Differences in Levodopa Response for Progressive and Non-Progressive Micrographia in Parkinson's Disease

Zham, Poonam; Poosapadi, Sridhar A.; Kempster, Peter; Raghav, Sanjay; Nagao, Kanae Jennifer; Wong, Kitty K.; Kumar, Dinesh

doi:10.3389/fneur.2021.665112

Cited by 6 publications

(6 citation statements)

References 30 publications

(48 reference statements)

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“…It is suggested that the sequence effect is resistant to treatment, although this conclusion flies in the face of clinical experience. The conclusion that the sequence effect is unresponsive to dopamine replacement rests on prior studies in chronically treated subjects, which did not isolate the SDR and LDR 57‐61 . Examining whether our current findings extend to the sequence effect is an interesting avenue for future research.…”

Section: Discussionmentioning

confidence: 65%

Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa

Brissenden,

Scerbak,

Albin

et al. 2023

Movement Disorders

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BackgroundImpaired movement vigor (bradykinesia) is a cardinal feature of Parkinson's disease (PD) and hypothesized to result from abnormal motivational processes—impaired motivation‐vigor coupling. Dopamine replacement therapy (DRT) improves bradykinesia, but the response to DRT is multifaceted, comprising a short‐duration response (SDR) and a long‐duration response (LDR) only manifesting with chronic treatment. Prior experiments assessing motivation‐vigor coupling in PD used chronically treated subjects, obscuring the roles of the SDR and LDR.MethodsTo disambiguate the SDR and LDR, 11 de novo PD subjects (6 male [M]:5 female [F]; mean age, 67) were studied before treatment, after an acute levodopa (l‐dopa) dose, and in both the practical “off” (LDR) and “on” (LDR + SDR) states after chronic stable treatment. At each visit, subjects were characterized with a standard battery including the Movement Disorder Society‐Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) and an incentivized joystick task to assess motor performance in response to varying rewards.Resultsl‐Dopa induced a robust SDR and LDR, with further improvement in the combined SDR + LDR state. At baseline, after acute treatment (SDR), and after LDR induction, subjects did not exhibit the normal increase in movement speed with increasing reward. Only in the combined SDR + LDR state was there restoration of motivation‐vigor coupling.ConclusionsAlthough consistent with prior results in chronically treated PD subjects, the significant improvement in motor performance observed with the SDR and LDR suggests that bradykinesia is not solely secondary to deficient modulation of motivational processes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Section: Discussionmentioning

confidence: 65%

Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa

Brissenden,

Scerbak,

Albin

et al. 2023

Movement Disorders

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“…Although different components of bradykinesia can be treated with levodopa and/or deep brain stimulation (DBS), a critical unmet need for improving the lives of people with PD is that the sequence effect does not respond to dopaminergic medication [1,3,4,[20][21][22]. No study to our knowledge has directly examined the effect of DBS on the sequence effect in PD.…”

Section: It Has Been Observed That Fog Frequently Resultsmentioning

confidence: 99%

The Sequence Effect Worsens Over Time in Parkinson’s Disease and Responds to Open and Closed-Loop Subthalamic Nucleus Deep Brain Stimulation

Kehnemouyi

Petrucci

Wilkins

et al. 2023

JPD

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Background: The sequence effect is the progressive deterioration in speech, limb movement, and gait that leads to an inability to communicate, manipulate objects, or walk without freezing of gait. Many studies have demonstrated a lack of improvement of the sequence effect from dopaminergic medication, however few studies have studied the metric over time or investigated the effect of open-loop deep brain stimulation in people with Parkinson’s disease (PD). Objective: To investigate whether the sequence effect worsens over time and/or is improved on clinical (open-loop) deep brain stimulation (DBS). Methods: Twenty-one people with PD with bilateral subthalamic nucleus (STN) DBS performed thirty seconds of instrumented repetitive wrist flexion extension and the MDS-UPDRS III off therapy, prior to activation of DBS and every six months for up to three years. A sub-cohort of ten people performed the task during randomized presentations of different intensities of STN DBS. Results: The sequence effect was highly correlated with the overall MDS-UPDRS III score and the bradykinesia sub-score and worsened over three years. Increasing intensities of STN open-loop DBS improved the sequence effect and one subject demonstrated improvement on both open-loop and closed-loop DBS. Conclusion: Sequence effect in limb bradykinesia worsened over time off therapy due to disease progression but improved on open-loop DBS. These results demonstrate that DBS is a useful treatment of the debilitating effects of the sequence effect in limb bradykinesia and upon further investigation closed-loop DBS may offer added improvement.

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“…Finally, non-dopaminergic mechanisms are unaffected by dopaminergic medication but can be altered by STN-DBS. For instance, the sequence effect, the progressive decrement in movement amplitude with repetitive movement, does not respond to dopaminergic medication ( 95 – 97 ) but has been shown to improve with STN-DBS ( 98 ). It should be noted that our sample of participants with PD were going to undergo STN-DBS surgery; as such they had a physician documented positive response to a supra-threshold dose of levodopa but were fluctuators with regards to their response to levodopa.…”

Section: Discussionmentioning

confidence: 99%

Encoding type, medication, and deep brain stimulation differentially affect memory-guided sequential reaching movements in Parkinson's disease

David

Rivera²,

Entezar³

et al. 2022

Front. Neurol.

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Memory-guided movements, vital to daily activities, are especially impaired in Parkinson's disease (PD). However, studies examining the effects of how information is encoded in memory and the effects of common treatments of PD, such as medication and subthalamic nucleus deep brain stimulation (STN-DBS), on memory-guided movements are uncommon and their findings are equivocal. We designed two memory-guided sequential reaching tasks, peripheral-vision or proprioception encoded, to investigate the effects of encoding type (peripheral-vision vs. proprioception), medication (on- vs. off-), STN-DBS (on- vs. off-, while off-medication), and compared STN-DBS vs. medication on reaching amplitude, error, and velocity. We collected data from 16 (analyzed n = 7) participants with PD, pre- and post-STN-DBS surgery, and 17 (analyzed n = 14) healthy controls. We had four important findings. First, encoding type differentially affected reaching performance: peripheral-vision reaches were faster and more accurate. Also, encoding type differentially affected reaching deficits in PD compared to healthy controls: peripheral-vision reaches manifested larger deficits in amplitude. Second, the effect of medication depended on encoding type: medication had no effect on amplitude, but reduced error for both encoding types, and increased velocity only during peripheral-vision encoding. Third, the effect of STN-DBS depended on encoding type: STN-DBS increased amplitude for both encoding types, increased error during proprioception encoding, and increased velocity for both encoding types. Fourth, STN-DBS was superior to medication with respect to increasing amplitude and velocity, whereas medication was superior to STN-DBS with respect to reducing error. We discuss our findings in the context of the previous literature and consider mechanisms for the differential effects of medication and STN-DBS.

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Differences in Levodopa Response for Progressive and Non-Progressive Micrographia in Parkinson's Disease

Cited by 6 publications

References 30 publications

Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa

Motivational Vigor in Parkinson's Disease Requires the Short and Long Duration Response to Levodopa

The Sequence Effect Worsens Over Time in Parkinson’s Disease and Responds to Open and Closed-Loop Subthalamic Nucleus Deep Brain Stimulation

Encoding type, medication, and deep brain stimulation differentially affect memory-guided sequential reaching movements in Parkinson's disease

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