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Non-Convulsive Status

Epilepticus (NCSE):
Our Experience at a Tertiary Care Center


Brennen Bittel, DO
Clinical Neurophysiology Fellow
Overview
Background
information:
Epidemiology
Clinical features
Electrographic definition
EDX pitfalls
Treatment
Pathology
Outcomes




KU Data
2009-2013
Incidence/prevalence
SE* in emergency room or intensive care
units ~ 150,000/yr
NCSE:
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
Ambulatory confused patients, mildly
confused hospitalized patients




Lethargic and comatose patients in intensive
care units
Diminished Level of
Consciousness, Confusion
Clinical presentations


NCSE
CPSE
(complex partial SE)
ESE
(electrographic SE)
SPSE
(Simple partial SE)
ASE
(absence SE)
Intermittent Continuous
20-40%
35-40%
Krumholz 1999, Meierkord 2007








NCSE
ASE
(absence SE)
CPSE
(complex partial SE)
ESE
(electrographic SE)

SPSE
(Simple partial SE)
Continuous Intermittent
Confused
Bizarre behavior
Fluctuations
+/- automatisms
Aphasia

Stuporous
Comatose
GTC at onset
Medical illness
Other sxs/signs
Agitation
Lethargy
Mutism
Disruptive behavior
Staring
Laughter
Crying
Rigidity
Perseveration

Subtle motor
movements
Hallucinations

DDx
Metabolic/toxic encephalopathy
Complicated migraine/aura
Prolonged post-ictal state
Psychiatric disorders
Substance abuse/withdrawal/intoxication
DTs
TIA
Transient global amnesia


Husain 2003
12 in the NCSE group and 36 in the non-
NCSE group
100% sensitivity
Ocular movements
Rhythmic blinking, deviation, nystagmus, rhythmic hippus
Recent or remote risk factor for seizure
Previous stroke, tumor, previous neurosurgery, dementia,
epilepsy, and meningitis

Epileptiform EEG
2. Epileptiform EEG
Frequency
Morphology
Evolution
Rhythmicity

Treiman criteria- GCSE
Five characteristic stages:
1. Discrete seizures
2. Merging seizures
3. Continuous seizures
4. 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
Primary Criteria
1. Repetitive generalized or
focal spikes, sharp waves,
spike-wave or sharp-slow
wave complexes at >3/sec
2. Repetitive generalized or
focal spikes, sharp waves,
spike-wave or sharp-slow
wave complexes at >3/sec
AND #4
3. Sequential rhythmic waves
and 1-3, +/- 4

Secondary Criteria
1. Incrementing onset: voltage
or slowing
2. Decrementing offset:
voltage or frequency
3. Post-discharge slowing or
voltage attenuation
4. 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
Inevitably subjective

Which tracing shows NCSE?
PLEDS
Triphasic waves
GPEDS
L Temp/parietal CPSE
Diagnostic pitfalls
PLEDs, BiPLEDs, GPEDs, SIRPIDs
Encephalopathy
Status myoclonus
CJD


PLEDs
No absolute frequency criterion can be used to
distinguish PLEDs from seizures
Frequency
1 - 4 seconds (short periodicity)
>4 seconds (long periodicity)

Acute, serious neurologic illness
Mortality is highup to 50% within 2 months

Walsh 1987
PLEDs
Associated with:
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
CreutzfeldJakob disease

PLEDs
80-90% of pts had recent clinical seizures
66% had some form of SE
Risk for more seizures
Half patients without prior epilepsy developed
subsequent epilepsy
Most PLEDs will resolve after days to weeks

Part of an ictal-interictal spectrum
Snodgrass 1989, Kaplan 2007, Chong 2005, Walsh 1987
PLEDs
PLEDs regression- 1 week later
Triphasic waves
Seen commonly in metabolic encephalopathies
Classically in renal or hepatic failure
Bursts
1-2Hz
Blunted, low-moderate amplitude
Dominant positive second phase, slow rise
Phase lag
not seen in NCSE
Increased with stimulation
not seen in NCSE
Sometimes suppressed with BZDs (40-60%)
Kaplan 2006
Encephalopathies w/Epileptic Features
Reversible
Usually no hx of epilepsy
Medication related
BZD withdrawal
Cephalosporin Abx
Ifosfamide
Baclofen
Psychotropics

Rhythmic, semirhythmic
delta
Drislane 2000
Irreversible
Post-anoxic
Creutzfeld-Jacob




Importance of c-VEEG
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. AMS with subtle motor signs
3. AMS in epileptic w/ acute medical illness
4. Post-stroke pt faring worse or recovery
halted
5. Elderly pt with AMS (post BZD withdrawal)
DeLorenzo 1998, Drislane 2000
Risk factors
Mental status changes
ICH
SAH
Large vessel CVA
Meningoencephalitis
CHI/TBI
Tumor
Post-surgical



Drislane 2000
3. Treatment Response
Treatment response less often considered
diagnostic
Clinical response may be delayed hours to days





Shneker 2003

Treatment
CPSE
BZDs
IV AEDs
Usually recurs
ESE
60% respond to initial BZD (clinical delay)
15% resistant to BZD
Require IV AEDs
+/- Anesthesia
Granner 1994, Shneker 2003





Anesthesia- Claassen 2002
193 pts w/ refractory SE
Tx with midazolam vs propofol vs pentobarbitol
Midazolam
Increased breakthrough seizures
Less hypotension
Pentobarbitol
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
No consensus on NCSE
More harm than good?
Hypotension
Sepsis/line infection
DVT
Ultimate effect on brain?
Outcomes



Pathologic changes
Animal models
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

Bertram 1990
Pathologic changes
Human autopsy studies
GCSE > epilepsy w/o SE > normal
Synergistic damage
Increase in excitatory neurotransmitters
Metabolic changes (lactate, pyruvate)



Earnest 1992, Kruhmholz 1995

Outcomes: Mortality
Vary highly based on the underlying etiology of the
condition
Brain tumors (30-40%)
Acute stroke (35%)
Epilepsy (3%)
Duration of seizures
43 ICU pts in NCSE on VEEG
<10h = death in 10%
>20h = death in 85%
Age > 60y
Rarely fatal in isolation

Young 1996, Meierkord 2007, Towne 1994


Outcomes: Morbidity
CPSE
No difference between continuous and intermittent
electrographic sz activity
Return to baseline cognitive status (n=20)
Cognitive decline, memory issues (n=10)
ESE
Determined by primary etiology
Tend to have poorer prognosis
Drislane 1999, Cockerell 1994, Krumholz 1995
Outcomes: MICU vs NICU
168 visits over 3 yrs
27% NICU
More pts w/ stroke
More CPSE
Avg age: 59
Alert/somnolent pts
Fewer pts intubated,
more tracheostomized



Varelas 2013


73% MICU
More toxic/metabolic enceph
More GCSE
Avg age: 51
Obtunded/comatose pts
Higher APACHE 2 scores

MICU vs NICU
No difference in outcomes
Length of ICU/hospital stay
Functional status at discharge (mRS)

Limitations:
Smaller NICU population
Neuro illness with longer recovery period?
KU Data
KU Cohort
Objective:
Review and describe non-convulsive status
epilepticus (NCSE) cases
Etiology
Co-morbidities
Medical treatment
Clinical outcomes
KU Cohort
Methods:
Medical records reviewed from Jan 2009-2013
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:
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
M: 9
F: 14
Average age: 54




Presentation
30% (7):
GTC, tonic seizure(s)
48% (11):
confusion, lethargy, somnolent
22% (5):
obtunded, stuporus, comatose
Data
35% (8): Automatism, subtle motor mvts
Head turning
Subtle limb, facial, tongue movements
Eyelid flutter

22% (5): eye deviation


Data
CPSE (74%)
LOS: 19.2 d
ICU: 11.1 d
VEEG: 6.1 d

# AEDs: 2.6
Anesthesia: 4.6 d
ESE (13%)
LOS: 45.7 d
ICU: 20.7 d
VEEG: 8 d

# AEDs: 3
Anesthesia: 7.5 d
Data- CPSE (17)
Data- ESE (3)

Etiology
Severe sepsis
OLT, ESRD on HD
(2) CJD
+14-3-3
Characteristic MRI (2)
Data
CPSE
AEDs:
1
st
: PHT (73%)
Increase dose of AED
Sedation
VPA or Vimpat
Anesthesia:
Propofol (9/13)
2pt + Versed
Ketamine, pentobarb
Versed (3/13)*
Pentobarb (1/13)*

ESE
AEDs:
1
st
: PHT (3)
2
nd
: Keppra (3)
Vimpat, PHB, topiramate (1)


Anesthesia:
1
st
: Propofol (2)
Transition to Pentobarb =
Versed
1pt: no tx


EEG diagnosis not reported/unclear (3)
Pt#1: OLT on prograf
L facial movements

Pt#2: Brain tumor
3 GTC szs prolonged
postictal

Pt#3: Hx of epilepsy, liver
failure
Poor responsiveness,
eye flutter



Age 56

LOS 23.7 d
ICU 10 d
VEEG 6.5 d
AEDs 2
Sedation 4.5 d
Data
CSF:
46% abnormal (6/13)
5/13: 15 WBCs (lymph)
Meningoencephalitis (3)
Inflamm WMD
CJD
+14-3-3 (1)
Imaging
22/23*
5 CT
17 MRI
Data
CPSE



ESE
Time to resolution:
Refractory (2)
Transition to PLEDs (1)*

Data
CPSE
Outcome:
Death - 41%
LTACH/SNF - 18%
Home 29%
Rehab 12%
One death within 30d





ESE
Outcome:
Death or hospice 100%


CPSE Outcomes
Home (29%): 51.2 y
Epilepsy (2)
Remote stroke (1)
Autoimmune enceph/SDH (1)
Tumor (1)
Rehab (12%): 57.5 y
Post-stroke epilepsy
Autoimmune enceph
LTACH/SNF (18%): 44 y
Epilepsy + illness or NC (3)

Death (41%): 55.6 y
Peritumoral stroke
Remote stroke + sepsis
Inflam WM lesions*
CJD*
MS + sepsis
Meningoencephalitis (2)*


CPSE
5/17 (29%): Sepsis
Death or hospice- 4pts
CJD
MS
Peritumoral stroke
Inflammatory WM lesions

LTACH- 1pt
Hx of epilepsy

Clinical outcome- CPSE
Follow-up in 5/10
2 pt: no new cognitive deficits
Epilepsy + NC
<8 hr, <24h

3 pt: memory impairment, assistance w/ ADLs,
cognitive decline
Tumor, AIE, menignoencephalitis
<96h, unknown (2)

Limitations
Limited number of patients
Majority from 2012, only 3 from 2009, 1 from 2010
Inclusion of patients with CJD
100% mortality
Encephalopathy with epileptic features
Documentation, access to archived studies
Lack of clinical follow-up information
No cases of NCSE in acute stroke

Conclusions
Outcomes worse is ESE
Worse if underlying dx is CJD
Underlying epilepsy portends better outcome
Longer duration of uncontrolled NCSE adverse
cognitive impact
Pts treated with Versed as initial agent, worse
outcomes (2/3) death
Outcomes worse when pt diagnosed with sepsis
Thanks
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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References
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References
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