Top

Published in:

Open Access 01-12-2023 | Epileptic Seizure | Review

The role of creatine kinase in distinguishing generalized tonic–clonic seizures from psychogenic non-epileptic seizures (PNES) and syncope: a retrospective study and meta-analysis of 1300 patients

Authors: Ramy Abdelnaby, Anas Elgenidy, Jan Heckelmann, Mahmoud Mostafa Bedewy, Ahmed Samy Shabib, Mohamed Ayman Ebrahim, Khaled Abdelmoneim Elmenawi, Imene Maallem, Merna Wagih Youssef, Abdelrahman M. Attia, Mostafa Hossam Moawad, Khaled Ashraf Mohamed, Ahmed Gaballa

Published in: Neurological Research and Practice | Issue 1/2023

Abstract

Background/aim

As the clinical differentiation between epileptic seizures, psychogenic non-epileptic seizures (PNES), and syncope depends mainly on a detailed report of the event, which may not be available, an objective assessment of a potential biochemical analysis is needed. We aimed to investigate whether serum creatine kinase (CK) could be used to differentiate epileptic seizure from PNES and syncope and to assess the strength of evidence present.

Methods

We directed a retrospective cohort study coupled with a systematic review and meta-analysis of studies that measured CK in patients with epilepsy, PNES, syncope, and healthy controls.

Results

The cohort study, which traced 202 patients, showed that the CK level was significantly higher 48 h after the event in the epilepsy group versus patients with syncope (p < 0.01) Along with 1086 patients obtained through a database search for meta-analysis, CK level compared to different types of seizures from PNES was higher in epileptic seizure patients with a mean difference of 568.966 mIU/ml (95% CI 166.864, 971.067). The subgroup analysis of CK showed that it was higher in GTCS compared to syncope with a mean difference of 125.39 mIU/ml (95% CI 45.25, 205.52).

Discussion

Increased serum levels of CK have been associated mainly with epileptic seizures in relation to non-epileptic events. However, further studies would try to explore the variation in measurements and any other potential diagnostic marker.

Conclusion

The cohort study shows that the CK level in epilepsy seizures is higher after 48 h from the event compared to syncope. Moreover, the meta-analysis results show the present diagnostic utility of CK and its importance to be used in accordance with a detailed report of the event.

Available only for authorised users

da Silva, R. M. F. L. (2014). Syncope: epidemiology, etiology, and prognosis. Frontiers in Physiology, 5, 471.CrossRefPubMedPubMedCentral

Martin, R., Burneo, J. G., Prasad, A., Powell, T., Faught, E., Knowlton, R., et al. (2003). Frequency of epilepsy in patients with psychogenic seizures monitored by video-EEG. Neurology, 61, 1791–1792. https://doi.org/10.1212/01.wnl.0000098890.13946.f5CrossRefPubMed

Alsaadi, T. M., Thieman, C., Shatzel, A., & Farias, S. (2004). Video-EEG telemetry can be a crucial tool for neurologists experienced in epilepsy when diagnosing seizure disorders. Seizure, 13, 32–34. https://doi.org/10.1016/s1059-1311(03)00072-4CrossRefPubMed

Dobesberger, J., Walser, G., Unterberger, I., Seppi, K., Kuchukhidze, G., Larch, J., et al. (2010). Video-EEG monitoring: safety and adverse events in 507 consecutive patients. Epilepsia, 52, 443–452. https://doi.org/10.1111/j.1528-1167.2010.02782.xCrossRefPubMed

Brigo, F., Igwe, S. C., Erro, R., Bongiovanni, L. G., Marangi, A., Nardone, R., et al. (2014). Postictal serum creatine kinase for the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures: a systematic review. Journal of Neurology, 262, 251–257. https://doi.org/10.1007/s00415-014-7369-9CrossRefPubMed

von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gøtzsche, P. C., & Vandenbroucke, J. P. (2007). STROBE initiative. PLoS Medicine, 4, e296.

Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JPT, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019. https://doi.org/10.1002/14651858.ed000142.

Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., et al. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 372, n71–n71. https://doi.org/10.1136/bmj.n71CrossRefPubMedPubMedCentral

Computer Program, The EndNote Team, 2013, Philadelphia, PA, Clarivate, EndNote X9, 64 bit. 2013.

10.

Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. 2000

11.

National Heart, L., and Blood Institute. (2019). Study Quality Assessment Tools. Retrieved from https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools n.d.

12.

Wallace, B. C., Dahabreh, I. J., Trikalinos, T. A., Lau, J., Trow, P., & Schmid, C. H. (2012). Closing the gap between methodologists and end-users: R as a computational back-end. Journal of Statistical Software. https://doi.org/10.18637/jss.v049.i05CrossRef

13.

Hozo, S. P., Djulbegovic, B., & Hozo, I. (2005). Estimating the mean and variance from the median, range, and the size of a sample. BMC Medical Research Methodology, 5, 13. https://doi.org/10.1186/1471-2288-5-13CrossRefPubMedPubMedCentral

14.

DerSimonian, R., & Laird, N. (1986). Meta-analysis in clinical trials. Controlled Clinical Trials, 7, 177–188. https://doi.org/10.1016/0197-2456(86)90046-2CrossRefPubMed

15.

Ijaz, F., Ahmad, A., Tauseef, A., Rashid, H., Aftab, R. R., Kamran, R., et al. (2020). Role of inflammation and serum creatine phospho kinase in seizures. Int J Med Res Health Sci, 9, 43–48.

16.

Javali, M., Acharya, P., Shah, S., Mahale, R., Shetty, P., & Rangasetty, S. (2017). Role of biomarkers in differentiating new-onset seizures from psychogenic nonepileptic seizures. J Neurosci Rural Pract, 8, 581–584. https://doi.org/10.4103/jnrp.jnrp_139_17CrossRefPubMedPubMedCentral

17.

Petramfar, P., Yaghoobi, E., Nemati, R., & Asadi-Pooya, A. A. (2009). Serum creatine phosphokinase is helpful in distinguishing generalized tonic–clonic seizures from psychogenic nonepileptic seizures and vasovagal syncope. Epilepsy & Behavior, 15, 330–332. https://doi.org/10.1016/j.yebeh.2009.04.016CrossRef

18.

Willert, C., Spitzer, C., Kusserow, S., & Runge, U. (2004). Serum neuron-specific enolase, prolactin, and creatine kinase after epileptic and psychogenic non-epileptic seizures. Acta Neurologica Scandinavica, 109, 318–323. https://doi.org/10.1046/j.1600-0404.2003.00232.xCrossRefPubMed

19.

Belton, N. R., Backus, R. E., & Millichap, J. G. (1967). Serum creatine phosphokinase activity in epilepsy: clinical and experimental studies. Neurology, 17, 1073–1073. https://doi.org/10.1212/wnl.17.11.1073CrossRefPubMed

20.

Matz, O., Heckelmann, J., Zechbauer, S., Litmathe, J., Brokmann, J. C., Willmes, K., et al. (2018). Early postictal serum lactate concentrations are superior to serum creatine kinase concentrations in distinguishing generalized tonic–clonic seizures from syncopes. Internal Emergency Med, 13, 749–755.CrossRef

21.

Dafotakis, M., Heckelmann, J., Zechbauer, S., Litmathe, J., Brokmann, J., Willmes, K., et al. (2018). Labordiagnostik bei transienten Bewusstseinsstörungen. Der Nervenarzt, 89, 922–927. https://doi.org/10.1007/s00115-018-0505-5CrossRefPubMed

22.

Neufeld, M. Y., Treves, T. A., Chistik, V., & Korczyn, A. D. (1997). Sequential serum creatine kinase determination differentiates vaso-vagal syncope from generalized tonic-clonic seizures. Acta Neurologica Scandinavica, 95, 137–139. https://doi.org/10.1111/j.1600-0404.1997.tb00084.xCrossRefPubMed

23.

Libman, M. D., Potvin, L., Coupal, L., & Grover, S. A. (1991). Seizure vs. syncope. Journal of General Internal Medicine, 6, 408–412.CrossRefPubMed

24.

Nass, R. D., Sassen, R., Elger, C. E., & Surges, R. (2017). The role of postictal laboratory blood analyses in the diagnosis and prognosis of seizures. Seizure, 47, 51–65. https://doi.org/10.1016/j.seizure.2017.02.013CrossRefPubMed

25.

Nass, R. D., Zur, B., Elger, C. E., Holdenrieder, S., & Surges, R. (2019). Acute metabolic effects of tonic-clonic seizures. Epilepsia open, 4(4), 599–608.CrossRefPubMedPubMedCentral

26.

LaFrance, W. C., Jr., Baker, G. A., Duncan, R., Goldstein, L. H., & Reuber, M. (2013). Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: A staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia, 54(11), 2005–2018. https://doi.org/10.1111/epi.12356CrossRefPubMed

27.

Patel, J., Tran, Q. K., Martinez, S., Wright, H., & Pourmand, A. (2022). Utility of serum lactate on differential diagnosis of seizure-like activity: a systematic review and meta-analysis. Seizure, 102, 134–142. https://doi.org/10.1016/j.seizure.2022.10.007CrossRefPubMed

28.

Benzon, H. T., Toleikis, J. R., Meagher, L. L., Shapiro, B. A., Ts’ao, C.-h, & Avram, M. J. (1988). Changes in venous blood lactate, venous blood gases, and somatosensory evoked potentials after tourniquet application. Anesthesiology, 69(5), 677–682.CrossRefPubMed

29.

Chioléro, R. L., et al. (2000). Effects of cardiogenic shock on lactate and glucose metabolism after heart surgery. Critical Care Medicine, 28(12), 3784–3791.CrossRefPubMed

30.

Puskarich, M. A., et al. (2012). Prognostic value and agreement of achieving lactate clearance or central venous oxygen saturation goals during early sepsis resuscitation. Acad Emergency Med, 19(3), 252–258.CrossRef

31.

Wang, L., Hong, S., Huang, H., & Yang, M. (2018). Rhabdomyolysis following status epilepticus with hyperuricemia: a case report and literature review. Medicine (Baltimore), 97(26), e11281. https://doi.org/10.1097/md.0000000000011281CrossRefPubMed

32.

Chavez, L. O., Leon, M., Einav, S., & Varon, J. (2016). Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice. Critical Care, 20(1), 135. https://doi.org/10.1186/s13054-016-1314-5CrossRefPubMedPubMedCentral

33.

Torres, P. A., Helmstetter, J. A., Kaye, A. M., & Kaye, A. D. (2015). Rhabdomyolysis: pathogenesis, diagnosis, and treatment. The Ochsner Journal, 15(1), 58–69.PubMedPubMedCentral

34.

Brigo, F., et al. (2015). Postictal serum creatine kinase for the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures: a systematic review. Journal of Neurology, 262(2), 251–257. https://doi.org/10.1007/s00415-014-7369-9CrossRefPubMed

Title: The role of creatine kinase in distinguishing generalized tonic–clonic seizures from psychogenic non-epileptic seizures (PNES) and syncope: a retrospective study and meta-analysis of 1300 patients
Authors: Ramy Abdelnaby
Anas Elgenidy
Jan Heckelmann
Mahmoud Mostafa Bedewy
Ahmed Samy Shabib
Mohamed Ayman Ebrahim
Khaled Abdelmoneim Elmenawi
Imene Maallem
Merna Wagih Youssef
Abdelrahman M. Attia
Mostafa Hossam Moawad
Khaled Ashraf Mohamed
Ahmed Gaballa
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Epileptic Seizure
Non-Epileptic Seizure
Epilepsy
Published in: Neurological Research and Practice / Issue 1/2023
Electronic ISSN: 2524-3489
DOI: https://doi.org/10.1186/s42466-023-00286-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The role of creatine kinase in distinguishing generalized tonic–clonic seizures from psychogenic non-epileptic seizures (PNES) and syncope: a retrospective study and meta-analysis of 1300 patients

Abstract

Background/aim

Methods

Results

Discussion

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background/aim

Methods

Results

Discussion

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2023

Author response to “Stroke thrombolysis or not for an intraventricular thrombus”

Telestroke networks for area-wide access to endovascular stroke treatment

Ulnar nerve thickness at the elbow on longitudinal ultrasound view in control subjects

Facial nerve neurographies in intensive care unit-acquired weakness

Clinical characteristics and outcomes of patients with recurrent status epilepticus episodes

Video-EEG monitoring as a valuable tool for antiseizure medication withdrawal in patients with epilepsy: implications for clinical practice and public health policies