Clinical trial NCT03138876
Conditions: Nonconvulsive Status Epilepticus Subclinical Seizure Altered Mental Status Nonepileptic Seizures Encephalopathy
Sponsor: Mayo Clinic
Start date: 2017-05-30; Completion date: 2018-08-16
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Altered mental status (AMS) is one of the most common reasons for inpatient neurology consultation. Non-convulsive status epilepticus (NCSE) is frequently on the differential diagnosis of the patient with AMS. NCSE becomes more refractory to treatment after one hour of seizure activity, making rapid identification and treatment of NCSE of great clinical importance. Currently, an electroencephalogram (EEG) technologist must be called in from home during non-workday hours in order to obtain a stat EEG. The investigators propose the time required for diagnosis of NCSE at Mayo Clinic can be significantly decreased with rapid placement of an EEG cap by the onsite neurology residents.

Detailed description:
At the completion of neurology evaluation, if NCSE is in the differential diagnosis according to institution best practice, then consented participants will undergo placement of a large size, 20-channel EEG cap from Electro-Cap International with a Natus E-2-2520-26 electrode board adapter with initiation of recording. The placement of the EEG cap will be restricted to residents formally trained in its placement by an EEG tech. This study will only be performed during times when EEG techs are not available onsite for rapid placement of standard 21-channel EEG electrodes, such as during night-call shifts.

Prior to placement of EEG cap, evaluating staff member will request immediate standard-electrode EEG. The investigators will record time from neurology consultation request to placement of EEG cap as well as time from consultation request to obtaining a standard EEG. The investigators will also record time to confirmation or exclusion of NCSE. Initial diagnosis or exclusion of NCSE will be performed by on call resident, if the resident received prior training regarding EEG cap placement, and attending. Secondary quality assessment will be performed by two independent EEG interpreters blinded to clinical history. Secondary assessment will be qualified as acceptable or inacceptable interpretation based on whether greater or less than 50% of the recording is judged interpretable. Secondary assessment will also include interpretation of NCSE by a third independent reader if there is disagreement between first two. The number of patients excluded from the study will also be recorded, including the reason for exclusion.

Arms: arm 1: Single arm study, where every participant gets assessed by EEG cap and then standard EEG. Some subjects may be treated with anti-seizure medications before standard EEG, due to ethical responsibility, if clear NCSE is identified on cap EEG. If the subject is treated with anti-seizure medication, the primary care provider will choose which medication will be given.
Interventions: intervention 1: EEG Cap intervention 2: Anti-seizure medication intervention 3: Standard EEG
Intervention descriptions: intervention 1: Patient will be fitted with an EEG cap by the on-call neurology resident to assess for NCSE. intervention 2: Patients may be treated for NCSE or seizures based on EEG cap findings, if the findings are clear to an attending EEG reviewer. If the subject is treated with anti-seizure medication, the primary care provider will choose which medication will be given. intervention 3: An electroencephalogram (EEG) is a test used to find problems related to electrical activity of the brain. An EEG tracks and records brain wave patterns. Small metal discs with thin wires (electrodes) are placed on the scalp, and then send signals to a computer to record the results.

Protocol documents:
Prot_SAP_000.pdf: 
EEG Cap for Identification of 
Non-Convulsive Status 
Epilepticus 
NCT# 03138876 
February 22, 2017 


RESEARCH PROTOCOL OUTLINE 
 
Title: EEG Cap Placement for Expedited Identification of Non-Convulsive Status 
Epilepticus 
Principal Investigator: William Tatum D.O. 
Co-Investigators: Jake McKay M.D., Ugur Sener M.D., Caitlin D’Souza D.O., Donnie K. 
Starnes M.D., Chris Smelick M.D., Michael A. Pizzi D.O., Kirsten H. Yelvington 
 
Abstract 
Altered mental status (AMS) is one of the most common reasons for inpatient neurology 
consultation. Non-convulsive status epilepticus (NCSE) is frequently a differential 
diagnosis of the patient with AMS. NCSE becomes more refractory to treatment after 
one hour of seizure activity, making rapid identification and treatment of NCSE of great 
clinical importance. Currently, an EEG technician must be called in from home during 
non-workday hours in order to obtain a stat EEG. We propose the time required for 
diagnosis of NCSE in our institution can be significantly decreased with rapid placement 
of an EEG cap by the onsite neurology residents.  
 
A. Specific Aims 
1. Utilize EEG cap for rapid assessment of seizure activity in 20 patients with suspected 
NCSE 
2. Rapid EEG review by on-call resident & attending physicians 
3. Employ existing standard of care for NCSE evaluation with standard electrodes as soon 
as technician can apply them (cap to not delay standard of care) 
4. Evaluate endpoints for cap vs. standard electrodes of time from consultation to: 
a. completed EEG 
b. Diagnosis or exclusion of NCSE 
 
B. Background and Significance 
Status epilepticus is operationally defined as a seizure greater than five minutes in duration or 
more than one seizure within a five minute period without return to normal baseline mental 
status. Convulsive status epilepticus is a medical emergency.  Status epilepticus is more likely 
to become refractory to medical therapy when treatment is delayed for over 1 hour (DeLorenzo 
et al).  NCSE is a persistent change in behavior and processes from baseline associated with 
continuous epileptiform EEG changes, but without major motor signs. Nonconvulsive status 
epilepticus (NCSE) in a comatose patient cannot be diagnosed without electroencephalography 
(EEG). A previous study has demonstrated the urgency of rapid identification and treatment of 
NCSE (Meierkord et al). Hospital neurology programs frequently rely on EEG technologists who 
are on-call but not onsite to place EEG electrodes that are used for assessment of NCSE. EEG 
caps allow for more rapid electrode placement and EEG analysis, but there exists ambiguity 
whether rapidly placed caps are sufficiently accurate to reliably identify NCSE for clinical 
decision-making. Use of EEG cap (also referred to as EEG headsets) in the inpatient setting by 
onsite neurology providers, if sufficiently reliable versus standard of care electrode-placement, 
may allow for more rapid identification of NCSE and associated expedited pharmacological 
treatment. 
 
C.  Study Design, Methods, & Statistics 
Study will be of prospective design involving 20 patients evaluated at the Mayo Clinic 
emergency department or hospital that are referred to neurology for evaluation of mental status 
changes or suspected seizures. 


 
---- 
Review type: minimal risk 
Is this an interventional study? Yes  No    
 
--- 
 
At the completion of neurology evaluation, if NCSE is in the differential diagnosis according to 
institution best practice, then consented participants will undergo placement of a large size, 20-
channel EEG cap from Eectro-Cap International with a Natus E-2-2520-26 electrode board 
adapter with initiation of recording. The placement of the EEG cap will be restricted to residents 
formally trained in its placement by an EEG tech. The EEG-cap is already owned by the Mayo 
Clinic Neurology department, and therefore we will not require further funds to obtain equipment 
for this study. This study will only be performed during times when EEG techs are not available 
onsite for rapid placement of standard 21-channel EEG electrodes, such as during night-call 
shifts. We will not bill for the EEG cap placement, only the subsequent standard EEG protocol 
which will be followed after the EEG-cap placement.  
 
Prior to placement of EEG cap, evaluating staff member will request stat standard-electrode 
EEG. We will record time from neurology consultation request to placement of EEG cap as well 
as time from consultation request to obtaining a standard EEG. We will also record time to 
confirmation or exclusion of NCSE. Initial diagnosis or exclusion of NCSE will be performed by 
on call resident, if they received prior training regarding EEG cap placement, and attending. 
Secondary quality assessment will be performed by two independent EEG interpreters blinded 
to clinical history. Secondary assessment will be qualified as acceptable or inacceptable 
interpretation based on whether greater or less than 50% of the recording is judged 
interpretable. Secondary assessment will also include interpretation of NCSE by a third 
independent reader if there is disagreement between first two. The number of patients excluded 
from the study will also be recorded, including the reason for exclusion. 
 
Specific data points for statistical analysis include: 
• 
Time of consultation 
• 
Time of standard-electrode EEG order 
• 
Time that 10 minutes of EEG have been completed (for both cap & standard-electrodes) 
• 
Time that 20 minutes of EEG have been completed (for both cap & standard-electrodes) 
• 
Time of diagnosis or exclusion of NCSE 
 
Primary outcome measure: time from stat EEG order to diagnosis or exclusion of NCSE 
 
Secondary outcome measures include: 
• 
Overall quality of cap recordings as operationalized by: 
o 
Aforementioned >50% interpretability 
o 
Concordance between cap & standard-electrode diagnostic assessments 
• 
comparison of diagnostic assessments/concordance between 10 and 20 minute 
captures  
 
Statistical methodology: chi-square and Student T-test will be employed to compare 
categorical variables. 
 


Data storage and PHI: Initial data collection will be to a password-protected Excel spreadsheet 
that is only accessible by the study authors. No PHI will be collected, but a unique identifying 
number will be used to initially distinguish between patients. Data will then be aggregated for 
statistical analysis. The final paper will only include patient data in aggregate form. 
 
D. Preliminary Studies/Progress Report 
EEG is the only definitive way to diagnose NCSE. Although useful, standard surface EEG can 
be a cumbersome, complex and time-consuming process, all of which can limit its applicability 
in emergent time-sensitive clinical situations and rural areas without available technology, 
financial resources or neurophysiologic expertise. EEG headsets, caps or “dry EEG” have been 
developed and have become commercially available over the past few decades and have been 
used in multiple brain computer interface (BCI) studies, evoked potentials and biofeedback 
(Halford, et al, Slater et al). This novel technology does not require measurement of relative 
electrode differences by EEG technologists or pose increased risk for skin abrasions. 
Disadvantages EEG caps do exist which may affect its clinical suitability, including movement 
artifact, sweat artifact and increased weight of the system (Halford, et al). 
 
Some studies have investigated the time differences and validity of EEG headsets versus 
standard EEG recordings in various clinical scenarios. For instance, a study demonstrated that 
application of an EEG caps in comparison to a standard EEG was performed over 15 minutes 
faster, with 87% of the EEG being interpreted as technically adequate. In addition, patients 
preferred the EEG caps over the standard EEG (Halford, et al). The EEG headset recordings 
were also felt to be adequate in identifying status epilepticus and were significantly faster to set 
up (Slater et al). “Light” EEG has also been shown to be comparable to standard EEG in 
detecting findings suggestive of hepatic encephalopathy, but with higher proportion of light EEG 
samples being discarded due to artifact (Schiff et al). 
 
Data in identifying epileptiform activity or NCSE utilizing EEG caps is lacking.  Disposable 
forehead electrodes have also been shown to identified status epilepticus, although studies 
have included a limited number of patients with NCSE and the results have been variable 
(Myllymaa et al) (Muraja-Murro, et al). In one study, only two out of four patients with status 
epilepticus were identified with forehead electrodes due to EEG abnormalities being restricted to 
the posterior regions of the brain (Muraja-Murro, et al). 
 
Due to the small sample sizes, limited number of patients with NCSE and variable electrode 
placements in prior studies, it remains unclear the applicability of EEG caps in the identification 
of NCSE, which our study seeks to investigate further. In addition, we plan to readdress the 
quality and interpretability, as well as the time taken from ordering to interpretation of the EEG 
cap compared to standard EEG. 
  
 
 
 
 
E. Gender/Minority/Pediatric Inclusion for Research 
Gender and ethnicity will not be used as exclusion criteria when selecting patients. The study 
will include both men and women. Pediatric patients under the age of 18 will be excluded from 
our study to permit use of adult size EEG cap for all participants. 
 
 
 
 
 
 
 
 
 
 
F. Human Participants 
Inclusion: 
1. Patients with suspected NCSE in the Mayo Clinic Florida hospital, emergency room or 
intensive care unit.  
2. Age: Patients  of 18 years or older will be included in this study 
 


3. Education: All education levels will be included 
 
Exclusion: 
1. Patients younger than 18 years of age. 
 
2. Patients with open head trauma. 
3. Patients with anatomy that would preclude EEG cap placement. 
4. Patients excluded for anatomical or age-related reasons will be tracked to determine 
applicability of the EEG cap to the patient population at Mayo Clinic. 
 
5. Pregnant females 
 
6. Large head size not amenable to cap placement 
7. Scalp infection 
8. Inability to obtain informed consent 
 
Informed Consent: 
Patients will lack the capacity to consent, as by definition patients in NCSE have very impaired 
mental status. NCSE is an emergency, and our protocol is an emergency evaluation. The 
procedure we are following is minimal risk, and we will still provide the typical standard of care 
for patients with suspected NCSE. Therefore we will obtain prior verbal consent from a 
healthcare proxy. If patients regain ability to interact and accurately answer questions while the 
study is being performed, the study will be stopped, as they would be unlikely to be in NCSE.  
 
Standard of care will be followed in context of emergent intervention. Consent from HCPOA or 
next of kin or will be obtained, per Florida hierarchy. If the legally authorized representative 
(LAR) is not available at bedside, an attempt will be made to contact them by way of phone. 
Given the treatment of NCSE is an emergency, if the first LAR is not available, the Florida 
hierarchy of consent will be followed with regard to an alternate source of consent. 
 
The use of EEG caps is acceptable for assessment of epilepsy, and, additionally, we will still 
provide our typical standard of care. The research presents no more than minimal risk of harm 
to subjects and involves no procedures for which written consent is normally required outside of 
the research context. Therefore, verbal consent following the Florida Hierarchy of Consent with 
documentation of the individual consenting in the chart is appropriate.  
 
The consent will be obtained through a discussion with the patient's healthcare proxy at bedside 
if possible. If no healthcare proxy is available at bedside, a call will be placed to the appropriate 
healthcare proxy. As the placement of the EEG cap for detection of NCSE if an emergency, the 
time dedicated to discussion is anticipated to be 2-3 minutes in order to present the risks and 
benefits of the procedure. The healthcare proxy will be clearly described the risks and benefits 
of the procedure. They will be offered a waiting period between discussion and decision, and 
they will be explicitly told that the patient's overall care, outside of the context of the study, will 
not change based on their decision. Residents responsible for consenting patients in the study 
will formally complete the consent training in the Mayo Clinic Simulation Center regarding 
proper technique. Informed verbal consent will be documented on the neurology consult note.  
 
Given the nature of the project aimed at expeditiously identifying NCSE the following details will 
be verbally provided to health care proxies prior to placement of the EEG cap: 
• 
The study involves assessing patient brain waves with an experimental EEG cap to 
attempt to diagnose and treat seizures that do not produce convulsive movements, but 
can alter mental status.  


• 
The cap could identify seizures before the normal method of analyzing brain waves will 
be performed, which could potentially allow for earlier treatment. 
• 
There is minimal risk, with main risk being that cap may be inaccurate and might be 
misinterpreted. The risk of misdiagnoses, leading to inappropriate diagnosis and 
treatment is likely small, but exact data is not available.  
• 
The normal method of analyzing brain waves will be used either way as fast as possible 
• 
Do not feel obligated to consent if you prefer for our typical protocol to be followed. The 
patient’s overall care, outside of the context of this study, will not change based on your 
decision. 
• 
If you would like some time to think about this decision, I will attempt to return at a time 
of your choosing.  
 
 
 
G. Risks and benefits: 
This study is considered minimal risk given the only deviation from standard of care involves 
application of EEG cap prior to standard of electrodes. To the extent that cap electrodes might 
be misinterpreted due to theoretically poorer quality risks include: 
• 
Misinterpretation of EEG so as to miss seizure activity, which would not affect time to 
treatment, given we will still be following and giving priority to our standard protocol. 
• 
Misinterpretation of EEG so as to diagnose non-seizure activity as epileptiform, which 
his unlikely as attendings will avoid diagnosing NCSE if there is any uncertainty in the 
EEG. 
 
1. Procedures protecting against or minimizing potential risks: 
a. Patients will be evaluated by neurology residents or faculty members 
 
b. EEG cap will be applied by neurology staff and cleaned between each use 
c. Electronic data will be stored in a password-protected Excel spreadsheet that 
 
contains no PHI 
d. Regular EEG  protocol will be followed in addition to EEG cap placement. 
Standard electrode placement will be given priority in the event EEG 
 
technician is available before EEG cap is placed. There will be no 
 
deviation from the current standard of care.   
2. Future  benefits and importance to the participants and others: 
a. Use of EEG cap technology can expedite diagnosis of or exclusion of NCSE. 
b. Rapid  identification of NCSE can reduce time to treatment, which may 
 
improve patient outcomes 
5. Justification of risks in relation to benefits: Since this study adds use of an EEG cap to 
existing NCSE protocol without modification of existing method of diagnosis and 
treatment, risk to patients is minimal and consists of incorrect diagnosis of NCSE and 
administration of medications that would not otherwise be indicated. However, we 
believe that verification of EEG findings by a faculty member experienced in EEG 
interpretation will minimize this risk.  Further, misdiagnosis is an existing risk under the 
current NCSE protocol. If seizure activity is missed on cap electrodes, this would have 
been missed anyways prior to standard electrode application 
 
H. Data and Safety Monitoring 
1. Data and Safety Monitoring Board 
 


a. 
Patient charts will only be accessed at the Mayo Clinic by neurology residents and 
faculty members. This study will involve review of the medical chart only as in required for 
treatment of the patient in the hospital setting. 
b. 
All study data will be electronically stored in a password-protected Excel spreadsheet. 
No PHI will be recorded. Study results will be presented in aggregate form only.  
c. 
Adverse events will be limited to misdiagnosis of NCSE and administration of anti-
seizure medication to a patient with an alternate diagnosis. However, this is an existing risk with 
current NCSE protocol. 
d. 
In the event of an unexpected disclosure, the IRB will be notified. The affected 
 
patients and their care providers will be informed about the disclosure. 
2. Data and Safety Monitoring Plan: Dr. Tatum will supervise the research and data collection 
process. All procedures will be recorded as a part of video EEG monitoring. In the unlikely event 
that unforeseen safety concerns arise, the study will be brought back to the IRB for further 
review or terminated. 
I. Literature Cited 
1. DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospective, population-based epidemiologic 
study of status epilepticus in Richmond, Virginia. Neurology 1996; 46:1029. 
2. Meierkord H, Holtkamp M. Non-convulsive status epilepticus in adults: clinical forms and 
treatment. Lancet Neurol. 2007 Apr;6(4):329-39. Review. 
3. Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and 
Prognosis, International League Against Epilepsy. Epilepsia 1993; 34:592. 
4. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of 
status epilepticus. Neurocrit Care 2012; 17:3. 
5. Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus--
Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015; 56:1515. 
6. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. 
Epilepsia 1999; 40:120. 
7. Beniczky S, Hirsch LJ, Kaplan PW, Pressler R, Bauer G, Aurlien H, Brøgger JC, Trinka 
E.  Unified EEG terminology and criteria for nonconvulsive status epilepticus. 
8. Epilepsia. 2013 Sep;54 Suppl 6:28-9. 
9. Bauer G, Trinka E. Nonconvulsive status epilepticus and coma. Epilepsia. 2010 
Feb;51(2):177-90. Epub 2009 Sep 10. 
10. Sutter R, Kaplan PW. Electroencephalographic criteria for nonconvulsive status epilepticus: 
synopsis and comprehensive survey. Epilepsia. 2012 Aug;53 Suppl 3:1-51. 
11. Halford, J. J., et al. "Comparison of a Novel Dry Electrode Headset to Standard Routine 
EEG in Veterans." Journal of Clinical Neurophysiology (2016). 
12. Sami, Schiff, et al. "A low‐cost, user‐friendly EEG recording system for the assessment of 
hepatic encephalopathy." Hepatology (2016). 
13. Slater, Jeremy D., Giridhar P. Kalamangalam, and Omotola Hope. "Quality assessment of 
electroencephalography obtained from a “dry electrode” system." Journal of neuroscience 
methods 208.2 (2012): 134-137. 
14. Myllymaa, Sami, et al. "New disposable forehead electrode set with excellent signal quality 
and imaging compatibility." Journal of neuroscience methods 215.1 (2013): 103-109. 
15. Muraja-Murro, Anu, et al. "Forehead EEG electrode set versus full-head scalp EEG in 100 
patients with altered mental state." Epilepsy & Behavior49 (2015): 245-249.