THREE

Do I Qualify for Surgery?

Now that you know what DBS does and what it can potentially do, the next question you probably want to know is: Am I a candidate for this procedure? Believe it or not, not all physicians (and not even all neurologists) will know the answer to this question. However, knowing the answer to this question is critical to the success of DBS. After all, if you are not a good candidate in the first place, you will likely not have a good outcome. The best way for you to find out if you are a good candidate for DBS is to go to a center where they have a multidisciplinary team that specializes in the evaluation and care of individuals undergoing DBS; finding that team is the topic of Chapter 4. In this chapter, we go over the basics of what makes a good DBS candidate. This may give you an idea of whether or not you might qualify.

PARKINSON’S DISEASE

When to Consider DBS

Because DBS surgery does have risks, it should be offered only when the benefits of the surgery outweigh those risks. Therefore, if you have Parkinson’s disease, we are going to start with when you should be evaluated for DBS surgery. You should only consider surgery if you have one of the following conditions.

  1. You are having motor fluctuations that interfere with activities and cannot be resolved with medication changes.

  2. You have a tremor that interferes with activities and is not helped by medications.

  3. You cannot tolerate any of the Parkinson’s disease medications because of side effects such as nausea or impulse control problems.

If none of these conditions describes you, then you should hold off on getting an evaluation for DBS surgery because you likely will not be considered.

So what do we mean by motor fluctuations? Motor fluctuations occur when you start experiencing wearing off and/or dyskinesias. Remember that, in the last chapter, we talked about levodopa and what can happen with the response to levodopa as Parkinson’s disease progresses. Early on in Parkinson’s disease, levodopa helps the motor symptoms such as slowness, stiffness, and tremor and frequently lasts from one dose to another, even if a whole night goes by without taking medication. However, as time goes on, the levodopa effect gets shorter and shorter. This is called wearing off. As the disease progresses, people living with Parkinson’s disease start to depend on the levodopa to function. As they take levodopa, the medication “kicks in,” relieves stiffness, and makes movements more fluid, but it only lasts for a short period of time. The cycle then begins again with another dose, and this cycle recurs throughout the waking day, with frequent periods of “on” time followed by frequent “off” times. In addition, in more advanced disease, the “on” times are complicated by dyskinesias, the abnormal, involuntary movements that make someone look fidgety. Both dyskinesias and frequent “off” times can interfere with your ability to do things and reduce the quality of your life. DBS can reduce these motor fluctuations potentially for at least 10 years after surgery.

However, many people can delay the need for surgery with adjustments in their medications, so a concerted effort should be made to alter the timing and doses of dopaminergic medications before considering DBS. Below, we list some strategies that can be tried to help wearing off.

  1. Adding or increasing the dose of a dopamine agonist (e.g., pramipexole or ropinirole; in countries where available, cabergoline and lisuride may also be used). This class of medications stimulates the dopamine receptors in the brain. They are also longer-acting than levodopa and can make “on” times last longer.

  2. Adding a COMT inhibitor such as entacapone or tolcapone. These medications prevent the breakdown of dopamine in the brain, allowing dopamine to hang out for a longer period of time and prolonging “on” times. Tolcapone is associated with liver toxicity, so liver function has to be monitored regularly in individuals taking these medications.

  3. Adding an MAO-B inhibitor such as selegiline or rasagiline. Similar to entacapone, these medications can also reduce dopamine breakdown in the brain.

  4. Shortening intervals between levodopa doses.

  5. Trying apomorphine, an injectable dopamine agonist, for individuals with sudden and unpredictable “off” periods.

Here are some strategies that can be used to help reduce dyskinesias.

  1. A trial of amantadine.

  2. Reducing the amount of levodopa given per dose and taking it more frequently. For example, if you are taking one full pill of levodopa every 4 hours, but have severe dyskinesias, taking only a one-half pill of levodopa and increasing the frequency to every 2–3 hours may help.

  3. If you are taking a sustained or controlled release levodopa preparation, switching to regular release levodopa may help.

  4. Increasing the dose of the dopamine agonist and reducing the dose of the levodopa may help.

Please keep in mind that not all strategies can be tried in everyone. You should talk with your neurologist to see if any of these strategies can be employed before considering DBS.

The other two situations we listed that may warrant an evaluation for DBS include a disabling tremor that does not respond to medications and people living with Parkinson’s disease who are intolerant of medications because of severe nausea or vomiting, or impulse control problems. Impulse control problems are those in which you get strong urges that you cannot control. Common examples of impulse control problems include gambling, hypersexuality, or compulsive shopping.

If you have a tremor that interferes with activities, you should at least be tried on high doses of levodopa (up to 1500 mg/day) and a medication called trihexyphenidyl, which helps only tremor in Parkinson’s disease, before going for DBS evaluation. If you are intolerant to Parkinson’s disease medications because of severe nausea, adding extra carbidopa (25 to 100 mg) or domperidone (not available in the U.S.) may help. If you have an impulse control disorder, an effort should be made to wean off your dopamine agonist.

DBS Selection Criteria for Parkinson’s Disease

You are a good candidate for DBS if you have:

  1. A diagnosis of Parkinson’s disease without evidence of an atypical parkinsonian syndrome.

  2. A robust and sustained response to levodopa.

  3. Presence of complications from chronic levodopa therapy such as dyskinesias, wearing off, and on–off phenomena or, alternatively, a tremor-predominant presentation.

  4. Absence of dementia or active psychiatric illnesses such as severe depression.

The most important criterion for consideration of DBS is that you actually have Parkinson’s disease. You might think, “Of course I have Parkinson’s disease. That’s what my doctor told me.” However, there are many disorders that mimic Parkinson’s disease, and because there is no definitive test, neurologists are only about 80% accurate with the initial diagnosis. These disorders that mimic Parkinson’s disease can be difficult to pin down, and neurologists often use terms like atypical Parkinson’s disease, atypical parkinsonism, parkinsonism, or a parkinsonian syndrome to characterize these other disorders. Yet, these people are often referred for consideration of DBS.

The atypical parkinsonisms include multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), and corticobasal degeneration (CBD). One of the main things that distinguish these atypical parkinsonisms from Parkinson’s disease is the response to Parkinson’s disease medications, specifically levodopa. People with Parkinson’s disease respond well to levodopa, whereas people with atypical parkinsonism do not. They are often sent for consideration of DBS because there often are no other treatment options. However, DBS systems have been placed in many individuals with atypical parkinsonism, only to fail. A prominent DBS center in Florida looked at all the individuals that had been referred to their center as “DBS failures” and found that about 12 percent of these people had atypical parkinsonisms that would not be expected to respond to DBS. This is why we recommend that you be evaluated at a center specializing in DBS. These centers have neurologists that specialize in movement disorders such as Parkinson’s disease and can confirm that you actually have Parkinson’s disease in addition to making sure that you are an appropriate candidate for surgery.

The second criterion for DBS for Parkinson’s disease is a robust and sustained response to levodopa. Why? If you have a good response, you are likely to have Parkinson’s disease, as mentioned earlier. Additionally, response to levodopa is also one of the best indicators of a good outcome from DBS. Several studies have shown that the improvement you get from DBS is directly related to the amount of improvement you get from levodopa. Furthermore, DBS does not make you better than your medications, which means that your best “on medication” function will be your best “DBS” function. Because DBS is delivered constantly, though, you will feel like you are “on medications” for the entire day.

To evaluate response to levodopa, many centers will conduct an off–on evaluation. This is where you come to the clinic appointment without having taken your Parkinson’s disease medications overnight. You are then examined using the Unified Parkinson Disease Rating Scale (UPDRS), which is the most commonly used scale to rate motor symptoms in Parkinson’s disease. On the UPDRS, higher scores indicate more impairment. You then take your Parkinson’s disease medications, and after they have kicked in, the UPDRS is administered again. In general, most centers use an improvement of at least 30% in the UPDRS score as a benchmark for DBS approval. However, the more you improve on this test, the better a candidate you are.

On the flip side, those features that do not improve with Parkinson’s disease medications also will not improve with DBS. Some people may not get offered surgery, even if they have Parkinson’s disease and have a response to levodopa, because they are hoping to improve a symptom that does not improve with medication. The most common example is independent walking. Many people have a good response to levodopa, where the levodopa relieves tremor or rigidity and may even cause dyskinesias, but when the medication is working at its best, they still need to use a walker or are wheelchair bound. Unfortunately for these people, DBS will not help them walk independently. If you need a walker when off medications and can walk independently when the medications are working for you, then DBS will help you maintain independent walking. Other features that do not improve with DBS include speech and balance. The one exception to this rule is tremor, which may not respond to levodopa or other Parkinson’s disease medications, but responds nicely to stimulation. This is why you should consider DBS if you have a tremor that interferes with activities and is not helped by medications.

The third criterion for selection of appropriate DBS candidates is the presence of motor fluctuations such as dyskinesias or wearing off that cannot be corrected by medication adjustments and interfere with quality of life. We have already mentioned that DBS does not improve your absolute motor function above medications. However, what DBS can do is make you feel like you are in the “on medication” state for longer periods of time. Therefore, instead of fluctuating from off to on to off to on throughout the day, DBS is designed to make you feel like you are “on” the entire day. In addition, if the electrodes are placed in the STN (see Chapter 2 for more information about the different targets), the total dose of medications may be reduced. When levodopa is reduced, there is also less dyskinesia. Therefore, to picture what DBS can do for you, imagine yourself in your “on” medication state all day, without dyskinesias, and you will have an idea of the possibility of DBS. You may also be a candidate for DBS if you have a tremor that does not respond to medications.

The final selection criterion includes the absence of dementia or active psychiatric illness. DBS centers should have potential candidates undergo detailed neuropsychological testing to determine the presence or absence of dementia. Neuropsychological testing generally takes a couple of hours to complete and tests not only your memory but also your ability to pay attention, your language function, your visual–spatial function, and your ability to process information. Preoperative screening for dementia is mandatory because people with dementia may be unable to provide appropriate feedback when the DBS device is tested. This, in turn, may affect the ability of the surgical team to place the DBS electrode in the right place, and definitely would affect the ability of the neurologist or nurse programmer to set the DBS device at the best settings. More importantly, however, cognition in people with Parkinson’s disease may worsen after DBS surgery. Long-term studies on people with Parkinson’s disease undergoing DBS have shown that mild cognitive decline after surgery is fairly common. Because the cognitive changes are relatively mild, people with no problems in thinking or memory prior to surgery may not notice much difference after surgery. However, those with significant problems in thinking and memory prior to surgery may worsen into a dementia.

In addition, there are reports of people becoming severely depressed after DBS surgery to the point where some even attempt suicide. We still do not know what other factors put people at risk for becoming depressed after surgery other than a previous history of depression. Depression, however, does seem to be more common when electrodes are placed in the STN as opposed to the GPi. The presence of active depression when being evaluated for surgery can also cause significant problems with attention, memory, and executive function, resulting in a neuropsychological evaluation consistent with dementia. These deficits may disappear when the depression is controlled. Thus, if mood is not assessed or improperly evaluated, it may result in the exclusion of candidates who might otherwise be appropriate. Because of this, it makes sense to exclude people with uncontrolled psychiatric illness from having DBS surgery.

OTHER CONSIDERATIONS FOR PARKINSON’S DISEASE

Age

Many people have questions about DBS regarding age. Some surgical centers have been using 70 years of age as a cutoff because early studies demonstrated that people under age 70 tended to show greater motor improvement than people over 70. However, it has also been clearly reported in the medical literature that people over the age of 70 can still have great benefit from DBS. Why younger people have better DBS motor outcomes is not entirely clear, but older people may have more medical problems that increase surgical risk and may take longer to recover from surgery. Older individuals are also more likely to have more problems with thinking and memory. We feel that a strict age requirement for DBS may exclude some good candidates. Thus, potential candidates over the age of 70 should be evaluated on an individual basis. If the DBS center you have chosen has an age cutoff, and you want to be evaluated, you may have to find a different center.

General Health

The entire DBS procedure is a lengthy process. Depending on the center, some individuals can be in the operating room for up to 8 hours or more, in unusually long cases. The surgery is demanding because you have to be awake. For people with Parkinson’s, you also have to be off medications during much of the procedure. To tolerate the surgery, it is essential that you be in good general health. One of the purposes of the DBS evaluation process is to identify problems that put you at high risk for surgery. Medical illnesses that put you at risk of surgical complications, such as uncontrolled high blood pressure, diabetes, or severe cardiopulmonary disease, may cause the DBS team to exclude you from surgery.

Support of Family and Friends

We cannot overemphasize the importance of emotional support from friends, families, or caregivers. After surgery, it can take months to optimize the stimulator settings while adjusting medication. This is a time of constant change, and it may seem like things are not improving or not improving as quickly as you would like. You may also need help around the house or someone to take you to the clinic for the frequent stimulator adjustments. We have seen firsthand how a lack of family support can negatively affect an otherwise successful surgery. See Chapter 5 for more details on getting family and friends involved.

Expectations

DBS surgery cannot be considered successful if your expectations are not met. One of the purposes of this book is to help you have a realistic expectation of the surgical results. If you expect to run a marathon after the surgery when you have never run a marathon in your life, then DBS surgery is never going to be successful. If you understand what the DBS surgery can realistically accomplish, and you are OK with that, then you increase the chances of success.

ESSENTIAL TREMOR

When to Consider DBS

As mentioned in Chapter 2, there are several medications available to treat essential tremor, with propranolol and primidone being the top agents. Many people will respond to medications, but about 30% have no response or minimal response to medications. It obviously does not make sense to opt for DBS when the medications are controlling symptoms. However, what if they do not? It then depends on whether or not the tremors affect your ability to do things and whether you can live with them. You should only consider surgery for essential tremor if:

  1. You have tremors that limit your ability to do things.

  2. You have tried at least three medications for essential tremor and none of them have worked, or you have had side effects that prevent you from taking higher doses.

The first criterion is somewhat vague because different people have different ideas of when the tremors are limiting. For example, if you were a surgeon, a very mild tremor may limit your ability to perform your job and may force you to consider DBS. However, if you had that same tremor, but had retired from the workplace and it did not interfere with any daily activities such as eating or writing, you may not consider DBS. We once had a person whose job required him to work with explosive chemicals. He had such a mild tremor that it would not have triggered a DBS evaluation in most other people. However, his tremor limited his ability to perform his job because of its very nature, and he underwent DBS surgery. (He did well, by the way, and has not caused any accidental explosions.) Because of the risk of surgical complications, you should only consider DBS if you cannot live with your tremors the way they are.

One of the most common mistakes we see in individuals who have been referred to us is that, although they may have tried several different medications in the past, they may not have taken high-enough doses to see an effect. Therefore, we have listed in a table the common medications used for essential tremor with upper limits of the dose by which we would expect an effect on tremor. If your physician has not prescribed the doses of these medications to the doses listed, you may consider going back to your physician to try higher doses before going for DBS evaluation.

Doses of Essential Tremor Medications
Clonazepam: up to 6 milligrams daily
Gabapentin: up to 2700 milligrams daily
Mirtazepine: up to 45 milligrams daily
Primidone: up to 350 milligrams daily
Propranolol: up to 320 milligrams daily
Topiramate: up to 400 milligrams daily

DBS Selection Criteria for Essential Tremor

Most DBS centers will consider you for DBS if:

  1. You have a diagnosis of essential tremor, and your tremors limit or interfere with your activities.

  2. You have not responded to high doses of at least three tremor medications.

  3. You do not have dementia or active psychiatric illnesses.

Other Considerations for Essential Tremor

The target for essential tremor is the VIM thalamus, which is not as deep as the target for Parkinson’s disease. In addition, DBS is usually done only on one side for essential tremor. This cuts down the risks for cognitive decline and other surgical complications. As a result, age is not as much of an exclusion factor for DBS surgery in essential tremor as it is in Parkinson’s disease. We would encourage you to read the section Other Considerations for Parkinson’s Disease in this chapter, as the subsections on general health, support, and expectations apply to people living with essential tremor as well.

DYSTONIA

When to Consider DBS

If you have dystonia, you should consider DBS when your dystonia interferes with daily activities or your quality of life. Again, the decision as to when the dystonia is severe enough to interfere with your life is an individual one. Furthermore, you should also make sure that there are no other medications that can be tried that could help restore some of that quality of life. Strategies/medications that should be tried include the following.

  1. Botulinum toxin. There are many brands of botulinum toxin, including rimabotulinumtoxinB (Myobloc), incobotulinum-toxinA (Xeomin), and abobotulinumtoxinA (Dysport), but the best known of the botulinum toxins is onabotulinumtoxinA (Botox). These medications are injected into the affected muscles and block the signal from the nerve to the muscle. Because the muscles never get the signal to contract, the muscle relaxes and relieves symptoms of dystonia. Unfortunately, expert injectors of botulinum toxin are not available everywhere. People may not respond to botulinum toxin for a number of reasons, but the most common reasons are that not high enough a dose was injected or that incorrect muscles were targeted. It is also possible that you may be resistant to botulinum toxin. To make sure that you truly do not respond to botulinum toxin, we would recommend that you be evaluated by a movement disorder specialist (a neurologist with specialty training in movement disorders such as Parkinson’s disease, essential tremor, and dystonia) with at least 2 years experience injecting for dystonia. There may be a good chance that you might respond to botulinum toxin if it is injected in the correct muscles with the correct doses.

  2. Trihexyphenidyl. This is an anticholinergic medication that often helps dystonia, especially in children. Unfortunately, the side effects including sleepiness, dry mouth, urinary retention, and confusion limit its use. Doses greater than 20 mg/day have been shown to be effective in children with dystonia, but in adults, such high doses may not able to be reached because of negative side effects.

  3. Benzodiazepines. These are agents commonly used for anxiety but may also help in dystonia. Valium, clonazepam, lorazepam, and alprazolam are the most commonly used medications in this class.

  4. Muscle relaxants. In our experience, this class of medication rarely helps dystonia but is still worth a try before considering DBS. Common names for medications in this class include baclofen, cyclobenzaprine, tizanidine, methocarbamol, carisoprodol, and metaxalone.

Please keep in mind that not all strategies can be tried in everyone. You should talk with your neurologist to see if any of these strategies can be employed before considering DBS.

DBS Selection Criteria for Dystonia

The selection criteria for dystonia are not as clear as they are for Parkinson’s disease or essential tremor. However, most DBS centers will consider you for DBS if:

  1. You have a diagnosis of primary dystonia (can be focal or generalized) or a tardive dystonia.

  2. The dystonia causes you to be in pain or to adopt abnormal postures that limit or interfere with your activities.

  3. You do not have fixed contractures.

  4. You have not responded to medications.

  5. You do not have dementia or active psychiatric illnesses.

Primary dystonias are dystonic conditions that either are genetic or do not have another identifiable cause. They can be focal, which means that they affect only one body part, or generalized, which means that they affect the entire body. If you have a secondary dystonia, that means that your dystonia is due to something else, such as a structural lesion in the brain (tumor), a neurodegenerative disease (Huntington’s disease), or a number of other causes. Secondary dystonias, in general, do not respond to DBS. The exception is tardive dystonia, which is a secondary dystonia that occurs after long-term exposure to dopamine-blocking agents such as antipsychotics or antinausea medications. Tardive dystonias may respond very well to DBS.

The absence of fixed contractures is important. A contracture is a permanent shortening of muscle, tendon, or scar tissue that produces a deformity, especially around a joint. Contractures can develop in individuals for multiple reasons, but in dystonia, it usually occurs because the joint/limb is not used. Because the contracture results from shortening of a muscle or tendon, or because of scar tissue, and not from abnormal signals in the brain, DBS will not be able to treat contractures.

Other Considerations for Dystonia

Similar to essential tremor, there is no established upper age limit for dystonia. However, because generalized and severe cases of dystonia often occur in children, and children are still growing, implantation of a DBS device has special considerations. First of all, there have been reports of DBS lead migration. That is, after the DBS has been placed in the target, it may lose its effectiveness because the lead moves out of the target as the child grows and matures. Also, many revisions may be needed to place new extension wires as the body gets bigger. The benefits of the surgery should be weighed against these risks in addition to the typical surgical risks that accompany DBS. As people with dystonia are typically younger than people with Parkinson’s disease, they are in better general health, but we would encourage you to read the section Other Considerations for Parkinson’s Disease regarding family support and expectations.

THE DBS EVALUATION PROCESS

While there are no established requirements for what constitutes a comprehensive DBS evaluation, most DBS centers will have an evaluation process in place. The critical evaluations in this DBS evaluation process regardless of whether you have Parkinson’s disease, essential tremor, or dystonia include the following.

  1. Evaluation and examination by a movement disorder specialist for the surgery. A movement disorder specialist is a neurologist who specializes in the care of people with Parkinson’s disease, essential tremor, or dystonia. The purpose of this visit is to make sure that your diagnosis is correct and that you are an appropriate candidate for DBS. The movement disorder neurologist will perform a complete neurological examination and evaluate mood and cognition as well. Please be aware that the movement disorder specialist may have suggestions for other medications to try before completing the rest of the DBS evaluation. If you have Parkinson’s disease, this particular visit may include an off/on medication evaluation using the UPDRS (described earlier). Alternatively, the off/on evaluation may be scheduled separately after you have tried other medications. If you have essential tremor, the severity of your tremors will be rated as you perform tasks with your hands, such as handwriting or drinking from a cup. If you have dystonia, a different rating scale will be used to rate its severity.

  2. Evaluation and examination by a neurosurgeon who specializes in DBS surgery. One of the purposes of this visit is to meet the person who will perform the surgery. The neurosurgeon will also confirm the movement disorder specialist’s opinion that you are an appropriate candidate and will also evaluate for other factors that might impact the surgery, such as your other medical problems. The risks and benefits of DBS surgery should be discussed with you, and the neurosurgeon should also talk to you about the most appropriate target in the brain. At this visit, you should ask questions about the surgeon’s experience and complication rate.

  3. Neuropsychological examination. The purpose of this visit is to make sure that you do not have significant cognitive problems such as dementia. The neuropsychologist will perform a full battery of tests to evaluate your cognition and memory. The effects of mood disorders such as anxiety and depression on cognitive testing will also be looked at. This may last a couple of hours. The test is designed to be extremely difficult, so do not be surprised if you think you failed after you complete the testing.

  4. Magnetic resonance imaging (MRI) of the brain. While you may have had MRIs in the past, most centers will repeat brain imaging. This is because there are special sequences that the neurosurgeon needs to plan your surgery and the approach he or she will take.

The above is the minimum that a DBS center will do as part of the evaluation. Some centers will have other evaluations. For example, some may have you see a psychiatrist prior to surgery to make sure you have no active psychiatric problems. Some centers may have individuals undergo a social work evaluation to discuss family and other social support, expectations from the surgery, and insurance issues regarding the surgery. These issues may also be discussed by the neurologist, neurosurgeon, neuropsychologist, or psychiatrist at other centers.

DBS is a big thing to consider. We believe that the best outcomes are seen at a center that conducts a comprehensive evaluation prior to surgery. We have seen people that were just sent to see a neurosurgeon and then underwent surgery a couple of weeks later. Although many of these people did just fine, the ones who had the poorest results seem to have been evaluated in this fashion. If you want to consider DBS and think it is appropriate for you, we would encourage you to seek out a DBS center that specializes in this type of procedure and make sure you feel comfortable with their approach. We tell you how to choose your DBS team in the next chapter.