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Xiaoyun Liu,1,* Liling Yang,1,* Yuxiang Han,1 Jingjing Xu,2 Zaiying Pang,1 Yifeng Du,1 Yabo Feng,1,* Youting Lin1,* 1Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province, 250021, People’s Republic of China; 2Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province, 250021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yabo Feng; Youting LinDepartment of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Huaiyin Zone, Jinan City, Shandong Province, 250021, People’s Republic of ChinaTel/Fax +86-531‐68776354Email fyb-sd@hotmail.com; youtinglin2019@126.comObjective: The purpose of this study was to illustrate the electrophysiological features of sleep disturbances in patients with anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis in both active and recovery stages.Methods: Retrospectively filed video electroencephalogram (VEEG) and polysomnography (PSG) data in 24 patients with anti-LGI1 encephalitis were analyzed in comparison with that in 20 individuals without sleep disorders as control group.Results: Sleep efficiency (SE) and total sleep time involving REM and NREM sleep were significantly decreased in patients with anti-LGI1 encephalitis during the active stage compared to that during the recovery stage and in the control group. Imbalanced sleep structure was found, demonstrated by elevated N1, decreased N3 and REM components, as well as abnormal N2 structure characterized with significantly lower spindle duration and density during the active stage. These findings were independent of the presence of nocturnal episodic events or sleep hyperkinetic movements (HMs). HMs were present in 11/23 patients throughout NREM and REM sleep (nonspecific in sleep stages) during the active stage. During the recovery stage, SE and sleep structures were dramatically improved, including the percentage of N3 and REM sleep, spindle duration and density. Ten of 11 patients with HMs were followed up. HMs were totally remitted in 3 patients and still persistent in 1, while evolved into REM sleep behavior disorder (RBD) in 4 with comorbid periodic limb movement syndrome (PLMS) in 3/4, and only PLMS in 2.Conclusion: Sleep disturbances were remarkable and intrinsic features in active anti-LGI1 encephalitis, marked by overall disruptions of both NREM and REM sleep, as well as the presence of HMs, which tend to evolve into RBD or PLMS during the recovery stage. Long-term follow-up with PSG is needed, especially for those patients with severe sleep disturbances during the active phase.Keywords: anti-leucine-rich glioma-inactivated protein 1 encephalitis, video electroencephalogram, polysomnography, sleep disturbances, REM sleep behavior disorder, periodic limb movement in sleep

Purpose Late-onset epilepsy due to autoimmune dysfunction has been reported. However, definitive diagnosis requires positive antibody results. As a result, patients with negative antibody results, but presenting with classical manifestation of autoimmune epilepsy, may be managed as suspected cases. In this study, we aim to isolate and profile the concentration of cytokines/chemokines in the cerebrospinal fluid (CSF) and the serum to ascertain if they could act as alternative diagnostic biomarkers. Patients and methods Twenty patients aged ≥50 years were considered in this study. Ten patients were diagnosed with suspected autoimmune epilepsy (sAE) based on clinic manifestation, electroencephalogram, magnetic resonance imaging, and with negative antibody results of the serum and the CSF. The equivalent control group exhibited neurological disorders due to non-inflammatory pathologies. Serum and CSF were analyzed for cytokines/chemokines concentration, including interleukin (IL)-6, IL-10, IL-17, chemokine (C-X-C motif) ligand (CXCL)12 and CXCL13, as well as high-mobility group box protein 1 (HMGB1) and B cell activation factor (BAFF)). Results The CSF levels of IL-6, IL-17, HMGB1, and CXCL12 were significantly higher in the sAE group than in the control group. There was no difference in the CSF levels of IL-10, CXCL13 and BAFF. The serum levels of HMGB1 and CXCL12 were elevated in the sAE group compared with the control group, and there was no statistical difference in the serum levels of IL-6, IL-10, IL-17, CXCL13, and BAFF between the two groups. Conclusion Our study shows that cytokines/chemokines may act as alternative biomarkers for diagnosis of sAE. The activation of both HMGB1/CXCL12-mediated immunity and T helper cells 17 (Th17) cells may be playing a central role in the pathogenesis of sAE. We suggest that cytokines/chemokines be treated as adjuvant biomarkers, instead of solely relying on antibody screening test. However, a larger cohort in a prospective approach is required to validate our findings.

Background Although antibody-mediated immune responses are considered pathogenic and responsible for neural injury in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis, previous studies have indicated that cytokines and chemokines might play roles in the pathogenic process by serving as B cell enhancers. In this study, we detected the profiles of cytokines and chemokines in the cerebral fluid (CSF) and serum of patients with anti-LGI1 encephalitis to identify potential biomarkers. Methods Sixteen patients diagnosed with anti-LGI1 encephalitis and nine patients diagnosed with noninflammatory neurologic disorders were included in the study. Cytokines and chemokines including IL-6, IL-10, IL-17, CXCL12, CXCL13, BAFF and HMGB1 in serum and CSF were measured. Results The serum and CSF levels of CXCL13 were significantly higher in patients with anti-LGI1 encephalitis (36.32±34.71 pg/mL and 2.23±2.41 pg/mL, respectively) than in controls (10.84±5.02 pg/mL and 0.34±0.21 pg/mL, respectively). There was no significant difference in serum or CSF levels of IL-6, IL-10, IL-17, CXCL12, BAFF and HMGB1 between the two groups. Conclusion CXCL13 is a potential biomarker of active inflammation in anti-LGI1 encephalitis. The distinctive response of cytokines and chemokines might be closely linked to the mechanisms underlying this condition.