Daniel M. Keller, PhD

June 24, 2016

BERLIN — Patients with restless legs syndrome (RLS) for whom conventional therapies are contraindicated may benefit from a treatment usually reserved for patients with advanced Parkinson's disease and augmentation phenomena, a case report suggests.

In a presentation here at the 20th International Conference of Parkinson's Disease and Movement Disorders, Jesús Pérez-Pérez, MD, of the Movement Disorders Unit at the Hospital de la Santa Creu i Sant Pau, in Barcelona, Spain, described the case of a 70-year-old man who had experienced RLS with augmentation for 3 years. The patient was successfully treated using a 24-hour infusion of carbidopa/levodopa enteral gel (Duopa, AbbVie Inc).

His condition had initially responded well to dopaminergic medication, but after 1 year of therapy with dopaminergic drugs, augmentation began, and RLS was present all day and was worse at night. Augmentation is a phenomenon of worsening symptoms after dopaminergic drug exposure.

The patient had severe, chronic obstructive pulmonary disease and had undergone several hospitalizations in less than a year because of respiratory decompensation. For these reasons, drugs such as benzodiazepines, opioids, gabapentin (multiple brands), and pregabalin (Lyrica, PF Prism CV) were contraindicated. Because of RLS, the patient was unable to use nocturnal continuous positive airway pressure, which led to hypercapnic respiratory failure.

The treating physicians then offered, and the patient accepted, 24-hour constant infusion with carbidopa/levodopa enteral gel delivered by pump directly into the small intestine through a tube with a jejunal extension introduced percutaneously into the stomach. Because of the continuous drug delivery, this system avoids the pulsatile dosing effect that leads to augmentation.

Three months after starting therapy with the enteral gel formulation, the patient's RLS symptoms were greatly improved, as was his quality of life, Dr Pérez-Pérez reported.

Table. Results of Switching Patient From Oral to Enteral Infusion Medication

Intervention/Period RLS Rating Scale Score RLS Quality-of-Life Questionnaire
Oral/preintervention* 36 (very severe) 22
Enteric gel at 3 months 9 (mild) 74
Enteric gel at 1 year 4 (mild) 100

*Levodopa/carbidopa 150 mg 5x/day plus levodopa/carbidopa retard 200 mg at night.

 

Symptoms and quality-of-life scores continued to improve during the first year of treatment, as reflected in Clinical Global Impression–Improvement scale scores.

The patient has not experienced any adverse effects or complications from the medication or the implantation procedure and was hospitalized only once during the year.

Olga Klepitskaya, MD, associate professor of neurology at the University of Colorado, in Denver, who has a special interest in the use of deep brain stimulation to treat RLS, commented to Medscape Medical News that although the presentation involved a single case report, it was well done and is important. "They described very well why they did [it] and what they did and what are the implications of that," she said.

"Just like in Parkinson's disease, with RLS...pulsatile dopaminergic stimulation is not healthy for our dopamine receptors in the brain, and that's why it causes all these problems of augmentation," she said. The mainstream treatment of augmentation is to use longer-acting dopaminergic medications, such as rotigotine transdermal patches (Neupro, UCB Pharma, Inc), longer-acting pramipexole (Miraprex ER, Boehringer Ingelheim Pharmaceuticals, Inc), and ropinirole (Requip XL, GlaxoSmithKline).

The treatments that provide constant dopaminergic stimulation are better physiologically for the brain, "and Duopa is the ultimate long-acting medication," she said. "It's administered through the GI system, and I assume it can be used for very, very severe RLS with augmentation that cannot be treated by anything else."

Calling delivery of the medication through a percutaneous indwelling tube "a little bit extreme," she said the authors "really justified why they used this...for this particular patient, because he had a lot of comorbidities that can [lead to] a lot of side effects."

For this patient, the choice of this continuous but somewhat invasive treatment, which led to significant improvement in quality of life, appeared correct, she said.

Dr Klepitskaya said she believes that treatments that provide continuous stimulation ― whether pharmacologic or electrical ― would be best.

"That's why I have put my hopes in my study, deep brain stimulation for RLS,” she said, "and deep brain stimulation and Duopa now can be not completely interchangeable, but we are considering both as treatments available in the United States in patients with very advanced Parkinson's disease and trying to find which of those treatments will fit that particular patient profile the best."

The current case report and other reports on the use of deep brain stimulation suggest that difficult-to-treat RLS may be amendable to these treatments as well.

Dr Pérez-Pérez and Dr Klepitskaya have disclsoed no relevant financial relationships.

20th International Conference of Parkinson’s Disease and Movement Disorders: Abstract 953. Presented June 21, 2016.

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