What did the authors study?

In “Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease,”¹ Dr. Hacker and coauthors studied the effects that deep brain stimulation (DBS) has when it is used early in the course of Parkinson disease (PD).

DBS is a system to help symptoms of PD. There are 3 main parts of this system. The first is a lead—a series of coiled wires—that have a tiny electrode on the end. These electrodes are surgically implanted deep in brain tissue. The lead is connected to an extension wire that is attached to a battery-powered electrical stimulator that is placed in the chest or abdomen. The stimulator sends electric currents into the brain.

There are many reasons why a study like this is important. First, DBS is used in addition to medications for PD. Second, it is almost always used when PD is in its middle or late stages. In other words, DBS is considered only when a person's PD has advanced to the point where medications are either no longer working or are working in a less-than-optimal way.

Part of the reason that DBS is used late in the course of PD is that a deep brain stimulator is invasive. In order for DBS to be used, an electronic device must be surgically implanted. Electrodes are most often placed in the subthalamic nucleus, a group of nerve cells in the brain that are affected by PD. DBS is not new. For many years, DBS has been used to send a small electrical impulse to the cells of the subthalamic nucleus, thereby reducing or stopping the tremor (and other symptoms) that occurs in PD.

Although not new, DBS has not been applied to early PD. What Dr. Hacker wanted to know was this: What if DBS was used earlier? How does it affect PD? More specifically, could DBS change the course of PD? It is known that PD is a slowly progressive illness. We have medications that treat the symptoms of PD, but we do not have a treatment that slows or stops the progression of PD. In other words, even with treatment, the PD gradually gets worse. What if early DBS slowed the course of PD? That would mean that a person would live with minimal or no symptoms for longer. It may also mean that a person would need less medication over time.

How did the authors perform the study?

Studying the effects of DBS in early PD is challenging. First, there is no placebo. It is not ethical to implant people with placebo device in order to study the effects of a device. Instead, the authors chose to study the effects of usual medications (which they called optimal drug therapy [ODT]) vs a combination of ODT plus the DBS. However, they realized that they could not measure the PD while the person was on treatment, because the treatments suppress the symptoms of PD. Knowing that the treatments (both DBS and medications) stay in the system for a short time, they decided that at 6-month intervals, they would stop all treatments for 1 week. At the end of the week (of no treatment), they would then measure symptoms of PD, like the person's tremor.

In order to minimize any bias, the authors videotaped the patients at the end of the week without treatment. They sent the videos to a doctor for review. This doctor did not know what treatments the person may have had, and gave each person's video a score. The score was based on the Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III). To further reduce bias, the person who received the videos did not know when in the course of the person's PD the video had been taken. In short, the assessor reviewed each video independently, using the UPDRS-II rating scale.

The researchers studied 28 people, all of whom had early PD. The duration of illness was short: the patients had been taking medications for PD for 6–48 months before entering the study. The people were 50–75 years old. They could not have another neurologic illness like dementia (Alzheimer disease)—that way, the researchers could eliminate the possible effects that another neurologic illness might have on PD. The patients stopped their PD treatments for 1 week at the following time points: 6 months, 1 year, 18 months, and 2 years, which was the end of the study. In other words, each patient would have had 5 videos: 1 that was done before the study treatment occurred and 1 from each of the 6-month time periods.

What did the study show?

When assessing the videos, the most accurate measurements occur with regards to tremor. In the DBS group, over 2 years (24 months), there was a minimal change in the severity of tremor. This was in comparison to the medication-only group (ODT group), where the tremor severity scores worsened. In fact, when comparing the 2 groups, the risk of tremor worsening was 2.6 times higher in the ODT group.

In PD, the tremor usually starts in one limb (one arm or leg), and spreads to affect other limbs. The researchers looked at this as well: how often does a new tremor occur? In the DBS group, the number of affected limbs either stayed the same or went down slightly. This was in comparison to the ODT group, where PD was observed to double. In other words, if the tremor affected one limb, at the end of 2 years, it now affected two. Another way of thinking about this is that there was a new tremor in about half (46%) of the DBS group over a 2-year period. For the medication-only group, 86% developed a new tremor.

What does this mean?

There are many ways to interpret a study like this. First, the study findings need to be confirmed in a larger trial. If both trials show the same thing, it may mean that early use of DBS is an effective way to manage PD. Not only would DBS reduce the symptoms of PD, but it may also decrease the speed at which PD progresses.