NCS

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

2. Overview
 Background
information:
 Epidemiology
 Clinical features
 Electrographic definition
 EDX pitfalls
 Treatment
 Pathology
 Outcomes
 KU Data
 2009-2013

3. 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

4. Definition
1. Diminished level of consciousness,
confusion
2. Epileptiform EEG (continuous or discrete)
3. Response to treatment??

5. 1. Change in mental status- Semiology
 Ambulatory confused patients, mildly
confused hospitalized patients
 Lethargic and comatose patients in intensive
care units

6. Diminished Level of
Consciousness, Confusion

8. Clinical presentations

10. 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

11. 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

12. Other sxs/signs
 Agitation
 Lethargy
 Mutism
 Disruptive behavior
 Staring
 Laughter
 Crying
 Rigidity
 Perseveration
 Subtle motor
movements
 Hallucinations

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

14. 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

15. Epileptiform EEG

16. 2. Epileptiform EEG
 Frequency
 Morphology
 Evolution
 Rhythmicity

17. 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)

18. 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***

19. 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.

20. EEG Diagnosis
 Inevitably subjective

21. Which tracing shows NCSE?

22. PLEDS

23. Triphasic waves

24. GPEDS

25. L Temp/parietal CPSE

26. Diagnostic pitfalls
 PLEDs, BiPLEDs, GPEDs, SIRPIDs
 Encephalopathy
 Status myoclonus
 CJD

27. 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

28. 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

29. 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

30. PLEDs

31. PLEDs regression- 1 week later

32. 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

34. 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

36. CJD – EEG progression

37. 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

38. Risk factors
 Mental status changes
 ICH
 SAH
 Large vessel CVA
 Meningoencephalitis
 CHI/TBI
 Tumor
 Post-surgical
Drislane 2000

39. 3. Treatment Response
 Treatment response less often considered
diagnostic
 Clinical response may be delayed hours to days
 Shneker 2003

40. 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

41. 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

42. Anesthesia
 No consensus on NCSE
 More harm than good?
 Hypotension
 Sepsis/line infection
 DVT
 Ultimate effect on brain?
 Outcomes…

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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?

49. KU Data

50. KU Cohort
 Objective:
 Review and describe non-convulsive status
epilepticus (NCSE) cases
 Etiology
 Co-morbidities
 Medical treatment
 Clinical outcomes

51. 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

52. 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

53. Data
 35% (8): Automatism, subtle motor mvts
 Head turning
 Subtle limb, facial, tongue movements
 Eyelid flutter
 22% (5): eye deviation

54. 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

55. Data- CPSE (17)

56. Data- ESE (3)
 Etiology
 Severe sepsis
 OLT, ESRD on HD
 (2) CJD
 +14-3-3
 Characteristic MRI (2)

57. Data
CPSE
 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

58. 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

59. 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

60. Data
CPSE ESE
 Time to resolution:
 Refractory (2)
 Transition to PLEDs (1)*

61. Data
 CPSE
 Outcome:
 Death - 41%
 LTACH/SNF - 18%
 Home – 29%
 Rehab – 12%
 One death within 30d
 ESE
 Outcome:
 Death or hospice – 100%

62. 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)*

63. CPSE
 5/17 (29%): Sepsis
 Death or hospice- 4pts
 CJD
 MS
 Peritumoral stroke
 Inflammatory WM lesions
 LTACH- 1pt
 Hx of epilepsy

64. 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)

65. 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

66. 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

67. Thanks
 Nancy Hammond, MD
 Utku Uysal, MD
 Ivan Osorio, MD
 William Nowack, MD
 Rhonda Reliford

68. References
 Celesia CG. Modern concepts of status epilepticus. JAMA 1976: 235:1771-4.
 Tomson T, Svanbog, E, Wedlund J.E. Nonconvulsive status epilepticus: high incidence of
complex partial status. Epilepsia. 1986;27:276-85.
 Drislane F. Presentation, Evaluation, and Treatment of Nonconvulsive Status Epilepticus.
Epilepsy and Behavior. 2000;1:301-314.
 Towne AR. Prevalence of nonconvulsive status epilepticus in comatose patients.
Neurology. 2000;54(2):340-4.
 Krumholz A. Epidemiology and evidence for morbidity of nonconvulsive status epilepticus.
J Clin Neurophysiology. 1999;16(4):314-22.
 Meierkord H. The risk of epilepsy after status epilepticus in children and adults. Epilepsia.
2007; 48 suppl 8:94-5.
 Husain AM, Horn GJ, Jacobson MP. Non-convulsive status epilepticus: Usefulness of
clinical features in selecting patients for urgent EEG. J. Neurol Neurosurg Psychiatry.
2003 Feb;74(2):189-91.
 Young GB, Jordan KG, Doig GS. An assessment of nonconvulsive seizures in the intensive
care unit using continuous EEG monitoring: An investigation of variables associated with
mortality. Neurology. 1996 Jul;47(1):83-9.
 Treiman DM, Walton NY, Kendrick C. A progressive sequence of electrographic changes
during generalized convulsive status epilepticus. Epilepsy Res. 1990;5:49-60.
 Walker M. Nonconvulsive status epilepticus: Epilepsy research foundation workshop
reports. Epileptic Disord. 2005 Sep;7(3):253-96.
 Walsh JM, Brenner RP. Periodic lateralized epileptiform discharges: long-term outcome in
adults. Epilepsia 1987;28:533– 6.

69. References
 Snodgrass SM, Tsuburaya K, Ajmone-Marsan C. Clinical significance of periodic
lateralized epileptiform discharges: Relationship with status epilepticus. J Clin
Neurophysiol. 1989 Apr;6(2):159-72.
 Kaplan PW. EEG criteria for nonconvulsive status epilepticus.
Epilepsia. 2007;48 Suppl 8:39-41.
 Chong DJ, Hirsch LJ. Which EEG patterns warrant treatment in the critically ill?
Reviewing the evidence for treatment of periodic epileptiform discharges and
related patterns. J Clin Neurophysiol. 2005 Apr;22(2):79-91.
 Kaplan PW. EEG monitoring in the intensive care unit. Am J
Electroneurodiagnostic Technol. 2006 Jun;46(2):81-97.
 DeLorenzo RJ, et al. Persistent nonconvulsive status epilepticus after the
control of convulsive status epilepticus. Epilepsia. 1998 Aug;39(8):833-40.
 Shneker BF, Fountain NB. Assessment of acute morbidity and mortality in
nonconvulsive status epilepticus. Neurology. 2003 Oct 28;61(8):1066-73.
 Granner MA, Lee SI. Nonconvulsive status epilepticus: EEG analysis in a large
series. Epilepsia.1994 Jan-Feb;35(1):42-7.
 Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status
epilepticus with pentobarbital, propofol, or midazolam: a systematic review.
Epilepsia. 2002 Feb;43(2):146-53.
 Lothman EW, et al. Recurrent spontaneous hippocampal seizures in the rat as a
chronic sequela to limbic status epilepticus. Epilepsy Res. 1990 Jul;6(2):110-8.

70. References
 Earnest MP, Thomas GE, Eden RA, Hossack KF. The sudden unexplained death
syndrome in epilepsy: demographic, clinical, and postmortem features.
Epilepsia. 1992 Mar-Apr;33(2):310-6.
 Krumholz A. Complex partial status epilepticus accompanied by serious morbidity and
mortality. Neurology. 1995 Aug;45(8):1499-504.
 Drislane FW. Evidence against permanent neurologic damage from nonconvulsive status
epilepticus. J Clin Neurophysiol. 1999 Jul;16(4):323-31
 Cockerell OC, Walker MC, Sander JW, Shorvon SD. Complex partial status epilepticus: a
recurrent problem. J Neurol Neurosurg Psychiatry.1994 Jul;57(7):835-7.
 Varelas PN, et al. Emergent EEG: indications and diagnostic yield. Neurology. 2003 Sep
9;61(5):702-4.

71. Thank you
Questions?
Comments?