Pathophysiology of Motor Dysfunction in Parkinson’s Disease as the Rationale for Drug Treatment and Rehabilitation

Abstract

Cardinal motor features of Parkinson's disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation. Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways. Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment. The present review will focus on classical notions and recent insights into the neuropathology, neuropharmacology, and neurophysiology of motor dysfunction of PD. These pieces of information represent the basis for the pharmacological, neurosurgical, and rehabilitative approaches to PD.

A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond

“…So far, review articles tend to treat motor network‐focused studies (Burciu & Vaillancourt, ; Magrinelli et al, ) and whole‐brain studies (Cozac et al, ) separately. Although some efforts have been made to relate findings from motor networks to nonmotor symptoms (Oswal, Brown, & Litvak, ), it is unknown to what extent findings from motor networks and whole‐brain networks can be compared and if so, which similarities and discrepancies are present.…”

“…The source-level approach can resolve some of these ambiguities and enables interpretation of the functional results in an anatomical context (Baillet, Mosher, & Leahy, 2001;Brookes et al, 2007;Hillebrand, Barnes, Bosboom, Berendse, & Stam, 2012;Hillebrand, Singh, Holliday, Furlong, & Barnes, 2005;Schoffelen & Gross, 2009). So far, review articles tend to treat motor network-focused studies (Burciu & Vaillancourt, 2018;Magrinelli et al, 2016) and wholebrain studies separately. Although some efforts have been made to relate findings from motor networks to nonmotor symptoms (Oswal, Brown, & Litvak, 2013b), it is unknown to what extent findings from motor networks and whole-brain networks can be compared and if so, which similarities and discrepancies are present.…”

Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine

“…Parkinson's disease is characterized by progressive damage to dopaminergic neurons in the substantia nigra; bradykinesia and other extrapyramidal signs are the major features of the disease [1][2][3]. Age is the largest risk factor for the development of parkinsonism [4]; alternatively, tobacco smoking decreases the incidence of the illness [5].…”

Neuromagnetic investigations of mechanisms and effects of STN-DBS and medication in Parkinson's disease

“…The pathophysiology of each of the PD motor symptoms is still debatable (Berardelli et al, 2001;Rodriguez-Oroz et al, 2009;Magrinelli et al, 2016). Akinesia is thought to be a disorder related to failure of timing mechanisms in the basal ganglia circuitry.…”

“…Akinesia is thought to be a disorder related to failure of timing mechanisms in the basal ganglia circuitry. Since dopamine plays an important role in central pattern generators, loss of the neurotransmitter may lead to timing problems (Buhusi and Meck, 2005;Yuste et al, 2005;Magrinelli et al, 2016). Self-paced movements show more marked pre-movement abnormalities than externally paced ones, again suggesting timing mechanisms as a potential root cause (Jahanshahi et al, 1995;Berardelli et al, 2001;Buhusi and Meck, 2005).…”