Research

Kathy Dujardin, PhD, Pascal Sockeel, PhD, David Devos, MD, PhD, Marie Delliaux, PhD, Pierre Krystkowiak, MD, PhD, Alain Deste´e, MD, PhD, and Luc Defebvre, MD, PhD (2007).. Characteristics of Apathy in Parkinson’s Disease.. , Movement Disorders, Vol. 22, No. 6, 2007, pp. 778–784.Movement Disorders, Vol. 22, No. 6, 2007, pp. 778–784.

The authors of this study wanted to look at apathy among people with Parkinson’s disease (PWP).  They describe apathy as having reduced participation in tasks that one used to enjoy, difficulty initiating activities, feeling indifferent, and having little expression or feeling “flat.”  The authors wanted to evaluate an apathy scale, possibly identify if there is a specific “apathy profile” for PD, as well as to evaluate if depression, cognitive decline, or disease severity affected apathy.  Approximately 1/3 of the PWP (none had DBS) in this study were classified as apathetic compared to less than 2% of the non-PD control group.  Other research studies have suggested that the range of PWP that have apathy is 16-38%.  The apathetic PWP also had more depression and cognitive impairment than the non-apathetic PWP.



One aspect of apathy that was measured revealed that the PWP showed less activity and less initiation than the non-pd group.  They also found that PWP who had “fluctuating” motor symptoms or dementia demonstrated a flat affect that was not as evident with the non-PD group or the other PD groups (non-demented, constant motor symptoms). The researchers found that impaired cognitive state was more predictive of apathy than severity of motor dysfunction.  The authors readily noted that there are many similar symptoms between depression and apathy but they classify them as distinct entities, which suggests that clinicians and researchers should use appropriate assessment tools to gain a clear understanding of both depression and apathy in PWP.



In the introduction as well as the conclusion of the paper, the authors discuss in detail the role of the frontal lobe (frontal portion in the brain) in apathy and suggest that apathy is not solely related to motor dysfunction and that additional therapies focusing on that area of the brain may improve quality of life in PWP.  These authors as well as others discuss the importance of monitoring apathy as well as depression within the PD population, as some studies suggest that both can be a side effect of DBS-STN.  It is clear that more research is needed to study both apathy and depression to best treat PWP with and without DBS.

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Vesper, J., Haak, S., Ostertag, C., & Nikkhah, G. (2007).. Subthalamic nucleus deep brain stimulation in elderly patients--analysis of outcome and complications. , BMC Neurology. Mar 16; 7: 7.BMC Neurology. Mar 16; 7: 7.

The authors of this study readily acknowledged the benefit of DBS and set out to examine if there were differences in the successes as well as adverse event rates for DBS in an older (65+) and younger (<65) PD population.   Both groups showed improvement in their motor scores across various points up to 24 months from surgery.  Both groups also had improved quality of life and reduced need for medication after surgery.  Immediately after surgery, the younger group had more improvement than the older group in completing tasks independently within the home.   However, that difference was small and disappeared by the 6-month follow up.  In regard to adverse events, it should be noted that there were few severe complications in either group.  Nonetheless, the older group had more infections (4 vs. 1 out of 73) and a higher death rate (5 vs. 2) than the younger group.  The authors concluded overall that DBS was effective for both age groups suggesting that there need not be an age limit for DBS.  They suggested that both groups be screened for appropriate candidacy for DBS, especially as the older adults had more adverse infections than the younger group.  The authors also noted that as DBS continues to be a treatment option in older adults that the group should be followed as long term effects are not as well studied in the literature.



Last month we reviewed an article (Derost et al., 2007) also addressing younger versus older adults in regard to effectiveness of DBS.  It should be noted that the previous study used more measures, specifically related to Quality of Life, which may explain the difference in findings of these two studies.  All else within the studies were comparable and suggestive that DBS is effective for both young and older adults with PD.

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Derost PP, Ouchchane L, Morand D, Ulla M, Llorca PM, Barget M, Debilly B, Lemaire JJ, Durif F.. DBS-STN appropriate to treat severe Parkinson disease in an elderly population?. , Neurology, 68(17):1345-55IsNeurology, 68(17):1345-55Is

This study looked at the age of patient’s undergoing DBS STN and if there is a difference (short and long term) in efficacy, adverse events, or PD symptoms between an older (65+) and younger (<65) group of people with Parkinson’s disease.  Patients were tested 1 month prior to surgery and 3, 6, 12, and 24 months post surgery with various measures.  The authors found that acutely both groups experienced significant motor improvement from DBS STN.  Younger patients had more improvement in quality of life related to mobility, activities of daily living, stigma, cognition, and communication as compared to the older group.  These areas generally stayed the same or slightly worsened for the older group.  Both groups had a reduction in their levodopa dose and stimulation parameters were not different between the groups.  The most common adverse events for both groups was worsened dysarthria, weight gain, and transient mood elevation (hypomania improved within weeks after surgery).  There were no significant differences between the groups in regard to adverse events.  All adverse events are listed in the article.  It is notable that both groups did not experience significant cognitive change after DBS STN.  Overall the authors concluded that DBS STN is effective in the short and long term for motor symptoms of both young and older patients but that younger patients may experience more benefit in regard to quality of life than their older counter parts

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Winge, K., Kroyer Nielsen, K., Stimple, H., Lokkegaard, A., Jensen, S. and Werdelin, L. Lower Urinary Tract Symptoms and Bladder Control in Advanced Parkinson’s Disease: Effects of Deep Brain Stimulation in the Subthalamic Nucleus.. , Movement Disorders 2007, 22(2), 220-225.Movement Disorders 2007, 22(2), 220-225.

This article was a prospective study looking at the short-term effects of DBS STN on problematic bladder symptoms commonly seen in patients with PD. These bladder problems are often due to the disease or medication side effects.  This study looked at patient’s report as well as direct measurement of bladder function prior to surgery and within 6 months after surgery.  Patients had improvement in their motor symptoms (UPDRS motor score and dyskinesia) and in overactive bladder symptoms.  However, they found that patients report of being “bothered by” their bladder symptoms initially decreased but then worsened as time went on after DBS STN.  Two possibilities explain the increase in patient report of worsened symptoms at the 6 month point.  The first possibility is that patients may have had such improvement in their motor symptoms due to surgery that previously less bothersome symptoms (e.g. nonmotor symptoms) are more evident.  The second possibility is that DBS STN had worsened the way people cope with their illness or situation. It is difficult to say which possibility best explains the decline, as there is not much research on changes in coping strategies as PD progresses.  This study is in direct contrast to two other studies mentioned on our site (Finazzi-Agro et al. & Seif et al.), but the participants in the current study and the time since the DBS surgery was different.   The authors of this study only looked at bladder problems up to 6 months after DBS STN, whereas the other studies looked at long-term bladder dysfunction (both studies showed significant improvement).  This suggests that with time DBS STN likely has a beneficial effect on the bladder functioning, but that it may not be as evident within the first six months after surgery.  The ideal study would look at both short term and long term gain in bladder function before and after DBS STN, which has yet to be done in the literature.

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Friedman JH, Brown RG, Comella C, Garber CE, Krupp LB, Lou JS, Marsh L, Nail L, Shulman L, Taylor CB; Working Group on Fatigue in Parkinson's Disease. (2007). Fatigue in Parkinson's disease: a review. Movement Disorders. 2007 Feb 15;22(3):297-308. NonMotor Symptoms. ,

This article was a review of the literature discussing fatigue in PD.  Fatigue has been recently more recognized in PD patients.  Fatigue is not currently measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) but is often experienced by the PWP.  The UPDRS is one of the most common instruments used by treatment providers to monitor PD symptoms; future revisions have indicated that fatigue will be included in the assessment tool. It is unclear why PD patients experience fatigue.  Studies have shown that fatigue in PD is not always related to disease severity or motor dysfunction.  Some PWP indicated that they felt fatigued prior to the diagnosis of PD.  Studies have shown that fatigue often co-occurs with other nonmotor symptoms, which makes it difficult to tease out if one is causing the other (e.g. sleep problems, depression, anxiety).  Fatigue has been studied in animal models and may be related to dopamine depletion (a chemical in the brain whose depletion causes PD symptoms).  Studies have shown that exercise in those animals had less dopamine loss.  Researchers have also studied fatigue in cancer and multiple sclerosis to help understand fatigue in PD.  It is also unknown what causes fatigue in those diseases as well.  In cancer studies aerobic exercise was shown to improve fatigue but researchers don’t fully understand the process of why.  Also in multiple sclerosis they found that fatigue was linked to patient perceptions of their general health and control over their disease.  More research needs to be done to better understand fatigue in PD.  There currently are not consistent answers as to why the PWP does or does not experience fatigue or how best to treat it.

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Stefani, A., Lozano, AM., Peppe, A., Stanzione, P., Galati, S., Tropepi, D., Pierantozzi, M., Brusa, L., Scarnati, E., & Mazzone, P.. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. , Brain, 2007 Jan 24; [Epub ahead of print]Brain, 2007 Jan 24; [Epub ahead of print]

This study looked at concurrent stimulation of two areas within the brain (subthalamic [STN] and pedunculopontine nuclei [PPN]) to treat symptoms of PD.  The authors found that stimulation of the PPN added to benefits of DBS-STN specifically in the areas of gait, postural instability, and increased efficacy of postsurgical medications.  The patients were only followed for a short time afterward so long term adverse events are unknown.  The only adverse event noted was a parasthesia (unusual feeling, burning, itching, etc.) in the legs at higher stimulation frequencies.  Follow up studies from this group are on-going.

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Deuschl, G.,Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, & Voges J (2006). A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease.. , 355, 9, 896-908355, 9, 896-908

Intro

This study looked at treatment efficacy in patients with PD treated with deep brain stimulation and medications to those patients treated only with medication.



Who were the patients in the study and what were they asked to do?

There were 156 patients in this study between 2001 and 2004. Patients were carefully screened for appropriateness for surgical candidacy before being assigned to surgery or medication only treatment groups. The authors created 78 pairs to be treated so they could evaluate of the pair, which had a better response to their therapy. There were 78 patients that underwent bilateral DBS-STN and 78 patients that were treated with the best medication practices available at that center. The patient's were not different demographically (age: around 60, Duration of levodopa treatment 13-13.8 years, 50 males in each group, and similar Hoehn and Yahr stages). Patient's were asked to complete the PDQ-39 (Parkinson's Disease Questionnaire), Schwab and England Scale (test of functioning), Mattis Dementia Rating Scale (test of cognitive functioning), Montgomery and Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale (both for neuropsychiatric functioning), Medical Outcomes Study 36-item Short Form General Health Survey (SF-36; quality of life measure), and were evaluated by the neurologist on the Unified Parkinson's Disease Rating Scale (UPDRS). Patients were also asked to keep a diary of their mobility throughout the study before and after treatment initiation.



Who were the researchers? 

The research in this study was conducted at 10 academic centers in Germany and Austria 



What did the researchers find?

The researchers found that those patients treated with neurostimulation had more improvement in motor symptoms, dyskinesias, general health status, quality of life, mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort as compared to those only treated with medication. Activities of daily living slightly declined in the medication only group. There were no improvements or differences between the groups in terms of social support, cognition, depression, or communication. According to the diaries kept by the patients, the group treated with neurostimulation showed significant improvement in their objective rating of their immobility, time of mobility w/o dyskinesia, time spent sleeping, and decreased time of bothersome dyskinesia and mobility.



Were there any serious adverse effects of treatment?

There were a total of 13 severe adverse events recorded between the groups (10 neurostimulation and 3 medication only). Three patients died in the neurostimulation group (1 from a bleed in the brain during surgery, 1 from pneumonia, and 1 suicide). In the medication group 1 patient died in a motor vehicle accident while in a psychotic state. The other events resolved without complication. There were a total of 173 non-severe adverse events in 89 patients (39 stimulator and 50 medication) between the groups. Many of these events are known medical problems due to advanced Parkinson's disease.



What were the author's conclusions?

The authors concluded that their study is the first controlled clinical trial to focus on effects of treatment in regard to not only motor symptoms but also quality of life in patients with advanced PD under the age of 75. They found that those patients treated with DBS-STN had more improvement than those patients only treated with medication.



Why was this study important?

This study is important to evaluate the efficacy of DBS on difficulties with motor functioning as well quality of life in patients with PD. DBS is a treatment modality that has known risks but it is vital to have studies that document its efficacy and symptomatic benefits as compared to other treatment options so that patients and clinicians can make informed choices in regards to treating Parkinson's disease.

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Deuschl, G.,Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR. A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease. , 355, 9, 896-908355, 9, 896-908

Intro

This study looked at treatment efficacy in patients with PD treated with deep brain stimulation and medications to those patients treated only with medication. 



Who were the patients in the study and what were they asked to do?

There were 156 patients in this study between 2001 and 2004. Patients were carefully screened for appropriateness for surgical candidacy before being assigned to surgery or medication only treatment groups. The authors created 78 pairs to be treated so they could evaluate of the pair, which had a better response to their therapy. There were 78 patients that underwent bilateral DBS-STN and 78 patients that were treated with the best medication practices available at that center. The patient's were not different demographically (age: around 60, Duration of levodopa treatment 13-13.8 years, 50 males in each group, and similar Hoehn and Yahr stages). Patient's were asked to complete the PDQ-39 (Parkinson's Disease Questionnaire), Schwab and England Scale (test of functioning), Mattis Dementia Rating Scale (test of cognitive functioning), Montgomery and Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale (both for neuropsychiatric functioning), Medical Outcomes Study 36-item Short Form General Health Survey (SF-36; quality of life measure), and were evaluated by the neurologist on the Unified Parkinson's Disease Rating Scale (UPDRS). Patients were also asked to keep a diary of their mobility throughout the study before and after treatment initiation.



Who were the researchers?

The research in this study was conducted at 10 academic centers in Germany and Austria



What did the researchers find?

The researchers found that those patients treated with neurostimulation had more improvement in motor symptoms, dyskinesias, general health status, quality of life, mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort as compared to those only treated with medication. Activities of daily living slightly declined in the medication only group. There were no improvements or differences between the groups in terms of social support, cognition, depression, or communication.



According to the diaries kept by the patients, the group treated with neurostimulation showed significant improvement in their objective rating of their immobility, time of mobility w/o dyskinesia, time spent sleeping, and decreased time of bothersome dyskinesia and mobility.



Were there any serious adverse effects of treatment?

There were a total of 13 severe adverse events recorded between the groups (10 neurostimulation and 3 medication only). Three patients died in the neurostimulation group (1 from a bleed in the brain during surgery, 1 from pneumonia, and 1 suicide). In the medication group 1 patient died in a motor vehicle accident while in a psychotic state. The other events resolved without complication.



There were a total of 173 non-severe adverse events in 89 patients (39 stimulator and 50 medication) between the groups. Many of these events are known medical problems due to advanced Parkinson's disease.



What were the author's conclusions?

The authors concluded that their study is the first controlled clinical trial to focus on effects of treatment in regard to not only motor symptoms but also quality of life in patients with advanced PD under the age of 75. They found that those patients treated with DBS-STN had more improvement than those patients only treated with medication.



Why was this study important?

This study is important to evaluate the efficacy of DBS on difficulties with motor functioning as well quality of life in patients with PD. DBS is a treatment modality that has known risks but it is vital to have studies that document its efficacy and symptomatic benefits as compared to other treatment options so that patients and clinicians can make informed choices in regards to treating Parkinson's disease.

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Moro, Poon, Lozano, Saint-Cyr, & Lang. Subthalamic nucleus stimulation: improvements in outcome with reprogramming. , Arch Neurol. 2006 Jul 10; Epub ahead of printArch Neurol. 2006 Jul 10; Epub ahead of print

Note from the reviewers at The Parkinson Alliance: The following Current Science Review was made intentionally lengthy as it is our opinion that the area of DBS programming is a vital challenge to the PD community and this article expressly addresses these concerns.  We hope that you read it with as much interest as we did.    This article discusses issues relevant to patients with DBS.  The authors discuss that DBS-STN is an effective treatment for PD; however, it does not come without significant cost of money, time, and well-trained professionals.  Treatment with DBS can be challenging in that it requires professional familiarity with programming of the device as well as ability to modify medications to treat PD.  Similarly to other areas involving DBS, there are no guidelines for DBS programming or specific qualifications to be a programmer, which can be at the expense to the patient.  This article suggests that such guidelines and training would help to promote clinical efficacy, battery life, and negative side effects associated with the programming.  The authors suggest that currently the task of programming is given to various individuals with various levels of training.  They then went on to cite an example of postoperative care at Toronto Western Hospital Movement Disorders Program (authors affiliated with this program include: Drs. Moro and Lang, and Ms. Poon), including hiring a movement disorder neurologist that took over the postoperative care of their patients.  This doctor reportedly completed the majority of the programming as well as the medications adjustments based on the individual patient responses to both the stimulator and the medication management.   With the changes they made they expressed an interest to evaluate the efficacy of the system, which they had set up.  Their initial hypothesis was that the improvements they made to their postoperative care would result in improved patient response for new patients as well as patients that were reportedly stable following their older system.     



They studied 44 patients with PD (only 1 patient had surgery outside of their facility) that had DBS STN for at least one year.  All patients had the same stimulator and underwent postoperative MRI to confirm the placement of the electrodes.  Their "old method" involved programming that was completed 2-3 weeks after surgery, off medication, and staying overnight at the hospital.  Patients then went through testing of all electrode sites on each side (if bilateral stimulation) and effects were noted (method is listed specifically in this article).  After the "optimal contact" was located on each side then a combination of trials were conducted to evaluate additional efficacy.  Patients continued to have additional adjustments made over the course of the following 3 months (daily or weekly).  The authors noted that a supervising movement disorder neurologist discussed the setting parameters with the individual making them, but that the neurologist did not "directly observe" all of the effects. 



They found that regardless of using the old or new method, patients undergoing the surgery had improvement on the majority of outcome measures administered (e.g. UPDRS, dyskinesia disability score, off duration score, and levodopa equivalent daily dose).    According to the authors, the original 44 patients underwent "reprogramming" (new method) at a routine follow up appointment.  Patients were evaluated in their off state by the movement disorder neurologist (method is listed specifically in this article, but includes the UPDRS) and then went through reprogramming.  The authors noted that the voltage of the stimulator was slightly lower than that needed to produce "disabling dyskinesias."  Medication adjustments were then made based on the patient experienced symptoms after the reprogramming.  Patients were kept at the hospital setting for 1-2 hours in the event of delayed adverse events (e.g. worsened dyskinesia, general worsening).  The authors reported that they kept patients from out of town for a few days for monitoring and those that lived in Toronto could go home but were kept in close phone contact over the course the following few days.  Patients were reassessed at a minimum of two times over the course of 14 months after the reprogramming for any additional changes in programming or medications.  The authors were interested in changes in patient UPDRS scores.     



They found that patients could be divided into three groups, 1.  Those that experienced improvement in symptoms (N=24, 54.6%), 2. those with no significant change (N=16, 36.4%), and 3. those that worsened (N=4, 9.1%).  The authors found that those that improved (Group 1) tended to be younger, had better preoperative UPDRS motor scores, and worse dyskinesia duration.  All patients in Group 1 had stimulator setting changes.  Many of these individuals experienced improvement right away in the areas of "resting tremor, rigidity, and bradykinesia."  A little over half of these patients developed stimulator induced dyskinesias (SID) after the reprogramming, all of which were managed over the course of 1-2- weeks by either stimulator adjustments or medication changes.  On average these patients were seen five times within 14 months (range was 1-16 visits).   The patients seen fewer times generally had difficulties coming into the office for follow-up but were contacted via phone for continued contact.  Typical areas of improvement after reprogramming included reduced freezing, walking difficulties, dyskinesia disability scores, and levodopa equivalent daily dose.  Improvements were not seen in the areas of speech and falling.  Only five (31.2%) of the patients in Group 2 required stimulator-setting changes.  This group did not evidence significant change and on average were seen 3 times over the 14 months (range 1-8).  Of the four patients in Group 3, all experienced worsening in speech and gait, which required changing their settings back to the original values.



The authors concluded this article by noting that their hypothesis for better care with the involvement of a movement disorder specialist was correct in more than half of the patients studied.  They highlighted the need for a movement disorder neurologist was necessary as the direct observation of parameter settings and patient responses was beneficial in determining additional settings as well as necessary medication changes.  They also noted that need in the medical field for more neurologist trained in movement disorders that is capable of managing patients that have undergone DBS.  The authors opined that this neurologist has to have a good balance between programming and medication management of patients to improve general clinical care and possibly reduce the need for medications.  The authors indicated that the management of patients treated with DBS does not necessarily have to be hard if a movement disorder neurologist know the benefits, adverse effects, and interactions of the stimulator and medications used to treat PD.  The authors suggested that the parameters and dosages of necessary medications typically do not change much over time once optimization is established.   The authors suggested that a movement disorder neurologist is also mandatory in treating SID, which the exact method to do so is discussed in the article.  They also discussed hypothesis as to why Groups 2 and 3 may not have experienced improvement as compared to Group 1.  They also discussed the limitations to their study, which they did not feel affected the results they found.  The authors end the article by noting that it is very important to have a movement disorder neurologist affiliated with patients undergoing DBS for at least the first few months after surgery for the best possible optimization of treatment that they can receive.

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Schupbach, W. et al. Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up. , 2005 Dec;76(12):1640-42005 Dec;76(12):1640-4

This article discusses the results of 37 patients with PD that underwent bilateral DBS-STN at a clinic in France. Patients were evaluated at 1 month prior to surgery and 6, 24, and 60 months after surgery. They had strict criteria for inclusion of patients for surgery and had attrition of 6 patients by the end of the study (5 deaths, 1 relocated). They found that the patients had more motor improvement with stimulation and levodopa combined versus either treatment alone. They also found less dyskinesias and less need for levodopa, but that the benefit decreased across time. Patients also had improvement in their activities of daily living at the 6 month point, which was lost at the later testing times.



Scores on depression and cognitive screening remained the same across testing through 24 months, but performance on a cognitive screening measure began to worsen at the 60 month evaluation. Their patients did not experience permanent adverse events during the 5 year trial but had various transient events (e.g. emotional fluctuations, urinary retention, eyelid opening difficulties, weight gain). A total of 13 stimulators had to be replaced in the group of patients due to low power (anticipated or experienced) in the battery. The authors listed multiple side effects of intermittent stimulation due to the battery. One of the limitations of this article was that there was no control group of patients with PD to compare to those who underwent DBS-STN. The authors suggest that regardless of a control group there was sustained improvement five years after DBS-STN. They also suggested the possibility of neuroprotective factors of DBS-STN but noted the literature is mixed and mostly completed on animal models. They concluded by suggesting more long term studies to measure the efficacy and possible protective factors of DBS-STN.

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Benabid AL, Chabardes S, Seigneuret E. Deep-brain stimulation in Parkinson's disease: long-term efficacy and safety - What happened this year. , 2005 Dec; 18(6):623-302005 Dec; 18(6):623-30

These authors reviewed 260 articles from 2/04-3/05 involving PD and DBS looking at what researchers have covered and discovered over a year. It should be noted that this article is not a meta-analysis of the literature but simply a review of content and new discoveries. They discuss that the debate over neuroprotective factors, methodology, and placement continue to be controversial issues. The authors noted that in the reviewed articles there is consensus in regard to beneficial effects of stimulation, stability of effects, inclusion criteria, that other conditions may not respond to stimulation, and that stimulation mimics the effects of ablative surgery as well as dopatherapy. They indicated that patients undergoing brain stimulation experienced improvement in gait, balance, and sleep. They reported that quality of life is greatly linked to improved motor symptoms and not as much to improved cognitive or social difficulties, which is not surprising as the stimulation treatments are not purported to improve cognition or social support. The authors completed a cost analysis and found that over the course of 5-7 years that surgical options are cheaper than medications. They discussed the debate regarding stimulator placement, which continues as the studies looking at placement are usually completed on small groups, there are team differences (sites have different methods, outcomes, etc. which makes it hard to compare to each other), patients may not have severe symptoms, and research has shown between the placement sites (STN vs. GPi) a lack of difference on various measures. This article also discussed other diseases that are under review for treatment with DBS (Essential tremor, Obsessive Compulsive Disorder). The authors also discussed side effects of surgery (hypophonia, swallowing, weight gain) as well as surgical complications (stroke 1.15%) due to infections, misplaced leads, and hardware problems. The article also mentions psychological complications such as increased apathy yet mildly improved depression. It is unclear why there are psychological complications such as is it due to the surgery, improper programming, poor stimulator placement, or poor patient selection criteria. Overall they concluded that DBS has been shown to be a reliable and valid treatment with stable effects. However, they stated that the debate sadly continues regarding very important information for DBS (location, subcomponents of the surgical procedures, side effects, questionable neuroprotective effects, and the exact mechanism of action) and suggested that these problems will only be solved with methodological improvement.

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Neurology

Frysinger RC, Quigg M, & Elias WJ. (2006). Bipolar deep brain stimulation permits routine EKG, EEG, and polysomnography. Neurology, Jan 24;66(2):268-70Jan 24;66(2):268-70

This article discussed medical complications/issues of two DBS-STN patients that required additional "electrodiagnostic procedures" (procedures that measure electrical impulses in the body) for other medical conditions. The authors frankly discuss that DBS-STN is being used more often for PD as well as other conditions and that the population that undergoes DBS is getting older and likely will require other tests (EEG for brain activity, EKG for heart activity, Polysomnography for measurement of multiple body functions during sleep) for other non-PD medical conditions. As the DBS stimulator is electrical it tends to distort the electrical recording of the EEG and EKG so the data is not as interpretable as when the patient does not have a DBS stimulator. Obviously, when a patient requires an EEG or EKG the patient and doctor want the best possible recordings for correct diagnosis for treatment of the "other" condition being evaluated. The two patients discussed in this article had successful DBS surgery (one bilateral then other unilateral) but as they aged needed an EKG and an EEG for various reasons. The authors found that when the DBS was set at bipolar stimulator settings there was little to no effect on the EEG, EKG, and sleep studies. However when the DBS was set at monopolar settings there was a lot of interference with both EEG and EKG, to the point it was uninterpretable. This study is very important for DBS patients as the alternative to bipolar or unipolar setting changes during an EEG or EKG would be to turn the stimulator off, which also causes problems for the testing (tremor effects can distort other electrical tests) as well as for the patient (changes may cause discomfort or inability to walk for up to 1 hour). The authors also noted that there is great debate about the most optimal DBS parameters and that setting configurations should be made based on each patient and each disease. Additionally, they noted that when other electrically based tests need to be performed, physicians should consider various setting configurations for the best possible results and minimization of patient discomfort.

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Lancet Neurology

Chaudhuri, KR, Healy DG, Schapira AH; & National Institute for Clinical Excellence (2006). Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurology, Mar; 5(3):235-45Mar; 5(3):235-45

This was a great article that reviewed the nonmotor symptoms of PD (depression, psychosis, falls, and sleep disturbances), which the authors discuss is significantly related to quality of life in patients with PD. They discuss that the research in PD lacks specific studies to look at nonmotor symptoms and subsequent treatment within the community. The authors noted that the cause of the nonmotor difficulties is relatively unknown. However, there are many hypotheses as to the causes and they specifically listed a 6 stage speculation by Braak and colleagues that indicated Nonmotor symptoms may occur prior to the later stage motor dysfunction: 1. Loss of smell due to the loss of dopamine in the brain/smell areas 2. Disruption of systems in the brain meant to maintain the homeostasis (balance or maintenance of order in one's body to function well) of the individual such as sleep disruption, sweating, inability to control temperature 3. and 4. (combined) Tremor and motor symptoms 5. and 6. (combined) Lewy body (abnormal grouping of protein in a cell that causes various diseases) involvement causing psychosis and hallucinations

The authors then went through commonly seen sleep disturbances (nocturnal non-motor symptoms, REM sleep behavior disorder, excessive daytime sleepiness), neuropsychiatric symptoms (depression, anxiety and apathy, psychosis and visual hallucinations, and cognitive impairments), and dysautonomia (dysfunction of the system in the body that controls automatic functions, for example constipation, sexual dysfunction, and pain). After discussing what the nonmotor symptoms are they then went on to discuss recognition of nonmotor symptoms by patients, carers, and treating physicians. They went through multiple measures of nonmotor symptoms as well as common treatments. They concluded with suggesting that nonmotor symptoms need to be identified early in the disease process to address the quality of life for the patient as well as his/her family and carers.

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Journal of Neurosurgical Anesthesiology

Venkatraghavan, L., Manninen P, Mak P, Lukitto K, Hodaie M, Lozano A. (2006). Anesthesia for functional neurosurgery: review of complications. Journal of Neurosurgical Anesthesiology, Jan;18(1):64-7Jan;18(1):64-7

The purpose of this study was to evaluate anesthesia difficulties that may occur during functional neurosurgery, such as in DBS. The authors indicated that there are few studies that discuss the management of anesthesia during functional neurosurgery nor is there much literature discussing the incidence of intraoperative (during the surgery) complications. The study only looked at adults and was relatively basic including looking at demographics, medical condition, type and duration of surgery, anesthetic management, and complications (during and post surgery). They studied 178 patients (mean age 51, weight 75 kg, 109 women, 69 men, duration of surgery 353 minutes, 87 pts had PD, 128 had a movement disorder, DBS was done in 172 cases). They found that 28 patients (16%) had intraoperative complications, including seizures (n=8; most common), severe headache, vomiting, shortness of breath (possibly related to anxiety), hypertension, and drowsiness. Of those patients experiencing a seizure five did not require medications and the other three responded to administered medications but all went through with the procedure. Five patients experienced neurological changes, including speech difficulties, fluctuating level of consciousness (later found to have a small bleed at site of electrode), and one experienced a large bleed in the brain (this pt had a poor outcome). After surgery 11 patients had complications including, intracranial bleed (n=4), confusion (2), seizure (1), neurological deficit (3), and a cerebrospinal fluid leak (1). They concluded that their anesthesia method was successful in all but two of the patients and that most of their patients did not require sedation during their procedure. They acknowledged that a small proportion of the patients had intra and postoperative complications but added that none of the patients received sedation during electrode placement, which is thought to be critical. They purported that the use of sedation during procedures has been shown to "affect the quality of microelectrode recordings." They also reported a study in the literature suggesting that patients that underwent local anesthesia had better improvement in motor difficulties due to more precise targeting of the STN than those that underwent general anesthesia. They highly suggested early awareness and monitoring of patient's breathing, blood pressure, and fluid management from the anesthesiologist during surgery to avoid intra and postoperative complications such as intracranial bleeding, airway obstruction, and embolism. They also indicated that the anesthesiologist should treat any difficulties early to avoid additional complications. They noted the importance of a multidisciplinary treatment team to make sure that patient's are correctly selected for this procedure to minimize any complications.

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Plaha, P. & Gill, S. (2005). Bilateral deep brain stimulation of the pedunculopontine nucleus for Parkinson's disease. , Neuroreport. Nov 28; 16(17):1883-7Neuroreport. Nov 28; 16(17):1883-7

The purpose of this article was to look at stimulation of the Pedunculopontine nucleus (PPN) in 2 patients with PD, specifically for better control of gait and postural instability. They reviewed the literature that suggests stimulation of the STN or GPi improves many of the motor features of PD but does not assist with gait or postural instability predominantly in the "off" medication state. They reviewed animal literature that showed stimulation of the PPN increases motor activity. They also discussed that in autopsy studies researchers have found that patients with motor dysfunction (in various diseases) had signs of dysfunction in this nucleus. Patient 1 (60 years old, duration of disease 30 years) and Patient 2 (60 years old, duration of disease 12 years) went through multiple motor/balance tests prior to and after surgery to evaluate the success of bilateral stimulation placement in the PPN. Generators were turned on after 24 hours and adjusted over the course of a few days. They found that both patients had improvement in gait, postural instability, and other motor features of PD in both the on and off medication states. The authors noted there were no medical or cognitive complications for either patient. They also discussed the stimulation parameters and found in both patients that lower frequencies worked better than higher frequencies. It should be noted that there was a relatively short follow-up time of these patients and that they should be followed long term to fully evaluate improvement in motor functions as well as other possible long term effects. They concluded by discussing the proposed pathways of the PPN that improve gait and postural and recommend that additional research focus on the PPN to improve motor functioning in patients with PD.

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Annals of Neurology

Silva M.F., Faria P., Regateiro F.S., Forjaz V., Januario C., Freire A., Castelo-Branco M. (2005). Independent patterns of damage within magno-, parvo- and koniocellular pathways in Parkinson's disease. Annals of Neurology, Brain. Oct;128(Pt 10):2260-71Brain. Oct;128(Pt 10):2260-71

This was a very detailed article discussing the literature for visual disturbances in patients with PD as well as a study looking at different patterns of visual dysfunction. They began by discussing that the measurement of contrast sensitivity in patients with PD needs to be precise and some studies have used imprecise measures, which contributes to the variability amongst studies in the literature. They described the various methods to measure contrast sensitivity and the pros and cons of each. They noted that visual tests also need to be as free as possible from other cognitive skills (e.g. visuospatial), that may be mediated by other areas in the brain that may have dopamine receptors or depletion. They added that studies should also take age of one's brain, retina, and other ocular structures into consideration when doing this type of research. These authors attempted to look at visual performance in the fovea (A part of the eye responsible for sharp central vision) and the periphery (A part of vision that occurs outside the very center of gaze). Doing this, also allowed them to look at multiple visual layers associated with the visual system including; magnocellular layers (associated with achromatic vision [not color] and luminence), parvocellular layers (associated with chromatic [color] vision, specifically the colors red-green) and koniocellular (associated with chromatic vision, specifically the colors yellow-blue) in order to specify areas affected by PD. They noted that in this type of research it is important to exclude common age-related visual difficulties, such as glaucoma, cataracts, maculopathy, and diabetic retinopathy as all of the above can affect the multiple visual pathways. This study was conducted in Portugal and looked at thirty patients (16 female, 14 male, mean duration 4.6 years, age 61.1, Hoehn and Yahr 1.9, UPDRS motor 25.0) and 32 controls (19 female, 13 males, mean age 57.9). There were no educational differences between groups. Notably 10 of the PD patients were newly diagnosed and were not receiving medication at the time of visual testing. Other patients receiving medication for PD were tested in the ON state. They found that patients with PD had deficits in all layers of the visual pathway (magno-, parvo-, and koniocellular) using different methods, suggesting pathways were affected independently not as a result of each other. Duration and age were not found to fully explain these findings, as those recently diagnosed also showed chromatic difficulties. The authors also found predominantly more differences in parvocellular (red-green) pathways between groups. They suggested that prior research that suggested more difficulties with koniocellular (yellow-blue) pathways may have been related to age. They also found that magnocellular pathway dysfunction was related to Hoehn and Yahr stage, suggesting deterioration with stage, as well as age. Additionally they found, as seen in previous literature, that there was reduced dopamine supply around the fovea that resulted in poor contrast sensitivity in patients with PD. The authors also cited a series of studies that discussed what causes the reduction in dopamine at the retina, including ganglion cell (a type of neuron located in the retina of the eye that receives visual information) changes and thinning of the retinal nerve fiber. They suggested that future studies evaluate the role of medications, disease duration, Hoehn and Yahr stage, and specific tests to measure the different visual pathways in patients with PD.

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Journal of Neurosurgery

Balash, Y., Peretz C., Leibovich G., Herman T., Hausdorff J.M., Giladi N. (2005). Falls in outpatients with Parkinson's disease: frequency, impact and identifying factors. Journal of Neurosurgery, 2005 Nov; 252(11):1310-52005 Nov; 252(11):1310-5

These researchers wanted to look at frequency of falls and associated factors in patients with PD. They briefly reviewed why studying falls, a gait difficulty with serious complications (physical injury, fears, restriction of activities, and admission to nursing homes) for the patient with PD, is important. They reported that the frequency of falls in the literature is approximately 38-68% but that associated factors are not as well documented or understood. This study was conducted in the UK on 350 patients with PD (230 males, 120 females; mean age 69.7, duration of PD 8.6 years). The authors also looked at cognitive function, depression, general health, activities of daily living, balance, gait, and bladder dysfunction (they cited literature that showed urinary urge incontinence is associated with falls in older women). Patients were asked to count how many falls (those requiring and not requiring medical attention) they had in the previous week, month, and year. Thirty-two percent of the patients had 2 or more falls in the previous week, month, or year of the study. Additionally, 10.6% of patients had a fall that required medical attention (cut, fracture, and bleeding in the brain). The authors also found that urinary incontinence and duration of PD were the only significant predictors of falling. Additionally, they found that patients prone to falling had worse Hoehn and Yahr scores, depressive symptoms, lower activities of daily living, and identified their health as "poorer." Additional statistics suggested that if a patient had PD and urinary incontinence, he/she was 6 times more likely to have repeated falls. Also, a slowed performance on a measure of gait and disease duration also suggested that patients were more likely to have repeated falls. The authors also discussed a limitation to their study including that it was retrospective (asking patients and carers to remember how many falls occurred over the last year may be difficult and inaccurate), which may have lowered the actual number of falls that individuals had. They cited a study suggesting patients tend to underreport the number of falls they've had, which suggests that the actual number of falls in their group may be higher than that reported. They also discussed that based on their data, falls are associated with progression of PD and may be due to the loss of postural reflexes and postural instability. They also encouraged medical professionals and family members to be aware that if a patient with PD has incontinence that they are more likely to have difficulties with falls and may require more fall precautions or associated therapies. They ended by suggesting continued study of medications, urinary incontinence, orthostatic hypotension, and autonomic dysfunction in regards to fall risks for patients with PD.

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Bodis-Wollner I.(2002). Visualizing the next steps in Parkinson's disease. , Aug;59(8):1233-4Aug;59(8):1233-4

This article is an editorial written collaboratively to the Diederich article also reviewed in the current science reviews. This author added that visual complaints are common in patients with PD. He noted that the difficulties are often attributed to aging, macular (central portion of the retina) changes, or other eye conditions that are not related to PD. Through his research he has found that vision deficits can be found in patients with PD that do not have age or disease related optical or retinal changes, that levodopa has shown improved performances on visual tests, and that dopamine blockers have been shown to cause impairments in visual processing. This author has also found that vision can fluctuate concurrently with ON/OFF states. He hypothesizes, similarly to Diederich, that visual impairment is related to reductions in dopamine related to PD. He also cited studies that have show the visual deficits are not due to poor acuity that instead it is due to contrast sensitivity causing spatial problems. He noted that spatial difficulties also tend to be worse in environments with low lighting as there is less contrast between objects, steps, words, etc. This author also noted the importance of the Diederich article in discussing that visual impairments correlate with "motor severity, progresses along with the motor symptoms, and fluctuates in parallel with motor fluctuations." The author discussed various hypotheses regarding the cite of injury in the brain/eye that would cause visual disturbances but at this time it is unclear whether retinal changes causes changes in the processing areas of the brain or vice versa. The author also questioned what type of damage to the visual system is responsible for walking/balance/gait disturbances that are seen in patients with PD. The author correctly discussed that a single lesion may not be identifiable to explain visual deficits as well as there are likely multiple processes (specific lesions, changes between areas in the brain that communicate and work cooperatively, etc.) to explain these deficits. He suggested that additional pathophysiological work needs to be done to explore PD in general but to also explore visual deficits.

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Diederich NJ, Raman R, Leurgans S, Goetz CG. (2002).. Progressive worsening of spatial and chromatic processing deficits in Parkinson's disease. , Aug;59(8):1249-52Aug;59(8):1249-52

This article began by reviewing how the visual system can be affected by Parkinson disease. They cited studies that suggest visual deficits are due to reduced dopamine concentration in the retina, abnormal electrical responses in the brain related to visual processing, and reduced metabolism in the area of the brain that controls visual processing. They also mentioned that intoxication to MPTP (a byproduct of an illicit narcotic drug that when taken persons will have the same signs and symptoms of PD) has been found to cause abnormal electrical functioning in the eye. They suggested that patients have reduced contrast sensitivity (used for spatial processing), which they suggested are related to stage and duration of PD as well as the time of the day (e.g. morning versus evening). They also suggested that poor color discrimination (processing different colors) can be found early in PD. The stated hypothesis was to evaluate patients with PD longitudinally (across time) to evaluate the potential changes in contrast sensitivity as well as color discrimination. Twenty eight patients with PD (mean age 65.2 years, PD duration=13.53 years, duration of treatment with levodopa=8.57 years) were evaluated in their "on" state at two separate times approximately 19.8 months apart. Patients with dementia, other neurological conditions, psychosis, or preexisting low visual acuity or color blindness were excluded. Patients were also given the UPDRS as well as a measure of psychiatric symptoms. The authors found that both contrast sensitivity and color discrimination worsened across time for the patients with PD. The authors specifically made the distinction that both conditions worsened independently versus a decline in one visual ability causing worsening in the other. Deterioration of contrast sensitivity was correlated with age, duration of PD, Hoehn and Yahr stage, and UPDRS motor and ADL assessments. Vision change was not correlated with medications or mental status on the UPDRS. Interestingly, color discrimination was only correlated with age. They also found that those patients that had more severe visual impairments after 19 months showed the highest scores on the measure of psychiatric symptoms. They suggested that aging alone does not explain their findings because PD patients typically have more decline in color discrimination and contrast sensitivity as compared to age matched controls, and aging typically affects different frequencies of contrast sensitivity than seen in this group. However they correctly note that aging combined with PD likely explains some of their findings, as it is difficult to tease out exactly how much each condition explains visual changes in this group of patients. In regards to the psychiatric symptoms, the results of this study do not allow the reader or researcher to determine which difficulty came first, the vision or the psychiatric. The authors noted that previous research has shown that patients with PD and visual deterioration "are at a higher risk of developing visual hallucinations." The authors concluded by discussing how deteriorating vision (both contrast sensitivity and color discrimination) causes difficulties with walking as the patient may over interpret or misinterpret incoming visual information, which may in turn cause falls, tripping, illusions, poor depth perception, poor distance judging, and possible visual hallucinations. They suggested that future research should evaluate more patients in a longitudinal study to evaluate deterioration of vision also using more complex statistical calculations.

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Journal of Neurology

Spliethoff-Kamminga NG, Zwinderman AH, Springer MP, Roos RA. A disease-specific psychosocial questionnaire for Parkinson's disease caregivers. Journal of Neurology, Oct; 250(10):1162-8Oct; 250(10):1162-8

This article purported to look at a questionnaire measuring psychosocial difficulties faced by patients with PD and associated carers. This is a European study that begins by discussing the prevalence and demographic information for patients with PD in Europe, which were similar to the numbers for the United States. They whole heartedly discuss the importance of physicians focusing not only on the patient but on the carer as well, as both parties are involved on a day to day basis with this disease. The assessment tool they used, The Belasungsfragebogen Parkinson Angehorigen-kurzversion (BELA-A-k), looks at specific problems (physical, emotional, social, and family functioning) related to being a carer for someone with PD and the individual need for help related to that problem. The BELA-A-k has 15 items grouped into four subscales (achievement capability/physical symptoms, fear/emotional symptoms, social functioning, and partner-bonding/family) and are scored on a scale of 0 (not at all) to 4 (a great deal). Patients in this study were also given a functional health assessment scale, loneliness scale, and a quality of life scale. A total of 50 patients with partners (34 women, mean age 71.1, duration of patients PD=7.0 years, average carer hours given per day 3.5 [range 0-24], education most were high school educated or above) were assessed and asked to fill out the aforementioned materials. The authors found that caregivers were most concerned about fear/emotional functioning and achievement capability/physical symptoms. Carers reported that they were bothered by the future and less frequently bothered by sexuality difficulties and worsened financial position. The carers indicated that needed help due to feeling psychologically overwhelmed in their interactions with the partner. The authors found that their results were also related to the patient's physical disability as measured by the Hoehn and Yahr scores. Interestingly the authors also reported observed comments from participants including that the carer appreciated focus on their concerns but also wanted to make sure their partner received full attention for his/her difficulties. The authors discussed that this scale was beneficial in discussing carers concerns and that it was more beneficial than a general quality of life scale as it focused on issues related to PD. The authors also discussed another quality of life scale for caregivers (the Scale of Quality of Life of Care-Givers, SQLC), which also sounds promising. The authors discussed the limitations of their study (small sample size, only looking at spouses not other carers. They ended by again highlighting the need for physicians to pay attention and ask questions about carer burden as it also has an effect on their patient and his/her quality of life.

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