Seizures and Epilepsy - Vanderbilt University Medical · PDF fileSeizures and Epilepsy Medical Director Acute Neurological Services Swedish Medical Center ... • Seizure precaution:

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


ABCs

Terminate seizures


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


ABCs

Terminate seizures


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


ABCs

Terminate seizures


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


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


MERGING OF I.R. SEIZURES Waxing and Waning Ictal Discharges


Rat 06, 75 min after KA

Rat 206, 37 min after HCT

Rat 325, 24 min after Pilo

CONTINUOUS ICTAL DISCHARGES


CONTINUOUS ICTAL DISCHARGES





CONTINUOUS DISCHARGES

WITH FLAT PERIODS


CONTINUOUS DISCHARGES

WITH FLAT PERIODS





PERIODIC EPILEPTIFORM

DISCHARGES


PERIODIC EPILEPTIFORM

DISCHARGES


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

Documents

Seizures and Epilepsy - Vanderbilt University Medical · PDF fileSeizures and Epilepsy Medical Director Acute Neurological Services Swedish Medical Center ... • Seizure precaution: