1、Epilepsy For the Non-Neurologist 2008,S. Andrew Josephson, MD,Department of Neurology, Neurovascular Division University of California San Francisco,Talk Like a Neurologist: Seizure Types,1. Partial Seizures-Simple Partial-Complex Partial 2. Generalized Seizures-Clonic-Tonic-Tonic-Clonic-Absence-Myo
2、clonic-Atonic,Which of the following medications treats primary generalized seizures?,A. Phenytoin B. Valproic Acid C. Carbamazepine D. Oxcarbazepine E. Gabapentin,Focal vs. Generalized Onset- The Key Distinction,Make the Distinction History, physical exam, EEG and Video EEG Tele Distinct Etiologies
3、 Focal lesion in brain vs. usually none Distinct Work-up Extensive search for underlying lesion vs. none Distinct Treatments Different drugs Different surgical options,Non-Epileptic Spells,Diagnosis of Exclusion Comprise 20% of epilepsy clinic new patients Only established via Video EEG Telemetry Co
4、mplex partial seizure similar by history More common in those with true epilepsy Comprehensive approach with neuropsychology is a must for treatment,Non-Epileptic Spells,Long term outcome: 164 patients with diagnosed non-epileptic spells followed for 1-10 years 71.2% still had spells and 56.4% on di
5、sability21. Neurology Sept 2003;61: 714-5, 2. Ann Neurol 2003;53:305-11,Seizure Management in the ED,ABCs O2, position on side, suction Prevent patient from injuring self Ativan, thiamine, D50 Determine: Was this event a seizure? Consider: syncope, migraine, TIA, movement disorders, etc (many more i
6、n kids),1st seizure or known epilepsy?,Seizure Management in the ED: Single First Seizure,Careful history of the spell: before (including recent events), during, after Determine all meds patient is on Family History Pregnancy, Birth, and Development history especially in young Careful neuro exam loo
7、king for focal signs,Seizure Management in the ED: Single First Seizure,Work-up for provokers Head trauma? Utox, EtOH history and possible level CBC, Lytes, Ca/Mg/Phos, BUN/Cr, LFTs, +/- ABG CT (usually with contrast) Low threshold to LP Needs outpatient work up including: EEG, MRI,Seizure Managemen
8、t in the ED: Should We Treat a First Seizure?,“Provoked”: Do not treat Data for recurrence if 1st seizure not provoked 26-71% 2 year recurrence Many models: Non-evidenced based rule of thumb involving neuro exam, EEG and MRISudden unexpected death in epilepsy (SUDEP) (1.21/1000 patient years),Seizur
9、e Management in the ED: Known Epilepsy,Determine AEDs including doses Send levels of AEDs Valproate, Phenytoin, Phenobarb, Carbamaz. Lack of compliance is common trigger Work-up for provokers Infection (CXR, urine, ?LP, ?blood cx), Utox CBC, Lytes, BUN/Cr, Ca/Mg/Phos, LFTs, +/- ABG Best to curbside
10、neuro regarding any medication changes to current regimen,Quick Cases: Seizures in ED,45 yo male with recent +PPD wont stop seizing55 yo female on bone marrow transplant service given amphotericinMost new seizures over 40 in urban areas,Case #1,A 67F is hospitalized with a community-acquired pneumon
11、ia. On Day#3 she is feeling much better awaiting discharge when her nurse finds her unresponsive with rhythmic shaking of all limbs. PMHx: COPD Meds: Ceftriaxone, NKDA SH: 100pk yr hx tobacco, no hx EtOH FH: No neurologic disease,Case #1,You are called to the bedside and after 3 minutes, these movem
12、ents have not stopped. Options for your next course of action are. A. Continue to wait for the spell to subside B. Administer IV Diazepam C. Administer IV Lorazepam D. Administer IV Fosphenytoin,Status Epilepticus,Incidence: 100,000 to 150,000 per year nationally Causes 55,000 deaths per year nation
13、ally 12 to 30 percent of epilepsy first presents as status epilepticus Generalized convulsive status most dangerousN Engl J Med 1998; 338:970-976, Apr 2, 1998,Status Epilepticus Algorithm,Status Epilepticus Algorithm: Real World,Lorazepam 2mg IV q2 minutes up to 6mg Fosphenytoin 18-20mg/kg (Dilantin
14、 Equivalents) IV 2a. Fosphenytoin additional 10mg/kg or Phenobarbital 3. General Anesthesiaa. IV Midazolam gttb. IV Propofol gtt,Status Epilepticus: New Advances,Change in definition and time window IV Depakote (Depacon): 15mg/kg as bridge to Depakote therapy, alternative to IV DPH Out of hospital b
15、enzos in field effective Tailored Therapy? Decrease incidence in epileptics with prescribed “Status Rescue Meds”,A healthy 36M with a hx of seizures on Dilantin 300mg/d comes to your office for routine care. He has had no seizures and has a normal exam. A phenyotin level is 36 (10-20). Your next cou
16、rse of action is,A. Check an albumin level and renal function B. Reduce the Dilantin dose C. Make no changes to the Dilantin dose D. Switch to carbamazepine E. Admit to the hospital for dialysis,Monotherapy for Seizures,70 percent of epilepsy can be managed with monotherapy, most on first drug tried
17、1 Concept of Maximal Tolerated Dose (MTD) Rarely check levels Assess compliance Steady state level Not practically available with newer AEDsN Engl J Med. 2000 Feb 3;342(5):314-9,New Drugs: Clinical Pearls,IV formulations: VPA, DPH, PHB, LVT Levels to Monitor: VPA, DPH, CBZ, PHB Lamotrigine (Lamictal
18、) Rash (1/1000) progressing to Stevens-Johnson Levetiracetam (Keppra) No drug interactions (useful on HAART), but NOT a first line agent Topiramate (Topamax) Well tolerated: weight loss and cognitive side effects,New Drugs: Clinical Pearls,Oxcarbazepine (Trileptal) Tegretol pro-drug, hyponatremia Fe
19、lbamate (Felbatol) Aplastic Anemia with required registry Pregabalin (Lyrica) Useful for neuropathic pain Gabapentin (Neurontin) Not a great AED,Women and Epilepsy,Some medications less tolerated by women Example: Depakote causes hirsutism, weight gain and often coarsening of facial features so rela
20、tively contraindicated in growing young women and girls Catamenial epilepsy Brief AED pulses Other agents: Diamox Menstruation control,Women and Epilepsy: OCPs,Pregnancy must be planned due to neural tube defect risk on AEDs Many AEDs decrease levels of OCPs and therefore higher OCP dosing (40mcg es
21、trogen) recommended for efficacy Always recommend double contraception AEDs can lead to reproductive dysfunction and PCOS, especially with VPA and CBZ,Which of the following drugs is not associated with teratogenic effects?,A. Valproic Acid B. Phenytoin C. Lamotrigine D. Carbamazepine E. Phenobarbit
22、al,Women and Epilepsy: Pregnancy,Once pregnancy achieved: balance risk of AED exposure with risk of in utero seizures Most AEDs have increased clearance in pregnancy and women should be followed closely by neuro/high risk OB Vitamin K supplementation in last 4 weeks,Women and Epilepsy: Pregnancy,Fol
23、ic acid to decrease neural tube defects (NTDs) in women on AEDs NTD risk doubles from 2-3% to 4-6% Folate deficiency implicated in NTDs 4mg/day regardless of AED PRIOR to conception Prenatal diagnostic ultrasound “AED syndrome” Microcephaly, low set ears, short neck, transverse palmar crease, skelet
24、al abnormalities,Neurology 2003 61S2:S23-7,Women and Epilepsy: Osteoporosis,Increased risk of fracture due to trauma from seizures and increased falls Independent decrease in bone density in patients on many AEDs Decreased serum Vitamin D levels Supplementation with Vitamin D, consider earlier and m
25、ore frequent evaluation of bone mineral density (DEXA, etc),Neurology 2003 61S2:S16-7,Other Epilepsy Treatments,Vagal Nerve Stimulator (VNS)Diet,Other Epilepsy Treatments,Epilepsy Surgery Temporal lobectomy, focal resections, callosotomy, functional hemispherectomy Randomized trial to finish in next 2-3 years for early intervention,
