1. Epilepsy in children Amira Masri Prof of child neurology
Faculty of medicine –The university of Jordan

2. Objectives History Epidemiology
Definitions : seizure , epilepsy , febrile convulsion , status epilepticus ,epileptic encephalopathy
Classification
Aetiology
Treatment
Outcome

3. History of epilepsy
Epilepsy : comes from the latin word epilepsia which means : to be ceased , to be attacked by surprise
Hippocrate 400 B.C.: the sacred disease
Ibn Sina +Al Tabari :1000 years ago =Al Saraa, disease of the brain

4. Epidemiology
incidence rates of epilepsy in childhood :0.5 to 8 per 1,000
%: experience at least one afebrile seizure by age adolescence.
Of all children, 3 - 5% will have a single febrile seizure
30 %: will have additional febrile seizures
3 – 6% of those with febrile seizures will develop afebrile seizures or epilepsy
3.6% risk of experiencing at least one seizure in an 80-year lifespan
focal seizures (with or without impairment of awareness) are the most common seizure type in all age groups and account for more than 50 percent of all seizures in children
Focal seizures with alterations of awareness are the most common subtype
Uptodate 2019

5. Basic mechanisms
The basic mechanism of neuronal excitability is the action potential
Action potentials occur due to depolarization of the neuronal membrane
Membrane potential thus varies with
1-activation of ligand- gated channels :conductance is affected by binding to neurotransmitter
2- activation of voltage-gated channels: conductance is affected by changes in transmembrane potential; or with changes in intracellular ion compartmentalization.

6. various glutamate receptor subtypes and locations GABA receptors
GABA site
Barbiturate site
Benzodiazepine
site

7. Definitions Seizure Epilepsy Febrile convulsions
Epileptic encephalopathy
Status epilepticus

8. Seizure Disorder of cerebral function
characterized by sudden brief attacks of: loss of consciousness
-motor activity
-sensory phenomena
- inappropriate behavior
Caused by excessive discharge of cerebral neurons.

9. Epilepsy

10. At least two unprovoked (or reflex) seizures occurring > 24 h apart
Epilepsy is a disease of the brain defined by any of the following:
At least two unprovoked (or reflex) seizures occurring > 24 h apart
2.One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years
3.Diagnosis of an epilepsy syndrome
Epilepsy is considered to be resolved for the following individuals:
Those who had an age-dependent epilepsy syndrome but are now past the applicable age
Those who have remained seizure-free for the last 10 years, with no antiseizure medicines for the last 5 years

11. Febrile convulsion
A seizure in association with febrile illness in the absence of CNS or acute electrolyte imbalance in children >1 month of age without prior afebrile seizures
Age :6m-6years (peak 18 m )
2-5% of children
Most common form of seizures in children
Simple and complex

12. Epileptic encephalopathy
A condition in which the epileptiform abnormalities themselves are believed to contribute to the progressive disturbance of cerebral dysfunction.

13. Developmental and/or Epileptic encephalopathies
Epileptic activity itself
contributes to severe cognitive and behavioral impairment above and beyond that expected from the underlying pathology and that these can worsen over time
Berg et al 2010

14. Status epilepticus Emergency room definition : 5 minutes
shortening the required seizure duration from 30 min to 5 min
Why ??????
The longer SE persists:
1-the lower is the likelihood of spontaneous cessation
2-the harder it is to control
3-the higher is the risk of morbidity and mortality
Seizures that do not cease in 5-10min are less likely to terminate without intervention

15. Classification of epilepsy
1- According to the clinical picture : generalized ,focal 2 - According to the aetiology: genetic , structural , metabolic infections, immune, unknown. 3-According to the epilepsy syndrome: age of onset , type of seizures and EEG findings

16. International league against epilepsy website

18. Purpose of the new classification 2017: for clinical diagnosis
Transparent language: use words that mean what they say

19. Co-morbidities Seizure types Etiology Epilepsy types
Unknown
Immune
Infectious
Structural
Etiology
Metabolic
Genetic
Co-morbidities
Seizure types
Focal
onset
Generalized onset
Unknown onset
Epilepsy types
Focal
Generalized
Combined
& Focal
Unknown
Epilepsy Syndromes

20. Generalized seizures
Originate at some Originate at some point within and rapidly engage bilaterally distributed networks
Can include cortical and subcortical structures but not necessarily the entire cortex
Here is a diagram that shows a conceptual network for generalized seizures involving the corticothalamic circuitry. Theoretically a generalized seizure could start at different points in the network and engage bilaterally distributed networks. Thus a seizure could start frontally or even parietally.The key point is that a generalized seizure can start from a focal point. 20

21. Focal seizures Originate within net
Originate within networks limited to one hemisphere
May be discretely localized or more widely distributed.… 21

22. Free text can be added to characterise sz
Note
When a seizure type begins with ”focal, generalized or absence” then the word “onset” can be presumed

23. Pedalling grouped in hyperkinetic rather than automatisms (arbitrary)
Cognitive seizures
impaired language
other cognitive domains
positive features eg déjà vu, hallucinations, perceptual distortions
Emotional seizures: anxiety, fear, joy, etc

24. Aetiology Structural :example porencephalic cyst
Genetic :example : absence epilepsy
Metabolic : example :penylketonurea
Infection :example : meningitis
Immune :example :Rasmussen
Unknown

25. Tuberous Sclerosis GLUT1 deficiency Seizure types Etiology
Generalized onset
Unknown onset
Focal
onset
Structural
Genetic
Tuberous Sclerosis
Infectious
Metabolic
Immune
GLUT1 deficiency
Unknown

26. Tuberous sclerosis : 2 genes ( TSC1 and TSC2 )

27. Terms no longer used Complex partial Simple partial Partial Psychic
Dyscognitive
Secondarily generalized tonic- clonic

28. Genetic versus idiopathic
‘Idiopathic’ = presumed hereditary predisposition
Genetic ≠ inherited
Importance of de novo mutations in both mild and severe epilepsies
Critical problem of stigma in some parts of the world

29. Benign Self-limited Pharmacoresponsive Many epilepsies not benign
Childhood hood absence epilepsy : psychosocial impact
Benign epilepsy with centrotemporal spikes : learning concerns
Replaced by terms:
Self-limited
Pharmacoresponsive
No longer use
Malignant
Catastrophic

30. Changing Lexicon and Concepts for the Epilepsies
New Terminology
Old Terminology
Person with epilepsy
Epileptic
Epilepsy seizures
Epileptic seizures
Antiseizure medications
Antiepileptic drugs
Focal onset
Partial
Focal dyscognitive
Complex partial
Epileptic spasms
Infantile spasms
Genetic
Idiopathic
Structural-metabolic
Symptomatic
Unknown
Cryptogenic

31. Epilepsy syndromes

32. Epilepsy syndromes by age
NEONATAL
Benign familial neonatal epilepsy
Early myoclonic encephalopathy
Ohtahara syndrome
INFANCY
Epilepsy of infancy with migrating focal seizures
West syndrome (infantile spasms, hypsarrhythmia; to be distinguished from benign myoclonus of early infancy, a nonepilepsy)
Myoclonic epilepsy in infancy (benign Dravet variant)
Benign infantile epilepsy
Benign familial infantile epilepsy
Severe myoclonic epilepsy of infancy (classic Dravet syndrome)
Myoclonic encephalopathy in nonprogressive disorders
Epilepsy syndromes by age

33. Epilepsy syndromes by age
CHILDHOOD
Genetic epilepsy with febrile seizures plus (GEFS +; can begin in infancy)
Panayiotopoulos syndrome
Epilepsy with myoclonic atonic (previously astatic) seizures (Doose syndrome)
Benign epilepsy with centrotemporal spikes (BECTS, or benign rolandic epilepsy)
Autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE)
Late-onset childhood occipital epilepsy (Gastaut syndrome)
Epilepsy with myoclonic absences (Tassinari syndrome)
Lennox–Gastaut syndrome
Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)
Landau–Kleffner syndrome (LKS)
Childhood absence epilepsy (pyknolepsy)
Generalized epilepsy with eyelid myoclonia (Jeavons syndrome)*
ADOLESCENCE–ADULT
Juvenile absence epilepsy (JAE)
Juvenile myoclonic epilepsy (JME)
Epilepsy with generalized tonic-clonic seizures alone
Progressive myoclonus epilepsies (PME)
Autosomal-dominant epilepsy with auditory features
Other familial temporal lobe epilepsies
LESS SPECIFIC AGE RELATIONSHIP
Familial focal epilepsy with variable foci (childhood to adult)
Reflex epilepsies (e.g., photosensitive, audiogenic, or reading-induced seizures; may or may not coexist with spontaneous seizures)
Epilepsy syndromes by age

36. How to confirm the diagnosis
History + examination : most important = 30% of subjects diagnosed with epilepsy had been misdiagnosed and do not have epilepsy
Rule out disorders that mimic seizures
Role of neuroimaging : Brain MRI superior to CT scan
EEG:standard=positivity rate 60%
Sleep =positivity rate 90%

37. Misdiagnosis of epilepsy is common :Rule out epilepsy imitators
False tendency : think of epilepsy as a single disorder
Diagnosis : history , usually no confirmatory test: There is a large differential diagnosis
Many clinicians charged with diagnosing paroxysmal disorders do not have sufficient
knowledge of the clinical features of epileptic and non-epileptic seizure disorders
Abuse of EEG =overreading
Most clinicians with responsibility for diagnosing epilepsy do not have easy access to the full range of appropriate investigations.
There is a false perception that to miss a diagnosis of epilepsy carries grave risks

38. Differential diagnosis: epilepsy imitators
Huge list >36 disorders
Breath holding spells
GE reflux
cardiogenic syncope
Pseudoseizures
Benign infantile myoclonus
Migraine
Night terrors
Paroxysmal dyskinesisa
Self gratification
Somnambulism
hyperekplexia

39. When should we start ttt
First seizure : general rule :do not ttt (risk of recurrence 30% )
First prolong seizure (status ) : risk of recurrence same ( however higher risk of recurrence of prolonged seizures
Multiple seizures within 24 hours : considered first seizure : recurrence risk same

40. Recurrence of unprovoked seizures
First seizure : 40% will have recurrence
Second seizure : 80% will have recurrence
Recurrence usually within the first 6 m (first 2 years )
Recurrence : rare after 2 years

41. Evaluating a first non febrile seizure in children:
Laboratory tests :If suggestive historic or clinical findings such as vomiting, diarrhea, dehydration, or failure to return to baseline alertness. (Option)
Toxicology screening :if there is any question of drug exposure or substance abuse (option)
LP :if possible meningitis or encephalitis (option)
EEG : recommended for all :Establish Dx + recurrence risk
If a neuroimaging study is obtained, MRI is the preferred modality

42. Non urgent neuroimaging Urgent neuroimaging
in any age who exhibits a postictal focal deficit (Todd’s paresis) not quickly resolving
or who has not returned to baseline within several hours after the seizure
in any child with a significant cognitive or motor impairment of unknown etiology
unexplained abnormalities on neurologic examination
a seizure of partial (focal) onset with or without secondary generalization.
an EEG that does not represent a benign partial epilepsy of childhood or primary generalized epilepsy
children under 1 year of age.

43. Principles and goals of treatment
60-70% of children : seizure-free with no treatment or a low-to- moderate dose of monotherapy
30–40% : likely to continue to have seizures despite multiple AED
Seizure control with one AED and without adverse events
for some no treatment is appropriate
equilibrium between maximum seizure control with minimum adverse effects, to ensure the best quality of life

44. Which drug to use type of seizure + epileptic syndrome
Patient age
Presence of other associated diseases (eg :patients with kidney stones avoid topiramate + zoisamide, patients with psychiatric disorders avoid leveteracitam )
Most likely to be effective
Least likely to cause side effects
Evidence based approach

50. Which is better the old or new
In terms of efficacy : both same
If patient fails to respond to one drug due to lack of efficacy : the success with 2nd or 3rd drug is only 11%
Refractory epilepsy : 1/3 of patients

51. Refractory epilepsy : what to do ?
Other non pharmacological modalities
Ketogenic diet
Epilepsy surgery
Brain stem stimulation

52. Ketogenic diet Available since 1920
High fat (80%), low carbohydrate , adequate protein (20%)=results in ketosis
Supplemented with vitamins + calcium
Needs admission for few days to hospital : to induce ketosis
Common SE: non compliance , acidosis, constipation, failure to gain weight, increase cholesterol
Successful control of seizures :equal or surpasses that of AED
Children who become seizure free will continue to be seizure free even when diet is discontinued

53. Epilepsy surgery Lesionectomy Lobectomy Corpus callosotomy
Hemispherectomy
Multilobar resection
Multiple subpial transection

54. Vagal nerve stimulation
First implantation in humans :1988
FDA approved : 1997
Tech. : pacemaker behind left carotid ( electrode for regulation of stimulation)=transmit intermittent electrical stimulation to an electrode wrapped around the left vagus nerve

55. Mech.: stimulation with high frequency : desynchronisation of EEG ( anticonvulsant effect ), increase GABA , decrease excitatory a.a
Indication : pharmacoresistant epilepsy that is not candidate for surgery
Rarely causes seizures to remit completely
Decrease seizure frequency : 25-30%
Adjunctive ttt to AED

56. Deep brain stem stimulation

57. Prognosis of epilepsy in children
When to stop treatment
50% will outgrow their epilepsy and stop treatment
Syndromic approach to discontinuation of ttt.
Depends on epileptic syndrome
In general : 2 years seizure free

58. Thank you for supporting epilepsy