Daniel M. Keller, PhD

June 29, 2015

SAN DIEGO — An intriguing study shows that deep-brain stimulation (DBS) may be an effective treatment for symptoms of restless leg syndrome (RLS).

In patients with Parkinson's disease (PD), devices for DBS of the subthalamic nucleus (STN) were implanted. Among those who also had RLS, follow-up showed substantial reduction in RLS symptoms and benefit on RLS impact.

"This is the first observation on 22 patients, which is the largest number so far, that RLS symptoms are improving, and improvement is sustained up to 2 years despite significant decrease of dopaminergic treatment," Olga Klepitskaya, MD, associate professor of neurology at the University of Colorado Denver Anschutz Medical Campus in Aurora, told Medscape Medical News.

 
RLS symptoms are improving, and improvement is sustained up to two years despite significant decrease of dopaminergic treatment. Dr Olga Klepitskaya
 

The results were reported here at the 19th International Congress of Parkinson's Disease and Movement Disorders (MDS).

RLS occurs in up to 50% of patients with PD and often responds well to dopaminergic therapy. DBS is an effective therapy for dopamine-responsive PD symptoms, so it is reasonable to think that RLS may respond to DBS.

However, studies have been inconclusive with variable effects, including improvement in or emergence of RLS after STN DBS. There has also been moderate improvement or no effect after DBS of other basal ganglia areas for various other movement disorders.

In the current study, all patients at this institution undergoing STN DBS surgery for PD between 2008 and 2013 filled out questionnaires about several conditions, including RLS and RLS quality of life preoperatively and out to 2 years after surgery. The study involved patients with moderate to severe RLS (International RLS Study Group rating scale [IRLS] sum scores >10).

In this study of 12 women and 10 men, patients had a mean age of 58.3 years and a baseline mean IRLS sum score of 19.59±6.95.

Effect Evident by 6 Months

At 6 months, the IRLS sum score diminished by 5.06 and further diminished slightly by 2 years.

Other RLS scores also reflected persistent benefit of the DBS out to 2 years. Quality-of-life scores trended toward benefit but were not significantly different from baseline.

Table. Effect of DBS on Mean RLS Scores

Time Point IRLS Sum Score
IRLS Severity Score IRLS Impact Score RLS Quality-of-Life Score
Baseline (n = 22) 19.59±6.95 12.91±4.33 4.45±2.72 68.29±20.26
2 y (n = 10) 12.83±11.26 8.12±7.17 3.5±3.47 78.78±22.15
Difference from baselinea –7.80 (P = .0109) –5.43 (P = .0041) –1.20 (P < .001) 4.31 (P = .3627)

aDifference between baseline and averaged postoperative scores.

 

The baseline levodopa equivalent mean dosage was 1203 mg; this decreased to 371 at 6 months but began to rise by year 1 and year 2 (500 mg and 788 mg, respectively).

Fifty percent of the patients responded to DBS with a greater than 50% reduction in IRLS sum scores. Similarly, 50% of patients achieved IRLS scores of 10 or less, considered to be in the mild range. About one quarter of patients had complete remission (IRLS score of 0).

Dr Klepitskaya commented that these findings indicate that STN DBS may be effective in the treatment of RLS and open the door to further studies. "Idiopathic RLS can be very severe and affect patients' quality of life — affect their sleep, their depression, [and] cognitive deficits," she said.

Some RLS is resistant to drugs, and she noted that augmentation can occur: When treatment is increased, RLS symptoms can occur earlier in the day and get more severe. "So in these patients with severe RLS and augmentation, DBS might be a possible treatment in the future," she postulated.

Angus MacLeod, MBChB, from the University of Aberdeen in Scotland, commented to Medscape Medical News that the study looked interesting to him, with meaningful changes in RLS symptom scores, but he questioned how much was placebo effect.

"I appreciate measurements out to 2 years are going to have less of a placebo effect for sure, but you need a randomized, controlled trial before you can be more definite about it," he advised.

Dr. Klepitskaya replied that a placebo group — such as delaying the DBS once implanted — would be unethical because patients were having surgery and expecting the treatment to improve their PD symptoms, not their RLS. And furthermore, the influence of any placebo effect is diminished by the fact that the patients did not expect any benefit in terms of their RLS.

Dr MacLeod suggested enlisting a group of patients with RLS but no PD, in which case a randomized, controlled trial with a delayed-start placebo group would be appropriate and ethical. Dr Klepitskaya agreed, saying that her present study suggests performing a pilot trial with patients with idiopathic RLS, not secondary to PD.

Dr MacLeod predicted that it should not be too difficult to recruit patients with "desperately severe restless leg syndrome who would do anything to get relief."

A looming question is whether idiopathic RLS is the same as RLS in PD. Dr Klepitskaya says she has an idea to look at outcomes of RLS in other, non-PD conditions for which DBS is used, including essential tremor, dystonia, and neuropsychiatric disorders (such as obsessive-compulsive disorder and depression). In contrast to PD, RLS should not be more prevalent in these patients. Such an investigation may shed light on the nature of idiopathic RLS and RLS in PD as well as response to therapy in these and other settings.

Other remaining questions are the most efficacious targets for DBS to treat RLS; the effect of DBS on various degrees of RLS, including severe and intractable RLS; and on RLS with various underlying primary causes.

There was no commercial funding for the study. Dr Klepitskaya and Dr MacLeod have disclosed no relevant financial relationships.

19th International Congress of Parkinson's Disease and Movement Disorders (MDS). Abstract 1245. Presented June 18, 2015.

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