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Deep Brain Stimulation in Parkinson's Disease: Expected outcomes

General | September 2, 2014 | Author: The Super Pharmacist

general, parkinson's disease

Deep Brain Stimulation in Parkinson's Disease: Expected outcomes

Deep brain stimulation is an increasingly popular, effective and safe procedure typically carried out to correct or compensate for abnormal signalling in the relevant brain regions. It is applied to severe cases of neurological disorder that do not respond to other treatment options. An example of these is Parkinson's disease. This is a progressive neurological disorder, often resulting in characteristic symptoms such as tremors, stiffness, rigidity and difficulties with walking and co-ordination. It may be associated with other characteristics, such as mild to moderate psychiatric symptoms (e.g. depression) and working memory discrepancies. Parkinson's disease is associated with important structures deep within the brain, and is often not fully addressed by conventional therapies associated with this condition.

Targets for Deep Brain Stimulation in Parkinson's Disease

Deep brain stimulation is an increasingly common option for Parkinson's disease patients in whom pharmacological treatment is ineffective and/or elicits further motor anomalies. The main targets of this stimulation are brain regions that regulate or modulate the signals of the brain structures damaged by Parkinson's disease. The most common of these are:

  • The subthalamic nucleus (STN): A popular option as different parts of this nucleus can play a role in modulating the behavioural, cognitive and motor symptoms of Parkinson's appropriately and effectively.
     
  • The globus pallidus interna (GPi): Stimulation of this region has shown efficacy and motor improvements comparable to those of STN stimulation.
     
  • The pedunculo-pontine nucleus (PPN): Some researchers have proposed this as a target as it may elicit greater improvements in walking and balance control.

A major drawback of deep brain stimulation is the often extensive period of time required for the implant to stabilise and take effect, and thus for responses in the patient to become apparent. However, STN stimulation may considerably improve motor control, and also the life quality of patients. A ten-year study of GPi and STN stimulation showed that both types maintained clinical efficacy over that period, but that STN stimulation alone was associated with a significant reduction in medication use.

When should Deep Brain Stimulation be considered? 

When should Deep Brain Stimulation be considered? Deep brain stimulation is most often recommended for patients who have treatment-resistant, dopamine-responsive Parkinson's disease and exhibit little or no cognitive impairment. The procedure is typically performed approximately 15 years after diagnosis. Unfortunately, these delays in confirming both eligibility for deep brain stimulation and conventional therapy failure often translates in the development of motor symptoms too severe to allow for surgical intervention.

Deep brain stimulation may be applicable and beneficial to a greater number of patients currently denied effective treatment.

Outcomes for Deep Brain Stimulation in Parkinson's Disease

Recent reviews of the research into treatment (both pharmacological and surgical) of Parkinson's disease indicates that deep brain stimulation alone or in combination with other conventional treatments results in better outcomes, compared to conventional therapy alone. Deep brain stimulation is associated with up to 60% of motor symptom correction, and may reduce drug requirements by up to 80%. However, this treatment option is also associated with adverse or unwanted effects, the more common of which are outlined below. The typical responses of patients to deep brain stimulation may include some or all of the effects listed below. This research concerns bilateral stimulation (i.e. stimulation of targets in both halves of the brain) unless stated otherwise.

Emotional and behavioural effects

Early trials of STN stimulation in Parkinson's disease patients found that this treatment may induce hypomania (i.e. a state of agitation or high energy, which may be marked by either euphoric or irritable moods) and also inappropriate and/or uncontrollable laughter. This indicates a risk of malfunction in the deep brain stimulator device. On the other hand, stimulation that may cause hypomania is associated with the potential for improved motor control. STN stimulation may also mimic the symptoms of depression.

Outcomes for Deep Brain Stimulation in Parkinson's DiseaseMany studies have found that patients report improvements in mood as a result of this treatment. A trial comparing STN stimulation to that of the GPi found that mood changes were similar for both treatment groups. Some evidence suggests that patients may experience increased anger (as measured by Visual Analogue Mood Scale scores) as a result of unilateral STN or GPi stimulation.

Motor effects

Patients with Parkinson's disease often experience significant difficulties in timing-based tasks, including working to or keeping a beat. This indicates an inability to maintain conscious control of regular or rhythmic motor activity. STN stimulation can correct these discrepancies to some degree, indicating that it is associated with improvements in conscious motor control. However, finer degrees of timekeeping control (i.e. to hundreds of milliseconds, of which healthy control subjects were capable) was not improved (or worsened) by STN stimulation. Low-frequency (10Hz) stimulation of this area may worsen the common symptom of rigidity. In general, this form of deep brain stimulation is associated with increased motor control in Parkinson's disease patients. Long-term studies of GPi stimulation indicate comparable improvements. A trial of PPN stimulation found that this was associated with significant improvements in gait and balance control, but that these effects were inferior compared to STN stimulation. Further improvements were elicited by a combination of stimulation at both targets and medication.

Cognitive effects

Different types of timing (e.g. internal timing and interval timing) are crucial to cognition and conscious time processing. Again, brain regions affected by Parkinson's disease play a role in these functions. Sub-optimal STN stimulation (i.e. 10Hz) in 12 patients was found to exacerbate timing discrepancies significantly compared to control with no stimulation. Stimulation at therapeutic frequencies (approximately 130 Hz) reversed this effect, however. A trial comparing two types of deep brain stimulation in Parkinson's treatment (STN vs. GPi) found no significant differences in cognitive changes between the respective patient groups. Some research indicates that patients may experience increased confusion as a result of GPi stimulation, in comparison with STN stimulation.

Verbal and memory effects

STN stimulation may result in a slight reduction of the ability to recall and choose words that correspond appropriately to a given meaning, or verbal fluency. On the other hand, 10Hz STN stimulation resulted in significant verbal fluency improvements, compared to frequencies of 0Hz and 130Hz.

A study of cognition in 46 patients with STN stimulator implants found that their verbal memory had declined at six and twelve months post-surgery.

Another trial comparing 26 patients with STN implants to 21 without found that the verbal fluency deficiencies in patients with implants were associated with increased delays in word recognition. 
 

A study comparing 23 patients with GPi stimulation to 22 with STN stimulation found that verbal fluency deterioration was significantly worse in the STN group.

may indicate a consequence of the surgical procedure used in the course of STN device implantation, rather than an effect of implant activation. Other studies have found that working memory may be improved by STN stimulation.

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