Device-assisted and surgical therapies for more advanced issues with motor fluctuations in OFF episodes are described.
Daniel E. Kremens, MD, JD: We’ve spent a lot of time focusing on the medical treatment of OFF episodes, but at a certain point the fluctuations and OFF episodes may not respond as well to medications. What surgical options are available for these patients?
Rajeev Kumar, MD: Typically, we’ve used the term device-aided therapies to refer to both deep-brain stimulation [DBS] and to pump therapies. If we think about surgical options, we could potentially talk about lesioning therapies also.
In general, we consider device-aided therapies appropriate for patients who have troublesome motor fluctuations—often troublesome dyskinesia despite very aggressive or maximal drug therapy—without contraindications to the specific therapy.
Let’s first talk about deep-brain stimulation. That’s perhaps the most widely applied device-aided therapy in the United States. Typically, we’re placing electrodes into the subthalamic nucleus or globus pallidus, either on 1 side of the brain (unilaterally) or both sides of the brain (bilaterally). We hook these things up to pulse generators. The generators need programming. The main risk is of having a hemorrhage in the brain, which is roughly 1% to 2% for each side of the brain operated on. For bilaterally operated patients, the risk is roughly 2% or 3% for symptomatic intracerebral hemorrhage.
Other adverse effects can occur, such as cognitive impairment. Therefore, patients should undergo a detailed cognitive assessment prior to surgery. Those patients who test well prior to surgery are unlikely to experience clinically important cognitive worsening with surgery. Hardware complications and infections can occur in 5% to 10% of patients’ lifetimes. Typically, these occur in the first few months after surgery and are easily remediable without additional brain surgery.
There’s dramatic improvement. OFF time reduction and improvement in troublesome dyskinesia is typically huge in appropriately selected patients. This is probably the most potent therapy that we have for bad motor fluctuations and dyskinesia—an 80% to 90% reduction in troublesome dyskinesia, and compared with the preoperative state, 5 or 6 hours of OFF time reduction. If we compare it with patients undergoing sham stimulation, then it’s 2 or 3 hours of OFF time reduction. Truly well-validated excellent therapies, but they require a fair bit of careful patient selection and careful ongoing management of the patient. This can be applied, as I mentioned, either in the subthalamic nucleus or globus pallidus.
There are small differences. In STN [subthalamic nucleus], we typically use smaller currents. The patients can have substantially greater drug reduction than in the GPI [globus pallidus interna]. Whereas with GPI, we use larger currents, have less complex stimulation programming and much less drug reduction—typically on the order of 0% to 25% as opposed to 50% or 60% for an STN-stimulated patient.
Duopa [carbidopa-levodopa] therapy refers to a patient receiving continuous levodopa-carbidopa intestinal gel via PEG-J tube. They have to tote around a fairly large cassette hooked up to a fairly clunky pump that weighs approximately 1 to 2 pounds. They carry it in either a fanny pack in a bandolier fashion or in a holster. This really is a very good therapy. It can be applied either during the waking day or—in more severe patients who have troublesome OFF episodes during the night—for 24 hours. It’s a gel formulation and can reduce OFF time by more than 2 hours compared with placebo-treated patients. It does reduce dyskinesia, but not as reliably or as quickly as deep-brain stimulation, and you’re applying a lot of levodopa.
You can often get rid of most orally administered drugs, and that is nice in terms of pill burden. However, it does require stoma care, and it requires carrying around this pump. For many patients, that is not socially acceptable. For others, it is. It’s also a matter of risk. Sometimes we have the frank discussion, “Would you rather have a hole in your stomach or a hole in your head?” That’s a colloquial way of putting it, but it really comes down to a quality-of-life discussion. For most patients who are candidates for deep-brain stimulation, Duopa [carbidopa-levodopa] therapy can be considered.
When you have troublesome dissimultaneous dyskinesia with severe tremor, that’s a situation where DBS has greater efficacy than levodopa therapy. That’s a patient you would preferentially want to treat with deep-brain stimulation. Somebody who’s having trouble because of tolerance to high doses of drug is somebody you’d probably want to go with deep-brain stimulation, especially subthalamic stimulation.
On the other hand, if you have a patient with cognitive impairment—maybe psychosis or dementia—you may have real concerns about DBS potentially worsening cognitive function, especially dementia. If you have a patient who had, for example, gastric bypass or stomach anatomical issues, then you’re probably going to preferentially go toward deep-brain stimulation. There are reasons to choose 1 therapy or another.
Daniel E. Kremens, MD, JD: Although I’ve had patients who simply are not interested in brain surgery.
Rajeev Kumar, MD: That is very true. Absolutely.
Daniel E. Kremens, MD, JD: Then they’ll opt for Duopa [carbidopa-levodopa] therapy. You are right: The size can be challenging. However, I’ve had a lot of clever patients come up with all sorts of ways to hide their pump in clothing. They design stuff.