Kinematic mechanism of the rehabilitative effect of 4-channel NMES: post-hoc analysis of a prospective randomized controlled study – Scientific Reports

Study design and participants

This was a post-hoc analysis of a multicenter, prospective, double-blind, randomized controlled clinical trial on the clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES for the treatment of dysphagia. The detailed trial design and study results have been published previously¹³. Briefly, from October 2018 to August 2019, patients from five hospitals were identified who met the following criteria; (1) within 3 months of a cerebral infarction or hemorrhage diagnosis, (2) at least one symptom of dysphagia, and (3) confirmed diagnosis of dysphagia via VFSS. The exclusion criteria were: (1) severe cognitive dysfunction and could not follow 1-step commands; (2) serious psychiatric disorder; and (3) a history of cervical surgery and respiratory difficulty. Patients who were pregnant or breastfeeding, patients who had cancer, and patients who had allergic reactions to the electrodes of NMES were also excluded.

For this post-hoc analysis, we included a subset of participants who’s initial and follow-up VFSS data could be kinematically identified and analyzed (Fig. 1). Exclusion criteria for analyzing hyoid bone tracking of VFSS data included low-image resolution, inappropriate photography conditions, and too much head/neck shaking during swallowing. These factors led to excessive missing frames during the automatic hyoid bone tracking process, and therefore, these cases were excluded from the current study.

Patients were assigned in a 1:1 ratio to receive the 4-channel NMES or 2-channel NMES. All participants received 2- or 4-channel NMES for 2–3 weeks (minimal session: 7 times, treatment duration: 300–800 min). The interventions started within 1 week after the initial clinical and VFSS evaluations, and follow-up evaluations were performed within 1 week after the last intervention. The maximal duration between the initial and follow-up evaluations was 4 weeks. The reporting of this study conforms to all CONSORT 2010 guidelines. The study protocol was approved by the institutional review board of each hospital (IRB Nos.: E-1806/475-002, 2018-07-012, JEJUNUH 2018-07-010, J-1810-064-979, DFH19DPOS033, respectively), approved by the Ministry of Food and Drug Safety in the Republic of Korea, and registered at clinicaltrial.gov (registration number: NCT03670498, initial release: 13/09/2018, first registration date: 01/10/2018, actual study completion date: 04/08/2019, last release: 23/07/2020). Written informed consent was obtained from all participants.

Equipment: sequential 4-channel NMES and 2-channel NMES

The sequential 4-channel NMES has four channels with adaptable amplitude, frequency, duration, and latency of current. (Supplementary Fig. S1a: STF-1000, Stratec Co., Ltd, Anyang, South Korea). It also includes four pairs of round-shaped electrodes which are 22 mm in diameter. The gaps between the electrodes were either 0.5 cm (type 1 electrode) or 1 cm (type 2 electrode). The type 1 electrode was used for channels 1, 2, and 4, and the type 2 electrode was used for channel 3 (Supplementary Fig. S1b; One Bio Medic Co., Ltd, Bucheon-si, Gyeonggi-do, South Korea).

Channel 1 (right) and channel 2 (left) electrodes were placed superior to the hyoid bone and posterior to the mandible, 1 cm lateral to the midline, and the targeted muscles were the bilateral digastric and mylohyoid muscles. Channel 3 electrodes were placed on the bilateral superior poles of the thyroid cartilage to target the bilateral thyrohyoid muscles, and channel 4 electrodes were placed medial to the sternocleidomastoid muscle and inferior to the thyroid cartilage, and the targeted muscles were the other infrahyoid muscles (sternohyoid, omohyoid, and sternothyroid muscles) (Supplementary Fig. S2a). All electrical stimulation parameters were based on previous studies^7,11. Electrical stimulation was started in channels 1 and 2 first, and stimulation via channels 3 and 4 started 150 ms and 250 ms later, respectively. The stimulation durations of channels 1, 2, 3, and 4 were 1200 ms, 1200 ms, 1050 ms, and 950 ms respectively. Hence, all stimulations in the sequence ended concurrently⁷.

In the 2-channel NMES group, electrical stimulation was applied via two sets of electrodes attached to the suprahyoid and thyrohyoid muscles, whereas no electrical stimulation was applied to the other electrodes that were placed for blinding purposes (Supplementary Fig. S2b). The 2-channel NMES (Vitalstim^®; Chattanooga Group, Hixson, TN, USA) and 4-channel NMES had the same stimulation parameters. The pulse frequency, duration, and interphase interval were 80 Hz, 300 µs, and 100 µs, respectively. The stimulus intensity was increased until the subjects could no longer tolerate the discomfort or pain (between 0 and 25 mA)¹⁸.

Kinematic analysis of videofluoroscopic swallowing study data

For the VFSS, subjects were tested with the following boluses sequentially: thin fluid (International dysphagia diet standardization initiative (IDDSI) 0), mildly thick fluid (IDDSI 2), soft and bite-sized food (IDDSI 6), and regular food (IDDSI 7)¹⁹. Each patient received an initial 3 mL bolus, followed by two 5 mL boluses. Fluids (thick and thin) were delivered using 10-mL syringes and the others were consumed using a spoon. All fluoroscopic images taken during swallowing were digitally recorded.

Kinematic analysis was performed for the VFSS video clips. VFSS video clips were cut and recorded at 30 images/s. Two-dimensional hyoid bone tracking was performed using AKAP based on MATLAB (The MathWorks Inc., Natick, MA)¹⁶. In the first image, we marked the reference points in the following manner: the anterior border of the hyoid bone, anterosuperior and anteroinferior edge of the C3 vertebral body, and anteroinferior edge of the C2, C3, and C4 vertebral bodies (Fig. 2a). Afterwards, AKAP automatically marked the remaining frames and analyzed hyoid bone movement based on the reference points (Fig. 2b).

This figure shows the automated kinematic analysis program (AKAP, C-2015-019815). (a) After marking the anterior border of the hyoid bone, the anterosuperior and anteroinferior edges of the C3 vertebral body and anteroinferior edges of the C2, C3, and C4 vertebral bodies are marked in the first frame of the recording. (b) Then, the MATLAB program automatically analyzed the position of the hyoid bone based on the position of C2, C3, and C4 vertebral bodies from the first to the last frame of the recording. AKAP measures the distance and timing parameters between the points (A–D). A(0, 0): the starting point of the hyoid bone when swallowing, B: the most upward point, C: the most anterior location, D: the endpoint of swallowing.

Based on the two-dimensional moving trajectory of the hyoid bone, four points were identified: point A was the starting point of the hyoid bone when swallowing, point B was the most upward point, point C was the most anterior location (equilibrium state of supra-and infrahyoid muscles), and point D was the endpoint of swallowing (Fig. 2b). We calculated the distance and timing parameters for each point from A to D. The AKAP variables include the vertical distance between A–B, A–C, B–C, and A–D; the horizontal distance between A–B, A–C, and A–D; the Euclidean distance between A–D; the time interval between A–B, between A–B–C, between A–B–C–D; total time; and mean velocity of the Euclidean distances between A–B, A–C, and A–D (Fig. 2(b))¹⁶.

Statistical analysis

As this was a pilot study, a formal sample size calculation was not conducted. The main aim of this pilot study was to determine feasibility of the 4-channel NMES for the main study and to estimate the effect size to inform a future sample size calculation for the main clinical trial. Therefore, a sample of 24 participants was chosen (12 in each group). Considering a dropout rate of 10%, the final sample size was determined to be a total of 26 participants²⁰.

Descriptive statistics were used to summarize participant characteristics using mean (SD) or number (percentage) as appropriate. Continuous data were assessed for skewness by visual inspection and using a normality test. The Mann − Whitney test was used to compare the two groups. The paired t-test or Wilcoxon signed rank test (if the assumptions of parametric statistical analysis were not satisfied) was used to compare data from the initial and follow-up evaluations. The Statistical Package for the Social Sciences software (version 25.0; SPSS Inc., Chicago, IL, USA) was used for all statistical analyses. Statistical significance was set at P < 0.05.

Ethics approval and consent to participate

The study protocol was approved by the institutional review board of each hospital (IRB No.: E-1806/475-002, 2018-07-012, JEJUNUH 2018-07-010, J-1810-064-979, DFH19DPOS033) and all methods were performed in accordance with relevant guidelines and regulations. All patients or their representatives provided written informed consent prior to study participation. The study was also approved by the Ministry of Food and Drug Safety in Republic of Korea.