title: Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms.
abstract: A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
authors.affiliation: Department of Neurology, Clinica Universitaria and Medical School and Neuroscience, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Rodriguez-Oroz
authors.forename: Marjan
authors.initials: M
authors.lastname: Jahanshahi
authors.forename: Paul
authors.initials: P
authors.lastname: Krack
authors.forename: Irene
authors.initials: I
authors.lastname: Litvan
authors.forename: Raúl
authors.initials: R
authors.lastname: Macias
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.forename: José A
authors.initials: JA
authors.lastname: Obeso
mesh_terms: D000368:Aged; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D056344:Executive Function; D006801:Humans; D001523:Mental Disorders / Q000209:etiology / Q000523:psychology; D008875:Middle Aged; D008954:Models, Biological; D009068:Movement / Q000502:physiology; D009069:Movement Disorders / Q000503:physiopathology; D009123:Muscle Hypotonia / Q000209:etiology; D010300:Parkinson Disease / Q000175:diagnosis* / Q000503:physiopathology* / Q000523:psychology; D014202:Tremor / Q000209:etiology