edited_osorio.qxp 9/1/09 11:22 am Page 69
Realtime Detection, Quantification, Warning, and Control of Epileptic Seizures
How does a median filter work? Unlike a mean or average filter
Figure 4: Seizure Intensities (y-axis) (Same Subject, Same
(commonly used in seizure detection algorithms) that takes into account
Epileptogenic Zone) and Durations (x-axis) as a Function of
all values in a distribution (e.g. for the set 1, 1, 1, 1, 96; mean = 20), a
Frequency of Stimulation (Intensity and Pulse Width Were Identical)
median filter selects the one in the middle (1, 1, 1, 1, 96; median = 1), a
90th percentile of ratios, time-locked by detection time
filtering operation that instills the requisite insensitivity to outliers (96 in
(at t=120s), for each group of stimulation parameters
the numerical example above and EDs in the ECoG) into the process.
More explicitly, in the generic algorithm embodiment, EDs must last for
350
at least one second or comprise at least 50% of the two-second
300
foreground window to have any effect on the ratio/output. This filtering
step markedly reduces detections that do not merit issuance of warnings 250
or treatment.
200
What Is the Clinical Value of Realtime Automated Seizure
150
Detection and Quantification?
There is the ability to deliver therapy in close temporal proximity to
100
seizure onset and to objectively assess efficacy using not only one
(frequency or rate) but three additional relevant variables (intensity, 50
Threshold
duration, and extent of spread). The results of a clinical trial
5
performed
by these authors will be used to illustrate these benefits in detail.
0
110 115 120 125 130 135 140
For this trial, subjects with localization-related, pharmaco-resistant
epilepsies were assigned to two groups based on the results of
Time (seconds)
invasive monitoring. One group consisted of four subjects, deemed to be
No stim (n=56) 333Hz RFG1 to RFD2 (n=29) 500Hz RFG1 and RFG25 to RFD2 (n=10)
good candidates for resection of epileptogenic tissue (three mesial
50Hz RFG1 and RFG25 to RFD2 (n=6) 333Hz RFG1 and RFG25 to RFD2 (n=10)
temporal and one dorsal frontal), to whom high-frequency (>100Hz)
High frequencies (red, magenta, and cyan curves) defined as >100Hz abated seizures, compared
charge-balanced square pulses at safe intensities were delivered to the with baseline (blue curve), whereas treatment with 50Hz (green curve) intensified and prolonged
primary epileptogenic zone. The other group comprised four subjects
the seizure. Assessment of any antiseizure therapy in realtime with this degree of accuracy,
which is not possible with seizure diaries, will advance clinical epileptology. Seizure detection
whose seizures originated independently from both mesial temporal threshold (dashed horizontal line) = 22.
regions and were thus inoperable. This group was also treated with high-
frequency currents, but these were delivered to the anterior thalamic
Figure 5: Temporal Evolution of Seizure Intensity (y-axis) During
nuclei, not to the epileptogenic tissue. This trial had two phases: the
Baseline and Experimental Phase (with and without Stimulation)
baseline/control phase, which corresponded to the surgical evaluation
90th percentile of ratios, time-locked by detection time (at t=120s),
phase, and the experimental phase, during which every other seizure was
for baseline and experimental phase (with and without stimulation)
stimulated electrically.
Seizure quantification allows precise assessment of the effects of therapy.
Figure 4 compares the intensities and durations of seizures during the
control phase (blue curve) with those treated with different frequencies.
Currents at 300Hz (red curve) markedly decrease intensity and duration, 10
2
whereas those at 50Hz (green curve) increase intensity and duration.
Seizure quantification also uncovers effects of therapy that otherwise are
likely to be overlooked. The beneficial effect of electrical stimulation on Threshold
seizure intensity and duration can outlast its duration (‘carry-over’ effect),
but is less marked than for seizures that are actually stimulated (see
10
1
Figure 5). The intensity and duration of seizures stimulated at onset are
considerably decreased (red curve) compared with those in the control
(blue) phase. Note that in this experimental paradigm,
5
stimulation was
delivered to every other seizure, and non-stimulated seizures (green
curve) in the experimental phase had lower intensity than those in the
90 100 110 120 130 140 150 160 170
control phase but were more intense and longer than those receiving
Time (seconds)
electrical stimulation.
Baseline No stim Stim
Seizure intensity and duration (same subject, same epileptogenic zone) of a baseline seizure
Current clinical practice ignores seizure intensity, duration, and extent of (blue curve), a seizure treated with high-frequency currents shortly after onset (red curve), and a
spread and lacks accurate logging of the time between seizures (and
seizure in the experimental phase that was not treated (the experimental design called for
stimulation of every other seizure). The ability to quantify intensity and duration allowed
their frequency of occurrence), variables that are complexly inter-related. identification of a ‘carry-over’ effect. The effect of high-frequency stimulation outlasts its
For example, electrical stimulation directly to the epileptogenic zone may
duration. This effect, although beneficial, is inferior to that of stimulation at seizure onset,
which may suggest that contingent stimulation is superior to periodic stimulation, as it not only
decrease seizure intensity significantly (p<0.05) in certain subjects and abates seizures but also has a protective effect that outlasts its duration.
US NEUROLOGY 69
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