Adult Epilepsy Update Annual Incidence J. Layne Moore, MD, MPH Associate Professor Department of Neurology and Pharmacy Director, Division of Epilepsy The Ohio State University Used by permission Health Press Oxford Epilepsy Affects 1 to 2% of US Population Chronic Condition Multiple Drug Therapies Issues Patients Compliance Drug Interactions Education Social and Behavioral the spontaneous cessation of the disease is an event too rare to be reasonably anticipated in any give case. Gowers 1881 1
Refractory Epilepsy Newly Diagnosed (n=470) Seizure-free 47% (n=222) 1 st drug What is refractory epilepsy? Uncontrolled with multiple medications Intolerable side-effects to achieve control How to fight back? Uncontrolled 53% (n=248) Seizure-free 13% (n=61) Uncontrolled 40% (n=187) 2 nd drug Seizure-free 4% (n=18) 3 rd drug Kwan & Brodie NEJM 2000 Uncontrolled 36% (n=169) Which patients respond? Early response in key Response to the 1 st drug 11% response to 2 nd drug if 1 st was ineffective 41% for SE 55% idiosyncratic reaction Kwan and Brodie 2
Seeking a Cause For most persons with epilepsy or seizures no cause is found People without a clear cause have the best prognosis. Risk Ratios for Selected Causes Alzheimers 10 Encephalitis 16 Aseptic Meningitis 2 HTN LVH Stroke 7.3 20 Risk Ratio Mild HI 1.5 Moderate HI 4 Severe HI 29 Baseline 1 0 5 10 15 20 25 30 35 3
Diagnostic Pitfalls Is the diagnosis correct? Does the patient have epilepsy? Seizure or Spell Evaluation Careful history hopefully with collateral history Past Medical History Risk factors Neurological examination EEG Neuroimaging Our Differential Diagnoses Syncope Often prominent autonomic symptoms Seizure An aura is a seizure symptoms may be positive, negative, or mixed psychogenic spell Almost anything goes other Stuff cataplexy migraine TIA Seizure Evaluation EEG Awake and asleep increase sensitivity Looking for evidence of epilepsy *Less than 2% of normal people have epileptiform discharges Evidence of focal-onset vs. generalized-onset seizure This will dictate our choice of AEDs 4
Seizure Evaluation Neuroimaging MRI with thin coronal cuts through hippocampus CT scan is only indicated if: Patient has contraindications to MRI It is emergent to look for a bleed or mass effect Sleep Stages MTS Awake Stage I Stage II Stage III Stage IV REM Most Interictals Seizures 5
Strategies for Management of Epilepsy Medication Partial Generalized Resective Surgery Vagal Nerve Stimulator Ketogenic Diet/ Atkins Diet Stimulators Older Drugs Dilantin (Phenytoin) PHT Phenobarbital Tegretol, Carbatrol (Carbamazepine) CBZ Depakote, Depakene (Valproic Acid) VPA Bones loss Aging population, post-menopausal women Hormonal birth control failure (except VPA) And may decrease the levels of other AEDs High protein binding displacing drugs like coumadin and synthroid Antiepileptic Drug (AED) Therapy TGB TPM FOS LTG ZNS GBP LVT PB PHT CBZ VPA FBM OCBZ PGB Long-Term Management Strategies for Epilepsy 1900 1920 1940 1960 1980 2000 1st Generation 2nd Generation 2 nd Generation Drugs Neurontin (Gabapentin) Felbatol (Felbamate) Lamictal (Lamotrigine) Topamaz (Topiramate) Gabitril (Tiagabine) No enzyme induction Low protein binding Less interference with other drugs 6
3 rd Generation Drugs Trileptal (Oxcarbazepine) Zonegran (Zonisamide) Keppra (Leviteracitam) Lyrica (Pregabalin) Little interaction with other drugs Renal excretion The End Newly Diagnosed (n=470) Seizure-free 47% (n=222) Uncontrolled 53% (n=248) 1 st drug Pediatric Epilepsy Seizure-free 13% (n=61) Uncontrolled 40% (n=187) 2 nd drug Seizure-free 4% (n=18) 3 rd drug Jorge Vidaurre M.D. Director Epilepsy Center Nationwide Children s Hospital- OSU Kwan & Brodie NEJM 2000 Uncontrolled 36% (n=169) 7
Epilepsy Convulsive disorders are among the most frequently occurring neurological condition in children 181,000 new Cases Per year Epilepsy: Incidence/100,000 200 150 100 50 0 0 20 40 60 80 100 Hauser, Epilepsia 33:1992 Age Incidence Incidence of seizures is higher in childhood, especially the first year of life (100/100,000) and in older patients Causes of Childhood- Acquired Epilepsy Prematurity Poison Birth injury Infection Trauma Tumors 45%-55% 45%-55% Genetic or idiopathic Metabolic Disturbances Fever 8
Definitions Seizure: Clinical manifestation of an abnormal, excessive activity of a set of cortical neurons Epilepsy: Chronic brain disorder of various etiologies characterized by recurrent, unprovoked seizures Epilepsy syndromes: Grouping of similar patients according to seizure type EEG, age of onset, familial episodes, prognosis, and other clinical signs Non-epileptic paroxysmal events in childhood Syncope Breath-holding spells Movement disorders (tics) Sleep disorders (parasomnias, night terrors, sleep walking) Day dreaming, inattentiveness & distractibility Self stimulatory behavior Gastroesophageal reflux Psychogenic Was the Event a Seizure? Breath Holding Event Video 9
Seizure Classification Partial seizures: originating in a focal area of the brain. Simple: Do not impair consciousness Complex: Impairment of consciousness Generalized seizures Absences, clonic, tonic, tonic-clonic, atonic and myoclonic Benign Rolandic Epilepsy (BRE) One of the most frequent syndromes, occurring in up to 24% of all epileptic seizures in children between ages 5 and 14 Age of presentation: 3-13 year Remission rate almost 100% at age 16. Seizures are usually infrequent. Benign Partial Epilepsies of Childhood Benign Rolandic Epilepsy (BRE) Seizures usually occur during sleep Partial sensorimotor: hemi facial twitching, drooling, arrest of speech, numbness of tongue, lips. GTC in 20-30% of cases 10
BRE Video Idiopathic Generalized Epilepsies 11
Childhood Absence Epilepsy (Pyknolepsy, Petit Mal Epilepsy) Very frequent (several to many per day) absence seizures Brief in duration (usually 5-30 seconds) Sudden behavioral arrest, with staring and quick return to normal baseline activities Otherwise normal child Childhood Absence Epilepsy (Pyknolepsy, Petit Mal Epilepsy) Often precipitated by hyperventilation An EEG demonstrating bilateral, synchronous spike-waves, usually 3 HZ, on a normal background activity Absence Video 12
Commonly used Medications Ethosuxamide Valproic acid Lamotrigine Juvenile Myoclonic Epilepsy(JME) Seizures are precipitated by sleep deprivation, alcohol, stress. Photosensitivity Intelligence remain normal Juvenile Myoclonic Epilepsy(JME) Age of onset: 8-24 years. Peak between 12-18 years The characteristic seizure type is myoclonus, usually affecting shoulders GTC seizures appear usually more than 3 years after myoclonus. Absences occur in up to 30% of patients. Myoclonus video Child during sleep 13
Photic Induced Seizure Symptomatic Generalized Epilepsies Infantile spasms Lennox Gastaut syndrome Medications used for JME Broad spectrum medications: Valproic Acid Lamotrigine Topiramate Levetiracetam Medications that can worsen seizures: Phenytoin, carbamazepine Infantile Spasms Age of onset: 4-6 months Types: flexor (Jackknife, salaam attacks), extensor or mixed. Usually occur in cluster, during awakening or falling sleep Usual EEG shows hypsarrhythmia interictaly. Most frequent ictal manifestation: electrodecremental response 14
West Syndrome Hypsarrhythmia Sleep Infantile spasms Hypsarrhythmia Mental retardation Hypsarrhythmia-Wakefulness Ictal Event: IS 15