Elke Heremans

Freezing of Gait in Parkinson’s Disease: Where Are We Now?

Freezing of gait (FOG) is defined as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. It is one of the most debilitating motor symptoms in patients with Parkinson’s disease (PD) as it may lead to falls and a loss of independence. The pathophysiology of FOG seems to differ from the cardinal features of PD and is still largely unknown. In the present paper, we review the studies that were performed since 2011 on methods to provoke and assess FOG and discuss new insights into behavioral and neural mechanisms underlying this clinical phenomenon. We conclude that most of the work reviewed confirms that gait pattern generation disturbances are central to FOG. The finding that FOG reflects a combined motor and cognitive de-automatization deficit, which may not be sufficiently offset by executive control, probably acts as parallel mechanism.

Cognitive aspects of freezing of gait in Parkinson’s disease: a challenge for rehabilitation

Freezing of gait (FOG) is a very disabling symptom affecting up to half of the patients with Parkinson’s disease (PD). Evidence is accumulating that FOG is caused by a complex interplay between motor, cognitive and affective factors, rather than being a pure motor phenomenon. In the current paper, we review the evidence on the specific role of cognitive factors in FOG. Results from behavioral studies show that patients with FOG experience impairments in executive functioning and response selection which predict that motor learning may be compromised. Brain imaging studies strengthen the neural basis of a potential association between FOG and cognitive impairment, but do not clarify whether it is a primary or secondary determinant of FOG. A FOG-related reduction of cognitive resources implies that adaptation of rehabilitation interventions is indicated for patients with FOG to promote the consolidation of learning.

Motor Imagery Ability in Patients With Early- and Mid-Stage Parkinson Disease

Background. Motor imagery has recently gained attention as a promising new rehabilitation method for patients with neurological disorders. Up to now, however, it has been unclear whether this practice method can also be successfully applied in the rehabilitation of patients with Parkinson disease (PD). Objective. This study aimed to investigate whether the motor imagery ability of patients with PD is still intact despite basal ganglia dysfunctioning. Methods. A total of 14 patients with early- and mid-stage PD (Hoehn and Yahr 1-3) and 14 healthy controls were evaluated by means of an extensive imagery ability assessment battery, consisting of 2 questionnaires, the Chaotic Motor Imagery Assessment battery, and a test based on mental chronometry. Results. PD patients performed the imagery tasks more slowly than controls, but the motor imagery vividness and accuracy of most patients were well preserved. Conclusions. These results are promising regarding the potential use of motor imagery practice in the rehabilitation of patients with PD.

Abnormalities and Cue Dependence of Rhythmical Upper-Limb Movements in Parkinson Patients With Freezing of Gait

Background. Freezing of gait (FOG) is a significant clinical problem in Parkinson disease (PD). Similar freezing-like episodes occur during finger movements, but little is known about ongoing motor problems during repetitive hand movements. Objective. To investigate if the regulation of bimanual movements is impaired in those with FOG and if withdrawal of an auditory cue amplifies this problem. Methods. A total of 23 PD patients (11 with and 12 without FOG) and 11 controls (CTRLs) performed repetitive finger movements, either externally paced or following cue withdrawal. Movement frequency, amplitude, and coordination pattern were manipulated. The stability and accuracy of movement were evaluated after exclusion of freezing trials. Results. With auditory pacing present, movement performance was comparable between groups. Following cue withdrawal, motor control deteriorated in those with FOG, resulting in smaller and less stable amplitudes, hastened and more variable frequency, and decreased coordination stability. Conversely, the performance of those without FOG remained mostly similar to that of CTRLs. Conclusions. Compared with those without FOG, those with FOG show greater continuous dyscontrol of bimanual movements, similar to the continuous timing and scaling difficulties during locomotion. Those with FOG also benefit from auditory cueing during upper-limb movements, but these are highly cue dependent. This implies that internal timekeeping functions are more disturbed in those with FOG, who may require rehabilitation strategies for repetitive upper-extremity tasks that include cueing and imagery.

Freezing in Parkinson's disease: a spatiotemporal motor disorder beyond gait.

Freezing of gait (FOG) is an incapacitating problem in Parkinsons disease that is difficult to manage therapeutically. We tested the hypothesis that impaired rhythm and amplitude control is a common mechanism of freezing which is also present during other rhythmic tasks. Therefore, we compared the occurrence and spatiotemporal profiles of freezing episodes during upper limb motion, lower limb motion, and FOG. Eleven freezers, 12 non‐freezers, and 11 controls performed a rhythmic bilateral finger movement task. The triggering effect of movement speed, amplitude, and coordination pattern was evaluated. Regression slopes and spectral analysis addressed the spatial and temporal kinematic changes inherent to freezing episodes. The FOG Questionnaire score significantly predicted severity of upper limb freezing, present in 9 freezers, and of foot freezing, present in 8 freezers. Similar to gait, small‐amplitude movements tended to trigger upper limb freezing, which was preceded by hastened movement and a strong amplitude breakdown. Upper limb freezing power spectra were broadband, including increased energy in the “freeze band” (3–8 Hz). Contrary to FOG, unilateral upper limb freezing was common and occurred mainly on the disease‐dominant side. The findings emphasize that a core motor problem underlies freezing which can affect various movement effectors. This deficit may originate on the disease‐dominant body side and interfere with amplitude and timing regulation during repetitive limb movements. These results may shift current thinking on the origins of freezing as being not exclusively a gait failure.

Explaining freezing of gait in Parkinson's disease: Motor and cognitive determinants

Freezing of gait (FOG) is part of a complex clinical picture in Parkinsons disease (PD) and is largely refractory to standard care. Diverging hypotheses exist about its origins, but a consolidated view on what determines FOG is lacking. The aim of this study was to develop an integrative model of FOG in people with PD. This cross‐sectional study included 51 Parkinson subjects: 24 patients without FOG and 27 with FOG matched for age, gender, and disease severity. Subjects underwent an extensive clinical test battery evaluating general disease characteristics, gait and balance, nongait freezing, and cognitive functions. The relative contribution of these outcomes to FOG was determined using logistic regression analysis. The combination of the following four independent contributors provided the best explanatory model of FOG (R2 = 0.49): nongait freezing; levodopa equivalent dose (LED); cognitive impairment; and falls and balance problems. The model yields a high‐risk profile for FOG (P > 95%) when Parkinson patients are affected by at least one type of nongait freezing (e.g., freezing of other repetitive movements), falls or balance problems during the last 3 months, and a Scales for Outcomes in Parkinsons Disease‐Cognition score below 28. A high LED further increases the risk of FOG to 99%. Nongait freezing, increased dopaminergic drug dose, cognitive deficits, and falls and balance problems are independent determinants of FOG in people with PD and may play a synergistic role in its manifestation.

The Neural Correlates of Upper Limb Motor Blocks in Parkinson's Disease and Their Relation to Freezing of Gait

Due to basal ganglia dysfunction, bimanual motor performance in Parkinson patients reportedly relies on compensatory brain activation in premotor-parietal-cerebellar circuitries. A subgroup of Parkinsons disease (PD) patients with freezing of gait (FOG) may exhibit greater bimanual impairments up to the point that motor blocks occur. This study investigated the neural mechanisms of upper limb motor blocks and explored their relation with FOG. Brain activation was measured using functional magnetic resonance imaging during bilateral finger movements in 16 PD with FOG, 16 without FOG (PD + FOG and PD - FOG), and 16 controls. During successful movement, PD + FOG showed decreased activation in right dorsolateral prefrontal cortex (PFC), left dorsal premotor cortex (PMd), as well as left M1 and bilaterally increased activation in dorsal putamen, pallidum, as well as subthalamic nucleus compared with PD - FOG and controls. On the contrary, upper limb motor blocks were associated with increased activation in right M1, PMd, supplementary motor area, and left PFC compared with successful movement, whereas bilateral pallidum and putamen activity was decreased. Complex striatofrontal activation changes may be involved in the difficulties of PD + FOG to perform bimanual movements, or sequential movements in general. These novel results suggest that, whatever the exact underlying cause, PD + FOG seem to have reached a saturation point of normal neural compensation and respond belatedly to actual movement breakdown.

Turning and unilateral cueing in Parkinson's disease patients with and without freezing of gait.

BACKGROUND Freezing of gait (FOG) is one of the most disabling symptoms in Parkinsons disease (PD), and cueing has been reported to improve FOG during straight-line walking. Studies on how cueing affects FOG during turning are lacking. Given the asymmetrical nature of turning and the asymmetrical disease expression, we aimed to gain a new perspective on how unilateral cueing may alleviate FOG. OBJECTIVE To explore disease dominance and turning side as contributing factors to turning problems and FOG and to investigate the effect of unilateral cueing. METHODS In the first study, 13 PD patients with FOG (freezers) and 13 without FOG (nonfreezers) turned toward their disease-dominant and nondominant side (off medication). During the second study, 16 freezers and 14 nonfreezers turned with and without a unilateral auditory cue at -10% of preferred cadence. Total number of steps, turn duration, cadence, and FOG episodes were measured using VICON. RESULTS Cadence, but not FOG frequency, was higher when turning toward the disease-dominant side. FOG started more frequently (64.9%) on the inner side of the turning cycle. Unilateral cueing seemed to prevent FOG in most patients, irrespective of the side at which the cue was offered. A carryover effect was found for cadence during turning, but the effect on FOG disappeared when the cue was removed. CONCLUSIONS The occurrence of FOG is not influenced by turning toward the disease-dominant or nondominant side, which is confirmed by the fact that it does not make a difference at which side unilateral cueing is applied. Cueing reduces FOG during turning, but these effects disappear dramatically after cue removal. This raises further questions as to the influence of training on cue dependency and on the feasibility of either continuous application of cues or using cognitive strategies as an alternative.

External Cueing Improves Motor Imagery Quality in Patients With Parkinson Disease

Background. Patients with Parkinson disease (PD) are often profoundly slow in their performance of physical tasks, as well as in motor imagery (MI). This may limit the implementation and potential benefits of MI practice during rehabilitation. Objective. The authors investigated whether the quality of MI could be improved by external cueing. Methods. Fourteen patients with PD and 14 healthy controls physically executed and visually imagined a goal-directed aiming task and a box-and-block task, both in the presence and absence of visual and auditory cues. Mental chronometry and eye movement recording allowed objective evaluation of the temporal and spatial characteristics of MI when compared with physical execution. Visual analogue scales were used to assess imagery vividness. Results. The presence of visual cues significantly reduced the patients’ bradykinesia during MI and increased their imagery vividness. Conclusions. Visual cueing optimizes MI quality for PD patients and is a potential tool to increase the efficacy of MI practice in PD rehabilitation.

Transcranial direct current stimulation in Parkinson's disease: Neurophysiological mechanisms and behavioral effects

Recent research has highlighted the potential of transcranial direct current stimulation (tDCS) to complement rehabilitation effects in the elderly and in patients with neurological diseases, including Parkinsons disease (PD). TDCS can modulate cortical excitability and enhance neurophysiological mechanisms that compensate for impaired learning in PD. The objective of this systematic review is to provide an overview of the effects of tDCS on neurophysiological and behavioral outcome measures in PD patients, both as a stand-alone and as an adjunctive therapy. We systematically reviewed the literature published throughout the last 10 years. Ten studies were included, most of which were sham controlled. Results confirmed that tDCS applied to the motor cortex had significant results on motor function and to a lesser extent on cognitive tests. However, the physiological mechanism underlying the long-term effects of tDCS on cortical excitability in the PD brain are still unclear and need to be clarified in order to apply this technique optimally to a wider population in the different disease stages and with different medication profiles.