Non-Convulsive Status Epilepticus (NCSE): Our Experience at a Tertiary Care Center Brennen Bittel, DO Clinical Neurophysiology Fellow.

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

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