Epilepsi hastalarında serum nörogranin ve glial fibriler asidik protein düzeyinin tanısal değeri ve elektroensefalografi ile ilişkisi
[ X ]
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Kırıkkale Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve amaç: Epileptik nöbet (EN), acil servise yapılan tüm başvuruların %1-2'si olup, bu hastaların %25'inde "ilk nöbet" şeklinde olabilir. Acil servise nöbet nedeniyle başvuran hastalarda EN taklitçisi olabilecek birçok klinik durum bulunmaktadır. Senkop, Geçicici iskemik atak, Migren, Panik atak, Anksiyete bozukluğu, Geçici global amnezi ve Paroksismal hareket bozukluğu gibi hastalıklar bu klinik durumlara örnek olarak gösterilmekle birlikte, EN ile en çok karışan ve klinik tanıda dikkat edilmesi gereken bir başka tablo Psikojenik nöbet (PN)'dir. Nörogranin (NG), serebral korteks nöronlarının hücre gövdelerinde ve piramidal nöronların apikal ve bazal dendritlerinde bulunan, nöronal iletimde görevli küçük yapılı bir proteindir. Glial Fibriler Asidik Protein (GFAP) ise hücreler arası destek ve iletişimi sağlamanın yanı sıra nöronal çatının desteklenmesinde de görevli bir ara filamen proteinidir. Her iki proteinde, beyin dokusunun hasar gördüğü akut veya kronik patolojilerde serumda veya Beyin omurilik sıvısında (BOS)'ta tespit edilebilir. Bu çalışmanın amacı: serum NG ve GFAP düzeyi ölçümünün EN tanısındakini yerini, EN ile PN ayrımında kullanılıp kullanılamayacağını ve EN hastalarında her iki biyomarker düzeyi ile Elektroensefalografi (EEG) sonuçları arasına ilişki olup olmadığını araştırmaktır. Gereç ve Yöntem: Çalışma, Kırıkkale Üniversitesi Tıp Fakültesi Acil Servisine nöbet nedeniyle başvuran hastalar ve sağlıklı gönüllüler üzerinde prospektif olarak yapıldı. Katılımcılar Grup EN, Grup PN ve Grup Kontrol olmak üzere 3 gruba ayrıldı. Hastalar Nöroloji uzmanının değerlendirme sonucuna göre gruplandırıldı. Tüm katılımcıların demografik özellikleri, nöbet nedeniyle başvuran hastaların (Grup EN ve PN) ise ek olarak özgeçmiş özellikleri, fizik muayene (FM) bulguları, laboratuvar verileri ve EEG sonuçları kaydedildi. Tüm katılımcılardan serum NG ile GFAP düzeyi ölçümü için kan örnekleri alındı. Grupların karşılaştırılmasında One-way ANOVA, ikili grupların karşılaştırılmasında Student's t-testi kullanıldı. Serum NG ve GFAP düzeyi ile hasta gruplarının demografik verileri, FM bulguları, laboratuvar ve EEG sonuçları arasındaki ilişki Bivariate Correlation analizi ile değerlendirildi. p < 0.05 değeri istatistiksel olarak anlamlı kabul edildi. Bulgular: Çalışmaya 125 katılımcı (Grup EN, n=45; Grup PN, n=20; Grup Kontrol, n=60) dahil edildi. Katılımcıların %56.8 (n=71)'i erkek ve yaş ortalaması 34.28 ± 11.86 /yıl (aralık: 18-59) idi. Gruplar arasında yaş ve cinsiyet bakımından farklılık saptanmadı. Epilepsi öyküsü ve antiepileptik kullanımı oranı EN grubunda %75.6 (n=34) iken, PN grubunda ise %20 (n=4) idi (p<0.001). Nöbet süresi median değeri EN grubunda 3 dk (aralık:1-60), PN grubunda 2 dk (aralık:0-45) iken (p=0.547); postiktal dönem süresi median değeri ise EN grubunda 15 dk (aralık: 0-120), PN grubunda 4.5 dk (aralık: 0-45) olarak saptandı (p=0.078). EN ve PN grubu arasında ateş, nabız, diastolik kan basıncı ve oksijen saturasyonu bakımından farklılık saptanmazken (Sırasıyla, p=0.886; 0.204; 0.068; 0.159), solunum sayısı ve sistolik kan basıncı ölçümleri PN grubunda anlamlı olarak daha yüksekti (Sırasıyla, p=0.005; 0.016). pH değeri ortalaması Grup EN'de 7.38 ± 0.04 iken, Grup PN'de ise 7.41 ± 0.05 idi (p=0.045). Diğer laboratuvar sonuçları bakımından her iki grup arasında farklılık saptanmadı. EN grubundaki hastaların 26 (%57.8)'sının, PN grubundakilerin ise sadece 1(%5)'inin EEG sonucu nöbetle uyumlu bulundu. Nöbet olarak değerlendirilen hastalar için EEG'nin bu çalışmadaki epileptik nöbeti saptamadaki sensitivitesi %57.8, spesifitesi %95, pozitif prediktif değeri %96.3 ve negatif prediktif değeri %50 olarak hesaplandı. EN grubundaki ortalama serum NG düzeyi (208.32 ± 84.35 ng/dl) hem PN grubundan (167.77±48.88 ng/dl) hem de Kontrol grubundan (159.48 ± 54.68 ng/dl) daha yüksekti. Bununla birlikte Grup EN ile PN arasında veya Grup PN ile Kontrol grubu arasında farklılık saptanmazken (Sırasıyla p=0.083; 0.317), sadece Grup EN ile Kontrol grubu arasında anlamlı farklılık olduğu saptandı (p=0.002). Serum GFAP düzeyi ortalaması EN grubunda 3.78 ± 1.93 ng/dl olup, hem PN grubundan (2.54 ± 1.26 ng/dl) hem de Kontrol grubundan (2.23 ± 0.80 ng/dl) anlamlı olarak daha yüksekti (Sırasıyla, p=0.005; <0.001). Serum GFAP düzeyi bakımından Grup PN ile Kontrol grubu arasında farklılık saptanmadı (p=0.951). EN grubundaki hastaların serum NG ve GFAP düzeyleri arasında pozitif korelasyon bulunmaktayken (r = 0.601, p<0.001), her iki biyobelirtecin düzeyi ile hastaların demografik verileri, FM bulguları ve laboratuvar sonuçları arasındaki ilişki saptanmadı. EEG sonuçları ile serum NG ve GFAP sonuçları arasında korelasyon saptanmadı (Sırasıyla, r=0.137, p=0.371; r=0.195; p=0.200). ROC analizine göre "cut-off" değeri NG için 164.37 ng/ml, GFAP için ise 2.375 ng/ml olarak hesaplandı. Eğri altında kalan alan (AUC, Area Under Curve), sensitivite ve spesifite değerleri NG için sırasıyla 0.656, %60.0, %61.3; GFAP için ise 0.750, %68.9, %70.0 idi. Sonuç: Elde ettiğimiz veriler acil servise nöbetle başvuran hastalarda beyin dokusunda hasar oluştuğunu ve bu hasarın serum NG ve GFAP düzeyi ölçümü ile gösterilebileceğini düşündürmektedir. Bununla birlikte serum NG düzeyi ölçümü nöbet nedeniyle başvuran hastaların yalnızca tanısında kullanılabilecek olup, EN ile PN ayrımını yapmada yetersizdir. Serum GFAP düzeyi ölçümü ise NG'nin aksine hem nöbetle başvuran hastaların tanısının konmasında hem de EN ile PN ayrımının yapılmasında faydalı olabilir. Her iki biyomarker düzeyi ile EEG sonuçları arasında korelasyon bulunmamıştır. Nöbet nedeniyle başvuran hastalarda EN tanısının konulmasında veya EN ile PN ayrımı yapılmasına yönelik ileri çalışmalara ihtiyaç vardır. Anahtar Kelimeler: Epileptik Nöbet, Nörogranin, Glial Fibriler Asidik Protein, Psikojenik Nöbet, Elektroensefalografi
Introduction and aim: Epileptic seizure (ES) is 1-2% of all admissions to the emergency room, and about 25% of these patients happens as "first seizure". Many clinical conditions may mimic ES in patients presenting to the emergency room with seizures. Although diseases such as Syncope, Transient ischemic attack, Migraine, Panic attack, Anxiety disorder, Transient global amnesia, and Paroxysmal movement disorder are shown as examples of these clinical conditions. Another disease that is mostly confused with EN and should be considered in the clinical diagnosis is Psychogenic seizure (PS). Neurogranin (NG) is a small protein in neuronal transmission found in the cell bodies of neurons of the cerebral cortex and the apical and basal dendrites of pyramidal neurons. Glial Fibrillary Acidic Protein (GFAP), on the other hand, is an intermediate filament protein that is responsible for supporting the neuronal framework as well as providing intercellular support and communication. Both proteins can be detected in acute or chronic pathologies in which brain tissue is damaged, in serum or cerebrospinal fluid (CSF). This study aims to investigate the importance of measurement of serum NG and GFAP levels in the diagnosis of ES, whether it can be used to distinguish between ES and PS, and whether there is a relationship between both biomarker levels and Electroencephalography (EEG) results in EN patients. Materials and Methods: The study was conducted prospectively on healthy volunteers and patients who applied to Kirikkale University Medical Faculty Emergency Department due to seizures. Participants were divided into three groups as Group ES, Group PS, and Group Control. The patients were grouped according to the evaluation result of the neurologist.Demographic characteristics of all participants and additional history, physical examination findings, laboratory data, and EEG results of patients presenting with seizures (Group ES and PS) were recorded. Blood samples were taken from all participants for measurement of serum NG and GFAP levels. One-way ANOVA was used to compare groups, and Student's t-test was used to compare paired groups. The relationship between serum NG and GFAP levels and demographic data of the patient groups, physical examination findings, laboratory and EEG results were evaluated with Bivariate Correlation analysis. A value of p < 0.05 was considered statistically significant. Results: Hundred and twenty-five participants (Group ES, n=45; Group PS, n=20; Group Control, n=60) were included in the study. 56.8% (n=71) of the participants were male, and the mean age was 34.28 ± 11.86 /year (age range: 18-59). There was no difference between the groups in terms of age and gender. The rate of epilepsy history and antiepileptic use was 75.6% (n=34) in the ES group, while it was 20% (n=4) in the PS group (p<0.001). The median seizure duration was 3 min(range:1-60) in the ES group and 2 min(range: 0-45) in the PS group (p=0.547); the median duration of the postictal period was 15 min(range 0-120) in the ES group and 4.5 min(range: 0-45) in the PS group (p=0.078). While there was no difference between ES and PS groups in terms of fever, pulse, diastolic blood pressure, and oxygen saturation (p=0.886; 0.204; 0.068; 0.159, respectively), respiratory rate and systolic blood pressure measurements were significantly higher in the PS group (p=0.005; 0.016, respectively). While the mean pH value was 7.38 ± 0.04 in Group ES, it was 7.41 ± 0.05 in Group PS (p=0.045). There was no difference between the two groups in terms of other laboratory results. EEG results of 26 (57.8%) patients in the ES group and only 1 (5%) of the patients in the PS group were found to be compatible with seizures. For patients evaluated as seizures, the sensitivity of EEG in detecting epileptic seizure in this study was 57.8%, specificity was 95%, positive predictive value was 96.3%, and negative predictive value was 50%. The mean serum NG level (208.32 ± 84.35 ng/dl) in the ES group was higher than both the PS group (167.77±48.88 ng/dl) and the Control group (159.48 ± 54.68 ng/dl). While there was no difference between Group ES and PS or between Group PS and Control group (p=0.083; 0.317, respectively), there was only a significant difference between Group ES and Control group (p=0.002). The mean serum GFAP level was 3.78 ± 1.93 ng/dl in the ES group and was significantly higher than both the PS group (2.54 ± 1.26 ng/dl) and the Control group (2.23 ± 0.80 ng/dl) (p=0.005; <0.001, respectively). There was no difference between Group PS and Control group in terms of serum GFAP level (p=0.951). While there was a positive correlation between serum NG and GFAP levels of the patients in the ES group (r = 0.601, p < 0.001), no correlation was found between the levels of both biomarkers and patients' demographic data, physical examination findings, and laboratory results. No correlation was found between EEG results and serum NG and GFAP results (r=0.137, p=0.371; r=0.195; p=0.200, respectively). According to the ROC analysis, the cut-off value was calculated as 164.37 ng/ml for NG and 2.375 ng/ml for GFAP. The area under the curve (AUC), sensitivity, and specificity values were 0.656, %60.0, %61.3 for NG, respectively; For GFAP, it was 0.750, %68.9, %70.0. Conclusion: The data suggest that brain tissue damage occurs in patients presenting to the emergency room with seizures, and this damage can be demonstrated by measuring serum NG and GFAP levels. However, measurement of serum NG level can only be used in the diagnosis of patients presenting with seizures, and it is insufficient to distinguish between ES and PS. Contrary to NG, measurement of serum GFAP level can be useful both in diagnosing patients presenting with seizures and in distinguishing between ES and PS. There was no correlation between both biomarker levels and EEG results. Further studies are needed to diagnose ES in patients presenting with seizures or to distinguish between ES and PS. Keywords: Epileptic Seizure, Neurogranin, Glial Fibrillary Acidic Protein, Psychogenic Seizure, Electroencephalography
Introduction and aim: Epileptic seizure (ES) is 1-2% of all admissions to the emergency room, and about 25% of these patients happens as "first seizure". Many clinical conditions may mimic ES in patients presenting to the emergency room with seizures. Although diseases such as Syncope, Transient ischemic attack, Migraine, Panic attack, Anxiety disorder, Transient global amnesia, and Paroxysmal movement disorder are shown as examples of these clinical conditions. Another disease that is mostly confused with EN and should be considered in the clinical diagnosis is Psychogenic seizure (PS). Neurogranin (NG) is a small protein in neuronal transmission found in the cell bodies of neurons of the cerebral cortex and the apical and basal dendrites of pyramidal neurons. Glial Fibrillary Acidic Protein (GFAP), on the other hand, is an intermediate filament protein that is responsible for supporting the neuronal framework as well as providing intercellular support and communication. Both proteins can be detected in acute or chronic pathologies in which brain tissue is damaged, in serum or cerebrospinal fluid (CSF). This study aims to investigate the importance of measurement of serum NG and GFAP levels in the diagnosis of ES, whether it can be used to distinguish between ES and PS, and whether there is a relationship between both biomarker levels and Electroencephalography (EEG) results in EN patients. Materials and Methods: The study was conducted prospectively on healthy volunteers and patients who applied to Kirikkale University Medical Faculty Emergency Department due to seizures. Participants were divided into three groups as Group ES, Group PS, and Group Control. The patients were grouped according to the evaluation result of the neurologist.Demographic characteristics of all participants and additional history, physical examination findings, laboratory data, and EEG results of patients presenting with seizures (Group ES and PS) were recorded. Blood samples were taken from all participants for measurement of serum NG and GFAP levels. One-way ANOVA was used to compare groups, and Student's t-test was used to compare paired groups. The relationship between serum NG and GFAP levels and demographic data of the patient groups, physical examination findings, laboratory and EEG results were evaluated with Bivariate Correlation analysis. A value of p < 0.05 was considered statistically significant. Results: Hundred and twenty-five participants (Group ES, n=45; Group PS, n=20; Group Control, n=60) were included in the study. 56.8% (n=71) of the participants were male, and the mean age was 34.28 ± 11.86 /year (age range: 18-59). There was no difference between the groups in terms of age and gender. The rate of epilepsy history and antiepileptic use was 75.6% (n=34) in the ES group, while it was 20% (n=4) in the PS group (p<0.001). The median seizure duration was 3 min(range:1-60) in the ES group and 2 min(range: 0-45) in the PS group (p=0.547); the median duration of the postictal period was 15 min(range 0-120) in the ES group and 4.5 min(range: 0-45) in the PS group (p=0.078). While there was no difference between ES and PS groups in terms of fever, pulse, diastolic blood pressure, and oxygen saturation (p=0.886; 0.204; 0.068; 0.159, respectively), respiratory rate and systolic blood pressure measurements were significantly higher in the PS group (p=0.005; 0.016, respectively). While the mean pH value was 7.38 ± 0.04 in Group ES, it was 7.41 ± 0.05 in Group PS (p=0.045). There was no difference between the two groups in terms of other laboratory results. EEG results of 26 (57.8%) patients in the ES group and only 1 (5%) of the patients in the PS group were found to be compatible with seizures. For patients evaluated as seizures, the sensitivity of EEG in detecting epileptic seizure in this study was 57.8%, specificity was 95%, positive predictive value was 96.3%, and negative predictive value was 50%. The mean serum NG level (208.32 ± 84.35 ng/dl) in the ES group was higher than both the PS group (167.77±48.88 ng/dl) and the Control group (159.48 ± 54.68 ng/dl). While there was no difference between Group ES and PS or between Group PS and Control group (p=0.083; 0.317, respectively), there was only a significant difference between Group ES and Control group (p=0.002). The mean serum GFAP level was 3.78 ± 1.93 ng/dl in the ES group and was significantly higher than both the PS group (2.54 ± 1.26 ng/dl) and the Control group (2.23 ± 0.80 ng/dl) (p=0.005; <0.001, respectively). There was no difference between Group PS and Control group in terms of serum GFAP level (p=0.951). While there was a positive correlation between serum NG and GFAP levels of the patients in the ES group (r = 0.601, p < 0.001), no correlation was found between the levels of both biomarkers and patients' demographic data, physical examination findings, and laboratory results. No correlation was found between EEG results and serum NG and GFAP results (r=0.137, p=0.371; r=0.195; p=0.200, respectively). According to the ROC analysis, the cut-off value was calculated as 164.37 ng/ml for NG and 2.375 ng/ml for GFAP. The area under the curve (AUC), sensitivity, and specificity values were 0.656, %60.0, %61.3 for NG, respectively; For GFAP, it was 0.750, %68.9, %70.0. Conclusion: The data suggest that brain tissue damage occurs in patients presenting to the emergency room with seizures, and this damage can be demonstrated by measuring serum NG and GFAP levels. However, measurement of serum NG level can only be used in the diagnosis of patients presenting with seizures, and it is insufficient to distinguish between ES and PS. Contrary to NG, measurement of serum GFAP level can be useful both in diagnosing patients presenting with seizures and in distinguishing between ES and PS. There was no correlation between both biomarker levels and EEG results. Further studies are needed to diagnose ES in patients presenting with seizures or to distinguish between ES and PS. Keywords: Epileptic Seizure, Neurogranin, Glial Fibrillary Acidic Protein, Psychogenic Seizure, Electroencephalography
Açıklama
Tıp Fakültesi, Acil Tıp Ana Bilim Dalı
Anahtar Kelimeler
İlk ve Acil Yardım, Emergency and First Aid
