Transcript Document

3rd
Kuei-Cheng Lim, MD PhD
Annual Neuro Rehab Symposium
March 7, 2015
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None
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Cynthia V Anderson is a 74 year old post-menopausal
woman with atrial fibrillation on anticoagulation but
stopped warfarin 4 days ago due to elevated INR with mild
cognitive impairment and diabetes
She present to ED after waking up with right hemiparesis
involving face and arm more than leg. She is aphasic.
Admitted for stroke evaluation. Six hours into
hospitalization she had a convulsive seizure and returned
to baseline after 2 hours post-ictal state.
What is her risk of another seizure?
What AED would you recommend?
How long would you keep AED going?
Does seizure affect her ability to participate in
rehabilitation?
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Seizures and Epilepsy are not the same
◦ Seizure is the event and epilepsy is the disease
◦ Conceptual
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Epileptic Seizure
◦ Transient occurrence of signs/symptoms due to
abnormal excessive or synchronous neuronal
activity in the brain
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Epilepsy
◦ A disease characterized by an enduring
predisposition to generate epileptic seizures and by
the neurobiological, cognitive, psychological and
social consequences of this condition
ILAE website – www.ilae.org/Visitors/Definition-2014-Perspective.cfm
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At least 2 unprovoked (or reflex) seizures occurring
more than 24 hours apart
One unprovoked seizure and a probability of further
seizures similar to the general recurrence risk (at
least 60%) after 2 unprovoked seizures, occurring
over the next 10 years
Diagnosis of an epilepsy syndrome
Epilepsy is considered to be resolved for individuals
who had age-dependent epilepsy syndrome but are
now past the applicable age or those who have
remained seizure-free for at least 10 years; with no
seizure medications for the last 5 years
Fisher RS et al. A practical clinical definition of epilepsy, Epilepsia 2014; 55:475-482
Hauser WA et al. Mayo Clin Proc 1996: 71; 576-86.
Kim DW et al. Epilepsia 2014: 55; 67-75.
Encephalopathy
Eclasmpsia 2%
5%
Other 10%
Head Trauma
16%
Cerebrovascular
Withdrawal 14%
16%
Metabolic 9%
Infection 15%
Toxic 6%
Brain Tumor 8%
Modified from Hauser WA. “Ch. 8. Epidemiology of Acute Symptomatic Seizures.” in The Epilepsies; A
comprehensive textbook. Ed. Engel and Pedley.
Neurodegenerative
4.0%
MR/CP 3.5%, Other
1.3%
Alcohol 5.8%
Infection 2.2%,
Tumor 2.7%
Trauma 8.8%
Idiopathic
Cryptogenic
62.4%,
Stroke 9.3%
Modified from Banerjee PN and Hauser WA.
“Ch. 5. Incidence and Prevalence” in The
Epilepsies; A comprehensive textbook. Ed.
Engel and Pedley.
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Cerebrovascular disease is a common cause of secondary
epilepsy
◦ Especially in the elderly >60 years old population
◦ Accounts for about a third of epilepsy pts
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Post-stroke seizures occur in 4-14% of strokes (some
ranges from 5-20%)
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Do early onset seizures develop into epilepsy?
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Late onset seizures increase the risk of epilepsy
◦ Risk of recurrent seizures varies with the definition of early versus
late onset seizures
◦ Early seizures is 8-16 times more likely to have late onset
seizures than those without early seizures
◦ About one-third of early onset seizures have recurrent seizures
◦ About 50-90% of late onset seizures have recurrent seizures
Silverman et al. Arch Neurol. 2002: 59; 195-202,
Burneo et al Eur J Neurol 2010: 17; 52-58,
Arboix A, et al. Stroke 1997: 28; 1590-4
Camilo V and Goldstein LB. Stroke 2004: 35; 1769-75
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0.2-0.8% of all strokes complicated by status
epilepticus
◦ About 10% of early onset seizures are in status
◦ About 50-75% status cases are nonconvulsive
◦ Have higher functional disability and mortality
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Risk of seizures increases with cortical location,
ICH/SAH
Mortality and morbidity is higher in stroke
patients with seizures
◦ Studies show that seizures increase risk of mortality by 2
to 3 times
Silverman et al. Arch Neurol. 2002: 59; 195-202,
Burneo et al Eur J Neurol 2010: 17; 52-58,
Arboix A, et al. Stroke 1997: 28; 1590-4
Camilo V and Goldstein LB. Stroke 2004: 35; 1769-75
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Community stroke register of a population of 105,000 residents
2-6.5 years of follow-up 1981-1986 with follow-up to 1988
675 patients with 52 pts with one or more post stroke seizure
Onset seizure defined as <24 hours
Estimated 5 year risk of post-stroke seizure 11.5% (5-18% 95 CI)
Burn J et al. BMJ 1997: 315; 1582-7
Onset
Post-stroke (%)
Total
675
14
5
36%
IS
545
10
4
40%
ICH
66
2
1
50%
SAH
33
2
0
0%
Unknown
31
0
0
Burn J et al. BMJ 1997: 315; 1582-7
Any seizures
Single
Recurrent
Total
48
23
25
52%
IS
35
17
18
51%
ICH
7
3
4
57%
SAH
6
3
3
50%
Unknown
0
0
0
Burn J et al. BMJ 1997: 315; 1582-7
No sz / No pt
%
All
strokes
37/904
4.10%
deep
infarct
2/356
lobar
infarct
20/341
5.90%
11
4/101
4%
8
7/49
14%
25.3
4/50
8%
13.2
deep
ICH
lobar
ICH
SAH
OR
0.60% 1 (Ref)
Labovitz DL et al. Neurology 2001: 57; 200-6
Burn J et al. BMJ 1997: 315; 1582-7
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1897 patients with IS/ICH stroke excluding brainstem
strokes, AVMs, SAH, TIAs
168 / 1897 pts (8.9%) had a seizure
◦ Ischemic stroke 140 / 1632 (8.6%)
 Early onset 78pts
 Late onset 62pts  34 pts had recurrent seizures
◦ Hemorrhagic 28 / 265 (10.6%)
 Early onset 21 pts
 Late onset 7 pts
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Patient with ischemic strokes and seizures had a worse
prognosis, 30-d mortality 25% vs 7%
Seizures were more likely with cortical location of the
stroke
◦ HR 2.09 (1.19 - 3.68) for a seizure
◦ HR 2.13 (0.60 - 7.53) for recurrent seizures
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Late onset seizures have a HR of 12 for recurrent seizures
Bladin CF et al. Arch Neurol 2000: 57; 1617-22.
Arntz R et al., PLoS One 2013;8: e55498
Type
# patients n seizures
Incidence Cumulative Risk
%
%
Total
697
79
11.3
14
IS
425
61
14.4
16
ICH
66
11
16.7
31
TIA
206
7
3.4
5
Arntz R et al., PLoS One 2013;8: e55498
Early seizure (n=25)
Late seizures (n-54)
Total
Single
Multiple
Total
Single
Multiple
IS
20
ICH
6
(30%)
1
(25%)
41
4
14
(70%)
3
(75%)
19
(46%)
1
(14%)
22
(53%)
6
(86%)
TIA
1
1
0
6
3
3
7
Arntz R et al., PLoS One 2013;8: e55498
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Are the underlying causes of acute and late
seizures different?
◦ Focal irritability
◦ Network irritability
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Where is the line between early and late onset
seizures?
◦ Cellular / Neuronal Death
◦ Gliosis
◦ Blood brain barrier
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What is the natural history of acute symptomatic
and remote symptomatic seizures?
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Rochester Epidemiology Project
◦ Rochester, Minnesota
◦ Limited population
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Records-linkage system 1955-1984
◦ All medical records are linked between medical
facilities in Southeastern Minnesota
◦ Retrospective
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Select patients first time seizures
◦ Classify as acute symptomatic versus remote
symptomatic
◦ Assess for 30 day and 10 years mortality
◦ Assess for etiology of seizures
Hesdorffer DC et al. Epilepsia. 2009: 50; 1102-8
Acute
Remote
N, subsequent
seizures
5 yr, Risk of
subsequent seizure
262
34
148
72
19% (14-25%)
65% (55-75%)
Stroke
TBI
Infection
33% (21-50%)
13% (7-25%)
17% (10-28%)
72% (60-82%)
47% (30-66%)
64% (21-99%)
Total N
Hesdorffer DC et al. Epilepsia. 2009: 50; 1102-8
Hesdorffer DC et al. Epilepsia. 2009: 50; 1102-8
Acute
Remote
Mortality,
30 days
56/262 (21.4%)
5/148 (3.4%)
Stroke
42% (32-53%)
5% (2-11%)
TBI
11% (6-20%)
None
Infection
10% (5-19%)
None
Caveat – Acute seizures may not be an INDEPENDENT risk
factor for mortality but is associated with hemorrhagic
strokes and larger infarct size and disability.
Hesdorffer DC et al. Epilepsia. 2009: 50; 1102-8
Szalflarski JP et al. Epilepsia 2008: 49; 974-981
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Acute stroke is the 3rd most common cause
of SE (~20-36% of all SE cases)
8% of all post-stroke seizures present in SE
10-20% of early onset seizures are in SE
Subclinical seizures are missed unless there is
continuous EEG monitoring
◦ Subclinical/nonconvulsive seizures are 4 times
more likely to occur than convulsive seizures.
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Patients in SE are at twice the risk of mortality
Varelas PN and Hacein-Bey L. “Stroke and Critical Care Seizures” in Current Clinical
Neurology: Seizures in Critical Care:.” Ed. PN Varels. Chapter 2, pg 21-82.
Knaker et al. Epilepsia. 2006: 47; 2020-6.
DeLorenzo RJ et al. Neurology 1995: 46; 1029-35.
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232 patients with EEG in first 24hrs then followed up for 1 week
15 patients had seizures in first 24hrs (6.5%)
10% of EEGs had epileptiform discharges
6% had periodic lateralized epileptiform discharges (PLEDs)
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195/232 had diffuse or focal slowing only
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23/232 had epileptiform discharges
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14/232 had PLEDs
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◦ 71.4% evolved to status epilepticus
◦ No seizures
◦ 3/23 had seizures
◦ 10 were in status epilepticus (mostly convulsive)
◦ 2 had focal seizures
◦ 3/14 died compared to 30/218 without PLEDs
Mecorelli O et al Cerebrovasc Dis 2011; 31: 191-8
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At least 2 unprovoked (or reflex) seizures occurring
more than 24 hours apart
One unprovoked seizure and a probability of further
seizures similar to the general recurrence risk (at
least 60%) after 2 unprovoked seizures, occurring
over the next 10 years
Diagnosis of an epilepsy syndrome
Epilepsy is considered to be resolved for individuals
who had age-dependent epilepsy syndrome but are
now past the applicable age or those who have
remained seizure-free for at least 10 years; with no
seizure medications for the last 5 years
Fisher RS et al. A practical clinical definition of epilepsy, Epilepsia 2014; 55:475-482
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The risk of seizure recurrent
Risk of mortality
Underlying cause of seizure
◦ Is it self-limiting?
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Medication interactions
Co-morbidities of the patient
Risk of adverse events
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Newer generation medications are preferred and are likely better
tolerated
◦ Lamotrigine and gabapentin are better tolerated than carbamazepine
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Older generation medications may interact with oral
anticoagulation or anti-thrombotic medications
CYP3A4 induction/inhibition
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Phenytoin
Carbamazepine, oxcarbazepine
Phenobarbital
Valproate
Electrolyte disturbances
◦ Topiramate, zonisamide (carbonic anhydrase activity)
◦ Oxcarbazepine (hyponatremia)
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Dementia/sundowning/psychosis
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Multiple drug rashes
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Woman of child bearing age
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Anemia
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Kidney disease
◦ Levetiracetam
◦ Lamotrigine, phenytoin, carbamazepine (HLA-B* 1502),
zonisamide
◦ Valproate, carbamazepine, benzodiazepine, phenytoin,
phenobarbital
◦ Felbamate, valproate, carbamazepine
◦ Topiramate, zonisamide