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Lempka SF, McIntyre CC. Theoretical analysis of the local field potential in deep brain stimulation applications.. , PLoS One. 2013;8(3):e59839. doi: 10.1371/journal.pone.0059839. Epub 2013 Mar 28.PLoS One. 2013;8(3):e59839. doi: 10.1371/journal.pone.0059839. Epub 2013 Mar 28.



Intro:  Many things are not known about the cause of the debilitating motor symptoms seen in Parkinson’s disease (PD), but it is known that the basal ganglia is very involved.  Many things are also not known about why deep brain stimulation (DBS) works to reduce motoric symptoms of PD.  The goal of this study was to look closer at the electrical systems of the basal ganglia, specifically the subthalamic nucleus (STN), regarding etiology and understanding of motoric symptoms as well as to evaluate the DBS device in interacting with and measuring that system.


Methods:Complex theoretical computational models were created simulating PD as well as the DBS device based on various known factors about both (e.g. electrical amplitudes, different types of tissue, etc.).


Conclusion:  The model created by the authors provided significant very detailed information about multiple aspects of recording models within the electrical system of the STN in PD.  This study provides very technical information for a variety of people involved in the treatment of PD such as those completing surgery, creating stimulators, etc. but it is notable that it is very challenging to represent the complexities of the brain and its vast neural network on a computer.  Although this study didn’t utilize human subjects, studies such as this one are helping to get one-step closer to fully advance the understanding of this disease at such a detailed technical level as well as evaluating the therapeutic intervention without causing any adverse events in a person with PD (PWP).


This article was available free at the time of this write up.  Click here and then click on the blue “Open access to full text PLOS/One” or “Free in PMC free full-text archive” buttons in the upper right hand corner of the page.



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Desouza R, Moro E, Lang A, Schapira A. Ann Neurol.. Timing of deep brain stimulation in Parkinson. , 2013 Mar 8. doi: 10.1002/ana.23890. [Epub ahead of print] 2013 Mar 8. doi: 10.1002/ana.23890. [Epub ahead of print]

Intro:  PD is a common and costly neurodegenerative disease that affects people worldwide.  This disease affects both young/old, motor/nonmotor systems, quality of life for individuals/families, and truly is a “complex, chronic, multifaceted disease.” 

Methods:  The authors reviewed multiple articles available in the literature regarding “timing of DBS in PD”  questioning whether the idea of utilizing DBS earlier in the disease course could have better motor as well as quality of life outcomes (QoL) for people with PD (PWP). 

Findings:  
Medication is the most widely used treatment for PD; however, in the early 2000s DBS received FDA approval to treat PWP.  Debate continues regarding the best stimulation site for DBS and it often is used later in the disease course after medications are no longer as effective, there are significant side effects, or the off-periods are quite long.  The criteria for surgical candidacy often requires that the PWP is “medically and psychologically fit” enough to undergo the surgery, they do not have “cognitive dysfunction” (e.g. dementia, mild cognitive impairment, etc.), and their PD must have been responsive to dopamine medications.  The criteria as written can be challenging for the PWP that has had the disease for decades, effectively robbed of their physical ability to complete such a surgery.  Clinicians and researchers have recognized this limitation resulting in the suggestion of “individualized criteria” for each PWP to insure the optimal treatment outcomes.  DBS continues to show promise in improving motor symptoms and some nonmotor symptoms, decreased medication levels, and improved QoL.  However, there are also adverse outcomes with this treatment including hardware issues, “infection, bleeding, stroke, death, depression, apathy, weight gain, speech,” and cognitive changes.  Notably, the article reported that adverse event rates are lower at facilities that complete the surgery more frequently.  The authors also posited that there might be a difference in effects on QoL from DBS between younger and older PWP with younger PWP reporting more benefit.

Some small studies have looked at DBS in PWP completed earlier (defined in various lengths of times) in their disease course.  These studies have shown that the PWP had similar rates of surgical complications as well as improvements in motor symptoms, QoL, and reduced need for medications as those PWP that received their DBS later in their disease.  Critics of such studies note that the possible surgical complications and adverse events should make this a “last resort” therapy while proponents cite the possibility of multiple years of improved motor symptoms and general functionality. 

Animal studies have also shown that DBS has neuroprotective factors regarding neuronal loss and dopamine levels, but often these findings are not reproducible in humans.  Hypothetically, if such neuroprotection was there for humans as well, completing the surgery earlier on should have benefit, as there would be more neurons to protect.  Unfortunately, the long-term studies to date have not shown such neuroprotection from DBS.  These long-term studies have shown that there continues to be motor benefit from DBS, but the disease remains progressive.

Conclusion:   Research on treatments for PD has flourished over the past decades and the authors suggest that clinicians and researchers alike challenge themselves to continue to look for new and inventive ways to combat this disease.  They raise the possibility of earlier usage of DBS in PWP in order to improve motor symptoms and QoL based on some very promising small studies.  The authors encourage studies looking at early DBS as compared to typical medicinal treatments to test that hypothesis.



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Epub

Effect of deep brain stimulation on speech performance in Parkinson's disease.. Effect of deep brain stimulation on speech performance in Parkinson's disease.. Epub, S. Parkinsons Dis. 2012;2012:850596. doi: 10.1155/2012/850596. Epub 2012 Nov 21.S. Parkinsons Dis. 2012;2012:850596. doi: 10.1155/2012/850596. Epub 2012 Nov 21.

Intro:  Difficulties with speech are a common finding in people with Parkinson’s (PWP) that can occur at any point in the disease.  Some may have soft, low speech (hypophonia) while others have challenges initiating talking or experience slurring (dysarthria).  All of the speech difficulties can lead to significant frustration for the PWP as well as a reduction in interacting with others.  Speech therapy has shown benefits to improve speech in PWP, while medicinal (e.g. dopamine) and surgical (ablative and stimulation) treatments have shown considerable variability.  The goal of this article was to review the literature regarding DBS, speech, and PWP.

Methods:  The author reviewed 35 studies, completed in 2012 or earlier, that evaluated speech in PWP that underwent DBS.  Most of the studies looked at DBS-STN and the author noted that there were many differences in procedures, as well as the instruments used to measure speech, which made it difficult to compare each study to one another.

Findings/Conclusions:   After review of the available articles, the author discussed continued variability in DBS effects on speech in PWP.  The author attempted to find predictive trends usable to help PWP and their treatment teams plan the most efficacious treatments in regards to motor improvement and speech.  Although no definitive pattern surfaced, the studies suggested that there might be both positive and negative effects of DBS on speech.  Some of the studies showed improvement after DBS in vocal tremor and hypophonia while others showed worsening dysarthria.  The etiology of speech dysfunction also remained elusive in this review.  The author hypothesized, based on the studies, that if a PWP had significant motor impairment prior to DBS that the person had a higher chance of speech difficulties after implantation.  However, such decisions regarding treatment often are made for optimal motor control versus speech symptoms.  The author also noted that attention to speech problems after DBS is necessary and attempts at optimal stimulator settings may alleviate the speech difficulties.  Different stimulator placement sites were also briefly discussed with some indication that there were less dysarthric adverse events with DBS GPi (globus pallidus interna) than DBS STN but the number of studies were small with small numbers of PWP in each study.  Other sites such as caudal zona incerta (cZi) and ventral intermediate nucleus of the thalamus (Vim) simply needed more studies to draw conclusions about speech.  Simply put, more research on speech in PWP is necessary in order to better understand the causes and predict which patients may be at a higher risk of developing or experiencing worsening of speech difficulties.  The studies should look at speech before and after DBS and utilize multiple measurements to evaluate speech, including subjective ratings from the PWP themselves and/or family members.  The goal of DBS ultimately is improved
motor control but ability to talk is quite important in one’s quality of life.



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Parkinsonism & Related Disorders

Chan H-F, Kukkle PL, Merello M, Lim SY, Poon YY, Moro E.. Amantadine improves gait in PD patients with STN stimulation.. Parkinsonism & Related Disorders, Parkinsonism and Related Disorders. 2012 Dec 6. pii: S1353-8020(12)00438-5. doi: 10.1016/j.parkreldis.2012.11.005.Parkinsonism and Related Disorders. 2012 Dec 6. pii: S1353-8020(12)00438-5. doi: 10.1016/j.parkreldis.2012.11.005.

Intro:  Although DBS STN has been shown to be efficacious to improve classic motor symptoms of Parkinson’s disease (PD) such as tremor, rigidity, and slowed movement it has not shown comparable results in regards to “axial symptoms” such as speech, balance, and walking difficulties which have been found to worsen as the disease progresses.  Studies have also found that speech difficulties can worsen, specifically after DBS STN.  Clinicians and researchers alike continue to search for treatments for classic motor as well axial symptoms.  Amantadine is such a drug treatment.  It is an antiviral drug that has multiple uses including for the flu (influenza A)1, reducing fatigue in autoimmune disorders2, as well as it works on multiple neurotransmitters (dopamine and acetylcholine) related to movement disorders.  Treatment with amantadine for PD has been around for some time (1960’s) and has been shown to reduce dyskinesias but has mixed findings on gait.  According to this article, there were no published studies looking at the use of amantadine to improve speech in people with Parkinson’s disease (PWP). However, they used clinical experience from a patient who showed improvement in the aforementioned axial symptoms when taking this drug so the authors wanted to evaluate formally such possibilities in a multicenter study.

Methods:  Forty-six PWP (M=36, F=10; Mean age at surgery: 57 years; duration of PD: 13 years) were evaluated across three international surgical sites.  Each PWP had DBS STN (all but one bilateral) and remained on levodopa as well as had maximal stimulator settings during the study.  The amantadine was introduction slowly and increased over a few weeks.  The authors used a portion of a motor rating scale (UPDRS III) as well as asked for subjective ratings by the PWP regarding their speech, gait, and balance before and after the amantadine.

Findings:   The amantadine was started at various times after surgery (3-120 months) specifically for difficulties with the axial symptoms.  It was notable that 72% of the PWP had tried amantadine prior to DBS with no improvements in the axial symptoms. After DBS STN, the study showed that around 30% of the PWP taking amantadine had improvements in walking, but there was not improvement in balance.  Speech symptoms showed a trend of improvement but not at the level of statistical significance.  When looking at the subjective ratings of the PWP, approximately half reported improved speech, two-thirds improved gait and balance, and one third improved in all three areas. As with any drug, there can be side effects that are not tolerable to some who take it.  In this study, 11% of the participants had adverse effects from the amantadine including hallucinations, confusion, or edema.  An additional 4% did not find the medicine to be helpful.

Conclusion:   There are many challenges in having PD and the classic motor symptoms have received a great deal of attention in the research arena.  However, it is important to continue to evaluate treatments for the PWP related to difficulties that can cause decreased quality of life due to significant disability such as the axial symptoms of speech, balance, and gait.  This study’s results are promising in that PWP experienced measurable improvement in gait as well as felt as though they had improvement in all three axial areas.  It was noted that many of the patients experienced an improvement after stimulation with the amantadine compared to no improvement prior to DBS from the amantadine with minimal adverse effects, suggesting there could be an interaction with the stimulator and the medication, which should be further explored.


1.  www.webmd.com
2.  www.nationalmssociety.org



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Journal of Neurosurgery

Rocchi L, Carlson-Kuhta P, Chiari L, Burchiel KJ, Hogarth P, Horak FB. . Effects of deep brain stimulation in the subthalamic nucleus or globus pallidus internus on step initiation in Parkinson disease.. Journal of Neurosurgery, 2012 Dec;117(6):1141-9. doi: 10.3171/2012.8.JNS112006. Epub 2012 Oct 5.2012 Dec;117(6):1141-9. doi: 10.3171/2012.8.JNS112006. Epub 2012 Oct 5.

Intro:   One of the motor complications with PD is difficulty in starting or initiating steps while walking.  Although walking may seem simple and easy to most adults, there is a myriad of complex neural connections and multiple motor pathways that are involved in taking a simple step.  The literature shows that levodopa usage can help with this difficulty but it is less clear if DBS provides similar benefit.

Methods:  Twenty-nine patients with PD that underwent DBS (14 GPi, 15 STN) were studied as were 28 healthy age matched volunteers (control group) and nine individuals with PD that did not undergo DBS.  General ages of the groups were 60-62 and the DBS groups were mostly males that had been diagnosed with PD approximately 11-12 years prior to surgery.  The surgeries were completed by the same Neurosurgeon and all patients were followed by Neurology for stimulator settings and medication dosages for optimal symptom control.  Each of the DBS groups was tested before surgery, on and off their medications, as well as 6 months post surgery, on/off medication and on/off stimulator.  Testing consisted of participants standing on and taking steps from flat plates designed to record multiple measurements related to stepping/walking (e.g. pressure, position, velocity/speed, step length, etc.)

Findings:   The control group had less difficulty initiating steps compared to the PWP in all medication and stimulator settings, which was an expected finding.  However, the authors found that when PWP were evaluated before surgery while taking levodopa there were improved effects on multiple measures such as adjusting ones' posture in anticipation of taking and shortened amount of time planning to take a step.  These findings did not persist after either the DBS STN or GPi surgery for the PWP.  The authors also looked at length and speed of taking a step and found that the PWP had slower and shorter steps than the control group.  The study again found improvement from taking levodopa in the length and speed of taking a step before the surgery and this result remained in the stimulator on/medication on condition after surgery.  However when looking specifically at DBS STN vs. DBS GPi they found that the speed of taking a step while taking levodopa after surgery when the stimulator was on was slower in the STN group.  When the authors looked at step initiation in the PWP that did not undergo DBS, they found that this group did better than either of the DBS groups both before and after surgery on the stepping measures.  It should also be noted that both the DBS STN and GPi groups showed improvement in overall motor symptoms after the surgery.

Conclusion: This study showed some differing findings of what DBS versus levodopa can do to step initiation in PWP after 6 months of stimulation.  It showed that step initiation improved with levodopa prior to surgery but worsened after DBS.  Additionally the levodopa response disappeared after surgery.  An important point to note about this study is the usage the control group without PD.  Comparing the PWP that did not undergo DBS to those that did indicated that the finding of worsened step initiation was not due to disease progression as the non-DBS group did better after a 6 month follow up than the DBS groups.  Although many studies have shown improvement in many motor symptoms after DBS surgery, this study is important to show that it may also have an adverse event of worsening gait, specifically hesitating when starting to walk and freezing.  More research was recommended using the pre and post designs as well as the control groups to continue to understand the positive and negative implications of DBS for PWP.



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Calleo, J., Burrows, C., Levin, H., Marsh, L., Lai, E., York, M. (2012). Cognitive Rehabilitation for Executive Dysfunction in Parkinsonís Disease. , Parkinsonís Disease, vol. 2012, Article ID 512892, 6 pagesParkinsonís Disease, vol. 2012, Article ID 512892, 6 pages

The purpose of the review was to determine whether or not cognitive rehabilitation has potential to improve cognitive skills and quality of life in patients with cognitive dysfunction in PD.  Click here to download a PDF of this review.



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Neurology

Weaver FM, Follett KA, Stern M, Luo P, Harris CL, Hur K, Marks WJ Jr, Rothlind J, Sagher O, Moy C, Pahwa R, Burchiel K, Hogarth P, Lai EC, Duda JE, Holloway K, Samii A, Horn S, Bronstein JM, Stoner G, Starr PA, Simpson R, Baltuch G, De Salles A, Huang GD, Reda DJ; For the CSP 468 Study Group.. Randomized trial of deep brain stimulation for Parkinson disease: Thirty-six-month outcomes.. Neurology, 2012 Jul 3;79(1):55-65. Epub 2012 Jun 20.2012 Jul 3;79(1):55-65. Epub 2012 Jun 20.

Intro:   There are numerous studies that have shown effectiveness of deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD).  However, there are few long-term studies and even fewer that have looked at DBS subthalamic nucleus (STN) vs. DBS globus pallidus interna (GPi).  The authors of this study wanted to add such information to the literature so they created a well-designed study looking at the effectiveness of DBS for these two brain structures and compared the outcomes against each other. 

Methods:  One hundred and fifty-nine people with Parkinson’s disease (PWP) from 13 different medical centers in the United States (Veteran’s Affairs Medical Centers and affiliated Universities) were followed for 36 months after DBS implantation.  The PWP were randomly assigned to either the DBS STN (N=70) or DBS GPi (N= 89) groups.  Each group was given baseline motor, cognitive, and mood measures before surgery as well as follow up evaluations at months “3, 6, 12, 18, 24, and 36” in combinations of the on/off medications stage and the on/off stimulator stage.  Each group also kept “motor diaries” to track their impression of motor abilities throughout the time of the study.

Findings: Baseline Data:  The STN and GPi groups were not significantly different from each other in terms of demographic information (e.g. age, sex, marital status) at baseline (prior to surgery).  However, the STN group reported more difficulties prior to surgery with mobility, mood, feeling stigmatized in public or in relationships, receiving support from others, and communicating with others.  The GPi group also did better prior to surgery on a task requiring them to come up with words in specific categories, as quickly as they could as well as on a task where they had to learn verbal information. 

Post-surgical data:  Motor: Both groups had stable improvements in formally tested motor functioning from surgery through the end of the study.  It is notable that there was not a significant difference between the groups.  Both groups also had improvement in “tremor, rigidity, akinesia, postural stability, and gait.”  The DBS STN group was found to have worsened motor function in the off medication/off stimulator setting than the DBS GPi group at the 36-month evaluation.  Interestingly, in the on medication/on stimulator settings at the 36 month mark, the DBS STN group was not as stable as the DBS GPi group.  However, both groups had a reduction in medication, although greater for the DBS STN group.  The PWP in both groups noticed an improvement in their motor function as measured by their motor diaries of over 5 hours per day by the 6 month mark, which was generally sustained at the 36 month mark (STN: 4.1 and GPi: 4.6 hrs/day gain in functioning).  Off time and dyskinesias were reduced for both groups throughout the 3-year study. 

Sleep and Quality of Life: Both groups had an increase of hours asleep per night, sustained over the three-year mark.  Additionally, both groups reported a decline in the support/assistance received from others at the end, as compared to the beginning, of the study.

Cognition:  The DBS STN group experienced slightly more cognitive decline (memory and executive tasks) as compared to the DBS GPi group, but both groups had evidenced cognitive decline over time. 

Mood:  Neither group had significant changes in mood when comparing the scores at the beginning to the end of the three-year study.

Conclusion: The authors previously reported that the DBS STN and DBS GPi groups both generally experienced sustained improvement in motor abilities after a two-year period.  This study continues to show sustainable findings for both targets after a three-year period.  However, there were some mild differences between the two targets as it relates to medications and stimulation effects.  The authors hypothesized that the medications were not as effective at the end of the study for the DBS STN group, which is thought to be due to the greater reduction in medications after surgery.  In contrast, the medications in the DBS GPi group were increased over time.  As the DBS STN group had less stable motor functioning at the end of the study as discussed above, it was unclear to the authors if the DBS GPi or the higher medication dosages may have contributed to a more stable progression of PD for that group.  Both groups were found to have decline in cognitive functioning likely related to progression of their PD, but the DBS STN group evidenced slightly more cognitive decline in aspects of memory and executive functioning.  The two groups had comparable mood scores.  Quality of life and ability to complete activities of daily living scores initially showed improvements, but these improvements were not sustained at the end of the study.  The scores at the end of the study were comparable to the PWP scores prior to surgery, which was likely due to the progression of PD.  Previous research had suggested that DBS GPi was not as sustainable as DBS STN, but this study suggests both targets are sustainable over time although there may be some differences with progression of the disease due to possible medication effects or the targets.  The authors conclude that there is more consensus of sustainability for both targets and that previous studies may have different findings due to different patient characteristics as well as advancements in the techniques/knowledge of the therapies.  This study nicely showed that both targets are beneficial in improving motor functioning in PWP, but further intervention to improve quality of life and nonmotor symptoms as it relates to PD appears indicated.



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Fasano, A., Herzog, J., Seifert, E., Stolze, H., Falk, D., Reese, R., Volkmann, J., Deuschl, G. (2011).. Controlling Gait Coordination with STN-DBS Improves Freezing of Gait in Parkinsonís disease. , Modulation of gait coordination by subthalamic stimulation improves freezing of gait. Movement Disorders, 26(6): 844-851.Modulation of gait coordination by subthalamic stimulation improves freezing of gait. Movement Disorders, 26(6): 844-851.

A recent study conducted by researchers of the University of Kiel and the Deaconess Hospital in Germany, establishes that STN-DBS may provide an opportunity to improve FOG in PD by allowing doctors to adjust the symmetry and coordination of patient gait. According to the study, since FOG patients often display abnormal symmetry and coordination between each leg, these factors may impair the gait process and contribute to freezing in PD. However, by adjusting the voltage (electrical intensity) of stimulation in each side of the brain that controls the dysfunction in the respective leg, researchers suggest that STN-DBS may be able to alter gait symmetry and coordination and, thus, improve FOG in PD. This suggestion was based on a comparison of gait coordination and FOG frequency and duration in 13 patients with PD under four different stimulation conditions (i.e. voltage settings) of STN-DBS. Click here to download a PDF of this review.



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Bologna M, Fasano A, Modugno N, Fabbrini G, Berardelli A.. Effects of subthalamic nucleus deep brain stimulation and L-dopa on blinking in Parkinson. , Exp Neurol. 2012 Feb 14. Doi: 10.1016/j.expneurol.2012.02.004Exp Neurol. 2012 Feb 14. Doi: 10.1016/j.expneurol.2012.02.004

Intro:   People with Parkinson’s disease (PWP) often have difficulties with blinking (voluntary, reflexive, and spontaneous) due to depleted dopamine as well as changes within the brain, predominately the basal ganglia.  The authors note that DBS-STN has been effective on improving motor functioning in many motor regions but some areas have received less study such as what the treatment does for blinking difficulties.
 
Methods:  Sixteen PWP (4Females/12Males; Mean age 63, Mean disease duration 19 years.) were studied that had undergone bilateral DBS-STN.  The PWP were compared to 15 age matched healthy control subjects.   The PWP were evaluated at least 1 year post DBS-STN to insure that stimulator settings and medications were at effective settings/dosages.

Infrared cameras were used to evaluate voluntary, reflexive, and spontaneous blinking. The measurements were taken at four different points across time: stimulator only, medication only, no medication/ stimulator off, and medication/stimulator on.  PWP were off of their medication for 12 hours before being studied for the no medication conditions and the stimulator was turned off three hours prior for the no stimulator conditions.    

Findings: PWP had less global motor difficulties when they were on their medication as well as when the stimulator was on.  Specific information about blinking is listed below:
Voluntary blinking:  IT was found that when the stimulator was turned on, blinking took longer and was slower.  The results also showed that the pauses between blinking were slower when the stimulator was turned on.

Spontaneous blinking:  It was found that the spontaneous blinking rate was lower for the PWP when there was no medication and no stimulator.

Reflexive blinking: General differences were not found between the PWP and the healthy controls on this measure.  However, it was found that when there were more stimuli and a longer amount of time in between the presentation of those stimuli that there were changes for the PWP with the stimulator on and with medication.  Although there was a difference, the applicability of this finding is pretty small in one’s general ability to reflexively blink to something coming at one’s eye.

Conclusion:  DBS-STN changes PWP’s ability to blink in various ways.  The authors hypothesized two reasons to explain this phenomenon:


1.  It is possible that it is due to spread of the stimulator’s charge to areas beyond the STN.


2. It is due to changes from the DBS to the basal ganglia and the involved neurotransmitters communicating with the brain stem. 

The authors favored hypothesis 2.  It is noted that the authors hoped to add information to the side effect of ocular apraxia (inability to initiate opening one’s eye) that can be seen after DBS-STN but none of the patient’s studied experienced that adverse event after their surgeries.  However, they suggest that their findings on difficulty with voluntary and spontaneous blinking and possible etiology may provide utility to the apraxia research. 



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Borgohain R, Kandadai RM, Jabeen A, Kannikannan MA.. Nonmotor outcomes in Parkinson's disease: is deep brain stimulation better than dopamine replacement therapy?. , 2012 Jan;5(1):23-412012 Jan;5(1):23-41

(The full article was available free online at the time of this writing through the pubmed link below. Click on the button in the top right area of the screen.  This should take you to the PubMed Central articles section and you can click on the PDF or HTML option to read or access the article.)

Intro:  This article reviewed the known success rates of the stimulation therapies on motor symptoms in People with Parkinson’s disease (PWP).  However, the authors truly wanted to focus on the lesser known effects on nonmotor symptoms of Parkinson’s disease (PD) treatment with medicinal (dopamine replacement therapy) as well as stimulation (DBS or GPi) therapies.  They focused on four nonmotor domains:  “Neuropsychiatric, autonomic, sleep, and sensory dysfunction.”

Methods:  After a literature search for articles that looked at Parkinson’s disease, treatments, and adverse events the authors compiled various studies that compared stimulation and medicinal treatment in the four areas mentioned above.

Findings:
1. Neuropsychiatric Dysfunction:  The authors broke this category down further into cognitive (decision making, memory, language, etc.) and behavioral (depression, anxiety, etc.) changes.



  • Cognition:   Meta-analyses have shown that around 40% of individuals that undergo DBS-STN treatment will have a “mild” reduction in cognitive functioning.  However there is inconsistency in the literature about why and what type of cognitive changes occur from stimulation therapy due to a variety of reasons including various methods used to evaluate cognition, unknown effects of the surgery and stimulator (trajectory of leads, electrode placement, stimulator settings) on surrounding brain areas, electrode placement (STN vs. GPi), and stimulation site (bilateral vs. unilateral).  Research has also shown that older individuals with impairments in attention as well as that are not as responsive to dopamine therapy are more likely to experience cognitive side effects from DBS.  The research from medicinal therapy has shown that most individuals do not have cognitive side effects from such treatment.  When looking at meta-analyses and comparison of the two groups, the majority of studies have found reduced verbal fluency (ability to come up with words rapidly) in the group that underwent stimulation therapy.  Additionally, a few studies also found changes in the stimulator group in executive functioning (organization, planning, decision making) and verbal memory.


  • Behavior and Mood:  As there was inconsistency in cognitive issues related to stimulation therapy in PWP, there too is inconsistency in behavioral manifestations after DBS.  Reported changes after DBS include depression, suicidal ideation and attempts, hypomania, transient confusion, apathy, anxiety, and impulsivity.  However, there are a variety of psychiatric conditions that can be seen with medicinal treatment of PD as well including “depression, mania, anxiety, apathy,” hallucinations, psychosis, social dysfunction, and impulse control disorders.  Within both stimulator and medicinal treatment there were studies that showed improvement, worsening, or no change in various psychiatric conditions which again addresses fluctuations in the findings.  There is a notable challenge to researchers when comparing these groups after surgery as many patients will also have a reduction in needed medication, which may also improve psychiatric symptoms caused by dopamine therapies.  When the authors compared the stimulator groups to the medicinal groups they concluded that DBS may increase the risk of worsened psychiatric symptoms but that there is a lot of variability in PWP.


2. Autonomic Dysfunction:  Research has consistently shown that the progression of PD causes problems with autonomic functioning in PWP due to degeneration of various brain areas.  Such changes can occur in the cardiovascular, genitourinary, gastrointestinal, and perspiration/thermoregulation systems.



  • Cardiovascular:   Stimulation of the STN has been shown to cause tachycardia (increased heart rate), while GPi has not shown any cardiovascular change.   Medicinal therapies have been shown to cause orthostatic hypertension in PWP.   The authors concluded that DBS STN may help to alleviate orthostatic hypertension after surgery but that the reduction in medication is also a likely cause.


  • Genitourinary:  Approximately one- to two-thirds of PWP will experience difficulties with bladder urgency, frequency, and nocturia (excessive urination at night).  PWP will also commonly experience sexual dysfunction.  Stimulation therapies have been shown to have variable results on bladder functions but improvement in sexual abilities.  Medication treatments have also shown improvement in bladder difficulties but variable results on sexual dysfunction.  No studies were listed that directly compared the two groups in this area of nonmotor difficulty.


  • Gastrointestinal: Approximately 80% of PWP were listed to experience difficulties with “constipation, nausea, vomiting,” drooling, indigestion, delayed emptying of the stomach, and swallowing difficulties.  There were few stimulation studies that looked at gastrointestinal events.  Of those, there was improvement in swallowing, constipation, and over production of saliva. Medication studies showed mixed results depending on the type of dopamine replacement medication used. No studies were listed that directly compared the two groups in this area of nonmotor difficulty.


  • Perspiration/Thermoregulation:  Around 2/3 of PWP will experience difficulties in regulating their internal temperature and many may also have hyperhidrosis (excessive sweating).  Stimulation therapy has been found to be beneficial in reduction of sweating during “off” periods but has not been studied in “on” periods.  Medication therapies have been shown to have increases in sweating during wearing off times, which has been controlled with modification in medication dosages and reduction of wearing off times.  No studies were listed that directly compared the two groups in this area of nonmotor difficulty.


3. Sleep Dysfunction:  The majority of PWP will experience sleep disturbances that cover the gamut of sleep disorders.  Sleeping difficulties are caused by a multitude of factors including degeneration of various areas in the brain, medications, and motor dysfunction.  Stimulator therapies have shown benefit to PWP in regard to sleep with the exception of not necessarily improving daytime sleepiness.  Medication therapies have shown to be beneficial at lower dosages but become problematic at higher dosages often required with disease progression.  When comparing the therapies head to head, DBS was found to better control motor symptoms which were thought to then lead to better sleep for PWP.

4. Sensory Dysfunction:  There are a variety of sensory changes due to PD.



  • Smell:  Loss of one’s sense of smell is thought to be an early sign of PD.  Stimulator studies have shown improvement in smell versus medication therapies that have not shown any change.


  • Pain:  Many PWP will complain of pain.  Both stimulator and medication therapies have been shown to improve levels of pain experienced by PWP by improving pain thresholds, reducing intensity, and minimizing fluctuation of pain experienced.  No studies were listed that directly compared the two groups in this area of nonmotor difficulty.


  • Thermal Detection (sensitivity to heat/cold): Occasionally, PWP will have difficulties with detection of temperature.  One study showed that DBS improved PWP’s detection of temperature while medication therapy had no effect.


5. Overall Nonmotor symptoms:  There are measures used to look at the overall quality of life of PWP that covers both motor and nonmotor symptoms.  Multiple studies were listed that showed an improved quality of life for those that underwent DBS therapies versus the medication only group in the areas of improved movement, ability to complete activities of daily living, “stigma and bodily discomfort.”  It is noted that the two groups were not different in the areas of cognitive functioning, language abilities, and “social support.”  The inclusion of such assessment tools is absolutely necessary in continuing to evaluate treatment modalities so that PWP can make informed choices in management of their PD. 



Conclusion:  Both therapies are useful in controlling motor symptoms as well as have effects on nonmotor symptoms in PD.  These authors conclude that DBS therapies are “more effective in reducing sensory, sleep, gastrointestinal, and urological symptoms” compared to medicinal therapies.  The effects of medications as well as stimulation therapies have mixed effects on cognition, psychiatric concerns, and autonomic functions.  They conceded that DBS STN has generally shown to have effects on language fluency.  It is also noted that one advantage of DBS therapy is a reduction in the need for medication afterward, which likely minimizes some of the adverse events from the medication therapy.  Lastly, it is suggested that decisions about targets (STN vs. GPi; bilateral vs. unilateral) may be determined by nonmotor symptoms that each individual PWP is experiencing as both stimulator therapies have shown improved motor control. The evaluation of motor and nonmotor effects from medicinal as well as stimulator therapies needs to continue to be evaluated to help clear up the inconsistencies within the literature in order to provide the best possible care for PWP and insuring that they are able to make informed choices about each possible therapy suggested.



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Skodda, S., Flasskamp, A., Schlegel, U.. Instability of syllable repetition in Parkinsonís diseaseóinfluence of levodopa and deep brain stimulation.. , 26(4): 728-730.26(4): 728-730.

Patients with Parkinson’s disease (PD) often develop alterations of speech rate that inhibit their ability to communicate effectively, which may worsen quality of life. Although altered speech rate is frequently attributed to hypokinesia (weakness or loss of movement) of the speech organs, newer studies suggest that it may actually stem from an underlying impairment of vocal pace performance (speed in voice production) in PD. Click here to download a PDF of this review.



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Neurosurgery

Okun MS, Wu SS, Foote KD, Bowers D, Gogna S, Price C, Malaty I, Rodriguez RL, Jacobson CE, Ward H.. Do stable patients with a premorbid depression history have a worse outcome after deep brain stimulation for Parkinson disease?. Neurosurgery, 2011 Aug;69(2):357-60; discussion 360-1.2011 Aug;69(2):357-60; discussion 360-1.

The exact relationships between DBS for PD and nonmotor symptoms are commonly unknown.  Such is the case for depression.  The purpose of this study was to look at postsurgical outcomes for people with Parkinson’s disease (PWP) who also had a history of depression prior to the surgery versus those without any depression.  An equal number of participants in this study had either unilateral DBS STN or GPi.  It is also notable that the depressed individuals were successfully treated for their depression prior to the surgery. After surgical intervention, the authors found that the previously depressed group reported more symptoms of feeling depressed but their scores would still be classified in the “normal to mild” range.  They also found that the younger patients and those who had PD for a longer length of time had better improvement in their motor testing.  However, the previously depressed group and those taking higher dosages of levodopa experienced less improvement in their motor scores after surgery.  These results are significant in assisting in the decision for one to undergo DBS.  The authors concluded that PWP who have a history of depression may experience milder improvement in motor symptoms as well as mild worsening of nonmotor symptoms (e.g. depressive symptoms).  It is noted that although there were statistical differences, the clinical significance of the differences was very small. The reasoning for such postsurgical differences still remains unknown, but the authors recommend the use of a multidisciplinary team (neurology, neurosurgery, neuropsychology, and psychiatry) to try to better understand 1. the relationship between a history of pre-surgery depression and outcome following DBS, 2. factors that can improve outcome predictions in DBS for those individuals with a history of depression, 3. best surgical candidates, and 4. best treatment options/best medical intervention for the PWP.



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Donovan, S., Lim, C., Diaz, N., Browner, N., Rose, P., Sudarsky, L.R., Tarsy, D., Fahn, S., Simon, D.K. Parkinsonism & Related Disorders, 17(4): 240-245.. Laserlight cues for gait freezing in Parkinsonís disease: an open-label study.. ,

Background of the Study: Freezing of gait (FOG), or a sudden, brief inability to start or maintain normal stepping movements, is prevalent symptom of Parkinson's disease (PD) that affects about 32% of patients with PD. Unfortunately, unlike other symptoms of PD, FOG is resistant to Parkinson's medications and shows little improvement with ordinary walking aids. Since FOG often leads to falls and can contribute to disability and quality of life impairment in patients with PD, there is a significant need for more effective strategies for controlling FOG in PD.

Accordingly, a recent study conducted by researchers of the Harvard Medical School (Boston) and Columbia University (New York), establishes that the use of laserlight visual cues (laserlight “rods” or horizontal floor markers that help to signal or initiate walking) is an effective strategy for managing FOG and reducing falls in patients with PD. This suggestion was based on a comparative analysis of freezing and fall frequency in patients with FOG in PD when using a standard walking aid (i.e. cane and/or walker) and when using a walking aid with a laserlight feature.

Purpose of Study
: The purpose of the study was to assess the effectiveness of laserlight visual cues for controlling FOG in 26 Parkinson's patients with FOG. Click here to download a PDF of this study.

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Ahlberg E, Laakso K, Hartelius L.. Perceived Changes in Communication as an Effect of STN Surgery in Parkinson's Disease: A Qualitative Interview Study.. , Parkinsons Dis. 2011;2011:540158. Epub 2011 Aug 14. Parkinsons Dis. 2011;2011:540158. Epub 2011 Aug 14.

This article looked at the impressions/perspectives of four people with Parkinson’s disease (PWP) that underwent DBS-STN and had improvements in motor symptoms (increased mobility and reduced tremor) but also subsequent changes in their speech.  The article begins by listing what research has shown regarding how speech is affected by PD (“hypokinetic dysarthria, weakness, breathiness, monotony, imprecise articulation, and variable rate”) as well as by DBS-STN (variable findings, “improved phonatory and articulatory components,” reduced “speech intelligibility.”  All four of the individuals indicated that they believed that the surgery was life improving and that it was their only option for improvement.  The authors also looked at the impressions of the four individuals and ran analyses that looked for themes that ran through the PWP.  They found three main themes:



1. All four PWP experienced negative speech side effects, including:


       
  • Re-emergence of childhood stuttering

  •    
  • Dysarthria

  •    
  • Reduced intelligibility

  •    
  • Worsened micrographia

  •    
  • Mental Fatigue

  •    
  • Reduced concentration

  •    
  • Weak/Monotonous Voice

  •    
  • Hollow sounding speech

  •    
  • Reduction in feeling comfortable when talking with others

  •    
  • Worsening of experienced speech problems when fatigued or anxious

       


2.  All found ways to improve communication, including:


       
  • Slowing rate of speech.

  •    
  • Increase volume of speech.

  •    
  • Adjusting schedule to maximize their good speech times.

  •    
  • Having supportive others to assist when needed.

  •    
  • Adjusting medications.

  •    
  • Adjusting stimulator settings.

       


3.  Mixed feelings about the surgery:


       
  • Worsening of motor symptoms necessitated surgical intervention.

  •    
  • Expectations varied so there was some disappointment but no regrets of having the surgery.

  •    
  • Wanting more information both pre and post-surgery, such as talking with PWP who have undergone DBS-STN.

  •    
  • Uncertainty about what the future holds.

       


This paper concludes that there is a significant amount of individual variability in what each PWP experiences due to their PD as well as variability in the adverse events experienced after one undergoes DBS-STN.  It was also pointed out that this group wished they were more informed before and after the surgery, suggesting continued patient education is very necessary by researchers as well as medical professionals.  Lastly, we should be reminded by this study and others like it that the perception of the PWP should not be ignored as those individuals are living with the disease as well as any adverse events from the treatments and that their opinions directly relate to their quality of life and that their voices must be heard. 



This article was available free through PubMed as of this writing November 2011.  After clicking the link below, it will take you to the abstract page.  Once there, two bubble shaped boxes are located towards the top of the page listed as “Free full text article at Hindawi” or “Free full text article in PubMed Central.” Either button will take you directly to the full article.

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Lepmkal, S.F., Johnson, M.D., Miocinovic, S., Vitek, J.L., McIntyre, C.C. (2010). DBS Therapy for Parkinsonís disease: Current-controlled DBS vs. Voltage-Controlled DBS. , 121(12): 2128-2133.121(12): 2128-2133.

Deep brain stimulation (DBS) is a surgical treatment used to relieve some of the most debilitating symptoms of advanced Parkinson’s disease (PD). The treatment helps to control motor symptoms of PD using a surgically implanted DBS medical system, a device that sends electrical stimulation through electrodes (metal conductors) to specific parts of the brain that control movement. Currently, two types of DBS systems are available for DBS therapy: Voltage-controlled (VC) systems and Current-controlled (CC) systems.  Click here to download a PDF of this review.

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Okun MS, Foote KD.. Parkinsonís disease DBS: what, when, who and why? The time has come to tailor DBS targets.. , Expert Rev Neurother. 2010 Dec; 10(12):1847-57Expert Rev Neurother. 2010 Dec; 10(12):1847-57

This article answers the questions of what, when, who, and why in regards to DBS for PD.  The authors initially point out that all of the research so far on DBS for PD has shown that a single target and single approach to the surgery is not in the best interest of the patient or the field.  Much of the research done to this point has shown that DBS needs to be tailored to each individual.  The authors also highly recommend the use of an interdisciplinary approach ("neurosurgery, neurology, neuropsychology, and psychiatry") to screen individuals for such therapy in order to facilitate optimal surgical outcome. 



The what: 


       
  • The authors recommended that the surgical target be selected based on all available information about the patient and their symptoms which should be collected by the interdisciplinary team.

  •    
  • The topic of unilateral versus bilateral DBS was also discussed and the consensus was that there are still questions about which approach is best for various patients, and it may also depend upon the brain region targeted (e.g. GPi vs. STN).  Research has shown that both the STN and GPi are effective targets to reduce motor symptoms.  They recommended more studies look at this information.

  •    
  • The article also discussed the pros and cons about simultaneous implantation of the DBS leads versus a staged approach over the course of days, weeks, or months. There is not a consensus about either strategy, and it depends on the comfort levels of the treating team as well as facility.

  •    
  • The authors also discussed that the more "microelectrode passes" required in the surgery as well as poorer cognitive performance on a screening measure were indicators of likely longer stays within the hospital for various patients.  They recommended more studies look at this information.

  •    
  • In the research and clinical observations summarized to date, there have been positives and negatives to all of the targeted brain areas thus far.

       




The when: 


       
  • Due to the invasive nature of the surgery, most physicians make the determination for appropriateness of surgical intervention for PD patients after all medicinal therapies have failed and motor symptoms are difficult to manage.  However, the authors also talk about questions and scenarios regarding patients that have not advanced to the point of medication failure and could possibly benefit from surgical therapy.

  •    
  • They noted that surgery for the questionable cases described should be completed within a clinical research setting.

  •    
  • One rationale for waiting on the surgery is the possibility that the condition is not truly Parkinson's disease and may be another neurological condition that mimics PD early in the disease course.

  •    
  • Studies to address this topic are ongoing, and the authors expect there to be continued debate on study outcomes, particularly as it relates to the studies’ research methodology.

       




The who: 


       
  • After a review of the larger studies on DBS the authors conclude that the most likely patient to benefit from DBS would be one that has a failed response to medications and poorly controlled on-off motor fluctuations.

  •    
  • They noted that the most common cognitive difficulty that has occurred after DBS is a reduction in patient’s verbal fluency (e.g. ability to get words out quickly).

  •    
  • The authors also discussed that depression has been shown to improve immediately after surgery but may worsen after a longer period of time.  Anger was also found to be problematic.  It is unclear whether or not these changes are due to the stimulation in and of itself or from the lesion created during the surgery.

  •    
  • It is suggested that patient selection be done by a multidisciplinary or interdisciplinary team.  Patient goals and expectations about the surgery should also be sought by the team and outcome measures need to be patient centered for motor and nonmotor symptoms. 

       




The why:


       
  • Surgical intervention can be very successful for appropriate PD candidates in the “moderate to advanced” stages.

  •    
  • It was suggested that studies continue looking at other surgical treatment options compared to DBS to determine how effective those options are.

  •    
  • The ultimate goal of DBS is to maximize therapeutic benefit in reducing specific motor symptoms; while at the same time minimizing risks for the patient (key areas were discussed in the article).

  •    
  • Success also depends upon adequate programming of the device after the surgery.



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Volkmann, J., Albanese, A., Kulisevsky, J., Tornqvist, A., Houeto, J., Pidoux, B., Bonnet, A., Mendes, A., Benabid, A., Fraix, V., Blercom, N.V., Xie, J., Obeso, J., Rodrigues-Oroz, M.C., Guridi, J., Schnitzler, A., Timmermann, L., Gironell, A., Molet, J., Pascual-Sedano, B., Rehncrona, S., Moro, E., Lang, A., Lozano, A.M., Bentivoglio, A.R., Scerrati, M., Contarino, M.F., Romito, L., Janssens, M., Agid, Y. (2009). Long-term effects of pallidal or subthalamic deep brain stimulation on quality of life in Parkinson’s disease.. , 24(8): 1154-6124(8): 1154-61

Background of the Study



Deep brain stimulation (DBS) is an effective surgical treatment used to improve motor symptoms in patients with advanced Parkinson’s disease (PD). However, despite its potential therapeutic value, the treatment has two key limitations:


       
  • DBS cannot cure or stop the progression of PD

  •    
  • DBS, like any brain surgery, is a risky procedure with possible adverse effects.

       


As a result, it is important to ensure that the benefits of DBS outweigh the potential adverse effects and, in the long run, have an overall positive impact on patient quality of life.



Accordingly, an international team of researchers from Germany, Italy, Spain, Sweden, France, Canada, and the Netherlands conducted a recent study to evaluate how the leading types of DBS therapies affect quality of life in patients with advanced PD. The study found that while both subthalamic DBS (STN-DBS) and internal pallidum DBS (GPi-DBS) led to significant early improvements in patient quality of life, many of these initial benefits diminished after three years.



Purpose of the Study



The purpose of the study was to assess the longterm impact of DBS on patient quality of life by evaluating a group of patients who have been followed for at least 3 years after STN-DBS or GPi-DBS surgery.



Click here to download a PDF of the complete study.

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Kramer DR, Halpern CH, Buonacore DL, McGill KR, Hurtig HI, Jaggi JL, Baltuch GH.. Best surgical practices: a stepwise approach to the University of Pennsylvania deep brain stimulation protocol.. , Neurosurg Focus. 2010 Aug; 29(2): E3Neurosurg Focus. 2010 Aug; 29(2): E3

This article discussed a step by step approach to how the University of Pennsylvania's Movement Disorder Clinic works with DBS patients in order to best improve motor function and minimize adverse events.   The authors initially discussed preoperative preparation, which includes choosing patients carefully in order to have a successful intervention.  They noted that good prognostic indicators include:  "a PD diagnosis, medication responsiveness, tremor, bradykinesia, rigidity, frequent on-off fluctuations, and decreased functional on-times."  Indicators of poor surgical outcomes include:  "moderate to severe cognitive decline and other Parkinsonian syndromes" (e.g. Parkinson plus syndromes).  If patients are deemed appropriate, they then undergo a battery of lab tests and a physical exam.  A multidisciplinary approach is used for appropriate surgical candidate selection. On the day of the surgery, the emphasis truly becomes precision of the intervention.  To assist with developing precision, a specialized frame is placed on the head of the PD patient in order to hold the patient's head in place for imaging and surgery.  Each patient undergoes an MRI with continual and specific measurements (detailed information is available in the article) made in order to contribute to surgical precision.  The authors continued to discuss specific techniques during patient prep as well as actual surgical interventions (e.g. incisions, lead placements, and studies to conduct during the procedure).  After the leads are placed in the brain, the battery pack of the stimulator is then placed in the right side of the patient's chest wall.  The authors also described postoperative care including restarting medications, imaging, and restorative therapies.  Programming of the device typically occurred between 10 days and a few months following surgery with the concurrent goal of medication reduction.  It is very admirable of the University of Pennsylvania to thoroughly discuss their methodology with the goal of improving the outcomes of this effective surgical intervention.  The authors were also upfront about their nonpermanent adverse event rate of 12.6% (4.6% for permanent adverse events), which is relatively low.  It is imperative that successful Movement Disorder treatment teams follow the University of Pennsylvania's lead in sharing their methodology in order for other treatment centers to have similar levels of success for PD patients.

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Tripoliti E, Zrinzo L, Martinez-Torres I, Frost E, Pinto S, Foltynie T, Holl E, Petersen E, Roughton M, Hariz MI, Limousin P.. Effects of subthalamic stimulation on speech of consecutive patients with Parkinson disease.. , 2010 Nov 102010 Nov 10

This article systematically looked at patients over time to evaluate the short and long-term effect(s) of deep brain stimulation of the subthalamic nucleus (DBS-STN) on speech in people with Parkinson's disease (PWP) as there has been significant variability in the literature to its effect.  It has been unclear in prior studies if the speech problems commonly seen are due to the surgery itself, disease severity, response to medication, spread of the current from the stimulator, patient specific characteristics (e.g. age, gender, etc.), or other unknown factors.  The PWP who underwent DBS-STN in this study showed improved motor control, reduced medication usage, and variable speech effects.  Although some patients had improvements in their speech after surgery, the majority did not (78% reported decline within 1 year of surgery).  The decline in speech typically was observed over the three year time frame and remained even when the stimulator was turned off.  The authors found that speech decline was related to a few factors, including the area within the STN in which the stimulator was placed, a pre-test motor score in the “on” medication state, and the higher amplitude of stimulation specifically in the left side of the brain (possibly due to the spreading of the current from the stimulator when it was on). Although DBS-STN improves motor symptoms of PD, this study confirms that this treatment could have deleterious effects on speech.  Such research studies need to be conducted for this population so that PWP can make informed decisions about this surgical treatment option.

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Espay AJ, Vaughan JE, Marras C, Fowler R, Eckman MH.. Early versus delayed bilateral subthalamic deep brain stimulation for Parkinson's disease: A decision analysis.. , 2010 May 21. [Epub ahead of print]2010 May 21. [Epub ahead of print]

The purpose of this article was to look at the utility of a statistical model to predict the effectiveness of DBS-STN on motor functioning, cognitive abilities, and quality of life when the surgical intervention is done early or later in the disease course.  The typical reasoning behind eligibility requirements for people with Parkinson's disease (PWP) to undergo DBS-STN either early or later is based on length of time that the individual has had Parkinson's disease (PD) as well as their responses to medicinal intervention (e.g. levodopa medications).  Typically, DBS-STN has been used as a therapeutic option later in the disease course (average 14 years) once multiple medicinal treatments have been tried and the PWP often have more motoric disability.  These authors suggest that there may be better effectiveness and less disability if PWP undergo DBS-STN earlier in the disease course.  They created a statistical model based on the available literature on DBS-STN, a group of PWP that had undergone DBS-STN, and a group of PWP that had not undergone DBS-STN.  Their model suggested that early intervention was effective most of the time.  They also found that early intervention would have greater effect on quality of life for those who had DBS-STN and that those who had not undergone the surgery preferred the delayed intervention.  It was suggested that the discrepancy between the two groups regarding when to have the surgery may have to do with the uncertainty that the non DBS-STN group may have about the risks and complications about the surgery while the DBS-STN group may be more focused on the benefits that they have experienced.  The model also indicated that for those PWP whom had a fast progressing motor decline a delayed surgery would be more effective as it was possible that the underlying cause of the decline was mixed and not purely PD.  This study was also very upfront about the limitations of using such a model and suggested that clinical trials would be the best way to determine actual effectiveness of early versus delayed surgical intervention.  They noted that there are two such trials in process that have looked directly at the question of effectiveness of the early surgical intervention.  We at DBS-STN.org are very interested as well in the results of these clinical trials and will review those studies when they are available, so stay tuned for the update!

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