13455 (2021). Wieser HG. ILAE Commission on Neurosurgery of Epilepsy. ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia. 45(6):695-714. https://doi: 10.1111/j.0013-9580.2004.09004.x (2004). Yoo RE. et al.Identifification of cerebral perfusion using arterial spin labeling in patients with seizures in acute settings. PLoS ONE. 12:3538. https://doi: 10.1371/journal.pone. 0173538 (2017). Tables Table 1 Clinical Characteristics of patients with anti-LGI1 encephalitis. Clinical features Number Sex Female (age, Mean±Std.Deviation) Male (age, Mean±Std.Deviation) 23 (55.87±15.36) 23 (55.87±15.36) Symptom presentation Behavioral changes 18 Epileptic seizures 25 Cognitive impairment 32 Involuntary movements FBDS 11 5 Hyponatremia 6 LGI1 antibody positive In serum and CSF Only in serum Only in CSF 32 11 3 CSF Increased white blood cells Increased protein concentration (Std.Deviation) 1 ( 9 white blood cells/µl) 71±34mg/dL MRI finding Total 46 Unilateral MTL lesion (T2/Flair) Bilateral MTL lesion (T2/Flair) 16 14 ASL Total Unilateral MTL with increased CBF Bilateral MTL with increased CBF 27 17 10 EEG during peak stage Background activity (BA) Normal Mild DS Moderate DS Focal abnormality 8 9 11 13 Immunotherapy First-line alone First-line and second-line Azathioprine Mycophenolate mofetil 46 30 16 1 15 Prognosis ( follow-up from 10 to 78 months) Relapse Tumor (Gastrointestinal tumor) 7 1 Std. deviation: standard deviation; FBDS: faciobrachial dystonic seizures; LGI1: leucine-rich glioma-inactivated 1; MRI: magnetic resonance imaging; ASL: arterial spin labeling; EEG: electroencephalogram; DS: diffuse slowing. TABLE 2 Brain regions with increased CBF in patients with . Regions Coordinates in MNI (x, y, z) Cluster-level FWE Peak t values Cluster size (Voxels) Putamen_R 28, -6, -12 p=0.001 5.20 603 Amygdala_R 28, -6, -12 p=0.001 5.20 227 Hippocampus_R 28, -6, -12 p=0.001 5.20 222 Insula_R 28, -6, -12 p=0.001 5.20 185 Parahippocampus_R 28, -6, -12 p=0.001 5.20 159 Hippocampus_L -28, -26, -14 p=0.001 6.03 588 Parahippocampus_L -28, -26, -14 p=0.001 6.03 276 Putamen_L -28, -26, -14 p=0.001 6.03 271 Amygdala_L -28, -26, -14 p=0.001 6.03 144 CBF: cerebral blood flow. MNI: Montreal Neurological Institute. R:right; L:left. TABLE 3 Group differences in CBF connectivity ROI Regions of decreased CBF connectivity with ROI Cluster size (Voxels) Coordinates in MNI (x, y, z) Peak t values Hippocampus_R STG_R RO_R Caudate_R STP_R MCG_R ACG_R 900 537 187 169 361 273 44, -4, -6 44, -4, -6 44, -4, -6 44, -4, -6 -2, 30, 30 -2, 30, 30 -5.09 -5.09 -5.09 -5.09 -5.39 -5.39 Amygdala_R STG_R RO_R STP_R Putamen_R Caudate_R MCG_R SMA_R 504 346 226 262 235 406 269 58, 2, -4 58, 2, -4 58, 2, -4 20, 4,18 20, 4,18 6, 22, 46 6, 22, 46 -4.95 -4.95 -4.95 -4.11 -4.11 -5.22 -5.22 Insula_R MTG_R STG_R 401 365 66, -30, 2 66, 30, 2 -4.47 -4.47 Parahippocampus_R STP_R RO_R Insula_R MCG_R MCG_L 624 485 477 1062 626 58, 4, -6 58, 4, -6 58, 4, -6 0, -16, 42 0, -16, 42 -5.35 -5.35 -5.35 -5.60 -5.60 Hippocampus_L STG_L Insula_L 268 191 -40, -16, -4 -40, -16, -4 -5.11 -5.11 Parahippocampus_L Lingual_L Precuneus_L 900 819 -6, -58, 16 -6, -58, 16 -6.85 -6.85 CBF: cerebral blood flow. MNI: Montreal Neurological Institute; MCG: middle cingulate gyrus; SMA: supplementary motor area; ACG: anterior cingulate gyrus; STG: superior temporal gyrus; MTG: middle temporal gyrus; STP: superior temporal pole; RO: rolandic operculum; L: left; R: right. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4432471","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":307903511,"identity":"ef01debe-4878-4728-810f-5eeb6af5e95a","order_by":0,"name":"yongwei shi","email":"","orcid":"","institution":"Taizhou Fourth People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"yongwei","middleName":"","lastName":"shi","suffix":""},{"id":307903512,"identity":"1380393e-f0b0-472e-a0cb-3e133d03c011","order_by":1,"name":"chuanyong yu","email":"","orcid":"","institution":"Nanjing Brain Hospital","correspondingAuthor":false,"prefix":"","firstName":"chuanyong","middleName":"","lastName":"yu","suffix":""},{"id":307903513,"identity":"9396c9a7-b41c-4587-a268-ef8915077aea","order_by":2,"name":"zonghong li","email":"","orcid":"","institution":"Nanjing Brain Hospital","correspondingAuthor":false,"prefix":"","firstName":"zonghong","middleName":"","lastName":"li","suffix":""},{"id":307903514,"identity":"2a6a13c8-6df6-4b23-835e-70e077a34d29","order_by":3,"name":"yun ma","email":"","orcid":"","institution":"Affiliated Suqian First People's Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"yun","middleName":"","lastName":"ma","suffix":""},{"id":307903515,"identity":"e5f3fd71-cc17-4469-87d4-0367b00c9950","order_by":4,"name":"yulei sun","email":"","orcid":"","institution":"Nanjing Brain Hospital","correspondingAuthor":false,"prefix":"","firstName":"yulei","middleName":"","lastName":"sun","suffix":""},{"id":307903517,"identity":"4e624b47-1e2c-4b39-9fa0-c1ed847db9b3","order_by":5,"name":"ailiang miao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYDACZuaGAyCaDYgPfKiwkWNjbz9AQAsjXAvjwRln0oz5eM4kELCGsQGu+zBv26HEeRIOBng18LczNh74uaM2mo/98IHDPGcOpLdJMCQw/KjYhlOLxGHGhoO9Z47ntvGkJRycU3Ent0268QBjz5nbuK0BajnA23Yst40hx+DAmzPPcttkDiQwM7bh1iIPsuUvSAv/GwOg3sPpbBIJBni1GAC1AH1dk9smkWNwEKglgaAWQ5AW2bYDQC3PEkCBbNgGDOSD+Pwid/7w4Y9v2+py5/cnH/4AjEp5+fb2gw9+VODxPjQQULkHCKkHgjoi1IyCUTAKRsGIBQB1e2dXjEa0KwAAAABJRU5ErkJggg==","orcid":"","institution":"Nanjing Brain Hospital","correspondingAuthor":true,"prefix":"","firstName":"ailiang","middleName":"","lastName":"miao","suffix":""}],"badges":[],"createdAt":"2024-05-16 16:56:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4432471/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4432471/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57728654,"identity":"5e845193-ade9-4502-957e-05a901eea500","added_by":"auto","created_at":"2024-06-04 21:47:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1289911,"visible":true,"origin":"","legend":"\u003cp\u003eIncreased CBF in the bilateral putamen, bilateral amygdala, bilateral hippocampus, bilateral parahippocampus and right insula was detected in patients with anti-LGI1 encephalitis (P=0.001, cluster-level FWE corrected). CBF: cerebral blood flow. Warm colors indicate an increase in CBF. Anti-LGI1: anti-leucine-rich glioma inactivated 1.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-4432471/v1/976eb015b4ac7aceecbea178.png"},{"id":57728653,"identity":"84c564b9-5d24-4f5f-b413-368b40c60af8","added_by":"auto","created_at":"2024-06-04 21:47:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":169936,"visible":true,"origin":"","legend":"\u003cp\u003eIn contrast to healthy subjects, patients displayed decreased CBF connectivity between the Hippocampus_R and the STG_R, RO_R, Caudate_R, STP_R, MCG_R and ACG_R (P=0.001, cluster-level FWE corrected). Scatter plots illustrate the CBF connectivity in each group. \u0026nbsp;STG: superior temporal gyrus; RO: rolandic operculum; STP: superior temporal pole; MCG: middle cingulate gyrus; ACG: anterior cingulate gyrus; R: right; L: left.\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-4432471/v1/ab0626c4d853d7afbb012e48.png"},{"id":57728652,"identity":"5fe39573-cf7e-4e8a-a15c-f2641eefaf75","added_by":"auto","created_at":"2024-06-04 21:47:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":553832,"visible":true,"origin":"","legend":"\u003cp\u003eDecreased CBF connectivity was observed between the Amygdala_R and the STG_R, RO_R, STP_R, Putamen_R, Caudate_R, MCG_L, and SMA_R; between the Insula_R and the MTG_R and STG_R; between the Parahippocampus_R and the STP_R, RO_R, Insula_R, MCG_R and MCG_L; between the Hippocampus_L and the STG_L and Insula_L; and between the Parahippocampus_L and the Lingual_L and Precuneus_L. STG: superior temporal gyrus; RO: rolandic operculum; STP: superior temporal pole; MCG: middle cingulate gyrus; SMA: supplementary motor area; MTG: middle temporal gyrus; ACG: anterior cingulate gyrus;. R: right; L: left. Scatter plots illustrate the CBF connectivity in each group.\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-4432471/v1/da4c5d59556612c78b63463a.png"},{"id":61560643,"identity":"59decc77-367d-4a40-8247-14dbd521523b","added_by":"auto","created_at":"2024-08-01 08:37:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3421469,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4432471/v1/41f67920-0e2f-4807-b2e6-82f393a3e2f7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acute cerebral blood flow and its connectivity in patients with anti-LGI1 encephalitis: an arterial spin labeling study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis is a subtype of autoimmune encephalitis (AE), that manifests as behavioral changes, memory impairment, epileptic seizures, and involuntary movements, including facial brachial dystonic seizures (FBDSs) \u003csup\u003e1, 2\u003c/sup\u003e. Early diagnosis of anti-LGI1 AE is necessary to improve the clinical prognosis of patients \u003csup\u003e3\u003c/sup\u003e. In China, the diagnosis of anti-LGI1 AE is achieved through antibody detection in serum and cerebrospinal fluid (CSF) lasting at least 3 days in China, which might delay treatment and contribute to worse outcomes. The clinical criteria formulated by experts aim to assist in promptly identifying AE and expediting the initiation of immunotherapy [4]. In addition to the assessment of antibodies in CSF, brain magnetic resonance imaging (MRI) is the commonly used as a preferred radiographic technique for the diagnosis of anti-LGI1 AE \u003csup\u003e4\u003c/sup\u003e. Although 74% of the patients with anti-LGI1 AE have abnormal MRI findings \u003csup\u003e2\u003c/sup\u003e, many other immune etiologies can mimic these MRI manifestations of patients with anti-LGI1 encephalitis \u003csup\u003e5\u003c/sup\u003e. Compared to MRI, \u003csup\u003e18\u003c/sup\u003eF-fluoro-2-deoxy-\u003cem\u003ed\u003c/em\u003e-glucose positron emission tomography (\u003csup\u003e18\u003c/sup\u003eF-FDG-PET) has greater sensitivity in AE diagnosis \u003csup\u003e6, 7\u003c/sup\u003e. In the previous studies, \u003csup\u003e18\u003c/sup\u003eF-FDG-PET examination of patients with anti-LGI1 encephalitis revealed increased metabolic activity in the basal ganglia (BG) or medial temporal lobe (MTL) \u003csup\u003e8\u0026ndash;11\u003c/sup\u003e. The BG and MTL consist of numerous distinct brain structures, each serving a unique function, and the structures within the BG and MTL that exhibited hypermetabolism were not identified. The metabolic connectivity pattern between brain regions with hypermetabolism in patients with anti-LGI1 AE has not been well characterized or established. Notably, the cost of \u003csup\u003e18\u003c/sup\u003eF-FDG-PET is prohibitive for its widespread clinical utilization, and pseudocontinuous arterial spin labeling (PCASL) is being increasingly utilized as an innovative functional method. This noninvasive MRI technique utilizes magnetically labeled arterial blood water as a natural tracer to measure cerebral blood flow (CBF) \u003csup\u003e12\u0026ndash;17\u003c/sup\u003e. The clinical implementation of ASL has been further refined since the release of a consensus by the Perfusion Study Group of the International Society for Magnetic Resonance in Medicine (ISMRM) and the European Consortium for ASL in Dementia in 2015, facilitating its transition to broader clinical application \u003csup\u003e16\u003c/sup\u003e. As opposed to the lack of disease-specific guidance in the 2015 consensus paper \u003csup\u003e16\u003c/sup\u003e, the 2023 ASL guidance offers comprehensive recommendations for utilizing ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative diseases, seizures/epilepsy, and pediatric neuroradiology applications \u003csup\u003e17\u003c/sup\u003e. The guidelines focus on disease-specific factors in sequence optimization and interpretation \u003csup\u003e17\u003c/sup\u003e. We have previously reported that PCASL revealed increased CBF in the putamen and temporal lobe and decreased CBF in the precuneus and occipital lobe in patients with anti-N-methyl-d-aspartate receptor AE (NMDAR) AE \u003csup\u003e18\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe main aim of the current study was to elucidate the specific brain regions with CBF alterations in patients with anti-LGI1 AE. Additionally, we aimed to assess the connectivity of CBF between these brain regions with altered CBF in patients with anti-LGI1 AE.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eA total of 46 patients were admitted to the Department of Affiliated Brain Hospital of Nanjing Medical University from May 2017 to Jan 2023. The acute phase (within 3 months) and chronic phase (over 3 months) were defined according to the clinical consensus criteria \u003csup\u003e4\u003c/sup\u003e. The included patients had a definitive diagnosis of anti-LGI1 AE, and their serum and/or CSF were positive for anti-LGI1 antibodies. The data collected included demographic information, neurological symptoms, MRI findings, electroencephalography (EEG) results, laboratory test results, lumbar puncture results, therapeutic interventions and assessments of their efficacy, Mini-Mental State Examination scores assessing global cognitive function, and prognosis evaluation outcomes obtained through routine outpatient consultations or telephone surveys. The ASL data of 27 patients were successfully recorded during the acute phase (within 3 months) prior to receiving immunotherapy, and the ASL data from 81 healthy subjects were also recorded. The study was approved by the ethical boards of the Affiliated Brain Hospital of Nanjing Medical University, and all steps were performed in accordance with relevant guidelines. The patients/guardians provided informed consent to participate in this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMRI data\u003c/h2\u003e \u003cp\u003eMRI data were acquired using a 3.0-T MR system manufactured by General Electric in the United States. Resting-state perfusion imaging was performed using a PCASL sequence with a 3D fast spin‒echo acquisition and background suppression (repetition time\u0026thinsp;=\u0026thinsp;4886 ms, echo time\u0026thinsp;=\u0026thinsp;10.5 ms, post-label delay\u0026thinsp;=\u0026thinsp;2025 ms, spiral in readout of eight arms with 512 sample points; flip angle\u0026thinsp;=\u0026thinsp;111\u0026deg;; field of view\u0026thinsp;=\u0026thinsp;240 mm*240 mm; reconstruction matrix\u0026thinsp;=\u0026thinsp;128*128; slice thickness\u0026thinsp;=\u0026thinsp;4 mm, no gap; 36 axial slices; number of excitations\u0026thinsp;=\u0026thinsp;3; and 1.9 mm*1.9 mm in-plane resolution).The total acquisition time for the resting state ASL scan was 4 min and 41 s. During MRI scans, all participants were instructed to close their eyes, remain physically relaxed, minimize movement, and avoid falling asleep.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCBF calculation\u003c/h2\u003e \u003cp\u003eLabel maps were subtracted from control maps to generate ASL difference maps \u003csup\u003e18, 19, 20\u003c/sup\u003e. CBF images were generated by averaging the three ASL difference images in conjunction with the proton-density-weighted reference images. CBF maps were obtained from the ASL difference maps as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) The CBF maps were registered to a PET-perfusion template in Montreal Neurological Institute space using Statistical Parametric Mapping (SPM, version 12, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.fil.ion.ucl.ac.uk/spm\u003c/span\u003e\u003cspan address=\"https://www.fil.ion.ucl.ac.uk/spm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) based on MATLAB R2018b software (MathWorks Inc., Natick, MA, USA) to generate the purpose of generating standardized CBF maps, thereby facilitating group-level statistical analysis. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Normalized CBF images were generated by dividing the standardized CBF maps of each voxel by the mean CBF of the entire brain. This step was implemented to mitigate potential variations in labeling efficiency and individual hemodynamic disparities. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) The standardized CBF maps were smoothed with a Gaussian kernel of 8 mm \u0026times; 8 mm \u0026times; 8 mm full-width at half maximum (FWHM).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eNormalized CBF analyses\u003c/h2\u003e \u003cp\u003eThe CSF antibody tiers and sex were used as grouping criteria. The differences in CBF between groups were compared using two-sample t tests of SPM12. Age and sex were considered covariates. To control for multiple comparisons (MCs), the cluster-level familywise error (FWE) method was employed with an adjusted significance threshold of P\u0026thinsp;=\u0026thinsp;0.001. Clusters exhibiting a significant disparity among groups were utilized for illustration.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eCBF connectivity analyses\u003c/h2\u003e \u003cp\u003eCBF connectivity among specific brain regions was assessed by analyzing the correlation coefficient of concurrent changes in CBF in these regions using SPM12. The specific procedures were as follows: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Brain regions with CBF alterations in all patients were selected as the seed region of interest (ROI). (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The DPABI software was used to measure the CBF measurement of each ROI for each subject from their respective CBF maps. The connectivity of the CBF between each ROI and all other global voxels across individuals was computed using a single-sample t test for each group, while controlling for confounding variables such as sex and age. Statistical analyses were performed to identify the voxels exhibiting positive or negative correlations with the CBF value of each seed ROI within each group. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) For each seed ROI, a spatial mask was created using the CBF connectivity images of the two groups, where the CBF values of each voxel were associated with those of the ROI in either group. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) CBF connectivity exhibited distinct slopes between the two groups for any given pair of voxels, indicating variations in CBF connectivity of CBF across the groups. The voxels expressing a meaningfully different CBF connectivity for each ROI between healthy subjects and patients with anti-LGI1 AE were mapped by performing a specific two-sample t test within the connectivity spatial mask generated in the previous step, while controlling for age and sex. The MCs were adjusted for using the cluster-level FWE method (P\u0026thinsp;=\u0026thinsp;0.001). (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) DPABI software was used to measure the CBF measurement of each seed ROI from an individual CBF image. The correlation between ROIs was determined using the Pearson correlation (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) \u003csup\u003e18, 21, 22\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 46 patients diagnosed with anti-LGI1 AE (23 men; 23 women) were identified.\u0026nbsp;The features\u0026nbsp;of the patients diagnosed with\u0026nbsp;anti-LGI1 AE\u0026nbsp;are displayed in Table\u0026nbsp;1. CBF images during the acute stage of disease were recorded for 27 patients with\u0026nbsp;anti-LGI1 AE.\u0026nbsp;Cognitive impairment was observed in 32 (69.6%) patients, and 25 (53.4%) patients exhibited epileptic seizures. The primary types of epileptic seizures were focal seizures with\u0026nbsp;awareness or impaired awareness\u0026nbsp;and focal to bilateral tonic‒clonic seizures, as identified based on EEG recordings.\u0026nbsp;Fifteen (32.6%) patients demonstrated\u0026nbsp;involuntary movement. Only 1 patient exhibited increased CSF pleocytosis.\u0026nbsp;Fifteen\u0026nbsp;patients had an increased protein concentration (71±34\u0026nbsp;mg/dL).\u0026nbsp;Gastrointestinal tumors were observed in only one patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.1 CBF alterations in patients with anti-LGI1 AE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn contrast to\u0026nbsp;healthy subjects, the patients with anti-LGI1 AE demonstrated increased CBF in the bilateral putamen (Putamen_Bi), bilateral amygdala (Amygdala_Bi), bilateral hippocampus (Hippocampus_Bi), bilateral parahippocampus (Parahippocampus_Bi) , and right insula (Insula_R) (Fig. 1 and Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Changes in CBF connectivity between ROIs\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn contrast to the healthy subjects, the patients with anti-LGI1 AE displayed decreased CBF connectivity between the right hippocampus (Hippocampus_R) and the right superior temporal gyrus (STG_R), right rolandic operculum (RO_R), right caudate (Caudate_R), right superior temporal pole (STP_R), right middle cingulate gyrus (MCG_R), and right anterior cingulate gyrus (ACG_R) (Fig. 2 and Table 3); between the right amygdala (Amygdala_R) and the STG_R, RO_R, STP_R, right putamen (Putamen_R), Caudate_R, MCG_R, and right supplementary motor area (SMA_R); and between the Insula_R and the right middle temporal gyrus (MTG_R) and STG_R (Fig. 3 and Table 3). Decreased CBF connectivity was also observed between the right parahippocampus (Parahippocampus_R) and the STP_R, RO_R, Insula_R, MCG_R and left MCG (MCG_L); between the left hippocampus (Hippocampus_L) and STG_L, and left insula (Insula_L); and between the left parahippocampus (Parahippocampus_L) and the left lingual gyrus (Lingual_L), and left precuneus (Precuneus_L). Furthermore, increased CBF connectivity was observed between and the Amygdala_Bi and Hippocampus_Bi (Fig. 3 and Table 3).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study demonstrated that the patients with anti-LGI1 AE displayed increased CBF and decreased CBF connectivity associated with the Putamen_Bi, Amygdala_Bi, Hippocampus_Bi, Parahippocampus_Bi, and Insula_R and these changes might contribute to the diagnosis of anti-LGI1 AE (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBoth intentional and unintentional movements rely on coordinated muscle contractions, which are initiated and controlled by various structures within the central nervous system according to specific spatial and temporal patterns. Prior to the transmission of signals from the cerebral motor cortex to the brainstem or spinal motor neurons that control muscle movement, the BG affects both the motor and premotor cortex through the intermediary involvement of the thalamus \u003csup\u003e23\u0026ndash;27\u003c/sup\u003e. The putamen and caudate are vital components of the BG \u003csup\u003e25\u003c/sup\u003e. Neurons associated with active or passive lower limb movements are situated in a lengthy rostrocaudal extension of the dorsolateral putamen. Orofacial movement-related neurons can be found ventromedially, while those related to upper limb movements occupy an intermediate position \u003csup\u003e27\u003c/sup\u003e. The putamen is associated with various involuntary and stereotyped movements \u003csup\u003e27\u003c/sup\u003e. Increased CBF in the Putamen_Bi was observed in patients with anti-LGI1 AE (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The SMA plays a role in maintaining posture, coordinating movements involving both hands, internally generating motion, and constructing movements sequences \u003csup\u003e28\u0026ndash;31\u003c/sup\u003e. The SMA projects more in a caudally direction, mainly toward the putamen \u003csup\u003e25\u003c/sup\u003e. The putamen transmits outputs to the outer section of the globus pallidus, which subsequently extends toward the subthalamic nucleus. Finally, the circuit is completed by projections that are sent back to the motor area \u003csup\u003e23\u003c/sup\u003e. Interestingly, the patients with Parkinson\u0026rsquo;s disease exhibited abnormal connectivity between the putamen and the SMA \u003csup\u003e32\u003c/sup\u003e. Notably, the anterior cingulate cortex is linked to the amygdala and orbitofrontal cortex (OFC), both of which play a role in processing emotions and learning from action outcomes. This process involves acquiring knowledge about actions that lead to specific goals based on the reward or punishment received for different behaviors \u003csup\u003e33, 34\u003c/sup\u003e. The region in the MCG, known as the motor cingulate area, receives information from the ACG and is involved in controlling skeletal muscles during the process of learning action\u0026ndash;outcome associations. This region also sends signals to motor areas \u003csup\u003e35\u0026ndash;37\u003c/sup\u003e. Increased CBF in the Putamen_Bi might have resulted in involuntary movements in the patients in this study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe amygdala, a significant component of the limbic system, is responsible for encoding emotions in response to external stimuli. This information is then transmitted to the ventral caudate and putamen, which are involved in regulating emotional responses \u003csup\u003e25, 38, 39\u003c/sup\u003e. The involvement of the anterior and midcingulate cortical regions in emotion is evident, as they facilitate goal-oriented behaviors that act as stimuli for emotional responses \u003csup\u003e33, 40, 41\u003c/sup\u003e. Emerging evidence has indicated that the SMA might play a crucial role in human volition, executive function, and the amalgamation of affective, behavioral, and cognitive operations \u003csup\u003e43\u0026ndash;44\u003c/sup\u003e. Many mental diseases are associated with SMA functions \u003csup\u003e45, 46\u003c/sup\u003e. Increased CBF in the Amygdala_Bi contributed to abnormal emotions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Decreased CBF connectivity between the Amygdala_R and the Putamen_R, Caudate_R, MCG_R, and SMA_R was observed in patients with anti-LGI1 AE, which might have resulted in involuntary movements in response to abnormal emotion (Fig.\u0026nbsp;3; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe STP plays an important role in social and emotional processing [47, 48], the STG is associated with auditory activity \u003csup\u003e49\u003c/sup\u003e, and the MTG plays a crucial role in integrating the auditory and visual processing streams \u003csup\u003e50, 51\u003c/sup\u003e. The cortical areas of the primate temporal lobe provide inputs to the amygdala, which is highly developed \u003csup\u003e52\u0026ndash;55\u003c/sup\u003e. The insular cortex exhibits connections with the STG, temporal pole, amygdala, ACG, OFC, primary and association auditory cortices, visual association cortex, hippocampus, and entorhinal cortex. It plays a crucial role in processing attentional, emotional, verbal, and motor information as well as visual and auditory data. Decreased CBF connectivity between the Amygdala_R and the STG_R, RO_R, and STP_R and between the Insular_R and MTG_R, and STG_R might contribute to mental symptoms (auditory and visual hallucinations) in patients with anti-LGI1 AE (Fig.\u0026nbsp;3; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe formation and retrieval of episodic memories rely heavily on the pivotal function of the hippocampus. The ACG obtains reward-related data from the OFC and amygdala and transmits this information to the hippocampal memory system via the perirhinal and entorhinal cortex for processing \u003csup\u003e56, 57\u003c/sup\u003e. Along with the entorhinal cortex, the parahippocampal gyrus, particularly the lateral and medial regions, functions as a conduit for spatial information transmission to the hippocampal memory system \u003csup\u003e56, 57\u003c/sup\u003e. The OFC is also known to have a direct connection with the posterior cingulate cortex (PCC) \u003csup\u003e49, 56, 57\u003c/sup\u003e. The midcingulate motor area receives reward or outcome information from the ACG and action information from the PCC and subsequently transmits signals to premotor cortex area 6 and the SMA \u003csup\u003e49\u003c/sup\u003e. Decreased CBF connectivity between the Hippocampus_R and the Caudate_R, MCG_R, and ACG_R and between the Parahippocampus_R and the MCG_R and MCG_L might not allow the preservation of the memory of learned reward actions (Fig.\u0026nbsp;3 and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Connecting bridges were observed between the temporal lobes and hippocampus \u003csup\u003e49\u003c/sup\u003e. Patients with LGI1 encephalitis displayed decreased CBF connectivity between the Hippocampus_R and the STG_R, RO_R and STP_R; between the Hippocampus_L and the Insula_L and STG_L; between the Parahippocampus_R and the STP_R, RO_R, and Insula_R; and between the Parahippocampus_L and the Lingual_L and Precuneus_L (Fig.\u0026nbsp;3 and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Abnormal CBF connectivity between the hippocampus and temporal lobe might prevent auditory and visual information from being integrated with reward actions, i.e., \u0026ldquo;what\u0026rdquo; and \u0026ldquo;where\u0026rdquo; information, which contributes to memory impairment.\u003c/p\u003e \u003cp\u003eEpileptic seizures were observed in 25 patients. Fifteen patients with increased CBF in the MTL showed epileptic seizures. The remaining 10 patients only exhibited increased CBF in the MTL without epileptic seizures. Abnormal structures of the hippocampus and amygdala play a crucial role in the initiation and spread of epileptic seizures in patients diagnosed with temporal lobe epilepsy \u003csup\u003e58, 59\u003c/sup\u003e. Increased CBF in the Amygdala_Bi, Hippocampus_Bi, Parahippocampus_Bi and Insula_R also contributed to epileptic seizures, similar to CBF changes during the ictal state of seizures \u003csup\u003e60\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe present study had several limitations. First, the patient population was small. Second, patients were not classified based on faciobrachial dystonic seizures (FBDSs) for further analysis. In addition to FBDSs, patients with anti-LGI1 AE exhibited other involuntary movements. Only 6 patients with anti-LGI1 AE displayed definite FBDSs. However, significant increases in CBF and connectivity were observed in patients with anti-LGI1 AE.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSignificantly increased CBF in the Putamen_Bi, Amygdala_Bi, Hippocampus_Bi, and Parahippocampus_Bi was observed in patients with anti-LGI1 AE. Furthermore, patients also exhibited decreased CBF connectivity originating from the Putamen_R, Amygdala_Bi, Hippocampus_Bi, and Parahippocampus_R. Decreased CBF connectivity associated with subcortical hypertransfusion might be a pattern in patients with anti-LGI1 AE.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge the physicians and nurses at Department of Neurology, Nanjing Brain Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAiliang Miao: design and study supervision; Yunlei Sun: draft/revise the manuscript. Yongwei Shi: collect clinical data. Yun Ma and Chuanyong Yu: clinical work. Zonghong Li: acquire imaging data.\u0026nbsp;All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to Yulei Sun and Ailiang Miao\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work was supported by\u0026nbsp;Training Project for Young Talents of Nanjing Brain Hospital, and General project of Nanjing Municipal Health Commission (No.YKK21110), General project of Jiangsu Provincial Health Commission (M2022065), Supported by Suqian Sci\u0026amp;Tech Program (S202007).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study was reviewed and approved by\u0026nbsp;the ethical boards of the Affiliated Brain Hospital of Nanjing Medical University, and written informed consent was obtained from the family of all participants. All steps\u0026nbsp;were\u0026nbsp;performed in accordance with relevant guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eIrani SR. et al. Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis. \u003cem\u003eAnn Neurol.\u003c/em\u003e 69(5):892-900. http://doi: 10.1002/ana.22307 (2011).\u003c/li\u003e\n\u003cli\u003evan Sonderen A. et al. 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Mesial temporal lobe epilepsy with hippocampal sclerosis. \u003cem\u003eEpilepsia.\u003c/em\u003e 45(6):695-714. https://doi: 10.1111/j.0013-9580.2004.09004.x (2004). \u003c/li\u003e\n\u003cli\u003eYoo RE. et al.Identifification of cerebral perfusion using arterial spin labeling in patients with seizures in acute settings. \u003cem\u003ePLoS ONE.\u003c/em\u003e 12:3538. https://doi: 10.1371/journal.pone. 0173538 (2017). \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Clinical Characteristics of patients with anti-LGI1 encephalitis.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"555\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical features\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eFemale (age, Mean\u0026plusmn;Std.Deviation)\u003c/p\u003e\n \u003cp\u003eMale (age, Mean\u0026plusmn;Std.Deviation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (55.87\u0026plusmn;15.36)\u003c/p\u003e\n \u003cp\u003e23 (55.87\u0026plusmn;15.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymptom presentation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003eBehavioral changes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003eEpileptic seizures\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003eCognitive impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003eInvoluntary movements\u003c/p\u003e\n \u003cp\u003eFBDS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHyponatremia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLGI1 antibody positive\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u003c/strong\u003eIn serum and CSF\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Only in serum\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Only in CSF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCSF\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIncreased white blood cells\u003c/p\u003e\n \u003cp\u003eIncreased protein concentration (Std.Deviation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u0026nbsp;( 9 white blood cells/\u0026micro;l)\u003c/p\u003e\n \u003cp\u003e71\u0026plusmn;34mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMRI finding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Total\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Unilateral MTL lesion (T2/Flair)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Bilateral MTL lesion (T2/Flair)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eASL\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Total\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Unilateral MTL with increased CBF\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBilateral MTL with increased CBF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEEG during\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epeak stage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eBackground activity (BA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003cp\u003eMild DS\u003c/p\u003e\n \u003cp\u003eModerate DS\u003c/p\u003e\n \u003cp\u003eFocal abnormality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eImmunotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eFirst-line alone\u003c/p\u003e\n \u003cp\u003eFirst-line and second-line\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cstrong\u003eAzathioprine\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMycophenolate mofetil\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"64.50450450450451%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrognosis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u003c/strong\u003efollow-up from 10 to 78 months)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Relapse\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Tumor (Gastrointestinal tumor)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.4954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eStd. deviation: standard deviation; FBDS: faciobrachial dystonic seizures; LGI1: leucine-rich glioma-inactivated 1; MRI: magnetic resonance imaging; ASL: arterial spin labeling; EEG: electroencephalogram; DS: diffuse slowing.\u003c/p\u003e\n\u003cp\u003eTABLE 2\u0026nbsp;Brain regions with increased CBF in patients with .\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoordinates in\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMNI (x, y, z)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCluster-level\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFWE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeak \u003cem\u003et\u003c/em\u003e values\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCluster size\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Voxels)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePutamen_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e28, -6, -12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e5.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e603\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAmygdala_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e28, -6, -12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e5.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e227\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHippocampus_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e28, -6, -12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e5.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsula_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e28, -6, -12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e5.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParahippocampus_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e28, -6, -12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e5.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e159\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHippocampus_L\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e-28, -26, -14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e6.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e588\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eParahippocampus_L\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e-28, -26, -14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e6.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e276\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePutamen_L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e-28, -26, -14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e6.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e271\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.08896797153025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAmygdala_L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.395017793594306%\" valign=\"top\"\u003e\n \u003cp\u003e-28, -26, -14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.19217081850534%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep=0.001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.462633451957295%\" valign=\"top\"\u003e\n \u003cp\u003e6.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.86120996441281%\" valign=\"top\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCBF: cerebral blood flow. MNI: Montreal Neurological Institute. R:right; L:left.\u003c/p\u003e\n\u003cp\u003eTABLE 3\u0026nbsp;Group differences in CBF connectivity\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.823943661971832%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eROI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.06338028169014%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegions of decreased CBF connectivity with ROI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.02112676056338%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCluster size (Voxels)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.190140845070424%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoordinates in MNI (x, y, z)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.901408450704224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeak t values\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.823943661971832%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHippocampus_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.06338028169014%\" valign=\"top\"\u003e\n \u003cp\u003eSTG_R\u003c/p\u003e\n \u003cp\u003eRO_R\u003c/p\u003e\n \u003cp\u003eCaudate_R\u003c/p\u003e\n \u003cp\u003eSTP_R\u003c/p\u003e\n \u003cp\u003eMCG_R\u003c/p\u003e\n \u003cp\u003eACG_R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.02112676056338%\" valign=\"top\"\u003e\n \u003cp\u003e900\u003c/p\u003e\n \u003cp\u003e537\u003c/p\u003e\n \u003cp\u003e187\u003c/p\u003e\n \u003cp\u003e169\u003c/p\u003e\n \u003cp\u003e361\u003c/p\u003e\n \u003cp\u003e273\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.190140845070424%\" valign=\"top\"\u003e\n \u003cp\u003e44, -4, -6\u003c/p\u003e\n \u003cp\u003e44, -4, -6\u003c/p\u003e\n \u003cp\u003e44, -4, -6\u003c/p\u003e\n \u003cp\u003e44, -4, -6\u003c/p\u003e\n \u003cp\u003e-2, 30, 30\u003c/p\u003e\n \u003cp\u003e-2, 30, 30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.901408450704224%\" valign=\"top\"\u003e\n \u003cp\u003e-5.09\u003c/p\u003e\n \u003cp\u003e-5.09\u003c/p\u003e\n \u003cp\u003e-5.09\u003c/p\u003e\n \u003cp\u003e-5.09\u003c/p\u003e\n \u003cp\u003e-5.39\u003c/p\u003e\n \u003cp\u003e-5.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.823943661971832%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAmygdala_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.06338028169014%\" valign=\"top\"\u003e\n \u003cp\u003eSTG_R\u003c/p\u003e\n \u003cp\u003eRO_R\u003c/p\u003e\n \u003cp\u003eSTP_R\u003c/p\u003e\n \u003cp\u003ePutamen_R\u003c/p\u003e\n \u003cp\u003eCaudate_R\u003c/p\u003e\n \u003cp\u003eMCG_R\u003c/p\u003e\n \u003cp\u003eSMA_R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.02112676056338%\" valign=\"top\"\u003e\n \u003cp\u003e504\u003c/p\u003e\n \u003cp\u003e346\u003c/p\u003e\n \u003cp\u003e226\u003c/p\u003e\n \u003cp\u003e262\u003c/p\u003e\n \u003cp\u003e235\u003c/p\u003e\n \u003cp\u003e406\u003c/p\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.190140845070424%\" valign=\"top\"\u003e\n \u003cp\u003e58, 2, -4\u003c/p\u003e\n \u003cp\u003e58, 2, -4\u003c/p\u003e\n \u003cp\u003e58, 2, -4\u003c/p\u003e\n \u003cp\u003e20, 4,18\u003c/p\u003e\n \u003cp\u003e20, 4,18\u003c/p\u003e\n \u003cp\u003e6, 22, 46\u003c/p\u003e\n \u003cp\u003e6, 22, 46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.901408450704224%\" valign=\"top\"\u003e\n \u003cp\u003e-4.95\u003c/p\u003e\n \u003cp\u003e-4.95\u003c/p\u003e\n \u003cp\u003e-4.95\u003c/p\u003e\n \u003cp\u003e-4.11\u003c/p\u003e\n \u003cp\u003e-4.11\u003c/p\u003e\n \u003cp\u003e-5.22\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; -5.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.823943661971832%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsula_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.06338028169014%\" valign=\"top\"\u003e\n \u003cp\u003eMTG_R\u003c/p\u003e\n \u003cp\u003eSTG_R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.02112676056338%\" valign=\"top\"\u003e\n \u003cp\u003e401\u003c/p\u003e\n \u003cp\u003e365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.190140845070424%\" valign=\"top\"\u003e\n \u003cp\u003e66, -30, 2\u003c/p\u003e\n \u003cp\u003e66, 30, 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.901408450704224%\" valign=\"top\"\u003e\n \u003cp\u003e-4.47\u003c/p\u003e\n \u003cp\u003e-4.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.823943661971832%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eParahippocampus_R\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.06338028169014%\" valign=\"top\"\u003e\n \u003cp\u003eSTP_R\u003c/p\u003e\n \u003cp\u003eRO_R\u003c/p\u003e\n \u003cp\u003eInsula_R\u003c/p\u003e\n \u003cp\u003eMCG_R\u003c/p\u003e\n \u003cp\u003eMCG_L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.02112676056338%\" valign=\"top\"\u003e\n \u003cp\u003e624\u003c/p\u003e\n \u003cp\u003e485\u003c/p\u003e\n \u003cp\u003e477\u003c/p\u003e\n \u003cp\u003e1062\u003c/p\u003e\n \u003cp\u003e626\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.190140845070424%\" valign=\"top\"\u003e\n \u003cp\u003e58, 4, -6\u003c/p\u003e\n \u003cp\u003e58, 4, -6\u003c/p\u003e\n \u003cp\u003e58, 4, -6\u003c/p\u003e\n \u003cp\u003e0, -16, 42\u003c/p\u003e\n \u003cp\u003e0, -16, 42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.901408450704224%\" valign=\"top\"\u003e\n \u003cp\u003e-5.35\u003c/p\u003e\n \u003cp\u003e-5.35\u003c/p\u003e\n \u003cp\u003e-5.35\u003c/p\u003e\n \u003cp\u003e-5.60\u003c/p\u003e\n \u003cp\u003e-5.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.823943661971832%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHippocampus_L\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.06338028169014%\" valign=\"top\"\u003e\n \u003cp\u003eSTG_L\u003c/p\u003e\n \u003cp\u003eInsula_L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.02112676056338%\" valign=\"top\"\u003e\n \u003cp\u003e268\u003c/p\u003e\n \u003cp\u003e191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.190140845070424%\" valign=\"top\"\u003e\n \u003cp\u003e-40, -16, -4\u003c/p\u003e\n \u003cp\u003e-40, -16, -4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.901408450704224%\" valign=\"top\"\u003e\n \u003cp\u003e-5.11\u003c/p\u003e\n \u003cp\u003e-5.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.823943661971832%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eParahippocampus_L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.06338028169014%\" valign=\"top\"\u003e\n \u003cp\u003eLingual_L\u003c/p\u003e\n \u003cp\u003ePrecuneus_L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.02112676056338%\" valign=\"top\"\u003e\n \u003cp\u003e900\u003c/p\u003e\n \u003cp\u003e819\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.190140845070424%\" valign=\"top\"\u003e\n \u003cp\u003e-6, -58, 16\u003c/p\u003e\n \u003cp\u003e-6, -58, 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.901408450704224%\" valign=\"top\"\u003e\n \u003cp\u003e-6.85\u003c/p\u003e\n \u003cp\u003e-6.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCBF: cerebral blood\u0026nbsp;flow. MNI: Montreal Neurological Institute;\u0026nbsp;MCG: middle\u0026nbsp;cingulate\u0026nbsp;gyrus; SMA:\u0026nbsp;supplementary motor area;\u0026nbsp;ACG: anterior cingulate gyrus; STG:\u0026nbsp;superior temporal gyrus; MTG: middle\u0026nbsp;temporal gyrus; STP: superior temporal\u0026nbsp;pole; RO: rolandic operculum; L: left; R: right.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"anti-LGI1 autoimmune encephalitis, pseudocontinuous arterial spin labeling, cerebral blood flow, cerebral blood flow pattern, cerebral blood flow connectivity","lastPublishedDoi":"10.21203/rs.3.rs-4432471/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4432471/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePseudocontinuous arterial spin labeling (PCASL) is an innovative technique for measuring cerebral blood flow (CBF). The aim of this study was to identify diagnostic CBF connectivity in patients with anti-leucine-rich glioma inactivated 1 autoimmune encephalitis (anti-LGI1 AE) .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 46 patients with anti-LGI1 AE including 27 patients with CBF during the acute stage were recruited from May 2017 to Jan 2023. The CBF in 27 patients with anti-LGI1 AE during the acute stage and 65 healthy subjects was analyzed using arterial spin labeling. Regions with CBF alterations were identified and designated as regions of interest (ROIs). Subsequently, the CBF connectivity of the ROIs was also compared between the groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients in the acute stage of disease exhibited increased CBF in the bilateral putamen, bilateral amygdala (Amygdala_Bi), bilateral hippocampus (Hippocampus_Bi), bilateral parahippocampus and right insula (Insula_R) (P=0.001, cluster-level familywise error [FWE] corrected). Decreased CBF connectivity was observed between the right hippocampus and the right superior temporal gyrus (STG_R), right rolandic operculum (RO_R), right caudate (Caudate_R), right superior temporal pole (STP_R), right middle cingulate gyrus (MCG_R), and right anterior cingulate gyrus; between the right amygdala and the STG_R, RO_R, STP_R, right putamen, Caudate_R, MCG_R, and right supplementary motor area; and between the Insula_R and the right middle temporal gyrus (MTG_R) and STG_R (P=0.001, cluster-level FWE corrected). Furthermore, the patients also showed decreased CBF connectivity between the right parahippocampus and the STP_R, RO_R, Insula_R, MCG_R and left MTG; between the left hippocampus and the left STG, and left insula; and between the left parahippocampus and the left lingual gyrus, and left precuneus. Increased CBF connectivity was observed between Amygdala_Bi and Hippocampus_Bi (P=0.001, cluster-level FWE corrected).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe PCASL technique demonstrated high sensitivity in identifying anti-LGI1 AE patients, who in which patients exhibited decreased CBF connectivity originating from subcortical regions with increased CBF.\u003c/p\u003e","manuscriptTitle":"Acute cerebral blood flow and its connectivity in patients with anti-LGI1 encephalitis: an arterial spin labeling study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-04 21:47:52","doi":"10.21203/rs.3.rs-4432471/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dcf6a488-803b-4042-b653-7648b8574731","owner":[],"postedDate":"June 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32523871,"name":"Biological sciences/Immunology"},{"id":32523872,"name":"Biological sciences/Neuroscience"},{"id":32523873,"name":"Health sciences/Neurology"}],"tags":[],"updatedAt":"2024-08-01T08:29:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-04 21:47:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4432471","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4432471","identity":"rs-4432471","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}