Seizures and Epilepsy
Medical Director
Acute Neurological Services
Swedish Medical Center
Englewood, Colorado
Assistant Clinical Professor
University of Colorado
School of Medicine
Denver, Colorado
Ira Chang, MD
Board Review Course: NCS, Montreal 2011
Seizures in Critical Care
Principles
• Seizures are common in critically ill
patients
– variety of etiologies, including metabolic
• Definitions of status epilepticus has
shortened to 5min
• NCSE is common after treating CSE
• Immediate goal is to stop seizure activity
(after ABCs) – clinical and electrographic
Principles (cont)
• Inc morbidity and mortality the longer the
seizures (CSE/NCSE) last
• Standard treatment algorithm for early
seizure tx (0-20min)
• Various definitions and approaches for
refractory status (30-60min or lack of
response to 2 IV agents)
• Standard approach to weaning off cIV
agents
Principles (cont)
• Increasing role of continuous EEG
• Increasing experience in newer agents
• Consider autoimmune etiologies
• Consider adjunctive use of hypothermia
• Prevention of recurrence depends on
etiology and choice of AED
• Increasing recognition of SUDEP
Incidence of seizures • Seizures
– Medical ICU -217 pts (Bleck 1993)
• 28.8% encephalopathy
• 28.1% seizures
• 0.5% status epilepticus
• Status epilepticus
– 3-5% of all ED admissions (Hauser 1990)
– 125,000-195,000 cases/year (DeLorenzo 1995,1996)
• Refractory SE
– 43% of SE pts (no response to 2 IV AEDs) (Holtkamp
2005)
Predisposing Factors
• Hypoxia/ischemia
• Drug/substance tox
– Antibiotics
– Antidepressants
– Antipsychotics
– Bronchodilators
– Local anesthetics
– Immunosuppressives
– Stimulant drugs
• Drug/subs withdrawal
– Barbiturates
– Benzos
– Opioids
– Alcohol
• Infection/fever
• Metabolic – Ca2+, Na+,
Glu, Phos, renal
• craniotomy
NCSE Incidence
• After control of CSE: 164 pt in eval with cEEG x 24 hrs
(DeLorenzo 1998)
– 48% with sz on EEG
– 14% with NCSE, mostly complex partial
• ICU: 236 pts in coma with 30min EEG (Towne 2000)
– 8% with NCSE
– Of these, 42% due to anoxia, 22% with stroke
• NICU: 124 pts monitored by cEEG (Jordon 1999)
– 34% with NCS
– 27% with NCSE
High risk neurological factors
Stroke
• Hemorrhagic
• Larger cortical
• Acute confusional state
Neoplasm
• cortical
• Primary
• metastatic
Head trauma
• Contusion
• SDH
• Depressed skull fx
• Penetrating missile
• Post surgical
Mirski, M. in Seizures in Crit Care 2005
Etiology
Adults (Claassen 2009)
• 42% prior h/o epilepsy
– 34% had low AED level
– 12% present with SE
• 22% new stroke
• 22% discont. AEDs
• 10% anoxia/hypoxia
• 10% metabolic
• 10% etoh withdrawal
(From Chen 2006)
Pediatric (Lacroix 1994)
• PICU population
– 32% epilepsy
– 13.6% atypical febrile
convulsions
– 13% meningitis
– 13% encephalitis
– 1.5-5% intox, tumor,
anoxia, Htn crisis, metab
NCS Etiology
ICU : NCSE
• 42% anoxia/hypoxia
• 22% stroke
• 5% infection
• 5% head trauma
• 5% metabolic
• 5% etoh/AED withdrawal
• 5% tumor
(Towne 2000)
NICU: NCS
• 60% metabolic coma
• 56% epilepsy
• 54% brain tumor
• 33% CNS infection
• 28% head trauma
• 26% CNS ischemia
• 22% ICH
(Jordan 1999)
Definitions
• Continuous or intermittent seizure activity
> 30 min without consciousness
• Seizure
– Lasts > 5 min
– 2 seizures with persistent alt mental status
Status Epilepticus
• Seizure subtypes
– Generalized convulsive
– Nonconvulsive status (altered to comatose)
• Absence or petit mal status
• Secondary generalized seizures
• Complex partial seizures
• Subclinical SE
– focal motor SE (face, arm twitching)
Pathophysiology • Not just a prolonged seizure
– Reconfiguration of excitatory/inhibitory brain
pathways into positive feedback loop
• Direct mechanisms (Lothman 1998)
– Facilitation – inc excitotoxins (glu), Ca2+ influx via
NMDA or AMPA receptors
– Fading of inhibition – dec GABA release due to
repetitive activation of presynaptic storage site
• Longer term effects – gene expression, hippocamp
apoptosis
• Secondary epileptogenesis – local process disseminates
– Seizures beget seizures (Fountain 1995)
Differential Diagnosis • Myoclonus
– Toxic/metabolic
– Infec/inflamm/autoimm
– Spinal cord disease
– Brainstem/subcortical
– Cortical
– Epileptic
• Tics
• Tremor
• Asterixis
• Clonus
• Posturing
• Opisthotonus from HCP
• Shivering/rigors
• Hiccoughs
• Post-anesthesia
psychogenic SE
• Narcolepsy/cataplexy
• Syncope
• TIA
• TGA
• Pseudoseizures
(Varelas 2005, Table 5)
Evaluation of Etiology
Laboratory Evaluations
• Blood count
• Glucose
• Electrolytes
• Liver enzymes
• Toxicology screen
• ABG
• AED level
Diagnostic Evaluations
• Head CT
• Lumbar puncture
– Benign postictal elevation
in 20% (WBC > 70)
– Protein elevation in 15%
(>50 ) (Aminoff 1980)
• Stat EEG – if pt not
waking up
• Continuous EEG
• MRI – can mimic infarct
DO NOT DELAY SEIZURE TX FOR
WORKUP
Brief single ICU Seizure Mgt
• Observe. Eliminate etiology
• Consider AED load and maintenance
– Phenytoin (15-20 mg/kg, then 300-400mg/day)
– Fosphenytoin (15-20 mg/kg PE, then 300-400mg/d)
– Valproate (15-20 mg/kg, then 600-3000mg/d)
– Levetiracetam (1000 mg, then 1000-3000mg/d)
• Seizure precaution: padded bed rails, increase
observation
From Varelas 2005, table 6
Adaptation from Varelas, Mirski 2001
SE Algorithm
Emergency med mgt –
ABCs
Terminate seizures
Prevent recurrence of
seizures
Treat complications
ABCs: Med mgt
• ABC’s
• Intubation
– Short acting – rocuronium or vecuronium
– Thiopental (3mg/kg) can also treat seizures
– Avoid overcorrecting to resp alkalosis
• No need to treat BP unless extreme (>230 mmHg
systolic)
• Thiamine 100mg IV if etoh or history unknown
• Glucose (D/W 50%) – only if BS < 40-60 or few minutes
to get result
SE Algorithm
Emergency med mgt –
ABCs
Terminate seizures
Prevent recurrence of
seizures
Treat complications
First known description of
status epilepticus
(Sakikku cuneiform,
ca. 700 B.C)
give lorazepam
Courtesy of Dr. Bleck
SE Algorithm
• First line agent – lorazepam
– Midazolam ( buccal, IM, IN) or rectal diazepam
• Second line agents
– Fosphenytoin or phenytoin
– Phenobarbital
– Valproate (Shorvon 2011)
IV levetiracetam – open
label trials (CPSE)
Good efficacy
Low toxicity and
interactions
VA Cooperative Trial
• 570 pts in RCT; 4 iv tx arms
• overt SE or subtle SE
• First line treatment options
• Second, third line tx algorithm
• End pt: seizure cessation < 20min
• No return of seizure activity for 40 min
Treiman, Meyers, Walton 1998
VA Study Results
Success rate Lorazepam Phenobarb Diaz/Pheny Phenytoin
First drug 64.9% 58.2% 55.8% 43.5%
Second drug PHT 7.2 % PHT 3.3% LRZ 3.2% LRZ 13.9%
Third drug PB 2.1 % LRZ 2.2% PB 2.1 % PB 3.0%
Other drugs 17.5% 25.3% 23.2 % 26.7%
No response 8.3% 11.0% 15.8% 12.9%
•Lorazepam was the most effective first line agent
•Overall, if first line agent fail, second line choice had low success rates
•If LZP and PHT fail to control < 30min, consider going to refractory
agent
Treatment Principles
• Treat quickly
– 80% response to 1st line meds if tx < 30min
– < 40% response if tx < 2 hrs
– 2x mortality if tx delayed > 24 hr (NCSE)
• Risk of respiratory depression less than
risk of prolonged seizures
(Claassen 2009)
BZDs – First Line
Agent • Pharmacokinetics
– Less rapid redistribution
– Longer half-life (8-25 hr)
– Less CV depression
• 81 episodes of SE (Leppik 1983) DZ vs
LZP
– 89% controlled with lorazepam
– 76% controlled with diazepam
• Pediatric study (Appleton 1995)
– 76% controlled w/LZP
– 51% controlled w/DZP
– less respiratory depression (3% vs
15% w/DZP
• High tendency for tolerance
•Enhance GABA
inhibition
•Lorazepam
•0.1mg/kg (4 mg
bolus q 10 min)
•Diazepam
•Midazolam
BZDs – First Line
Agent
• Pharmacokinetics
– Highly lipid soluble
– Redistributes out of brain rapidly
(distribution half-live 30-60 min)
– Long elimination half-life (24 – 57 h)
– Persistent and cumulative sedation
– Respiratory depression
• Rectal diazepam
– 2 RCT’s ( Cereghino 1998, Dreifuss
1998)
– 55-62% were seizure free
– Somnolence most frequent side eff
– No episode of respiratory depression
in 500 patients
•Enhance GABA
inhibition
•Lorazepam
•Diazepam
•10-20mg IV(5-10mg
boluses)
•Rectal gel
•Midazolam
BZDs – First Line
Agent • Pharmacokinetics
– Water-soluble that converts to
lipophilic in serum
– Rapidly absorbed by IM, IN, buccal
– Short distrib half-life < 5min
– Short elimination half-life 1.5-4 hr
• best as continuous infusion
• IM when no IV access
• Buccal (McIntyre 2005)
– 219 seizure episodes in children
– 56% sz cessation < 10min for 1 hr
– 29% for rectal dzp < 15min
•Lorazepam
•Diazepam
•Midazolam
• 0.1-0.3mg/kg
bolus (< 4mg/min),
then 0.08-
0.4mg/kg/hr
•Buccal - first line
in children without
IV access, pre-
hospital
•IM – 5-10mg
Second Line
Agents • Phenytoin – Water insoluble
– pH 12; caustic to veins
– Hypotension, QT prolongation
– Peak brain levels in 15min
– Slow redistribution out of CNS
– 96% protein bound
• Low cost, so consider for
maintenance
•Phenytoin
•20mg/kg load
•5 mg/kg addtl
•300-400mg/d
•Fosphenytoin
•Phenobarbital
•(Valproate)
Second Line
Agents • Fosphenytoin – PHT pro-drug; water soluble
– Therapeutic levels within 10min
– Need to wait for conversion to PHT
before measuring level (1-1.5 hrs)
– Expressed in phenytoin equivalents
• Fewer local side effects
• Less hypotension (7.7%)
• Preferred for IV loading dose
•Phenytoin
•Fosphenytoin
•20mg/kg PE
•5 mg/kg PE
addtl load
•Phenobarbital
•(Valproate)
Second Line
Agents
• Does not cause sedation or
respiratory depression
• Broad efficacy – GTC, focal,
absence, myoclonic
• European study (Giroud 1993)
– 23 pts with CSE or NCSE
– 83% had sz cessation < 20min
• Multiple studies show efficacy
comparable to PHT (Trinka 2009)
• Absence SE or myoclonic SE
• Pts who do not want mech
ventilation
• Pts intolerant to phenytoin
• Considered third line agent
•Phenytoin
•Fosphenytoin
•Phenobarbital
•(Valproate)
•15-20mg/kg
•400-600mg q
6hr maint.
First line agent
Lorazepam
Rectal diazepam
Buccal midazolam
Second line agent
Fosphenytoin
Phenytoin
Valproate
PB (CPSE)
Alt. second line agent
cIV midazolam
cIV propofol
Alternate 2nd / 3rd
line agent - cIV • cIV drips can be second line
agent after lorazepam
• Systematic review of RSE
(Claasen 2002)
– No difference in mortality (48%)
between cIV mdz, prop, pentobarb
– Acute tx failure, breakthrough sz
• cIV mdz = cIV prop
• Less with cIV pentobarb - ?due to highest
rate of burst suppression goal
– Hypotension highest with cIV pentob
•cIV midazolam
•cIV propofol
Alternate 2nd / 3rd
line agent - cIV • Effective in minutes
• Easy to titrate
• Minimal cardiovascular effects
• Tachyphylaxis in 24-48 hrs
• cEEG may be diffuse slow, burst-
suppression or flat
• Wean after 12-24 hrs of sz
suppresion
•cIV midazolam
•0.2-0.4mg/kg
boluses q 5min
•Max of 2.0
mg/kg/hr
•cIV propofol
Alternate 2nd / 3rd
line agent - cIV
• Non-barbiturate anesthetic
• GAB A-R effects similar to BZD
and barbiturates
• Rapid onset < 3min
• Rapid recovery 5-10min
• Liver metabolism
• Seizure like phenomenon (SLP)
– Rigidity, myoclonus, opisthoclonus
– Subcortical disinhibition
• Hypotension, bradycardia
• Propofol infusion syndrome
– Cardiac failure, metab acidosis,
rhabdomyolysis, renal failure
•cIV midazolam
•cIV propofol
•3-5mg/kg bolus
•1-15 mg/kg/hr
Propofol Infusion Syndrome (PIS)
• Tx > 48 hr, dose > 5mg/kg/hr (350mg)
• 41 pts with RSE (retrospective) (Lyer 2009)
– 31 pt - propofol
– 10 pt – other anesthetics
• 3 pts in prop grp had sudden unexplained cardioresp.
arrest with no prior disease
• 11 pts with non-life threatening PIS
– Median admin = 63 hr, dose of 12,750mg cumulative
Stat EEG
• not recommended in first 15min (Epilep Found 1993)
• if pt not waking up after tx (15-30min) (Bleck 1993)
• EEG (30min) – diagnose 1/3 of NCS (24hr cEEG)
• Limited montages (6 channels, hairline) not sensitive
• cEEG –
– 24hr detect 95% in altered MS and 80% of comatose pts
• VideoEEG – need to distinguish artifacts, pseudosz
Newer
Second/Third line
agents
• Pharmacokinetics
– Unique mechanism of action
– Metabolism by hydrolysis in serum
– Renal excretion
– No significant drug interactions
• Multiple open label studies in
various types of epilepsy
(Shorvon 2011)
– Excellent efficacy
– Low toxicity
• Increasing use off label as
second line drug of choice
• Important in CPSE
•Levetiracetam
•1000-4000mg IV
•Lacosamide
•400mg bolus
Third Line
Agents • Rarely used anymore as second
line agent for GSE
– Slower entry into brain
– Long half-live of 4 days
• Respiratory depression
• Hypotension common
• May be useful in partial SE
• Can use when weaning from high
dose midazolam or barbiturates
•cIV midazolam
•cIV propofol
•cIV phenobarbital
•20mg/kg at 50-
100mg/min
•IV valproate
Refractory Status Epilepticus
• Definitions
– Sz > 60 min (Shorvon 2011)
– Sz not responding to 2 IV drugs (Delorenzo 1995, Holtkamp
2005)
• 1/3 of SE pts – refractory to 1st/2nd line agents (Mayer 2002)
– 83 episodes of status, retrospective
– Seizure after BZD – 69%
– Seizure after second agent – 31%
– Risk factors:
• NCSE
• Focal motor seizure at onset
RCT in RSE
• First RCT (Rosetti 2010) – single-blind, multicenter
• After failure of BZD and second line agent
• enrolled 24/150 target in 3 yrs
– Propofol – 43% termination of RSE (not statis sig)
– Barbiturates – 22% term of RSE
• Mortality and recovery to baseline similar
• Mechanical ventilation time – much longer for barbs
RSE (fourth line)
Agents • Barbiturates
– Long half-life
– Cardiovascular depression
• Hypotension, myocardial
depression, dec renal perfusion
– Suppress cough, ciliary immob
– Immunosuppression
– Poikilothermia
– GI hypomotility
– Immobilization (DVT, decub)
• Goal of EEG to burst suppression
to flat
•Pentobarbital
•Thiopental
RSE (fourth line)
Agents • Pentobarbital
– Shorter elimination half-life than
phenobarb (24 hr)
– Sz can occur in w/d period
• Duration- 24 - > 96 hrs
– 44 RSE episodes (Krishnamurthy
1996) - >96hr tx and phenobarb use
during taper less relapse
– Reports of very long duration with
good functional recovery (Mirski 1995)
•Pentobarbital
•6-15mg/kg (1hr)
•1mg/kg/hr (0.25-
10mg/kg/hr
•Thiopental
•Isoflurane
•Ketamine
•Lidocaine
RSE (fourth line)
Agents • Thiopental
– Rapid onset, AED efficacy
– Potential neuroprotective
– Dec ICP, CBF, cerebral metab
• Preferred in europe for barb anesth
in RSE
• Bispectral Index Monitor (BIS)
– 10 RSE pt tx with propofol
(Musialowicz 2010)
– Score of 30 correlates with burst supp
on EEG; sens 99%, spec 98%
•Pentobarbital
•Thiopental
•2-4mg/kg bolus
(100-250mg bolus
over 20s, then
50mg q 3min)
•3-5mg/kg/hr cIV
RSE Treatments
Pharmacologic
• Isoflurane • End-tidal concen of 1.2-5%
• Ketamine – NMDA antagonist
• Lidocaine
– Stabilizes cell membranes
– Risk for toxicity and inc sz
with repeated dose
• Topiramate
• IVIG, methylprednisolone,
rituximab, cytoxan
Non-pharmacologic
• Hypothermia (31-24° C)
– 4 adults RSE (Corry 2008)
– 2 sz control, 1 dec sz
• Vagal nerve stimulation
• Surgical resection
• Ketogenic diet
• Electroconvulsive tx
• Plasma exchange
Autoimmune epilepsy
• Cryptogenic epilepsies - assoc with cognitive
decline or personality changes (Tan 2010, Dalmau
2009)
• 25-50% of adult onset temporal lobe epilepsy +
hippocampal sclerosis = limbic encephalitis (Bien
2007)
• NMDA-R Ab (Tan 2010, Dalmau 2008,2009, Lancaster 2010)
• Voltage-gated potassium channel Abs – VGKC-complex
(CASPR2, LGI1, Contactin-2) (Irani 2010)
• GABAB1, AMPA-R Abs (Lancaster 2010, Lai 2009)
SE Algorithm
Emergency med mgt –
ABCs
Terminate seizures
Prevent recurrence of
seizures
Treat complications
Weaning Protocols
Continue cIV for 12-24 hrs
after stopping seizure activity (clinical/cEEG)
taper over 24
hrs
Seizures recur
Longer taper +
inc AEDs
Long term AEDs + cEEG
SE Algorithm
Emergency med mgt –
ABCs
Terminate seizures
Prevent recurrence of
seizures
Treat complications
Complications in SE Caused by SE
• Rhabdomyolysis
– Saline diuresis
– Neuromuscular blockade
• Hyperthermia
– Resolve with term of SE
– External cooling devices
• Vasogenic edema
• Drug interactions
• ICU complications
– Sedation, mech ventilation,
immobility
Considerations in SE
• Hepatic failure
– PHT- free levels
– PB - 25% metab in urine
• Half-life – to 130 hrs
– BDZ - reduce dose
– Pentob,thiop – do not use
– VPA – inc ammonia levels
• Renal failure
– No effect on BDZ, VPA
• Hematopoetic dysfx – PHT, PB – megaloblastic anemia
– VPA – thrombocytopenia
– CBZ – neurotropenia, aplastic
anemia
Outcome in SE
• Dependent on cause, clinical type, age (Tsai 2009)
• Adherence to 1st line tx protocol – 7x increase in
seizure termination (Aranda 2010)
• RSE prospective study (Novy 2010)
– 23% were refractory to 1st / 2nd line agents
– 39% mortality
– 1 in 5 returned to clinical baseline
• Conclusion: pt with prolonged SE can survive with good
outcome ;depends on underlying cause and
complications rather than duration (Holtkamp 2011)
Focal SE
Clinical types (> 30min)
• Epilepsy partialis
continua – distal limb
• Opercular myoclonic –
glossopharyngeal
• Sensory
• Aphasic
• Occipital lobe- visual loss
(Varelas 2005)
Etiologies
• Focal cerebral pathology
• Diffuse process (Schomer
1993)
– Nonketotic hyperglycemia
– Hyponatremia
– Mitochondrial
encephalopathy
– Rasmussen’s encephalitis
– Antibiotics – PCN,
azlocillin/cefotaxime
Focal SE Treatment
• No convincing data re: significant long term
effects independent of etiology (Holtkamp 2011)
• Less aggressive treatment – 1st / 2nd line agents
trying to avoid general anesthesia
• Systemic complications – HR, temp, rhabdo
• May require polypharmacy
• Choose potent AED with low sedation/resp dep
• Response to AED may be delayed up to 48hrs (Drislane 1999)
Focal SE Agents
• Levetiracetam
– Second line after BZD
– Third line after valproate or
phenytoin
• Lacosamide
– Retrospective case series
(Kellinghaus 2011)
• 39 pts (6 GSE,17 CPSE, 16
SPSE)
• Median dose 400mg (40-
80mg/min)
• 44% success rate (17 pts)
•Levetiracetam
•valproate
•Phenobarbital
•lacosamide
•Oral AEDs
•Carbamazepine
•Oxcarbazepine
•Topiramate
•zonisamide
•Gabapentin
•Lamotrigine
•Pregabalin
Focal SE Agents
• Topiramate
– Multiple mech of action, via NG tube
– Effective in 6 pts in GSE, NCSE
(Towne 2003)
• Zonisamide – Sodium and calcium channel blocker
– Approved in Japan for adjunctive tx for
refractory partial epilepsy
• Lamotrigine
– NCSE (Trinka 2002)
– myoclonic SE (Guerrini 1999)
• Pregabalin
– Retrosp study in RSE (Novy 2010)
– 8/11 pts response (5/11 definite)
– No side effects
•Levetiracetam
•valproate
•Phenobarbital
•lacosamide
•Oral AEDs
•Carbamazepine
•Oxcarbazepine
•Topiramate
•zonisamide
•Lamotrigine
•Pregabalin
Pediatric SE
• Cardioresp support while treating motor/EEG sz
• focus on prehospital treatments (Alldredge 1995, 2001)
– Shorter duration SE: 32 min vs 60min
– Less recurrent sz in ED: 58% vs 85%
• Lorazepam – fewer repeat doses and less respiratory
depression than diazepam (Appleton 1995)
• cIV midazolam in refractory SE – assoc with lower
mortality in children (Gilbert 1999)
• Pentobarbital therapy – burst supp for 12 hrs (Kinoshita
1995)
ICU EEG monitoring
• Seizure detection – Acute, unexplained change in mental status
– MS exam out of proportion to underlying injury
– Persistent unresponsiveness after tx CSE
– Comatose with subtle motor/eye movements
• Titration of medications
• Ischemia detection
• Prognostication
• Characterization of clinical spells
Duration of cEEG
Claassen Neurol 2004
N=105 Clin events EEG szs
Routine EEG (>= 30 mins) 21% 11%
cDVEEG (mean 2.9 d) 40% 27%
P 0.01 0.01
Pandian Arch Neurol 2004
Monitor
Altered MS-
24 hr
Comatose-
48 hr
NCSE Treatment • Controversial patterns: ictal-interictal
continuum
– PLEDs, GPEDs, BiPLEDs
– Triphasics, SIRPIDs
• BZD trial with clinical improvement or
resolution of EEG pattern or appearance
of background pattern. If EEG improves
but pt does not, result is equivocal.
Good luck!
PLEDs
• Sharp/spike waves/slow waves that occur in regular
periodic intervals (Young 1988)
• Usually occurs with cortical injury
• Also in metabolic or post SE (Raroque 1993)
• Considered cerebral response to acute focal process
– Ischemic stroke
– Linked to parox depolarizing shift at cellular level/
membrane/chemical disruption
– Linked to basal ganglia circuit
• Inconclusive relationship to outcomes (Garcia-Morales
2002)
Outcomes in NCSE
• 134 pt with subtle SE (Treiman study) – worse outcomes
than with CSE
• 100 pts with NCSE (Shneker 2003)
– Overall mortality 18%
• 27% in medical group
• 17% in cryptogenic group
• 3% in epilepsy group
– No correlation between sp/w discharge on EEG and mortality
– Independent assoc. of mental status change and mortality
• Duration > 36-72 hrs leads to inc. morbidity and mortality
(Krumholz 1995)
Outcomes in NCSE
• Clinical data:
• Nontraumatic ICH: nonconvulsive szs may be associated with mass
effect and shift Vespa ‘03, Claassen, ’07
• NCSZ post TBI may be a/w long-term hippocampal atrophy Vespa
‘10
• Neurochemistry:
• NSE: levels highest with acute brain injury + szs; szs alone can
cause elevation DiGiorgio ’95 + ‘99
• Glutamate: szs may be associated with glutamate spikes, including
to toxic levels Vespa ‘98
• Lactate pyruvate ratio increased in post traumatic seizures Vespa
‘07
Outcomes in NCSE
• 134 pt with subtle SE (Treiman study) – worse outcomes
than with CSE
• 100 pts with NCSE (Shneker 2003)
– Overall mortality 18%
• 27% in medical group
• 17% in cryptogenic group
• 3% in epilepsy group
– No correlation between sp/w discharge on EEG and mortality
– Independent assoc. of mental status change and mortality
• Duration > 36-72 hrs leads to inc. morbidity and mortality
(Krumholz 1995)
Evolution of SE
• Phases of progression of electrographic
findings in status epilepticus
(Treiman 1990)
ISOLATED REPETITIVE GTC
SEIZURES
Treiman, et al., Epilepsy Res 5:49-60, 1990
ISOLATED REPETITIVE GTC
SEIZURES
Treiman, et al., Epilepsy Res 5:49-60, 1990
26 min after 10 mg/kg KA Rat 06, 26 min after KA, 10 mg/kg IP
Rat 206, 30 min after HCT, 5.5 mmol/kg IP (cobalt lesion left frontal cortex)
Rat 325, 21 min after Pilo, 25 mg/kg IP (LiCl, 3 mmol/kg IP given 24 hrs earlier)
MERGING OF I.R. SEIZURES Waxing and Waning Ictal Discharges
Treiman, et al., Epilepsy Res 5:49-60, 1990
MERGING OF I.R. SEIZURES Waxing and Waning Ictal Discharges
Treiman, et al., Epilepsy Res 5:49-60, 1990
Rat 06, 75 min after KA
Rat 206, 37 min after HCT
Rat 325, 24 min after Pilo
CONTINUOUS ICTAL DISCHARGES
Treiman, et al., Epilepsy Res 5:49-60, 1990
CONTINUOUS ICTAL DISCHARGES
Treiman, et al., Epilepsy Res 5:49-60, 1990
Rat 06, 103 min after KA
Rat 206, 48 min after HCT
Rat 325, 28 min after Pilo
CONTINUOUS DISCHARGES
WITH FLAT PERIODS
Treiman, et al., Epilepsy Res 5:49-60, 1990
CONTINUOUS DISCHARGES
WITH FLAT PERIODS
Treiman, et al., Epilepsy Res 5:49-60, 1990
Rat 06, 148 min after KA
Rat 206, 75 min after HCT
Rat 325, 109 min after Pilo
PERIODIC EPILEPTIFORM
DISCHARGES
Treiman, et al., Epilepsy Res 5:49-60, 1990
PERIODIC EPILEPTIFORM
DISCHARGES
Treiman, et al., Epilepsy Res 5:49-60, 1990
Rat 06, 5 hr 46 min after KA
Rat 206, 2 hr 12 min after HCT
Rat 325, 2 hr 19 min after Pilo
Prognostication EEG findings associated with poor prognosis:
• Seizures
• Status epilepticus
• Generalized or lateralized periodic epileptiform discharges
• Nonreactivity
• Absent sleep architecture
• Percent alpha variability within 3 d post TBI correlates with fct outcome
at 6 m
Bricolo EGCN 1978; Jaitly J Clin Neurophysiol. 1997; DeLorenzo Epilepsia. 1998; Lawn Clin
Neurophysiol. 2000; Vespa Neurology 2003; Claassen NCC 2006 and Neurology 2007;
Vespa JNsurg 2002, Hebb J Neurotr 2007
Caveat: unclear if these EEG findings are markers of the extent of brain
injury or if they cause additional brain injury
From Claassen
EEG pattern: discrete seizure
EEG patterns: Discrete seizures
Discrete seizures
EEG patterns: Triphasics
57 yr old with acute renal failure; COPD and acute mental status changes
EEG patterns; BiPEDs
45 yr old with acute encephalopathy following a third ventricular tumor resection
EEG pattern: GPEDs
55 yr old with anoxic brain injury (post cardiac arrest)
EEG pattern: PLEDs
50 yr old S/p Right sided AVM resection. Witnessed seizure followed by
obtundation
EEG pattern: Suppression-Burst
EEG pattern: SIRPIDS
SIRPIDS can be focal or generalized
