IEEE Circuits and Systems Magazine - Q3 2022 - 25

associated with seizures have a different time course from
that of heart rate increases associated with nonseizurerelated
activities [9], [11]). The pulse generator delivers
stimulation right after the seizure onset is detected. The
SenTiva has a detect-and-respond mode, and thereby it
can receive programming signals from a wireless wand
and transmit back telemetry information. The surgical
procedure necessary for the SenTiva involves implanting
both a pulse generator beneath the skin of the upper
chest and a subcutaneous bipolar electrode that extends
from the pulse generator and wraps around the left vagus
nerve as it passes through the neck [12]. The SenTiva was
approved by the U.S. FDA in October 2017 for treating RE
in both adults and children older than 4 years.
The ADNS-300 (Neurotech, Louvain-la-Neuve, Belgium)
is a rechargeable and responsive VNS (Fig. 1(b)) [13]. It
not only stimulates the vagus nerve but also records compound
action potentials (CAP) from the left vagus nerve
using an innovative cuff electrode. This unique feature enables
the physician to capture the CAP generated by the
stimulation, resulting in an improved and personalized
treatment. Patients use a remote controller and a charger
to turn the system on and off and to change the parameters
of the neurostimulator. The ADNS-300 obtained the
European CE Mark Approval to treat RE in June 2012.
B. Closed-Loop DBS
The Percept™ PC Neurostimulator with BrainSense™
(Fig. 1(c)), produced by Medtronic (Minneapolis, MN,
USA), is a closed-loop DBS therapy for Parkinson's disease,
essential tremor, dystonia, obsessive-compulsive
disorder and RE [14]. This device monitors and records
brain activity to allow the doctor to check how a patient responds
to the therapy and improve the therapy by adjusting
the parameters of the stimulating pulses accordingly.
The device weighs about 61g with a height of 68mm and
a width of 51 mm. It has two electrode arrays, two extension
leads, and a pulse generator. In the surgical procedure,
each electrode array and extension lead implantation takes
an average of 1-2 h [15]. It is conducted as follows. First,
the scalp is anesthetized locally and a stereotactic head
frame is fixed to the head. Second, the brain undergoes a
CT or an MRI scan. Third, according to the results of the
scan, the surgeon uses a surgical planning system to locate
the surgical target. A hole about the size of a 5-cent coin
(USD) is drilled in the target area of the skull. Fourth, using
microelectrode recording technology to detect the electrophysiological
characteristics of the intended target and accurately
locate the nuclear mass where the electrode lead
is to be implanted. The electrode lead is then affixed to the
skull. The other end of the electrode lead is passed through
the scalp and connected to the extension lead. The implantation
of the pulse generator is similar to that for VNS.
THIRD QUARTER 2022
Compared to the previous version, the Activa PC+S,
the Percept™ PC Neurostimulator with BrainSense™ offers
full-body MR conditional neurostimulation for both
3T and 1.5T MRI scans, improves battery longevity (over
5 years on average), and enables expanded capabilities
in the future via software upgrades [14]. It received CE
Mark Approval in January 2020.
C. RNS
The responsive neurostimulation (RNS®) System, developed
by Neuropace (Mountain View, CA, USA), is a responsive
cortical neurostimulator in which an epileptic seizure
is detected by recorded intracranial EEG (iEEG) signals [16]
(Fig. 1(d)). It comprises a neurostimulator implanted in the
cranium, a stimulation strip lead implanted deep in the
brain, and a cortical recording strip lead implanted in the
subdural cortex at one or two identified seizure foci. Each
lead contains four electrode contacts. The RNS System also
includes a program for the physician, a remote monitor (or
wand) for the patient, and a secure internet-accessed database
for data storage. It continuously senses and monitors
electrographic activity via the cortical strip lead. The size
of the device is 28 × 60 × 7.7 mm3, it weighs about 17 g, and
is powered by a battery that lasts around 2-3.5 years [17].
When an oncoming epileptic seizure is detected, it triggers
the stimulation strip to deliver current-regulated biphasic
pulses (40-1000 μs) to the seizure foci [18]. At the same
time, the recorded brain data is transferred wirelessly to
the Patient Data Management System. The physician uses
the program to control the stimulator and the wand to
monitor brain activity. Long-term trials of the RNS System
have shown an average reduction in seizure frequency of
72% (at 7 years) [19]. The RNS System received U.S. FDA
approval in November 2013 to treat adults with partial-onset
seizures. Currently, more than 1300 patients are using
the RNS System [17].
D. Summary of Closed-Loop Neurostimulators
for Treatment of Refractory Epilepsy
The closed-loop VNS has smaller truma and it takes
shorter surgical time than the closed-loop DBS. Moreover,
the side effects of the closed-loop VNS (including
voice alteration, headache, neck pain, dyspnea, cough,
and hoarseness or throat discomfort [10]) are milder
than that of the closed-loop DBS (including infection,
hemorrhage, status epilepticus, depression, and memory
impairment [15]). However, the epileptic seizure detection
accuracy of the closed-loop DBS is higher than
that of the closed-loop VNS since the recording electrodes
in the closed-loop DBS is close to the seizure foci.
In addition, the treatment efficacy (reduction on seizure
frequency) of the closed-loop DBS (about 80% [15]) is
higher than that of the closed-loop VNS (about 71% [10]).
IEEE CIRCUITS AND SYSTEMS MAGAZINE
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IEEE Circuits and Systems Magazine - Q3 2022

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