Table 1.
Summary characteristics of the cross-sectional included studies.
| Study and Country | Participants | Subtypes of PSP and criteria for PSP | Cognitive and Mood status | Assessment | Walking aids (YES/NO) and type | Measurement Tool | Clinical motor outcomes/other outcomes | Objective gait outcomes | Objective balance outcomes | Correlational analysis | Author’s conclusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Ali et al. (20) USA | PSP: n=16, age (70.4±7.1 years), disease duration (4.4±2.8 years), men (n=10), women (n=6) HC: n=25, age (72.7±6.6 years), women (n=25) | PSPRS UPDRS-III Richardson’s syndrome (n=10), Cortico-basal syndrome (n= 3), Parkinsonism predominant (n=2), Speech and language disorder (n=2), Frontal predominant (n=1) | Not Reported | Patients were not on any dopaminergic medications. | Not reported | Force plate, 3D motion system | UPDRS-III scores were average 50 (range: 20, 85) for PSP, while PSPRS scores average was 39 (range:24, 58). | PSP patients walked with a slower velocity, lower cadence, shorter stride, and step lengths, and reduced single support times compared to healthy older adults. Total sagittal plane ROM in the hip, knee and ankle showed significant decreased ROM (p<0.05) when comparing patients with PSP to healthy adults | PSP exhibited significantly larger amplitudes of COP displacement (7.0±3.9) compared to the healthy individuals (3.4±2.2) for the eyes open task (p<0.01). PSP patients exhibited less displacement in the ML (2.2±1.1) but significantly increased displacement in the AP (7.2±4.0) direction compared to the healthy individuals (5.1±1.6) in the eyes closed task (p<0.04). | There were significant correlations between PSPRS and UPDRS with gait velocity, (rs=0.597, p=0.015; rs=0.756, p=0.001), total support (rs=0.591, p=0.016; rs=0.546, p=0.029), single support (rs=0.557, p=0.025; rs=0.500, p=0.049), and step length (rs=0.561, p=0.024; rs=0.764, p=0.001). Significant correlations were also found for UPDRS only and initial double support (rs=0.582, p=0.018) and hip ROM (rs=0.728, p=0.003). | Patients with PSP have increased anteroposterior sway, slower gait velocity, wider stance, and lower cadence. The gait stability ratio and Romberg ratio was high consistent with postural imbalance and increased reliance on vision for stability, experienced by PSP patients. Motion analysis metrics correlated with clinical scales reflecting that they are a marker of disease severity. |
| Amano et al. (10) USA | PSP: n= 12, age (66 ± 8.0 years), disease duration (6.5 ± 4.9 years), men (n=5), women (n=7) PD: n=12, age (64 ± 7 years), disease duration (7.8 ± 7.1 years), men (n=5), women (n=7) HC: n=12, age (67 ± 7 years), men (n=5), women (n=7) | NINDS-SPSP UPDRS Subtypes not reported | Not reported. | ON-assessment | Not reported | 3D motion system | UPDRS-III (PSP: 49.6±10.4; PD: 23.5±8.5). UPDRS PIGD (PSP:6.33±2.46; PD:3.33±2.42) | The PSP group exhibited significantly reduced cadence, gait velocity, step length, and step duration compared to the other two groups. | COP displacement AP (PSP 0.71±1.55, PD –1.14±0.71, HC –2,61±1.56) COP displacement ML (PSP 2.46±3.62, PD –0.81±1.03, HC –1.85±1.28) The maximum distance between COP and COM significantly differed among the groups. | Not reported. | The study identified significant differences in specific biomechanical characteristics during gait initiation and gait between PSP and PD. Abnormally shorter and slower step during GI in PSP was observed and may result from the inability to execute APAs. The compensatory GI strategy, characterized by diminished posterior COP shift and weight shift toward the stance limb, is therefore very distinct from PD and paradoxically induces lateral postural instability. PSP gait, which prioritizes stability over mobility, may be compensatory and could be the consequence of lateral instability and fear of falling. |
| Amboni et al. (14) Italy | PSP Total: n= 21, age (67.8 ± 7.4 years), disease duration (2.5 ± 1.1 years), men (n=11), women (n=10) PD Total: n=83, age (63.2 ± 8.5 years), disease duration (3.4 ± 3.2 years), men (n=55), women (n=28) Early PSP: n= 12, age (63.5 ± 5.9 years), disease duration (1.7 ± 0.4 year), men (n=7), women (n=5) De novo PD: n=27, age (63.3 ± 8.7 years), disease duration (< 1 year), men (n=17), women (n=10) | PSPRS NDS-UPDRS-III Richardson’s syndrome (n=11), Parkinsonism predominant (n=5), Freezing of gait predominant (n=4) | MMSE: PSP Total (25.1 ± 3.0), PD Total (26.8 ± 2.3), Early PSP (25.5 ± 2.7), De novo PD (26.9 ± 2.2) | ON-assessment | No | SMART DX system (3D motion system + force plate) | MDS-UPDRS-III (PD Total): 19.46±8.99; MDS-UPDRS-III (De novo PD): 12.85±6.17; PSP-RS-V (PSP total): 5.81±2.73; PSP-RS-VI (PSP total): 7.28±4.55; PSP-RS-V (Early PSP): 5,.3±2.87 PSP-RS-VI (Early PSP): 6.58±3.73 | Compared to PD, PSP patients exhibited reduced velocity and cadence, shortened step and cycle lengths, increased cycle duration mainly due to longer double support stance phase duration, and increased swing duration variability during single task. During dual task, PSP patients exhibited the same gait features as those displayed during the single task, except for swing duration and step length variability. Compared to newly diagnosed PD patients, early PSP patients exhibited reduced velocity and cadence, shortened step and cycle length, and increased cycle duration; these patients tended to rely on a longer double support stance phase during single task. During dual task, early PSP patients exhibited a gait pattern similar to that during the single task except for swing duration and swing duration variability. | Not reported. | Not reported. | The study demonstrates that quantitative gait evaluation clearly distinguishes PSP patients from PD patients since the earliest stages of disease. These findings indicate that gait analysis could be a candidate as a reliable biomarker in both clinical and research setting. In addition, results may offer speculative clues for conceiving early disease-specific rehabilitation strategies. |
| Dale et al. (19) USA | PSP: n= 12, age (70 ± 6.3 years), disease duration (2.6 ± 1.5 years), men (n=6), women (n=6) PD: n=12, age (67.8 ± 7.3 years), disease duration (8.1 ± 5.6 years), men (n=6), women (n=6) HC: n=12, age (not reported), men (not reported), women (not reported) | NINDS-SPSP UPDRS Subtypes not reported | Not reported | OFF-assessment | Not reported | NeuroCom Balance Master Clinical Research System | UPDRS-III (PD): 33.7 ± 7.5; UPDRS-III (PSP): 34.4 ± 9.1; PSP-RS: 26.9 ± 11.9 | Not reported | PSP displaced their CoP significantly less than PD subjects (p≤0.006) and slightly less than healthy subjects during the forward translation of the platform. The CoP of subjects with PSP remained more posterior after the platform shifted back to the initial position compared to subjects with PD (p≤0.01), while only a slight difference was found compared to healthy subjects. When the body was displaced backward by toes-up platform rotation, PSP exerted a significantly larger destabilizing plantar-flexion torque (as evidenced by forward CoP displacement) than subjects with PD (p≤0.008), and only slightly larger compared to healthy subjects. | Not reported | The study demonstrates inappropriate adaptive postural motor control with excessive forward CoP displacement in response to toes-up surface tilts in PSP. |
| De Vos et al. (22) United Kingdom | PSP: n= 21, age (71 years), disease duration (2 years), men (n=12), women (n=9) PD: n=20, age (66.4 years), disease duration (11.4 years), men (n=11), women (n=9) Healthy Control: n=39, age (67.1 years), men (19), women (20) | UPDRS-III Richardson’s syndrome (n=4), Parkinsonism predominant (n=17) | MoCA: PSP (mean 22), PD (mean 26.6), HC (mean 28.5). MMSE: PSP (mean 25.8), PD (mean 26.6), HC (mean 27.6). | ON-assessment | Not reported | IMUs | UPDRS-III (PSP: 44.6; PD: 27.9) | Gait cadence distinguished PSP from PD and HC showing a high specificity (90 %) when using 6 sensors (Mobility Lab™, APDM) over the lumbar spine, sternum, left and right wrists, and left and right feet. | Mean postural sway velocity in the coronal plane during the sway test, mean time taken to sit from standing during the timed up-and-go (TUG) task, mean time taken to turn during the gait task, mean time taken to turn during the TUG task, standard deviation of time taken to turn during the gait task distinguished PSP from PD and HC showing a high specificity (90 %) when using 6 sensors (Mobility Lab™, APDM) over the lumbar spine, sternum, left and right wrists, and left and right feet. | Not reported | A wearable inertial measurement unit array and machine learning methods can accurately differentiate PSP from PD and from control. |
| Hatanaka et al. (12) Japan | PSP: n= 20, age (71,8 ±5.9 years), disease duration (3.4±1.8 years), men (n=14), women (n=6) PD: n=124, age (68.4 ± 11.2 years), disease duration (6.7±7.4 years), men (n=64), women (n=60) HC: n=24, age (73.7 ± 3.8 years), men (5), women (19) | NINDS-SPSP Subtypes not reported | Not Reported | ON-assessment | No | Portable triaxial accelerometer rhythmogram device | Not reported | Compared with the accelerogram of HC, both PSP and PD patients showed a smaller amplitude (acceleration) and increased shuffle frequency over a certain period, indicating a reduced acceleration and shorter step time. Compared with HC (1.10 ± 0.22 m/s), velocity was reduced in PSP patients (0.83 ± 0.23 m/s, p < 0.01 vs. control) and in all PD patients (0.89 ± 0.24 m/s, p < 0.01). The cadence of the PSP patients (100.5 ± 11.5 steps/min, p < 0.01 vs. control) was significantly lower than HC (115.9 ± 11.2 steps/min) and of PD patients (109.3 ± 15.9 steps/min, # p < 0.05 vs. PSP). The vertical displacement of PSP patients (2.3 ± 1.1 cm) was significantly lower than HC (5.6 ± 1.7 cm, p< 0.01 vs. PSP), all PD patients (4.4 ± 2.2 cm, p< 0.01 vs. PSP). | Not reported | There was a close relationship between cadence and acceleration for all groups. The relationships were positive and linear with R2 values > 0.4 (controls, R2 = 0.54; PSP patients, R2 = 0.56; PD patients, R2 = 0.48). | Lower vertical displacement could be a feature of gait disturbance in PSP patients, and which could be used to better discriminate PSP from PD patients. |
| Liao et al. (17) USA/ Germany | PSP-tVOR: n=9, age (median 68 years, range 61-75), men (n=5), women (n=4) PSP-VEMPs: n=10, age (median 68 years, range 60-76), men (n=7), women (n=3) HC-tVOR: n=9, age (median 67 years, range 60-72), men (n=6), women (n=3) HC-VEMPs: n=30, age (median 67 years, range 56-80), men (n=19), women (n=11) | NINDS-SPSP Subtypes not reported | Not reported | Not reported | Not reported | Magnetic search coil + Infrared reflection system | Not reported | Not reported | Vestibulo-ocular reflex: Patients with PSP tend to show smaller values of aVOR RR than control subjects, but with some overlap of data. For tVOR, patients with PSP’s RR were smaller than controls during far viewing, but with overlap of data. However, during near-viewing conditions, PSP RR values for tVOR were significantly smaller than controls, with no overlap of data. The range of tVOR RR of our control subjects was similar to those previously reported during rapid oscillatory head translations, but responses of patients with PSP during near viewing were, on average, only 12% of controls. Vestibulo-spinal reflex: The median P1-N1 amplitude of all 60 ears of the HC was 149 μV (range: 11.6 to 466); that of all 20 ears of the patients with PSP 54.3 μV (range: 16.8 to 214). | Not reported | The study results indicate that abnormal otolith-mediated reflexes may be at least partly responsible for frequent falls in progressive supranuclear palsy. |
| Ondo et al. (18) USA | PSP: n= 20, age (68 ±5.4 years), disease duration (3.5±1.5 years), men (n=8), women (n=12) PD: n=20, age (65.4 ± 5.3 years), disease duration (4.4±1.5 years), men (n=13), women (n=7) HC: n=20, age (69 ± 3 years), men (8), women (12) | Clinical criteria Subtypes not reported | Not reported | OFF-assessment | Not reported | Computerized posturography | PSP group was significantly worse than both other groups (POAG, z = −5.13 [P<.001]; POAB, z = −5.02 [P<.001]). The FR measures showed significant differences among the groups (F2 = 48.2; P<.001, univariate ANOVA). PSP group scores were significantly lower than those of both other groups (P<.001), and that PD group scores were significantly lower than those of controls (P= .003). | Not reported. | The total stability score (SOT) showed that PSP group total scores were worse than those of both other groups (P<.001). CT sway was greater in the PSP than in the PD or control groups (P=.02); and total LOS measures of path time to target (P<.001) and path sway from a straight line to target (P<.001) were significantly prolonged in the PSP compared with the PD and control groups. The PSP group tended to have better performance with lateral movement and worse with anterior/posterior movements | Total LOS correlated with total POA scores (Pearson correlation, 0.67). | Results demonstrate significant abnormalities of postural control in patients with PSP that were markedly worse than those seen in a PD group matched for age and disease duration, and in age-matched healthy controls. Although clinical assessments also showed significant differences among the groups, CP more accurately discriminated early PSP from early PD. |
| Palmisano et al. (24) Italy | PSP: n= 20, age (66.6 ±4.7 years), disease duration (5.3±3.1 years), men (n=6), women (n=14) HC: n=25, age (65.1 ± 3.4 years), men (9), women (14) | PSPRS All had Richardson’s Syndrome | Not reported | OFF-assessment | Not reported | Force plate, 3D motion system | PSPRS Total (33 ± 9,7); PSPRS limb motor (5.6± 1.9); PSPRS gait and midline (9.3 ± 2.7) Brain metabolic measures: there are six hypometabolic brain regions in the PSP group: the right dorsolateral prefrontal cortex, the left supplementary motor area, the middle cingulate cortex, the left caudate Nucleus, the medial thalamus and the Midbrain. | Not reported. | CoM movement was significantly impaired in the PSP group as revealed by lower values of the velocity and acceleration of the CoM at the unloading phase end, as well as the velocity and position of the CoM with respect to the CoP at the stance foot toe-off. Patients with PSP also showed a significantly reduced first step length, average and maximum velocity compared to HC. | In healthy controls, the velocity, acceleration and position of the CoM with respect to the CoP at IMB end were influenced by AM and BoS parameters. In the same cohort, during the unloading phase the CoP displacement and the average and maximum velocity of the CoP in the ML direction were influenced by the BoS. In the PSP group, no correlations of GI parameters with BoS measurements were found. The study also showed a significant correlation between the PSPRS subscores related to motor impairment (i.e., Limb motor, and Gait and midline) and the kinematic measurements of all GI phases. The caudate nucleus, together with the middle cingulate cortex, correlated with the velocity of the CoM at the end of the unload phase and, together with the thalamus, with the distance between CoP and CoM at stance foot toe-off. | The results of the study provide evidence to support the hypothesis that dysfunctional postural control at GI in PSP patients involves poor APA programming and execution. Multiple brain regions of the supraspinal locomotor network specifically contributes in a principled, controlled manner to an efficient GI. |
| Pasha et al. (23) India | PSP: n= 29, age (60.8 ± 8.2 years), disease duration (2.2±1.2 years), men (n=21), women (n=8) HC: n=30, age (59.8 ± 7.6 years), men (17), women (13) | NINDS-SPSP Richardson’s syndrome (17); Parkinsonism predominant (12) | MMSE: PSP (24.8±5.04); HC (29.7 ± 1.0) | ON and OFF-assessments | Not reported | Dynamic posturography | PSPRS, TPG, and TPT scores were found to be statistically significant among the subtypes of PSP (P=0.045; P=0.031; and P=0.037) while UPDRS-III was not significant (P=0.7). The PSP-R subtype performed poorly in comparison to the PSP-P subtype on these scales. MRI measures: The PSP-R subtype, compared to the PSP-P subtype, had more often radiological signs such as HBS (P < 0.001), MGS (P <0.008), and GCA (P <0.001). | The mean values of balance indices were almost similar between the subtypes of PSP as compared to controls. The most significant of all the parameters in DP was LOS (P < 0.001) and the PSP-R subtype had lower scores. | There was a significant correlation of PSPRS with BBS (r = −0.642, P < 0.001), TPT (r = −0.516, P=0.004), TPG (r = −0.449, P=0.013), and TPB (r = −0.505, P=0.004). LOS-BW-LT had significant positive correlation with BBS (r = 0.381, P=0.038), TPB (r = 0.417, P=0.022), and TPT scores (r = 0.362, P=0.049). There was a significant correlation of the midbrain axial AP diameter (r = 0.4; P=0.03) and the ratio of midbrain to pons with BBS (r = 0.4; P=0.02), indicating that these are worse in patients with midbrain atrophy. In DP, API correlated negatively with the midbrain axial AP diameter (r = −0.5; P=0.01) and midbrain area (−0.39; P=0.03). The LOS-BW correlated positively with the area of midbrain (r = 0.49; P=0.001) and the midbrain to pons ratio (r = 0.57; r = 0.001). In addition, LOS-BW-LT correlated with the midbrain to pons ratio (r = 0.37; P=0.43) | The study shows that the measurements of balance severity in the PSP-P group correlate with the predominant pathology of the midbrain (midbrain atrophy); while in PSP-R subtype, the balance abnormalities could be a result of pathology in different or overlapping areas. | |
| Picillo et al. (16) Italy | PSP-RS: n= 10, age (69.9 ±7.6 years), disease duration (2.5 ± 1.17 years), men (n=5), women (n=5) PSP (other subtypes): n=9, age (66.5 ± 5.9 years), disease duration (2.33 ± 1 years), men (n=6), women (n=3) | MDS-UPDRS-III PSPRS Richardson’s syndrome (n=10), Parkinsonism predominant (n=5), Freezing of Gait predominant (n=4) | MoCA: PSP-R (15.3 ± 5.7), PSP-other (19.5 ± 4.2). | Not Reported | No | SMART DX system (3D motion system + force plate) | PSPRS (PSP-R: 34.9 ± 13.8; PSP-other: 28.33 ± 9.38) | PSP-R showed worse gait parameters than did other subtypes of PSP during single task. In detail, PSP-RS exhibited reduced cadence and increased cycle duration (p=0.018), mainly due to longer stance duration (p=0.034). For the dual task analysis, PSP-RS continued to roughly show the same gait features displayed during the single task. In addition, PSP-RS showed increased stance phase and reduced swing phase (p=0.031). There was a trend for significance for greater variability in step length (p=0.069) and lower velocity (p= 0.098) in PSP-RS. | Not reported | In patients with PSP-RS, constructional apraxia and right ideomotor apraxia presented an inverse relationship with cycle and swing duration and a direct correlation with cadence (p<0.05). TMT parts A and B showed a direct correlation with swing duration and cycle duration, respectively (p<0.05). No significant correlations were shown for other subtypes of PSP. | PSP-RS presents greater gait dynamic instability since the earliest stages of disease compared with other subtypes of PSP. In addition, these findings indicate that gait quantitative evaluation can help to distinguish PSP-RS from other subtypes of PSP. |
| Raccagni et al. (6) Austria | PSP: n= 12, age (67.4 ±8.7 years), disease duration (5.0±3.6 years), men (n=9), women (n=3) PD: n=25, age (66.6 ± 7.9 years), disease duration (7.5±4.5 years), men (n=13), women (n=12) HC: n=25, age (63.7 ± 9.7 years), men (13), women (12) | MDS-UPDRS-III PSPRS Subtypes not reported | Not reported | ON-assessment | Not reported | Wearable sensor-based gait analysis system | MDS-UPDRS-III (PSP: 41.7±15.5; PD: 31.7±9.3) | Gait speed was significantly reduced in PD patients (1.20 ± 0.23m/s) compared to controls 1.38 ± 0.20 m/s; p=.011) and even more impaired in APD patients (0.98 ± 0.18 m/s). 1.38 ± 0.20 m/s; p=.011) and even more impaired in APD patients (0.98 ± 0.18 m/s). Results showed significant difference for stride length in controls (1.47 ± 0.15 m), PD (1.27 ± 0.22 m) and APD (1.11 ± 0.18m). Maximum toe clearance was significantly reduced in PD (7.8 ± 2.6 cm; p=.001) and APD patients (6.9 ± 2.8 cm; p=.000) compared to controls (10.8 ± 3.3 cm) | Not reported | Stride length correlated with PSP-RS scores in the PSP patients (r=0.59, p=.021). There was a significant correlation between maximum toe clearance and MDS-UPDRS-3 (r =−.444, p=.026) in APD. | The significant difference of objective gait parameters among patient groups suggests that sensor-based technology may support and complement the clinical assessment provided by validated rating scales. |
| Ricciardi et al. (21) Italy | PSP: n= 7, age (70.5 ±8.9 years), disease duration (2.6±0.5 years), men (n=3), women (n=4) De novo PD: n=15, age (63.3 ± 6.7 years), disease duration (0), men (n=11), women (n=4) Stable PD: n=24, age (61.9 ± 6.7 years), disease duration (5.9±2.5), men (17), women (7) | MDS-UPDRS-III PSPRS Richardson’s syndrome (n=4); Parkinsonism predominant (n=3) | Not reported | Not reported | No | SMART DX system (3D motion system + force plate) | MDS-UPDRS-III (De novo PD: 14.3±7.5; Stable PD: 21.3±6.3), PSPRS (16.8±3.3) | The PSP group showed the highest sensitivity and specificity among all patients, both overcame the threshold of 90% and, particularly, the specificity went beyond 95%. De Novo PD’s sensitivity and specificity scores were remarkable as well as the previous group, getting close to the value of 90%. The Stable PD group achieved the lowest sensitivity (between 65% and 70%) but high specificity; this metric, that represents the capacity to classify correctly the examined group but not the others, overcame the value of 90%. | Not reported | Not reported | The study’s methodology allowed a good overall accuracy and re- markable sensitivities in the classification of PSP and De Novo PD patients. This indicates that the present approach could provide the clinician with a reliable, low-cost, non-invasive tool to distinguish early PSP from PD, in the first phases of the diseases’ courses when the diagnosis of atypical forms of Parkinsonism is challenging. |
| Selge et al. (13) Germany | PSP: n= 38, age (69 ±6.3 years), disease duration (3.5 ± 2.2), men (n=20), women (n=18) iNPH: n=27, age (63.3 ± 6.7 years), disease duration (1.9 ± 1.6), men (n=21), women (n=6) HC: n=38, age (68.9 ± 7.6 years), men (20), women (18) | NINDS-SPSP Subtypes not reported | MMSE (PSP: 27.3 ± 3.1; iNPH; 23.4 ± 3.3) and FAB (PSP: 13.9 ± 2.3) | Not reported | No | GAITRite (6.7-m-long pressure-sensitive carpet system) | PSPRS (31.1±8.9) | Compared to HC, both patients with PSP and those with iNPH had a significantly inferior gait performance. Compared with patients with PSP, the gait of patients with iNPH was characterized by a lower velocity (p=0.001) and shorter stride length (p < 0.001). The main differences were a more broad-based gait in iNPH (p < 0.001) and a higher CV of stride time in PSP (p=0.009). Cognitive dual task led to a significant impairment of gait in all 3 groups. Patients with PSP were significantly more sensitive to dual-task perturbation than patients with iNPH. Especially gait velocity was clearly more reduced in patients with PSP, while the reduction in patients with iNPH was comparable to that in HC. Motor dual task led to a significant decrease of gait velocity and stride length in patients with PSP, but to a lesser extent than cognitive dual task. | Not reported | In patients with PSP, the CV of stride length increased at the time when the CV of step width decreased (r = −0.338). This correlation was not seen in patients with iNPH or HC. | Compared with patients with PSP, the gait of patients with iNPH was slower and broader based; gait variability was higher in patients with PSP; and patients with PSP were more sensitive to dual-task perturbation. Under motor dual task, patients with iNPH tended to even improve. |
| Sintini et al. (25) USA | PSP: n= 19, age (71 ±7 years), disease duration (4.7 ± 2.6), men (n=11), women (n=8) | MDS-UPDRS-III PSPRS Richardson’s syndrome (n=13), Parkinsonism predominant (n=3), Cortico-basal syndrome (n= 1), Speech and language disorder (n=2) | Not reported | Not reported | No | Force plate, 3D motion system | PSPRS (39 ± 10); MDS-UPDRS-III (49 ± 17) Neuroimaging measures: MRI atrophy, white matter tracts degeneration and flortaucipir-PET uptake were measured. Typically, DTI-FA and MRI volumes are reduced in PSP relative to healthy controls, while DTI-MD and flortaucipir SUVR are increased. | Stride length, cadence, velocity and step width were measured. Compared to HC, velocity, cadence and stride length are typically lower in PSP patients, while step width and stride length coefficient of variation are typically higher. | Gait stability ratio, total support, initial double support, postural imbalance and dynamic stability were measured. Compared to HC, velocity, cadence, stride length and dynamic stability are typically lower in PSP patients, while step width, gait stability ratio, total support, initial double support, postural imbalance, and stride length coefficient of variation are typically higher. | PSP rating scale and MDS-UPDRS III scores strongly correlated to velocity, stride length, gait stability ratio and dynamic stability. The gait midline sub-scale score of the PSP rating scale strongly correlated to velocity, dynamic stability, and stride length CV. Velocity was negatively correlated to DTI-MD in the cerebellar peduncle and positively correlated to volume in the supplementary motor area, superior frontal, and lateral parietal cortex. Velocity was positively correlated to subcortical flortaucipir-PET uptake (subthalamic nucleus, pallidum, caudate, red nucleus). Cadence was positively associated with DTI-MD in various tracts, especially the sagittal stratum and the cingulum (hippocampus). Stride length was strongly associated with DTI-MD in the body and splenium of the corpus callosum and with volume in the precentral, superior, and medial frontal, and parietal cortex. Step width was strongly related to DTI-MD in the superior cerebellar peduncle and flortaucipir-PET uptake in the dentate nucleus, cerebellum, and pons. Total support time was higher (i.e., more impaired gait) in patients with lower DTI-FA in many tracts, particularly the posterior thalamic radiation, sagittal stratum, external capsule and splenium of the corpus callosum. Greater postural imbalance with eyes open correlated to reduced metabolism in the cerebellar crus and lateral parietal cortex and greater postural imbalance with eyes closed correlated to reduced metabolism in the dentate nucleus. Lower dynamic stability strongly correlated with lower volume in the lateral parietal cortex. | The study showed that gait and postural impairments in PSP are associated with imaging abnormalities on different sets of regions and tracts that belong to the PSP system of neurodegeneration and the supraspinal locomotor network. The results suggest that gait and balance impairments might be driven by different mechanisms in PSP. |
| Takamatsu et al. (15) Japan | PSP: n= 27, age (73.4 ± 5.3 years), disease duration (5.0±4.4 years), men (n=19), women (n=8) PD: n=25, age (74.2 ± 5.3 years), disease duration (4.7±3.4 years), men (n=14), women (n=11) HC: n=25, age (73.1 ± 5.3 years), men (11), women (14) | UPDRS-III PSPRS-V and VI Richardson’s syndrome (n=19), Progressive gait freezing (n=5) Parkinsonism predominant (n=3) | Not reported | Not reported | Not reported | WalkWay MW-1000 (2.4-m-long pressure-sensitive carpet system) | PSPRS-V mean (3); PSPRS-VI mean (9); UPDRS-III mean (25) | Walking speed (PSP:75.1± 19.1, HC: 119±21, P < 0.001), CV of cadence (PSP: 5.3 ± 3.9, HC: 2.6±2.5, P=0.001), step length (PSP: 42.2 ± 8.9, HC: 62.2 ± 7.1, P < 0.001), step width (PSP:10.6 ± 3.5, HC:7.7 ± 3.4, P=0.007), foot angle (PSP: 9.6 ± 6.9, HC: 5,8 ± 4.8, P=0.010), time of stance phase (PSP: 0.73±0,12, HC: 0.63± 0,08, P=0.031), and double supporting phase (PSP: 0.15±0,04, HC: 0.11±0,02, P < 0.001) showed significant differences between PSP and HC. CV of cadence (PSP: 5.3 ± 3.9, PD: 2.8±2.6, P=0.015) and foot angle (PSP: 9.6 ± 6.9, PD: 5.1±4.7, P=0.016) showed significant differences between PSP and PD. | Not reported | Not reported | Results suggests that the gait of patients with PSP was unstable with parkinsonism and wide-based, which might be similar to combining features of PD and cerebellar disorders. |
AP=anteroposterior; APAs = anticipatory postural adjustments; aVOR = angular vestibulo-ocular reflex; BBS = Berg Balance scale; BOS = base of support; COP=center of pressure; COM = center of mass; CP=Computerized posturography; CV = coefficient of variation; DP=dynamic posturography; DTI-FA = Diffusion tensor imaging—fractional anisotropy; DTI-MD = Diffusion tensor imaging—mean diffusivity; GI = gait initiation; HC = Healthy Control; iNPH = idiopathic normal pressure hydrocephalus; LOS = limits of stability; MDS-UPDRS-III = Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III motor subscale score; ML = mediolateral; MMSE = Mini Mental state examination. MoCA = Montreal Cognitive Assessment; MRI = magnetic resonance imaging; NINDS-SPSP=National Institute of Neurological Disorders and Society for Progressive Supranuclear Palsy criteria for PSP; PD = Parkinson’s disease; POA = performance-oriented assessments; POAB = performance-oriented assessment for balance; POAG = performance-oriented assessment for gait; PSP=Progressive Supranuclear Palsy; PSPRS = PSP rating scale; PSPRS-V = PSP rating scale-limb motor subscale; PSPRS-VI = PSP rating scale—gait and midline subscale; RR = responsivity ratio; SOT: sensory organization testing; SUVR = standard uptake value ratios; TPB, TPG and TPT = Tinetti performance-oriented mobility assessment (POMA) balance, gait and total; tVOR = translational vestibular-ocular reflex; UPDRS-III = Unified Parkinson’s Disease Rating Scale part III motor subscale score.