Epilepsy in children

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 • 0.5 - 1%: 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 depolarizationof 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

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 Generalized onset Unknown onset Focal onset Structural Genetic Epilepsy types Infectious Generalized Unknown Focal Combined Generalized & Focal Focal Metabolic Immune 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

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

22. 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. 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 • 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

31. Epilepsy syndromes

32. Epilepsy syndromes by age

33. Epilepsy syndromes by age

34. https://www.epilepsydiagnosis.org

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) • Toxicologyscreening :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. • anEEGthat 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 • Most likely to be effective • Least likely to cause side effects • Evidence based approach 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 )

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