Brain implant offers hope for early-stage Parkinson's

'A new highly accurate form of brain surgery could bring hope to thousands of Parkinson's sufferers,' the Mail Online website has reported.

The story is based on a new and encouraging study that suggests that a technique currently used to treat advanced Parkinson's disease could benefit people with the early form of the disease.

The study, which involved 251 people with early-stage Parkinson's disease, looked at the quality of life of participants after they received different treatments for two years. One group of patients was treated with brain stimulation and medication, while the other group only received medication.

Deep brain stimulation acts like a kind of neural pacemaker, using electrical pulses to stimulate areas of the brain that have been damaged by Parkinson's.

Researchers found that quality of life improved significantly by 26% among patients who received brain stimulation and medical therapy, compared with a decline of 1% in quality of life among participants who only received medication.

While these are very impressive results, we need to bear in mind that this was a small study. The findings need to be replicated in larger studies before we can say that this type of treatment is safe and effective.  

Where did the story come from?

The study was carried out by researchers from the University of Kiel, Germany and other institutions. It was funded by the German Ministry of Research and other unnamed sources.

It was published in the peer-reviewed New England Journal of Medicine.

The story was picked up by the Mail Online website, who covered the findings of the study accurately.

Parkinson's disease is a progressive neurological condition where part of the brain gradually becomes more damaged over many years. There is currently no cure.

The three main symptoms of Parkinson's disease are:

• involuntary shaking of particular parts of the body (tremor)
• muscle stiffness that can make everyday tasks difficult (rigidity)
• slow physical movements (bradykinesia)

Other symptoms can include:

• involuntary muscle jerking (dyskinesia)
• depression
• daytime sleepiness
• swallowing difficulties (dysphagia)

Read more about the symptoms of Parkinson's disease.

A drug called levodopa is used to relieve symptoms, although its effectiveness is reduced after three to five years of use. Its long-term use can trigger side effects such as:

• temporary immobility
• uncontrollable, jerky muscle movements (dyskinesias)

This research was carried out in order to see if deep brain stimulation could relieve some of the side effects associated with levodopa.

What kind of research was this?

This was a randomised controlled trial (RCT) assessing whether a particular type of brain stimulation (neurostimulation) would be beneficial for patients with early-stage Parkinson's disease.

This is the best type of study design to determine whether a treatment is effective.

What did the research involve?

The researchers recruited 251 people from Germany and France with Parkinson's disease and early movement problems. To be included, patients had to be between 18 and 60 years, have had Parkinson's for at least four years, and not have a severe form of the disease.

Patients with major depression or dementia were not included in this study. They were randomly assigned to receive either neurostimulation plus medical therapy (124 people), or medical therapy only (127 people).

The neurostimulation group underwent surgery to have electrodes implanted into certain parts of the brain and were fitted with a neurostimulator that was connected to the electrodes.

The electrical implant generated small electrical signals to stimulate the brain and was controlled by a handheld device. These electrical signals block abnormal nerve signals, which are thought to trigger the symptoms of Parkinson's disease.

Medical therapy involved standard drug therapy for Parkinson's disease. All patients were then assessed at five months, one year and two years.   

The primary outcome of the trial was disease-related quality of life at two years, which was assessed using the Parkinson's disease questionnaire (PDQ-39). The PDQ-39 is essentially a scoring system that assesses the extent that the disease has impacted a person's quality of life. Scores in the questionnaire ranged from 0 to 100, with higher scores indicating worse function.

Other outcomes measured were:

• parkinsonian motor disability
• activities of daily living (ADLs)
• levodopa-induced motor complications
• time with good mobility and no dyskinesia
• adverse events

The researchers compared the outcomes of participants who received neurostimulation and medical therapy with those who only received medical therapy.

They used a statistical technique called an intention-to-treat analysis, which takes into account all participants that started the study and is the best way of analysing data from this type of study.

What were the basic results?

The participants (average age 52 years) had lived with Parkinson's disease for an average of 7.5 years. At the two-year follow-up, the key finding was that quality of life significantly improved by 26% in the neurostimulation plus medical therapy group, an average change from a baseline of eight points on the PDQ-39.

This is in comparison with a 1% decline in quality of life among the medical therapy alone group (an average decline of 0.2 points on the PDQ-39).

Researchers also found that neurostimulation plus medical therapy was superior to medical therapy alone when looking at:

• motor disability
• activities of daily living (ADLs)
• levodopa-induced motor complications
• time with good mobility and no dyskinesia

A total of 68 (54.8%) patients in the neurostimulation group had at least one serious adverse event, compared with 56 (44.1%) in the medical therapy only group. Statistical testing comparing adverse events between groups was not reported. A serious adverse event was defined as an event that led to hospitalisation, disability or death.

Depression was reported more frequently in the neurostimulation group, and psychosis was reported more frequently in the medical therapy only group. There were 26 serious adverse events related to surgery or the implanted device, of which 25 resolved completely and one left a skin scar. 

Medication use was significantly changed in both treatment groups. The levodopa-equivalent daily dose was reduced by 39% in the neurostimulation group, but was increased by 21% in the medical therapy group, with a difference of 609mg between the groups.

How did the researchers interpret the results?

The researchers report that neurostimulation is superior to medical therapy alone at a relatively early stage of Parkinson's disease, before the appearance of severe disabling motor complications. They conclude that neurostimulation may be a therapeutic option for patients earlier than current recommendations suggest.

Discussing the study findings, lead researcher Professor Gunther Deushcl is quoted as saying,
"These results signal a shift in the way patients with Parkinson's disease can be treated. They prove that deep brain stimulation therapy can improve patients' quality of life, even in the earlier stages of Parkinson's disease, when clinicians traditionally rely solely on drugs."

Conclusion

This study provides some compelling early evidence that earlier intervention using brain stimulation and medication together may benefit patients with early-stage Parkinson's disease.

Improvements in patients' quality of life were found after two years of therapy when compared with patients who took medication alone. Currently, deep brain stimulation is only used in people with advanced Parkinson's disease.

However, this study did have some limitations. Participants were not blinded to which group they had been assigned to – unlike acupuncture, for example, you cannot carry out 'sham' brain surgery. This means there may have been a placebo effect at work, where patients may have reported quality of life scores differently because they knew they were receiving a new treatment.

These findings need to be replicated in larger studies before definitive conclusions can be drawn about the effectiveness and safety of this type of treatment. If further studies find similar results, this could change the way early-stage Parkinson's disease is treated.