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Clinical interventions in aging

Tan ZG, Zhou Q, Huang T, Jiang Y. Clin. Efficacies of globus pallidus stimulation and subthalamic nucleus stimulation for advanced Parkinson. Clinical interventions in aging, 2016 Jun 21;11:777-86. doi: 10.2147/CIA.S105505. eCollection 2016.2016 Jun 21;11:777-86. doi: 10.2147/CIA.S105505. eCollection 2016.

Introduction:   Parkinson’s disease (PD) is a common neurological condition that is initially treated with levodopa to control the motor symptoms.  The medications are frequently effective but as the disease progresses the medications are frequently not as effective and can cause adverse motor side effects (e.g. freezing and dyskinesias) for People with Parkinson’s disease (PWP).  Additional therapies were created, deep brain stimulation (DBS), in the 1990’s and have consistently shown efficacy in controlling motor symptoms for PWP.  Much of the earlier research focused on the motor control and did not pay as close attention to the nonmotor symptoms which can also be very disabling.  Recent research has focused on neurocognitive outcomes and these authors conducted a meta-analysis to review such studies.  

Method:  After establishing multiple exclusion and inclusion criteria, a review of the literature was completed and ten randomized clinical trials (9 bilateral STN or Gpi, 1 unilateral) were analyzed.  The trials had evaluations at a variety of times including 6, 12, and 24 months postsurgery.

Results:  

      Motor: The results were slightly mixed before 24 months but at the 24 month mark the DBS STN group had more motor improvement. Notably the score difference was only a few points which showed to be statistically significant but likely was not clinically noticeable.  

      Medications: Results showed that more medication was needed after DBS GPi.
 
      Mood: The results showed that the DBS STN group had statistically significant lower mean depression scores but only by a few points.  Notably both groups had clinically meaningful depression mean scores with variability within each group.
 
      Cognition: A variety of cognitive domains were evaluated including language (fluency and naming), processing speed, executive functioning, and a broad screening measure.  Most of the cognitive measures showed no difference between groups but the DBS STN group had lower scores on the fluency measures and one task of executive functioning.  Mean test scores were not provided so it was unclear to what level each group was experiencing cognitive changes in general.
 
      Quality of Life (QoL): QoL was measured by the PDQ-39 which is a self-report measure looking at multiple dimensions of QoL (scales: mobility, activities of daily living; ADLs, emotions, stigma, social support, cognitions, communication, body pain, and an overall score). The DBS GPi group had higher scores in all areas but stigma which still tended towards the GPi group.  

Conclusion:  The authors concluded that both groups had improvement in motor functioning after DBS regardless of the target site and the minimal findings between the two were clinically insignificant.  They suggested that the choice for surgical intervention may be better suggested by the medicinal needs and nonmotor symptoms present prior to surgery.  As an example, they noted that DBS STN may be a better option for a PWP that had more levodopa induced dyskinesias prior to surgery as they likely would have a lower dose of levodopa after DBS which may minimize that adverse event.  They note that it is important to monitor depression symptoms in all PWP undergoing DBS.  The neurocognitive findings also noted that the DBS STN had more cognitive challenges on three specific measures that may have been due to surgical effect as the challenges remained even when the DBS was off.  Interestingly the DBS GPi group had higher QoL in most areas but was based on limited data with some possible presurgical differences as well.   This meta-analysis is a great first approach in looking at the nonmotor symptoms of DBS treatment for PWP.  These findings continue to suggest that the best approach to choosing the appropriate target for DBS should be based on the individual PWP after evaluation by a multidisciplinary team.


(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. 



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Parkinsonism & Related Disorders

Mochizuki H1, Taniguchi A2, Nakazato Y3, Ishii N4, Ebihara Y5, Sugiyama T6, Shiomi K7, Nakazato M8. Increased body mass index associated with autonomic dysfunction in Parkinson. Parkinsonism & Related Disorders, 2016 Mar;24:129-31. doi: 10.1016/j.parkreldis.2016.01.007. Epub 2016 Jan 92016 Mar;24:129-31. doi: 10.1016/j.parkreldis.2016.01.007. Epub 2016 Jan 9

Introduction:   There is inconsistent research regarding body mass index (BMI) in Parkinson’s disease (PD).  Some studies have found an increase while others have found a decrease.  Some postulates regarding decreased BMI in PD is related to the constant motor movements in PD causing increased expenditure of energy.  Another is PWP experience a reduction from decreased eating related to loss of smell that can be seen early in the disease.  These authors specifically wanted to look at the role of autonomic dysfunction as it relates to BMI in PWP.

Method:  One hundred and twenty four people with PD (PWP; 68 women, mean age 68, duration of PD 25 months, BMI 22.6) were studied across 6 years prior to taking medications for PD.  Each PWP was given two specific tests, one to measure parasympathetic and the other for sympathetic activity.  

Results:  The authors found that BMI was negatively correlated (as one goes up the other goes down) to the parasympathetic and sympathetic activity measured.  BMI was not found to be related to disease duration or severity.  PWP that had higher BMI also had lower sympathetic and parasympathetic activity.
 
Conclusion:  The authors concluded that their study showed that increased BMI was related to autonomic dysfunction in PWP.  They noted that when there was dysfunction in both the sympathetic and parasympathetic systems there was an increase in BMI for the PWP.  They also found that their sympathetic measurements showed that those with early stage PD had lower heart rates that also led to increased BMI.  This study showed that there may be multiple causative factors for increased and decreased BMI in PWP and that it is important for medical providers to consider such possibilities for treatment purposes.



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Parkinsonism & Related Disorders

Hariz GM, Limousin P, Hamberg K.. "DBS means everything - for some time". Patients. Parkinsonism & Related Disorders, 2016 Mar 17.2016 Mar 17.

Introduction:   Deep brain stimulation (DBS) for Parkinson’s disease (PD) has shown great efficacy in treating motor symptoms of PD.  As with other treatments, DBS has known side effects such as speech and gait changes but the treatment likely affects each person with PD (PWP) differently as there are many factors that determine each PWPs outcome.  The goal of this study was to take an in-depth look at PWP narratives regarding the quality of life (QoL) in day to day functioning as it may better capture information than the typical less personal self-report inventories commonly used in research studies.   
 
Method:  The study took place in Sweden and involved 42 PWP (11 women; mean age 64; PD duration 11.4 years; time since surgery 2.8 years; 43% DBS STN bilateral; 31% Zona Incerta unilateral) who underwent 1.5-2.5 hour open ended interviews regarding QoL with two of the authors of the study.  Most of the interviews were completed in the PWP’s home and focused on daily functioning.  

Results:  Most of the PWP described improvement regarding the impact on their life from DBS (93%) but there were others that did not find benefit (7%).  A little over half of the PWP also experienced adverse events after the DBS (speech, gait, balance, and memory).  The authors decided to break down the QoL into five separate areas which are discussed below.

1. Reduced tremor.  Many of the PWP of this study reported disabling tremors prior to DBS.  After DBS they described that they were better able to complete activities of daily living (e.g. eating, dressing, computer usage) due to reduced tremor which resulted in improved QoL.  They were able to resume various independent tasks, having to rely less on others, as well as increase their leisure pursuits.  PWP also commented that having less visible tremulousness was helpful to increase their social interactions and reduce the insecurity and embarrassment that some felt prior to surgery.  

2. Reduce cramps and pain.  PWP had reduction in cramps in various body parts which resulted in improved walking and sleep.  Expectedly, the reduction in pain was also found to be beneficial to improve QoL.  

3.  Reduced motor freezing and improved prediction of ability to complete tasks.  The PWP experienced significant freezing and stiffness pre DBS that greatly limited the ability to go to events/activities as well as independently complete tasks in the home that they wanted to do.  They explained that DBS helped to “widen” their living spaces as they were not as confined to their homes as they were before surgery.  

4. Adverse events: Many of the PWP were accepting of the adverse events that they experienced after DBS in exchange for the benefits from the procedure.  There were three PWP that described that their adverse events of balance, speech, and memory difficulties greatly impacted their QoL in ways that were worse than they had expected.  Notably all three of those PWP also described their symptoms before DBS as “relatively mild.”  

5. Disease progression.  The PWP interviewed were very open about understanding that their PD would progress and the DBS was only for symptom relief.  Various PWP were taking advantage of the improved motor symptoms and time that gave them to complete tasks or travels that they wanted to complete before the disease worsened.  

Conclusion:  The majority of the PWP reported that their QoL and day to day functioning was improved with DBS but knew that their disease would progress.  This study found that the PWP reported tremor was a very disabling symptom prior to DBS which the authors suggest medical professionals may instead describe as a “less problematic symptom.”  Having reduction in tremor from DBS directly improved QoL from the PWP’s perspective and should not be ignored.  The authors also noted that the PWP had a great understanding that DBS would not cure their disease and instead only treat the symptoms, for a while.  This is important to note as the group was appropriately educated about expectations, limitations, risks, and benefits of the procedure.  It is so important to insure that PWP are going to facilities that give accurate and thorough information so they can make informed decisions about undergoing such a procedure as DBS.  This study also highlights the importance of listening and measuring the PWP’s perspective about DBS as they too are a part of the treatment team and their voice should be heard, especially about their QoL.



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Neuromodulation

Heldman DA, Pulliam CL, Urrea Mendoza E, Gartner M, Giuffrida JP, Montgomery EB Jr, Espay AJ, Revilla FJ.. Computer-Guided Deep Brain Stimulation (DBS) Programming for Parkinson. Neuromodulation, 2016 Feb;19(2):127-32. doi: 10.1111/ner.12372. Epub 2015 Dec 1. PMID: 266217642016 Feb;19(2):127-32. doi: 10.1111/ner.12372. Epub 2015 Dec 1. PMID: 26621764

Introduction:   The efficacy of DBS surgery for Parkinson’s disease (PD) is well known.  However there has to be effective follow-up programming after the surgery for continued success of the device to control symptoms of PD.  There are multiple challenges with programming including finding an expert programmer, programmers being available only in larger cities/medical centers, not overwhelming and exhausting the patient during time consuming programming, necessary individualized settings, and great variability in approaches across institutions.  Typically programmers use subjective measures such as the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure symptom control, however additional studies have found incorporating objective computer based measurements increase ease, efficacy, and stability of the settings.  Therefore the goal of this research was to evaluate using such a process to determine optimal DBS settings.  

Method:  Seven people (2 women, mean age 54-71; PD duration 6-17 years) with Parkinson’s disease (PWP) that had recent bilateral DBS of the subthalamic nucleus (STN) were studied.  Each PWP came back for programming a few days after sugery, off medication, and had a motion sensor placed on “the index finger of the participant’s more affected hand.”  Due to time constraints, only the lead on the contralateral side was programmed using this method and the ipsilateral lead was turned off.  The programming settings were made by a clinician at the direction of multiple algorithms created by a computer program based on the tremors and bradykinesia in various activities of the PWP.  The clinician was able to intervene if the PWP was having side effects of any setting.  An “internal symptom response map” was created for each PWP regarding optimal settings for symptom control, reduced side effects, and optimization of battery usage.  

Results:  An “Internal symptom response map” was successfully created for each PWP. Each PWP had approximately 35% improvement in tremor and bradykinesia.

Conclusion:  The computer based programming was successful in all of the PWP.  The settings were found to improve symptoms of PD while also showing care and caution about safety and side effects of the PWP.  The findings of this study are very promising as it may open up access to those in rural settings or those without access to “expert” programmers.  It also addresses the need for individualized settings that are based on objective measurements.  As in all research studies there were limitations to this study.  As this research is in its infancy, only monopolar programming was evaluated and it was suggested that for optimal symptom control that bilateral programming was necessary.  Additionally, only two motor symptoms were studied, tremor and bradykinesia.  Including rigidity, another common symptom in PD, would be beneficial.  There also remains the concern regarding the amount of time needed to complete the programming to minimize PWP fatigue while at the same time giving enough time for the programmed setting to show an effect.  It was suggested that instead of including many different motor variables that it would make more sense to choose those motor symptoms based on various factors to reduce the necessary programming time.  There are also no long term studies on using such a method so it is promising to see the benefits but research should continue to monitor for improvements as well as possible adverse effects over time.  Simply, as the researchers appropriately concluded, this study is a first in many necessary steps to evaluate computer based programming of DBS in PWP.



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Hacker ML, Tonascia J, Turchan M, Currie A, Heusinkveld L, Konrad PE, Davis TL, Neimat JS, Phibbs FT, Hedera P, Wang L, Shi Y, Shade DM, Sternberg AL, Drye LT, Charles D.. Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson. , 2015 Oct;21(10):1177-83. doi: 10.1016/j.parkreldis.2015.08.008. Epub 2015 Aug 11. PMID:2015 Oct;21(10):1177-83. doi: 10.1016/j.parkreldis.2015.08.008. Epub 2015 Aug 11. PMID:

Introduction:   This article is an analysis of a pilot study completed at Vanderbilt University as a part of a clinical trial looking at the efficacy of early deep brain stimulation (DBS) for people with Parkinson’s disease (PWP).  The information gained was used to inform additional phases of the trial.
 
Method:  Two groups of PWP, early in their stages of Parkinson’s disease (PD), aged 50-75, were studied.  One group was given DBS and optimal drug therapy (N=9) while the other was only given optimal drug therapy (N=11). The group had a series of multidisciplinary evaluations over a two year time frame.  

Results:  The authors found that the medication only group experienced more significant worsening of motor and quality of life symptoms than the DBS plus medication group at the two year mark.  Notably symptom improvement was documented by the PWP as well as medical personnel.
 
Conclusion:  The authors note the limitations of their study (e.g. small sample size, post hoc analyses) but discuss the improvements they have made for the larger phase III trial.  They also note the significant finding that the group of PWP that underwent DBS and took medications for their PD had better results than those who only took medications in a variety of areas.  The next phase of their research is going to be bigger and address concerns brought up by multiple groups studying PD and DBS.  Hopefully they will find similar results in the larger well designed FDA approved trial as PWP would then have access to a treatment that shows better promise to minimize motor and nonmotor symptoms in this challenging disease.



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Translational Neurodegeneration

Martinez-Ramirez D, Hu W, Bona AR, Okun MS, Wagle Shukla A.. Update on deep brain stimulation in Parkinson. Translational Neurodegeneration, 2015 Jun 27;4:12. doi: 10.1186/s40035-015-0034-0. eCollection 2015. PMID: 26257895 Free PMC Article2015 Jun 27;4:12. doi: 10.1186/s40035-015-0034-0. eCollection 2015. PMID: 26257895 Free PMC Article

Introduction:    This article is a review of recent updates regarding deep brain stimulation (DBS) in Parkinson’s disease (PD). 

Parkinson’s disease is a common neurological condition with motor and nonmotor symptoms.  Medicinal treatment has been available since the 60’s and has undergone significant improvements since that time.  As there are side effects from the medication and the disease progresses even with the very beneficial medicinal options, surgical intervention has shown significant benefit for people with PD (PWP). 

DBS Mechanism of action:  It remains unclear how DBS fully works to reduce PD symptoms and the authors hypothesize that there likely are multiple contributory mechanisms of action. 

Targets: Initially the ventral intermediate nucleus (VIM) was the target for DBS.  After years of treatment and much research the subthalamic nucleus (STN) and globus pallidus interna (GPi) were found to show more promise.  Recent randomized controlled studies have not shown significant differences between STN and GPi for motor control but there are other noted nonmotor symptoms and complications for each option depending on the study.  More recently, the idea of tailoring the target for stimulation is gaining momentum as a “one size fits all” approach may not work as well as once thought and that each patient has specific symptoms that would benefit from specific targeting.  Appropriate patient selection by a multidisciplinary team for DBS truly affects surgical outcome.  Interestingly, the authors note that the future may show that multiple stimulation targets are needed as PD rarely affects just one area of the brain.  Additional targets undergoing research include the motor cortex, substantia nigra, centromedian thalamus, zona incerta ZI, and the pedunculopontine nucleus.

Timing of DBS: Typically surgical options are years after disease onset and multiple years of medications.  Newer research has shown that in a young group of PWP that underwent DBS early in their disease benefited motorically as well as regarding quality of life.  There is a study currently evaluating if such benefits are also found in an older subset of PWP.

Surgical procedure:  There is a lot of variability in technique for DBS.  Clinical work and research will continue to evolve as there are continued improvements in technology.  Careful planning prior to surgery to minimize complications and best use the technology available is important. 

Adverse events:  There are multiple complications that can arise during and after any neurosurgery.  DBS is no different and has relatively low rates of adverse events.  Specific incidence rates of specific complications are listed in the article.



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Movement Disorders

Metman LV, Slavin KV.. Advances in functional neurosurgery for Parkinson's disease.. Movement Disorders, 2015 Sep 15;30(11):1461-70. doi: 10.1002/mds.26338. Epub 2015 Aug 142015 Sep 15;30(11):1461-70. doi: 10.1002/mds.26338. Epub 2015 Aug 14

Introduction:  Approximately 50 years ago, levodopa was introduced to treat Parkinson’s disease (PD) and many thought that such medication would generally replace invasive surgical techniques.  Although medication continues to be the first line therapy for PD, surgical intervention has actually grown and improved quite a bit.  The purpose of this article was to discuss the advances of deep brain stimulation (DBS), lesioning techniques, and gene and cellular therapies over the past few years.  

DBS: 

Timing: Typically DBS has been performed in people with PD (PWP) after medication trials are no longer effective many years into their disease.  However, recent studies have been completed with PWP that have had shorter duration PD and it was found that surgical intervention was promising as they had improved motor control, improved quality of life, and comparable adverse side effects with resolution as compared to medication treatment alone.  As a result of these studies there is now a FDA approved, double blind, placebo controlled, phase III clinical trial underway to better evaluate early intervention with DBS for PWP.

Target: There are conflicting studies regarding which target of DBS, subthalamic nucleus (STN) or globus pallidus interna (GPi), has the best outcomes for PWP.  Consensus generally indicates that the target of DBS should be chosen on a case by case basis for each individual with PD to tailor treatment for their disease, situation, and symptoms.  There is also an additional target, the peduncolupontine nucleus (PPN) but there are fewer studies regarding this target with variable results.  

Surgical Techniques: Intraoperative MRI (iMRI) is a newer technique that obviates the need for PWP to be awake during DBS and typically improves surgical accuracy.  iMRI involves the surgical procedure taking place in the same room as the MRI scanner and the surgeon receiving real time pictures to guide DBS lead placement.  So far, this imaging advancement has similar successful outcomes to the typical stereotactic frame/awake patient methodology.  There is a similar procedure for CT scanning, intraoperative CT (iCT) that is more readily available but does not have as much outcome research.  Lastly, surgeons have been evaluating whether or not DBS surgery can be performed with the same accuracy levels using a frameless approach versus the stereotactic frame.  Results are still pending but PWP undergoing DBS may find it more comfortable not to use the stereotactic frame during surgery and may spend less time in the operating room.

Technical Development: There have been significant advancements in how the programmer can set the stimulation settings for the PWP.  Research has not been overwhelming regarding shaping and steering approaches for the majority of PWP but some have greatly benefitted in improved motor control and reduced adverse events.  Research has also been done on routine low frequency stimulation which has improved swallowing difficulties, freezing of gait, postural control, and gait in some patients but the general conclusion is that one size does not fit all when it comes to stimulator frequency or patterns of DBS.  Another area of interesting research regarding the technology of DBS lies in the open versus closed loop system designs.  Current DBS uses an open loop system which does not monitor the PWP in-vivo symptoms, neurotransmitter levels, or needs to determine stimulator settings.  A closed loop system would do all of those things and may significantly increase stimulator battery life.  Animal model research has been promising but the closed loop system is still under significant development.  

Lesioning:  Ultrasound can be used for incisionless thalamotomy, pallidotomy, and subthalamic nucleotomy.  MRI guided ablation procedures (MRI guided focused ultrasound; MRgFU)have shown efficacy in small numbers of patients and is attractive as it does not involve opening the skull but such studies need to have improved study design that can show safety, accuracy, any adverse events, and efficacy of such treatment.  Concern will also remain that ablation destroys tissue which may make DBS more attractive for treatment of PD.  

Gene and Cellular Therapy:  Gene and cellular therapy has mixed findings in a variety of different types of studies.  Continued research in the safety, efficacy, and type of gene and cellular therapy will be important to determine benefits to PWP.
   
Conclusion:  Surgical intervention has shown great promise and efficacious treatment for PWP.  It will continue to be refined along with the collaboratively used technology for treatment of PD.  Surgery may change dramatically when the cure for PD is found but until then the surgical treatments are a very efficacious option for PWP.



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Akbar U, Dham B, He Y, Hack N, Wu S, Troche M, Tighe P, Nelson E, Friedman JH, Okun MS.. Incidence and mortality trends of aspiration pneumonia in Parkinson, 1979-2010.. , Parkinsonism Relat Disord. 2015 Sep; 21(9):1082-6. doi: 10.1016/j.parkreldis.2015.06.020. Epub 2015 Jul 2.Parkinsonism Relat Disord. 2015 Sep; 21(9):1082-6. doi: 10.1016/j.parkreldis.2015.06.020. Epub 2015 Jul 2.

Introduction:  Parkinson’s disease (PD) is typically known for tremulousness, bradykinesia, and gait disturbance.  However, other motor symptoms, such as swallowing difficulties, are common for people with PD (PWP).  Swallowing difficulties can lead to aspiration pneumonia which can cause death.  Aspiration pneumonia is a condition caused when an individual breathes in instead of swallows food, saliva, liquids, or other foreign materials that cause a bacterial infection in one’s lungs.   A 1999 longitudinal study found that aspiration pneumonia was the leading cause of death for PWP followed by cardiovascular issues, cancer, and stroke.  Due to improved medicinal and surgical treatment of PD survival rates of PWP have increased by about 5 years.  The authors of this study suggested that although the rates of aspiration pneumonia likely will increase in the PD population due to PWP living longer it is hoped that due to increased awareness of the condition and improved medical services since 1999 that the mortality rates will not.  The authors sought to additionally evaluate the incidence and mortality rates of aspiration pneumonia by looking at a national database of such data from 1979-2010.
 
Methods:  The authors divided the PWP data into five age groups spanning a decade each, starting at age 50 through 90+.  There was also a control group of people that did not have PD.  Multiple analyses were conducted across the 32 year span as well as within each decade but due to changes in medications and surgical interventions they also looked at a subset of the data over the last five years. 

Results:  
Incidence:    Those more likely to have aspiration pneumonia were older men (mean age = 77) with PD.  Over the 32 year span there was a large increase of the number of cases of aspiration pneumonia that required hospitalization those with and without PD.  They also found that as time went on the age of the patients requiring hospitalization increased (e.g. 74 years old vs. 82).  Looking at the gender differences it was noted that men with PD were 2 times more likely to develop aspiration pneumonia than women.  Similar findings were observed only looking at the last five year subset as well.
 
Mortality:  Notably, PWP had less mortality during hospitalization for aspiration pneumonia than those without PD.  Both groups had a reduction in mortality across time PD from 30% (1979-1985) to 14% (2006-2010) and non-PD, 36-17%.  Again a gender effect was found that men with PD were more likely to die from the pneumonia while hospitalized than women.  Interestingly the age range with the highest mortality was the 50-60 year olds with PD over the three decades.  However, in looking at the last five year subset the reduced mortality information generally did not change with the exception that the mortality increased as the PWP got older and was not specific to the 50-60 year old group as found above.  



Conclusion:  As hypothesized the authors found that the incidence of aspiration pneumonia is greater for PWP (3.8x) than those without PD and has increased across the last three decades but the mortality has decreased significantly by about 30%.  As PWP aged the incidence of aspiration pneumonia also increased.  Notably the mortality in PWP from aspiration pneumonia was greatly reduced from prior studies and was less than those who don’t have PD.  This finding is likely due to increased awareness of swallowing difficulties in PWP and possibly earlier detection and initiation of treatment.  Both groups also had a reduction in mortality likely due to improved medical care, better antibiotics, and increased awareness of aspiration pneumonia as medical care typically improves with time.  There were multiple limitations of this study which were clearly addressed in the article but as the authors discussed it is very important to look at large epidemiological estimates of disease information to improve detection, treatment, long term care options, and patient survival.



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Alexoudi A, Shalash A, Knudsen K, Witt K, Mehdorn M, Volkmann J, Deuschl G.. The medical treatment of patients with Parkinson. , 2015 Jun;21(6):555-60. doi: 10.1016/j.parkreldis.2015.03.003. Epub 2015 Mar 202015 Jun;21(6):555-60. doi: 10.1016/j.parkreldis.2015.03.003. Epub 2015 Mar 20

Introduction:  Pharmacotherapy is the first line treatment for symptoms of Parkinson’s disease (PD).  However medications have side effects and lose efficacy as the disease progresses.  Surgical intervention, such as deep brain stimulation of the subthalamic nucleus (DBS STN), is an additional treatment approach that has shown successful reduction in motor symptoms as well.  Typically after DBS STN the person with PD (PWP) also does not require as much dopaminergic medications and reductions are common.  The purpose of this study was to take a closer look at the specifics regarding medication reduction over 3-10 years postsurgery.

Methods:  Subjects of this study initially included one hundred PWP that underwent bilateral DBS STN in Germany between 1999 and 2007 (2/3 male, 1/3 female).  Multiple age groups and disease duration groups were stratified.  The authors looked at retrospective longitudinal data at 6 months, 3 years, 5-6 years (N=58), and 10 years + (N=15) postsurgery.  

Results:  The dosages for levodopa and dopamine agonists were reduced by half at 6 months and around 45% at three years.  Notably 9% of the PWP were medication free at 6 months and 6% at three years.  There was also a switch, 6 months postsurgery, to many more patients only having to take one medication versus multiple (27 vs. 56%, pre to post) which continued at the three year mark.  The usage of amantadine was also reduced along with the dosage amount of the medication at both the 6 months and 3 year mark.    Anticholinergics were almost entirely stopped.  The PWP had reduction in their motor symptoms and medication costs declined by 50-60% over time.    When looking at the stratified age of onset groups, it was found that the older group (>45 vs.
Continued reduction from baseline levels were found when looking at the 5-6 year and 10 year follow ups.  Only one patient at the 5 and 10 year follow ups remained medication free. Other medications were also monitored and there was a reduction in the usage of neuroleptics (refers to antipsychotic medications to treat hallucinations or psychosis) at six months but increases in usage at the 3 year follow up.  A similar finding occurred with antidepressants with an increase at 3 and 5-6 years.  

 Conclusion:   This study found significant reductions in levodopa medications and dosages after DBS STN that continued up to 10 years postsurgery.  Other adjuvant medications were also reduced or eliminated.  It was noted that there was an increase in usage of antidepressants which was thought possibly related to dopaminergic medication withdrawal from reduction of the levodopa.  Continued monitoring and treatment of psychiatric symptoms was necessary due to disease progression.  Lastly, the reduced cost of medications over the years was highlighted and should be taken into consideration.  Although the aforementioned data provides findings from 1999 and 2007, the impact of DBS on symptom improvement and medication utilization continues to be investigated.



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Movement Disorders

Rowland NC, Starr PA, Larson PS, Ostrem JL, Marks WJ Jr, Lim DA. Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease.. Movement Disorders, Mov Disord. 2014 Dec 17. doi: 10.1002/mds.26083.Mov Disord. 2014 Dec 17. doi: 10.1002/mds.26083.

Review:  Parkinson’s disease (PD) affects 1-2% of people over 60 and is a very costly disease to treat.  Current treatment reduces symptoms but does not stop or slow the disease nor reverse the neuronal loss that occurs.  This article presents a “conceptual framework” for cell transplant or gene therapy in combination with current medicinal and surgical treatments that may actually address the neuronal loss in PD.  Prior research has not shown great effectiveness with such therapy. The cell treatments have shown improvement over time, however, and may prove to be beneficial with continued randomized trials. A similar route was tried and proven beneficial with deep brain stimulation (DBS) and medications for reduction of symptoms of PD.  The authors suggest that adding a third treatment to DBS and medications may continue the symptom reduction as well as address the neuronal loss.  One challenge with randomized trials studying cell transplants is having a group that does not receive therapy to compare to the group that does.  Some researchers have excluded patients that have undergone DBS, as it has been shown to be a very effective symptom reducing treatment.  People with PD (PWP) may not want to volunteer for cell transplant trials as they may prefer to undergo the symptom reducing treatment to improve their quality of life rather than try an experimental treatment that 1. may not show improvement for “months or years” and 2. may have a variety of risk factors.  The authors suggest that future studies could complete DBS and cell transplant at the same time in surgery for one group and only complete DBS for a second group. This approach would permit  both groups to receive desired symptom reduction treatment, and provide a way to compare the effectiveness of the additional gene therapy treatment.  The dual DBS/cell transplant option would also reduce the cost of such a clinical trial as the DBS surgery is already covered by healthcare systems.  This approach would likely be more amenable to approval by research regulating bodies, as the patient would not need an additional surgery for the experimental treatment; the patient could have both surgeries completed at the same time, reducing many risks for the PWP.   The addition of cell transplants or gene therapies may prove to be yet another step forward in the treatment of PD, improving the quality of life for many PWP.



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DeLong MR, Huang KT, Gallis J, Lokhnygina Y, Parente B, Hickey P, Turner DA, Lad SP.. Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease.. , 2014 Oct;71(10):1290-5. doi: 10.1001/jamaneurol.2014.1272.2014 Oct;71(10):1290-5. doi: 10.1001/jamaneurol.2014.1272.

Introduction:  Parkinson’s disease (PD) is a common neurological condition that typically strikes after age 60.  PD is often successfully treated by deep brain stimulation (DBS) but there are known surgical risks even for those deemed “good candidates” for such treatment.  In general, older adults also have a higher likelihood of surgical complications but there are few studies specifically looking at such risk factors in older adults with PD.  Age quickly becomes an issue for this disease/treatment due to PD having older onset, mean duration of 14 years before DBS surgery, and a higher likelihood with advancing age of comorbid conditions that could affect surgical candidacy. Additionally, recent studies have found DBS plus medications are more efficacious than medications alone in a younger group of PD patients, suggesting that it may be beneficial to consider earlier surgical treatment to minimize adverse events and risks of DBS.  As age is an important factor with this treatment, the stated goal of this study was to look at adverse events in older people with PD (PWP) that have undergone DBS.   

Methods:  A retrospective review of a national database of approximately 1700 PWP that underwent DBS (590 unilateral, 551 bilateral, 122 staged, 494 indeterminate) from 2000-2009 was evaluated.  Neuroanatomical location of DBS placement was not known.  


Results:  Patient demographics included mean age of 61.2 years, 33% over age 65, 7% over 70, and 36% women.  When looking at the entire group of PWP, the study found that 7% of the patients had one or more complication within ninety days of having surgery.  The most common adverse events were “infection, pneumonia, hemorrhage, or pulmonary embolism.”  Hardware or lead issues were few (2.9%) as were patient deaths (0.3%).  When only the older PWP were reviewed the results did not significantly change at the 30 day or 5 year marks.  They also found that older PWP did not have longer hospital stays.

Conclusion:  Research over the last 10 years has been lacking on older PWP that have undergone DBS which is problematic as PD affects many older adults.  This study found that older PWP did not have higher rates of adverse events which may be beneficial information for those considering such treatment.  The authors highlight that the older PWP in this study benefited from multiple years of improved motor functioning and possibly improved quality of life.  Limitations of this study include unknown selection criteria for those undergoing DBS (e.g. healthier individuals), possibility of inaccurate reporting to the database, and no additional but usually relevant clinical or demographic variables available due to the use of the database (e.g. duration of PD, age at onset, etc.).  This study is informative however as it suggests that broadening the age range to those offered such treatment may be beneficial to the older PWP.



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Lewis CJ, Maier F, Eggers C, Pelzer EA, Maarouf M, Moro E, Zurowski M, Kuhn J, Woopen C, Timmermann L.. Parkinson's disease patients with subthalamic stimulation and carers judge quality of life differently.. , Parkinsonism Relat Disord. 2014 May;20(5):514-9. doi: 10.1016/j.parkreldis.2014.02.009. Epub 2014 Feb 20.Parkinsonism Relat Disord. 2014 May;20(5):514-9. doi: 10.1016/j.parkreldis.2014.02.009. Epub 2014 Feb 20.

Introduction:  DBS STN has repeatedly shown that it is beneficial in improving the motor symptoms commonly seen in Parkinson’s disease (PD).  Research has also shown that quality of life (QoL) is often reported as improved by the people with PD (PWP).  However this may not always be the opinion of the family or caregiver of the PWP.  The reason for this discrepancy may be multiple and was the purpose of this study.  
 
Methods:  The researchers developed a prospective study to look at QoL ratings as measured by PWP as well as their caregivers.  They looked at a variety of factors that may explain such differences (e.g. motor, cognitive symptoms, social functioning, etc.).  Twenty eight PWP that underwent DBS STN and their caregivers were assessed before surgery, 3 months following, and 1 year post surgery with a battery of tests.  PWP and caregivers were excluded if they had dementia or severe psychological disturbances.  

Results:  The mean age of the PWP was 61, they had PD on average for 12 years, and they showed improvement in motor scores after DBS.  The caregivers were slightly younger, mean age 56.  Most of the caregivers were spouses but there were a few that were adult children.  In looking at the QoL measure, both the PWP and caregivers rated improvement in QoL after surgery, however there was a discrepancy in the measure at the 1 year follow-up between the two groups.  Some of the changes within the PWP and possible causal factors included increases in apathy early on after surgery, symptoms of mania, decreased language skills, and decreased simple attention.  There was an interesting finding that those PWP with less depression rated their QoL higher than their caregiver counterparts.

Conclusion:  At the one year post surgery mark, the caregivers rated that the PWP were more impaired than the PWP thought they were.  This may have been due to unrealistic expectations of the caregivers going into the surgery.  DBS has repeatedly shown that it can improve motor symptoms but the PD will still progress which is disheartening to many caregivers.  There also may have been cognitive and psychological changes from the DBS that were unexpected to the caregivers which also lowered their QoL ratings.   Regarding the cognitive changes, the PWP may not have been as aware of the deficits as much as the caregiver so the discrepancy in QoL may have been related to the intactness of the caregiver but decline in abilities to monitor self-awareness in the PWP.  Regarding the psychological changes, it is possible that caregivers were less attentive to the decreased depression in the PWP which didn’t translate into the QoL rating.  The PWP that also experienced increases in apathy may have an inadequate impression of their QoL compared to the caregivers.  Interestingly, they did not find a decline in social functioning in the PWP which has been reported as a possibility for the QoL rating differences in the literature.  This study highlights the importance of assessing, treating and educating not just the PWP but also the caregiver about PD and DBS as PD affects the patient as well as the family.  Sitting down prior to surgery and discussing all facets and possible changes with the surgery in order to have realistic expectations of outcomes is very important.  Appropriate surgical candidate selection is also necessary as it relates to surgery outcomes, expectations, and QoL ratings for both the PWP and caregiver(s).  Clinicians as well as researchers should continue to look at the nonmotor as well as motor issues related to DBS in order to provide the utmost best treatment for PWP and their family/caregiver.



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Williams NR, Foote KD, Okun MS.. STN vs. GPi Deep Brain Stimulation: Translating the Rematch into Clinical Practice. , 2014 Apr 1;1(1):24-352014 Apr 1;1(1):24-35

Intro:  There are multitudes of studies that have shown DBS’s efficacy in treating motor symptoms in people with Parkinson's disease (PWP).  Typically, the treatment is implemented for advanced stages of PD but there is some literature suggesting the treatment may also benefit PWP earlier in the disease course.  Throughout the past couple of decades there has been changing opinions about the "best" surgical site for DBS (globus pallidus internus-GPi or subthalamic nucleus-STN).  This article reviewed the evidence for and against the different sites for DBS, motor and nonmotor symptoms, adverse events, as well as how best to optimize this treatment for PWP.  

DBS vs. Medications: DBS has shown to be a better therapy than medications only for advanced stages of PD.  The jury is still out regarding using the surgical treatment with known surgical risks as an earlier treatment.

Surgical Candidacy:  Selection of good surgical candidates is very important for PWP to insure that the person will have good effects from the treatment.  Notably, not everyone will benefit from this therapy and the decision regarding candidacy, follow up care, and surgical site should be made by a multidisciplinary team ("neurology, neurosurgery, neuropsychology, psychiatry, and rehabilitation specialist").  This team should meet with each PWP individually and discuss the best approach to treat motor and nonmotor symptoms.  Preexisting behavioral difficulties should attempt to be stabilized before the PWP undergoes treatment and monitoring of depression and suicidality should be monitored after DBS regardless of surgical site.

Surgical Site: Review of the recent literature that directly compared STN to GPi found that both were effective in treating PD but each had different strengths and weaknesses.  Table 1 in the article went through multiple points and specifically identified "superiority" of the treatment in defined areas.  Generally, they found no differences between GPi and STN regarding tremor, rigidity, or off-time motor symptoms. 

STN showed superiority for bradykinesia, ability to reduce L-dopa after surgery that may reduce overall treatment costs, and longer battery life.  Weaknesses of the STN included the size of the surgical target being small and more prone to adverse events due to erroneous spread of current from the stimulator.  Additionally speech and swallowing abilities were affected.   

GPi showed superiority for gait and balance outcomes, suppression of dyskinesias, less cognitive adverse events, more flexibility to make L-dopa medication adjustments after stimulation, easier programming settings and maintenance options, unilateral DBS placement leading to motor and quality of life improvements, and mood outcomes.  A weakness of the GPi included more battery usage due to the larger size target of the GPi, which resulted in increased cost of treatment. 

Conclusion:  The authors note that there is not a one size fits all approach to DBS for PD.  They encourage tailoring the surgical site to each patient based on all of the above information as well as based on the strengths and challenges of the PWP.  Much has been learned over the past couple of decades about DBS and more knowledge will be gained with improvements in imaging, surgical techniques, technology, and other possible targets related to the multiple symptoms of PD.



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Tripoliti E1, Limousin P, Foltynie T, Candelario J, Aviles-Olmos I, Hariz MI, Zrinzo L.. Predictive factors of speech intelligibility following subthalamic nucleus stimulation in consecutive patients with Parkinson. , Mov Disord. 2014 Apr;29(4):532-8. doi: 10.1002/mds.25816. Epub 2014 Feb 14.Mov Disord. 2014 Apr;29(4):532-8. doi: 10.1002/mds.25816. Epub 2014 Feb 14.

Intro:   People with Parkinson’s disease (PWP) can have changes in their speech due to the disease.  Research has also shown that there are speech adverse effects from DBS therapy.  The goal of this article was to evaluate various aspects of speech (“articulation, respiration, resonance, phonation, prosody, and rate”) before and after DBS and if there were any predictive factors to explain speech side effects.



Methods:  Fifty four patients that had bilateral DBS STN were evaluated.  Each patient was administered a speech assessment that was analyzed by a Speech Language Pathologist before surgery (off and on medication) and one year later (on meds/on stimulation and off meds/on stimulation). 



Results:  The authors found that speech deteriorated on average by 12-14% after one year of DBS STN.  Almost all areas of speech showed decline except prosody and phonation.  Predictive factors for those that had speech side effects included presurgical speech problems, disease duration, and left hemisphere medial STN placed contacts.  Notably they found that even in those patients that did not have presurgical speech problems, the medially placed left hemisphere contact remained problematic with speech. 



Conclusion:  As in other studies, this study also found speech adverse effects from DBS STN.  The study went a few steps further and discussed specific contact placement (left hemisphere medial STN) as a predictive factor as well as that the pattern of speech problems after DBS STN is different than those experienced from PD alone.  Patient complaints, while taking medication and under stimulation conditions, included articulation problems, reduced lip and tongue movements, and hard to control voice volume.  Presurgical predictors of speech difficulties after surgery included having speech difficulties prior to the surgery and those that had PD for longer periods of time.  Surprisingly age was not a predictive factor in the face of those having PD for longer was a predictive factor.    The authors suggest that more research needs to be done to  continue to evaluate speech issues in PWP with and without DBS.



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Lukins TR, Tisch S, Jonker B.. The latest evidence on target selection in deep brain stimulation for Parkinson. , Neurosci. 2014 Jan; 21(1):22-7. doi: 10.1016/j.jocn.2013.05.011. Epub 2013 Nov 5.Neurosci. 2014 Jan; 21(1):22-7. doi: 10.1016/j.jocn.2013.05.011. Epub 2013 Nov 5.

Intro:   This article begins with an overview of the strengths and weaknesses of typical medicinal and surgical treatment for PD.  Traditionally DBS has been a secondary treatment option after medicinal therapies are no longer effective or there are disabling side effects for the person with PD.  However, studies are beginning to show that there may be beneficial effects to implement surgical treatment earlier in the disease course.  Researchers also have varied in surgical target selection and it is thought that a “one size fits all” approach is no longer adequate.  The author’s purpose was to discuss the typically chosen surgical targets for DBS in PD.

Methods:  Research articles were reviewed from 1999 to 2013 and summarized by surgical target.
 
Results: 



  • Subthalamic Nucleus (STN) and Globus Pallidus Interna (GPi):  The STN and GPi have received the most research regarding DBS and have consistently shown improvement in motor symptoms of PD.  A large multicenter Veterans Affairs trial found that there was not a significant difference between the two targets to improve motor function, on quality of life, or adverse effects.  Some differences found were that the STN group required a smaller dosage of dopamine therapy after DBS, they had a higher depression score, and their processing speed was slower.  On a second randomized study (COMPARE trial), it was found that there really were no differences in mood scores but the STN group had worsened speech fluency.  Other smaller studies were discussed with generally similar findings with some slight differences.  Regarding adverse events, the authors purport that there is significant variability within the studies but generally, that DBS STN is more likely to have increased “depression, impulsivity, fatigue, paresthesias, weight gain, and edema.”  A long-term study also showed that DBS STN had a reduced need for dopamine therapy and “greater improvements in tremor, rigidity, akinesia, postural stability, and gait” after 5-6 years compared to the DBS GPi group.

  • Pedunculopontine nucleus (PPN):  Research on this target is much less but it remains a target of interest as it possibly could improve gait disturbances.  One study found that stimulation of both the STN and PPN was beneficial but has only been completed in a small number of patients.  Regarding adverse events of this target, dysaesthesias were the most common.  Multiple studies with small patient numbers were discussed but randomized control trials need to be completed for more conclusive information on this target.

  • Thalamus:  The target discussed was the ventral intermediate nucleus (VIM) of the thalamus.  The studies reviewed suggested long-term improvement specifically for tremor but not the other features of PD.  Adverse events were low, 4% of the 73 patients experienced an intracranial hemorrhage, and others noted mild speech and stability difficulties.  This is a target predominant for essential tremor and is rarely done for PD.

  • Posterior subthalamic area (PSA):  Target areas include the zona incerta (Zi) and prelemniscal radiations.  One study found that stimulation of the PSA improved tremor in those that had essential tremor but people with PD (PWP) were not included in that study.  Another study found that Zi stimulation improved “tremor, rigidity, and bradykinesia” in those with parkinsonism but again PWP were not evaluated.

  • Centre median-parafascicular complex (CMPf):  This region of the thalamus was stimulated in rats and was found to improve pain, attention, tremor, and dyskinesias.


 
Conclusion:  There isn’t a one-size fits all approach to DBS and the procedure should be tailored to the individual patient’s symptom presentation although the targets of most promise continue to be the STN and GPi.  Continued randomized clinical trial research on the above noted targets will provide more information on treating the motor and nonmotor symptoms of PD.



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Müller B1, Assmus J, Herlofson K, Larsen JP, Tysnes OB.. Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson. , 2013 Nov;19(11):1027-32. doi: 10.1016/j.parkreldis.2013.07.010. Epub 2013 Aug 2013 Nov;19(11):1027-32. doi: 10.1016/j.parkreldis.2013.07.010. Epub 2013 Aug

Intro:     There are multiple motor and non-motor symptoms of Parkinson’s disease (PD) and many research studies have focused on one or the other in people with PD (PWP) concerning quality of life.  The authors of this study wanted to evaluate a variety of motor and non-motor symptoms that predicted quality of life scores in PWP that had yet to undergo treatment for PD.

Methods:  One hundred and sixty six PWP underwent evaluation prior to undergoing any medicinal treatments and then again three years later.  The PWP took a questionnaire measuring quality of life, multiple physical measurements were taken, and questions were asked during a medical exam regarding many symptoms of PD. 
Results:   Participants were PWP from Norway, about 67 years old at the onset of the study and classified as having mild motor symptoms.  The researchers looked at the motor and non-motor symptoms that predicted quality of life scores and found that prior to treatment, sensory complaints (e.g. pain), autonomic symptoms, fatigue, and depression were the biggest factors to explain the scores.  After three years of treatment, the study showed fatigue, gait disturbance, sensory complaints, and depression as the best predictors of quality of life scores for the PWP.  They also found that fatigue became more problematic and significantly worsened the quality of life scores at the three-year mark.  The study used statistical analyses to determine which symptoms were the best predictors and found that certain motor symptoms also contributed, though not as much, to quality of life scores including walking difficulties, ability to complete daily tasks, sleep related motor symptoms, and rigidity.

Conclusion:   The researchers found that the nonmotor symptoms were better predictors of quality of life scores in the PWP than the motor symptoms.  They discussed that non-motor symptoms have shown similar findings in other studies but such studies have often times hypothesized that result was due to the motor symptoms being treated while the non-motor symptoms were not.  The current study found that even before medical treatment was initiated for motor symptoms, non-motor symptoms were a better predictor of quality of life.



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Strauss I, Kalia SK, Lozano AM.. Where are we with surgical therapies for Parkinson. , 2014 Jan;20 Suppl 1:S187-91. doi: 10.1016/S1353-8020(13)70044-0.2014 Jan;20 Suppl 1:S187-91. doi: 10.1016/S1353-8020(13)70044-0.

This article was a discussion of current surgical therapies for Parkinson’s disease (PD).  There are multiple treatments for PD and the typical primary therapy is the medicinal route (levodopa/carbidopa) which has shown to reduce common motor symptoms.  However, after long-term medication use there are known side effects (45% of people taking them for greater than 5 years will experience them) including dyskinesia, “wearing off,” and fluctuant levels during the day causing “on-off” periods.  Due to these challenges, surgical intervention is a secondary treatment option for people with PD (PWP).  The article noted that multiple studies have shown the efficacy of DBS and that approximately 100,000 PWP have undergone DBS over the past 20 years.  Even after 20 years though, there are still unanswered questions about this treatment, which the authors commented upon.

What about the timing of the surgery?  Typically, surgical intervention is suggested later in the disease course when the PWP has severe symptoms, longer disease duration, and has more difficulties with the above-mentioned medicinal side effects.  However, review of a 2013 randomized trial showed that when surgery was completed on younger PWP, earlier in the disease course, combined with optimal medication management compared to those only taking medication the PWP that underwent DBS reported higher quality of life and better motor scores.  The surgery group also had less dyskinesias attributable to the medications.  A challenge with earlier surgical intervention was reported to include the unknown long-term risks of this treatment, there are unresolved hardware issues, and risks associated with multiple surgeries needed as the PWP has the DBS for longer periods.  Researchers also do not know the long-term risks to the brain, having continuous electrical stimulation on cognition or psychological functioning.  Conversely, researchers also do not know about the possible beneficial effects of long-term stimulation from either a disease modification or protective point of view.

What is the optimal target for DBS?  There has been a long-standing debate regarding the optimal target for DBS.  Initially GPi was the focus but in the early 1990s, STN became the target of choice.  As studies continued there were mixed findings regarding cognitive and psychological side effects from STN so focus returned to GPi.  A 2013 European study compared the two targets concerning such side effects and the results did not show a significant difference between the two groups.  The authors rightfully note that this debate likely will continue for quite some time.

What about non-motor symptoms?  Although both targets are effective for reducing motor symptoms of PD, the DBS intervention has not been effective in treating the non-motor symptoms of PD.  The basal ganglia is the target for treatment of motor symptoms but it is suggested that the nonmotor symptoms (speech, cognition, and gait) are mediated by different anatomical areas.  This suggests that researchers may need to widen the scope for stimulation to other brain areas or possibly have multiple targets to address both motor and non-motor symptoms. 

What about the methodology for DBS?  Historically there has been a requirement for PWP undergoing DBS to be awake during the surgery to assist with verification of target placement as well as specific devices used (e.g. microelectrode recording, stereotactic frames).  This can present a challenge to medical teams not having access to such tools as well as challenges to patients who may have fatigue or anxiety that would interfere with such participation in surgery.  There have been a couple of studies that have attempted DBS implantation while the patient is instead under general anesthesia and with different specialized equipment that have found similar levels of accurate DBS placement which may make the treatment more tolerable and available to more patients. 

There is still more to learn about DBS regarding maximization of stimulator settings to best control motor symptoms as well as minimize the need for battery changes and setting modifications.  There are multiple hypotheses regarding "closed loop" systems within the brain done by the stimulators that would monitor the basal ganglia and instead of applying constant stimulation would provide specific stimulation based on the needs and functions of that individual’s basal ganglia recordings.  So far, only animal studies have been done in this area with PD in creating a system that could accomplish such goals but treatment of other diseases (e.g. seizures) currently has similar technology.

What about other treatments?  Ablation treatments (e.g. to the thalamus and globus pallidus) were much more common before DBS in treating motor symptoms of PD.  Notably these treatments were non- reversible and often PWP would have cognitive side effects.  The article discussed a newer type of ablative treatment done by a specific “MR-guided focused ultrasound (MRgFUS)” has shown promise for those PWP that cannot undergo DBS.  The treatment can provide an immediate temporary lesion prior to a permanent lesion, which allows for an accurate specific individualized treatment. 

The study of gene therapy for PWP has shown some mixed and some promising results after 6-18 months but more research needs to be completed in this area with improvements and standardization in methodology.



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Ngoga D, Mitchell R, Kausar J, Hodson J, Harries A, Pall H.. Deep brain stimulation improves survival in severe Parkinson. , 2013 Jul 102013 Jul 10

Intro:     The authors of this study are from the United Kingdom and cite that Parkinson’s disease is a common neurological condition there as much as it is here, in the United States.  They discuss typical medicinal treatments being effective early in the disease course and the longer that a person takes them the more motoric challenges will occur (e.g. dyskinesias).  They also discuss DBS-STN being an effective treatment to improve motor control as well as quality of life and often reduced need for PD medications.  However, they note that there is little to no research looking at DBS-STN on mortality rates of people with PD (PWP). 

Methods:  A surgical/medical center looked at PWP classified as severe over a 10-year time span that either underwent DBS-STN or declined surgery and continued to only take medications.  One hundred and forty seven PWP were studied (41 medication only, 106 DBS-STN), aged 40-70 (mean age in years: 61 medication, 60 DBS-STN). 

Results:   The two groups were not significantly different from each other in terms of demographics or levels of depression and both were healthy enough to undergo surgery.  Each group was offered to have surgical intervention around the 10-11 year mark of having PD and was on about the same levels of levodopa/carbidopa at the time surgery was discussed. 

The study found that the DBS-STN group had “longer survival” than the medication only group.  The study did not specify a length of time for additional survival and instead looked at rates of survival.  Further analysis found that women had lower survival rates, as were people who had PD greater than 10 years prior to the surgical discussion.  Cause of death was also more likely to be respiratory related in the medication only group than the DBS-STN group. 

The study also looked into rates of placement into nursing home settings and found that the group only treated with medication was more likely to be admitted to a residential care setting. 

Conclusion:   The DBS-STN group had better survival rates and was less likely to be admitted into a nursing home setting than the group that chose to be treated only with medications.  Various reasons were discussed including improved “motor functioning, mobility, quality of life,” and possibly swallowing leading to less nursing home admissions and fewer deaths.  The groups, although not randomized, were similar on the majority of demographic and medical variables studied suggesting that the differences in mortality were due to the type of treatment chosen.  This study is very important as it contributes to PWP and clinicians being informed consumers when having to choose treatment options for severe PD.



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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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