Benign Epilepsy With Centrotemporal Spikes (BECTS) 

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Benign Epilepsy With Centrotemporal Spikes (BECTS) – Introduction

  •  BECTS, commonly known as benign rolandic epilepsy, is the most common type of benign epilepsy of childhood.
  •  BECTS is characterized by focal seizures that occur during nonrapid eye movement sleep (sleep onset or early morning) and is associated with oropharyngolaryngeal symptoms (unilateral sensory or motor symptoms), speech arrest, and hypersalivation.
  •  The pathogenesis of BECTS possibly involves the interaction of multiple genes and environmental factors, although siblings and parents rarely have similar seizures.
  •  Patients with BECTS may have an increase in cognitive dysfunction, behavior problems, psychologic disorders, migraine headaches, and sleep apnea.

Evaluation

  •  Consider BECTS in children aged 3-12 years with focal seizures that mostly occur at sleep onset, or just before awakening.
  •  Perform a wake-sleep electroencephalography (EEG) to confirm the diagnosis of BECTS.
  • Neuroimaging, such as a brain magnetic resonance imaging, is not necessary in children or adolescents with BECTS who have a characteristic history with the typical EEG findings of centrotemporal spikes.

Management

  •  Most children with BECTS do not require antiseizure medications (ASMs).
  •  Indications for ASMs include children with frequent seizures, daytime seizures, or trouble learning.
  •  If treatment is required, the first-line ASMs to consider are carbamazepine, valproate, levetiracetam, or lamotrigine.
  •  For uncontrolled BECTS, consider other first-line ASMs, second-line ASMs, or combination therapy.
  •  Involve a seizure specialist if ASM therapy is used.

General Information

Description

  •  most common type of benign epilepsy of childhood characterized by focal seizures that occur during nonrapid eye movement sleep and is associated with oropharyngolaryngeal symptoms, speech arrest, and hypersalivation(1,2,3,4)

Also Called

  •  benign childhood epilepsy with centrotemporal spikes (BCECTS)
  •  benign epilepsy of children with rolandic (centrotemporal) paroxysmal foci
  •  benign rolandic epilepsy (BRE)
  •  benign rolandic epilepsy of childhood (BREC)
  •  benign epilepsy of childhood with rolandic spikes (BECRS)
  •  centrotemporal epilepsy
  •  childhood epilepsy with centrotemporal spikes (CECTS)
  •  rolandic epilepsy (RE)
  •  sylvian epilepsy

Epidemiology

Who Is Most Affected

  •  children and adolescents with onset age of 3-12 years (peak age 7-9 years)(1,2)
  •  male predominance (male to female ratio 3:2)(1,2)

Incidence/Prevalence

  • most common benign epilepsy in children with(1,2)
    •  15% prevalence in children aged 1-15 years with nonfebrile seizures
    •  incidence of 10-20 cases per 100,000 children aged 0-15 years
  • 7% prevalence of BECTS in Norwegian patients with epilepsy
    •  based on population-based cohort study in Norway
    •  1,771 patients with epilepsy were assessed from Buskerud county (272,228 inhabitants)
    • epilepsies included
      •  BECTS in 7%
      •  focal seizures of unknown cause in 62%
      •  general tonic-clonic seizures only without detectable focal start and normal electroencephalography in 16%
      •  continuous spike and waves during slow sleep in 0.8%
      •  myoclonic epilepsy in infancy in 0.6%
      •  early-onset benign occipital epilepsy in 0.3%
      •  epilepsy of infancy with migrating focal seizures in 0.2%
      •  undetermined in 11%
    •  Reference – Epilepsia 2015 May;56(5):699full-text

Possible Risk Factors

  • genetic as well as environmental factors may affect manifestation of BECTS(1,2)
    •  rarely siblings or parents of children with BECTS have same type of seizures, or other types of benign childhood seizure susceptibility syndrome (Brain 2008 Sep;131(Pt 9):2264)
    • possible genetic risk factors include
      •  certain chromosomal loci such as 16p12-11.2, 15q14, and 11p13
      •  variants in genes GRIN2A, ELP4, BDNF, KCNQ, DEPDC5, RBFOX1/3, and GABAA-R
      •  Reference – Seizure 2017 Apr;47:99
    • several studies have found little to no concordance of BECTS among monozygous or dizygous twins
      • retrospective cohort study of 418 twin pairs with confirmed epilepsy were assessed for zygosity, epilepsy classification, and molecular testing
      • population-based study of 1,952 twin pairs with seizure in twin registries from Denmark, United States, Norway, and Australia were assessed for electroencephalography data
        •  18 children had classic BECTS, 10 in monozygous pairs and 8 in dizygous pairs
        •  no pairwise concordance for classic BECTS
        •  4 children had atypical BECTS, 2 in monozygous pairs and 2 in dizygous pairs; all co-twins had seizures
        •  Reference – Epilepsia 2006 Mar;47(3):550full-text
      • case-control study of 8 twin pairs (6 monozygous, 2 dizygous) with BECTS compared with 26 twin pairs with idiopathic generalized epilepsy
    • centrotemporal spikes reported to have autosomal dominant inheritance in families with BECTS
      •  based on case series
      •  30 children aged 4-16 years with a sibling with BECTS (representing 23 families) were assessed by sleep-deprived electroencephalography (EEG) recording
      •  13 with EEG recordings with centrotemporal spikes (adjusted segregation ratio 0.48) in 6 boys and 7 girls
      •  sex-linked mode of inheritance unlikely with approximately equal sex ratio
      •  Reference – Epilepsia 2007 Dec;48(12):2266full-text

Etiology and Pathogenesis

Pathogenesis

  • Pathogenesis of BECTS possibly involves interaction of multiple genes and environmental factors
    • Several studies have examined the occurrence of centrotemporal spikes (BECTS) in twins and have observed little or no concordance; this suggests that the heritability of centrotemporal spikes or BECTS is complex
    • Genes linked to BECTS include variants in
      • Glutamate ionotropic receptor NMDA type 2A (GRIN2A) – ligand gated ion channel that has important roles in brain development and function
      • Elongator protein complex 4 (ELP4) – involved in regulation of cortical projection neuron maturation
      • Brain-derived neurotrophic factor (BDNF) – member of neurotrophin family of growth factors
      • Potassium voltage-gated channel subfamily Q members 2 and 3 (KCNQ2 and KCNQ3) – encode alpha subunits of potassium channels and certain mutations may be associated with benign familial neonatal convulsions type 1 (BFNC)
      • DEP domain containing 5 (DEPDC5) – encodes member of the IML1 family of proteins that regulate mechanistic target of rapamycin complex (mTORC1) pathway
      • RNA binding protein fox – 1 homolog 1/3 (RBFOX1/3) genes encode RNA-binding proteins that are high-level, neuron-specific RNA spicing factors that may regulate certain important epilepsy candidate genes including SCL1A3 and KCNQ2
      • Gamma-aminobutyric acid type A receptor (GABAA-R) – ligand-gated chloride channel that mediates most fast inhibitory synaptic transmissions in brain
    • Reference – Seizure 2017 Apr;47:99

History and Physical

Clinical Presentation

  • typically presents in children aged 3-12 years with characteristic features including(1,2)
    •  focal seizures that occur at the onset of sleep or in the morning, which are usually 1-3 minutes long and can generalize in up to 50% (with rare status epilepticus)
    • oropharyngolaryngeal (OPL) symptoms (reported in 53%) such as
      •  unilateral sensory symptoms inside mouth, teeth, inner cheek, gums, tongue, and pharyngolaryngeal regions with numbness, or paresthesia in mouth (reported in 30%)
      • motor OPL symptoms (such as grunting, gurgling, death rattle, or guttural sounds)
        •  hemifacial sensory-motor seizures may be localized to lower lip and may spread to ipsilateral hand
        •  motor symptoms with pulling/ twitching and clonic contractions associated with ipsilateral tonic deviation of mouth angle
    •  speech arrest (reported in 40%)
    •  hypersalivation (reported in 30%)
  • atypical BECTS may include seizure characteristics such as(1,2)

History

History of Present Illness (HPI)

  • ask about(1,2)
    • seizure timing, duration, and frequency
      •  seizures often occur at sleep onset or in the morning with awakening; seizures during the day suggest atypical BECTS
      •  focal seizures usually 1-3 minutes long, then can become generalized
      •  generalized seizure may be hemiconvulsions or generalized tonic-clonic seizures (family members may hear rhythmic thumping or knocking as bed shakes during generalized tonic-clonic phase)
    • features include
      • at seizure onset
        •  unilateral aura of the tongue (paresthesias of 1 side of the tongue)
        •  perioral paresthesia
      •  simple partial or impartial seizures involving face and tongue when awake or drowsy
      •  postictal behaviors, such as Todd paralysis (rare) that is preceded by long convulsions (suggests atypical BECTS)(1,2)
      •  level of consciousness (typically retained in > 50%)

Family History (FH)

Diagnosis

Making the Diagnosis

  • suspect diagnosis in children aged 3-12 years with focal seizures that mostly occur at sleep onset, or just before awakening and are characterized by(1,2)
    • oropharyngolaryngeal (OPL) symptoms such as
      •  unilateral facial sensory-motor features (pulling/twitching, numbness, and paresthesia in mouth)
      •  motor OPL symptoms (such as grunting, gurgling, death rattle, or guttural sounds)
      •  hemifacial sensory-motor seizures localized to lower lip that may spread to ipsilateral hand
    •  speech arrest
    •  hypersalivation
    •  progression into generalized tonic-clonic seizure
  • suspect atypical BECTS with seizure characteristics such as(1,2)
  • perform electroencephalography (EEG) to confirm BECTS(1,2)
    •  centrotemporal spikes are the characteristic feature of BECTS
    •  obtain wake-sleep EEG as spike-wave discharges are activated as patient enters sleep phase

Differential Diagnosis

  • rule out other childhood idiopathic occipital epilepsies, particularly those with sleep potentiation of epileptiform activity such as
    • early-onset benign occipital epilepsy (Panayiotopoulos syndrome)
    •  late-onset idiopathic occipital epilepsy
    •  continuous spikes and waves during slow-wave sleep (
    • syndromes of electrographic status epilepticus in sleep
    •  Reference – Epileptic Disord 2016 Sep 1;18(3):252
  • other conditions with centrotemporal spikes on electroencephalogram(1)
    •  cerebral tumors
    • Rett syndrome
    • fragile X syndrome
    •  focal cortical dysplasia
    • autism spectrum disorders
    • attention deficit hyperactivity disorder (ADHD) in children and adolescents

Testing Overview

  • perform wake-sleep electroencephalography (EEG) to confirm diagnosis
    •  centrotemporal spikes composed of high amplitude sharp and slow wave complexes in C3/C4 (high central) and C5/C6 (low central region, midway between central and temporal) are the characteristic findings in BECTS
    •  perform wake-sleep EEG as spike-wave discharges typically become activated as patient enters sleep phase of study
  •  consider neuroimaging in patients with atypical features such as persistent or long-duration seizures

Imaging Studies

  • magnetic resonance imaging (MRI)(1,2,4)
    •  consider neuroimaging in patients with atypical features such as persistent or long-duration seizures
    •  neuroimaging is not necessary in children or adolescents with typical BECTS who have characteristic history and electroencephalography findings; brain MRI is usually normal except for incidental findings

Other Diagnostic Testing

Electroencephalography (EEG)

  • EEG BECTS – This EEG of a child with BECTS shows the typical bilateral centro-temporal spike and wave discharges. Abbreviations: BECTS, benign epilepsy with centrotemporal spikes; EEG, encephalography.Copyright© 2014, EBSCO Information Services.
  • perform wake-sleep electroencephalography (EEG) in children with suspected BECTS(1,2,4)
    •  consider performing sleep EEG through sleep deprivation or use of melatonin, if necessary(4)
    •  seizures associated with BECTS are mostly likely to occur during nonrapid eye movement sleep, as well as at sleep onset and awakening(1,2)
    • typical EEG findings are centrotemporal spikes characterized by(1)
      •  high amplitude sharp and slow wave complexes in C3/C4 (high central) in 30% and C5/C6 (low central region, midway between central and temporal) in 70%
      • wave complexes that are composed of
        •  small positive waves
        •  a main spike (or sharp wave) component (often > 200 microvolts) and diphasic with a maximum negative surface, negative, and rounded peak
        •  prominent positive wave with amplitude frequency ≤ 50% of preceding sharp wave
      •  typical field distribution that forms transverse dipole with surface negativity seen in midtemporal central region and surface positivity seen in superior front region
      • spike foci that can either have
        •  unilateral discharge (reported in 60%) with almost equal distribution between both hemispheres
        •  bilateral discharge (reported in 40%) that shifts from side to side and occurs synchronously or asynchronously
      •  discharges that often occur in clusters with frequency 1.5-3 hertz
      •  spikes that increase in sleep stages 1-4 by 2-5 times without disturbance in sleep organization
    • in serial EEG, spikes may appear(1)
      •  right or left
      •  infrequent or abundant
      •  small or giant
      •  alone or with functional spikes in other locations
  • 11.5% children with incidental centrotemporal spikes detected by EEG reported to develop BECTS
    •  based on case series
    •  26 children aged 3-9 years without prior history of seizure with centrotemporal spikes identified incidental by EEG were assessed and followed for mean 2.6 years
    •  most common reasons for obtaining EEG were abnormal sleep study, obstructive sleep apnea screen, staring spells, and behavioral abnormalities
    •  7 (27%) developed seizures, including 3 children who developed BECTS at 15, 16, and 24 months after initial abnormal EEG
    •  Reference – Epilepsy Behav 2015 Feb;43:135

Management

Management Overview

  •  in most children with BECTS, antiseizure medication (ASM) is not necessary(2)
  • in children with frequent seizures, daytime seizures, or trouble learning, consider starting ASM(1)
    • first-line ASMs include carbamazepine, valproate, levetiracetam, or lamotrigine
    •  if carbamazepine, valproate, or lamotrigine not tolerated or effective, consider additional epileptic drugs such as oxcarbazepine, gabapentin, sulthiame, clobazam, or topiramate
    •  consider giving combinations of ASMs if ≥ 2 ASMs are well tolerated but ineffective
    •  carbamazepine and lamotrigine are reported to unmask certain types of seizures in children with BECTS
  • consider discontinuing ASMs after > 2 years of seizure freedom under guidance of specialist and with follow-up electroencephalogram
  •  consider specialist referral as appropriate(4)

Activity

  • 35-week exercise program reported to improve attention, executive function, and internalization behavior in children aged 8-12 years with BECTS (level 3 [lacking direct] evidence)
    •  based on case series
    • 10 children aged 8-12 years with BECTS participated in exercise program and followed for 35 weeks, with regimen including
      •  supervised sports activities for 5 weeks followed by
      •  home-based exercise program for 30 weeks
    • children and parents participated in neurocognitive and psychological evaluations at baseline and follow-up, including
      •  Children’s Color Trails Test (CCTT) for attention and executive function
      •  Korean version of Wechsler Intelligence Scales for Children III (K-WISC-III) and Comprehensive Attention Test (CAT) for attention
      •  Korean Child Behavior Checklist (K-CBCL) for competence and behavioral problems
      •  Quality of Life in Childhood Epilepsy Questionnaire (K-COLQE)
    • compared to baseline reported improvements in
      •  symbol search (attention) on K-WISC-III
      •  divided and sustained attention, and executive function on CCTT
      •  improvement in internalization behavior on K-CBCL
    •  no significant difference in digit span, simple selective attention, working memory, competence, total behavior problems, behavior externalization, withdrawal, somatic complaints, anxiety, depression, social problems, aggressive behavior, or thought, or delinquent problems
    •  Reference – J Child Neurol 2016 Jul;31(8):985

Medications

Antiseizure Medications (ASM)

  • consider antiseizure medications to children with(1)
    •  frequent seizures
    •  daytime seizures
    •  trouble learning
  • first-line ASMs include
    • carbamazepine (Tegretol) (ILAE Level C)(3,4)

Table 1: Pediatric Dosages of Carbamazepine Tablet Monotherapy

Patient AgeInitial DoseSubsequent DoseMaximum Dose
< 6 years10-20 mg/kg/day given in 2-3 divided dosesIncrease weekly to maximum clinical response by increasing to 3-4 doses per day35 mg/kg/day
6-12 years200 mg/day given in 2 divided dosesIncrease ≤ 100 mg/day in weekly intervals by increasing to 3-4 doses per day1,000 mg/day
> 12 years400/mg/day given in 2 divided dosesIncrease ≤ 200 mg/day in weekly intervals by increasing to 3-4 doses per dayFor ages 12-15 years 1,000 mg/dayFor age > 15 years 1,200 mg/day

Citation: Reference – FDA DailyMed 2008 Jan 29.

  • precipitation of atypical absences and atonic seizures, as well as epileptic negative myoclonus and myoclonic seizures involving eyelids, have been reported (Dev Med Child Neurol 2006 May;48(5):394full-text)
  • may be associated with
    •  severe or fatal reactions including toxic epidermal necrolysis and Stevens-Johnson syndrome
    •  aplastic anemia and/or agranulocytosis
    •  Reference – FDA DailyMed 2008 Jan 29

Table 2: Initial Daily Dosing of Depakene (15 mg/kg/day)

WeightTotal Daily DoseNumber of Capsules or Teaspoonfuls of Syrup
Dose 1Dose 2Dose 3
10-24.9 kg (22-54.9 lbs)250 mg001
25-39.9 kg (55-87.9 lbs)500 mg101
40-59.9 kg (88-131.9 lbs)750 mg111
60-74.9 kg (132-164.9 lbs)1,000 mg112
75-89.9 kg (165-197.9 lbs)1,250 mg212

Citation: Reference -FDA DailyMed 2016 Nov 10

  • not recommended for children < 2 years old due to increased risk of developing fatal hepatotoxicity
    •  risk of hepatotoxicity also includes children with mitochondrial disease or pancreatitis
    •  perform serum liver tests prior to therapy and at frequent intervals thereafter, especially during the first 6 months
  •  for girls with current or future childbearing potential, discuss risk of malformation and neurodevelopmental impairments in unborn child with prenatal exposure
  •  Reference – FDA DailyMed 2016 Nov 10

Table 3: Pediatric Dosages of Levetiracetam Tablet Monotherapy

Patient WeightDosage
20 mg/kg/day40 mg/kg/day60 mg/kg/day
> 20-40 kg500 mg/day (1 × 250 mg twice daily)1,000 mg/day (1 × 500 mg twice daily)1,500 mg/day (1 × 750 mg twice daily)
> 40 kg1,000 mg/day (1 × 500 mg twice daily)2,000 mg/day (2 × 500 mg twice daily)3,000 mg/day (2 × 750 mg twice daily)

Citation: Reference -FDA DailyMed 2010 Apr 19

Table 4: Recommended Pediatric Dosages of Immediate-release Lamotrigine Monotherapy*

Week of TherapyChildren Aged 2-12 YearsChildren > 12 Years Old
Weeks 1 and 20.3 mg/kg/day in 1 dose or 2 divided doses25 mg/day
Weeks 3 and 40.6 mg/kg/day in 1 dose or 2 divided doses50 mg/day
Week 5 onwardIncrease dosage in increments of 0.6 mg/kg/day every 1-2 weeks until an effective maintenance dosage is reachedIncrease dosage in increments of 50 mg/day every 1-2 weeks until an effective maintenance dosage is reached
Usual maintenance dosage4.5-7.5 mg/kg/day (maximum 200 mg/day in 1 dose or 2 divided doses)100-400 mg/day in 1 dose or 2 divided doses

Citation: * Dosing of lamotrigine should be adjusted if using with other antiseizure medications. Reference -FDA DailyMed 2016 Nov 23

  • may be associated with an increased risk of adverse events including
    •  appearance of absence seizures, particularly when combined with valproate (Dev Med Child Neurol 2006 May;48(5):394full-text)
    •  serious rashes requiring hospitalization
    •  infections such as bronchiolitis, bronchitis, ear or eye infection, otitis externa, pharyngitis, urinary tract infection, and viral infection
    •  respiratory complications such as nasal congestion, cough, and apnea
    •  Reference – FDA DailyMed 2016 Nov 23
  •  worsening of proximal negative myoclonus reported in 5-year-old boy with BECTS taking lamotrigine (25 mg per day) plus valproate (400 mg per day) in case report (Brain Dev 2012 Mar;34(3):248)

Table 5: Pediatric Maintenance Dosages of Oxcarbazepine Suspension Monotherapy

Patient WeightDose
20 kg600-900 mg/day
25-30 kg900-1,200 mg/day
35-40 kg900-1,500 mg/day
45 kg1,200-1,500 mg/day
50-55 kg1,200-1,800 mg/day
60-65 kg1,200-2,100 mg/day
70 kg1,500-2,100 mg/day

Citation: Reference -FDA DailyMed 2015 Dec 9

  • gabapentin (Neurontin) (ILAE Level D)(3)
    • dosing for gabapentin monotherapy
      •  maximum time between doses ≤ 12 hours
      •  titrate gabapentin over approximately 3 days to reach maintenance dose

Table 6: Pediatric Dosages of Gabapentin Monotherapy

Patient AgeInitial DoseMaintenance DoseMaximum Dose
3-11 years10-15 mg/kg/day orally given in 3 divided dosesFor ages 3-4 years, 40 mg/kg/day orally given in 3 divided dosesFor ages 5-11 years, 25-35 mg/kg/day orally given in 3 divided doses50 mg/kg/day orally
≥ 12 years300 mg orally 3 times daily300-600 mg orally 3 times daily2,400 mg/day orally (long-term)3,600 mg/day orally (short-term)

Citation: Reference – FDA DailyMed 2017 Apr 19.

Predicting Responsiveness to ASM

  • onset of afebrile seizures at age ≤ 5 years and history of febrile seizure associated with poor initial response to ASM in children with BECTS
    •  based on retrospective cohort study
    •  57 children aged 3-13 years (mean age at onset 7.3 years) with BECTS treated with ASMs were assessed by EEG in both awake and sleep states (mean follow-up 3.2 years)
    •  children taking 1 ASM were classified as good initial response and children taking 2 ASMs were classified as poor initial response
    • comparing children with good initial response to children with poor initial response, poor initial response associated with
      •  onset of afebrile seizure at age ≤ 5 years (odds ratio [OR] 5.65, 95% CI 1.41-22.68)
      •  history of febrile seizures (OR 4.97, 95% CI 1.07-23.36)
    • no significant difference in response to ASM with
      •  frequency of afebrile seizure before treatment
      •  type of seizure
      •  family history of febrile seizure or epilepsy
      •  abnormalities on magnetic resonance imaging
      •  lateralization of centrotemporal spikes
      •  presence of focal slowing or generalized epileptiform discharge on EEG
    •  Reference – J Epilepsy Res 2015 Dec;5(2):70full-text
  • seizure onset at age < 4 years associated with poor response to ASM treatment in children with BECTS
    •  based on retrospective cohort study
    •  84 children aged 3-12 years (mean age 7.1 years) with BECTS and treated with ASM were assessed by EEG during wakefulness and during sleep (mean follow-up 4.05 years)
    •  children taking 1 ASM were classified as good initial response (in 85.7%) and children taking 2 ASMs were classified as poor initial response (in 14.3%)
    • in multivariate analysis
      •  age < 4 years at seizure onset associated with poor initial response
      • no significant difference in response to ASM with
        •  gender
        •  history of neonatal seizures or febrile seizure
        •  consanguinity
        •  family history of epilepsy
        •  type, time, and frequency of seizures
        •  Todd paralysis
        •  history of behavioral disorder
        •  duration from diagnosis to start of first treatment
        •  EEG findings (epileptic focus, lateralization, or generalization)
    •  Reference – Brain Dev 2015 Jan;37(1):66

Efficacy of ASMs

  • ASMs may improve seizure control in patients with BECTS (level 2 [mid-level] evidence)
    • based on individual patient data meta-analysis of randomized trials limited by clinical heterogeneity
    • systematic review and individual patient data meta-analysis of 6 randomized trials evaluating ASM in 308 patients with BECTS
      • medications evaluated with sulthiame, levetiracetam, oxcarbazepine, carbamazepine, topiramate, and clobazam
      • comparator was another medication in 4 trials, placebo in 1 trial, and no treatment in 1 trial
    • follow-up ranged across trials from 6 to 24 months
    • comparing any medication to placebo or no treatment, medication associated with increase in seizure control (p < 0.0001)
    •  levetiracetam, sulthiame, and clobazam had pooled seizure control rates > 80%
    • pooled discontinuation rates due to adverse event
      • 29% with topiramate
      • 14% with carbamazepine
      • 14% with levetiracetam
      • 5.5% with clobazam
      • 3.2% with oxcarbazepine
      • 1.9% with sulthiame
    • Reference – Clin Neuropharmacol 2021 Mar;44(2):39
  • levetiracetam associated with similar seizure control compared to each of valproic acid, carbamazepine, sulthiame, and oxcarbazepine, but may increase treatment discontinuation or change due to adverse events compared to sulthiame (level 2 [mid-level] evidence)
    • based on systematic review with limited evidence
    • systematic review of 27 randomized trials evaluating ASM in patients with BECTS
    • 12 trials with 790 patients were included in meta-analysis of seizure control
    • no significant differences in seizure control comparing
      • levetiracetam to valproic acid, carbamazepine, sulthiame, or oxcarbazepine in analyses of 2-3 trials
      • oxcarbazepine to valproic acid in analysis of 3 trials with 274 patients
    • compared to sulthiame, levetiracetam associated with increase in treatment discontinuation or change due to adverse event (risk ratio 5.12, 95% CI 1.19-22.01) in analysis of 2 trials with 87 patients
    • no significant difference in any adverse event comparing levetiracetam to valproic acid, carbamazepine, or oxcarbazepine in analyses of 2-3 trials
    • Reference – Front Pharmacol 2022;13:821639full-text
  • sulthiame
    •  available in Europe and Middle East(1)
    • sulthiame monotherapy may reduce seizure recurrence in children with BECTS (level 2 [mid-level] evidence)
      •  based on small randomized trial
      •  66 patients aged 3-10 years with BECTS were randomized to sulthiame 5 mg/kg/day orally vs. placebo for 6 months and were assessed by seizure history, physical examinations including thorough neurological examinations, and laboratory studies
      •  trial terminated early after preplanned interim analysis due to clear benefit of sulthiame
      •  2 children were removed from each group; unclear how many children were included in final analysis
      •  treatment failure defined as seizure recurrence, intolerable adverse effects, development of second epileptic syndrome, or termination from trial
      • comparing sulthiame vs. placebo
        •  recurrent seizure in 13% vs. 60% (p < 0.05, NNT 2)
        •  completion without treatment failure in 80.6% vs. 28.6% (p < 0.0001, NNT 2)
        •  no significant differences in adverse events
      •  Reference – Epilepsia 2000 Oct;41(10):1284PDF
      • CLINICIANS’ PRACTICE POINT: Twenty nine children with sulthiame and 31 children with placebo were left following patient dropout. It is unclear whether the recurrence quantified in the final analyses were performed with the 60-patient sample, or with the 66-patient sample that would have been included in intention-to-treat analyses.
    • levetiracetam may be less effective than sulthiame for seizure control in children with BECTS (level 2 [mid-level] evidence)
      •  based on small randomized trial with early termination
      •  44 children aged 6-12 years (mean age 9 years, 63% male) with BECTS were randomized to levetiracetam 10-30 mg/kg orally vs. sulthiame 2-6 mg/kg orally for 24 weeks, and were followed for 27 weeks
      •  43 were included in analysis
      •  trial terminated early due to failure to meet recruitment for statistical power and noninferiority analyses
      •  no significant differences in treatment failure (19% with levetiracetam vs. 9.1% with sulthiame) or adverse events
      •  Reference – Eur J PASMiatr Neurol 2013 Sep;17(5):507
      •  no additional trials found comparing sulthiame to levetiracetam in patients with BECTS in Cochrane review (Cochrane Database Syst Rev 2021 Sep 23;9(9):CD010062full-text)
  • topiramate 2 mg/kg nightly appears to have similar efficacy for seizure control as topiramate 2 mg/kg twice daily, and may be associated with fewer adverse events in children with BECTS (level 2 [mid-level] evidence)
    •  based on randomized trial without blinding
    • 88 children aged 3.3-13 years (mean age 8 years, 61% male) with BECTS were randomized to 1 of 2 topiramate regimens and were followed for mean 12.2 months
      •  topiramate 2 mg/kg orally nightly (2 mg/kg group)
      •  topiramate 2 mg/kg orally twice daily (4 mg/kg group)
    •  all patients completed follow-up and were analyzed by EEG
    • comparing 2 mg/kg vs. 4 mg/kg
      • for seizure control (no significant differences for any comparison)
        •  > 75% seizure reduction in 27 children vs. 27 children
        •  50%-75% seizure reduction in 13 children vs. 10 children
        •  < 50% seizure reduction in 4 children vs. 3 children
      • for occurrence of epileptiform discharges on EEG (no significant differences for any comparison)
        •  complete disappearance in 5 children vs. 5 children
        •  > 50% reduction in 19 children vs. 17 children
        •  25%-49% reduction in 14 children vs. 13 children
        •  no change in 6 children vs. 5 children
      •  adverse events in 9.1% vs. 29.3% (p < 0.05)
    •  Reference – Childs Nerv Syst 2016 May;32(5):839

Consultation and Referral

  •  specialist should initiate antiseizure medication (ASM) therapy
  •  withdrawal of ASMs should be managed or guided by specialist

Follow-up

Complications and Prognosis

Complications

  • common cognitive dysfunction and behavioral problems include
    •  verbal fluency
    •  speeded naming (differentiating and recognizing simple stimuli verbally under time constraints)
    •  instruction comprehension tasks
    •  language
    •  visuospatial tasks
    •  nonverbal memory
    •  attention
    •  inhibition
    •  attention deficit hyperactivity disorder
    •  anxiety
    •  depression
    •  aggression
    •  social problems
    •  Reference – Epilepsy Behav 2015 Apr;45:85
  •  generalized status epilepticus is rare(1)
  • in some cases, particularly in patients with atypical features, severe neuropsychological impairments may develop; in these patients, BECTS may progress to
    •  atypical benign focal epilepsy of childhood
    •  status of benign rolandic epilepsy
    • syndromes of electrographic status epilepticus in sleep (Landau-Kleffner)
    •  continuous spike and waves during slow sleep syndrome
    •  Reference – Epilepsia 2009 Aug;50 Suppl 7:9full-text
  • self-limited epilepsy with centrotemporal spikes associated with reduced inhibitory control, cognitive flexibility, and verbal fluency (level 2 [mid-level] evidence)
    •  based on systematic review of observational studies
    • systematic review of 43 observational studies evaluating executive functioning in 1,179 children with self-limited epilepsy with centrotemporal spikes and 1,086 children without self-limited epilepsy with centrotemporal spikes (controls)
      • age ranged from 4 to 18 years in 39 studies
      • mean age of epilepsy onset was 7.15 years in 26 studies
      • mean duration of epilepsy at neuropsychological assessments was 2.18 years in 20 studies
    • 19 studies were included in meta-analysis
    • comparing patients with self-limited epilepsy with centrotemporal spikes to controls
      • self-limited epilepsy with centrotemporal spikes associated with
        • reduced inhibitory control (standardized mean difference [SMD] 0.64, 95% CI 0.29-0.98) in analysis of 6 studies
        • reduced cognitive flexibility (SMD – 0.79, 95% CI -1.19 to -0.39) in analysis of 7 studies
        • reduced verbal fluency (SMD -0.74, 95% CI -1.15 to -0.32) in analysis of 9 studies
      • no significant difference in working memory in analysis of 8 studies
    • Reference – Child Neuropsychol 2022 Jan;28(1):30
  • 10.3% prevalence of atypical complications and 11.7% prevalence of behavioral or psychological disorders in children with BECTS at mean 4.4-year follow-up
    •  based on retrospective cohort study
    •  196 children aged 1.5-14 years (mean age 7.6 years, 60% male) with BECTS from 4 medical centers in Israel were analyzed for clinical features for mean 4.4 years after diagnosis
    • 10.3% had atypical features including
      •  electrical status epilepticus during sleep (ESES) in 4.6%
      •  Landau-Kleffner syndrome in 2%
      •  BECTS with frequent refractory seizures in 1.5%
      •  BECTS presented as falls in 1%
      •  classic atypical variant of BECTS in 0.5%
      •  transient oromotor dysfunction in 0.5%
    • children with ESES had
      •  younger age at BECTS diagnosis (5.4 years vs. 7.8 years in children without ESES, no p value reported)
      •  onset ESES mean 16 months after BECTS diagnosis
    • 11.7% had ≥ 1 behavioral or psychological problems including
      •  aggression in 7.6%
      •  anxiety disorder in 2.5%
      •  pervasive developmental disorder in 1%
      •  depression in 0.5%
    •  Reference – Epilepsia 2011 Aug;52(8):1483full-text
  • migraine may be more common in children with Todd paralysis and BECTS
    •  based on retrospective cohort study
    •  108 children aged 2-16 years with BECTS had clinical history taken, analysis of electroencephalography (EEG) findings, and were assessed for migraine by International Classification of Headache Disorders questionnaire
    •  12 children had postictal transient motor deficits diagnosed as Todd paralysis
    • comparing children with Todd paralysis to children without Todd paralysis
      •  Todd paralysis associated with increased incidence of migraine (83.3% vs. 13.5%, p < 0.001)
      •  no significant differences in seizure semiology or duration and EEG
    •  Reference – J Child Neurol 2016 Mar;31(3):289
  • children with BECTS and their family may have increased risk of migraine
    •  based on case-control study
    •  72 children with BECTS and 88 siblings were compared with 150 age- and geographically matched children without epilepsy and 188 siblings were assessed by questionnaire for relative risk of migraine using International Classification of Headache Disorders (ICHD-2) criteria
    • prevalence of migraine with
      •  BECTS in 15%
      •  siblings of BECTS in 14%
      •  without BECTS in 7%
      •  siblings of without BECTS in 4%
    • in analyses adjusted for gender, increased likelihood of migraine in
      •  proband with BECTS (adjusted hazard ratio [HR] 2.46, 95% CI 1.06-5.7)
      •  siblings of proband with BECTS (adjusted HR 2.86, 95% CI 1.1-7.43)
    •  Reference – Epilepsia 2009 Nov;50(11):2428full-text
  • BECTS appears to be associated with higher likelihood of depression and anxiety
    •  based on case-control study
    • 89 children aged 8-14 years (61% male) with BECTS were compared with 75 healthy age-matched controls children and were assessed by EEG, and completed surveys for
      •  depression status with Depression Self-Rating Scale for Children (DSRSC) on 0- to 36-point scale with higher scores indicating higher severity of depression
      •  anxiety disorders with Screen for Child Anxiety-Related Emotional Disorders (SCARED) on 0- to 82-point scale with higher scores indicating higher anxiety severity
    •  mean length of BECTS 2.8 years
    • no child met criteria for clinically significant anxiety or depression; however comparing BECTS vs. control groups, BECTS associated with
      •  higher depression score (mean DSRSC 19.43 vs. 13, p < 0.01)
      •  higher anxiety score (mean SCARED 25.4 vs. 14.4, p < 0.01)
    •  Reference – BMC Pediatr 2016 Aug 17;16(1):128full-text
  • BECTS may be associated with decreased rapid eye movement sleep and increased apnea
    •  based on case-control study
    •  15 children (mean age 11 years) with BECTS and 27 healthy children had medical history and clinical examination, and were assessed by overnight polysomnography
    •  polysomnography parameters were analyzed for sleep architecture and sleep respiratory events by American Academy of Sleep Medicine criteria
    • comparing BECTS vs. without BECTS
      • BECTS associated with
        •  decreased rapid eye movement sleep in 17.4% vs. 21.2% (p = 0.01)
        •  increased apnea-hypopnea score (p < 0.01)
        •  increased obstructive apnea score (p < 0.01)
      • no significant difference in
        •  sleep architecture factors including total sleep time, sleep onset latency, sleep efficiency, arousal index, or periodic leg movements
        •  sleep respiratory parameters factors including central apnea score, subcutaneous oxygen saturation of hemoglobin, end-tidal carbon dioxide, or longest apnea
    •  Reference – Neuropediatrics 2017 Feb;48(1):30

Prognosis

  •  seizures and electroencephalogram abnormalities typically resolve by age 16 years(1,2)
  •  97% probability of achieving 5 years of remission without antiepileptic treatment at 14-year follow-up in children with well-defined BECTS
    •  based on prospective cohort study
    • 680 children < 14 years old with ≥ 2 unprovoked seizures at single hospital between 1994 and 2011 were followed until 5-year initial remission without antiepileptic treatment, 14-year follow-up from second seizure, or until August 15, 2020, whichever occurred first
    • follow-up ranged from 9 to 14 years
    • 45 patients had well-defined BECTS and 39 patients had uncertain BECTS
    • all patients with BECTS had no associated neurologic deficit
    • probability of achieving remission of ≥ 5 years at 14 years free from second seizure
      • 97% for well-defined BECTS
      • 82% for uncertain BECTS
    • Reference – J Child Neurol 2022 Jan;37(1):89
  • withdrawal of antiseizure medications might be associated with 10% recurrence risk in children with BECTS
    •  based on prospective cohort study
    •  353 children < 14 years old with ≥ 2 seizures (not specifically BECTS) were followed for 1-5 years
    •  238 children had seizure remission at mean 2.2 years
    •  among 31 children with BECTS, Kaplan-Meier estimated 2-year risk for seizure recurrence 10%
    •  Reference – Eur J Paediatr Neurol 2010 Mar;14(2):116
  • in rare cases (1.6%) BECTS may be associated with sudden unexpected death in epilepsy
    •  based on population-based study
    •  189 children with suspected sudden unexpected death in epilepsy (SUDEP) in North American SUDEP Registry were assessed for BECTS
    •  3 (1.6%) boys (aged 9, 12, and 13 years) had BECTS
    •  Reference – JAMA Neurol 2017 Jun 1;74(6):645
  •  BECTS reported to develop into Landau-Kleffner Syndrome then to revert back to BECTS in case report of boy aged 10.8 years (aged 8.2 years at diagnosis) can be found in Epilepsy Behav 2013 Apr;27(1):107

Prevention and Screening

  • Not applicable

Guidelines

  •  International League Against Epilepsy (ILAE) guideline on imaging infants and children with recent-onset epilepsy can be found in Epilepsia 2009 Sep;50(9):2147full-text
  • Canadian Society of Clinical Neurophysiologists (CSCN) guideline on minimal standards for electroencephalography in Canada can be found in Can J Neurol Sci 2017 Nov;44(6):631
  •  National Institute for Health and Care Excellence (NICE) guideline on epilepsies in children, young people, and adults can be found at NICE 2022 Apr 27:NG217PDF.

Review Articles

  •  to search MEDLINE for (Benign rolandic epilepsy) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis

Patient Information

References

  1. Parakh M, Katewa V. A Review of the Not So Benign- Benign Childhood Epilepsy with Centrotemporal Spikes. J Neurol Neurophysiol 2015 Aug;6(4):314-7PDF.
  2. Park JT, Shahid AM, Jammoul A. Common pediatric epilepsy syndromes. Pediatr Ann. 2015 Feb;44(2):e30-5.
  3. Glauser T, Ben-Menachem E, Bourgeois B, et al. ILAE Subcommission on AED Guidelines. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013 Mar;54(3):551-63full-text.
  4. National Institute for Health and Clinical Excellence (NICE). The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. NICE 2012 Jan:CG137PDF (guideline updated Feb 2016) .

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