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The triumph of inertia over innovation: The story of a cure for a common neurological disease that destroys lives, reduces productivity, and generates huge medical bills …and why it is so underused.

The triumph of inertia over innovation: The story of a cure for a common neurological disease that destroys lives, reduces productivity, and generates huge medical bills …and why it is so underused.

Well maybe that’s a bit harsh, but when it comes to the use of deep brain stimulation for Parkinsonism, the evidence is fairly clear…a relatively simple neurosurgical procedure can transform a rigid immobilized sufferer from Parkinson’s disease into a functional member of society who is free to enjoy life and return to work.

In 1817 Dr. James Parkinson (right) wrote a short paper entitled, An Essay on the Shaking Palsy (1817). In the paper, he described patients afflicted with "involuntary tremulous motion, with lessened muscular power”. fig1fig2 Parkinsonism is now understood to be a neurodegenerative disease. In Parkinsonism there is degeneration of neurons in the substantia nigra (a part of the brain stem). Interestingly, some forms of Parkinsonism are heritable and the neuronal death related to mutations in proteins called PINK1 and Parkin, which mark neuronal mitochondria for elimination through a process called mitophagy. fig3 Afflicting approximately 1% of the population, Parkinsonism is prevalent enough to represent a public health problem. There is an effective medical therapy for Parkisonism: L-dopa. But treatment loses efficacy over time and there are troublesome adverse effects and periods during the day when the drug does not work. Enter a new approach. Consider that neurons are electrical generators. Why not treat an electrical problem with an electrical solution? There is a long history of this in cardiology. The implantable pacemaker has been around since the 1960s to treat slow heart rates and restore cardiac rhythm. Interestingly Deep brain stimulation (DBS) has been available since the 1990s; a similar concept but the electricity is delivered to the brain. Studies have consistently established the benefit of DBS to be a reduction in tremor of >80%. Although the mechanism of benefit is complex and not fully understood, stimulation of the ventral intermediate nucleus of the thalamus can dramatically relieve tremor associated with essential tremor or Parkinson disease (PD). Similarly, stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can substantially reduce bradykinesia, rigidity, tremor, and gait difficulties in people with PD. DBS has also been used for essential tremor, management of refractory pain and even compulsive disorders, including medicine’s newest disease, obesity. In Parkinsonism DBS seems to mimic the effect of ablating brain tissue even though it actually both activates efferent axons and inhibits neuronal cell bodies. Thus, DBS somehow leads to an interruption of information flow or processing. However that’s dry. Let’s see the moment of truth, as captured in this BBC documentary clip:


Does DBS improve quality of life? A definitive yes.


Deuschl G, Schade-Brittinger C, Krack P, et al. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 2006;355:896-908. Indeed it was approved by the FDA as adjunctive therapy for Parkinsonism over a decade ago, in 2002. Even though treatment for Parkinsonism has improved, DBS remains superior to optimal medical therapy, including an apopmorphine pump. Stuart Reid Who should get this procedure? Per Dr. Stuart Reid, Parkinsonism expert (left), it is the patients that have severe disease but a stable and supportive environment and no evidence of depression or dementia (those in the green column below). fig6So do we need to be doing this at Queen’s/KGH? In Ontario? In Dr. Reid’s excellent lecture he summarized the data. Essentially, the technology assessment agency for Ontario, OHTAC, felt in 2006 that in applying the indications for DBS there would be justification for >1850 procedures on the 36,000 Parkinsonism patients in Ontario, annually. Despite this, there are only 50 DBS procedures performed annually. So, the answer is a resounding yes. fig7 Taking nothing away from L-dopa - a useful drug - and acknowledging the cost of DBS, we should be doing more of this procedure in Ontario. It is not only the right thing to do for Parkinson’s patients, it would likely put some of these debilitated individuals back into theworkforce. There might also be cost savings. fig8Can we afford DBS? Dr. Reid estimates the costs are significant, but not unreasonable for the quality of life that is offered to the patient. Moreover, the cost of the DBS is partially offset by reduced use of Parkinsonism medications. So finally, why is DBS underused? It is not the reluctance of patients or the lack of teams of neurosurgeons, radiologists and neurologists. Rather it is often the simple question of “who pays?” Perhaps that, combined with an older, less vocal patient advocacy movement (compared to HIV-AIDs or breast cancer). If funding is provided, the procedure can and will be done and patients will likely benefit (with the usual caveat that the procedure is complex and can have adverse outcomes, some of which are serious).  It is time to roll out DBS in Ontario! Is it time for DBS in the SE LHIN (#10 on the map)? It would seem so, since the rates of the procedure are low. The feasibility and financing for this complex procedure are being considered. Reid, Pari, Levi As you can see above, we have the team of experts: Dr. Ron Levy, a neurosurgeon at Queen's/KGH with extensive DBS experience  (left), Dr. Stuart Reid (centre) and Dr. Giovanna Pari (right), both experts in Parkinsonism at Queen's/KGH. We are ready to go, and with funding secured, our team would be able to perform this state of the art, effective procedure on the many patients who suffer from debilitating Parkinsonism.

John Fisher

Thu, 07/18/2013 - 04:51

Stephen, great blog. The deep brain story and its translation to superior treatment for Parkinson’s diseases is one from the emerging field of “electroceuticals” (1,2). Drs. Levy, Reid and Pari are part of a growing field “Correcting such disorders with treatment in their own electrical language…”(1). A recent commentary in Nature, by Famm (Head of Bioelectronics research at Glaxo Smith Kline, GSK) trumpeted the remarkable potential for electroceuticals to impact human health, which generated 12,000 views since April. The field weaves together the skillsets of engineers, neurosurgeons, clinical investigators, neuroscientists, pain biologists and other PhD scientists into an apparently coherent pattern. Interestingly, GSK has announced plans to fund 20 projects related to “bioelectronic medicine’ (2), as well as a global research leaders forum to identify a “ key hurdle” followed by a potential $1M international prize for solutions (1). Electroceuticals are a Darwinian leap for big pharma, from compounds to electrons. 1. Famm et al “Drug Discovery: a jump start for eletroceuticals. Nature 496, 159–161 (11 April 2013) doi:10.1038/496159a ( 2. Sinha, G. Charged by GSK investment, battery of electroceuticals advance. Nature Medicine 19, 654 (2013) doi:10.1038/nm0613-654

John Fisher

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