Freezing of gait unresponsive to dopaminergic stimulation in patients with severe Parkinsonism

Gamo, Julia Vaamonde; Cabello, J; Alcañiz, Manuela; Barragán, José Manuel Flores; León, Sira Carrasco García de; Alonso, R.E. Ibañez

doi:10.1016/s2173-5808(10)70005-5

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…However, despite its negative consequences and prevalence, there is currently no effective treatment for FOG and it does not respond well to the treatments currently used for PD, such as dopamine replacement or deep brain stimulation. 1-3 Therefore, investigation of adjunct therapies is highly warranted. In consideration of the most common triggers of FOG (ie, darkness, dual-tasking, fear, etc), it is likely that these triggers may be related to underlying cognitive, limbic, and proprioceptive mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Investigating Therapies for Freezing of Gait Targeting the Cognitive, Limbic, and Sensorimotor Domains

Chow

Tripp

Rzondzinski

et al. 2021

Neurorehabil Neural Repair

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Background Freezing of gait (FOG) is arguably the most disabling motor symptom experienced with Parkinson’s disease (PD), but treatments are extremely limited due to our poor understanding of the underlying mechanisms. Three cortical domains are postulated in recent research (ie, the cognitive, limbic, and sensorimotor domains), thus, treatments targeting these mechanisms of FOG may potentially be effective. Cognitive training, cognitive behavioral therapy (CBT, a well-known anxiety intervention), and proprioceptive training may address the cognitive, limbic, and sensorimotor domains, respectively. Objective To investigate whether these 3 treatments could improve functional outcomes of FOG. Methods In a single-blind, randomized crossover design, 15 individuals with PD and FOG were randomized into different, counterbalanced orders of receiving the interventions. Each consisted of eight 1-hour sessions, twice weekly for 4 weeks. FOG severity was assessed as the primary outcome using a novel gait paradigm that was aimed at evoking FOG when the cognitive, limbic, or sensorimotor domains were independently challenged. Results FOG severity significantly improved after the cognitive intervention, with strong trends toward improvement specifically in the baseline and cognitive-challenge assessment conditions. CBT, as the anxiety intervention, resulted in significantly worse FOG severity. In contrast, proprioceptive training significantly improved FOG severity, with consistent trends across all conditions. Conclusions The cognitive and proprioceptive treatments appeared to improve different aspects of FOG. Thus, either of these interventions could potentially be a viable treatment for FOG. However, although the results were statistically significant, they could be sensitive to the relatively small number of participants in the study. Considering the significant results together with nonsignificant trends in both FOG and gait measures, and given equal time for each intervention, proprioceptive training produced the most consistent indications of benefits in this study. (clinicaltrials.gov NCT03065127).

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Section: Introductionmentioning

confidence: 99%

Investigating Therapies for Freezing of Gait Targeting the Cognitive, Limbic, and Sensorimotor Domains

Chow

Tripp

Rzondzinski

et al. 2021

Neurorehabil Neural Repair

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“…Freezing of gait (FOG) is commonly observed in Parkinson's disease (PD) with the manifestation that “brief, episodic absence, or marked reduction of forwarding progression of the feet despite the intention to walk.” 1 According to the response of PD patients with FOG (PD‐FOG) to dopamine, they can be divided into PD patients with “levodopa‐unresponsive” FOG (ONOFF‐FOG), “OFF‐period” FOG (OFF‐FOG), and “levodopa‐induced” FOG 1,2 . ONOFF‐FOG commonly exists in the middle and late stages of PD, which is characterized by freezing of gait in both medication “ON” and “OFF” conditions 3 . PD patients with ONOFF‐FOG are more likely to experience the inconvenience brought by freezing than other types.…”

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confidence: 99%

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

Sun,

Gan,

Wang

et al. 2023

Movement Disorders

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BackgroundDysfunction of the primary motor cortex, participating in regulation of posture and gait, is implicated in freezing of gait (FOG) in Parkinson's disease (PD).ObjectiveThe aim was to reveal the mechanisms of “OFF‐period” FOG (OFF‐FOG) and “levodopa‐unresponsive” FOG (ONOFF‐FOG) in PD.MethodsWe 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.ResultsIn “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.ConclusionsMotor 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.

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Managing Gait, Balance, and Posture in Parkinson’s Disease

Debû

Godeiro-Júnior

Lino

et al. 2018

Curr Neurol Neurosci Rep

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It remains very difficult to satisfactorily alleviate gait and postural disturbances in advanced PD. Medical and surgical interventions often fail to provide satisfactory or durable alleviation of these axial symptoms, that may actually call for differential treatments. Exercise and adapted physical activity programs can contribute to improving the patients' condition. Gait, balance, and postural disabilities are often lumped together under the Postural Instability and Gait Difficulties umbrella term. This may lead to sub-optimal patients' management as data suggest that postural, balance, and gait problems might depend on distinct underlying mechanisms. We advocate for a multidisciplinary approach from the day of diagnosis.

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Freezing of gait unresponsive to dopaminergic stimulation in patients with severe Parkinsonism

Cited by 4 publications

References 34 publications

Investigating Therapies for Freezing of Gait Targeting the Cognitive, Limbic, and Sensorimotor Domains

Investigating Therapies for Freezing of Gait Targeting the Cognitive, Limbic, and Sensorimotor Domains

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

Managing Gait, Balance, and Posture in Parkinson’s Disease

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