Freezing Of Gait Questionnaire Scores Research Articles

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

Abnormal functional connectivity density involvement in freezing of gait and its application for subtyping Parkinson's disease.

The pathophysiological mechanisms at work in Parkinson's disease (PD) patients with freezing of gait (FOG) remain poorly understood. Functional connectivity density (FCD) could provide an unbiased way to analyse connectivity across the brain. In this study, a total of 23 PD patients with FOG (PD FOG + patients), 26 PD patients without FOG (PD FOG- patients), and 22 healthy controls (HCs) were recruited, and their resting-state functional magnetic resonance imaging (rs-fMRI) images were collected. FCD mapping was first performed to identify differences between groups. Pearson correlation analysis was used to explore relationships between FCD values and the severity of FOG. Then, a machine learning model was employed to classify each pair of groups. PD FOG + patients showed significantly increased short-range FCD in the precuneus, cingulate gyrus, and fusiform gyrus and decreased long-range FCD in the frontal gyrus, temporal gyrus, and cingulate gyrus. Short-range FCD values in the middle temporal gyrus and inferior temporal gyrus were positively correlated with FOG questionnaire (FOGQ) scores, and long-range FCD values in the middle frontal gyrus were negatively correlated with FOGQ scores. Using FCD in abnormal regions as input, a support vector machine (SVM) classifier can achieve classification with good performance. The mean accuracy values were 0.895 (PD FOG + vs. HC), 0.966 (PD FOG- vs. HC), and 0.897 (PD FOG + vs. PD FOG-). This study demonstrates that PD FOG + patients showed altered short- and long-range FCD in several brain regions involved in action planning and control, motion processing, emotion, cognition, and object recognition.

Combination of Clinical and Gait Measures to Classify Fallers and Non-Fallers in Parkinson's Disease.

Individuals with mild-to-moderate PD were classified as fallers (n = 31) or non-fallers (n = 96) based on the previous 12 months' falls. Clinical measures (demographic, motor, cognitive and patient-reported outcomes) were assessed with standard scales/tests, and gait parameters were derived from wearable inertial sensors (Mobility Lab v2); participants walked overground, at a self-selected speed, for 2 min under single and dual-task walking conditions (maximum forward digit span). Receiver operating characteristic curve analysis identified measures (separately and in combination) that best discriminate fallers from non-fallers; we calculated the area under the curve (AUC) and identified optimal cutoff scores (i.e., point closest-to-(0,1) corner). Single gait and clinical measures that best classified fallers were foot strike angle (AUC = 0.728; cutoff = 14.07°) and the Falls Efficacy Scale International (FES-I; AUC = 0.716, cutoff = 25.5), respectively. Combinations of clinical + gait measures had higher AUCs than combinations of clinical-only or gait-only measures. The best performing combination included the FES-I score, New Freezing of Gait Questionnaire score, foot strike angle and trunk transverse range of motion (AUC = 0.85). Multiple clinical and gait aspects must be considered for the classification of fallers and non-fallers in PD.

Objective quantification of responses to the clinical pull-test in people with Parkinson’s disease

BackgroundPostural instability can occur in the later-stages of Parkinson’s disease (PD). The clinical pull-test is scored on a 0–4 scale on the Unified Parkinson’s disease rating scale (UPDRS), with postural instability scored 2 or higher. This ordinal scale does not adequately track progression in early-PD or predict development of postural instability. Research QuestionTo develop a test that quantifiably measured the backward stepping response on the pull-test in early-PD. MethodsParticipants (35 controls and 79 PD participants) were prospectively enrolled in this study. Participants stepped backwards with each shoulder pull at four strengths on an instrumented gait mat. Four spatiotemporal parameters (reaction-time, step-back-time, step-back-distance, step-back-velocity) were quantified using Protokinetics Movement Analysis Software. Spatiotemporal pull-test parameters were compared to standard PD measures using linear regression and correlation coefficients. Repeated measures analysis was used to determine group differences in pull-test parameters. In a subset of participants repeated testing was performed and Bland-Altman plots were used to determine reproducibility of the pull-test parameters. ResultStep-back-distance and step-back-velocity were inversely related to motor UPDRS and freezing of gait questionnaire scores. PD participants had shorter step-back-distance than controls adjusted for age and sex. Repeat assessments in 16 participants, on average 0.7 years apart, showed good agreement on most of the quantified parameters. SignificanceThe backward stepping response in PD participants was quantifiable, reproducible, and related to disease severity and could be used to quantify progression towards postural instability in early-PD.

Validity and Reliability of the Thai Version of the Freezing of Gait Questionnaire in Individuals With Parkinson's disease.

To evaluate the validity and reliability of the Thai version of the Freezing of Gait Questionnaire (FOG-Q) in individuals with Parkinson's disease (PD). The FOG-Q was translated into Thai according to the standard process. Fifty-six individuals with PD participated in the study. The content validity was assessed using the content validity index (CVI). The construct validity was evaluated by correlating Thai FOG-Q with Thai version of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) items 2.13 and 3.11, Thai version of the Falls Efficacy Scale-International (FES-I), Timed Up and Go test (TUG) and Berg Balance Scale (BBS) using Spearman's correlation coefficient (rS). The correlation between Thai FOG-Q and clinical characteristics, for example, duration of PD and modified Hoehn and Yahr (mH&Y) stage was evaluated. Internal consistency and test-retest reliability were evaluated with Cronbach's alpha (Cα) and intraclass correlation coefficient (ICC), respectively. The Thai FOG-Q had high content validity (CVI=0.96). The mean FOG-Q score was 9.0±4.9. The construct validity showed a strong positive correlation with MDS-UPDRS item 2.13 (rS=0.81), and moderate correlations with MDS-UPDRS item 3.11, FES-I, and TUG (rS=0.42-0.60). A negative correlation with BBS was found (rS=-0.32). It had a moderate correlation with mH&Y stage (rS=0.40). The Thai FOG-Q had good internal consistency (Cα=0.87) with excellent test-retest reliability (ICC=0.91). The Thai FOG-Q has excellent validity and reliability. It is a useful instrument for the evaluation of FOG in individuals with PD.

Neuromelanin magnetic resonance imaging of substantia nigra and locus coeruleus in Parkinson's disease with freezing of gait.

The downregulation of monoamines, especially dopamine in substantia nigra (SN) and norepinephrine in locus coeruleus (LC), may be responsible for freezing of gait (FOG) pathological basis in Parkinson's disease (PD). Thirty-two Parkinson's disease patients with freezing of gait (PD-FOG), 32 Parkinson's disease patients without freezing of gait (PD-NFOG) and 32 healthy controls (HC) underwent neuromelanin magnetic resonance imaging (NM-MRI). The volume, surface area and contrast to noise ratio (CNR) of SN and LC were measured and compared. The correlation analyses were conducted between the measurements of SN and LC with clinical symptoms. We plotted the receiver operating characteristic (ROC) curve and determined the sensitivity and specificity of the CNR of SN and LC for discriminating the PD-FOG from the PD-NFOG. Both PD-FOG and PD-NFOG showed decreased volume, surface area and CNR of SN compared with HC. The PD-FOG exhibited decreased volume and surface area of LC compared with both PD-NFOG and HC groups, and decreased CNR of LC compared with HC group. The volume, surface area and CNR of SN were negatively correlated with the Unified Parkinson's Disease Rating Scale part III scores. The illness durations in PD patients were negatively correlated with the volume, surface area of SN, while not the CNR. And the volume and surface area of LC were negatively correlated with new freezing of gait questionnaire scores. ROC analyses indicated that the area under the curve (AUC) was 0.865 and 0.713 in the CNR of SN and LC, respectively, in PD versus HC, whereas it was 0.494 and 0.637 respectively, in PD-FOG versus PD-NFOG. Among these, for discriminating the PD from the HC, the sensitivity and specificity in the CNR of the SN was 90.6 and 71.9%, respectively, when the cut-off value was set at 2.101; the sensitivity and specificity in the CNR of the LC was 90.6 and 50.0%, respectively, when the cut-off value for CNR was set at 1.411. The dopaminergic changes in the SN were found across both PD-FOG and PD-NFOG, whilst LC noradrenergic neuron reduction was more evident in PD-FOG.

Subjective Assessments of Voice in Parkinson's Disease Subjects with and without STN-DBS Therapy.

The causal relation between STN-DBS and speech problems and the associated clinical features are in the incipient stages of being investigated. All the Parkinson's disease (PD) subjects with and without STN-DBS who applied to our movement disorders outpatient clinics between January 2022 and June 2022 and agreed to participate in the study were enrolled. The demographic data and clinical features were noted. Besides, the MDS-UPDRS was administered during the medication off-state in all subjects. All the participants completed the voice handicap index (VHI). Besides, the Freezing of Gait Questionnaire (FOGQ) and the quality of life (QoL) scales including the Parkinson's Disease Questionnaire (PDQ-39) and the Schwab and England Activities of Daily Living (ADL) scale were also administered to all the individuals. We have included 66 patients with PD (F/M = 23/43). Thirty-five patients were those with DBS therapy whereas 31 patients were without. The results of the comparative analyses between the patients with and without DBS therapy revealed that the DBS group had a higher disease duration (P = 0.006) and FOGQ scores (P = 0.008). The VHI scores did not differ between groups (P = 0.577), and the correlation analyses did not reveal an association between the VHI scores and the duration of DBS therapy. However, the VHI scores correlated with the disease duration as well as the FOG scores. We did not find convincing evidence supporting the increased risk of speech disturbance with STN-DBS therapy. We suggest that the frequent existence of speech disturbance in this patient subgroup with STN-DBS is associated with the classical nature of PD.

Impaired structural and reserved functional topological organizations of brain networks in Parkinson’s disease with freezing of gait

Freezing of gait (FOG) is a common disabling motor disturbance in Parkinson's disease (PD). Our study aimed to probe the topological organizations of structural and functional brain networks and their coupling in FOG. In this cross-sectional retrospective study, a total of 30 PD patients with FOG (PD-FOG), 40 patients without FOG, and 25 healthy controls (HCs) underwent clinical assessments and magnetic resonance imaging (MRI) scanning. Large-scale structural and functional brain networks were constructed. Subsequently, global and nodal graph theoretical properties and functional-structural coupling were investigated. Finally, correlations between the altered brain topological properties and freezing severity were analyzed in PD-FOG. For structural networks, at the global level, PD-FOG exhibited increased normalized characteristic path length (P=0.040, Bonferroni-corrected) and decreased global efficiency (P=0.005, Bonferroni-corrected) compared with controls, and showed reduced global (P=0.001, Bonferroni-corrected) and local (P=0.032, Bonferroni-corrected) efficiency relative to patients without FOG. At the nodal level, nodal efficiency of structural networks was reduced in PD-FOG compared with PD patients without FOG, located in the left supplementary motor area (SMA), gyrus rectus, and middle cingulate cortex (MCC) (all P<0.05, Bonferroni-corrected). Notably, altered global and nodal properties of structural networks were significantly correlated with Freezing of Gait Questionnaire scores [all P<0.05, false discovery rate (FDR)-corrected]. However, only an increase in local efficiency (P=0.003, Bonferroni-corrected) of functional networks was identified in PD-FOG compared with those without FOG. No significant structural-functional coupling was detected among the 3 groups. This study demonstrates the extensively impaired structural and relatively reserved functional network topological organizations in PD-FOG. Our results also provide evidence that the pathogenesis of PD-FOG is primarily attributable to network vulnerability established by crucial structural damage, especially in the left SMA, gyrus rectus, and MCC.

Efficacy of short pulse and conventional deep brain stimulation in Parkinson's disease: a systematic review and meta-analysis.

Deep brain stimulation (DBS) is a common treatment for Parkinson's disease. However, the clinical efficacy of short pulse width DBS (spDBS) compared with conventional DBS (cDBS) is still unknown. This meta-analysis investigated the effectiveness of spDBS versus cDBS in patients with PD. Four databases (PubMed, Cochrane, Web of Science, and Embase) were independently searched until October 2021 by two reviewers. We utilized the following scales and items: therapeutic windows (TW), efficacy threshold, side effect threshold, Movement Disorder Society-Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III off-medication score, Speech Intelligence Test (SIT), and Freezing of Gait Questionnaire (FOG-Q). The analysis included seven studies with a total of 87 patients. The results indicated that spDBS significantly widened the therapeutic windows (0.99, 95% CI = 0.61 to 1.38) while increasing the threshold amplitudes of side effects (2.25, 95% CI = 1.69 to 2.81) and threshold amplitudes of effects (1.60, 95% CI = 0.84 to 2.36). There was no statistically significant difference in UPDRS part III, SIT, and FOG-Q scores between spDBS and cDBS groups, suggesting that treatment with both cDBS and spDBS may result in similar effects of improved dysarthria and gait disorders. Compared with cDBS, spDBS is effective in expanding TW. Both types of deep brain stimulation resulted in improved gait disorders and speech intelligibility.

Altered Degree Centrality of Brain Networks in Parkinson's Disease With Freezing of Gait: A Resting-State Functional MRI Study.

Freezing of gait (FOG) in Parkinson's disease (PD) leads to devastating consequences; however, little is known about its functional brain network. We explored the differences in degree centrality (DC) of functional networks among PD with FOG (PD FOG+), PD without FOG (PD FOG–), and healthy control (HC) groups. In all, 24 PD FOG+, 37 PD FOG–, and 22 HCs were recruited and their resting-state functional magnetic imaging images were acquired. The whole brain network was analyzed using graph theory analysis. DC was compared among groups using the two-sample t-test. The DC values of disrupted brain regions were correlated with the FOG Questionnaire (FOGQ) scores. Receiver operating characteristic curve analysis was performed. We found significant differences in DC among groups. Compared with HCs, PD FOG+ patients showed decreased DC in the middle frontal gyrus (MFG), superior temporal gyrus (STG), parahippocampal gyrus (PhG), inferior temporal gyrus (ITG), and middle temporal gyrus (MTG). Compared with HC, PD FOG– presented with decreased DC in the MFG, STG, PhG, and ITG. Compared with PD FOG–, PD FOG+ showed decreased DC in the MFG and ITG. A negative correlation existed between the DC of ITG and FOGQ scores; the DC in ITG could distinguish PD FOG+ from PD FOG– and HC. The calculated AUCs were 81.3, 89.5, and 77.7% for PD FOG+ vs. HC, PD FOG– vs. HC, and PD FOG+ vs. PD FOG–, respectively. In conclusion, decreased DC of ITG in PD FOG+ patients compared to PD FOG– patients and HCs may be a unique feature for PD FOG+ and can likely distinguish PD FOG+ from PD FOG– and HC groups.

Integrating Structural and Functional Interhemispheric Brain Connectivity of Gait Freezing in Parkinson's Disease.

Freezing of gait (FOG) has devastating consequences for patients with Parkinson's disease (PD), but the underlying pathophysiological mechanism is unclear. This was investigated in the present study by integrated structural and functional connectivity analyses of PD patients with or without FOG (PD FOG+ and PD FOG–, respectively) and healthy control (HC) subjects. We performed resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging of 24 PD FOG+ patients, 37 PD FOG– patients, and 24 HCs. Tract-based spatial statistics was applied to identify white matter (WM) abnormalities across the whole brain. Fractional anisotropy (FA) and mean diffusivity (MD) of abnormal WM areas were compared among groups, and correlations between these parameters and clinical severity as determined by FOG Questionnaire (FOGQ) score were analyzed. Voxel-mirrored homotopic connectivity (VMHC) was calculated to identify brain regions with abnormal interhemispheric connectivity. Structural and functional measures were integrated by calculating correlations between VMHC and FOGQ score and between FA, MD, and VMHC. The results showed that PD FOG+ and PD FOG– patients had decreased FA in the corpus callosum (CC), cingulum (hippocampus), and superior longitudinal fasciculus and increased MD in the CC, internal capsule, corona radiata, superior longitudinal fasciculus, and thalamus. PD FOG+ patients had more WM abnormalities than PD FOG– patients. FA and MD differed significantly among the splenium, body, and genu of the CC in all three groups (P < 0.05). The decreased FA in the CC was positively correlated with FOGQ score. PD FOG+ patients showed decreased VMHC in the post-central gyrus (PCG), pre-central gyrus, and parietal inferior margin. In PD FOG+ patients, VMHC in the PCG was negatively correlated with FOGQ score but positively correlated with FA in CC. Thus, FOG is associated with impaired interhemispheric brain connectivity measured by FA, MD, and VMHC, which are related to clinical FOG severity. These results demonstrate that integrating structural and functional MRI data can provide new insight into the pathophysiological mechanism of FOG in PD.

Association between freezing of gait and bone mineral density in patients with Parkinson's disease.

Parkinson's disease (PD) patients are at risk for developing bone health problems, and freezing of gait (FOG) in PD is associated with a high risk of falling and fracture. This study aimed to determine the association between FOG and bone mineral density (BMD) in patients with PD. We included 148 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q), and BMD was measured by dual-energy X-ray absorptiometry. Of 148 PD patients, 102 (68.9%) had FOG. PD patients with FOG were older and had longer disease duration, higher levodopa equivalent dose, higher modified Hoehn and Yahr stage, higher Unified PD Rating Scale motor score, higher FOG-Q score, higher total Non-Motor Symptom Scale score, and lower BMD scores in the femoral neck area than those without FOG. Pearson correlation analysis revealed that age, sex, body mass index, and age at onset were significantly correlated with areal BMDs in all areas. FOG-Q scores correlated negatively with areal BMDs in the total hip area and femoral neck, but not with areal BMD in the lumbar spine. Multivariate regression analysis showed that FOG-Q score was significantly correlated with areal BMD in the femoral neck, but not with areal BMDs in the lumbar spine or total hip. FOG in PD patients correlates significantly with BMD in the femoral neck area. Therefore, PD patients with FOG should be screened for osteoporosis.

Clinical and Oculomotor Correlates With Freezing of Gait in a Chinese Cohort of Parkinson's Disease Patients.

Accumulating evidence suggests that freezing of gait (FOG) is a unique gait disturbance in Parkinson’s disease (PD), and its pathophysiology is not fully elucidated. The present study aims to investigate the clinical and oculomotor associations with FOG in Chinese PD patients. From Jan 2017 to Dec 2019, a total of 210 PD patients were consecutively registered for FOG evaluation based on item-3 of the Freezing of Gait Questionnaire (FOGQ). We explored the demographic, motor, and non-motor symptom differences in FOG positive (PD+FOG, n = 45) vs. negative (PD-FOG, n = 165) group. In addition, 40 PD patients and 37 healthy controls (HC) also underwent oculomotor test via videonystagmography (VNG). Visually guided saccade (VGS) latency, saccade accuracy and gain in smooth pursuit eye movement (SPEM) at three frequencies of horizontal axis were compared among PD+FOG (n = 20), PD-FOG (n = 20), and HC (n = 37). Compared with PD-FOG, PD+FOG had longer disease duration, more severe motor symptoms, lower cognitive scores, more severe depressive and autonomic impairments, as well as higher daily levodopa equivalent dosage. FOG occurred more frequently in patients with wearing-off. VNG subgroup analysis demonstrated that PD+FOG had prolonged saccade latency and decreased saccade accuracy relative to PD-FOG or HC. SPEM gain at 0.1 and 0.2 Hz was also decreased in PD+FOG compared with HC. Furthermore, prolonged saccade latency was correlated with higher FOGQ scores in PD patients. Our results verify that PD with FOG patients suffer from more severe motor and non-motor symptoms, indicating more extensive neurodegeneration. Prolonged saccade latency could be a practical oculomotor parameter both for identification and progression of FOG in PD.

Repetitive transcranial magnetic stimulation improves Parkinson\u2019s freezing of gait via normalizing brain connectivity

Robust, effective treatments for Parkinson’s freezing of gait remain elusive. Our previous study revealed beneficial effects of high-frequency rTMS over the supplementary motor area. The present study aims to explore the neural mechanisms of rTMS treatments utilizing novel exploratory multivariate approaches. We first conducted a resting-state functional MRI study with a group of 40 Parkinson’s disease patients with freezing of gait, 31 without freezing of gait, and 30 normal controls. A subset of 30 patients with freezing of gait (verum group: N = 20; sham group: N = 10) who participated the aforementioned rTMS study underwent another scan after the treatments. Using the baseline scans, the imaging biomarkers for freezing of gait and Parkinson’s disease were developed by contrasting the connectivity profiles of patients with freezing of gait to those without freezing of gait and normal controls, respectively. These two biomarkers were then interrogated to assess the rTMS effects on connectivity patterns. Results showed that the freezing of gait biomarker was negatively correlated with Freezing of Gait Questionnaire score (r = −0.6723, p < 0.0001); while the Parkinson’s disease biomarker was negatively correlated with MDS-UPDRS motor score (r = −0.7281, p < 0.0001). After the rTMS treatment, both the freezing of gait biomarker (0.326 ± 0.125 vs. 0.486 ± 0.193, p = 0.0071) and Parkinson’s disease biomarker (0.313 ± 0.126 vs. 0.379 ± 0.155, p = 0.0378) were significantly improved in the verum group; whereas no significant biomarker changes were found in the sham group. Our findings indicate that high-frequency rTMS over the supplementary motor area confers the beneficial effect jointly through normalizing abnormal brain functional connectivity patterns specifically associated with freezing of gait, in addition to normalizing overall disrupted connectivity patterns seen in Parkinson’s disease.

A Randomized, Controlled Trial of Exercise for Parkinsonian Individuals With Freezing of Gait.

Exercises with motor complexity induce neuroplasticity in individuals with Parkinson's disease (PD), but its effects on freezing of gait are unknown. The objective of this study was to verify if adapted resistance training with instability - exercises with motor complexity will be more effective than traditional motor rehabilitation - exercises without motor complexity in improving freezing-of-gait severity, outcomes linked to freezing of gait, and brain function. Freezers were randomized either to the adapted resistance training with instability group (n = 17) or to the active control group (traditional motor rehabilitation, n = 15). Both training groups performed exercises 3 times a week for 12 weeks. The primary outcome was the New Freezing of Gait Questionnaire. Secondary outcomes were freezing of gait ratio (turning task), cognitive inhibition (Stroop-III test), motor signs (Unified Parkinson's Disease Rating Scale part-III [UPDRS-III]), quality of life (PD Questionnaire 39), anticipatory postural adjustment (leg-lifting task) and brain activation during a functional magnetic resonance imaging protocol of simulated anticipatory postural adjustment task. Outcomes were evaluated before and after interventions. Only adapted resistance training with instability improved all the outcomes (P < 0.05). Adapted resistance training with instability was more effective than traditional motor rehabilitation (in improving freezing-of-gait ratio, motor signs, quality of life, anticipatory postural adjustment amplitude, and brain activation; P < 0.05). Our results are clinically relevant because improvement in the New Freezing of Gait Questionnaire (-4.4 points) and UPDRS-III (-7.4 points) scores exceeded the minimally detectable change (traditional motor rehabilitation group data) and the moderate clinically important difference suggested for PD, respectively. The changes in mesencephalic locomotor region activation and in anticipatory postural adjustment amplitude explained the changes in New Freezing of Gait Questionnaire scores and in freezing-of-gait ratio following adapted resistance training with instability, respectively. Adapted resistance training with instability is able to cause significant clinical improvement and brain plasticity in freezers. © 2020 International Parkinson and Movement Disorder Society.

Validation of the Freezing of Gait Questionnaire in patients with Parkinson's disease treated with deep brain stimulation.

The Freezing of Gait Questionnaire (FoG-Q) is a fast and sensitive assessment tool for freezing (FoG). The objective of the study is for validation of a Czech version of FoG-Q. A further, explorative aim was to examine what FoG-Q indicates about the presence and severity of gait impairment in patients treated with DBS in their full OFF state. The study was a cross-sectional validation study. We translated FoG-Q following standardized validation protocol. We assessed 35 patients with PD and STN DBS using history taking, UPDRS, Hoehn and Yahr staging, Mini Mental State Examination, Frontal Assessment Battery, FoG-Q, Short Falls Efficacy Scale International, and Beck Depression Inventory, Second Edition. UPDRS III, clinical and instrumental gait assessment, was repeated OFF MED/DBS OFF and OFF MED/DBS ON. Internal consistency of FoG-Q was excellent (α = 0.91) as well as convergent (significant correlations with UPDRS II item 14, UPDRS III item 29, several TUG parameters, and FoG Score) and divergent validity (no association with UPDRS I). OFF MED/DBS OFF, the total FoG-Q score correlated with UPDRS III items 29, 30, and PIGD subscore, step time variability, and negatively with step length and velocity. Limitation of the study is a relatively small sample size. In conclusion, the Czech translation of FoG-Q is valid. With respect to gait and balance, FoG-Q does, to a certain extent, reflect the native state of the disease in patients treated with high frequency STN DBS.

Long-term effect of subthalamic nucleus deep brain stimulation on freezing of gait in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN DBS) is effective against freezing of gait (FOG) in Parkinson's disease (PD); however, whether this effect persists over the long term is debated. The aim of the current study was to investigate the long-term effect of STN DBS on FOG in patients with PD. Data on 52 cases in which PD patients received bilateral STN DBS were obtained from a prospective registry. The authors blindly analyzed FOG incidence and its severity from the videotapes of a 5-m walking task at the baseline and at the 1-, 2-, and 5- or 7-year follow-up visits. They also compared the axial score from the Unified Parkinson's Disease Rating Scale (UPDRS) part III, UPDRS part II (UPDRS-II) item 14, and the FOG questionnaire (FOG-Q). Postoperatively, video-based FOG analysis and the axial score were evaluated under 4 conditions (off-medication/off-stimulation, off-medication/on-stimulation, on-medication/off-stimulation, and on-medication/on-stimulation), and UPDRS-II item 14 and the FOG-Q score were evaluated under 2 conditions (off-medication/on-stimulation and on-medication/on-stimulation). During the off-medication state, the on-stimulation condition improved FOG outcomes, except for video-based FOG severity, up to the last follow-up compared with the baseline. Video-based FOG outcomes and the axial score during the off-medication state were improved with the on-stimulation condition up to the last follow-up compared with the off-stimulation condition. During the on-medication state, the on-stimulation condition did not improve any FOG outcome compared with the baseline; however, it improved video-based FOG outcomes up to the 2-year follow-up and the axial score up to the last follow-up compared with the off-stimulation condition. Our findings suggest that STN DBS has a long-term effect on FOG in the off-medication state. However, STN DBS did not show a long-term effect on FOG in the on-medication state, although it had a short-term effect until the 2-year follow-up.

Association of freezing of gait and clinical features in patients with Parkinson's disease.

Freezing of gait (FOG) is a disabling symptom that affects the quality of life of patients with Parkinson's disease (PD) and its pathophysiology is not fully understood yet. The aim of the present study is to evaluate the relationship between FOG and other clinical characteristics in patients with PD. The clinical characteristics, modified Hoehn and Yahr (mHY) stages, Unified Parkinson's Disease Rating Scale (UPDRS) scores, and total Freezing of Gait Questionnaire (FOG-Q) scores of the patients with PD were recorded. FOG-Q item 1.3 was used to evaluate patients with or without FOG. A total of 65 patients with PD (32 with FOG and 33 without FOG) were included to the study. Disease duration was longer, mHY stages were higher, bradykinesia and dyskinesia were more common in patients with FOG compared to patients without (p = 0.001, p = 0.036, p = 0.019 and p = 0.021; respectively). Patients with FOG had lower UPDRS part III tremor subscores (p = 0.020), although gait, postural balance subscores and part IV motor fluctuations scores were higher (p = 0.003, p = 0.023 and p<0.001; respectively). A positive correlation was found between FOG-Q scores and mHY stages (p < 0.001), UPDRS part II and III total scores (p = 0.020 and p = 0.001) and part III bradykinesia, and gait and postural balance subscores (p = 0.003, p = 0.036 and p = 0.003, respectively), and part IV motor fluctuation scores (p = 0.006). The results of the present study point to an association between FOG and bradykinesia rather than tremor, prolonged disease duration and advanced disease stage reflecting its association with more severe and extensive neurodegenerative processes.

High-frequency rTMS over the supplementary motor area improves freezing of gait in Parkinson's disease: a randomized controlled trial

IntroductionFreezing of gait (FOG) contributes to falls in Parkinson's disease (PD), but robust, effective treatments remain elusive. There is evidence indicating that the supplementary motor area (SMA) plays an important role in the pathogenesis of FOG and may therefore be a potential neuromodulation target. The present study explored the clinical efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the SMA on FOG in PD patients. MethodsA group of 30 PD patients with FOG were enrolled in a randomized, double-blind, sham-controlled trial. Patients were randomly allocated 2:1 to receive ten sessions of either real (N = 20) or sham (N = 10) 10 Hz rTMS over SMA. The patients were assessed at baseline (T0), after the 5th (T1) and 10th (T2) sessions, and then 2 weeks (T3) and 4 weeks (T4) after the last session. The primary clinical outcome was the Freezing of Gait Questionnaire score (FOGQ), with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor scores (MDS-UPDRS III) and Timed Up and Go test as secondary clinical outcomes. All the assessments were carried out at the “ON” state. ResultsWith a four week's follow-up, there were significant interaction effects in the FOGQ (effect of group*time, p = 0.04), MDS-UPDRS III (p = 0.02) and several gait variables (total duration, p < 0.01; cadence, p = 0.04; turn duration, p = 0.01; and turn to sit duration, p = 0.02). Post-hoc analyses revealed a significantly decreased FOGQ score at T2 and T4, and significant improvements of MDS-UPDRS III and gait variables at T1, T2, T3 and T4 in the rTMS group. No significant improvements were found in the sham group. ConclusionHigh-frequency rTMS over SMA may ultimately serve as an add-on therapy for alleviating FOG in PD patients.

Clinical effects of robot-assisted gait training and treadmill training for Parkinson's disease. A randomized controlled trial.

Although gait disorders strongly contribute to perceived disability in people with Parkinson's disease, clinical trials have failed to identify which task-oriented gait training method can provide the best benefit. Freezing of gait remains one of the least investigated and most troublesome symptoms. We aimed to compare the effects of robot-assisted gait training and treadmill training on endurance and gait capacity in people with Parkinson disease; the secondary aim was to compare the effect of the treatments in people with freezing and/or severe gait disability and assess changes in overall disease-related disability and quality of life. Outpatients with Parkinson disease (Hoehn and Yahr stage≥2) were randomly assigned to receive 20 sessions of 45-min gait training assisted by an end-effector robotic device (G-EO System) or treadmill training. Outcome assessments were the 6-min walk test, Timed Up and Go test, Freezing of Gait Questionnaire, Unified Parkinson's Disease Rating Scales and Parkinson's Disease Quality of Life Questionnaire-39 administered before (T0) and after treatment (T1). We included 96 individuals with Parkinson disease: 48 with robot-assisted gait training and 48 treadmill training. Both groups showed significant improvement in all outcomes. As compared with baseline, with robot-assisted gait training and treadmill training, endurance and gait capacity were enhanced by 18% and 12%, respectively, and motor symptoms and quality of life were improved by 17% and 15%. The maximum advantage was observed with the Freezing of Gait Questionnaire score, which decreased by 20% after either treatment. On post-hoc analysis, dependent walkers benefited more than independent walkers from any gait training, whereas freezers gained more from robot-assisted than treadmill training in terms of freezing reduction. Repetitive intensive gait training is an effective treatment for people with Parkinson disease and can increase endurance and gait velocity, especially for those with severe walking disability. Advantages are greater with robot-assisted gait training than treadmill training for individuals with freezing of gait - related disability.