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Epilepsy

Sergiu Sabetay M.D. Epilepsy. Alexander the Great. Agatha Christie. Lewis Carroll. Joan of Arc. Epilepsy. Basic mechanisms underlying seizures and epilepsy Clinical epilepsy Antiepileptic drugs Status epilepticus Epilepsy surgery. Basic Mechanisms Underlying Seizures and Epilepsy.

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Epilepsy

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  1. Sergiu Sabetay M.D. Epilepsy

  2. Alexander the Great Agatha Christie Lewis Carroll Joan of Arc

  3. Epilepsy • Basic mechanisms underlying seizures and epilepsy • Clinical epilepsy • Antiepileptic drugs • Status epilepticus • Epilepsy surgery

  4. Basic Mechanisms Underlying Seizures and Epilepsy

  5. Epilepsy and Seizure- Etymology • Epilepsy- from the Greek word “to seize” or “take hold of” • Seizure- from the Latin sacrire- “to take possession of”

  6. Definitions  Seizure: the clinical manifestation of an abnormal and excessive excitation and synchronization of a population of cortical neurons  Epilepsy: a tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insults Epileptogenesis: sequence of events that converts a normal neuronal network into a hyperexcitable network

  7. Definitions cont. • Convulsion: overt, major motor manifestations of a seizure • Aura: subjective disturbance of perception representing a focal electrical disturbance

  8. Definitions: phases of seizures • Ictus or ictal phase: the seizure itself; consists of paroxysmal firing of brain neurons. • Post-ictal phase: period after the seizure with temporary neurological dysfunction. • Inter-ictal: in-between seizures.

  9. Seizures vs. Epilepsy • Seizure is the symptom; epilepsy is the disease • Seizure disorder = epilepsy • A person can have seizures and not have epilepsy • meningitis, drug intoxication, metabolic dist. etc... • Specific Epilepsy types (or syndromes) can be recognized • specific seizures, age of onset, EEG features, prognosis • management

  10. Basic Mechanisms Underlying Seizures and Epilepsy  Feedback and feed-forward inhibition, illustrated via cartoon and schematic of simplified hippocampal circuit Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed. Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540.

  11. Cellular Mechanisms of Seizure Generation  Excitation (too much) • Ionic—inward Na+, Ca++ currents • Neurotransmitter—glutamate, aspartate  Inhibition (too little) • Ionic—inward CI-, outward K+ currents • Neurotransmitter—GABA

  12. Etiology of seizures • I. Primary neurologic disorders • II. Systemic disorders

  13. Etiology of seizuresI. Primary neurologic disorders • 1. Benign febrile convulsions of childhood • 2-4% of children 3 months old to 5 years old • Absence of CNS infection • Family history may be positive • Usually less than 15’, no focal features • Significant risk of recurrence • Treatment usually unnecessary • 2-6% probability to develop a chronic seizure disorder

  14. Etiology of seizuresI. Primary neurologic disorders • 2. Idiopathic epilepsy • 75% of epilepsy cases • Peak ages 5-25 years (>75% before 18 years) • Recurrence rates differ (30-70%) • Higher recurrence in patients with EEG abnormalities, Todd paralysis, persistent neurological abnormalities, multiple seizures prior to presentation, family history of afebrile seizures.

  15. Etiology of seizuresI. Primary neurologic disorders • 3. Head trauma • Mostly when occurring perinatally or when related to depressed skull fracture or intracerebral or subdural hematoma • Prophylaxis in head injury patients?

  16. Etiology of seizuresI. Primary neurologic disorders • 4. Stroke • 5-15% of patients • Secondary to • embolic or thrombotic stroke • hemorrhagic stroke • vascular malformation with or without rupture

  17. Etiology of seizuresI. Primary neurologic disorders • 5. Mass lesions • Brain tumors • Abscesses

  18. Etiology of seizuresI. Primary neurologic disorders • 6. Meningitis or encephalitis • Bacterial • Viral • Tuberculous • Fungal • Parasitic • AIDS patients • AIDS dementia complex • Toxoplasma • Cryptococcus

  19. Etiology of seizuresII. Systemic disorders • 1.Hypoglycemia • 2.Hyponatremia (Na<120 mEq or rapid level decline) • 3.Hyperosmolar states • 4.Hypocalcemia • 5.Uremia • 6.Hepatic encephalopathy • 7.Porphyria (Bromide treatment, Vigabatrin and Gabapentin seem safe)

  20. Etiology of seizuresII. Systemic disorders • 8.Drug overdose (antidepressants, cocaine, insulin, isoniasid, lidocaine, methylxantines) • 9.Drug withdrawal (alcohol or sedative drugs) • 10. Global cerebral ischemia (myoclonus, tonic –clonic seizures) • 11.Hypertensive encephalopathy • 12.Eclampsia • Pregnant woman with hypertension, proteinuria, edema- treat with Magnesium sulfate • 13.Hyperthermia

  21. Etiology of Seizures and Epilepsy  Infancy and childhood • Prenatal or birth injury • Inborn error of metabolism • Congenital malformation  Childhood and adolescence • Idiopathic/genetic syndrome • CNS infection • Trauma

  22. Etiology of Seizures and Epilepsy (cont.)  Adolescence and young adult • Head trauma • Drug intoxication and withdrawal*  Older adult • Stroke • Brain tumor • Acute metabolic disturbances* • Neurodegenerative *causes of acute symptomatic seizures, not epilepsy

  23. Clinical Epilepsy

  24. Evaluation/Diagnosis • History • Examination • “Routine laboratory tests” • EEG • Neuroimaging • Differential Diagnosis

  25. Evaluation/Diagnosis: History • details are critical! • circumstances of the event • interview observers • do not be satisfied by medical terms used by others (lay people or medical)! • “he had an absent seizure”-- typically unreliable!!! • be wary of hearsay evidence-- usually incorrect!!! • medical and social background

  26. Evaluation/Diagnosis: Exam • the neurological examination is often normal • in acute setting: look for tell-tale signs of seizure • tongue lacerations, lip biting, bruises, rug burns, Babinski signs, asymmetric motor signs • look for cutaneous manifestations of disease • general exam findings of disease • neurological findings of underlying disease

  27. Evaluation/Diagnosis: Laboratory • some tests are basically always needed • CBC • electrolytes, glucose, calcium, magnesium • Urine tests • others are commonly needed • toxic screen and ethanol: any suspicion at all • lumbar puncture: • suspect infection, subarachnoid hemorrhage • CT scan of brain generally first! • imaging

  28. Neuroimaging • MRI vs. CT • choice depends on circumstances • MRI • generally preferable if time permits • CT • in acute setting when LP or urgent info needed • if blood is supected • small infants

  29. Electroencephalogram (EEG)  Graphical depiction of cortical electrical activity, usually recorded from the scalp.  Advantage of high temporal resolution but poor spatial resolution of cortical disorders.  EEG is the most important neurophysiological study for the diagnosis, prognosis, and treatment of epilepsy.

  30. Physiological Basis of the EEG (cont.) Electrical field generated by similarly oriented pyramidal cells in cortex (layer 5) and detected by scalp electrode

  31. Electroencephalogram (EEG) • generally obtain “routine,” inter-ictal EEG • may be normal in up to 40% of epileptics • focal vs. generalized epileptiform discharges • focal or generalized slowing less useful • prolonged EEG monitoring • more expensive, difficult; try to capture event • unsuccessful treatment • uncertainty regarding events • epileptic vs, non-epileptic

  32. Electroencephalogram (EEG)  Clinical applications • Seizures/epilepsy • Sleep • Altered consciousness • Focal and diffuse disturbances in cerebral functioning

  33. Normal Adult EEG •  Normal alpha rhythm

  34. Classification of seizures

  35. Classification of seizures (International League Against Epilepsy) • I. Partial (focal, local) seizures • Simple partial seizures • Complex partial seizures • With impairment of consciousness at onset • Partial seizures evolving to secondarily generalized seizures • II. Generalized seizures • Absence seizures • Myoclonic seizures • Clonic seizures • Tonic seizures • Tonic-clonic seizures • Atonic seizures • III. Unclassified epileptic seizures

  36. Simple partial seizures • Begins on one side of the body • Do not impair consciousness • May have motor or sensory manifestations • Ictal EEG: usually a focal contralateral discharge

  37. Simple Partial Seizure Subclassification  With motor signs  With somatosensory or special sensory symptoms  With autonomic symptoms or signs  With psychic symptoms (disturbance of higher cerebral function)

  38. Complex partial seizures • Typically seen in temporal lobe epilepsy • Impairment of consciousness, automatisms • Often preceded by aura of olfactory or visceral sensations or déjà vu • Common postictal phase- minutes to hours • Ictal EEG: unilateral or bilateral temporal discharges • May also emanate from frontal lobes

  39. Complex partial seizures

  40. Absence seizures • Sudden onset of unresponsiveness lasting seconds, with interruption of ongoing activity but no loss of muscle tone • Induced by hyperventilation • No postictal phase • Reduced performance in school !!! • Ictal EEG: generalized 3 Hz spike and wave

  41. Absence seizures

  42. Tonic–clonic seizures • Sudden loss of consciousness with onset of rigid muscle tone (tonic phase) followed by rhythmic convulsive movements lasting up to several minutes (clonic phase) • Sometimes brief prodromal sensation • Postictal phase –minutes to hours • Ictal EEG: bilateral 10 Hz activity (tonic) followed by slow wave complexes (clonic)

  43. Tonic-clonic seizures

  44. Myoclonic seizures • Brief contractions of trunk or extremities without loss of consciousness, often occurring at sleep onset and on awakening • Differentiate from other types of myoclonus • Ictal EEG: polyspike and waves • May be idiopathic or associated with neurodegenerative disorders

  45. Atonic seizures • Sudden loss of axial muscle tone, causing precipitous falls, and often, head injury • Ictal EEG: generalized polyspike and waves or low-voltage fast activity

  46. Secondarily Generalized Seizures  Begins focally, with or without focal neurological symptoms  Variable symmetry, intensity, and duration of tonic (stiffening) and clonic (jerking) phases  Typical duration up to 1-2 minutes  Postictal confusion, somnolence, with or without transient focal deficit

  47. Seizure types

  48. Differential diagnosis

  49. Differential Diagnosis of Non-epileptic Events  Syncope  Migraine  Cerebral ischemia  Movement disorder  Sleep disorder  Metabolic disturbance  Psychiatric disturbance  Breath-holding spells

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