Postural sensory correlates of freezing of gait in Parkinson's disease

IntroductionTo elucidate the unique patterns of postural sensory deficits contributing to freezing of gait (FOG) in patients with Parkinson's disease (PD) and to identify postural sensory modalities that correlate with FOG severity.MethodsTwenty-five PD patients with FOG, 22 PD patients without FOG, and 26 age-matched controls were evaluated using a sensory organization test and clinical measures including the Unified Parkinson's Disease Rating Scale motor score, Montreal Cognitive Assessment, Frontal Assessment Battery, Activities-specific Balance Confidence, Beck Anxiety Inventory, Beck Depression Inventory, and Berg Balance Scale. Multivariable logistic regression analysis was performed for posturographic parameters and possible confounders to determine postural sensory contributors to FOG. We also correlated FOG severity, measured using a New Freezing of Gait Questionnaire, with posturographic parameters.ResultsPD patients with FOG showed worse postural sensory processing compared with those without FOG. In particular, the inability to use the vestibular information (odds ratio [OR] 1.447; 95% confidential interval [CI]: 1.120, 1.869) and poor control over the perturbed somatosensory inputs (OR 2.904; 95% CI: 1.028, 8.202) significantly contributed to FOG. Among PD patients with FOG, FOG severity was correlated with higher reliance on visual information (ρ = −0.432, p = 0.039).ConclusionsPostural sensory deficits involving specific sensory modalities are strongly associated with FOG. Quantitative measurement of postural sensory deficits in PD patients with FOG may provide a better understanding of pathomechanisms of FOG and increase the efficacy of sensory cueing strategies for alleviating FOG, by more accurately identifying suitable patients for rehabilitative therapies.     

帕金森病伴冻结步态患者的静息态磁共振研究

目的 探讨帕金森病患者冻结步态与静息态脑功能成像之间的关系。方法 2021年9月-2022年9月于襄阳市第一人民医院就诊的28例伴有冻结步态的帕金森病患者以及32例不伴有冻结步态的帕金森病患者接受了全脑结构像和静息状态下的功能磁共振扫描,计算并比较2组全脑百分率振幅(Percent amplitude of fluctuation,PerAF)的差异,同时探寻2组被试者间差异脑区与大脑其他区域功能连接性(Functional connectivity,FC)的不同。结果 在静息状态下与非冻结组比较,冻结组双侧额中回的PerAF信号显著减低,同时冻结组快速动眼期(Rapid eye movement,REM)睡眠行为异常筛查量表得分分别与左侧额中回(r=0.436,P=0.020)和右侧额中回(r=0.453,P=0.015)的显著区域的PerAF信号均呈正相关。此外,右侧脑干与双侧额中回之间的功能连接性增加,且右侧脑干区域与脚桥核部分重合;同时左侧额上回与额中回之间的功能连接性显著增加,且两者之间的FC信号与新冻结步态问卷得分呈显著的负相关(r=-0.510,P=0.006)。结论 冻...     

Validation of the freezing of gait questionnaire in patients with Parkinson's disease

To revalidate the Freezing of Gait Questionnaire (FOG‐Q), patients with Parkinson's disease (PD) were randomly assigned to receive rasagiline (1 mg/day) (n = 150), entacapone (200 mg with each dose of levodopa) (n = 150), or placebo (n = 154). Patients were assessed at baseline and after 10 weeks using the FOG‐Q, Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), and Parkinson's Disease Questionnaire (PDQ‐39). FOG‐Q dimensionality, test–retest reliability, and internal reliability were examined. Convergent and divergent validities were assessed by correlating FOG‐Q with UPDRS, BDI, and PDQ‐39. Comparisons between FOG‐Q item 3 and UPDRS item 14 were also made. Principal component analysis indicated that FOG‐Q measures a single dimension. Test–retest reliability and internal reliability of FOG‐Q score was high. FOG‐Q was best correlated to items of the UPDRS relating to walking, general motor issues, and mobility. Correlations between baseline and endpoint suggested that FOG‐Q item 3 is at least as reliable as UPDRS item 14. At baseline, 85.9% of patients were identified as “Freezers” using FOG‐Q item 3 (≥1) and 44.1% using UPDRS item 14 (≥1) (P < 0.001). FOG‐Q was a reliable tool for the assessment of treatment intervention. FOG‐Q item 3 was effective as a screening question for the presence of FOG. © 2007 Movement Disorder Society     

Heart rate changes during freezing of gait in patients with Parkinson's disease

Freezing of gait (FOG) is one of the most disabling symptoms that affect patients with Parkinson's disease (PD). Although the pathophysiology underlying FOG largely remains an enigma, several lines of evidence suggest that the autonomic nervous system might be involved. To this end, we tested the hypothesis that heart rate (HR) increases during FOG and, further, that HR increases just before FOG. To evaluate these hypotheses, 15 healthy older adults, 10 patients with PD who experienced FOG, and 10 patients who did not were studied. Patients with PD were tested during their “off” medication state. HR and HR variability were measured as subjects carried out tasks that frequently provoke FOG; 120 FOG episodes were evaluated. During FOG, HR increased (P = 0.001) by an average of 1.8 bpm, compared with HR measured before the beginning of FOG. HR also increased just before FOG, by 1 bpm (P < 0.0001). In contrast, during sudden stops and 180° turns, HR decreased by almost 2 bpm (P < 0.0001). HR variability was not associated with FOG. To our knowledge, these findings are the first to document the association of FOG to autonomic system activation, as manifested by HR dynamics. One explanation is that the changes in HR before and during FOG may be a sympathetic response that, secondary to limbic activation, contributes to the development of freezing. Although further studies are needed to evaluate these associations, the current results provide experimental evidence linking impaired motor blockades to autonomic nervous system function among patients with PD. © 2010 Movement Disorder Society     

Early phenotypic differences between Parkinson's disease patients with and without freezing of gait

BackgroundPrevious studies have associated freezing of gait in Parkinson's disease with the presence of specific phenotypic features such as mood disturbances, REM sleep behavior disorder and selective cognitive impairments. However, it is not clear whether these features are present in the earlier stages of disease or simply represent a more general pattern of progression. To investigate this issue, the current study evaluated motor, cognitive, affective and autonomic features as well as REM sleep behavior disorder in Parkinson's disease patients in the early stages of the condition.MethodsThirty-eight freezers and fifty-three non-freezers with disease duration of less than five years and a Hoehn and Yahr stage of less than three were included in this study. The groups were matched on a number of key disease features including age, disease duration, motor severity and dopamine dose equivalence. Furthermore, patients were assessed on measures of motor, cognitive, affective and autonomic features, as well as REM sleep behavior disorder.ResultsCompared to non-freezers, patients with freezing of gait had significantly more non-tremor symptoms and a selective impairment on executive functions, such as set-shifting ability and working memory. Freezers and non-freezers did not differ on measures of tremor, autonomic function, REM sleep behavior disorder, mood or more general cognition.ConclusionThese results suggest the pathophysiological mechanisms underlying freezing of gait in the early clinical stages of Parkinson's disease are likely to be related to specific changes in the frontostriatal pathways rather than being due to brainstem or more diffuse neuropathology.     

Evidence for subtypes of freezing of gait in Parkinson's disease

Background: The purpose of this study is to identify and characterize subtypes of freezing of gait by using a novel questionnaire designed to delineate freezing patterns based on self‐reported and behavioral gait assessment. Methods : A total of 41 Parkinson's patients with freezing completed the Characterizing Freezing of Gait questionnaire that identifies situations that exacerbate freezing. This instrument underwent examination for construct validity and internal consistency, after which a data‐driven clustering approach was employed to identify distinct patterns amongst individual responses. Behavioral freezing assessments in both dopaminergic states were compared across 3 identified subgroups. Results : This novel questionnaire demonstrated construct validity (severity scores correlated with percentage of time frozen; r = 0.54) and internal consistency (Cronbach's α = .937), and thus demonstrated promising utility for identifying patterns of freezing that are independently related to motor, anxiety, and attentional impairments. Conclusions : Patients with freezing may be dissociable based on underlying neurobiological underpinnings that would have significant implications for targeting future treatments. © 2018 International Parkinson and Movement Disorder Society     

Progression of postural control and gait deficits in Parkinson's disease and freezing of gait: A longitudinal study

Background and aimsThe relationship between impaired postural control and freezing of gait (FOG) in Parkinson's disease (PD) is still unclear. Our aim was to identify if postural control deficits and gait dysfunction progress differently in freezers compared to non-freezers and whether this relates to FOG development.Methods76 PD patients, classified as freezer (n = 17) or non-freezer (n = 59), and 24 controls underwent a gait and postural control assessments at baseline and after 12 months follow-up. Non-freezers who developed FOG during the study period were categorized as FOG converters (n = 5). Gait was analyzed during walking at self-preferred pace. Postural control was assessed using the Mini-BESTest and its sub-categories: sensory orientation, anticipatory, reactive and dynamic postural control.ResultsMini-BESTest scores were lower in PD compared to controls (p < 0.001), and in freezers compared to non-freezers (p = 0.02). PD has worse anticipatory (p = 0.01), reactive (p = 0.02) and dynamic postural control (p = 0.003) compared to controls. Freezers scored lower on dynamic postural control compared to non-freezers (p = 0.02). There were no baseline differences between converters and non-converters. Decline in postural control was worse in PD compared to controls (p = 0.02) as shown by a greater decrease in the total Mini-BESTest score. Similar patterns were found in freezers (p = 0.006), who also showed more decline in anticipatory (p < 0.001) and dynamic postural control (p = 0.02) compared to non-freezers. FOG converters had a greater decline in the total Mini-BESTest (p = 0.005) and dynamic postural control scores (p = 0.04) compared to non-converters. Gait outcomes showed no significant differences in any of the analyses.ConclusionFOG is associated with more severe decline in postural control, which can be detected by the clinical Mini-BESTest.     

Prediction of the effect of deep brain stimulation on gait freezing of Parkinson's disease

ObjectiveThe response of freezing of gait (FOG) to deep brain stimulation of the subthalamic nucleus (STN-DBS) is controversial and depends on many poorly controlled factors. On the other hand, a clinical predictor for the individual patient is needed to counsel the patient regarding this symptom.MethodsA cohort of 124 patients undergoing STN-DBS was evaluated based on the video-documented Levodopa test at baseline in the OFF- and ON-drug condition and postoperatively in the best condition (ON-drug/ON-stim) and the worst condition (OFF-drug/ON-stim). We compared the freezing item of the Unified Parkinson's disease rating scale (#14), the UPDRS III total score, and FOG severity rated during four provoking situations with regard to its predictive value.ResultsWe found ‘FOG during the turning task’ to be the best predictor with an ROC-value of 0.857 compared to 0.603 for the UPDRS Item 14 and 0.583 for the total UPDRS III. An improvement of 1 or 2 grades of the turning item during the preoperative levodopa test predicts an improvement during the worst condition postoperatively of 1 grade or more with an 80% probability.ConclusionThis FOG prediction test is simple and clinically useful. The test needs to be studied in a prospective study.     

Mild depressive symptoms are associated with gait impairment in early Parkinson's disease

The association between nonmotor characteristics and gait in Parkinson's disease (PD) is well established, particularly the role of cognition. Evidence is emerging that depression, an underrecognized symptom in PD is also associated with gait impairment. This cross‐sectional study examined the association between depressive symptomatology and gait in early PD. Depression was measured with the Geriatric Depression Scale (GDS), disease severity with the Unified Parkinson's Disease Rating Scale III, and cognition with the Mini Mental Status Examination. Gait speed and gait variability were measured using a 7‐m walkway (GAITRite). Linear regression was used to examine the association between depression and gait for PD and controls, controlling for age, cognition, and severity. PD participants who presented with clinically relevant depressive symptoms (GDS ≥ 5) were compared with those who scored < 5. One hundred and twenty‐two people with newly diagnosed PD and 184 controls were assessed. Depression scores were significantly higher for PD patients than for controls (P < .001), although neither group presented with clinically relevant symptomatology (mean [SD] for PD, 2.7 [2.3]; for controls, 1.1 [1.8]). For gait speed there was a main effect for depression (P < .001) and a group × depression interaction that approached significance (P = .054). For gait variability there was a main effect for depression (P < .01). PD participants with GDS scores ≥ 5 had a slower and more variable gait. Very mild depressive symptoms are associated with gait disturbance in early PD. Depression may be a marker for degeneration in nondopaminergic systems in early PD and influence mechanisms of gait disturbance. © 2013 Movement Disorder Society     

Action observation improves sit-to-walk in patients with Parkinson's disease and freezing of gait. Biomechanical analysis of performance

IntroductionFreezing of gait (FoG) is one of the most disabling gait disorders in Parkinson's disease (PD), reflecting motor and cognitive impairments, mainly related to dopamine deficiency. Recent studies investigating kinematic and kinetic factors affecting gait in these patients showed a postural instability characterized by disturbed weight-shifting, inappropriate anticipatory postural adjustment, worse reactive postural control, and a difficulty executing complex motor tasks (i.e. sit-to-walk). These symptoms are difficult to alleviate and not very responsive to Levodopa. For this reason, additional therapeutic actions based on specific therapeutic protocols may help patients with their daily lives. We conducted a randomized control trial aimed to test if two clinical protocols for PD patients with FoG were effective to improve postural control.MethodsRehabilitation protocols, conceived to improve gait, were based on learning motor exercises with the Action Observation plus Sonification (AOS) technique, or by the use of external sensory cues. We collected biomechanical data (Center of Mass COM, Center of Pressure COP, and moving timings), using the sit-to-walk task as a measure of motor and gait performance.ResultsKinetic and kinematic data showed that when treatment effects consolidate, patients treated with AOS protocol are more efficient in merging subsequent motor tasks (sit-to-stand and gait initiation), and diminished the total moving time and the area of the COP positions.ConclusionWe demonstrated for the first time that PD patients with FoG treated with an AOS protocol aimed at relearning appropriate gait patterns increased balance control and re-acquired more efficient postural control.     

Levodopa changes the severity of freezing in Parkinson's disease

Oral levodopa has been proposed to be one of the more effective medications to alleviate freezing of gait, but there is limited data on its efficacy. We evaluated the gait phenomenology of 20 Parkinson's disease patients with freezing of gait before and 60 min after a standardized levodopa dose using a rating scale based on the assumption that festination and akinetic freezing share a common pathophysiology. Levodopa abolished festination and freezing in 20% of patients (p < 0.0001), and reduced the freezing sum score from a median of 15 (IQR 6.75–27.5) to 3.5 (1–11.25), p < 0.001) in all but one of the remainder. Pre-dose ratings correlated with post-dose ratings, in that those patients with lower pre-dose item-scores also showed lower post-dose outcome scores. Levodopa's effect on both festination and akinetic freezing was linear, thereby supporting the concept that festination and freezing are variants on a continuity of episodic gait disorders in PD.     

Speech and gait in Parkinson's disease: When rhythm matters

IntroductionSpeech disturbances in Parkinson's disease (PD) are heterogeneous, ranging from hypokinetic to hyperkinetic types. Repetitive speech disorder has been demonstrated in more advanced disease stages and has been considered the speech equivalent of freezing of gait (FOG). We aimed to verify a possible relationship between speech and FOG in patients with PD.MethodsForty-three consecutive PD patients and 20 healthy control subjects underwent standardized speech evaluation using the Italian version of the Dysarthria Profile (DP), for its motor component, and subsets of the Battery for the Analysis of the Aphasic Deficit (BADA), for its procedural component. DP is a scale composed of 7 sub-sections assessing different features of speech; the rate/prosody section of DP includes items investigating the presence of repetitive speech disorder. Severity of FOG was evaluated with the new freezing of gait questionnaire (NFGQ).ResultsPD patients performed worse at DP and BADA compared to healthy controls; patients with FOG or with Hoehn-Yahr >2 reported lower scores in the articulation, intellibility, rate/prosody sections of DP and in the semantic verbal fluency test. Logistic regression analysis showed that only age and rate/prosody scores were significantly associated to FOG in PD. Multiple regression analysis showed that only the severity of FOG was associated to rate/prosody score.ConclusionsOur data demonstrate that repetitive speech disorder is related to FOG and is associated to advanced disease stages and independent of disease duration. Speech dysfluency represents a disorder of motor speech control, possibly sharing pathophysiological mechanisms with FOG.     

Effects of curved-walking training on curved-walking performance and freezing of gait in individuals with Parkinson's disease: A randomized controlled trial

IntroductionThe purpose of this study was to investigate the effects of curved-walking training (CWT) on curved-walking performance and freezing of gait (FOG) in people with Parkinson's disease (PD).MethodsTwenty-four PD subjects were recruited and randomly assigned to the CWT group or control exercise (CE) group and received 12 sessions of either CWT with a turning-based treadmill or general exercise training for 30 min followed by 10 min of over-ground walking in each session for 4–6 weeks. The primary outcomes included curved-walking performance and FOG. All measurements were assessed at baseline, after training, and at 1-month follow-up.ResultsOur results showed significant improvements in curved-walking performance (speed, p = 0.007; cadence, p = 0.003; step length, p < 0.001) and FOG, measured by a FOG questionnaire (p = 0.004). The secondary outcomes including straight-walking performance (speed, cadence and step length, p < 0.001), timed up and go test (p = 0.014), functional gait assessment (p < 0.001), Unified Parkinson's disease Rating Scale III (p = 0.001), and quality of life (p < 0.001) were also improved in the experimental group. We further noted that the improvements were maintained for at least one month after training (p < 0.05).ConclusionA 12-session CWT program can improve curved-walking ability, FOG, and other measures of functional walking performance in individuals with PD. Most of the improvements were sustained for at least one month after training.     

Microstructural changes in white matter associated with freezing of gait in Parkinson's disease

In Parkinson's disease (PD), freezing of gait (FOG) is associated with widespread functional and structural gray matter changes throughout the brain. Previous study of freezing‐related white matter changes was restricted to brainstem and cerebellar locomotor tracts. This study was undertaken to determine the spatial distribution of white matter damage associated with FOG by combining whole brain and striatofrontal seed‐based diffusion tensor imaging. Diffusion‐weighted images were collected in 26 PD patients and 16 age‐matched controls. Parkinson's disease groups with (n = 11) and without freezing of gait (n = 15) were matched for age and disease severity. We applied tract‐based spatial statistics to compare fractional anisotropy and mean diffusivity of white matter structure across the whole brain between groups. Probabilistic tractography was used to evaluate fractional anisotropy and mean diffusivity of key subcortico‐cortical tracts. Tract‐based spatial statistics revealed decreased fractional anisotropy in PD with FOG in bilateral cerebellar and superior longitudinal fascicle clusters. Increased mean diffusivity values were apparent in the right internal capsule, superior frontal cortex, anterior corona radiata, the left anterior thalamic radiation, and cerebellum. Tractography showed consistent white matter alterations in striatofrontal tracts through the putamen, caudate, pallidum, subthalamic nucleus, and in connections of the cerebellar peduncle with subthalamic nucleus and pedunculopontine nucleus bilaterally. We conclude that FOG is associated with diffuse white matter damage involving major cortico‐cortical, corticofugal motor, and several striatofrontal tracts in addition to previously described cerebello‐pontine connectivity changes. These distributed white matter abnormalities may contribute to the motor and non‐motor correlates of FOG. © 2015 International Parkinson and Movement Disorder Society     

Doorway-provoked freezing of gait in Parkinson's disease

Freezing of gait in Parkinson's disease can be difficult to study in the laboratory. Here we investigate the use of a variable-width doorway to provoke freeze behavior together with new objective methods to measure it. With this approach we compare the effects of anti-parkinsonian treatments (medications and deep-brain stimulation of the subthalamic nucleus) on freezing and other gait impairments. Ten "freezers" and 10 control participants were studied. Whole-body kinematics were measured while participants walked at preferred speed in each of 4 doorway conditions (no door present, door width at 100%, 125%, and 150% of shoulder width) and in 4 treatment states (offmeds/offstim, offmeds/onstim, onmeds/offstim, onmeds/onstim). With no doorway, the Parkinson's group showed characteristic gait disturbances including slow speed, short steps, and variable step timing. Treatments improved these disturbances. The Parkinson's group slowed further at doorways by an amount inversely proportional to door width, suggesting a visuomotor dysfunction. This was not improved by either treatment alone. Finally, freeze-like events were successfully provoked near the doorway and their prevalence significantly increased in narrower doorways. These were defined clinically and by 2 objective criteria that correlated well with clinical ratings. The risk of freeze-like events was reduced by medication but not by deep-brain stimulation. Freeze behavior can be provoked in a replicable experimental setting using the variable-width doorway paradigm, and measured objectively using 2 definitions introduced here. The differential effects of medication and deep-brain stimulation on the gait disturbances highlight the complexity of Parkinsonian gait disorders and their management.     

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     

Oral festination in Parkinson's disease: biomechanical analysis and correlation with festination and freezing of gait.

In Parkinson's disease (PD), festination corresponds to a tendency to speed up when performing repetitive movements. First described in gait (and then in handwriting and speech), festination is one of the most disabling axial symptoms. To establish the phenomenology of oral festination (OF) and the condition's potential links with other axial disorders, we submitted a simple, rhythmic, repetitive, vocal motor task to 40 PD patients and 20 controls. Forty-five percent of the 40 patients presented OF, which was strongly associated with gait festination but not with the severity of freezing of gait (FOG) or dysarthria. With respect to the two pathophysiological hypotheses that have been put forward, a possible link with tremor (as previously suggested in tapping) was not confirmed in this study and so, in view of the significant increase in variability observed, we conclude that OF shares the same pathophysiology as gait disorders.