1. SEIZURES, BRAIN DEVELOPMENT AND THEIR CONSEQUECES Agus Soedomo Department Of Neurology Faculty Of Medicine Sebelas Maret University / Dr. Moewardi General Hospital Surakarta

2. Outline  Introduction  Definition  Etiology  Pathogenesis  Consequence / Influences  Tackling / Prevention  Summary

3. Introduction  Seizures occur in 1-5% of infants  Seizures are triggered by an acute illness  Seizure in the new born  signal brain pathology  Neonates seizures  sign of acute neonatal encephalopathy  major risk factor for death and subsequent neurologic disability  Neurologist & neonatologist face a number in resolved facts & some controversies : define, monitor, treat seizures,& consequences  INFANT : neonates seizures – febrile seizures & status epilepticus

4. Seizures and Epilepsy Secondary Symptomatic Partial Age disease related Primary Idiopathic Partial General Age Related Transient Symptomatic Metabolic Toxic Non recurrentRecurrent ( Epilepsy )

5. Definition Definition of seizures  Time limited paroxysmal, that result from sudden, temporary change in brain dysfunction caused by abnormal, rhythmic, involuntary neuronal discharge (Clancy&Geyer, 2010)  Seizures are usually unpredictable  Seizures usually brief (<5 minutes) self terminating or stop spontaneously  Convulsion ictus, event, spell, attack, fit

6. Definition of Epilepsy  A disease as paroxysmal of cerebral dysfunction, characterized by spontaneous recurrence of unprovoked seizures ( at least 2 time per year ), ILAE, 1993  Seizures are symptoms, while epilepsy is a disease  Epilepsy is seizures disorder  Epilepsy is a syndrome disease

7. Each Epilepsy Syndrome is Determine Based on :  Type of seizure  Age at seizures onset  Family history  Physical examination  EEG findings  Neuroimaging findings

8. Definition of Febrile Seizures  A simple febrile seizure is generalized seizure occurring in infant or child between age of six months and five years, lasting less than 15 minutes and occurring only once in 24 hours. The child should not have an intracranial infection or a severe metabolic disturbances ( American Academy of Pediatrics Practice Parameter, 1999)

9.  A seizure occurring in childhood after one month of age, associated with a febrile illness not caused by an infection of central nervous system, without previous neonatal seizures or previous unprovoked seizures and not meeting criteria for other acute symptomatic seizures ( ILAE, 1993 )

10. Three Critical Element of Febrile Seizures  Age of first seizures onset  Temperature of fever  Type seizures

11. Neonatal Seizures  Under recognized  Especially in sick neonates  Often difficult to treat  Manifestation of underlying neurological conditions  Most common caused by HIE : 50 – 60%

12. Epidemiology  Seizures are common in human  Incidence ± 80 / 100.000 population  Overall risk of epilepsy of 1% - 3%  3% - 4% at least one FS before 7 years  Incidence FS depend of regional variation

13. Cumulative Incidence of FS  United State : 2 – 5%  South America : 2 – 5%  Western Europe : 2 – 5%  India : 5 – 10%  Japan : 8,8%  Guam : 14% ( Hauser WA at Liu at al, 2010 )

14. Prevalence of Neonates Seizure (Jkt)  RS Ciptomangunkusuma : 0,9%  RS Harapan Kita : 0,3%  RS Padmawati : 0,3% Daisy et al, 2006

15. Etiology  Toxic / metabolic cause of seizures  Drug intoxication  Drug withdrawal  Electrolyte  Heavy metals : lead and mercury  Hyperosmolarity  Hypoxia

16. Causes of Fever in Febrile Seizures  Upper Respiratory Tract Infection : 38%  Otitis Media : 23%  Pneumonia :15%  Gastroenteritis : 7%  Roseola Infantum : 5%  Non Infectious Illness : 12%

17. Genetic Causes of Epilepsy  Aminoacidurias  Channelopathies  Lisosomal Storage Disease  Phakomatosis  Phenylketonuria  Sturge Weber Syndrome

18. Pathogenesis  Seizure arise secondary to a number etiologies  Idiopathic  Cryptogenetic  Symptomatic

19. Idiopathic  No apparent cause  No brain lesion  Presumably - genetic alterations in brain excitability  Knowledge about the cause of epilepsy increase  the number of idiopathic cases will diminished

20. Cryptogenic  Cases of epilepsy where the cause is unknown, but lesion & dysfunction pathogenesis are presumed  The lesion of temporal lobe epilepsy is mesial temporal sclerosis but the cause of the lesion is unknown

21. Symptomatic  Cases of epilepsy in known which the disorder is due to a cause some but not all, symptomatic cause are also lesional, meaning that an identified structural brain abnormality or lesion is present

22. Trauma Early Post Traumatic Seizures :  Intracranial hemorrhage  Focal neurological deficits  Post traumatic amnesia > 24 hours  Linier skull fractures Late post traumatic seizures  Some as above, but :  Depressed skull fractures  Injury after age 16 years

23. Congenital Malformations  Structural anomalies  Genetic cause of epilepsy ( table )  Not associated with structural malformations

24. Infection  Meningitis, encephalitis  fever  Bacterial  abscess formations  HSV,  seizures & catastrophic  CMV, various viral, fungal & toxoplasmosis Developing seizures

25.  Cerebral ischemia  Common cause of seizures in the neonates but uncommon in older pediatric populations  Tumor slow growing  seizures  Supratentorial more frequently than cerebellar or brain stem tumor  Toxic metabolic  Table  The derengement can cause seizures can worsen pre-existing epilepsy

26. The Pathophysiology of Febrile Seizure Unknowns  Possible three pictures interact :  Immature brain  Fever  Genetic predisposition

27. Consequences / Influences  Direct effect of seizures in human brain are difficult to detect  Recently :  Animal studies  Neuroimaging examination  Amplitude integrated EEG or video EEG monitoring

28. Influence of Neonatal Seizures  Recurrent neonatal seizures  reduced cell number, but not causing cell death  Recurrent seizures during early life pronounced effect on brain development are different from those occurring in mature brain  Brain of neonatal seizures are smaller  The long term functional consequences can be detrimental

29. Influence of Febrile Seizures  Recurrent febrile seizures  Recurrent later epilepsy

30. Risk Factors for Recurrent Febrile Seizures  Young age of onset, the earlier, the greater  Relative low fever, the lower, the greater  Family history : first degree relative  Duration between fever onset & seizure onset, the shorter, the greater

31. Risk Factors for Later Epilepsy  Abnormal neurological or development status prior to onset  Family history of a febrile seizures  Complex febrile seizures  Onset FS after the age of 5 years  no risk  15% of children with epilepsy have one or more preceding FS  Less 7% FS developed epilepsy  The risk were higher : family history of epilepsy, cerebral palsy, or low APGAR score

32. Tackling / Prevention  Neonatal seizures and complex febrile seizures may have a global effect on brain development, especially in immature brain  Neonatal seizure must early detect and be able effective therapy especially for underlying etiologies  Febrile seizure are usually brief and self limited but if the convulsion is prolonged, airway & oxygenation should be kept  After resolution of neonatal seizures still be needed less frequent and shorter phenobarbital treatment, although there remains considerable variation in practice

33. Summary  Seizure in infant : neonatal seizures, febrile seizures and status epilepticus  Seizures are symptom, while epilepsy is a disease  Incidence FS depend on regional variation  Etiologies seizures : toxic / metabolic, and genetic causes  Pathogenesis is divided into : idiopathic, symptomatic, and cryptogenic  Consequence of seizures are detected by animal study, neuroimaging examination and video EEG monitoring  Neonatal seizure and complex febrile seizure may have a global effect on brain development  Neonatal seizures must early detected and treated

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