Epilepsy

An introduction to the ever dynamic field of epileptology

1. EPILEPSY DR MALLUM C.B NEUROLOGY UNIT DEPT OF INTERNAL MEDICINE JUTH

2. Temporal lobe epilepsy Describe personality changes that take place in long standing or poorly controlled epilepsy Define epilepsy;classify the epileptic syndrome a)Define epilepsy b)list 4 drugs used in treatment of epilepsy,their doses for adult and side effects c)How would u recognize a named complex partial seizure? Dicuss the management of a 27 year old man presenting with two episodes of generalised seizures in the last one month.

3. QUESTION 1 Primarily generalised seizure includes: A. complex partial seizures B. Grand mal C. Absence seizure D. Atonic seizure E. Tics

4. QUESTION 2 Causes of seizure include: A. Tumours B.Hypoglycemia C. Drugs D. Head injury E. sleep deprivation

5. QUESTION 3 The following are generalised epilepsies A. Jacksonian epilepsy B. Grand mal epilepsy preceded by aura C. grand mal epilepsy without aura D. petit mal epilepsy E. psychomotor epilepsy (temporal lobe)

6. QUESTION 4 The following features may differentiate between a syncopal attack and a seizure A. Upright posture at onset B convulsive movements of the limbs C. A bitten tongue D. Urinary incontinence e. confusion after the episode

7. QUESTION 5 The following statements are true of epilepsy: A.Epilepsy should not be diagnosed on the basis of a single fit B.Most cases of epilepsy appearing in adult life are partial (focal) C.complex partial seizures always cause impairment of consciousness D. Any abnormal neurological signs present more than 4 hours after a grand mal fit suggests a structural brain lesion E petit mal seizures usually become more common as patient gets older

8. OUTLINE Definition Epidemiology - causes of seizures in adulthood Classification of seizures Classification of epilepsy syndromes Aetiology of seizures and epilepsy Differential diagnosis Evaluation of a patient with seizures Management of epilepsy -Drugs - surgery

9. DEFINITIONS A seizure is a paroxysmal event due to abnormal, excessive, hypersynchronous discharges from an aggregate of central nervous system (CNS) neurons Epilepsy describes a condition in which a person has recurrent seizures due to a chronic, underlying process A seizure can be evoked by any pathology affecting the brain, transient or permanent

10. CLASSIFICATION OF SEIZURES Partial seizures are those in which the seizure activity is restricted to discrete areas of the cerebral cortex: usually associated with structural abnormalities of the brain Generalized seizures involve diffuse regions of the brain simultaneously: may result from cellular, biochemical, or structural abnormalities . Unclassified epileptic seizures:

11. Classification of Epileptic Seizures

12. Partial Seizures simple partial seizure: consciousness is fully preserved during the seizure Complex partial seizure :consciousness is impaired. partial seizures with secondary generalization: Begin as partial seizures then spread diffusely through out the cortex

13. Partial Seizure

14. Simple Partial Seizures cause motor, sensory, autonomic, or psychic symptoms without an obvious alteration in consciousness Motor seizures: arise from the contralateral motor cortex Jacksonian march: movements arise from a restricted region and progresses over seconds to minutes to a larger portion of the extremity

15. Motor seizures : arise from the contralateral motor cortex Jacksonian march: movements arise from a restricted region and progresses over seconds to minutes to a larger portion of the extremity Todd’s paresis: localized paresis for minutes to hours following a seizure Epilepsia partialis continua: simple motor seizure that continue for hours or days

16. Sensory seizures -Somatosensory seizures: paraesthesias or numbness epigastric sensation that rises from the stomach or chest to the head Special sensory seizures: Visual: flashing lights, hallucination Auditory: crude sounds to music Gustatory: taste hallucinations, crude or complex Olfactory: unusual odours (burning rubber,kerosene ) Vertiginous: falling in space or floating

17. AUTONOMIC SEIZURES vomiting, pallor, flushing, sweating, piloerection , pupil dilatation, boborygmi , and incontinence These usually arise from the frontal or temporal region. Aura: simple partial seizures preceding complex partial seizure or secondarily generalized seizure.

18. PSYCHIC SYMPTOMS These are disturbances of higher cortical function. Usually occur in complex partial seizures Dysmnesic symptoms : déjà vu: a naive experience had been experienced before. jamais-vu:a previously experienced sensation had not been experienced, deja-entendu or jamais-entendu .

19. PSYCHIC SYMPTOMS Cognitive: dreamy states; distortions of the time sense; sensations of unreality, detachment, or depersonalization. Affective: fear, intense depression, Anger or rage, Fear or terror, Illusions: macropsia or micropsia , Depersonalization,

20. Complex Partial Seizures patient is unable to respond appropriately to visual or verbal commands during the seizure impaired recollection or awareness of the ictal phase aura is stereotypic for patient sudden behavioral arrest or motionless stare patient is typically confused following the seizure, and the transition to full recovery of consciousness may range from seconds up to an hour

21. Partial seizures with impairment of consciousness

22. COMPLEX PARTIAL SEIZURES Clinical features ·        Psychomotor triad :motor changes, automatism, psychic changes Aura (focal symptoms and signs as in simple partial seizures) ·        Absence (altered consciousness) ·        Automatism eg mimicry ( gelastic , lacrimic ) ambulatory, verbal, oro -alimentary, responsive ·        sudden onset and gradual recovery ·        Complex partial seizures arise from temporal lobe (60%), or frontal lobe (30%). MTLS Mayowa O Owolabi

23. Interictal personality disorders Very common in complex partial seizures - humorlessnes , religiosity, obsessionalism , hypersexuality -Violent behaviour -Memory loss -Psychosis – paranoid schizophrenia Automatisms :walk repetitively in small circles ( volvular epilepsy), run ( epilepsia procursiva ), or simply wander aimlessly, either as an ictal or postictal phenomenon ( poriomania

24. Automatisms consist of very basic behaviors such as chewing, lip smacking, swallowing, or "picking" movements of the hands, or more elaborate behaviors such as a display of emotion or running

25. Partial Seizures with Secondary Generalization Secondary generalization is observed frequently following simple partial seizures Eye witnesses may overlook the subtle onset of partial seizures History of an aura may be suggestive EEG analysis may be helpful in uncovering a focal onset Distinguishing between partial and generalized seizures has important implications in treatment

26. Generalized Seizures Generalised tonic clonic seizures(Grand mal) Absence seizures (petit mal) Myoclonic seizures Atonic seizures Clonic seizures Tonic seizures

27. Generalized seizures Seizure that begin over the entire surface of the brain are called generalized seizure. Convulsion start in generalized seizure because of the involvement of motor system.

28. Generalised tonic clonic seizures(Grand mal) Most common seizure type encountered in clinical settings seizure usually begins abruptly without warning Some patients may have vague premonitory symptoms( prodrome ) hours before the seizure Tonic phase:

29. Tonic phase : tonic contraction of muscles throughout the body. lasts 10–20 s muscles of expiration and the larynx at the onset : ictal cry Respirations impaired, cyanosis, Jaw muscle contraction: tongue biting Increaed sympathetic tone leads to increases in heart rate, blood pressure, and pupillary size

30. CLONIC & POSTICTAL PHASE periods of muscle relaxation on the tonic muscle contraction 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 Patients gradually regain consciousness over minutes to hours, and during this transition there is typically a period of postictal confusion headache, fatigue, and muscle ache may last hours

31. Absence Seizures (Petit Mal) sudden, brief lapses of consciousness without loss of postural control The seizure typically lasts for only seconds no postictal confusion subtle, bilateral motor signs such as rapid blinking of the eyelids, chewing movements, or small-amplitude, clonic movements of the hands Absence seizures usually begin in childhood or early adolescence, Most patients (60-70% have spontaneous remission in adolescence ) Precipitated by drowsiness, relaxation, hyperventilation, photic stimulation

32. Atypical Absence Seizures the lapse of consciousness is usually of longer duration, less abrupt in onset and cessation Accompanying motor signs EEG shows a generalized, slow spike-and-wave pattern with a frequency of 2.5/s, EEG in typical absence seizures Typical 3-Hz spike.

33. Myoclonic Seizures Myoclonus is a sudden and brief muscle contraction that may involve one part of the body or the entire body EEG may show bilaterally synchronous spike-and-wave discharges May be seen in association with juvenile myoclonic epilepsy

34. Atonic Seizures sudden loss of postural muscle tone lasting 1–2 s Consciousness is briefly impaired, but there is usually no postictal confusion Also known as “drop attacks” EEG shows brief, generalized spike-and-wave discharges followed immediately by diffuse slow waves usually seen in association with known epileptic syndromes

35. Epilepsy Syndromes An epileptic syndrome is an epileptic disorder characterized by a cluster of signs and symptoms customarily occurring together; these include such items as type of seizure, etiology , anatomy, precipitating factors, age of onset, severity , chronicity, diurnal and circadian cycling, and sometimes prognosis.

36. CLASSIFICATION OF EPILEPSY Two divisions of the classification: Idiopathic or genetic- No underlying cause other than a possible hereditary predisposition Symptomatic or structural/ metabolic :a known or suspected disorder of the central nervous system (CNS). Cryptogenic or unknown Generalized epilepsies : epilepsies with generalised seizures localization-related , partial or focal epilepsies: Epilepsies with focal or partial seizures

37. Causes of epilepsy / epileptic syndromes Idiopathic / genetic epilepsies Localisation related: Benign centrotemporal epilepsy Benign occipital epilepsy Autosom dominant nocturnal frontal lobe epilepsy Idiopathic generalised epilepsy: Childhood and juvenile absence Juvenile myoclonic epilepsy Grand mal seizures on awakening Symptomatic epilepsies Localisation related : Temporal lobe epilepsy Frontal lobe epilepsies Parietal, occipital lobe epilepsies Symptomatic generalised epilepsies: West- syndrome Lennox-Gastaut syndrome Cryptogenic epilepsies

38. Genetics Risk of a non-provoked seizure in offsprings of a parent with epilepsy: 6% Idiopathic generalised epilepsies: 9-12% Over 140 single gene diseases are accompanied by epilepsy Inborn metabolic, storage diseases Mitochondrial diseases Neurocutaneous diseases Chromosomal diseases Tuberous sclerosis

39. Common causes of symptomatic epilepsies Head injury Tumors Infarcts, hemorrhages Blood vessel malformations Infections Cortical dysgenesis Cause of newly diagnosed epilepsies is unknown in 60-65% (cryptogenic).

40. Some types of focal epilepsy Temporal lobe epilepsy http://www.wiredtowninthemovie.com/mindtrip-xml.html Frontal lobe epilepsy http://www.wiredtowninthemovie.com/mindtrip-xml.html

41. TEMPORAL LOBE EPILEPSY History of febrile seizures Aura Behavioral arrest/stare Complex automatisms Postictal disorientation, memory loss MRI- hippocampal sclerosis Often refractory to therapy Treatment- surgical resection

42. Temporal lobe epilepsy Symptoms: Often aura, experience feelings, emotions, sensation rising up from stomach, hear voices, odd smell or taste Lip smacking, hand rubbing, shouting, laughing or fiddling with buttons on clothes Seizures usually last 1-2 minutes Confusion and headache afterwards

43. Lennox- Gastaut Syndrome Onset between 1 -7 years Severe, with multiple seizure types (myoclonic, atypical absence, tonic, tonic-clonic) Precipitated by drowsiness, or understimulation, not hyperventilation Progressive mental retardation EEG 1-2.5Hz spike and wave Many causes (cryptogenic, symptomatic, cerebral palsy, West syndrome, tuberous sclerosis) Poor prognosis Mayowa O Owolabi

44. West Syndrome Infantile spasm described by DJ West in 1841 Rare syndrome Family hx in 7-17% Usu develop between 4-8 mo Salaam attacks Hypsarrhythmia on EEG Response to cortocosteroids , ACTH Usu remit on therapy or spont . Poor long term prognosis, mental retardation and continuing seizures are common sequalae Mayowa O Owolabi

45. CAUSES OF SEIZURES Metabolic disturbances electrolyte imbalance, hypo- or hyperglycemia, renal failure, and hepatic failure. Endocrine disorders , hematologic disorders, vasculitides , systemic diseases medications – antidepressants,antipsychotics abused substances – Alcohol,barbiturate withdrawal, amphetamine, cocaine

46. Causes for Acute Seizures Idiopathic Trauma Encephalitis Drugs Withdrawal from depressants Tumor High fever Hypoglycemia Extreme acidosis Extreme alkalosis Hyponatremia Hypocalcemia TRIGGERS : Fatigue, stress, poor nutrition, alcohol and sleep deprivation .

47. CAUSES OF EPILEPSY perinatal hypoxia and trauma- Obstetric injury, neonatal hypoxia etc Head Injury Brain Tumours Cerebrovascular Disease Febrile Seizures Genetic Factors- family history

48. CAUSES OF EPILEPSY I nfections parasitic infections like neurocysticercosis , Schistosomiasis , and Paragonimiasis Viral infections-Measles ,Herpes simplex, HIV Bacterial infections: meningitis( meningococcal,tuberculous ),encephalitis, opportunistic infections in HIV: cryptococcosis , herpes simplex virus, toxoplasmosis, and tuberculosis.

49. CAUSES OF EPILEPSY BY AGE Adolescents: -Trauma -Genetic disorders. -Infection. -Brain tumors. -Idiopathic Young adults: -Trauma -Brain tumors. -Idiopathic. -Alcohol withdrawal -illicit drugs.   53 NMCP UPDATE 2009- OWOLABI LF

50. CAUSES OF EPILEPSY BY AGE Older Adults: -CVD -Brain tumors. -Degenerative disorders. -Idiopathic. 54 NMCP UPDATE 2009- OWOLABI LF

51. DIFFERENTIALS Syncope Migraine Transient ischemic attack (TIA ) Sleep disorders Movement disorders Psychogenic seizure Hyperventilation Panic attack

52. Diagnosis / differential diagnosis Is it an epileptic seizure? ? Yes No Seizure type? Acute symptomatic seizure or epilepsy? Epilepsy Idiopathic or symptomatic? Acute symptomatic seizure Cause? Symptomatic epilepsy Cause? Syncope? TIA? Psychogenic?

53. Epileptic seizure versus syncope Syncope Tonic-clonic seizure Position Upright Any Facial colour Paleness Cyanosis Onset Gradual; introduced by dizziness, blurring of vision Sudden; can start by ‘aura’ (simplex partial seizure) Twitchings Rarely (‘convulsive syncope’) Always Enuresis Rarely Often Tongue bite No Often Duration 10-20 seconds Few minutes Postictal confusion No Yes Perspiration Pronounced Not typical

54. EVALUATION A complete history is the cornerstone for establishing a diagnosis of epilepsy Eye witness accounts essential symptoms before, during, and after the episode Hx of early childhood events, such as perinatal encephalopathy, febrile seizures, brain infections, or head injurie

55. MANAGEMENT OF EPILEPSY EVALUATION: This is to establish that patient has epilepsy and to determine the type of seizures and epilepsy. HISTORY: from patient or eyewitness. Line of questioning include: Tell me about the attacks or spells (patient may deny epilepsy) Is there a warning sign? If so, what is the warning sign Is there loss of consciousness, convulsions, biting of the tongue, injury, incontinence of urine etc.? Is it associated with abnormal behaviour? What does the patient do after the seizure? When did the attack begin. How often do they occur Are the attacks related to time of the day, food intake, position, sleep, emotional upset, fever, and fatigue, drugs or alcohol?

56. MANAGEMENT OF EPILEPSY What other factors precipitate the attacks? Any past history of febrile convulsions, head injury, brain infections? Any family history of epileptic seizures of febrile convulsions? What is the occupation of the patient, his social habits, income and education? Physical examination: This is done to identify any focal neurological signs. Complete neurological examination. Mental status and other higher cerebral function, visual field, motor, sensory, coordination and reflexes.

57. EXAMINATION Careful examination of the skin may reveal signs of neuro -cutaneous disorders, such as tuberous sclerosis or neurofibromatosis , complete neurological examination : focal signs may indicate brain lesion

58. INVESTIGATIONS Investigations of epilepsy may be grouped into those that are structural (MRI and CT), functional (EEG, psychological, PET, SPECT) and biochemical (blood tests, CSF examination).

59. EEG For diagnosis of epilepsy by providing findings of epileptiform changes To determine whether the seizure disorder is partial onset or generalised . To check for evidence of background encephalopathy All patients with a suspected seizure disorder should have an EEG done A normal Interical EEG does not rule out a seizure disorder.

60. EEG OF ABSENCE SEIZURES

61. MRI Indications for MRI in evaluation of seizure disorders .    Partial seizures, on history and/or EEG. 2.    Fixed or progressive neurological or psychological deficit. 3.    Onset of generalized seizures before the age of 1 year and after 20 years. 4.    Difficulty obtaining seizure control with AEDs. 5.    Unexplained loss of seizure control or status Epilepticus .

62. OTHER TESTS Functional imaging procedures such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are used to evaluate patients with medically refractory seizures being considered for surgery Routine blood tests and lumbar puncture are not usually indicated in evaluation of patients but in context of acute illnesses and also to provide a baseline(in the case of biochemical tests) prior to commencement of AEDS. Measurement of serum prolactin can be done to rule out psychogenic seizures

63. TREATMENT Drug therapy is the mainstay of treatment Seizure classification is important for determining treatment Patients with recurrent seizures of unknown should be treated

64. TREATMENT Single seizures should be treated in the following situations: 1) an abnormal neurologic examination , (2) seizures presenting as status epilepticus , (3) postictal Todd's paralysis , (4) a strong family history of seizures, (5) an abnormal EEG

65. AEDs Old Primidon e Phenobarbit one Fosphenytoin Phenytoin Clobazam Clonazepam Ethosuximid Valproate Carbamazepine New Levatiracetam Lamotrigine Oxcarbazepine Topiramate Gabapentin Felbamate Vigabatrin Zonisamide Tiagabin

66. TREATMENT OF SPECIFIC SEIZURE TYPES Primarily generalised tonic clonic seizures: Valproate (200mg tds ), Phenytoi n(300mg nocte ), Lamotrigine , Topiramate Partial seizures : Carbamazepine (200mg BD), Valproate, Phenytoin, Phenobarbital. Absence seizures: Valproate or ethosuximide Myoclonic seizures: Valproate

67. PHENYTOIN Adverse effects Ataxia and nystagmus. Cognitive impairment. Hirsutism Gingival hyperplasia, Coarsening of facial features. folate dependent megaloblastic anaemia , Osteomalacia , Inhibition of ADH, inhibition of insulin secretion→hyperglycemia and glycosuria Hypoprothrominemia —coagulopathy Exacerbates absence seizures.

68. SODIUM VALPROATE inhibits P450 system Adverse effects: Elevated liver enzymes including own. Tremor, hair loss, changes in hair growth increased appetite Weight gain. coagulopathy (inhibition of platelet aggregation), Idiosyncratic hepatotoxicity. Negative interactions with other antiepileptics. Teratogen : spina bifida

69. CARBAMAZEPINE Adverse effects Stupor, coma, respiratory depression, drowsiness, dizziness, vertigo, ataxia, blurred vision, diplopia, bradycardia, skin rashes, GI upsets. Hyponatremia in elderly The 10,11-epoxide metabolite →blood dyscrasias (leukopenia and aplastic anaemia), and serious liver toxicity.

70. LEVETIRACETAM ( Keppra ) Adjunct Rx of refractory Partial Seizure Unknown mechanism of action but binds to presynaptic vesicle protein ADVERSE EFFECT Dizziness, sleep disturbances, headache, and asthenia (LACK OF ENERGY)

71. DISCONTINUATION OF TREATMENT Withdrawal of anti epileptic drug treatment may be attempted in patients who have been seizure free for 3 years and who have a normal EEG at time of consideration. Antiepileptic drug therapy should be tapered off and not stopped abruptly

72. OTHER MANAGEMENT OPTIONS Surgical therapy -Temporal lobectomy -  Frontal lobectomy -  Lesionectomy - Corpus callosotomy , hemispherectomy Non-pharmacologic treatment - Vagal nerve stimulation - Ketogenic diet

73. MANAGEMENT OF STATUS EPILEPTICUS Status epilepticus refers to repeated seizures with no intervening recovery of consciousness OR a single seizure that lasts up to 30 mins . However, for practical purposes it is advised to treat any seizure that lasts more than 5 mins .

74. CAUSES OF STATUS EPILEPTICUS anticonvulsant withdrawal or noncompliance, metabolic disturbances, drug toxicity , CNS infection , CNS tumors, refractory epilepsy, head trauma

75. NMCP UPDATE 2009- OWOLABI LF 80

76. Status Epilepticus Treatment Time post onset Treatment Onset Ensure adequate ventilation/O2 2-3 min. IV line with NS, rapid assessment, blood draw 4-5 min. Lorazepam 4 mg (0.1 mg/kg) or diazepam 10 mg (0.2 mg/kg) over 2 minutes via second IV line or rectal diazepam 7-8 min. Thiamine 100 mg, 50% glucose 25 mg IV Phenytoin or fosphenytoin 20 mg/kg IV (phenytoin PE) at  50 mg/per minute phenytoin or 150 mg per minute fosphenytoin (  0.75 mg/kg/min) Pyridoxine 100-200 mg IV in children under 18 mo.

77. Status Epilepticus Treatment (cont.) Time post onset Treatment 10 min. Can repeat lorazepam or diazepam if seizures ongoing 30-60 min. EEG monitoring unless status ended and patient waking up 40 min. Phenobarbital 20 mg/kg at  5 mg per minute (0.75 mg/kg per minute) continued Reference: Lowenstein DH, Alldredge BK, Status Epilepticus. NEJM 1998; 338: 970-976.

78. Status Epilepticus Treatment (cont.) Time post onset Treatment 70 min. Pentobarbital 3-5 mg/kg load, 1 mg/kg per hour infusion, increase to burst- suppression OR Propofol 3-5 mg/kg load, 5-10 mg/kg/hr initial infusion then 103 mg/kg/hr OR Midazolam 0.2 mg/kg load, .25-2 mg/kg infusion Reference: Lowenstein DH, Alldredge BK, Status Epilepticus. NEJM 1998; 338: 970-976.

79. First Aid Stay calm Do not insert anything into the person's mouth Keep person safe, remove dangerous objects Do not restrain

80. OTHER MANAGEMENT ISSUES Restrictions on Driving, Climbing heights, Working with heavy machinery, Swimming alone Seizures in Pregnancy/ Catamenia Social stigma Trauma Job limitation/medication expenses Medication side effects