The 26th RSCANP Congress

We invite you to participate in the 26th SNPCAR Congress and the 48th National Conference of Neurology, Psychiatry, and Associated Professions for Children and Adolescents in Romania.

October 21–24, 2026 – Cluj-Napoca

We look forward to welcoming you!

Assist. Prof. Dr. Adriana Cojocaru
President of RSCANP


THERAPEUTIC STRATEGIES IN CHILDHOOD EPILEPSY

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Autor: Patrick Berquin
Distribuie pe:

Available antiepileptic drugs:

Gabapentine

Lamotrigine

Levetiracetam

Oxcarbazepine

Tiagabine

Topiramate

Vigabatrin

Felbamate

Pregabalin

Stiripentol

Carbamazepine

Valproate

Future:

Zonisamide Rufinamide

PHENYTOINE PHENOBARBITAL

How to choose AED?

Secificity in children

  • Epileptic syndromes are different than in adults
  • Take in account

 

  • changes due to physiological development and brain maturation
  • abnormal cortical organisation and epileptogenesis: dysplasia, heterotopic neurons.

 

  • response to AED and side effects are dif­ferent
  • learning and cognitive functions are ma­jor concern

AED and cognition

Avoid

  • Phénobarbital: effect on global IQ
  • Phenytoin

VPA& CBZ: seem to have mild effects on atention and executive function

TPM: mood disorder, speech regression

 

LVT: no data in children (sedative effects) LTG and OXC: no effect?

Define the epileptic syndrome

  • Age of onset
  • Familial and personal history
    • Electro-clinical semiology – Seizure type (partial, generalised)

A good EEG is better than repeated EEG

  • Etiology: Idiopathic or symptom atic/cryp-togenic epilepsy
  • Brain imaging: focal versus diffuse or multifocal lesion.
  • Neurological or genetic disease

 

Symptomatic and Cryptogenic epileptic sd in children and adolescent

often chronic and refractory epilepsies effect on cognitive functions ++ polytherapy may be necessary absences or myoclonics: VPA, LTG generalised tonic-clonic seizures or partial seizures: most of AED are effective: PHT, CBZ, VPA, LTG, OXC, LVT, TPM.. Choose first an effective AED with no significant enzymatic induction, and with low rate of adverse effect Partial Symptomatic or cryptogenic epilepsies: “For initial monotherapy for complex partial seizures, carbamazepine and oxcarbazepine were treatments of choice, with valproate also first line.”

Tretment of pediatric epilepsy: European expert opinion, 2007. Wheless et al. Epileptic Disord. 2007

 

Surgery?

Surgery must be early discussed if: Chronic Refractory epilepsy Focal seizures or secondary generalised seizures Focal lesion: focal resection, lobectomy

Rasmussen: Hemispherotomy not in generalised epilepsy: callosotomy

Mesio-Temporal Epilepsy

Febrile seizures → Temporal Epilepsy

Partial and complex partial seizures

Normal neurological examination

Hipocampal sclerosis: MRI, SPECT, PET 90% refractory epilepsy

Surgical approach

 13 years

Partial seizures

Gelastic seizures

Hyperphagia

 

Vagal nerve stimulation

 For non surgical refratory epilepsy Lennox-Gastaud sd

Dravet sd

Non surgical focal lesion

Plurifocal epilepsy

Refractory absences

Adverse effects:

Transitory Cough

Respiratory effect during sleep (Heberlé,

Berquin et al Epilepsia 2003)

 

 

Vagal nerve stimulation

Steroids (po, IV)

West

Lennox-Gastaut

Doose

Landu-Leffner

ESESS

Ketogenic diet

Catastrophic epilepsy

Rasmussen hemispherotomy

IV Immunoglobulines? Plasmapheresis?

 

Idiopathic generalised epilepsies in children and adolescent

Childhood absence epilepsy

Epilepsy with myoclonic-absences

Juvenile Myoclonic Epilepsy

AED effective: sodium valproate, lamotrigine, ethosuximide, BZD add-on: topiramate levetiracetam

Generalised epilepsy with only tonicclonic seizures

± Carbamazepine, Oxcarbazepine

 

Partial idiopathic epilepsy

Benign epilepsy with Centro-Temporal Spikes:

BETCS (rolandic epilepsy)

Valproate, Carbamazepine, Gabapentine, Oxcarbazepine, Sulthiam

 

Continuous Spikes and Waves during Slow

Sleep

May occur spontaneously

May be induced by AED

Carbamazepine ++, Gabapentine, Phenytoin, Valproate, Oxcarbazepine

 

Oxcarbazepine and BECTS

Long-term use of oxcarbazepine oral suspension in childhood epilepsy: open-label study (Rufo–Campos et a., J Child Neurol. 2006)

62 patients (2 months – 14 years old)

  • 80.6% reduced seizures ≥ 50%,,
  • 71% reduction in seizure frequency ≥ 75%
  • 46.8% seizure free at tthe end of tthe sttudy.
  • Adverse event: 6,4%

Coppola et al., Brain Dev. 2007

Levetiracetam or oxcarbazepine as monotherapy in newly diagnosed benign epilepsy of childhood with centrotemporal spikes (BECTS).

Tzitiridou et al. Epilepsy Behav. 2005 70 children with BECTS 18 months follow-up

  • 74% seizure free (53% seizure free after first dose)
  • 21% reduction of seizure frequency> 50%
  • 7% no change
  • No deterioration EEG :
  • normalization 74%, Improvement: 19 %
  • No Change 7%
  • No CSWS, some patients had temporary marked activation of epileptogenic acti vity in sleep

 

Exacerbation during sleep Possible seizure exacerbation ?

Oxcarbazepine and atypical evolution of benign idiopathic focal epilepsy of childhood.. Grosso et al., Eur J Neurol.2006 2 patients manifested atypical absences, neuropsychological disturbances, and generalized spike-and-wave discharges on EEGs that became continuous during sleep.

The third patient showed, during OXC therapy, more frequent partial motor seizures which ended with ictal vomiting and post-ictal obnubilation Vendrame et al., Epilepsiia 2007 (retrospective):

12 patients/290: worsening of preexisting seizures, new seizure types, and/or EEG deterioration EEG: new onset of generalized epileptiform activity (not reported on the initial baseline EEG) Following substitution of OXC with a broad spectrum AED, significant improvement of seizure control and improvement in the EEG was observed. Myoclonic seizures 2 cases reported by Kaddurah & Holmes

 

(2006 ) (16-year-old girl with 22q del, 23- month-old boy with global development delay)

1 case reported by Hahn (2004) (negative myoclonusdrop atacks boy with partial symptomatic epilepsy) Chapman (2003) in idiopathic focal epilepsy of childhood Juvenile Myoclonic Epilepsy :Gelisse et al., Epilepsia 2004

 

Experience in Amiens 

Exacerbation of myoclonic seizures in Juvenile Myclonic Epilepsy: N = 3

Define the epileptic syndrome first !!

Exacerbation of myoclonic seizures in BECTS without CSWS: N = 1 Myoclonia and atypical absences in Atypical Benign Partial Epilepsy: N = 1

Less frequentt than with CBZ, TPM, VGB

 

Oxcarbazepine Initiation

Oxcarbazepine:

  • low propensity for drug interaction
  • rapid titration
  • no need for plasma monitoring 

 

Oxcarbazepine is efective in monotherapy

Partial and tonic clonic seizures ages 5 -18 years

 

 Trileptal and seizures in children. Open studies

 Partial and generalised seizures N = 42 (> 4 years old) 6 months follow-up 87,5% seizure free

  • 81,2% of partial epilepsies
  • 91,7% of generalised epilepsies

Serdaroglu et al. Pediatr Neurol. 2003

Partial seizures N=40 (30 months to 18 y)

Cryptogénétic: N= 18 or Symptomatic: N= 19

  • Seizure free: N= 13 35%
  • seizure reduction ≥ 50%: N= 22 59,5%
  • Idiopathic N=3: 100% Seizure free

Lamaa, EEC , Madrid 2002,

Khotare Paediatr Neurol 2006)

 

Oxcarbazepine tolerability add-on ttherapy Hyponatremia

Less frequent than in adults and usually mild (>125 mmol/l) 75 children: Holtmann neuropediatrics 2002

Natremia < 135 mmol/l: 26,6%

Hyponatremia < 125 mmol/l: 2 children

Hyponatremia clinically significant: 1 child

1/24 children: Northam et al. Pediatr Neurol 2005

Hyponatremia =124 mmol/l

Returned to normal after ↓ OXC from 60 to 30 mg/kg/d

Experience in Amiens:

2 temporary mild hyponatremia < 132 mmol/l

1 hyponatremia < 125 mmol/l in an infant

(9 months) seizure free: discontinuing OXC, relapse seizures

 

Global IQ and Cognitive functions

No significant cognitive deficit with advised dose in adults

Open label study: 99 children, 6 to 17 old-year newly diagnosed partial seizures neuropsychological test batery

FePsy computerized battery

Rey auditory Verbal Learning Test

Raven’s Progressive Matrice for children

OXC did not differ from CBZ or VPA

 

The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures

Donati et al., Seizure. 2007

Computerized Visual Searching Task (CVST) 112 patients randomised, 99 completed the study

Mean CVST time decreased in all groups:

  • indicating an improvement of mental processing speed and no cognitive impairment in any treatment group
  • No statistically significant difference was observed between oxcarbazepine and carbamazepine/valproate.

 

 

Moyennes des TR sans et avec distracteur chez les enfants sains et épileptiques

Reaction times are impaired Trileptal, Cognitive functions and behaviour

Tzitiridou et al. Epilepsy& Behav 2005

70 children with newly diagnosed BECTS WISC III, Illinois Test of Psychomottor Abilities, DSM-IV,, Bender-Santuci test

No impact on cognitive function when comparison was made

with 45 matched healthy controls

with baseline (before treatment)

Epilepsy in infancy < 2 years generalised epileptic syndromes

  • Idiopathic epileptic syndromes in infancy
    • Non frequent, good outcome
    • Benign myoclonic epilepsy in infancy
  • Symptomattiic and cryptogenic epilepsiies
    • Often refractory epilepsy
    • Dramatic effect on brain development
    • West syndrome
    • Dravet syndrome
    • Epileptic syndrome associated with encephalopathy

 

Vigabatrin: 100-150 mg/kg/d

Steroids (hydrocortisone,ACTH)

Topiramate

Nitrazepam, Clobazam

Valproate ??

 

Epilepsy in infancy < 2 years

  • Partial seizures are underestimated
    • Usually brief seizures
    • sometimes occuring in cluster
    • motor arrest, eyes and head deviation
  • Symptomatic partial or multifocal epilepsies
    • Often complex partial seizures
  • Benign Infantile Convulsions: not so rare !
    • Benign Familial Infantile Convulsions
    • Infantile Convulsions and Choreo-Athetosis
    • Partial benign non familial seizures (Watanabe)

Short duration of treatment.

  • AED first line therapy
    • Avoid phenobarbital and phenytoin (except in emergency and for a short time)
    • Vigabatrin for spasms
    • Valproate
    • Clobazam and clonazepam (add on)
    • Carbamazepine (avoid before 1 year)
    • Oxcarbazepine

When efficacy is quite similar always take in account Tolerability and Safety

 

Trileptal efficacy in infants and young children:

  • Patients 1 month to < 4 years old (N=128)
  • Partial seizures (ILAE Classification)
  • One or 2 seizure–type
  • At least 3 electro-clinical seizures during a 3 days video-EEG
  • Add on therapy: 1 or 2 other AED

 

 OXC in monotherapy or adjunctive therapy

24 infants with Partial seizures 1 month to<4 years of age (> 3 kg)

Newly diagnosed or not controlled epilepsy

 

Experience in Amiens 

  • 15 infants 1 month to 4 years old with reffractory partial seizures
  • Several seizures per day (up to 9O seizures/day)
    • Seizure free: 4
    • Seizure reduction > 50 % : 7
    • No change: 4
  • Tolerability
    • Irritability: 1
  • Lola: 8 months: Brief right hemiclonic seizures (30 to 90 seizures/d) Refractory to PB, PHT, CBZ, VGB

 

 

  • Trileptal 60mg/kg/day: seizure free one month later (3 days video-EEG monitoring)
  • Remain seizure free for 22 months
  • Then, relapse a few seizure per week

Follow-up: MRI normal, taylor dysplasia suspected

  • Deep intracranial EEG performed: epilptetic focus include central area
  • Oxcarbazepine + Levetiracetam

 

Localisation de source par la méthode de Dipol Fit sur modèle réaliste

Maximilien

  • 14 months, Tuberous Sclerosis
  • complex partial seizures
  • secondary generalised seizures (No infantile spasms)
  • 2 to 4 seizures per day
  • Refractory to Vigabatrin, Sodium Valproate, Clobazam
  • Trileptal 60 mg/kg/d (add on with VGB then monotherapy) seizure free during 2 years

 

Probable spectrum of new AEDs in childhood epilepsies Summary

Trileptal improves seizure control in children as young as 4 months and is equally effective whether added to carbamazepine or any other AEDs

Trileptal is safe and well tolerated in children Effective in non idiopathic epilepsies: in partial, tonic and tonic-clonic seizures not effective in absences and myoclonia Generalised Idiopathic epilepsy : rather not (absences, JME) Partial Idiopathic epilepsy (BECTS) : most often ffective but unfrequent worsening need to be aware

 

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