Enteral Levodopa Therapy in Advanced Parkinson's Disease with Gastroparesis

Levodopa is almost completely (~98%) absorbed in the distal part of the duodenum and the proximal jejunum.1 In advanced Parkinson's disease (PD), transit of l-dopa from the stomach to the duodenum is erratic with delayed gastric emptying time, leading to fluctuations.2 By administering l-dopa directly into the proximal small intestine, the influence of gastric emptying rate can be negated. A 37-year-old right-handed woman developed a right-hand rest tremor in 2010. One year later, she noticed similar symptoms in her right foot with slowness of gait, micrographia, hypophonia, and masked facies. She was aware of anosmia for 1 year and constipation for 6 years before onset of tremor. There was no history of head injury, exposure to toxins, or psychiatric medications. Family history was negative. When first observed in the movement disorders clinic in 2011, Mini–Mental State Examination was 30/30. Cranial nerve examination was normal outside of masked facies. She demonstrated rigidity, bradykinesia, and resting tremor on the right side. Gait was bradykinetic with impaired postural reflexes. MRI brain was normal. Workup for Wilson's disease and secondary parkinsonian disorders were negative. She satisfied diagnostic criteria for PD and was started on pramipexole with good response, but it was discontinued because of significant nausea and vomiting. She was then started on l-dopa/carbidopa, but could not tolerate it because of nausea. The l-dopa/benzaseride tablet combination resulted in a good response with minimal nausea. Owing to increasing wearing off with freezing episodes and akinesia, l-dopa/benzaseride 100/25 mg was increased to 1 capsule every 2 hours by 2014. However, each dose provided only 1 hour of benefit and she remained off for more than 50% of the day with significant off dystonia. She was tried on other dopamine agonists (ropinorole, rotigotine), but, again, could not tolerate them because of severe nausea. Domperidone was not effective in controlling the nausea. Gradually, she began complaining of worsening gastrointestinal symptoms with persistent nausea and vomiting. She was unable to consume both solids and liquids and started vomiting as soon as she took anything orally. There was further worsening of her parkinsonian symptoms with increasing fluctuations and orthostatic symptoms. She experienced 3 hours of peak-dose dyskinesia per day and was off for more than 75% duration while awake. Because the patient had intractable nausea and vomiting, nuclear medicine gastric emptying studies could not be performed. A presumptive diagnosis of gastroparesis was made based on symptoms and the absence of a structural abnormality in the gastrointestinal tract (abdominal X-ray, CT abdomen, and gastroscopy studies were normal). She was started on prucalopride 2 mg twice-daily as a prokinetic agent with some benefit. Because of persistent nausea, she underwent a trial of nasojejunal (NJ) tube placement and started on NJ feeds with good benefit. She was given l-dopa/benzaseride 100/25 every 2 hours 8 times a day through an NJ tube. l-dopa provided benefit within 15 minutes and she remained completely on for the next 2 hours until the next dose. She underwent percutaneous gastrojejunostomy feeding tube placement (G-J). After G-J tube placement, similar effectiveness of her medication was noted. She remains on G-J feeds and is currently taking her medications (l-dopa/benzaseride 100/25; 2 capsules every 2 hours) through a G-J tube. She remains on for essentially 100% of the time with no significant dyskinesia or fluctuations. We present a case of advanced PD disease with gastroparesis resulting in significant fluctuations, prolonged off time, and peak-dose dyskinesias. When she received the medications through the G-J tube, the medication began taking effect within 10 to 15 minutes, with sustained benefit. She remains on throughout the day with no side effects to l-dopa/benzaseride or nausea. The effect noted in our patient was similar to that observed in patients on l-dopa carbidopa intestinal gel (LCIG) therapy, wherein the medication is given at a continuous rate directly into the intestine. Studies have shown this method to be beneficial in advanced PD with improved effectiveness of l-dopa and a lesser severity of l-dopa-induced side effects.3-5 LCIG infusions provide stable l-dopa plasma levels with an increase in functional on time (~4.11 h/day), reduced off time (~4.04 h/day), and reduced motor fluctuations with no increase of dyskinesia.5 However, LCIG is expensive, not available in all countries, and not covered by all insurance plans. The only difference in our approach was that, instead of using a continuous infusion of l-dopa, the medication was given every 2 hours through a G-J tube. G-J tube placement is well documented as a modality for treatment of gastroparesis6. The management of gastroparesis includes dietary modification, nutritional support, pharmacological therapy, and optimizing any contributing factors. Promotility agents, such as domperidone, erythromycin, and prucalopride, are usually used. Enteral jejunal tube feeding is considered if oral feeding is not tolerated by the patient despite dietary modification and medical management. However, we were unable to find any reports in the literature where it has been used in patients with PD with an improved effectiveness of medications. This should be considered to be a reasonable alternative for patients with advanced PD. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique. A.V.: 1A, 1B, 1C, 3A, 3B A.L.: 1A, 1B, 1C, 3B O.S.: 1A, 1B, 1C, 3B Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest. Financial Disclosures for previous 12 months: A.L. is on the advisory board for AbbVie. O.S. has received research grants from the National Institutes of Health, Canadian Institutes of Health Research CIHR, AbbVie, and Adamas. She is on the advisory board for AbbVie and receives honoraria from UpToDate. She is the Toupin Research Chair of Neurology, University of Alberta (Edmonton, Alberta, Canada).

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