title: Pharmacodynamics of a low subacute levodopa dose helps distinguish between multiple system atrophy with predominant Parkinsonism and Parkinson's disease.
abstract: The differential diagnosis between multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) may be challenging at disease onset. Levodopa responsiveness helps distinguish the two groups, but studies evaluating this issue using objective standardized tests are scanty. We retrospectively examined the extent of levodopa response by an objective kinetic-dynamic test in a series of patients prospectively followed up for a parkinsonian syndrome and eventually diagnosed as MSA-P or PD. Sixteen MSA-P and 31 PD patients under chronic levodopa therapy received a first morning fasting dose of levodopa/benserazide (100/25 mg) or levodopa/carbidopa (125/12.5 or 100/25 mg) and underwent simultaneous serial assessments of plasma levodopa concentration and alternate finger tapping frequency up to 3 h post dosing. The main levodopa pharmacodynamic variables were the maximum percentage increase in tapping frequency over baseline values (ΔTapmax %) and the area under the tapping effect-time curve (AUCTap). Levodopa pharmacokinetics did not show significant differences between MSA-P and PD, whereas both the magnitude and overall extent of levodopa tapping effect were markedly reduced in the MSA-P group (p < 0.001). The combined use of specific cut-off values for both the main pharmacodynamic variables, ΔTapmax % <20% and AUCTap <1900 [(tapping/min)·min], correctly discriminated 15 out of 16 MSA-P patients from PD patients. A combined estimation of these pharmacodynamic variables after a subacute low levodopa dose may be a simple and practical clinical tool to aid the differential diagnosis between MSA-P and PD.
authors.affiliation: IRCCS, Institute of Neurological Sciences of Bologna, c/o Padiglione G, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Calandra-Buonaura
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
authors.affiliation: IRCCS, Institute of Neurological Sciences of Bologna, c/o Padiglione G, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lopane
authors.affiliation: Neurology Outpatient Clinic, Department of Primary Care, Modena Local Health Authority, Modena, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Guaraldi
authors.affiliation: IRCCS, Institute of Neurological Sciences of Bologna, c/o Padiglione G, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Martinelli
authors.affiliation: IRCCS, Institute of Neurological Sciences of Bologna, c/o Padiglione G, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy. pietro.cortelli@unibo.it.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy. pietro.cortelli@unibo.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.affiliation: IRCCS, Institute of Neurological Sciences of Bologna, c/o Padiglione G, Ospedale Bellaria, Via Altura 3, 40139, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Contin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001545:Benserazide / Q000493:pharmacokinetics; D003937:Diagnosis, Differential; D015259:Dopamine Agents / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D019578:Multiple System Atrophy / Q000175:diagnosis*; D010300:Parkinson Disease / Q000175:diagnosis*; D012189:Retrospective Studies
chemical_list: D015259:Dopamine Agents; D004338:Drug Combinations; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide
keywords: Levodopa; Multiple system atrophy; Parkinson’s disease; Pharmacodynamic monitoring