1. In the name of GOD

3. Seizure & epilepsy in children S. Inaloo Department of Pediatric Shiraz University of Medical Sciences

4. Definitions Seizure: the clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical or brain stem neurons Seizure: the clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical or brain stem neurons Epilepsy: two or more recurrent seizures with interval more than 24 hours unprovoked by systemic or acute neurologic insults Epilepsy: two or more recurrent seizures with interval more than 24 hours unprovoked by systemic or acute neurologic insults Convulsion : motor seizure Convulsion : motor seizure

5. Epidemiology of Seizures and Epilepsy Seizures Seizures Incidence: approximately 80/100,000 per year Incidence: approximately 80/100,000 per year Lifetime prevalence: 9% (1/3 benign febrile convulsions) Lifetime prevalence: 9% (1/3 benign febrile convulsions) Epilepsy Epilepsy Incidence: approximately 45/100,000 per year Incidence: approximately 45/100,000 per year Point prevalence: 0.5-1% Point prevalence: 0.5-1%

6. International League Against Epilepsy (ILAE) Classification of epilepsy

7. 1989 (ILAE) classification 1. Localization related epilepsy (focal or partial) a. Simple b. Complex c. Partial with secondary generalization 2. Generalize (convulsive – non convulsive) a. Absence (typical, atypical) b. Myoclonic c. Clonic d. Tonic e. Tonic clonic (grandmal) f. Atonic 3. Unclassified

8. Classification Primary (idiopathic) Secondary (symptomatic) Cryptogenic Reactive seizure (F.C, toxic, metabolic, infection, early post- trauma) Special syndromes

9. Diagnosis of seizure Clinical Hx: (aura, postictal, video monitoring) Clinical Hx: (aura, postictal, video monitoring) Repeated EEG EEG after sleep deprivation, hyperventilation, or 24 hr ambulatory EEG Prolactin

10. Questions Raised by a First Seizure Seizure or not? Seizure or not? Focal onset? Focal onset? Evidence of interictal CNS dysfunction? Evidence of interictal CNS dysfunction? Metabolic precipitant? Metabolic precipitant? Seizure type? Syndrome type? Seizure type? Syndrome type? Studies? Studies? Start AED? Start AED?

11. Seizure Precipitants Metabolic and Electrolyte Imbalance Metabolic and Electrolyte Imbalance Stimulant/other proconvulsant intoxication and medication Stimulant/other proconvulsant intoxication and medication Sedative or ethanol withdrawal Sedative or ethanol withdrawal Sleep deprivation Sleep deprivation Antiepileptic medication reduction or inadequate AED treatment Antiepileptic medication reduction or inadequate AED treatment Hormonal variations Hormonal variations Stress, excitation, fatigue Stress, excitation, fatigue HV, Alkalosis HV, Alkalosis Fever or systemic infection Fever or systemic infection Concussion and/or closed head injury Concussion and/or closed head injury

12. Evaluation of a First Seizure History, physical (HC, BP, ophtal, skin, CV, NE) History, physical (HC, BP, ophtal, skin, CV, NE) Blood tests: CBC, electrolytes, glucose, Calcium, Magnesium, phosphate, hepatic and renal function Blood tests: CBC, electrolytes, glucose, Calcium, Magnesium, phosphate, hepatic and renal function Lumbar puncture only if meningitis or encephalitis or subarachnoid hemorrhage suspected and potential for brain herniation is ruled out Lumbar puncture only if meningitis or encephalitis or subarachnoid hemorrhage suspected and potential for brain herniation is ruled out Blood or urine screen for drugs Blood or urine screen for drugs EEG EEG CT or MRI brain scan CT or MRI brain scan

13. Indication of CT or MRI 1. Abnl neurologic exam 2. Dysmorphic feature 3. Skin lesion 4. Focal EEG abnormalities (63%) * 5. Hx of neonatal seizure (100%) * 6. Hx of compatible with simple partial or complex partial seizure * 7. Before epileptic surgery 8. Sign of  ICP 9. Unresponsive to anticonvulsant 10. Change of seizure type 11. Seizure after trauma

14. EEG Abnormalities Background abnormalities: significant asymmetries and/or degree of slowing inappropriate for clinical state or age Background abnormalities: significant asymmetries and/or degree of slowing inappropriate for clinical state or age Interictal abnormalities associated with seizures and epilepsy Interictal abnormalities associated with seizures and epilepsy Spikes Spikes Sharp waves Sharp waves Spike-wave complexes Spike-wave complexes May be focal, lateralized, generalized May be focal, lateralized, generalized

15. Medical Treatment of First Seizure Whether to treat first seizure is controversial 16-62% will recur within 5 years 16-62% will recur within 5 years Relapse rate might be reduced by antiepileptic drug treatment Relapse rate might be reduced by antiepileptic drug treatment Abnormal imaging, abnormal neurological exam, abnormal EEG or family history increase relapse risk Abnormal imaging, abnormal neurological exam, abnormal EEG or family history increase relapse risk Quality of life issues are important Quality of life issues are important Reference: First Seizure Trial Group. Randomized Clinical Trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. Neurology 1993; 43 (3, part1): 478-483. Reference: Camfield P, Camfield C, Dooley J, Smith E, Garner B. A randomized study of carbamazepine versus no medication after a first unprovoked seizure in childhood. Neurology 1989; 39: 851-852.

16. Choosing Antiepileptic Drugs  Seizure type  Age and sex  Epilepsy syndrome  Pharmacokinetic profile  Interactions/other medical conditions  Efficacy  Expected adverse effects  Cost  Availability

17. Febrile seizure is the most common ped. neurologic problems incidence 3 – 5%  10%-15%

18. Definition Age (2 month-6 yr) Age (2 month-6 yr) Fever (Temp >38) Fever (Temp >38) No Hx of previous afebrile seizure No Hx of previous afebrile seizure No acute systemic metabolic abnormality that may produce convulsion No acute systemic metabolic abnormality that may produce convulsion No CNS infection or inflammation No CNS infection or inflammation

19. Simple Simple Febrile seizure Duration > 15 -30 min Complex > 1 episode / 24 hr Complex > 1 episode / 24 hr Focal seizure or todd’s Focal seizure or todd’s paralysis paralysis

20. Indication for Admission 1. Suspicion of a more serious underlying condition 2. Complex F.S 3. Age less than 18 months 4. Early review by a doctor is not possible 5. Home circumstance are inadequate or parents unable to cooperate

21. Investigations B.S ± calcium ± electrolyte B.S ± calcium ± electrolyte Age < 12m specially < 6 months Age < 12m specially < 6 months Lp Long lasting or otherwise atypical convulsion Lp Long lasting or otherwise atypical convulsion Faille promptly to recover full consciousness Faille promptly to recover full consciousness Suspicious to meningitis or encephalitis or subarachnoid Suspicious to meningitis or encephalitis or subarachnoid hemorrhage hemorrhage EEG EEG Neuroimaging Neuroimaging

22. Prognosis  single of FC 60-70% > 3 episodes 9% > 3 episodes 9% 2-3 episodes Others 2-3 episodes Others Risk of afebrile seizure  2-5%

23. Treatment - Long term Anti convulsant therapy (PB VPA)  2/3 in recurrence - PHT, CBZ not effective - Diazepam prophylaxy 1 mg/kg/day Divided Q 8 hr during febrile illness - Rectal diazepam 0.3-0.5 mg/kg/dose if seizure happen

24. Diazepam rectally during seizure Children 1-3 y/o or < 10 kg  5mg Children over 3 y/o and adult or > 10 kg  10mg if necessary repeated after 5 min.

26. Management of seizure (acute) 1. ABC 2. IV lineD/W 10% 5cc/kg 3. Diazepam IV 0.1-0.3 mg/kg 2mg/min or rectal 0.3 – 0.5 mg/kg rectal 0.3 – 0.5 mg/kg Dilanthin 15-30 mg/kg IV (1mg/kg/min) [N/S] 12 hr later 3-9 mg/kg Q 12yr Or phenobarbital 15-20 mg/kg over 10-30 min then 3- mg/kg Q12 hr

27. Seizure type Generalize Tonic Clonic Aura  partial seizure Postictal ± Drug  Carbamazepinlamotrigine Valporate, Topiramate Phenytoin Oxcarbazepin PrimidoneZonisamide Phenobarbital Levetiraceta

28. Absence (petitmal) Brief arrest of consciousness 5 – 10 sec20/day 5 – 10 sec20/day Aura ΘPostictal Θ automatism ± 64%  5-9 y/oF>M EEG 3CPS 90% HV 40% GTC70% Minor movement Drug  Ethosuximide, Valporate, Lamotrigine, Benzodiazepine, Levetiracetam, Topiramate, Zonisamide Carbamazepine & Phenytoin, aggravate, absence

30. Juvenile myoclonic (Janz) 30% absence  Brief myoclonic jerk early morning awake Age  15 y/oIQ  Nl 1/day EEG 3CPS  4-6 HZ/sec 1/3 photosensitive Drug  Valporate, Lamotrigine, Clonazepam, Levetiracetam, Topiramat, Zonisamide Carbamazepine & Phenytoin, lamotrigine, aggravate, myoclonic

32. Complex partial seizure Psychomotor seizure, temporal lobe epilepsy Focus  frontal, occipital, temporal Aura  automatism  Postictal ± Flushing or pallor, rubbing, staring,  LOC, nausea, vomiting, oral movement, dreaming, speech disorder, incontinence, aggressive activity Pathology  MTS, Tumor R/: CBZ, VPA, PHY, PMD, PB?, LMC, GBP, Tpx, VGB, Oxcarbazepine, Levetiracetam, zonisamide

33. Simple partial Most common form in child  versive EEG 1/3  nl Focal motor seizure  hemiplegic todd paralysis R/: CBZ, VPA, PHY, PMD, PB?, LMC, GBP, Tpx, VGB, Oxcarbazepine, Levetiracetam, zonisamide

35. Rolandic Most common idiopathic focal epilepsy Benign childhood epilepsy with centrotemporal spike sylvian epilepsy A.D. 10% of epilepsy Age 5-10 y/o (75%) less frequent  3-4 episode Aura  somatosensory  mouth & tongue speech arrest, or facial movement ¾  in sleep EEG  mid temporal spike R/: CBZ 2y or age 13-14 y.o

37. Benign occipital 15 m to 17 y.ovisual symptom EEG  near continous HV spike wave occipital (HVSW) or post temporal (close eye) Good prognosis recovered = 13 y/o Eye open Θ EEG Treatment: CBZ

38. Lennox Gastaut Syndrome (LGS) Mixed type seizure MR, NDD Spike wave 1.5-2.5 Hz, multiple spike, slow background VPA, LMC, TPX, FBM, KDG, IVIG, ACTH, Prednisolone, BNZ

39. Infantile spasm Flexion extension mixed 66% EEG hypsarrlythmia R/: ACTH, prednisolon, Vit B6, BZN, VGB VPA, LMC, TPx Cryptogenic Symptomatic (PKU, MSUD, T.S, Pyridoxin, urea cycle, HIE, CNS infection, CNS dysgenesis)

40. Abdominal epilepsy Periumblical pain 5-10 min  24-36 hr  awarness 1. Abnl EEG 2. Associated with other symptoms of epilepsy (cps) 3. Good response to AED

41. Follow-up Monitoring response of patients to medication Drug adverse effect Other work-up in follow-up? What time of DC drug?

42. Duration of therapy Dependent to Type of seizure Etiology of seizure Response to treatment At least two years Taper over 2-6 months

43. Discontinuing AEDs Seizure freedom for  2 years implies overall >60% chance of successful withdrawal in some epilepsy syndromes Seizure freedom for  2 years implies overall >60% chance of successful withdrawal in some epilepsy syndromes Favorable factors Favorable factors Control achieved easily on one drug at low dose Control achieved easily on one drug at low dose No previous unsuccessful attempts at withdrawal No previous unsuccessful attempts at withdrawal Normal neurologic exam and EEG Normal neurologic exam and EEG Primary generalized seizures except JME Primary generalized seizures except JME “ Benign ” syndrome “ Benign ” syndrome Consider relative risks/benefits (e.g., driving, pregnancy) Consider relative risks/benefits (e.g., driving, pregnancy)

44. Non-Drug Treatment/ Lifestyle Modifications Adequate sleep Adequate sleep Avoidance of alcohol, stimulants, etc. Avoidance of alcohol, stimulants, etc. Avoidance of known precipitants Avoidance of known precipitants Stress reduction — specific techniques Stress reduction — specific techniques

45. Other therapy Ketogenic Diet Ketogenic Diet Vagus nerve stimulation Vagus nerve stimulation Surgery Surgery IVIG IVIG Steroid Steroid

46. Differential Diagnosis of seizure Breath-holding spells Breath-holding spells Syncope Syncope Migraine Migraine Cerebral ischemia Cerebral ischemia Movement disorder (Tic, Chorea, …) Movement disorder (Tic, Chorea, …) Sleep disorder Sleep disorder Psychiatric disturbance Psychiatric disturbance

47. First Aid Tonic-Clonic Seizure Turn person on side with face turned toward ground to keep airway clear, protect from nearby hazards Turn person on side with face turned toward ground to keep airway clear, protect from nearby hazards Transfer to hospital needed for: Transfer to hospital needed for: Multiple seizures or status epilepticus Multiple seizures or status epilepticus Person is pregnant, injured, diabetic Person is pregnant, injured, diabetic New onset seizures New onset seizures DO NOT put any object in mouth or restrain DO NOT put any object in mouth or restrain