LAS VEGAS—In patients with Parkinson’s disease, deep brain stimulation (DBS) can improve gait significantly and reduce vocal tremor. Some patients may fail to improve following implantation, however, and others who do improve may later worsen. In such cases, neurologists can address problems with gait and voice tremor using various steps to optimize DBS treatment, according to two lectures delivered at the 21st Annual Meeting of the North American Neuromodulation Society.
Refractory Gait Impairment
Gait impairment and freezing of gait may persist for years in some patients, despite DBS treatment at the traditional frequency of 130 Hz. Studies by Moreau and colleagues indicate that stimulation at 60 Hz improves these outcomes in previously refractory patients, said Helen M. Brontë-Stewart, MD, MSE, the John E. Cahill Family Professor and Director of the Stanford Movement Disorders Center at Stanford University School of Medicine in California. Research by Ricchi et al shows that low-frequency DBS also reduces gait impairment and freezing of gait in the early stages after implantation.
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Helen M. Brontë-Stewart, MD, MSE |
The factors that predict which patients will benefit from low-frequency DBS of the subthalamic nucleus (STN) are increased age, severe axial phenotype at five years after surgery, and lower preoperative levodopa responsiveness. But low-frequency DBS may not be adequate to improve other motor signs such as tremor, said Dr. Brontë-Stewart. Improvements on low-frequency DBS also may not last long.
The literature about which part of the STN should be stimulated for more effective treatment contains mixed results. Several investigations, including a 2011 study by McNeely et al, showed that high-frequency DBS is most efficacious when applied to the dorsolateral margin of STN. Other studies, including one performed by Dr. Brontë-Stewart and colleagues, indicate that stimulating the ventral area of the STN is more effective. Khoo et al found that 60-Hz stimulation was superior to 130-Hz stimulation for axial motor signs in Parkinson’s disease. “Clearly, we do not have consensus,” said Dr. Brontë-Stewart.
Postsurgical Gait Worsening
If a patient’s gait worsens shortly after DBS surgery, one possible explanation is that the leads were misplaced. Gait also could worsen if high-frequency DBS is applied outside the STN, especially in the anterior, medial, and dorsal regions, said Dr. Brontë-Stewart. If a patient’s gait and akinesia worsen with high-frequency STN DBS, but his or her tremor and rigidity improve, the cause may be diffusion of the stimulatory field into the pallido-fugal fibers before decussation of the pallido-pedunculopontine nucleus (PPN) pathway.
“The combination of STN DBS and medication may lead to lower-extremity dyskinesias,” which may account for gait worsening in some patients, said Dr. Brontë-Stewart. “It is important to look at these patients off medication. It may show that the dyskinesias are interfering with the gait studies, and whether the medication is affecting their cognition, which may also worsen gait.”
Patients’ gait and balance may worsen years after implantation. For example, stimulation-resistant axial symptoms may emerge after five years of DBS even if treatment remains effective for appendicular symptoms. This outcome may follow progression of the disease into nondopaminergic networks. Another possible cause is increased voltage that involves pallido-fugal pathways, thus enlarging the field of stimulation, said Dr. Brontë-Stewart.
For patients with delayed worsening, Dr. Brontë-Stewart advises that “if you reprogram DBS, focusing on gait symmetry, you can improve gait, including freezing of gait. Many of us program DBS for appendicular symptoms, and we fail to do this for gait…. Perhaps use bipolar or interleaving programming to restrict field extension.”
Preoperative improvement in Unified Parkinson’s Disease Rating Scale Part III scores in response to levodopa treatment is the best predictor of the effect of DBS on gait and freezing of gait. Improvement in freezing of gait following STN DBS has, in turn, been related to reduced medication dosing and lack of worsening of cognition, concluded Dr. Brontë-Stewart.
An Initial Approach to Vocal Tremor
The literature suggests that in patients with Parkinson’s disease, STN DBS often results in deterioration of speech that may not improve when the stimulation is stopped. Predictors of vocal problems include presurgical dysarthria, duration and severity of presurgical disease progression, and contact placement around the left STN.
“There is no large evidence base upon which to work when you are trying to … deal with someone who comes to you with speech problems,” said Bryan T. Klassen, MD, Assistant Professor of Neurology at the Mayo Clinic in Rochester, Minnesota. Addressing potential speech problems before implantation “should be a major part of any DBS protocol,” he added. A neurologist should document a patient’s pre-existing speech issues carefully. At Mayo Clinic, all patients scheduled to undergo implantation visit a speech pathologist first, and the examination is recorded.
In addition, patients need to understand that vocal tremor may be a symptom of Parkinson’s disease and may not result from DBS. On the other hand, neurologists also should inform patients that inserting the leads may cause dysarthria even before the battery for the device is implanted. Patients ultimately may have to choose between optimal tremor control and optimal speech, said Dr. Klassen.
Disease-Related Vocal Abnormalities
When a patient presents with speech problems, the neurologist must determine whether they result from the disease or from stimulation. Symptoms that have responded insufficiently to DBS are likely related to the disease, as are symptoms consistent with disease progression, such as gradually progressive dysarthria. These symptoms may respond to more aggressive stimulation. A patient with worsening hypokinetic dysarthria, however, may not improve, and could worsen, with more aggressive stimulation.
No clear criteria can help a neurologist determine whether to consider abnormal speech nonresponsive to stimulation. This determination relies on clinical judgment and should be communicated clearly to the patient, said Dr. Klassen. At that point, the neurologist and patient may consider speech therapy.
Stimulation-Related Vocal Abnormalities
DBS implantation itself sometimes causes dysarthria that may improve over the course of weeks or months. Implantation also may worsen pre-existing dysarthria. “That [side effect] does not necessarily have to limit what or how you are stimulating for tremor control,” said Dr. Klassen. If the symptom results from stimulation, it will improve when stimulation is stopped. It may take as little as a few seconds or as long as several weeks for vocal abnormalities to improve, but tremor worsens while stimulation is turned off.
A neurologist should locate the source of any stimulation-dependent vocal abnormality so that he or she can focus the stimulation field on that source. Although the left lead tends to be implicated in vocal abnormalities more often than the right lead, the neurologist needs to determine the leads’ contributions empirically by turning the leads off individually. “Depending on the washout [period], that may take more time than you would like,” said Dr. Klassen.
A review of the initial monopolar thresholds can indicate which regions along the electrode tend to affect speech the most. Postoperative imaging may help in this determination. If the patient has a prolonged washout period, the neurologist can give him or her “homework,” said Dr. Klassen. To do this, the neurologist sets the DBS device to run several programs and asks the patient to record his or her experiences in a notebook.
Optimizing the Stimulation Settings
Vocal abnormalities that arise after surgery may indicate that the stimulation parameters need to be modified. First, neurologists must choose the optimal lead location along the electrode. Eccentric steering or multiple-source current steering may reduce vocal tremor by better defining the distribution of current. To reduce the volume of tissue activated, the neurologist can increase the pulse width, reduce the amplitude, or switch to a bipolar configuration. If a particular setting causes side effects, reducing the voltage may increase tolerability, albeit at the expense of efficacy. Switching from a high frequency to a low frequency also may reduce vocal tremor.
If it is impossible to control limb tremor and vocal abnormalities optimally with a single setting, the patient may choose the setting that provides the most acceptable overall control. Another option is to allow the patient to switch as necessary between a program optimized for tremor control and one optimized for speech. A patient may also choose to turn stimulation on and off as needed. Finally, adjunctive speech therapy can reduce vocal tremor, said Dr. Klassen.
—Erik Greb
Suggested Reading
Fasano A, Aquino CC, Krauss JK, et al. Axial disability and deep brain stimulation in patients with Parkinson disease. Nat Rev Neurol. 2015;11(2):98-110.
Fleury V, Pollak P, Gere J, et al. Subthalamic stimulation may inhibit the beneficial effects of levodopa on akinesia and gait. Mov Disord. 2016;31(9):1389-1397.
Khoo HM, Kishima H, Hosomi K, et al. Low-frequency subthalamic nucleus stimulation in Parkinson’s disease: a randomized clinical trial. Mov Disord. 2014;29(2):270-274.
Matsumoto JY, Fossett T, Kim M, et al. Precise stimulation location optimizes speech outcomes in essential tremor. Parkinsonism Relat Disord. 2016;32:60-65.
McNeely ME, Hershey T, Campbell MC, et al. Effects of deep brain stimulation of dorsal versus ventral subthalamic nucleus regions on gait and balance in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2011;82(11):1250-1255.
Moreau C, Defebvre L, Devos D, et al. STN versus PPN-DBS for alleviating freezing of gait: toward a frequency modulation approach? Mov Disord. 2009;24(14):2164-2166.
Østergaard K, Aa Sunde N. Evolution of Parkinson’s disease during 4 years of bilateral deep brain stimulation of the subthalamic nucleus. Mov Disord. 2006;21(5):624-631.
Ricchi V, Zibetti M, Angrisano S, et al. Transient effects of 80 Hz stimulation on gait in STN DBS treated PD patients: a 15 months follow-up study. Brain Stimul. 2012;5(3):388-392.
Vercruysse S, Vandenberghe W, Münks L, et al. Effects of deep brain stimulation of the subthalamic nucleus on freezing of gait in Parkinson’s disease: a prospective controlled study. J Neurol Neurosurg Psychiatry. 2014;85(8):871-877.
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