On September 17th the Stanford Parkinson’s Community Outreach presented a webinar on deep brain stimulation (DBS).  Jaimie Henderson, MD, Stanford Neurosurgery, discussed the Latest Developments in DBS Surgery as well as future enhancements.  Dr. Henderson spoke for about 50 minutes about how patients are prepared for DBS surgery, what patients can expect, and the DBS systems available.  Then, he answered questions for about a half hour.

Watch this webinar on the Stanford APDA YouTube channel here. 

For more information about DBS, the Stanford Parkinson’s Community Outreach Program has several excellent sources here.  

Before undergoing something as involved as DBS surgery, it is often helpful to hear about other people’s experience.  You can read about and watch DBS stories here.  

Now … on to our notes from the webinar.

– Denise 

___________________________________________________________

Deep Brain Stimulation – Latest Updates

Presenter: Jaimie M. Henderson, MD, Professor of Neurosurgery at Stanford University

Presented by the Stanford Parkinson’s Community Outreach Program

September 17, 2020
Summary by Denise Dagan, Stanford Parkinson’s Community Outreach

Neurosurgeons performing deep brain stimulation (DBS) surgery must hit a target (the subthalamic nucleus), about the size of a small lima bean, located deep in the brain with an electrode about the thickness of a pencil lead.  This used to be done using stereotaxis, a technique developed around the turn of the last century for surgery on animals.  Stereotaxis uses a head frame and imaging, developed in the 1940s, which allows proper positioning of the deep brain stimulation (DBS) electrodes.  
Having the stereotaxis frame applied to the head is an uncomfortable procedure requiring pins to be placed into the skull.  Even though most people become accustomed to the presence of the head frame after 10-15 minutes, there had to be a better way…

Frameless DBS surgery was developed in 2004 and approved for widespread use in 2006.  Performing DBS surgery without having to apply the stereotactic frame is more comfortable for the patient, especially since DBS surgery is usually done with the patient awake.  Frameless surgery is better for the surgeon because all the imaging can be done the day before surgery, rather than the morning of surgery, making planning of the surgery more leisurely and less of a time crunch.  The amount of time spent in the operating room and with fiducial (markers) in place is much shorter.

Steps to accomplishing frameless DBS (after patient’s candidacy for DBS surgery is approved):

• Preoperative visit – MRI imaging to identify location of:
  • structures in the brain where electrodes will be targeted
  • blood vessels to avoid during surgery

• Day before surgery – fiducial (markers) placement on the head 
  • local anesthetic
  • insert markers into the skull with thin 4mm screws (more comfortable than stereotactic frame)
• CT imaging
  • identifies location of markers to guide insertion of electrodes
• Planning (takes about 30 minutes)
  • neurosurgeon reviews MRI & CT imaging of markers to plan:
    • where to make incisions
    • path for insertion of electrodes
• Day of surgery
  • Registration / Aiming – tell the computer where your head is in space
  • Micro electrode recording – verify target placement
  • DBS electrode placement and testing

Imaging – Day before surgery
MRI imaging is obtained without markers to minimize distortion.  If the MRI was done with the markers in place, the image would be warped and inaccurate due to the metal in the markers.
CT imaging is obtained with markers for optimum accuracy.  CT has no distortions sometimes seen in MRI imaging.
CT/MRI image fusion allows the best of both imaging modalities:

• Tissue definition of the MRI
• High accuracy of the CT

Fiducial (marker) Placement – Day before surgery
[Two photos of part of the procedure to place markers.  This patient was the first Dr. Henderson did frameless DBS surgery for.  Frameless surgery was a necessity for this patient because she had a neck deformity that prevented proper positioning of the stereotactic frame.]

• 5 small skull screws inserted under local anesthetic
• Takes about 1/2 hour.
• Less discomfort than frame.  

CT/MRI Image Fusion – Day before surgery 

• Special software allows
  • overlay of both CT and MRI imaging
  • simulate insertion of electrodes in the brain to plan each DBS surgery
  • 3D model of the patient’s head with markers in place
• Planning a DBS surgery takes about 1/2 hour using this software

Registration – Day of surgery
In this step the surgeon touches an instrument with an infrared camera to each of the markers on the patient’s head.  This instrument translates the location of the markers on the 3D model to the actual location of the markers on the patient’s head.
The surgeon also attaches a reference apparatus to the patient’s forehead with a strap around the back of the patient’s head.  This reference apparatus allows the modeling software to keep track of the patient’s head movements so the markers in the modeling software move with the patient’s head in real time.
Once registration is complete, when the surgeon moves the pointer on the head an identical pointer moves in the 3D modeling software.  This allows the surgeon to identify the exact place on the patient’s head to make the incision, according to the plan made using the modeling software the night before.

NeXframe Tower – Day of surgery
The NeXframe Tower spreads the skin and holds it in place out of the way so the surgeon can drill the burr hole through the skull.  It is through the burr hole that the electrode will be inserted.  The NeXframe Tower also provides a platform onto which equipment can be mounted during surgery.  It also has a reference apparatus attached to it, making the system more accurate than a stereotactic frame.

Alignment – Day of surgery
The alignment device is attached to the NeXframe Tower.  The alignment device allows the surgeon to use the modeling software to align the aim point with the target according to the plan made the night before.  The surgeon can lock the alignment in place, so the path the electrode follows is the safest path to the targeted brain structure.
The micro drive also attached to the NeXframe Tower, allows the surgeon to advance the electrode into the brain microns at a time and listen to brain signals during the procedure.  Listening to micro recording is how the surgeon determines whether the electrodes are in the correct place.

Micro recording – Day of surgery

• Tungsten or platinum-iridium electrode 
• Electrode has a 1 to 10-micron tip [human hair is 70 microns]
• Objectives:
  • Identify individual brain cells – by differing firing patterns
  • Identify the subthalamic nucleus (STN) – very characteristic
  • Search for cells driven by joint movement – optimal target

[Video of surgeon using a paintbrush to stimulate the fingers on the right hand of a patient undergoing DBS surgery.  When the thumb is touched with the paintbrush there is a change in the sound on the micro recording.  That tonal change is the nerves of the thalamus responding to the touch of the paintbrush on the thumb.]
Since there was no tonal change when any of the fingers were stimulated with the paintbrush, the surgeon could tell the electrode was in the “thumb area of the thalamus.”  Surgeons can get very specific in their placement of the electrodes by this method, locating the face, arm, leg, etc.  
Surgeons can also find tremor-responsive cells:
[Video of a patient’s hand tremor during DBS surgery alongside a trace on a monitor showing the trace is synchronized with the hand tremor.]

Surgeons use several strategies to map the targeted structure in the brain where the electrodes will be placed.  The main one, in addition to paintbrushes on fingers, is to move the patient’s arms and legs to find movement-related cells in the thalamus. 

Movement-Related Cells – Day of surgeryThe surgeon makes several passes of the electrode through the brain to map the movement-related cells in the thalamus.  Software creates this map on several planes (much like CT or MRI scan slices) so the surgeon can determine which part of the thalamus the most effective placement of the DBS leads.  

Once the DBS lead is placed, they are tested to get the most reduction of Parkinson’s symptoms and ensure there are no intolerable side-effects.  
The patient is admitted to the hospital overnight and usually discharged home the next day.  

Pulse Generator Placement – Post operative procedures

• Usually performed as staged procedure (in a few steps)
• Generator placed 1-2 weeks after DBS lead implant
  • Procedure takes about 4 hours, which is usually exhausting for patients.
  • Stanford invites in a massage therapist to help the patient tolerate such a long procedure.
• Generator is activated 4 weeks after lead implant
• This delay allows for resolution of inflammation and tissue reaction.  
  • Although it is difficult for patients to wait, if these issues were still resolving while programming the DBS leads, there would be constant adjustments and reprogramming as the inflammation and any tissue reactions diminished.  

[Photo of a first-generation DBS, Medtronic SOLETRA single channel electro pulse generator and 3389 lead.]  To give viewers an idea of the size of the pulse generator and lead.  The Medtronic 3389 lead is still in use.  There are a couple successive generations of this device.
[Graphic of a man with the DBS device superimposed to show placement of the leads and generator through the skin.]  All parts of the DBS system are under the skin.  The generator/pacemaker is usually placed on the right side, just below the collar bone and over the pectoral muscle.  If you want it placed on your left side, discuss that possibility with your surgeon.

Current Generation DBS Systems
There are three manufacturers of DBS systems:

• Boston Scientific Vercise IPG
  • Smallest device currently on the market and Dr. Henderson’s preference for rechargeable DBS systems.
  • 15-year battery life (estimated, as rechargeable DBS hasn’t been in use that long)
  • Battery can last up to 3 weeks if unable to charge (conservative estimate)
  • “Zero volt” technology – if the battery completely discharges you can wake it up.
    • If Medtronic rechargeable battery is completely discharged, you must replace it.
  • Individual current sources – allows very fine tuning/programming of the device
    • apply electricity to any of the 8 contacts on the lead, and 
    • vary the amount of energy that goes to each contact.
  • Steerable stimulation – you can vary the current in different directions to avoid some potential side effects
  • Wider range of parameters – can program different frequencies at different parts of the lead
  • MRI conditional – 1.5 Tesla (field strength of the magnet) MRI scan okay under certain circumstances
    • The stronger the field strength, the higher the resolution of the images.
    • Most MRI machines are 3T.  1.5T are becoming less common.
  • [Image of the Vercise Gevia generator, with leads, patient programmer, and programming screen on a tablet.]
    • There are two types of leads: 
      • 8 linear contacts
      • segmented leads
    • Segmented leads have several contacts, each of which has three segments around the shaft.  Each segment can be on or off and have different levels of energy allowing for creative and precise programming of the system.
  • [Image of the Vercise Charging System.]
    • Place the wireless charger on the charging base until it is completely charged.
    • Then, place the wireless charger in a pouch over the patient’s shoulder so it rests over the generator.
    • The patient can be active while the generator’s battery is charging, about 10 minutes per day
• Medtronic Percept PC
  • Improved battery life compared to Activa PC (earlier generation)
  • Smaller, thinner and with more comfortable curved edges than Activa PC
  • Non-rechargeable – better for people who would forget to charge it or don’t want the bother
  • 4 contacts – apply energy to any or all, but
    • can’t adjust the amount of energy that goes to each contact.
  • Sensing capability of neural signals in future (no timeline available for this)
  • Future ability to do closed-loop stimulation (at least a year away, but not as long as five years)
  • Wider range of parameters
  • MRI conditional up to 3T – works with all MRI scanners currently available
  • [Image of the Medtronic DBS system, including the patient programmer and programming screens on tablets.]
    • The patient programmer is like a Samsung smart phone, so it is a familiar format for many users.
    • Using closed-loop stimulation will increase battery life and reduce side effects.
    • [Image of the patient programmer, including controls for battery life and preprogrammed settings for varying levels of activity (e.g. walking, talking, etc.)]
      • Patient can indicate when an activity begins, which starts a short recording of the DBS system for things like medication tracking, exercise, dyskinesia, on times, etc.  The recorded data provides movement disorder specialist more information to fine tune the DBS system and aid in medication adjustments.
  • In 1997 Dr. Henderson was involved in the first DBS trials in the US for essential tremor.
  • Dr. Henderson finds Medtronic’s rechargeable DBS system to be bulky and difficult to use.
    • Hard to get it aligned with the pulse generator.
• Abbott – not discussed

DBS Outcomes
Complications

• Hemorrhage – 1.5% 
  • Can look like a stroke
• Infection – 3-5%
• Stimulation side effects – common, especially during initial programming
  • Tingling, muscle contractions, double vision, speech difficulties
  • Can be mitigated by reprogramming

Common DBS Recovery Issues

• Fatigue – can last a few weeks
• Confusion – almost always temporary
• Headache – to be expected after surgery on the head and some loss of cerebral spinal fluid
• Impatience with programming – it can take a long time to maximize programming
• Rehab, or not?  
  • When you have been used to your muscles working in a certain way, some retraining can be helpful.

Results – reduction in Parkinson’s symptoms

• Tremor – 80%
• Rigidity – 68%
• Akinesia – 55%
• Gait – 54%
• Postural Stability – 60%

[5-minute video of a man with Parkinson’s, named Art.  First, he demonstrated how he managed to get around his home before DBS.  Art was then shown walking quickly and without assistance onto a stage for an interview about DBS with Dr. Henderson.]

Conclusions

• Subthalamic nucleus (STN) and globus pallidus pars interna (GPi) DBS can improve all cardinal signs and symptoms of PD
• Refinements in technique:
  • Improved targeting
  • Improved patient comfort
  • Improved outcomes
• Current generation DBS systems add exciting new capabilities, like closed loop/adaptive technology
• For more info call Dr. Henderson’s nurse: Erika Lim, 650-721-4936

Questions & Answers
Q. What precautions are being taken for DBS surgeries during Covid-19?A. Stanford is testing every patient before coming into the clinic.  Patients may also be tested before coming in for DBS surgery, as well.Staff does daily temperature and symptom screening.  Dr. Henderson has had a Covid-19 test, which was negative.  No patients have become Covid-19 positive after DBS pre-operative appointments or surgery. 

Q. Is there an advantage to waiting for a better DBS version to come along?A. I didn’t talk about Abbott’s DBS system because I haven’t worked with them.  I believe they are a bit behind, technologically.  I don’t know if there’s anything on the horizon with Abbott.  Boston Scientific and Medtronic have both pushed to get the latest systems out.  The FDA takes a long time to approve these systems and there’s nothing I know that’s super exciting that’s coming down the pike.  So, now is a good time, but these systems are just like other technologies where if you wait long enough there is some cool new feature in the next generation.  If the time is right for you and your neurologist agrees, I say go for it.
Q. Is there any age limit (either young or old) to having DBS surgery?
A. There is no age limit.  I have implanted DBS devices in people in their mid-80s.  I think 86 is the oldest I’ve done DBS for.  The older you get, the more likely you are to have complications.  That is probably not a linear correlation, but age clearly increases the likelihood of complications.  Some of Dr. Henderson’s patients with the worst complications have been in their 80s.  If someone over 80 wants DBS I have a very careful conversation with them about the timing of the surgery and whether they will be able to tolerate it.

Q. Is there a time limit after diagnosis that is optimal for DBS surgery?A. The timing of when to have DBS surgery after diagnosis is variable.  It depends on the individual.  The average is probably about 10 years after diagnosis.  The reason I think that timeframe is the average is that is when people often begin to develop side effects from the medication, or the medication is no longer as effective.  There have been studies looking at earlier intervention by DBS.  I don’t know that there is any clear recommendation that people should have DBS early in the course of Parkinson’s progression.  If I developed Parkinson’s tomorrow, in my mid-50s, I would begin medication, but I wouldn’t wait very long.  Early intervention has never been proven to be more effective, but I believe the brain learns to be parkinsonian, so to intervene early on is often better.  That has never been proven to be the case, so it is an individual choice between the patient, the neurologist and with the care team.

Q. Does Stanford do awake and asleep DBS surgery?
A. Yes.  Dr. Henderson has experience with both techniques.  There’s no clear benefit to one vs. the other in the literature.  To do such a study would be difficult and probably not show much difference between the two outcomes.  Dr. Henderson’s slight preference is to do the surgery while the patient is awake.  That is because he can get feedback during surgery as to what side effects the patient will experience and adjust the position of the leads to minimize those side effects during the procedure.  During awake surgeries it is common to make several passes through the brain to adjust the position of the leads based on talking to and testing the patient.  During asleep surgeries it is also common to make a few passes through the brain to adjust the position of the leads based on the imaging done during surgery.  So, either way is good.

Q. You don’t see much of a difference between the outcomes in patients between asleep or awake DBS surgeries?
A. Right.  My own intuition about it is that there really is no difference between whether patients are asleep or awake during DBS surgery.  A review article of all the literature about outcomes between the two types of surgeries found no difference in outcomes between the two.  I personally prefer the awake version.

Q. Please speak about the screening process to determine who is a good candidate for DBS surgery.
A. At Stanford we have patients undergo a pretty vigorous screening process.  
First, you do an ON/Off exam.  You come into the clinic one day on medications and another day off medications.  That way, we can see your symptoms at their worst and best.  That differential gives us a good sense of whether you really have Parkinson’s disease.  Sometimes, people may have a parkinsonism or Parkinson’s plus syndrome.  If medications don’t have much of an effect on your symptoms so that when you don’t take them there isn’t much difference in the severity of your symptoms, that gives a good indication that maybe you don’t have Parkinson’s.  It also tells us your medication response.  There is a bit of a correlation that if a person has a good medication response, they will have a good DBS response.  
Then, we do neuropsychological testing.  That gives an idea if there will be any changes in memory, verbal processing, multi-tasking, or visual-spacial skills.  If you already have some problems in those areas, we may make those worse with surgery.  If that is the case, you may want to think very carefully about having DBS surgery. 
Once we have all that information, we review that in a multi-disciplinary surgical review committee.  On that committee we have neurosurgeons, neuropsychologists, speech pathologists and others to help decide about whether it is advisable for someone to have DBS surgery.

Q. How effective is DBS on affecting freezing of gait?
A. This is an area that Dr. Bronte Stuart at Stanford is really interested in.  She does some testing called dynamic posturography.  With that that is a balance machine, gait testing, etc.  There are several different types of gaits in Parkinson’s.  There are certain types of those that, if you undergo the dynamic posturography, we can sort out the one that will respond best to surgery and not.  
Early in the course of the disease DBS works pretty well for freezing of gait.  This is where the closed loop system comes in because there are certain frequencies associated with gait freezing so we may be able to do better at improving freezing with closed loop.  Later, it tends to work less well.  We can reduce tremor and rigidity but there are some things aren’t as well treated later on and one of those is gait.  We’re starting to learn more about who’s going to respond well and who isn’t.

Q. Do you have an idea or guess when the closed loop system might be approved?
A. There’s an ongoing multi-center study that’s looking at closed loop neurostimulation.  Once that concludes we may see approval.  It is easily a year off at a minimum, but not as long as five years.

Q. A listener is having trouble enunciating.  Does DBS help with control of the facial muscles?
A. Unfortunately, no.  Speech is one thing DBS doesn’t help.  It’s important to know that DBS doesn’t help with blood pressure and other non-motor symptoms like sleep issues, cognitive processing that don’t respond to DBS. 

Q. Please talk about reduction of medication after DBS.
A. Globus pallidus interna (GPi) and the subthalamic nucleus (STN) are both accepted targets for DBS.   One of the differences between those is that with STN DBS we can often reduce medications.  Often as much as 50-60%.  With GPi DBS we can reduce medications, but not as much.  That is one advantage of STN.  On the flip side, GPi may be associated with fewer cognitive side effects – although that has never been proven, it is just a hunch.  When we have someone for whom we are worried about cognitive issues, we may choose a GPi target, knowing we will have higher medication doses because sometimes it is higher doses of medications that are causing cognitive problems.  It is a real chicken and egg problem.  This is why we have an interdisciplinary team to help tease these things apart and choose the best target for the patient.
Moderator:  Some people pursue DBS with the goal of reducing medications.Dr. Henderson:  There are cases where we can take people entirely off medications.  They do that a lot in Europe after DBS.  My own bias is that a little bit of medicine after DBS works best. 

Q. Have you seen behavioral changes after DBS?
A. Yes.  It is uncommon, but some people have cognitive changes that result in behavioral changes.  Some have been as bad as to be diagnosed with dementia, but that is very rare.  Over the years we’ve gotten better at targeting and improving the procedure so that happens less frequently, but that can still happen.

Q. Is DBS reversible?
A. We believe DBS is reversible.  Nobody has ever has them taken out, so we don’t know for sure.  There is the rare case when the DBS leads get infected and we must take the leads out, treat with antibiotics, then reinsert the leads.  There have been some cases where someone will say they have slight speech issues with the leads in place, but those issues usually resolve with time. 

Q. Please talk about focused ultrasound.
A. We are doing focused ultrasound for Parkinson’s tremor.  It won’t help other symptoms of PD.  We can only do it on one side.  It can be effective for tremor.  Stanford is also participating in a study of GPi ablation using focused ultrasound, so we’ll see if that turns out to be effective.  It is a single treatment.  The downside is that if you have a side effect it is permanent.

Q. Is the presurgical testing process happening with telemedicine?
A. We can do the initial assessment via telemedicine.  To really assess you thoroughly we have to be able to feel rigidity and interact with you and get to know you. 

Q. How about programming by telemedicine?
A. Medtronic is working hard on having a telemedicine method for programming DBS.  Medtronic developed remote programming for pacemakers years ago.

Q. What is the waiting list like?
A. Not very long.  We can get somebody scheduled in a month, or two.

Q. What happens if the patient suddenly moves while you’re doing surgery?A. In over 700 DBS surgeries I’ve never had that happen.  There are only a few minutes during the entire procedure during which we need to ask the patient not to move, but it doesn’t last long.  Through most of the procedure the patient can shift their position and it isn’t a problem. 

Q. If I have DBS, how long should I plan to take off from work?
A. I tell people 4-6 weeks.  I often hear patients tell me they won’t need that much time to recover, but it is brain surgery.  You might want to take a little time to recover.