Multifaceted Sensory Electrical Stimulation cueing for Freezing of Gait in Parkinson's disease

Abstract

Sensory Electrical Stimulation (sES) cueing of the lower limb may provide a means to ameliorate on-state Freezing of Gait (FoG) [[1]Sweeney D. ÓLaighin G. Richardson M. Meskell P. Rosenthal L. McGeough A. Cunnington A.L. Quinlan L.R. Immediate Effects of Auditory, Visual and Somatosensory cueing systems on on-state freezing of gait in Parkinson's disease.Park. Relat. Disord. 2020; 77: 1-4Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar]. Here, we report the results from a multifaceted sES cueing strategy, which aims to compensate for the multiple physiological abnormalities reported to be associated with FoG (internal rhythm generation, cognitive/attentional mechanisms, and proprioceptive information processes [2Azulay J.P. Mesure S. Amblard B. Blin O. Sangla I. Visual control of locomotion in Parkinson's disease.Brain. 1999; 122: 111-120Crossref PubMed Scopus (274) Google Scholar, 3Peterson D.S. King L.A. Cohen R.G. Horak F.B. Cognitive contributions to freezing of gait in Parkinson disease: implications for physical rehabilitation.Phys. Ther. 2016; 96: 659-670Crossref PubMed Scopus (59) Google Scholar, 4Pereira M.P. Gobbi L.T. Almeida Q.J. Freezing of gait in Parkinson's disease: evidence of sensory rather than attentional mechanisms through muscle vibration.Park. Relat. Disord. 2016; 29: 78-82Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar]). A cross-over study was performed, with 10 non-cognitively impaired idiopathic Parkinson's disease participants (8 males and 2 females, mean age 70.9 ± 6.89 years and disease duration 14.6 ± 2.8 years). All participants experienced a history of on-state FoG, which was rated as at least 2 (Moderately) on item 2 (affecting daily activities and independence) and at least a 3 (often, about once a day) on item 3 (freezing when walking) on the Freezing of Gait Questionnaire (FOGQ) [[5]Giladi N. Shabtai H. Simon E.S. Biran S. Tal J. Korczyn A.D. Construction of freezing of gait questionnaire for patients with Parkinsonism.Park. Relat. Disord. 2000; 6: 165-170Abstract Full Text Full Text PDF PubMed Scopus (540) Google Scholar]. To screen for cognitive impairment, all participants were required to have a Mini-Mental Status Examination score >24 [[6]Tombaugh T.N. McIntyre N.J. The mini‐mental state examination: a comprehensive review.J. Am. Geriatr. Soc. 1992; 40: 922-935Crossref PubMed Scopus (3473) Google Scholar]. sES cueing was delivered using an electrical stimulator (NUI Galway, Ireland), which provided sES cueing to the left and right thighs in an alternating rhythmic manner scaled to the participant's step rate. Initially, participant step-rate was determined by measuring the time taken and the number of steps performed by the participant over a straight 8 m pathway. The cueing rhythm was set to 10% below the participant's measured step-rate for participants with festination [[7]Spildooren J. Vercruysse S. Meyns P. Vandenbossche J. Heremans E. Desloovere K. Vandenberghe W. Nieuwboer A. Turning and unilateral cueing in Parkinson's disease patients with and without freezing of gait.Neuroscience. 2012; 207: 298-306Crossref PubMed Scopus (66) Google Scholar]. For all other participants, the cueing rhythm was set to 10% above the participant's measured step-rate [[8]Chen P.H. Liou D.J. Liou K.C. Liang J.L. Cheng S.J. Shaw J.S. Walking turns in Parkinson's disease patients with freezing of gait: the short-term effects of different cueing strategies.Int. J. Gerontol. 2016; 10: 71-75Crossref Scopus (11) Google Scholar]. The sES amplitude was adjusted for each participant to achieve maximum sensory response, while avoiding a motor or pain response [[1]Sweeney D. ÓLaighin G. Richardson M. Meskell P. Rosenthal L. McGeough A. Cunnington A.L. Quinlan L.R. Immediate Effects of Auditory, Visual and Somatosensory cueing systems on on-state freezing of gait in Parkinson's disease.Park. Relat. Disord. 2020; 77: 1-4Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar]. Participants were instructed to step each leg in time to the rhythm of the sES cue. The “Percentage of Time in FoG” (PTF) and the “Number of FoG Episodes Occurring” (NFO) were assessed, as the participants performed, within their home, a self-identified, short, uninterrupted walking-task (one-minute duration) which normally elicited FoG episodes for the participant. The PTF is reported as the gold standard for FoG assessment [[9]Barthel C. Nonnekes J. van Helvert M. Haan R. Janssen A. Delval A. Weerdesteyn V. Debû B. Van Wezel R. Bloem B.R. Ferraye M.U. The laser shoes: a new ambulatory device to alleviate freezing of gait in Parkinson disease.Neurol. 2018; 91: 164-171Crossref Scopus (47) Google Scholar]. Furthermore, it was recommended that PTF should be utilised as a metric in conjunction with NFO for the clinical assessment of FoG [[10]Morris T.R. Cho C. Dilda V. Shine J.M. Naismith S.L. Lewis S.J. Moore S.T. A comparison of clinical and objective measures of freezing of gait in Parkinson's disease.Park. Relat. Disord. 2012; 18: 572-577Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar]. The walking-task was performed while the PwP was in the on-state, as reported by their attending PD nurse specialist. The common features in each of the walking tasks performed by each participant were: (i) performing a turn during walking, (ii) walking through a doorway, (iii) walking across a room and (iv) walking in a hallway. Participants repeated the walking-task in the following chronological order. Baseline condition: Not wearing electrical stimulator. Control condition: Wearing electrical stimulator but it is inactive. Intervention condition: Wearing electrical stimulator and it is active. Residual condition: Not wearing electrical stimulator. Evaluation of NFO and PTF was performed by two independent expert raters (PD Nurse Specialist and Highly Specialized Physiotherapist Movement Disorders), through post-hoc video analysis. Before the video analysis, a researcher randomized the order of the videos for the different conditions. The experts were only blinded to the baseline-residual and the control-intervention conditions due to the sES cueing stimulator being visible in the videos. Differences between baseline-control, baseline-intervention, baseline-residual and control-intervention conditions were tested using the Friedman test and Wilcoxon signed-rank test. A Holm-Bonferroni correction was applied and statistical significance was defined as: α = 0.0125 for the lowest p-value, α = 0.0167 for the second lowest p-value, α = 0.025 for the third lowest p-value, and α = 0.05 for the fourth lowest p-value. Intraclass correlation coefficient (ICC) estimates and their 95% confident intervals were calculated based on a mean-rating (k = 2), consistency, and 2-way random model. Agreement between raters was high, with ICC of 0.94 (95% CI 0.94–0.78) and 0.72 (95% CI -0.14 – 0.93) for PTF and NFO, respectively. Therefore, in line with previous studies, the average scores of the two raters was used as the measure of PTF and NFO. Fig. 1A and B shows the changes in the mean PTF and NFO for each test condition. Results from Friedman tests showed a statistically significant difference between one or more conditions for both the mean PTF (χ2(3) = 19.92, p = 0.001) and for the mean NFO (χ2(3) = 14.02, p = 0.003). In comparison to baseline (PTF: 28.74 ± 14.94%; NFO: 5.15 ± 1.65), the control condition was associated with similar PTF (27.75 ± 14.95%, p = 0.799 and α = 0.05) and NFO (6.2 ± 3.47, p = 0.478 and α = 0.05) values. However, the intervention condition was associated with lower PTF (6.86 ± 4.48%, p = 0.005 and α = 0.0125) and NFO (2.25 ± 1.34, p = 0.007 and α = 0.0125), when compared to the baseline condition. In comparison to baseline, the residual condition was associated with a lower PTF (9.99 ± 8.23%, p = 0.009 and α = 0.025). However, the residual condition was not associated with a lower NFO (3.10 ± 2.08, p = 0.027 and α = 0.025). In comparison to control, the intervention condition was associated with lower PTF (p = 0.005 and α = 0.0167) and NFO (p = 0.012 and α = 0.0167) values. Fig. 1C and D shows the control, intervention, and residual conditions for each participant, based on reductions in the PTF and NFO from baseline. During the intervention condition the PTF reduced by 72.36 ± 24.79% and NFO reduced by 52.64 ± 30.64%. The presented multifaceted sES cueing strategy provided three mechanisms that may have compensated for the disrupted physiological processes associated with FoG.•Delivery of a fixed rhythm sES cue scaled to each participant's step rate may have provided temporal information to compensate for disrupted internal rhythm generation.•Requiring the participants to pay attention to the cue (i.e. step to the sensation of the cue) may have compensated for disrupted cognitive/attentional mechanisms.•Possible artificial stimulation of the proprioceptive inputs may have provided enhanced information on the positioning of both lower limbs, to compensate for disrupted proprioception. However, the authors acknowledge that whether or not these mechanisms explain the effectiveness of the cueing strategy is speculative and as such this is an area that merits further investigation. Overall, there was no associated difference between the mean outcome measures during baseline and control conditions, Fig. 1A and B. However individual difference between the baseline and control were observed, Fig. 1C and D. While speculative, we propose that the observed difference may be related to a placebo effect [[11]Mariani L.L. Corvol J.C. Maximizing placebo response in neurological clinical practice.Int. Rev. Neurobiol. 2020; 153: 71-101Crossref PubMed Scopus (3) Google Scholar,[12]Lidstone S.C. Schulzer M. Dinelle K. Mak E. Sossi V. Ruth T.J. de la Fuente-Fernández R. Phillips A.G. Stoessl A.J. Effects of expectation on placebo-induced dopamine release in Parkinson disease.Arch. Gen. Psychiatr. 2010; 67: 857-865Crossref PubMed Scopus (200) Google Scholar] and a shift from a non-anxious to an anxious situation [[13]Ehgoetz Martens K.A. Ellard C.G. Almeida Q.J. Does anxiety cause freezing of gait in Parkinson's disease?.PloS One. 2014; 9e106561Crossref PubMed Scopus (86) Google Scholar]. Results also suggest that the benefits of the described cueing strategy are at least in part retained for a short time after the cessation of cueing for some PwP. The actual mechanism of residual effects of cueing remains an area of speculation and warrants further investigation. The study linked a lower PTF and NFO to the described sES cueing strategy for non-cognitively impaired PwP with on-state FoG and compares favorably with our previously reported sES cueing strategy, which resulted in a mean reduction in the PTF of 55.34 ± 25.29% and NFO 48.23 ± 24.19% [[1]Sweeney D. ÓLaighin G. Richardson M. Meskell P. Rosenthal L. McGeough A. Cunnington A.L. Quinlan L.R. Immediate Effects of Auditory, Visual and Somatosensory cueing systems on on-state freezing of gait in Parkinson's disease.Park. Relat. Disord. 2020; 77: 1-4Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar]. Our conclusions are limited, as the non-randomized sequencing of the conditions, with potential task learning effects, may have impacted the results. However, to reduce possible learning effects, each participant performed a self-identified walking task, that was both familiar to them and carried out within their own homes. Furthermore, our study population was small, ten participants. However, and in line with our previously reported study [[1]Sweeney D. ÓLaighin G. Richardson M. Meskell P. Rosenthal L. McGeough A. Cunnington A.L. Quinlan L.R. Immediate Effects of Auditory, Visual and Somatosensory cueing systems on on-state freezing of gait in Parkinson's disease.Park. Relat. Disord. 2020; 77: 1-4Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar], participants recruited were a subset of on-state freezers, more likely to freeze. As such, all participants displayed FoG during baseline, enabling the proposed sES cueing strategy to be assessed on all participants. In addition, our subset of freezers, reported FoG that interfered moderately or severely with daily activities and independence. Currently, a clear definition of “troublesome” FoG is lacking in the literature. Nevertheless, for some PwP, FoG can be “troublesome” (e.g., FoG that interferes moderately or severely with mobility or quality of life). In comparison to PwP with mild FoG [[14]Nonnekes J. Snijders A.H. Nutt J.G. Deuschl G. Giladi N. Bloem B.R. Freezing of gait: a practical approach to management.Lancet Neurol. 2015; 14: 768-778Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar], a reduction in troublesome FoG could potentially have a more clinically meaningful effect on those affected (e.g., increased walking and access to their community, with a consequent positive impact on quality of life). This study was approved by the Limerick Hospital Research Ethics Committee (ref: 053/18). All participants were informed about the nature of the study and provided informed written consent.