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Epilepsy in the Elderly
Mark C. Spitz, M.D.
Anschutz Center for Advanced MedicineDenver Veterans Administration Medical Center
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76- year -old manStroke age 74GT
C 3 months laterPhenytoin 300 mg/day startedBreak through seizure -- phenytoinincreased to 300/ 4 00 alternating days
Doesn t feel too bad on the days hetake 300 mg
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Epilepsy in the ElderlyNot rare
Often misdiagnosedCerebrovascular etiology underratedBrain tumors overrated
Usually easy to controlNewer meds may be better thantraditional drugs
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I ncidence of Epilepsy
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Elderly (> 65 years)I ncidence of Alzheimer's 123/100,000Incidence of Epilepsy 13
4 /100,000
Olmsted County Data
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Etiology Of Epilepsy, Age 65 +Idiopathic 51%
Stroke 38 %
Degenerative 12 %
Tumor 5 %
Trama 2 %Infection 2 %
Hauser et. al.
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I ncidence Annual I ncidence of Stroke(Williams, 2001) 75 0,000 in U.S. (199 6 )Seizures after Stroke Cooperative Study(Bladin, 2000) Prospective, 9 -month follow -up, n=2021 Seizures in 8.9% 2.3% recurrent seizures
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Seizures in Alzheimers Autopsy verified, n=8 6
10% had seizures
Hauser, 198 6
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DemographicsDifferent for younger people withepilepsy
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Epilepsy in the Elderly:Seizure Type
Complex Partial 38%Generalized Tonic -Clonic 27 %Simple Partial 1 4 %Mixed 20%
VA Co-op 2003
n=593
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Epilepsy in the Elderly:Concurrent diseases
Hypertension 64 %Stroke 5 3%Cardiac Disease 4 9%Diabetes 2 7 %
History of Cancer 22%
VA Co-op 2003
n=593
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Epilepsy in the Elderly:I maging
Normal 18%CVA 44 %Small vessel disease 4 0%Diffuse atrophy 3 5 %
Encephalomalacia 9%
VA Co-op 2003
n=593
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Epilepsy in the Elderly:EEG
Normal 31%Epileptiform 39%Focal Slow 4 0%Generalized Slow 1 6 %
VA Co-op 2003
n=593
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Epilepsy in the ElderlyEpilepsy in the elderly is oftenmisdiagnosed
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Delay I n Diagnosis VA Co-op, 2003, n= 5 93
9 months to seek medical attention1.7 years to correct diagnosisGT C: immediate diagnosis in 67 % Less dramatic seizures often ignored
Concomitant cardiac or cerebrovasculardisease caused delays in diagnosis
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Diagnosis of Epilepsy:Elderly compared to younger people
Higher percentage of partial seizuresMore extra - temporal onset complexpartial seizures (missing classic auras)More prominent post - ictal symptomsWeaker historiansEEG less helpfulMore concomitant illnesses
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Ocham s RazorExplain all of the patient s complaints bya single diagnosis
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Some diagnostic dilemmasGT C vs. syncopeComplex partial seizure vs. T I ATransient G lobal Amnesia
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GT C compared to SyncopeGT C Syncope
History of Cardiac Disease Common CommonPositional Variable Orthostatic
Warning Variable Pre-syncopeTongue biting Common UnlikelyColor Normal Pale
After Event Confused, sleepy Alert Movements Tonic -clonic Loss of tone,
brief clonic
movementsDuration 1 -2 minutes seconds to
then post - ictal minutesI ncontinence varies varies
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Complex partial seizures compared to T I A
CPS T I AHx of CV Disease Common Common
Anatomic disibration Not Vascular VascularConfusion, unresponsiveness Present Absent (may be aphasic)Frequency Can be frequent Rarely frequent
Amnesia Common Absent Aura Common Absent
Automatisms Common Absent
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Transient G lobal AmnesiaEtiology is controversial I schemic Venous Stasis Epileptic (post - ictal)
Multiple etiologies are likelyEpileptic cause is underdiagosed
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TG A Diagnostic CriteriaProposed by Caplan, Hodges, and Warlow
An attack must be witnessed by an observer who canprovide additional information
Anterograde amnesia must be present No clouding of consciousness or loss of personalidentityCognitive impairment is limited to amnesia, noapraxia, or aphasia
No recent history of head trauma, no history of seizures in the preceding 2 yearsThere are no focal neurologic signs, and no epilepticfeatures
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Transient G lobal Amnesia Are many of these cases a one - timeexpression of transient epilepticamnesia?
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Transient Epileptic AmnesiaClassic literature considers it anuncommon relative of Transient G lobal
AmnesiaFeatures Recurrent Spells
EEG
Additional presence of obvious seizure Responsive to AED
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Transient G lobal Amnesia Annual incidence of 3. 4 to 5 .2 per100,000 each year,23. 5 per 100,000 > 5 0 years oldMiddle-aged or elderly, but otherwisehealthyRecurrent attacks < 2 5 %
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TG A Diagnostic CriteriaProposed by Caplan, Hodges, and Warlow
An attack muscle be witnessed by an observer whocan provide additional information
Anterograde amnesia must be present No clouding of consciousness or loss of personalidentityCognitive impairment is limited to amnesia, noapraxia, or aphasia
No recent history of head trauma, no history of seizures in the preceding 2 yearsThere are no focal neurologic signs, and no epilepticfeatures
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Transient G lobal Amnesia Annual incidence of 3. 4 to 5 .2 per100,000 each year,23. 5 per 100,000 > 5 0 years oldMiddle-aged or elderly, but otherwisehealthyRecurrent attacks < 25%
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Pre -existing DementiaConsider post - ictal phenomenon in ademented person when unexplaineddramatic transient worsening incognitive function is observedDementia is a major risk factor for
epilepsy
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Further testingWhen seizures continue despitetreatment the diagnosis may be wrongConsider further testing
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Special TestingProlonged EE G /Video monitoring 10/23 NES were physiologic
(Kellinghaus, 200 4 ) 14 /2 7 NES were physiologic
(E. Bride, 2002) Ambulatory EE GLoop ECG monitoring for cardiac anythmics
T ilt table 33/128 referrals from a seizure clinic were given a newdefinitive diagnosis(Razvi, 2003)
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Epilepsy in the Elderly
Unique Considerations in choosing a medication
Milder epilepsyMore adverse effects More susceptible to cognitive side effects More susceptible to ataxia and falls More prone to hyponatremia Drug/Drug interactions
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Epilepsy in the Elderly is milder
VA Coop 118 (PH T , CB2, PB, PRM)
Seizure freedom at 2 years< 4 0 years old 32%4 0-65 years old 22%> 65 years old 6 2%
VA Co-op 2003
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Age and adverse effects VA Coop 118 (PH T , CB2, PB, PRM) and
VA Coop 2 64 (CB2, VPA) combined
Withdrawal rate due to adverse effects< 4 0 years old 33%4 0-65 years old 4 9%> 65 years old 64 %
VA Co-op 2003
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Epilepsy in the Elderly
Pharmacologic Problems
Reduced hepatic clearanceReduced renal clearanceReduced protein bindingI ncreased pharmacodynamic sensitivityT
aking multiple medications
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Epilepsy in the Elderly
Number Of Drugs Prescribed
02
4
6
8
10
12
14
1 2 3 4 5 6 7 8 9 10 11 12
# patients
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Veterans Administration database
Fiscal Year 199980% with epilepsy 65 years oldprescribed phenytoin
Berlowitz, 2003
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Expert Consensus Guideline Series:
Treatment of Epilepsy Medically stable elderly man or woman
How would you rate these drugs?scored 1 -9
Lamotrigine 8. 5 0.9Levetiracetam 8.0 0.9Gabapentin 6 .9 2.0Carbamazepine 6 .8 1. 4Oxcarbazepine 6 .7 1. 6Topiramate 5 .9 1. 5
Valproate 5 .9 1. 6Zonisamide 5 .9 1. 7Pregabalin 5 .7 1.9Phenytoin 5 .4 1.9
Survey done 200 4
Karceski et al 200 5
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Only 2 double -blind control studies
of AEDs in the elderlyBrodie, 1999
VA Coop, 2003
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Lamotrigine vs Carbamazepine
in newly diagnosed elderlyretention
at 1 6 8 days
LTG 7 1%CBZ 45 %
p < 0.001
Brodie, Epilepsy Research 1999
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New Onset Epilepsy in the Elderly
VA Coop, 2003retention at 1 year
Carbamazepine 3 6 .6 % *Gabapentin 4 9.2%Lamotrigine 57 .9%
CBZ vs LMG 0.0003CBZ vs GPN 0.01GPN vs LMG 0.10
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Thoughts on Specific DrugsFirst Line
LamotrigineGabapentinLevetiracetamTopiramate
Zonisamide
Second LinePhenytoinCarbamazepineOxcarbazepine
Valproate
Phenobarbital
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Epilepsy in the Elderly
ConclusionsNot rareOften misdiagnosedCerebrovascular etiology underratedBrain tumors overratedUsually easy to controlNewer meds may be better thantraditional drugs
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