Research Insights

Nonmotor outcomes in Parkinson’s disease: is deep brain stimulation better than dopamine replacement therapy?

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

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

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

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

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

  • Cognition:   Meta-analyses have shown that around 40% of individuals that undergo DBS-STN treatment will have a “mild” reduction in cognitive functioning.  However there is inconsistency in the literature about why and what type of cognitive changes occur from stimulation therapy due to a variety of reasons including various methods used to evaluate cognition, unknown effects of the surgery and stimulator (trajectory of leads, electrode placement, stimulator settings) on surrounding brain areas, electrode placement (STN vs. GPi), and stimulation site (bilateral vs. unilateral).  Research has also shown that older individuals with impairments in attention as well as that are not as responsive to dopamine therapy are more likely to experience cognitive side effects from DBS.  The research from medicinal therapy has shown that most individuals do not have cognitive side effects from such treatment.  When looking at meta-analyses and comparison of the two groups, the majority of studies have found reduced verbal fluency (ability to come up with words rapidly) in the group that underwent stimulation therapy.  Additionally, a few studies also found changes in the stimulator group in executive functioning (organization, planning, decision making) and verbal memory.
  • Behavior and Mood:  As there was inconsistency in cognitive issues related to stimulation therapy in PWP, there too is inconsistency in behavioral manifestations after DBS.  Reported changes after DBS include depression, suicidal ideation and attempts, hypomania, transient confusion, apathy, anxiety, and impulsivity.  However, there are a variety of psychiatric conditions that can be seen with medicinal treatment of PD as well including “depression, mania, anxiety, apathy,” hallucinations, psychosis, social dysfunction, and impulse control disorders.  Within both stimulator and medicinal treatment there were studies that showed improvement, worsening, or no change in various psychiatric conditions which again addresses fluctuations in the findings.  There is a notable challenge to researchers when comparing these groups after surgery as many patients will also have a reduction in needed medication, which may also improve psychiatric symptoms caused by dopamine therapies.  When the authors compared the stimulator groups to the medicinal groups they concluded that DBS may increase the risk of worsened psychiatric symptoms but that there is a lot of variability in PWP.

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

  • Cardiovascular:   Stimulation of the STN has been shown to cause tachycardia (increased heart rate), while GPi has not shown any cardiovascular change.   Medicinal therapies have been shown to cause orthostatic hypertension in PWP.   The authors concluded that DBS STN may help to alleviate orthostatic hypertension after surgery but that the reduction in medication is also a likely cause.
  • Genitourinary:  Approximately one- to two-thirds of PWP will experience difficulties with bladder urgency, frequency, and nocturia (excessive urination at night).  PWP will also commonly experience sexual dysfunction.  Stimulation therapies have been shown to have variable results on bladder functions but improvement in sexual abilities.  Medication treatments have also shown improvement in bladder difficulties but variable results on sexual dysfunction.  No studies were listed that directly compared the two groups in this area of nonmotor difficulty.
  • Gastrointestinal: Approximately 80% of PWP were listed to experience difficulties with “constipation, nausea, vomiting,” drooling, indigestion, delayed emptying of the stomach, and swallowing difficulties.  There were few stimulation studies that looked at gastrointestinal events.  Of those, there was improvement in swallowing, constipation, and over production of saliva. Medication studies showed mixed results depending on the type of dopamine replacement medication used. No studies were listed that directly compared the two groups in this area of nonmotor difficulty.
  • Perspiration/Thermoregulation:  Around 2/3 of PWP will experience difficulties in regulating their internal temperature and many may also have hyperhidrosis (excessive sweating).  Stimulation therapy has been found to be beneficial in reduction of sweating during “off” periods but has not been studied in “on” periods.  Medication therapies have been shown to have increases in sweating during wearing off times, which has been controlled with modification in medication dosages and reduction of wearing off times.  No studies were listed that directly compared the two groups in this area of nonmotor difficulty.

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

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

  • Smell:  Loss of one’s sense of smell is thought to be an early sign of PD.  Stimulator studies have shown improvement in smell versus medication therapies that have not shown any change.
  • Pain:  Many PWP will complain of pain.  Both stimulator and medication therapies have been shown to improve levels of pain experienced by PWP by improving pain thresholds, reducing intensity, and minimizing fluctuation of pain experienced.  No studies were listed that directly compared the two groups in this area of nonmotor difficulty.
  • Thermal Detection (sensitivity to heat/cold): Occasionally, PWP will have difficulties with detection of temperature.  One study showed that DBS improved PWP’s detection of temperature while medication therapy had no effect.

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

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

Click here to read the abstract.

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