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Media Article
DBS Parkinson's

Table of Contents


1. Introduction2. Neuroscientific Context2.1 Parkinson's Disease2.2 Treatment for Parkinson's Disease2.2.1 Drug treatments2.2.2. Non-Drug Treatments2.3 Deep Brain Stimulation and Parkinson's Disease2.4 Future Goals3. Analysis4. Appendix4.1 Search strategies4.2 Reviewers Comments5. References
Our Group
Lauren Schramko z3419378
Michelle Riesel z3415949
Grace O'Sullivan z3419377
Marie Duong z3414671


1. Introduction

Parkinson's is a debilitating motor-neuron disease characterized by loss of somatic motor control, rigidity, and severe tremors. It has a high co-morbidity rate with depression and Alzheimer's, meaning that many people suffering from Parkinson's also develop these diseases.

Our chosen media piece depicts a man suffering from severe Parkinson's disease and who has undergone Deep Brain Stimulation (DBS) surgery to implant a neurostimulator in his brain to treat his condition. The man turns off his neurostimulator, and records the severity of his condition, which involves intense tremors and shaking progressively getting worse as the device is left off. The man then turns the implant back on, and the tremors immediately cease.

The media piece is worth exploring as the legitimacy of the video cannot be otherwise assessed. There are many skeptical comments on the video's original page, and while the man claims he is not lying, there is no evidence of this. The speed from which the man recovers from his seizures is incredible, and somewhat unbelievable. Therefore, we believe it requires critical analysis and research to determine if the man was really experiencing such sudden physiological changes.


2. Neuroscientific Context

2.1 Parkinson's Disease

2.1.1 What is Parkinson’s disease?Parkinson’s disease (PD) is a progressive, degenerative neurological disease, displaying a combination of motor and non-motor symptoms. PD is a result of the deficiency of dopamine being produced in the brain, causing a lack of smooth, controlled movements.
PD has been determined to originate in the substantia nigra, which is located in the midbrain, as seen in Figure 1. It is composed of the pars compacta and the pars reticulata. The dopaminergic neurons located in the substantia nigra send fibres out to the rest of the brain, in particular the corpus striatum, which is responsible for smooth muscle movement. Here the dopaminergic neurons release the neurotransmitter, dopamine. When approximately 70% of these dopaminergic neurons die, symptoms of Parkinson’s begin to develop. (University of Maryland Medical Centre, 2012)

substantia nigra.jpg
Figure 1: Shows the location of the Substantia Nigra and how it is diminished in Parkinson's patients

Source: Stemcell Therapy, 2012


2.1.2 Symptoms
Generally, the symptoms of PD develop slowly, over a period of years. These symptoms can be treated with medication (expanded further below), but there is no cure. Symptoms vary between patients, however there are three key symptoms for the diagnosis of Parkinson's (Abudi, Bar-Tal, Ziv & Fish, 1997).
Key Symptoms:
1. TremorEven though the tremors are absent in approximately 1/3 of Parkinson's patients, it is one of the primary characteristics of PD patients. Also known as a resting tremor, it usually begins in one hand and gradually spreads throughout the rest of the body. The tremor normally disappears when asleep or moving, and is more noticeable when the patient is tired or stressed. This symptom is a result of an imbalance between the neurotransmitters acetylcholine and dopamine. Medications cannot always control these tremors, and this is when other measures such as DBS is used.
2. Rigid and Stiff MusclesTightness of muscles as well as the inability to relax is another key symptom of Parkinson’s. This rigidity usually occurs in the neck, wrist and shoulder. The pain that patients with Parkinson's feel is associated with muscle rigidity.
3. BradykineseaBradykinesea is the slowness of voluntary muscle movements and can often be the most debilitating symptom of Parkinson’s disease. All activities of daily life, including walking and facial expressions are affected by the bradykinesea. Bradykinesea is a result of the degeneration of the substantia nigra as the brain is now unable to control the smooth, fluid muscle movements.
Other SymptomsDepression, anxiety, memory problems, slowness of thinking, bladder problems and constipation can also be symptoms of PD, however these symptoms aren’t used to make a diagnosis. Postural instability develops after the disease's onset and is a result of the tremor, bradykinesea and muscle rigidity, as the muscles are damaged (Parkinson's Australia, 2008).
2.1.3 CausesThere is no known cause for the degeneration and death of the dopaminergic neurons involved in the onset of PD. However, it is believed that environmental factors, genetics and oxidative stress or a combination of these factors result in PD.
Long term exposure to toxins (pesticides, herbicides and insecticides) as well as medications (neuroleptics and antiemetics) have been related to the onset of PD. Dopamine production reduces with age and there is a theory that PD may be caused by an accelerated ageing process. There is also a genetic link to the causes of PD. Approximately 15% of PD cases have familial hisotry of the disease and these symptoms often present earlier.
(Parkinson's Australia, 2008).

2.2 Treatment for Parkinson's Disease

There is currently no cure for PD, but several treatments exist to help cope with the symptoms.

2.2.1 Drug treatments

As PD results from a deficiency of dopamine, drug treatments aim to increase the amount of dopamine that reaches the brain. It also aims to stimulate the substantia nigra, and to block other compounds that affect dopamine. The amount and severity of symptoms differs from person to person. As a result, the medication prescribed depends on the needs of the individual. Often a variety of different combinations and doses of drugs are taken at specific times throughout the day (Parkinson's Australia, 2008).

A common drug treatment for PD is Levodopa. It is often mixed with Cabidopa, which minimises side effects and also increases the amount of Levodopa available to cross the blood brain barrier. Using the enzyme DOPA decarboxylase, Levodopa is converted to dopamine after it has crossed the BBB (Fung, et al. 2001). This is shown in Figure 2, below. Due to the large range of side effects associated with Levodopa, it is a last-resort treatment, only used once other treatments can no longer help. These other drug treatments are discussed below.


L_Dopa PARKINSONS.jpg
Figure 2: How Levodopa (L-dopa) acts to relieve the symptoms of Parkinson's

Source: Abusio Pharmaceuticals, 2012.

A wide variety of dopamine agonists are used as treatments by acting on dopamine receptors and mimicking it, tricking the brain into thinking it is receiving sufficient dopamine (Parkinson's Disease Foundation, 2013).

Anticholinergic drugs are mainly used in the early stages of PD, as they help relieve tremor but offer little other relief (Parkinson's Disease Foundation, 2013). Anticholinergics used in the treatment of Parkinson’s (ACP) are competitive muscarinic receptors, but the exact mechanism of how they work is unknown (Brocks, 1999). It is believed that ACP can correct the imbalance between dopaminergic and cholinergic pathways, the main cause of Parkinson’s (Fong, et al. 2001).

Monoamine oxidase B (MAO-B) inhibitors act to block MAO-B, an enzyme that breaks down dopamine. This results in higher levels of dopamine, thus minimising the effects of PD (Parkinson's Disease Foundation, 2013).

Catechol-O-methytransferase (COMT) inhibitors are a recent addition to the PD treatment market. It has no effect on the symptoms of Parkinson’s, but is able to extend the effectiveness of levodopa by blocking its metabolism (Parkinson's Disease Foundation, 2013).

2.2.2. Non-Drug Treatments

Alternative treatments include neurosurgery to lesion part of the thalamus, acting to decrease some tremors, or a pallidotomy, in which an electrical probe is placed into the globus pallidus and heated, destroying the neurons in that area (Parkinsons Australia, 2008). A Pallidotomy is performed to decrease dyskinesia. A new and controversial treatment for PD is DBS, which will be discussed in greater detail below.

2.3 Deep Brain Stimulation and Parkinson's Disease

DBS is a recently developed treatment for several neurological disorders, including PD. It involves an electrical device implanted into the brain that emits electrical signals to influence surrounding neurons. They are most effective in treating disorders involving involuntary movement or actions, such as PD and Tourette's syndrome, and have been known to provide effective treatment for Major Depressive Disorder. Due to the new and highly invasive nature of DBS, it is often reserved for patients with high aggressive Parkinson's, or patients who are unresponsive to pharmaceutical treatment. Thus far, DBS has shown very promising results, helping many Parkinson's sufferers and significantly reducing seizures, tremors and bradykinesia.

The devices are inserted into specific parts of the brain, depending on the individual patient, and are connected to a pacemaker/impulse generator located outside the brain via a wire (Okun, 2012). (See the diagram below). The most significant problem with the devices is that they are a very recent development, and the mechanism by which they work is not known. There are several highly-disputed theories, none of which have enough empirical evidence to be argued conclusively. The development of an accurate theory as to how DBS works would enable the development of devices able to effectively treat a wider range of disorders.
brain implant.PNG
Figure 3: Diagram showing implanted DBS device

Source: (Okun, 2012)

The DBS system consists of three components: the electrode, the lead, and the pulse generator. These are pictured in the diagram above. The electrode, which is inserted into a very specific part of the brain, is tailored specifically for each patient. It is common for neurosurgeons to conduct several tests to determine the most effective location for implantation. The electrode is located on the end of a long, very narrow lead, which projects out of the brain and skull, where it is connected to the wire. The wire is simply an insulated conductive lead, allowing electrical impulses to travel from the impulse-generator to the electrode without interfering with any other part of the body. Typically it passes from the skull behind the neck to the collar bone, where the impulse-generator, or neurostimulator is located. The neurostimulator is usually implanted near the collar bone, and is responsible for producing regular electrical impulses of a specific current and voltage to stimulate the neural tissue ("National Parkinson Foundation: Deep Brain Stimulation," 2013).


Once implanted, the electrode stimulates three different types of neurons. These are: local cells, which are physically near the implant, afferent inputs, which synapse onto the local cells, and fibers of passage, which are physically distant from the implant, but whose axons come into within close proximity (Cameron C. McIntyre, 2004). In a similar manner, neuroscientists are investigating the mechanisms behind DBS implants on three different levels; a molecular level, a neuronal level and on the level of an electrical circuit. A full understanding of the implant on all three levels will allow scientists to develop more sophisticated devices able to treat a wider range of disorders more effectively.


The main hypothesis as to the mechanism behind DBS is that it inhibits the target area, serving to reduce depolarization and thus neurotransmission. With relation to PD, one theory is DBS in the basal ganglia reduces tremors due to this inhibition. There currently exist a few different theories as to how this is achieved (Montgomery Jr & Gale, 2008). One theory proposes DBS blocks neuronal depolarisation, preventing neurons from reaching threshold and firing an action potential. Another posits that it depletes stores of excitatory neurotransmitters, which decreases action potential firing rate in the surrounding area. Although both of these postulates are very plausible, they lack evidence, and much more research is needed before either can be confirmed.


It is obvious more research needs to be done before DBS is optimised. However, it has already helped to ease the suffering of many Parkinson's patients, and will continue to do so as neuroscientists learn more about the mechanisms behind it and develop more refined models to help a larger range of patients more effectively.

2.4 Future Goals

The past 20 years has seen significant advancements in technologies treating Parkinson's disease including pharmaceutical drugs, pallidotomy and DBS. DBS has seen dramatic improvements in quality of life for patients with Parkinson's, tremor, dystonia, and other basal ganglia-related brain disorders. However, the technology is still in the experimental stage and must be refined in order to further improve the treatment of motor (tremors, stiffness, balance, etc) and non-motor (mood, cognition, behavioural) functioning (Okun, Fernandez & Foote 2012).

How DBS works is still not fully understood, therefore, further research is necessary in order to determine which physical, psychiatric, neurophysiological, and social factors are involved in the inhibition or reduction of it's effectiveness (Duboille & Kramer et al. 2013). Thus, long-term outcome studies and research must be conducted in order to identify and reduce or eliminate any negative or dangerous effects on neuronal structure and/or function (Lyons, 2011).

Those involved in the experimentation and development of DBS procedures are additionally striving for a more user friendly, comfortable and accessible future for the technology (Rothman, 2009). In the future, researchers say that we can expect to see:

Improvements in Battery Technology
- More power in smaller devices
- Rechargeable/extended life batteries
- Up to 9 years maximum battery life

Smaller/More Discrete Stimulator Size
- Less visible
- Implantation closer to electrodes
- Thinner, more flexible and conforming devices
- Direct electrode connection to eliminate the need for electrode wires to be placed under the skin down the neck.

Tailored Stimulation and Therapy Delivery
- Advanced, customised programming sequences and patterns
- MRI compatible components
- Devices that work on a closed-loop circuit, allowing them to turn on automatically when needed

Remote Monitoring and Care
- To allow for less frequent routine hospital outpatient appointments

The understanding and development of DBS procedures has advanced exponentially over the past two decades and has been revolutionary in providing significant clinical improvement in patients suffering from Parkinson's and several other neurodegenerative disorders. However, there is still much to be studied; ongoing research and studies to assess the safety and clinical effectiveness of DBS in multiple diseases are being pursued internationally, bringing the field closer to the ultimate goal of curing disease and relieving suffering (Duboille & Kramer et al. 2013).


3. Analysis

The video 'The effects of DBS on the motor symptoms of Parkinson's Disease' was posted on YouTube in June 2013, by a sufferer of PD named Andrew Johnson (AJ) who had undergone Deep Brain Stimulation surgery. While we initially found the video embedded on the website wimp.com, this was simply a means of sharing the video from the original source by an anonymous author who found interest in the subject matter. The original video had been posted on YouTube by AJ with the intent of showing the general public how DBS can be hugely beneficial in controlling the motor symptoms associated with PD.

Upon further investigation we came across AJ's blog, youngandshaky.com (Johnson, 2013), which documents his experience with PD and the effects of deep brain stimulation surgery, all while raising awareness of the consequences of this motor-degenerative neurological disease. AJ's blog states that he created the video initially as a personal experiment to see what would happen when he turned the neuro-stimulator off in preparation for flying to a conference, where he anticipated the possibility of a screening device turning off his DBS implant without his knowledge.

The intent of the Youtube video, although it did not have a specific target audience, was to demonstrate the effects of DBS on the motor symptoms of PD rather than explaining the mechanisms of the DBS procedure itself.
As a result, we researched how DBS implants work as opposed to proving or disproving the neuroscientific content of the video.

Although the complete legitimacy of the video cannot be assessed, our main verficiation came from AJ's blog which contains evidence through further writing by AJ regarding his experience with DBS and PD research. The webpage legitimises his claims as the YouTube video itself was open to the criticism that he was faking the effects of DBS. Additionally, it is sponsored by ‘Parkinson’s New Zealand’ and ‘The Neurological Foundation of New Zealand’, further legitimising it as a reliable source.


4. Appendix

Initially, we were interested in children savants, with our first article being about Autistic savants. However the first article we found did not contain a significant amount of neurological and scientific data or evidence. We found the video of AJ and how he underwent DBS to treat his Parkinson's. Upon viewing this video, we all decided that it had enough neurological aspects for us to develop on further, thus deciding to focus on Parkinson's Disease and DBS.

4.1 Search strategiesWe all used a variety of search strategies and search engines, including Google, Google Scholar as well as UNSW databases and PubMed. All these search strategies enabled us to access a wide variety of journal articles and other information relating to Parkinson’s disease and DBS. Official websites, such as Parkinson’s Australia were also very helpful in providing a general overview of the disease.

4.2 Reviewers CommentsA common weak point mentioned by all our peers was that our language, syntax and grammar were too colloquial and not concise enough. Individually, we went through our own sections and adjusted our language accordingly. Abbreviations were not consistent throughout for our draft and as a group we went through and made sure that they were all uniform.

One of the reviews suggested that the causes, future goals and analysis sections all needed revision. Those that wrote these initially then went back and revised them.
Two reviewers went through our Wiki and edited our grammar and wording. We took some of these suggestions into consideration, however there were other suggestions that we disregarded as we felt the same message was said and it was a matter of personal preference.
A general suggestion for improving our Wiki page was for us to number our titles and subtitles consecutively to improve the overall flow of our page. We revised our references and ensured that all statistics and information that wasn’t our own was referenced.

Another comment made by our peers was that our figures, though relevant and present, were not referenced in our page and felt out of place. We changed this and ensured that we referred to our figures.

5. References

Abudi, S., Bar-Tal, Y., Fish, M., Ziv, L. (1997). Parkinson's disease symtoms - patients' perceptions. Journal of Advanced Nursing. Accessed online August 25, 2013 via <http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2648.1997.1997025054.x/abstract>

Ahn, A., Amin, N., Hopkins, P., Kelman, A., Rahman, A., Yang, P. (2003). Future Prospects. Deep Brain Stimulation. Accessed online August 30, 2013 via <http://biomed.brown.edu/Courses/BI108/BI108_2003_Groups/Deep_Brain_Stimulation/future.html>

Asubio Pharmaceuticals. (2012). L-dopa administration in Parkinson's Disease. Accessed online August 22, 2013 via <
http://www.asubio.com/team/LDopa_Illustration.html>

Brocks, A.R. (1999). Anticholinergic drugs used in Parkinson's Disease: An overlooked class of drugs from a pharmacokinetic perspective. J Pharm Pharmaceut Sci 2 (2): 39-46.

Duboille, A., Kramer, R., et al. (2013). The Future of Neuromodulation. The Parkinson Alliance: Deep Brain Stimulation for Parkinson's Disease. Accessed online August 29, 2013 via <http://www.dbs4pd.org/articlesdetails.php?ID=12>

Fung, V.S.C., De Moore G. & Morris J.G.L. (2001). Drugs for Parkinson's disease. Australian Prescriber, 24:92-5. Retrieved from <www.australianprescriber.com/magazine/24/4/92/5>

Johnson, A. (2013). The effects of DBS on the motor symptoms of Parkinson's Disease. youngandshaky.com. Accessed online August 22, 2013 via <http://youngandshaky.com/?p=405>

Lyons, M.K., (2011). Deep Brain Stimulation: Current and Future Clinical Applications. Mayo Clinic Proceedings, 86(7), 662-672.

Montgomery Jr, E. B., & Gale, J. T. (2008). Mechanisms of action of deep brain stimulation (DBS). Neuroscience & Biobehavioral Reviews, 32(3), 388-407. doi: http://dx.doi.org/10.1016/j.neubiorev.2007.06.003

National Parkinson Foundation: Deep Brain Stimulation. (2013). Retrieved 5/9/13, from http://www.parkinson.org/Parkinson-s-Disease/Treatment/Surgical-Treatment-Options/Deep-Brain-Stimulation

Okun, M. S. (2012). Deep-Brain Stimulation for Parkinson's Disease. New England Journal of Medicine, 367(16), 1529-1538.

Okun, M.S., Fernandez, H.H., Foote, K.D. (2012). What is the Future for Deep Brain Stimulation? Centre for Movement Disorders and Neurorestoration. Accessed [[#|online]] August 29, 2013 via <http://mdc.mbi.ufl.edu/surgery/am-i-a-candidate-for-deep-brain-stimulation-intro/what-is-the-future-for-deep-brain-stimulation>

Parkinson's Australia (2008). What is Parkinson's?., Retrieved August 25, 2013, from <http://www.parkinsons.org.au/about-ps/whatps.html>

Parkinson's Australia (2008). Treatments and Symptom Management. Retrieved August 23, 2013 via <www.parkinsons.org.au/about-ps/treatments.htm>

Parkinson's Disease Foundation (2013). Prescription Medications. Retrieved August 23, 2013 via <www.pdt.org/parkinson_prescription_meds>

Parkinson's New Zealand. Deep Brain Stimulation. Parkinson's New Zealand. Accessed online September 2, 2013 via <http://www.parkinsons.org.nz/what-parkinsons/deep-brain-stimulation-support-group>

Rothman, L. (2009) Future Developments. The Parkinson's Appeal for Deep Brain Stimulation. Accessed [[#|online]] August 30, 2013 via <http://www.parkinsonsappeal.com/dbs/futuredevelopments.html>

Stemcell Therapy. (2012) Treatment - Parkinson's Disease. Accessed online September 8, 2013 via <http://www.stemcell.net/in/treatments.php?cats=Parkinson%20Disease#>

University of Maryland Medical Center. (2012) Parkinson's Disease. Retrieved August 25, 2013 via <http://umm.edu/health/medica/reports/articles/parkinsons-disease>




This looks fine. The science of DBS and Parkinson's is interesting.
I don't know anything about wimp.com, but you need to consider the media analysis side carefully. It will probably be difficult to determine the intention of the 'author' but I think it would be fruitful to explore how the target audience can determine/verify the veracity of the information presented.

Approved.//

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Proof of Groupwork:

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Division of Labour:

Lauren: How neurostimulators work/Intro
Michelle: Methods of Treatment for Parkinson's Disease/Analysis
Grace: Parkinson's Disease/Appendix
Marie: Future Goals/Analysis

Deadlines:
Each person to have a draft their section done by Wednesday, September 4th.
All group members to read through all sections done by others, to suggest improvements, to be done by Saturday, September 7.
Draft is due Monday, September 9.
Separate review comments due Monday, September 16.
Each group member to fix up their own section based on review comments by Saturday, September 21.
All group members to read through all sections done by others and suggest final improvements by Sunday, September 22.
Final assignment due Monday, September 23.