Seizure & Epilepsy (qggakbhghfccbbjklvcf

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1. SEMINAR PRESENTATION ON SEIZURE AND EPILEPSY PRESENTERS: 1, Birhane D esta 2, B israt E nedeg 3, B ruktwit Asfaw venue: MODERATOR: Dr. Tadewos 1

2. Outline Definition Epidemiology Classification Epilepsy Syndromes Causes 2

3. Definition Seizure is a paroxysmal event due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a condition in which a person has recurrent seizures due to a chronic, underlying process. 3

4. Epidemiology Seizure: - incidence: 5–10% - highest incidence in early childhood and late adulthood Epilepsy: - incidence: 0.3–0.5% - prevalence: 5–10 persons per 1000 4      

5. Epidemiology typical absence seizures - the main seizure type in 15–20% of children with epilepsy generalized-onset tonic-clonic seizures -most common seizure type -10% of all persons with epilepsy 5

6. Classification of Seizures Focal seizures -without dyscognitive features -with dyscognitive features Generalized seizures -Absence : typical vs. atypical -Tonic clonic -Clonic -Tonic -Atonic -Myoclonic 6

7. The basic difference Focal - limited to one cerebral hemisphere - associated with structural abnormalities of the brain Generalized - involves both cerebral hemispheres - cellular, biochemical, or structural abnormalities 7

8. Focal Seizures without dyscognitive features -no impairment of cognitive function -no anterograde amnesia or post ictal aphasia. with dyscognitive features - transient impairment of cognitive function - anterograde amnesia or post ictal aphasia. 8

9. Clinical features can cause motor, sensory, autonomic, or psychic symptoms Motor symptoms -Jacksonian march -Todd's paralysis -epilepsia partialis continua -automatisms 9

10. Sensory somatic sensation (e.g., paresthesias), vision (flashing lights or formed hallucinations), equilibrium (sensation of falling or vertigo), Hearing (crude or highly complex sounds) Olfaction(unusual, intense odors e.g., burning rubber or kerosene) 10

11. Autonomic symptoms -flushing, sweating, piloerection Psychic symptoms - subjective, "internal" events that are not directly observable by someone else are referred to as auras . 11

12. Evolution of Focal Seizures to Generalized Seizures usually of the tonic-clonic variety. often difficult to distinguish from a primary generalized-onset tonic-clonic seizure. Can be differentiated through careful history and EEG. 12

13. Generalized Seizures 13

14. Absence Seizures Typical - brief lapses of consciousness with abrupt onset - EEG: rapid spike-and wave pattern(3-Hz) -more responsive to anticonvulsants Atypical - lapse of consciousness is usually of longer duration and less abrupt in onset -EEG: slow spike-and-wave pattern ( < 2.5 Hz) -less responsive to anticonvulsants 14

15. Clinical features bilateral motor signs such as rapid blinking of the eyelids, chewing movements, or small-amplitude, clonic movements of the hands. decline in school performance motor signs that may include focal or lateralizing features 15

16. Generalized, Tonic-Clonic Seizures metabolic derangements Has no warning signs Two phases -tonic -clonic 16

17. Tonic phase tonic contraction of muscles causes: -loud moan or "ictal cry" -Impaired respiration and cyanosis -biting of the tongue Increase in sympathetic tone leads to: -increases in HR, BP, and pupillary size 17

18. Clonic phase evolves 10-20 seconds after of tonic phase and lasts no more than 1 minute superimposition of periods of muscle relaxation on the tonic muscle contraction leads to: -unresponsiveness and muscular flaccidity -excessive salivation -bladder or bowel incontinence postictal confusion Patients subsequently complain of headache, fatigue, and muscle ache that can last for many hours 19

19. Atonic Seizures sudden loss of postural muscle tone lasting 1-2 s. Consciousness is briefly impaired, but no postictal confusion may cause only a quick head drop substantial risk of direct head injury 20

20. Myoclonic Seizures sudden and brief muscle contraction that may involve one or the entire part of the body Can be physiologic or pathologic considered to be true epileptic events 21

21. Currently Unclassifiable Seizures Epileptic spasms - occur predominantly in infants -characterized by a briefly sustained flexion or extension of predominantly proximal muscles - The EEG in these patients usually shows hypsarrhythmias , which consist of diffuse, giant slow waves with a chaotic background of irregular, multifocal spikes and sharp waves - EMG) also reveals a characteristic rhomboid pattern 22

22. Epilepsy Syndromes Disorders in which epilepsy is a predominant feature and there is sufficient evidence to suggest a common underlying mechanism. Exs Juvenile Myoclonic Epilepsy Lennox-Gastaut Syndrome Mesial Temporal Lobe Epilepsy Syndrome 23

23. Juvenile Myoclonic Epilepsy Is of unknown cause and common in early adolescence myoclonic seizures is common feature Many patients also experience generalized tonic-clonic seizures, and up to one-third have absence seizures Consciousness is preserved Has family history and respond well to appropriate anticonvulsant medication 24

24. Lennox-Gastaut Syndrome Common in children -triad: 1, multiple seizure types 2, EEG <3 Hz spike-and-wave discharges 3, impaired cognitive function - is associated with CNS disease or dysfunction from a variety of causes 25

25. Mesial Temporal Lobe Epilepsy Syndrome is the most common syndrome associated with focal seizures with dyscognitive features Has distinctive clinical, EEG, and pathologic features characteristic hippocampal sclerosis on MRI refractory to anticonvulsants but responds well to surgical intervention 26

26. 27 History History of febrile seizures Family history of epilepsy Early onset Rare generalized seizures Seizures may remit and reappear Seizures often intractable

27. Causes of seizure Seizures are a result of a shift in the normal balance of excitation and inhibition within the CNS 3 factors determine why certain conditions may cause seizures or epilepsy in a given patient. 1) there are differences between individuals in the susceptibility or threshold for seizures 2) There are a variety of conditions that have an extremely high likelihood of resulting in a chronic seizure disorder 3) Seizures are episodic

28. Causes of Seizures Neonates Perinatal hypoxia and ischemia trauma Acute CNS infection Metabolic disturbances Drug withdrawal Developmental disorders Genetic disorders 29

29. Infants and children Febrile seizures Genetic disorders CNS infection Developmental disorders Trauma Idiopathic 30

30. Adolescents Trauma Genetic disorders Infection Brain tumor Illicit drug use Idiopathic Young adults Trauma Alcohol withdrawal Illicit drug use Brain tumor Idiopathic 31

31. Older adults Cerebrovascular disease Brain tumor Alcohol withdrawal Metabolic disorders degenerative CNS diseases Idiopathic 32

32. Drugs and Other Substances Alkylating agents Antimalarials Antimicrobials/antivirals Anesthetics and analgesics Immunomodulatory drugs Psychotropics Radiographic contrast agents Sedative-hypnotic drug withdrawal Drugs of abuse 33

33. ROAD MAP Pathophysiology Risk Factors Precipitating Factors Differential Diagnosis 34 ROAD MAP Pathophysiology Risk Factors Precipitating Factors Differential Diagnosis

34. Major Neurotransmitters of the CNS Excitatory Neurotransmitters Stimulate neuron towards an action potential Create excitatory postsynaptic potentials Inhibitory Neurotransmitters Reduce the probability that a neuron shows an action potential. Create inhibitory postsynaptic potentials 35

35. Classification 37

36. Excitatory Neurotransmitters Acetylcholine Aspartate Dopamine Norepinephrine Epinephrine Glutamate Serotonin Inhibitory Neurotransmitters GABA Glycine 38

37. Mechanisms of Seizure Initiation and Propagation Seizure activity begin in discrete region of the cortex and spread to neighboring regions. Initiation Phase (1) High-frequency bursts of action potentials and (2) Hyper-synchronization. Propagation Phase 39

38. … What causes the bursting activity? Long-lasting depolarization of the neuronal membrane due to influx of extracellular calcium (Ca 2+ ), which leads to the opening of voltage dependent sodium (Na + ) channels, influx of Na + , and generation of repetitive action potentials. Synchronized bursts 40

39. Recruitment of Surrounding Neurons (Synchronization) * An increase in extracellular K + * Accumulation of Ca 2+ in pre-synaptic terminals * Depolarization-induced activation of the N - methyl-D- aspartate (NMDA) * ephaptic interactions related to changes in tissue osmolarity and cell swelling 41

40. 42

41. Factors Controlling Neuronal Excitability Intrinsic Change in conductance of ion channel Response of membrane receptors Cytoplasmic buffering Secondary-messenger systems Protein expression as determined by gene modification Extrinsic Change in amount or type of neurotransmitters present at the synapse Modulation of receptors by extracellular ions or other molecules Non-neuronal cells like astrocytes and oligodendrocytes are also involved. 43

42. Mechanisms of Epileptogenesis Epileptogenesis refers to the transformation of a normal neuronal network into one that is chronically hyper-excitable. There is often a delay of months to years between an initial CNS injury such as trauma, stroke, or infection and the first seizure. 44

43. The injury appears to initiate a process that gradually lowers the seizure threshold in the affected region until a spontaneous seizure occurs. Some forms of epileptogenesis are related to structural changes in neuronal networks . 45

44. Risk Factors Previous Brain Injury Previous Brain infection Brain Tumor History of Stroke History of Complex Febrile Seizures Use of certain Medications Drug Overdose Exposure to Toxins 46

45. . . . Family History of Seizure Degenerative Diseases like Alzheimer Pre- eclampsia Chemical abnormalities (decreased or excess blood sodium or glucose, low blood calcium) Liver or Kidney Failure Severe, Untreated High Blood Pressure 47

46. Precipitating Factors Sleep Deprivation Fever Alcohol Hypoxia Infection Hormonal Changes Stress Flashing lights, especially strobe lights Missing doses of anti-epileptic medicines 48

47. Differential Diagnosis 1. Syncope 2. Psychological Disorders - Psychogenic seizure, panic attack 3. Metabolic Disturbances - Alcoholic blackouts, Hypoglycemia & Hypoxia 4. Psychoactive Drugs (E.g. hallucinogens) 5. Transient Ischemic Attack 6. Sleep Disorders 7. Movement Disorders 8. Special Considerations in Children -Apnea, night terror . . . 49

48. Syncope Syncope is the phenomenon of loss of consciousness associated with loss of postural tone . The episode is caused by global impairment of blood flow to the brain; occasionally, hypo-perfusion may be confined to the cerebral hemispheres or the brain stem, and involvement of either structure produces unconsciousness. 50

49. 51

50. Psychogenic Seizures Psychogenic seizures are non-epileptic behaviors that resemble seizures. Certain behaviors, such as side-to-side turning of the head, asymmetric and large-amplitude shaking movements of the limbs, twitching of all four extremities without loss of consciousness, and pelvic thrusting Last longer than epileptic seizures and may wax and wane over minutes to hours. 52

51. Special situations Status Epilepticus Women and epilepsy 53

52. Status epilepticus refers to continuous seizures or repetitive, discrete seizures with impaired consciousness in the interictal period The duration of seizure traditionally > 15–30 min 54

53. Subtypes of SE Generalized convulsive SE(GCSE) persistent, generalized electrographic seizures, coma, and tonic- clonic movements Non convulsive SE persistent absence seizures or partial seizures, confusion or partially impaired consciousness, and minimal motor abnormalities GCSE is an emergency and must be treated immediately,since cardiorepiratory dysfunction,hyperthemia and metabolic derangement can develop as a consequence of prolonged seizure 55

54. Most common cause of GCSE -anticonvulsant withdrawal or - metabolic disturbances - drug toxicity - head trauma - CNS infection - CNS tumors 56

55. Management of a patient in GCSE Attend to any acute cardiorespiratory problem or hyperthermia Perform a brief medical and neurological examination Establish venous access and send for laboratory studies to identify metabolic abnormalities Anticonvulsant therapy should then begin without delay Treatment of nonconvulsive status epilepticus is less urgent than GCSE 57

56. Special issues related to women & epilepsy Catamenial epilepsy Some women experience a marked increase in seizure frequency around the time of menses. This is believed to be mediated by either the effects of estrogen and progesterone on neuronal excitability or changes in antiepileptic drug levels due to altered protein binding or metabolism. 58

57. Pregnancy Most women with epilepsy who become pregnant will have an uncomplicated gestation and deliver normal baby Seizure frequency ~50% unchanged , ↑in 30%, and ↓ in 20% (endocrine effect and pharmacokinetic) 59

58. Incidence of fetal abnormality 2-3% ( healthy women ). 5-6% ( epileptic mothers ). Cleft lip, cleft palate, → lamotrigine Carbamazepine , valproic acid : neural tube defects Management - MonoRx , at the lowest possible effective dose - Folate 1-4mg/d. - Oral vit K ,20mg/d @ the last 2 wks of pregnancy 60

59. Approach to a patient with seizure History an indepth history is essential, for in many cases the diagnosis of a seizure is based solely on clinical grounds—the examination and laboratory studies are often normal . Focus on the symptoms before, during, and after the episode:-in order to differentiate a seizure from other paroxysmal events Interview witnesses to the event The history should also focus on the risk factors and predisposing enents 61

60. Risk factors History of febrile seizures; unrecognized earlier auras or brief seizures; family history of seizures Epileptogenic factors : Identify prior head trauma, stroke, tumor, or vascular malformation Precipitating factors sleep deprivation, systemic diseases, electrolyte or metabolic derangements, CNS infection, drugs that lower the seizure threshold, or alcohol or illicit drug use. 62

61. Physical examination Signs of infection or systemic illness Skin : signs of neurofibromatosis, tuberous sclerosis, chronic liver or renal disease Organomegaly : metabolic storage disease Limb asymmetry : developmental brain injury Signs of head trauma, alcohol or drug abuse Auscultation of the heart and carotid arteries: cerebrovascular disease 63

62. Complete neurologic examination Required in all patients Focus on cerebral hemisphere signs. Assess mental status (including memory, language function, and abstract thinking) for suggestion of lesions in the anterior frontal, parietal, or temporal lobes. 64

63. Test visual fields to screen for lesions in the optic pathways and occipital lobes. Motor function testing : Pronator drift, deep tendon reflexes, gait, and coordination may suggest lesions in motor (frontal) cortex. Cortical sensory testing (e.g., double simultaneous stimulation) may detect lesions in the parietal cortex 65

64. search for signs of infection or systemic illness HEENT – head trauma CVS - auscultation of the heart and carotid arteries GIS- HSM - a metabolic storage disease INTEGU- neurocutaneous disorders, such as tuberous sclerosis or neurofibromatosis, or chronic liver or renal disease MSK - limb asymmetry may provide a clue to brain injury early in development CNS - All patients require a complete neurologic examination 66

65. Investigations Laboratory studies to identify the more common metabolic causes of seizures such as abnormalities in electrolytes, glucose, calcium, or magnesium, and hepatic or renal disease. A screen for toxins in blood and urine should also be obtained from all patients in appropriate risk groups, especially when no clear precipitating factor has been identified. 67

66. A lumbar puncture(LP) is indicated if there is any suspicion of meningitis or encephalitis, and it is mandatory in all patients infected with HIV , even in the absence of symptoms or signs suggesting infection. Complete blood count To help identify infectious causes 68

67. Electrophysiologic studies All patients who have a possible seizure disorder should be evaluated with an EEG as soon as possible. Electrographic seizure activity during an event clearly establishes diagnosis. Absence of electrographic seizure activity does not exclude a seizure disorder. 69

68. EEG is used for classifying seizure disorders and aiding in the selection of anticonvulsant medications. in general, a normal EEG implies a better prognosis, whereas an abnormal background or profuse epileptiform activity suggests a poor outlook 70

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70. Brain imaging Almost all patients with new-onset seizures should have a brain imaging study to determine whether there is an underlying structural abnormality that is responsible . 72

71. MRI MRI > CT : cerebral lesions In some cases MRI will identify lesions such as tumors, vascular malformations, or other pathologies that need immediate therapy CT CNS infection and mass lesion,if MRI is not available 73

72. PET & SPECT for medically refractory seizure Serum prolactin level organic Vs psychogenic seizure elevate in generalized seizure and complex partial seizure but not in psychogenic seizure 74

73. ECG Cardio vascular risk factor 75

74. Treatment Therapy for a patient with a seizure disorder is almost always multimodal and includes :- treatment of underlying conditions avoidance of precipitating factors suppression of recurrent seizures addressing a variety of psychological and social issues. 76

75. Surgical Tx of RE Approximately 20–30% of patients with epilepsy continue to have seizures despite efforts to find an effective combination of antiepileptic drugs. Usually done in focal seizure for patients with temporal lobe epilepsy 77

76. Mmt of psychological & social issues Societal stigmas can be devastating. Effect on quality of life can be immense. Driving is restricted in all 50 states of the U.S. for patients who have experienced a seizure. Restrictions vary, requiring that the patient be free of seizures from 3–24 months before being allowed to drive. 78

77. REFERENCES Harrison Principle of Internal Medicine 18ed. Up to Date 21.6 79

78. Thank you THANK YOU 80