Clinical neurophysiology of Parkinson's disease and parkinsonism

Abstract

This review is part of the series on the clinical neurophysiology of movement disorders. It focuses on Parkinson's disease and parkinsonism. The topics covered include the pathophysiology of tremor, rigidity and bradykinesia, balance and gait disturbance and myoclonus in Parkinson's disease. The use of electroencephalography, electromyography, long latency reflexes, cutaneous silent period, studies of cortical excitability with single and paired transcranial magnetic stimulation, studies of plasticity, intraoperative microelectrode recordings and recording of local field potentials from deep brain stimulation, and electrocorticography are also reviewed. In addition to advancing knowledge of pathophysiology, neurophysiological studies can be useful in refining the diagnosis, localization of surgical targets, and help to develop novel therapies for Parkinson's disease.

Keywords: Bradykinesia; Deep brain stimulation; Electroencephalography; Electromyography; Gait and balance; Local field potentials; Long latency reflexes; Microelectrode recording; Transcranial magnetic stimulation; Tremor.

Fig. 1

Tremor recording and time–frequency representations of Parkinson’s disease tremors. Panel A shows EMG and accelerometry recordings (left) and power spectral analysis (right) in a Parkinson’s disease (PD) patient with re-emergent tremor. The patient made a rapid wrist extension at the beginning of the trace, after which the tremor amplitude was transiently reduced (resetting). The extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles show an alternating pattern of rhythmic EMG bursts at 5 Hz with harmonic at double tremor frequency (10 Hz). Panels B and C show time–frequency representations (TFR) of two different PD patients with re-emergent tremor (panel B) or pure postural tremor (panel C). The plots show EMG power (of a tremulous muscle, color coding) over the course of 70 s (x-axis) and as a function of frequency (y-axis). At 10 s, both patients extend their wrist. Panel B illustrates three key characteristics of PD tremor: (1) power at tremor frequency and double tremor frequency (first harmonic); (2) suppression of tremor power after wrist extension; (3) waxing and waning of tremor power over time. Panel C illustrates a patient with a typical “pure postural tremor”, which typically starts immediately after posturing and occurs at a relatively high frequency of ± 8 Hz. ECR = extensor carpi radialis muscle; EMG = electromyography; FCR = flexor carpi radialis muscle.

Fig. 2

Schematic illustrations of Parkinson’s disease gait. (A) Parkinson’s disease gait is characterized by step length reduction, swing phase shortening, narrowing of the base of support and reduced foot clearance (shuffling gait); bradykinesia also contributes to ‘sequence effect’, defined as the progressive shortening of step length (bottom row). The asymmetry of these gait features tends to persist during disease progression. (B) The pharmacokinetics of levodopa provides a useful framework to understand how axial motor problems can respond to dopaminergic treatment, be caused by or be resistant to levodopa.

Fig. 3

Reduced I1 response of cutaneomuscular reflex in Parkinson’s disease. The cutaneomuscular reflex obtained from abductor pollicis brevis muscle with superficial radial nerve stimulation showed reduced I1 response in two Parkinson’s disease patients (gray) compared to two normal subjects (red). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Examples of ipsilateral silent period (iSP) from a normal subject and a corticobasal syndrome patient. (A) iSP from a healthy subject. Rectified and averaged surface EMG recorded from the abductor pollicis brevis muscle with 10 trials. The vertical dashed lines indicate iSP onset and offset. The iSP onset is 31 ms and the offset time is 63 ms after TMS. The horizontal dashed line represented the mean baseline EMG level −50 to −10 ms before TMS. (B) iSP from a patient with corticobasal syndrome. Rectified, averaged surface EMG recording from the left (more affected side) APB muscle with 10 trials. There was no iSP. TMS: transcranial magnetic stimulation; EMG: electromyography.

Fig. 5

Parkinsonian beta activity in the subthalamic nucleus is suppressed with deep brain stimulation. Local field potentials (LFP) can be recorded directly through implanted DBS electrodes (A). In the medication and stimulation OFF state, the amplitude of beta oscillatory activity is increased (A left) and suppressed with deep brain stimulation (DBS) switched ON (right). Recently, the dose dependence of beta and DBS could be revealed through sensing enabled implantable devices (B; Feldmann et al., 2021a, Feldmann et al., 2021a).