1. A Practical Approach to The Diagnosis and Evaluation of Seizures Prof. Dr. Alaa H. Alwan TUCOM/ 2015 TUCOM/ 2015

2. Three basic questions 1. Is it a seizure? 1. Is it a seizure? –If so, what kind? 2. What caused it? 2. What caused it? 3. What should be done? 3. What should be done?

3. Seizure A seizure is a set of clinical symptoms associated with abnormal electrical activity in neurons in the cortex of the brain. The clinical characteristics of a seizure are the result of the area of the brain that is abnormally stimulated. Epilepsy is a clinical condition in which there are multiple seizures that are unprovoked.

4. Types of seizures Generalized seizures Generalized seizures Focal (or partial seizures) Focal (or partial seizures)

5. Generalized seizures –Generalized seizures arise from both sides of the brain simultaneously. Motor activity is symmetrical and alteration of consciousness occurs. –Ex. Primary generalized seizures (grand mal) Absence seizures (petit mal) Absence seizures (petit mal) Myoclonic seizures, atonic seizures Myoclonic seizures, atonic seizures

6. Focal (Partial seizures) Arise from one area of the cortex and may spread to involve adjacent areas or distant areas Arise from one area of the cortex and may spread to involve adjacent areas or distant areas Examples: Examples: –Simple partial seizures Symptoms are referable to the area of the brain involved, no alteration of consciousness Symptoms are referable to the area of the brain involved, no alteration of consciousness –Complex partial seizures Partial seizures with alteration of consciousness Partial seizures with alteration of consciousness –Partial seizures with secondary generalization Partial seizure at onset (aura) followed by generalized convulsive activity Partial seizure at onset (aura) followed by generalized convulsive activity

8. Seizure like episodes Syncope Syncope –Syncopal seizures may have tonic stiffening, clonic jerking and/or post-ictal confusion Parasomnias Parasomnias –Sleepwalking, night terrors Hyperventilation Hyperventilation Stereotypies/Tics Stereotypies/Tics Staring spells Staring spells

9. Diagnosis is largely based on the history of the event* Precipitating factors Precipitating factors –Position, activity, intercurrent illness, medications Description of the episode Description of the episode –Eye movements, body movements, one sided or both sides, loss of consciousness or alteration of consciousness, incontinence, duration, aftereffects Predisposing factors Predisposing factors –Past medical history, recent illness or neurological symptoms, family history *Is it a seizure, if so what kind? *Is it a seizure, if so what kind?

10. Etiology of Seizure –Symptomatic seizures Acute/subacute Acute/subacute –Metabolic causes Hypoglycemia, hypo or hypernatremia, hypocalemia Hypoglycemia, hypo or hypernatremia, hypocalemia Intoxications/ toxins (lead) Intoxications/ toxins (lead) –Infectious/Inflammatory Meningitis, encephalitis, sepsis Meningitis, encephalitis, sepsis Post-infectious or autoimmune causes Post-infectious or autoimmune causes –Fever* –Trauma –Vascular accidents

11. Symptomatic seizures, part 2 Chronic/ Progressive Chronic/ Progressive –Remote insults Perinatal asphyxia or vascular insult Perinatal asphyxia or vascular insult Past head injury Past head injury –Developmental brain abnormalities Agenesis of the corpus callosum, schizencephaly, cortical dysplasia Agenesis of the corpus callosum, schizencephaly, cortical dysplasia –Inborn errors of metabolism Storage disorders, amino acid disorders, organic acid disorders Storage disorders, amino acid disorders, organic acid disorders –Neurocutaneous disorders –Cerebral degenerative diseases

12. Idiopathic seizures The cause of the seizure can not be determined by conventional testing or The cause of the seizure can not be determined by conventional testing or Seizures of genetic origin in which seizures are the only manifestation. Seizures of genetic origin in which seizures are the only manifestation. This category may comprise as much as 60% of all childhood seizure disorders. This category may comprise as much as 60% of all childhood seizure disorders.

13. Determining the cause of a child’s seizure(s) * History History –Associated symptoms, intercurrent illness, recent medications, exposures (drugs,toxins, pets), past medical history ( birth history, developmental history, family history) Examination Examination –Fever or other abnormal vital signs –Head size, skin abnormalities (hypo/hyperpigmented areas),menigismus, asymmetry of the face or the extremities, enlarged organs, dysmorphic features –Alteration of mental status, cranial nerve abnormalities, motor tone or strength or reflex changes, gait abnormalities,ataxia, sensory abnormalities. *What caused it? *What caused it?

14. Diagnostic Studies Bloodwork - electrolytes, Ca, glucose Bloodwork - electrolytes, Ca, glucose Urine - toxicology, amino acid and organic acid measurement* Urine - toxicology, amino acid and organic acid measurement* EEG EEG –Useful for evaluating interictal abnormalities –Occasionally useful for determining nature of a clinical symptom (absence seizures, tics or other frequent movements) –Helpful in predicting recurrence of seizures. –A normal EEG does not exclude a diagnosis of seizure.

15. Diagnostic studies #2 Ambulatory EEG Ambulatory EEG –Allows for Ictal recording- ie, EEG activity during a suspected episode Drawbacks- technical, availability, depends on patient/parent to indicate when the episodes are occurring Drawbacks- technical, availability, depends on patient/parent to indicate when the episodes are occurring Videotelemetry Videotelemetry –Simultaneous recording of EEG and video of patient. –Can be done as a day procedure or as inpatient –Episodes must occur with some frequency

16. Diagnostic Studies#3 Imaging procedures Imaging procedures –CTT is not the procedure of choice but is appropriate in emergencies, especially trauma –MRI is the imaging procedure of choice Abnormal neurological examination Abnormal neurological examination Focal seizure activity Focal seizure activity Focal findings on EEG Focal findings on EEG –PET scanning is a specialized procedure done in limited circumstances (usually as part of evaluation of intractable seizures or when a surgical treatment is proposed.

17. Treatment Decisions* The decision to treat depends on evaluation of risks and benefits The decision to treat depends on evaluation of risks and benefits –Risk of subsequent seizures –Risk of treatment –Particular circumstances of patient –*What to do about it?

18. Risks of further seizures Risk of a second seizure is 20-30% if: Risk of a second seizure is 20-30% if: –Examination, EEG and CTT (imaging study) is normal (and careful review of history discloses no other events) –Exceptions: Absence seizures. Myoclonic seizures Risk of a second seizure if EEG is abnormal is 60% Risk of a second seizure if EEG is abnormal is 60% Risk of a third seizure is 70% Risk of a third seizure is 70%

19. Risk of having another seizure Most seizures do not produce injury to the brain. Most seizures do not produce injury to the brain. Seizures in a bad place- bath, driving a car, climbing, riding a bicycle etc. Seizures in a bad place- bath, driving a car, climbing, riding a bicycle etc. Prolonged seizure which can lead to hypoxia or secondary complications. Prolonged seizure which can lead to hypoxia or secondary complications. Sudden unexplained death- a very rare complication of seizures, particularly in children. Sudden unexplained death- a very rare complication of seizures, particularly in children.

20. Risk of treatment Medication side effects Medication side effects –Severe- liver failure, aplastic anemia, severe allergic reaction (Stevens-Johnson syndrome) –Decreased alertness, personality/behavior changes, weight loss/gain Social stigma Social stigma

21. Treatment Discuss risks and benefits with patient and parent based on available statistics Discuss risks and benefits with patient and parent based on available statistics If 1st seizure with lower risk of recurrence, consider no treatment. If 1st seizure with lower risk of recurrence, consider no treatment. Use of rectal valium as a “rescue measure” Use of rectal valium as a “rescue measure” If decision to treat, choose a medication based on seizure type, age of patient and side effect profile. If decision to treat, choose a medication based on seizure type, age of patient and side effect profile. Monotherapy is generally preferable, especially in first line treatment. Monotherapy is generally preferable, especially in first line treatment.

22. Anticonvulsant medications Generalized seizures Generalized seizures Divalproex sodium Divalproex sodium Zonisamide Zonisamide Topiramate Topiramate Lamotrigine Lamotrigine Levetiracetam Levetiracetam Rufinamide Rufinamide Ethosuximide* Ethosuximide* Partial Seizures Partial Seizures –Carbamazepine –Oxycarbazepine –Zonisamide –Topiramate –Levetiracetam –Lamotrigine –Phenytoin –Phenobarbital*

23. Other Treatment Alternatives Dietary treatment Dietary treatment –Ketogenic diet –Modified Atkins diet Surgical treatment Surgical treatment –Vagal nerve stimulator –Surgical removal of seizure focus

24. Historical Clues Precipitating factors Precipitating factors –Seizures may be precipitated by flashing lights, hyperventilation, illness or being overtired (stress?) –Syncope is precipitated by standing up, being overheated, sight of blood, frightening event State of alertness- syncope doesn’t occur in sleep, Seizures may occur in sleep or wakefulness. Parasomnias only occur in sleep. State of alertness- syncope doesn’t occur in sleep, Seizures may occur in sleep or wakefulness. Parasomnias only occur in sleep.

25. Further historical cues Position- seizures may occur in any position, syncope usually occurs when sitting or standing Position- seizures may occur in any position, syncope usually occurs when sitting or standing Eye movements- eyes are usually closed or partially open during a syncopal episode, more likely to be open during a seizure. The presence of deviation of the eyes to one side or another suggests a partial seizure. Eye movements- eyes are usually closed or partially open during a syncopal episode, more likely to be open during a seizure. The presence of deviation of the eyes to one side or another suggests a partial seizure. Seizures that affect one side of the body more than the other are likely to be focal in origin. Syncopal episodes are usually symmetrical. Seizures that affect one side of the body more than the other are likely to be focal in origin. Syncopal episodes are usually symmetrical.

26. Staring vs. Absence vs. Partial Complex seizures Staring spells are more apt to occur when the patient is passive, listening to a teacher, or parent or watching TV. They can be of indeterminate length and are interruptible by voice or touch. Staring spells are more apt to occur when the patient is passive, listening to a teacher, or parent or watching TV. They can be of indeterminate length and are interruptible by voice or touch. Absence seizures can occur in the midst of activity, usually brief 10-20 seconds. There may be eye blinking/fluttering or subtle head movements. The patient recovers very quickly. Incontinence may occur. Absence seizures can occur in the midst of activity, usually brief 10-20 seconds. There may be eye blinking/fluttering or subtle head movements. The patient recovers very quickly. Incontinence may occur. Partial complex seizures are usually 1-2 minutes in length, and can not be interrupted. There are often stereotypic movements and postictal confusion is common. Partial complex seizures are usually 1-2 minutes in length, and can not be interrupted. There are often stereotypic movements and postictal confusion is common.

27. Generalized seizures vs Partial Seizures Generalized seizures have sudden onset without warning. Motor symptoms are symmetrical. Postictal state is common when there is convulsive activity but not for absence or myoclonic seizures Generalized seizures have sudden onset without warning. Motor symptoms are symmetrical. Postictal state is common when there is convulsive activity but not for absence or myoclonic seizures Partial seizures may begin with localized symptoms that the patient is aware of (aura) and may have asymmetric motor symptoms. Postictal state is common, even without convulsive activity. Partial seizures may begin with localized symptoms that the patient is aware of (aura) and may have asymmetric motor symptoms. Postictal state is common, even without convulsive activity.

28. Algorithm Algorithm Initial Event History- eyewitness report if possible Physical Examination EEG, imaging study if EEG focal If isolated event, no treatment or Rectal valium If multiple episodes discuss medication NormalAbnormal Probable seizure Other Another lecture EEG,Imaging study, consider more emergent evaluation

29. Neonatal seizures Subtle seizures Subtle seizures –Deviation of the eyes –Eyelids are flickering –Swimming or pedaling movements –Apnoeic spells Tonic Tonic Clonic Clonic Myoclonic Myoclonic Seldom tonic clonic seizures Seldom tonic clonic seizures

30. Aetiology of neonatal seizures Perinatal: Perinatal: –HIE Metabolic Metabolic –Hypoglycemia, hypocalcemia –hypomagnesemia –Other Infections Infections Structural abnormalities Structural abnormalities

31. Treatment of neonatal seizures Optimize ventilation, cardiac output, BP, glucose, electrolytes and pH. Optimize ventilation, cardiac output, BP, glucose, electrolytes and pH. Treat the underlying disease Treat the underlying disease Intravenous line is essential Intravenous line is essential Treat the seizures promptly and vigorously Treat the seizures promptly and vigorously Phenobarbitone Phenobarbitone Phenytoin Phenytoin

32. Febrile seizures Definition: Definition: –Seizure in children between the age of 6 months and 3-4(5) years in association with fever but without evidence of an intracranial infection Majority occurs before the age of 3 years Majority occurs before the age of 3 years Average age of onset: 18 months to 22 months Average age of onset: 18 months to 22 months Boys more than girls Boys more than girls

33. Pathophysiology Seizure threshold is low in children Seizure threshold is low in children Susceptible to infections i.e urti, LRTI Susceptible to infections i.e urti, LRTI Possible role of endogenous pyrogens IL1 Possible role of endogenous pyrogens IL1 –May increase neuronal activity Probable role of cytokines Probable role of cytokines

34. 2 Types Simple febrile seizures Simple febrile seizures –Generalise –<15min duration –Do not recur within 24hrs Complex Complex –Prolonged seizures –Usually more than one in a 24hr period –Or may be focal –Indicative of a more serious condition

35. Febrile seizures Recurrence Recurrence –1/3 may have at least one recurrence –The younger the age of onset the greater the risk of recurrence –Low fever at first seizure –Family hx Risk of developing epilepsy Risk of developing epilepsy –2% (vs 1% in gen pop) –Risk increases with: Complex Complex Abnormal neurological state Abnormal neurological state

36. Investigation of febrile seizures Lab investigations, although routine, usually unhelpful, in the evaluation of first time seizure – possible just a Na and Glucose Lab investigations, although routine, usually unhelpful, in the evaluation of first time seizure – possible just a Na and Glucose CT is not warranted in the evaluation of simple febrile convulsions but considered for complex CT is not warranted in the evaluation of simple febrile convulsions but considered for complex –Study of 71 patient with complex seizures None had an intracranial condition requiring treatement None had an intracranial condition requiring treatement Routine EEG is seldom necessary Routine EEG is seldom necessary ??LP ??LP –Simple febrile seizure probable not indicated Probable those with prolonged post-ictal phase Probable those with prolonged post-ictal phase –Current recommendation should be routine in the under 12 month group

37. Treatment of febrile convulsion Oxygen and supportive care Oxygen and supportive care Benzodiazapines Benzodiazapines Antipyretics Antipyretics –Do not appear to prvent recurrence Councel parents Councel parents

38. Treatment of Epilepsy –Drug treatment should be regular –Simple as possible –Minimum of side effects –Monotherapy –Changes should be made gradually –High initial dosages increases side effects –Rapid withdrawal carries the risk of provoking status –Always calculate the dosage according to the weight

39. Treatment of Epilepsy Drugs commonly used Drugs commonly used –Carbamazepine –Sodium valproate –Clonazepam –Phenobarbitone –Phenytoin Newer drugs Newer drugs –Clobazam –Oxcarbazepine –Gabapentin –Vigabatrin –Lamotrigine

40. Treatment of Epilepsy Antiepileptics can cause convulsions Antiepileptics can cause convulsions –Benzodiazepines can induce TC seizures in LGS –Carbamazepine may exacerbate absence seizures What is used as first line treatment. What is used as first line treatment. –Absence: Sodium valproate Sodium valproate –Focal and Generalized TC: Carbamazepine Carbamazepine

41. Status epilepticus (SE) presents in a multitude of forms, dependent on aetiology and patient age (myoclonic, tonic, subtle, tonic-clonic, absence, complex partial etc.) Status epilepticus (SE) presents in a multitude of forms, dependent on aetiology and patient age (myoclonic, tonic, subtle, tonic-clonic, absence, complex partial etc.) Generalized, tonic-clonic SE (GCSE) is the most common form of SE Generalized, tonic-clonic SE (GCSE) is the most common form of SE

42. Definition Conventional “textbook” definition of status epilepticus: Conventional “textbook” definition of status epilepticus: –Single seizure > 30 minutes –Series of seizures > 30 minutes without full recovery

43. Why 30 minutes ? Animal experiments in the 1970s and 1980s had shown that... … neuronal injury could be demonstrated after 30 min of seizure activity, even while maintaining respiration and circulation Nevander G. Ann Neurol 1985;18(3):281-90.

44. More practical: Mechanistic definition GCSE is a condition which most likely will not terminate rapidly and / or spontaneously GCSE is a condition which most likely will not terminate rapidly and / or spontaneously GCSE is a condition which requires prompt intervention GCSE is a condition which requires prompt intervention Lowenstein DH. Epilepsia 1999

45. The longer SE persists, –the lower is the likelihood of spontaneous cessation –the harder it is to control –the higher is the risk of morbidity and mortality Bleck TP. Epilepsia 1999;40(1):S64-6 The Status Epilepticus Working Party. Arch Dis Child 2000;83(5):415-9.

46. Typical seizure duration Children > 5 years: Children > 5 years: Typical, generalized tonic-clonic seizure lasts < 5 minutes Young children and infants: Young children and infants: little data. latsts < 10-15 minutes Reviewed in: Lowenstein DH. It's time to revise the definition of status epilepticus. Epilepsia 1999;40(1):120-2.

47. Revised Definition Generalized, convulsive status epilepticus in older children (> 5 years) refers to > 5 minutes of continuous seizure or >2 discrete seizures with incomplete recovery of consciousness Generalized, convulsive status epilepticus in older children (> 5 years) refers to > 5 minutes of continuous seizure or >2 discrete seizures with incomplete recovery of consciousness

48. Causes Fever Fever Medication change Medication change Unknown Unknown Metabolic Metabolic Congenital Congenital Anoxic Anoxic Other (trauma, vascular, infection, tumor, drugs) Other (trauma, vascular, infection, tumor, drugs)36%20% 9% 9% 8% 8% 7% 7% 5% 5%15% \

49. Mortality Adults Adults Children Children 15 to 22% 3 to 15% 3 to 15% Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23- 30

50. Mortality The primary determinant of mortality and morbidity of SE in children is its aetiology The primary determinant of mortality and morbidity of SE in children is its aetiology With the highest mortality rates caused by an acute neurological condition (infection, trauma, stroke) With the highest mortality rates caused by an acute neurological condition (infection, trauma, stroke) Mitchell WG. J Child Neurol 2002;17 Suppl 1:S36-43.

51. Prolonged seizures Duration of seizure Lifethreateningsystemicchanges Death Temporarysystemicchanges

52. Respiratory Hypoxia and hypercarbia Hypoxia and hypercarbia – Ventilation (chest rigidity from muscle spasm) (chest rigidity from muscle spasm) –Hypermetabolism (  O 2 consumption,  CO 2 production) (  O 2 consumption,  CO 2 production) –Poor handling of secretions –Neurogenic pulmonary oedema

53. Hypoxia Hypoxia/anoxia markedly increase (triple?) the risk of mortality in SE Hypoxia/anoxia markedly increase (triple?) the risk of mortality in SE Seizures (without hypoxia) are much less dangerous than seizures and hypoxia Seizures (without hypoxia) are much less dangerous than seizures and hypoxia Towne AR. Epilepsia 1994;35(1):27-34

54. Acidosis Respiratory Respiratory Lactic Lactic –Impaired tissue oxygenation –Increased energy expenditure