Deep brain stimulation: What can patients expect from it?
ABSTRACTDeep brain stimulation has largely replaced ablative procedures for the treatment of advanced Parkinson disease, essential tremor, and dystonia. It is also approved for obsessive-compulsive disorder. Although not curative, it improves symptoms and quality of life.
KEY POINTS
- Compared with ablative procedures, deep brain stimulation has the advantage of being reversible and adjustable. It is considered safer than ablative surgery, in particular for bilateral procedures, which are often needed for patients with advanced Parkinson disease and other movement disorders.
- For Parkinson disease, deep brain stimulation improves the cardinal motor symptoms, extends medication “on” time, and reduces motor fluctuations during the day.
- In general, patients with Parkinson disease are likely to benefit from this therapy if they show a clear response to levodopa. Patients are therefore asked to stop their Parkinson medications overnight to permit a formal evaluation of their motor response before and after a dose of levodopa.
- Candidates require a thorough evaluation to assess whether they are likely to benefit from deep brain stimulation and if they can comply with the maintenance often required for a successful outcome.
WHAT CAN PARKINSON PATIENTS EXPECT FROM THIS THERAPY?
Typically, some parkinsonian symptoms predominate over others, although some patients with advanced disease present with a severe combination of multiple disabling symptoms. Deep brain stimulation is best suited to address some of the cardinal motor symptoms, particularly tremor, rigidity, and bradykinesia, and motor fluctuations such as “wearing off” and dyskinesia.
Improvement in some motor symptoms
As a general rule, appendicular symptoms such as limb tremor and rigidity are more responsive to this therapy than axial symptoms such as gait and balance problems, but some patients experience improvement in gait as well. Other symptoms, such as swallowing or urinary symptoms, are seldom helped.
Although deep brain stimulation can help manage key motor symptoms and improve quality of life, it does not cure Parkinson disease. Also, there is no evidence to date that it slows disease progression, although this is a topic of ongoing investigation.
Fewer motor fluctuations
A common complaint of patients with advanced Parkinson disease is frequent—and often unpredictable—fluctuations between the “on” state (ie, when the effects of the patient’s levodopa therapy are apparent) and the “off” state (ie, when the levodopa doesn’t seem to be working). Sometimes, in the on state, patients experience involuntary choreic or ballistic movements, called dyskinesias. They also complain that the on time progressively lasts shorter and the day is spent alternating between shorter on states (during which the patient may be dyskinetic) and longer off states, limiting the patient’s independence and quality of life.
Deep brain stimulation can help patients prolong the on time while reducing the amplitude of these fluctuations so that the symptoms are not as severe in the off time and dyskinesias are reduced in the on time.
Some patients undergo deep brain stimulation primarily for managing the adverse effects of levodopa rather than for controlling the symptoms of the disease itself. While these patients need levodopa to address the disabling symptoms of the disease, they also present a greater sensitivity for developing levodopa-induced dyskinesias, quickly fluctuating from a lack of movement (the off state) to a state of uncontrollable movements (during the on state).
Deep brain stimulation typically allows the dosage of levodopa to be significantly reduced and gives patients more on time with fewer side effects and less fluctuation between the on and off states.
Response to levodopa predicts deep brain stimulation’s effects
Whether a patient is likely to be helped by deep brain stimulation can be tested with reasonable predictability by giving a single therapeutic dose of levodopa after the patient has been free of the drug for 12 hours. If there is an obvious difference on objective quantitative testing between the off and on states with a single dose, the patient is likely to benefit from deep brain stimulation. Those who do not respond well or are known to have never been well controlled by levodopa are likely poor candidates.
The test is also used as an indicator of whether the patient’s gait can be improved. Patients whose gait is substantially improved by levodopa, even for only a brief period of time, have a better chance of experiencing improvement in this domain with deep brain stimulation than those who do not show any gait improvement.
An important and notable exception to this rule is tremor control. Even Parkinson patients who do not experience significant improvement in tremor with levodopa (ie, who have medication-resistant tremors) are still likely to benefit from deep brain stimulation. Overall, tremor is the symptom that is most consistently improved with deep brain stimulation.
Results of clinical trials
Several clinical trials have demonstrated that deep brain stimulation plus medication works better than medications alone for advanced Parkinson disease.
Deuschl et al1 conducted a randomized trial in 156 patients with advanced Parkinson disease. Patients receiving subthalamic deep brain stimulation plus medication had significantly greater improvement in motor symptoms as measured by the Unified Parkinson’s Disease Rating Scale as well as in quality-of-life measures than patients receiving medications only.
Krack et al2 reported on the outcomes of 49 patients with advanced Parkinson disease who underwent deep brain stimulation and then were prospectively followed. At 5 years, motor function had improved by approximately 55% from baseline, activities-of-daily-living scores had improved by 49%, and patients continued to need significantly less levodopa and to experience less drug-induced dyskinesia.
Complications related to deep brain stimulation occurred in both studies, including two large intracerebral hemorrhages, one of which was fatal.
Weight gain. During the first 3 months after the device was implanted, patients tended to gain weight (mean 3 kg, maximum 5 kg). Although weight gain is considered an adverse effect, many patients are quite thin by the time they are candidates for deep brain stimulation, and in such cases gaining lean weight can be a benefit.
Patients with poorly controlled Parkinson disease lose weight for several reasons: increased calorie expenditure from shaking and excessive movements; diet modification and protein restriction for some patients who realize that protein competes with levodopa absorption; lack of appetite due to depression or from poor taste sensation (due to anosmia); and decreased overall food consumption due to difficulty swallowing.
DEEP BRAIN STIMULATION FOR ESSENTIAL TREMOR
Essential tremor is more common than Parkinson disease, with a prevalence in the United States estimated at approximately 4,000 per 100,000 people older than 65 years.
The tremor is often bilateral and is characteristically an action tremor, but in many patients it also has a postural, and sometimes a resting, component. It is distinct from parkinsonian tremor, which is usually predominantly a resting tremor. The differential diagnosis includes tremors secondary to central nervous system degenerative disorders as well as psychogenic tremors.
Drinking alcohol tends to relieve essential tremors, a finding that can often be elicited in the patient’s history. Patients whose symptoms improve with an alcoholic beverage are more likely to have essential tremor than another diagnosis.
Response to deep brain stimulation
Most patients with essential tremor respond well to deep brain stimulation of the contralateral ventral intermedius thalamic nucleus.
Treatment is usually started unilaterally, usually aimed at alleviating tremor in the patient’s dominant upper extremity. In selected cases, preference is given to treating the nondominant extremity when it is more severely affected than the dominant extremity.
Implantation of a device on the second side is offered to some patients who continue to be limited in activity and quality of life due to tremor of the untreated extremity. Surgery of the second side can be more complicated than the initial unilateral procedure. In particular, some patients may present with dysarthria, although that seems to be less common in our experience than initially estimated.
In practice, patients with moderate tremors tend to have an excellent response to deep brain stimulation. For this particular indication, if the response is not satisfactory, the treating team tends to consider surgically revising the placement of the lead rather than considering the patient a nonresponder. Patients with very severe tremors may have some residual tremor despite substantial improvement in severity. In our experience, patients with a greater proximal component of tremor tend to have less satisfactory results.
For challenging cases, implantation of additional electrodes in the thalamus or in new targets currently under investigation is sometimes considered, although this is an off-label use.
Treatment of secondary tremors, such as poststroke tremor or tremor due to multiple sclerosis, is sometimes attempted with deep brain stimulation. This is also an off-label option but is considered in selected cases for quality-of-life management.
Patients with axial tremors such as head or voice tremor are less likely to be helped by deep brain stimulation.
