Transcript Non-Convulsive Status Epilepticus (NCSE):

Non-Convulsive Status
Epilepticus (NCSE):
Our Experience at a Tertiary Care Center
Brennen Bittel, DO
Clinical Neurophysiology Fellow
Overview
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Background
information:
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Epidemiology
Clinical features
Electrographic definition
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EDX pitfalls
Treatment
Pathology
Outcomes
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KU Data
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2009-2013
Incidence/prevalence
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SE* in emergency room or intensive care
units ~ 150,000/yr
NCSE:
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25 % of all SE
1.5 – 60/100,000/yr
34% of all SE in a tertiary care center
27% of ICU pts w/ altered mental status
8% of pts in coma
Celesia 1976, Tomson 1992, Drislane 2000, Towne 2000
Definition
1.
Diminished level of consciousness,
confusion
2.
Epileptiform EEG (continuous or discrete)
3.
Response to treatment??
1. Change in mental status- Semiology
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Ambulatory confused patients, mildly
confused hospitalized patients
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Lethargic and comatose patients in intensive
care units
Diminished Level of
Consciousness, Confusion
Clinical presentations
NCSE
ASE
(absence SE)
CPSE
(complex partial SE)
Intermittent
Continuous
20-40%
Krumholz 1999, Meierkord 2007
ESE
(electrographic SE)
35-40%
SPSE
(Simple partial SE)
NCSE
ASE
(absence SE)
Continuous
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ESE
(electrographic SE)
CPSE
(complex partial SE)
Confused
Bizarre behavior
Fluctuations
+/- automatisms
Aphasia
Intermittent
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Stuporous
Comatose
GTC at onset
Medical illness
SPSE
(Simple partial SE)
Other sxs/signs
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Agitation
Lethargy
Mutism
Disruptive behavior
Staring
Laughter
Crying
Rigidity
Perseveration
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Subtle motor
movements
Hallucinations
DDx
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Metabolic/toxic encephalopathy
Complicated migraine/aura
Prolonged post-ictal state
Psychiatric disorders
Substance abuse/withdrawal/intoxication
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DTs
TIA
Transient global amnesia
Husain 2003
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12 in the NCSE group and 36 in the nonNCSE group
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100% sensitivity
Ocular movements
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Rhythmic blinking, deviation, nystagmus, rhythmic hippus
Recent or remote risk factor for seizure
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Previous stroke, tumor, previous neurosurgery, dementia,
epilepsy, and meningitis
Epileptiform EEG
2. Epileptiform EEG
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Frequency
Morphology
Evolution
Rhythmicity
Treiman criteria- GCSE
Five characteristic stages:
1.
2.
3.
4.
Discrete seizures
Merging seizures
Continuous seizures
Continuous seizures with brief "flat" periods on the
EEG
-- (usually no convulsions)
5.
Prolonged flat periods with periodic discharges
-- (usually no convulsions)
Young 1996- NCSE
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Primary Criteria
1.
2.
3.
Repetitive generalized or
focal spikes, sharp waves,
spike-wave or sharp-slow
wave complexes at >3/sec
Repetitive generalized or
focal spikes, sharp waves,
spike-wave or sharp-slow
wave complexes at >3/sec
AND #4
Sequential rhythmic waves
and 1-3, +/- 4
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Secondary Criteria
1.
2.
3.
4.
Incrementing onset: voltage
or slowing
Decrementing offset:
voltage or frequency
Post-discharge slowing or
voltage attenuation
Significant improvement in
clinical state or baseline
EEG after AED***
Walker 2005
1. Frequent/continuous focal
electrographic szs, with ictal
patterns that wax and wane with
change in amplitude, frequency,
and/or spatial distribution.
2. Frequent/continuous generalized
spike-wave discharges in pts
without a previous history of
epileptic encephalopathy or
epilepsy syndrome.
3. Frequent/continuous generalized
spike-wave discharges, which
showed significant changes in
intensity or frequency (usually a
faster frequency) when compared
to baseline EEG, in patients with an
epileptic encephalopathy or
epilepsy syndrome
4. PLEDs/ BIPEDs in patients in coma in
the aftermath of a generalized tonic–
clonic status epilepticus (subtle status
epilepticus).
5. EEG patterns that were less easy to
interpret included:
Frequent/continuous EEG
abnormalities (spikes, sharp-waves,
rhythmic slow activity, PLEDs,
BIPEDs, GPEDs, triphasic waves) in
patients whose EEGs showed no
previous similar abnormalities, in the
context of acute cerebral damage
(e.g., anoxic brain damage, infection,
trauma).
6. Frequent/continuous generalized EEG
abnormalities in pts w/ epileptic
encephalopathies in whom similar
interictal EEG patterns were seen, but
in whom clinical symptoms were
suggestive of NCSE.
EEG Diagnosis
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Inevitably subjective
Which tracing shows NCSE?
PLEDS
Triphasic waves
GPEDS
L Temp/parietal CPSE
Diagnostic pitfalls
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PLEDs, BiPLEDs, GPEDs, SIRPIDs
Encephalopathy
Status myoclonus
CJD
PLEDs
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No absolute frequency criterion can be used to
distinguish PLEDs from seizures
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Frequency
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Acute, serious neurologic illness
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1 - 4 seconds (short periodicity)
>4 seconds (long periodicity)
Mortality is high—up to 50% within 2 months
Walsh 1987
PLEDs
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Associated with:
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Stroke (the most common cause in many reports)
Tumors
Infections- Viral (acute and chronic)
Metabolic disturbances
Head injury
SDH
Anoxia
Brain abscess
Congenital lesions
Tuberous sclerosis
Multiple sclerosis
Creutzfeld–Jakob disease
PLEDs
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80-90% of pts had recent clinical seizures
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66% had some form of SE
Risk for more seizures
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Half patients without prior epilepsy developed
subsequent epilepsy
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Most PLEDs will resolve after days to weeks
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Part of an ictal-interictal spectrum
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Snodgrass 1989, Kaplan 2007, Chong 2005, Walsh 1987
PLEDs
PLEDs regression- 1 week later
Triphasic waves
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Seen commonly in metabolic encephalopathies
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Bursts
1-2Hz
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not seen in NCSE
Increased with stimulation
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Blunted, low-moderate amplitude
Dominant positive second phase, slow rise
Phase lag
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Classically in renal or hepatic failure
not seen in NCSE
Sometimes suppressed with BZDs (40-60%)
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Kaplan 2006
Encephalopathies w/Epileptic Features
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Reversible
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Usually no hx of epilepsy
Medication related
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Irreversible
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Post-anoxic
Creutzfeld-Jacob
BZD withdrawal
Cephalosporin Abx
Ifosfamide
Baclofen
Psychotropics
Rhythmic, semirhythmic
delta
Drislane 2000
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Importance of c-VEEG
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Look for subtle clinical
changes a/w rhythmicity
CJD – EEG progression
Patients at risk
1.
Following seizures or GCSE
-- Up to 50% in NCSE after convulsions cease
2.
3.
4.
5.
AMS with subtle motor signs
AMS in epileptic w/ acute medical illness
Post-stroke pt faring worse or recovery
halted
Elderly pt with AMS (post BZD withdrawal)
DeLorenzo 1998, Drislane 2000
Risk factors
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Mental status changes
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ICH
SAH
Large vessel CVA
Meningoencephalitis
CHI/TBI
Tumor
Post-surgical
Drislane 2000
3. Treatment Response
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Treatment response less often considered
diagnostic
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Clinical response may be delayed hours to days
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Shneker 2003
Treatment
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CPSE
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BZDs
IV AEDs
Usually recurs
ESE
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60% respond to initial BZD (clinical delay)
15% resistant to BZD
Require IV AEDs
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+/- Anesthesia
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Granner 1994, Shneker 2003
Anesthesia- Claassen 2002
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193 pts w/ refractory SE
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Tx with midazolam vs propofol vs pentobarbitol
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Midazolam
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Pentobarbitol
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Increased breakthrough seizures
Less hypotension
Lowest treatment failure/recurrence
More hypotension
Refractory NCSE- more common with propofol and
midazolam
No standardized treatment regimen for use of
anesthesia in SE
Anesthesia
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No consensus on NCSE
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More harm than good?
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Hypotension
Sepsis/line infection
DVT
Ultimate effect on brain?
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Outcomes…
Pathologic changes
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Animal models
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Induced GCSE, up to 5 hours, in baboons
Hippocampal volume loss
 ↑ with frequent, prolonged seizures
 ↓ if paralytic used to abolish convulsions
 Hyperpyrexia, hypotension, hypoxia, acidosis, and
hypoglycemia
Changes in high-frequency (10Hz) vs low frequency
(1Hz) discharges
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Bertram 1990
Pathologic changes
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Human autopsy studies
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GCSE > epilepsy w/o SE > normal
Synergistic damage
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Increase in excitatory neurotransmitters
Metabolic changes (lactate, pyruvate)
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Earnest 1992, Kruhmholz 1995
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Outcomes: Mortality
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Vary highly based on the underlying etiology of the
condition
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Brain tumors (30-40%)
Acute stroke (35%)
Epilepsy (3%)
Duration of seizures
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43 ICU pts in NCSE on VEEG
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<10h = death in 10%
>20h = death in 85%
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Age > 60y
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Rarely fatal in isolation
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Young 1996, Meierkord 2007, Towne 1994
Outcomes: Morbidity
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CPSE
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No difference between continuous and intermittent
electrographic sz activity
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Return to baseline cognitive status (n=20)
Cognitive decline, memory issues (n=10)
ESE
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Determined by primary etiology
Tend to have poorer prognosis
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Drislane 1999, Cockerell 1994, Krumholz 1995
Outcomes: MICU vs NICU
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168 visits over 3 yrs
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27% NICU
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More pts w/ stroke
More CPSE
Avg age: 59
Alert/somnolent pts
Fewer pts intubated,
more tracheostomized
Varelas 2013
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73% MICU
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More toxic/metabolic enceph
More GCSE
Avg age: 51
Obtunded/comatose pts
Higher APACHE 2 scores
MICU vs NICU
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No difference in outcomes
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Length of ICU/hospital stay
Functional status at discharge (mRS)
Limitations:
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Smaller NICU population
Neuro illness with longer recovery period?
KU Data
KU Cohort
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Objective:
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Review and describe non-convulsive status
epilepticus (NCSE) cases
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Etiology
Co-morbidities
Medical treatment
Clinical outcomes
KU Cohort
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Methods:
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Medical records reviewed from Jan 2009-2013
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ICD9 for status epilepticus, at discharge
CPT code for video-EEG monitoring
ICU room charge during hospital stay
Patients selected based on the following inclusion criteria:
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Age: 10- 110 years of age
Diagnosis made utilizing routine or continuous video
electroencephalogram
Patients with hypoxic-ischemic brain injury were excluded
Data
Demographics
 56 charts reviewed
 23 cases identified
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M: 9
F: 14
Average age: 54
Presentation
 30% (7):
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48% (11):
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GTC, tonic seizure(s)
confusion, lethargy, somnolent
22% (5):
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obtunded, stuporus, comatose
Data
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35% (8): Automatism, subtle motor mvts
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Head turning
Subtle limb, facial, tongue movements
Eyelid flutter
22% (5): eye deviation
Data
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CPSE (74%)
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ESE (13%)
LOS: 19.2 d
ICU:
11.1 d
VEEG: 6.1 d
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# AEDs:
2.6
Anesthesia: 4.6 d
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LOS: 45.7 d
ICU: 20.7 d
VEEG:
8d
# AEDs:
3
Anesthesia: 7.5 d
Data- CPSE (17)
Data- ESE (3)
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Etiology
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Severe sepsis
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OLT, ESRD on HD
(2) CJD
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+14-3-3
Characteristic MRI (2)
Data
CPSE
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AEDs:
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ESE
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1st: PHT (73%)
Increase dose of AED
Sedation
VPA or Vimpat
AEDs:
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1st: PHT (3)
2nd: Keppra (3)
Vimpat, PHB, topiramate (1)
Anesthesia:
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Propofol (9/13)
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2pt + Versed
 Ketamine, pentobarb
Versed (3/13)*
Pentobarb (1/13)*
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Anesthesia:
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1st: Propofol (2)
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Transition to Pentobarb =
Versed
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1pt: no tx
EEG diagnosis not reported/unclear (3)
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Pt#1: OLT on prograf
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Pt#2: Brain tumor
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L facial movements
3 GTC szs prolonged
postictal
Pt#3: Hx of epilepsy, liver
failure
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Poor responsiveness,
eye flutter
Age
56
LOS
23.7 d
ICU
10 d
VEEG
6.5 d
AEDs
2
Sedation
4.5 d
Data
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CSF:
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46% abnormal (6/13)
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5/13: ≤ 15 WBCs (lymph)
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Meningoencephalitis (3)
Inflamm WMD
CJD
+14-3-3 (1)
Imaging
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22/23*
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5 CT
17 MRI
Data
CPSE
ESE
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Time to resolution:
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Refractory (2)
Transition to PLEDs (1)*
Data
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CPSE
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Outcome:
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Death - 41%
LTACH/SNF - 18%
Home – 29%
Rehab – 12%
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One death within 30d
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ESE
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Outcome:
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Death or hospice – 100%
CPSE Outcomes
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Home (29%): 51.2 y
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Epilepsy (2)
Remote stroke (1)
Autoimmune enceph/SDH (1)
Tumor (1)
Rehab (12%): 57.5 y
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Post-stroke epilepsy
Autoimmune enceph
LTACH/SNF (18%): 44 y
 Epilepsy + illness or NC (3)
Death (41%): 55.6 y
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Peritumoral stroke
Remote stroke + sepsis
Inflam WM lesions*
CJD*
MS + sepsis
Meningoencephalitis (2)*
CPSE
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5/17 (29%): Sepsis
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Death or hospice- 4pts
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CJD
MS
Peritumoral stroke
Inflammatory WM lesions
LTACH- 1pt
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Hx of epilepsy
Clinical outcome- CPSE
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Follow-up in 5/10
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2 pt: no new cognitive deficits
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Epilepsy + NC
<8 hr, <24h
3 pt: memory impairment, assistance w/ ADLs,
cognitive decline
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Tumor, AIE, menignoencephalitis
<96h, unknown (2)
Limitations
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Limited number of patients
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Majority from 2012, only 3 from 2009, 1 from 2010
Inclusion of patients with CJD
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100% mortality
Encephalopathy with epileptic features
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Documentation, access to archived studies
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Lack of clinical follow-up information
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No cases of NCSE in acute stroke
Conclusions
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Outcomes worse is ESE
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Worse if underlying dx is CJD
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Underlying epilepsy portends better outcome
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Longer duration of uncontrolled NCSE adverse
cognitive impact
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Pt’s treated with Versed as initial agent, worse
outcomes (2/3) death
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Outcomes worse when pt diagnosed with sepsis
Thanks
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Nancy Hammond, MD
Utku Uysal, MD
Ivan Osorio, MD
William Nowack, MD
Rhonda Reliford
References
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Tomson T, Svanbog, E, Wedlund J.E. Nonconvulsive status epilepticus: high incidence of
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Drislane F. Presentation, Evaluation, and Treatment of Nonconvulsive Status Epilepticus.
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Towne AR. Prevalence of nonconvulsive status epilepticus in comatose patients.
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Kaplan PW. EEG criteria for nonconvulsive status epilepticus.
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Thank you
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