Approach to seizure

seizure

1. Approach to seizure/epilepsy Dr Biplave Karki

2. Introduction Seizure an abnormal, excessive, paroxysmal discharge of the cerebral neurons 5–10% of the population will have at least one seizure, with the highest incidence occurring in early childhood and late adulthood Epilepsy a chronic condition characterized by recurrent, unprovoked seizures if a patient has 2 or more seizures, he/she is diagnosed as having epilepsy Incidence 0.3–0.5% Prevalence 5–30 persons per 1000.

3. Differential Diagnosis of Seizures Benign positional vertigo Breath holding spells in children Cardiac arrhythmia Hypoglycemia Migraine Narcolepsy/Cataplexy Night terrors Nightmares Nocturnal myoclonus Panic attacks Periodic paralysis Pseudoseizures/Hysterical seizures Sleep apnea Syncope Transient ischemic attacks

4. Syncope A transient loss of consciousness due to brief interruption of blood supply to the brain. Convulsive movements of the extremities may follow some prolonged episodes. Vasovagal syncope secondary to fear, pain or unpleasant sights such as blood or medical procedures. Reflex syncope coughing, micturition, defecation or Valsalva’s maneuver. Other causes, especially in the elderly, orthostatic hypotension and cardiac arrhythmias. Clinical presentation dizzy/light-headed fullness in ears Nauseous often gradual graying or blurring of the vision.

5. Syncope contd.. Patients who fall tend to go down more “gracefully” than those with seizures Stereotypical provoking factors such as prolonged periods of standing in the heat, sight of blood, micturition, or abruptly assuming an erect posture after prolonged recumbence. The absence of an aura , tongue bite, urinary incontinence and prolonged tonic-clonic activity in the presence of a provoking factor would be more suggestive of syncope.

6. Transient Ischemic Attacks TIA result from temporary interruption of blood supply in the distribution of a cerebral vessel. “Negative symptoms” such as numbness and weakness are more likely to manifest as compared to the “positive symptoms” (stiffness and twitching) seen with seizures. Patients will likely have risk factors for cerebrovascular disease such as hypertension, diabetes and/or coronary artery disease.

7. Migraines A classic migraine with visual aura, nausea/vomiting and pounding hemicranial headache can be differentiated easily from a seizure based on history alone. However, migraines presenting with isolated symptoms such as vertigo, episodic vomiting (cyclic vomiting), visual changes and aphasia with/without headaches can be a challenge. A detailed history of previous attacks Certain triggers (caffeine, sleep withdrawal, chocolate) Family history of migraines Empirical treatment with antiepileptic/anti-migraine medications may clarify the diagnosis in some instances

8. Pseudoseizures and Hysterical Seizures Pseudoseizures are paroxysmal attacks of non-epileptic etiology waxing and waning movements during a single attack prolonged tonic-clonic activity without postictal disorientation non-rhythmic pelvic thrusting non-physiological evolution of symptoms such as motor activity spreading from one hand to the other without first affecting the ipsilateral face or leg.

9. Classification of seizure Seizures may be either focal or generalized. Focal seizures originate within networks limited to one cerebral hemisphere Focal seizures with or without impairment of cognition Generalized seizures arise within and rapidly engage networks distributed across both cerebral hemispheres. Focal seizures are usually associated with structural abnormalities of the brain. In contrast, generalized seizures may result from cellular, biochemical, or structural abnormalities that have a more widespread distribution.

10. FOCAL SEIZURES Arise from a neuronal network either discretely localized within one cerebral hemisphere or more broadly distributed but still within the hemisphere Focal seizures with or without dyscognitive features (“simple focal seizures” and “complex focal seizures”) Focal seizures can also evolve into generalized seizures (focal seizures with secondary generalization) Interictal EEG often normal or may show brief discharges termed epileptiform spikes, or sharp waves.

11. Focal Seizures Without Dyscognitive Features Focal seizures can cause motor, sensory, autonomic, or psychic symptoms without impairment of cognition Ictal EEG abnormal discharges in a very limited region over the appropriate area of cerebral cortex if the seizure focus involves the cerebral convexity Focal motor seizures abnormal motor movements may begin in a very restricted region such as the fingers and gradually progress (over seconds to minutes) to include a larger portion of the extremity “Jacksonian march” spread of seizure activity over a progressively larger region of motor cortex. Localized paresis (Todd’s paralysis) may occur for minutes to many hours in the involved region following the seizure Seizure may continue for hours or days epilepsia partialis continua

12. Focal Seizures Without Dyscognitive Features Focal seizures may also manifest as changes in somatic sensation (e.g., paresthesias) Vision (flashing lights or formed hallucinations) Equilibrium (sensation of falling or vertigo), or Autonomic function (flushing, sweating, piloerection). Focal seizures arising from the temporal or frontal cortex may also cause alterations in hearing, olfaction, or higher cortical function (psychic symptoms) sensation of unusual, intense odors (e.g., burning rubber or kerosene) or sounds (crude or highly complex sounds) epigastric sensation that rises from the stomach or chest to the head Fear sense of impending change, detachment, depersonalization, déjá vu illusions that objects are growing smaller (micropsia) or larger (macropsia). These subjective, “internal” events that are not directly observable by someone else are referred to as auras.

13. Focal Seizures with Dyscognitive Features Transient impairment of the patient’s ability to maintain normal contact with the environment unable to respond appropriately to visual or verbal commands during the seizure impaired recollection or awareness of the ictal phase Aura (i.e., a focal seizure without cognitive disturbance) Sudden behavioral arrest or motionless stare Automatisms involuntary, automatic behaviors very basic behaviors such as chewing, lip smacking, swallowing, or “picking” movements of the hands more elaborate behaviors such as a display of emotion or running. The patient is typically confused following the seizure Transition to full recovery of consciousness may range from seconds up to an hour. Anterograde amnesia Postictal aphasia

14. EVOLUTION OF FOCAL SEIZURES TO GENERALIZED SEIZURES Tonic-clonic variety Focal seizures arising from a focus in the frontal lobe H/O of preceding aura

15. GENERALIZED SEIZURES Arise at some point in the brain but immediately and rapidly engage neuronal networks in both cerebral hemispheres

16. Typical Absence Seizures Sudden, brief lapses of consciousness without loss of postural control Typically lasts for only seconds No postictal confusion Subtle, bilateral motor signs such as rapid blinking of the eyelids chewing movements small-amplitude, clonic movements of the hands. Associated with a group of genetically determined epilepsies onset usually in childhood or early adolescence main seizure type in 15–20% of children with epilepsy EEG generalized, symmetric, 3-Hz spike-and-wave discharge that begins and ends suddenly, superimposed on a normal EEG background

17. Atypical Absence Seizures Lapse of consciousness longer duration less abrupt in onset and cessation More obvious motor signs EEG generalized, slow spike-and-wave pattern with a frequency of ≤2.5 Hz Diffuse or multifocal structural abnormalities of the brain signs of neurologic dysfunction such as mental retardation Less responsive to anticonvulsants

18. Generalized, Tonic-Clonic Seizures Main seizure type in ~10% of all persons with epilepsy Most common seizure type resulting from metabolic derangements The seizure usually begins abruptly without warning, Vague premonitory symptoms in the hours leading up to the seizure distinct from the stereotypic auras associated with focal seizures that generalize. Tonic contraction of muscles throughout the body muscles of expiration and the larynx loud moan or “ictal cry.” Respirations are impaired Secretions pool in the oropharynx Cyanosis jaw muscles biting of the tongue Marked enhancement of sympathetic tone increases in heart rate, blood pressure, and pupillary size

19. Generalized, Tonic-Clonic Seizures After 10–20 s Clonic phase superimposition of periods of muscle relaxation on the tonic muscle contraction. periods of relaxation progressively increase until the end of the ictal phase, which usually lasts no more than 1 min. Postictal phase Unresponsiveness, muscular flaccidity, and excessive salivation that can cause stridorous breathing and partial airway obstruction Bladder or bowel incontinence Postictal confusion Headache, fatigue, and muscle ache

20. Generalized, Tonic-Clonic Seizures EEG tonic phase progressive increase in generalized low-voltage fast activity, followed by generalized high-amplitude, polyspike discharges clonic phase high-amplitude activity is typically interrupted by slow waves to create a spike-and-wave pattern postictal EEG diffuse slowing that gradually recovers as the patient awakens Brief tonic seizures lasting only a few seconds Lennox-Gastaut syndrome

21. Atonic Seizures Sudden loss of postural muscle tone lasting 1–2 s Consciousness is briefly impaired No postictal confusion EEG brief, generalized spike-and-wave discharges followed immediately by diffuse slow waves that correlate with the loss of muscle tone Atonic seizures are usually seen in association with known epilepsy syndromes.

22. Myoclonic Seizures Myoclonus is a sudden and brief muscle contraction that may involve one part of the body or the entire body. Physiologic form of myoclonus sudden jerking movement observed while falling asleep. Pathologic myoclonus metabolic disorders degenerative CNS diseases anoxic brain injury Myoclonic seizures are considered to be true epileptic events because they are caused by cortical dysfunction. EEG bilaterally synchronous spike-and-wave discharges synchronized with the myoclonus Myoclonic seizures juvenile myoclonic epilepsy

23. Epilepsy syndromes Epilepsy syndromes are disorders in which epilepsy is a predominant feature There is sufficient evidence (e.g., through clinical, EEG, radiologic, or genetic observations) to suggest a common underlying mechanism

24. Juvenile myoclonic epilepsy (JME) Generalized seizure disorder of unknown cause Appears in early adolescence Bilateral myoclonic jerks that may be single or repetitive most frequent in the morning after awakening and can be provoked by sleep deprivation. Consciousness is preserved unless the myoclonus is especially severe. Many patients also experience generalized tonic-clonic seizures Up to one-third have absence seizures. Although complete remission is relatively uncommon, the seizures usually respond well to appropriate anticonvulsant medication. There is often a family history of epilepsy, and genetic linkage studies suggest a polygenic cause

25. Lennox-Gastaut syndrome Occurs in children Triad: Multiple seizure types generalized tonic-clonic, atonic, and atypical absence seizures EEG slow (<3 Hz) spike-and-wave discharges and a variety of other abnormalities; and Impaired cognitive function in most but not all cases. Associated with CNS disease or dysfunction from a variety of causes De novo mutations Developmental abnormalities Perinatal hypoxia/ischemia Trauma Infection Unfortunately, many patients have a poor prognosis underlying CNS disease severe, poorly controlled epilepsy.

26. Mesial temporal lobe epilepsy (MTLE) Most common syndrome associated with focal seizures with dyscognitive features High resolution MRI hippocampal sclerosis Refractory to treatment with anticonvulsants but responds well to surgical intervention

27. History 1. When did you experience the first seizure in your life? 2. Do you experience some kind of a warning or unusual feeling at the onset, or immediately preceding the seizure? 3. What happens during the seizure? 4. What happens immediately following the seizure? 5. Is there a diurnal variation? 6. Are there any known triggering factors? 7. What is the seizure frequency? 8. What has been the maximum seizure-free period since the seizure onset? 9. Is there more than one kind of seizure? 10. Has the patient sustained injuries related to the seizures? 11. What is the frequency of visits to the emergency department?

28. 1. When did you experience the first seizure in your life? Early neonatal period perinatal insults metabolic disorders, and congenital malformation. Generalized seizures tend to present in early childhood or teenage years Elderly with new onset seizures structural pathology such as a stroke or brain tumor

29. 2. Do you experience some kind of a warning or unusual feeling at the onset, or immediately preceding the seizure? The warning symptoms that are perceived at the onset of a seizure are called “aura.” An aura actually indicates that the seizure is focal in origin. Temporal lobe epilepsy déjà vu epigastric sensation, Parietal lobe epilepsy Paresthesias Occipital lobe epilepsy visual distortions transient blindness

30. 3. What happens during the seizure? Is there head or eye deviation to one side? Seizures originating from the frontal eye fields may cause head and eye deviation to the contralateral side Is there excessive eye blinking at the onset? Occipital lobe seizures can present with excessive blinking at the onset, negative visual symptoms or visual distortions If automatisms (defined as involuntary, organized sequences of movement that are not causally related to the external environment) occur, are these more pronounced on one side? Temporal lobe seizures are often manifested with lip smacking and other oral and alimentary automatic behavior most pronounced in the ipsilateral extremity, along with dystonic posturing of the contralateral arm Does the patient bite his tongue or lose control of the bladder function? more often seen with generalized seizures

31. 4. What happens immediately following the seizure? Postictal period Generalized tonic-clonic seizure postictal sleep disorientation and lack of awareness of the surroundings Hemiparesis or hemiplegia following a seizure (Todd’s paralysis) focal seizure Aphasia with otherwise normal awareness language areas in the dominant hemisphere. Absence seizures brief or no postictal disorientation

32. 5. Is there a diurnal variation? Tonic-clonic and myoclonic seizures seen in primary generalized epilepsies more common on awakening or in early morning. Temporal lobe seizures occur any time. Certain frontal lobe seizures nocturnal presentation

33. 6. Are there any known triggering factors? Sleep deprivation Flickering lights Menses Alcohol consumption Non-compliance of medication Use of antihistamines Stress Fever Exercise

34. 7. What is the seizure frequency? Response to treatment

35. 8. What has been the maximum seizure-free period since the seizure onset? To determine if any specific antiepileptic drug was more efficacious than the others.

36. 9. Is there more than one kind of seizure? Different seizure types

37. 10. Has the patient sustained injuries related to the seizures? do not have auras do not have enough time after the aura to take preventive measures

38. 11. What is the frequency of visits to the emergency department? Degree of seizure control

39. PAST MEDICAL HISTORY Central nervous system infections such as meningitis, encephalitis, Lyme disease, cysticercosis. Head injuries, especially associated with depressed skull fracture, intracerebral hemorrhage, loss of consciousness prolonged amnesia Brain tumor Cerebrovascular accident

40. SOCIAL HISTORY Level of education Job description construction worker, heavy equipment mechanic, driver Planning pregnancy in the near future Teratogenicity of antiepileptic drugs Lower efficacy of oral contraceptives with enzyme-inducing medication (phenytoin, carbamazepine, and phenobarbital), Alcohol use risk factor for a first generalized tonic-clonic seizure interact with the metabolism of the antiepileptic drugs seizure exacerbation, especially after continued or binge drinking.

41. FAMILY HISTORY Specific epilepsy syndromes and Genetically mediated neurological disorders that have seizures as one manifestation. Juvenile myoclonic epilepsy (JME), Familial neonatal convulsions, Benign rolandic epilepsy

42. Examination Asymmetries in the size of limbs or one half of the body (hemiatrophy) perinatal cerebral insult Marks or ulcerations on the side of tongue or oral mucous membranes Gingival hyperplasia Phenytoin Dupytrens contractures chronic use of barbiturates Dystonic posturing of one arm on stressed gait, such as walking on the sides of the feet remote insult to the corticospinal tracts Multiple bruises or injuries falls secondary to seizures End gaze nystagmus, diplopia and difficulty in tandem walking toxicity related to antiepileptic medications such as carbamazepine, phenytoin, and lamotrigine

43. Examination Stigmata of neurocutaneous syndrome Neurofibramatosis café au lait spots iris hamartoms Tuberous sclerosis Ash leaf spots shahgreen patches subungal fibromas adenoma sebaceum Sturge-Weber syndrome port-wine stain (capillary hemangioma)

44. INVESTIGATING THE FIRST SEIZURE A seizure is a symptom of an underlying pathology. Investigations are directed at identifying the precipitating etiology and conditions that can be arrested, reversed, or treated. A detailed history and physical examination can provide direction to the extent of investigations

45. Laboratory Investigations Hyponatremia, hypoglycemia, hypomagnesemia, uremia and hepatic encephalopathy Serum and urine toxicology should be done when substance abuse or drug overdose is suspected. In newborns and young children appropriate metabolic screen can be requested

46. Neuroimaging CT scan subdural hematoma, subarachnoid hemorrhage, abscess, neoplastic processes, and other space occupying lesions. MRI cerebral dysplasia mesial temporal scleroses when history and physical examination is suggestive of focal pathology and the CT does not show the cause

47. Electroencephalogram (EEG) EEG tests the cerebral function rather than structure. Epileptiform discharges on the EEG can help classify the seizure types Focal and generalized slowing is reflective of focal and generalized disturbance of cerebral function respectively. Focal disturbance strokes, tumors, and abscess. Generalized disturbance toxic, metabolic, or diffuse structural abnormalities

48. Treatment Treatment of underlying condition Avoidance of precipitating factors Antiepileptic drugs Refractory epilepsy

49. Antiepileptic drugs Appear to act primarily by blocking the initiation or spread of seizures Inhibition of Na+-dependent action potentials in a frequency-dependent manner (e.g., phenytoin, carbamazepine, lamotrigine, topiramate, zonisamide, lacosamide, rufinamide), Inhibition of voltage-gated Ca2+ channels (phenytoin, gabapentin, pregabalin), Facilitating the opening of potassium channels (ezogabine), Attenuation of glutamate activity (lamotrigine, topiramate, felbamate),

50. Antiepileptic drugs Potentiation of GABA receptor function (benzodiazepines and barbiturates), Increase in the availability of GABA (valproic acid, gabapentin, tiagabine), Modulation of release of synaptic vesicles (levetiracetam). Inhibiting T-type Ca2+ channels in thalamic neurons. ethosuximide and valproic acid

51. When to Initiate Antiepileptic Drug Therapy Recurrent seizures of unknown etiology or a known cause that cannot be reversed Patients with a single seizure due to an identified lesion such as a CNS tumor, infection, or trauma, in which there is strong evidence that the lesion is epileptogenic, should be treated. Most patients with one or more of these risk factors should be treated an abnormal neurologic examination, seizures presenting as status epilepticus, postictal Todd’s paralysis, a strong family history of seizures, an abnormal EEG.

52. Antiepileptic Drug Selection for Focal Seizures Carbamazepine (or oxcarbazepine), lamotrigine, phenytoin, and levetiracetam drugs of choice approved for the initial treatment of focal seizures Carbamazepine first-order pharmacokinetics leukopenia, aplastic anemia, or hepatotoxicity Oxcarbazepine avoids an intermediate metabolite fewer drug interactions Lamotrigine skin rash Stevens-Johnson syndrome low initial doses and slow titration Phenytoin long half-life once or twice daily dosing nonlinear kinetics Long-term use of phenytoin untoward cosmetic effects (e.g., hirsutism, coarsening of facial features, gingival hypertrophy) and effects on bone metabolism

53. Antiepileptic Drug Selection for Focal Seizures Levetiracetam no known drug-drug interactions irritability, anxiety, and other psychiatric symptoms Topiramate focal and generalized seizures significant psychomotor slowing and other cognitive problems Avoid in glaucoma or renal stones Valproic acid is an effective alternative for some patients with focal seizures, especially when the seizures generalize. Gastrointestinal side effects are fewer when using the delayed-release formulation Reversible bone marrow suppression Hepatotoxicity Zonisamide, tiagabine, gabapentin, lacosamide, and ezogabine additional drugs currently used for the treatment of focal seizures with or without evolution into generalized seizures. Phenobarbital and other barbiturate compounds were commonly used in the past as first-line therapy for many forms of epilepsy sedation in adults hyperactivity in children subtle cognitive changes

54. Antiepileptic Drug Selection for Generalized Seizures Lamotrigine and valproic acid DOC for primary generalized, tonic-clonic seizures Topiramate, zonisamide, phenytoin, carbamazepine, and oxcarbazepine suitable alternatives Valproic acid absence, myoclonic, and atonic seizures DOC in patients with generalized epilepsy syndromes having mixed seizure types Carbamazepine, oxcarbazepine, and phenytoin worsen certain types of generalized seizures, including absence, myoclonic, tonic, and atonic seizures . Ethosuximide uncomplicated absence seizures not useful for tonic-clonic or focal seizures bone marrow suppression. Lamotrigine epilepsy syndromes with mixed, generalized seizure types such as JME and Lennox-Gastaut syndrome. Topiramate, zonisamide, and felbamate similar broad efficacy

55. Guidelines for antiepileptic therapy Start with one first-line drug Start at a low dose; gradually increase dose until effective control of seizures is achieved or side-effects develop Optimise compliance If first drug fails start second first-line drug, followed if possible by gradual withdrawal of first If second drug fails start second-line drug in combination with preferred first-line drug at maximum tolerated dose If this combination fails replace second-line drug with alternative second-line drug If this combination fails check compliance and reconsider diagnosis (Are events seizures? Occult lesion? Treatment compliance/alcohol/drugs confounding response?) Consider alternative, non-drug treatments (e.g. epilepsy surgery, vagal nerve stimulation) Use minimum number of drugs in combination at any one time

56. Definition of drug resistant epilepsy The International League Against Epilepsy (ILAE) has proposed the following  definition of drug resistant epilepsy  and suggests that this term be used instead of the term 'refractory epilepsy'. Drug resistant epilepsy occurs when a person has failed to become (and stay) seizure free with adequate trials of two seizure medications (called AEDs). These seizure medications must have been chosen appropriately for the person’s seizure type, tolerated by the person, and tried alone or together with other seizure medications

57. Surgical treatment Temporal lobe epilepsy resection of the anteromedial temporal lobe (temporal lobectomy) limited removal of the underlying hippocampus and amygdala (amygdalohippocampectomy) Focal seizures arising from extratemporal regions focal neocortical resection with precise removal of an identified lesion (lesionectomy). When the cortical region cannot be removed multiple subpial transection Hemimegalencephaly or other dysplastic abnormalities Hemispherectomy or multilobar resection Disabling tonic or atonic seizures, usually when they are part of a mixed-seizure syndrome (e.g., Lennox-Gastaut syndrome). corpus callosotomy

58. Surgical treatment Vagus nerve stimulation (VNS) Implantable device can detect the onset of a seizure and deliver an electrical stimulation Responsive NeuroStimulation Stereotactic radiosurgery, Laser thermoablation Deep brain stimulation (DBS)

59. When to Discontinue Therapy Withdrawal of therapy can be attempted after 2 years of seizure free interval in a patient who meets all of the following criteria complete medical control of seizures for 1–5 years single seizure type, either focal or generalized normal neurologic examination, including intelligence normal EEG In most cases, it is preferable to reduce the dose of the drug gradually over 2–3 months Most recurrences occur in the first 3 months after discontinuing therapy

60. Epilepsy in pregnancy Pre-conception counselling folic acid 5 mg daily for 2 mths before conception Fetal malformation Single drug Carbamazepine and lamotrigine have the lowest incidence of major fetal malformations Sodium valproate has relatively higher risk Levetiracetam may be safe Learning difficulties in children Lower IQ with valproate Haemorrhagic disease of the newborn oral vitamin K 20 mg daily to the mother during the last month of pregnancy IM vitamin K 1 mg to the infant at birth Increased frequency of seizures carbamazepine levels may fall in the third trimester. Lamotrigine and levetiracetam levels may fall early in pregnancy adjust the dose regimen

61. References Davidsons principle and practice of medicine, 22 nd edition Harrisons principle of internal medicine 19 th edition Wisconsin Medical Journal 2004 An Approach to the Evaluation of a Patient for Seizures and Epilepsy S. Nizam Ahmed, MD, FRCPC; Susan S. Spencer, MD

62. Thank you