I have no financial relationships to disclose.

Transcription

1 Julia B. Toub, MD Providence Brain & Spine Institute April 14, 2016 I have no financial relationships to disclose. 1

2 1. Seizure: the clinical manifestation of an abnormal and excessive synchronization of a population of cortical neurons. 2. Practical definition of epilepsy (2014) 2 unprovoked seizures separated by at least 24 hours. 1 unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years. EEG MRI Epilepsy Syndrome spasms.org/ emedicine.com 2

3 Worldwide prevalence ~ 50,000,000, underestimated due to: Limited access to healthcare Social/cultural stigma ~3,000,000 Americans As common as breast cancer with a similar mortality 10% of the population will have a seizure at some point in their lives; 1-3% will be diagnosed with epilepsy. 4 th most common neurological disease after migraine, stroke, and Alzheimer s disease Seizures arising from the whole brain all at one time Seizure subtypes a. Absence b. Tonic-Clonic c. Tonic d. Clonic e. Myoclonic f. Atonic/Astatic Generalized Epilepsy Syndromes a. Childhood absence epilepsy (CAE) b. Juvenile absence epilepsy (JAE) c. Juvenile myoclonic epilepsy (JME) d. Generalized epilepsy with febrile seizures plus (GEFS+) e. Benign myoclonic epilepsy in infancy f. Epilepsy with myoclonic absences 3

4 Common ~25% of genetically-based generalized epilepsy and ~10% of all epilepsies +/- seizures in childhood Onset usually during teenage years; infrequently in 20s and 30s. Hereditary component; genetically heterogeneous and often no family history Clinical GTC, myoclonic, sometimes absences, especially in AM Klutzy, frequently dropping things Triggers: sleep-deprivation, EtOH, psychological stressors Photosensitivity Requires lifelong therapy Lamotrigine Levetiracetam Valproic acid Clonazepam Avoid AEDs indicated only for focal epilepsy EEG: Generalized spike/poly-spike wave Seizures arise from one (or more than one) part of the brain Focal seizure subtypes a. Without dyscognitive features: No alteration in level of consciousness *** Previously simple partial b. With dyscognitive features: Accompanied by altered consciousness. *** Previously complex partial c. Motor, sensory d. Secondarily generalized Focal epilepsy syndromes a. Most focal epilepsies are not associated with any classified epilepsy syndrome b. Benign Rolandic epilepsy c. Childhood Epilepsy with Occipital Paroxysms d. Autosomal Dominant Nocturnal Frontal Lobe Epilepsy 4

5 Frontal: Primary motor area: Jacksonian march, often escalating to GTC. Supplementary motor area (SMA): Hypermotor, asymmetric tonic, brief, may lack postictal period. Lateral Temporal: Auditory/visual hallucinations, vestibular symptoms, language impairment (dominant) Mesial Temporal: Epigastric/olfactory/gustatory aura, prodromal fear, orolingual automatisms, dysautonomia. Memory compaints Parietal: Somatosensory symptoms, visual illusions/hallucinations, distortions of body image. Occipital: Forced eye deviation, visual hallucinations, visual perseverations (palinopsia). Isolated unprovoked generalized tonic-clonic seizure lasting < 3 minutes: History CMP CBC Tox screen Driving restriction EEG (ideally within 24 hours of seizure) Pregnancy test CT/MRI: MRI ideal Provoked seizure: Remove offending agent 5

6 In most circumstances, we no longer wait for a second unprovoked seizure to evaluate and treat. A patient with a single unprovoked seizure and an EEG with epileptiform activity (and/or abnormal MRI) should be started on antiepileptic medications. Diagnosis: Establishing a diagnosis (epileptic vs. nonepileptic events) Characterization of epilepsy (generalized vs. focal) Identification of epilepsy syndrome Identify triggers (photosensitivity, sleep deprivation) Management: Assessing risk of recurrence after single unprovoked seizure Guiding selection of appropriate anticonvulsant Localizing seizure focus Surgical planning Assessing mental status change Evaluating for nonconvulsive status epilepticus Monitoring/guiding treatment in status epilepticus Risk stratification for seizure recurrence prior to taper off anticonvulsants Prognostication in the ICU setting 6

7 Psychiatric: Buproprion (common), Clozapine Analgesic: Tramadol (common), Tapentadol Antibiotics: PCN, Cephalosporins, Imipenem, Amphotericin B Pulmonary: Aminophylline Immunologic: Cyclosporin 7

8 Confirm a diagnosis of epilepsy (+/-) Determine seizure subtype (history, EEG, imaging) How quickly does medication needs to be introduced? Consider comorbid conditions, social circumstances, finances, etc. Cost Mechanism of action BROAD SPECTRUM NARROW SPECTRUM OLDER Valproic Acid/Divalproex * Carbamazepine (focal) Ethosuximide (absence) Phenobarbital (focal>generalized) Phenytoin (focal>generalized) Primidone (focal) NEWER Lamotrigine * Levetiracetam * Topiramate * Zonisamide Perampanel Brivaracetam (focal) Clobazam (Lennox Gastaut) Eslicarbazepine (focal) Ezogabine (focal) Felbamate (focal; severe refractory) Gabapentin (focal) Lacosamide (focal) Oxcarbazepine * (focal) Pregabalin (focal) Rufinamide (Lennox Gastaut) Tiagabine (focal) Vigabatrin (focal, infantile spasms) * Available in once-daily extended release formulation 8

9 Newer AEDs have fewer side-effects. Choose broad spectrum coverage if unsure of seizure subtype: 1. Levetiracetam 2. Lamotrigine 3. Valproic acid 4. Topiramate 5. Zonisamide (approved only as an adjunct in treatment of partial seizures, though it does have broad-spectrum efficacy). Focal epilepsy agents can exacerbate generalized epilepsies CBZ, OXC, ESL, GBP, PRG 9

10 Comorbid mood disorder? Consider LTG, VPA, OXC (focal epilepsy only) Avoid LEV Neuropathic pain? GBP, PRG, CBZ, OXC Migraine? TPM, VPA, GBP, PRG Hepatic dysfunction? LEV Poor compliance or wearing off? Consider XR formulations Stevens Johnson Syndrome with lamotrigine Rare Most often associated with rapid initiation Increased risk with co-administration of VPA PHT, CBZ, PHB, PRM, and VPA hasten bone loss. Assess for vitamin D deficiency Supplement vitamin D at least 2,000 IU per day DEXA VPA: weight gain, tremor, hair loss, GI upset, hematologic, hepatic/pancreatic dysfunction, osteoporosis Patients on warfarin: Avoid VPA, PHT, PHB, CBZ, and primidone if possible 10

11 TPM: Cognitive slowing, kidney stones, weight loss, rare acute angle closure glaucoma LEV: Dizziness, fatigue, insomnia, irritability, mood changes/depression, rare overt psychosis. Renally cleared; needs re-dosing after dialysis Patients of Asian decent with HLA-B*1502 have increased risk of Stevens Johnson Syndrome with CBZ, OXC, ESL CBZ, OXC, ESL: hyponatremia Felbatol: Aplastic anemia XR formulations more expensive All AEDs carry small increased risk of suicide Esp. LEV and Permapanel Perampanel: Homicidal ideation Marijuana: No FDA indication 11

12 Chronic adverse effects: Gingival hyperplasia, osteoporosis, hepatic dysfunction, hirsutism, weight gain, dermatitis, neuropathy, cerebellar atrophy Multiple drug-drug interactions At high doses, beware of dramatic changes in serum levels with small change in dose Phenytoin metabolism is dose dependent. c/p1/ch20/ch2003.html Women of childbearing age Potential for teratogenicity of ALL AEDs Newer AEDs better than older AEDs Folic acid in ALL women of childbearing potential LTG and LEV levels drop in pregnancy Other AEDs: Possible reduction in contraceptive efficacy; secondary contraception should be used. Women of all ages LTG: Estrogen-containing OCPs increases LTG clearance and may decrease levels by as much as 50%. VPA: Hirsutism, weight gain 12

13 ~1/3 epileptic patients Several surgical and non-surgical options for patients living with medically refractory seizures. Epilepsy surgery (focal epilepsy) RNS (focal epilepsy) VNS (focal and generalized epilepsy) Diet (focal and generalized epilepsy) Medically refractory cases should be managed at an epilepsy center. 13

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16 Elective admission for diagnostic purposes, seizure classification, medication titration, and/or pre-surgical evaluation Continuous video EEG monitoring Candidates: Patients with or without diagnosis of epilepsy experiencing continued seizures despite therapeutic levels of AEDs Patients requiring expedient medication adjustment in a controlled atmosphere Patients undergoing pre-surgical evaluation Patients with deficits out of proportion to reported seizure frequency (e.g. persistent memory problems, weakness) Introduce stressors to provoke events in question: Reduced/discontinuation of medications Sleep deprivation Hyperventilation Photic stimulation Exposure to agents known to provokes seizures in individual patients Important to capture ALL of the patient s events *Some patients may have epileptic and nonepileptic events. 16

17 Epilepsy is common. All that shakes is not seizure; All seizures do not shake. EEG and neuroimaging are warranted after a single unprovoked seizure. There is no one-size fits all approach to epilepsy management. When seizure subtype isn t clear, choose a broad-spectrum AED. Use of the EMU to differentiate between epileptic and nonepileptic events is imperative to providing patients with appropriate treatment. Non-epileptic events do not preclude the coexistence of epileptic seizures. Berg, etal. New concepts in classification of the epilepsies: Entering the 21st century inepilepsia, 52(6): , Bodde, NMG et.al. Psychogenic Non-Epileptic Seizures-Diagnostic Issues: A Critical Review in Clinical Neurology and Neurosurgery 111(2009) 1-9. Fattore, Cinzia; Perucca, Emilio. Novel Medications for Epilepsy. Drugs 2011: 71 (16) Fischer, et al. A practical Definition of Epilepsy in Epilepsia, 55(4): , Knake, Susanne et.al. Status Epilepticus: A Critical Review in Epilepsy and Behavior 15 (2009) Kohrman, Michael H. What Is Epilepsy? Clinical Perspectives in the Diagnosis and Treatment in J Clin Neurophysiol 2007;24: Noachtar, S et. al. Epilepsy surgery: a critical review. Epilepsy Behavior May;15(1): Epub 2009 Feb 21. Pitkanen, et. al. Mechanisms of epileptogenesis and potential treatment targets. The Lancet Neurology, Vol. 10, February Rabinstein, Alejandro. Management of Status Epilepticus in Adults in Neurol Clin 28(2010) Rosetti, A and Lowenstein, D. Management of refractory status epilepticus in adults: still more questions than answers in Lancet Neurology 2011; 10: Schmidt, Dieter. Drug Treatment of Epilepsy: Options and Limitations in Epilepsy and Behavior 15 (2009) Shorvon. Sudden Unexplained Death In Epilepsy.The Lancet, Volume 378, issue 9808 (December ), p

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