Evolving Concepts on Bradykinesia

Matteo Bologna; Giulia Paparella; Alfonso Fasano; Mark Hallett; Alfredo Berardelli

Disclosures

Brain. 2020;143(3):727-750. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

Bradykinesia, which, as derived from the Greek, means slowness (brady-) of movement (kinesis), is one of the main motor symptoms of Parkinson's disease (Berardelli et al., 2001, 2013; Postuma et al., 2015; Berg et al., 2018) and it is also present in atypical parkinsonisms (McFarland and Hess, 2017). Bradykinesia is the 'palsy' part of the 'shaking palsy' as originally described by James Parkinson, who referred to this aspect as 'lessened muscular power' (Parkinson, 2002; Obeso et al., 2017). Although the term is apparently simple, and despite the widespread use of bradykinesia in clinical practice and scientific literature, several issues on bradykinesia are still under debate.

In some circumstances, the term bradykinesia is used to refer to a broad range of motor disturbances, and it is often used interchangeably with the terms hypokinesia, which means low amplitude movement, and akinesia, no movement at all (Schilder et al., 2017). Over the past few decades, bradykinesia in Parkinson's disease and atypical parkinsonism have been better characterized with the aid of neurophysiological measures, and a broad range of motor abnormalities have been described including the so-called sequence effect, i.e. amplitude and velocity decrement with repetitive and continuing movements. These studies indicate that the various bradykinesia features may vary considerably within and between different patients, in relation to several factors, including disease subtype and progression, dopaminergic medications and other interventions (Berardelli et al., 2001; Agostino et al., 2003; Espay et al., 2009, 2011; Kang et al., 2010; Bologna et al., 2016a, b; Hasan et al., 2017). Bradykinesia has been traditionally considered the consequence of a failure of basal ganglia output to the primary motor cortex (M1) (Albin et al., 1989; DeLong, 1990; Berardelli et al., 2001). More recent evidence based on direct basal ganglia recordings through deep brain stimulation (DBS) electrodes, as well as data from non-invasive brain stimulation and neuroimaging studies, have better defined the role of basal ganglia and indicated that other brain structures may be implicated in the pathophysiology of bradykinesia in Parkinson's disease, and these include the cerebellum. Moreover, altered mechanisms of sensorimotor integration may also play a role in the pathophysiology of bradykinesia. Insight into the pathophysiology of bradykinesia is relevant for understanding the therapeutic rationale of both pharmacological and non-pharmacological intervention in patients.

In the present paper, we will first discuss the issues of bradykinesia terminology and characterization in clinical and experimental studies in Parkinson's disease. We then focus on the pathophysiology of bradykinesia by discussing the role of basal ganglia and the possible involvement of alternative neural structures that provide further insight into a network perspective. Despite being less studied than in Parkinson's disease, clinical and experimental observations on bradykinesia in patients with atypical parkinsonisms will be also discussed. We emphasize how a better comprehension of the rationale and mechanisms of action of levodopa and other interventions (DBS) may help in understanding bradykinesia pathophysiology in Parkinson's disease and atypical parkinsonisms.

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