J Neurol DOI 10.1007/s00415-014-7369-9

REVIEW

Postictal serum creatine kinase for the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures: a systematic review Francesco Brigo • Stanley C. Igwe • Roberto Erro • Luigi Giuseppe Bongiovanni • Antonio Marangi • Raffaele Nardone • Michele Tinazzi • Eugen Trinka

Received: 23 April 2014 / Accepted: 6 May 2014 Ó Springer-Verlag Berlin Heidelberg 2014

Abstract The aim of this review was to evaluate the sensitivity and specificity of postictal creatine kinase (CK) levels in the differential diagnosis of epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES). A systematic search was conducted for studies that evaluated postictal CK levels in patients with ES (all types) and PNES. Sensitivity and specificity with 95 % confidence intervals were determined for each study, taking into account: (a) the upper limits adopted; and (b) the 95.7th percentile values, which are recently proposed practical upper reference limits for CK activity. Four studies, comprising a total of 343 events (248 ES and 95 PNES), were available for analysis. Most patients (47/78, 60 %) with ES considered had primarily or secondarily generalized tonic– clonic seizures. The sensitivity of increased postictal CK

levels for ES ranged from 14.6 to 87.5, whereas specificity ranged from 85.0 to 100.0. At the 95.7th percentile threshold, sensitivity ranged from 14.6 to 62.5 and specificity was 100.0. The limited number of studies available, their small sample size, and lack of individual event data prevented further stratification analysis by seizure type. Despite the clinical heterogeneity and the limitations of the included studies, increased postictal CK levels are highly specific for the diagnosis of ES, although no definite conclusion on its role in differentiating between convulsive and non-convulsive ES can be drawn. Postictal serum CK levels can provide valuable retrospective information at the later stages of the differential diagnosis of ES and PNES. Due to low sensitivity, normal postictal CK levels do not exclude ES.

Electronic supplementary material The online version of this article (doi:10.1007/s00415-014-7369-9) contains supplementary material, which is available to authorized users.

Keywords Creatine kinase  Differential diagnosis  Epileptic seizure  Psychogenic non-epileptic seizure  Sensitivity  Specificity

F. Brigo (&)  R. Erro  L. G. Bongiovanni  A. Marangi  M. Tinazzi Section of Clinical Neurology, Department of Neurological and Movement Sciences, University of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy e-mail: [email protected]

R. Nardone  E. Trinka Department of Neurology, Christian Doppler Medical Centre, Paracelsus Medical University, Salzburg, Austria

F. Brigo  R. Nardone Department of Neurology, Franz Tappeiner Hospital, Merano, Italy

E. Trinka Department of Public Health Technology Assessment, UMITUniversity for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria

E. Trinka Centre for Cognitive Neuroscience, Salzburg, Austria

S. C. Igwe Department of Neuro-Psychiatry, Federal Teaching Hospital, Abakaliki, Ebonyi State, Nigeria R. Erro Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL) Institute of Neurology, London, UK

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Introduction The differential diagnosis between psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES) can represent a diagnostic challenge. Differentiating these two conditions is complicated in some patients by the coexistence of both phenomena [1, 2]. The clinical suspicion of PNES relies on an accurate description of the event by witnesses. Presence or absence of such physical signs as tongue bite or urinary incontinence may provide additional information to support or rule out the initial diagnostic suspicion [3–6]. Videoelectroencephalography (EEG) recording represents the gold diagnostic standard in the differential diagnosis between PNES and ES [7, 8]. However, this technique is time consuming, expensive, not without adverse effects [9] and, above all, requires a PNES event to happen during the recording. Hence, a postictal test to retrospectively differentiate between ES and PNES would be of relevant clinical utility [10]. Postictal serum creatine kinase (CK) has been suggested as a possible useful marker to distinguish between tonic– clonic ES and PNES, although the existing data are conflicting with regard to its diagnostic utility in clinical practice. We, therefore, aimed to undertake a systematic review of the literature to evaluate the sensitivity and specificity of postictal CK levels for the differential diagnosis between ES and PNES.

Methods Only studies evaluating the diagnostic role of postictal serum CK levels in patients with ES (all types, including status epilepticus) and patients with PNES were included in the analysis. No limitations were applied regarding the time of CK assessments after the acute event. Other conditions that also need to be considered in the differential diagnosis of epilepsy (e.g., vasovagal syncope) were excluded. CK values obtained in patients with only one type of event (i.e., ES or PNES) were taken into account. No age, race, or gender restrictions were applied. A direct observation of an event by means of video-EEG recording, or an accurate examination made by an expert epileptologist, was considered the reference diagnostic standard. The MEDLINE (accessed via Pubmed for indexed literature between 1966 and February 2014) electronic database was searched using the following Medical Subject Headings terms (MeSH terms): ‘‘Creatine Kinase’’, ‘‘Epilepsy, Generalized’’, ‘‘Epilepsy, Tonic–Clonic’’, and ‘‘Seizures’’. The following free text terms were also applied, and were combined in multiple search strategies

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with Boolean operators to find relevant articles: ‘‘pseudoseizure*’’, ‘‘psychog*’’, ‘‘non-epileptic’’, ‘‘CK’’, ‘‘CPK’’, ‘‘creatine kinase’’, and ‘‘creatine phosphokinase’’. For a full description of the search strategy, see the Online Appendix 1. All reference lists in the studies identified were subsequently scrutinized for studies not indexed in the electronic database. Both published and unpublished data were considered for inclusion. In the case of missing or incomplete data, the principal investigators of included trials were contacted and additional information requested. Sensitivity and specificity with 95 % confidence intervals (CIs) were determined for each study using the equations reported in Online Appendix 1 [11, 12]. Given the different normal ranges of serum CK across different studies, the accuracy measures were calculated by considering both the upper limits adopted in each study and the 95.7th percentile values (defining the upper level of CK range values in a normally distributed population), as published in a study from the Netherlands [13]. Such values have been subsequently proposed by an EFNS (European Federation of Neurological Societies) committee as threshold for redefining the practical upper reference limits for CK activity, according to patient race and gender [14]. We also planned to combine accuracy measures from each study to obtain summary estimates in a meta-analysis. The sensitivity measures the proportion of positives that are correctly identified, whereas the specificity measures the proportion of negatives that are correctly identified. Therefore, in this systematic review, sensitivity reflects the proportion of patients with ES who have elevated postictal serum CK levels, while specificity refers to the proportion of patients without ES (but with PNES) and without increased CK levels. Accuracy measures for each study were calculated using Meta-DiSc 1.4 software (available online at: ftp.hrc.es/pub/programas/metadisc/Metadisc_ update.htm).

Results The search strategy yielded 121 studies (119 MEDLINE, 2 in reference lists). After reading the abstracts, 18 studies were provisionally selected (Online Appendix 2). After reading the full text of the retrieved articles, four studies were included for detailed analysis [10, 15–17]. The clinical characteristics of patients in the included studies are reported in Table 1. Table 2 reports the upper serum CK limits used in each study, the time of CK assessment after the acute event (ES or PNES), the ratio of events where pathologically elevated CK levels were observed, and the accuracy measures (sensitivity and specificity) with reference to both the upper

33.6 ± 10.8 (18–57)

27.1 ± 7.6 (18–42)

39.5 ± 21.1

Willert et al. [15]

Holtkamp et al. [16]

Petramfar et al. [17]

NR

NR

10a; 5/5

20; 14/6

NR

32; 11/21

NR NR

12; NR

4; NR

GTCS

GTCS

Refractory generalized convulsive status epilepticus

Complex partial, focal motor, absence, tonic 32 focal epilepsy, 27 complex partial, 5 secondarily GTCS

NR

NR

F 59.4 ± 22.2 M 77.4 ± 33.6

F, M within 20 and 180

Basal CK values (U/L)

38.95 ± 14.6

45.6 ± 19.1 (19–77)

37.8 ± 13.1 (18–62)

NR

20; 9/11

9; 7/2

12; 6/6

6; NR

Number of patients; F/M ratio

NR

NR

NR

NR

Race

NR

Generalized convulsions

NR

89 % of the episodes involved vigorous muscular activity

Type of PNES

NR

NR

F 53.4 ± 28.2 M 67.2 ± 31.2

F, M within 20 and 180

Basal CK values (U/L)

NR

NR

No

NR

Other drugs

No

NR

NR

No

Intramuscular injections

a

Not available CK data for one PNES patient (female) and two ES patients (one male, one female)

CK creatine kinase, ES epileptic seizures, F female, GTCS generalized tonic–clonic seizure, M male, NR not reported, PNES psychogenic non-epileptic seizures, SD standard deviations, U/L international Units/L

ES, PNEE 28 ± NR (5–47)

Type of ES

Age (years) mean ± SD (range)

Race

Age (years) mean ± SD (range)

Number of patients; F/M ratio

PNES

ES

Wyllie et al. [10]

Study

Table 1 Clinical characteristics of patients with ES and PNES in the included studies

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J Neurol Table 2 Accuracy measures (sensitivity, specificity) of postictal serum CK levels in the differential diagnosis between ES and PNES Study

Normal serum CK limit (U/L)

Time of CK assessment after the acute event

Rate of events with pathologically elevated serum CK levels ES

PNES

GTCS 6/41

0/55

Wyllie et al. [10]

M, F \180

Willert et al. [15]

F \168a M \195

Within 24 h

11/32

Holtkamp et al. [16]

F \70 M \80

Within 24 h

Petramfar et al. [17]

F \160b M \160b

Within 12–15 h

Within 96 h

Sensitivity (95 % CI)

Specificity (95 % CI)

Rate of events with pathologically elevated serum CK levelsa ES

PNES

Sensitivity (95 % CI)a

Specificity (95 % CI)a

14.6 (5.6–29.2)

100.0 (93.5–100)

6/41

0/55

14.6 (5.60–29.2)

100.0 (93.5–100.0)

ND

ND

ND

ND

ND

ND

0/12

34.4 (18.6–53.2)

100.0 (73.5–100)

11/32

0/12

34.4 (18.6–53.2)

100.0 (73.5 ± 100)

7/8

1/8

87.5 (47.3–99.7)

87.5 (47.3–99.7)

5/8

0/8

62.5 (24.5–91.5)

100.0 (63.1–100)

15/20

3/20

75.0 (53.1–88.8)

85.0 (64.0–94.8)

NDc

NDc

NDc

NDc

Other ES* 0/147

CI confidence intervals, CK creatine kinase, ES epileptic seizures, GTCS generalized tonic–clonic seizures, ND not determinable, PNES psychogenic non-epileptic seizures, U/L international Units/L a

Calculated according to the 97.5th percentile internationally proposed as practical upper reference limits for CK activity expressed as U/L: 217 (non-black female); 336 (non-black male) [14] * Complex partial, focal motor, absence, tonic seizures b Expressed in the text of the article reporting the results of this study as mg/dL (measure of unit likely to be a typographical error, and to be considered as U/L) c

Not determinable, due to lack of individual patient data

limits adopted in each study and the internationally proposed practical upper reference limits for CK activity [13, 14]. When performing the latter analysis, we assumed that all patients were not black, as all included studies were conducted in Europe [10, 15, 16] and Western Asia [17] where most of the population is Caucasian. Despite our primary intention, the marked clinical heterogeneity across studies prevented us from performing a meta-analysis to combine accuracy measures from each study and obtain a summary estimate of their values. In total, 343 events (248 ES, 95 PNES) were available for analysis. Most patients (47/78, 60 %) with ES considered in the studies had primarily or secondarily generalized tonic–clonic seizures (GTCS) (including ten patients with refractory generalized convulsive status epilepticus [16]), and two studies also included patients with other types of ES (31/78; 40 %) [10, 15]. Only two studies reported the clinical features of PNES [10, 16] and the basal CK values [10, 15]. Three studies included patients with single events [15–17], whereas one study included participants with repeated ones [10]. Across different studies, normal serum CK upper limits varied considerably [ranging from \70 to

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\180 Units/Liter (U/L)], and postictal CK values were measured up to 96 h after the acute event. The sensitivity of increased postictal CK levels for ES ranged from 14.6 to 87.5, whereas specificity ranged from 85.0 to 100.0. After correction for the internationally proposed 95.7th percentile [13, 14], sensitivity ranged from 14.6 to 62.5 and specificity was 100.0. A subgroup analysis stratifying by convulsive versus non-convulsive ES was extremely difficult, due to lack of individual event data in the single study that included both convulsive and non-convulsive ES [15]. In this study, which assessed CK levels after 32 ES of different types (27 complex partial, five secondarily GTCS), sensitivity was 34.4 and specificity 100.0. Conversely, in the study conducted by Wyllie [10], among 147 ES (complex partial, focal motor, absence, tonic) other than GTCS, no single case of increased postictal CK levels was reported. Across studies evaluating CK levels after convulsive ES (69 events overall; 61 GTCS occurring in 32 patients, and eight episodes of refractory generalized convulsive status epilepticus occurring in eight patients), sensitivity ranged from 14.6 to 100.0, whereas specificity ranged from 85.0 to 100.0.

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Discussion

Table 3 Causes for ‘‘false-positive’’ or not-seizure-related CK elevations

In our study, we found that a marked rise in postictal CK levels (usually above the 95.7th percentile [14]) has a high specificity, but a low sensitivity, for ES in the differential diagnosis with PNES. Whether a difference in postictal CK levels exists between convulsive and non-convulsive ES remains debatable; the present review was not able to definitely address this issue due to the limited study available in the literature, their small sample size, and the lack of individual event data to perform a stratification by seizure type for all included studies. A marked CK elevation is thought to be characteristic for GTCS, due to the amount and intensity of muscular contraction, the concomitant hypoxia or muscle ischemia, and other predisposing factors (e.g., chronic alcohol abuse, malnutrition, minor trauma) [10]. Previous reports in the literature indicate that serum CK levels markedly rise after GTCS, usually with a delay of at least 3 h and with a peak concentration occurring after more than 36–40 h [10, 18–20]. Elevations in CK may last between 3 and 8 days [19], and may therefore prove useful in differentiating between ES and PNES, although at later stages of the diagnostic process. Unlike sequential assessments beyond 24–48 h, a serum CK determination performed within the first 24 h after the acute event might detect normal levels (risk of false negative results). The progressive elevation in CK levels over time and the degree of muscular activity are responsible for the relatively wide range of CK serum levels reported in the studies included in our review. As expected, the higher sensitivity values were those reported in the study conducted by Holtkamp [16], which included patients with refractory generalized convulsive status epilepticus. In fact, the only patient with normal CK levels within the first 24 h (57 U/L) showed a marked increase in CK values 40 h after seizure onset (317 U/L). Although one study showed no CK elevation [180 U/L in patients with complex partial, focal motor, absence, and tonic ES [10], a subsequent study, including patients with focal epilepsy (not otherwise specified), complex partial seizures, and secondarily GTCS, found increased postictal CK levels within 24 h of the event in 11/32 cases [15]. There are, therefore, conflicting results in the literature as to whether a marked postictal CK elevation, which has been definitively demonstrated in GTCS [18–20], occurs also in other types of ES. Even after correction for muscle mass, serum levels of CK can vary among healthy subjects depending on age, gender, ethnic origin, and physical exercise. Among the studies included here, none explicitly reported the race of the patients. Furthermore, not all studies reported the concomitant use of drugs (including intramuscular

Systemic causes Acute kidney disease Cancer Cardiac disease (CK-MB) Celiac disease Drugs and toxins Angiotensin receptor blocking agents Anti-psychotic drugs (including Neuroleptic malignant syndrome) Anti-retroviral drugs Beta-blockers Clozapine Cocaine Colchicine Ethanol Fibrates Heroin Hydroxychloroquine Isotretinoin Statins Zidovudine Endocrine disorders Hyperthyroidism Hypoparathyroidism Hypothyroidism ‘Idiopathic’ Hyper-CK-emia (sporadic and familial) Macro-CK Malignant hyperthermia syndrome Metabolic disturbances Hypokalemia Hyponatremia Hypophosphatemia Muscle trauma Intramuscular injections Needle electromyography Neuroacanthocytosis syndromes Pregnancy Rheumatologic and connective tissue disorders (e.g., Sarcoidosis) Surgery Toxins Cocaine Ethanol Heroin Vigorous muscle exercise (especially eccentric) Viral illness Neuromuscular disorders Congenital myopathies (e.g., multicore myopathy) Inflammatory myopathies (e.g., Polymyositis, Inclusion-body myositis) Metabolic myopathies (e.g., Mitochondrial myopathies, McArdle’s disease)

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injections) or disorders that may affect overall CK levels (including minor trauma), and only two determined the basal CK values. Considered overall, the studies included in the present review did not provide enough data to rule out the possibility of coexistent subclinical myopathies or iatrogenic CK elevation. This is a major shortcoming of these studies, since epidemiological data show that up to 20 % of ‘‘normal’’ individuals have increased serum CK levels [14]. Furthermore, with one exception [10], all the included studies measured CK values within 24 h of the acute event, yet serum CK values can increase thereafter. This may have accounted for the relatively low sensitivity of CK levels for the diagnosis of ES. Finally, only one study explicitly and systematically reported the clinical features of all the PNES patients examined [16]. Despite the clinical heterogeneity (e.g., different types of ES) and the limitations of the examined studies, CK appears to be highly specific for ES, although no definite conclusion on its role in differentiating between convulsive and non-convulsive ES can be drawn. Hence, in the differential diagnosis between PNES and ES, the presence of markedly elevated CK levels should prompt the physician to consider the diagnosis of ES, provided that other causes of CK elevation (‘‘false-positives’’, Table 3, [14, 21]) have been ruled out. This finding could prove especially useful in patients with unclear clinical features and/or with infrequent events not recordable on (video)-EEG. [10] Conversely, normal levels of CK, especially if obtained in the first 24 h after the event, do not accurately differentiate between ES and PNES. Thus, normal postictal CK levels do not rule out that the event was epileptic, and only positive results are diagnostically useful [10]. However, several questions remain open. The clinical utility of measuring postictal CK levels in pediatric populations is debatable, as GTCS are rare in infants, who usually have seizures without vigorous muscle contractions. It should, however, be considered that, rather than supporting a diagnosis of seizures, CK measurements might have a role in the differential diagnosis between motor seizures (tonic and/or clonic seizures, and myoclonic seizures) and PNES with generalized motor features, both in children and in adults. This should require a comparison between baseline and postictal CK levels, which may be difficult to obtain especially in patients with intractable epilepsy having both frequent seizures and PNES. On the other hand, currently available data do not provide definite evidence on the role of postictal CK measurements in the differential diagnosis between ES and PNES without motor activity. Despite the useful information provided by an evidencebased approach to the evaluation of a physical sign or a serum biomarker, the diagnosis of ES or PNES requires careful integration of history, ictal signs, and other clinical

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and investigational information, and should never be driven by any single finding. Clinical signs alone should not be used to confirm or rule out the diagnosis of ES, but to refine the initial (pre-test) probability of ES [22, 23]. However, to date the additional diagnostic utility of postictal CK levels is unknown. In general terms, CK assessment may only provide some diagnostic information in patients with unclear paroxysmal motor events (epileptic or non-epileptic), but the ultimate confirmation still requires a videoEEG evaluation, which should be performed regardless of the postictal CK values. Further studies conducted in ES (both convulsive and non-convulsive ES) evaluating the occurrence of postictal CK elevations after 24 h from the onset of the event are required to definitively determine the diagnostic utility of this parameter in the differential diagnosis. These studies should: (1) explore postictal CK levels in different types of ES and PNES (with and without motor activity); (2) systematically exclude the presence of a concomitant hyperCK-emia (related to other drugs, subclinical myopathy, or intramuscular injections); and (3) report single patient details to allow pooling of data in a meta-analysis of the various studies conducted so far. Conflicts of interest to disclose. Ethical standard or patient data.

None of the authors has any conflict of interest

The manuscript does not contain clinical studies

References 1. Benbadis SR, Agrawal V, Tatum WO IV (2001) How many patients with psychogenic nonepileptic seizures also have epilepsy? Neurology 57:915–917 2. Martin R, Burneo JG, 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 3. Brigo F, Nardone R, Bongiovanni LG (2012) Value of tongue biting in the differential diagnosis between epileptic seizures and syncope. Seizure 21(8):568–572 4. Brigo F, Nardone R, Ausserer H, Storti M, Tezzon F, Manganotti P et al (2012) The diagnostic value of urinary incontinence in the differential diagnosis of seizures. Seizure 22(2):85–90 5. Brigo F, Storti M, Lochner P, Tezzon F, Fiaschi A, Bongiovanni LG et al (2012) Tongue biting in epileptic seizures and psychogenic events. An evidence-based perspective. Epilepsy Behav 25:251–255 6. Brigo F, Ausserer H, Nardone R, Tezzon F, Manganotti P, Bongiovanni LG (2013) Clinical utility of ictal eyes closure in the differential diagnosis between epileptic seizures and psychogenic events. Epilepsy Res 104:1–10 7. Cascino GD (2002) Clinical indications and diagnostic yield of video-electroencephalographic monitoring in patients with seizures and spells. Mayo Clin Proc 77:1111–1120 8. Alsaadi TM, 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

J Neurol 9. Dobesberger J, Walser G, Unterberger I, Seppi K, Kuchukhidze G, Larch J, Bauer G, Bodner T, Falkenstetter T, Ortler M, Luef G, Trinka E (2011) Video-EEG monitoring: safety and adverse events in 507 consecutive patients. Epilepsia 52:443–452 10. Wyllie E, Lueders H, Pippenger C, VanLente F (1985) Postictal serum creatine kinase in the diagnosis of seizure disorders. Arch Neurol 42:123–126 11. Simel DL, Samsa GP, Matchar DB (1991) Likelihood ratios with confidence: sample size estimation for diagnostic test studies. J Clin Epidemiol 44:763–770 12. McGee SR (2007) Diagnostic accuracy of physical findings. In: McGee SR (ed) Evidence-based physical diagnosis. Elsevier Saunders, Philadelphia, pp 3–19 13. Brewster LM, Mairuhu G, Sturk A, van Montfrans GA (2007) Distribution of creatine kinase in the general population: implications for statin therapy. Am Heart J 154:655–661 14. Kyriakides T, Angelini C, Schaefer J, Sacconi S, Siciliano G, Vilchez JJ et al (2010) European federation of neurological societies. EFNS guidelines on the diagnostic approach to paucior asymptomatic hyperCKemia. Eur J Neurol 17:767–773 15. Willert C, Spitzer C, Kusserow S, Runge U (2004) Serum neuronspecific enolase, prolactin, and creatine kinase after epileptic and psychogenic non-epileptic seizures. Acta Neurol Scand 109:318–323 16. Holtkamp M, Othman J, Buchheim K, Meierkord H (2006) Diagnosis of psychogenic nonepileptic status epilepticus in the emergency setting. Neurology 66:1727–1729

17. Petramfar P, Yaghoobi E, Nemati R, Asadi-Pooya AA (2009) Serum creatine phosphokinase is helpful in distinguishing generalized tonic–clonic seizures from psychogenic nonepileptic seizures and vasovagal syncope. Epilepsy Behav 15:330–332 18. Chesson A, Kasarskis EJ (1980) Serum CPK elevation after seizures. JAMA 244:2414–2415 19. Chesson AL, Kasarskis EJ, Small VW (1983) Postictal elevation of serum creatine kinase level. Arch Neurol 40:315–317 20. Neufeld MY, Treves TA, Chistik V, Korczyn AD (1997) Sequential serum creatine kinase determination differentiates vaso-vagal syncope from generalized tonic-clonic seizures. Acta Neurol Scand 95:137–139 21. Silvestri NJ, Wolfe GI (2013) Asymptomatic/pauci-symptomatic creatine kinase elevations (hyperckemia). Muscle Nerve 47:805–815 22. Brigo F (2011a) Refining probability: a simple concept to be considered when interpreting interictal epileptiform discharges in EEG. J Clin Neurophysiol 28:334 23. Brigo F (2011b) An evidence-based approach to proper diagnostic use of the electroencephalogram for suspected seizures. Epilepsy Behav 21:219–222

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Postictal serum creatine kinase for the differential diagnosis of epileptic seizures and psychogenic non-epileptic seizures: a systematic review.

The aim of this review was to evaluate the sensitivity and specificity of postictal creatine kinase (CK) levels in the differential diagnosis of epile...
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