Accuracy of acute levodopa challenge for clinical prediction of sustained long‐term levodopa response as a major criterion for idiopathic Parkinson's disease diagnosis

Abstract

Clinical idiopathic Parkinson's disease (PD) diagnosis requires following strict clinical criteria. Final definitive diagnosis can only be made after pathological confirmation and, despite following clinical criteria, several cases are misdiagnosed. We assessed sensitivity and specificity of acute challenge with levodopa (L-dopa) to predict sustained long-term L-dopa responsiveness as a major criterion for clinical diagnosis of PD. A consecutive series of 82 patients first seen at a movement disorders clinic with a parkinsonian syndrome without specific diagnosis was included. A second examiner, blind to the presumptive diagnosis, performed in each patient an acute challenge with 250/50 mg of L-dopa-carbidopa and rated the test as positive or negative according to whether values reached a minimal 30% of improvement on UPDRS scores. Positive tests were considered supportive of presumptive clinical diagnosis of Parkinson's disease. Blind to test results and according to clinical presumption, the first examiner started patient treatment with the necessary L-dopa dose or, alternatively, until reaching 1 g for 1 month in those who failed to display a positive test response. At 24 month follow-up, they were re-tested with 1 g for 1 month when required. At this point, clinical criteria of the U.K. Parkinson's Disease Society Brain Bank were applied and definitive clinical diagnosis of PD was made. Sensitivity, specificity, and positive predictive ratio for acute challenge were calculated. Overall sensitivity and specificity of acute L-dopa challenge to predict clinical diagnosis of PD was 70.9% and 81.4%, respectively; positive predictive ratio was 88.6%. When patients were divided into three groups according to their UPDRS motor section score at initial examination, sensitivity and specificity varied: Group I (<or= 10), 71.4% and 100%; Group II (11-20), 75% and 75%; and Group III (>or=21), 36.4% and 87%, respectively. Positive predictive ratio increased to 100% in Group I and to 87.5% in Group III. The positive result of initial acute L-dopa challenge predicts chronic L-dopa responsiveness as major criterion of PD in all patients with UPDRS motor scores lower than 10.

Clinical correlates of levodopa-induced dopamine release in Parkinson disease

“…1 In the early stages of the disease, responses to an acute LD challenge reflect chronic LD responsiveness. Moreover, serial LD challenges performed at different stages of disease have helped clarify how the pharmacologic response to LD evolves over the time.…”

INPH and Parkinson disease: differentiation by levodopa response

“…24 Furthermore, a study of 82 patients, in which the examiner conducting the levodopa chal lenge was blind to the original diagnosis, revealed that the levodopa challenge test had 70.9% sensitivity and 81.4% specificity for predicting a clinical diagnosis of PD. 25 The same study also showed that the specificity of the levodopa test for predicting a clinical diagnosis of PD at early stages of the disease was 100%. 25 The levodopa challenge test is non invasive, costeffective, and easy to administer; tablets of carbidopa-levodopa are taken orally and motor symptoms are scored using the Unified Parkinson's Disease Rating Scale (UPDRS).…”

“…25 The same study also showed that the specificity of the levodopa test for predicting a clinical diagnosis of PD at early stages of the disease was 100%. 25 The levodopa challenge test is non invasive, costeffective, and easy to administer; tablets of carbidopa-levodopa are taken orally and motor symptoms are scored using the Unified Parkinson's Disease Rating Scale (UPDRS). These scores are compared with UPDRS scores obtained before levodopa treatmentpractitioners typically expect a 30% improve ment in PD motor sy mptoms.…”

“…perspeCtives NATURE REvIEWS | neurOlOgy vOLUmE 6 | JANUARY 2010 | 55 publications have highlighted its useful ness as a diagnostic test for PD. 24,25 Hughes et al have reported that a positive response to levodopa medication-attenuation of parkin sonian symptoms-accurately pre dicted longterm responsiveness to therapy. 24 Furthermore, a study of 82 patients, in which the examiner conducting the levodopa chal lenge was blind to the original diagnosis, revealed that the levodopa challenge test had 70.9% sensitivity and 81.4% specificity for predicting a clinical diagnosis of PD.…”

Diffusion Tensor Imaging in Idiopathic Parkinson's Disease and Multisystem Atrophy (Parkinsonian Type)

“…Paraclinical tests like drug response testing and neurophysiological examinations are routinely employed, but are of limited sensitivity and specificity [3]. Single photon emission tomography and positron emission tomography visualize deficits in central neurotransmission pathways, but lack sufficient specificity and sensitivity to differentiate between PD and AP [4].…”