Evolving Concepts on Bradykinesia

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

Disclosures

Brain. 2020;143(3):727-750. 

In This Article

Bradykinesia: Terminology and Clinical Aspects

Terminology

In Parkinson's disease, Barbeau et al. (1981) proposed the terms bradykinesia, hypokinesia and akinesia, respectively, to indicate the increasing degree of motor impairment. Others considered instead bradykinesia as synonymous of the slowness of voluntary movement and akinesia as a delay/failure of the willed movement to occur. Subsequently, the term bradykinesia has encompassed the other terms in the clinical context as well as in research (Gibb and Lees 1988; Calne et al., 1992; Gelb et al., 1999; Goetz et al., 2008; Berardelli et al., 2013; Berg et al., 2013). In the first formal diagnostic criteria for Parkinson's disease, bradykinesia refers to slowness of initiation of voluntary movement with a progressive reduction in speed and amplitude of repetitive actions (Gibb and Lees, 1988). The definition was maintained by the European Federation of Neurological Societies (EFNS) criteria for Parkinson's disease diagnosis (Berardelli et al., 2013) and by the current Movement Disorders Society (MDS) criteria, that define bradykinesia as slowness of movement and decrement in amplitude or speed (sequence effect) as movements are continued (Postuma et al., 2015; Berg et al., 2018).

In atypical parkinsonisms, the terminological use of bradykinesia is even less clear than in Parkinson's disease, because of the heterogeneity of these neurological conditions and the limited number of experimental studies. The MDS criteria for the diagnosis of progressive supranuclear palsy (PSP) (Höglinger et al., 2017) indicate akinesia (and not bradykinesia) as one of the core features of the disease and as a synonymous of parkinsonism. For the clinical diagnosis of multiple system atrophy (MSA) (Gilman et al., 2008), bradykinesia features are even not explicitly defined. For the diagnosis of cortical basal syndrome (CBS) (Armstrong et al., 2013), the terms bradykinesia and akinesia are used interchangeably. Finally, according to the clinical criteria for dementia with Lewy bodies diagnosis (McKeith et al., 2017), bradykinesia indicates slowness of movement and decrement in amplitude or speed as in Parkinson's disease, although this assumption only relies on clinical observations and there has not been a neurophysiological study of these patients.

In summary, there is still an ongoing debate on the terminology of bradykinesia in Parkinson's disease and atypical parkinsonisms. Bradykinesia terminology is nowadays based only on clinical observations; relying on neurophysiological concepts might improve the appropriateness of the terminological use of bradykinesia in Parkinson's disease and atypical parkinsonism.

The Assessment of Bradykinesia

The clinical assessment of bradykinesia in Parkinson's disease is currently based on the MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (Goetz et al., 2008), although other scales such as the Modified Bradykinesia Rating Scale (MBRS) (Kishore et al., 2007) have also been proposed. In the MDS-UPDRS scale, limb bradykinesia is evaluated during different manoeuvres. The examiner is asked to rate speed, amplitude, hesitations and halts or decrement during 10 repeated movements, and all these abnormalities exert the same influence on the global score. Similarly, spontaneous eye-blink frequency reduction, masked faces or loss of facial expression, including spontaneous smiling and the parting of lips are all considered for assessing hypomimia, i.e. facial bradykinesia. Differently from the MDS-UPDRS scale, in the MBRS the evaluator is asked to separately rate speed, amplitude and rhythm, possibly providing increased sensitivity in identifying different bradykinesia features (Kishore et al., 2007; Heldman et al., 2011). Nevertheless, the MBRS scale is not commonly used in clinical and experimental settings. The motor part of UPDRS is also consistently used to rate bradykinesia in atypical parkinsonisms patients. However, Golbe and Ohman-Strickland (2007) developed a disease-specific rating scale for PSP that scores several motor elements not included in the UPDRS (eye movements, bulbar function, neck extension, dystonia). This scale also allows a specific assessment of PSP staging (Golbe and Ohman-Strickland, 2007). Similarly, the European MSA Study Group developed a novel Unified MSA Rating Scale, whose motor part includes oculomotor dysfunction and ataxia evaluation (Wenning et al., 2004).

Bradykinesia rating using clinical scales is significantly affected by inter- and intra-rater variability, and low reliability. To improve the reliability of bradykinesia rating, several technology-based tools have been proposed (Hasan et al., 2017; Merola et al., 2018). These tools provide continuous quantitative measurements and remote data collection. Some of them were approved by the Food and Drug Administration to quantify kinematics in movement disorders. Except for gait analysis systems and actigraphy, the effectiveness of technology-based tools in clinical practice has not been clearly established. Interestingly, less than 3% of ongoing clinical trials of neurodegenerative disorders have employed technology-based tools as an outcome measure (Merola et al., 2018).

In summary, the clinical assessment of bradykinesia in Parkinson's disease and atypical parkinsonisms is currently based on the specific assessment of dedicated clinical rating scales. Bradykinesia rating, however, may be affected by inter- and intra-rater variability as well as by low reliability; technology-based tools can theoretically help to provide more accurate measurements. However, their role in clinical practice has not been fully established yet.

Features Associated or Contributing to Bradykinesia

A further issue is the role of secondary contributing factors to bradykinesia, and their burden in the clinical evaluation of bradykinetic patients. It has been suggested that in Parkinson's disease weakness can contribute to bradykinesia. A correlation between muscle weakness and slowness of movement was found (Corcos et al., 1996), as well as an effectiveness of strength training on UPDRS motor scores (David et al., 2016; Ni et al., 2016; Krumpolec et al., 2017). Moreover, antiparkinson medications improved force generation (Brown et al., 1997). Fatigue, defined as an overwhelming sense of tiredness and lack of energy (Krupp et al., 1989), has also been described in Parkinson's disease (Friedman, 2009; Berardelli et al., 2012; Fabbrini et al., 2013; Friedman et al., 2016; Siciliano et al., 2018). However, there is no clear evidence of any relationship between fatigue, assessed by clinical rating scale, and bradykinesia tested with the Purdue pegboard test or finger tapping (Kang et al., 2010; Bologna et al., 2016b), probably in light of the several involved factors other than movement impairment (i.e. motivation, apathy, and depression). It could be that a relationship between fatigue and sequence effect is present but this has not yet been demonstrated (Berardelli et al., 2012). Tinaz et al. (2016), for example, showed that sequence effect in Parkinson's disease cannot be explained by excessive peripheral fatigue. Additionally, there was no significant correlation between fatigue and the severity of progressive micrographia, considered a manifestation of the sequence effect (Wu et al., 2016). Another possible factor contributing to bradykinesia is tremor (Berardelli et al., 2001). The possible mechanisms previously suggested include the prolongation of reaction times, an incompletely fused muscle contraction caused by tremor, thus determining muscle weakness and bradykinesia (Brown et al., 1997), as well the 'pacing' effect of tremor on voluntary movements (Hallett et al., 1977; Logigian et al., 1991). More recent data on large samples of Parkinson's disease patients, however, showed no positive correlations between action tremor and bradykinesia severity (Gigante et al., 2015; Belvisi et al., 2018). Finally, bradyphrenia or mental slowness is another possible contributing factor for bradykinesia. Some studies report cognitive slowing in Parkinson's disease (Wilson et al., 1980; Pillon et al., 1989; Cooper et al., 1994; Sawamoto et al., 2002; Lee et al., 2003; Jokinen et al., 2013; Vlagsma et al., 2016). Although the relationship between cognitive abnormalities and movement execution remains poorly investigated, it has been observed that Parkinson's disease patients with cognitive impairment have prolonged reaction times compared to those with preserved cognitive capacities (Revonsuo et al., 1993). Furthermore, bradykinesia score, as assessed by clinical scales, seems to be associated with mild cognitive impairment in Parkinson's disease and to deteriorate in parallel with motor disease progression (Poletti et al., 2012; Domellöf et al., 2013; Stojkovic et al., 2018). However, other observations imply otherwise (Vlagsma et al., 2016). Recently, Hanakawa et al. (2017) measured the agility of Parkinson's disease patients performing a series of movement, motor imagery, and calculation tasks with a progressive increase in task rate. They also performed functional MRI and diffusion tractography to test whether dysfunctions of basal-ganglia-thalamo-cortical circuits underlying motor and cognitive processing were associated with motor and cognitive slowing. The authors concluded that cognitive slowing was associated with dysfunction of different basal-ganglia-thalamo-cortical circuits from those causing motor impairments, providing a further insight in the understanding of the relation between cognitive and motor slowness.

In summary, the features associated with or contributing to bradykinesia remain poorly investigated. Weakness can contribute, at least in part, to bradykinesia. Also, cognitive abnormality may impair the movement preparation phase, thus resulting in increased reaction times. Finally, there is not enough evidence to establish a firm relationship between bradykinesia and other features like fatigue and tremor.

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