Bradykinesia is one of the cardinal motor symptoms of Parkinson’s disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the pathophysiological mechanisms underlying bradykinesia are, however, still unclear. In this article, we review clinical and experimental studies on bradykinesia performed in patients with Parkinson’s disease and atypical parkinsonism. We also review studies on animal experiments dealing with pathophysiological aspects of the parkinsonian state. In Parkinson’s disease, bradykinesia is characterized by slowness, the reduced amplitude of movement, and sequence effect. These features are also present in atypical parkinsonisms, but the sequence effect is not common. Levodopa therapy improves bradykinesia, but treatment variably affects the bradykinesia features and does not significantly modify the sequence effect. Findings from animal and patients demonstrate the role of the basal ganglia and other interconnected structures, such as the primary motor cortex and cerebellum, as well as the contribution of abnormal sensorimotor processing. Bradykinesia should be interpreted as arising from network dysfunction. A better understanding of bradykinesia pathophysiology will serve as the new starting point for clinical and experimental purposes.

The aim of this paper is to summarise the main clinical and pathophysiological features of facial bradykinesia in Parkinson's disease (PD) and in atypical parkinsonism. Clinical observation suggests that reduced spontaneous and emotional facial expressions are features of facial bradykinesia in PD and atypical parkinsonism. In atypical parkinsonism, facial bradykinesia is complicated by additional dystonic features. Experimental studies evaluating spontaneous and emotional facial movements demonstrate that PD is characterised by a reduction in spontaneous blinking and emotional facial expression. In PD, neurophysiological studies show that voluntary orofacial movements are smaller in amplitude and slower in velocity. In contrast, movements of the upper face (eg, voluntary blinking) are normal in terms of velocity and amplitude but impaired in terms of switching between the closing and opening phases. In progressive supranuclear palsy (PSP), voluntary blinking is not only characterised by a severely impaired switching between the closing and opening phases of voluntary blinking, but is also slow in comparison with PD. In conclusion, in PD, facial bradykinesia reflects abnormalities of spontaneous, emotional and voluntary facial movements. In PSP, spontaneous and voluntary facial movements are abnormal but experimental studies on emotional facial movements are lacking. Data on facial bradykinesia in other atypical parkinsonism diseases, including multiple system atrophy and corticobasal degeneration, are limited. In PD, facial bradykinesia is primarily mediated by basal ganglia dysfunction whereas in PSP, facial bradykinesia is a consequence of a widespread degeneration involving the basal ganglia, cortical and brainstem structures.

Many neurophysiological abnormalities have been described in the primary motor cortex of patients with Parkinson's disease. However, it is unclear whether there is any relationship between them and bradykinesia, one of the cardinal motor features of the condition. In the present study we aimed to investigate whether objective measures of bradykinesia in Parkinson's disease have any relationship with neurophysiological measures in primary motor cortex as assessed by means of transcranial magnetic stimulation techniques. Twenty-two patients with Parkinson's disease and 18 healthy subjects were enrolled. Objective measurements of repetitive finger tapping (amplitude, speed and decrement) were obtained using a motion analysis system. The excitability of primary motor cortex was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and facilitation. Plasticity-like mechanisms in primary motor cortex were indexed according to the amplitude changes in motor-evoked potentials after the paired associative stimulation protocol. Patients were assessed in two sessions, i.e. OFF and ON medication. A canonical correlation analysis was used to test for relationships between the kinematic and neurophysiological variables. Patients with Parkinson's disease tapped more slowly and with smaller amplitude than normal, and displayed decrement as tapping progressed. They also had steeper input/output curves, reduced short-interval intracortical inhibition and a reduced response to the paired associative stimulation protocol. Within the patient group, bradykinesia features correlated with the slope of the input/output curve and the after-effects of the paired associative stimulation protocol. Although dopaminergic therapy improved movement kinematics as well as neurophysiological measures, there was no relationship between them. In conclusion, neurophysiological changes in primary motor cortex relate to bradykinesia in patients with Parkinson's disease, although other mechanisms sensitive to dopamine levels must also play a role.

Objective: Compensatory reorganization of the nigrostriatal system is thought to delay the onset of symptoms in early Parkinson disease (PD). Here we sought evidence that compensation may be a part of a more widespread functional reorganization in sensorimotor networks, including primary motor cortex. Methods:Several neurophysiologic measures known to be abnormal in the motor cortex (M1) of patients with advanced PD were tested on the more and less affected side of 16 newly diagnosed and drug-naive patients with PD and compared with 16 age-matched healthy participants. LTP-like effects were probed using a paired associative stimulation protocol. We also measured short interval intracortical inhibition, intracortical facilitation, cortical silent period, and input/output curves. Results:The less affected side in patients with PD had preserved intracortical inhibition and a larger response to the plasticity protocol compared to healthy participants. On the more affected side, there was no response to the plasticity protocol and inhibition was reduced. There was no difference in input/output curves between sides or between patients with PD and healthy participants. Conclusions:Increased motor cortical plasticity on the less affected side is consistent with a functional reorganization of sensorimotor cortex and may represent a compensatory change that contributes to delaying onset of clinical symptoms. Alternatively, it may reflect a maladaptive plasticity that provokes symptom onset. Plasticity deteriorates as the symptoms progress, as seen on the more affected side. The rate of change in paired associative stimulation response over time could be developed into a surrogate marker of disease progression in PD. Neurology ® 2012;78:1441-1448 GLOSSARY ADM ϭ abductor digiti minimi; AMT ϭ active motor threshold; APB ϭ abductor pollicis brevis; CS ϭ conditioning stimulus; CSP ϭ cortical silent period; DaT ϭ dopamine transporter; I/O ϭ input/output; ICF ϭ intracortical facilitation; ISI ϭ interstimulus interval; LTP ϭ long-term potentiation; MEP ϭ motor evoked potential; PAS ϭ paired associative stimulation; PD ϭ Parkinson disease; RMT ϭ resting motor threshold; SICI ϭ short-latency intracortical inhibition; TMS ϭ transcranial magnetic stimulation; UPDRS ϭ Unified Parkinson's Disease Rating Scale.Motor signs in Parkinson disease (PD) appear when striatal dopamine is depleted beyond a critical threshold of ϳ60%-80%.1 Neuropathologic and neuroimaging evidence suggests that presynaptic and synaptic changes in the nigrostriatal system compensate for dopamine deficiency.1-6 Indeed, given the extent of preclinical dopaminergic denervation, 7 it is conceivable that compensatory changes extend also beyond the nigrostriatal portion of the motor circuit.Patients with clinically asymmetric PD represent a valuable model to study compensatory reorganization within the motor system since functional changes that prevent motor symptom progression are likely to be more evident on the less affected side. A previous [ 18 F]-fluorodeo...