USE OF sEMG TO INFORM GTC SEIZURE

SEMIOLOGY

Jose E. Cavazos, Jonathan J. Halford, Michael R. Sperling, Dennis J. Dlugos, William O. Tatum, Jay Harvey, Jacqueline A. French, John R. Pollard, R. Edward Faught, Katherine H. Noe, Thomas R. Henry, Gina M. Jetter, Octavian V. Lie, Lola Morgan, Michael R. Girouard, Damon P. Cardenas, Luke E. Whitmire

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DISCLOSURES

➢The Brain Sentinel® Monitoring and Alerting

System received FDA de-novo clearance for

marketing on February 16, 2017 and sponsored

this regulatory clinical trial

➢JE Cavazos and MR Girouard are co-founders

and stockholders of the company

➢DP Cardenas, MR Girouard, and LE Whitmire

are employees of the company

➢JE Cavazos and JJ Halford are consultants for

the company

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Overview of Multicenter, Prospective, Blinded, Comparative Trial

▪ Automated detection using sEMG compared to vEEG review by three independent

neurologists (ABPN certified in epilepsy) to identify GTC seizures

▪ 11 NAEC Level IV EMUs

▪ 199 Subjects from the U.S. and Europe

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The Brain Sentinel® Monitoring and Alerting System detected

100% of GTC seizures when properly placed

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Cohort

Properly Placed

Cohort (all)

n = 149

Properly Placed

Cohort (adults)

n = 106

Total GTCS per epileptologists 29 21

GTCS detected by device 29 21

PPA (95% CI)100%

(88%, 100%)

100%

(84%,100%)

Total false positives 442 357

Total hours of sEMG 7,369 5,637

Mean false positives per 24

hours1.44 1.52

Time to alarm

Mean (s) 7.70 5.34

SEM (s) 2.32 2.86

Range (s) -30.82 – 25.06 -30.82 – 25.06

0.5

1

1.5

2

2.5

50%

60%

70%

80%

90%

100%

95 115 135 155 175 195 215 235 255

Fa

lse A

larm

Rate

(F

AR

) p

er

24h

Positiv

e P

erc

ent A

gre

em

ent (P

PA

)

ThresholdPPA PPC FAR PPC

The length of tonic and clonic phases are similar between adults

and adolescents as well as 1° and 2° generalized GTCS

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Primary Generalized

(n=9) a

SecondaryGeneralized

(n=26) b

ANOVA

Length of Tonic Phase (s) 12.8 14.4 0.71

Length of Clonic Phase (s) 39.3 39.3 0.31

Length of Tonic-Clonic Phases (s)

50.8 52.8 0.22

a Nine subjects experienced a total of 17 1° generalized GTC seizures.b Twenty-six subjects experienced a total of 39 2° generalized GTC seizures.Each subject contributed once to the average median length of each phase. Median values were calculated for subjects with replicate data.

2° generalized GTC seizures

Adults (22-61)(n=19) a

Adolescents (8-21)(n=7) b

ANOVA

Length of Tonic Phase (s) 16.5 14.3 0.50

Length of Clonic Phase (s) 39.7 46.0 0.21

Length of Tonic-Clonic Phases (s)

52.2 54.7 0.66

a Nineteen adult subjects experienced a total of 21 2° generalized GTC seizures.b Seven adolescent subjects experienced a total of 18 2° generalized GTC seizures. Each subject contributed once to the average median length of each phase. Median values were calculated for subjects with replicate data.

Phase Lengths in 1°and 2°Generalized GTCPhase Lengths in Adults and Adolescents

The average length of tonic-clonic motor activity of GTC

seizures was 51 seconds

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Mean 15.65 40.19 51.37

Length of tonic-clonic duration are similar by vEEG or sEMG

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Paired t-test

P = 0.72

Paired t-test

P = 0.009Paired t-test

P = 0.08

Epileptologist A Epileptologist B Epileptologist C

▪ Raw sEMG is broken down into 2 frequency

range bins using the output from wavelet-

transform operation show in the middle and

bottom plots

▪ Frequency bins were selected to emphasize

the difference between tonic (high frequency,

pink) and clonic (lower frequencies, blue)

phases of GTC seizures

▪ The bottom plot is scaled to highlight the

transition from tonic to clonic phase for a GTC,

and is meant to augment physician’s review of

sEMG data

On the Horizon – Frequency and amplitude analysis to quantify

length of tonic and clonic phases

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Differentiating PNES from GTC using single channel sEMG

▪ This data processing technique has been applied to GTC seizures and other

seizure or seizure-like events, particularly psychogenic non-epileptic spells (NES)

▪ High frequency sEMG is associated with the tonic phase of GTC seizures and less

prevalent in PNES than GTC seizures

▪ The middle plot, or unscaled frequency-transformed waves, best elucidates this

case

PNESGTC

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AUC Analysis – PNES vs. GTC

▪ Using an area under the curve (AUC) analysis of the frequency bin

components provides a mechanism for quantitative evaluation

▪ The ratio of the AUC for both the high frequency

and low frequency ranges were statistically

different (P < .01) between GTCS and PNES

* - PNES data is significantly different (P < .01) from GTC for AUC analysis (n = 10 events)

PNES

GTC

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SUMMARY

➢The Brain Sentinel® Monitoring and Alerting System detected

100% of GTC seizures when properly placed

➢The length of tonic and clonic phases are similar between

adults and adolescents as well as 1° and 2° generalized

GTCS

➢The average length of tonic-clonic motor activity of GTC

seizures was 51 seconds

➢Length of tonic-clonic duration are similar by vEEG or sEMG

➢May be able to differentiate PNES from GTC

using single channel sEMG

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