Current Science Review

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 Parkinson’s 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
  
     

   
• 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.
  
     

   
• 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.
  
     

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Lepmkal, S.F., Johnson, M.D., Miocinovic, S., Vitek, J.L., McIntyre, C.C. (2010). DBS Therapy for Parkinson’s 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.. Parkinson’s 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.
  
     

   
• 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.
  
     

   
• 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. 
  
     

   
• 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.
  
     

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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.

Click here to go to Pub Med Abstract.

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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.

Click here to go to Pub Med Abstract.

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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!

Click here to go to Pub Med Abstract.

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Ravina, B., Tanner, C., DiEuliis, D., Eberly, S., Flagg, E., Galpern, W.R., Fahn, S., Goetz, C.G., Grate, S., Kurlan, R., Lang, A.E., Marek, K., Kieburtz, K., Oakes, D., Elliott, R., Shoulson, I., Parkinson Study Group LAPBS-PD Investigators.. A Longitudinal Program for Biomarker Development in Parkinson’s Disease: A Feasibility Study. , Movement Disorders, 24(14): 2081-90Movement Disorders, 24(14): 2081-90

Background of the Study

When it comes to Parkinson's disease (PD), patient follow-up is crucial to provide longterm data that can help to predict symptoms of PD and develop therapies to treat or prevent them. Longterm data is also valuable for developing PD biomarkers, specific biological traits used to indicate PD severity or progression. Unfortunately, few studies have attempted to monitor patients for more than five years, since it is costly and difficult to maintain the follow-up of any participant study group.

To address these setbacks, a nonprofit association of researchers known as the Parkinson’s Study Group (PSG) developed the Longitudinal and Biomarker Studies in Parkinson’s Disease (LABS-PD), a program designed to re-recruit groups of PD patients from earlier studies and evaluate them through their disease in order to:

   
• Provide longterm data on the course of PD symptoms
     

   
• Develop biomarkers that measure risk for and progression of PD.
     

   
1.  A large group of PD patients
   
      

   
2.  A second group of control subjects including:
   
      

   
• Healthy controls: Participants who do not have PD.
  
     

   
• Disease controls: Participants with other neurological disorders that resemble PD.
  
     

   
• Inviting patients and research sites from PRECEPT (a former PD drug trial) to participate in PostCEPT—the firstPD study group in LABS-PD

   
• Inviting healthy and disease controls to join the control group for the Prognostic Biomarkers (PROBE) study, a LABS-PD study that collects four different patient biological samples in order to analyze their potential as PD biomarkers.

   
• Researchers met with patients annually and at 3-year intervals to evaluate progression of motor and non-motor symptoms of PD and changes in cognition and behavior
  
     

   
• FOUND Study: Researchers invited patients to participate in the Follow-up of Persons with Neurologic Diseases (FOUND) study, a LABS-PD clinical study that conducts mail and telephone follow-up to update: patient diagnosis, medications, hallucinations, fatigue, sleep disorders, use of health care services, available social supports, and the economic impact of Parkinson’s.

   
1. Blood Samples: Patients were invited to donate blood samples to a DNA repository, where their cell samples were prepped and preserved to provide a source of DNA.
   
      

   
2. Imaging Study: Patients were invited to continue the PRECEPT drug trial’s DAT imaging study, where patients received a series of brain imaging scans to monitor dopamine-related damage.
   
      

   
3. PROBE Study: Patients were invited to participate in the LABS-PD Prognostic Biomarkers (PROBE) study, where researchers collected four different patient biological samples to analyze their potential as PD biomarkers.
   
      

   
• Researchers developed a unique identifier system that provides each patient with a special ID so that s/he can be tracked across multiple studies without being personally identified
  
     

   
• Researchers created the PD-DOC website (a public-access website of clinical, environmental, and biological patient data) so that new LABS-PD data can be readily stored and accessed.
  
     

   
• Over two-thirds, 67% (537 of 806), of all PRECEPT patients were recaptured for the PostCEPT study group
  
     

   
• Over 100 subjects (54 healthy controls, 53 disease controls) were recruited for the Prognostic Biomarkers (PROBE) control study group.
  
     

   
• Blood Samples: 72% of PostCEPT patients have donated blood samples to the DNA repository.
  
     

   
• Imaging Study: 95% of PostCEPT patients have received follow-up imaging scans under the DAT imaging study.
  
     

   
• PROBE Study: 100% of PROBE participants (102 PostCEPT patients, 107 control subjects) have completed biomarker processing for all four biological samples.
  
     

   
• FOUND Study: 51 of 55 PostCEPT sites—and 92% (454 of 489) of their patients—have agreed to participate in the Follow-up of Persons with Neurological Diseases (FOUND) study.

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Chaturvedi A, Butson CR, Lempka SF, Cooper SE, McIntyre CC.. Patient-specific models of deep brain stimulation: Influence of field model complexity on neural activation predictions.. , Brain Stimul. 2010 Apr;3(2):65-77.Brain Stimul. 2010 Apr;3(2):65-77.

The purpose of this article was to evaluate different DBS STN settings as created by a computer based model in order to predict patient specific optimal settings for the best possible motor improvement.  The authors utilized various imaging and recording devices to evaluate five different models that produced stimulation from the DBS.  They also focused on the different types of brain tissue that surrounds the stimulator to evaluate possible causes of adverse events from possible spread of the stimulation.  This study was very detailed in the methodology used and recommended that continued work needs to be completed to better understand this therapy for People with Parkinson's (PWP) in order to avoid oversimplification of stimulator settings, maximize stimulation benefit, and minimize adverse events.  This study highlights that even though DBS STN has been around for years clinicians, researchers, patients, and families are still learning about this treatment option and improving upon techniques of the past in order to provide the best treatment possible.

Click here to go to Pub Med Abstract.

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Vitek JL, Lyons KE, Bakay R, Benabid AL, Deuschl G, Hallett M, Kurlan R, Pancrazio JJ, Rezai A, Walter BL, Lang AE. Mov Disord. 2010 Jun 11.. Standard guidelines for publication of deep brain stimulation studies in Parkinson's disease. ,

The purpose of this article was to provide standardized guidance for researchers and clinicians when creating and publishing studies that involve DBS.  One of the largest difficulties in current DBS research is that it is difficult to compare the strengths and weaknesses of studies as there is no consensus on how the treatment works, programming, surgical site, measures used to evaluate change, times to complete assessments, lead locations, length of time when measuring “off” or “on” DBS parameters, etc.  With studies having so many differences in how they complete the procedure and how outcomes were measured makes it difficult for the field to move forward on improving the technique in order to maximize efficacy. Notable suggestions by the group were for researchers to look at the typical PD motor issues but also to include evaluation of non-motor difficulties and issues related to quality of life.  They also recommended utilization of a multi-disciplinary team to evaluate participants pre and post stimulation as well as guidelines to reporting complications and adverse events.  The authors made a great point in the importance of reporting adverse events in studies not to be punitive to the authors or the study but so other researchers and clinicians can learn from each other in determining risks and efficacy of this procedure so that the individuals that undergo this procedure are fully informed in their decision to undergo this treatment.  Lastly, an easy to follow check list was provided in the article for those planning a study or preparing a manuscript for publication.

Click here to go to Pub Med Abstract.

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Chan DT, Zhu XL, Yeung JH, Mok VC, Wong E, Lau C, Wong R, Lau C, Poon WS.. Complications of deep brain stimulation: a collective review.. , Asian Journal of Surgery 2009 Oct; 32(4):258-63.Asian Journal of Surgery 2009 Oct; 32(4):258-63.

The purpose of this article was to discuss what these authors have learned from completing the DBS surgery as well as to discuss the possible complications as well as what can be done to prevent such difficulties while moving forward with this treatment.  The authors reviewed their cases from 1997-2008 and broke the complications into those related to the surgery, the hardware, or the stimulation and provided discussion of each as follows: 



The surgery: 

   
• One complication during the surgery involved having to move the DBS electrode to determine the best placement which increased the risk of hemorrhages.  In their patient group, less than 1% experienced a hemorrhage.  They suggested that the best way to prevent such complication was to extensively plan the surgery, utilize imaging techniques, and continue to develop surgical equipment that minimized the invasive nature of the surgery. 

   
• Another complication from the surgery involves poor positioning of the electrode for a variety of reasons that reduced the efficacy of the treatment.  Prevention techniques for this complication include intraoperative recording of brain activity as well as improved surgical devices that keep the electrode placed in the correct position.  Approximately 2% of their patients experienced this complication.

   
• The authors found that approximately 10% of their patients had electrodes that fractured, short circuited, or moved from their original placement site.  Reasons included improper tightening of the devices that hold the electrode in place as well as not enough tightening in other areas.  One patient experienced a fall that also led to the electrode moving from the original site.  Prevention techniques include improvement in the surgical devices as well as improved education and experience of the surgeons as they completed more and more of the surgeries.

   
• Infection is a concern for any surgery involving placement of a foreign body/device into one’s body.  DBS surgery is no different and this study found approximately 10% of the patients experienced an infection related to the surgery and electrode placement.  The infections were usually detected very early and all of the patients that had infections had the implants removed.  The authors suggest that prevention of infections by taking precautions before the surgery is of utmost importance (e.g. antibiotics, antiseptic shampoo, etc.).

   
• A common stimulator complication is stimulation of surrounding tissues of the STN or GPi that cause a variety of motor and non-motor complications (e.g. speech, blinking, cognitive, psychiatric, weight gain, etc.).  Prevention techniques include changing stimulator settings and monitoring of patient’s condition for such complications.  Additionally, making sure that the patients are good surgical candidates and that they do not have pre-existing conditions (e.g. psychiatric or cognitive) that would worsen the chance of complications after the surgery.

   
• Patients with DBS also have to be cautious and alert about having the stimulator and undergoing other medical procedures that may interfere with or cause damage to the stimulator or surrounding areas (specifics mentioned were radiofrequency and monopolar diathermy used in some dental procedures).  Prevention possibilities include that patients be given a card or other way of identifying that they have DBS as well as that they receive education on the importance of letting their medical professionals know about their surgical history. 

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McIntyre CC, Frankenmolle AM, Wu J, Noecker AM, Alberts JL.. Customizing deep brain stimulation to the patient using computational models.. , Conf Proc IEEE Eng Med Biol Soc. 2009; 2009:4228-9.Conf Proc IEEE Eng Med Biol Soc. 2009; 2009:4228-9.

The purpose of this article was to compare DBS STN stimulator settings on cognitive and motor tasks in people with Parkinson’s disease (PWP) that were created on either a clinician’s skill and experience or settings generated by a computerized model.  One problem with DBS stimulator settings is that there are 1000’s of possible settings and it is not feasible (time or discomfort) for clinicians or PWPs to go through all of the possibilities in order to find the “perfect” setting.  Therefore, it would be ideal to find the least invasive and most efficient method to set stimulator parameters for the best possible motor improvement and minimization of cognitive dysfunction for PWP.



The study found that utilizing the computer based model resulted in less power used by the stimulator and the same amount of improvement in motor scores as found in the model created by the clinician.  When they looked specifically at the cognitive tasks they found no difference between the two models when tasks were easy.  However, as complexity increased, when the computer generated stimulator settings were used, the PWP did better than when the settings were generated by clinicians alone.  The authors suggest that the difference was caused by the DBS stimulation spreading to areas adjacent to the motor portion of the STN, which then disrupts the full potential of one’s cognitive abilities.  A goal of the computer based model would then be to prevent spreading of the DBS stimulation to areas that are involved in cognitive functions while at the same time stimulating areas to maximize motoric treatment efficacy.  The authors suggest that based on their results, the computer based models should be used to supplement the stimulator parameter selection along with the clinician in order to best optimize the efficacy of the DBS STN.

Click here to go to Pub Med Abstract.

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Resnick AS, Foote KD, Rodriguez RL, Malaty IA, Moll JL, Carden DL, Krock NE, Medley MM, Burdick A, Haq IU, Okun MS.. The number and nature of emergency department encounters in patients with deep brain stimulators.. , 2010 Jan; 257(1):122-312010 Jan; 257(1):122-31

The purpose of this article was to look at reasons why people who have DBS go to the emergency room as well as to provide education and guidance on how to best treat those patients.  The most common type of patient that presented to the ER was a male in his mid 50’s with either unilateral or bilateral implantation. Four main disease groups were looked at including Parkinson’s disease, essential tremor, dystonia, and other (multiple sclerosis, obsessive-compulsive disorder, or other tremor).  Approximately one forth of the Parkinson’s disease group utilized the ER and most commonly went for evaluation of mental status changes (changes in one’s cognitive abilities).  Other reasons were headache, infection related as well as not related to the hardware, pain, and passing out.  It was not surprising that the main reason for PD patients to go to the ER was neurological in nature as that is a common effect of the disease itself.  The amount of time that had passed since their surgery ranged quite a bit from 1 day post-op to 48 months post-op.  The authors also looked to see if the ER visit was related to the DBS surgery or hardware and found that about half of the time the reason was not related to the procedure or resultant hardware for the PD patients.  The study also provided easy to follow treatment algorithms (see article for specifics) for patients presenting to the ER that has DBS, regardless of the disease state.  The researchers conclude that as DBS continues to be a successful treatment for movement disorders, as well as other neurological conditions, that our health care systems need to be better educated and prepared for that DBS patient walking through the door regardless if that reason is DBS related or not.

Click here to go to Pub Med Abstract.

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Stefani A, Roberto C, Livia B, Mariangela P, Alberto C, Salvatore G, Fabio P, Andrea R, Cesare I, Francesco M, Antonella P. (2009). Non-motor functions in parkinsonian patients implanted in the pedunculopontine nucleus: Focus on sleep and cognitive domains.. , J Neurol Sci. 2009 Sep 16. [Epub ahead of print].J Neurol Sci. 2009 Sep 16. [Epub ahead of print].

This is a follow-up article from an earlier study (see citation below) that looked at the efficacy of bilateral deep brain stimulation of both the Subthalamic Nucleus (STN) and the Pedunculopontine (PPN; another target under evaluation for the surgical treatment of PD).  The researchers initially wanted to look at the efficacy of both targets combined on motor functioning in the person with Parkinson ’s disease (PWP).  Their findings suggested that both targets were effective in reducing motor difficulties but more so for DBS-STN (STN 54% vs. PPN 32% improvement).  The follow-up study focused on how this dual-targeted treatment affects various non-motor functions in the PWP, specifically sleep and cognition.  The authors found that all six of the patients were classified as poor sleepers but with the PPN and STN in specific settings, patients had an increase in the quality of nighttime sleep as compared to DBS-STN settings alone.  Patients also reported less “restlessness, psychosis, and daytime sleepiness.”  In regard to cognitive functioning, the patients were found to have better working memory, executive functioning, response times, and delayed memory with various settings of the PPN as compared to when the PPN stimulator settings were off.  Metabolism changes in various frontal lobe brain areas were also found and discussed (we would refer the reader to the article for those details).  The authors purported that although the DBS-PPN was not as efficacious as the DBS-STN for motor improvement, it did have less cognitive side effects, which suggests it may be used as an alternative for patients that do not qualify for STN due to existing cognitive deficits.  They noted that research must continue to look into how the DBS works in various sites in the brain as well as maximizing the PWP’s quality of life as well as reduction in motor difficulties.

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Smeding HM, Speelman JD, Huizenga HM, Schuurman PR, Schmand B. . Predictors of cognitive and psychosocial outcome after STN DBS in Parkinson Disease.. , 2009 May 21. [Epub ahead of print]2009 May 21. [Epub ahead of print]

The purpose of this article was to look at the effects of DBS STN on cognition, mood, and quality of life in people with Parkinson's disease (PWP) as well as to evaluate any predictive factors for such changes.    The researchers tested two groups, one that had PD without DBS and another that had PD and underwent DBS STN surgery.  Each group was tested at baseline and then 12 months later.  No significant differences were found at baseline testing between the two groups on cognitive testing.  Twelve months after surgery, the DBS STN group showed improvement in their motor scores as well as a reduction in usage of levodopa.  In regard to the cognitive testing the DBS group showed decline, as compared to the control group, in the areas of verbal fluency (naming items as fast as one can that are from a category or that start with a letter; this finding is common), immediate and delayed memory, a Stroop task (a difficult task requiring naming the color of ink that a word is printed in, while ignoring the word itself), reading speed, and visuospatial reasoning.  Regarding the mood and behavior questionnaires, they found that the DBS STN group had more improvement in their quality of life as compared to the control group regardless of whether or not they experienced change in cognitive functioning.  It is notable that although there was a decline noted in scores on research measures, not all of the PWP that experienced change were able to detect a difference in their everyday lives.  As the findings of cognitive decline after DBS STN has been mixed, the authors suggest replication of this study, and continued attention is needed to this area.



The researchers also wanted to examine possible predictors of cognitive decline and quality of life in PWP.  They found that those PWP who had impaired attention, advanced age, and did not respond well to levodopa at baseline were more likely to experience cognitive decline after DBS STN.  They also found that how the PWP responded to levodopa prior to surgery was the best predictor of improvement in quality of life after surgery.



The authors concluded that DBS STN is an efficacious treatment for improved motor symptoms of PD as well as quality of life in the PWP.  However, the treatment has been found to have adverse effects that PWP need to know about before undergoing such treatment.  They discuss that physicians should also pay attention to premorbid factors before surgical intervention that may help predict who is more likely to have such adverse cognitive events after the surgery.

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Richardson RM, Ostrem JL, Starr PA. Surgical repositioning of misplaced subthalamic electrodes in Parkinson's disease: location of effective and ineffective leads.. , 2009;87(5):297-303. Epub 2009 Jul 292009;87(5):297-303. Epub 2009 Jul 29

The purpose of this article was to look at repositioning lead placements in people with Parkinson’s disease (PWP) that experienced suboptimal results after their initial DBS surgery.  It is notable that the researchers had patients from within their own practice as well as from other practices, suggesting that suboptimal surgical results happen at various facilities and more importantly that those suboptimal results should be individually reviewed in order to improve the effects of the DBS as well as reduce adverse events for such patients.   It should be noted that none of the patients in this study had surgical complications at either the initial or repositioning surgery that explained the suboptimal results.   We would refer the reader to the article for detailed and specific locations of each patient's initial lead as well as where the revised lead was placed (typically 2-5mm change towards the central zone of the dorsolateral STN).  All 8 of the PWP that underwent revision experienced improvement in their motor and nonmotor symptoms observed after the initial surgery and none reported any adverse events (improvements included general motor symptoms, gait, tremor, dystonia, depression, dysarthria, freezing of gait, and rigidity).



There continues to be mixed findings regarding the best lead placement site for DBS in PWP and this article contributes to that debate.  It is promising, that there is a large research study soon to come out that may best address the lack of consensus.  Although the debate continues, articles such as this remain important because there are individuals out there that are having suboptimal results from their initial surgery that may feel that there is nothing else to be done for them.  Research should and will continue regarding the best neuroanatomical lead placement sites but we cannot forget or ignore those PWP that are out there that did not benefit as much from the surgery as hoped.  This article is a great example that one option, lead repositioning, was appropriate for specific patients and those patients showed improvement after the second surgery.

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Kim HJ, Paek SH, Kim JY, Lee JY, Lim YH, Kim MR, Kim DG, Jeon BS.. Chronic subthalamic deep brain stimulation improves pain in Parkinson disease.. , Dec; 255(12):1889-94. Epub 2009 Jan 22Dec; 255(12):1889-94. Epub 2009 Jan 22

The purpose of this article was to look at pain in a subset of PWP before and after DBS STN. The article cites a prevalence rate of “40-78%” of the general group of PWP experiencing pain.  Approximately 80% of the PWP in this study reported pain in multiple areas of the body preoperatively.  The majority of the patients reported here had bilateral STN but a few had unilateral STN for specific reasons mentioned in the article.  Three months after surgery, the majority of those patients that were experiencing pain endorsed improvement (87%) in regard to their pain.  The authors found that dystonic pain was the most improved and back pain was the least reduced of the pain complaints.  It should be noted that not all patients had improvement in their pain and other patients developed pain where none existed prior to the DBS STN (24%).  After 6 months, most of the patients that had experienced a reduction in pain continued to report such reduction.  The authors also postulated ideas why DBS STN would reduce pain including reduced muscle tone, possible basal ganglia involvement, and other neuroanatomical possibilities.  More research needs to be done on pain in PWP to better understand how a treatment option for improved motor control may also be beneficial in reduction in yet another non-motor symptom of PD.  The authors also suggest that pain and DBS STN needs to be looked at longitudinally versus at a single point in time to best represent pain control or reduction in this group of people.

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Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE 4th, Wang X, Gordon CW Jr, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD. . Cognition and mood in Parkinson's disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: The COMPARE Trial.. , March 13, 2009March 13, 2009

The purpose of this article was to compare the effects of DBS-STN vs. DBS-GPi, in regard to mood and cognition.  The authors looked at various settings and stimulation parameters of both devices with patients off medication so they could evaluate the stimulators alone.  Patients were also given various cognitive and mood measures prior to surgery and then again 7 months after surgery.  It is notable that 7 patients did not continue the study after surgery due to adverse events (could not tolerate protocol, hemorrhage, and pneumonia related death [one]).  We would refer the reader to the supplementary tables in the article for more specific information about adverse events for those that remained in the study, although most were mild and did not last long.  However, the authors noted that the STN group had more adverse events than the GPi group.  



Generally, this article showed that there were few differences in mood and cognition between STN and GPi when both groups were at their optimal settings.  They concluded that the verbal fluency finding (naming as many words that start with a specified letter as fast as one can) likely is a result of the surgery as the effect was still there when the stimulator was not on for the DBS-STN group.   The authors also discussed that their findings suggest that the target of DBS may best be done based on individual patient characteristics (e.g. cognitive issue, behavioral concern, medication reduction, etc.).  It also showed different stimulator settings and areas that should be avoided in individuals with specific complaints (e.g. less energetic, less happy, etc.), which is very beneficial information for those doing the placement as well as the programming of the devices in improving the care and quality of life of individuals with DBS STN or GPi.

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Ellis TM, Foote KD, Fernandez HH, Sudhyadhom A, Rodriguez RL, Zeilman P, Jacobson CE 4th, Okun MS. (2008).. Reoperation for suboptimal outcomes after deep brain stimulation surgery.. , Neurosurgery. 2008 Oct;63(4):754-60; discussion 760-1.Neurosurgery. 2008 Oct;63(4):754-60; discussion 760-1.

The purpose of this article was to look at and learn from a group of patients (PD, Essential Tremor, or dystonia) that had suboptimal motoric results after their DBS surgery.  They discussed that one reason for poor results after surgery is suboptimally placed leads (even 2-3mm off target has been shown to affect results).  These authors looked at a group of patients that underwent reoperation with revision or replacement of the leads.  It should be noted that the group of patients from this study had their original surgery at a variety of sites, including that of the authors, which suggests that lead difficulties are possible regardless of where the surgery takes place or how careful the team is in placing the leads.  The authors suggested various precautions and techniques for movement disorder multidisciplinary teams to minimize such lead problems.  As DBS is a relatively new surgery for movement disorders, there will continue to be different surgical techniques used and implantation sites completed on various patients.  Researchers and clinicians need to continue to monitor and report their data to each other in order to come up with the best practice to successfully treat patients with movement disorders.



After reoperation the majority of the patients in this study had improvement in motor complaints and multiple areas of quality of life.  As can be seen with any DBS surgery, there were some adverse events noted with reoperation for 3 of the patients (infection, lead fracture, and wound closure difficulty due to thin skin).  The authors concluded that reoperation showed benefit for these patients.  They also discussed the strong need to have multidisciplinary teams create policies and guidelines for selection of patients that are good candidates for reoperation so that the subsequent surgery can be successful.

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