Clinical and neuroradiological findings in patients with Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis: Associations with outcomes

Clinical and neuroradiological findings in patients with Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis: Associations with outcomes | 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 Research Article Clinical and neuroradiological findings in patients with Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis: Associations with outcomes Shu Jiang, Chao Zhang, Xinyi Wang, Peng Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7438732/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Jan, 2026 Read the published version in BMC Neurology → Version 1 posted 10 You are reading this latest preprint version Abstract Background Encephalitis associated with antibodies against the α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor (AMPAR) is an extremely rare type of antibody-mediated encephalitis. Its clinical phenotype and neuroradiological characteristics remain incompletely described. Methods We present four cases of with neurological involvement, and a comprehensive literature review highlighted the diverse clinical experiences, with specific attention to the clinical and radiographic characteristics of anti-AMPAR encephalitis, as well as the association between clinical, neuroradiological presentations and outcomes. Results A total of 89 patients with anti-AMPAR encephalitis were included in this review. Clinical presentations at the onset of anti-AMPAR encephalitis were diverse, including behavioral, cognitive, motor, and sensory manifestations. Neuroradiological findings cannot be restricted to the limbic system. They may spread to unexpected sites, like basal ganglia, cerebellum, cerebral cortex regions, and even diffuse hyperintensities, or patient may have completely normal brain magnetic resonance imaging (MRI). Pearson’s χ 2 test showed a statistical trend towards limbic encephalitis (P = 0.091) and convulsions (P = 0.078) at presentation associating with the MRI presentations. Limbic system hyperintensities were more common in patients of partial recovery (P = 0.015). However, logistic regression analysis showed no significant correlations between clinical, neuroradiological findings and unfavorable outcome. Conclusion Anti-AMPAR encephalitis mainly presents as limbic encephalitis, and most of the patients had positive brain MRI results. As a sensitive diagnostic tool for this condition, MRI may provide more valuable information related to clinical presentation and outcomes. For the expanding clinical profile of encephalitis associated with antibodies against AMPAR, careful databasing of new cases will facilitate more definitive study in the future. Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor Limbic encephalitis Brain MRI Outcome Figures Figure 1 Figure 2 Introduction First described by Lai et al. [ 1 ] in 2009, encephalitis associated with anti-α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor (AMPAR) represents a subtype of autoimmune encephalitis linked to anti-neuronal surface antigens. The initial characterization of this encephalitis involved 10 patients, all diagnosed with limbic encephalitis, whose cerebrospinal fluid (CSF) and serum harbored antibodies that cross-reacted with the neuropil of rat brains and the cell surface of cultured rat hippocampal neurons [ 2 , 3 ]. As ionotropic glutamate receptors, AMPARs assemble into tetramers consisting of GluR1, GluR2, GluR3, and GluR4 subunits, with the GluR2 subunit showing enriched distribution in the hippocampus, amygdala, and cerebral cortex [ 3 , 4 ]. AMPARs mediate fast synaptic transmission in the central nervous system and are essential for synaptic plasticity, learning, and memory. Patients typically present with diverse symptoms such as confusion, amnesia, seizures, encephalopathy, and psychosis [ 5 ]. To date, fewer than 100 cases of anti-AMPAR encephalitis have been described in the published literature, presenting substantial diagnostic hurdles owing to the condition’s clinical heterogeneity and low incidence [ 6 – 12 ]. Magnetic resonance imaging (MRI) frequently demonstrates abnormalities with a stereotyped distribution, including a distinct predilection for the bilateral temporal lobes—a pattern that correlates with the expression topography of GluA1 and GluA2 subunits. Moreover, these MR imaging abnormalities are likely reflective of the underlying pathophysiological mechanisms. In the present study, we report four cases of AMPAR-associated encephalitis, describe their corresponding clinical and neuroradiological findings, discuss their clinical courses and outcomes, and review the existing literature on brain MRI and clinical features of this disease. Detailed characterization of the clinical presentation, neuroradiological findings, and outcomes of anti-AMPAR encephalitis may facilitate improved recognition of patients with suspected AMPAR-associated encephalitis. Materials and methods Clinical cases By retrospectively reviewing patients with positive AMPAR antibodies in CSF or serum, a total of 4 patients diagnosed with AMPAR-associated encephalitis were enrolled in this study between April 2021 and November 2023. Demographic data, clinical manifestations, laboratory findings (including CSF analysis, anti-neuronal antibodies in serum/CSF), scalp electroencephalography (EEG), brain MRI, and oncological screening results, as well as treatment regimens and therapeutic responses, were extracted from the patients’ outpatient and inpatient medical records. Written informed consent was obtained from each patient. This study was approved by the Research Ethics Committee of XXX Hospital. Systematic review and data extraction To identify relevant literature on AMPAR encephalitis, we conducted a systematic search of the PubMed database using the key terms "autoimmune encephalitis" and "AMPA receptor antibodies". This search was repeated periodically to ensure comprehensiveness, with the final search conducted on May 25, 2025. Abstracts of the retrieved records were screened for eligibility, and a total of 62 manuscripts were selected for full-text review. Twenty-seven manuscripts were excluded: these either did not report unique cases of AMPAR encephalitis or focused primarily on other disease entities. Data were subsequently extracted from the unique cases documented in the remaining 35 manuscripts. Data Analysis Abnormal findings on brain MRI were extracted and categorized based on the cortical anatomical regions as defined in Freesurfer [13]. T2-weighted hyperintensity was the most frequently observed lesion type. All analyses were conducted using the statistical software of SPSS (version 19.0; IBM). The associations between different MRI presentations and clinical symptoms, outcomes were quantified using Pearson’s χ 2 test. The relationship between demographic, clinical variables and neuroradiological presentation on outcomes were quantified using logistic regression. Death and partial recovery were defined as unfavorable outcome, and return to baseline was defined as favorable outcome. Statistical significance was defined as p<0.05. Result We identified 4 patients with anti-AMPAR encephalitis, including 2 women and 2 men. Their median age was 56 years (range 32-57 years). All patients were positive for AMPAR-Abs in both serum and CSF samples (antibody titer range, 1:10 to greater than 1:320). In 3 of the 4 patients, the clinical diagnosis of LE was confirmed by the MRI findings of mesiotemporal increased fluid-attenuated inversion recovery (FLAIR)/T2WI signal abnormalities. In patient 3, the brain MRI was normal. The main clinical data of our 4 cases are reported in Table 1. Case reports Patient no. 1 A 32-year-old woman presented to the hospital with perioral numbness accompanied by limb weakness for more than 10 days. The patient caught a cold 10 days ago and then developed perioral numbness, accompanied by general fatigue, accompanied by sleep disorders, manifested as difficulty falling asleep and irritability at night. The patient gradually showed memory loss, slow reaction, and reduced speech. Neurological examination showed that the reaction was slow, the comprehension and calculation power decreased, and negative Babinski signs as well as negative meningeal irritation signs. After admission, the blood test showed an increase in white blood cells and neutrophils. And other routine serum tests were normal. Routine CSF tests exhibited normal results. However, the EEG showed increased slow-wave activity during the waking period and no typical epileptic discharge. Brain MRI revealed increased T2WI and T2-FLAIR signal involving bilaterally medial temporal lobe and hippocampus, right caput nuclei caudate (Fig. 1 A~D) . PET-CT indicated circular nodules in the mediastinum with a slight increase in metabolism and a high possibility of benign lesions. Anti-AMPAR antibodies were both detected in CSF(1:100) and serum(1:100). Methylprednisolone pulse therapy and intravenous immunoglobulin (IVIG) were started. MRI revealed that scattered T2WI and T2-FLAIR hyperintensity had decreased compared with 7 days (Fig. 1 E~J) after onset. However, the symptoms of the patient did not improve, and then further aggravated, almost unable to speak, unable to walk, and the right upper limb involuntary movement. At the follow-up 20 days later, this patient demonstrated an improvement in symptoms but still had persistent cognitive impairment (mainly including memory deficits and executive dysfunction), while the region of hyperintense decreased significantly in brain MRI (Fig. 1 K, J). Patient no. 2 The patient, a 52-year-old woman, was admitted to the hospital because of memory loss, accompanied by fever, weakness of limbs, slow reaction, dull expression, and decreased sleep. There was no headache, dizziness, syncope, seizure during the course of disease. No clear positive findings were observed in the physical examination except for decreased muscular strength in the right lower limb. Blood routine, biochemical, thyroid function tests, and routine CSF were all normal. Brain MRI showed increased scattered T2WI and T2-FLAIR hyperintensity in the bilateral temporal lobe and hippocampus (Fig. 2 A, B) . The slow-wave activity was observed in the right hemisphere of the brain in the background of the EEG examination (Fig. 2 E) . PET-CT did not detect any tumors. AMPA2-R antibody was positive in both serum and CSF (the titer of serum and CSF were both 1:100) (Fig. 2 F, G) , while other paraneoplastic antibodies in serum and CSF were negative. Methylprednisolone pulse therapy (500 mg/day for 5 days) was commenced, and then IVIG was added to the therapeutic regime. The patient was poorly responsive to treatment. The patient remained unconscious, silent, expressionless, weak in both lower limbs, and unable to walk. After 42 days, the hyperintense of brain MRI decreased significantly (Fig. 2 C, D) while reexamination of AMPAR antibody showed the level in serum remained 1:100 (Fig. 2 H) , respectively, and the condition was not improved. Patient no. 3 A 57-year-old man was admitted to our hospital, presenting with anterograde memory loss for a month His memory disturbances, particularly short term memory loss and disorientation, had aggravated gradually. Neurological examination showed no obvious abnormality. Normal investigations included blood tests, liver and renal function tests, antinuclear antibodies, ECG, and blood cultures. HIV and Treponema pallidum serology were negative. Routine white blood cell count in cerebrospinal fluid, biochemical, protein, no obvious abnormalities. CT and MRI brain were both normal. Oncologic screening was negative. AMPA2-R antibody was positive in both serum and CSF (the titer of serum was 1:100 and CSF was 1:10). Methylprednisolone pulse therapy was started. The symptom of memory loss has no significant improvement. After discharge, the patient did not experience memory impairment, mental symptoms, and sleep disorders were noted. Patient no. 4 The patient, a 53-year-old male, appeared perinasal herpes 10 days ago, and then gradually developed trance and memory decline, slow response and reduced voluntary speech. Neurological examination showed the higher nerve function was decreased and Kernig’s sign is suspiciously positive. Blood routine, biochemical, and thyroid function tests were all normal. Routine CSF analysis showed an elevated white blood cell count (87×10 6 /L, 90% monocytes) and others were normal. MRI showed scattered hyperintensity of the bilateral hippocampus and temporal lobes on T2WI and T2-FLAIR sequences. AMPA2-R antibody was positive in both serum and CSF (the titer of serum and CSF were both 1:320), while other paraneoplastic antibodies in serum and CSF were negative. Methylprednisolone pulse therapy and IVIG were started. After 2 weeks of treatment, the effect was not obvious and the patient developed respiratory failure. The patient was transferred to the ICU for treatment. IVIG and rituximab treatment was given again. After treatment, the patient's consciousness was improved, but still can not speak. At the last follow-up, cognitive function was improved, and no abnormal mental symptoms, dystonia, seizures, and autonomic dysfunction were noted. Systematic literature review To evaluate the clinical presentations, outcomes and neuroradiological characteristics of anti-AMPA encephalitis, we reviewed the previously reported studies. A systematic review of the literature revealed a total of 89 patients with anti-AMPAR encephalitis and neurological involvement. Demographic features and clinically relevant symptoms and signs are presented in Table 2. Sixty-six percent (59 of 89) of the cases occurred in women, and themedian patient age was 51.5 years (range, 12-92 years). Clinical presentations at the onset of anti-AMPA encephalitis were diverse, and amnesia was the most frequent feature, noted in 52.8% (47 of 89) of the reported cases. Limbic encephalitis (45 patients), confusion (31 patients), convulsions (18 patients) and psychiatric complaints (27 patients) were also the prominent symptoms of anti-AMPA encephalitis. Other clinical symptoms and signs were reported sporadically, including fever, focal weakness, dysphagia, sleep disorders, ataxia, involuntary movements, autonomic dysfunction, aphasia, sensory symptoms. Cancer was found in 40 of 89 patients (44.9%) with known cancer status, most commonly lung carcinoma and thymoma (16 thymoma, 12 lung cancers, 5 breast cancers, 4 ovary cancers, 1 thyroid cancer, 1 osteosarcoma, 1bladder carcinoma). Treatment of anti-AMPAR encephalitis includes immunotherapy and oncological treatment if tumors are comorbid. Immunotherapy is composed of first-line therapies (IVIG, steroids, and plasmapheresis). In general, outcomes were favorable. Ten patients with AMPAR encephalitis died (11.2%), most commonly of complications related to underlying malignancy. 34 patients returned to baseline and 45 patients remained partial impairment. Up to 74.2% of the patients had abnormal brain MRI with a stereotyped topography including a clear predilection for bilateral temporal lobes. However, it should be noted that patients with anti-AMPAR encephalitis may have completely normal brain MRI and the imaging abnormalities may spread to unexpected sites, like basal ganglia, cerebellum, cerebral cortex regions, and even diffuse hyperintensities. We classified the MRI presentations of 89 cases into three groups of normal group (n=23), limbic system hyperintensities group (n=43) and non-limbic system hyperintensities group (n=23). Pearson’s χ 2 test was performed to determine if the clinical symptoms and outcomes of anti-AMPAR encephalitis depended on the MRI presentations (Table 3). The results showed that there was a statistical trend towards limbic encephalitis (P=0.091) and convulsions (P=0.078) at presentation associating with the MRI presentations. Limbic system hyperintensities were more common in patients of partial recovery (P=0.015). To determine the clinical and neuroradiological factors that predicted the unfavorable outcome, we used logistic regression to quantify the relationship of outcomes against variables corresponding to demographics (age, sex), clinical symptoms (presence of confusion, limbic encephalitis, amnesia, convulsions, psychiatric symptoms) and MRI presentations (Table 4). The results showed that these factors did not have statistical significance. Discussion We summarize local experience with 4 patients and findings from a systematic review of reported AMPAR encephalitis cases. Our findings highlight the marked variability in clinical symptoms, brain MRI manifestations, and clinical outcomes observed in patients with AMPAR encephalitis. Furthermore, neuroradiological abnormalities are not confined to the limbic system; they may extend to atypical sites, including the basal ganglia, cerebellum, and cerebral cortical regions, present as diffuse hyperintensities, or even be absent (i.e., normal brain MRI). Additionally, we identified a statistical trend indicating an association between the presence of limbic encephalitis and convulsions at initial presentation and specific MRI manifestations. Using logistic regression analysis, no significant associations were identified between clinical symptoms, brain MRI findings, disease-associated malignancies, and unfavorable clinical outcomes. A prior study [ 14 ] demonstrated that early recognition and prompt initiation of treatment can improve outcomes in this potentially life-threatening disorder. These observations may be utilized to enhance the identification of patients with suspected AMPAR encephalitis, thereby facilitating earlier therapeutic intervention with the objective of improving long-term clinical outcomes. Based on our case and cases reported in the literature, we observed that the clinical manifestations—including behavioral, cognitive, motor, and sensory symptoms—and clinical outcomes of patients with AMPAR encephalitis exhibit marked variability [ 5 , 10 ]. We observed that the onset phenotype was autoimmune encephalitis in 50.6% (45 of 89) of cases. It is well established that cognitive dysfunction constitutes a common manifestation of autoimmune encephalitis, and a growing body of evidence supports an autoimmune pathogenesis underlying cognitive impairment even in the absence of limbic encephalitis [ 12 , 15 , 16 ]. Recent studies have indicated that in younger patients, the presence of confusion at onset is associated with a more favorable prognosis; conversely, the presence of confusion at onset correlates with a poor prognosis during follow-up [ 5 , 17 – 19 ]. Previous research has noted a high prevalence of neoplasms in anti-AMPA receptor encephalitis, with the incidence of paraneoplastic syndrome ranging from 60% to 70% [ 12 , 20 , 21 ]. More recent case series and case reports have also documented a lower frequency of malignancy compared with those in earlier literature, which may be attributed to differences in sample size and follow-up duration. In our retrospective study, malignancy was identified in 40 out of 89 patients (44.9%) with known cancer status. Tsubasa et al. [ 22 ] proposed a hypothesis that specific tumor antigens may trigger the production of anti-AMPAR antibodies, thereby contributing to the pathogenesis of AMPAR encephalitis. The review of previously reported cases with tumors suggested that the presence of concurrent paraneoplastic autoimmunity constituted a key prognostic factor for unfavorable outcomes [ 1 , 7 , 8 , 23 , 24 ]. These findings suggest the necessity of extensive screening for malignancy in patients with psychiatric symptoms. Brain MRI is considered as a sensitive but not specifc diagnostic tool for anti-AMPAR encephalitis [ 10 ]. Patients with anti-AMPAR encephalitis most commonly exhibit imaging findings consistent with limbic encephalitis, characterized by bilateral or unilateral T2-FLAIR hyperintensities in the medial temporal lobes [ 25 ]. According to the systemic review, brain MRI was frequently abnormal (86% of cases) with a stereotyped topography, including a clear predilection for bilateral temporal lobes, which was related to the topography of GluA1 and GluA2 expression [ 5 ]. Considering the broad distribution of GluR2 AMPA receptors in the CNS, it is likely that the clinical involvement of anti-AMPAR encephalitis is not restricted to the limbic system and may spread to unexpected sites, like basal ganglia, cerebellum, cerebral cortex regions, and even diffuse hyperintensities. Elamin et al. [ 26 ] reported a case of anti-AMPAR encephalitis presenting with mental symptoms, while brain magnetic resonance imaging showed no limbic system involvement but posterior cerebral cortex and subcortical white matter involvement. Quaranta et al. [ 27 ] reported a case of anti-AMPAR encephalitis complicated with Turner's syndrome, which started with anxiety, tension, speech rigidity, and other mental symptoms and cognitive decline, followed by rapid bidirectional affective disorder. Since the brain MRI and EEG were normal, doctors have been treating the patient with antipsychotic drugs. Anti-AMPAR encephalitis was not diagnosed until six years later. Although MRI findings can confirm the clinical diagnosis of LE, it should be noted that patients with anti-AMPAR encephalitis may have completely normal brain MRI [ 28 ]. Our study demonstrated about 74.2% (66 of 89) patients showed abnormalities in brain MRI, with limbic system hyperintensities in 43 patients (Table 2). These findings are consistent with the previously published data. Furthermore, Zhang et al. [ 25 ] characterized the cortical ribbon sign in anti-AMPAR encephalitis—an imaging finding that closely mimics that of Creutzfeldt-Jakob disease. On MRI (particularly diffusion-weighted imaging, DWI), this sign manifests as a band of abnormally increased signal intensity traversing the cerebral cortex, conforming to the gray-white matter junction and exhibiting a morphological pattern analogous to a cortical "ribbon". Pathophysiologically, the emergence of the cortical ribbon sign in anti-AMPAR encephalitis is hypothesized to be secondary to cytotoxic edema within the cortical lesions. This underlying pathological process offers a plausible mechanistic explanation for the distinct radiological hallmark observed in this subset of autoimmune encephalitides. Wei et al. [ 9 ] reported a patient with anti-AMPAR encephalitis who developed progressive hippocampal atrophy and increased T2-FLAIR signal intensity; such progressive hippocampal sclerosis was correlated with short-term memory deficits and long-term cognitive impairments during follow-up [ 28 ]. Additionally, magnetic resonance spectroscopy (MRS) revealed a decrease in the NAA peak, indicating neuronal cell damage, and an increase in the Cho peak, suggesting cellular inflammatory edema, cellular membrane disintegration, demyelination of white matter, and heightened cellular metabolic function. EEG usually shows focal or generalized slowing, epileptiform activity, and periodic lateralized epileptiform discharges and is helpful in excluding other causes of non-convulsive seizures and encephalitis [ 13 ]. However, it was reported in the literature that EEG was less sensitive than brain MRI, and only 44% of patients had EEG abnormalities [ 27 ]. CSF studies often show predominant lymphocytic pleocytosis and the presence of AMPAR antibodies. The diagnosis requires the detection of cerebrospinal fluid and serum AMPAR antibody. Once the antibody is detected, the diagnosis can be made [ 29 ]. Treatment of anti-AMPAR encephalitis includes first-line therapies (IVIG, steroids, and plasmapheresis) and second-line therapies (rituximab and immunosuppressants, etc.) and therapy usually combines two or more treatment options [ 28 ]. Early treatment and no admission to an intensive care unit were identified as predictors of good outcome [ 30 , 31 ]. More than half of the patient’s memory deficits did not completely recover despite the administration of immunotherapy. The persistence of the neurologic deficits and eventual fatality may occur depending on the severity of the disease and complications of other organs [ 32 ]. During the follow-up, residual memory deficit was the most common symptom by reviewing literature, and most of the patients would improve gradually after reasonable immunotherapy [ 33 ]. In this study, Pearson’s χ 2 test showed that there was a statistical trend towards limbic encephalitis (P = 0.091) and convulsions (P = 0.078) at presentation associating with the MRI presentations. Limbic system hyperintensities were more common in patients of partial recovery (P = 0.015). By using logistic regression, we found no significant relationships between clinical symptoms, Brain MRI, disease-associated malignancy and unfavorable outcome. We supposed that it was related to the small sample size limiting the statistical power and hindering a firm conclusion, or to the multicollinearity among the independent variables. Additionally, two of our patients with brain MRI hyperintense reduced still had no significant relief during follow-up. We suspected that the reduction of brain MRI hyperintense during follow-up may not have relationship with patient’s recovery in progress. Further, Hoftberger et al. [ 11 ] reported clinical features and treatment profile of 22 subjects and found that patients with or without tumor did not show any difference in the clinical outcomes but those patients with tumor and associated autoimmune antibodies had poor prognosis. Gresa-Arribas et al. [ 34 ] found that NMDAR-Ab titers were higher in patients with poor outcome or teratoma than in patients with good outcome or no tumor, and the titer change in CSF was more closely related to relapses than was that in serum. Yang et al. [ 35 ] reported that additional neuronal antibodies (CRMP5) were detected in the patient, which may be associated with a poor prognosis. Further studies are needed to decipher more risk factors related to clinical outcomes. Conclusions We presented four typical cases of anti-AMPAR encephalitis; in addition, we summarized the clinical and neuroradiological features of the patients with anti-AMPAR encephalitis, while discussing the relationship between neuroradiological presentations and outcomes. The current findings, taken together with those of previous studies, have several practical implications. First, it is likely that the clinical involvement of anti-AMPAR encephalitis is not restricted to the limbic system and may spread to unexpected sites, like basal ganglia, cerebellum, cerebral cortex, and even diffuse hyperintensities, and it should be noted that patients with anti-AMPAR encephalitis may have completely normal brain MRI. Second, MRI as a sensitive diagnostic tool for anti-AMPAR encephalitis may provide more valuable information related to clinical presentations and outcomes. Third, for the expanding clinical profile of encephalitis associated with antibodies against AMPAR, careful databasing of new cases will facilitate more definitive studies in the future. Abbreviations AMPAR: α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor; CSF: Cerebral spinal fluid; ECG: Electroencephalogram; FLAIR: Fluid-attenuated inversion recovery; IVIG: Intravenous injection of immunoglobulin; MRI: Magnetic resonance imaging; MRS: magnetic resonance spectroscopy. Declarations Ethics approval and consent to participate All procedures were performed according to the Declaration of Helsinki and ethical approval was obtained from the Ethics Committee from The First Affiliated Hospital of Shandong First Medical University. All participants gave written informed consent. Consent for publication The patients gave written informed consent for their personal or clinical details along with any identifying images to be published in this study. Availability of data and material All data contained within the article. Competing interests The authors declare that they have no competing interests. Funding This study was funded by the Natural Science Foundation of Shandong Province, China (ZR2024QH270); the National Natural Science Foundation of China (82101421); Taishan Scholar Program of Shandong Province (tsqn202211334); and Postdoctoral Innovation Project of Shandong Province (SDCX-ZG-202302016). Authors' contributions S.J. and C.Z. finished the study and wrote this paper. S.J., C.Z. and X.W. made data collection and analysis. S.J., P.Z., X.W. revised the manuscript and edited English. P.Z. contributed to the conception and design of this study and proposed the amendments. S.J., C.Z., X.W. and P.Z. took full responsibility for the data, the analyses and interpretation, and the conduct of the research. Acknowledgements None. References Lai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol. 2009 Apr;65(4):424-34. https://doi.org/10.1002/ana.21589. Peng X, Hughes EG, Moscato EH, Parsons TD, Dalmau J, Balice-Gordon RJ. Cellular plasticity induced by anti-AMPA receptor encephalitis antibodies. Ann Neurol. 2015 Mar;77(3):381-98. https://doi.org/10.1002/ana.24293. Palmer CL, Cotton L, Henley JM. The molecular pharmacology and cell biology of alphaamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Pharmacol Rev. 2005 Jun;57(2):253-77. https://doi.org/10.1124/pr.57.2.7. Sprengel R. Role of AMPA receptors in synaptic plasticity. Cell Tissue Res. 2006;326(2): 447-55. https://doi.org/10.1007/s00441-006-0275-4. Laurido‑Soto O, Brier MR, Simon LE, McCullough A, Bucelli RC, Day GS. Patient characteristics and outcome associations in AMPA receptor encephalitis. J Neurol. 2019;266:450‑60. https://doi.org/10.1007/s00415-018-9153-8. Gleichman AJ, Panzer JA, Baumann BH, Dalmau J, Lynch DR. Antigenic and mechanistic characterization of anti-AMPA receptor encephalitis. Ann Clin Transl Neurol. 2014;1:180-189. https://doi.org/10.1002/acn3.43. Bataller L, Galiano R, Garcia-Escrig M, et al. Reversible paraneoplastic limbic encephalitis associated with antibodies to the AMPA receptor. Neurology. 2010;74:265-267. https://doi.org/10.1212/WNL.0b013e3181cb3e52. Graus F, Boronat A, Xifro X, et al. The expanding clinical profle of anti-AMPA receptor encephalitis. Neurology. 2010;74:857-859. https://doi.org/10.1212/WNL.0b013e3181d3e404. Wei YC, Liu CH, Lin JJ, et al. Rapid progression and brain atrophy in anti-AMPA receptor encephalitis. J Neuroimmunol. 2013;261:129-133. https://doi.org/10.1016/j.jneuroim.2013.05.011. Joubert B, Kerschen P, Zekeridou A, et al. Clinical spectrum of encephalitis associated with antibodies against the alpha-amino-3-hydroxy-5-methyl -4-isoxazolepropionic acid receptor: case series and review of the literature. JAMA Neurol. 2015;72:1163-1169. https://doi.org/10.1001/jamaneurol.2015.1715. Hoftberger R, van Sonderen A, Leypoldt F, et al. Encephalitis and AMPA receptor antibodies: novel fndings in a case series of 22 patients. Neurology. 2015;84:2403-2412. https://doi.org/10.1212/WNL.0000000000001682. Lin J, Wang J, Li J. Patient characteristics and outcome in patients with anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis. Neurol Sci. 2023;Sep;44(9):3253-3259. https://doi.org/10.1007/s10072-023-06769-x. Fischl B. FreeSurfer. Neuroimage. 2012 Aug 15;62(2):774-81. https://doi.org/10.1016/j.neuroimage.2012.01.021. Navira Samad, Jennifer Wong. Anti-AMPA receptor encephalitis associated with Medullary thyroid cancer. BMJ Case Rep. 2018;Aug 27:2018: bcr2018225745. https://doi.org/10.1136/bcr-2018-225745. Mahajan S, Appleby BS. Comprehensive and methodical: diagnostic and management approaches to rapidly progressive dementia. Curr Treat Options Neurol. 2017;19:40. https://doi.org/10.1007/s11940-017-0474-1. Day GS, Yarbrough MY, Kortvelyessy P, et al. Prospective quantifcation of CSF biomarkers in antibody-mediated encephalitis. Neurology. 2021;96:e2546–e2557. https://doi.org/10.1212/WNL.0000000000011937. V R Ashok, D Nagabushana, G Yashwanth, A Mahadevan, M Netravathi. A Rare Case of Wobbly, Psychotic Patient with Frozen Eyes - Anti-AMPA Receptor Encephalitis. Neurol India. 2021;Jan-Feb;69(1):149-152. https://doi.org/10.4103/0028-3886.310087. Murashko AA, Pavlov KA, Pavlova OV, Gurina OI, Shmukler A. Antibodies against N-Methyl D-aspartate receptor in psychotic disorders: a systematic review. Neuropsychobiology. 2021;17:1-18. https://doi.org/10.1159/000515930. Cleland N, Lieblich S, Schalling M, Rahm C. A 16-year-old girl with antiNMDA-receptor encephalitis and family history of psychotic disorders. Acta Neuropsychiatr. 2015;27:375-9. https://doi.org/10.1017/neu.2015.32. Yang J, et al. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis: A case report. Medicine(Baltimore). 2021;100:17. https://doi.org/10.1097/MD.0000000000025694. Zhu H, Hou YB, Gao JG, Zhao T, Zhou CK, Liu JY. Limbic encephalitis associated with antibodies against the α-Amino-3-Hydroxy-5-Methyl-4- Isoxazolepropionic acid receptor: a case report. Neuro Endocrinol Lett. 2018;May; 39(2):85-87. https://pubmed.ncbi.nlm.nih.gov/30183201. Tsubasa Omi, Makoto Kinoshita, Akira Nishikawa, Takahito Tomioka, Kenichi Ohmori, Kei Fukada, Hidenori Matsunaga. Clinical Relapse of Anti-AMPAR Encephalitis Associated with Recurrence of Thymoma. Intern Med. 2018;Apr 1;57(7):1011-1013. https://doi.org/10.2169/internalmedicine.9682-17. Dogan Onugoren M, Deuretzbacher D, Haensch CA, et al. Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series. J Neurol Neurosurg Psychiatry Epub. 2014;Oct 9. https://doi.org/10.1136/jnnp-2014-308814. Elizabeth Matthews, Barrie Schmitt, Michlene Passeri, Christopher Mizenko, Karen Orjuela, Amanda Piquet. AMPA Receptor Encephalitis in a Patient With Metastatic Breast Cancer Receiving Palbociclib: A Case Report. Neurol Neuroimmunol Neuroinflamm. 2022;Jul 6;9(5):e200012. https://doi.org/10.1212/NXI.0000000000200012. Zhuangzhuang Zhang, Feng Gao, Weiping Sun, Zhaoxia Wang, Yiming Zheng. Cortical ribbon sign in AMPAR antibody-associated encephalitis mimicking Creutzfeldt-Jakob disease. Neurol Sci. 2025 Mar;46(3):1443-1446. https://doi.org/10.1007/s10072-024-07850-9. Elamin M, Lonergan R, Killeen RP, O Riordan S, Tubridy N, McGuigan C. Posterior cortical and white matter changes on MRI in anti-AMPA receptor antibody encephalitis. Neurol Neuroimmunol Neuroinfamm. 2015;2(4):e118. https://doi.org/10.1212/NXI.0000000000000118. Giuseppe Quaranta, Angelo Giovanni Icro Maremmani, Giulio Perugi. Anti-AMPA-Receptor Encephalitis Presenting as a Rapid-Cycling Bipolar Disorder in a Young Woman with Turner Syndrome. Case Rep Psychiatry. 2015:273192. https://doi.org/10.1155/2015/273192. Zhang Z, Fan S, Ren H, Zhou L, Guan H. Clinical characteristics and prognosis of anti-alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor encephalitis. BMC Neurol. 2021;Dec 16;21(1):490. https://doi.org/10.1186/s12883-021-02520-1. Collingridge GL, Peineau S, Howland JG, Wang YT. Long-term depression in the CNS. Nat Rev Neurosci. 2010;11, 459-473. https://doi.org/10.1038/nrn2867. Yuanyuan Luo, et al. Autoimmune Encephalitis With Psychotic Manifestations and Cognitive Impairment Presenting as Schizophrenia: Case Report and Literature Review. Front Psychiatry. 2022;Feb 14:13:827138. https://doi.org/10.3389/fpsyt.2022.827138. Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12:157-65. https://doi.org/10.1016/S1474-4422(12)70310-1. Broadley J, Seneviratne U, Beech P, Buzzard K, Butzkueven H. Prognosticating autoimmune encephalitis: a systematic review. J Autoimmun. 2019;96:24-34. https://doi.org/10.1016/j.jaut.2018.10.014. Yu Jia, Mingyu Li, Huifang Wang, Mengyao Zhang, Yuping Wang. The Peculiar Clinical Symptoms and Treatment of Limbic Encephalitis Associated with AMPA Receptor Antibody. Eur Neurol. 2021;84(3):206-211. https://doi.org/10.1159/000515592. Gresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, et al. Antibody titres at diagnosis and during followup of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014;13(2): 167-77. https://doi.org/10.1016/S1474-4422(13)70282-5. Shuangshuang Yang, Jie Qin, Jinghong Li, Yuan Gao, Lu Zhao, Jun Wu, Bo Song, Yuming Xu, Shilei Sun. Rapidly progressive neurological deterioration in anti-AMPA receptor encephalitis with additional CRMP5 antibodies. Neurol Sci. 2016 Nov;37(11):1853-1855. https://doi.org/10.1007/s10072-016-2680-0. Tables Table 1 Clinical presentation of 4 cases with anti-AMPAR encephalitis Case number Age, y/sex Clinical presention Other symptoms during course of the disease Brain MRI AMPAR antibodies Tumor state Treatment 1 32/F Memory loss, limb weakness Perioral numbness, slow response, fever Bilateral temporal lobe CFS 1:100, serum 1:100 Not found IVIG, steroids 2 52/F Memory loss, limb weakness Fever, weakness of limbs, slow reaction Left frontal parietal lobe, bilateral hippocampal and temporal lobe CFS 1:100, serum 1:100 Not found IVIG, steroids 3 57/M Memory loss (-) Bilateral hippocampal and temporal lobe CFS 1:10, serum 1:10 Not found Steroids 4 53/M Confusion, memory loss Slow response Bilateral hippocampal and temporal lobe CFS 1:320, serum 1:320 Not found IVIG, steroids Abbreviations: MRI, magnetic resonance imaging; AMPAR, α-Amino-3-Hydroxy -5-Methyl-4-Isoxazolepropionic acid receptor; CSF, cerebrospinal fluid; IVIG intravenous immunoglobulin. Table 2 Demographic features and clinically relevant symptoms Variables Range Mean Sex 30 M/59 F Age (years) 12–92 51.5 Clinical symptoms N % positive Limbic encephalitis 45 50.6 Confusion 31 34.8 Amnesia 47 52.8 Convulsions 18 20.2 Psychiatric complaints 27 30.3 Clinical studies N % positive Tumor identified 40 44.9 Thymoma 16 Lung 12 Breast 5 Ovary 4 Thyroid 1 Osteosarcoma 1 Bladder carcinoma 1 MRI abnormal 66 74.2 Treatment 87 available Steroids 11 IVIG 8 Seroids+IVIG(+plasmapheresis) 41 (32+9) Steroids+plasmapheresis 3 Tumor treatment(+IVIG) 8 (3+5) Tumor treatment+steroids 5 Tumor treatment+steroids+IVIG 8 Tumor treatment+steroids+IVIG+plasmapheresis 3 Abbreviations: MRI, magnetic resonance imaging; IVIG, Intravenous immunoglobulin. Table 3 Comparison of Clinical symptoms and outcomes associations among different MRI presentations Brain MRI Normal group (n=23) Limbic system hyperintensities group (n=43) Non- limbic system hyperintensities group (n=23) χ2 value p value Clinical symptoms Limbic encephalitis at presentation 3 9 3 4.800 0.091 Confusion at presentation 3 6 2 2.364 0.307 Amnesia at presentation 9 12 11 0.438 0.804 Convulsions at presentation 1 7 3 5.091 0.078 Psychiatric symptoms at presentation 7 9 4 1.900 0.387 Clinical outcomes Death 2 5 3 1.400 0.497 Partial recovery 9 24 12 8.400 0.015 Return to baseline 12 14 8 1.647 0.439 Abbreviations: MRI, magnetic resonance imaging. Persistence of cognitive defucits Table 4 Logistic regression predicting unfavorable outcome OR (95% CI) z value p value Sex 0.892(0.362-2.196) -0.249 0.803 Age (years) 0.628(0.215-1.830) -0.853 0.394 Clinical symptoms Limbic encephalitis at presentation 1.289(0.400-4.155) 0.425 0.671 Confusion at presentation 1.759(0.433-7.149) 0.789 0.430 Amnesia at presentation 0.835(0.351-2.071) -0.352 0.725 Convulsions at presentation 1.094(0.295-4.055) 0.134 0.893 Psychiatric symptoms at presentation 0.694(0.253-1.904) -0.709 0.479 Tumor identified 1.901(0.789-4.538) 1.431 0.152 Brain MRI Normal 0.458(0.175-1.203) -1.585 0.113 Limbic system hyperintensities 1.539(0.672-3.781) 1.057 0.219 Non- limbic system hyperintensities 1.219(0.453-3.280) 0.392 0.695 Abbreviations: MRI, magnetic resonance imaging. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Jan, 2026 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 25 Nov, 2025 Reviews received at journal 21 Nov, 2025 Reviewers agreed at journal 20 Nov, 2025 Reviews received at journal 17 Nov, 2025 Reviewers agreed at journal 13 Nov, 2025 Reviewers invited by journal 05 Nov, 2025 Editor invited by journal 09 Oct, 2025 Editor assigned by journal 16 Sep, 2025 Submission checks completed at journal 13 Sep, 2025 First submitted to journal 13 Sep, 2025 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. 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09:54:55","extension":"html","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101419,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7438732/v1/f4ff521768bb45c3d206b426.html"},{"id":96071331,"identity":"d95644a6-db90-4946-8508-1b6e81d9c85a","added_by":"auto","created_at":"2025-11-17 09:54:57","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1136376,"visible":true,"origin":"","legend":"\u003cp\u003eBrain MRI findings of patient No.1. (A ~ D) After symptom onset, increased T2WI and T2-fluid-attenuated inversion recovery (FLAIR) signal could be observed in bilaterally medial temporal lobe and hippocampus, right caput nuclei caudati. (E ~ J) Follow-up imaging 7 days later, the lesion of the T2WI and T2-FLAIR hyperintense decreased slightly. Contrast image showed no enhancement. (K, L) Follow-up imaging 20 days later, the lesion of hyperintense decreased significantly.\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7438732/v1/659937812871d46144669e56.jpg"},{"id":96071322,"identity":"f909226d-2280-49d7-8ce0-5e79366297ae","added_by":"auto","created_at":"2025-11-17 09:54:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1112066,"visible":true,"origin":"","legend":"\u003cp\u003eBrain MRI and clinical findings of patient No.2. Brain MRI showing increased scattered T2WI and T2-FLAIR hyperintensity in bilateral temporal lobe and hippocampus (A, B) and 42 days (C, D) after onset, the hyperintense decreased significantly. (E) EEG showed slow-wave activity in right hemisphere of the brain background slowing suggestive of diffuse encephalopathy. (F, G) Presence of autoimmune antibodies in serum and CSF. (H) At 42 days after onset, the titer of antibodies in the serum was decreased.\u003c/p\u003e","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7438732/v1/ce866119b322409794bfe34e.jpg"},{"id":99545169,"identity":"2c57faa9-660a-4a09-85ba-78c7799c599c","added_by":"auto","created_at":"2026-01-05 16:00:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3104870,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7438732/v1/edb8f291-8625-4923-98fc-c81ac8e5f03d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical and neuroradiological findings in patients with Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis: Associations with outcomes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFirst described by Lai et al. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] in 2009, encephalitis associated with anti-α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor (AMPAR) represents a subtype of autoimmune encephalitis linked to anti-neuronal surface antigens. The initial characterization of this encephalitis involved 10 patients, all diagnosed with limbic encephalitis, whose cerebrospinal fluid (CSF) and serum harbored antibodies that cross-reacted with the neuropil of rat brains and the cell surface of cultured rat hippocampal neurons [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. As ionotropic glutamate receptors, AMPARs assemble into tetramers consisting of GluR1, GluR2, GluR3, and GluR4 subunits, with the GluR2 subunit showing enriched distribution in the hippocampus, amygdala, and cerebral cortex [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. AMPARs mediate fast synaptic transmission in the central nervous system and are essential for synaptic plasticity, learning, and memory. Patients typically present with diverse symptoms such as confusion, amnesia, seizures, encephalopathy, and psychosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTo date, fewer than 100 cases of anti-AMPAR encephalitis have been described in the published literature, presenting substantial diagnostic hurdles owing to the condition\u0026rsquo;s clinical heterogeneity and low incidence [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Magnetic resonance imaging (MRI) frequently demonstrates abnormalities with a stereotyped distribution, including a distinct predilection for the bilateral temporal lobes\u0026mdash;a pattern that correlates with the expression topography of GluA1 and GluA2 subunits. Moreover, these MR imaging abnormalities are likely reflective of the underlying pathophysiological mechanisms. In the present study, we report four cases of AMPAR-associated encephalitis, describe their corresponding clinical and neuroradiological findings, discuss their clinical courses and outcomes, and review the existing literature on brain MRI and clinical features of this disease. Detailed characterization of the clinical presentation, neuroradiological findings, and outcomes of anti-AMPAR encephalitis may facilitate improved recognition of patients with suspected AMPAR-associated encephalitis.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical cases\u003c/em\u003e\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBy retrospectively reviewing patients with positive AMPAR antibodies in CSF or serum, a total of 4 patients diagnosed with AMPAR-associated encephalitis were enrolled in this study between April 2021 and November 2023. Demographic data, clinical manifestations, laboratory findings (including CSF analysis, anti-neuronal antibodies in serum/CSF), scalp electroencephalography (EEG), brain MRI, and oncological screening results, as well as treatment regimens and therapeutic responses, were extracted from the patients\u0026rsquo; outpatient and inpatient medical records. Written informed consent was obtained from each patient. This study was approved by the Research Ethics Committee of XXX Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSystematic review and data extraction\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo identify relevant literature on AMPAR encephalitis, we conducted a systematic search of the PubMed database using the key terms \u0026quot;autoimmune encephalitis\u0026quot; and \u0026quot;AMPA receptor antibodies\u0026quot;. This search was repeated periodically to ensure comprehensiveness, with the final search conducted on May 25, 2025. Abstracts of the retrieved records were screened for eligibility, and a total of 62 manuscripts were selected for full-text review. Twenty-seven manuscripts were excluded: these either did not report unique cases of AMPAR encephalitis or focused primarily on other disease entities. Data were subsequently extracted from the unique cases documented in the remaining 35 manuscripts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Analysis\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAbnormal findings on brain MRI were extracted and categorized based on the cortical anatomical regions as defined in Freesurfer [13]. T2-weighted hyperintensity was the most frequently observed lesion type.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll analyses were conducted using the statistical software of SPSS (version 19.0; IBM). The associations between different MRI presentations and clinical symptoms, outcomes were quantified using Pearson\u0026rsquo;s\u0026nbsp;\u0026chi;\u003csup\u003e2\u003c/sup\u003e test. The relationship between demographic, clinical variables and neuroradiological presentation on outcomes were quantified using logistic regression. Death and partial recovery were defined as unfavorable outcome, and return to baseline was defined as favorable outcome. Statistical significance was defined as p\u0026lt;0.05.\u003c/p\u003e"},{"header":"Result","content":"\u003cp\u003eWe identified 4 patients with anti-AMPAR encephalitis, including 2 women and 2 men. Their median age was 56 years (range 32-57 years). All patients were positive for AMPAR-Abs in both serum and CSF samples (antibody titer range, 1:10 to greater than 1:320). In 3 of the 4 patients, the clinical diagnosis of LE was confirmed by the MRI findings of mesiotemporal increased fluid-attenuated inversion recovery (FLAIR)/T2WI signal abnormalities. In patient 3, the brain MRI was normal. The main clinical data of our 4 cases are reported in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCase reports\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient no. 1\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 32-year-old woman presented to the hospital with perioral numbness accompanied by limb weakness for more than 10 days. The patient caught a cold 10 days ago and then developed perioral numbness, accompanied by general fatigue, accompanied by sleep disorders, manifested as difficulty falling asleep and irritability at night. The patient gradually showed memory loss, slow reaction, and reduced speech. Neurological examination showed that the reaction was slow, the comprehension and calculation power decreased, and negative Babinski signs as well as negative meningeal irritation signs.\u003c/p\u003e\n\u003cp\u003eAfter admission, the blood test showed an increase in white blood cells and neutrophils. And other routine serum tests were normal. Routine CSF tests exhibited normal results. However, the EEG showed increased slow-wave activity during the waking period and no typical epileptic discharge. Brain MRI revealed increased T2WI and T2-FLAIR signal involving bilaterally medial temporal lobe and hippocampus, right caput nuclei caudate (Fig. 1 A~D) . PET-CT indicated circular nodules in the mediastinum with a slight increase in metabolism and a high possibility of benign lesions. Anti-AMPAR antibodies were both detected in CSF(1:100) and serum(1:100).\u003c/p\u003e\n\u003cp\u003eMethylprednisolone pulse therapy and intravenous immunoglobulin (IVIG) were started. MRI revealed that scattered T2WI and T2-FLAIR hyperintensity had decreased compared with 7 days (Fig. 1 E~J) after onset. However, the symptoms of the patient did not improve, and then further aggravated, almost unable to speak, unable to walk, and the right upper limb involuntary movement. At the follow-up\u0026nbsp;20 days later, this patient demonstrated an improvement in symptoms but still had persistent cognitive impairment (mainly including memory deficits and executive dysfunction), while the region of hyperintense decreased significantly in brain MRI (Fig. 1 K, J).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient no. 2\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient, a 52-year-old woman, was admitted to the hospital because of memory loss, accompanied by fever, weakness of limbs, slow reaction, dull expression, and decreased sleep. There was no headache, dizziness, syncope, seizure during the course of disease. No clear positive findings were observed in the physical examination except for decreased muscular strength in the right lower limb. Blood routine, biochemical, thyroid function tests, and routine CSF were all normal. Brain MRI showed increased scattered T2WI and T2-FLAIR\u0026nbsp;hyperintensity in the bilateral temporal lobe and hippocampus (Fig. 2 A, B)\u0026nbsp;. The slow-wave activity was observed in the right hemisphere of the brain in the background of the EEG examination (Fig. 2 E)\u0026nbsp;. PET-CT did not detect any tumors. AMPA2-R antibody was positive in both serum and CSF (the titer of serum and CSF were both 1:100) (Fig. 2 F, G)\u0026nbsp;, while other paraneoplastic antibodies in serum and CSF were negative.\u003c/p\u003e\n\u003cp\u003eMethylprednisolone pulse therapy (500 mg/day for 5 days) was commenced, and then IVIG was added to the therapeutic regime. The patient was poorly responsive to treatment. The patient remained unconscious, silent, expressionless, weak in both lower limbs, and unable to walk. After 42 days, the hyperintense of brain MRI decreased significantly (Fig. 2 C, D) while\u0026nbsp;reexamination of AMPAR antibody showed the level in serum remained 1:100 (Fig. 2 H)\u0026nbsp;, respectively, and the condition was not improved.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient no. 3\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 57-year-old man was admitted to our hospital, presenting with anterograde memory loss for a month His memory disturbances, particularly short term memory loss and disorientation, had aggravated gradually. Neurological examination showed no obvious abnormality. Normal investigations included blood tests, liver and renal function tests, antinuclear antibodies, ECG, and blood cultures. HIV and Treponema pallidum serology were negative. Routine white blood cell count in cerebrospinal fluid, biochemical, protein, no obvious abnormalities. CT and MRI brain were both normal. Oncologic screening was negative. AMPA2-R antibody was positive in both serum and CSF (the titer of serum was 1:100 and CSF was 1:10).\u003c/p\u003e\n\u003cp\u003eMethylprednisolone pulse therapy was started. The symptom of memory loss has no significant improvement. After discharge, the patient did not experience memory impairment, mental symptoms, and sleep disorders were noted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient no. 4\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient, a 53-year-old male, appeared perinasal herpes 10 days ago, and then gradually developed trance and memory decline, slow response and reduced voluntary speech. Neurological examination showed the higher nerve function was decreased and Kernig\u0026rsquo;s sign is suspiciously positive. Blood routine, biochemical, and thyroid function tests were all normal. Routine CSF analysis showed an elevated white blood cell count (87\u0026times;10\u003csup\u003e6\u003c/sup\u003e /L, 90% monocytes) and others were normal. MRI showed scattered hyperintensity of the bilateral hippocampus and temporal lobes on T2WI and T2-FLAIR sequences. AMPA2-R antibody was positive in both serum and CSF (the titer of serum and CSF were both 1:320), while other paraneoplastic antibodies in serum and CSF were negative.\u003c/p\u003e\n\u003cp\u003eMethylprednisolone pulse therapy and IVIG were started. After 2 weeks of treatment, the effect was not obvious and the patient developed respiratory failure. The patient was transferred to the ICU for treatment. IVIG and rituximab treatment was given again. After treatment, the patient\u0026apos;s consciousness was improved, but still can not speak. At the last follow-up, cognitive function was improved, and no abnormal mental symptoms, dystonia, seizures, and autonomic dysfunction were noted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSystematic literature review\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the clinical presentations, outcomes and neuroradiological characteristics of anti-AMPA encephalitis, we reviewed the previously reported studies. A systematic review of the literature revealed a total of 89 patients with anti-AMPAR encephalitis and neurological involvement.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemographic features and clinically relevant symptoms and signs are presented in Table 2. Sixty-six percent (59 of 89) of the cases occurred in women, and themedian patient age was 51.5 years (range, 12-92 years). Clinical presentations at the onset of anti-AMPA encephalitis were diverse, and amnesia was the most frequent feature, noted in 52.8% (47 of 89) of the reported cases. Limbic encephalitis (45 patients), confusion (31 patients), convulsions (18 patients) and psychiatric complaints (27 patients) were also the prominent symptoms of anti-AMPA encephalitis. Other clinical symptoms and signs were reported sporadically, including fever, focal weakness, dysphagia, sleep disorders, ataxia, involuntary movements, autonomic dysfunction, aphasia, sensory symptoms. Cancer was found in 40 of 89 patients (44.9%) with known cancer status, most commonly lung carcinoma and thymoma (16 thymoma, 12 lung cancers, 5 breast cancers, 4 ovary cancers, 1 thyroid cancer, 1 osteosarcoma, 1bladder carcinoma). Treatment of anti-AMPAR encephalitis includes immunotherapy and oncological treatment if tumors are comorbid. Immunotherapy is composed of first-line therapies (IVIG, steroids, and plasmapheresis). In general, outcomes were favorable. Ten patients with AMPAR encephalitis died (11.2%), most commonly of complications related to underlying malignancy. 34 patients returned to baseline and 45 patients remained partial impairment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUp to 74.2% of the patients had abnormal brain MRI with a stereotyped topography including a clear predilection for bilateral temporal lobes. However, it should be noted that patients with anti-AMPAR encephalitis may have completely normal brain MRI and the imaging abnormalities may spread to unexpected sites, like basal ganglia, cerebellum, cerebral cortex regions, and even diffuse hyperintensities. We classified the MRI presentations of 89 cases into three groups of normal group (n=23), limbic system hyperintensities group (n=43) and non-limbic system hyperintensities group (n=23). Pearson\u0026rsquo;s\u0026nbsp;\u0026chi;\u003csup\u003e2\u003c/sup\u003e test was performed to determine if the clinical symptoms and outcomes of anti-AMPAR encephalitis depended on the MRI presentations (Table 3). The results showed that there was a statistical trend towards limbic encephalitis (P=0.091) and convulsions (P=0.078) at presentation associating with the MRI presentations. Limbic system hyperintensities were more common in patients of partial recovery (P=0.015). To determine the clinical and neuroradiological factors that predicted the unfavorable outcome, we used logistic regression to quantify the relationship of outcomes against variables corresponding to demographics (age, sex), clinical symptoms (presence of confusion, limbic encephalitis, amnesia, convulsions, psychiatric symptoms) and MRI presentations (Table 4). The results showed that these factors did not have statistical significance.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe summarize local experience with 4 patients and findings from a systematic review of reported AMPAR encephalitis cases. Our findings highlight the marked variability in clinical symptoms, brain MRI manifestations, and clinical outcomes observed in patients with AMPAR encephalitis. Furthermore, neuroradiological abnormalities are not confined to the limbic system; they may extend to atypical sites, including the basal ganglia, cerebellum, and cerebral cortical regions, present as diffuse hyperintensities, or even be absent (i.e., normal brain MRI). Additionally, we identified a statistical trend indicating an association between the presence of limbic encephalitis and convulsions at initial presentation and specific MRI manifestations. Using logistic regression analysis, no significant associations were identified between clinical symptoms, brain MRI findings, disease-associated malignancies, and unfavorable clinical outcomes. A prior study [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] demonstrated that early recognition and prompt initiation of treatment can improve outcomes in this potentially life-threatening disorder. These observations may be utilized to enhance the identification of patients with suspected AMPAR encephalitis, thereby facilitating earlier therapeutic intervention with the objective of improving long-term clinical outcomes.\u003c/p\u003e\u003cp\u003eBased on our case and cases reported in the literature, we observed that the clinical manifestations\u0026mdash;including behavioral, cognitive, motor, and sensory symptoms\u0026mdash;and clinical outcomes of patients with AMPAR encephalitis exhibit marked variability [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. We observed that the onset phenotype was autoimmune encephalitis in 50.6% (45 of 89) of cases. It is well established that cognitive dysfunction constitutes a common manifestation of autoimmune encephalitis, and a growing body of evidence supports an autoimmune pathogenesis underlying cognitive impairment even in the absence of limbic encephalitis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRecent studies have indicated that in younger patients, the presence of confusion at onset is associated with a more favorable prognosis; conversely, the presence of confusion at onset correlates with a poor prognosis during follow-up [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Previous research has noted a high prevalence of neoplasms in anti-AMPA receptor encephalitis, with the incidence of paraneoplastic syndrome ranging from 60% to 70% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. More recent case series and case reports have also documented a lower frequency of malignancy compared with those in earlier literature, which may be attributed to differences in sample size and follow-up duration. In our retrospective study, malignancy was identified in 40 out of 89 patients (44.9%) with known cancer status. Tsubasa et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] proposed a hypothesis that specific tumor antigens may trigger the production of anti-AMPAR antibodies, thereby contributing to the pathogenesis of AMPAR encephalitis. The review of previously reported cases with tumors suggested that the presence of concurrent paraneoplastic autoimmunity constituted a key prognostic factor for unfavorable outcomes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These findings suggest the necessity of extensive screening for malignancy in patients with psychiatric symptoms.\u003c/p\u003e\u003cp\u003eBrain MRI is considered as a sensitive but not specifc diagnostic tool for anti-AMPAR encephalitis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Patients with anti-AMPAR encephalitis most commonly exhibit imaging findings consistent with limbic encephalitis, characterized by bilateral or unilateral T2-FLAIR hyperintensities in the medial temporal lobes [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. According to the systemic review, brain MRI was frequently abnormal (86% of cases) with a stereotyped topography, including a clear predilection for bilateral temporal lobes, which was related to the topography of GluA1 and GluA2 expression [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Considering the broad distribution of GluR2 AMPA receptors in the CNS, it is likely that the clinical involvement of anti-AMPAR encephalitis is not restricted to the limbic system and may spread to unexpected sites, like basal ganglia, cerebellum, cerebral cortex regions, and even diffuse hyperintensities. Elamin et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] reported a case of anti-AMPAR encephalitis presenting with mental symptoms, while brain magnetic resonance imaging showed no limbic system involvement but posterior cerebral cortex and subcortical white matter involvement. Quaranta et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] reported a case of anti-AMPAR encephalitis complicated with Turner's syndrome, which started with anxiety, tension, speech rigidity, and other mental symptoms and cognitive decline, followed by rapid bidirectional affective disorder. Since the brain MRI and EEG were normal, doctors have been treating the patient with antipsychotic drugs. Anti-AMPAR encephalitis was not diagnosed until six years later. Although MRI findings can confirm the clinical diagnosis of LE, it should be noted that patients with anti-AMPAR encephalitis may have completely normal brain MRI [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Our study demonstrated about 74.2% (66 of 89) patients showed abnormalities in brain MRI, with limbic system hyperintensities in 43 patients (Table\u0026nbsp;2). These findings are consistent with the previously published data. Furthermore,\u003c/p\u003e\u003cp\u003eZhang et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] characterized the cortical ribbon sign in anti-AMPAR encephalitis\u0026mdash;an imaging finding that closely mimics that of Creutzfeldt-Jakob disease. On MRI (particularly diffusion-weighted imaging, DWI), this sign manifests as a band of abnormally increased signal intensity traversing the cerebral cortex, conforming to the gray-white matter junction and exhibiting a morphological pattern analogous to a cortical \"ribbon\". Pathophysiologically, the emergence of the cortical ribbon sign in anti-AMPAR encephalitis is hypothesized to be secondary to cytotoxic edema within the cortical lesions. This underlying pathological process offers a plausible mechanistic explanation for the distinct radiological hallmark observed in this subset of autoimmune encephalitides. Wei et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] reported a patient with anti-AMPAR encephalitis who developed progressive hippocampal atrophy and increased T2-FLAIR signal intensity; such progressive hippocampal sclerosis was correlated with short-term memory deficits and long-term cognitive impairments during follow-up [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Additionally, magnetic resonance spectroscopy (MRS) revealed a decrease in the NAA peak, indicating neuronal cell damage, and an increase in the Cho peak, suggesting cellular inflammatory edema, cellular membrane disintegration, demyelination of white matter, and heightened cellular metabolic function.\u003c/p\u003e\u003cp\u003eEEG usually shows focal or generalized slowing, epileptiform activity, and periodic lateralized epileptiform discharges and is helpful in excluding other causes of non-convulsive seizures and encephalitis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, it was reported in the literature that EEG was less sensitive than brain MRI, and only 44% of patients had EEG abnormalities [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. CSF studies often show predominant lymphocytic pleocytosis and the presence of AMPAR antibodies. The diagnosis requires the detection of cerebrospinal fluid and serum AMPAR antibody. Once the antibody is detected, the diagnosis can be made [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTreatment of anti-AMPAR encephalitis includes first-line therapies (IVIG, steroids, and plasmapheresis) and second-line therapies (rituximab and immunosuppressants, etc.) and therapy usually combines two or more treatment options [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Early treatment and no admission to an intensive care unit were identified as predictors of good outcome [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. More than half of the patient\u0026rsquo;s memory deficits did not completely recover despite the administration of immunotherapy. The persistence of the neurologic deficits and eventual fatality may occur depending on the severity of the disease and complications of other organs [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. During the follow-up, residual memory deficit was the most common symptom by reviewing literature, and most of the patients would improve gradually after reasonable immunotherapy [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eIn this study, Pearson\u0026rsquo;s χ\u003csup\u003e2\u003c/sup\u003e test showed that there was a statistical trend towards limbic encephalitis (P\u0026thinsp;=\u0026thinsp;0.091) and convulsions (P\u0026thinsp;=\u0026thinsp;0.078) at presentation associating with the MRI presentations. Limbic system hyperintensities were more common in patients of partial recovery (P\u0026thinsp;=\u0026thinsp;0.015). By using logistic regression, we found no significant relationships between clinical symptoms, Brain MRI, disease-associated malignancy and unfavorable outcome. We supposed that it was related to the small sample size limiting the statistical power and hindering a firm conclusion, or to the multicollinearity among the independent variables. Additionally, two of our patients with brain MRI hyperintense reduced still had no significant relief during follow-up. We suspected that the reduction of brain MRI hyperintense during follow-up may not have relationship with patient\u0026rsquo;s recovery in progress. Further, Hoftberger et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] reported clinical features and treatment profile of 22 subjects and found that patients with or without tumor did not show any difference in the clinical outcomes but those patients with tumor and associated autoimmune antibodies had poor prognosis. Gresa-Arribas et al. [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] found that NMDAR-Ab titers were higher in patients with poor outcome or teratoma than in patients with good outcome or no tumor, and the titer change in CSF was more closely related to relapses than was that in serum. Yang et al. [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] reported that additional neuronal antibodies (CRMP5) were detected in the patient, which may be associated with a poor prognosis. Further studies are needed to decipher more risk factors related to clinical outcomes.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWe presented four typical cases of anti-AMPAR encephalitis; in addition, we summarized the clinical and neuroradiological features of the patients with anti-AMPAR encephalitis, while discussing the relationship between neuroradiological presentations and outcomes. The current findings, taken together with those of previous studies, have several practical implications. First, it is likely that the clinical involvement of anti-AMPAR encephalitis is not restricted to the limbic system and may spread to unexpected sites, like basal ganglia, cerebellum, cerebral cortex, and even diffuse hyperintensities, and it should be noted that patients with anti-AMPAR encephalitis may have completely normal brain MRI. Second, MRI as a sensitive diagnostic tool for anti-AMPAR encephalitis may provide more valuable information related to clinical presentations and outcomes. Third, for the expanding clinical profile of encephalitis associated with antibodies against AMPAR, careful databasing of new cases will facilitate more definitive studies in the future.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAMPAR: \u0026alpha;-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor; CSF: Cerebral spinal fluid; ECG: Electroencephalogram; FLAIR: Fluid-attenuated inversion recovery; IVIG: Intravenous injection of immunoglobulin; MRI: Magnetic resonance imaging; MRS: magnetic resonance spectroscopy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures were performed according to the Declaration of Helsinki and ethical approval was obtained from the Ethics Committee from The First Affiliated Hospital of Shandong First Medical University. All participants gave written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients gave written informed consent for their personal or clinical details along with any identifying images to be published in this study.\u003cbr\u003e\u0026nbsp;\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data contained within the article.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Natural Science Foundation of Shandong Province, China (ZR2024QH270); the National Natural Science Foundation of China (82101421); Taishan Scholar Program of Shandong Province (tsqn202211334); and Postdoctoral Innovation Project of Shandong Province (SDCX-ZG-202302016).\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;Authors\u0026apos; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.J. and C.Z. finished the study and wrote this paper. S.J., C.Z. and X.W. made data collection and analysis. S.J., P.Z., X.W. revised the manuscript and edited English. P.Z. contributed to the conception and design of this study and proposed the amendments. S.J., C.Z., X.W. and P.Z. took full responsibility for the data, the analyses and interpretation, and the conduct of the research.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;None.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLai M, Hughes EG, Peng X, et al. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Ann Neurol. 2009 Apr;65(4):424-34. https://doi.org/10.1002/ana.21589.\u003c/li\u003e\n\u003cli\u003ePeng X, Hughes EG, Moscato EH, Parsons TD, Dalmau J, Balice-Gordon RJ. Cellular plasticity induced by anti-AMPA receptor encephalitis antibodies. Ann Neurol. 2015 Mar;77(3):381-98. https://doi.org/10.1002/ana.24293.\u003c/li\u003e\n\u003cli\u003ePalmer CL, Cotton L, Henley JM. The molecular pharmacology and cell biology of alphaamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Pharmacol Rev. 2005 Jun;57(2):253-77. https://doi.org/10.1124/pr.57.2.7.\u003c/li\u003e\n\u003cli\u003eSprengel R. Role of AMPA receptors in synaptic plasticity. Cell Tissue Res. 2006;326(2): 447-55. https://doi.org/10.1007/s00441-006-0275-4.\u003c/li\u003e\n\u003cli\u003eLaurido‑Soto O, Brier MR, Simon LE, McCullough A, Bucelli RC, Day GS. Patient characteristics and outcome associations in AMPA receptor encephalitis. J Neurol. 2019;266:450‑60. https://doi.org/10.1007/s00415-018-9153-8.\u003c/li\u003e\n\u003cli\u003eGleichman AJ, Panzer JA, Baumann BH, Dalmau J, Lynch DR. Antigenic and mechanistic characterization of anti-AMPA receptor encephalitis. Ann Clin Transl Neurol. 2014;1:180-189. https://doi.org/10.1002/acn3.43.\u003c/li\u003e\n\u003cli\u003eBataller L, Galiano R, Garcia-Escrig M, et al. Reversible paraneoplastic limbic encephalitis associated with antibodies to the AMPA receptor. Neurology. 2010;74:265-267. https://doi.org/10.1212/WNL.0b013e3181cb3e52.\u003c/li\u003e\n\u003cli\u003eGraus F, Boronat A, Xifro X, et al. The expanding clinical profle of anti-AMPA receptor encephalitis. Neurology. 2010;74:857-859. https://doi.org/10.1212/WNL.0b013e3181d3e404.\u003c/li\u003e\n\u003cli\u003eWei YC, Liu CH, Lin JJ, et al. Rapid progression and brain atrophy in anti-AMPA receptor encephalitis. J Neuroimmunol. 2013;261:129-133. https://doi.org/10.1016/j.jneuroim.2013.05.011.\u003c/li\u003e\n\u003cli\u003eJoubert B, Kerschen P, Zekeridou A, et al. Clinical spectrum of encephalitis associated with antibodies against the alpha-amino-3-hydroxy-5-methyl -4-isoxazolepropionic acid receptor: case series and review of the literature. JAMA Neurol. 2015;72:1163-1169. https://doi.org/10.1001/jamaneurol.2015.1715.\u003c/li\u003e\n\u003cli\u003eHoftberger R, van Sonderen A, Leypoldt F, et al. Encephalitis and AMPA receptor antibodies: novel fndings in a case series of 22 patients. Neurology. 2015;84:2403-2412. https://doi.org/10.1212/WNL.0000000000001682.\u003c/li\u003e\n\u003cli\u003eLin J, Wang J, Li J. Patient characteristics and outcome in patients with anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis. Neurol Sci. 2023;Sep;44(9):3253-3259. https://doi.org/10.1007/s10072-023-06769-x.\u003c/li\u003e\n\u003cli\u003eFischl B. FreeSurfer. Neuroimage. 2012 Aug 15;62(2):774-81. https://doi.org/10.1016/j.neuroimage.2012.01.021.\u003c/li\u003e\n\u003cli\u003eNavira Samad, Jennifer Wong. Anti-AMPA receptor encephalitis associated with Medullary thyroid cancer. BMJ Case Rep. 2018;Aug 27:2018: bcr2018225745. https://doi.org/10.1136/bcr-2018-225745.\u003c/li\u003e\n\u003cli\u003eMahajan S, Appleby BS. Comprehensive and methodical: diagnostic and management approaches to rapidly progressive dementia. Curr Treat Options Neurol. 2017;19:40. https://doi.org/10.1007/s11940-017-0474-1.\u003c/li\u003e\n\u003cli\u003eDay GS, Yarbrough MY, Kortvelyessy P, et al. Prospective quantifcation of CSF biomarkers in antibody-mediated encephalitis. Neurology. 2021;96:e2546\u0026ndash;e2557. https://doi.org/10.1212/WNL.0000000000011937.\u003c/li\u003e\n\u003cli\u003eV R Ashok, D Nagabushana, G Yashwanth, A Mahadevan, M Netravathi. A Rare Case of Wobbly, Psychotic Patient with Frozen Eyes - Anti-AMPA Receptor Encephalitis. Neurol India. 2021;Jan-Feb;69(1):149-152. https://doi.org/10.4103/0028-3886.310087.\u003c/li\u003e\n\u003cli\u003eMurashko AA, Pavlov KA, Pavlova OV, Gurina OI, Shmukler A. Antibodies against N-Methyl D-aspartate receptor in psychotic disorders: a systematic review. Neuropsychobiology. 2021;17:1-18. https://doi.org/10.1159/000515930.\u003c/li\u003e\n\u003cli\u003eCleland N, Lieblich S, Schalling M, Rahm C. A 16-year-old girl with antiNMDA-receptor encephalitis and family history of psychotic disorders. Acta Neuropsychiatr. 2015;27:375-9. https://doi.org/10.1017/neu.2015.32.\u003c/li\u003e\n\u003cli\u003eYang J, et al. Anti-\u0026alpha;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis: A case report. Medicine(Baltimore). 2021;100:17. https://doi.org/10.1097/MD.0000000000025694.\u003c/li\u003e\n\u003cli\u003eZhu H, Hou YB, Gao JG, Zhao T, Zhou CK, Liu JY. Limbic encephalitis associated with antibodies against the \u0026alpha;-Amino-3-Hydroxy-5-Methyl-4- Isoxazolepropionic acid receptor: a case report. Neuro Endocrinol Lett. 2018;May; 39(2):85-87. https://pubmed.ncbi.nlm.nih.gov/30183201.\u003c/li\u003e\n\u003cli\u003eTsubasa Omi, Makoto Kinoshita, Akira Nishikawa, Takahito Tomioka, Kenichi Ohmori, Kei Fukada, Hidenori Matsunaga. Clinical Relapse of Anti-AMPAR Encephalitis Associated with Recurrence of Thymoma. Intern Med. 2018;Apr 1;57(7):1011-1013. https://doi.org/10.2169/internalmedicine.9682-17.\u003c/li\u003e\n\u003cli\u003eDogan Onugoren M, Deuretzbacher D, Haensch CA, et al. Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series. J Neurol Neurosurg Psychiatry Epub. 2014;Oct 9. https://doi.org/10.1136/jnnp-2014-308814.\u003c/li\u003e\n\u003cli\u003eElizabeth Matthews, Barrie Schmitt, Michlene Passeri, Christopher Mizenko, Karen Orjuela, Amanda Piquet. AMPA Receptor Encephalitis in a Patient With Metastatic Breast Cancer Receiving Palbociclib: A Case Report. Neurol Neuroimmunol Neuroinflamm. 2022;Jul 6;9(5):e200012. https://doi.org/10.1212/NXI.0000000000200012.\u003c/li\u003e\n\u003cli\u003eZhuangzhuang Zhang, Feng Gao, Weiping Sun, Zhaoxia Wang, Yiming Zheng. Cortical ribbon sign in AMPAR antibody-associated encephalitis mimicking Creutzfeldt-Jakob disease. Neurol Sci. 2025 Mar;46(3):1443-1446. https://doi.org/10.1007/s10072-024-07850-9.\u003c/li\u003e\n\u003cli\u003eElamin M, Lonergan R, Killeen RP, O Riordan S, Tubridy N, McGuigan C. Posterior cortical and white matter changes on MRI in anti-AMPA receptor antibody encephalitis. Neurol Neuroimmunol Neuroinfamm. 2015;2(4):e118. https://doi.org/10.1212/NXI.0000000000000118.\u003c/li\u003e\n\u003cli\u003eGiuseppe Quaranta, Angelo Giovanni Icro Maremmani, Giulio Perugi. Anti-AMPA-Receptor Encephalitis Presenting as a Rapid-Cycling Bipolar Disorder in a Young Woman with Turner Syndrome. Case Rep Psychiatry. 2015:273192. https://doi.org/10.1155/2015/273192.\u003c/li\u003e\n\u003cli\u003eZhang Z, Fan S, Ren H, Zhou L, Guan H. Clinical characteristics and prognosis of anti-alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor encephalitis. BMC Neurol. 2021;Dec 16;21(1):490. https://doi.org/10.1186/s12883-021-02520-1.\u003c/li\u003e\n\u003cli\u003eCollingridge GL, Peineau S, Howland JG, Wang YT. Long-term depression in the CNS. Nat Rev Neurosci. 2010;11, 459-473. https://doi.org/10.1038/nrn2867.\u003c/li\u003e\n\u003cli\u003eYuanyuan Luo, et al. Autoimmune Encephalitis With Psychotic Manifestations and Cognitive Impairment Presenting as Schizophrenia: Case Report and Literature Review. Front Psychiatry. 2022;Feb 14:13:827138. https://doi.org/10.3389/fpsyt.2022.827138.\u003c/li\u003e\n\u003cli\u003eTitulaer MJ, McCracken L, Gabilondo I, Armangu\u0026eacute; T, Glaser C, Iizuka T, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12:157-65. https://doi.org/10.1016/S1474-4422(12)70310-1.\u003c/li\u003e\n\u003cli\u003eBroadley J, Seneviratne U, Beech P, Buzzard K, Butzkueven H. Prognosticating autoimmune encephalitis: a systematic review. J Autoimmun. 2019;96:24-34. https://doi.org/10.1016/j.jaut.2018.10.014.\u003c/li\u003e\n\u003cli\u003eYu Jia, Mingyu Li, Huifang Wang, Mengyao Zhang, Yuping Wang. The Peculiar Clinical Symptoms and Treatment of Limbic Encephalitis Associated with AMPA Receptor Antibody. Eur Neurol. 2021;84(3):206-211. https://doi.org/10.1159/000515592.\u003c/li\u003e\n\u003cli\u003eGresa-Arribas N, Titulaer MJ, Torrents A, Aguilar E, McCracken L, Leypoldt F, et al. Antibody titres at diagnosis and during followup of anti-NMDA receptor encephalitis: a retrospective study. Lancet Neurol. 2014;13(2): 167-77. https://doi.org/10.1016/S1474-4422(13)70282-5.\u003c/li\u003e\n\u003cli\u003eShuangshuang Yang, Jie Qin, Jinghong Li, Yuan Gao, Lu Zhao, Jun Wu, Bo Song, Yuming Xu, Shilei Sun. Rapidly progressive neurological deterioration in anti-AMPA receptor encephalitis with additional CRMP5 antibodies. Neurol Sci. 2016 Nov;37(11):1853-1855. https://doi.org/10.1007/s10072-016-2680-0.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1 Clinical presentation of 4 cases with anti-AMPAR encephalitis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"597\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.71022%;\"\u003e\n \u003cp\u003eCase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.20268%;\"\u003e\n \u003cp\u003eAge, y/sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.0653%;\"\u003e\n \u003cp\u003eClinical presention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2529%;\"\u003e\n \u003cp\u003eOther symptoms \u0026nbsp; \u0026nbsp; during course of the disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.598%;\"\u003e\n \u003cp\u003eBrain MRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.2278%;\"\u003e\n \u003cp\u003eAMPAR antibodies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7203%;\"\u003e\n \u003cp\u003eTumor state\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2228%;\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.71022%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.20268%;\"\u003e\n \u003cp\u003e32/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.0653%;\"\u003e\n \u003cp\u003eMemory loss, limb weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2529%;\"\u003e\n \u003cp\u003ePerioral numbness, slow response, fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.598%;\"\u003e\n \u003cp\u003eBilateral temporal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.2278%;\"\u003e\n \u003cp\u003eCFS 1:100, serum 1:100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7203%;\"\u003e\n \u003cp\u003eNot found\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2228%;\"\u003e\n \u003cp\u003eIVIG, steroids\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.71022%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.20268%;\"\u003e\n \u003cp\u003e52/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.0653%;\"\u003e\n \u003cp\u003eMemory loss, limb weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2529%;\"\u003e\n \u003cp\u003eFever, weakness of limbs, slow reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.598%;\"\u003e\n \u003cp\u003eLeft frontal parietal lobe, bilateral hippocampal and temporal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.2278%;\"\u003e\n \u003cp\u003eCFS 1:100, serum 1:100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7203%;\"\u003e\n \u003cp\u003eNot found\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2228%;\"\u003e\n \u003cp\u003eIVIG, steroids\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.71022%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.20268%;\"\u003e\n \u003cp\u003e57/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.0653%;\"\u003e\n \u003cp\u003eMemory loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2529%;\"\u003e\n \u003cp\u003e(-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.598%;\"\u003e\n \u003cp\u003eBilateral hippocampal and temporal lobe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.2278%;\"\u003e\n \u003cp\u003eCFS 1:10,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eserum 1:10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7203%;\"\u003e\n \u003cp\u003eNot found\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2228%;\"\u003e\n \u003cp\u003eSteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 8.71022%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.20268%;\"\u003e\n \u003cp\u003e53/M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.0653%;\"\u003e\n \u003cp\u003eConfusion, memory loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.2529%;\"\u003e\n \u003cp\u003eSlow response\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.598%;\"\u003e\n \u003cp\u003eBilateral hippocampal and temporal lobe\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.2278%;\"\u003e\n \u003cp\u003eCFS 1:320,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eserum 1:320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7203%;\"\u003e\n \u003cp\u003eNot found\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.2228%;\"\u003e\n \u003cp\u003eIVIG, steroids\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: MRI, magnetic resonance imaging; AMPAR, \u0026alpha;-Amino-3-Hydroxy -5-Methyl-4-Isoxazolepropionic acid receptor; CSF, cerebrospinal fluid; IVIG intravenous immunoglobulin.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Demographic features and clinically relevant symptoms\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"554\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e30 M/59 F\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e12\u0026ndash;92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e51.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;% positive\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u0026nbsp; Limbic encephalitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e50.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eConfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e34.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u0026nbsp; Amnesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e52.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u0026nbsp; Convulsions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e20.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003ePsychiatric complaints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e30.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical studies\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;% positive\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eTumor identified \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e44.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u0026nbsp; Thymoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eLung\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u0026nbsp; Breast\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u0026nbsp; Ovary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eThyroid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u0026nbsp; Osteosarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003e\u0026nbsp; Bladder carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eMRI abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e74.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e87 available\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eSteroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eIVIG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eSeroids+IVIG(+plasmapheresis)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e41 (32+9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eSteroids+plasmapheresis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eTumor treatment(+IVIG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e8 (3+5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eTumor treatment+steroids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eTumor treatment+steroids+IVIG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 55.9567%;\"\u003e\n \u003cp\u003eTumor treatment+steroids+IVIG+plasmapheresis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22.2022%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21.8412%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eAbbreviations: MRI, magnetic resonance imaging; IVIG, Intravenous immunoglobulin.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Comparison of Clinical symptoms and outcomes associations among different MRI presentations\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"565\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 358px;\"\u003e\n \u003cp\u003eBrain MRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003eNormal group\u003c/p\u003e\n \u003cp\u003e(n=23)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003eLimbic system hyperintensities group\u003c/p\u003e\n \u003cp\u003e(n=43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNon- limbic system hyperintensities group\u003c/p\u003e\n \u003cp\u003e(n=23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026chi;2 \u0026nbsp;value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 565px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003eLimbic encephalitis at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e4.800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003eConfusion at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e2.364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003eAmnesia at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e0.438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003eConvulsions at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e5.091\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003ePsychiatric symptoms at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.387\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 565px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003ePartial recovery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e8.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 160px;\"\u003e\n \u003cp\u003eReturn to baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 103px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e1.647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.439\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: MRI, magnetic resonance imaging.\u003c/p\u003e\n\u003cp\u003ePersistence of cognitive defucits\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 Logistic regression predicting unfavorable outcome\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"554\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003ez value\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e0.892(0.362-2.196)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e-0.249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.803\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e0.628(0.215-1.830)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e-0.853\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 453px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical symptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eLimbic encephalitis at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.289(0.400-4.155)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.425\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.671\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eConfusion at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.759(0.433-7.149)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.789\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.430\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eAmnesia at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e0.835(0.351-2.071)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e-0.352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.725\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eConvulsions at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.094(0.295-4.055)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.893\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003ePsychiatric symptoms at presentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e0.694(0.253-1.904)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e-0.709\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.479\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eTumor identified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.901(0.789-4.538)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e1.431\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 453px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBrain MRI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e0.458(0.175-1.203)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e-1.585\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eLimbic system hyperintensities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.539(0.672-3.781)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e1.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.219\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 223px;\"\u003e\n \u003cp\u003eNon- limbic system hyperintensities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e1.219(0.453-3.280)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.392\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.695\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: MRI, magnetic resonance imaging.\u003cstrong\u003e\u003c/strong\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, Limbic encephalitis, Brain MRI, Outcome","lastPublishedDoi":"10.21203/rs.3.rs-7438732/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7438732/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eEncephalitis associated with antibodies against the α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor (AMPAR) is an extremely rare type of antibody-mediated encephalitis. Its clinical phenotype and neuroradiological characteristics remain incompletely described.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe present four cases of with neurological involvement, and a comprehensive literature review highlighted the diverse clinical experiences, with specific attention to the clinical and radiographic characteristics of anti-AMPAR encephalitis, as well as the association between clinical, neuroradiological presentations and outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 89 patients with anti-AMPAR encephalitis were included in this review. Clinical presentations at the onset of anti-AMPAR encephalitis were diverse, including behavioral, cognitive, motor, and sensory manifestations. Neuroradiological findings cannot be restricted to the limbic system. They may spread to unexpected sites, like basal ganglia, cerebellum, cerebral cortex regions, and even diffuse hyperintensities, or patient may have completely normal brain magnetic resonance imaging (MRI). Pearson\u0026rsquo;s χ\u003csup\u003e2\u003c/sup\u003e test showed a statistical trend towards limbic encephalitis (P\u0026thinsp;=\u0026thinsp;0.091) and convulsions (P\u0026thinsp;=\u0026thinsp;0.078) at presentation associating with the MRI presentations. Limbic system hyperintensities were more common in patients of partial recovery (P\u0026thinsp;=\u0026thinsp;0.015). However, logistic regression analysis showed no significant correlations between clinical, neuroradiological findings and unfavorable outcome.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eAnti-AMPAR encephalitis mainly presents as limbic encephalitis, and most of the patients had positive brain MRI results. As a sensitive diagnostic tool for this condition, MRI may provide more valuable information related to clinical presentation and outcomes. For the expanding clinical profile of encephalitis associated with antibodies against AMPAR, careful databasing of new cases will facilitate more definitive study in the future.\u003c/p\u003e","manuscriptTitle":"Clinical and neuroradiological findings in patients with Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis: Associations with outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-17 09:54:47","doi":"10.21203/rs.3.rs-7438732/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-25T08:06:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-22T01:48:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"43341454864094428625494974034949579276","date":"2025-11-20T15:53:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-17T16:04:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"264728705009193333922544509873406746941","date":"2025-11-13T06:01:37+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-05T10:41:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-09T15:37:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-16T17:44:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-13T14:22:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-09-13T14:19:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6a7385d5-e602-4ef9-bb16-8c86dfd353ac","owner":[],"postedDate":"November 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-05T15:58:48+00:00","versionOfRecord":{"articleIdentity":"rs-7438732","link":"https://doi.org/10.1186/s12883-025-04608-4","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2026-01-02 15:56:54","publishedOnDateReadable":"January 2nd, 2026"},"versionCreatedAt":"2025-11-17 09:54:47","video":"","vorDoi":"10.1186/s12883-025-04608-4","vorDoiUrl":"https://doi.org/10.1186/s12883-025-04608-4","workflowStages":[]},"version":"v1","identity":"rs-7438732","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7438732","identity":"rs-7438732","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}