Clinical Features, Etiological Spectrum, and Outcomes of Neurological Patients Initially Presenting with Psychiatric Symptom

Clinical Features, Etiological Spectrum, and Outcomes of Neurological Patients Initially Presenting with Psychiatric Symptom | 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 Features, Etiological Spectrum, and Outcomes of Neurological Patients Initially Presenting with Psychiatric Symptom Chao Chen, Yiya Xu, Zixiong Zhan, Yingchao He, Shifu Xiao, Ting Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8353793/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Neurological disorders can manifest with psychiatric symptoms as the initial presentation (PSIP), leading to diagnostic challenges and risk of delayed treatment. Data on the clinical trajectory of this specific patient population remain limited. Methods This retrospective cohort study analyzed 51 inpatients admitted to the Department of Neurology between 2019 and 2023, selected based on PSIP at admission. We extracted and analyzed demographic, clinical, laboratory, neuroimaging, and outcome data from electronic medical records. Results The cohort (mean age 56.5 ± 17.9 years; 39.2% female) predominantly exhibited nonspecific agitation and disturbed behavior (60.8%) rather than classic psychiatric syndromes. Acute onset was common (92.2%). Notably, 16 patients (31.4%) presented with isolated psychiatric symptoms without neurological signs or fever. Hyponatremia was a frequent finding (23.5%). Cerebrospinal fluid (CSF) abnormalities and brain MRI lesions were detected in 57.8% and 60.0% of patients, respectively. The leading etiologies were CNS infections (56.9%), predominantly viral encephalitis, followed by cerebrovascular diseases (15.7%) and autoimmune encephalitis (9.8%). Subgroup analysis of viral encephalitis patients revealed that those with PSIP had significantly higher rates of hyponatremia (42.9% vs. 14.7%, p = 0.007) and poorer outcomes (61.9% vs. 90.5% good outcome, p = 0.003) compared to those without PSIP, despite similar profiles in other clinical markers. Conclusion PSIP is a critical clinical scenario where underlying neurological disorders, particularly viral encephalitis, are common. Hyponatremia emerges as a key biomarker suggesting an organic etiology. The absence of neurological signs does not rule out a serious neurological condition. Early comprehensive investigation, including CSF analysis and neuroimaging, is essential for timely diagnosis and improved prognosis. Psychiatric Symptoms Neurological Disorders Organic Causes Viral Encephalitis Hyponatremia Autoimmune Encephalitis New-onset Psychosis Figures Figure 1 Introduction Psychiatric symptoms are frequently observed in various neurological diseases, such as CNS infections( 1 , 2 ), autoimmune encephalitis( 3 , 4 ), epilepsy( 5 ), and systemic metabolic disorders( 6 ). In some cases, psychiatric symptoms can be the initial and most prominent feature, closely mimicking primary psychiatric disorders such as schizophrenia or mood disorders( 7 , 8 ). This diagnostic mimicry often leads to misdiagnosis, and delays in initiating appropriate neurological workup or treatment, which is associated with poorer patient outcomes. Despite its clinical importance, the systematic characterization of neurological patients presenting with psychiatric symptoms as initial presentation (PSIP) is limited. Most existing evidence comes from studies focused on specific diseases like autoimmune encephalitis (AE)( 3 , 4 , 9 ), with a paucity of population-based studies describing the broader etiological spectrum and clinical profile of PSIP patients in a general neurological setting. To address this gap, we conducted a retrospective study of patients admitted to a tertiary neurological department with PSIP. Our primary objectives were to: ( 1 ) describe their demographic and clinical characteristics; ( 2 ) identify the etiological spectrum; ( 3 ) analyze short-term treatment outcomes; and ( 4 ) identify clinical features that may help distinguish PSIP patients from those with primary psychiatric disorders or neurological patients without psychiatric presentation. Subjects and Methods This retrospective, observational study analyzed data from the medical records of neurological patients who initially presented with psychiatric symptoms and were admitted to the Department of Neurology at Fujian Provincial Hospital of Fuzhou University between January 1, 2019, and December 31, 2023. Using the hospital's electronic medical record system, we screened discharged patients whose chief complaint contained the Chinese word "精神" (jīngshén), which means "psychic" or "psycho," during the study period. This term was selected because it is commonly used in the habitual description of psycho-behavioral disturbances ("精神异常," jīngshén yìcháng) in most non-psychiatric clinical settings in the region. The medical records of screened patients were jointly assessed by senior neurologists and psychiatrists. Patients were excluded if they had insufficient clinical data, if their psychiatric symptoms were attributed to pre-existing known disorders, if the diagnosis for the current condition was confirmed elsewhere prior to admission, or if the discharge diagnosis was inconclusive. The study was conducted in accordance with the Declaration of Helsinki, and was approved by the Ethical Review Committee of Fujian Provincial Hospital. Statistics Descriptive statistics are presented as mean (± standard deviation) for continuous variables and frequencies (percentages) for categorical variables. Group comparisons (e.g., PSIP vs. non-PSIP viral encephalitis patients) were performed using Student's t-test for continuous variables and the Chi-square or Fisher's exact test for categorical variables. A two-sided p-value < 0.05 was considered statistically significant. Analyses were conducted using SPSS Statistics 27.0 (IBM SPSS Corp.; Armonk, NY, USA). Results Patient Enrollment A total of 16473 patients were admitted in the Department of Neurology between 1st Jan 2019 and 31st Dec 2023, among which 55 patients with PSIP were screened and reviewed. Three patients were excluded due to a related previous mental illness. Another patient was excluded due to insufficient investigation record. 51 patients with PSIP were enrolled for analysis (Fig. 1 ). Patients Demographics Demographic characteristics and baseline comorbidity data are summarized in Table 1 . Patient ages ranged from 14 to 86 years (56.51 ± 17.90). Females accounted for 39.2% of the cohort, and 84.3% were married. Fifteen patients (29.4%) were current smokers, and 8 (15.7%) had a history of alcohol abuse. Common comorbidities at admission included diabetes mellitus (12 patients, 23.5%) and hypertension (11 patients, 21.6%). Six patients (11.8%) had a previous stroke, and 6 (11.8%) had hyperlipidemia. Malignancy was previously diagnosed in 6 patients (11.8%). A history of syphilis was reported in 4 patients (7.8%). In terms of neurological history, 2 patients (3.9%) had CNS trauma and 1 (2.0%) had a neurodegenerative disorder. None of the patients reported a past history of epilepsy, CNS infection or HIV/AIDS. Table 1 Demographics and Comorbidities of Patients with PSIP Characteristic Value (n = 51) Age, years 56.51 ± 17.90 Female sex 20(39.2%) Past history/Comorbidity Epilepsy 0 CNS infection 0 Stroke 6(11.8%) Neurodegeneration 1(2.0%) CNS trauma 2(3.9%) Hypertension 11(21.6%) Diabetes mellitus 12(23.5%) Hyperlipidemia 6(11.8%) HIV/AIDS 0 Syphilis 4(7.8%) Tumor 6(11.8%) Smoking 15(29.4%) Alcohol abuse 8(15.7%) Marital status Single 5(9.8%) Married 43(84.3%) Bereaved 2(3.9%) Divorced 1(2.0%) PSIP, psychiatric symptoms as initial presentation; CNS, central nervous system. Clinical features of the patients Clinical features of the patients are summarized in Table 2 . Disease onset was defined as acute if psychiatric symptoms developed within three days of initial symptom presentation. In this cohort, most patients (47 patients, 92.2%) experienced an acute onset. We analyzed the frequency of various psychiatric phenotypes, along with associated neurological symptoms and signs at admission. Through a joint review of medical records conducted by senior psychiatrists and neurologists, 31 patients (60.8%) exhibited non-specific psycho-behavioral disturbances, such as agitation, meaningless speech, or mutism, in the absence of well-defined psychiatric symptoms. This pattern suggests a distinct symptomatic phenotype in a neurological context. The three most frequently documented well-defined psychiatric symptoms were memory impairment (11 patients, 21.6%,), mood disturbance (9 patients, 17.3%,), and paranoid thought (2 patients, 3.9%). No cases of auditory hallucination were recorded; however, visual hallucinations were reported in 4 patients (7.8%). Among commonly reported systemic and neurological symptoms or signs at admission, fever was observed in 22 patients (43.1%), followed by headache (17 patients, 33.3%), seizures (11 patients, 21.6%), and altered consciousness (10 patients, 19.6%). These manifestations are often associated with diffuse central nervous system (CNS) involvement or systemic injury. Documented symptoms suggestive of focal impairments included nuchal rigidity (8 patients, 15.7%,), hemiparesis (6 patients, 11.8%,), aphasia (5 patients, 9.8%), and ataxia (4 patients, 7.8%). Table 2 Characteristics Features of Symptoms Characteristic Number of patients (percentage) Acute Onset 47(92.2%) Psychiatric manifestation Non-specific symptoms only 31(60.8%) Memory impairment 11(21.6%) Mood disturbance 9(17.3%) Paranoid delusions 2 (3.9%) Auditory Hallucination 0 (0%) Visual Hallucination 4(7.8%) Altered consciousness 10(19.6%) Fever 22(43.1%) Headache 17(33.3%) Hemiparalysis 6(11.8%) Sensory disturbance 4 (7.8%) Ataxia 4(7.8%) Seizures 11(21.6%) Aphasia 5(9.8%) Nuchal rigidity 8(15.7%) Incontinence 6(11.8%) Gastrointestinal / Urinary symptoms 2 (3.9%) Auxiliary Examination Results of auxillary examination are presented in Table 3 . All patients underwent routine blood and biochemistry tests at admission. Leukocytosis and hyponatremia were found in 14 (27.5%) and 12 (23.5%) patients, respectively. Lumbar puncture (LP) was performed in forty-five patients. Among all the cases, 17 (37.8%) exhibited increased intracranial pressure (ICP). CSF pleocytosis and elevated CSF protein were observed in 26 (57.8%) and 26 (57.8%) of the patients respectively. 18 patients were tested for serum and/or CSF antibodies associated with autoimmune encephalitis; 2 were positive for anti-NMDA receptor antibodies, and 3 others were positive for anti-MOG, anti-GABA, and anti-GM1 antibodies, respectively. Non-specific abnormal EEG recordings were observed in 15 of the 26 patients who underwent EEG during hospitalization. None of the patients demonstrated spikes or sharp waves on EEG, even those with seizures. Brain MRI was performed in 50 patients. Abnormal T2/FLAIR hyperintensities were observed in 30 patients, involving the cortex in 21 (42.0%), thalamus in 2, basal ganglia in 3, deep white matter in 1, and brainstem/cerebellum in 3 patients. No spinal lesions were observed. Meningeal enhancement on contrast-enhanced T1-weighted images was seen in 14 patients (28.0%). Table 3 Laboratory test and other technical investigations Characteristic Number of patients (%) Peripheral blood Leukocytosis 14(27.5%) Hyponatremia 12(23.5%) Syphilis positive 1(2.0%) CSF Elevated opening pressure 17(37.8%) Pleocytosis 26(57.8%) Elevated protein level 26(57.8%) Plasma/CSF autoimmune antibodies Anti-NMDAR positive 2(11.1%) Anti-MOG positive 1(5.6%) Anti-AQP4 positive 0 Anti-GABA positive 1(5.6%) Anti-GM1 positive 1(5.6%) EEG abnormality 15(57.7%) T2WI-MRI abnormality Cortical 21(42.0%) Thalamic 2(4.0%) Basal ganglia 3(6.0%) Deep white matter 1(2.0%) Brainstem or cerebellum 3(6.0%) Spine 0 Meningeal enhancement 14(28.0%) NMDAR, N-methyl-D-aspartate receptor; MOG, myelin oligodendrocyte glycoprotein; AQP4, aquaporin-4; GABA, gamma-aminobutyric acid Diagnosis and Outcomes of Patients with PSIP The final etiological diagnoses of the 51 enrolled PSIP patients are summarized in Table 4 . Central nervous system (CNS) infections constituted the leading cause, accounting for 29 cases (56.9%). Among these, viral encephalitis was the most prevalent, diagnosed in 21 patients (41.2%), followed by bacterial meningitis (3 patients, 5.9%), neurosyphilis (4 patients, 7.8%), and tuberculous meningitis (1 patient, 2.0%). Cerebrovascular diseases (CVDs) were the second most common etiology, identified in 8 patients (15.7%), including ischemic stroke (5 patients, 9.8%), intracerebral hemorrhage (2 patients, 3.9%), and cerebral venous thrombosis (1 patient, 2.0%). Autoimmune encephalitis (AE) was diagnosed in 5 patients (9.8%), with anti-NMDA receptor encephalitis being the most frequent (3 patients, 5.9%). Other diagnoses included Creutzfeldt-Jakob disease (CJD) (1 patient, 2.0%), carcinomatous meningitis (1 patient, 2.0%), and non-CNS systemic illnesses causing encephalopathy (7 patients, 13.7%), such as metabolic/nutritional deficiencies and systemic infections. Regarding short-term outcomes at discharge, complete symptomatic relief was achieved in 10 patients (19.6%), while partial relief was observed in 36 patients (70.6%). Five patients (9.8%) showed no significant change in their clinical condition. Table 4 Diagnosis and outcomes Diagnosis Number of patients (%) CNS infection 29(56.9%) Viral 21(41.2%) Bacteria 3(5.9%) TB 1(2.0%) Neurosyphilis 4(7.8%) CJD 1 (2.0%) Autoimmune encephalitis 5 (9.8%) Anti-NMDA positive 3 (5.9%) Anti-GABA positive 1 (2.0%) Anti-GM1 positive 1(2.0%) Cerebrovascular 8(15.7%) Ischemic stroke 5(9.8%) Intracerebral hemorrhage 2(3.9%) Cerebral venous thrombosis 1(2.0%) Carcinomatous meningitis 1(2.0%) Non-CNS illness 7(13.7%) Metabolic/nutritional deficiency 2(3.9%) Infectious encephalopathy 2(3.9%) Unknown 3(5.9%) Outcomes Complete relief 10(19.6%) Partial relief 36(70.6%) No change 5(9.8%) TB, tuberculous meningistis; CJD, creutzfeldt-jakob disease. Subgroup Analysis of Clinical Features and Outcomes for Viral Encephalitis A subgroup analysis was conducted comparing 21 viral encephalitis patients with PSIP and 95 viral encephalitis patients without PSIP (non-PSIP) who admitted in the Department of Neurology during the same study period, with the detailed results shown in Table 6 . The two groups were comparable in terms of age, gender distribution, time from symptom onset to hospital presentation, and the prevalence of fever, seizures, focal neurological dysfunction, leukocytosis, CSF pleocytosis, elevated CSF protein, and brain MRI abnormalities. However, a significantly higher frequency of hyponatremia was observed in the PSIP group compared to the non-PSIP group (42.9% vs. 14.7%, p = 0.007). Psychiatric symptoms that were not the initial presentation, were documented in 17 (17.9%) cases in the non-PSIP group. Patient outcomes were categorized based on the modified Rankin Scale (mRS) score, which is a widely used scale developed to assess global disability and dependance of patients with stroke and other neurological diseases including encephalitis( 10 , 11 ). In the study, a score of 0–2 at discharge was defined as a "good outcome," and a score greater than 2 was defined as a "poor outcome." A good outcome was achieved in 61.9% (13/21) of PSIP patients, which was significantly lower than the 90.5% (86/95) observed in the non-PSIP group (p = 0.003). No significant differences were found in other clinical parameters, including the need for intubation or the duration of hospitalization. Table 6 Comparison of clinical features in viral encephalitis patients with or without PSIP Characteristic PSIP (n = 21) Non-PSIP (n = 95) P Age, years 52.24 ± 17.69 44.64 ± 19.89 0.093 Female sex 10(47.6%) 35(36.8%) 0.359 Time to presentation, days 14.62 ± 21.65 10.82 ± 16.43 0.423 Psychiatric manifestation 21(100%) 17(17.9%) <0.001 Fever 15(71.4%) 52(54.7%) 0.161 Seizures 6(28.6%) 33(34.7%) 0.588 Focal neurological deficits 7(33.3%) 40(42.1%) 0.459 Leukocytosis 6(28.6%) 32(33.7%) 0.651 Hyponatremia 9(42.9%) 14(14.7%) 0.007 CSF pleocytosis 12(57.1%) 56(58.9%) 0.879 CSF elevated protein 13(61.9%) 52(54.7%) 0.549 MRI abnormality 15(71.4%) 61(64.2%) 0.529 Intubation 1(4.8%) 5(5.3%) 1 Duration of hospitalization 14.76 ± 8.20 days 15.83 ± 7.47 days 0.346 Good Outcome (mRS 0–2) 13(61.9%) 86(90.5%) 0.003 Discussion This retrospective study analyzed clinical characteristics, etiological spectrum, and outcomes of 51 neurological inpatients whose initial and predominant presentation was psychiatric symptoms. The diagnosis and management of new-onset psychiatric disorders is often challenging due to the overlapping manifestation between the organic and primary psychiatric disorders. This situation is particularly common in neurological departments. As far as we know, this is the first population-based study focusing on this distinctive group of patients who is often misdiagnosed initially and at risk for delayed appropriate care. Our findings enhance the understanding of neurological disorders initially presenting with psychiatric symptoms and offer valuable insights for improving early diagnosis and management. In the study, almost all the patients demonstrated organic causes for their psychiatric presentation. We found that the most frequent phenotype of psychiatric manifestations were atypical symptoms like agitation and disturbed behaviors, which far exceeded well-defined psychiatric symptoms of hallucinations, delusion or manic-depressive mood. Similar results were seen in studies focusing on AE, which though recognized only relatively recently, has been established as one of the most common neurological causes of acute new-onset psychiatric symptoms( 3 , 12 ). A recent systematic review identified 505 NMDA receptor antibody encephalitis (NMDAR-AE) with detailed description of their psychiatric presentation found that behavioral disturbance (68%) was the most common symptom category, followed by psychosis (67%), mood disorder (47%), catatonia (30%) and sleep disturbance (21%)( 13 ). In another review study enrolling 544 NMDAR-AE, Sakis et al, reported that 77% of the cases presented with psychiatric symptoms initially, and agitation was the most frequent manifestation (59%), as compared with psychotic symptoms (54%)( 12 ). Similar phenotypic features of psychiatric manifestation were reported by single case reports or case series of viral encephalitis, CNS demyelinating disorders( 14 , 15 ), subacute sclerosing panencephalitis (SSE)( 16 ), or encephalopathy caused by systemic illness( 17 ). These efforts, together with our study, indicated the psychiatric symptoms attributed by organic disorders may be phenotypically distinguishable from that in primary psychiatric disorders. The other clinical feature of our cohort is that most patients exhibited acute onset. Though acute onset can be seen in some primary psychiatric disorders such as bipolar disorder or acute and transient psychotic disorder( 18 , 19 ). Most of these primary psychiatric disorders have a subacute or insidious onset, which usually preceded by a prodromal period of several weeks or month. Like previous reports of AE and other organic CNS disorders, headache, fever, seizure and altered consciousness are common neurological symptoms in our cohort, but it is noted that 16 patients have no additional neurological manifestations or fever at admission, suggesting that the absence of neurological or physical symptoms and signs can not exclude an underlying organic cause for psychiatric manifestation. Taken together, in patients of new-onset, poorly-defined psychiatric symptoms, especially of acute onset, an organic cause should be considered and further exploration such as CSF analysis or neuroimaging study should be conducted. This is in consistence with recommendations proposed on AE by Oldham, that atypical psychiatric presentations, such as personality change, multi-symptom onset, and non-auditory hallucinations should raise suspicion for an organic cause( 3 ). Incorporation of peripheral blood (PB) test results in early diagnosis is an easy and minimally invasive way to reveal important clues for the underlying organic causes. A particularly notable PB-based red flag identified in our study is hyponatremia, occurring in over one third of the cohort. Severe hyponatremia can directly contribute to psychiatric symptoms by causing cerebral edema or synaptic dysfunction( 20 – 22 ). More often, hyponatremia may coexist with psychiatric symptoms attributed to underlying neurological diseases. Numerous reports indicate a high frequency of hyponatremia in various neurological conditions, such as tubercular meningitis( 23 ), infectious or autoimmune encephalitis( 24 , 25 ), subarachnoid hemorrhage (SAH)( 26 ), CNS neoplasms( 27 ), and CNS demyelinating disorders( 28 ). These disorders may cause hyponatremia through shared mechanisms like the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt-wasting syndrome (CSWS)( 23 , 29 , 30 ). Alternatively, hyponatremia could result from limited food intake due to disease-associated dysphagia or altered consciousness. In the context of new-onset psychosis, hyponatremia can serve as a readily available, low-cost clue suggesting an organic CNS disorder, warranting urgent CSF analysis and neuroimaging. CSF abnormality can provide direct evidence of underlying neurological disorders. Most of the patients in our cohort undertook CSF analysis, however, nearly half showed no pleocytosis or elevated protein, indicating that a normal CSF profile does not exclude organic illness. This is consistent with reports on AE, where initial CSF findings may be unremarkable( 31 ). Nevertheless, abnormal CSF findings strongly argue against a primary psychiatric disorder, reinforcing the essential role of lumbar puncture even in the absence of clear neurological signs. The brain MRI findings in our cohort underscore the critical role of neuroimaging in the diagnostic workup of new-onset psychosis, even in the absence of focal neurological signs. While a substantial proportion of patients (60.0%) exhibited cortical T2/FLAIR hyperintensities, a common but non-specific finding associated with a broad range of encephalitic processes, the detection of meningeal enhancement in 28.0% of cases is a particularly significant radiological clue. This finding is frequently overlooked in initial assessments of psychiatric presentations but is a powerful indicator of underlying infectious, autoimmune, or neoplastic meningitis, conditions that are treatable yet carry high morbidity if missed. Its presence should mandate immediate lumbar puncture and aggressive diagnostic pursuit. Etiological analysis showed CNS infections, particularly viral encephalitis, constituted the most common cause, followed by cerebrovascular diseases (CVDs) and AE in the cohort. This distribution may reflect the epidemiological profile (much higher prevalence of CVDs than other disease entities) and referral patterns of our tertiary hospital, which serves as a regional center for infectious and neurological diseases. It is noted that more and more reports suggest AE, instead of CNS infection, is frequent cause of new-onset psychiatric symptoms, especially among young adults( 3 , 8 , 32 , 33 ). This discrepancy may be attributed to possibly higher rates of CNS infectious in our clinical setting. Nevertheless, not all the patients in the cohort were tested for autoantibodies of AE, this may also have impact on the result. It indicates the importance of a full screening of AEs in patients with new-onset psychiatric symptoms in future. The subgroup analysis between viral encephalitis patients with psychiatric presentation (PSIP) and those without reveals several clinically meaningful distinctions. Most notably, patients with PSIP exhibited a significantly higher frequency of hyponatremia and a markedly lower rate of favorable outcome. The absence of significant differences in conventional markers such as fever, seizures, CSF pleocytosis, or neuroimaging abnormalities indicates that traditional red flags of encephalitis may be less reliable in this subgroup. Instead, hyponatremia emerges as a critical, readily available biomarker that should raise suspicion of encephalitis in patients presenting with acute psychosis, even when other neurological signs are absent. The poorer outcomes in PSIP patients may reflect delays in diagnosis and treatment initiation due to initial misattribution of symptoms to primary psychiatric disorders. The overall outcomes observed in this cohort were notably favorable, with the majority of patients achieving either complete (19.6%) or partial (70.6%) remission of symptoms upon discharge. This high rate of symptomatic improvement underscores the importance of early detection and etiologically targeted treatment in patients presenting with psychiatric symptoms due to underlying neurological disorders, which was further supported by the results of subgroup analysis of viral encephalitis. Limitations This study has several limitations. First, as a single center study with a relatively small sample size, the patient population and characteristics are influenced by the specific region and institution, and thus the results reflect the features of this particular patient cohort. Second, being a retrospective, observational study, the recording of symptoms and admission criteria lacked strict standardization, which may have affected the results. Third, a considerable number of patients did not undergo serum or CSF autoantibody testing to rule out autoimmune encephalitis. Therefore, future multi-center, prospective cohort studies are needed to further validate the findings of this research. Conclusion For patients with acute onset of atypical, non-specific new psychiatric symptoms, regardless of the presence or absence of neurological signs, underlying organic causes for the psychiatric manifestations should be suspected, especially in the presence of hyponatremia. For neurological patients presenting initially with psychiatric symptoms, the possibility of viral encephalitis should be considered. Active investigation with CSF analysis and neuroimaging, along with early initiation of antiviral treatment, is important for improving patient outcomes. Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki and was reviewed and approved by the Ethical Review Committee of Fujian Provincial Hospital (Approval Number: K2025-11-006). The requirement for informed consent was waived by the Ethics Committee due to the retrospective nature of the study, which involved only the analysis of anonymized medical records. Consent for publication Not applicable. This manuscript does not contain any individual person’s data in any form. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the Natural Science Foundation of Fujian Province, China (Grants: 2022J011008, 2023J02024, 2023J011168), Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant: 2024Y9602), and Fujian Provincial Program for Middle-aged and Young Talents (Grant: 2018-ZQN-7). The funding bodies had no role in the design of the study, data collection, analysis, interpretation, or writing of the manuscript. Authors' contributions CC conceived and designed the study, collected and analyzed data, and drafted the manuscript. YX contributed to data collection, statistical analysis, and drafting parts of the manuscript. TC supervised the study, provided guidance, and oversaw the research process. SX contributed to the study design and provided expertise in the definition and differentiation of psychiatric symptoms. YH contributed to language polishing and manuscript editing. ZZ contributed to data verification and organization. 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Inappropriate Antidiuretic Hormone Secretion and Cerebral Salt-Wasting Syndromes in Neurological Patients. Front Neurosci. 2019;13:1170. Harrigan MR. Cerebral salt wasting syndrome. Crit Care Clin. 2001;17(1):125-38. Hebert J, Gros P, Lapointe S, Amtashar FS, Steriade C, Maurice C, et al. Searching for autoimmune encephalitis: Beware of normal CSF. J Neuroimmunol. 2020;345:577285. Paval D, Gherghel-Paval N, Capatina OO, Stan A, Raduly L, Budisan L, et al. Neural Antibodies in First-episode Psychosis Patients with Warning Signs for Autoimmune Encephalitis. Clin Psychopharmacol Neurosci. 2024;22(3):520-30. McKee J, Brahm N. Medical mimics: Differential diagnostic considerations for psychiatric symptoms. Ment Health Clin. 2016;6(6):289-96. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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10:36:58","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":104576,"visible":true,"origin":"","legend":"","description":"","filename":"baa33781a6414914909d123298bc622b1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8353793/v1/c9ecb28c01f84d16490d7790.xml"},{"id":98779986,"identity":"5978cb09-b4bb-459b-b5c9-701832b3e848","added_by":"auto","created_at":"2025-12-22 12:30:58","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":113013,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8353793/v1/6a0383e6d42b07400e00c85a.html"},{"id":98769909,"identity":"2f1ef38d-3063-46e2-9422-b75de15de329","added_by":"auto","created_at":"2025-12-22 10:36:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":91279,"visible":true,"origin":"","legend":"\u003cp\u003eThe flowchart for the selection of eligible cases.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8353793/v1/2b8cafd0dbe834ae7afd0efd.png"},{"id":103505399,"identity":"5b406eb3-8365-4b86-a211-699055e003da","added_by":"auto","created_at":"2026-02-26 13:30:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":987564,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8353793/v1/852b69bd-a4c4-4616-8dca-b6a18aa2b445.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eClinical Features, Etiological Spectrum, and Outcomes of Neurological Patients Initially Presenting with Psychiatric Symptom\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePsychiatric symptoms are frequently observed in various neurological diseases, such as CNS infections(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), autoimmune encephalitis(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), epilepsy(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), and systemic metabolic disorders(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In some cases, psychiatric symptoms can be the initial and most prominent feature, closely mimicking primary psychiatric disorders such as schizophrenia or mood disorders(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This diagnostic mimicry often leads to misdiagnosis, and delays in initiating appropriate neurological workup or treatment, which is associated with poorer patient outcomes.\u003c/p\u003e \u003cp\u003eDespite its clinical importance, the systematic characterization of neurological patients presenting with psychiatric symptoms as initial presentation (PSIP) is limited. Most existing evidence comes from studies focused on specific diseases like autoimmune encephalitis (AE)(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), with a paucity of population-based studies describing the broader etiological spectrum and clinical profile of PSIP patients in a general neurological setting. To address this gap, we conducted a retrospective study of patients admitted to a tertiary neurological department with PSIP. Our primary objectives were to: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) describe their demographic and clinical characteristics; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) identify the etiological spectrum; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) analyze short-term treatment outcomes; and (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) identify clinical features that may help distinguish PSIP patients from those with primary psychiatric disorders or neurological patients without psychiatric presentation.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cp\u003eThis retrospective, observational study analyzed data from the medical records of neurological patients who initially presented with psychiatric symptoms and were admitted to the Department of Neurology at Fujian Provincial Hospital of Fuzhou University between January 1, 2019, and December 31, 2023. Using the hospital's electronic medical record system, we screened discharged patients whose chief complaint contained the Chinese word \"精神\" (jīngsh\u0026eacute;n), which means \"psychic\" or \"psycho,\" during the study period. This term was selected because it is commonly used in the habitual description of psycho-behavioral disturbances (\"精神异常,\" jīngsh\u0026eacute;n y\u0026igrave;ch\u0026aacute;ng) in most non-psychiatric clinical settings in the region. The medical records of screened patients were jointly assessed by senior neurologists and psychiatrists. Patients were excluded if they had insufficient clinical data, if their psychiatric symptoms were attributed to pre-existing known disorders, if the diagnosis for the current condition was confirmed elsewhere prior to admission, or if the discharge diagnosis was inconclusive. The study was conducted in accordance with the Declaration of Helsinki, and was approved by the Ethical Review Committee of Fujian Provincial Hospital.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistics\u003c/h2\u003e \u003cp\u003eDescriptive statistics are presented as mean (\u0026plusmn;\u0026thinsp;standard deviation) for continuous variables and frequencies (percentages) for categorical variables. Group comparisons (e.g., PSIP vs. non-PSIP viral encephalitis patients) were performed using Student's t-test for continuous variables and the Chi-square or Fisher's exact test for categorical variables. A two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Analyses were conducted using SPSS Statistics 27.0 (IBM SPSS Corp.; Armonk, NY, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePatient Enrollment\u003c/h2\u003e \u003cp\u003eA total of 16473 patients were admitted in the Department of Neurology between 1st Jan 2019 and 31st Dec 2023, among which 55 patients with PSIP were screened and reviewed. Three patients were excluded due to a related previous mental illness. Another patient was excluded due to insufficient investigation record. 51 patients with PSIP were enrolled for analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatients Demographics\u003c/h3\u003e\n\u003cp\u003eDemographic characteristics and baseline comorbidity data are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patient ages ranged from 14 to 86 years (56.51\u0026thinsp;\u0026plusmn;\u0026thinsp;17.90). Females accounted for 39.2% of the cohort, and 84.3% were married. Fifteen patients (29.4%) were current smokers, and 8 (15.7%) had a history of alcohol abuse. Common comorbidities at admission included diabetes mellitus (12 patients, 23.5%) and hypertension (11 patients, 21.6%). Six patients (11.8%) had a previous stroke, and 6 (11.8%) had hyperlipidemia. Malignancy was previously diagnosed in 6 patients (11.8%). A history of syphilis was reported in 4 patients (7.8%). In terms of neurological history, 2 patients (3.9%) had CNS trauma and 1 (2.0%) had a neurodegenerative disorder. None of the patients reported a past history of epilepsy, CNS infection or HIV/AIDS.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics and Comorbidities of Patients with PSIP\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue (n\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.51\u0026thinsp;\u0026plusmn;\u0026thinsp;17.90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20(39.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePast history/Comorbidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpilepsy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCNS infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurodegeneration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCNS trauma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(3.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(21.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(23.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIV/AIDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSyphilis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(7.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(29.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol abuse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(15.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarital status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43(84.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBereaved\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(3.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDivorced\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePSIP, psychiatric symptoms as initial presentation; CNS, central nervous system.\u003c/p\u003e\n\u003ch3\u003eClinical features of the patients\u003c/h3\u003e\n\u003cp\u003eClinical features of the patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Disease onset was defined as acute if psychiatric symptoms developed within three days of initial symptom presentation. In this cohort, most patients (47 patients, 92.2%) experienced an acute onset. We analyzed the frequency of various psychiatric phenotypes, along with associated neurological symptoms and signs at admission. Through a joint review of medical records conducted by senior psychiatrists and neurologists, 31 patients (60.8%) exhibited non-specific psycho-behavioral disturbances, such as agitation, meaningless speech, or mutism, in the absence of well-defined psychiatric symptoms. This pattern suggests a distinct symptomatic phenotype in a neurological context. The three most frequently documented well-defined psychiatric symptoms were memory impairment (11 patients, 21.6%,), mood disturbance (9 patients, 17.3%,), and paranoid thought (2 patients, 3.9%). No cases of auditory hallucination were recorded; however, visual hallucinations were reported in 4 patients (7.8%). Among commonly reported systemic and neurological symptoms or signs at admission, fever was observed in 22 patients (43.1%), followed by headache (17 patients, 33.3%), seizures (11 patients, 21.6%), and altered consciousness (10 patients, 19.6%). These manifestations are often associated with diffuse central nervous system (CNS) involvement or systemic injury. Documented symptoms suggestive of focal impairments included nuchal rigidity (8 patients, 15.7%,), hemiparesis (6 patients, 11.8%,), aphasia (5 patients, 9.8%), and ataxia (4 patients, 7.8%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics Features of Symptoms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of patients (percentage)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute Onset\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(92.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychiatric manifestation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-specific symptoms only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31(60.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMemory impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(21.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMood disturbance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(17.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParanoid delusions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuditory Hallucination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual Hallucination\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(7.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAltered consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(19.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22(43.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(33.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemiparalysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSensory disturbance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtaxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(7.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(21.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAphasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNuchal rigidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(15.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIncontinence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal / Urinary symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAuxiliary Examination\u003c/h2\u003e \u003cp\u003eResults of auxillary examination are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. All patients underwent routine blood and biochemistry tests at admission. Leukocytosis and hyponatremia were found in 14 (27.5%) and 12 (23.5%) patients, respectively. Lumbar puncture (LP) was performed in forty-five patients. Among all the cases, 17 (37.8%) exhibited increased intracranial pressure (ICP). CSF pleocytosis and elevated CSF protein were observed in 26 (57.8%) and 26 (57.8%) of the patients respectively. 18 patients were tested for serum and/or CSF antibodies associated with autoimmune encephalitis; 2 were positive for anti-NMDA receptor antibodies, and 3 others were positive for anti-MOG, anti-GABA, and anti-GM1 antibodies, respectively. Non-specific abnormal EEG recordings were observed in 15 of the 26 patients who underwent EEG during hospitalization. None of the patients demonstrated spikes or sharp waves on EEG, even those with seizures. Brain MRI was performed in 50 patients. Abnormal T2/FLAIR hyperintensities were observed in 30 patients, involving the cortex in 21 (42.0%), thalamus in 2, basal ganglia in 3, deep white matter in 1, and brainstem/cerebellum in 3 patients. No spinal lesions were observed. Meningeal enhancement on contrast-enhanced T1-weighted images was seen in 14 patients (28.0%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory test and other technical investigations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of patients (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral blood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(27.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyponatremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(23.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSyphilis positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated opening pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(37.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePleocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(57.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated protein level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(57.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlasma/CSF autoimmune antibodies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-NMDAR positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(11.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-MOG positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(5.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-AQP4 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-GABA positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(5.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-GM1 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(5.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEEG abnormality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(57.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2WI-MRI abnormality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCortical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(42.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThalamic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(4.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasal ganglia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(6.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep white matter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrainstem or cerebellum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(6.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeningeal enhancement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(28.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eNMDAR, N-methyl-D-aspartate receptor; MOG, myelin oligodendrocyte glycoprotein; AQP4, aquaporin-4; GABA, gamma-aminobutyric acid\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eDiagnosis and Outcomes of Patients with PSIP\u003c/h2\u003e \u003cp\u003eThe final etiological diagnoses of the 51 enrolled PSIP patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Central nervous system (CNS) infections constituted the leading cause, accounting for 29 cases (56.9%). Among these, viral encephalitis was the most prevalent, diagnosed in 21 patients (41.2%), followed by bacterial meningitis (3 patients, 5.9%), neurosyphilis (4 patients, 7.8%), and tuberculous meningitis (1 patient, 2.0%). Cerebrovascular diseases (CVDs) were the second most common etiology, identified in 8 patients (15.7%), including ischemic stroke (5 patients, 9.8%), intracerebral hemorrhage (2 patients, 3.9%), and cerebral venous thrombosis (1 patient, 2.0%). Autoimmune encephalitis (AE) was diagnosed in 5 patients (9.8%), with anti-NMDA receptor encephalitis being the most frequent (3 patients, 5.9%). Other diagnoses included Creutzfeldt-Jakob disease (CJD) (1 patient, 2.0%), carcinomatous meningitis (1 patient, 2.0%), and non-CNS systemic illnesses causing encephalopathy (7 patients, 13.7%), such as metabolic/nutritional deficiencies and systemic infections. Regarding short-term outcomes at discharge, complete symptomatic relief was achieved in 10 patients (19.6%), while partial relief was observed in 36 patients (70.6%). Five patients (9.8%) showed no significant change in their clinical condition.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDiagnosis and outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of patients (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCNS infection\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29(56.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eViral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21(41.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacteria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurosyphilis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4(7.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCJD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAutoimmune encephalitis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-NMDA positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-GABA positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-GM1 positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCerebrovascular\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8(15.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemic stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5(9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntracerebral hemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2(3.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral venous thrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCarcinomatous meningitis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1(2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-CNS illness\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7(13.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetabolic/nutritional deficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2(3.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfectious encephalopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2(3.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3(5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOutcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplete relief\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10(19.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePartial relief\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36(70.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5(9.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eTB, tuberculous meningistis; CJD, creutzfeldt-jakob disease.\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup Analysis of Clinical Features and Outcomes for Viral Encephalitis\u003c/h2\u003e \u003cp\u003eA subgroup analysis was conducted comparing 21 viral encephalitis patients with PSIP and 95 viral encephalitis patients without PSIP (non-PSIP) who admitted in the Department of Neurology during the same study period, with the detailed results shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The two groups were comparable in terms of age, gender distribution, time from symptom onset to hospital presentation, and the prevalence of fever, seizures, focal neurological dysfunction, leukocytosis, CSF pleocytosis, elevated CSF protein, and brain MRI abnormalities. However, a significantly higher frequency of hyponatremia was observed in the PSIP group compared to the non-PSIP group (42.9% vs. 14.7%, p\u0026thinsp;=\u0026thinsp;0.007). Psychiatric symptoms that were not the initial presentation, were documented in 17 (17.9%) cases in the non-PSIP group. Patient outcomes were categorized based on the modified Rankin Scale (mRS) score, which is a widely used scale developed to assess global disability and dependance of patients with stroke and other neurological diseases including encephalitis(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In the study, a score of 0\u0026ndash;2 at discharge was defined as a \"good outcome,\" and a score greater than 2 was defined as a \"poor outcome.\" A good outcome was achieved in 61.9% (13/21) of PSIP patients, which was significantly lower than the 90.5% (86/95) observed in the non-PSIP group (p\u0026thinsp;=\u0026thinsp;0.003). No significant differences were found in other clinical parameters, including the need for intubation or the duration of hospitalization.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical features in viral encephalitis patients with or without PSIP\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePSIP (n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-PSIP (n\u0026thinsp;=\u0026thinsp;95)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.24\u0026thinsp;\u0026plusmn;\u0026thinsp;17.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.64\u0026thinsp;\u0026plusmn;\u0026thinsp;19.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(47.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35(36.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.359\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to presentation, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.62\u0026thinsp;\u0026plusmn;\u0026thinsp;21.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.82\u0026thinsp;\u0026plusmn;\u0026thinsp;16.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.423\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychiatric manifestation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(17.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52(54.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33(34.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.588\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal neurological deficits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40(42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.459\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(33.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.651\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyponatremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(42.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(14.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF pleocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(57.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56(58.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF elevated protein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(61.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52(54.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMRI abnormality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(71.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61(64.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of hospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.76\u0026thinsp;\u0026plusmn;\u0026thinsp;8.20 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.83\u0026thinsp;\u0026plusmn;\u0026thinsp;7.47 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.346\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGood Outcome (mRS 0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(61.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86(90.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study analyzed clinical characteristics, etiological spectrum, and outcomes of 51 neurological inpatients whose initial and predominant presentation was psychiatric symptoms. The diagnosis and management of new-onset psychiatric disorders is often challenging due to the overlapping manifestation between the organic and primary psychiatric disorders. This situation is particularly common in neurological departments. As far as we know, this is the first population-based study focusing on this distinctive group of patients who is often misdiagnosed initially and at risk for delayed appropriate care. Our findings enhance the understanding of neurological disorders initially presenting with psychiatric symptoms and offer valuable insights for improving early diagnosis and management.\u003c/p\u003e \u003cp\u003eIn the study, almost all the patients demonstrated organic causes for their psychiatric presentation. We found that the most frequent phenotype of psychiatric manifestations were atypical symptoms like agitation and disturbed behaviors, which far exceeded well-defined psychiatric symptoms of hallucinations, delusion or manic-depressive mood. Similar results were seen in studies focusing on AE, which though recognized only relatively recently, has been established as one of the most common neurological causes of acute new-onset psychiatric symptoms(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). A recent systematic review identified 505 NMDA receptor antibody encephalitis (NMDAR-AE) with detailed description of their psychiatric presentation found that behavioral disturbance (68%) was the most common symptom category, followed by psychosis (67%), mood disorder (47%), catatonia (30%) and sleep disturbance (21%)(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In another review study enrolling 544 NMDAR-AE, Sakis et al, reported that 77% of the cases presented with psychiatric symptoms initially, and agitation was the most frequent manifestation (59%), as compared with psychotic symptoms (54%)(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Similar phenotypic features of psychiatric manifestation were reported by single case reports or case series of viral encephalitis, CNS demyelinating disorders(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), subacute sclerosing panencephalitis (SSE)(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), or encephalopathy caused by systemic illness(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). These efforts, together with our study, indicated the psychiatric symptoms attributed by organic disorders may be phenotypically distinguishable from that in primary psychiatric disorders. The other clinical feature of our cohort is that most patients exhibited acute onset. Though acute onset can be seen in some primary psychiatric disorders such as bipolar disorder or acute and transient psychotic disorder(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Most of these primary psychiatric disorders have a subacute or insidious onset, which usually preceded by a prodromal period of several weeks or month. Like previous reports of AE and other organic CNS disorders, headache, fever, seizure and altered consciousness are common neurological symptoms in our cohort, but it is noted that 16 patients have no additional neurological manifestations or fever at admission, suggesting that the absence of neurological or physical symptoms and signs can not exclude an underlying organic cause for psychiatric manifestation. Taken together, in patients of new-onset, poorly-defined psychiatric symptoms, especially of acute onset, an organic cause should be considered and further exploration such as CSF analysis or neuroimaging study should be conducted. This is in consistence with recommendations proposed on AE by Oldham, that atypical psychiatric presentations, such as personality change, multi-symptom onset, and non-auditory hallucinations should raise suspicion for an organic cause(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIncorporation of peripheral blood (PB) test results in early diagnosis is an easy and minimally invasive way to reveal important clues for the underlying organic causes. A particularly notable PB-based red flag identified in our study is hyponatremia, occurring in over one third of the cohort. Severe hyponatremia can directly contribute to psychiatric symptoms by causing cerebral edema or synaptic dysfunction(\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). More often, hyponatremia may coexist with psychiatric symptoms attributed to underlying neurological diseases. Numerous reports indicate a high frequency of hyponatremia in various neurological conditions, such as tubercular meningitis(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), infectious or autoimmune encephalitis(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), subarachnoid hemorrhage (SAH)(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), CNS neoplasms(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), and CNS demyelinating disorders(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). These disorders may cause hyponatremia through shared mechanisms like the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt-wasting syndrome (CSWS)(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Alternatively, hyponatremia could result from limited food intake due to disease-associated dysphagia or altered consciousness. In the context of new-onset psychosis, hyponatremia can serve as a readily available, low-cost clue suggesting an organic CNS disorder, warranting urgent CSF analysis and neuroimaging.\u003c/p\u003e \u003cp\u003eCSF abnormality can provide direct evidence of underlying neurological disorders. Most of the patients in our cohort undertook CSF analysis, however, nearly half showed no pleocytosis or elevated protein, indicating that a normal CSF profile does not exclude organic illness. This is consistent with reports on AE, where initial CSF findings may be unremarkable(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Nevertheless, abnormal CSF findings strongly argue against a primary psychiatric disorder, reinforcing the essential role of lumbar puncture even in the absence of clear neurological signs.\u003c/p\u003e \u003cp\u003eThe brain MRI findings in our cohort underscore the critical role of neuroimaging in the diagnostic workup of new-onset psychosis, even in the absence of focal neurological signs. While a substantial proportion of patients (60.0%) exhibited cortical T2/FLAIR hyperintensities, a common but non-specific finding associated with a broad range of encephalitic processes, the detection of meningeal enhancement in 28.0% of cases is a particularly significant radiological clue. This finding is frequently overlooked in initial assessments of psychiatric presentations but is a powerful indicator of underlying infectious, autoimmune, or neoplastic meningitis, conditions that are treatable yet carry high morbidity if missed. Its presence should mandate immediate lumbar puncture and aggressive diagnostic pursuit.\u003c/p\u003e \u003cp\u003eEtiological analysis showed CNS infections, particularly viral encephalitis, constituted the most common cause, followed by cerebrovascular diseases (CVDs) and AE in the cohort. This distribution may reflect the epidemiological profile (much higher prevalence of CVDs than other disease entities) and referral patterns of our tertiary hospital, which serves as a regional center for infectious and neurological diseases. It is noted that more and more reports suggest AE, instead of CNS infection, is frequent cause of new-onset psychiatric symptoms, especially among young adults(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). This discrepancy may be attributed to possibly higher rates of CNS infectious in our clinical setting. Nevertheless, not all the patients in the cohort were tested for autoantibodies of AE, this may also have impact on the result. It indicates the importance of a full screening of AEs in patients with new-onset psychiatric symptoms in future.\u003c/p\u003e \u003cp\u003eThe subgroup analysis between viral encephalitis patients with psychiatric presentation (PSIP) and those without reveals several clinically meaningful distinctions. Most notably, patients with PSIP exhibited a significantly higher frequency of hyponatremia and a markedly lower rate of favorable outcome. The absence of significant differences in conventional markers such as fever, seizures, CSF pleocytosis, or neuroimaging abnormalities indicates that traditional red flags of encephalitis may be less reliable in this subgroup. Instead, hyponatremia emerges as a critical, readily available biomarker that should raise suspicion of encephalitis in patients presenting with acute psychosis, even when other neurological signs are absent. The poorer outcomes in PSIP patients may reflect delays in diagnosis and treatment initiation due to initial misattribution of symptoms to primary psychiatric disorders.\u003c/p\u003e \u003cp\u003eThe overall outcomes observed in this cohort were notably favorable, with the majority of patients achieving either complete (19.6%) or partial (70.6%) remission of symptoms upon discharge. This high rate of symptomatic improvement underscores the importance of early detection and etiologically targeted treatment in patients presenting with psychiatric symptoms due to underlying neurological disorders, which was further supported by the results of subgroup analysis of viral encephalitis.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study has several limitations. First, as a single center study with a relatively small sample size, the patient population and characteristics are influenced by the specific region and institution, and thus the results reflect the features of this particular patient cohort. Second, being a retrospective, observational study, the recording of symptoms and admission criteria lacked strict standardization, which may have affected the results. Third, a considerable number of patients did not undergo serum or CSF autoantibody testing to rule out autoimmune encephalitis. Therefore, future multi-center, prospective cohort studies are needed to further validate the findings of this research.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFor patients with acute onset of atypical, non-specific new psychiatric symptoms, regardless of the presence or absence of neurological signs, underlying organic causes for the psychiatric manifestations should be suspected, especially in the presence of hyponatremia. For neurological patients presenting initially with psychiatric symptoms, the possibility of viral encephalitis should be considered. Active investigation with CSF analysis and neuroimaging, along with early initiation of antiviral treatment, is important for improving patient outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003cbr\u003e\u003c/strong\u003eThis study was conducted in accordance with the Declaration of Helsinki and was reviewed and approved by the Ethical Review Committee of Fujian Provincial Hospital (Approval Number: K2025-11-006). The requirement for informed consent was waived by the Ethics Committee due to the retrospective nature of the study, which involved only the analysis of anonymized medical records.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003cbr\u003e\u003c/strong\u003eNot applicable. This manuscript does not contain any individual person’s data in any form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003cbr\u003e\u003c/strong\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003cbr\u003e\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003cbr\u003e\u003c/strong\u003eThis work was supported by the Natural Science Foundation of Fujian Province, China (Grants: 2022J011008, 2023J02024, 2023J011168), Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant: 2024Y9602), and Fujian Provincial Program for Middle-aged and Young Talents (Grant: 2018-ZQN-7). The funding bodies had no role in the design of the study, data collection, analysis, interpretation, or writing of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003cbr\u003e\u003c/strong\u003eCC conceived and designed the study, collected and analyzed data, and drafted the manuscript. YX contributed to data collection, statistical analysis, and drafting parts of the manuscript. TC supervised the study, provided guidance, and oversaw the research process. SX contributed to the study design and provided expertise in the definition and differentiation of psychiatric symptoms. YH contributed to language polishing and manuscript editing. ZZ contributed to data verification and organization. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003cbr\u003e\u003c/strong\u003eThe authors thank all patients for their participation.\u003cbr\u003e\u0026nbsp;Not applicable for further acknowledgements.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKvam KA, Stahl JP, Chow FC, Soldatos A, Tattevin P, Sejvar J, et al. Outcome and Sequelae of Infectious Encephalitis. J Clin Neurol. 2024;20(1):23-36.\u003c/li\u003e\n\u003cli\u003eArmangue T, Olive-Cirera G, Martinez-Hernandez E, Rodes M, Peris-Sempere V, Guasp M, et al. Neurologic complications in herpes simplex encephalitis: clinical, immunological and genetic studies. Brain. 2023;146(10):4306-19.\u003c/li\u003e\n\u003cli\u003eOldham M. Autoimmune Encephalopathy for Psychiatrists: When to Suspect Autoimmunity and What to Do Next. Psychosomatics. 2017;58(3):228-44.\u003c/li\u003e\n\u003cli\u003eHerken J, Pruss H. 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J Neuroimmunol. 2019;332:91-8.\u003c/li\u003e\n\u003cli\u003eCui H, He G, Yang S, Lv Y, Jiang Z, Gang X, et al. Inappropriate Antidiuretic Hormone Secretion and Cerebral Salt-Wasting Syndromes in Neurological Patients. Front Neurosci. 2019;13:1170.\u003c/li\u003e\n\u003cli\u003eHarrigan MR. Cerebral salt wasting syndrome. Crit Care Clin. 2001;17(1):125-38.\u003c/li\u003e\n\u003cli\u003eHebert J, Gros P, Lapointe S, Amtashar FS, Steriade C, Maurice C, et al. Searching for autoimmune encephalitis: Beware of normal CSF. J Neuroimmunol. 2020;345:577285.\u003c/li\u003e\n\u003cli\u003ePaval D, Gherghel-Paval N, Capatina OO, Stan A, Raduly L, Budisan L, et al. Neural Antibodies in First-episode Psychosis Patients with Warning Signs for Autoimmune Encephalitis. Clin Psychopharmacol Neurosci. 2024;22(3):520-30.\u003c/li\u003e\n\u003cli\u003eMcKee J, Brahm N. Medical mimics: Differential diagnostic considerations for psychiatric symptoms. Ment Health Clin. 2016;6(6):289-96.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Psychiatric Symptoms, Neurological Disorders, Organic Causes, Viral Encephalitis, Hyponatremia, Autoimmune Encephalitis, New-onset Psychosis","lastPublishedDoi":"10.21203/rs.3.rs-8353793/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8353793/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eNeurological disorders can manifest with psychiatric symptoms as the initial presentation (PSIP), leading to diagnostic challenges and risk of delayed treatment. Data on the clinical trajectory of this specific patient population remain limited.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study analyzed 51 inpatients admitted to the Department of Neurology between 2019 and 2023, selected based on PSIP at admission. We extracted and analyzed demographic, clinical, laboratory, neuroimaging, and outcome data from electronic medical records.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe cohort (mean age 56.5\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9 years; 39.2% female) predominantly exhibited nonspecific agitation and disturbed behavior (60.8%) rather than classic psychiatric syndromes. Acute onset was common (92.2%). Notably, 16 patients (31.4%) presented with isolated psychiatric symptoms without neurological signs or fever. Hyponatremia was a frequent finding (23.5%). Cerebrospinal fluid (CSF) abnormalities and brain MRI lesions were detected in 57.8% and 60.0% of patients, respectively. The leading etiologies were CNS infections (56.9%), predominantly viral encephalitis, followed by cerebrovascular diseases (15.7%) and autoimmune encephalitis (9.8%). Subgroup analysis of viral encephalitis patients revealed that those with PSIP had significantly higher rates of hyponatremia (42.9% vs. 14.7%, p\u0026thinsp;=\u0026thinsp;0.007) and poorer outcomes (61.9% vs. 90.5% good outcome, p\u0026thinsp;=\u0026thinsp;0.003) compared to those without PSIP, despite similar profiles in other clinical markers.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePSIP is a critical clinical scenario where underlying neurological disorders, particularly viral encephalitis, are common. Hyponatremia emerges as a key biomarker suggesting an organic etiology. The absence of neurological signs does not rule out a serious neurological condition. Early comprehensive investigation, including CSF analysis and neuroimaging, is essential for timely diagnosis and improved prognosis.\u003c/p\u003e","manuscriptTitle":"Clinical Features, Etiological Spectrum, and Outcomes of Neurological Patients Initially Presenting with Psychiatric Symptom","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-22 10:36:52","doi":"10.21203/rs.3.rs-8353793/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7de4f49d-8ac8-4273-9530-60b293011f00","owner":[],"postedDate":"December 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T08:11:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-22 10:36:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8353793","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8353793","identity":"rs-8353793","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}