Influence of epileptic activity during sleep on cognitive performance in benign childhood epilepsy with centrotemporal spikes

Influence of epileptic activity during sleep on cognitive performance in benign childhood epilepsy with centrotemporal spikes

Accepted Manuscript Influence of epileptic activity during sleep on cognitive performance in benign childhood epilepsy with centrotemporal spikes Andr...

692KB Sizes 0 Downloads 55 Views

Accepted Manuscript Influence of epileptic activity during sleep on cognitive performance in benign childhood epilepsy with centrotemporal spikes Andreea Nissenkorn, Adi Pappo, Yael Feldmann, Gali Heimer, Omer Bar-Yosef, Michal Tzadok, Orli Polack, Ayelet Bord, Miriam Levav, Bruria Ben-Zeev PII:

S1090-3798(17)31755-5

DOI:

10.1016/j.ejpn.2017.07.001

Reference:

YEJPN 2271

To appear in:

European Journal of Paediatric Neurology

Received Date: 31 May 2016 Revised Date:

27 April 2017

Accepted Date: 3 July 2017

Please cite this article as: Nissenkorn A, Pappo A, Feldmann Y, Heimer G, Bar-Yosef O, Tzadok M, Polack O, Bord A, Levav M, Ben-Zeev B, Influence of epileptic activity during sleep on cognitive performance in benign childhood epilepsy with centrotemporal spikes, European Journal of Paediatric Neurology (2017), doi: 10.1016/j.ejpn.2017.07.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

RI PT

Influence of epileptic activity during sleep on cognitive performance in benign childhood epilepsy with centrotemporal spikes Andreea Nissenkorn, 3,4Adi Pappo∗, 2 Yael Feldmann, 2,5 Gali Heimer, 2 Omer Bar-Yosef, 2 Michal Tzadok, 2 Orli Polack, 2Ayelet Bord, 2 Miriam Levav, 2,3 Bruria Ben-Zeev

SC

1,2,3

M AN U

1 Service for Rare Disorders, Edmond and Lilly Safra Children Hospital, Chaim Sheba Medical Center, Tel Ha Shomer, Israel 2 Pediatric Neurology Unit, Edmond and Lilly Safra Children Hospital, Chaim Sheba Medical Center, Tel Ha Shomer, Israel 3 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 4 Department of Pediatrics C, Schneider Children's Medical Center, Petah Tiqva, Israel

TE D

4 Pinchas Borenstein Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel Ha Shomer, Israel



Corresponding author: Andreea Nissenkorn

Tel 9723505061 Fax 97235305031 Conflict of interests: none

AC C

[email protected]

EP

∗ This study was performed as a partial requirement for MD degree from Tel Aviv University for Adi Pappo

RI PT

ACCEPTED MANUSCRIPT

Abstract

Background: Benign Childhood Epilepsy with Centrotemporal Spikes, is a benign childhood epilepsy, presenting between 4-10 years of age,

SC

characterized by typical clinical and EEG findings. Despite excellent prognosis, there are reports of mild cognitive, language, fine motor and behavioral difficulties. In its atypical form- Electrical Status Epilepticus during Slow Wave Sleep, continuous epileptiform activity during sleep

M AN U

lead to severe neurocognitive deterioration. Our objective was to investigate the influence of abundant sleep epileptiform activity, not fulfilling the criteria for Electrical Status Epilepticus during Slow Wave Sleep, discovered randomly in children without overt intellectual impairment. Methods: We retrospectively reviewed the charts and EEG`s of 34 children with Benign Childhood Epilepsy with Centrotemporal Spikes, who

TE D

underwent neurocognitive evaluation. The neurocognitive battery included items in the following domains: attention span, memory, language, fine motor and behavior. Patients were divided into two groups according to the spike wave index on sleep EEG, with a cut- off point of 50%.

EP

The groups were compared regarding to neurocognitive performance. Outcomes: Children with epileptiform activity of more than 50%, were diagnosed at a significantly younger age (5.13±1.94 years vs. 7.17±2.45, p=0.014 T test), had less controlled seizures and received more

AC C

antiepileptic drugs. However, there was no difference in neurocognitive performance, except in fine motor tasks (Pegboard), where children with more abundant activity were scored lower (-0.79±0.96 vs. 0.20±1.05, p=0.011, T test). Conclusion: Our study did not show negative cognitive effect of abundant epileptiform activity discovered randomly in children with Benign Childhood Epilepsy with Centrotemporal Spikes, warranting aggressive treatment.

ACCEPTED MANUSCRIPT

Keywords

RI PT

Rolandic epilepsy Spike wave index Epileptiform activity

SC

Attention span

Fine motor

Abbreviations

TE D

BECTS-Benign Childhood Epilepsy with Centrotemporal Spikes

AC C

EP

ESES- Electrical Status Epilepticus during Slow Wave Sleep SWI- spike wave index

M AN U

Language

ACCEPTED MANUSCRIPT

RI PT

Introduction Benign childhood epilepsy with centrotemporal spike (BECTS), or rolandic epilepsy, is a frequent epileptic syndrome in childhood, prevalent between 5-10 years of age 1. Despite relatively abundant epileptiform activity aggravated by sleep, originating from the frontocentrotemporal

SC

(rolandic) area, clinical outcome is benign. Seizures are usually controlled with antiepileptic drugs and tend to remit within two years. Cognitive

M AN U

outcome is also considered excellent, since intelligence is within normal range 2, however formal IQ testing reveals mean lower scores compared to general population3, 4. Several other studies revealed difficulties in other domains as language3, 5, 6, attention3, 7, executive and motor function, behavior and social recognition8. It is unclear if the cognitive issues are directly related to epilepsy, since they seem to be present already at epilepsy onset9, as well as in unaffected siblings3, but tend to progress during the first two years of the disease9. Cognitive performance is

TE D

unrelated to seizure control 5, 10, but probably influenced by antiepileptic treatment. In atypical BECTS evolving to Electrical Status Epilepticus during Slow Wave Sleep (ESES)7 it is clear that the abundance of continuous

EP

epileptiform activity during sleep is causing cognitive, behavior and autistic regression as in CSWS11-13 and Landau Kleffner syndrome 14.

AC C

In clinical practice, pediatric neurologists frequently encounter by chance abundant sleep epileptiform activity in children with BECTS without overt mental impairment, raising the question if one should treat these patients more aggressively in order to prevent intellectual decline. The aim of our study was to investigate whether abundant epileptiform activity which do not fulfill the criteria for ESES defined by Tassinari (85% spike wave index SWI) 12, 13negatively influences cognitive outcome.

ACCEPTED MANUSCRIPT

Material and Methods

RI PT

We performed a retrospective cross-sectional study on a cohort of 55 patients diagnosed with BECTS who underwent neuropsychological assessment at the Pediatric Neurology Unit at the Safra Children Hospital, Sheba Medical Center, Israel. The study was approved by the local

SC

Ethics Committee (IRB 9768-12-SMC).

M AN U

Patients were eligible for inclusion if they had at least one neuropsychological assessment and one sleep EEG. Since the scope of our work was to assess seemingly intellectually intact children, patients referred for cognitive decline, ESES/CSWS or Landau Kleffner syndrome, were excluded. Children with intellectual disability, within the autistic spectrum or attending special schools were excepted as well. Patients with seizure types

TE D

other than rolandic, abnormal neurological examination or neuro imaging or known neurogenetic syndromes were not included. Neurocognitive assessment is done in our Pediatric Neurology Unit by neuropsychologists, according to a battery compiled from items used in validated scales checking the following domains: attention span, memory, language, fine motor skills and behavior (see table 1). In our clinic we

EP

refer routinely every child with epilepsy to neurocognitive evaluation, regardless of intellectual complains (gross, subtle or none). However, the

neurocognitive assessment.

AC C

testing is done as a clinical service, and therefore there is no strict correlation between seizure or treatment onset, timing of EEG and the

The following items were extracted from the charts: age at diagnosis of epilepsy, age at EEG study, gender, seizure control and number of antiepileptic drugs.

ACCEPTED MANUSCRIPT

Quantification of spike wave index (SWI) was calculated in sleep EEG`s as described by Braakman et al, 2012 15: slow wave sleep was divided into

RI PT

10 second epochs. In each epoch the seconds in which secondary generalized, hypersynchronized or multifocal activity was present were calculated. Patients were divided into 2 groups: group 1 with ≥50% SWI and group 2 with <50%SWI according to their worst EEG.

SC

Statistical analysis: Cognitive test results as well as demographic data were compared between the two groups using unpaired t test for numeral

M AN U

parameters and Chi square for nominal parameters. The results of cognitive battery were compared to known results in the general Israeli population using one sample t test 16, 17. All tests were two sided and a p<0.05 was considered significant.

Results

TE D

From the cohort of 55 patients, 34 children, aged 6.24±2.43, were eligible for enrollment in this study. Sex ratio M:F was 14:20 (41% vs. 58.8%). 13 patients underwent one neuropsychological assessment, 15 patients underwent two and 6 patients underwent 3. The most frequent antiepileptic drug used was sulthiame (15 patients), followed by valproic acid (9 patients), oxcarbazepine (5 patients), clobasam (5 patients),

AC C

(methylphenidate).

EP

levetiracetam (2 patients), lamotrigine (1 patient) and zonisamide (1 patient). Only one patient was on treatment for attention deficit disorder

15 patients (44.2%) had SWI higher than 50% (group1) while 19 patients (55.8%) has lower than 50% SWI (group2).

ACCEPTED MANUSCRIPT

Age of epilepsy onset was earlier in patients with more abundant epileptic activity (group1), but the lag time between onset of seizures to

RI PT

neurocognitive testing was similar (table 2). In addition, children in this group (group1) were more likely to require polytherapy in order to control seizures (table 2). 5 patients in group 1 (35.7%) were on one antiepileptic drug at the time of the assessment vs. 15 (78.9%) in group 2.

SC

Polytherapy was used in 8 patients (57.1%) of group 1 vs. 1 patient (5.3%) in group 2. One patient (7.1%) in group 1 vs. 3 patients (15.3%) in group 2 were on no antiepileptic treatment. 5 patients in group 1 (33.3%) had active seizures vs. none in group 2. In group 1, seizures were

M AN U

controlled after first antiepileptic drug in 2 patients (13.3%) and after adding additional drugs in 8 patients (53.3%). In group 2, 5 patients (26.3%) were controlled after first antiepileptic drug and 14 (73.7%) after switching to other antiepileptic drug. There were no differences between the groups in gender, family history, type of schooling and hand dominance.

TE D

Neurocognitive performance of the whole population was within normal range (±1SD) in all tested domains (figure 1). However, when compared to results in the general Israeli population, z scores were significantly lower statistically for: CPT commission (0.45±0.83, p<0.05), CPT HRT (-

EP

0.41±0.86, p<0.05), CPT impulsivity (0.24±0.58, p<0.05), VMI Beery (-0.54±0.9, p=0.01), sentence memory (-0.52±1.13, p<0.05), phonemic

AC C

fluency (-0.79±0.96, p=0.01), and Boston naming test (-0.69±1.56, p<0.05) (figure 1). However, within the two groups statistically lower z scores for children in group 1 were found only for the performance in the graphomotor domain for peg board (-0.79±0.96 vs. 0.20±1.05, p<0.05), while difference was nonsignificant for VMI beery results (-0.82±0.9 vs. 0.33±0.86)(figure 2).

ACCEPTED MANUSCRIPT

In the domains of attention, memory and language there was no statistically significant difference in z scores between the two groups: digit

RI PT

span (-0.47±1.09 vs. -0.15±0.9), coding (-0.41±1.01 vs. -0.11±0.81), CPT omission (-0.9±1.93 vs. -0.16±0.74), CPT commission (0.35±0.62 vs. 0.50±0.94), CPT HRT (-0.61±1.03 vs. -0.3±0.77), CPT impulsivity (0.36±0.51 vs. 0.17±0.61), sentence memory (-0.88±1.31 vs. -0.26±0.93),

SC

phonemic verbal fluency (-0.87±0.96 vs. -0.76±0.99), semantic verbal fluency (0.08±0.63 vs. -0.23±0.88) and Boston naming test (-0.70±1.29 vs. -

M AN U

0.66±1.77) (figure 2).

The Achenabach test revealed no statistical difference in behavior between the two groups in Child Behavior check list (CBCL 52.08±13.34 vs. 53.38±9.88, NS t test) as well as Teacher Reporting Form (TRF 59.4±7.92 vs. 55.33±8.29, NS t test).

TE D

Discussion

The impact of epileptiform activity during sleep is a well- known concept in pediatric neurology, since it was defined by Tassinari at a cut- off

EP

point of 85% SWI in slow wave sleep12-14. However, this numerical definition is arbitrary and was challenged lately by the impression that even lower rate of SWI may impact cognitive and behavioral function18-22. In clinical practice one often encounters patients with well- controlled

AC C

rolandic epilepsy with high SWI index during sleep. When there are no overt cognitive or behavior symptoms, there is a debate within the pediatric neurology community whether to try to reduce the epileptiform activity by more aggressive antiepileptic treatment in order to prevent possible sequela23-27 .

ACCEPTED MANUSCRIPT

In our study, we assessed cognition in children with rolandic epilepsy in order to detect subtle cognitive deficits. As a routine, in our clinic in

RI PT

patients with benign epilepsies, we use a neuro-cognitive battery compiled of several subtests addressing the domains known to be affected in benign epilepsies of childhood (table 1). We compared the results between patients with abundant vs. less frequent epileptiform activity during

SC

slow wave sleep using an arbitrarily chosen cut-off point of 50% SWI. According to the selected EEG parameters and the neurocognitive battery

M AN U

that we used, there were no significant differences detected between the two groups.

There are several caveats to our study. Being a retrospective study in a clinical setting, the sleep EEG recordings were not necessarily performed at the time of the neurocognitive testing, within an interval between two weeks and 1 year, therefore the SWI at the time of neuropsychological assessment could be different. Since there were more patients on polytherapy in the group with more abundant epileptiform activity we would

TE D

have expected lowering of the cognitive performance due to direct drug effect. However, given the similarity in the cognitive performance between the groups we cannot rule out a positive effect of the antiepileptic drugs through reducing the frequency of the epileptiform activity at

EP

the time of the testing.

AC C

Another limitation of this study is the fact that we relied on one-hour sleep EEG study, usually with sleep deprivation, while most of the data related to ESES is based on overnight video EEG. Unfortunately, we had not enough video EEG`s in our cohort to perform an analysis, which corresponds to a realistic everyday practice. The decision to pick 50% SWI for a delineation between the two groups can be also criticized. By using an arbitrary dichotomy instead of a continuous variable some correlations might be lost. Selecting a higher a higher cut- off point (e.g.

ACCEPTED MANUSCRIPT

75%, 85% or 90% SWI) could have led to difference between the two groups, however, in this study, changing the SWI percentage caused the

RI PT

sample group to became too small to be analyzed.

In lack of a standardized mathematical tool for quantification of epileptiform activity, the calculation of SWI may be imprecise. In the method we

SC

used there is no difference between single spike and a train of spikes within the same second, while it may have a different impact on brain

M AN U

function. In addition, in calculating the SWI we did not differentiate between multifocal, hypersynchronized or generalized epileptiform activity and did not relate to the amplitude of the spikes, albeit these aspects might influence cognitive outcome. Since our study excluded children with intellectual disability or autism we cannot say that SWI less than 85% does not always impair cognition,

TE D

but rather that in those patients without clinically suspected cognitive impairment high SWI is unlikely to be affecting cognition, at the extent that it would be identified by the neuropsychological assessment. Our data does not support aggressive treatment for eradication of sleep spike and wave activity as a protective approach for neuropsychological function in patients without overt cognitive impairment, while being useless

EP

and potentially harmful. However, facing the limitations of the existing data, further prospective controlled studies using more rigorous criteria

AC C

and tools for epileptiform discharge assessment should be implemented.

ACCEPTED MANUSCRIPT

WISC IV16

Behavior

pegboard graphomotor Child behavior checklist Teacher report form

EP

Fine Motor

WRAML29 Boston naming test30, 31 Semantic verbal fluency17 Phonemic verbal fluency17 WRAVMA32 VMI Beery33 Achenbach ASEBA34

AC C

Memory Language

SC

Subtest omission commission vigilance impulsivity variability HRT digit span coding sentence memory

M AN U

Test CPT28

TE D

Domain Attention span

RI PT

Table 1- Neurocognitive assessment battery

ACCEPTED MANUSCRIPT

RI PT

Table 2 Demographic data

GROUP 2 (<50%SWI )

Age at diagnosis of epilepsy (years)

5.13±1.94

7.17±2.45

P<0.05*, t test

Age at neurocognitive test (years)

7.22±2.35

8.87±2.31

P<0.05*, t test

Lag (diagnosis to neurocognitive test) (years)

2.09±1.54

Male gender (number/percent)

6 (40%)

Antiepileptic drugs at cognitive assessment

Seizure free at cognitive assessment

M AN U

SC

GROUP 1 (≥50%SWI)

Not significant, t test

8 (42.1%)

Not significant, t test

1.6±0.82

0.89±0.45

P<0.01**, t test

10 (66.7%)

19 (100%)

P<0.05, Fisher exact test

AC C

EP

TE D

1.74±1.34

ACCEPTED MANUSCRIPT

Boston naming semantic fluency phonemic fluency sentence memory visuomotor integration Pegboard CPT vigilance CPT impulsivity CPT variability CPT hit reaction time CPT comision CPT omission WISC coding WISC digits

-0.69 -0.79 -0.52 -0.54

M AN U

-0.2

SC

-0.1

RI PT

Figure 1- Neurocognitive assessment in children with BECTS

0.03

0.24

-0.31 -0.41

0.45

-1

EP

-1.5

AC C

-2

TE D

-0.41 -0.24 -0.28 -0.5

0 Z SCORE

0.5

1

1.5

2

ACCEPTED MANUSCRIPT

RI PT

Table 2: Cognitive battery in group 1 (≥50%SWI) vs. Group 2 (<50%SWI)

M AN U

SC

Boston naming semantic fluency phonemic fluency sentence memory visuomotor integration Pegboard CPT vigilance CPT impulsivity CPT variability CPT hit reaction time CPT comision CPT omission WISC coding WISC digits

Group 2

-1.5

-1

AC C

-2

EP

TE D

Group 1

-0.5

0

Z score

0.5

1

1.5

2

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

Legend table 1 CPT, Connor Continues Performance Test; HRT, Hit reaction Time; WISC IV, Wechsler intelligence scale for Children; WRAML, Wide range assessment of memory and learning; BNT, Boston Naming Test; WRAVMA, wide range assessment visual motor abilities; VMI, visual motor integration; ASEBA, Achenbach System of Empirically Based Assessment

ACCEPTED MANUSCRIPT

RI PT

Bibliography

AC C

EP

TE D

M AN U

SC

[1] Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, 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;51:676-85. [2] Kwon S, Seo HE, Hwang SK. Cognitive and other neuropsychological profiles in children with newly diagnosed benign rolandic epilepsy. Korean journal of pediatrics. 2012;55:383-7. [3] Smith AB, Kavros PM, Clarke T, Dorta NJ, Tremont G, Pal DK. A neurocognitive endophenotype associated with rolandic epilepsy. Epilepsia. 2012;53:705-11. [4] Kim SE, Lee JH, Chung HK, Lim SM, Lee HW. Alterations in white matter microstructures and cognitive dysfunctions in benign childhood epilepsy with centrotemporal spikes. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2014;21:708-17. [5] Goldberg-Stern H, Gonen OM, Sadeh M, Kivity S, Shuper A, Inbar D. Neuropsychological aspects of benign childhood epilepsy with centrotemporal spikes. Seizure : the journal of the British Epilepsy Association. 2010;19:126. [6] Amaral MI, Casali RL, Boscariol M, Lunardi LL, Guerreiro MM, Colella-Santos MF. Temporal auditory processing and phonological awareness in children with benign epilepsy with centrotemporal spikes. BioMed research international. 2015;2015:256340. [7] Tovia E, Goldberg-Stern H, Ben Zeev B, Heyman E, Watemberg N, Fattal-Valevski A, et al. The prevalence of atypical presentations and comorbidities of benign childhood epilepsy with centrotemporal spikes. Epilepsia. 2011;52:1483-8. [8] Genizi J, Shamay-Tsoory SG, Shahar E, Yaniv S, Aharon-Perez J. Impaired social behavior in children with benign childhood epilepsy with centrotemporal spikes. Journal of child neurology. 2012;27:156-61. [9] Garcia-Ramos C, Jackson DC, Lin JJ, Dabbs K, Jones JE, Hsu DA, et al. Cognition and brain development in children with benign epilepsy with centrotemporal spikes. Epilepsia. 2015;56:1615-22.

ACCEPTED MANUSCRIPT

TE D

M AN U

SC

RI PT

[10] Filippini M, Boni A, Giannotta M, Pini A, Russo A, Musti MA, et al. Comparing cortical auditory processing in children with typical and atypical benign epilepsy with centrotemporal spikes: Electrophysiologic evidence of the role of non-rapid eye movement sleep abnormalities. Epilepsia. 2015;56:726-34. [11] Bolsterli Heinzle BK, Fattinger S, Kurth S, Lebourgeois MK, Ringli M, Bast T, et al. Spike wave location and density disturb sleep slow waves in patients with CSWS (continuous spike waves during sleep). Epilepsia. 2014;55:584-91. [12] Tassinari CA, Cantalupo G, Rios-Pohl L, Giustina ED, Rubboli G. Encephalopathy with status epilepticus during slow sleep: "the Penelope syndrome". Epilepsia. 2009;50 Suppl 7:4-8. [13] Tassinari CA, Michelucci R, Forti A, Salvi F, Plasmati R, Rubboli G, et al. The electrical status epilepticus syndrome. Epilepsy research Supplement. 1992;6:111-5. [14] Tassinari CA, Rubboli G, Volpi L, Meletti S, d'Orsi G, Franca M, et al. Encephalopathy with electrical status epilepticus during slow sleep or ESES syndrome including the acquired aphasia. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2000;111 Suppl 2:S94-S102. [15] Braakman HM, Ijff DM, Vaessen MJ, Debeij-van Hall MH, Hofman PA, Backes WH, et al. Cognitive and behavioural findings in children with frontal lobe epilepsy. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2012;16:707-15. [16] Wechsler D. Wechsler Intelligence Scale for Children- 4th Edition (WISC-IV). San Antonio, TX: Harcourt Assessment.

AC C

EP

HEB Israeli Norms (2010) Psychtech; 2003. [17] Kave G. The development of naming and word fluency: evidence from Hebrew-speaking children between ages 8 and 17. Developmental neuropsychology. 2006;29:493-508. [18] Raha S, Shah U, Udani V. Neurocognitive and neurobehavioral disabilities in Epilepsy with Electrical Status Epilepticus in slow sleep (ESES) and related syndromes. Epilepsy & behavior : E&B. 2012;25:381-5. [19] Sanchez Fernandez I, Chapman KE, Peters JM, Harini C, Rotenberg A, Loddenkemper T. Continuous Spikes and Waves during Sleep: Electroclinical Presentation and Suggestions for Management. Epilepsy research and treatment. 2013;2013:583531.

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

[20] Inutsuka M, Kobayashi K, Oka M, Hattori J, Ohtsuka Y. Treatment of epilepsy with electrical status epilepticus during slow sleep and its related disorders. Brain & development. 2006;28:281-6. [21] Van Hirtum-Das M, Licht EA, Koh S, Wu JY, Shields WD, Sankar R. Children with ESES: variability in the syndrome. Epilepsy research. 2006;70 Suppl 1:S248-58. [22] van den Munckhof B, van Dee V, Sagi L, Caraballo RH, Veggiotti P, Liukkonen E, et al. Treatment of electrical status epilepticus in sleep: A pooled analysis of 575 cases. Epilepsia. 2015;56:1738-46. [23] Uliel-Sibony S, Kramer U. Benign childhood epilepsy with Centro-Temporal spikes (BCECTSs), electrical status epilepticus in sleep (ESES), and academic decline--how aggressive should we be? Epilepsy & behavior : E&B. 2015;44:117-20. [24] Schneebaum-Sender N, Goldberg-Stern H, Fattal-Valevski A, Kramer U. Does a normalizing electroencephalogram in benign childhood epilepsy with centrotemporal spikes abort attention deficit hyperactivity disorder? Pediatric neurology. 2012;47:279-83. [25] Sanchez Fernandez I, Loddenkemper T, Galanopoulou AS, Moshe SL. Should epileptiform discharges be treated? Epilepsia. 2015;56:1492-504. [26] Besag F, Gobbi G, Aldenkamp A, Caplan R, Dunn DW, Sillanpaa M. Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Subtle behavioural and cognitive manifestations of epilepsy in children. Epileptic disorders : international epilepsy journal with videotape. 2016. [27] Fernandez IS, Chapman KE, Peters JM, Kothare SV, Nordli DR, Jr., Jensen FE, et al. The tower of Babel: survey on concepts and terminology in electrical status epilepticus in sleep and continuous spikes and waves during sleep in North America. Epilepsia. 2013;54:741-50. [28] Conners K, Staff M. Continous Performance Test II (CPT-II). MHS- Multi Health System.

AC C

PAR- Psychological Assessment Resources, INC.; 2001. [29] Sheslow D, Adams W. Wide Range Assessment of Memory and Learning. Wilmington, DE.: Jastak Associates; 1990. [30] Kaplan E, Goodglass H, Weintraub S. Boston Naming Test 2. Philadelphia: Lippincott, Williams & Wilkins; 2001. [31] Nawojczyk DL. Standardization of the Boston Naming Test at the Kindergarten and Elementary School Level. Tampa, Florida: University of South Florida; 1987.

ACCEPTED MANUSCRIPT

SC

RI PT

[32] Adams W, Sheslow D. Wide Range Assessment of Visual Motor Abilities- WRAVMA. Wilmington Delaware: Wide Range, Inc.; 1995. [33] Beery KE. The Beery- Buktenica Developmental Test of Visual- Motor Integration- VMI 4th Edition Parsippany, NJ: Modern Curriculum Press; 1997. [34] Achenbach TM, Edelbrock CS. Manual of the Child Behavior Checklist and Revised Child Behavior Profile. Burlington, VT: University of Vermont; 1983.

AC C

EP

TE D

M AN U



ACCEPTED MANUSCRIPT

Highlights

EP

TE D

M AN U

SC

RI PT

Abundant epileptic activity during sleep is a hallmark of BECTS ESES, defined as a spike wave index of 85% may cause various cognitive deficits A spike wave index over 50% did not adversely influence cognitive performance Aggressive therapy of interictal sleep activity in asymptomatic children is unneeded Further studies should determine the spike wave threshold for cognitive decline

AC C

• • • • •