Seizures and you. Michael B. Lloyd, MD

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1 Seizures and you Michael B. Lloyd, MD

2

3 Objectives Definition Epidemiology Classification Epileptic syndromes Differential and recognition Work-up Treatment Frequently asked questions

4 Definition Sudden discharge of electrical activity in the brain

5 Definitions An epileptic disorder is a chronic neurological condition characterized by recurrent epileptic seizures An epileptic syndrome consists of a complex of signs and symptoms that occur together more than by chance and define a unique epilepsy condition An epileptic disease is a pathologic condition with a single specific, well-defined etiology G.L. Holmes, 2003

6 Epidemiology 4% of children will have at least one generalized seizure prior to the fifth birthday Majority will be benign febrile convulsions

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8 Classification A. Focal Seizure 1. partial seizure - local cortical disruption 2. complex-partial seizure - impairment of consciousness 3. partial seizure with secondary generalization

9 Classification 2 B. Generalized seizures 1. absence - consider typical vs. atypical 2. myoclonic - sudden brief shocklike contraction 3. clonic - symmetrical jerking of extremity 4. tonic seizure - increase in tone 5. tonic/clonic seizure 6. atonic seizure

10 Epileptic syndromes A. focal/local/partial 1.benign childhood epilepsy with centrotemporal spikes (rolandic) 2. childhood epilepsy with occipital paroxysms - hallucinations, hemianopsia, amaurosis, visual distraction

11 Epilepsy syndromes 2 B. generalized 1. benign neonatal familial convulsions 2. benign idiopathic convulsions 3. benign myoclonic epilepsy of infancy 4. childhood or juvenile absence seizures 5. infantile spasms 6. Lennox-Gastaut syndrome

12 Epilepsy syndrome 3 7. epilepsy with myoclonic-astatic seizures 8. febrile convulsions 9. juvenile myoclonic epilepsy

13 Differential Includes: Breath holding spells - behavioral Syncope - vasovagal phenomenon, etc. Gastro-esophageal reflux Prolonged qt syndrome Psychogenic seizures - psychiatric Medication effects/substance abuse Other neurological condition migraine, etc.

14 Recognition of Seizure Ask for a description of the seizure before, during, and after 1. Before - recent illness, sleep deprivation or medication 2. During - gradual or sudden onset, appearance of seizure, duration, ability to talk during seizure, responsiveness during seizure 3. After post-ictal state, confusion, lethargy, abnormal speech, weakness, injuries

15 Recognition 2 Signalment Age, sex, previous health status, developmental status Ask when did seizure occur? 1. Awake or asleep especially upon awakening 2. Time of day 3. History of present or recent illness

16 Recognition 3 Is there a family history? DON T OVERLOOK THIS! A family history of seizures or epilepsy in otherwise healthy child may indicate a genetic epilepsy syndrome

17 Recognition 4 Was seizure associated with any particular activity? 1. JME absence seizures while using computers or riding in car 2. Seizures can be associated with reading, music or eating 3. Hair grooming syncope 4. Prolonged qt syndrome provoked by startle or exercise

18 Work-up of seizures A. Diagnostic Lab workup 1. cbc, electrolytes, bun, creatine, glucose, calcium, magnesium, tox screen B. LP- if 1 st febrile or nonfebrile seizure with concern of meningitis C. EEG - EEG within first 24 hours more likely to contain epileptic abnormality, need to contain sleep and awake time

19 Work-up 2 D. Neuroimaging studies 1. CT scan - abnormalities found on a CT are likely to be without therapeutic consequences in face of normal exam If child had one seizure and a n l exam, abnormal CT findings are not likely related to seizure 2. MRI - the preferred modality - more sensitive than CT Better able to find atrophy, infarction, evidence of trauma, cerebral dysgenesis and cortical dysplasia

20 Work-up 3 MRI (cont..) Non-urgent MRI should be considered in all children with significant cognitive or motor impairment, unexplained abnormality on neurological exam, seizure of focal onset with or with-out generalization or children under 1 year of age Emergent MRI should be done in child who exhibits a post-ictal focal deficit not quickly resolving, or who has not returned to baseline within several hours after the seizure

21 What about treatment? No one answer because

22 Therapeutic value Secondary effects J.M. Pellock, 2003

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24 Anticonvulsant Drugs Marketed in the U.S phenobarbital (Luminal) Winthrop 1935 mephobarbital (Mebaral) Winthrop 1938 phenytoin (Dilantin) Parke-Davis 1947 mephenytoin (Mesantoin) Sandoz 1954 primidone (Mysoline) Ayerst 1957 methsuximide (Celontin) Parke-Davis 1957 ethotoin (Peganone) Abbott 1960 ethosuximide (Zarontin) Parke-Davis 1968 diazepam (Valium) Roche 1974 carbamazepine (Tegretol) Ciba-Geigy 1975 clonazepam (Klonopin) Roche 1978 valproate (Depakene) Abbott 1981 chlorazepate (Tranxene) Abbott 1993 felbamate (Felbatol) Carter-Wallace 1993 gabapentin (Neurontin) Parke-Davis 1994 lamotrigine (Lamictal) Glaxo-Smith-Kline topiramate (Topamax) tiagabine (Gabitril) Ortho-McNeil Abbott zonisamide (Zonegran) levetiracetam (Keppra) oxcarbazepine (Trileptal) Elan Pharma UCB Pharma Novartis

25 Clinical Utility of Established and Newer AEDs Treatment Options Partial Seizures Generalized Seizures Infantile Spasms Simple, Complex, Secondarily generalized Tonicclonic Tonic Atonic Myoclonic Absence ACTH, VGB, TGB?, LTG?,TPM?, ZNS? PHT, CBZ, PB, GBP, TGB, LEV, OXC PHT, CBZ, OXC, GBP, TGB, LEV ESX VPA, LTG, TPM, ZNS, FBM Adapted from Pellock J. CNS Spectrums: New Developments in the Treatment of Epilepsy (Monograph). April, 2000.

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30 Why are patients with one seizure more likely to have another? No certain answer, but a hypothesis

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32 Epileptogenesis and Epilepsy Genetics Genetics Genetics +AGE+Sex Initial Precipitating Event First seizure Structural/ functional changes Epilepsy AGE Sex AGE Sex? Days to months to years

33 Let s see what you learned A quick case study

34 Double Trouble Seizures In Twins (1) Twins (Lily and Annika) born to 33 y/o G1P0-2 mother with polycystic ovaries by in vitro fertilization Gestational age 34 weeks Birth weights - 4 lb 1 oz and 4 lb 9 oz Apgars 7/8 and 8/9 Neonatal examination WNL for age G.L. Holmes, 2003

35 Double Trouble Seizures In Twins (2) On day 2, Lily developed periods of apnea and desaturations (SaO2 into the range within seconds); on day 5 Annike started having similar episodes LP/CT/metabolic W/U - WNL EEG - immature features (excessively discontinuous for age) G.L. Holmes, 2003

36 Double Trouble Seizures In Twins (3) Phenobarbital started and both twins stopped having seizures. Sent home and did well for 10 days until new type of spells started. Spells consisted of turning head and eyes to either right or left, extension of arms and legs, a high pitched cry, apnea and cyanosis. Duration of events <60 secs. Episodes occurred hourly. G.L. Holmes, 2003

37 Double Trouble - Seizures In Twins (4) Anneke consistently had less frequent and briefer seizures than her sister, Lily EEG and video monitoring performed MRI, LP, organic acids, amino acids, pyruvate, lactate, NH3, electrolytes, liver function tests, CBC WNL Pyridoxine (B6) given without any benefit What else do you want to know? G.L. Holmes, 2003

38 Double Trouble - Seizures In Twins (5) Mother had seizures as a newborn. Born at 42 weeks gestation. Had up to 14 episodes a day of tonic posturing with gaze deviation during the first weeks of life. Treated successfully with phenobarbital. No other family history of seizures. Subsequently a third daughter, born at term, developed seizures during day #2. Like her sisters, responded remarkably well to carbamazepine G.L. Holmes, 2003

39 Benign Familial Neonatal Seizures Autosomal-dominantly inherited epilepsy of the newborn Onset of epilepsy is typically on days 2-4; spontaneous remission of seizures occurs between 2-15 weeks Seizures typically start with a tonic posture, ocular symptoms and other autonomic features, which often progress to clonic movements and motor automatisms G.L. Holmes, 2003

40 Benign Familial Neonatal Seizures Neonates are normal between the seizures Evaluation for structural, infectious, metabolic disease is negative Clinical and EEG features suggest the seizures are generalized in type Seizures recur later in life in approximately 16% of cases, compared to 2% of normal population G.L. Holmes, 2003

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