title: The hidden sister of motor fluctuations in Parkinson's disease: A review on nonmotor fluctuations.
abstract: Only a few years after the introduction of levodopa, the first descriptions of motor fluctuations and dyskinesia related to dopaminergic therapy appeared. In PD, attention turned to their management, that had dampened the euphoria of the "levodopa miracle." It soon became clear that neuropsychiatric, autonomic, and sensory features also tend to develop fluctuations after chronic exposure to l-dopa. The diversity of fluctuating nonmotor symptoms, their largely subjective nature, coupled with a frequent lack of insight led to difficulties in identification and quantification. This may explain why, despite the high impact of nonmotor symptoms on patient autonomy and quality of life, evaluation of nonmotor fluctuations is not part of clinical routine. In view of the lack of specific validated assessment tools, detailed anamnesis should ideally be coupled with an evaluation in both ON and OFF drug conditions. The mechanisms of nonmotor fluctuations are not well understood. It is thought that they share dopaminergic presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms with the classical motor complications, but involve different neural pathways. Although symptoms fluctuate with dopaminergic treatment, serotonine and norepinephrine denervation, as well as interactions between neurotransmitter systems, probably contribute to their diversity. The lack of validated tools for assessment of these phenomena explains the almost complete absence of treatment studies. Management, largely resulting from expert opinion, includes psychiatric follow-up, nondopaminergic drugs, and advanced dopaminergic treatment, including drug delivery pumps and DBS. This review aims to provide a starting point for the understanding, diagnosis, and management of nonmotor fluctuations. © 2016 International Parkinson and Movement Disorder Society.
authors.affiliation: CINAC-Hospital Universitario HM Puerta del Sur, CEU-San Pablo University, Madrid, Spain.
authors.forename: Raul
authors.initials: R
authors.lastname: Martínez-Fernández
authors.affiliation: Movement Disorders Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Université de Grenoble Alpes and Grenoble Institut des Neurosciences, INSERM U386, Grenoble, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Schmitt
authors.affiliation: National Center of Epidemiology, Carlos III Institute of Health and CIBERNED, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Martin
authors.affiliation: Neurology Division, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Krack
mesh_terms: D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D001523:Mental Disorders / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D010300:Parkinson Disease / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D012678:Sensation Disorders / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D012893:Sleep Wake Disorders / Q000209:etiology / Q000503:physiopathology / Q000628:therapy
keywords: Parkinson's disease; dopamine; nonmotor fluctuations; nonmotor symptoms