Gait disturbances in Parkinson disease. Did freezing of gait exist before levodopa? Historical review

Ruiz, Pedro

doi:10.1016/j.jns.2011.05.019

Cited by 29 publications

(13 citation statements)

References 25 publications

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“…The L ‐dopa‐dependent element of FOG remains difficult to interpret, because freezers more often receive L ‐dopa‐therapy as an initial drug than nonfreezers 43. Chronic medication intake leading to reduced synaptic dopamine (DA) sensitivity could be a possible explanation for FOG in later stages,44 and may also explain that, once FOG exists, its severity is not adequately alleviated by L ‐dopa. In the present study, some patients also demonstrated FOG during clinical assessment while they were otherwise optimally medicated.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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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 (R(2) = 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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“…The linking between FoG and dopaminergic drugs is fascinating: the term “freezing” appeared relatively late in the literature (Garcia-Ruiz, 2011), after the introduction of levodopa as therapy for PD (Ambani and Van Woert, 1973). While the early appearance of FoG is considered a “red flag” to diagnose forms of atypical parkinsonism, its occurrence during the PD course usually represents a hypokinetic “off” phenomenon (Snijders et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

How Cognition and Motivation “Freeze” the Motor Behavior in Parkinson’s Disease

et al. 2019

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ObjectiveFreezing of gait (FoG) is a debilitating problem in patients with PD. The multifactorial pathogenesis of FoG remains poorly understood. We aimed to find which factors are most strongly associated with the occurrence of FoG.MethodsThree hundred five PD patients were enrolled and subdivided according to the presence (FoG +, n = 128) or absence (FoG-, n = 177) of FoG. Several clinical, functional, and neuropsychological data were collected and compared between groups. The association between the probability of presence of FoG and possible explanatory variables was assessed by logistic regression analysis.ResultsFoG + patients were younger at the diagnosis (p = 0.04), and their mean daily dose of dopaminergic drugs (p < 0.0001) was higher in comparison with FoG- patients. FoG + patients get worse in Frontal Assessment Battery (p = 0.005), had higher scores in Apathy Evaluation Scale (p = 0.03), and were much more impaired on Wisconsin Card Sorting Test (WCST) (p = 0.018), Trail Making Test A (p = 0.0013), and Ray Auditory Verbal Learning Test (p = 0.012). Levodopa equivalent dose, age (direct), age at disease onset (inverse), and WCST were significant predictors of FoG (p = 0.01, p = 0.0025, p = 0.0016, and p = 0.029, respectively).ConclusionFoG + patients show more deficits in executive functions and in motivation. The main explanatory variables of FoG occurrence are levodopa equivalent dose, age, age at disease onset, and WCST. These data suggest that a specific involvement of frontal cortical circuits in PD is responsible for certain cognitive–behavioral alterations related to the occurrence of FoG.

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“…Nonetheless, these patients showed differences in cognitive and gait assessments compared to controls, suggesting an overload of the dopaminergic system in PD may not improve or may worsen cognition and lower-limb movements, similar to levodopa-induced involuntary movements. Also, chronic levodopa treatment may lead to reduction in synaptic dopamine sensitivity, which may offer an explanation for cognitive and gait severities in the advanced stage of PD and why these severities are not adequately improved by levodopa [27].…”

Section: Discussionmentioning

confidence: 99%

Relationships between freezing of gait severity and cognitive deficits in Parkinson’s disease

Scholl

Espinoza

Leedom

et al. 2021

Preprint

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Introduction: Freezing of gait (FOG) is one of the most debilitating motor symptoms experienced by patients with Parkinson's disease (PD), as it can lead to falls and reduced quality of life. Evidence supports an association between FOG severity and cognitive functioning; however, results are varied. Methods: PD patients with (PDFOG+, n=41) and without FOG (PDFOG-, n=39) and control healthy subjects (n=41) participated in the study. The NIH toolbox cognition battery, Montreal cognitive assessment (MoCA), and interval timing task were used to test cognitive domains. Measurements were compared between groups using multivariable models and adjusting for covariates. Correlation analyses, linear regression, and mediation models were applied to examine relationships among disease duration and severity, FOG severity, and cognitive functioning. Results: Significant differences were observed between controls and PD patients for all cognitive domains. PDFOG+ and PDFOG- exhibited differences in the dimensional change card sort (DCCS) test, interval timing task, and MoCA scores. After adjusting for covariates in two different models, PDFOG+ and PDFOG- differed in both MoCA and DCCS scores. In addition, significant relationships between FOG severity and cognitive function (MoCA, DCCS, and interval timing) were also found. Regression models suggest that FOG severity may be a predictor of cognitive impairment, and mediation models show the effects of cognitive impairment on the relationship between disease severity and FOG severity. Conclusions: Overall, this study provides insight into the relationship between cognitive and gait impairments in patients with PD, which could aid in the development of therapeutic interventions to manage both.

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Gait disturbances in Parkinson disease. Did freezing of gait exist before levodopa? Historical review

Cited by 29 publications

References 25 publications

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

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

How Cognition and Motivation “Freeze” the Motor Behavior in Parkinson’s Disease

Relationships between freezing of gait severity and cognitive deficits in Parkinson’s disease

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