Benefit from jejunal levodopa in a patient with apomorphine pump

Abstract

Swings of the bioavailability of orally administered levodopa are considered an important factor of motor fluctuations in Parkinson’s disease (PD) [1]. In this regard, a pump system for continuous jejunal levodopa infusion (Duodopa ) has been introduced in some countries for patients with PD who suffer from troublesome motor fluctuations [2–4]. Since systematic comparisons with deep brain stimulation (DBS) or continuous apomorphine are not available, opinions on how this treatment relates to therapeutic alternatives rely on the observation of case histories for the time being [3, 5–7]. In this regard, we consider of note the therapeutic gain of Duodopa in a patient who had been successfully treated with an Apomorphine pump for years but finally redeveloped extremely severe and unpredictable off-states. Our patient was 60 years of age and noticed first hypokinetic symptoms 20 years ago. Therapy with levodopa was started in 1994, ever since in different combinations with dopamine receptor agonists, amantadine, selegiline and acetylcholine antagonists. Already, in 1999 he underwent surgery for subthalamic DBS for increasing wearing-off and dyskinetic symptoms, but postoperatively developed a brain abscess from the left DBS-electrode, which consequently was removed. He fully recovered from this complication, but did not further pursue DBS. Instead, medication of oral drugs together with apomorphine was started, first given as subcutaneous ‘rescue’ injections (APO-go ) for intermittent akinetic periods. Since off-states became, however, increasingly frequent and prolonged, apomorphine was administered continuously via pump since 2003, effectively stabilizing the patient’s condition with off-time reduction to tolerable levels. Under this therapy further dopaminergic drugs could be reduced by about fifty percent, but comedication remained necessary. With disease progression the initial delivery of apomorphine during 16 h waking time had to be raised to 24 h with a final dosage of 200 mg/day to effectively suppress unpredictable and sudden off-states. Nonetheless, in 2008 he began to suffer from Yo-Yoing with dystonic and tremulous next to hypokinetic symptoms, alternating with strongly hyperkinetic on-periods, both progressive in duration, frequency and severity. At last, he intermittently was completely akinetic (with literally maximal UPDRS motor score). Such off-states did no longer respond to rescue injections of apomorphine or to other drugs in a predictable manner, occurred within minutes five to ten times per day, altogether covering some 10 h. Consequently, he was predominantly bedridden, but still experienced short good or hyperkinetic movement states. In this situation jejunal levodopa infusion was started as substitution of 200 mg apomorphine, 800 mg levodopa (plus 200 mg benserazide), 800 mg entacapone, 2.8 mg pramipexole and 400 mg amantadine sulphate per day (earlier on, levodopa was taken up to ten times daily; reduction to four times was tried under the idea that dyskinesias might partly have been biphasic so that lowering intake frequency would have flattened fluctuations; however, this was not the case and occurrence of motor changes remained temporally random). Under 5,000 mg/24 h jejunal levodopa as monotherapy less severe hypokinetic episodes remained around cassette changes, cumulating about 60 min/day. Apart from this, the patient was constantly in a slightly hyperkinetic state (UPDRS motor score of 25), since even with minor dose reductions he F. Klostermann (&) C. Jugel F. Marzinzik Department of Neurology, CBF, Charite, University Medicine Berlin, Berlin, Germany e-mail: fabian.klostermann@charite.de