Treatment of restless legs syndrome with subcutaneous apomorphine in a patient with short bowel syndrome

Abstract

Sirs: The Restless Legs Syndrome (RLS) is characterised by dysaesthesia of the legs associated with an urge to move which occurs exclusively at rest and can be ameliorated by walking [2, 8]. There are primary and secondary forms of RLS. Primary RLS is often familial and the genetics of familial RLS are currently a topic of intense research. Secondary RLS may be drug-induced, e. g. due to antipsychotic or antiemetic treatment with dopamine antagonists. The aetiology of secondary RLS furthermore includes iron deficiency and uraemia as its two most common causes (for review, see Allen and Earley [1]). Therefore, patients with uraemia and renal anaemia due to terminal renal failure are particularly prone to develop secondary RLS. There are various treatment options: in secondary RLS, the underlying pathology should be identified and treated. This includes substitution of iron for iron deficiency anaemia and treatment of uraemia and uraemic anaemia in chronic renal failure with drugs, haemodialysis and ultimately renal transplantation. If causal treatment does not prove sufficient, there is a wide range of agents for symptomatic treatment, most of which require oral administration. These include levodopa, dopamine agonists, opioids, benzodiazepines, gabapentin and some other antiepileptic drugs [4, 5]. We report a 38-year old female patient with terminal renal failure and short bowel syndrome, who was admitted to our neurological clinic with an uncontrollable exacerbation of uraemic RLS. The past medical history of the patient included polycystic kidneys resulting in chronic renal failure with uraemia and renal anaemia, as well as familial polyposis coli, which had led to a total colectomy and a subtotal resection of the small intestine due to postoperative adhesions. She also suffered from severe malabsorption and therefore required chronic total parenteral nutrition via a venous port system. The patient first developed symptoms of RLS in 2001 when she became uraemic. Chronic haemodialysis treatment had to be started in 2002 but did not have a marked effect on her RLS symptoms. Concomitant treatment with erythropoietin was introduced in 2002 and the dose was consequently increased up to 4000 IU three times a week. This treatment regime led to normalisation of red blood cell count but RLS symptoms persisted and gradually became more severe. Therefore, additional symptomatic RLS treatment was initiated. Oral dosage with 300/ 75 mg levodopa/benserazide, 2.5 mg lorazepam, and up to 20 mg diazepam did not have any effect on the RLS symptoms and it was concluded that the patient did not benefit from this oral medication owing to her short bowel syndrome with malabsorption. Transdermally applied fentanyl at an initial dose of 25μg/h (Durogesic® patch) led to a marked reduction of symptoms. However, the therapeutic effect wore off in the course of several months and necessitated a dose increase of up to 150 μg/h and eventually no longer sufficiently controlled symptoms. The patient then suffered from severe sleep disturbances and difficulty in enduring haemodialysis. Therefore, subcutaneous injections of up to 30 mg of the opioid pirtramid were given additionally on demand. As symptoms became worse, in spite of high-dose opioid therapy, we decided to introduce subcutaneous injections of the potent dopamine-D1/D2 receptor agonist apomorphine. The initial dose of 0.5 mg did not have a sufficient therapeutic effect but led to nausea and vomiting. Antiemetic co-medication with 60 mg of oral domperidone solution consequently controlled the nausea. We then increased the dose of apomorphine to 1 mg, which controlled RLS symptoms sufficiently when applied at night time and additionally before each haemodialysis. The efficacy of apomorphine was reflected by a decrease of the severity score on the International Restless Legs Syndrome Rating Scale (IRLSRS [7]) from 37 points (i. e. very severe symptoms) to 20 points (i. e. moderate symptoms) and the patient felt very much relieved because she was now able to endure lying still for the haemodialysis procedure. She was trained in subcutaneous self-administration of apomorphine in order to minimise dependency on health care professionals. She also tolerated a reduction of fentanyl patches to 100 μg/h and a reduction of the dose and frequency of pirtramid injections (maximum daily dose now 15 mg) at discharge from hospital. Several days later, the patient presented again to our outpatients department with a severe relapse of symptoms. The history revealed that there had been a change in LETTER TO THE EDITORS