S1548 GI Dysmotility Symptoms Are Not Associated With Increased L-Dopa Requirements in Parkinson’s Disease Patients

Abstract

Introduction: Gastrointestinal (GI) motility disorders like gastroparesis or small bowel bacterial overgrowth are thought to impair efficacy of L-dopa, which is absorbed in the proximal small intestine, resulting in motor fluctuations among Parkinson’s Disease (PD) patients that prompt dosage increases. While symptoms of dysmotility are frequently reported in PD, results are mixed concerning their effect, if any, on L-dopa pharmacokinetics. In this study, we compare L-dopa equivalent daily dose (LEDD) and motor function among patient with 5 upper GI symptoms to study the possible relationship between dysmotility symptoms and increased L-dopa requirement. Methods: Two hundred PD patients evaluated by outpatient neurology at Mass General Brigham Healthcare between 2018-2019 were included. History of 5 upper GI symptoms (dysphagia, nausea, vomiting, epigastric pain, and bloating), as well as LEDD were obtained from the medical record. Unified PD Rating Scale (UDPRS) part III motor exam scores off medication were extracted from clinical notes. Differences between LEDD and UDPRS motor scores among patients with and without a history of each of the 5 GI symptoms were calculated via Student t-tests. Results: Dysphagia was significantly associated with increased LEDD (230mg, P=0.0067) as well as increased motor severity (4.6 UDPRS, P=0.036). In contrast, nausea was associated with decreased LEDD (-187 mg, P=0.030) despite similar motor severity (1.1 UDPRS, P=0.63) to those without nausea (Table). There were no differences in LEDD and UDPRS scores among patients with and without vomiting, epigastric pain, and bloating. Conclusion: Except dysphagia, we found that GI dysmotility symptoms were not associated with increased LEDD nor increased motor severity. This suggests that symptomatic GI dysmotility may not be directly related to poor L-dopa absorption, a common clinical question for PD patients referred to GI. While dysphagia was linked with higher LEDD, this may have stemmed from higher UDPRS scores in this population. Interestingly, those with nausea required lower LEDD despite comparable motor severity. Nausea, a frequent symptom of delayed intestinal transit, may extend absorption time leading to better motor outcomes on less L-dopa. However, further studies are needed to discern any underlying mechanism. Our results nonetheless indicate that clinical management of dysmotility may not reduce motor fluctuations and the need for increased L-dopa as previously presumed. Table 1. - Changes in L-dopa Requirements and Motor Severity in the Presence of Dysmotility Symptoms GI Symptom ΔLEDD, mg (SD) P value ΔUDPRS III (SD) P value Nausea -187 (86) 0.03 1 (2) 0.633 Vomiting 11 (95) 0.91 -2 (2) 0.343 Dysphagia 230 (84) 0.007 5 (2) 0.036 Epigastric pain 101 (104) 0.33 0 (3) 0.881 Bloating 62 (99) 0.533 1 (2) 0.764 LEDD—L-dopa equivalent daily dose UDPRS—Unified Parkinson's Disease Rating Scale.