Differential Diagnosis of Seizure and Syncope by the Means of Biochemical Markers in Emergency Department Patients

Babak Masoumi, Safoura Mozafari, Keihan Golshani, Farhad Heydari, Mohammad Nasr‑Esfahani

Abstract


Background: Seizure and syncope have similar clinical symptoms but different etiologies. Hence, differential diagnosis is crucial prior to intervention. This study evaluates the diagnostic importance of neuron specific enolase (NSE), creatine phosphokinase (CPK), and serum lactate dehydrogenase (LDH) for admitting patients with seizure medical history to emergency department (ED) in order for differential diagnosis between syncope and seizure. Methods: Patients with a short‑lasting loss of consciousness admitted to the ED were recruited. All patients with a short‑lasting loss of consciousness were eligible and EEG was conducted several times and was taken over a long period. Patients were then divided into two groups of seizure and syncope. The biochemical markers levels of all the eligible patients were measured by a reputable laboratory. Results: In order to define specificity and sensitivity of different levels of biomarkers and the optimal cut‑off points, ROC curves for each biomarker of syncope and seizure patients admitted to ED were performed. AUC for NSE, CPK, and LDH were 0.973 ± 0.023, 0.827 ± 0.047, and 0.836 ± 0.043 respectively in 95% confidence level. Cut‑off points for NSE, CPK, and LDH were determined 25.12, 218.09, and 193.88 respectively. Conclusions: It was concluded that NSE, CPK and LDH levels were different significantly in seizure patients compared to syncope ones. The seizure group showed an increase in NSE, CPK and LDH level. Determining biomarkers level for differential diagnosis of seizure and syncope can be applied as a supplementary test in addition to tests like EEG.

Keywords


Biomarkers; emergencies; seizures; syncope

Full Text:

PDF

References


Ma J‑F, Zeng R. Syncope. In: Handbook of Clinical Diagnostics.

Singapore: Springer; 2020. p. 89‑90.

Habibabadi JM, Zare M, Naghibi SN, Afzali M, Adibi I,

Tabrizi N, et al. Frequency of seizure clusters and their

associated risk factors in adult patients with epilepsy referred

to epilepsy center of Kashani Hospital in Isfahan from 2011 to

Int J Prev Med 2020;11:19.

Hamilton K, Parko K. Epileptic and nonepileptic seizures

after traumatic brain injury. In: Traumatic Brain Injury. Cham:

Springer; 2020. p. 181‑96.

Eizadi‑Mood N, Ghandehari M, Mansourian M,

Sabzghabaee AM, Samasamshariat S, Sadeghi E. Risk of seizure

after naloxone therapy in acute tramadol poisoning: A systematic

review with meta‑analysis. Int J Prev Med 2019;10:183.

Lee SCM, Lueck CJ. Cerebrospinal fluid pressure in adults.

J Neuroophthalmol 2014;34:278‑83.

Lee SY, Choi YC, Kim JH, Kim WJ. Serum neuron‑specific

enolase level as a biomarker in differential diagnosis of seizure

and syncope. J Neurol 2010;257:1708‑12.

Sabu J, Regeti K, Mallappallil M, Kassotis J, Islam H, Zafar S, et al. Convulsive syncope induced by ventricular arrhythmia

masquerading as epileptic seizures: case report and literature

review. J Clin Med Res 2016;8:610‑5.

Bergfeldt L. Differential diagnosis of cardiogenic syncope and

seizure disorders. Heart 2003;89:353‑8.

Ghearing GR, Munger TM, Jaffe AS, Benarroch EE, Britton JW.

Clinical cues for detecting ictal asystole. Clin Auton Res

;17:221‑6.

Mckeon A, Vaughan C, Delanty N. Erratum: Seizures versus

syncope (Lancet Neurology (2006) 5 (171‑180)). Lancet Neurol

;5:293.

Britton JW, Benarroch E. Syncope and seizures. Clin Auton Res

;14:148‑59.

Sahu S, Nag DS, Swain A, Samaddar DP. Biochemical changes

in the injured brain. World J Biol Chem 2017;8:21‑31.

Francis A, Rivett AJ, Roth JA. Activity of neuron‑specific enolase

in normal and lesioned rat brain. Brain Res 1983;263:89‑95.

Marangos PJ, Schmechel DE. Neuron specific enolase, a

clinically useful marker for neurons and neuroendocrine cells.

Annu Rev Neurosci 1987;10:269‑95.

Naeimi ZS, Weinhofer A, Sarahrudi K, Heinz T, Vécsei V.

Predictive value of S‑100B protein and neuron specific‑enolase

as markers of traumatic brain damage in clinical use. Brain Inj

;20:463‑8.

Wijdicks EFM, Hijdra A, Young GB, Bassetti CL, Wiebe S,

Quality Standards Subcommittee of the American Academy

of Neurology. Practice parameter: Prediction of outcome

in comatose survivors after cardiopulmonary resuscitation

(an evidence‑based review): Report of the quality standards

subcommittee of the American academy of neurology. Neurology

;67:203‑10.

Hu Y, Meng R, Zhang X, Guo L, Li S, Wu Y, et al. Serum

neuron specific enolase may be a marker to predict the

severity and outcome of cerebral venous thrombosis. J Neurol

;265:46‑51.

Göksülük H, Güleç S, Özyüncü N, Kürklü ST, Vurgun VK,

Candemir B, et al. Comparison of frequency of silent cerebral

infarction after coronary angiography and stenting with

transradial versus transfemoral approaches. Am J Cardiol

;122:548‑53.

Cunningham RT, Young IS, Winder J, O’Kane MJ, McKinstry S,

Johnston CF, et al. Serum neurone specific enolase (NSE) levels

as an indicator of neuronal damage in patients with cerebral

infarction. Eur J Clin Invest 1991;21:497‑500.

Oh SH, Lee JG, Na SJ, Park JH, Choi YC, Kim WJ. Prediction

of early clinical severity and extent of neuronal damage

in anterior‑circulation infarction using the initial serum

neuron‑specific enolase level. Arch Neurol 2003;60:37‑41.

Thelin EP, Jeppsson E, Frostell A, Svensson M, Mondello S,

Bellander B‑M, et al. Utility of neuron‑specific enolase in

traumatic brain injury; relations to S100B levels, outcome, and

extracranial injury severity. Crit Care 2016;20:285.

Wolf H, Krall C, Pajenda G, Hajdu S, Widhalm H, Leitgeb J,

et al. Preliminary findings on biomarker levels from extracerebral

sources in patients undergoing trauma surgery: Potential

implications for TBI outcome studies. Brain Inj 2016;30:1220‑5.

Glushakova OY, Valadka AB, Hayes RL, and Glushakov AV,

The potential of brain specific blood biomarkers for TBI patient

management, diagnosis, and clinical research. In: Wang KKW, editors.

Neurotrauma: A Comprehensive Textbook on Traumatic Brain Injury

and Spinal Cord Injury. Oxford University Press; 2018. p. 189-99.

Honda M, Tsuruta R, Kaneko T, Kasaoka S, Yagi T, Todani M,

et al. Serum glial fibrillary acidic protein is a highly specific

biomarker for traumatic brain injury in humans compared with

S‑100B and neuron‑specific enolase. J Trauma 2010;69:104‑9.

Gmitterová K, Heinemann U, Krasnianski A, Gawinecka J,

Zerr I. Cerebrospinal fluid markers in the differentiation of

molecular subtypes of sporadic Creutzfeldt‑Jakob disease. Eur J

Neurol 2016;23:1126‑33.

Crowell JL, Wooten GF, Barrett MJ. MM1‑Type sporadic

Creutzfeldt‑Jakob disease with early behavioral changes and

prolonged symptom duration. J Neuropsychiatry Clin Neurosci

;28.2:e31‑2.

Samancı Y, Samancı B, Şahin E, Altıokka‑Uzun G, Küçükali Cİ,

Tüzün E, et al. Neuron‑specific enolase levels as a marker for

possible neuronal damage in idiopathic intracranial hypertension.

Acta Neurol Belg 2017;117:707‑11.

Backman S, Westhall E, Dragancea I, Friberg H, Rundgren M,

Ullén S, et al. Electroencephalographic characteristics of

status epilepticus after cardiac arrest. Clin Neurophysiol

;128:681‑8.

Atici Y, Alehan F, Sezer T, Tuygun N, Haberal A, Yazici AC,

et al. Serum S100B levels in children with simple febrile

seizures. Seizure 2012;21:175‑7.

Hemmer W, Wallimann T. Functional aspects of creatine kinase

in brain. Dev Neurosci 1993;15:249‑60.

Petramfar P, Yaghoobi E, Nemati R, Asadi‑Pooya AA. Serum

creatine phosphokinase is helpful in distinguishing generalized

tonic–clonic seizures from psychogenic nonepileptic seizures and

vasovagal syncope. Epilepsy Behav 2009;15:330‑2.

Willert C, Spitzer C, Kusserow S, Runge U. Serum

neuron-specific enolase, prolactin, and creatine kinase after

epileptic and psychogenic non-epileptic seizures. Acta Neurol

Scand 2004;109:318‑23.

Brigo F, Igwe SC, Erro R, Bongiovanni LG, Marangi A,

Nardone R, et al. Postictal serum creatine kinase for the differential

diagnosis of epileptic seizures and psychogenic non‑epileptic

seizures: A systematic review. J Neurol 2015;262:251‑7.

Rho JM. Inhibition of lactate dehydrogenase to treat epilepsy.

N Engl J Med 2015;373:187‑9.

Wong KC. Correlation between serum lactate

dehydrogenase (LDH) and seizure–an observation in clinical

cases. Int J Adv Sci Eng Inf Technol 2016;4:99‑103.

Khosroshahi N, Alizadeh P, Khosravi M, Salamati P, Kamrani K.

Spinal fluid lactate dehydrogenase level differentiates between

structural and metabolic etiologies of altered mental status in

children. Iran J Child Neurol 2015;9:31‑6.

Ehsanipour F, Mo’adabi H, Shayanfar N. A comparison of CSF

lactic dehydrogenase in children with simple and complex febrile

convulsion. Razi J Med Sci 2008;15:7-12.

Rash A, McRae M, Fatehi J, Richie D, Solbiati M, Pillay N,

et al. Assessment of endothelin and copeptin as biomarkers for

vasovagal syncope. Eur J Clin Invest 2016;46:141‑5.

Jaykaran C, Tamoghna B. How to calculate sample size for

different study designs in medical research? Indian J Psychol

Med 2013;35:121‑6.

Jean G. A few thoughts on “What is a seizure?”. Epilepsy Behav

;22(Suppl 1):S2‑3.

Bringnol M, Moya A, de Lange F, Deharo J, Elliott P, Fanciulli A,

et al. "Practical Instructions for the 2018 ESCGuidelines for the

diagnosis and management of syncope." European heart journal

;39:21:e43 e80.

Ambrosius WT. Topics in Bio Statics. New York, Humana Press;

Kumar R, Indrayan A. Receiver operating characteristic (ROC)

curve for medical researchers. Indian Pediatr 2011;48:277‑87.