1. Status epilepticus (SE) is a medical emergency defined as a seizure lasting more than 5 minutes or recurrent seizures without regaining consciousness. SE can be convulsive or non-convulsive. 2. The annual incidence of SE is estimated to be between 9,000-14,000 new cases per year in the UK. Mortality is about 20-30% and is higher in the elderly. 3. SE is initially treated with benzodiazepines like lorazepam or diazepam. If seizures continue, second line drugs like fosphenytoin or phenytoin are used. For refractory SE, anesthetic drugs under ICU care may be required

1. STATUS EPILEPTICUSDR.SRIRAMA.ANJANEYULU

2. INTRODUCTION Medical emergency Hunter noted that SE was rare before the advent of powerful antiepileptic drugs, and the consequent risk of drug withdrawal. Incidence of SE have varied from 10 to 60 per 100000 person-years. The annual incidence in the UK is about 9000–14 000 new cases per year. Accounts for 3.5% of admissions to emergency departments in the developed nations and for 11% in a developing country.(MEENA AK,2000).

3. INCIDENCE About 5% of all epileptic adult clinic patients will have at least one episode of SE in the course of their epilepsy , and in children the proportion is higher (10-25%). Mortality for SE is about 20%-30% (dying of the underlying condition, rather than the SE itself.) Mortality is age related, and is much lower in children and higher in the elderly. The risks of morbidity are greatly increased the longer the duration of the SE episode .

4. Mortality of status epilepticus Dead of status 1.8% Dead of underlying cause 28.8% Dead other causes 6.5% Alive 63.1%

5. A comparison of survival by duration in status epilepticus shows a marked increase in mortiality for patients in prolonged status epilepticus. (Towne et al. 1994)

6. Five population-based studies of status epilepticus (convulsive and non convulsive)

7. Seizure type and epilepsy classification in five population-based studies

8. DEFINITIONS (nanda gopal,pgmj,2006)

9. ILAE CLASSIFICATION OF SE, Continuous seizure types Generalized status epilepticus Generalized tonic-clonic status epilepticus Clonic status epilepticus Absence status epilepticus Tonic status epilepticus Myoclonic status epilepticus Focal status epilepticus Epilepsiapartialis continua of Kojevnikov Aura continua Limbic status epilepticus (psychomotor status) Hemiconvulsive status with hemiparesis

10. Revised classification of status epilepticus (shorvon s) Status epilepticus confined to early childhood Neonatal status epilepticus Status epilepticus in specific neonatal epilepsy syndromes Infantile spasms Status epilepticus confined to later childhood Febrile status epilepticus Status in childhood partial epilepsy syndromes Status epilepticus in myoclonic-astatic epilepsy Electrical status epilepticus during slow-wave sleep Landau-Kleffner syndrome Status epilepticus occurring in childhood and adult life Tonic-clonic status epilepticus Absence status epilepticus Epilepsiapartialis continua Status epilepticus in coma (subtle generalized tonic-clonic seizure) Specific forms of status epilepticus in mental retardation Syndromes of myoclonic status epilepticus Non-convulsive simple partial status epilepticus Complex partial status epilepticus Status epilepticus confined to adult life De novo absence status of late onset

11. Stepwise approach to classification of status epilepticus

12. Clinical features and electroencephalographic abnormalities in subtypes of NCSE

13. SE Vs PSYCHOGENIC SE

14. Status epilepticus and neuronal damage Cerebral cortex Hippocampus Amygdala Thalamus Cerebellum

15. Hippocampal atrophy

16. Drug pharmacokinetics Fast drug absorption is essential in the treatment of status epilepticus Route of administration Volume of distribution Acidosis Hepatic&renal dysfunction due to SE

17. Diazepam drug levels

18. Concentration-time profile of acutely administered drugs showing two phases

19. Stages of status epilepticus Discrete seizures Merging seizures Continuous ictal activity Continuous ictal activity, punctuated by low voltage flat activity Periodic epileptiform discharges on a quiet background (Treiman et al. 1990)

20. Aetiologies of status epilepticus

21. Drugs and Other Substances that Can Cause Seizures

22. Aetiologies of status epilepticus

23. PATHOPHYSIOLOGY SE requires a pool of neurones capable of initiating and sustaining abnormal firing. Abnormal discharge is facilitated by loss of inhibitory synaptic transmission mediated by gamma-amino butyric acid (GABA) and sustained by excitatory transmission mediated by glutamate. Postsynaptic GABA(A) and N-methyl-D-aspartate receptors have a vital role in the inhibitory and excitatory transmissions, respectively. Increased neuronal activity can also lead to loss of inhibition by accelerated internalisation of the GABA(A) receptor. Neuropeptide Y and galanin serve as endogenous anticonvulsants that terminate status epilepticus. Brain injury from trauma, epilepsy, infections and other causes leads to increased cortical excitability and impaired seizure termination.

24. PATHO PHYSIOLOGY OF SE

25. Medical management Oxygen and cardiorespiratory resuscitation Monitoring Emergency anticonvulsant therapy Intravenous lines Emergency investigations Intravenous glucose and thiamine Acidosis Establish aetiology Seizure and EEG monitoring Long-term anticonvulsant therapy

26. Diagnosis and early management ofseizures

27. Protocol for drug treatment, general measures, and emergency investigations of convulsivestatus epilepticus as function of time from the onset of the seizure

28. Protocol for drug treatment, general measures, and emergency investigations of convulsivestatus epilepticus as function of time from the onset of the seizure

29. Diazepam vslorazepam Four randomised trials of anticonvulsants in patients with status epilepticus showed that both lorazepam and diazepam are effective as initial treatment. Intravenous lorazepam given by trained paramedics in prehospital settings was also found to be therapeutically beneficial. Ease of administration, longer effective duration of action and better side effect profile,most prefer lorazepam to diazepam for the initial treatment.

30. Diazepam was effective in controlling brief (10 min) seizuresbut lost potency after prolonged (45 min) seizures in a lithium pilocarpine ,rat model of status epilepticus.

31. Protocol for drug treatment, general measures, and emergency investigations of convulsivestatus epilepticus as function of time from the onset of the seizure

32. phenytoin or fosphenytoin? Fosphenytoin advantages. It can be infused using standard intravenous solutions, whereas phenytoin should not be given in dextrose containing fluids (because of drug precipitation). It can be given intramuscularly. Rate of infusion is three times as fast with fosphenytoin.

33. Phenytoinvsphosphenytoin

34. treatment protocol for RSE

35. Protocol for drug treatment, general measures, and emergency investigations of convulsivestatus epilepticus as function of time from the onset of the seizure

36. rse

37. Se protocol

38. Mayo Clin Protocol

39. Pharmacotherapy of generalised convulsive status epilepticus

40. Pharmacotherapy of generalised refractory status epilepticus

41. Non-convulsive status epilepticus 1/3rd of all cases of SE. 14-24 per 100000 population per year. The diagnosis of non-convulsive status epilepticus is critically dependent on EEG. In patients of epilepsy,any prolonged change in personality, prolonged postictal confusion (greater than 30 min) or recent onset psychosis should be investigated. Subtle manifestations such as twitching of the limbs, or facial muscles or nystagmoid eye jerking.

42. definitions of nonconvulsivestatus epilepticus (a) Unequivocal electrographic seizure activity. (b) Periodic epileptiform discharges or rhythmic discharge with clinical seizure activity. (c) Rhythmic discharge with either clinical or electrographic response to treatment.

43. Typical absence status epilepticus Prolonged absence attacks with continuous or discontinuous 3 Hz spike and wave occurring in patients with primary generalized epilepsy. Absence status epilepticus can be divided into Childhood absence status epilepticus (those usually already receiving treatment). Late onset absence status epilepticus with a history of primary generalized history (often a history of absences in childhood) . Late onset absence status epilepticus developing de novo (usually following drug or alcohol withdrawal). No evidence that absence status induces neuronal damage,and thus aggressive treatment is not warranted. Responds rapidly to intravenous benzodiazepines. Sodium valproate is one of the alternative.

44. Complex partial status epilepticus ‘A prolonged epileptic episode in which focal fluctuating or frequently recurring electrographic epileptic discharges, arising in temporal or extratemporal regions, result in a confusional state with variable clinical symptoms‘. Oral clobazam over a period of 2-3 days given early at home. Persistent or resistant complex partial status epilepticus intravenous therapy should be used , and lorazepam followed by phenytoin (or fosphenytoin) are the drugs of choice.

45. Non-convulsive status epilepticus in coma Electrographic status epilepticus in coma is not uncommon and is seen in up to 8% of patients in coma with no clinical evidence of seizure activity. Non-convulsive status epilepticus in coma consists of three groups: Those who had convulsive status epilepticus. Those who have subtle clinical signs of seizure activity . Those with no clinical signs. Should be treated aggressively with deep anaesthesia and concomitant antiepileptic drugs.

46. Atypical absence status epilepticus Associated with the epileptic encephalopathies such as Lennox-Gastaut syndrome. Should be considered if there is change in behaviour, personality, cognition or increased confusion in a patient with one of these epilepsies. The EEG characteristics are usually that of continuous or frequent slow (<2.5Hz) spike and wave. Oral rather than intravenous treatment is usually more appropriate, and the drugs of choice are valproate, lamotrigine,clonazepam, clobazam and topiramate.

47. Tonic status epilepticus Tonic status epilepticus is not uncommon in patients with syndromes such as Lennox-Gastaut. Tonic status epilepticus can also rarely occur in the setting of normal premorbid intelligence. The tonic seizures may not necessarily be clinically apparent; the EEG, however, demonstrates bursts of paroxysmal, generalized fast discharges. Worsened with benzodiazepines. Stimulants such as methylphenidate can be effective. Oral lamotrigine, ACTH and corticosteroids can be helpful.

48. Epilepsiapartialis continua Status equivalent of simple partial motor seizures. Defined as regular or irregular clonic muscular twitching affecting a limited part of the body, occurring for a minimum of 1 h, and recurring at intervals of no more than 10 s. Can result from structural abnormalities such as stroke, trauma, cerebral infarction, cerebral abscess, neuronal migration disorders and vascular malformation. 50% of cases, the MRI is normal. Associated with a variety of encephalitides, commonly Rasmussen's encephalitis, but also SSPE,CJD. Treatment is best targeted at the underlying cause. Oral corticosteroid, nimodipine. Neurosurgical resection.

49. TREATMENT OF NCSE

50. The use of valproate and new antiepileptic drugs in status epilepticus VALPROATE LEVETIRACETAM TOPIRAMATE