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Seizures in childhood
1. SEIZURES IN CHILDHOOD
- DR CHAKKARAVARTHY R K
- MODERATOR – DR ASHISH SAHANI
- SRI BALAJI ACTION MEDICAL INSTITUTE
2. A seizure is a transient occurrence of signs or symptoms resulting from abnormal excessive or synchronous
neuronal activity in the brain.
Epilepsy is a disorder of brain characterized by an enduring predisposition to generate seizures and by the
neurobiologic, cognitive, psychological, and social consequences of this condition.
A seizure disorder is a general term that is usually used to include any one of several disorders including epilepsy,
febrile seizures and symptomatic seizures secondary to metabolic, infectious, or other etiologies.
3. Epilepsy has been defined as 1) 2 or more unprovoked seizures occurring more than 24 hours apart or 2)
unprovoked or reflex seizure with a probability of recurrent of at least 60% or higher over the subsequent years
or 3) diagnosis of an epilepsy syndrome.
An epileptic encephalopathy is an epilepsy syndrome in which the severe EEG abnormality is thought to result in
cognitive and other impairments in the patient.
4.
5. Seizures can be
• Provoked : seizure with an acute antecedent cause, such as:
• CNS infection (meningitis, encephalitis)
• Trauma
• Metabolic abnormality (abnormal levels of glucose, sodium)
• Toxic exposure (drugs, alcohol)
• Fever
• Unprovoked seizure: no immediate provoking factor
6. • A cause is identifiable in < 20% of children with seizures.
• Other causes of seizures include:
• Brain malformations
• Genetic disorders
• Disorders of metabolism
• Traumatic or previous infectious injury of the brain
• Neoplasms
• Neurodevelopmental abnormalities make it more likely a cause will be identified.
7. FEBRILE SEIZURES
Febrile seizures are seizures that occur between the ages of 6 and 60 months (peak 12 – 18 months) with a
temperature of 38oC (100.4oF) or higher, that are not the result of CNS infection or any metabolic imbalance, and
that occur in the absence of a history of prior afebrile seizures.
A simple febrile seizure is primary generalized, usually tonic clonic, attack associated with fever, lasting for a
maximum of 15 mins and not recurrent within a 24 hour period.
A complex febrile seizure is more prolonged (> 15 mins) and or/is focal and or recurs within 24 hours.
Febrile status epilepticus is a febrile seizure lasting longer than 30 mins.
8.
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11. Management includes definitive diagnosis, restraint in investigations, treatment of acute episode, prophylaxis for
future episodes and family counselling.
Lumbar puncture should be done in children with a suspected meningitis, especially in infants and EEG and
neuroimaging have no role in simple febrile seizures.
Parents can be taught to use rectal liquid diazepam (0.5 mg/kg) or buccal or nasal(12,15) midazolam (0.3 mg/kg)
for acute termination of seizures that last for two minutes or more.
Intermittent prophylaxis with oral clobazam in a dose of 0.75 mg/kg for 2-3 days in 2 divided doses during fever is
useful to prevent recurrence.
Febrile status, complex and recurrent febrile seizures (> 6 per year in spite of intermittent prophylaxis) may need
EEG, neuroimaging and continuous prophylaxis with AED. Phenobarbitone and valproate may be used in infants
and older children respectively, for 1-2 years.
12.
13.
14. BENIGN EPILEPSY SYNDROMES WITH FOCAL SEIZURES
The most common syndrome is Benign childhood Epilepsy with Centrotemporal Spikes (BECTS).
It typically starts during childhood (3 – 10 years).
Child wakes up at night due to focal seizure with preserved awareness causing buccal and throat tingling and
tonic or clonic contractions of one side of the face.
EEG typically shows wide based centrotemporal spikes that are markedly increased during sleep and drowsiness.
Patients respond very well to oxcarbazepine and carbamazepine.
15. Benign epilepsy with occipital spikes (Panayiotopoulos type) manifests as focal seizures with impaired
awareness with severe nocturnal vomiting, followed by eye deviation and status epilepticus and occur in early
childhood.
This syndrome has excellent outcome and treatment with carbamazepine and valproate are preferred for long
term therapy.
16. SEVERE EPILEPSY SYNDROMES WITH FOCAL SEIZURES
Epilepsy of infancy with migrating focal seizures occurs in infants as multifocal severe partial seizures with
progressive mental regression and cerebral atrophy.
Brain malformations causing focal epilepsy include focal cortical dysplasia, sturge weber syndrome, tuberous
sclerosis and congenital tumors.
These intractable seizures can be focal with or without impaired awareness, focal to bilateral tonic clonic
seizures.
These secondary generalized seizures predominate and mimics the generalized epilepsy syndrome of Lennox –
Gestaut Syndrome (LGS) and hence termed as pseudo – LGS.
17. BENIGN GENERALIZED EPILEPSIES
Childhood absence epilepsy (mid – childhood)
Benign myoclonic epilepsy of infancy (first year of life)
Febrile seizures plus syndrome
Juvenile myoclonic epilepsy (early adolescence)
Photoparoxysmal epilepsy
18. SEVERE GENERALIZED EPILEPSIES
Severe generalized epilepsies are associated with intractable seizures and developmental delay.
Early myoclonic infantile encephalopathy – first 2 months of life – myoclonic seizures – burst suppression on EEG
– caused by inborn error of metabolism – nonketotic hyperglycinemia.
Early infantile epileptic encephalopathy (Ohtahara syndrome) – first 2 months of life – tonic seizures – caused
by brain malformations.
19. Dravet syndrome is caused by mutations in SCN1A and onset occurs in infancy, initially characterized by febrile
and afebrile unilateral clonic seizures that recur every 1 or 2 months.
During the second year, myoclonus, absence seizures occur frequently and developmental delay usually follows.
West syndrome starts between ages of 2 and 12 months and consists of a triad of infantile epileptic spasms,
developmental regression and EEG picture called hypsarrhythmia (high voltage, slow, chaotic, background with
multifocal spikes).
Lennox – Gestaut syndrome starts between ages of 2 and 10 years and consists of a triad of multiple seizure
types, developmental regression and EEG abnormalities.
20. Landau – Kleffner syndrome is characterized by loss of language skills and by verbal auditory agnosia in a
previously normal child.
Seizures can be focal with or without preserved awareness, focal to bilateral tonic clonic, atypical absences and
occasionally myoclonic seizures.
Spike discharges are more apparent during non REM sleep and hence EEG should be done during sleep.
CT and MRI brain yields normal results.
For the therapy of aphasia, nocturnal diazepam along with oral prednisone is used as first line drugs.
If the seizures persist, then IV immunoglobulins should be considered.
Speech therapy should be initiated.
21. EPILEPSY SYNDROMES BASED ON AGE AT PRESENTATION
NEONATAL /
INFANTILE
ONSET
SYNDROME
CHILDHOOD
ONSET
SYNDROME
Benign familial neonatal seizures Childhood absence epilepsy
Early myoclonic encephalopathy Epilepsy with myoclonic absences
Ohtahara syndrome Lennox – Gastaut syndrome
Epilepsy in infancy with migrating
focal seizures
Benign childhood epilepsy with
centrotemporal spikes
West syndrome Mesial temporal lobe epilepsy
Dravet syndrome Rasmussen syndrome
Benign familial and non familial
infantile epilepsy
Epileptic encephalopathy with
electrical status epilepticus in sleep
Myoclonic epilepsy in infancy Epilepsy with eyelid myoclonia
22. JUVENILE
ONSET
SYNDROME
VARIABLE
AGE OF
ONSET
SYNDROME
Juvenile absence epilepsy Mesial temporal lobe epilepsy
Juvenile myoclonic epilepsy Startle epilepsy
Epilepsy with generalized tonic
clonic seizures
Reflex seizures
Idiopathic photosensitive occipital
lobe epilepsy
Drug or chemically induced seizures
Progressive myoclonic epilepsies Immediate and early posttraumatic
seizures
23. MECHANISMS OF EPILEPSY
Four distinct sequential processes participate in the pathophysiology of epilepsy.
1. Underlying etiology - pathologic process that can disrupt neuronal function and connectivity and that eventually
leads to second process
2. Epileptogenesis , a mechanism through which the brain or part of it, turns epileptic
3. Epileptic state of increased excitability caused by dysregulation between glutamatergic excitation and GABAergic
inhibition creating a seizure focus or network
4. Seizure related neuronal injury
24.
25. MANAGEMENT OF NEWLY DIAGNOSED EPILEPSY
Long term AED should be started after second seizure.
The aim of treatment is complete control of seizures without significant side effects.
All drugs are started in low doses and increased gradually up to a maximum dose till seizure control is
achieved or side effects appear.
Dosage needs to be adjusted to the child’s daily activity. Extended release formulations in twice a day
dosing are preferable.
If no control is obtained with maximum doses of the first drug, then a second first line drug is initiated
and the first drug tapered.
If partial control is achieved, then a second AED should be added to obtain control.
26. A seizure diary should be kept by the parents.
Therapeutic drug monitoring is useful in only few situations, including breakthrough or refractory seizures, to
assess compliance, for diagnosis of clinical toxicity.
In most epilepsy, AED is withdrawn after 2 year of seizure freedom.
Adolescent onset, remote symptomatic epilepsy and abnormal EEG after 2 years are predictors of relapse,
warranting drug withdrawal after 4 years.
Drug withdrawal is over 3-6 months and one drug at a time in cases of polytherapy.
27. COMMONLY USED ANTI EPILEPTIC DRUGS
MEDICATION FDA APPROVAL DAILY DOSE (mg/kg/day) SIDE EFFECTS
Phenobarbitone Myoclonic, focal and tonic clonic
seizures and status (all ages)
<5 years 3 – 5
>5 years 2 – 3
Neurotoxicity, hyperactivity,
insomnia, liver toxicity, Stevens –
Johnson syndrome
Phenytoin Focal and tonic clonic seizures
and status (all ages)
<3 years 8 – 10
>3 years 4 – 7
Gingival hyperplasia, hirsutism,
nystagmus, ataxia, liver toxicity,
Stevens – Johnson syndrome
Valproate Absence, myoclonic, focal and
tonic clonic seizures (age > 2
years)
15 – 40
(≤ 60 mg/kg/day)
Weight gain, tremor, alopecia, loss
of appetite, menstrual
irregularities, liver and pancreatic
toxicity
carbamazepine Focal and GTC (all ages) 10 – 20 Tics, transient leucopenia, liver
toxicity, Stevens – Johnson
syndrome
oxcarbazepine Focal seizures (> 2 years) 20 – 60 Somnolence, headache, dizziness
29. KETOGENIC DIET IN EPILEPSY
The ketogenic diet (KD) is a stringently controlled high fat and low protein/carbohydrate diet given with/without
a restricted fluid intake to maintain ketosis on a long term basis.
It is more efficacious than newer AEDs in controlling refractory seizures and is more cost effective.
It can be used with both non-vegetarian and vegetarian diets at any age and for all types of seizures.
It can be tried in all children above the age of 1 year with drug-resistant epilepsy, especially those who are not a
surgical candidates or where surgery cannot be performed due to availability/affordability issues.
30. Referral to centers providing the KD should be considered once adequate trials of three AEDs have failed,
suggestive of drug resistant epilepsy.
Adverse effects include GI disturbances, acidosis, increased susceptibility to infections, drowsiness, weight loss,
nutritional deficiencies and rarely, renal calculi and pancreatitis.
The diet should be considered a failure if there is no benefit in 3-6 months and it should be discontinued after
this time. In responders, it should be continued for 2-3year after which it is gradually tapered.
31. SURGICALLY REMEDIABLE SYNDROMES
If a patient has failed three drugs, the chance of achieving seizure freedom using AEDs is generally <10%.
Proper evaluation for surgery is necessary as soon as patient fails two or three AEDs, usually within 2 year of
onset of epilepsy and often sooner than 2 years.
Focal resection of the epileptogenic zone is the most common procedure.
Hemispherectomy is used for diffuse hemispheric lesions in cases such as Rasmussen encephalitis, hemispheric
epilepsies with pre existing contralateral hemiplegia and large unilateral gliotic regions / atrophy.
32. Common lesions like developmental tumors, cortical dysplasias, AVMs require lesionectomy.
In Lennox – Gastaut syndrome, corpus callosotomy is used as a palliative cure for drop attacks.
Responsive neurostimulation is a technique that has been used in adults with epilepsy – it is done by implanting a
subdural or deep electrode to monitor seizure activity on a long term basis to detect and abort the seizures.
Gamma knife stereotactic radiosurgery is less invasive surgical procedure that uses a gamma radiation beam to
ablate the epileptic areas in the cortex.
Vagus nerve stimulation is often used for drug resistant epilepsy and it is palliative.
33. TREATABLE METABOLIC ETIOLOGIES LEADING TO SEIZURES
ETIOLOGY CLUES TREATMENT
Pyridoxine dependent or
pyridoxal – 5 – phosphate
dependent epilepsy
Early onset refractory epilepsy,
Encephalopathy, Developmental delay
Pyridoxine supplementation (100 mg orally or
iv) and pyridoxal phosphate (enteral
administration of 50mg/kg/day every 6 hour )
Biotinidase deficiency Early onset epilepsy, Developmental
delay, Skin rash, hearing and vision loss
Biotin supplementation
Glucose transporter
deficiency (GLUT – 1)
Early onset absence seizures,
Microcephaly, ataxia, Developmental
delay
Ketogenic diet
Cerebral folate deficiency Intractable generalized tonic clonic
seizures in infancy or childhood
Folinic acid (1 – 3 mg/kg/day)
Serine deficiency Intractable epilepsy, microcephaly,
Developmental delay
L – serine supplementation
Late infantile neuronal ceroid
lipofuscinosis (CLN 2)
Myoclonic epilepsy, Developmental
delay, vision loss
Cerliponase alfa (recombinant tripeptidyl
peptidase 1)
34. COMORBIDITIES IN CHILDREN WITH EPILEPSY
Intellectual disability (25%)
Learning disabilities (50%)
Attention deficit hyperactivity disorder (30%)
Autism (risk is 7 fold higher in children with epilepsy)
Anxiety (25%)
Depression (20%)
Behavior problems
Sleep problems
35. SUDDEN UNEXPECTED DEATH IN EPILEPSY (SUDEP)
SUDEP is a rare but devastating complication of epilepsy and is responsible for 17% of deaths in patients with
epilepsy.
Risk factors include more than three AEDs, male gender, young age at epilepsy onset, developmental delay, poor
AED compliance, nocturnal seizures, poorly controlled convulsive seizures, high frequency of seizures and
epilepsy for > 30 years in adults.
Patients are usually found dead in their bed in a prone position with evidence suggesting a recent seizure.
It is currently recommended to counsel the patients and family regarding SUDEP, even if the topic is not
comfortable to talk about.
38. Seizures are the most important and common indicator of significant neurologic dysfunction in the
neonatal period.
Seizure incidence is higher during this period than in any other period in life:
57.5/1,000 in infants with birth weights <1,500 g 2.8/1,000 in infants weighing between 2,500 and
3,999 g have seizures.
39. PATHOPHYSIOLOGY
Immature brain more excitable more liable for seizures.
Defective balance between excitatory and inhibitory neurotransmission.
5 main types of neonatal seizures:
1. Subtle
2. Tonic
3. Clonic
4. Spasms
5. Myoclonic
40. SUBTLE SEIZURES
Subtle seizures include:
1. Transient eye deviations, nystagmus, blinking,
2. Mouthing,
3. Abnormal extremity movements (rowing, swimming, bicycling, pedaling, and stepping),
4. Fluctuations in heart rate, hypertension episodes.
5. Apnea.
Subtle seizures occur more commonly in premature than in full-term infants.
41. TONIC SEIZURES
Tonic seizures can be focal or generalized (generalized are more common).
Focal tonic seizures include persistent posturing of a limb or neck in an asymmetric way often with persistent
horizontal eye deviation.
Generalized tonic seizures are bilateral tonic limb extension or tonic flexion of upper extremities often
associated with tonic extension of lower extremities.
CLONIC SEIZURES:
Clonic seizures can be focal or multifocal.
Multifocal clonic seizures incorporate several body parts and are migratory in nature.
Generalized clonic seizures, which are bilateral, symmetrical, and synchronous, are uncommon in the neonatal
period .
42. SPASMS
Spasms are sudden generalized jerks lasting 1-2 sec that are distinguished from generalized tonic spells by their
shorter duration and by the fact that spasms are usually associated with a single, very brief, generalized
discharge.
MYOCLONIC SEIZURES:
Myoclonic seizures are divided into focal, multifocal, and generalized types.
Myoclonic seizures can be distinguished from clonic seizures by the rapidity of the jerks and by their lack of
rhythmicity.
Focal myoclonic seizures affect the flexor muscles of the upper extremities.
Multifocal myoclonic movements involve asynchronous twitching of several parts of the body.
Generalized myoclonic seizures involve bilateral jerking.
46. ETIOLOGY
Hypoxic ischemic encephalopathy (50 – 60 %) Most common cause of neonatal seizure.
Vascular events (10 -20 %)
Intracranial infection (5-10%)
Brain malformation (5-10%)
Metabolic disturbances
Drugs ( withdrawal or toxicity)
Neonatal seizure syndromes : rare . AD.
47. DIAGNOSIS
History: Prenatal and postnatal history
Careful neurologic examination
Investigations: complete blood count, serum level of glucose, sodium, magnesium, calcium, blood urea nitrogen,
bilirubin, blood and urine culture, serological tests for TORCH infections and specific test for inborn error of
metabolism if suspected.
48. Lumbar puncture is indicated in virtually all neonates with seizures, unless the cause is obviously related to a
metabolic disorder such as hypoglycemia or hypocalcemia which usually respond promptly to appropriate
therapy.
LP may reveal features of meningitis. Bloody CSF may indicate SAH.
Electroencephalography is considered as a main tool for diagnosis.
Other investigations include USG cranium, CT or MRI brain.
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50. DURATION OF THERAPY
The duration of therapy is related to the risk of developing epilepsy later in infants suffering from neonatal
seizures, neurologic examination, etiology of the seizures and EEG at the time of discharge.
If the EEG before the time of discharge doesn’t show evidence of epileptiform activity, medications are usually
tapered at that time.
If the EEG remains paroxysmal, the decision is usually delayed until several months after discharge.
51. PROGNOSIS
EEG was found to be highly associated with the outcome in neonatal seizures.
Prolonged electrographic seizures (>10 min / hour), multifocal periodic electrographic discharges and spread of
electrographic seizures to the contralateral hemisphere are correlated with a poorer outcome.
Underlying etiology is the major determinant of outcome.
Seizures secondary to HIE have a 50% chance of developing normally whereas seizures secondary to primary
subarachnoid hemorrhage or hypocalcemia have a much better prognosis.
Overall mortality rates have decreased from 40% to 20%.
52. STATUS EPILEPTICUS
The ILAE has redefined the definition of SE to reflect the time at which the treatment to be initiated (t1) and time
at which continuous seizure activity leads to long term sequelae (t2) such as neuronal injury, depending on type
of SE.
For generalized tonic clonic seizures, SE is defined as continuous convulsive activity or recurrent generalized
convulsive seizure activity without regaining of consciousness (t1 = 5 min, t2 ≥ 30 min).
The definition differs for focal seizures with impaired awareness (t1 = 10 min, t2 = 30 min) and absence SE (t1 = 10
– 15 min, t2 = unknown).
The most common form of SE is convulsive status epilepticus.
53. Incidence of SE ranges between 10 and 60 per 100,000 population in various studies.
SE is most common in children younger than 5 years of age.
Febrile SE is the most common type of SE in children.
Non convulsive SE manifests as a confusional state, dementia, hyperactivity with behavioral problems, fluctuating
impairment of consciousness , paranoia, hallucinations, fluctuating mental status, aggressiveness and or
psychotic symptoms.
54. Refractory SE is SE that has failed to respond to therapy, usually with at least two medications (such as
benzodiazepine and other medication).
Super refractory SE is SE that has failed to resolve, or recurs within 24hr or more despite therapy that includes a
continuous infusion such as midazolam and or pentobarbital.
Devastating epileptic encephalopathy in school age children (DESC), also called as fever induced refractory
epileptic encephalopathy in school age children (FIRES) is a syndrome of refractory SE that is associated with
acute febrile infections, appears to be highly drug resistant but is often responsive to ketogenic diet.
55. ETIOLOGY
New onset epilepsy
Metabolic abnormalities
Acute head trauma
Encephalitis / meningitis
Ischemic / hemorrhagic stroke
Drug intoxication in children and drug and alcohol
abuse in adolescents.
Drug withdrawal or overdose in patients taking AEDs
Folinic acid and pyridoxine and pyridoxal phosphate
dependency
Inborn errors of metabolism
Brain tumors
Systemic conditions such as hypertensive, renal or
hepatic encephalopathy
56. MECHANISMS OF SE
1. Failure of desensitization of glutamate receptors persistence of increased excitability.
2. Reduction of GABA mediated inhibition
3. During SE, there is an increased cerebral metabolic rate and a compensatory increase in cerebral blood flow that,
after approximately 30 mins, is not able to keep up with the increasing cerebral metabolic rate inadequate
cerebral oxygen tensions neuronal injury resulting from SE.
60. `
Non epileptic paroxysmal disorders are classified according to age at presentation and clinical manifestations.
1. Syncope and other generalized paroxysms
2. Movement disorders and other paroxysmal movements and postures
3. Oculomotor and visual hallucinations
4. Sleep related disorders.
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67. REFERENCES
Nelson Textbook of Pediatrics, 21st edition.
Fine A, Wirrell EC. Seizures in Children. Pediatrics in Review. 2020 Jul 1;41(7):321-47.
Expert Committee on Pediatric Epilepsy I. Guidelines for diagnosis and management of childhood epilepsy. Indian
pediatrics. 2009 Aug;46(8):681.
International League against Epilepsy (ILAE) Guidelines.
American Epilepsy Society Guidelines.
