Procedures
All subjects completed the experimental protocol. One patient was not able to perform five repetitions of each static assessment of standing balance performance due to fatigue. Three repetitions of each assessment were performed instead.
Two patients were able to perform a semi-tandem stance for 60 s with the non-paretic leg ahead of the paretic leg, ten patients were able to perform a semi-tandem stance with the non-paretic leg a small step in front of the paretic leg, and three patients were able to perform a semi-tandem stance with the paretic leg a small step in front of the non-paretic leg. Nine healthy controls were able to perform a tandem stance with the dominant leg ahead, and one healthy control performed a semi-tandem stance with the dominant leg ahead.
Successfulness of Blinding Procedures
When asked to indicate the sham condition at the end of the protocol, four out of ten healthy controls answered correctly, five incorrectly, and one could not make a choice. From the patients, seven answered correctly, six incorrectly, and two patients could not make a choice.
Possible Side Effects, Fatigue
No subjects reported headaches or nausea during any of the sessions. Three healthy controls reported to be somewhat fatigued, but no differences in VAS on fatigue between sham: median (md) = 0, interquartile ranges (iqr) = 0–0.15 and cb_tDCS: md = 0, iqr = 0–0, were found, z = − 0.54, p = 0.60. Eleven patients reported a higher VAS on fatigue after stimulation, but no differences were found between the sham: md = 1.1, iqr = 0–3; contra-lesional: md = 1, iqr = 0–2.6; and ipsi-lesional: md = 1.3, iqr = 0–2.1, χ2 = 0.98, p = 0.61 conditions. Only one patient reported 7 out of 100 points on the VAS for depressed mood at the start of one of the sessions; no increase was reported after stimulation.
Baseline Differences Between Patients and Healthy Controls
Characteristics of both groups are displayed in Table 1. Healthy subjects and patients did not differ significantly in age, weight, and height. Patients had a lower score on the BBS md = 50, iqr = 48–53, as well as on the EmNSA-LE: md = 38, iqr = 34–39 and were slower on the TUG: mean = 14.3 s, sd = 7.9 s, compared to healthy controls (BBS—md = 56, iqr = 56–56, p < 0.01; EmNSA-LE—md = 39, iqr = 39–40, p = 0.02; TUG—mean = 6.1, sd = 0.99, p < 0.01).
Table 1 Baseline characteristics and clinical assessments The baseline CoP parameters are displayed in Fig. 3. Patients showed significant larger excursion on all baseline CoP parameters for the eyes open; ACoP: mean healthy = 2.90 mm, sd = 0.47, mean patients = 4.17 mm, sd = 1.53, CI of the mean difference = − 2.16 to − 0.38, t(17.6) = − 3.01, g = 1.00; varCoP: healthy = 3.67 mm, sd = 0.58, patients = 5.35 mm, sd = 1.99, CI = − 2.83 to − 0.53, t(17.3) = − 3.07, g = 1.02; range: healthy = 20.68 mm, sd = 0.22, patients = 32.21 mm, sd = 0.42, CI = − 18.88 to − 4.17, t(16.4) = − 3.31, g = 31.37; VCoP: md healthy = 7.10 mm/s, iqr = 5.88–7.81, md patients = 10.78 mm/s, iqr = 8.80–15.48, CI = 0.43–0.78, ratio due to log transformation, t (23) = 0.02, g = 1.71; varVCoP: md healthy = 5.79 mm/s, iqr = 5.79–6.62, patients = 8.81 mm/s, iqr = 7.76–13.87, CI = 0.40 to 0.75, ratio due to log transformation, t(23)=0.02, g = 1.57, all p < 0.05.
This was also the case for the eyes closed position when compared to healthy age-matched controls; ACoP: mean healthy = 3.66 mm, sd = 0.65, mean patients = 5.71 mm, sd = 2.02, CI = − 3.23 to − 0.88, t(18) = − 3.67, g = 1.22; varCoP: healthy = 4.66 mm, sd = 0.83, patients = 7.21 mm, sd = 2.57, CI = − 4.06 to − 1.07, t (18)= − 3.60, g = 1.20, range: healthy = 26.49 mm, sd = 5.23, patients = 42.16 mm, sd = 15.20, CI = − 24.59 to − 6.74, t(18.5) = − 3.68, g = 1.23; VCoP: healthy = 11.62 mm/s, sd = 2.28, patients = 20.44 mm/s, sd = 8.91, CI = − 13.91 to − 3.73, t(16.6) = −3.66, g = 1.20; varVCoP: healthy = 9.42 mm/s, sd = 1.94, patients = 17.26 mm/s, sd = 7.56, CI = − 12.16 to − 3.51, t(16.6) = − 3.83, g = 1.26, all p < 0.05. For the (semi-)tandem stance position, no significant differences were found between patients and healthy controls; ACoP: md healthy = 5.17 mm, iqr = 4.65–6.34, md patients = 5.86 mm, iqr = 4.65–7.89, ratio due to log transformation, CI = 0.63 to 1.15, t (23) = 0.33; varCoP: md healthy = 6.55 mm, iqr = 5.80–8.45, md patients = 7.31 mm, iqr = 5.82–10.09, ratio due to log transformation, CI = 0.63 to 1.15, t[23]=0.33; range: md healthy = 40.29 mm, iqr = 36.65–55.94, md patients = 47.72 mm, iqr = 33.14–64.73, ratio due to log transformation, CI = 0.64 to 1.17, t(23) = 0.37; md VCoP: healthy 30.25 = mm/s, iqr = 26.22–32.48, md patients = 26.33 mm/s, iqr = 23.90–36.83, U = 61, z = − 0.78; varVCoP: md healthy 26.24 = mm/s, iqr = 21.40–28.96, md patients = 23.84 mm/s iqr = 19.47–31.16, U = 71, z = − 0.22, all p > 0.5.
Effect of Stimulation on CoP Parameters
The tested model revealed no significant changes in CoP comp-score associated with cb_tDCS in the eyes open: β = 0.02, CI = − 0.09 to 0.12, p = 0.73; eyes closed: β = 0.08, CI = − 0.01 to 0.16, p = 0.07; and tandem: β = − 0.08, CI = − 0.41–0.25, p = 0.64 for the healthy controls, see Table 2. Adding the stimulation order to the model did not change β values with more than 10%.
In the patient group, a significant association between contra-lesional stimulation and a decrease in CoP comp-score in the tandem position was found: β = − 0.25, CI = − 0.48 to − 0.03, p = 0.03. Post hoc analysis showed a significant decrease in ACoP: β = − 0.86, CI = − 1.58 to − 0.15, p = 0.02; varCoP: β = − 1.10, CI = − 1.93 to − 0.26, p = 0.01; range: ratio due to log transformation, β = 0.94, CI = 0.90–0.98, p = 0.01; and VCoP: ratio due to log transformation, β = 0.97, CI = 0.94 to 0.99, p = 0.02 but not in varVCoP: ratio due to log transformation, β = 0.97, CI = − 0.93 to 1.01, p = 0.11, see Fig. 4. The GEE-model constructed for the eyes open position revealed a significant association between ipsi-lesional stimulation and a lower CoP comp-score: β = − 0.09, CI = − 0.18 to − 0.01, p = 0.03; after correcting for randomization order, the association was no longer significant and changed to β = 0.00, CI = − 0.09 to 0.90, p = 0.94.
No changes in CoP comp-score in the eyes closed position associated with cb_tDCS were found for patients, contra-lesional stimulation: β = 0.02, CI = − 0.11–0.16, p = 0.73 and ipsi-lesional stimulation: β = − 0.01, CI = − 0.19–0.16, p = 0.89. Adding the stimulation order to the model changed β values with more than 10% to contra-lesional stimulation: β = 0.06, CI = − 0.10–0.22, p = 0.44 and ipsi-lesional stimulation: β = 0.09, CI = − 0.08–0.26, p = 0.30 (Fig. 5). See Table 2 for an overview of the corresponding β values and confidence intervals.
Performance on the Tracking Task
The healthy controls showed a significantly higher tracking task performance during the second measurement, m = 99.33, sd = 0.57, β = 0.80, CI = 0.10 to 1.50, p = 0.03, as compared to the first measurement, m = 98.53, sd = 1.31. No effect of stimulation was found β = 0, CI = − 0.70 to 0.70, p = 1.0.
The patient group showed a significantly higher tracking task performance during the second measurement; m = 92.90, sd = 7.5, with a ratio of β = 1.62, CI = 1.23 to 2.14, p < 0.01 and on the third measurement, m = 94.60, sd = 6.11, with a ratio of β = 2.06, CI = 1.51 to 2.80, p < 0.01 as compared to the first measurement, m = 88.60, sd = 9.29.
No effect of contra-lesional stimulation was found with a ratio due to log transformation of β = 1.15, CI = 0.89 to 1.50, p = 0.29, nor an effect of ipsi-lesional stimulation, β = 1.16, CI = 0.91–1.49, p = 0.23.
Responders and Non-responders
Ten patients had a reduction in CoP comp-score in the tandem stance in response to contra-lesional stimulation (responders). Five patients did not show a change when compared to sham stimulation (non-responders). The group responders did not differ on any of the baseline CoP comp-scores, fatigue level, or clinical characteristics from the non-responders (see Table 3). Out of the five non-responders, two patients could be identified as responders on the ipsi-lesional stimulation, while five patients responded to both stimulation types.
Table 3 Differences in characteristics and clinical assessments between responders and non-responders Table 2 Overview of the tested models for the effect of stimulation