84 Original Article
Is there a Predictive Value of EEG and MRI after a First Afebrile Seizure in Children?
Authors
W. Tews1, S. Weise2, S. Syrbe2, W. Hirsch3, A. Viehweger3, A. Merkenschlager2, A. Bertsche2, W. Kiess4, M. K. Bernhard2
Affiliations
Affiliation addresses are listed at the end of the article
Key words ▶ epileptogenic lesion ● ▶ cMRI ● ▶ EEG ● ▶ first afebrile seizure ● ▶ seizure relapse ● ▶ incidental finding ●
Abstract
Zusammenfassung
Background: After a first afebrile seizure, EEG in addition to cMRI is recommended for pediatric patients. Once indications requiring immediate treatment are excluded, it is of interest to determine if the results provide a prognostic tool for seizure relapses. Methods: Patients aged between 1 month and 18 years who had a first afebrile seizure between 2006 and 2008 were retrospectively studied and monitored for another 48 months. Results: Out of 248 patients, 62.5 % had generalized and 36.3 % focal seizures. 34.7 % of the EEG results were pathological. 176 patients had a cMRI that showed in 23.3 % probable epileptogenic lesions. 3 patients with benign cerebral tumours needed surgical therapy. In the following 48 months 29.4 % of the children showed seizure relapses. There was a correlation between epileptic patterns in the EEG and further seizures (p = 0.0001). However, the sensitivity of the EEG based diagnoses was 0.6, the specificity 0.78 and the positive predictive value 0.52. There was no correlation between epileptogenic lesions and the probability of seizure relapses. The sensitivity of the cMRI to this effect was 0.36, the specificity 0.74 and the positive predictive value 0.34. Discussion: The EEG is superior to cMRI for predicting seizure relapses. The percentage of noticeable cMRI findings is high but this has low therapeutic relevance and is assumed to largely represent "incidental findings". It is important to question the value of MRI investigations for sedated small children except in the case of emergencies. The key question is whether the cMRI should be deployed to diagnose epilepsy, the probability of seizure recurrences or to classify the entity of a most likely epilepsy.
Hintergrund: Nach ersten afebrilen Krampf anfall wird neben einer EEG-Untersuchung ein cMRT empfohlen. Außerhalb von Notfällen ist von Interesse, ob sich dadurch eine Aussage über das Risiko von Anfallsrezidiven machen lässt. Methoden: Patienten im Alter zwischen 1 Monat und 18 Jahren, die zwischen 2006 und 2008 einen ersten afebrilen Krampfanfall hatten, wurden für 48 Monate retrospektiv analysiert. Ergebnisse: Von 248 Patienten hatten 62,5 % generalisierte, 36,3 % fokale Anfälle. 34,7 % der EEG-Befunde waren pathologisch. 176 Patienten erhielten ein cMRT, das in 23,3 % der Fälle wahrscheinlich epileptogene zerebrale Läsionen zeigte. 3 Patienten mit benignen zereb ralen Tumoren wurden operiert. 29,4 % der Kinder bekamen in den folgenden 48 Monaten Anfallsrezidive. Zwischen epileptogenen Mustern im EEG und weiteren Anfällen besteht ein Zusammenhang (p = 0,0001). Die Sensitivität der EEG-Diagnostik lag bei 0,6, die Spezifität bei 0,78 und der positiv prädiktive Wert bei 0,52. Es gab keine Korrelation zwischen epileptogenen Läsionen und der Wahrscheinlichkeit von Anfallsrezidiven. Die Sensitivität des cMRT lag bei 0,36, die Spezifität 0,74 und der positiv prädiktive Wert 0,34. Diskussion: Das EEG ist dem cMRT überlegen hinsichtlich der Prognose von Anfallsrezidiven. Der Anteil auffälliger cMRT-Befunde ist hoch, aber von geringer therapeutischer Relevanz und großteils als „incidental finding” zu sehen. cMRTUntersuchungen sind außer in Notfällen im Kleinkindesalter wegen der notwendigen Sedierung kritisch zu hinterfragen. Wichtig ist die Frage, ob das cMRT die Diagnose Epilepsie stellen soll, die Wahrscheinlichkeit von Anfallsrezidiven oder die Entität einer wahrscheinlichen Epilepsie angeben soll.
Schlüsselwörter ▶ epileptogene Läsion ● ▶ cMRT ● ▶ EEG ● ▶ erster afebriler Anfall ● ▶ Anfallsrezidiv ● ▶ incidental finding ●
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1394421 Published online: November 24, 2014 Klin Padiatr 2015; 227: 84–88 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Dr. Matthias K. Bernhard Neuropädiatrie Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig Liebigstraße 20a 04105 Leipzig Tel.: + 49/3419/726 242 Fax: + 49/3419/726 319 matthias.bernhard@medizin. uni-leipzig.de
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Tews W et al. Is there a Predictive … Klin Padiatr 2015; 227: 84–88
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Wie hilfreich sind EEG und cMRT nach erstem afebrilen Anfall im Kindes- und Jugendalter hinsichtlich der weiteren Prognose?
Original Article 85
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ly epileptogenic. A potentially epileptogenic lesion was defined as an MRI abnormality that appeared to be related to the seizure and may be causative. Based on previous studies [6, 17], the following MRI findings were considered potentially epileptogenic: leucomalacia, gliosis, other lesions of the grey matter (e. g. polymicrogyria, heterotopia, post-infectious lesions, sclerosis), tumours, haemorrhage, status post infarct, lesions of the hippocampus, ventricular enlargement greater than 1.5 cm and prominent extra-axial spaces greater than 1 cm. Ambiguous and imprecise neuro-imaging results were re-evaluated by a pediatric neurologist and a pediatric radiologist.
Epilepsy is one of the most common neurological disorders in childhood. A single seizure occurs in 0.5 % to 1 % of all children and adolescents [13]. In most cases, a first seizure leads to an emergency call and hospitalisation. Since most patients are presented in a stable condition after a self-limiting seizure the key question is the value and timing of further diagnostic investigations. After a first afebrile seizure, the guidelines of the American Academy of Neurology recommend electroencephalography (EEG) as standard and cranial magnetic resonance imaging (MRI) as an optional diagnostic method [14]. According to the guidelines of the German Society of Pediatric Neurology and those of the German Society of Neurology, MRI should be performed for every onset of epilepsy. An exception can be made for benign myoclonic epilepsy, juvenile absence epilepsy, benign epilepsy with centrotemporal spikes or juvenile myoclonic epilepsy. An emergency MRI should be performed if neurological symptoms or impaired attention are still present 2 h after a seizure [1]. The following study describes EEG and MRI results in children and adolescents after a first afebrile seizure. The purpose of this study is to investigate (1) the predictive value of MRI in determining the likelihood of seizure recurrence and (2) to explore the correlation between EEG and MRI findings.
The analysis of patient data were performed using the statistical software SPSS 17.0 (SPSS Inc., Chicago). The following values were calculated: data number, mean, standard deviation (SD), median, minimum and maximum. Nominally scaled data were analyzed using tables of abundance. Chi-square test and Fisher’s exact test were used to explore correlations between nominally scaled dichotomous data. The significance level was set p 20 min) history of febrile seizures family history of epilepsy
0.52 0.47 0.40 0.39 0.31
children and adults and observed epileptic activity in 54 % of the patients in the EEG, which was performed within 24 h of the seizure. Interestingly, the rate of pathological findings decreased to 34 % when the EEG was performed later than after 24 h [19]. Consequently, Yigit et al. suggested that EEG be performed in the emergency ward, or within at most 24 h of the seizure [23, 24]. In many hospitals brain imaging tools are used for emergency and elective diagnostic investigations. For both acute seizures and the investigation of long-standing epilepsy, MRI is superior to cranial computed tomography (CT), and therefore the method of choice [10, 14]. MRI should be used to identify structural alterations that could potentially underlie existing epilepsy, such as intracranial haemorrhage or tumours [8]. In addition, MRI might contribute to the diagnosis of syndromal diseases or other etiologies that may influence the therapy and the prognosis of an epilepsy. The guidelines of the German Society of Pediatric Neurology recommend MRI for every first epileptic episode except for benign myoclonic epilepsy, juvenile absence epilepsy,
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MRI findings
Table 2 MRI findings.
Percentage of patients without relapse
gy). Among these patients, focal epileptic activity was noted in 56 (72.7 %) and generalized epileptic activity in 21 (27.3 %) children. With increasing age of the patients, pathological EEG results were observed more frequently. In the age group with children younger than 3 years, only 23.1 % of EEG results showed abnormalities while in the group of patients aged 3–10 years 43.1 % of the EEG findings were pathological (p = 0.013).
benign epilepsy with centrotemporal spikes or juvenile myoclonic epilepsy [1, 2]. Therefore, the guidelines presume prior knowledge of the seizure type and its etiologic classification to set the indication for MRI diagnostics. In practice, this knowledge is often not available. In other words, in most cases it is only after performing an EEG and MRI analysis that one is able to state whether these diagnostics were initially indicated. Additionally, for patients and parents it is important to know whether the diagnostic findings have predictive value for the recurrence risk of seizures. In addition to the primary medical reasons, psychological and liability aspects must be considered in daily clinical practice; e. g. parents may have an irrational fear of a brain tumour, seizures that occur during school attendance or as the result of accidents, or need additional expert medicine opinions for insurance purposes. The proportion of abnormal MRI findings observed in our study (30.1 % in total, 23.3 % potentially epileptogenic lesions) is comparable to the results reported previously. In a study of neurologically healthy children between the age of 6 years and 14 years who suffered a first unprovoked seizure, 32.6 % of the children had an abnormal cranial MRI [6]. Sharma et al. examined 475 children with first seizures and observed an abnormal cranial MRI in 26 % of children in a high risk group. This group contained children with focal seizures at an age younger than 33 months, predisposing conditions for intracranial abnormalities such as sicklecell anaemia, tumours or HIV-infection [21]. In another investigation of children aged from 1 to 24 months with recent seizures, 35.2 % of cranial CT and 57 % of cranial MRI were abnormal [16]. Interestingly, even in patients with benign epilepsy showing centro-temporal spikes, brain imaging showed abnormal findings in 14.8 % cases [11]. This patient cohort is excluded from the recommendation for cranial MRI in the latest guidelines [1]. A recent study correlated the prevalence of cranial MRI abnormalities with the patient age at the time of manifestation of epilepsy. In young children 42.8 % showed abnormal cranial MRI, 18.2 % of the older children had an abnormal cranial MRI and only 15.5 % of adolescents (in total 21.9 % of 457 patients at the age of 1 month to 15 years) [7]. An Australian study found clinically significant CT results in 19.7 % of pediatric patients with new-onset seizures. The authors recommended immediate CT or MRI scanning in children aged less than 2 years with a first seizure [3]. Abnormalities in MRI do correlate with EEG deceleration [20]. A comparison of the prevalence of cranial MRI abnormalities in seizure and epilepsy patients with the incidental findings may reveal similar numbers. In one study, 21.5 % of all patients with "normal" headache did show abnormal MRI findings [12]. After observing cranial MRI results from patients without any medical indication, Kim et al. observed abnormalities in 21 % of children and adolescents at the age of 1 month to 18 years (n = 225). Among these patients, one suffered from a brain tumour [18]. In our investigation, 34.7 % of the children had an abnormal EEG. In previous studies, the percentage of abnormal EEG was 42 % and 65.7 %, respectively [6, 22]. However, the rate of non-definitive pathological EEG findings in this study was 18.9 % and the rate of clearly nonpathological findings was 46.4 %. With advancing age of the children, the rate of abnormal EEG findings seems to increase (p = 0.003). It is of special interest to know if EEG and MRI findings differ between the group with a single seizure and the group with recurring seizures over the observation period. In our study, there
was a significant positive correlation of abnormal EEG findings and the risk of seizure relapses. However, sensitivity (0.6), specificity (0.78) and positive predictive value (0.52) were low. There was no association between abnormal MRI findings and the likelihood of seizure relapses. This result seems to be surprising. Intracerebral lesions that are regarded as epileptogenic do not increase the risk of suffering a seizure relapse. There are few publications addressing this question. A 2010 study from Singapore compared 103 children and adolescents at the age of 1 month to 15 years with a single afebrile seizure to 108 children and adolescents with the diagnosis of epilepsy. During the observation period of 2.5 years, they found a highly significant correlation between abnormal EEG findings and seizure relapses. Brain imaging was abnormal in 20.3 % of patients who had a single seizure and in 33 % of patients with epilepsy. Unfortunately, this study did not differentiate between cranial CT and MRI. In addition, brain imaging was performed only in 27.2 % of the patients who had suffered a single seizure, but in 60.2 % of the epilepsy patients. This imbalance makes it difficult to compare the 2 cohorts [5]. However, this bias is also present in this study where only 70.6 % of the patients included in our analysis had MRI shortly after their first seizure. Similar to the study by Doescher et al. [6], we could not prove a correlation between EEG and MRI findings with respect to the recurrence risk of epileptic seizures. There are several limitations of this retrospective study that should be considered when interpreting the results. The initial medical history and physical examination was undertaken and documented, in most cases, by the pediatrician on duty who was not a pediatric neurologist. Repeated neurological anamnesis by an pediatric neurologist might be influenced by earlier imprecise questioning. This could explain the relative overrepresentation of tonicclonic seizures in our study compared to focal seizures. EEG and MRI investigations were only partly re-evaluated by pediatric neurologists and pediatric radiologists in cases where the findings were unclear or imprecise. Therefore the interpretation of normal vs. slightly abnormal findings may have been biased. As our hospital provides the only specialized pediatric neurology department of the area but is not the only pediatric hospital, there might be a bias towards more severe cases.
Conclusion
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Our study confirms the known correlation between the detection of an epileptic pattern in the EEG and the onset of epilepsy. The percentage of abnormal MRI findings seems high. However, in our study cohort, we could not clearly establish a correlation between potentially epileptogenic lesions in MRI and an elevated risk of developing epilepsy after having suffered a first afebrile seizure. The absence of correlation suggests that in otherwise healthy patients, most of the MRI abnormalities are incidental findings. Additionally, as young children require anaesthesia for brain imaging, the recommendation to perform MRI after a first afebrile seizure in pediatric departments apart from the emergency indications must be challenged. In those cases, it is important to clarify what question is to be answered through the MRI results. Is it the aim to diagnose or assess the likelihood of epilepsy after a first seizure or to classify the etiology of a highly probable epilepsy?
Tews W et al. Is there a Predictive … Klin Padiatr 2015; 227: 84–88
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Original Article 87
Contributor Statement
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W. Tews: data aquisition and collection, literature search, creation of the manuscript S. Syrbe: EEG-Evaluation, critically reviewed and creation of the manuscript A. Bertsche: EEG-Evaluation, critically reviewed the manuscript A. Viehweger: cMRT_Evaluation, critically reviewed the manuscript W. Hirsch: cMRT_Evaluation, critically reviewed the manuscript; Project-Idea W. Kiess: scientific supervision and Project-Idea, critically reviewed and creation of the manuscript A. Merkenschlager: EEG-Evaluation, critically reviewed and creation of the manuscript M. Bernhard: EEG-Evaluation, literature search, data interpretation
Conflict of interest: There is no conflict of interest. Affiliations 1 Zentrum für Frauen- und Kindermedizin, Universität Leipzig, Leipzig 2 Neuropädiatrie, Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig, Leipzig 3 Abteilung für Kinderradiologie, Universität Leipzig, Leipzig 4 Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig, Leipzig
References
1 AWMF-online. Diagnostische Prinzipien bei Epilepsien im Kindesalter. Leitlinie der Gesellschaft für Neuropädiatrie 2008: www.awmf.org (last online access 2014/10/13) 2 Baumgartner C, Beyenburg S, Dennig D et al. Leitlinie Erster epileptischer Anfall und Epilepsien im Erwachsenenalter. Aus: Leitlinien für Diagnostik und Therapie in der Neurologie. Georg Thieme Verlag, Stuttgart: 2012 5th edition 3 Bautovich T, Numa A. Role of head computed tomography in the evaluation of children admitted to the paediatric intensive care unit with new-onset seizure. Emerg Med Austra 2012; 24: 313–320 4 Berg AT, Berkovic S, Brodie M et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010; 51: 676–685 5 Chan D, Phuah HK, Ng YL et al. Pediatric epilepsy and first afebrile seizure in Singapore: Epidemiology and investigation yield at presentation. J Child Neurol 2010; 25: 1216–1222 6 Doescher JS, deGrauw TJ, Musick BS et al. Magnetic resonance imaging (MRI) and electroencephalographic (EEG) findings in a cohort of normal children with newly diagnosed seizures. J Child Neurol 2006; 21: 491–495 7 Dura-Trave T, Yoldi-Petri ME, Esparza-Estaun J et al. Magnetic resonance imaging abnormalities in children with epilepsy. Eur J Neurol 2012; 19: 1053–1059
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8 Eltze CM, Chong WK, Whitney A et al. A population-based study of newly diagnosed epilepsy in infants. Epilepsia 2013; 54: 437–445 9 Fisher RS, van Emde Boas W, Blume W et al. Epileptic seizures and epilepsy: definitions proposed by the International Legue Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46: 470–472 10 Gaillard WD, Chiron C, Cross JH et al. ILAE, Committee for Neuroimaging, Subcommittee for Pediatric. Guidelines for imaging infants and children with recent-onset epilepsy. Epilepsia 2009; 50: 2147–2153 11 Gelisse P, Corda D, Raybaud C et al. Abnormal neuroimaging in patients with benign epilepsy with centrotemporal spikes. Epilepsia 2003; 44: 372–378 12 Graf WD, Kayyali HR, Abdelmoity AT et al. Incidental neuroimaging findings in nonacute headache. J Child Neurol 2010; 25: 1182–1187 13 Hause WA, Beghi E. First seizure definitions and worldwide incidence and mortality. Epilepsia 2008; 49: 8–12 14 Hirtz D, Ashwal S, Berg A et al. Practice parameter: Evaluating a first nonfebrile seizure in children: Report of the Quality Standards Subcommittee of the American Academy of Neurology, the Child Neurology Society, and the American Epilepsy Society. Neurology 2000; 55: 616–623 15 Hirtz D, Berg A, Bettis D et al. Quality Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society. Practice parameter: treatment of the child with a first unprovoked seizure: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2003; 60: 166–175 16 Hsieh DT, Chang T, Tsuchida TN et al. New-onset afebrile seizures in infants: role of neuroimaging. Neurology 2010; 74: 150–156 17 Kalnin AJ, Fastenau PS, deGrauw TJ et al. Magnetic resonance imaging findings in children with a first recognized seizure. Pediatr Neurol 2008; 39: 404–414 18 Kim BS, Illes J, Kaplan RT et al. Incidental findings on pediatric MR images of the brain. Am J Neuroradiol 2002; 23: 1674–1677 19 King MA, Newton MR, Jackson GD et al. Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients. Lancet 1998; 352: 1007–1011 20 Noh BH, Berg AT, Nordli DR Jr. Concordance of MRI lesions and EEG focal slowing in children with nonsyndromic epilepsy. Epilepsia 2013; 54: 455–460 21 Sharma S, Riviello JJ, Harper MB et al. The role of emergent neuroimaging in children with new-onset afebrile seizures. Pediatrics 2003; 111: 1–5 22 Shinnar S, Kang H, Berg AT et al. EEG abnormalities in children with a first unprovoked seizure. Epilepsia 1994; 35: 471–476 23 Si Y, Liu L, Fang JJ et al. Evaluation of the efficiency of inpatient 24-h VEEG combined with MRI in consecutive patients with newly diagnosed epilepsies. Epilepsy Behav 2011; 20: 633–637 24 Yigit O, Eray O, Mihci E et al. The utility of EEG in the emergency department. Emerg Med 2012; 29: 301–305
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88 Original Article
Is there a Predictive Value of EEG and MRI after a First Afebrile Seizure in Children?
Authors
W. Tews1, S. Weise2, S. Syrbe2, W. Hirsch3, A. Viehweger3, A. Merkenschlager2, A. Bertsche2, W. Kiess4, M. K. Bernhard2
Affiliations
Affiliation addresses are listed at the end of the article
Key words ▶ epileptogenic lesion ● ▶ cMRI ● ▶ EEG ● ▶ first afebrile seizure ● ▶ seizure relapse ● ▶ incidental finding ●
Abstract
Zusammenfassung
Background: After a first afebrile seizure, EEG in addition to cMRI is recommended for pediatric patients. Once indications requiring immediate treatment are excluded, it is of interest to determine if the results provide a prognostic tool for seizure relapses. Methods: Patients aged between 1 month and 18 years who had a first afebrile seizure between 2006 and 2008 were retrospectively studied and monitored for another 48 months. Results: Out of 248 patients, 62.5 % had generalized and 36.3 % focal seizures. 34.7 % of the EEG results were pathological. 176 patients had a cMRI that showed in 23.3 % probable epileptogenic lesions. 3 patients with benign cerebral tumours needed surgical therapy. In the following 48 months 29.4 % of the children showed seizure relapses. There was a correlation between epileptic patterns in the EEG and further seizures (p = 0.0001). However, the sensitivity of the EEG based diagnoses was 0.6, the specificity 0.78 and the positive predictive value 0.52. There was no correlation between epileptogenic lesions and the probability of seizure relapses. The sensitivity of the cMRI to this effect was 0.36, the specificity 0.74 and the positive predictive value 0.34. Discussion: The EEG is superior to cMRI for predicting seizure relapses. The percentage of noticeable cMRI findings is high but this has low therapeutic relevance and is assumed to largely represent "incidental findings". It is important to question the value of MRI investigations for sedated small children except in the case of emergencies. The key question is whether the cMRI should be deployed to diagnose epilepsy, the probability of seizure recurrences or to classify the entity of a most likely epilepsy.
Hintergrund: Nach ersten afebrilen Krampf anfall wird neben einer EEG-Untersuchung ein cMRT empfohlen. Außerhalb von Notfällen ist von Interesse, ob sich dadurch eine Aussage über das Risiko von Anfallsrezidiven machen lässt. Methoden: Patienten im Alter zwischen 1 Monat und 18 Jahren, die zwischen 2006 und 2008 einen ersten afebrilen Krampfanfall hatten, wurden für 48 Monate retrospektiv analysiert. Ergebnisse: Von 248 Patienten hatten 62,5 % generalisierte, 36,3 % fokale Anfälle. 34,7 % der EEG-Befunde waren pathologisch. 176 Patienten erhielten ein cMRT, das in 23,3 % der Fälle wahrscheinlich epileptogene zerebrale Läsionen zeigte. 3 Patienten mit benignen zereb ralen Tumoren wurden operiert. 29,4 % der Kinder bekamen in den folgenden 48 Monaten Anfallsrezidive. Zwischen epileptogenen Mustern im EEG und weiteren Anfällen besteht ein Zusammenhang (p = 0,0001). Die Sensitivität der EEG-Diagnostik lag bei 0,6, die Spezifität bei 0,78 und der positiv prädiktive Wert bei 0,52. Es gab keine Korrelation zwischen epileptogenen Läsionen und der Wahrscheinlichkeit von Anfallsrezidiven. Die Sensitivität des cMRT lag bei 0,36, die Spezifität 0,74 und der positiv prädiktive Wert 0,34. Diskussion: Das EEG ist dem cMRT überlegen hinsichtlich der Prognose von Anfallsrezidiven. Der Anteil auffälliger cMRT-Befunde ist hoch, aber von geringer therapeutischer Relevanz und großteils als „incidental finding” zu sehen. cMRTUntersuchungen sind außer in Notfällen im Kleinkindesalter wegen der notwendigen Sedierung kritisch zu hinterfragen. Wichtig ist die Frage, ob das cMRT die Diagnose Epilepsie stellen soll, die Wahrscheinlichkeit von Anfallsrezidiven oder die Entität einer wahrscheinlichen Epilepsie angeben soll.
Schlüsselwörter ▶ epileptogene Läsion ● ▶ cMRT ● ▶ EEG ● ▶ erster afebriler Anfall ● ▶ Anfallsrezidiv ● ▶ incidental finding ●
Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1394421 Published online: November 24, 2014 Klin Padiatr 2015; 227: 84–88 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0300-8630 Correspondence Dr. Matthias K. Bernhard Neuropädiatrie Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig Liebigstraße 20a 04105 Leipzig Tel.: + 49/3419/726 242 Fax: + 49/3419/726 319 matthias.bernhard@medizin. uni-leipzig.de
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Tews W et al. Is there a Predictive … Klin Padiatr 2015; 227: 84–88
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Wie hilfreich sind EEG und cMRT nach erstem afebrilen Anfall im Kindes- und Jugendalter hinsichtlich der weiteren Prognose?
Original Article 85
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ly epileptogenic. A potentially epileptogenic lesion was defined as an MRI abnormality that appeared to be related to the seizure and may be causative. Based on previous studies [6, 17], the following MRI findings were considered potentially epileptogenic: leucomalacia, gliosis, other lesions of the grey matter (e. g. polymicrogyria, heterotopia, post-infectious lesions, sclerosis), tumours, haemorrhage, status post infarct, lesions of the hippocampus, ventricular enlargement greater than 1.5 cm and prominent extra-axial spaces greater than 1 cm. Ambiguous and imprecise neuro-imaging results were re-evaluated by a pediatric neurologist and a pediatric radiologist.
Epilepsy is one of the most common neurological disorders in childhood. A single seizure occurs in 0.5 % to 1 % of all children and adolescents [13]. In most cases, a first seizure leads to an emergency call and hospitalisation. Since most patients are presented in a stable condition after a self-limiting seizure the key question is the value and timing of further diagnostic investigations. After a first afebrile seizure, the guidelines of the American Academy of Neurology recommend electroencephalography (EEG) as standard and cranial magnetic resonance imaging (MRI) as an optional diagnostic method [14]. According to the guidelines of the German Society of Pediatric Neurology and those of the German Society of Neurology, MRI should be performed for every onset of epilepsy. An exception can be made for benign myoclonic epilepsy, juvenile absence epilepsy, benign epilepsy with centrotemporal spikes or juvenile myoclonic epilepsy. An emergency MRI should be performed if neurological symptoms or impaired attention are still present 2 h after a seizure [1]. The following study describes EEG and MRI results in children and adolescents after a first afebrile seizure. The purpose of this study is to investigate (1) the predictive value of MRI in determining the likelihood of seizure recurrence and (2) to explore the correlation between EEG and MRI findings.
The analysis of patient data were performed using the statistical software SPSS 17.0 (SPSS Inc., Chicago). The following values were calculated: data number, mean, standard deviation (SD), median, minimum and maximum. Nominally scaled data were analyzed using tables of abundance. Chi-square test and Fisher’s exact test were used to explore correlations between nominally scaled dichotomous data. The significance level was set p 20 min) history of febrile seizures family history of epilepsy
0.52 0.47 0.40 0.39 0.31
children and adults and observed epileptic activity in 54 % of the patients in the EEG, which was performed within 24 h of the seizure. Interestingly, the rate of pathological findings decreased to 34 % when the EEG was performed later than after 24 h [19]. Consequently, Yigit et al. suggested that EEG be performed in the emergency ward, or within at most 24 h of the seizure [23, 24]. In many hospitals brain imaging tools are used for emergency and elective diagnostic investigations. For both acute seizures and the investigation of long-standing epilepsy, MRI is superior to cranial computed tomography (CT), and therefore the method of choice [10, 14]. MRI should be used to identify structural alterations that could potentially underlie existing epilepsy, such as intracranial haemorrhage or tumours [8]. In addition, MRI might contribute to the diagnosis of syndromal diseases or other etiologies that may influence the therapy and the prognosis of an epilepsy. The guidelines of the German Society of Pediatric Neurology recommend MRI for every first epileptic episode except for benign myoclonic epilepsy, juvenile absence epilepsy,
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
MRI findings
Table 2 MRI findings.
Percentage of patients without relapse
gy). Among these patients, focal epileptic activity was noted in 56 (72.7 %) and generalized epileptic activity in 21 (27.3 %) children. With increasing age of the patients, pathological EEG results were observed more frequently. In the age group with children younger than 3 years, only 23.1 % of EEG results showed abnormalities while in the group of patients aged 3–10 years 43.1 % of the EEG findings were pathological (p = 0.013).
benign epilepsy with centrotemporal spikes or juvenile myoclonic epilepsy [1, 2]. Therefore, the guidelines presume prior knowledge of the seizure type and its etiologic classification to set the indication for MRI diagnostics. In practice, this knowledge is often not available. In other words, in most cases it is only after performing an EEG and MRI analysis that one is able to state whether these diagnostics were initially indicated. Additionally, for patients and parents it is important to know whether the diagnostic findings have predictive value for the recurrence risk of seizures. In addition to the primary medical reasons, psychological and liability aspects must be considered in daily clinical practice; e. g. parents may have an irrational fear of a brain tumour, seizures that occur during school attendance or as the result of accidents, or need additional expert medicine opinions for insurance purposes. The proportion of abnormal MRI findings observed in our study (30.1 % in total, 23.3 % potentially epileptogenic lesions) is comparable to the results reported previously. In a study of neurologically healthy children between the age of 6 years and 14 years who suffered a first unprovoked seizure, 32.6 % of the children had an abnormal cranial MRI [6]. Sharma et al. examined 475 children with first seizures and observed an abnormal cranial MRI in 26 % of children in a high risk group. This group contained children with focal seizures at an age younger than 33 months, predisposing conditions for intracranial abnormalities such as sicklecell anaemia, tumours or HIV-infection [21]. In another investigation of children aged from 1 to 24 months with recent seizures, 35.2 % of cranial CT and 57 % of cranial MRI were abnormal [16]. Interestingly, even in patients with benign epilepsy showing centro-temporal spikes, brain imaging showed abnormal findings in 14.8 % cases [11]. This patient cohort is excluded from the recommendation for cranial MRI in the latest guidelines [1]. A recent study correlated the prevalence of cranial MRI abnormalities with the patient age at the time of manifestation of epilepsy. In young children 42.8 % showed abnormal cranial MRI, 18.2 % of the older children had an abnormal cranial MRI and only 15.5 % of adolescents (in total 21.9 % of 457 patients at the age of 1 month to 15 years) [7]. An Australian study found clinically significant CT results in 19.7 % of pediatric patients with new-onset seizures. The authors recommended immediate CT or MRI scanning in children aged less than 2 years with a first seizure [3]. Abnormalities in MRI do correlate with EEG deceleration [20]. A comparison of the prevalence of cranial MRI abnormalities in seizure and epilepsy patients with the incidental findings may reveal similar numbers. In one study, 21.5 % of all patients with "normal" headache did show abnormal MRI findings [12]. After observing cranial MRI results from patients without any medical indication, Kim et al. observed abnormalities in 21 % of children and adolescents at the age of 1 month to 18 years (n = 225). Among these patients, one suffered from a brain tumour [18]. In our investigation, 34.7 % of the children had an abnormal EEG. In previous studies, the percentage of abnormal EEG was 42 % and 65.7 %, respectively [6, 22]. However, the rate of non-definitive pathological EEG findings in this study was 18.9 % and the rate of clearly nonpathological findings was 46.4 %. With advancing age of the children, the rate of abnormal EEG findings seems to increase (p = 0.003). It is of special interest to know if EEG and MRI findings differ between the group with a single seizure and the group with recurring seizures over the observation period. In our study, there
was a significant positive correlation of abnormal EEG findings and the risk of seizure relapses. However, sensitivity (0.6), specificity (0.78) and positive predictive value (0.52) were low. There was no association between abnormal MRI findings and the likelihood of seizure relapses. This result seems to be surprising. Intracerebral lesions that are regarded as epileptogenic do not increase the risk of suffering a seizure relapse. There are few publications addressing this question. A 2010 study from Singapore compared 103 children and adolescents at the age of 1 month to 15 years with a single afebrile seizure to 108 children and adolescents with the diagnosis of epilepsy. During the observation period of 2.5 years, they found a highly significant correlation between abnormal EEG findings and seizure relapses. Brain imaging was abnormal in 20.3 % of patients who had a single seizure and in 33 % of patients with epilepsy. Unfortunately, this study did not differentiate between cranial CT and MRI. In addition, brain imaging was performed only in 27.2 % of the patients who had suffered a single seizure, but in 60.2 % of the epilepsy patients. This imbalance makes it difficult to compare the 2 cohorts [5]. However, this bias is also present in this study where only 70.6 % of the patients included in our analysis had MRI shortly after their first seizure. Similar to the study by Doescher et al. [6], we could not prove a correlation between EEG and MRI findings with respect to the recurrence risk of epileptic seizures. There are several limitations of this retrospective study that should be considered when interpreting the results. The initial medical history and physical examination was undertaken and documented, in most cases, by the pediatrician on duty who was not a pediatric neurologist. Repeated neurological anamnesis by an pediatric neurologist might be influenced by earlier imprecise questioning. This could explain the relative overrepresentation of tonicclonic seizures in our study compared to focal seizures. EEG and MRI investigations were only partly re-evaluated by pediatric neurologists and pediatric radiologists in cases where the findings were unclear or imprecise. Therefore the interpretation of normal vs. slightly abnormal findings may have been biased. As our hospital provides the only specialized pediatric neurology department of the area but is not the only pediatric hospital, there might be a bias towards more severe cases.
Conclusion
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Our study confirms the known correlation between the detection of an epileptic pattern in the EEG and the onset of epilepsy. The percentage of abnormal MRI findings seems high. However, in our study cohort, we could not clearly establish a correlation between potentially epileptogenic lesions in MRI and an elevated risk of developing epilepsy after having suffered a first afebrile seizure. The absence of correlation suggests that in otherwise healthy patients, most of the MRI abnormalities are incidental findings. Additionally, as young children require anaesthesia for brain imaging, the recommendation to perform MRI after a first afebrile seizure in pediatric departments apart from the emergency indications must be challenged. In those cases, it is important to clarify what question is to be answered through the MRI results. Is it the aim to diagnose or assess the likelihood of epilepsy after a first seizure or to classify the etiology of a highly probable epilepsy?
Tews W et al. Is there a Predictive … Klin Padiatr 2015; 227: 84–88
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Contributor Statement
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W. Tews: data aquisition and collection, literature search, creation of the manuscript S. Syrbe: EEG-Evaluation, critically reviewed and creation of the manuscript A. Bertsche: EEG-Evaluation, critically reviewed the manuscript A. Viehweger: cMRT_Evaluation, critically reviewed the manuscript W. Hirsch: cMRT_Evaluation, critically reviewed the manuscript; Project-Idea W. Kiess: scientific supervision and Project-Idea, critically reviewed and creation of the manuscript A. Merkenschlager: EEG-Evaluation, critically reviewed and creation of the manuscript M. Bernhard: EEG-Evaluation, literature search, data interpretation
Conflict of interest: There is no conflict of interest. Affiliations 1 Zentrum für Frauen- und Kindermedizin, Universität Leipzig, Leipzig 2 Neuropädiatrie, Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig, Leipzig 3 Abteilung für Kinderradiologie, Universität Leipzig, Leipzig 4 Universitätsklinik und Poliklinik für Kinder und Jugendliche Leipzig, Leipzig
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