Gait and upper limb variability in Parkinson’s disease patients with and without freezing of gait

Patients with Parkinson’s disease (PD) and freezing of gait (FOG) (freezers) demonstrate high gait variability. The objective of this study was to determine whether freezers display a higher variability of upper limb movements and elucidate if these changes correlate with gait. We were the first group to compare directly objectively measured gait and upper limb movement variability of freezers between freezing episodes. Patients with objectively verified FOG (n = 11) and PD patients without FOG (non-freezers) (n = 11) in a non-randomized medication condition (OFF/ON) were analyzed. Uncued antiphasic finger tapping and forearm diadochokinetic movements were analyzed via three-dimensional ultrasound kinematic measurements. Gait variability of straight gait was assessed using ground reaction forces. Freezers had shorter stride length (p = 0.004) and higher stride length variability (p = 0.005) in the medication OFF condition. Movement variability was not different during finger tapping or diadochokinesia between the groups. There was a trend towards more freezing of the upper limb during finger tapping for the freezers (p = 0.07). Variability in stride length generation and stride timing was not associated with variability of upper limb movement in freezers. Our findings demonstrate that: (1) freezers have a higher spatial gait variability between freezing episodes; (2) freezing-like episodes of the upper limb occur in PD patients, and tend to be more pronounced among freezers than non-freezers for finger tapping; (3) spatial and temporal upper extremity variability is equally affected in freezers and non-freezers in an uncued task. Upper limb freezing is not correlated to lower limb freezing, implicating a different pathophysiology.     

The effects of gait impairment with and without freezing of gait in Parkinson's disease

ObjectiveTo compare the effects of gait impairment without freezing of gait (FOG) versus FOG without gait impairment in Parkinson’s disease (PD) on disability and quality of life.BackgroundFOG is frequently characterized as the major cause of gait-related disability in PD. However, gait impairment may also result from other PD symptoms including slowing, motor asymmetry, gait variability, dystonia or stooped posture.MethodsThe Unified Parkinson’s Disease Rating Scale (UPDRS), Older Americans Resources and Services Disability Scale (OARS) and the SF-12 Health Status Survey were used to evaluate patients with PD. Responses to UPDRS Items #14 (Freezing) and # 29 (Gait) were used to create 4 subgroups: 1) No FOG or gait impairment, 2) FOG, no gait impairment, 3) Gait impairment, no FOG, and 4) Both FOG and gait impairment. Disease severity, disability, and quality of life were compared across the subgroups with ANOVAs, and between subgroups with t-tests.Results916 PD patients were divided into 4 subgroups based on their gait and freezing score (#1: n = 213, #2: n = 41, #3: n = 323 and #4: n = 339). Total UPDRS progressively increased from Group 1 through Group 4 (1 = 25.2, 2 = 33.7, 3 = 39.2, 4 = 59.2; p < 0.001). Motor UPDRS also progressively increased (1 = 17.4, 2 = 19.7, 3 = 26.9, 4 = 36.5; p < 0.0001). Similarly, disability and health-related quality of life progressively increased from Group 1 through Group 4 (Total OARS: 1 = 15.3, 2 = 17.2, 3 = 18.9, 4 = 28.4; p < 0.001). Group 3 (Gait impairment, no FOG) showed greater disease severity than Group 2 (FOG, no gait impairment; Total and Motor UPDRS; p < 0.05), but the difference did not reach significance for disability or quality of life.ConclusionsGait impairment without FOG was associated with greater disease severity than FOG without gait impairment. The combination of gait impairment and FOG was associated with the greatest disease severity and disability. These results show differential effects of diverse features of gait impairment in PD and demonstrate the importance of gait features unrelated to freezing.     

Thalamic volume and related visual recognition are associated with freezing of gait in non-demented patients with Parkinson's disease

BackgroundThe pathophysiology of freezing of gait (FOG) in non-demented Parkinson's disease (PD) patients remains poorly understood. Recent studies have suggested that neurochemical alterations in the cholinergic systems play a role in the development of FOG. Here, we evaluated the association between subcortical cholinergic structures and FOG in patients with non-demented PD.MethodsWe recruited 46 non-demented patients with PD, categorized into PD with (n = 16) and without FOG (n = 30) groups. We performed neuropsychological test, region-of-interest-based volumetric analysis of the substantia innominata (SI) and automatic analysis of subcortical brain structures using a computerized segmentation procedure.ResultsThe comprehensive neuropsychological assessment showed that PD patients with FOG had lower cognitive performance in the frontal executive and visual-related functions compared with those without freezing of gait. The normalized SI volume did not differ significantly between the two groups (1.65 ± 0.18 vs. 1.68 ± 0.31). The automatic analysis of subcortical structures revealed that the thalamic volumes were significantly reduced in PD patients with FOG compared with those without FOG after adjusting for age, sex, disease duration, the Unified PD Rating Scale scores and total intracranial volume (left: 6.71 vs. 7.16 cm³, p = 0.029, right: 6.47 vs. 6.91 cm³, p = 0.026). Multiple linear regression analysis revealed that thalamic volume showed significant positive correlations with visual recognition memory (left: β = 0.441, p = 0.037, right: β = 0.498, p = 0.04).ConclusionsThese data suggest that thalamic volume and related visual recognition, rather than the cortical cholinergic system arising from the SI, may be a major contributor to the development of freezing of gait in non-demented patients with PD.     

Is freezing of gait in Parkinson's disease related to asymmetric motor function?

Freezing of gait (FOG) is a disabling phenomenon common in patients with advanced Parkinson's disease (PD). The cause of FOG is unclear. The objective of this study was to explore a novel hypothesis stating that FOG is related to asymmetric motor performance. We compared PD patients that experience FOG episodes (PD+FOG) with PD patients that do not (PD-FOG) and studied the relationship of FOG to asymmetry in gait and in rhythmic hand movement performance to determine whether potential FOG-related gait asymmetry is unique to walking or whether it is systemic. Subjects were tested in an "off" (unmedicated) and again in an "on" (medicated) state. Gait was more asymmetric in PD+FOG than in PD-FOG during "off" state (p = 0.005) and during "on" (p = 0.016). Rhythmicity of foot swing in one leg was correlated with the other leg in PD-FOG but not in PD+FOG. There was no difference in asymmetry in performance of rhythmic hand movements between the two groups. No correlation was found between asymmetry of clinical symptoms and gait asymmetry. Taken together, the results of this study suggest that bilateral uncoordinated gait and marked gait asymmetry, but not asymmetry in motor performance in general, are associated with FOG.     

Freezing of Gait Questionnaire: validity and reliability of the Swedish version

Background – Patient‐reported assessments of freezing of gait (FOG) in Parkinson’s disease (PD), such as the FOG questionnaire (FOGQ), are needed because FOG is difficult to assess objectively. However, the measurement properties of the FOGQ have been sparsely assessed. Aim – To assess the measurement properties of the Swedish FOGQ, and to explore relationships between FOGQ scores and other aspects of PD. Methods – Thirty‐seven people with PD were assessed with the FOGQ, Unified PD Rating Scale (UPDRS), Hoehn and Yahr (HY), Falls‐Efficacy Scale [FES(S)], timed gait tests, and the SF‐36 physical functioning (PF) scale. Results – Mean (SD) FOGQ item scores ranged between 1.3 and 2.1 (1.2–1.5); corrected item–total correlations ranged between 0.80 and 0.94. Reliability was 0.95. Mean (SD) and median (q1–q3) FOGQ scores were 9.6 (7.4) and 10 (2–15). Floor and ceiling effects were ≤5.4%. FOGQ correlated strongest with UPDRS part II (ADL), UPDRS item 14 (freezing), and HY (r_S 0.65–0.66). FOGQ scores correlated with PD duration, the Timed Up and Go test, dyskinesia, motor fluctuations, FES(S), and PF scores (r_S 0.40–0.62). Fallers had higher FOGQ scores than non‐fallers (median 12.5 vs 5.0). Conclusion – Data support the measurement properties of the Swedish FOGQ by replicating and extending previous psychometric reports.     

Serum uric acid levels and freezing of gait in Parkinson’s disease

Uric acid (UA) is a natural antioxidant and iron scavenger in the human body, which has been hypothesized to exert an anti-oxidative effect in Parkinson’s disease (PD). This study aimed to investigate the relationship between serum UA levels and freezing of gait (FOG) in PD. A total of 321 Chinese PD patients with fasting serum UA evaluated were included in the cross-sectional study. Demographics, clinical features, and therapeutic regimen were collected. The Unified PD Rating Scale (UPDRS) III and Hoehn and Yahr (H and Y) stage were used to evaluate the severity of disease, and the Frontal Assessment Battery (FAB) and Montreal Cognitive Assessment (MoCA) scales were used to assess the cognitive function. Patients with FOG showed lower proportion of male, longer disease duration, lower body mass index, lower concentrations of serum UA, higher total levodopa equivalent daily dosage, higher UPDRS III score, greater median H and Y stage, lower scores of FAB and MoCA, and higher frequencies of motor fluctuation, dyskinesia, falls, and festination compared to patients without FOG (P < 0.05). The binary logistic regression model indicated that high UPDRS III score (OR = 1.049, P < 0.001), fluctuation (OR = 2.677, P = 0.035), dyskinesia (OR = 6.294, P = 0.003), festination (OR = 3.948, P < 0.001), falls (OR = 7.528, P < 0.001), and low serum UA levels (OR = 0.990, P < 0.001) were associated with FOG. Our study suggests that low serum UA concentration is associated with the occurrence of FOG in PD.     

Treadmill gait training improves baroreflex sensitivity in Parkinson’s disease

Background

Partial weight supported treadmill gait training (PWSTT) is widely used in rehabilitation of gait in patient with Parkinson’s Diseases (PD). However, its effect on blood pressure variability (BPV) and baroreflex sensitivity (BRS) in PD has not been studied.

Aim

To evaluate the effect of conventional and treadmill gait training on BPV components and BRS.

Methods

Sixty patients with idiopathic PD were randomized into three groups. Twenty patients in control group were on only stable medication, 20 patients in conventional gait training (CGT) group (Stable medication with CGT) and 20 patients in PWSTT group (Stable medication with 20 % PWSTT). The CGT and PWSTT sessions were given for 30 min per day, 4 days per week, for 4 weeks (16 sessions). Groups were evaluated in their best ‘ON’ states. The beat-to-beat finger blood pressure (BP) was recorded for 10 min using a Finometer instrument (Finapres Medical Systems, The Netherlands). BPV and BRS results were derived from artifact-free 5-min segments using Nevrocard software.

Results

BRS showed a significant group with time interaction (F = 6.930; p = 0.003). Post-hoc analysis revealed that PWSTT group showed significant improvement in BRS (p < 0.001) after 4 weeks of training. No significant differences found in BPV parameters; systolic BP, diastolic BP, co-variance of systolic BP and low frequency component of systolic BP.

Conclusions

Four weeks of PWSTT significantly improves BRS in patients with PD. It can be considered as a non-invasive method of influencing BRS for prevention of orthostatic BP fall in patients with PD.     

The spectrum of preclinical gait disorders in early Parkinson’s disease: subclinical gait abnormalities and compensatory mechanisms revealed with dual tasking

Patients with early Parkinson’s disease (PD) may not complain of gait difficulties but subtle gait abnormalities may be revealed as part of a “preclinical gait syndrome” when they are challenged by dual tasks. 21 early PD patients (n = 21, mean age 63.5 years, H&Y 1.62, disease duration <5 years, mean UPDRS-III 7.7) who did not have gait complaints were as compared to age- and gender-matched healthy controls (n = 21). Memory function was not different between the two groups. Under normal walking conditions, there were no significant differences in gait parameters between the patients and the control group. In both groups, normalized gait velocity decreased in response to dual tasking in a parallel fashion (p < 0.001). Similarly, gait variability increased in both groups with dual tasking although not statistically significant. In PD patients, the performance of an additional task resulted in an increased number of cadences (p = 0.04), a reduction in swing time (p = 0.02) and cycle time (p = 0.04) compared with the control group but there was no significant reduction in normalized velocity. Stride width also increased in the PD patients. The addition of a cognitive task may affect certain aspects of gait and is able to elicit subclinical deficits in early PD patients. In an attempt to maintain velocity, early PD patients develop compensatory mechanisms by increasing cadence and decreasing swing time and cycle time. Increased step width helps support balance, and prevents going beyond the base-of-support which may predispose to unsteadiness and falls. We propose that these findings occur as part of a spectrum of a “preclinical gait syndrome” and longitudinal studies are needed to assess the predictive values of these early markers of gait deficits.     

A motor learning-based intervention to ameliorate freezing of gait in subjects with Parkinson’s disease

Freezing of gait (FOG) is an episodic gait disturbance that is commonly seen in Parkinson’s disease (PD). To date, treatment efficacy is limited. We tested the hypothesis that an intervention that utilizes motor learning provided through intensive cueing can alleviate this symptom. Fifteen subjects with PD suffering from FOG participated in a 6 week progressive motor learning program (three training sessions per week—open trial). A training session included FOG-provoking situations (e.g., turns). Prior to each presumed FOG provocation (e.g., just before a turn), rhythmic auditory stimulation (RAS) was elicited and the subject was trained to walk rhythmically, coordinate left–right stepping and to increase step size, utilizing the RAS cueing. Net training duration increased from week to week and secondary cognitive tasks while walking were added to increase FOG propensity. FOG symptom burden was assessed before, immediately, and 4 weeks after the training period. The mean number of FOG episodes (±SEM) per 10 m of walking in a standardized gait assessment decreased from 0.52 ± 0.29 in the pre-testing to 0.15 ± 0.04 in the post-testing (p < 0.05). The duration of FOG episodes decreased from 4.3 ± 2.1 to 2.6 ± 0.6 s (p < 0.05). Additional measures (e.g., FOG questionnaire, gait speed) varied in their responsiveness to the treatment. These effects were retained 4 weeks after the training. The results of this open label study support the possibility that a motor learning-based intervention is apparently effective in reducing FOG burden, suggesting that RAS can deliver ‘anti-FOG’ training.     

Relationship between freezing of gait (FOG) and other features of Parkinson's: FOG is not correlated with bradykinesia.

BACKGROUND: The pathophysiology of freezing of gait (FOG) is unclear. OBJECTIVE: To assess the relationships between FOG and other parkinsonian features in Parkinson's disease (PD), focusing on levodopa effects. METHODS: Nineteen PD patients with significant FOG in "off" were assessed while "off" and "on". Three observers independently viewed videotapes of a 130-m walk and scored FOG frequency. The Unified Parkinson's disease Rating Scale was used to evaluate clinical state. RESULTS: FOG frequency was not correlated with other parkinsonian features in "off" and only with speech and writing in "on". Levodopa significantly decreased FOG frequency (p<0.001). This reduction was strongly correlated with improvement of tremor (R=0.80, p<0.01) and speech (R=0.62, p<0.05), but not with improvement in rigidity, bradykinesia, or balance. CONCLUSION: Levodopa decreases FOG in PD. FOG is apparently an independent motor symptom, caused by a paroxysmal pathology that is different from that responsible for bradykinesia, rigidity or postural instability.     

Correlation between deep brain stimulation effects on freezing of gait and audio-spinal reflex

Objective

A network of cortical, subcortical and brainstem structures might be involved in freezing of gait (FOG). Subthalamic nucleus (STN) deep brain stimulation (DBS) could modulate this network. The audio-spinal reflex (ASR), reduced in PD, but increased by treatment, can be used to further investigate that locomotor network. The aim of this study is to find whether a correlation exists between ASR and FOG in PD patients under DBS.

Obstacle avoidance to elicit freezing of gait during treadmill walking

Freezing of gait (FOG) is a common and disabling feature of Parkinson's disease (PD). Detailed pathophysiological studies are hampered by the fact that FOG episodes are difficult to elicit in a gait laboratory. We evaluated whether the need to avoid sudden obstacles on a treadmill can provoke FOG. We included 21 PD patients (15 with self‐reported off‐period FOG). Patients were tested in the off‐state. FOG during overground walking was assessed using a standardized gait trajectory and axial 360° turns. Subsequently, patients walked on a motorized treadmill with suddenly appearing obstacles that necessitated compensatory stepping. Performance was videotaped, and presence of FOG was scored visually by two independent raters. Thirteen patients showed FOG during overground walking. During treadmill walking, obstacle avoidance was associated with 13 unequivocal FOG episodes in eight patients, whereas only one patient froze during undisturbed treadmill walking (Wilcoxon z = ?2.0, P = 0.046). FOG episodes elicited by obstacle avoidance were brief (typically <1 s). Almost all episodes were provoked when subjects had a longer available response time. In conclusion, suddenly appearing obstacles on a treadmill can elicit FOG in a controlled laboratory setting. However, the moving treadmill and the obstacle both act as cues, which apparently help to immediately overcome the provoked FOG episode. This may limit the ecological validity of this new approach. © 2009 Movement Disorder Society     

Initial center of pressure position prior to anticipatory postural adjustments during gait initiation in people with Parkinson's disease with freezing of gait

IntroductionFreezing of gait (FOG) in Parkinson's disease (PD) is associated with an altered posture during quiet stance as well as an impaired preparation and execution of the gait initiation process. We aimed to investigate whether an altered initial posture impacts anticipatory postural adjustments (APAs) and first-step execution during gait initiation in people with PD with FOG (PD + FOG).MethodsTwenty-seven PD+FOG, 30 PD patients without FOG and 27 age-matched healthy controls performed self-generated gait initiation. Initial mean center of pressure (COP) position prior to APA onset, characteristics of APAs and features of first-step execution were investigated.ResultsContrarily to controls, PD patients showed a COP that was initially positioned more towards the stance leg (p = 0.007). Moreover, significantly smaller backward COP shift, longer duration of swing-foot unloading phase, and lower first-step length and velocity characterized PD+FOG compared to controls. While size and duration of backward COP shift during APA and lateral COP shift during the unloading phase were main predictors of first-step length and velocity in all groups, the medio-lateral shift of the initial COP position in PD+FOG was a main predictor of first-step execution (β = −0.191, p = 0.001 for velocity).ConclusionIn PD+FOG, the more the COP was initially positioned towards the stance foot, the slower and shorter the first step. The initial medio-lateral COP position may be a compensatory strategy to address postural instability of PD+FOG. A specific training regarding postural control prior to gait preparation and execution could improve functional mobility in PD+FOG.     

Objective detection of subtle freezing of gait episodes in Parkinson's disease

Freezing of gait (FOG) is a clinically defined phenomenon of Parkinson's disease (PD). Recent evidence suggests that subtle FOG episodes can be elicited in a gait laboratory using suddenly appearing obstacles during treadmill walking. We evaluated which quantitative gait parameters identify such subtle FOG episodes. We included 10 PD patients with FOG, 10 PD patients without FOG, and 10 controls. Subjects walked on a motorized treadmill while avoiding unexpectedly appearing obstacles. Treadmill walking was videotaped, and FOG episodes were identified by two independent experts. Gait was also analyzed using detailed kinematics. Knee joint signals were processed using time–frequency analysis with combinations of sliding fast Fourier transform and wavelets transform. Twenty FOG episodes occurred during treadmill walking in 5 patients (all with clinically certified FOG), predominantly in relation to obstacle avoidance. FOG was brief when it occurred just before or after obstacle crossing and was characterized by short, rapid steps. Frequency analysis showed a typical qualitative pattern: before the FOG episode an increase in dominant frequency in the 0 to 3 Hz band (festination), followed by decreased power in 0 to 3 Hz band and an increased power in the 3 to 8 Hz band during the FOG episode. This pattern led to an increased FOG index as a qualitative measure. These approaches detected even very brief FOG with acceptable sensitivity (75–83%) and specificity (>95%). We conclude that time–frequency analysis is an appropriate approach to detect brief and subtle FOG episodes. Future work will need to decide whether this approach can support or even replace expert clinical opinion. © 2010 Movement Disorder Society     

The effect of medication and the role of postural instability in different components of freezing of gait (FOG)

Freezing of gait (FOG) is associated with gait asymmetry and arrhythmicity, cognitive impairment in Parkinson's disease (PD). However, the role of postural instability (PI) in and the effect of dopaminergic medication (meds) on FOG are unclear. We investigated the effect of meds on FOG using a validated metric, Stepping in Place (SIP) and the relationship between PI and FOG.MethodsWe assessed static posturography (off meds), SIP, UPDRS-III (off/on meds) and the FOG-questionnaire (FOG-Q) in 15 freezers/15 non-freezers and 14 healthy controls.ResultsUPDRS-III, rigidity, tremor (P < 0.01) and axial subscores (P < 0.05) improved with meds in freezers. Only UPDRS-III and tremor improved in non-freezers (P < 0.01). Meds improved freezing episode (FE) frequency, duration and stride duration in freezers (P < 0.01). Over 73% of freezers did not freeze on meds, although one freezer had more and longer duration FEs. Meds did not improve SIP cycle asymmetry and arrhythmicity, which remained greater in freezers compared to other groups on and off meds (P < 0.01, P < 0.05 respectively). Center of pressure (CoP) mediolateral displacement and velocity (V_CoP) in both directions were larger in freezers (P < 0.05). FOG-Q was correlated with CoP anteroposterior displacement and mediolateral V_CoP (R = 0.42; R = 0.40, P < 0.05).The improvement of FOG frequency and duration but not of gait asymmetry and arrhythmicity on meds suggests that both dopaminergic and non-dopaminergic networks contribute to FOG. The correlations between postural instability and FOG severity and SIP asymmetry on meds, suggest that as the disease progresses, postural instability interferes with gait symmetry and lead to on meds FOG and falls.     

Cortical Disinhibition Drives Freezing of Gait in Parkinson's Disease and an Exploratory Repetitive Transcranial Magnetic Stimulation Study

Background

Dysfunction of the primary motor cortex, participating in regulation of posture and gait, is implicated in freezing of gait (FOG) in Parkinson's disease (PD).

Objective

The aim was to reveal the mechanisms of “OFF-period” FOG (OFF-FOG) and “levodopa-unresponsive” FOG (ONOFF-FOG) in PD.

Methods

We measured the transcranial magnetic stimulation (TMS) indicators and gait parameters in 21 healthy controls (HCs), 15 PD patients with ONOFF-FOG, 15 PD patients with OFF-FOG, and 15 PD patients without FOG (Non-FOG) in “ON” and “OFF” medication conditions. Difference of TMS indicators in the four groups and two conditions and its correlations with gait parameters were explored. Additionally, we explored the effect of 10 Hz repetitive TMS on gait and TMS indicators in ONOFF-FOG patients.

Results

In “OFF” condition, short interval intracortical inhibition (SICI) exhibited remarkable attenuation in FOG patients (both ONOFF-FOG and OFF-FOG) compared to Non-FOG patients and HCs. The weakening of SICI correlated with impaired gait characteristics in FOG. However, in “ON” condition, SICI in ONOFF-FOG patients reduced compared to OFF-FOG patients. Pharmacological treatment significantly improved SICI and gait in OFF-FOG patients, and high-frequency repetitive TMS distinctly improved gait in ONOFF-FOG patients, accompanied by enhanced SICI.

Conclusions

Motor cortex disinhibition, represented by decreased SICI, is related to FOG in PD. Refractory freezing in ONOFF-FOG patients correlated with the their reduced SICI insensitive to dopaminergic medication. SICI can serve as an indicator of the severity of impaired gait characteristics in FOG and reflect treatments efficacy for FOG in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Rehabilitation treatment of gait in patients with Parkinson's disease with freezing: A comparison between two physical therapy protocols using visual and auditory cues with or without treadmill training

Freezing is a disabling symptom in patients with Parkinson's disease. We investigated the effectiveness of a new rehabilitation strategy based on treadmill training associated with auditory and visual cues. Forty Parkinsonian patients with freezing were randomly assigned to two groups: Group 1 underwent a rehabilitation program based on treadmill training associated with auditory and visual cues, while Group 2 followed a rehabilitation protocol using cues and not associated with treadmill. Functional evaluation was based on the Unified Parkinson's Disease Rating Scale Motor Section (UPDRS III), Freezing of Gait Questionnaire (FOGQ), 6‐minute walking test (6MWT), gait speed, and stride cycle. Patients in both the groups had significant improvements in all variables considered by the end of the rehabilitation program (all P = 0.0001). Patients treated with the protocol including treadmill, had more improvement than patients in Group 2 in most functional indicators (P = 0.007, P = 0.0004, P = 0.0126, and P = 0.0263 for FOGQ, 6MWT, gait speed, stride cycle, respectively). The most striking result was obtained for 6MWT, with a mean increase of 130 m in Group 1 compared with 57 m in Group 2. Our results suggest that treadmill training associated with auditory and visual cues might give better results than more conventional treatments. Treadmill training probably acts as a supplementary external cue. © 2009 Movement Disorder Society     

Freezing of gait and executive functions in patients with Parkinson's disease

Freezing of gait (FOG) is a frequent, disabling symptom of Parkinson's disease (PD). FOG usually lasts a few seconds. It refers to brief paroxysmal events during which a subject is unable to start or continue locomotion. Despite its frequency, FOG pathophysiology is unclear. Because a frontal lobe dysfunction or a disconnection between the frontal lobe and basal ganglia has been implicated in FOG, we explored frontal functions in PD patients using neuropsychological tests. Thirteen early‐stage PD patients [Hoehn & Yahr score (H&Y) ≤ 2.5] with freezing during “on ” state (FOG+), and 15 age‐, H&Y score‐, and disease‐duration‐matched PD patients without freezing (FOG?) were investigated. No patient was demented or depressed. Assessment included the Unified Parkinson's Disease Rating Scale (UPDRS), FOG questionnaire, Mini Mental State Examination (MMSE), frontal assessment battery (FAB), phonemic verbal fluency, Stroop test (parts II and III), and ten‐point clock test (TPCT). UPDRS and MMSE scores did not differ between the two groups. FAB, verbal fluency, and TPCT scores were significantly lower in FOG+ patients than in FOG? patients (FAB: P = 0.008; phonemic verbal fluency: P = 0.011; TPCT: P = 0.024). FOG correlated with lower scores at frontal tests in patients with early‐stage PD. © 2007 Movement Disorder Society     

Intravenous amantadine on freezing of gait in Parkinson’s disease: a randomized controlled trial

To compare the effects of intravenous amantadine and placebo therapy on freezing of gait in patients with Parkinson’s disease, this randomized, double-blind, placebo-controlled, multicenter trial compared the efficacy of 5 days intravenous amantadine and placebo treatments on freezing of gait in 42 subjects randomly allocated 2:1 to amantadine or placebo groups. Changes in freezing of gait questionnaire (FOG-Q) scores and in unified Parkinson’s disease rating scale (UPDRS) scores, from baseline to immediately (V1) and 1 month (V2) after treatments, were assessed. Among the 42 patients (amantadine n = 29, placebo n = 13, a mean age 65.5 ± 9.4 years and a mean FOG-Q score 17.4 ± 3.2), 40 subjects completed treatment. There was no significant group difference on the primary outcome measure as total FOG-Q score changes at V1. However a significant beneficial effect of amantadine on freezing was seen at V2 in the UPDRS Part II freezing and FOG-Q item 3 scores, and there was significant improvement in the UPDRS Part IV total score and in the UPDRS Part II getting out of bed score in the amantadine group at both V1 and V2. There was no serious adverse event reported during the study. The intravenous amantadine therapy did not show a significant improvement on overall FOG-Q scores in patients with moderate-to-severe freezing; however, it might be beneficial by attenuating freezing severity and improving patients’ mobility. To prove this finding further studies with larger sample sizes are warranted in the future.     

Freezing of gait in Parkinson's disease is associated with altered functional brain connectivity

BackgroundPatients with Parkinson's disease (PD) may develop several gait disturbances during the course of illness and Freezing of gait (FOG) is one of them. Several neuroimaging studies have been conducted to identify the neural correlates of FOG but results have not been uniform. Resting state functional MRI (rs-fMRI) is relatively less explored in PD patients with FOG. This study aims to compare the whole brain resting state connectivity of PD patients with and without FOG using rs-fMRI.Methodsrs-fMRI was obtained for 28 PD patients (15 with and 13 patients without FOG) who were matched for various demographic and clinical characteristics. Seed to voxel analysis was performed at whole brain level and compared between the two groups.ResultsWhen compared to patients without FOG, the patients with FOG had reduced functional connectivity across multiple seeds. Major finding was reduced inter-hemispheric connectivity of left parietal opercular cortex with multiple regions of the brain primarily involving the primary somatosensory and auditory areas, which also negatively correlated with the FOGQ scores.ConclusionOur findings suggest that alterations in the resting state functional connectivity of the opercular parietal cortex may be one of the substrates of FOG. Reduced interhemispheric connectivity probably is the reason for impairment of control and coordination in bilateral leg movements while walking.