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Methods This prospective, observational study was conducted at a tertiary research hospital between September 2023 and September 2024. Adult patients presenting to the emergency department with seizure complaints were screened and, after applying exclusion criteria, 59 patients were included. Patients were classified based on clinical, laboratory, and EEG findings into seizure or FDS groups. Serum CPT and interleukin-6 (IL-6) levels were measured using ELISA. Results Of the 59 patients, 24 were diagnosed with true seizures and 35 with FDS. No significant difference was found in serum CPT levels between the seizure and FDS groups (p = 0.755). However, absence seizures were associated with notably higher CPT concentrations compared to other seizure types. Glucose, base deficit, CRP (C-reactive protein), and IL-6 levels were significantly elevated in the seizure group relative to FDS. Serum CPT values were not predictive of clinical outcomes or the need for intensive care admission. Conclusion Serum CPT levels are not useful for differentiating between true seizures and FDS in adult emergency patients. Nevertheless, elevated CPT may have a role in the identification of absence seizures. Further multicenter studies with larger cohorts and standardized sampling times are warranted to clarify the diagnostic and prognostic value of CPT in seizure disorders. Copeptin Seizure Pseudoseizure Functional Dissociative Seizure Emergency Department Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction A seizure is the manifestation of altered cerebral function due to excessive and abnormal electrical discharges of brain cells. It is a common event, affecting approximately 8% to 10% of the population over a lifetime [ 1 – 2 ]. Seizures account for 1% to 2% of all emergency department admissions, and about a quarter of these are first-time seizures [ 3 ]. Functional/dissociative seizures (FDS), also known as psychogenic non-epileptic seizures (PNES; formerly pseudoseizures), are episodes that must be considered in the differential diagnosis of epileptic seizures or syncope attacks. FDS are involuntary, experiential, and behavioral responses to internal or external triggers [ 4 ]. There are no pathological changes in brain physiology (such as epileptiform EEG activity or cerebral oligemia) accompanying these events. Although FDS superficially resemble epileptic seizures, they are characterized by a typical subjective and observable seizure profile that distinguishes them from these episodic disorders. An acute symptomatic seizure refers to a seizure occurring at the time of a systemic injury or documented brain injury [ 5 ]. Such injuries include acute neurological disorders such as metabolic imbalance, drug or alcohol withdrawal, stroke, encephalitis, or head trauma [ 6 – 7 ]. This condition itself constitutes a significant stressor for the body or is observed following a stress event. Arginine vasopressin (AVP), a neuropeptide stored in the posterior pituitary, and copeptin (CPT) are released in response to acute and life-threatening situations. AVP is an important part of the endocrine stress response, resulting in the release of adrenocorticotropic hormone (ACTH) and cortisol [ 8 – 10 ]. As a biomarker, CPT is thought to reflect individual stress levels [ 8 , 11 – 13 ]. CPT concentrations are correlated with vasopressin levels in both healthy volunteers and critically ill patients who have had seizures [ 10 , 14 , 15 ]. Therefore, measuring CPT may provide insight into the underlying vasopressin response in the differentiation between seizure and FDS. The aim of this study is to evaluate the diagnostic value of serum CPT levels measured in patients admitted to the emergency department with seizures, in distinguishing seizure types and diagnoses. We also aimed to assess the utility of serum CPT values in differentiating between seizure and FDS, and to examine differences in CPT levels among patients diagnosed with different types of epilepsy. 2. Methods 2.1. Study Design This prospective, observational, and analytical study was conducted between 15.09.2023 and 15.09.2024 at the Emergency Medicine and Neurology Departments of XXX University Research Hospital. The study commenced after receiving approval from the local ethics committee (date: 07/09/2023, protocol code: B.30.2.ATA.0.01.00/1). Written informed consent was obtained from all volunteers participating in the study. For patients who arrived unconscious, consent was obtained from their legal guardians. The study was conducted in accordance with the Declaration of Helsinki and good clinical practices. All patients presenting to the emergency department with seizure or FDS during the study period were included as participants. 2.2. Participants During the study period, 189 seizure patients presented to the emergency department. Inclusion criteria were being at least 18 years old, not pregnant, and presenting to the emergency department with a seizure complaint. Patients were divided into two groups based on clinical, laboratory, and EEG findings. The first group comprised patients consistent with seizures. The second group included patients presenting with seizures but without supportive EEG, clinical, or laboratory findings, and were diagnosed as FDS. Fifty-two patients were excluded due to seizures secondary to coronary artery disease, acute coronary syndrome, or arrhythmia. Twenty-eight patients with ischemic/hemorrhagic cerebrovascular events or cerebral/cerebellar mass compressing the brainstem were also excluded. Thirteen patients with sepsis (per qSOFA) and altered consciousness/hypotension were not included. Five patients diagnosed with eclampsia during pregnancy were excluded. Twenty-seven post-traumatic seizure patients and 15 patients who did not consent were not included. A total of 59 patients met the study criteria and were included (Fig. 1 ). Patients under 18, those who were pregnant, those with systemic illnesses (cardiovascular, central nervous system, sepsis, or trauma) potentially affecting CPT levels, those with medication histories other than antiepileptics, or those with chronic illnesses apart from epilepsy, were excluded to avoid confounding acute or chronic effects on CPT levels. 2.3. Intervention Upon hospital admission, patients had blood samples drawn for diagnostic tests, including calcium, magnesium, glucose, pH, pCO2, HCO3, lactate, LDH, base deficit, and CRP. Laboratory analyses were performed on serum separated by centrifugation. Additionally, 2cc of serum was stored at -80°C for batch analysis of CPT and IL-6. Epidemiological, medical history, number of seizures, time from seizure to hospital admission, seizure types (absence, generalized tonic-clonic, partial), presence of trauma/incontinence, underlying causes, length of hospital stay, and type of admission (ward/ICU) were recorded. 2.4. Biochemical Analysis Blood samples were centrifuged at 3,000 rpm for 10 minutes to separate the serum. After routine tests, the remaining serum was stored at -80°C for CPT and IL-6 analysis. All analyses were performed at the Medical Biochemistry Laboratory of XXX University Health Research and Application Center. On the analysis day, samples were thawed, and serum CPT levels were measured using a commercially available ELISA kit (Cat. No. ABT1470Hu, Atlas Biotechnology Ltd., Ankara, Turkey) according to the manufacturer's protocol. Measurements were performed using an ELISA reader (BioTek PowerWave XS, USA). All samples were tested in duplicate, and the means were used for statistical analysis. The intra- and inter-assay coefficients of variation for the kit were less than 10%. 2.5. Statistical Analysis Statistical analyses were performed using SPSS 20.0 (SPSS, Chicago, IL, United States). The normality of parameters was assessed with the Kolmogorov-Smirnov test. Parameters with normal distribution were compared using the independent samples t-test and ANOVA. Categorical data were compared using the chi-square test. Results are presented as mean ± standard deviation (mean ± SD) and minimum-maximum values. A p-value of < 0.05 was considered statistically significant for differences between groups. 3. Results There was no statistical difference in age distribution among participants (p = 0.256). The female/male ratio was 32/27, with 14 female patients in the seizure group. Epidemiological and clinical variables of the participants are shown in Table 1 . Table 1 Epidemiological and Clinical variables of participants Seizure FDS Age (year) 36.18 ± 18.92 41.43 ± 19.85 Gender Male 10 17 Female 14 18 Hospital arrival time (n) 2 Hour 4 8 Outcome (n) Discharge 22 28 Inpatient admission 1 6 ICU admission 1 1 Condition upon arrival at hospital (n) Conscious 22 31 Postictal 2 4 Incontinence (n) None 20 31 Urine 4 4 Associate trauma (n) Trauma present 1 7 No trauma 23 28 (FDS: Functional/dissociative seizures ) Laboratory analysis showed that glucose, base deficit, IL-6, and CRP were the only statistically significant parameters differentiating seizure patients (p = 0.030, p = 0.020, p = 0.001, p = 0.001, respectively). Mean glucose levels in seizure patients were higher than those with FDS. Serum CRP and IL-6 levels were notably higher in seizure patients and were statistically significant between groups. Age, routine laboratory parameters, and CPT levels of patients are presented in Table 2 as mean ± SD and p values. Table 2 Comparison of laboratory parameters according to presence of seizure Parameters Patients with Seizure (n = 24) Patients with FDS (n = 35) p value Age 36.18 ± 18.92 41.43 ± 19.85 0.250 Serum Glucose level (mg/dL) 107.41 ± 25.42 95.38 ± 21.96 0.030 Serum Ca level (mg/dL) 9.24 ± 0. 68 9.07 ± 0.72 0.330 Serum Mg level (mg/dL) 1.86 ± 0.22 1.86 ± 0.22 0.930 Serum LDH Activity (U/L) 235.48 ± 140.62 246.74 ± 102.17 0.200 Serum Lactat Level (mmol/L) 3.82 ± 2.75 2.73 ± 2.2 0.060 pH 7.35 ± 0.06 7.31 ± 0.33 0.470 PCO2 (mmHg) 39.45 ± 6.95 40.24 ± 8.3 0.670 HCO3- (mmol/L) 20.91 ± 3.24 22.24 ± 3.2 0.080 Base deficite -2.55 ± 4.03 -0.74 ± 3 0.020 Serum CRP Level (mg/L) 5.30 ± 4.09 1.48 ± 0.72 p = 0.001 Serum IL-6 (pg/mL) 11.99 ± 6.07 2.24 ± 0.77 p = 0.001 Serum Copeptin Level (pg/mL) 498.62 ± 95.32 492.29 ± 81.23 0.750 (Ca:Kalsiyum, Mg:Magnezyum, pCO 2 :Parsiyel karbondioksit, HCO 3 :Bikarbonat, LDH:Laktat dehidrogenaz, CRP:C Reaktif Protein ve IL-6:İnterlökin-6, FDS:Fonksiyonel/disosiyatif seizure). There was no significant statistical difference in serum CPT levels between FDS and seizure patients (p = 0.755). Mean ± SD values for both groups are shown in Table 2 and Fig. 2 . The distribution of CPT levels by seizure type showed that patients with absence seizures had markedly higher CPT values (661.77 ± 15.45 pg/mL). However, CPT levels were not statistically significant determinants among different seizure types. CPT levels by seizure type are detailed in Table 3 and Fig. 3 . Table 3 CPT levels by seizure type Seizure Type N Mean Minimum Maximum P value Absans 2 661.77 ± 15.45 650.84 672.70 0.80 a 0.11 b 0.16 c Focal 10 512.86 ± 76.38 427.93 664.22 0.80 a 0.51 d 0.70 e Generalized 12 486.33 ± 91.63 356.32 631.67 0.11 b 0.51 d 0.96 f FDS 35 483.11 ± 77.64 375.28 685.58 0.16 c 0.70 e 0.96 f (a: Absans vs Focal, b: Absans vs Generalized, c: Absans vs None, d: Focal vs Generalized, e: Focal vs None, f: Generalized vs None, FDS: Functional/dissociative seizure) 37.3% of patients presented after a genuine seizure with preserved consciousness, while 6.8% appeared postictal but were actually diagnosed with FDS. No statistical difference in CPT levels was detected between these groups (p = 0.982). Time to hospital admission was earlier in the FDS group (Table 1 ). Etiological analysis revealed that psychogenic causes were more frequent in both groups, with dehydration as the second most common cause in the FDS group (n = 7). Other etiologies are shown in Fig. 4 . CPT levels were higher in the discharged patient group (502.38 ± 86.94 pg/mL). Two patients were admitted to the ICU: one in the seizure group (CPT = 552.32 pg/mL) and one in the FDS group (CPT = 394.04 pg/mL). CPT levels were not a determinant for ICU admission or discharge management. 4. Discussion In this study, we investigated the utility of serum CPT levels as a diagnostic and prognostic marker in patients presenting to the hospital with seizures. This is the first study in the literature to evaluate the role of CPT in differentiating seizure and FDS diagnoses. Our findings showed that serum CPT levels are not diagnostic in distinguishing between seizure and FDS but are elevated in absence seizures. A review of the literature reveals five studies related to seizures and CPT levels: two in adults and three in pediatric populations. One study compared CPT levels in focal and generalized tonic-clonic seizures; others assessed CPT in febrile convulsions, fever without seizures, and epileptic seizures. Our study is the first to compare CPT levels across epileptic seizure types other than febrile convulsions. Autonomic symptoms during epileptic seizures result from the activation of the central autonomic network by epileptic discharges [ 16 ]. This network includes the insular cortex, anterior cingulate cortex, amygdala, hypothalamus, periaqueductal gray, parabrachial nucleus, solitary nucleus, ventrolateral reticular formation of the medulla oblongata, and the medullary raphe. The interaction of these centers regulates autonomic, endocrine, and motor responses to visceral and somatosensory information [ 17 , 18 ]. The resulting responses affect CPT release from the posterior pituitary. Cardiac manifestations, respiratory changes, gastrointestinal symptoms, skin findings, and genitourinary symptoms during seizures result from this network's systemic interaction [ 19 ]. Laboratory parameters such as glucose, pH, pCO2, HCO3, lactate, LDH, base deficit, CRP, and IL-6 measured in our study are thought to be affected by this systemic response. A 2018 study by Robert D. Nass et al. demonstrated that CPT levels significantly increased after generalized convulsive seizures due to cardiac stress during seizures [ 20 ]. In their study of focal and generalized tonic-clonic seizures, mean CPT levels in generalized tonic-clonic seizure patients were 143.5 pg/mL, markedly lower than the mean CPT level in our group (486.33 ± 91.63 pg/mL). Our results showed even higher CPT levels in absence seizures (661.77 ± 15.45 pg/mL). The same study noted that CPT levels declined within 2 hours and returned to baseline 6 hours after a seizure [ 20 ]. In our study, only two patients presented more than 2 hours after seizure onset, and their CPT levels were below the mean for generalized tonic-clonic seizures, consistent with this decline. Most of our patients were evaluated within 2 hours, and no serial CPT measurements were performed, so we could not comment on the time course of CPT decrease. A pediatric study comparing febrile convulsions (FS), fever without seizures (F), and healthy controls (H) found that mean CPT levels in the FS group (123.65 pg/mL) were five times higher than F and six times higher than H [ 21 ]. Elevated CPT in FS was attributed to the combined effects of seizures, fever/infection, and dehydration. The lower CPT levels in our study may reflect differences in seizure type and patient population. Another pediatric study found higher CPT in febrile convulsions than in epileptic seizures and fever alone. Our finding of high CPT in absence seizures, which are often underdiagnosed in childhood, suggests a potential role for CPT in their detection and management. However, due to the small number of absence seizure patients, larger studies are needed. Studies on febrile and non-febrile convulsions in children have shown elevated CRP in febrile convulsions [ 22 , 23 ]. In our study, CRP was higher in true seizure patients, though there were no febrile convulsions. Other studies have shown that high-sensitivity CRP (hs-CRP) decreases with antiepileptic treatment, indicating its usefulness as a marker [ 24 ]. Abdel Salam et al. reported that IL-6 and CPT were elevated in febrile convulsions, sepsis, and hypotension, highlighting the interplay between anti-inflammatory processes, decreased circulating volume, and AVP/CPT [ 25 ]. In our study, 21% of true seizure patients had infection as a trigger, but none were hypotensive or septic, so the diagnostic value of elevated IL-6 needs further investigation. Base deficit, derived from arterial CO2, pH, and bicarbonate, indicates metabolic stress. In our study, base deficit was higher in seizure patients, reflecting hypoxia and acidosis associated with actual seizures. Freund Y et al. investigated CPT and S100B levels for evaluating post-seizure outcomes, finding that elevated CPT predicted poor outcomes [ 26 ]. Our study, however, could not establish a similar association, as only two ICU admissions occurred (one in each group), both due to post-traumatic seizures with higher CPT levels. Literature suggests that CPT is influenced by trauma severity [ 27 ]. We agree with Westermann et al. that elevated CPT in our patients may reflect trauma rather than seizure/FDS differentiation. Study Limitations The main limitation was the lack of standardized timing for blood sampling. Increasing the number and balance of seizure and FDS cases would allow for more robust conclusions. A multicenter, prospective design could also improve data variety and reliability. 5. Conclusion Serum CPT levels measured in patients presenting to the emergency department with seizures cannot be used to differentiate between true seizures and FDS. However, CPT may be useful in classifying seizure types, particularly for diagnosing absence seizures. Abbreviations CPT: Copeptin FDS: Functional/dissociative seizures EEG: Electroencephalography IL-6: Interleukin-6 CRP: C-reactive protein PNES: Psychogenic non-epileptic seizures AVP: Arginine vasopressin ACTH: Adrenocorticotropic hormone qSOFA: quick SOFA Ca:Kalsiyum, Mg:Magnezyum pCO 2 :Parsiyel karbondioksit HCO 3 : Bikarbonat LDH: Laktat dehidrogenaz SPSS: Statistical Package for the Social Sciences ANOVA: ANalysis Of VAriance Declarations Ethics approval and consent to participate The study commenced after receiving approval from the Atatürk University Faculty of Medicine Scientific Research Ethics Committee on 07.09.2023 Date and B.30.2.ATA.0.01.00/1 Decision No. The study was conducted in accordance with the Declaration of Helsinki and good clinical practices. Written informed consent was obtained from all volunteers participating in the study. For patients who arrived unconscious, consent was obtained from their legal guardians. Consent for publication There is not any identifying images or other personal or clinical details of participants are presented that compromise anonymity. Availability of data and materials Data are available on reasonable request. Competing Interests No, there are no competing interests. Funding Declaration This study received financial support from the Scientific Research Projects Coordination Unit of XXX University under project number 13129 and project code TCD-2023-13129. The funding for the Copeptin Elisa kits used in the study was covered by this support. Author Contributions Statement AÇ, STAG, MMÇ, NÖ, FŞ: Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work AÇ, MMÇ, NÖ: Drafting the work or reviewing it critically for important intellectual content AÇ, MMÇ, STAG: Final approval of the version to be published AÇ, FŞ, STAG: Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved References Annegers JF, Hauser WA, Lee JR, Rocca WA. Incidence of acute symptomatic seizures in Rochester, Minnesota, 1935-1984. Epilepsia 1995; 36:327. Brigo F, Lattanzi S, Igwe SC, et al. Zonisamide add‐on therapy for focal epilepsy. Cochrane Database Syst Rev. 2020 Jul 24;2020(7):CD001416. https://doi.org/ 10.1002/14651858.CD001416.pub5. Ali N, Dharamshi HA, Mustahsan S, Noorani S. 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13:10:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8721177/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8721177/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-026-04876-8","type":"published","date":"2026-04-14T15:59:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":102746060,"identity":"58ba1a7d-29d6-4196-9e99-bf0e78e9bfed","added_by":"auto","created_at":"2026-02-16 08:55:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":15077,"visible":true,"origin":"","legend":"\u003cp\u003eCase collection flow chart\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8721177/v1/d863ee7f50143d014b3684e4.png"},{"id":102746253,"identity":"183c20ad-be1b-4606-85de-5df8ce7caa52","added_by":"auto","created_at":"2026-02-16 08:56:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":144998,"visible":true,"origin":"","legend":"\u003cp\u003eThe mean ± SD values of serum CPT levels (FDS: Fonksiyonel/disosiyatif seizure)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8721177/v1/d2dd8bc11a3250199e931fc4.png"},{"id":102746197,"identity":"b5b409e1-49f6-47fb-bd8a-3cd015938570","added_by":"auto","created_at":"2026-02-16 08:56:03","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":79746,"visible":true,"origin":"","legend":"\u003cp\u003eCPT levels in seizure type (FDS: Functional/dissociative seizures)\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8721177/v1/85279a9fab4480e2a9c13a2e.jpg"},{"id":102439820,"identity":"71b00cf1-6726-4c2a-9971-83f3dc9fcf1e","added_by":"auto","created_at":"2026-02-11 16:43:23","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":24963,"visible":true,"origin":"","legend":"\u003cp\u003eUnderlying causes of seizures and FDS (FDS: Functional/dissociative seizures)\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-8721177/v1/bdf463a1fd8138545625f607.png"},{"id":107350806,"identity":"580f586f-7a41-4689-8c8b-20abaa52f17b","added_by":"auto","created_at":"2026-04-20 16:04:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":590503,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8721177/v1/d8232c98-dd05-48be-86bf-c3cc2152bd42.pdf"},{"id":102439813,"identity":"d422a3bf-e581-4341-a5b5-64b80c663df5","added_by":"auto","created_at":"2026-02-11 16:43:23","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":16039,"visible":true,"origin":"","legend":"","description":"","filename":"TABLES.docx","url":"https://assets-eu.researchsquare.com/files/rs-8721177/v1/4dc269870cd4f3f738d15228.docx"},{"id":102439818,"identity":"f5c3d026-a417-4c23-880c-0a8e11ded9be","added_by":"auto","created_at":"2026-02-11 16:43:23","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16039,"visible":true,"origin":"","legend":"","description":"","filename":"TABLES.docx","url":"https://assets-eu.researchsquare.com/files/rs-8721177/v1/b1cd882a64463ce1f99a32ea.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Copeptin as a Predictor of Seizure Diagnosis and Seizure Type in Emergency Department Patients","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA seizure is the manifestation of altered cerebral function due to excessive and abnormal electrical discharges of brain cells. It is a common event, affecting approximately 8% to 10% of the population over a lifetime [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Seizures account for 1% to 2% of all emergency department admissions, and about a quarter of these are first-time seizures [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Functional/dissociative seizures (FDS), also known as psychogenic non-epileptic seizures (PNES; formerly pseudoseizures), are episodes that must be considered in the differential diagnosis of epileptic seizures or syncope attacks. FDS are involuntary, experiential, and behavioral responses to internal or external triggers [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. There are no pathological changes in brain physiology (such as epileptiform EEG activity or cerebral oligemia) accompanying these events. Although FDS superficially resemble epileptic seizures, they are characterized by a typical subjective and observable seizure profile that distinguishes them from these episodic disorders.\u003c/p\u003e \u003cp\u003eAn acute symptomatic seizure refers to a seizure occurring at the time of a systemic injury or documented brain injury [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Such injuries include acute neurological disorders such as metabolic imbalance, drug or alcohol withdrawal, stroke, encephalitis, or head trauma [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This condition itself constitutes a significant stressor for the body or is observed following a stress event. Arginine vasopressin (AVP), a neuropeptide stored in the posterior pituitary, and copeptin (CPT) are released in response to acute and life-threatening situations. AVP is an important part of the endocrine stress response, resulting in the release of adrenocorticotropic hormone (ACTH) and cortisol [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. As a biomarker, CPT is thought to reflect individual stress levels [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. CPT concentrations are correlated with vasopressin levels in both healthy volunteers and critically ill patients who have had seizures [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Therefore, measuring CPT may provide insight into the underlying vasopressin response in the differentiation between seizure and FDS.\u003c/p\u003e \u003cp\u003eThe aim of this study is to evaluate the diagnostic value of serum CPT levels measured in patients admitted to the emergency department with seizures, in distinguishing seizure types and diagnoses. We also aimed to assess the utility of serum CPT values in differentiating between seizure and FDS, and to examine differences in CPT levels among patients diagnosed with different types of epilepsy.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study Design\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThis prospective, observational, and analytical study was conducted between 15.09.2023 and 15.09.2024 at the Emergency Medicine and Neurology Departments of XXX University Research Hospital. The study commenced after receiving approval from the local ethics committee (date: 07/09/2023, protocol code: B.30.2.ATA.0.01.00/1). Written informed consent was obtained from all volunteers participating in the study. For patients who arrived unconscious, consent was obtained from their legal guardians. The study was conducted in accordance with the Declaration of Helsinki and good clinical practices. All patients presenting to the emergency department with seizure or FDS during the study period were included as participants.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Participants\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eDuring the study period, 189 seizure patients presented to the emergency department. Inclusion criteria were being at least 18 years old, not pregnant, and presenting to the emergency department with a seizure complaint. Patients were divided into two groups based on clinical, laboratory, and EEG findings. The first group comprised patients consistent with seizures. The second group included patients presenting with seizures but without supportive EEG, clinical, or laboratory findings, and were diagnosed as FDS. Fifty-two patients were excluded due to seizures secondary to coronary artery disease, acute coronary syndrome, or arrhythmia. Twenty-eight patients with ischemic/hemorrhagic cerebrovascular events or cerebral/cerebellar mass compressing the brainstem were also excluded. Thirteen patients with sepsis (per qSOFA) and altered consciousness/hypotension were not included. Five patients diagnosed with eclampsia during pregnancy were excluded. Twenty-seven post-traumatic seizure patients and 15 patients who did not consent were not included. A total of 59 patients met the study criteria and were included (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003ePatients under 18, those who were pregnant, those with systemic illnesses (cardiovascular, central nervous system, sepsis, or trauma) potentially affecting CPT levels, those with medication histories other than antiepileptics, or those with chronic illnesses apart from epilepsy, were excluded to avoid confounding acute or chronic effects on CPT levels.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Intervention\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eUpon hospital admission, patients had blood samples drawn for diagnostic tests, including calcium, magnesium, glucose, pH, pCO2, HCO3, lactate, LDH, base deficit, and CRP. Laboratory analyses were performed on serum separated by centrifugation. Additionally, 2cc of serum was stored at -80\u0026deg;C for batch analysis of CPT and IL-6. Epidemiological, medical history, number of seizures, time from seizure to hospital admission, seizure types (absence, generalized tonic-clonic, partial), presence of trauma/incontinence, underlying causes, length of hospital stay, and type of admission (ward/ICU) were recorded.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Biochemical Analysis\u003c/h2\u003e \u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eBlood samples were centrifuged at 3,000 rpm for 10 minutes to separate the serum. After routine tests, the remaining serum was stored at -80\u0026deg;C for CPT and IL-6 analysis. All analyses were performed at the Medical Biochemistry Laboratory of XXX University Health Research and Application Center. On the analysis day, samples were thawed, and serum CPT levels were measured using a commercially available ELISA kit (Cat. No. ABT1470Hu, Atlas Biotechnology Ltd., Ankara, Turkey) according to the manufacturer's protocol. Measurements were performed using an ELISA reader (BioTek PowerWave XS, USA). All samples were tested in duplicate, and the means were used for statistical analysis. The intra- and inter-assay coefficients of variation for the kit were less than 10%.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical Analysis\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eStatistical analyses were performed using SPSS 20.0 (SPSS, Chicago, IL, United States). The normality of parameters was assessed with the Kolmogorov-Smirnov test. Parameters with normal distribution were compared using the independent samples t-test and ANOVA. Categorical data were compared using the chi-square test. Results are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) and minimum-maximum values. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant for differences between groups.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThere was no statistical difference in age distribution among participants (p\u0026thinsp;=\u0026thinsp;0.256). The female/male ratio was 32/27, with 14 female patients in the seizure group. Epidemiological and clinical variables of the participants are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \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\u003eEpidemiological and Clinical variables of participants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSeizure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFDS\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\u003eAge\u003c/b\u003e (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.18\u0026thinsp;\u0026plusmn;\u0026thinsp;18.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.43\u0026thinsp;\u0026plusmn;\u0026thinsp;19.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHospital arrival time\u003c/b\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1 Hour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;2 Hour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2 Hour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOutcome\u003c/b\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDischarge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInpatient admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCondition upon arrival at hospital\u003c/b\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConscious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostictal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIncontinence\u003c/b\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAssociate trauma\u003c/b\u003e (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrauma present\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo trauma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e(FDS: Functional/dissociative seizures )\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eLaboratory analysis showed that glucose, base deficit, IL-6, and CRP were the only statistically significant parameters differentiating seizure patients (p\u0026thinsp;=\u0026thinsp;0.030, p\u0026thinsp;=\u0026thinsp;0.020, p\u0026thinsp;=\u0026thinsp;0.001, p\u0026thinsp;=\u0026thinsp;0.001, respectively). Mean glucose levels in seizure patients were higher than those with FDS. Serum CRP and IL-6 levels were notably higher in seizure patients and were statistically significant between groups. Age, routine laboratory parameters, and CPT levels of patients are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and p values.\u003c/p\u003e \u003c/div\u003e \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\u003eComparison of laboratory parameters according to presence of seizure\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" 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\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients with Seizure (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients with FDS (n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e36.18\u0026thinsp;\u0026plusmn;\u0026thinsp;18.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e41.43\u0026thinsp;\u0026plusmn;\u0026thinsp;19.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum Glucose level (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e107.41\u0026thinsp;\u0026plusmn;\u0026thinsp;25.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e95.38\u0026thinsp;\u0026plusmn;\u0026thinsp;21.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.030\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum Ca level (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0. 68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e9.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum Mg level (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.930\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum LDH Activity (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e235.48\u0026thinsp;\u0026plusmn;\u0026thinsp;140.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e246.74\u0026thinsp;\u0026plusmn;\u0026thinsp;102.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum Lactat Level (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.82\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.73\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.470\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCO2 (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e39.45\u0026thinsp;\u0026plusmn;\u0026thinsp;6.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e40.24\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.670\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHCO3- (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e20.91\u0026thinsp;\u0026plusmn;\u0026thinsp;3.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e22.24\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBase deficite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e-2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;4.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e-0.74\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum CRP Level (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.30\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum IL-6 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.99\u0026thinsp;\u0026plusmn;\u0026thinsp;6.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum Copeptin Level (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e498.62\u0026thinsp;\u0026plusmn;\u0026thinsp;95.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e492.29\u0026thinsp;\u0026plusmn;\u0026thinsp;81.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.750\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 \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003e(Ca:Kalsiyum, Mg:Magnezyum, pCO\u003csub\u003e2\u003c/sub\u003e:Parsiyel karbondioksit, HCO\u003csub\u003e3\u003c/sub\u003e:Bikarbonat, LDH:Laktat dehidrogenaz, CRP:C Reaktif Protein ve IL-6:İnterl\u0026ouml;kin-6, FDS:Fonksiyonel/disosiyatif seizure).\u003c/p\u003e \u003cp\u003eThere was no significant statistical difference in serum CPT levels between FDS and seizure patients (p\u0026thinsp;=\u0026thinsp;0.755). Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD values for both groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe distribution of CPT levels by seizure type showed that patients with absence seizures had markedly higher CPT values (661.77\u0026thinsp;\u0026plusmn;\u0026thinsp;15.45 pg/mL). However, CPT levels were not statistically significant determinants among different seizure types. CPT levels by seizure type are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \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\u003eCPT levels by seizure type\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeizure Type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsans\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e661.77\u0026thinsp;\u0026plusmn;\u0026thinsp;15.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e650.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e672.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.80\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.11\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.16\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e512.86\u0026thinsp;\u0026plusmn;\u0026thinsp;76.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e427.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e664.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.80\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.51\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.70\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneralized\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e486.33\u0026thinsp;\u0026plusmn;\u0026thinsp;91.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e356.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e631.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.11\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.51\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.96\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e483.11\u0026thinsp;\u0026plusmn;\u0026thinsp;77.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e375.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e685.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.16\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.70\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e0.96\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e(a: Absans vs Focal, b: Absans vs Generalized, c: Absans vs None, d: Focal vs Generalized, e: Focal vs None, f: Generalized vs None, FDS: Functional/dissociative seizure)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003e37.3% of patients presented after a genuine seizure with preserved consciousness, while 6.8% appeared postictal but were actually diagnosed with FDS. No statistical difference in CPT levels was detected between these groups (p\u0026thinsp;=\u0026thinsp;0.982). Time to hospital admission was earlier in the FDS group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEtiological analysis revealed that psychogenic causes were more frequent in both groups, with dehydration as the second most common cause in the FDS group (n\u0026thinsp;=\u0026thinsp;7). Other etiologies are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eCPT levels were higher in the discharged patient group (502.38\u0026thinsp;\u0026plusmn;\u0026thinsp;86.94 pg/mL). Two patients were admitted to the ICU: one in the seizure group (CPT\u0026thinsp;=\u0026thinsp;552.32 pg/mL) and one in the FDS group (CPT\u0026thinsp;=\u0026thinsp;394.04 pg/mL). CPT levels were not a determinant for ICU admission or discharge management.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn this study, we investigated the utility of serum CPT levels as a diagnostic and prognostic marker in patients presenting to the hospital with seizures. This is the first study in the literature to evaluate the role of CPT in differentiating seizure and FDS diagnoses. Our findings showed that serum CPT levels are not diagnostic in distinguishing between seizure and FDS but are elevated in absence seizures.\u003c/p\u003e \u003cp\u003eA review of the literature reveals five studies related to seizures and CPT levels: two in adults and three in pediatric populations. One study compared CPT levels in focal and generalized tonic-clonic seizures; others assessed CPT in febrile convulsions, fever without seizures, and epileptic seizures. Our study is the first to compare CPT levels across epileptic seizure types other than febrile convulsions.\u003c/p\u003e \u003cp\u003eAutonomic symptoms during epileptic seizures result from the activation of the central autonomic network by epileptic discharges [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This network includes the insular cortex, anterior cingulate cortex, amygdala, hypothalamus, periaqueductal gray, parabrachial nucleus, solitary nucleus, ventrolateral reticular formation of the medulla oblongata, and the medullary raphe. The interaction of these centers regulates autonomic, endocrine, and motor responses to visceral and somatosensory information [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The resulting responses affect CPT release from the posterior pituitary. Cardiac manifestations, respiratory changes, gastrointestinal symptoms, skin findings, and genitourinary symptoms during seizures result from this network's systemic interaction [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Laboratory parameters such as glucose, pH, pCO2, HCO3, lactate, LDH, base deficit, CRP, and IL-6 measured in our study are thought to be affected by this systemic response.\u003c/p\u003e \u003cp\u003eA 2018 study by Robert D. Nass et al. demonstrated that CPT levels significantly increased after generalized convulsive seizures due to cardiac stress during seizures [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In their study of focal and generalized tonic-clonic seizures, mean CPT levels in generalized tonic-clonic seizure patients were 143.5 pg/mL, markedly lower than the mean CPT level in our group (486.33\u0026thinsp;\u0026plusmn;\u0026thinsp;91.63 pg/mL). Our results showed even higher CPT levels in absence seizures (661.77\u0026thinsp;\u0026plusmn;\u0026thinsp;15.45 pg/mL). The same study noted that CPT levels declined within 2 hours and returned to baseline 6 hours after a seizure [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In our study, only two patients presented more than 2 hours after seizure onset, and their CPT levels were below the mean for generalized tonic-clonic seizures, consistent with this decline. Most of our patients were evaluated within 2 hours, and no serial CPT measurements were performed, so we could not comment on the time course of CPT decrease.\u003c/p\u003e \u003cp\u003eA pediatric study comparing febrile convulsions (FS), fever without seizures (F), and healthy controls (H) found that mean CPT levels in the FS group (123.65 pg/mL) were five times higher than F and six times higher than H [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Elevated CPT in FS was attributed to the combined effects of seizures, fever/infection, and dehydration. The lower CPT levels in our study may reflect differences in seizure type and patient population. Another pediatric study found higher CPT in febrile convulsions than in epileptic seizures and fever alone. Our finding of high CPT in absence seizures, which are often underdiagnosed in childhood, suggests a potential role for CPT in their detection and management. However, due to the small number of absence seizure patients, larger studies are needed.\u003c/p\u003e \u003cp\u003eStudies on febrile and non-febrile convulsions in children have shown elevated CRP in febrile convulsions [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In our study, CRP was higher in true seizure patients, though there were no febrile convulsions. Other studies have shown that high-sensitivity CRP (hs-CRP) decreases with antiepileptic treatment, indicating its usefulness as a marker [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAbdel Salam et al. reported that IL-6 and CPT were elevated in febrile convulsions, sepsis, and hypotension, highlighting the interplay between anti-inflammatory processes, decreased circulating volume, and AVP/CPT [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In our study, 21% of true seizure patients had infection as a trigger, but none were hypotensive or septic, so the diagnostic value of elevated IL-6 needs further investigation.\u003c/p\u003e \u003cp\u003eBase deficit, derived from arterial CO2, pH, and bicarbonate, indicates metabolic stress. In our study, base deficit was higher in seizure patients, reflecting hypoxia and acidosis associated with actual seizures.\u003c/p\u003e \u003cp\u003eFreund Y et al. investigated CPT and S100B levels for evaluating post-seizure outcomes, finding that elevated CPT predicted poor outcomes [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Our study, however, could not establish a similar association, as only two ICU admissions occurred (one in each group), both due to post-traumatic seizures with higher CPT levels. Literature suggests that CPT is influenced by trauma severity [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. We agree with Westermann et al. that elevated CPT in our patients may reflect trauma rather than seizure/FDS differentiation.\u003c/p\u003e \u003cp\u003eStudy Limitations\u003c/p\u003e \u003cp\u003eThe main limitation was the lack of standardized timing for blood sampling. Increasing the number and balance of seizure and FDS cases would allow for more robust conclusions. A multicenter, prospective design could also improve data variety and reliability.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eSerum CPT levels measured in patients presenting to the emergency department with seizures cannot be used to differentiate between true seizures and FDS. However, CPT may be useful in classifying seizure types, particularly for diagnosing absence seizures.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCPT: Copeptin\u003c/p\u003e\n\u003cp\u003eFDS: Functional/dissociative seizures\u003c/p\u003e\n\u003cp\u003eEEG: Electroencephalography\u003c/p\u003e\n\u003cp\u003eIL-6: Interleukin-6\u003c/p\u003e\n\u003cp\u003eCRP: C-reactive protein\u003c/p\u003e\n\u003cp\u003ePNES: Psychogenic non-epileptic seizures\u003c/p\u003e\n\u003cp\u003eAVP: Arginine vasopressin\u003c/p\u003e\n\u003cp\u003eACTH: Adrenocorticotropic hormone\u003c/p\u003e\n\u003cp\u003eqSOFA: quick SOFA\u003c/p\u003e\n\u003cp\u003eCa:Kalsiyum,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMg:Magnezyum\u0026nbsp;\u003c/p\u003e\n\u003cp\u003epCO\u003csub\u003e2\u003c/sub\u003e:Parsiyel karbondioksit\u003c/p\u003e\n\u003cp\u003eHCO\u003csub\u003e3\u003c/sub\u003e: Bikarbonat\u003c/p\u003e\n\u003cp\u003eLDH: Laktat dehidrogenaz\u003c/p\u003e\n\u003cp\u003eSPSS: Statistical Package for the Social Sciences\u003c/p\u003e\n\u003cp\u003eANOVA: ANalysis Of VAriance\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe study commenced after receiving approval from the Atat\u0026uuml;rk University Faculty of Medicine Scientific Research Ethics Committee on 07.09.2023 Date and B.30.2.ATA.0.01.00/1 Decision No. The study was conducted in accordance with the Declaration of Helsinki and good clinical practices. Written informed consent was obtained from all volunteers participating in the study. For patients who arrived unconscious, consent was obtained from their legal guardians.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere is not any identifying images or other personal or clinical details of participants are presented that compromise anonymity.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eData are available on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting Interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo, there are no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding Declaration\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study received financial support from the Scientific Research Projects Coordination Unit of XXX University under project number 13129 and project code TCD-2023-13129. The funding for the Copeptin Elisa kits used in the study was covered by this support.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthor Contributions Statement\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA\u0026Ccedil;, STAG, MM\u0026Ccedil;, N\u0026Ouml;, FŞ: Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work\u003c/p\u003e\n\u003cp\u003eA\u0026Ccedil;, MM\u0026Ccedil;, N\u0026Ouml;: Drafting the work or reviewing it critically for important intellectual content\u003c/p\u003e\n\u003cp\u003eA\u0026Ccedil;, MM\u0026Ccedil;, STAG: Final approval of the version to be published\u003c/p\u003e\n\u003cp\u003eA\u0026Ccedil;, FŞ, STAG: Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAnnegers JF, Hauser WA, Lee JR, Rocca WA. Incidence of acute symptomatic seizures in Rochester, Minnesota, 1935-1984. Epilepsia 1995; 36:327.\u003c/li\u003e\n \u003cli\u003eBrigo F, Lattanzi S, Igwe SC, et al. Zonisamide add‐on therapy for focal epilepsy. Cochrane Database Syst Rev. 2020 Jul 24;2020(7):CD001416. https://doi.org/ 10.1002/14651858.CD001416.pub5.\u003c/li\u003e\n \u003cli\u003eAli N, Dharamshi HA, Mustahsan S, Noorani S. Etiology and outcomes of new onset seizure in adult patients: A clinical experience from emergency department of a tertiary care center. Pak J Med Sci. 2022 May-Jun;38(5):1382-1388. https://doi.org/10.12669/pjms.38.5.4411.\u003c/li\u003e\n \u003cli\u003eBrown RJ, Reuber M. Towards an integrative theory of psychogenic non-epileptic seizures (PNES). Clin Psychol Rev 2016; 47:55.\u003c/li\u003e\n \u003cli\u003ePingue V, Mele C, Biscuola S, et al. Impact of seizures and their prophylaxis with antiepileptic drugs on rehabilitation course of patients with traumatic or hemorrhagic brain injury. Front Neurol. 2022 Nov 11;13:1060008. https://doi.org/10.3389/fneur.2022.1060008. eCollection 2022.\u003c/li\u003e\n \u003cli\u003eMauritz M, Hirsch LJ, Camfield P, et al. Acute symptomatic seizures: an educational, evidence-based review. Epileptic Disord 2022; 24:26\u003c/li\u003e\n \u003cli\u003eBensken WP, Navale SM, Andrew AS, et al. Delays and disparities in diagnosis for adults with epilepsy: Findings from U.S. Medicaid data.. Epilepsy Res. 2020 Oct;166:106406. https://doi.org/10.1016/j.eplepsyres.2020.106406.\u003c/li\u003e\n \u003cli\u003eBolignano D, Cabassi A, Fiaccadori E, et al. Copeptin (CTproAVP), a newtool for understanding the role of vasopressin in pathophysiology. Clin Chem Lab Med. 2014; 52:1447\u0026ndash;56. https://doi.org/10.1515/cclm-2014-0379.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eNickel CH, Bingisser R, Morgenthaler NG. The role of copeptinas a diagnostic and prognostic biomarker for risk stratification in the emergency department. BMC Med. 2012; 10:7. https://doi.org/10. 1186/1741-7015-10-7.\u003c/li\u003e\n \u003cli\u003eChrist-Crain M, Fenske W. Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis. Nat Rev Endocrinol. 2016; 12:168\u0026ndash;76. https://doi.org/10.1038/nrendo.2015.224.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDanni Mu , Chaochao Ma , Jin Cheng , et al. Copeptin in fluid disorders and stress. Clin Chim Acta. 2022 Apr 1:529:46-60. https://doi.org/10.1016/j.cca.2022.02.002.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKelen D, Andorka C, Szab\u0026oacute; M, et al. Serum copeptin and neuron specific enolase are markers of neonatal distress and long-term neurodevelopmental outcome. PLoS One. 2017 Sep 20;12(9):e0184593. https://doi.org/10.1371/journal.pone.0184593.\u003c/li\u003e\n \u003cli\u003eR Jalleh, D J Torpy. The Emerging Role of Copeptin. Clin Biochem Rev. 2021 Feb;42(1):17-25. https://doi.org/10.33176/AACB-20-00001.\u003c/li\u003e\n \u003cli\u003eZou J, Chen H, Liu C, et al. Development and validation of a nomogram to predict the 30-day mortality risk of patients with intracerebral hemorrhage. Front Neurosci. 2022 Aug 10;16:942100. https://doi.org/10.3389/fnins.2022.942100.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eYalta K, Yetkin E, Yalta T. Serum Copeptin in Cardiooncology Practice: Review of Pathophysiological and Clinical Implications. Balkan Med J. 2023 Mar 8;40(2):82-92. https://doi.org/10.4274/balkanmedj.galenos.2023.2023-2-14.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCollard E, Germany Morrison E, Reina EA,et al. Vagal nerve signals are modulated by spontaneous seizures in Genetic Absence Epilepsy Rats from Strasbourg. Front Neurosci. 2025 Jul 7;19:1568261. https://doi.org/10.3389/fnins.2025.1568261.\u003c/li\u003e\n \u003cli\u003eDal N, Tok S, Balık\u0026ccedil;ı İ, et al. Comparison of Heart Rate Variability Psychological Responses and Performance in Virtual and Real Archery. Brain Behav. 2024 Oct;14(10):e70070. https://doi.org/10.1002/brb3.70070.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMather M. Autonomic dysfunction in neurodegenerative disease. Nat Rev Neurosci. 2025 May;26(5):276-292. https://doi.org/10.1038/s41583-025-00911-8.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBaumgartner C, Koren J, Britto-Arias M , et al. Epidemiology and pathophysiology of autonomic seizures: a systematic review. Clin Auton Res. 2019 Apr;29(2):137-150. https://doi.org/10.1007/s10286-019-00596-x.\u003c/li\u003e\n \u003cli\u003eNass RD, Motloch LJ, Paar V, et al. Blood markers of cardiac stress after generalized convulsive seizures. Epilepsia. 2019;60:201\u0026ndash;210. https://doi.org/10.1111/epi.14637.\u003c/li\u003e\n \u003cli\u003eEvers KS, H\u0026uuml;gli M, Fouzas S, et al. Serum Neurofilament Levels in Children With Febrile Seizures and in Controls. Front Neurosci. 2020 Sep 29;14:579958. https://doi.org/10.3389/fnins.2020.579958. eCollection 2020.\u003c/li\u003e\n \u003cli\u003eAbdullah S, Mahgoob M, Abdelazeem A (2019): Serum Copeptin Level in Children with Febrile Seizures. MJMR, 30(1): 181-183.\u003c/li\u003e\n \u003cli\u003eLiu Z, Li X, Zhang M, et al (2018): The role of Mean Platelet Volume/platelet count Ratio and Neutrophil to Lymphocyte Ratio on the risk of Febrile Seizure. Scientific Reports, 8:15123.\u003c/li\u003e\n \u003cli\u003eLiu Z, Li J, Yang F, et al. Sodium valproate combined with levetiracetam in pediatric epilepsy and its influence on NSE, IL-6, hs-CRP and electroencephalogram improvement. Experimental and Therapeutic Medicine, 20(3), 2043-2048.\u003c/li\u003e\n \u003cli\u003eSalam OA, El Sadek S, Abdel-Moneim M and Zakaria Mohamed Ahmed. Can Serum Levels of C-Reactive Protein (CRP), Interleukin-6 and Copeptin Discriminate between Simple and Complex Febrile Seizures? International Neuropsychiatric Disease Journal 8(2): 1-11, 2016; Article no.INDJ.28895 ISSN: 2321-723.\u003c/li\u003e\n \u003cli\u003eFreund Y, Bloom B, Bokobza Jet al. Predictive Value of S100-B and Copeptin for Outcomes following Seizure: The BISTRO International Cohort Study. PLOS ONE|DOI:10.1371/journal.pone.0122405 https://doi.org/10.1371/journal.pone.0122405.\u003c/li\u003e\n \u003cli\u003eSarkarinejad A, Paydar S, Khosrojerdi A and Hosseini M. Copeptin: a novel prognostic biomarker in trauma: a review article. J Health Popul Nutr. 2023 Nov 20;42(1):128. https://doi.org/10.1186/s41043-023-00468-1.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Copeptin, Seizure, Pseudoseizure, Functional Dissociative Seizure, Emergency Department","lastPublishedDoi":"10.21203/rs.3.rs-8721177/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8721177/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate the diagnostic utility of serum copeptin (CPT) levels in distinguishing true seizures from Pseudo or functional/dissociative seizures (FDS) in adult patients presenting to the emergency department, and to investigate possible differences in CPT levels among various seizure types.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective, observational study was conducted at a tertiary research hospital between September 2023 and September 2024. Adult patients presenting to the emergency department with seizure complaints were screened and, after applying exclusion criteria, 59 patients were included. Patients were classified based on clinical, laboratory, and EEG findings into seizure or FDS groups. Serum CPT and interleukin-6 (IL-6) levels were measured using ELISA.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 59 patients, 24 were diagnosed with true seizures and 35 with FDS. No significant difference was found in serum CPT levels between the seizure and FDS groups (p\u0026thinsp;=\u0026thinsp;0.755). However, absence seizures were associated with notably higher CPT concentrations compared to other seizure types. Glucose, base deficit, CRP (C-reactive protein), and IL-6 levels were significantly elevated in the seizure group relative to FDS. Serum CPT values were not predictive of clinical outcomes or the need for intensive care admission.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSerum CPT levels are not useful for differentiating between true seizures and FDS in adult emergency patients. Nevertheless, elevated CPT may have a role in the identification of absence seizures. Further multicenter studies with larger cohorts and standardized sampling times are warranted to clarify the diagnostic and prognostic value of CPT in seizure disorders.\u003c/p\u003e","manuscriptTitle":"Copeptin as a Predictor of Seizure Diagnosis and Seizure Type in Emergency Department Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-11 16:43:14","doi":"10.21203/rs.3.rs-8721177/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-16T12:19:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-13T16:25:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"94538876641525924967490518506176426537","date":"2026-02-11T15:45:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-11T02:41:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"166056766234337580227554130925615207146","date":"2026-02-10T05:02:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221763806141264305016844824148271214909","date":"2026-02-06T12:39:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-06T12:03:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-06T11:58:26+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-06T10:40:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-05T11:30:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2026-02-05T10:48:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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