Seizures

1. Seizures Presentation by Delin Wang Samir Patel

2. Introduction • A seizure is a paroxysmal event due to abnormal, excessive, hypersynchronous discharges from an aggregate of CNS neurons. • Depending on the distribution of discharges, various manifestations can occur • About 5 – 10 % of the population will have at least one seizure • The highest incidence occurs in early childhood and late adulthood.

3. Introduction • Epilepsy is a condition in which a person has recurrent seizures due to a chronic, underlying process. • The incidence of epilepsy is approximately 0.3 – 0.5 % in different populations throughout the world • The prevalence of epilepsy has been estimated at 5 – 10 persons per 1000. • Status epilepticus • Greater than 30 minutes of continuous seizure activity or recurrent seizures without full recovery between episodes • Practically, a seizure lasting > 5 minutes should be treated as status epilepticus

4. Classification of seizures • Partial seizures • Simple partial seizures (with motor, sensory, autonomic, or psychic signs) • Complex partial seizures • Partial seizures with secondary generalization • Primarily generalized seizures • Absence (petit mal) • Tonic-clonic (grand mal) • Tonic • Atonic • Myoclonic • Unclassified seizures (e.g. neonatal seizures, infantile spasms)

5. Partial seizures • Partial seizures occur within discrete regions of the brain • Simple partial seizure • Consciousness is not impaired • Features • Focal motor symptoms (eg, hand jerking) • “Jacksonian march” – the spread of seizure activity over a progressively larger region of motor cortex • E. g. abnormal motor movements begin in a very restricted region such as fingers and gradually progress to include a larger portion of the extremity • Todd’s paralysis – localized paresis that last minutes to many hours in the involved region following the seizure

6. Partial seizures • Simple partial seizures • Features (continued) • Somatosensory symptoms (eg, paresthesias or tingling) • Vision (eg, flashing lights) • Hearing (eg. buzzing) • Olfaction (eg, burning rubber or kerosene) • Equilibrium (sensation of falling or vertigo) • Autonomic function (sensation of epigastric rising, flushing, sweating, pupillary dilation) • Psychic symptoms (eg, déjà vu, jamais vu, hallucinations, illusions that objects are growing smaller or larger) • If the above symptoms precede a complex partial or secondarily generalized seizure, they serve as a warning, or aura.

7. Partial seizures • Complex partial seizure • Consciousness is impaired • It frequently begins with an aura (i.e., a simple partial seizure) that is stereotypic for the patient • The start of the ictal phase is often a sudden behavioral arrest or motionless start • This marks the onset of the period of amnesia • The behavioral arrest is usually accompanied by automatisms • Automatism are involuntary, automatic behaviors that have a wide range of manifestations • Examples include chewing, lip smacking, swallowing, or more elaborate behaviors such as a display of emotion or running

8. Partial seizures • Complex partial seizures • The patient is typically confused following the seizure • It may take from seconds up to an hour to have full recovery of consciousness • Examination immediately following the seizure may show an anterograde amnesia • In cases involving the dominant hemisphere, a postictal aphasia can occur

9. Partial seizures with secondary generalization • Partial seizures can spread to involve both cerebral hemispheres and produce a generalized seizure • Usually, the tonic-clonic type • It is often difficult to distinguish from a primary generalized tonic-clonic seizure • A careful history that identifies a preceding aura would help differentiate the secondary generalization from the generalized seizures

10. Generalized seizures • Generalized seizures arise from both cerebral hemispheres simultaneously • Absence seizures (Petit mal) • Characterized by sudden, brief lapses of consciousness without loss of postural control • Lasts for only seconds • Consciousness returns as suddenly as it was lost • No postictal confusion • May be accompanied by subtle, bilateral motor signs • E.g. rapid blinking of the eyelids, chewing movements, or small-amplitude, clonic movements of the hands

11. Generalized seizures • Absence seizures • Usually begin in childhood (ages 4 – 8) or early adolescence • Main seizure type in 15 – 20% of children with epilepsy • First clue to absence seizure is often unexplained “daydreaming” and a decline in school performance recognized by a teacher • Respond well to treatment with specific anticonvulsants • About 60 – 70% of patients will have a spontaneous remission during adolescence

12. Generalized seizures • Atypical absence seizures • The loss of consciousness is usually of longer duration and less abrupt in onset and cessation • Accompanied by more obvious motor signs • Usually associated with diffuse or multifocal structural abnormalities of the brain • Thus may have other signs of neurologic dysfunction such as mental retardation • Less responsive to anticonvulsants compared to typical absence seizures

13. Generalized seizures • Tonic-clonic seizures (Grand mal) • The most common seizure type resulting from metabolic derangements • Usually begins abruptly without warning • Initial phase is usually tonic contraction of muscles throughout the body • Tonic contraction of the muscles of expiration and the larynx at the onset will produce a loud moan or “ictal cry.” • Respirations are impaired, secretions pool in the oropharynx, and cyanosis develops

14. Generalized seizures • Tonic-clonic seizures • Tonic phase: • Contraction of the jaw muscles may cause biting of the tongue • A marked enhancement of sympathetic tone leads to increases in heart rate, blood pressure, and pupillary size • After 10-20 s, tonic phase typically evolves into the clonic phase • Clonic phase is produced by the superimposition of periods of muscle relaxation on the tonic muscle contraction • The periods of relaxation progressively increase until the end of the ictal phase • The postictal phase is characterized by • Unresponsiveness, muscular flaccidity, and excessive salivation that can cause stridorous breathing and partial airway obstruction • Bladder or bowel incontinence may occur at this point

15. Generalized seizures • Tonic-clonic seizures (Grand mal) • Patients gradually regain consciousness over minutes to hours • During this transition there is typically a period of postictal confusion • Patients may have complaints of headache, fatigue, and muscle ache that can last for many hours • The duration of impaired consciousness in the postictal phase can be extremely long (i.e. many hours) in patients with • Prolonged seizures or • Underlying CNS diseases such as alcoholic cerebral atrophy

16. Generalized seizures • Atonic seizures • Characterized by sudden loss of postural muscle tone lasting 1 – 2 seconds • Consciousness is briefly impaired • Usually no postictal confusion • A very brief seizure may cause only a quick head drop or nodding movement • A longer seizure will cause the patient to collapse • There is a substantial risk of direct head injury with the fall

17. Generalized seizures • Myoclonic seizures • Myoclonus is a sudden and brief muscle contraction that may involve one part of the body or the entire body • A normal, common physiologic form of myoclonus is the sudden jerking movement observed while falling asleep • Pathologic myoclonus is most commonly seen in association with • Metabolic disorders • Degenerative CNS diseases • Anoxic brain injury

18. Etiology of seizures • Seizures are a result of a shift in the normal balance of excitation and inhibition within the CNS. • Causes of seizures include • CNS infections • Fever • Hypoxic brain injury • Stroke (ischemic or hemorrhagic) • Tumors • Head injury • Eclampsia • Hyperthyroidism • Congenital brain malformations • Genetics (phenylketonuria, Sturge – Weber, tuberous sclerosis, etc.) • Toxic metabolic (porphyria, uremia, liver failure)

19. Etiology of seizures • Causes (continued) • Drug withdrawl (alcohol, barbiturates, benzodiazepine, AEDS) • Drug intoxication (TCAs, cocaine, amphetamine) • Electrolyte abnormalities • Hyponatremia • Hypocalcemia • Hypomagnesemia • Hypoglycemia/hyperglycemia • For patients with a known seizure disorder with an increasing seizure frequency • Consider anticonvulsive medication noncompliance, subtherapeutic anticonvulsant levels, or any infection

20. Differential diagnosis • Alternate diagnoses that may mimic seizures include: • Syncope, especially convulsive syncope in which seizure-like motor activity is observed • Pseudoseizures • Toxic-metabolic encephalopathy • Tremors, dyskinesias • Nonepileptic myoclonus following a hypoxic event • Rigors

21. Initial approach • If pts present shortly after a seizure pay attention to: • vital signs • Respiratory, and cardiovascular support, • resuming seizure medication if any, • life threatening conditions such as CNS infection, metabolic derangement or drug toxicity. • If patient is not acutely ill focus on history

22. Diagnosis The primary tool for seizure assessment is the history -age at onset -Risk factors such as family hx, prior history of stroke, history of febrile seizures, genetic disorders. -Developmental delays (i.e mental retardation, cerebral palsy, attention deficit, memory difficulties, and learning disorders) -behavior profile -psychoses, anxiety disorders, and eating disorders -Preictal and postictal symptoms -health at seizure onset, including fever, vomiting, diarrhea, or illness exposure. • any witness should be interviewed if the patient is in ictal or postictal phase. -precipitating events such as toxins, head trauma, systemic diseases, illicit drug or alcohol use -change in sleep pattern (eg sleep apnea) -dietary pattern

23. Diagnosis • Physical Examination • Signs of Fever help diagnose febrile seizures • Neck stiffness for meningitis • Complete neurological examination • Focal deficits, mental deficiency, stroke, cerebral palsy • Careful examination of the skin for Café-au-lait spots, adenoma sebaceum and hypopigmented spots (tuberous sclerosis), or port-wine stain (Sturge–Weber). • Signs such as automatisms, facial and extremity twitching, eye deviation, mental status changes( ie confusion, amnesia, postictal phase), changes in respiration • Look for signs of head trauma, use of alcohol or illicit drugs. • Auscultation of heart and carotid arteries may identify any heart abnormality that predisposes to Cerebrovascular disease.

24. Diagnosis Laboratory and Radiological Exams • Blood tests • Electrolytes (hyponatremia), glucose (hypoglycemia), blood urea nitrogen [BUN], creatinine, calcium (hypocalcemia), magnesium (hypomagnesemia) • especially indicated for age 6 mo or younger; continued illness; history of vomiting, diarrhea, or dehydration • Toxicology screening in case of drug or substance abuse • Lumbar puncture i.e. meningitis • Elevated Prolactin and creatine kinase levels • EEG: All patients who have possible seizure disorder -Abnormal, repetitive, rhythmic activity having an abrupt onset and termination establishes the diagnosis, but the absence does not rule out seizure disorder. -Diagnostic in only 30-50% of first time seizure victims -Accuracy improves to 90% with repetitive testing. - Used also to classify seizure disorders and aiding in selection of medications; for example episodic generalized spike-wave activity is usually seen in patients with typical absence seizure. -The clinical presentation should serve as a guide regarding who needs an EEG.

25. Diagnosis Brain imaging: almost all patients with new onset seizures should have a brain study to determine whether there is an underlying structural problem • Exception to this rule is children who have clear history and examination suggestive of benign, generalized seizure disorder such as absence seizure. • CT: limited largely to head trauma, and in acute setting • MRI is prefered over CT: Identify any lesions such as tumors, vascular malformations, or stroke • Used best for prolonged postictal paralysis, persistent neurologic abnormality, age younger than 12 months, abnormal EEG

26. Treatment A)Treatment of underlying conditions that cause or contribute to the seizures -Reversal of any metabolic disturbances. -Stopping any medications that may lower the seizure threshold (i.e beta lactams, tramadol, antidepressants, antipsychotics, lithium, barbiturates, benzos etc) -Seizures caused by structural CNS lesion such as brain tumor, vascular malformation, or brain abscess should be treated accordingly. .  B) Avoidance of precipitating factors -sleep deprivation -illicit drugs such as cocaine -alcohol intake -stress

27. Treatment C) Suppression with antiepileptic medications • When to initiate • Patient with recurrent seizures of unknown etiology or known cause that cannot be reversed. Not indicated after a single unprovoked seizure. • Recurrence rate ranges from 31%-71% in the 1st 12 months after the initial seizure. • Antiepileptic drugs • Older medications such as phenytoin, valporic acid, carbamazepine, and ethosuximide are generally used as 1st line therapy for most seizure disorders and most new ones are used as add-on or alternative therapy. • Efficacy, convenience of dosing, and side effects are factors that influence the choice of initial medication. • Almost all of the commonly used drugs can cause similar dose-related side effects such as sedation, ataxia, and diplopia • Initiation and monitoring of therapy • Careful education about the approach to therapy • Most drugs need to be introduced slowly to minimize side effects. • Monitoring of serum drug levels is very important especially for compliance and toxicity.

28. Treatment

31. Treatment

33. Status Epilepticus

35. Treatment D) Nonpharmacological treatments 1. Surgery -approximately 20% of patients are resistant to medical therapy - severing of the corpus callosum or temporal lobe resection, results in 80% seizure-free outcomes for specific epilepsy types. - Candidates for surgery should have recurrent uncontrolled seizures, focal EEGs, and consistent focal abnormalities on neuroimaging 2. VNS (vagal nerve stimulation) -treatment option used to treat refractory partial-onset epilepsy who are not candidates for resection brain surgery -involves placement of a bipolar electrode on the midcervical portion of left vagus nerve. The electrode is connected to a small, subcutaneous generator located in the infraclavicular region and is programmed to deliver intermittent electrical pulses to the vagus nerve. -This has shown to increase seizure threshold, but the precise mechanism of action is unknown. Shown to reduce seizures in about 40% of patients.

36. Treatment E) Other Management issues. 1. Psychological problems: patients with epilepsy are at risk of developing a variety of psychiatric problems including depression (20%), anxiety, and psychosis. 2. Referral: Neurological consultation. 3.Educate on Employment and Driving 4.Family counseling 5. Pregnancy: Seizure frequencies remain unchanged in around 50%, increase in around 30%, and decrease in 20%. -overall incidence of fetal abnormalities in childer born to mothers with epilepsy is 5-6%, compared to 2-3% in healthy mother -it is recommended that pregnant women with epilepsy be maintained on effective drug therapy as potential harm for uncontrolled seizures is higher that the teratogenic effects of the drugs.

37. Question #1 A mother comes to your office with her previously healthy 8-year-old son complaining that he is found to have multiple staring episodes. During those episodes, he is unresponsive to verbal or tactile stimuli and produces lip-smacking movements. Each of these episodes lasts for a few minutes. He remains confused for some time after the episode is over. He has no family history of any seizure disorder. His neurological examination is unremarkable. EEG performed before and after hyperventilation is normal. Based on these findings, which of the following is the most likely diagnosis? A). Complex partial seizure B). Typical absence seizure C). Atypical absence seizure D). Juvenile myoclonic epilepsy E). Lennox-Gastault syndrome

38. Answer: A • Complex partial seizures are characterized by brief episodes of impaired consciousness. The patient fails to respond to various stimuli during these episodes. He may be found to be staring. During these episodes, he shows automatisms like lip smacking, swallowing or picking movements of the hand. Each episode lasts for a few minutes and these is a post-ictal confusion state. EEG is usually normal or may show brief discharges. Hyperventilation neither precipitates a seizure nor produces any EEG abnormality. • A typical absence seizure is characterized by brief periods of impaired consciousness. There may be automatisms but there is no post-ictal state. Each episode typically lasts for seconds. Hyperventilation may precipitate a seizure as well as it may produce EEG abnormalities typical of absence seizure, which are generalized 3-Hz spike and wave pattern on a normal background. • An atypical absence seizure lasts longer and EEG shows slow spike and wave activity with a frequency less than 2.5. • Juvenile myoclonic epilepsy presents in adolescents with unilateral or bilateral myoclonic jerks. These jerks take place in the morning and may be precipitated by sleep deprivation. • Lennox-Gastault syndrome is characterized by seizures of multiple types, impaired cognitive function and slow spike and wave activity on EEG. It usually presents in childhood.

39. Question #2 A mother brings her 7-year-old child to her physician complaining that her son is found to be daydreaming frequently, and his teacher has noted a recent decline in his school performance. She also reported that sometimes he stares for few seconds and rolls his eyes without any reason. He has no family history of any seizure disorder and his psychomotor development is normal. His neurological examination is unremarkable. EEG is performed which shows generalized, symmetrical 3-Hz spike and wave activity on a normal background. Hyperventilation provokes these electrographic discharges. Which of the following medications is the most appropriate to treat this disorder? A). Phenytoin B). Phenobarbital C). Valproic acid D). Clonazepam E). Lamotrigine

40. Answer: C Absence seizures, also known as petit mal seizures occur in children aged 4-8 years and usually present with day dreaming episodes and decline in school performance. Clinically, typical absence seizures appear as brief staring spells. Patients have no warning or postictal phase and if engaged in gross motor activity, such as walking, may stop and stand motionless or may continue to walk. Children are not responsive during the seizure and have no memory of what happened during the attack. They are generally unaware that a seizure has occurred. EEG shows generalized, symmetrical 3-Hz spike and wave (classic finding), activity on a normal background. These findings are usually provoked by hyperventilation. The preferred treatment of absence seizures is ethosuximide or valproic acid. Clonazepam or Lamotrigine are alternative agents for the treatment of absence seizures. Phenytoin is currently the initial drug of choice for partial seizures. Phenobarbital is not used for the treatment of absence seizures; it can be used in primary generalized and partial seizures as an alternative agent.

41. References • Harrison’s Principles of Internal Medicine, 17e. “Chapter 363: Seizures and Epilepsy.” • Current Medical Diagnosis & Treatment 2010. “Chapter 24. Nervous System Disorders.” • The Washington Manual of Medical Therapeutics, 33e. • Seizures and Epilepsy, Overview and Classification: eMedicine.com • Current Diagnosis and Treatment in Family Medicine, 2e. “Chapter 9. Seizures.” • Epilepsy Ontario. www.epilepsyontario.org