EPILEPSY

Terminology and Classification Seizure Seizure Brief disturbance of cerebral dysfunction due to abnormal synchronized neuronal electrical discharge Brief disturbance of cerebral dysfunction due to abnormal synchronized neuronal electrical discharge “Provoked or acute symptomatic seizure” “Provoked or acute symptomatic seizure” Identifiable temporary or permanent isolated condition that disrupts cerebral structure or function Identifiable temporary or permanent isolated condition that disrupts cerebral structure or function Drug (ETOH) withdrawal, acute head trauma, hypoglycemia, CVA Drug (ETOH) withdrawal, acute head trauma, hypoglycemia, CVA “Unprovoked seizure” “Unprovoked seizure” Cryptogenic: Occult cause other then genetic etiology Cryptogenic: Occult cause other then genetic etiology Idiopathic: no cause other than genetic predisposition Idiopathic: no cause other than genetic predisposition Epilepsy: recurrent uprovoked seizures Epilepsy: recurrent uprovoked seizures Epilepsy is considered to have occurred after the 2 nd unprovoked event. Epilepsy is considered to have occurred after the 2 nd unprovoked event.

International Classification of Epilepsy Partial seizures Partial seizures Simple partial seizures ( unimpaired consciousness ) Simple partial seizures ( unimpaired consciousness ) Complex partial seizures ( impaired consciousness ) Complex partial seizures ( impaired consciousness ) Partial seizure evolving into Secondarily generalized Partial seizure evolving into Secondarily generalized Generalized seizures ( Primary seizure disorder ) Generalized seizures ( Primary seizure disorder ) Absence seizures Absence seizures Tonic-Clonic seizures Tonic-Clonic seizures Clonic seizures Clonic seizures Tonic seizures Tonic seizures Myoclonic seizures Myoclonic seizures Atonic seizures Atonic seizures

Secondary versus Primary Generalized seizures

Hauser et al,Epilepsia 1993;34: Epidemiology Incidence of 1st unprovoked seizures Overall incidence: 60/100K person-years

Hauser et al, Epilepsia 1993;34: Incidence of Epilepsy Overall incidence: 44/100K person-years

Hauser et al, Epilepsia 1993 Proportion of all incidence cases of epilepsy by seizure type

Hauser et al, Epilepsia 1993 Proportion of newly diagnosed epilepsy cases according to etiologic categories within age groups

DeLorenzo et al, JCN 1995;12: Age-specific distribution of the incidence of first status epilepticus per year per 100K in Richmond, VA

Hauser et al, Epilepsia 1993 Prevalence of Epilepsy age and sex

Diagnosis Case 1: 22 y/o male with 3 episodes of abnormal behavior for the past 3 months witnessed by his wife. With the 1 st 2 events, he suddenly felt “weird” in his stomach, few seconds later, stopped talking and was staring. No response when his name was called. He began to make lip smacking, chewing movements and fumbled with his shirt for a minute, following which became responsive but felt tired. Yesterday, he had similar spell, but after 15 seconds of staring and smacking movements with his mouth, he fell to the floor and had jerking of his trunk and all limbs. The jerking continued for 2 minutes; after that he fell into deep sleep. Case 1: 22 y/o male with 3 episodes of abnormal behavior for the past 3 months witnessed by his wife. With the 1 st 2 events, he suddenly felt “weird” in his stomach, few seconds later, stopped talking and was staring. No response when his name was called. He began to make lip smacking, chewing movements and fumbled with his shirt for a minute, following which became responsive but felt tired. Yesterday, he had similar spell, but after 15 seconds of staring and smacking movements with his mouth, he fell to the floor and had jerking of his trunk and all limbs. The jerking continued for 2 minutes; after that he fell into deep sleep. What type of seizure does the patient have? What type of seizure does the patient have? Based on the clinical manifestation, where is the neuroanatomic localization? Based on the clinical manifestation, where is the neuroanatomic localization? Identifying risk factors for epilepsy Identifying risk factors for epilepsy Evaluation Evaluation

Evaluating a patient with Epilepsy Risk factors for epilepsy Risk factors for epilepsy Febrile convulsion Febrile convulsion Perinatal insult Perinatal insult CNS infection CNS infection Mass lesion in the brain Mass lesion in the brain Family history of epilepsy Family history of epilepsy Head injury (LOC >30min) Head injury (LOC >30min) Developmental delay Developmental delay History of CVA History of CVA Focal neurological exam Focal neurological exam Laboratory Electrolytes Hypoglycemia Hepatic Renal dysfunction Drugs Toxins Alcohol CT MRI brain EEG

Noseworthy, Neuro therapeutics 2003; pg 289

EEG test Emergent EEG: To rule out NCSE Emergent EEG: To rule out NCSE Support diagnosis and localize seizure focus Support diagnosis and localize seizure focus Normal EEG during clinical spell suggest non-epileptic event Normal EEG during clinical spell suggest non-epileptic event Normal EEG does not rule out epilepsy Normal EEG does not rule out epilepsy ¼ of epileptics have normal EEG ¼ of epileptics have normal EEG Deep focus (hippocampus, parasagittal frontal cortex) Deep focus (hippocampus, parasagittal frontal cortex) Incr diagnostic yield: SD, HV and photic stimulation Incr diagnostic yield: SD, HV and photic stimulation Focal slowing: Focal brain dysfunction Focal slowing: Focal brain dysfunction

Luders EEG atlas 1994, page 60

Luders EEG atlas 1994, pg 103

What other diagnosis should be considered when evaluating a patient with suspected seizure disorder? Non-epileptic physiological Non-epileptic physiological Syncope Syncope Arrhythmias Arrhythmias Vasovagal Vasovagal Orthostatic hypotension Orthostatic hypotension Medication-induced Medication-induced Cerebrovascular : TIA/CVA Cerebrovascular : TIA/CVA Classic migraines Classic migraines Toxic-metabolic Toxic-metabolic ETOH, hypoglycemia ETOH, hypoglycemia Non-epileptic psychogenic Conversion disorder Anxiety or panic disorder

Medical Treatment of Epilepsy The patient with a single seizure The patient with a single seizure 50-70% will not have another seizure 50-70% will not have another seizure 50% of untreated patient: 2nd seizure within 5 yrs. 50% of untreated patient: 2nd seizure within 5 yrs. The decision to treat should be based on the presence or absence of risk factors associated with recurrence The decision to treat should be based on the presence or absence of risk factors associated with recurrence Abnormal NE, abnormal EEG Abnormal NE, abnormal EEG Partial seizure with or without secondary generalization Partial seizure with or without secondary generalization History of neurologic injury (CVA, hge, tumor) History of neurologic injury (CVA, hge, tumor) Possible consequence of second seizure Possible consequence of second seizure Risk of injury for patients taking anticoagulation Risk of injury for patients taking anticoagulation Risk of the patient’s job requires driving. Risk of the patient’s job requires driving.

Differentiating Epileptic from non-epileptic seizures FeatureEpilepticNon-epileptic OnsetSudden Maybe gradual Retained consciousness RarelyCommon Flailing, thrashing RareCommon Rolling movements RareCommon Starting and stopping RareCommon Resistance to passive limb movements UnusualCommon Induced by suggestion RareOften Postictal confusion Common Often absent

General Principles of AED Management Monotherapy is the goal Monotherapy is the goal Selection of AED is based mainly on the seizure type Selection of AED is based mainly on the seizure type In emergent situations loading dose is preferrable (Phenytoin, Valproic acid, PB) In emergent situations loading dose is preferrable (Phenytoin, Valproic acid, PB) “Start low and go slow”, when loading dose is not given. Therapeutic dose is guided by occurrence of breakthrough seizures or intolerable SE “Start low and go slow”, when loading dose is not given. Therapeutic dose is guided by occurrence of breakthrough seizures or intolerable SE T reat the patient and not the drug level T reat the patient and not the drug level T he risk of dose-related symptoms and acute idiosyncratic SE is minimized by slow and cautious dose escalation. T he risk of dose-related symptoms and acute idiosyncratic SE is minimized by slow and cautious dose escalation. If toxicity occurs during adjustment of AED, reduce dose by 25%, wait 2 weeks then increase again. If toxicity occurs during adjustment of AED, reduce dose by 25%, wait 2 weeks then increase again.

Selection of AED based on Seizure type

MKSAP 13, pg 52

AED withdrawal/ discontinuation Unprovoked seizures caused by neurologic illness (brain tumor) require continuous drug therapy. Unprovoked seizures caused by neurologic illness (brain tumor) require continuous drug therapy. If seizure-free for >2 years, re-evaluate. If seizure-free for >2 years, re-evaluate. Tapering considered if no factors associated with high recurrence risk (structural lesion, abnormal EEG, abnormal NE, severe epilepsy prior to being controlled). Tapering considered if no factors associated with high recurrence risk (structural lesion, abnormal EEG, abnormal NE, severe epilepsy prior to being controlled). Without risk: 25 % risk of having recurrence Without risk: 25 % risk of having recurrence 80% within 4 months, 90% within 1 year after 80% within 4 months, 90% within 1 year after Driving and potentially dangerous activities should be prohibited during tapering of AED for at least 4 months. Driving and potentially dangerous activities should be prohibited during tapering of AED for at least 4 months.

Status epilepticus Continuous seizure activity for at least 20 minutes Continuous seizure activity for at least 20 minutes (+/-) impairment of consciousness. (+/-) impairment of consciousness. The patient does not completely recover to baseline neurologic functioning between 2 or more seizures The patient does not completely recover to baseline neurologic functioning between 2 or more seizures Approx 12% of epileptics have SE as initial event. Approx 12% of epileptics have SE as initial event. 5 Major subtypes of SE 5 Major subtypes of SE GCSE: Overt Generalized Convulsive SE (primary and secondary generalized seizure) GCSE: Overt Generalized Convulsive SE (primary and secondary generalized seizure) Subclinical or Subtle GCSE (frequently referred as Myoclonic status) Subclinical or Subtle GCSE (frequently referred as Myoclonic status) CPSE: Complex Partial SE CPSE: Complex Partial SE Absence SE (Petit Mal status) Absence SE (Petit Mal status) Simple Partial SE (No impairment of consciousness) Simple Partial SE (No impairment of consciousness)

Treiman et al, NEJM 1998;339: Comparative Trial of initial IV treatment of GCSE

Neurologic Therapeutics 2003; pg 324

Noseworthy 2003, Neurologic Therapeutics; page 326 Management of Status Epilepticus

Special issues in Epilepsy CVA is the leading cause of epilepsy >60 y/o CVA is the leading cause of epilepsy >60 y/o Majority occurs within 3-12 months Majority occurs within 3-12 months Risk include cortical involvement, lobar hematomas close to the brain surface. Risk include cortical involvement, lobar hematomas close to the brain surface. Women with epilepsy: 30% have increased risk seizure frequency during pregnancy. Women with epilepsy: 30% have increased risk seizure frequency during pregnancy. Seizures poses more danger to the fetus than AED itself. Discourage patients from reducing or stopping AED during pregnancy. Seizures poses more danger to the fetus than AED itself. Discourage patients from reducing or stopping AED during pregnancy. 90% of epileptic women: Normal pregnancy/ deliver normal children. 90% of epileptic women: Normal pregnancy/ deliver normal children. Surgical treatment is more superior than medical treatment in medically intractable epilepsy. Referral to Epilepsy center Surgical treatment is more superior than medical treatment in medically intractable epilepsy. Referral to Epilepsy center Ketogenic diet, high fat, low-protein and low-carbohydrate diet, starve the body, increase ketones, increase seizure threshold. Ketogenic diet, high fat, low-protein and low-carbohydrate diet, starve the body, increase ketones, increase seizure threshold. Report seizure patients to Dept of Health/DMV. Report seizure patients to Dept of Health/DMV. Advise them not to drive, avoid heights, swimming, weaponry, equipment that can potentially harm self or others Advise them not to drive, avoid heights, swimming, weaponry, equipment that can potentially harm self or others