RESEARCH ARTICLE

Seizure Detection in Continuous Inpatient EEG

A Comparison of Human vs Automated Review
Taneeta Mindy Ganguly, MD, Colin A. Ellis, MD, Danni Tu, MS, Russell T. Shinohara, PhD, Correspondence
Kathryn A. Davis, MD, MSCE, Brian Litt, MD, and Jay Pathmanathan, MD, PhD Dr. Pathmanathan
jay.pathmanathan@
®
Neurology 2022;98:e2224-e2232. doi:10.1212/WNL.0000000000200267 pennmedicine.upenn.edu

Abstract MORE ONLINE

Background and Objectives Class of Evidence

The aim of this work was to test the accuracy of Persyst commercially available automated Criteria for rating
seizure detection in critical care EEG by comparing automated seizure detections to human therapeutic and diagnostic
studies
review in a manually reviewed cohort and on a large scale.
NPub.org/coe
Methods
Automated seizure detections (Persyst versions 12 and 13) were compared to human review in
a pilot cohort of 229 seizures from 85 EEG records and then in an expanded cohort of 7,924
EEG records. Sensitivity, specificity, positive predictive value (PPV), and negative predictive
value (NPV) were calculated for individual seizures (pilot cohort) and for entire records (pilot
and expanded cohorts). We assessed EEG features associated with the accuracy of automated
seizure detections.

Results
In the pilot cohort, accuracy of automated detection for individual seizures was modest
(sensitivity 0.50, PPV 0.60). At the record level (did the recording contain seizures or not?),
sensitivity was higher (pilot cohort 0.78, expanded cohort 0.91), PPV was low (pilot cohort
0.40, expanded cohort 0.08), and NPV was high (pilot cohort 0.88, expanded cohort 0.97).
Different software versions (version 12 vs 13) performed similarly. Sensitivity was higher for
records containing focal-onset seizures compared to generalized-onset seizures (0.93 vs 0.85,
p = 0.012).

Discussion
In critical care continuous EEG recordings, automated detection of individual seizures had rates
of both false negatives and false positives that bring into question its utility as a seizure alarm in
clinical practice. At the level of entire EEG records, the absence of automated detections
accurately predicted EEG records without true seizures. The true value of Persyst automated
seizure detection appears to lie in triaging of low-risk EEGs.

Classification of Evidence
This study provides Class II evidence that an automated seizure detection program cannot
accurately identify EEG records that contain seizures.

From the Department of Neurology (T.M.G., C.A.E., K.A.D., B.L., J.P.), and Penn Statistics in Imaging and Visualization Endeavor (PennSIVE) Center of Excellence (D.T., R.T.S.), Center
for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania; Department of Biostatistics, Epidemiology, & Informatics (D.T., R.T.S.) and
Center for Biomedical Image Computing and Analytics (R.T.S.), University of Pennsylvania, Philadelphia.

Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

e2224 Copyright © 2022 American Academy of Neurology

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Glossary
cEEG = continuous long-term EEG; EMU = epilepsy monitoring units; GEE = generalized estimating equation.
ICU = intensive care unit; NPV = negative predictive value; PPV = positive predictive value.
The use of continuous long-term EEG (cEEG) in critical care
settings continues to rise, supported by consensus recommen-
dations and emerging evidence that it improves outcomes.1,2
Manually reviewing large volumes of EEG data is labor intensive,
necessitating an alternative method of quickly interpreting cEEG.
Nearly all neurophysiologists use quantitative EEG, and up to half
do not review all pages of EEG.3 Automated seizure detectors
have the potential to facilitate the efficiency of cEEG review
through triaging low-risk EEGs and allows the timely identifica-
tion and treatment of seizures.3-6 The use of automated seizure
detection systems is becoming increasingly widespread, but data
proving their reliability and how best to apply them are limited.
Persyst is the most widely used commercially available auto-
mated seizure detection software with Food and Drug Ad-
ministration clearance. It is used by thousands of neurologists
at hundreds of hospitals worldwide, including 48 of the 50
U.S. News & World Report’s top-ranked hospitals.7 While
Persyst offers quantitative spectral arrays to reflect EEG pat-
terns, these quantitative visual tools have not been thoroughly
validated in adults, have demonstrated significant variability,
and require appropriate standardization before being applied
routinely for clinical decision-making.3,8-11 However, the
software does offer an automated seizure detection tool that
asserts a yes or no interpretation of whether a sample of EEG
is consistent with a seizure. Overall, there has been little in-
dependent assessment of the Persyst algorithms; the largest
and most rigorous studies have been performed in affiliation
with the company itself.12-14 Patient selection for validation is
also a potential issue that could influence reports of the
software performance: the accuracy of the Persyst automated
seizure detection tool has been studied primarily in epilepsy
monitoring units (EMUs)4,15 and ambulatory EEGs in
adults.16 Critical care patients present an additional challenge
for automated seizure detection due to abnormal background
rhythms and unusual ictal patterns that may confound auto-
mated algorithms.17 Yet, automated seizure detection is ar-
guably most relevant in the intensive care unit (ICU), where
seizures are common, rapid treatment is desired, and manual
review is often not immediately available.6,18,19
We studied the performance of Persyst automated seizure
detection in a large sample of continuous ICU EEG record-
ings. We measured the performance of automated detections
at the level of individual seizures (whether each seizure was
correctly detected) and the accuracy of automated detections
at the level of EEG records (whether records were correctly
identified as containing seizures, even if individual seizures
were not accurately detected). The ability of automated de-
tection software to correctly identify individual seizures is
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critical for use as a real-time alarm, while record-level de-
tection is relevant for triaging studies for manual EEG review.
The study presented here provides a systematic and unbiased
analysis of the automated seizure detection performance of
Persyst in inpatient long-term continuous EEG monitoring.
Our primary research question sought to evaluate the sensi-
tivity, specificity, and positive predictive value (PPV), and
negative predictive value (NPV) of this tool at both the in-
dividual seizure and record levels.
Methods
Standard Protocol Approvals, Registrations,
and Patient Consents
This study was approved by the institutional review board at
the University of Pennsylvania with waiver of informed
consent.
Data Collection
For this study, we considered only 24-hour cEEG recordings
performed on inpatients at the Hospitals of the University of
Pennsylvania (the Hospital of the University of Pennsylvania,
Presbyterian Medical Center, and Pennsylvania Hospital),
excluding patients admitted to the EMU. In all cases, cEEG
had been clinically requested by the primary inpatient team to
evaluate for seizures. EEG electrodes were placed by trained
and registered EEG technologists using the international 10-
20 system and with eye leads. EEG data were collected at a
minimum sampling rate of 256 Hz using Natus (Natus Inc,
Pleasanton, CA) XLtek equipment running Natus Neuro-
works version 8.5. Persyst version 12 or 13 (Persyst Inc,
Solana Beach, CA), henceforth labeled P12 or P13, was run
on each EEG, either at the time of data capture or later (as
outlined below). EEGs were interpreted by trained epi-
leptologists credentialed to interpret EEGs at the University
of Pennsylvania. EEG reports were generated with custom-
ized software that stores EEG interpretations in a searchable
SQL database. Searchable fields include demographic data
and terms from the American Clinical Neurophysiology So-
ciety ICU nomenclature (including background amplitude,
organization, symmetry, rhythmic and periodic patterns, and
details on seizures). Because these fields are required by our
EEG system for report generation, there were no missing data.
For this retrospective study, 2 EEG datasets were generated.
We first identified a pilot cohort of cEEG recordings that
contained seizures. We selected ICU EEG reports coded as
containing seizures, recorded from 2015 to 2019, and ran-
domly selected 23 EEG recordings from 23 different patients.
Because the prevalence of seizures among inpatient cEEGs
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 records at tertiary care centers can vary widely (8%–48%)1 and
because we did not know the exact prevalence of seizures in our
population before the outset of this study, we chose a large
study at a center similar to ours that demonstrated that 27% of
inpatient records contained seizures to guide our sample size.20
On the basis of this study, we randomly selected 62 additional
cEEGs without seizures mentioned in the EEG reports to
roughly imitate the prevalence of seizures in the ICU pop-
ulation at large. All 85 EEGs were manually reviewed by 2
expert reviewers (T.M.G., J.P.) blinded to any prior annota-
tions in the EEG records. Seizures were defined by standard-
ized, widely accepted criteria for electrographic seizures.21 The
onset and offset times of all seizures were marked in-
dependently, and differing marks were adjudicated via joint
review by both reviewers. These studies were then run through
the Persyst 13 analyzer using default parameters, and seizure
markings were extracted from the EEG comments.
In addition to seizures, the following features were extracted from
each EEG report and coded as present or absent: (1) low voltage
(<20 μV); (2) posterior dominant rhythm; (3) artifact severe
enough to obscure identification of epileptiform discharges; (4)
status epilepticus; (5) lateralized periodic discharges; (6) focal
slowing; (7) severe diffuse slowing; (8) state changes; (9) normal
sleep architecture; and (10) poor background organization de-
fined as any background that was not described in report as good
or fair (this includes backgrounds coded as suppressed, absent
organization, discontinuous, and poorly organized). Additional
clinical data extracted from the EEG report database included age,
sex, neurologic injury/condition, and mental status at the time of
recording. If an automated detection fell anywhere within the
span of the seizure annotated by the human reviewers or within
10 seconds before or after this window, the detection was marked
as concordant with the human read. Any other automated seizure
detection was coded as a false detection. For this study group, we
excluded Persyst seizure detections that occurred if a patient was
disconnected from EEG. We also manually rereviewed the EEG
at every Persyst seizure detection to ensure that no seizures
missed were by the human reviewers (this never occurred in our
dataset).
We next identified an expanded cohort to study algorithm
performance at scale. We examined all cEEGs recorded be-
tween December 1, 2017, and October 30, 2020, and included
all cEEGs that were analyzed by P12 or P13 at the time of
recording, a total of 7,924 cEEGs studies from 2,854 unique
patients. The report database was queried for human reported
seizures and compared to the presence or absence of Persyst
automated seizure detections at any point in the record. In
this dataset, no effort was made to exclude patient discon-
nections or excessive artifact as a cause of false automated
detection, reflecting real-world practice.
To examine the seizure detections across a dataset of this size,
an EEG comment extractor was created in collaboration with
Natus Neuroworks that allowed us to directly read the EEG
files, including both human- and Persyst-generated comments.
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We extracted 552,623 comments from this dataset, focusing on
detection events that included the terms “RhythmicBurst” or
“SeizureDetected.” These detection events were labeled by the
authors as automated seizure detections by Persyst. The soft-
ware used to extract comments was developed with permission
from Natus Medical Inc using algorithms from their software
developers kit. For this dataset, we queried report information,
including background details and presence of focal vs gener-
alized seizures. Precise seizure timing is not a queriable field in
the report database.
Statistical Analysis
Statistical analysis was performed in R (version 3.6.0, R
Foundation for Statistical Computing, Vienna, Austria). The
clinical characteristics of patients with and without seizures
were compared by Mann-Whitney U test for continuous
variables (age) and χ 2 or Fisher exact test for categorical
variables (sex, neurologic injury, mental status, for a total of 7
tests, Bonferroni-corrected α = 0.007).
First, we analyzed the pilot cohort for the accuracy of automated
seizure detections at the level of individual seizures. To account
for clustered data with multiple seizures within each EEG, we
used generalized estimating equations (GEEs) with exchange-
able working correlation structure to estimate the sensitivity and
PPV of Persyst-detected seizures compared to human-detected
seizures.22 The GEE estimates are different from the empirical
sensitivity and PPV in that they can be interpreted as marginal or
population-averaged quantities that account for within-cluster
correlation. GEE models were implemented with the R package
geepack.23 CIs for these estimates were then found with the
robust sandwich estimator. True negatives (no human-detected
seizure, no Persyst-detected seizure) were not countable events,
so specificity and NPV could not be calculated. Next, to de-
termine whether background features of the EEG affect the
accuracy of automated seizure detection, we stratified the EEGs
according to each of 10 background features and compared the
sensitivity of automated detections for records with presence vs
absence of each feature using Mann-Whitney U tests (10 tests,
Bonferroni-corrected α = 0.005).
Next, we analyzed the accuracy of automated seizure de-
tection in the pilot cohort at the level of the EEG record rather
than the individual seizure level. Each EEG record was coded
as having ≥1 human-detected seizures (yes/no) and as having
≥1 Persyst-detected seizures (yes/no), regardless of when
during the record these detections occurred. Sensitivity,
specificity, NPV, and PPV of Persyst-detected seizures
compared to human-detected seizures were calculated.
Adjustment for clustered data was not performed because
each EEG record in this cohort was an independent ob-
servation. Exact binomial CIs were calculated with the R
package epiR.24
For our expanded cohort of 7,924 EEG records, seizure de-
tection was again analyzed at the level of each entire EEG
record. Similar to our methods for pilot cohort -level review, we
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coded records as having human-detected seizures (yes/no)
and/or Persyst-detected seizures (yes/no). To account for
clustered data with multiple EEG recordings from the same
individual, we again used GEEs with exchangeable working
correlation structure22 to estimate the sensitivity, specific-
ity, NPV, and PPV of Persyst-detected seizures compared
to human-detected seizures. CIs were found with the ro-
bust sandwich variance. For subgroup analyses, we used
similar GEE models with a subgroup indicator variable to
enable comparisons. Subgroup comparisons were (1) re-
cords with low background voltage vs records with normal
background voltage, (2) records analyzed by different
software versions (P12 vs P13), and (3) records that con-
tained focal-onset seizures vs generalized-onset seizures.
This last subanalysis of seizure onset was limited to records
that contained human-detected seizures, so only sensitiv-
ities could be calculated. Statistical testing was performed
with the Wald test.
Data Availability
Anonymized data that support the findings of this study are
available from the corresponding author on reasonable request.
Results
Characteristics of the pilot and expanded cohorts are shown in
Tables 1 and 2, respectively. Patients with seizures vs those
without seizures did not differ in their clinical characteristics
except for mental status in the expanded cohort, which
reached marginal statistical significance but was not significant
when corrected for multiple comparisons (α = 0.007).
In the pilot cohort, the 23 records with seizures contained a
total of 229 human-detected seizures (median 7, range 1–33
seizures per record). Performance metrics are shown in
Table 3 and Figure 1. Persyst correctly detected 111 of 229
individual seizures (adjusted sensitivity 0.50, 95% CI 0.34,
0.66). In these 23 studies, Persyst detected a total of 183
seizures. Of these, 111 of 183 were true seizures according to
human readers (adjusted PPV 0.60, 95% CI 0.42, 0.75).
We next tested whether specific EEG features were associated
with successful Persyst detection of individual seizures, as
shown in Figure 2. Sensitivity was significantly lower in re-
cords with low-voltage background compared to records without

Table 1 Patient Characteristics, Pilot Cohort

Patient characteristic Patients with seizures (n = 23) Patients without seizures (n = 62) p Value

Age, median (range), y 61 (28–96) 63 (28–90) 0.45a

Female, n (%) 11 (48) 31 (50) 1.00b

Underlying neurologic injury, n (%) 0.63c

Epilepsy 3 (13) 7 (11)

CNS infection/inflammation 2 (9) 3 (5)

Brain tumor 3 (13) 11 (18)

Postneurosurgery 0 (0) 4 (7)

Hypoxic ischemic encephalopathy 1 (4) 9 (15)

Traumatic brain injury 4 (17) 3 (5)

Toxic/metabolic 3 (13) 5 (8)

Nontraumatic intracerebral hemorrhage 4 (17) 10 (16)

Ischemic stroke 2 (9) 7 (11)

Unexplained/other 1 (4) 3 (5)

Mental status, n (%) 0.84c

Awake 7 (31) 21 (34)

Somnolent or obtunded 6 (26) 19 (31)

Coma, sedated 4 (17) 11 (18)

Coma, unsedated 4 (17) 9 (15)

Unknown 2 (9) 2 (3)

a
Mann-Whitney U test.
b
The χ2 test.
c
Fisher exact test.

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 Table 2 Patient Characteristics, Expanded Cohort
Patient characteristic Patients with seizures (n = 353) Patients without seizures (n = 2,501) p Value

Age, median (range), y 63 (17–99) 63 (16–101) 0.43a

Female, n (%) 169 (48) 1,172 (47) 0.76b

Mental status, n (%) 0.02c

Awake 169 (45) 964 (39)

Somnolent or obtunded 104 (28) 773 (31)

Coma, sedated 90 (24) 562 (23)

Coma, unsedated 9 (2) 144 (6)

Unknown 2 (1) 37 (1)

a
Mann-Whitney U test.
b
The χ2 test.
c
Fisher exact test.

low-voltage background (Mann-Whitney U test, p = 0.001). No
other EEG feature was significantly associated with successful
automated detection of individual seizures.
Because detection of some but not all seizures within an EEG
record may be adequate for triaging EEG, we assessed the
performance of Persyst in identifying seizures at the record level.
That is, does the automated seizure detection identify the
presence of a seizure anywhere in the record? In our pilot cohort
of 85 EEG records, Persyst detected seizures in 18 of 23 records
that contained seizures (sensitivity 0.78, 95% CI 0.56, 0.93).
Persyst also detected seizures in 27 of 62 records that did not
contain seizures (false alarm rate 44%, 95% CI 31%, 57%).
On the basis of our finding that Persyst performed particularly
poorly at the individual seizure level for EEGs with low-
voltage backgrounds, we performed a post hoc analysis in
which we removed the low-voltage EEGs and then repeated
the record-level analysis. In the remaining 18 EEGs contain-
ing seizures and without low-voltage background, Persyst
correctly detected seizures in all 18 of 18 at the record level,
corresponding to both a sensitivity and an NPV of 100%.
We expanded these analyses to a dataset of 7,924 EEG records
from 2,854 unique individuals to determine the performance
of Persyst at the record level at scale. Human-detected
seizures were present in 786 of 7,924 records (10%). Auto-
mated seizure detections were present in 6,079 of 7,924 re-
cords (77%). The accuracy of Persyst at the record level is
shown in Figure 1 and Table 3. Results in this expanded
cohort overall showed trends similar to our pilot cohort.
Persyst detected seizures in 723 of 786 records that contained
seizures (adjusted sensitivity 0.91, 95% CI 0.88, 0.93). Persyst
also detected seizures in 5,356 of 7,138 records that did not
contain seizures (adjusted false alarm rate 0.74, 95% CI 0.72,
0.75). The PPV of Persyst detections was low (0.08, 95% CI
0.07, 0.09), meaning that a human reader would have to read
12.5 EEGs in which automated detections occurred to find 1
record with true seizures. On the other hand, the NPV was
high (0.97, 95% CI 0.96, 0.98), meaning that if Persyst did not
detect seizures, there was only a 3% chance that true seizures
were present. To account for potential bias from repeated
EEGs from single individuals, we limited the analysis to only
the first EEG from each subject (2,854 unique individuals/
EEGs). Results were similar, as demonstrated in eTable 1,
links.lww.com/WNL/B938. Assuming that each record in
which there were no human or automated seizure detections
was ≈24 hours (total 44,280 hours), Persyst accurately
identified 42,768 hours of EEG as being seizure-free.
We performed several subgroup analyses in this expanded
dataset, using the same GEE model as previously described

Table 3 Performance of Automated Seizure Detection

Cohort Total, n Sensitivity Specificity PPV NPV

Seizure level, pilot cohort 229 0.50 (0.34, 0.66) — 0.60 (0.42, 0.75) —

Record level, pilot cohort 85 0.78 (0.56, 0.93) 0.56 (0.43, 0.69) 0.40 (0.26, 0.56) 0.88 (0.73, 0.96)

Record level, expanded cohort 7,924 0.91 (0.88, 0.93) 0.26 (0.25, 0.28) 0.08 (0.07, 0.09) 0.97 (0.96, 0.98)

Abbreviations: NPV = negative predictive value; PPV = positive predictive value.

Values in parentheses are 95% CIs.

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Figure 1 Performance of Automated Seizure Detection

(A–D) Seizure level refers to detection of individual

seizures. Because the absence of both human-
and Persyst-detected seizures (true negatives)
was not a countable event, specificity and nega-
tive predictive value (NPV) were not calculated at
the seizure level. Record level refers to detection
of a seizure anywhere in the EEG record. PPV =
positive predictive value.

Figure 2 Sensitivity of Automated Seizure Detection Stratified by EEG Features

EEGs with low-voltage backgrounds had significantly lower sensitivities of automated seizure detection at the level of individual seizures compared to EEG
records with normal-voltage backgrounds (p = 0.001). All other features we assessed did not significantly affect the sensitivity of automated seizure detection.
LPD = lateralized periodic discharge; PDR = posterior dominant rhythm.

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 Table 4 Performance of Persyst 12 vs Persyst 13 Automated Seizure Detection
Software version Total, n Sensitivity
12 1,310 0.91 (0.80, 0.96)
13 6,605 0.91 (0.88, 0.93)
Abbreviations: NPV = negative predictive value; PPV = positive predictive value.
Values in parentheses are 95% CIs.
but with a subgroup indicator variable to enable comparisons. In
this expanded cohort, the estimated sensitivity of automated de-
tections was not significantly different in EEGs with low-voltage
backgrounds than in those with normal voltage (p > 0.05), in
contrast to the hypothesis generated by our pilot cohort. We then
examined the difference between versions P12 and P13, both of
which performed similarly (Table 4). In addition, we examined
the difference between focal and generalized seizures. Among the
786 records that contained human-detected seizures, 653 records
contained only focal-onset seizures, and 111 records contained
only generalized-onset seizures. Sensitivity of automated de-
tection was higher for focal-onset seizures than for generalized-
onset seizures (0.93 vs 0.85, p = 0.012, Table 5).
Last, to further account for potential bias from repeated EEGs
for some individuals in the cohort, we limited the analysis to
only the first EEG recorded for each of 2,854 unique indi-
viduals. Results were similar to those of the entire expanded
cohort, suggesting that repeated measures was not an im-
portant source of bias. This study provides Class II evidence
that an automated seizure detection program cannot accu-
rately identify EEG records that contain seizures.
Discussion
In this study, we measured the accuracy of Persyst for auto-
mated seizure detection in 24-hour critical care EEG records. At
the level of individual seizures, we found modest performance of
automated seizure detections, with fewer than half of seizures
detected. At the level of EEG records, in a large cohort of 7,924
records, we found that the presence of automated seizure de-
tections was a poor predictor of true seizures in the recording,
while the absence of automated seizure detections was an ex-
cellent predictor that the record did not contain true seizures.
Automated seizure detection can play at least 2 different roles
in clinical care. First, it could serve as a real-time seizure alarm,
Table 5 Sensitivity of Automated Seizure Detection for Focal vs Generalized Seizures
Seizure onset Records, n
Focal 653
Generalized 111
a
Wald test.
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Specificity PPV NPV
0.24 (0.21, 0.27) 0.05 (0.04, 0.07) 0.98 (0.95, 0.99)
0.27 (0.25, 0.28) 0.09 (0.08, 0.10) 0.97 (0.96, 0.98)
prompting immediate manual EEG review or treatment of the
patient. Our data argue against the use of Persyst for this
function in clinical practice. Relying on automated detections
would have missed more than half of all true seizures in our
pilot cohort. In addition, the false positives pose a challenge,
as evidenced by the low PPVs (i.e., the likelihood that an
automated detection is a true seizure) at the level of both
individual seizures and entire records across our cohorts. An
ideal seizure alarm will require a substantially higher sensi-
tivity (i.e., miss very few true seizures) and lower false alarm
rate than the values seen here.
A second potential role for automated seizure detection is to
reduce the volume of EEG for manual review. For example,
EEG records with a high probability of seizures could be
reviewed earlier or more often, whereas other records could be
reviewed less often or more briefly if the probability of seizures
were sufficiently low. The relevant metric here is the NPV,
i.e., the probability that the absence of automated detections
reflects the absence of true seizures. We found high NPVs at the
record level in both our pilot and expanded cohorts, up to 97%.
This may be adequate to justify clinically useful triage of records
with low probability of seizures based on lack of automated
detections. It is important to note that our data support this
kind of triaging only at the level of entire EEG records, not at
the level of individual automated detections. That is, if no
automated detections are present, one can be 97% confident
that the record contains no seizures; whereas if automated
detections were present, our data suggest that the entire record
should be reviewed for accurate seizure detection, rather than
limiting the review to only the individual detection events,
which would be likely to miss true seizures.
Prior studies on the accuracy of Persyst for automated seizure
detection have shown mixed findings. In the ICU setting,
there has been exploration of the use of spectral array
analysis,3,6,8,11 particularly in the pediatric population, but the
Sensitivity (95% CI) p Valuea
0.93 (0.90, 0.95) 0.012
0.85 (0.76, 0.91)
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automated seizure detection tool has not been investigated.9
Most studies have focused the EMUs and ambulatory EEG
recordings.4,14-16 The most recent study of the Persyst seizure
detection tool (P14) in EMU recordings showed noninferior
seizure detection performance compared to human experts.14
These studies may not be applicable to ICU settings because
EMU recordings are often higher fidelity (due to frequent
electrode maintenance) and seizures are more likely to occur as
discrete events against normal or mildly abnormal back-
grounds. In contrast, patients in the ICU requiring cEEG
typically have a grossly abnormal EEG background, with
rhythmic or periodic abnormalities superimposed. Those
background and interictal rhythms, including ictal-interictal
continuum patterns, have been shown to confound automated
algorithms, causing a decline in detection performance.17
Our study extends these prior findings in several ways. First,
this is the largest study of the automated seizure detection
accuracy on inpatient cEEGs outside the EMU, examining
performance at both the individual seizure and study levels.
Our findings indicate lower performance than has been
reported by previous studies in different patient populations.
This is important because critical care populations are a major
source of continuous EEG recording and the need for
automation-assisted interpretation is particularly acute. In
subgroup analyses, we found slightly higher automated sei-
zure detection sensitivity for focal rather than generalized
seizures, which, to the best of our knowledge, has not been
previously reported.11,16
The study has several limitations. Persyst version 14 (P14)
was not available at the time of data analysis in this report.
However, we did not find significant differences between
versions P12 and P13, and neither of those versions achieved
adequate performance for fully automated seizure detection.
We intend to compare P14 performance to these results in the
future. Second, we have not provided specificity or NPVs for
seizure-level analyses because true negatives (no human-
detected seizure, no Persyst-detected seizure) were not
countable events. These were countable at the record level
only. Third, the pilot cohort did not contain any EEG patterns
classified as ictal-interictal continuum, and we cannot com-
ment on the accuracy of Persyst in that context (although the
expanded cohort did contain such EEG patterns, we did not
analyze that subgroup specifically). Although the pilot cohort
allowed assessment of individual seizures, the expanded co-
hort was too large for such analyses, particularly for correla-
tion of individual automated markings with individual seizures
and for accounting for automated detections during periods of
excess artifact. These differences likely accounted for the
difference in PPVs between our pilot seizure-level and ex-
panded record-level cohorts. Our study was also limited by
the number of manually reviewed EEGs, and a larger pilot
cohort sample size may lead to more accurate results. The
expanded cohort, although with a much larger sample size,
was obtained from a single center. Performing this study
across multiple sites may more comprehensively represent
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inpatient EEGs at large. In addition, the pilot cohort and
expanded cohort reflected overlapping but not identical time
periods. However, we cannot identify any obvious con-
founding factors related to when the EEG was performed. We
also applied the Persyst seizure detector at default settings
only; it is possible that adjusted detection parameters would
lead to different performance results. In our expanded cohort,
we relied on the original clinical interpretation EEG according
to our reporting database. The clinicians reading the study
would have had access to the Persyst detections at the time of
their interpretation. In theory, this information could have
improved identification of seizures in real time. It should be
noted that Persyst offers more than seizure markings, and this
study did not investigate the value of visualizing EEG time
series as compressed spectral trends.
Automated seizure detection in critical care EEG is an im-
portant need, and the true value of Persyst lies in triaging
low-risk EEGs We found that its performance at detecting
individual seizures was not sufficient for use as a seizure alarm
in clinical practice, given a poor PPV. At the level of entire
records, we found that the absence of automated seizure de-
tections could be useful to triage studies with low probability
of containing seizures. In our dataset, Persyst accurately tri-
aged up to 42,000 hours of EEG recordings as seizure-free. On
the basis of these findings, our institution plans to use auto-
mated seizure detection as a tool in our morning workflow
and triage strategy but not as a seizure detector. Future studies
should aim to improve the accuracy of automated seizure
detection and to measure its accuracy in different patient
populations. It is anticipated that future seizure detection al-
gorithms will close the gaps identified here, but human efforts
cannot be minimized at present.
Acknowledgment
B. Litt is supported by the following NIH grant from the
National Institute of Neurological Disorders and Stroke:
DP1NS122038.
Study Funding
No targeted funding reported.
Disclosure
T.M. Ganguly, C. Ellis, D. Tu, R.T. Shinohara, and K.A. Davis
report no disclosures relevant to the manuscript. B. Litt has
licensed intellectual property through the University of Penn-
sylvania in exchange for equity in the following companies:
NeuroPace, MC10, and Blackfynn. He is a consultant for 4
Catalayzer, including Liminal Neurosciences, Tesseract, Hy-
perfine, Detect, and AI Therapeutics. None of these entities
have sponsored this work and their value is not affected by this
research. J. Pathmanathan reports no disclosures relevant to the
manuscript. Go to Neurology.org/N for full disclosures.
Publication History
Received by Neurology April 11, 2021. Accepted in final form
February 8, 2022.
Neurology | Volume 98, Number 22 | May 31, 2022 e2231
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