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Seizures lecture


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Seizures lecture

  1. 1. Seizures Olivia Jagger Academic Education F2
  2. 2. Learning Objectives Define what we mean by seizures Understand the different types of seizures Understand the causes of seizures Know the emergency and longterm management of seizures Know the complications of seizures and their management Demonstrate achievement of learning objectives through clinical cases
  3. 3. Definitions - what does it all mean? Seizure spontaneous uncontrolled abnormal brain activity Status Epilepticus Seizure >20 - 30minutes OR Multiple seizures frequent enough to prevent recovery between episodes >2030mins Epilepsy tendency to have spontaneous uncontrolled abnormal brain activity, resulting in recurrent seizures
  4. 4. Pathophysiology Pre-synaptic membrane excitatory neurotransmitter Post-synaptic membrane inhibitory neurotransmitter Na+ Action Potential Ca2+ Action Potential
  5. 5. Pathophysiology GABA (gammaaminobutyric acid) is the main inhibitory neurotransmitter Glutamate is the major excitatory neurotransmitter
  6. 6. Pathophysiology Seizures are caused by abnormal synchronised discharge of many neurons Every individual has a seizure threshold the level of excitability at which neurons will discharge uncontrollably Triggers that push neuron excitation past the seizure threshold include: ‣ Sleep deprivation ‣ Drugs ‣ ‣ Flickering lights Infection / metabolic disturbance In patients with epilepsy the seizure threshold is lowered and the neurons are hyperexcitable
  7. 7. Cause Intracranial Underlying brain abnormality Extracranial Pyrexia • Raised intracranial pressure - cerebral tumour - cerebral odema → pregnant - eclampsia • Stroke Hypoxia • - Thrombo-embolic - Haemorrhagic Brain infections • Biochemical ↑↓Sodium, Glucose ↓ Calcium, Magnesium ↑ Urate Drugs - Prescribed / Recreational - Intoxication / Withdrawal
  8. 8. Types of seizures specific area in one cerebral hemisphere Seizures Partial no loss of conciousness Generalised conciousness impaired Simple both cerebral hemispheres Complex Absence Myoclonic Tonic-Clonic Tonic Atonic
  9. 9. Tonic Clonic Seizures Convulsive seizure with tonic phase (stiffening) and clonic movements (jerking) Before • Prodrome • Aura • Sudden onset • Triggers During •Tonic Phase: stiffening, loss of consciousness, falls, cries out • Clonic Phase: convulsion, jerking of arms and legs •Excessive salivation (drooling or foaming) •Biting of the tongue •Loss of bowel and/or bladder control •No breathing / random breaths •Eye rolling After • Post-ictal • Drowsy • Confused • Agitated
  10. 10. Febrile convulsions Presentation • most common seizure disorder in childhood • Peak age of onset 1418 months • Pyrexial • Tonic-clonic • <10 mins • Don’t predispose to epilepsy Management Risk Factors for Epilepsy • ABCDE • First fit <9months • Rule out underlying infection • Atypical seizure • Paediatric review if first fit • REASSURE parents! • FH epilepsy • Evidence of developmental delay • Abnormal neurology on examination
  11. 11. Emergency Management You are the F1 on call and you’re bleeped... “Please come quickly a patient is having a seizure and we don’t know what to do!” What is your initial management?
  12. 12. Emergency Management A B C D Airway Breathing Circulation Disability • Patent? • Give airway support if needed • RR • O2 sats • give O2 • HR • BP • Cap refill • IV access and bleed • Head injury? • Infection? • Bleeding? • Temperature? • BM?
  13. 13. Management of seizures Stepwise approach Start treating underlying cause Initial A,B, C, D Benzodiazepine Phenytoin Paralysis and Ventilation
  14. 14. Benzodiazepine - mechanism of action If seizure does not resolve after a few minutes give a benzodiazepine GAB A Enhances the inhibitory effect of GABA Reduces excessive neuronal firing Action Potential Action Potential
  15. 15. Benzodiazepines First line IV Access Lorazepam 0.1mg/kg IV (2-4mg bolus repeated after 15 mins) Diazepam 10-20mg rectally (repeated after 15 mins) Second line No Access Midazolam 10mg buccally (repeated after 15 mins) Side Effects • sedation • suppressed breathing • hypotension (worse with IV)
  16. 16. Management of seizures Stepwise approach Start treating underlying cause Initial A,B, C, D Benzodiazepine Phenytoin Paralysis and Ventilation
  17. 17. Phenytoin - mechanism of action If seizure does not resolve after benzodiazepine start a phenytoin infusion Infusion dose 20mg/kg over 20 minutes Blocks voltage-sensitive sodium channels Na+ Action Potential Inhibits excitatory neuronal transmission Action Potential
  18. 18. Phenytoin - Pharmacokinetics • Mainly hepatic break down • Zero order kinetics • Narrow therapeutic range • Risk of toxicity Continuous BP and ECG monitoring
  19. 19. Phenytoin - Side Effects At therapeutic levels •Gum hypertrophy •Nausea / vomiting •Headaches •Skin rashes •Hypotension •Arrhythmias (bradycardia) •Bone marrow suppression Megaloblastic anaemia •Teratogenicity At toxic levels •Ataxia •Nytagmus •Drowsiness •Dysphasia •Coma death •Arrhythmias (bradycardia) •Hypotension Monitor serum levels, FBC, LFTs If IV: BP and ECG (especially QT interval)
  20. 20. Management of seizures Stepwise approach Start treating underlying cause Initial A,B, C, D Benzodiazepine Phenytoin Paralysis and Ventilation If seizure not resolved following initial management patient may need paralysis and ventilation Should be done in ITU by an expert * Never spend long than 20 minutes with a patient with a seizure before calling an anaesthetist! *
  21. 21. Longterm Management - Drugs Seizures Partial Generalised 1st line carbamazepine / 2ndnd line sodium valproate 2 line sodium valproate Simple 1st line sodium 1st line sodium valproate/ / valproate 2nd line ethosuximide Complex 1st line sodium 1st line sodium valproate/ / valproate 2nd line levetiracetam Absence Myoclonic 1st line sodium 1 line sodium valproate / valproate / 2nd line lamotrigine 2nd line lamotrigine st Tonic-Clonic Tonic Atonic 1st st linesodium valproate 1 line sodium valproate
  22. 22. Summary of longterm drug therapy Type of Seizure PARTIA L Simple and Complex Absence GENERA L Myoclonic 1st line drug 2nd line drug Carbamazepine Sodium Valproate (Inhibits sodium channels reducing action potential propagation ) Sodium Valproate (Inhibits GABA transaminase so enhances inhibitory affect of GABA) Sodium Valproate TonicClonic Sodium Valproate Tonic Sodium Valproate Atonic Sodium Valproate Ethosuximide (Calcium channel inhibitor) Levetiracetam (Mechanism of action unknown) Lamotrigine (Inhibits sodium channels reducing action potential propagation)
  23. 23. Sodium Valproate - mechanism of action Inhibits GABA transaminase (inhibits GABA breakdown) GAB A Enhances the inhibitory effect of GABA Reduces excessive neuronal firing Action Potential Action Potential
  24. 24. Sodium Valproate - side effects At therapeutic levels In Pregnancy •Significantly increased risk of • Thinning and curling of hair • Hepatotoxicity (P450 inhibitor) • Weight gain • Thrombocytopaenia • Pancreatitis • Teratogenicity birth defects with Sodium Valproate •The relative risk is 2-5x higher than other antiepileptic drugs •Extreme caution in women of childbearing age
  25. 25. Cytochrome P450 Enzymes • P450 cytochromes are the major enzymes involved in drug metabolism • mainly act in the liver P450 inducers speed up the metabolism of drugs (decrease drug availability) P450 inhibitors lead to build up of unmetabolised drugs (increase drug availability) INDUCERS INHIBITORS Phenytoin / Carbamazapine Sodium Valproate
  26. 26. Longterm Management - Surgery Surgery may be considered when there is: •A mass lesion in the brain •Uncontrolled epilepsy
  27. 27. Living well with Epilepsy Lifestyle Driving • Safety Advice • First fit - cannot drive for 6 months • Ensure treatment compliance • Second or further fits - cannot drive • Have a predetermined plan for seizure emergencies and rescue treatment for 12 months • Medication change in the last 6 months - cannot drive for 6 months • ‘night-time’ only seizures - they can drive, if they have not had a ‘day time’ seizure for 3 years
  28. 28. Complications Brain Injury Physical Injury Todd’s Paresis Sudden Unexpected Death in Epilepsy
  29. 29. Clinical Case 1 • A 70kg 27 year old male presents with five minutes of generalised tonic-clonic seizures. • The immediate management would be: A. 4mg Lorazepam IV B. Maintain a clear airway C. Call an anaesthetist D. 20mg Diazepam rectally
  30. 30. Clinical Case 1 • Following an ABCD assessment, with attainment of IV access, he continues to fit. • The appropriate management would be: A. Lorazepam IV B. Phenytoin IV C. Midazolam buccally D. Diazepam rectally
  31. 31. Clinical Case 1 • 20 minutes after the administration of 4mg lorazepam he continues to fit. • The appropriate management would be: A. Lorazepam IV B. Phenytoin IV C. Move to ITU for paralysis and assisted ventilation D. hold him down to prevent injury
  32. 32. Clinical Case 1 • His seizure resolves with an IV Phenytoin infusion. Baseline investigations are unremarkable. He is discharged home for follow up in the ‘first fit’ clinic. • What advice should he be given about driving? A. He cannot drive for 6 months B. He cannot drive for 12 months C. He can continue to drive until he has been reviewed by a Neurologist in clinic D. He cannot drive again until he retakes his driving test
  33. 33. Clinical Case 2 An ambulance brings a 15 month old boy to ED following a seizure. His mother reports he suddenly started shaking his arms and legs and his eyes had a blank stare. This went on for what seemed like 5 minutes so she called 999. There is no vomiting, diarrhea or rash. He has no significant past medical history. O/E Temperature 39C, slight cough and mild nasal congestion. Alert and interactive. Normal neurological examination. The immediate management would be: • Maintain a clear airway • 10mg Diazepam rectally • 5mls Calpol • IV access and bloods
  34. 34. Clinical Case 2 He was reviewed by a Paediatrician who found no evidence of developmental delay or systemic infection. His temperature settled with Calpol. The likely diagnosis is: • Epilepsy • Febrile Convulsion A.Absence Seizure B.Brain tumour
  35. 35. Clinical Case 2 • Which of the following are Risk Factors for development of epilepsy in febrile convulsions: • (select as many as apply) A. Family history of a febrile convulsion B. Generalised seizure C. Recurrent febrile seizures D. Febrile seizure onset in first nine months E. Evidence of developmental delay
  36. 36. Clinical Case 3 •An 85 year old gentleman is brought in by his grandson with acute confusion and frank haematuria. •Past medical history: Hypertension, Hypercholesterolaemia, AF and Epilepsy •Drug History: Warfarin, Simvastatin, Sodium Valproate •Which one initial investigation will most aid your diagnosis? • Sodium Valproate level • INR • CT head • Cystoscopy
  37. 37. Clinical Case 3 • Which of the following anti-epileptic drugs are INDUCERS of P450 cytochromes? • (select as many apply) A. Phenytoin B. Carbamazepine C. Sodium Valproate D. Lamotrigine
  38. 38. Clinical Case 4 • A 37 year old man presented to the Emergency department following an epileptic seizure. He had suffered from epilepsy since childhood and takes sodium valproate and levertiracetam. Two hours following the seizure he complained that he was still unable to move his right arm. • The likely diagnosis is: A. Partial Seizure B. Todd’s Paresis C. TIA D. Stroke
  39. 39. Clinical Case 4 • Which of the following statements are correct about Todd’s Paresis? • (select as many as apply) A. There is paralysis of limbs lasting several hours after a seizure B. It is a type of lower motor neurone paralysis C. It has to be differentiated from acute stroke D. It usually resolves within 1-2 weeks E. It is associated with dysphasia
  40. 40. AMK practice • The most appropriate longterm drug for treatment of generalised tonic-clonic seizures is: A. Sodium valproate B. Lamotrigine C. Ethosuximide D. Carbemazepine E. Lorazepam
  41. 41. AMK practice The most appropriate longterm drug for treatment of complex partial seizures is: (Select as many as apply) • Phenytoin A. Sodium valproate B. Carbamazepine B. Ethosuximide C. Lamotrigine
  42. 42. AMK practice • A 30 year old lady is started on phenytoin for recurrent tonic-clonic seizures. Past medical history includes prednisolone for brittle asthma. Two weeks later she returns to clinic and complains that her asthma has worsened since she began the phenytoin therapy. • A likely reason for this new change is that phenytoin: • interferes with absorption of the prednisone • stabilizes cell membranes, preventing the prednisone from diffusing to the site of action • accelerates hepatic degradation of prednisone • induce renal excretory pathways, accelerating urinary excretion of the prednisone • Decreases hepatic degradation of prednisolone
  43. 43. AMK practice • Select 3 drugs with similar proposed mechanisms of action: A. Phenytoin B. Carbamazepine C. Lamotrigine D. Sodium valproate E. Ethosuximide
  44. 44. AMK practice • Which of the following statements about Phenytoin are true: • (select as many as apply) A. It follows first-order kinetics B. It follows zero-order kinetics C. It is mainly metabolised by the kidneys D. It has a narrow therapeutic window E. It can cause bone marrow suppression
  45. 45. AMK practice • Symptoms of Phenytoin toxicity include: • (select as many as apply) A. Gingival hyperplasia B. Nystagmus C. Ataxia D. Dysphasia E. Bone marrow suppression
  46. 46. Seizures Summary Seizures are caused by abnormal synchronised discharge of many neurons Anything that lowers the excitation threshold of neurons (makes them hyper excitable or reduces inhibition) can result in seizures Seizures are classified as Partial (affect a small area of one cerebral hemisphere) and Generalised (affecting both cerebral hemispheres) A seizure is an emergency ‘Status Epilepticus’ if it lasts >20 - 30minutes OR multiple seizures frequent enough to prevent recovery >20-30mins The stepwise management of seizures is ABCD assessment, Benzodiazepine, Phenytoin, Paralysis and assisted ventilation The first line drug for longterm management of generalised seizures is Sodium Valproate The first line drug for the longterm management of partial seizures is Carbamazepine Phenytoin displays zero-order kinetics and has potential for toxicity Sodium Valoprate is 2-5x more teratogenic than any other anti-epileptic agent
  47. 47. Questions Please send any questions that occur to you later to