|Year : 2016 | Volume
| Issue : 4 | Page : 268-273
The subclinical epileptiform discharges among nonepileptic cerebral palsy patients
Mohamed K Elewa MD , Magdy A Mostafa
Department of Neurology, Ain Shams University, Cairo, Egypt
|Date of Submission||02-Jul-2016|
|Date of Acceptance||28-Sep-2016|
|Date of Web Publication||17-Mar-2017|
Mohamed K Elewa
Department of Neurology, Ain Shams University Hospitals, 38 El-Abbasia, Cairo - 11566
Source of Support: None, Conflict of Interest: None
Subclinical epileptiform discharges (SEDs) are assumed to play a role in the development of cognitive dysfunction in cerebral palsy (CP) patients.
The aim of this study was to estimate the prevalence of SEDs among nonepileptic CP patients and their cognitive correlates.
Patients and methods
Fifty-one nonepileptic CP patients were recruited. All patients were subjected to history taking, neurological examination, assessment using Gross Motor Function Classification System for CP, the Stanford–Binet scale (5th edition), encephalography, and MRI of the brain. They were divided into two groups: group 1, which included 19 CP patients without SEDs, and group 2, which included 32 CP patients with SEDs. A comparison between patients’ features studied in groups 1 and 2 was made using independent-samples t-test and the χ2-test. A correlation between SEDs and the studied features was made using Spearman’s rank correlation coefficient (ρ).
The prevalence of SEDs among nonepileptic CP patients was 62.7%. The presence of MRI abnormality and moderate mental retardation showed a highly significant positive correlation with SEDs. Meanwhile, central nervous system malformation and severe mental retardation showed a significant positive correlation with SEDs. However, normal intelligence showed a highly significant negative correlation with SEDs. Kernicterus and dyskinetic CP showed a significant negative correlation with SEDs.
SEDs are a common finding among nonepileptic CP children. They are positively correlated to cognitive dysfunction. This finding supports the assumption that SEDs are therapeutic target in mentally subnormal children. Larger studies are needed to confirm our results and to evaluate the clinical benefit of treating SEDs.
Keywords: cerebral palsy, cognitive dysfunction, epileptiform discharges
|How to cite this article:|
Elewa MK, Mostafa MA. The subclinical epileptiform discharges among nonepileptic cerebral palsy patients. Egypt J Neurol Psychiatry Neurosurg 2016;53:268-73
|How to cite this URL:|
Elewa MK, Mostafa MA. The subclinical epileptiform discharges among nonepileptic cerebral palsy patients. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2018 Apr 20];53:268-73. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/4/268/202379
| Introduction|| |
Cerebral palsy (CP) is a disorder caused by nonprogressive damage of the developing brain because of heterogeneous etiologies. It is characterized by permanent motoric dysfunction that results in limitation of daily activities. It is usually associated with problems of sensation, perception, cognition, communication, and behavior. Manifestations are attributed to structural damage of the central nervous system (CNS) that may result in epileptic activity and secondary musculoskeletal deformities . CP is a common disorder among Egyptian children. In El-Kharga District-New Valley and Al-Quseir City, Egyptian rural areas, the prevalence of CP was estimated to be 2.04 per 1000 of live births and 3.6 per 1000 of live births, respectively ,.
Cognitive dysfunction is a common problem among CP patients . A significant number of CP patients with cognitive dysfunction are lacking obvious clinical seizures. The presence of epileptiform discharges (EDs) among nonepileptic CP patients may act as a marker for subclinical epileptic activity. Evidence that subclinical epileptiform discharges (SEDs) are responsible for cognitive dysfunction is growing. Unfortunately, only few data about SEDs in nonepileptic CP are available despite its potential benefit. Identifying SEDs among nonepileptic CP patients and their correlates may support the causal relation with cognitive disabilities and hence improve the therapeutic approach.
| Patients and methods|| |
This case–control study included 51 patients with nonepileptic CP who regularly attended Suez Insurance Hospital outpatient pediatric neurology clinics from March 2011 to March 2014. The diagnosis of CP was confirmed once the patient was found to have motor dysfunction caused by nonprogressive lesion in the developing brain . Patients with parental consanguinity, family history of epilepsy, epileptic seizures (either neonatal or afterward), neurodegenerative or neurometabolic disorders were excluded. Moreover, patients who had severe auditory or visual dysfunction, those without motor deficit and those who suffered cerebral damage after the age of 2 years were excluded. Demographic data and history of the patients were collected from their parents. Clear history of the cause was obtained. General and neurological examinations were carried out for all patients. CP types were determined. Prematurity was defined for those born before the 37th week of pregnancy . Birth weight was categorized to be either less than 1.5 kg or more than 1.5 kg. Cognitive assessments were carried out for all patients using the standardized, valid Arabic version of the Stanford–Binet scale (5th edition) ,. Motor deficit was assessed using the Gross Motor Function Classification System (GMFCS) . MRI of the brain was performed for all patients to detect brain atrophy, periventricular white matter abnormalities, gray matter abnormalities, malformations, and other lesions. Ambulatory awake or sedated sleep encephalogram was performed for all patients for 1 h using a 32-channel electroencephalogram (EEG) device (GRAEL HD EEG & PSG; Compumedics, Melbourne, Australia). The electrodes were used according to 10–20 system. Both bipolar and referential montages were used. All EEG records were examined by the authors individually for the background activity and EDs either focal or generalized (spike and sharp wave with or without subsequent slow wave). A spike was defined as a pointed peak at the regular paper speed with duration from 20 to 70 ms. Its main component is negative compared with the surroundings . A sharp wave differs from spike wave only in duration (from 70 to 200 ms). Benign transients, which resemble EDs and background abnormality, were excluded. Informed consent was obtained from patients’ families before participation in the study. The study was approved by Ain Shams University Faculty of Medicine ethical committee.
Patients were divided into two groups according to the presence or absence of SEDs. A comparison between patients’ features studied in groups 1 and 2 was made followed by a correlation between SEDs and the studied features of all patients.
Data were analyzed using statistical program for social science, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean±SD. Qualitative data were expressed as frequency and percentage. Independent-samples t-test of significance was used when comparing between two means. The χ2-test of significance was used to compare proportions between two qualitative features. Spearman’s rank correlation coefficient (ρ) was used to assess the degree of association between two sets of variables if one or both of them were skewed. In all tests, P-value less than 0.05 was considered significant, P-value less than 0.001 was considered highly significant, and P-value greater than 0.05 was considered nonsignificant.
| Results|| |
Patients’ ages ranged from 3 to 12 years (5.50±2.29 years). Twenty-nine (56.9%) patients were boys and 22 (43.1%) patients were girls. As regards the etiology, hypoxic ischemic encephalopathy was the most frequent cause of CP in 28 (54.9%) patients. As regards CP types, the most common CP type was spastic hemiparesis in 18 (35.3%) patients. As regards the level of intelligence, eight (15.7%) patients had normal intelligence and 43 (84.3%) patients had mental retardation (MR) of variable severity. All patients had motor deficit of variable severity. MRI showed that 27 (52.9%) patients had abnormal brain imaging. As regards EEG monitoring, 32 (62.7%) patients had SEDs (either focal or focal with secondary generalization) ([Table 1]).
Patients were divided into two groups: group 1, which included 19 CP patients who did not have SEDs, and group 2, which included 32 CP patients who had SEDs. There was no significant difference in terms of the mean age and distribution of boys and girls between groups 1 and 2 (P>0.05).
As regards the distribution of patients with a history of prematurity between the two groups, there was a significant difference [seven (36.8%) patients in group 1 vs. five (15.6%) patients in group 2] ([Table 2]). However, there was no correlation between SEDs and gestational age ([Table 3]).
|Table 2 Comparison between patients’ features studied in groups 1 and 2 using the χ2-test|
Click here to view
|Table 3 Correlation between SEDs and the studied features in the study group (Spearman’s ρ correlation coefficient test)|
Click here to view
As regards the distribution of CP etiologies between the two groups, the differences were not statistically significant (P>0.05) with respect to hypoxic ischemic encephalopathy, CNS infection, intracranial hemorrhage, and stroke and significant (P<0.05) with respect to kernicterus [three (15.8%) patients in group 1 vs. zero patients in group 2] and CNS malformation [zero patients in group 1 vs. seven (21.9%) patients in group 2] ([Table 2]). As regards the correlation between SEDs and CP etiology, SEDs were significantly positively correlated to CNS malformation. Moreover, SEDs were significantly negatively correlated with kernicterus ([Table 3]).
As regards the distribution of different CP types between the two groups, there was no statistical difference with respect to spastic hemiparetic type, spastic diparetic type, ataxic type, and mixed type ([Table 2]). There was a significant difference as regards spastic quadriparetic type [three (15.8%) patients in group 1 and 11 (34.4%) patients in group 2] and dyskinetic type [four (21.1%) patients in group 1 and no patients in group 2]. As regards the correlation between SEDs and CP type, dyskinetic CP type showed a significant negative correlation with SEDs ([Table 3]).
As regards cognitive assessment, there was no significant difference between the two groups with respect to mild MR. Meanwhile, there was a significant difference in terms of severe MR [one (5.3%) patient in group 1 vs. nine (28.1%) patients in group 2]. Moreover, there was a highly significant difference as regards normal intelligence [seven (36.8%) patients in group 1 vs. one (3.1%) patient in group 2] and moderate MR [three (15.8%) patients in group 1 vs. 18 (56.3%) patients in group 2] ([Table 2]). As regards the correlation between SEDs and the cognitive assessment, a highly significant positive correlation was found between SEDs and moderate MR. In addition, a significant positive correlation was found between SEDs and severe MR. However, normal intelligence showed a highly significant negative correlation with SEDs ([Table 3]).
As regards the level of motor functions, there was no distribution difference between the two groups of the current study ([Table 2]). Moreover, there was no correlation between the level of motor function and SEDs ([Table 3]).
The prevalence of MRI abnormalities between the studied patients was 52.9%. A highly significant difference was found between the two groups in terms of distribution of patients who had MRI abnormalities [four (21.1%) patients in group 1 vs. 23 (71.9%) patients in group 2] ([Table 2]). A highly significant positive correlation was found between SEDs and the presence of MRI abnormalities ([Table 3]).
| Discussion|| |
The prevalence of focal SEDs among nonepileptic CP patients in the current study was 62.7%. The term SEDs was used in the current study instead of the term intericatal ED, which was used in previous studies, as the former term was not suitable for our participants (nonepileptic patients). We did not find data on EEG abnormalities among nonepileptic CP patients in the available literature, but the range of prevalence of EEG abnormalities among CP patients (either epileptic or nonepileptic) was 66–92.6% ,,,. A review of the literature showed that the prevalence rates of spontaneous EDs in healthy children volunteers vary from 0 to 5.6% . In attention deficit hyperactivity disorder children, EDs were present in 30% of patients with no prior history of seizures . The figure was higher in autistic patients (60%) with 24-h EEG monitoring . The available data support the concept that EDs were pathological even in the absence of witnessed seizures, whether EDs were a part of pathogenesis of the clinical manifestation or just a marker for the pathological process.
As regards the distribution of different etiologies between the two groups, there was a significant difference as regards CNS malformation [seven (21.9%) patients in group 2 and no patients in group 1] ([Table 2]). SEDs were positively correlated to CNS malformation as an etiology. This finding could be attributed to the fact that most of the CNS malformations affect cortical structures (either as a part of the malformation itself or secondary to interventions, which were carried out to manage hydrocephalic changes). This finding and its explanation were supported by Carlsson et al. . They found that CP patients who had CNS malformation that cause gyral damage had a higher probability of developing an epileptic activity. Kernicterus was significantly more prevalent in group 1 [three (15.8%) patients in group 1 and no patients in group 2]. Moreover, kernicterus was significantly negatively correlated with SEDs. This was explained by the fact that chronic bilirubin encephalopathy (kernicetrus) mainly affects subcortical structures . It should be considered that the small number of patients in subgroups has limited generalization of these results.
As regards the distribution of CP types between groups 1 and 2, spastic quadriparesis was significantly more prevalent in group 2 [three (15.8%) patients in group 1 and 11 (34.4%) patients in group 2]. This may be attributed to the severity of the illness (the most severe form) and was found to be more associated with the development of epileptic activity. The range of epileptic activity among quadriparetic CP patients was 42.6–54% (relatively higher) in comparison with other types: 34–60% for hemiparetic CP patients, 15.8–27% for diparetic CP patients, and 23–26% for dystonic CP patients ,,. Dyskinetic type was significantly more prevalent in group 1 [four (21.1%) patients in group 1 and no patients in group 2]. Moreover, dyskinetic CP type showed a significant negative correlation with SEDs. This could be explained by results of the previous studies that showed a lower rate of association between dyskinetic CP type and epileptic activity ,, and that three of five of those patients had kernicterus, which mainly affected subcortical structures.
As regards cognitive assessment, group 1 showed a higher number of mentally normal patients [seven (36.8%) patients in group 1 vs. one (3.1%) patient in group 2]; the difference was highly significant. However, group 1 showed lower numbers of patients with moderate MR (three patients, 15.8%) and severe MR (one patient, 5.3%) in comparison with group 2 [18 (56.3%) patients and nine (28.1%) patients, respectively]. Differences between the two groups were highly significant and significant, respectively. A highly significant positive correlation was found between SEDs and moderate MR. Meanwhile, a significant positive correlation was found between SEDs and severe MR. In addition, normal intelligence showed a highly significant negative correlation with SEDs. These findings showed that patients who had EDs were more likely to have MR and that mentally normal patients were unlikely to have SEDs. Several studies supported our findings; they showed that EDs were associated with a transient alteration of mental performance or behavior ,. The observation was termed ‘transitory cognitive impairment’ . Some researchers raised the possibility that these mild cognitive deficits can accumulate to and result in impairment of educational achievements and intelligence . In addition, EDs were responsible for 23.3% of total sleep arousals in CP patients’ polysomnography. The resulted sleep deprivation may cause further impairment of memory and learning process . Our findings were also consistent with those of Wallace , who reported that CP patients with paroxysmal EEG abnormalities had lower IQ scores and learning disabilities. In line with our findings, Steffenberg and colleagues , found that the risk for epilepsy was higher in CP patients who had MR. In contrast, Singhi et al.  did not find a significant difference as regards the level of intelligence between CP patients who had epileptic activity and CP patient who did not. They attributed the differences that were mentioned in the literature to the small number of studies on this issue.
According to the GMFCS, the level of motor functions showed no distribution difference between the two groups. Moreover, the level of motor functions was not correlated with SEDs ([Table 3]). These findings were logic and in line with Mert et al . They found no significant distribution difference as regards level of motor functions between CP patients who had epileptic activity and those who did not. They attributed it to the fact that the level of motor function generated by the GMFCS level reflects white matter dysfunction.
The prevalence of MRI abnormalities between the studied patients in the current study was 52.9%; however, the range of abnormal MRI findings among CP patients (either epileptic or nonepileptic) in other studies was reported as 84–88% . The lower incidence of MRI abnormality in the current study may be attributed to exclusion of epileptic CP patient, as abnormal neuroimaging was reported to be significantly correlated with epilepsy in CP patients . The highly significant difference between the two groups as regards the presence of MRI abnormality and the highly significant positive correlation of presence MRI abnormality and SEDs may be explained by the epileptogenic nature of the most of these abnormalities.
| Conclusion|| |
SEDs are a common finding among nonepileptic CP children. They are positively correlated to cognitive dysfunction. This finding supports the assumption that SEDs may present a potential therapeutic target in mentally subnormal children. Larger studies are needed to confirm our results and to evaluate the clinical benefit of treating SEDs.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M, Damiano D et al.
A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl 2007; 109:8–14.
El-Tallawy HN, Farghaly WM, Shehata GA, Metwally NA, Rageh TA, Abo-Elfetoh N. Epidemiology of cerebral palsy in El-Kharga District-New Valley (Egypt). Brain Dev 2011; 33:406–411.
El-Tallawy HN, Farghaly WM, Shehata GA, Rageh TA, Metwally NA, Badry R et al.
Cerebral palsy in Al-Quseir City, Egypt: prevalence, subtypes, and risk factors. Neuropsychiatr Dis Treat 2014; 10:1267–1272.
Odding E, Roebroeck ME, Stam HJ. The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil Rehabil 2006; 28:183–191.
Fleischman AR, Oinuma M, Clark SL. Rethinking the definition of term pregnancy. Obstet Gynecol 2010; 116:136–139.
Farag S. Stanford–Binet Intelligence test: standardized Arabic version. Cairo, Egypt: Anglo Press; 2011.
Becker KA. History of the Stanford-Binet intelligence scales: Content and psychometrics (Stanford-Binet Intelligence Scales, Fifth Edition Assessment Service Bulletin No. 1). Itasca, IL: Riverside Publishing; 2003.
Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol 1997; 39:214–223.
International Federation of Societies for Electroencephalography and Clinical Neurophysiology. Recommendations for the practice of clinical neurophysiology. Amsterdam, The Netherlands: Elsevier; 1983.
Kulak W, Sobaniec W. Risk factors and prognosis of epilepsy in children with cerebral palsy in north-eastern Poland. Brain Dev 2003; 27:499–506.
Singhi P, Jagirdar S, Khandelwal N, Malhi P. Epilepsy in children with cerebral palsy. J Child Neurol 2003; 18:174–179.
Zafeiriou DI, Kontopoulos EE, Tsikoulos I. Characteristics and prognosis of epilepsy in children with cerebral palsy. J Child Neurol 1999; 14:289–294.
Mert GG, Incecik F, Altunbasak S, Herguner O, Mert MK, Kiris N, Unal I. Factors affecting epilepsy development and epilepsy prognosis in cerebral palsy. Pediatr Neurol 2011; 45:89–94.
So EL. Interictal epileptiform discharges in persons without a history of seizures: what do they mean? J Clin Neurophysiol 2010; 27:229–238.
Hughes JR, deLeo AJ, Melyn MA. The electroencephalogram in attention deficit-hyperactivity disorder: emphasis on epileptiform discharges. Epilepsy Behav 2000; 1:271–277.
Chez MG, Chang M, Krasne V, Coughlan C, Kominsky M, Schwartz. et al.
Frequency of epileptiform EEG abnormalities in a sequential screening of autistic patients with no known clinical epilepsy from 1996 to 2005. Epilepsy Behav 2006; 8:267–271.
Carlsson M, Hagberg G, Olsson I. Clinical and etiological aspects of epilepsy in children with cerebral palsy. Dev Med Child Neurol 2003; 45:371–376.
Hamati AI. Neurological complications of systemic disease: children. In: Fenichel GM, Jankovic J, Mazziotta JC, Daroff RB. Bradley’s neurology in clinical practice. Philadelphia, PA. Elsevier; 2012: 924–925.
Jacobs IB Epilepsy. In: Rubin IL, Bilenker RM, Thompson GH, editors. Comprehensive management of cerebral palsy. New York, NY: Grune and Stratton; 1983.
Aicardi J. Epilepsy in brain injured children. Dev Med Child Neurol 1990; 32:191–202.
Aarts JH, Binnie CD, Smit AM, Wilkins AJ et al.
Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain 1984; 107(Pt 1):293–308.
Binnie CD, Channon S, Marston DL. Behavioral correlates of interictal spikes. Adv Neurol 1991; 55:113–126.
Kasteleijn-Nolst Trenite DG, Vermeiren R. The impact of subclinical epileptiform discharges on complex tasks and cognition: relevance for aircrew and air traffic controllers. Epilepsy Behav 2005; 6:31–34.
Aldenkamp AP, Arends J. Effects of epileptiform EEG discharges on cognitive function: is the concept of transient cognitive impairment still valid?. Epilepsy Behav 2004; 5(Suppl 1):S25–S34.
Kotagal S, Gibbons VP, Stith JA. Sleep abnormalities in patients with severe cerebral palsy. Dev Med Child Neurol 1994; 36:304–311.
Wallace SJ. Epilepsy in cerebral palsy. Dev Med Child Neurol 2001; 43:713–717.
Steffenberg U, Hagberg G, Kyllerman M. Characteristics of seizures in a population-based series of mentally retarded children with active epilepsy. Epilepsia 1996; 37:850–856.
Goulden KJ, Shinnar S, Koller H. Epilepsy in children with mental retardation: a chart study. Epilepsia 1991; 32:690–697.
Robinson MN, Peake JL, Ditchfield MR et al.
Magnetic resonance imaging findings in a population based cohort of children with cerebral epilepsy. Dev Med Child Neurol 2008; 51:39–45.
[Table 1], [Table 2], [Table 3]