Pros and Cons of Four Different Brain Surgeries For Parkinson’s Diseases

“We cannot change the cards we are dealt, just how we play the hand.”
– Randy Pausch, The Last Lecture

Well, my time has come. Seven years and three months post diagnosis and I find myself contemplating which kind of brain surgery to get to treat my form of Parkinson’s disease. It’s a stage of life no one wants to reach, especially at my age (36), but here I am. While it is a scary thing to have to consider, I find myself grateful to be going through it in this time and in this place. Let me explain…

Other than my age, I seem to have a pretty classical type of Parkinson’s Disease. Tremor and stiffness when medication is Off, dyskinesia (involuntary writhing) when On. A little ironic because I just co-wrote a whole book arguing that there is so much variability in this disease that calling it a single disease is a misnomer holding the field back (a book which btw, just two days ago won the 2021 PROSE award in neuroscience). Even my timeline is pretty typical, 7+ years post diagnosis is right around when one would expect to have to start really thinking about this decision. Funny how life goes.

Also, despite all the talks I have given harping on the slow pace of progress in medical science, only one of these options (DBS) would have even been an option when I was diagnosed. A welcome reminder that though this field can seem at times like it is just spinning itself in circles, progress is happening, you just have to stand back a little sometimes to see it.

I also happen to be lucky enough to be in Toronto where the first three procedures were in part developed and are either available or being tested, and the fourth is a short flight away to a clinical trial center. Much of the world still doesn’t even have access to the basic medications developed 60 years ago! So, like I said, I’m very grateful to be where and when I am. (On that last note, if I can ask a favor of those reading this. Consider supporting this launch of a great new charity trying to bring those basic Parkinson’s medications to people in need in Africa.)

But getting back to the topic at hand. Which of the brain surgeries available to me should I go for? Well, I’ll save you the suspense and tell you that I honestly don’t know which way to go. I thought of calling this piece – Knowledge, the Double-edged Sword, or something profound like that. For almost half a decade now I have been on a pretty committed quest to find out as much as I could about therapies in the pipeline so that, in part, I would be better prepared to make decisions like this. But, I actually find myself a bit paralyzed by all the information I have. At times I wish I could just close my eyes and blindly pick one because, as I hope you will see below, there are no easy answers here as each option is far from an ideal solution.

Well, what can you do? Life itself is a gamble. At some point I’ll make a decision, for now I hope that by laying out the choices I have I might spark some useful discussion on the topic that might help myself and others make this decision. Here are the four I am considering:

  • Deep Brain Stimulation (DBS)
  • Cell Replacement Therapy (CRT)
  • Focused Ultrasound (FUS)
  • Gene Therapy (GT)

Now, there are some things to keep in mind before I jump into them. This is intended as a high level overview. I have stuck to what I think are the top 4-5 pros and cons for each. There is a lot of nuance and caveats to what I am going to say that I have glossed over. Each technique below has a range of different options that change some of the variables, they can be tweaked to different targets in the brain, and some have different methods being tried or being developed that skew how each is considered. Also, I feel like I have done my homework on DBS and CRT, but have yet to do so properly for FUS and GT. However, I am hoping that people out there might help me fill in any gaps that I leave or correct any glaring mistakes that I make. So please feel free to make any suggestions in the comments section below. Would love to see other people’s top 5 pros and cons list for each.

But enough babbling, here are the options.

Deep Brain Stimulation (DBS)

Previous Interviews – World renowned authority Dr. Alfonso FasanoFirst hand account from 23andMe’s Dr. Paul CannonPartner perspective from Lisa Vanderburg
Previous Writing – Restorative Therapies on the HorizonNeuromodulation and the Future of the BrainThe Future of Parkinson’s Disease Therapies.


  • The most known knowns. Two decades of clinical experience, over 100,000 surgeries performed worldwide.
  • Adjustable. Some of the parameters can be tweaked to personalize the therapy and adjust to changing conditions over time. The leads can even be taken out and reinserted if needed.
  • New adaptive software may be available soon and will be applicable to current generation of devices. Should allow for even more tweaking and more prolonged benefit.
  • When done properly it has a fairly predictable and sustained symptomatic benefit for those that qualify.


  • Does not slow disease progression.
  • Common long-term side effects include speech and vision problems.
  • Pretty invasive surgery, they don’t use the words ‘deep brain’ for nothing. Recovery time can take anywhere from a couple weeks to a couple months.
  • Having DBS excludes one from participating in many clinical trials.
  • Though it can be removed and/or reinserted if needed, some of the damage and effects from the surgery may be permanent.

Cell Replacement Therapy (CRT)

Interviews with world renowned authorities – Prof. Jeanne Loring, Prof. Roger Barker, Prof. Lorenz Studer.

Expert Survey

Previous writing – CRT for Parkinson’s and the Future of the Brain, IPS Cells and the Future of the Brain.

(Note: New CRT trial just got FDA’s IND clearance three weeks ago. Expected to start soon.)


  • Once the transplanted cells graph they should provide a steady release of dopamine in the part of the brain where the loss is most acute for decades.
  • New and improved procedures and methods should make this generation of trials much safer and more effective than similar trials of the past. (Highly recommend Dr. Curt Freed’s book on past trials Healing the Brain)
  • Should have sustained benefit for the cardinal motor symptoms of the disease (tremor, rigidity, bradykinesia).
  • Transplants in non human primates using new procedures and techniques indicate the therapy is safe and effective.
  • Very early data from trials in Japan show the new surgical procedure is safe in humans. (Great overview of the new trials from the lead investigator in Japan Prof. Jun Takahashi.)


  • Expected to take 1-3 years post operation for the cells to graft and start releasing dopamine.
  • Not expected to slow the disease or treat non-motor symptom.
  • Requires going on a year of immunosuppressors. Though this issue will be addressed in autologous CRT, which should start clinical trials in the next few years. (Outstanding piece from one of the pioneers of this, Dr. Jeanne Loring)
  • Risk of runaway dyskinesia. (Though new technique may mitigate this)
  • More clinical data needed to better understand who this would work best for.

Focused Ultrasound

I have yet to see any really good and widely accessible reviews on the subject. Though I did mention FUS in a recent post, it was not what the article was about but there is some good information tacked on to the bottom from Dr. Julian Lo. (Here’s hoping the good people at SoPD tackle this topic in the not too distant future.)


  • Non-invasive surgery that is usually relatively quick and painless.
  • Immediate results.
  • No risk of infection.
  • Potentially has a multitude of uses with preliminary signs of efficacy in treating tremor, bradykinesia, and rigidity (Again, see links at the bottom of this piece for more). Also could be used to open up the blood-brain-barrier to allow more classes of medications to get to the brain.
  • Approved and very effective for treating essential tremor.


  • Creates an irreversible lesion.
  • Can not be tweaked or adjusted.
  • Typically only done to one hemisphere of the brain at the moment.
  • Lack of long-term follow up data.
  • Larger studies needed.

Gene therapy

Previous writing and interviews: Interview with Prof. Gao Guangping, Interview with Liz Parish,

For an excellent review on gene therapy and the latest trial news see this post from the Science of Parkinson’s.


  • Can target mechanism believed to play a role in disease progression. So, in theory, could slow or stop disease.
  • Promising approaches include precision therapies for people with specific mutations as well as potential replacement therapies for proteins that are under expressed or may have lost some functionality.
  • Permanent alteration of genes in targeted cells. Meaning any benefits may be long-lasting.
  • One-time stereotactic surgery similar to the one for CRT which should be less invasive than DBS.


  • Greatest number of unknowns (and unknown unknowns).
  • Very little human clinical data at the moment.
  • May take months to know if there is any benefit.
  • Permanent alteration of genes in targeted cells. Meaning any negative consequences may be long-lasting.

Well, there they are. But, it actually gets a little more complicated than that. There is also the possibility to pick more than one of the options above. GT, FUS and CRT have yet to pass clinical trial, until they do they all list other surgical brain procedures as exclusion criteria in their trials. If they pass the clinical trial phase (which mind you will take several years), then they may once again become an option. DBS is widely approved and should still be on the table regardless.

Also this is not an exhaustive list of all options available, these are just the ones I am considering. And of course, there is always the option to do none of the above and continue experimenting with tweaks to medication and lifestyle choices.

Regardless, as I hope you can see, this is not an easy decision to make. Which leads me to a challenge for the Parkinson’s disease field. There are more of these advanced therapies being tried than ever before, going forward many more people are going to face this same question. A question that is only going to become more complicated as more and more of these therapies either enter or pass clinical trial. (As seen in this brilliant paper giving an overview of therapies in development.)

So the question is this – how can we develop a method to weigh the advantages and disadvantages of each therapy against each other for each patient? How can we systematically answer this question for each individual such that the most people get the best possible outcome?

Finally, thinking back to the quote I started with…

“We cannot change the cards we are dealt, just how we play the hand.”
– Randy Pausch, The Last Lecture

While that is true to an extent, everyone in the Parkinson’s community can play a role in ensuring we get more cards in everyone’s hands. Whether that be by participating in trials, supporting research, doing what we can to get more (and improved) trials in the pipeline, or ensuring better access to care for patients so they can delay (hopefully indefinitely) having to make this choice and/or just have better outcomes down the road.

Disclaimer: I am not a doctor and do not have any formal medical or scientific training. None of this is meant as medical advice. Always consult with a healthcare professional before taking any actions. Also important to stress that in some ways the question I ask is still hypothetical as only DBS has actually passed the clinical trial phase and widely available.

Also for more on the latest developments in therapies for Parkinson’s disease and what to expect for the rest of 2021 I highly recommend the latest blog entry from The Science of Parkinson’s.


  1. Great summary! I found myself in the same situation, with the same feelings toward it, a few years ago simply deciding among DBS choices. I told competing reps I would evaluate their companies and select my brain surgery based on which company was a superior corporate citizen. That alone seemed to make a difference to at least one of the companies. The following year I spoke to 600 people at their annual corporate conference. Our faulty brains actually have significant value not only to a world looking to fix it, but to a world possessing same, at a minimum. This tactic may not be a healthy one for a marriage, least not initially anyway!

  2. Very helpful summary. With regard to FUS, however, I think it’s important to note that there are at least three distinct forms — two of which are FDA approved and available in the United States.
    I am copying part of a post by Lena McCullough on the Focused Ultrasound for Parkinson’s Disease Facebook page. Lena has now undergone PTT, a form currently not available in the United States, on both sides of her brain. In part, Lena writes:

    There are three surgeries for Parkinson’s. PTT (pallidothalamic tractotomy) in Switzerland is the only one that can be done on both sides and treats tremor, dystonia, dyskinesia, bradykinesis and rigidity and results hold for at least six years (ie halts progression of symptoms). Thalmotomy in the US and other countries is just for tremor dominant PD and is FDA approved and can only be done on one side. Pallidiotomy is US is for dyskinesia and is in trials in the US, Canada, maybe UK but seems to treat different symptoms as well, also only one side.

    1. Thank you James. I agree that FUS is not specific enough, but a similar argument can be made for the other techniques. As stated, this was a high level overview. If I were to do a more focused (pun intended) review on specific options I would probably compare and contrast:

      Autologous iPSc CRT
      Closed loop STN DBS
      FUS PTT
      AAV9 GBA GT

      GT is probably the most amorphous of the techniques, so much variability in application. And then there is also the ability to combine these techniques in different ways. I imagine in the future we may have a long menu of different combinations of differing techniques to choose from.

      The question at the end of the day, and where I think the most constructive discussions can be had, is how to figure out which technique is right for which individual as there will likely be no one size fits all approach.

  3. I wish you the best of luck in choosing the right treatment. You have so many years to enjoy life. I am 77 and was diagnosed at 73, but I’m sure that I had it for more years. Supposedly mine is a mild case but I’m starting to see more scary synproms.I hope you will be able to get relief so you can enjoy life to its fullest.

  4. Very comprehensive review and comparison. I have a slight different opinion about CRT which is not comparable with the other three interventions. CRT restores the function of the to some extent whereas the other three interventions manipulate the brain signals associated with the substantia Nigra. It will be interesting to see if CRT can be carried out after DBS (if DBS fails to provide relief)

  5. Congratulations on your book’s prose award, Benjamin, and thanks for another thoughtful post. I wish you as much clarity as possible when making your decision. I’m in my 13th year with PD and had DBS 6 months ago at 65 and have only good things to say about the results. But there’s a very big difference between choosing an intervention at age 36 and age 65, not the least of which is that I didn’t feel I had time to wait to see what else would come around. I will add that I walked out of the hospital 24 hours after the surgery and other than the night of sleep I lost (because…hospital…) there was no memorable recovery time like there is with other kinds of surgery.

  6. I was diagnosed 20 yers ago (at the age of 51) and underwent DBS surgery 6 years ago. Before the surgery, I went to a presentation by the Metronics Rep. He was a bit misleading with his optimistic description of the long term benefit. “when your PD gets worse, you just turn up your stimulator”. My most recent appt, my Neurologist,he said that my DBS was probably at its optimum setting. Yet I am taking Stalevo every 2 hours and falling at least 3-4 times a day. DBS is great for tremors but not so much for balance and gait. With all said, would do it again?? ABSOLUTELY. I shudder to to think what I would be like without it. But I would be remiss not to give you as realistic view as possible. However, remember that this solely my experience and PD presents differently in each individual. Plus, I am a 72 year old woman that has been fighting this disease for 20 years and still participates in Rock Steady Boxing which ain’t bad 🙂

  7. I just had bilateral MRg FUS PTT done (13 months apart) in Solothurn, Swtizerland at the SonoModul Clinic, which is the only place that uses this target, i.e., the Pallido-Thalamic Tractotomy. Check this out if you haven’t already decided. Also, there is a Face Book page called, “FUS for Parkinson’s.”


  8. My husband’s Parkinson’s disease is totally reversed! all thanks to tree of life herbal clinic visit (www .treeoflifeherbalclinic .com)

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