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.     

Explaining freezing of gait in Parkinson's disease: Motor and cognitive determinants

Freezing of gait (FOG) is part of a complex clinical picture in Parkinson's disease (PD) and is largely refractory to standard care. Diverging hypotheses exist about its origins, but a consolidated view on what determines FOG is lacking. The aim of this study was to develop an integrative model of FOG in people with PD. This cross‐sectional study included 51 Parkinson subjects: 24 patients without FOG and 27 with FOG matched for age, gender, and disease severity. Subjects underwent an extensive clinical test battery evaluating general disease characteristics, gait and balance, nongait freezing, and cognitive functions. The relative contribution of these outcomes to FOG was determined using logistic regression analysis. The combination of the following four independent contributors provided the best explanatory model of FOG (R² = 0.49): nongait freezing; levodopa equivalent dose (LED); cognitive impairment; and falls and balance problems. The model yields a high‐risk profile for FOG (P > 95%) when Parkinson patients are affected by at least one type of nongait freezing (e.g., freezing of other repetitive movements), falls or balance problems during the last 3 months, and a Scales for Outcomes in Parkinson's Disease‐Cognition score below 28. A high LED further increases the risk of FOG to 99%. Nongait freezing, increased dopaminergic drug dose, cognitive deficits, and falls and balance problems are independent determinants of FOG in people with PD and may play a synergistic role in its manifestation. © 2012 Movement Disorder Society     

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.     

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.     

Freezing of gait subtypes have different cognitive correlates in Parkinson's disease

BackgroundFreezing of gait (FOG) is a major concern for Parkinson's disease (PD) patients because it is a leading cause of falls and is associated with poor quality of life. The pathophysiology is unknown but it is hypothesized that it relates to cognitive abnormalities; particularly executive and visuospatial dysfunction. However, prior results have been discrepant. Pharmacologic subtypes of FOG include those that are responsive and unresponsive to levodopa.ObjectiveTo determine whether executive and visuospatial dysfunction are associated specifically with the levodopa unresponsive subtype of FOG.Methods135 PD subjects completed a single assessment included FOG questionnaire, UPDRS motor scale, comprehensive cognitive battery and measure of hallucinations. Analyses compared unresponsive (n = 16), responsive (n = 20) and no FOG (n = 99) subtypes.ResultsThe unresponsive subtype had a significantly older age of onset of PD than the responsive group (p = .03) and had worse motor scores (p = .003) than the no FOG group. Longer disease duration was associated with the responsive group compared to the no FOG group (p = .002). The unresponsive FOG group had significantly poorer visuospatial ability (p = .001) and executive functioning (p = .02) than both the no and responsive FOG subgroups. These latter groups were not significantly different. The responsive FOG group was associated with the presence of hallucinations.ConclusionAside from pharmacological differences, unresponsive FOG is associated with executive and visuospatial dysfunction implicating frontostriatal pathways while responsive FOG is associated with hallucinations suggesting involvement of posterior cortical regions. Further study and treatment of FOG should include appropriate subtype classification.     

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.     

The specific contributions of set‐shifting to freezing of gait in Parkinson's disease

Freezing of gait (FOG) in Parkinson's disease (PD) is common and the pathophysiology of FOG is poorly understood. It has been hypothesized to reflect complementary yet competing frontostriatal pathways that reduce the ability to keep different tasks (motor or cognitive) on‐line. This inability to “set‐shift” has been proposed to trigger a freezing episode. If correct, this hypothesis would predict a differential pattern of executive dysfunction with FOG being most specifically related to attentional set‐shifting. In this study, 31 patients with a range of self‐reported FOG symptom severities were administered tests of executive functioning. The results demonstrate that FOG symptoms were selectively correlated with poorer performance on tasks of set‐shifting, but not with a range of other executive tasks. This was apparent even after controlling for slowed processing speed, disease stage and depressive symptoms. The results support the recently proposed hypothesis for the pathophysiology underlying FOG in PD. © 2010 Movement Disorder Society     

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.     

Freezing of gait in Parkinson's disease: The paradoxical interplay between gait and cognition

BackgroundFreezing of gait is a disabling episodic gait disturbance common in patients with Parkinson's disease. Recent evidences suggest a complex interplay between gait impairment and executive functions.Aim of our study was to evaluate whether specific motor conditions (sitting or walking) influence cognitive performance in patients with or without different types of freezing.MethodsEight healthy controls, eight patients without freezing, nine patients with levodopa-responsive and nine patients with levodopa-resistant freezing received a clinical and neuropsychological assessment during two randomly performed conditions: at rest and during walking.ResultsAt rest, patients with levodopa-resistant freezing performed worse than patients without freezing on tests of phonological fluency (p = 0.01). No differences among the four groups were detected during walking. When cognitive performances during walking were compared to the performance at rest, there was a significant decline of verbal episodic memory task (Rey Auditory Verbal Learning Test) in patients without freezing and with levodopa-responsive freezing. Interestingly, walking improved performance on the phonological fluency task in patients with levodopa-resistant freezing (p = 0.04).ConclusionsCompared to patients without freezing, patients with levodopa-resistant freezing perform worse when tested while seated in tasks of phonological verbal fluency. Surprisingly, gait was associated with a paradoxical improvement of phonological verbal fluency in the patients with levodopa-resistant freezing whilst walking determined a worsening of episodic memory in the other patient groups.     

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.     

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.     

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     

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.     

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     

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.