RNS® System

RNS® System
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Category	Deep brain stimulation
Developer	NeuroPace, Inc. Mountain View, California
Announced	December, 2009
Released	Developers: Consumers: 2013
Price	35,000 USD (estimated)
Max output	11.5 mA11.5 T 0.0115 A ± 10%, at 500 Ohms;
Session duration	55 s 0.0833 minute (min 10 msec)
Scalp location	no settled location (in parietal skull upon recommendation)
Weight	18 g
Controls	laptop personal computer, magnet, NeuroPace Patient Data Management System, NeuroPace Programmer
Data available	good
Risk factor
Medical prescription	yes
http://www.neuropace.com/

RNS® System is medical device for epilepsy treatment. It can monitor and stimulate brain activity, for it is deep brain stimulation device. It is manufactured by privately held company named NeuroPace, which is located in Montain View, California. Therapy with RNS System consist in reducing the frequency of seizures in individuals, who have partial-onset, medically refractory (drug resistant) epilepsy. Those patients are treated with RNS System, when they have no more than two epileptogenic foci (epileptogenic focus is the source or starting point of seizures) and are resistant to more than two antiepileptic medications. The RNS System is thus only for medical prescription.

Main characteristics

The RNS Neurostimulator monitors electrical activity in the brain via the implanted patient leads and delivers therapy in the form of electrical stimulation, when the seizures begin.

Plain device consist of:

• RNS Neurostimulator, which is a responsive electrical stimulation medical devices (battery powered and microprocessor controlled) . Responsive electrical stimulation is a new approach to treating epilepsy and RNS System is the first device to provide it. . RNS Neurostimulator indicates and records certain patterns in the brain (electrocoticographic, ECoG patterns), which caused seizures. Then delivers short trains of current pulses through the leads to interrupt those patterns. Each stimulation can contain two bursts. Neurstimulator must be implanted in the skull together with leads. The Neurostimulator should work for about 2 to 3.5 years before battery power is drained.

• NeuroPace Leads are placed in the brain and are connected to Neurostimulator. One lead contains four electrodes. There are two kind of these leads. First, the Cortical Strip Leads are intended for subdural implant and are available in 15, 25 or 35 centimenters length. Four electrodes in leads are spaced 10 millimenters apart from each other. Second, the Depth Leads are intended for implant into brain. They are in four combinations - 30 centimeter length, 10 millimeter electrode spacing; 30 centimeter length, 3.5 millimeter electrode spacing; 44 centimeter length, 10 millimeter electrode spacing or 44 centimeter length, 3.5 millimeter electrode spacing.

• NeuroPace components and accessories contain several devices, for example cranial prosthesis or magnet, which might be used as suppressor of therapy or starter an electrocorticogram storage (records ECoG patterns), if it is placed over the implanted RNS Neurostimulator.

Patients also receive:

• NeuroPace Programmer, which contain a laptop personal computer with software developed by NeuroPace. It prescribe how the neurostimulator operates. Programmer might sets up recording ECoG patterns, perform detection analysis or communicate with NeuroPace Patient Data Management System (PDMS) via the Internet.

• Telemetry Wand permits communication with the programmer via a USB cable.

• NeuroPace Patient Data Management System (PDMS) contains obtained data from patient, who has access via the Internet. User must be authorized for using this system.

Purpose

Main purpose of RNS System is treating medical condition called epilepsy. The goal of the RNS System is not enhance human´s cognitive capabilities.

Company & People

• Frank Fischer (CEO NeuroPace, Inc.)

Enhancement/Therapy/Treatment

The RNS System is medical device to treat epilepsy. It was approved by Food and Drug Administration (FDA) in 2013 based on clinical studies. Those contain a Feasibility study, a Pivotal study, and a Long-term Treatment study. It is not designed for enhancing human capabilities, although it was demonstrates that RNS System has no adverse cognitive effect in epileptics. In several cases it come to some improvements in the cognitive capabilities. Although these findings are inconclusive for they result from very various data.

Epilepsy or “seizure disorder” is a chronic disorder, which cause unpredictable seizures all kinds, which might have all sorts of other consequences. Epilepsy usually has not simple or known cause. It might be caused some illness (for example brain tumors or Alzheimer’s disease, brain damage, abnormal brain development, genetic mutation (de novo mutations) etc.. But those causes might be very diverse. Epilepsy always arises from brain and is bound to sudden abnormal brain electrical activity. Clusters of neurons might fire signal faster than normal, which is as many as 500 times a second. That electric activity then cause seizure. This medical condition is considered, when individual has at least two or more unprovoked seizures separated by 24 hours. In the United States suffer from epilepsies up to 2.3 million adults and more than 450,000 children.

There are many possible triggers of seizures in epilepsy. The most common triggers are: missing medication, emotional stress and sleep deprivation. There exist more than 30 different types of seizures, but generally they are divided into two major groups – the focal seizures, which originate only in one part of the brain, and the generalized seizures, which come from both sides of the brain. These seizures might look very different, they might or might not cause loss of consciousness, or a muscle´s massive contractions. It might also appear for example in the intense feeling of déjà vu. Epilepsy has also many various types, for example the absence epilepsy, the frontal lobe epilepsy, the temporal lobe epilepsy (most common form in focal seizures) or the neocortical epilepsy.

Epilepsy has also some risk associated with the life-threatening conditions, such as status epilepticus and sudden unexpected death. However these cases are very rare. More common risks appear in connection with the injury during seizures.

With regard to the treatment of epilepsy, there are several possible scenarios. Epilepsy might be treated with medications (for example, Carbamezepine, Diazepam, Lorazepam, Topiramate etc.), diet (a hight-fat, very low carbonhydrate ketogenic diet), surgery (only if focal seizures persist after at least two medications or if it is identifiable brain lesions) or devices just like the RNS System. There are some different possible devices to treat the epilepsy, for instance, the Vagus nerve stimulator (approved by the FDA in 1997) or the experimental devices not approved by the FDA: the trigeminal nerve stimulation or the transcutaneous magnetic stimulation.

The treatment with the RNS System provides responsive cortical stimulation via neurostimulator connected to depth or subdural cortical strip leads. They are placed in the brain based on seizure focus. The neurostimulator continually scans electrocorticographic activity, detects abnormal activity and provides stimulation. The physician regulates and optimizes the parameters for each patient individually. It always depends upon where in the brain is the focus of epilepsy. Seizures might come from different cortical location, that include temporal, frontal, centroparietal, or occipital lobe regions. But the RNS System is adjust only for at the most two foci of seizures.

So the treatment with the help of RNS System is not intended for everyone. The patient must fulfil several conditions: he must have the focal (partial) seizures, have average three or more disabling seizures per month (over the three most recent month), and he have to be resistant to the medications or diet (drug resistant is in the case of RNS System defined according to ILAE as a failure to control seizures after two seizures medications).

Ethical & Health Issues

The use of RNS System is a relatively severe intervention in the brain and thus involves several health risks.

First of all there are some risks associate with surgery to implant the RNS Neurostimulator and Leads: post-implant infection (7%) and bleeding in the brain or under the skull because of the implant (4.7%). Those risks are comparable to other surgical procedures to treat epilepsy. Some other risks are associated with psychiatric symptoms (39.8%), changing in seizures (16%), and seizure related injury (49.2%). After about 2 or 3 years of using, the Neurostimulator have to be replaced with the new one, so the patient must get through another surgery. However the second one is not so dangerous, because the doctor will not have to do any surgery on the bone.<ref name="NeuropaceSystemPatientManual/">

The implanted devices also might negatively interact with another medical procedures, such as Computed Tomography or MR (magnetic resonance). It might also cause allergic reaction, skin erosion (around the Neurostimulator), lead migration (move from their desired implant location) etc. There always remain a risk of failure the RNS devices.

Serious risk might also come out from unknown effect of long-term brain stimulation. This conclusion support as well study conducted by Loring, Kapur, Meador and Morrell.<ref name="Differential neuropsychological outcomes following targeted responsive neurostimulation for partial-onset epilepsy">LORING, D.W., KAPUR, R., MEADOR, K.J., MORRELL, M.J. Differential neuropsychological outcomes following targeted responsive neurostimulation for partial-onset epilepsy. Wiley Online Library [online]. Available online at: http://onlinelibrary.wiley.com/doi/10.1111/epi.13191/epdf (Retrieved 6.11.2016) It is probably too soon to determine exact effect of the brain stimulation. The study for long time effect of the brain stimulation is still under way and the estimated completion date is May 2023. (https://clinicaltrials.gov/ct2/show/results/NCT02403843)

Some danger might arise also from hacker´s attack. The device interacts with the programmer, which is possible to replicates and then operates the Neurostimulator. But according to Frank Fisher, the CEO of the NeuroPace, it is very unlikely due to the fact, that it is significantly difficult and there is neither a reason for someone to do that. (http://spectrum.ieee.org/podcast/biomedical/bionics/neuropace-controlling-epilepsy-with-a-brain-implant)

On the other hand there are clear benefits of the RNS System. It was demonstrated that the RNS System significantly reduce epileptic seizures. According to clinical studies (Pivotal study – 191 subjects and Feasible study – 65 subjects), treatment patients come to the monthly reduction in seizure frequency averaging 37,9% compared to a 17.3% reduction in the Sham group (control group). (http://www.accessdata.fda.gov/cdrh_docs/pdf10/P100026B.pdf, s.66)

According to the FDA:

“Given the available information above [clinical studies], the data support that for the following indications for use the probable benefits outweigh the probable risks.” (http://www.accessdata.fda.gov/cdrh_docs/pdf10/P100026B.pdf 67)

So it is clear that the RNS System is risky, but at the same time it helps people with epilepsy to reduce seizures. It still does not help every patient with epilepsy, because the RNS System is designed only to certain type of the epileptic condition.

However according to Thomas and Jobst the RNS System might not be as effective in seizure reduction as epilepsy surgery. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598207/) On the other hand, epilepsy surgery is not always appropriate for certain type of epileptic illness. The RNS System thus remains suitable alternative to treat epilepsy.