Foot–Floor Contact Sequences: A Metric for Gait Assessment in Parkinson’s Disease after Deep Brain Stimulation

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This paper proposes a new metric, the percentage of atypical gait cycles, to assess motor skills by following up on gait before and after deep brain stimulation (DBS) surgery in Parkinson's disease (PD) patients. While typical gait analysis usually focuses on straight walking, the inclusion of turning in this study is noteworthy.

However, there is a need for better organization in the writing. Explanations of key concepts are scattered throughout the text, making it difficult to understand.

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In Section 2.2, there is insufficient explanation of the STEP32 system. It is unclear what the system does, what its inputs and outputs are. Is the STEP32 system equivalent to a foot switch, or does it incorporate additional functionalities?

Is the graph mentioned in Section 1.B a result derived from this system? The y-axis labeled "Gait Phases" includes F, H, P, and S, but it's unclear what these represent and how to interpret the graph. The explanation for HFPS only appears in Section 2.3.

Regarding the high-resolution camera, what is the resolution specified?

How is the attachment position of the three sensors determined?

Could attaching the sensors potentially affect gait?

It is unfortunate that reference [16] must be consulted for this information.

 

It would be helpful to clarify whether the percentage of forefoot and flatfoot initial-contact gait cycles mentioned many times in the manuscirpt refers to the percentage of “atypical” gait cycles in the introduction. 

Providing a proper definition early in the text will be very helpful in understanding the content, () and using an abbreviation for this metric might enhance the readability.

I found he definition of this metric finally in the discussion section.

The formula presented: 

(𝐹𝑜𝑙𝑙𝑜𝑤 𝑢𝑝 𝑡𝑖𝑚𝑒 𝑝𝑜𝑖𝑛𝑡 − 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑣𝑎𝑙𝑢𝑒) / 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑣𝑎𝑙𝑢𝑒 × 100 

could be presented more clearly as:

((𝐹𝑜𝑙𝑙𝑜𝑤 𝑢𝑝 𝑡𝑖𝑚𝑒 𝑝𝑜𝑖𝑛𝑡 𝑣𝑎𝑙𝑢𝑒 − 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑣𝑎𝑙𝑢𝑒) / 𝐵𝑎𝑠𝑒𝑙𝑖𝑛𝑒 𝑣𝑎𝑙𝑢𝑒 × 100).

 

 

Comments on the Quality of English Language

Some sentences are challenging to comprehend or ambiguous.

Author Response

Comment 1: This paper proposes a new metric, the percentage of atypical gait cycles, to assess motor skills by following up on gait before and after deep brain stimulation (DBS) surgery in Parkinson's disease (PD) patients. While typical gait analysis usually focuses on straight walking, the inclusion of turning in this study is noteworthy. However, there is a need for better organization in the writing. Explanations of key concepts are scattered throughout the text, making it difficult to understand.

Response 1: We sincerely thank Reviewer 1 for the time and effort spent reading our manuscript. We are pleased to hear that the Reviewer considers the assessment of direction changes during walking noteworthy. In the following, there are the point-by-point responses to the Reviewer’s comments.

 

Comment 2: In Section 2.2, there is insufficient explanation of the STEP32 system. It is unclear what the system does, what its inputs and outputs are. Is the STEP32 system equivalent to a foot switch, or does it incorporate additional functionalities?

Response 2: We thank the Reviewer for the comment. STEP32 is a multichannel acquisition system for clinical gait analysis that can capture up to 16 data channels, including foot-switch signals, joint-angle kinematics in the sagittal plane, and electromyographic signals. In this study, only foot-switch signals were analyzed. A more detailed description of the acquisition system was added in the revised manuscript (page 3, lines 115-118).

 

Comment 3: Is the graph mentioned in Section 1.B a result derived from this system? The y-axis labeled "Gait Phases" includes F, H, P, and S, but it's unclear what these represent and how to interpret the graph. The explanation for HFPS only appears in Section 2.3.

Response 3: In response to the Reviewer’s suggestion, we added the foot switch signal explanation in Figure 1’s caption to improve its clarity and readability (page 3).

 

Comment 4: Regarding the high-resolution camera, what is the resolution specified?

Response 4: Video recordings were captured using the built-in camera of the STEP32 system, with a resolution of 640 × 480 pixels and 6 fps. Although this resolution is lower than that of other cameras, it is important to note that the video recordings were solely used for manually segmenting turns, and no gait parameters were extracted from the videos. In the revised version of the manuscript, we amended the camera description by removing “high-resolution” (page 4, line 131).

 

Comment 5: How is the attachment position of the three sensors determined? Could attaching the sensors potentially affect gait? It is unfortunate that reference [16] must be consulted for this information.

Response 5: The experimenter determined foot-switch placement through foot-sole palpation, targeting the center of the heel and the heads of the first and fifth metatarsals. To ensure consistency and comparability of results, the same experimenter performed sensor placement on both the experimental and control populations. Due to the slim design of the foot-switch sensors (0.5 mm thick), no effects on gait were perceived by the volunteers or observed in either physiological or pathological conditions. In response to the Reviewer’s suggestion, we further detailed the sensor placement procedure in the revised manuscript (page 3, lines 121-123).

 

Comment 6: It would be helpful to clarify whether the percentage of forefoot and flatfoot initial-contact gait cycles mentioned many times in the manuscript refers to the percentage of “atypical” gait cycles in the introduction. Providing a proper definition early in the text will be very helpful in understanding the content, () and using an abbreviation for this metric might enhance the readability.

Response 6: Correct, the “percentage of forefoot and flatfoot initial-contact gait cycles” and the “percentage of atypical gait cycles" refer to the same parameter. Forefoot and flatfoot initial-contact gait cycles are subtypes of atypical gait cycles, characterized by foot-floor contact sequences that differ from HFPS (i.e., Heel contact, Flat foot contact, Push-off, and Swing). In response to the Reviewer’s suggestion, we have provided a clearer definition of this parameter (page 4, lines 145-153) and standardized its nomenclature throughout the manuscript.

 

Comment 7: I found the definition of this metric finally in the discussion section. The formula presented:

(?????? ?? ???? ????? − ???????? ?????) / ???????? ????? × 100 

could be presented more clearly as:

((?????? ?? ???? ????? ????? − ???????? ?????) / ???????? ????? × 100).

Response 7: We thank the Reviewer for the suggestion. We moved the metric definition to the Methods section and revised its formulation as per the Reviewer’s recommendation (page 4, lines 154-157).

Reviewer 2 Report

Comments and Suggestions for Authors

Foot-floor contact sequences: a metric for gait assessment in Parkinson's disease after deep brain stimulation

This study investigates gait performance in Parkinson’s disease (PD) patients before and after deep brain stimulation (DBS) neurosurgery, focusing on foot-floor contact sequences during straight-line and curvilinear walking. The primary goal is to evaluate changes in unusual gait cycles and to determine whether DBS improves gait performance in PD patients.

Abstract:

The abstract provides a concise overview of the study but could benefit from more specific details about the results. For example, include more precise statistics regarding the reduction in atypical gait cycles and improvements in other gait parameters (Abstract, Page 1). Consider explicitly stating the comparison of gait performance between PD patients and healthy controls over the study period.

Methods:

Clarification Needed: Please specify if the same evaluators were responsible for conducting pre- and post-DBS evaluations to ensure consistency in data collection (Methods, Page 3, Section 2.2).

 

Details on Participant Selection: Expand on the recruitment of participants. How were the 30 healthy controls selected? Were they matched for all demographic factors apart from neurological conditions? This would help ensure the validity of comparisons (Methods, Page 3, Section 2.1).

 

Statistical Analysis:

Details on Statistical Adjustments: The statistical analysis is well-designed, but more information on how adjustments for multiple comparisons (e.g., Bonferroni) were applied to the results would improve the robustness of the findings (Methods, Page 5, Section 2.4).

 

Results:

Sample Exclusion: Clarify why patients who had orthopedic surgery between T1 and T2 were excluded from the study, and whether this exclusion affected the overall study findings. Did the characteristics of these patients differ significantly from those who remained in the study? (Results, Page 5, Section 3).

 

Gait Performance: Result presentations are clear but providing the MCID for measures such as gait speed, turning time, and stride time variability would help readers understand the clinical relevance of these findings (Results, Page 5, Table 2).

 

Discussion:

The discussion is thorough but could benefit from more emphasis on the utility of using foot-floor contact sequences as digital biomarkers for assessing DBS effectiveness. Highlighting the implications of using these gait parameters in clinical practice for clinicians would be beneficial. (Discussion, Page 7, Section 4).

Author Response

Comment 1: This study investigates gait performance in Parkinson’s disease (PD) patients before and after deep brain stimulation (DBS) neurosurgery, focusing on foot-floor contact sequences during straight-line and curvilinear walking. The primary goal is to evaluate changes in unusual gait cycles and to determine whether DBS improves gait performance in PD patients.

Response 1: We thank Reviewer 2 for the time spent revising our manuscript. In the following, there are the point-by-point responses to the Reviewer’s comments.

 

Comment 2: Abstract: The abstract provides a concise overview of the study but could benefit from more specific details about the results. For example, include more precise statistics regarding the reduction in atypical gait cycles and improvements in other gait parameters (Abstract, Page 1). Consider explicitly stating the comparison of gait performance between PD patients and healthy controls over the study period.

Response 2: Thank you for the suggestion. In the revised manuscript, we have updated the abstract to explicitly include the comparison of gait performance between PD patients and healthy controls over the study period (page 1, lines 23-29).

 

Comment 3: Methods: Clarification Needed: Please specify if the same evaluators were responsible for conducting pre- and post-DBS evaluations to ensure consistency in data collection (Methods, Page 3, Section 2.2).

Response 3: Yes, the same evaluators were responsible for conducting gait assessment before and after DBS surgery. In the revised version of the manuscript, we added this aspect to the ‘Experimental protocol and data acquisitions’ section (page 3, lines 123-124).

 

Comment 4:Details on Participant Selection: Expand on the recruitment of participants. How were the 30 healthy controls selected? Were they matched for all demographic factors apart from neurological conditions? This would help ensure the validity of comparisons (Methods, Page 3, Section 2.1).

Response 4: We thank the Reviewer for the comment. Healthy controls were enrolled among the caregivers of PD patients, with the exclusion of individuals presenting neurological or musculoskeletal disorders that could potentially affect gait. Specifically, the wives and husbands (or partners) of PD patients were selected to better match the control group in terms of age. After PD patients and controls enrollment, demographic characteristics were tested for differences between groups. As represented in Table 1, no differences in age, weight, and height were detected, suggesting that PD and controls shared similar demographic characteristics. In the revised manuscript, we further described the control enrollment procedure (page 2, line 86).

 

Comment 5: Statistical Analysis: Details on Statistical Adjustments: The statistical analysis is well-designed, but more information on how adjustments for multiple comparisons (e.g., Bonferroni) were applied to the results would improve the robustness of the findings (Methods, Page 5, Section 2.4).

Response 5: We thank the Reviewer for the comment. Post-hoc analyses with Bonferroni corrections for multiple comparisons were performed to test gait performance differences among groups (i.e., between PD at baseline, PD at 3 months after DBS, PD at 12 months after DBS, and controls). Specifically, Bonferroni adjustments were applied to assess differences related to all within-subject variables in the 1-way MANOVA analysis (i.e., ν, T_turn, CoV_Stride, percentage of atypical gait cycles, stance, swing, and double support). Post-hoc analyses were performed using SPSS Statistical Software, version 27.0. In the revised manuscript, we further detailed the statistical adjustments performed (page 4, lines 176-178).

 

Comment 6: Results: Sample Exclusion: Clarify why patients who had orthopedic surgery between T1 and T2 were excluded from the study, and whether this exclusion affected the overall study findings. Did the characteristics of these patients differ significantly from those who remained in the study? (Results, Page 5, Section 3).

Response 6: We thank the Reviewer for the comment. Three out of thirty PD patients were excluded from the study due to orthopedic surgery (i.e., hip or knee prosthesis implantation) during follow-up visits. These patients were excluded from subsequent analyses to ensure that only PD-related motor symptoms were compared, thereby avoiding potential confounding factors from other comorbidities, which could significantly reduce the comparability of the results. The reduction in sample size (from 30 to 27 patients) did not impact the significance of the overall findings. At baseline (prior to DBS surgery), the excluded patients had demographic and clinical characteristics comparable to those of the remaining participants. In the revised manuscript, we better clarified the rationale behind the exclusion of orthopedic patients (page 5, lines 193-196).

 

Comment 7: Gait Performance: Result presentations are clear but providing the MCID for measures such as gait speed, turning time, and stride time variability would help readers understand the clinical relevance of these findings (Results, Page 5, Table 2).

Response 7: We are grateful that the reviewer appreciated the clarity of results presentation. This study did not focus on demonstrating the reliability and repeatability of the measured gait parameters. Therefore, intra-session and inter-session repeated measurements were not performed to assess the correspondent ICCs. Hence, unfortunately, it is not easy to estimate the Minimal Clinical Important Difference (MCID). We include this aspect as a limitation of the study (page 10, lines 328-331).

 

Comment 8: Discussion: The discussion is thorough but could benefit from more emphasis on the utility of using foot-floor contact sequences as digital biomarkers for assessing DBS effectiveness. Highlighting the implications of using these gait parameters in clinical practice for clinicians would be beneficial. (Discussion, Page 7, Section 4).

Response 8: We thank the Reviewer for the valuable suggestion. We widened the discussion section to highlight the implications of using the proposed parameters in clinical practice (page 9, lines 289-292).

Reviewer 3 Report

Comments and Suggestions for Authors

Manuscript: Foot-floor contact sequences: a metric for gait assessment in Parkinson’s disease after deep brain stimulation

 

This paper reviews the gait changes in PD patients after DBS, specifically foot-floor contact sequences and atypical gait cycles.

 

In the following sections, group major and minor concerns and list major first.

 

Adequacy and accuracy of the literature review and theoretical rationale: 

-   Good overview

-    

Adequacy and accuracy of the methodology:

-   Please clarify what you mean by “levodopa response” in the inclusion criteria.  What about DBS patients that had inadequate response to levodopa, e.g. tremor-predominant subtypes?  Were they included?  I ask as this subgroup typically has less severe gait disability in general.

-   For DBS on states at 3 months and 12 months, assume this is at optimal programming settings for that time?  Did you account for any programming changes between 3 months and 12 months? 

-   How did you determine the more impacted side?  Tremor, rigidity, and bradykinesia on impacted side?  What if symptoms were nearly symmetrical on both sides?

 

Adequacy and accuracy of the presentation and statistical treatment of the results:

-   Adequate

 

The accuracy and clarity of figures and tables:

-   Good figures

 

The accuracy and clarity of the discussion and interpretation:

-   Good discussion.  Would mention need to repeat a similar study and compare STN vs. GPi.

Author Response

Comment 1: This paper reviews the gait changes in PD patients after DBS, specifically foot-floor contact sequences and atypical gait cycles. In the following sections, group major and minor concerns and list major first. Adequacy and accuracy of the literature review and theoretical rationale: Good overview.

Response 1: We sincerely thank Reviewer 3 for the time and effort spent reading our manuscript. We are pleased that the Reviewer considers the introduction section a good overview of the relevant literature.

 

Comment 2: Please clarify what you mean by “levodopa response” in the inclusion criteria. What about DBS patients that had inadequate response to levodopa, e.g. tremor-predominant subtypes? Were they included? I ask as this subgroup typically has less severe gait disability in general.

Response 2: By “good levodopa response” it was intended the usual clinical inclusion criteria for selecting patients eligible for DBS surgery, i.e., the Levodopa Challenge Test (LCT). We agree with the Reviewer that the tremor-predominant subtype is often resistant to levodopa therapy and usually shows a less severe gait disability. However, in our population, only one patient showed a tremor-predominant behavior.

 

Comment 3: For DBS on states at 3 months and 12 months, assume this is at optimal programming settings for that time? Did you account for any programming changes between 3 months and 12 months?

Response 3: We appreciate the Reviewer’s comment. For DBS at 3-month and 12-month follow-up visits, the stimulation parameters were tailored to the patients’ needs for obtaining their best-ON condition (i.e., best pharmacological time window and optimal programming settings), also to comply with ethical committee requests. Since the focus of the present study was to assess PD gait performance during their best condition, programming adjustments were not accounted for in the subsequent analyses. In the revised manuscript, we better described this aspect to improve clarity (page 3, lines 103-106).

 

Comment 4: How did you determine the more impacted side? Tremor, rigidity, and bradykinesia on impacted side? What if symptoms were nearly symmetrical on both sides?

Response 4: We thank the Reviewer for the comment. For each patient, the more affected side was identified as the side where Parkinson's disease symptoms first appeared. This criterion allowed for clear identification of the more affected side, even in cases of nearly symmetrical symptom presentation.

 

Comment 5: Adequacy and accuracy of the presentation and statistical treatment of the results: Adequate.

Response 5: We are glad that the Reviewer considered the presentation and statistical treatment of the results adequate.

 

Comment 6: The accuracy and clarity of figures and tables: Good figures

Response 6: We are pleased that the Reviewers found the figures and tables to be accurate and clear.

 

Comment 7: The accuracy and clarity of the discussion and interpretation: Good discussion. Would mention need to repeat a similar study and compare STN vs. GPi.

Response 7: We thank the Reviewer for the valuable suggestion. In the revised manuscript, we widened the discussion section to highlight this important aspect as a direction for future research (page 9, lines 293-297).

Reviewer 4 Report

Comments and Suggestions for Authors

This is an excellent paper with very well-described methods and results. Proper discussion with reference to current literature is satisfying. 

The authors acknowledge the limitations of the study, in particular the evaluation done only in ON window.

Please find below my updated comments:   The main question is to assess the gait before and after DBS in PD patients.    I think the topic is relevant as gait abnormalities are prominent in PD patients, and quantifying gait abnormalities with gait analysis is helpful in evaluating the response to DBS.   This study adds the assessment of gait performance during turning, while previous studies focused on straight-line trajectories.   Authors should include both ON and OFF pharmacological time windows (as acknowledged in the discussion).   The discussion is clear, emphasizing also the limitations of this study.   The references are appropriate   The Figures and tables are extensive and clear.

Author Response

Comment 1: This is an excellent paper with very well-described methods and results. Proper discussion with reference to current literature is satisfying. The authors acknowledge the limitations of the study, in particular the evaluation done only in ON window. The main question is to assess the gait before and after DBS in PD patients. I think the topic is relevant as gait abnormalities are prominent in PD patients, and quantifying gait abnormalities with gait analysis is helpful in evaluating the response to DBS. This study adds the assessment of gait performance during turning, while previous studies focused on straight-line trajectories. Authors should include both ON and OFF pharmacological time windows (as acknowledged in the discussion). The discussion is clear, emphasizing also the limitations of this study. The references are appropriate. The Figures and tables are extensive and clear.

Response 1: We sincerely thank Reviewer 4 for the time and effort dedicated to reading our manuscript. We are pleased that the Reviewer finds it scientifically relevant. As mentioned in the discussion section, PD gait performance was assessed only during the best-ON pharmacological time window. This approach was chosen because, for many patients, completing a 5-minute walking task autonomously during the OFF-medication state would have been extremely challenging or impossible. Additionally, the experimental protocol approved by the Institutional Ethics Committee permitted assessments only during the ON-medication state.