Deep Brain Stimulation Used To Treat Early Stage Parkinson’s Disease

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[Source: Medtronic]

A device that delivers electrical shocks directly into the brain has been shown to alleviate symptoms in people with early stage Parkinson’s disease better than the best treatments being used today. Normally reserved as a last resort for patients with severe symptoms and for whom drugs are ineffective, the deep brain stimulation’s newly found effectiveness could promote it to the first line of attack against the disease at the earliest detection of symptoms.

The trial included 251 people diagnosed with Parkinson’s disease who were followed for two years at 21 centers in France and Germany. As a group, the participants had an average age of 52 years and had lived with the disease for an average of 7.5 years – a young group considering the general Parkinson’s population has an average age of 60. The participants were broken up into two groups: one receiving neurostimulation and the “best medical therapy” at their treatment center while the other group received only the best medical therapy. The stimulator was made by Minneapolis-based Medtronic.

Those that got neurostimulation therapy showed much greater improvement. The researchers attempted to assess changes to overall quality of life by measuring how the treatments affected daily activities such as speech, handwriting, dressing and walking, emotional well-being, stigma, bodily discomfort, social support, cognition and communication. Patients receiving neurostimulation improved in all of these categories except communication. Conversely, those who received medical therapy only improved in the daily activities and stigma, a measure of lacking social acceptance, categories. Another set of tests evaluating general motor skills also showed that people receiving neurostimultion performed better than those who were receiving medical therapy only.

Medtronic’s brain stimulator improved symptoms in early stage Parkinson’s patients better than conventional treatments.

The promising results could give doctors a new tool to treat Parkinson’s disease in its early stage. “These results signal a shift in the way patients with Parkinson’s disease can be treated,” Günther Deuschl, Professor of Neurology at Christian-Albrechts-University and lead investigator of the study said in a press release, “and prove that deep brain stimulation therapy can improve patients’ quality of life even in the early stages of Parkinson’s disease, when fluctuations and dyskinesia just start and clinicians traditionally solely rely on drugs.”

The study wasn’t all good news, however, as nearly 20 percent of those who received neurostimultion experience “serious adverse events” related to surgical implantation of the device or its stimulation activity. These included one case of brain abscess, one of edema, and one of impaired wound healing that resulted in scarring. Depression was also seen more frequently in the neurostimultion group, although the researchers didn’t speculate why that might be so.

Deep brain stimulation continues to break new ground in treating neurological disorders. In addition to Parkinson’s disease, essential tremor and dystonia are other movement disorders being treated with DBS. And researchers are currently investigating ways depression, epilepsy, and chronic pain can be alleviated with DBS. Alzheimer’s disease also joined the group of disorders treatable with neurostimulation this past October when a woman’s cognitive abilities greatly improved after receiving a brain pacemaker. Over 30,000 people around the world with Parkinson’s disease are being treated with neurostimulation. The current study means more people could turn to neurostimulation earlier, while their symptoms are milder, and stave off the onset of this debilitating disease.

Discussion — 5 Responses

  • DigitalGalaxy February 25, 2013 on 2:55 pm

    I don’t know if this is good or bad…we don’t really understand enough about the brain to really start this sort of treatment.

    I’m not against the trials, I’m just saying we shouldn’t jump to conclusions. This sounds unpleasantly reminiscent of electroshock “therapy”. The increase in depression was unfortunately all to present in the study.

    Brain stimulation can occur in more natural ways, such as encouraging video game playing, crosswords/Sudoku/ect. The DS has a whole game entitled “Brain Games”, designed specifically for mental stimulation. “Prescribing” a video game could have more positive results, or at least, positive results without the risks of unknown side effects.

    Until we understand more, or until we have nano-bots inside the brain, I think this is a bit too scattered an approach. Almost like treating brain cancer by exposing the entire head to radiation doses. Now, it’s done with a laser focus that can move the radiation beam and keep the focus on the cancer, while keeping exposure the other tissues to a minimum. The old way of simply flooding the entire brain with radiation to hopefully get the cancer seemed like a “one step forward, two steps back” approach, and this seems akin to that obsolete method.

    Not that it doesn’t hold promise, but I think its in too early stages, and our understanding of the brain is in too early of a stage, to really say on way or another.

    Also, just a technical question…do we really need a probe implanted in the brain itself? Can we just have a suction cup on the outside of the skull that transmits electrical impulses?

    • Ver Greeneyes DigitalGalaxy February 27, 2013 on 7:55 am

      As I hint in my post below, DBS isn’t as scattershot as you think. Think of it as inserting a (blunt) needle in the brain, then stimulating the tip. It certainly isn’t precise to the level of individual cells, but you can more or less target a single area of the brain with it.

      The main issues are that 1) each brain is different, and there’s no foolproof way to tell you’ve inserted the ‘needle’ in the right place (some methods do exist) and 2) a single area of the brain can be associated with multiple functions. In this case, the electrodes are usually inserted in the Subthalamic Nucleus (STN), a small area in the brain associated with motor control on the one hand and emotions on the other.

      From my understanding they basically stick the electrode right through this area (without damaging it, since the tissue is malleable enough to allow for small gaps), then stimulate all of it. So depending on exactly where the insertion takes place, the electrode might stimulate mostly the area responsible for motor control (as desired), or be off by a small amount and end up messing with the emotions too. This can lead to depression but can also alleviate it (though other areas of the brain have been found to be more affective for alleviating depression).

      In other words, this can’t really be compared to electroshock therapy. It is much more precise, only stimulating a small area of the brain, and (as I explain in my post below) it is the high frequency, pulsatile nature of the stimulation that causes its effectiveness. On the other hand, it also isn’t as precise as we’d like – better would be if after implantation, the pulses could be directed in the specific direction that proves most affective. Unfortunately the electrodes currently on the market generally only have at most 4 contacts (at several points along its length), which doesn’t allow for that much control.

      • DigitalGalaxy Ver Greeneyes March 1, 2013 on 1:31 am

        Very cool! Thanks for all the detailed info! (I’ve never seen somebody cite sources in a blog comment before!)

        On this one, I’m glad I was being too pessimistic!

        • Ver Greeneyes DigitalGalaxy March 1, 2013 on 1:39 am

          No problem :) It was easy because I could just take them from a paper I co-authored. The paper itself is in Dutch (and not published anywhere since it was a student project), or I would have been tempted to link it.

  • Ver Greeneyes February 27, 2013 on 7:42 am

    I’m not sure this is really news, unless this was simply the largest trial yet. A few points:
    1) Deep Brain Stimulation is usually applied to the Subthalamic Nucleus (when treating Parkinson’s). This part of the brain is associated with motor control but also with the experience of emotions – as such, stimulating the whole thing can affect both.
    2) It is theorized that the symptoms of Parkinson’s are caused by feedback loops between various areas in the brain. These feedback loops cause a resonance in the beta and theta frequency bands [1].
    3) The resonance in the beta frequency band causes heightened activity in the Globus Pallidus interna (which in turn inhibits the Thalamus) and is hypothesized to cause the symptoms of bradykinesia. To put it in different terms, the ‘background noise’ caused by the resonance makes it very hard for patients to generate a ‘signal’ strong enough to not be inhibited.
    4) The resonance in the theta frequency band corresponds with the frequency of the tremor frequently seen in patients suffering from Parkinson’s.
    5) Computational studies (e.g. [2]) have shown that high frequency stimulation (>100Hz, most affective at >130Hz [3]) is able to disrupt this resonance, thereby reducing both tremor and bradykinesia.
    6) Parkinson’s can also lead to damage of the inner ear, leading to balance issues. DBS has not been shown to improve this situation, presumably because it isn’t caused by resonant brain activity.

    Note that the above should be seen mostly as hypotheses although they are supported by various studies and models. Performing measurements on these structures deep in the brain is tough because they aren’t stacked like the cortex (and so the signals generally don’t propagate enough to be measurable with EEG). There are studies in progress that use the electrodes that produce the DBS to measure local activity, but most of these implants only really stimulate or measure one point – so it’s hard to get a full picture of brain activity in the relevant regions.

    [1] McIntyre, C. C. & Hahn, P.J. (2010). Network perspectives on the mechanisms of deep brain stimulation. Neurobiology of Disease, 38, 329–337.
    [2] Lee, K.H., Hitti, F.L., Chang, S.Y., Lee, D.C., Roberts, D.W., McIntyre, C.C., & Leiter, J.C. (2011). High frequency stimulation abolishes thalamic network oscillations: an electrophysiological and computational analysis. Journal of Neural Engineering, 8(4), 046001.
    [3] Moro, E., Esselink, R. J., Xie, J., Hommel, M., Benadid, A. L. & Pollak, P. (2002). The impact on Parkinson?s disease of electrical parameter settings in STN stimulation. Neurology, 59 (5), 706-713.