1. A Practical Approach to The Diagnosis and Evaluation of Seizures Carol Leicher MD Connecticut Children’s Medical Center University of Connecticut School of Medicine

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. 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

25. 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.

26. 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.

27. 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.

28. 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.

29. 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