I hate articles like these in "regular" newspapers as opposed to specialized journals.
My mom lost her sight and, to this day, asks me about updates for an electronic eye she once read about. The product existed, yes, but the company abandoned it [1] before it could be even remotely affordable and left existing patients one software bug away from the dark. Still, having no other hope other than a bionic eye, my mom regularly keeps asking me for news.
I also know someone living with Parkinson and I pray they don't see this article - the last they need is an article promising that someone, somewhere has "cured Parkinson" but with a procedure they may never get because it's not available in their country, it's too expensive, and/or they may not qualify for it. In my opinion "there's no cure" is easier to live with than "there is a cure, but you can't have it".
One time I was really hyped about so-called "molecular surgery"[0] - a technique which promised forming cartilage tissue - so the septum, tendons or even the cornea - with little effort and, crucially, no heating. The research looked as it was in an advanced stage with demonstrations on live specimens and whatnot.
At same time, this has real effects, so I wouldn't be so dismissive of it. I actually know a parent of a friend who had the whole "deep brain, computer in chest, app to adjust it" set up installed somewhat recently (not sure if exactly the same as article), and it's a game changer for her. I mean the difference is huge, and quite striking that it can be activated/deactivated at will and the effect so dramatic.
Bear in mind that the placebo effect from DBS for Parkinson's is 39% of the active treatment, so you can't really tell much from a single unblinded patient report.
"All results had a high risk of bias and the certainty of the evidence was very low for all primary outcomes. The information size was insufficient when assessing all cause mortality. Meta-analysis showed that deep brain stimulation increased the risk of serious adverse events, mainly because of an increased risk of perioperative complications, such as cerebral haemorrhages and postoperative confusion, and events related to hardware, such as infection at the stimulator site, dislocation of the device, or reoperations. Meta-analyses indicated that deep brain stimulation might reduce symptoms specific to Parkinson's disease, but the assessments of disease specific symptoms had several methodological limitations."
So, it's an interesting treatment, but more evidence is needed before we can conclude that it is actually helpful.
That placebo effect study is 20 years old. Most of the included trials in the meta analysis are 10-20 years old as well.
The BBC article is about a new device. The evidence base may be slim but the technology looks to be improving. I look forward to seeing new clinical trial results on modern DBS systems.
Has it been contradicted anywhere? I don't see any other studies that have looked into it.
>Most of the included trials in the meta analysis are 10-20 years old as well.
The meta-analysis is from less than 6 months ago, and looked at all the studies available, which cover a range from recent to 10-20 years ago. That is normal for a meta-analysis, so I'm not sure why you're making it sound like it's out of date.
>The BBC article is about a new device.
Yes, there seems to be one study underway, which is still recruiting:
>>That placebo effect study is 20 years old.
>Has it been contradicted anywhere? I don't see any other studies that have looked into it.
Somewhat tangentially, and not specific to Parkinson's or DBS, but placebo has been getting stronger for at least some classes of treatment. E.g.:
Tuttle AH, Tohyama S, Ramsay T, Kimmelman J, Schweinhardt P, Bennett GJ, Mogil JS. Increasing placebo responses over time in U.S. clinical trials of neuropathic pain. Pain. 2015 Dec;156(12):2616-2626. doi: 10.1097/j.pain.0000000000000333. PMID: 26307858.
Walsh BT, Seidman SN, Sysko R, Gould M. Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing. JAMA. 2002;287(14):1840–1847. doi:10.1001/jama.287.14.1840
So I would not be surprised if placebo got stronger in this area as well.
If DBS itself is not a viable treatment for Parkinsons, as the study suggests, then no amount of technological improvement of DBS-based devices will change that.
It would take a lot more than an old, low-confidence set of trials (which is how the meta-analysis describes its inputs) to convince me of your premise.
I'm (genuinely) quite surprised by that. A family member had the procedure a year ago and the difference is so immediate and dramatic. Thanks for the links
so the short story is - at the moment, the device is basically doing power spectra analysis w/ FFT and such from local field potential recordings, and only turning the device on when it's detecting a strong ~20 hz band.
Helps w/ motor symptoms only - does NOT address any dementia/psychosis symptoms.
I would say, maybe the other way around - gait is very much a cognitive task (think of all the compute power w/ reinforcement learning to get a robot to stand up or balance a stick). but it is probably a self-reinforcing cycle.
That being said, from DBS clinical series - we know the technology helps w/ limb rigidity, bradykinesia and tremor. It helps initially with gait but sometimes the gait declines despite DBS and meds, say, roughly a decade after implant (even as the upper limb symptoms stay well treated).
My father had Parkinson's and in my experience the lack of agency he had when trying to do daily tasks even other than walking was a real mind-killer. He was dependent on my mom (and later caretakers and skilled nursing facility) to do anything like feeding, toileting etc. Obviously when he was later bedridden mostly due to the inability to move, it probably drove him even more crazy.
He decided early on to never get this treatment and I feel sad to this day that he couldn't have lived a happier last few years.
My father was disqualified from getting DBS due to concerns around amplifying his dementia. Had I known then what I know now, I would have gladly signed a waiver, because DP has completely destroyed his body and mind.
Disagreed, exercise of all kind is known to help with neuroplasticity, complex movements such as dancing and compound lifts even more so. I can easily see how being unable to do any of those things could at least contribute to mental decline.
As I understand the medical science, it all comes down to stimulating the brain and there is no harder stimulation than physical feedback. Lack of mobility means lack of the biggest source of brain stimulation, which leads to accelerated degeneration.
movement/neuroplasticity/physical stimulation absolutely helps - hence PT, exercise classes, etc have being an important part of treatment
My point is, though - the onset of decline in gait ability typical of Parkinson's patients, is a sign of a decline of cognitive ability because the ability to perform gait and all the inherent brain commands associated with gait, is very much a cognitive function as much as it is motor.
One can argue that good DBS therapy by helping keep patients active and engaged does, at least indirectly, help cognition in that sense. BUT - it is consider not to directly treat Parkinson's dementia if a patient is unfortunate enough to come down with that aspect of disease. i.e. it's not like we can switch the device on or fiddle around w/ the programming and the patient's cognition directly improves from the brain stimulation itself.
Keep in mind that paper cited isn't really the clinical trial that shows improvements in symptoms. It just shows their device works and can record LFP properly....
The actual clinical results so far shows that the gizmo with recording is not necessarily worse than DBS devices that don't have recording ability. I don't know if they published those results in a paper yet, but it was shown in poster form at MDS congress in Philly.
not sure - but it will likely be quicker because the software is sort of already built into current generation Medtronic devices. They are not trying to approve a whole new device, probably just the software that switches the device on/off.
That being said, there are also reasons at the moment (better imaging support/stimulation programming abilities) to sometimes choose a competitor device over Medtronic (namely Boston Scientific)
Better DSP/ML techniques might make this more effective, but uh...the Parkinson's research community has never been known to be great at math...just saying
our understanding Parkinson's is that it can be described as a control system issue. The part of the brain affected (at least initially) by the disease is part of a network (the basal ganglia/cerebellar network) that evaluates environmental inputs and generates the output necessary for fine/precise motor control, amongst other things. So a Parkinson's patient cannot plan their movements as well and the main symptoms are slowness of movement, abnormal limb tone; yes tremor as well but the 1st 2 are what cause the most issues for most people (keep in mind, not everyone follows the textbook so there are subtypes that have more cognitive issues, i.e. hallucinations, executive dysfunction etc)
The stimulators seem to affect the signaling in that circuit (they are targeted by the implanting neurosurgeon to specific nodes in that circuit as best as targeting surgical technology allows) that seem to restore the ability to move well. Exactly why, no one knows. It's just a dumb signal at around 1-4 milliamps at 130-180 hz at those specific spots but presumptively it corrects some aberrant behavior in the whole network. It was observed in the '00s that recordings taken during or right after surgery often showed a strong peak at ~13-35 hz (give or take, but roughtly around 20 hz) during the disease state, and that's what Medtronic has been trying to target w/ these devices.
Of note - there actually isn't a system-wide dopamine "deficiency" - dopamine in general is fine for most of the body, it's just that the particular part of the brain that is affected happens to use dopamine as its signaling neurotransmitter so it's deficient in just that connection within the network.
Dementia is theorized to happen when the abnormal brain process spreads to other parts of the brain other than the substantia nigra (see the Braak hypothesis)
My company makes DBS devices. There are a lot of other possible indications like migraine and others where it could help too but progress is very slow. You can't "move fast and break things" with brain implants.
My Mom has had the surgery twice now, once for the left side and once for the right. Brain surgery is no joke. It takes a long time just to recover from that. And Parkinsons is a disease that will continue to get worse. The surgery adds quality of life but it will not stop or cure Parkinsons. The surgery is a wonderful option but it isn't a cure.
The logic is: we have no idea but must do something, surgical implants are something, let's do brain surgery and implant something!
My father died at the age of 82 from late stage Parkinson's, never got dementia but eventually whatever neurons in the brain control movements, they fail to do so not just for movement but also vegetative processes such as swallowing and gut transit so ... one cannot live without that. Also those neurons die so that can't be good. No amount of waves and vibrations can compensate for dead brain tissue.
Hard pass on the calomel. Come back when you actually got something that works.
I mean, this feels more like electroshock therapy to me, but that's made a big comeback and is apparently considered relatively safe and somewhat effective.
Bloodletting has some conditions it's actually appropriate for too.
Not sure mercury poisoning is going to turn out to be safe and effective anytime soon, though.
I'm not advocating for this, but if people are going to do it with informed consent, might as well collect proper data to try to determine if it objectively works. Snake oil that works, if it actually works, is something that works.
The parkinson brain surgeries work. They have proven to have worked. They wouldn't do them if they didn't work. They work almost miraculously. The problem is that Parkinson gets worse, you can't stop it. So the surgeries will work for a specific complaint but new symptoms will eventually arise.
Is this an all-new device, or a new software profile that can be applied to existing DBS controllers?
I know someone getting a DBS next month and the implanted controller gets replaced about every 10-15 years (rechargeable battery replacement), so it would suck to just miss getting this improvement and having to wait a decade.
I was in the vicinity of researchers doing this almost 10 years ago in Houston. Was surprised to see this making headlines today. They’re also using DBS to treat depression and other mental illness.
I hate articles like these in "regular" newspapers as opposed to specialized journals.
My mom lost her sight and, to this day, asks me about updates for an electronic eye she once read about. The product existed, yes, but the company abandoned it [1] before it could be even remotely affordable and left existing patients one software bug away from the dark. Still, having no other hope other than a bionic eye, my mom regularly keeps asking me for news.
I also know someone living with Parkinson and I pray they don't see this article - the last they need is an article promising that someone, somewhere has "cured Parkinson" but with a procedure they may never get because it's not available in their country, it's too expensive, and/or they may not qualify for it. In my opinion "there's no cure" is easier to live with than "there is a cure, but you can't have it".
[1] https://spectrum.ieee.org/bionic-eye-obsolete
One time I was really hyped about so-called "molecular surgery"[0] - a technique which promised forming cartilage tissue - so the septum, tendons or even the cornea - with little effort and, crucially, no heating. The research looked as it was in an advanced stage with demonstrations on live specimens and whatnot.
Never heard about it again.
[0] https://www.sciencefocus.com/news/molecular-surgery-gives-pa...
At same time, this has real effects, so I wouldn't be so dismissive of it. I actually know a parent of a friend who had the whole "deep brain, computer in chest, app to adjust it" set up installed somewhat recently (not sure if exactly the same as article), and it's a game changer for her. I mean the difference is huge, and quite striking that it can be activated/deactivated at will and the effect so dramatic.
Bear in mind that the placebo effect from DBS for Parkinson's is 39% of the active treatment, so you can't really tell much from a single unblinded patient report.
https://www.sciencedirect.com/science/article/abs/pii/S13538...
Here is a meta-analysis of DBS for Parkinson's: https://bmjmedicine.bmj.com/content/3/1/e000705
Principal findings:
"All results had a high risk of bias and the certainty of the evidence was very low for all primary outcomes. The information size was insufficient when assessing all cause mortality. Meta-analysis showed that deep brain stimulation increased the risk of serious adverse events, mainly because of an increased risk of perioperative complications, such as cerebral haemorrhages and postoperative confusion, and events related to hardware, such as infection at the stimulator site, dislocation of the device, or reoperations. Meta-analyses indicated that deep brain stimulation might reduce symptoms specific to Parkinson's disease, but the assessments of disease specific symptoms had several methodological limitations."
So, it's an interesting treatment, but more evidence is needed before we can conclude that it is actually helpful.
That placebo effect study is 20 years old. Most of the included trials in the meta analysis are 10-20 years old as well.
The BBC article is about a new device. The evidence base may be slim but the technology looks to be improving. I look forward to seeing new clinical trial results on modern DBS systems.
>That placebo effect study is 20 years old.
Has it been contradicted anywhere? I don't see any other studies that have looked into it.
>Most of the included trials in the meta analysis are 10-20 years old as well.
The meta-analysis is from less than 6 months ago, and looked at all the studies available, which cover a range from recent to 10-20 years ago. That is normal for a meta-analysis, so I'm not sure why you're making it sound like it's out of date.
>The BBC article is about a new device.
Yes, there seems to be one study underway, which is still recruiting:
https://clinicaltrials.gov/study/NCT04681534
>>That placebo effect study is 20 years old. >Has it been contradicted anywhere? I don't see any other studies that have looked into it.
Somewhat tangentially, and not specific to Parkinson's or DBS, but placebo has been getting stronger for at least some classes of treatment. E.g.:
Tuttle AH, Tohyama S, Ramsay T, Kimmelman J, Schweinhardt P, Bennett GJ, Mogil JS. Increasing placebo responses over time in U.S. clinical trials of neuropathic pain. Pain. 2015 Dec;156(12):2616-2626. doi: 10.1097/j.pain.0000000000000333. PMID: 26307858.
Walsh BT, Seidman SN, Sysko R, Gould M. Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing. JAMA. 2002;287(14):1840–1847. doi:10.1001/jama.287.14.1840
So I would not be surprised if placebo got stronger in this area as well.
^ I assume the meta-analysis covered the available data well.
My point is that the available data may not tell us much about the safety and efficacy of this new device.
that study is about "selfhypnotic placebo effects by gadgets showing promises against stress"?
Not sure what you’re referring to here. You may have clicked on the wrong link somewhere.
If DBS itself is not a viable treatment for Parkinsons, as the study suggests, then no amount of technological improvement of DBS-based devices will change that.
It would take a lot more than an old, low-confidence set of trials (which is how the meta-analysis describes its inputs) to convince me of your premise.
I'm (genuinely) quite surprised by that. A family member had the procedure a year ago and the difference is so immediate and dramatic. Thanks for the links
Parkinsons involves dopamine, which is very amenable to placebo. Surgery and devices like dbs are very effective placebos.
so the short story is - at the moment, the device is basically doing power spectra analysis w/ FFT and such from local field potential recordings, and only turning the device on when it's detecting a strong ~20 hz band.
Helps w/ motor symptoms only - does NOT address any dementia/psychosis symptoms.
Aren't the dementia symptoms greatly magnified by the lack of mobility in the first place?
If we could get this kind of treatment early it might alleviate the need for dementia treatment.
I would say, maybe the other way around - gait is very much a cognitive task (think of all the compute power w/ reinforcement learning to get a robot to stand up or balance a stick). but it is probably a self-reinforcing cycle.
That being said, from DBS clinical series - we know the technology helps w/ limb rigidity, bradykinesia and tremor. It helps initially with gait but sometimes the gait declines despite DBS and meds, say, roughly a decade after implant (even as the upper limb symptoms stay well treated).
My father had Parkinson's and in my experience the lack of agency he had when trying to do daily tasks even other than walking was a real mind-killer. He was dependent on my mom (and later caretakers and skilled nursing facility) to do anything like feeding, toileting etc. Obviously when he was later bedridden mostly due to the inability to move, it probably drove him even more crazy.
He decided early on to never get this treatment and I feel sad to this day that he couldn't have lived a happier last few years.
My father was disqualified from getting DBS due to concerns around amplifying his dementia. Had I known then what I know now, I would have gladly signed a waiver, because DP has completely destroyed his body and mind.
Disagreed, exercise of all kind is known to help with neuroplasticity, complex movements such as dancing and compound lifts even more so. I can easily see how being unable to do any of those things could at least contribute to mental decline.
As I understand the medical science, it all comes down to stimulating the brain and there is no harder stimulation than physical feedback. Lack of mobility means lack of the biggest source of brain stimulation, which leads to accelerated degeneration.
I think we're talking about 2 different things.
movement/neuroplasticity/physical stimulation absolutely helps - hence PT, exercise classes, etc have being an important part of treatment
My point is, though - the onset of decline in gait ability typical of Parkinson's patients, is a sign of a decline of cognitive ability because the ability to perform gait and all the inherent brain commands associated with gait, is very much a cognitive function as much as it is motor.
One can argue that good DBS therapy by helping keep patients active and engaged does, at least indirectly, help cognition in that sense. BUT - it is consider not to directly treat Parkinson's dementia if a patient is unfortunate enough to come down with that aspect of disease. i.e. it's not like we can switch the device on or fiddle around w/ the programming and the patient's cognition directly improves from the brain stimulation itself.
If the result actually holds up in clinical trials though this is still huge! Parkinson’s is absolutely debilitating and more common than ALS.
Results of their clinical trial look positive.
https://pubmed.ncbi.nlm.nih.gov/39289373/
Keep in mind that paper cited isn't really the clinical trial that shows improvements in symptoms. It just shows their device works and can record LFP properly....
The actual clinical results so far shows that the gizmo with recording is not necessarily worse than DBS devices that don't have recording ability. I don't know if they published those results in a paper yet, but it was shown in poster form at MDS congress in Philly.
Any idea what a clinical trial to approval roadmap might look like? Vested interest.
not sure - but it will likely be quicker because the software is sort of already built into current generation Medtronic devices. They are not trying to approve a whole new device, probably just the software that switches the device on/off.
That being said, there are also reasons at the moment (better imaging support/stimulation programming abilities) to sometimes choose a competitor device over Medtronic (namely Boston Scientific)
Better DSP/ML techniques might make this more effective, but uh...the Parkinson's research community has never been known to be great at math...just saying
DBS devices have been in the market for years already and helping patients. This is just an incremental improvement.
How does it work that it helps the motor symptoms?
And while it’s something if it doesn’t help with dementia it seems like it’s not addressing whatever is the root cause of dopamine deficiency
our understanding Parkinson's is that it can be described as a control system issue. The part of the brain affected (at least initially) by the disease is part of a network (the basal ganglia/cerebellar network) that evaluates environmental inputs and generates the output necessary for fine/precise motor control, amongst other things. So a Parkinson's patient cannot plan their movements as well and the main symptoms are slowness of movement, abnormal limb tone; yes tremor as well but the 1st 2 are what cause the most issues for most people (keep in mind, not everyone follows the textbook so there are subtypes that have more cognitive issues, i.e. hallucinations, executive dysfunction etc)
The stimulators seem to affect the signaling in that circuit (they are targeted by the implanting neurosurgeon to specific nodes in that circuit as best as targeting surgical technology allows) that seem to restore the ability to move well. Exactly why, no one knows. It's just a dumb signal at around 1-4 milliamps at 130-180 hz at those specific spots but presumptively it corrects some aberrant behavior in the whole network. It was observed in the '00s that recordings taken during or right after surgery often showed a strong peak at ~13-35 hz (give or take, but roughtly around 20 hz) during the disease state, and that's what Medtronic has been trying to target w/ these devices.
Of note - there actually isn't a system-wide dopamine "deficiency" - dopamine in general is fine for most of the body, it's just that the particular part of the brain that is affected happens to use dopamine as its signaling neurotransmitter so it's deficient in just that connection within the network.
Dementia is theorized to happen when the abnormal brain process spreads to other parts of the brain other than the substantia nigra (see the Braak hypothesis)
My company makes DBS devices. There are a lot of other possible indications like migraine and others where it could help too but progress is very slow. You can't "move fast and break things" with brain implants.
* exempting shrapnel
My Mom has had the surgery twice now, once for the left side and once for the right. Brain surgery is no joke. It takes a long time just to recover from that. And Parkinsons is a disease that will continue to get worse. The surgery adds quality of life but it will not stop or cure Parkinsons. The surgery is a wonderful option but it isn't a cure.
These deep brain surgical implants are the calomel of today: https://en.wikipedia.org/wiki/Calomel
The logic is: we have no idea but must do something, surgical implants are something, let's do brain surgery and implant something!
My father died at the age of 82 from late stage Parkinson's, never got dementia but eventually whatever neurons in the brain control movements, they fail to do so not just for movement but also vegetative processes such as swallowing and gut transit so ... one cannot live without that. Also those neurons die so that can't be good. No amount of waves and vibrations can compensate for dead brain tissue.
Hard pass on the calomel. Come back when you actually got something that works.
I mean, this feels more like electroshock therapy to me, but that's made a big comeback and is apparently considered relatively safe and somewhat effective.
Bloodletting has some conditions it's actually appropriate for too.
Not sure mercury poisoning is going to turn out to be safe and effective anytime soon, though.
I'm not advocating for this, but if people are going to do it with informed consent, might as well collect proper data to try to determine if it objectively works. Snake oil that works, if it actually works, is something that works.
The parkinson brain surgeries work. They have proven to have worked. They wouldn't do them if they didn't work. They work almost miraculously. The problem is that Parkinson gets worse, you can't stop it. So the surgeries will work for a specific complaint but new symptoms will eventually arise.
Same for my mother-in-law. But very little benefit unfortunately. It’s a shame it didn’t add much value for such big surgeries.
Is this an all-new device, or a new software profile that can be applied to existing DBS controllers?
I know someone getting a DBS next month and the implanted controller gets replaced about every 10-15 years (rechargeable battery replacement), so it would suck to just miss getting this improvement and having to wait a decade.
I was in the vicinity of researchers doing this almost 10 years ago in Houston. Was surprised to see this making headlines today. They’re also using DBS to treat depression and other mental illness.
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