Approach to seizures in children: A comprehensive review

M. Aakash

Consultant pediatric neurologist, Maa Kauvery, Trichy

Background

Seizure

A seizure is a transient occurrence of signs and/or symptoms resulting from abnormal excessive or synchronous neuronal activity in the brain.

Epilepsy

At least two unprovoked (or reflex) seizures occurring >24 hr apart. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%), occurring over the next 10 years

  • Epilepsy syndrome: Distinct electro clinical entities, typical seizure type, EEG, imaging and age dependent features
  • Epileptic encephalopathy: Epileptiform abnormalities themselves contribute to progressive disturbance of cerebral function. [1]

Epidemiology

4–10% children experience at least one seizure in first 16 years of life. Cumulative lifetime incidence of epilepsy – 3%. After 1st unprovoked seizure – the chances of a second seizure ranges from 30–55% over the next 2 to 5 years

After 2nd unprovoked seizure – the chances of a 3rd unprovoked seizure is 80–90% within 2 years if treatment is not initiated. [2]

ILAE 2017 – Classification of seizures

Focal Epileptic Syndrome

Generalized Epilepsy syndrome

Etiological classification (ILAE-2017)

  • Structural
  • Infectious
  • Genetic
  • Metabolic
  • Immune mediated
  • Unknown

Pathophysiology

Practical approach

History-taking

  • Age at onset and presentation (neonate, infancy, childhood)
  • Provocation factors (head trauma, fever etc.)
  • Preceding events (awake, sleep, playing, exercise, and following cry)
  • Presence of aura (somatosensory, auditory, visual, and abdominal) (Not all children can tell)
  • Ictal manifestations (motor, sensory, autonomic, cognitive, and behavioral)
  • Postictal period (postictal dizziness, loss of consciousness, todd’s paresis)
  • Birth history and developmental history

Etiology

  • Perinatal events
  • Head injury
  • CNS infection
  • Drug intake/intoxication

Family history of epilepsy, febrile seizure, intellectual disability

Medication history

Co morbidities

  • Developmental delay/regression
  • Visual or hearing impairment or any deficits
  • Autism/ADHD/Learning disability
  • Behavioural and psychiatric disorders (depression or anxiety)

Seizure mimicker

Examination criteria

  • Head circumference
  • Dysmorphism
  • Neurocutaneous markers
  • CNS examination: sensorium, fundus, vision and hearing, or any focal deficits
  • Direct visualization of seizure- video recording of event

Evaluation of child with 1st seizure like episode

Recurrence Risks

  • After a 1st GTCS in a normal child: 20-30%
  • After 2 seizures: 80%
  • In a child with developmental delay, focal seizure, and a spike discharge on EEG: 80–90%
  • 75% recurrences within first 6 months
  • Very few after 2 years

Management of Febrile seizure

Detailed History and examination

LP: < 6 months; 6–12 months

Counsel parents

  • No role of routine blood tests, imaging or EEG
  • No need for continuous ASM
  • Intermittent Clobazam prophylaxis (0.5 mg/kg/day in 2 divided doses: 3 days of febrile illness)

In case of recurrent febrile seizure

  • Management of febrile illness
  • Establishment of etiological diagnosis of fever
  • Abortive treatment
  • Intermittent prophylaxis of Clobazam

Role of neuroimaging

Need for neuroimaging

  • Seizure cluster
  • Focal deficits
  • Altered sensorium
  • Focal EEG BG change
  • Status epilepticus
CTMRI
TraumaMost sensitive
CalcificationBetter anatomy
Status epilepticusMorphometry
Inflammatory granulomaEpilepsy protocol

*Wright NB et al. Br J Radiol 2000; Hirtz D et al. Neurology 2003

High-resolution brain MRI

The ILAE Neuroimaging Task Force recommends Harmonized Neuroimaging of Epilepsy Structural Sequences (HARNESS-MRI) protocol

Mandatory sequences

  • High-resolution 3D T1 sequences, 1mm cuts
  • 3D fluid- attenuated inversion recovery (FLAIR) sequences, and
  • Axial and coronal T2-weighted, perpendicular to hippocampus
  • Axial and coronal fluid-attenuated inversion recovery (FLAIR) sequences

Optional sequences

  • 3D T1Gadolinium-enhanced sequence
  • 3D T2*-weighted SWI[5]

Contrast –enhanced CT axial images of the brain show ring enhancing lesions with scolex Right Frontal region without perilesional edema (A) and in the left parasagittal region with perilesional edema (B)

Right frontal FCD

Herpes simplex encephalitis

Role of EEG

Use EEGDo not use EEG
Supports a clinical diagnosis of seizureTo exclude diagnosis of epilepsy
Diagnosis of specific epilepsy syndromes
Reclassifying the syndrome in uncontrolled epilepsy
Predicts seizure recurrence
Before ASM discontinuation, predicting ROR
Unexplained cognitive, neurobehavioral or scholastic deterioration

*AAN recommendation: EEG – a standard part of diagnostic evaluation of a child with 1st unprovoked seizure

Examples

Absence

Burst suppression

LGS

Hyps

Guidelines: Initiation of ASMs

GTCS >= 2 Episodes

After first unprovoked seizure if;

  • High risk of seizure recurrence
  • Epileptiform anomalies on EEG;
  • Structural abnormalities: FCD
  • Focal seizure, Status [6]

The Decision to start ASM treatment following a first unprovoked seizure should be individualized and based on patient preference, clinical, legal, and socio-cultural factors

Reported risk factors for seizure recurrence

  • Remote symptomatic aetiology (pre-existing static brain abnormalities that are, by implication, causative)
  • Focal neurological findings
  • Focal seizure phenomenology (including Todd’s paresis)
  • Focal or generalised epileptiform activity on EEG
  • Tumours or other progressive lesions as the underlying pathology
  • Status epilepticus
  • Family history of epilepsy
  • Previous febrile seizures

Guidelines: Choosing the ASM

Initial mono-therapy

3 important considerations:

  • Age
  • Finances
  • Co-existing medical or neurological problems

Drugs of choice

Seizure typeFirst ChoiceSecond Choice
Focal SeizureCBZ, OXCVPA, PHT
GTCSVPAPHT, TPM
AbsenceEthosux, VPA, LTGLEV,TPM, ZNS
MyoclonicVPACLN, TPM, ZNS
TonicVPA, LTGPHT, TPM
AtonicVPA, LTGTPM

Principles of drug therapy

  • Attempt monotherapy initially
  • Start with low dose and increase gradually
  • Ensure compliance
  • If seizure recurrence- increase dose to maximum pharmacological dose or maximum tolerated dose level

Rational Polytherapy

  • Multiple seizure types
  • Failure of adequate monotherapy
  • Appropriate and rational drug combination
  • Avoid drugs with same mechanism of action
  • Avoid drugs with same toxicity profile

Prescribing Tips (One brand only)

  • Dilantin -125 mg/5 ml, in contrast to Syp. Eptoin – 30 mg/ 5ml
  • Evidence for PK non-equivalence of different brands of same drug & even same formulation
  • Always prescribe syrups in ml, NEVER as tsf
  • Always mention the strength of the syrup prescribed
  • DO NOT use bottle caps, spoons for measuring syrups, ALWAYS use syringe
  • Shake syrup/ susp. bottle before use (esp. phenytoin) [7]

Common side effects of ASM

ASMSide effects
Sodium ValproateHepatotoxicity, thrombocytopenia, menstrual disturbances, weight gain, transient hair loss
CarbamazepineDrug rash, worsening school performance
OxcarbazepineSomnolence, vomiting, SIADH
PhenytoinCosmetic issues, bone problems, gum overgrowth, hirsutism, acne
PhenobarbitoneSedation, hyperactivity, cognitive impairment
LamotrigeneDrug rash, Stevens-Johnson Syndrome
LevateracetamBehavior changes
TopiramateLanguage deterioration, fever, acidosis

Patient with Phenytoin side effect

Special considerations with ASMs

Patient groupDrugs to be avoided/ cautious use
Adolescent FemalesPhenytoin, valproate
Cognitive dysfunctionPhenobarbitone, BZDs,Topiramate
Mitochondrial diseaseValproate
Eating disordersTopiramate
Active liver diseaseValproate
Morbid obesityValproate, pregabalin
Advanced renal failureGabapentin, Pregabalin

When to stop ASM?

  • The chances of remaining seizure free after medication withdrawal is similar whether a 2-year or 4-year seizure-free interval is used [8]
  • –Studies that have utilized a seizure-free interval of 1 year or less have reported higher recurrence risks [9]

Tapering ASMs

  • Acute symptomatic seizures
    • Taper after 3 seizure free months, if cause is abolished, over 4-6 weeks
  • Symptomatic/ Idiopathic epilepsy
    • Seizure free for at least 2 years
    • EEG normal
    • Taper slowly over 2-3 months
    • One drug at a time
    • Continue ‘epilepsy precautions’
    • Explain risk of recurrence

Counselling of parents

  • Recurrence risk
  • Risks versus benefits of antiepileptic drug initiation
  • Abortive therapy Injury prevention / Positioning
  • School considerations
  • Recreational activity

At home Advise to parents

Stay calm.

DOESDON’T
Stay with your child.Do not panic.
If possible, note the time the seizure starts and ends.Do not try to hold or restrain your child.
Loosen tight clothing.Do not put anything in your child's mouth.
Roll your child onto his side into the recovery position.Do not try to put your child into cool or lukewarm water to cool off.
Move your child away from potentially harmful objects eg. furniture with sharp corners, water/fire sources.
Place something soft under your child's head to stop their head hitting the floor.
Wipe off any secretions from nose and mouth.

Abortive Treatment

Steps to give Intranasal midazolam 

  • Put the child in recovery position as demonstrated
  • Gently insert the nozzle of the spray bottle into one of the nostrils of the child.
  • Press down on the nozzle to deliver the required number of puffs (as advised by the doctor) to each nostril.

Drug resistant epilepsy

Failure to achieve sustained seizure freedom by 2 antiepileptic drugs that are

  • Appropriately chosen
  • Well tolerated
  • Given in adequate dosages
  • Either as monotherapy or in combination

Management options in Drug refractory epilepsy

Epilepsy Surgery

Dietary Therapy: Ketogenic diet, Modified Atkins Diet, Low glycemic index treatment

Immune mediated epilepsies

  • Small but potentially treatable form of epilepsy
  • 2 general forms: focal and diffuse
  • Features – acute or subacute onset of seizures, in the context of encephalopathy, and inflammation of the central nervous system
  • Include: NMDAR/VGKC/GABAAR/GABABR/GAD/glycine receptor
  • First-line immune therapy: corticosteroids and IVIG or PEX.
  • Second-line therapy: rituximab or cyclophosphamide

Status epilepticus

A child brought seizuring to emergency department from extramural setting or seizure lasting more than 5 minutes or consecutive seizures without gaining of consciousness between the seizures

Status epilepticus

Conclusion

  • Make a clinical diagnosis of seizure type/ epilepsy syndrome
  • Domiciliary management of seizure
  • Select appropriate ASM
  • Use monotherapy & rational polytherapy
  • Look for ASM side effects
  • Identify and manage co-morbidities
  • Counselling & lifestyle related issues
  • Refer or consult when required

Reference

  • Fisher R, et al. Practical clinical definition of epilepsy. Epilepsia 2014; 55: 475-482
  • Continum (Minneap Minn) 2013;19(3):656-681, American Academy of Neurology
  • Gulati et al Annals of Indian Academy of Neurology, January-March 2016
  • Signs and symptoms of meningitis,Partially treated pyomeningitis, partially immunised child
  • Wang et al a review from the ILAE Imaging Taskforce. Epileptic Disord. 2020
  • Update on first unprovoked seizure in children and adults: A narrative review Jiménez-Villegas et al.Seizure – European Journal of Epilepsy
  • Indian Pediatr. 2002 Sep;39(9):826-9.Rationalization of an antiepileptic drug formulation.Gulati S, Sriram CS, Kalra V. Department of Pediatrics, All India Institue of Medical Sciences, New Delhi 110 029, India
  • Berg et al. Epilepsy: A Comprehensive Textbook. Philadelphia Lippincott-Raven, 1997;1275–1284
  • Braathen et al. Epilepsia 1997; 38:561–569

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