Influence of white matter MRI hyper-intensities on acute l-dopa response in patients with Parkinson's disease

Arena, Julieta; Cerquetti, Daniel; Rossi, Malco; Cháves, Hernán; Rollán, Cecilia; Dossi, Daiana; Merello, Marcelo

doi:10.1016/j.parkreldis.2016.01.017

Cited by 22 publications

(14 citation statements)

References 10 publications

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“…Results showed that after adjusting for age, sex, striatal DAT availability and levodopa equivalent dose, the PD group with moderate to severe WMH showed a higher risk of developing FOG (HR = 3.29, P < 0.001) than the PD patients with minimal WMH. This study was consistent with previous studies which showed that increased WMH burden was associated with severe motor deficits, especially axial motor impairments [51,52]. Although the mechanisms linking WMH and motor disability are not fully understood, diffuse white matter damage including major cortico-cortical, motor-related cortico-fugal and several striato-frontal tracts are involved in the gait control network, which may contribute to FOG development.…”

Section: White Matter Hyperintensities (Wmh)supporting

confidence: 92%

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Gao

Tan

et al. 2020

Transl Neurodegener

120

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Background: Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD), but the mechanisms and treatments of FOG remain great challenges for clinicians and researchers. The main focus of this review is to summarize the possible mechanisms underlying FOG, the risk factors for screening and predicting the onset of FOG, and the clinical trials involving various therapeutic strategies. In addition, the limitations and recommendations for future research design are also discussed. Main body: In the mechanism section, we briefly introduced the physiological process of gait control and hypotheses about the mechanism of FOG. In the risk factor section, gait disorders, PIGD phenotype, lower striatal DAT uptake were found to be independent risk factors of FOG with consistent evidence. In the treatment section, we summarized the clinical trials of pharmacological and non-pharmacological treatments. Despite the limited effectiveness of current medications for FOG, especially levodopa resistant FOG, there were some drugs that showed promise such as istradefylline and rasagiline. Non-pharmacological treatments encompass invasive brain and spinal cord stimulation, noninvasive repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS), and physiotherapeutic approaches including cues and other training strategies. Several novel therapeutic strategies seem to be effective, such as rTMS over supplementary motor area (SMA), dual-site DBS, spinal cord stimulation (SCS) and VNS. Of physiotherapy, wearable cueing devices seem to be generally effective and promising.Conclusion: FOG model hypotheses are helpful for better understanding and characterizing FOG and they provide clues for further research exploration. Several risk factors of FOG have been identified, but need combinatorial optimization for predicting FOG more precisely. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggested that some therapeutic strategies showed promise.

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Section: White Matter Hyperintensities (Wmh)supporting

confidence: 92%

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Gao

Tan

et al. 2020

Transl Neurodegener

120

View full text Add to dashboard Cite

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“…Some centers measure the “ON” state at a specific time [2,38,39], typically 45 min [46,47], whereas others establish a peak score. There is also no uniformity in the size of the dose: most use an absolute dose [40,41,48] ranging from 150–400 mg of levodopa but others use some multiple of the usual morning dose [49,50,51].…”

Section: Discussionmentioning

confidence: 99%

Prediction of the Levodopa Challenge Test in Parkinson’s Disease Using Data from a Wrist-Worn Sensor

Khodakarami¹,

Ricciardi

Contarino

et al. 2019

Sensors

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The response to levodopa (LR) is important for managing Parkinson’s Disease and is measured with clinical scales prior to (OFF) and after (ON) levodopa. The aim of this study was to ascertain whether an ambulatory wearable device could predict the LR from the response to the first morning dose. The ON and OFF scores were sorted into six categories of severity so that separating Parkinson’s Kinetigraph (PKG) features corresponding to the ON and OFF scores became a multi-class classification problem according to whether they fell below or above the threshold for each class. Candidate features were extracted from the PKG data and matched to the class labels. Several linear and non-linear candidate statistical models were examined and compared to classify the six categories of severity. The resulting model predicted a clinically significant LR with an area under the receiver operator curve of 0.92. This study shows that ambulatory data could be used to identify a clinically significant response to levodopa. This study has also identified practical steps that would enhance the reliability of this test in future studies.

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“…6 Several studies have shown that neuromodulation of the aberrant motor maps has potential therapeutic implications for LID. 26,27 Ample evidence has suggested that comorbid WMHs could negatively influence the motor features 8,10 and poor levodopa response 11,28 in PD. Likewise, patients in the PD-WMH + group in this study showed more severe motor deficits than those in the PD-WMH-group despite the comparable striatal DAT availability between the groups at an initial assessment.…”

Section: Discussionmentioning

confidence: 99%

White matter hyperintensities and risk of levodopa‐induced dyskinesia in Parkinson’s disease

Chung

Yoo

Lee

et al. 2020

Ann Clin Transl Neurol

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Objective To investigate whether the burden of white matter hyperintensities (WMHs) is associated with the risk of developing levodopa‐induced dyskinesia (LID) in Parkinson’s disease (PD). Methods According to the Clinical Research Center for Dementia of South Korea WMH visual rating scale, 336 patients with drug‐naïve early stage PD (follow‐up >3 years) were divided into two groups of PD with minimal WMHs (PD‐WMH–; n = 227) and moderate‐to‐severe WMHs (PD‐WMH+; n = 109). The Cox regression model was used to estimate the hazard ratio for the development of LID in the PD‐WMH + group compared with the PD‐WMH– group, while adjusting for age at PD onset, sex, striatal dopamine depletion, and PD medication dose. Additionally, we assessed the effects of WMH burden rated by the Scheltens scale and regional WMH distribution on the development of LID. Results Patients in the PD‐WMH + group were older and had more severe parkinsonian motor signs despite comparable striatal dopamine transporter availability than those in the PD‐WMH– group. Patients in the PD‐WMH + group had a higher risk of developing LID (hazard ratio, 2.66; P < 0.001) than those in the PD‐WMH– group after adjustment for other confounding factors. A greater WMH burden was associated with earlier occurrence of LID (hazard ratio, 1.04; P = 0.001), although the effects of WMHs on LID development did not exhibit region‐specific patterns. Interpretation The present study demonstrates that the burden of WMHs is associated with occurrence of LID in patients with PD, suggesting comorbid WMHs as a risk factor for LID.

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Influence of white matter MRI hyper-intensities on acute l-dopa response in patients with Parkinson's disease

Cited by 22 publications

References 10 publications

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Freezing of gait in Parkinson’s disease: pathophysiology, risk factors and treatments

Prediction of the Levodopa Challenge Test in Parkinson’s Disease Using Data from a Wrist-Worn Sensor

White matter hyperintensities and risk of levodopa‐induced dyskinesia in Parkinson’s disease

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