Non-Convulsive Status Epilepticus (NCSE):Our Experience at a Tertiary Care Center
Brennen Bittel, DOClinical 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 comaCelesia 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 seizures2. Merging seizures3. Continuous seizures4. 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 Criteria1. 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 Criteria1. 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 20051. 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 high—up 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• Creutzfeld–Jakob 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)
DataCPSE
AEDs: 1st: 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:
1st: PHT (3) 2nd: Keppra (3) Vimpat, PHB, topiramate (1)
Anesthesia: 1st: 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
Pt’s 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
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Thank you
Questions?Comments?