scholarly journals Neurophysiological Predictors of Response to Medication in Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Saša R. Filipović ◽  
Aleksandra Kačar ◽  
Sladjan Milanović ◽  
Miloš R. Ljubisavljević
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intracortical Inhibition ◽  
Therapeutic Benefit ◽  
Short Latency ◽  
Clinical Effects ◽  
Intracortical Facilitation ◽  
Treatment Optimization ◽  
Dopaminergic Medication ◽  
Motor Cortex Excitability

Background: Although dopaminergic medication has been the foundation of Parkinson's disease (PD) therapy for decades, sensitive and specific therapeutic response biomarkers that allow for better treatment optimization are lacking.Objective: We tested whether the features of Transcranial Magnetic Stimulation-based neurophysiological measures taken off-medication are associated with dopaminergic medication-induced clinical effects.Method: Motor cortex excitability [short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), and input-output (IO) curve], and plasticity [paired associative stimulation (PAS) protocol] neurophysiological measures were examined in 23 PD patients off-medication. Clinical features were quantified by the motor section of the Unified Parkinson's Disease Scale (total score and lateralized total, bradykinesia, and rigidity sub-scores), and the differences between measures off-medication and on-medication (following the usual morning dose), were determined. Total daily dopaminergic medication dose (expressed as levodopa equivalent daily dose-LEDD), was also determined.Results: SICI significantly correlated with changes in lateralized UPDRS motor and bradykinesia sub-scores, suggesting that patients with stronger basal intracortical inhibition benefit more from dopaminergic treatment than patients with weaker intracortical inhibition. Also, ICF significantly negatively correlated with LEDD, suggesting that patients with stronger intracortical facilitation require less dopaminergic medication to achieve optimal therapeutic benefit. Both associations were independent of disease severity and duration.Conclusions: The results suggest variability of (patho) physiological phenotypes related to intracortical inhibitory and facilitatory mechanisms determining clinical response to dopaminergic medication in PD. Measures of intracortical excitability may help predict patients' response to dopaminergic therapy, thus potentially providing a background for developing personalized therapy in PD.

P74-T Reduced hand dexterity in Parkinson’s disease correlates with the level of short-latency intracortical inhibition impairment

2019 ◽  
Vol 130 (7) ◽  
pp. e60
Author(s):  
Kačar Aleksandra ◽  
A. Kačar ◽  
S. Filipović ◽  
S. Milanović ◽  
M. Ljubisavljević ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intracortical Inhibition ◽  
Short Latency ◽  
Hand Dexterity

scholarly journals Cortical disinhibition in Parkinson’s disease

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3408-3421 ◽  
Author(s):  
Claudia Ammann ◽  
Michele Dileone ◽  
Cristina Pagge ◽  
Valentina Catanzaro ◽  
David Mata-Marín ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Magnetic Stimulation ◽  
Short Interval ◽  
Intracortical Inhibition ◽  
Motor Threshold ◽  
Intracortical Facilitation ◽  
Low Intensity ◽  
Resting Motor Threshold ◽  
Conditioning Stimuli

Abstract In Parkinson’s disease, striatal dopamine depletion produces profound alterations in the neural activity of the cortico-basal ganglia motor loop, leading to dysfunctional motor output and parkinsonism. A key regulator of motor output is the balance between excitation and inhibition in the primary motor cortex, which can be assessed in humans with transcranial magnetic stimulation techniques. Despite decades of research, the functional state of cortical inhibition in Parkinson’s disease remains uncertain. Towards resolving this issue, we applied paired-pulse transcranial magnetic stimulation protocols in 166 patients with Parkinson’s disease (57 levodopa-naïve, 50 non-dyskinetic, 59 dyskinetic) and 40 healthy controls (age-matched with the levodopa-naïve group). All patients were studied OFF medication. All analyses were performed with fully automatic procedures to avoid confirmation bias, and we systematically considered and excluded several potential confounding factors such as age, gender, resting motor threshold, EMG background activity and amplitude of the motor evoked potential elicited by the single-pulse test stimuli. Our results show that short-interval intracortical inhibition is decreased in Parkinson’s disease compared to controls. This reduction of intracortical inhibition was obtained with relatively low-intensity conditioning stimuli (80% of the resting motor threshold) and was not associated with any significant increase in short-interval intracortical facilitation or intracortical facilitation with the same low-intensity conditioning stimuli, supporting the involvement of cortical inhibitory circuits. Short-interval intracortical inhibition was similarly reduced in levodopa-naïve, non-dyskinetic and dyskinetic patients. Importantly, intracortical inhibition was reduced compared to control subjects also on the less affected side (n = 145), even in de novo drug-naïve patients in whom the less affected side was minimally symptomatic (lateralized Unified Parkinson’s Disease Rating Scale part III = 0 or 1, n = 23). These results suggest that cortical disinhibition is a very early, possibly prodromal feature of Parkinson’s disease.

scholarly journals Implications of dopaminergic medication withdrawal in Parkinson’s disease

2021 ◽  
Author(s):  
J. Koschel ◽  
K. Ray Chaudhuri ◽  
L. Tönges ◽  
M. Thiel ◽  
V. Raeder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Medication ◽  
Medication Withdrawal

scholarly journals Bringing Advanced Therapies for Parkinson’s Disease to the Clinic: The Scientist’s Perspective

2021 ◽  
pp. 1-6
Author(s):  
Mark Tomishima ◽  
Agnete Kirkeby
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Phase I Clinical Trials ◽  
Preclinical Models ◽  
Preclinical Development ◽  
Dopaminergic Medication ◽  
Gene Therapies ◽  
Advanced Therapies ◽  
New Phase

After many years of preclinical development, cell and gene therapies have advanced from research tools in the lab to clinical-grade products for patients, and today they constitute more than a quarter of all new Phase I clinical trials for Parkinson’s disease. Whereas efficacy has been convincingly proven for many of these products in preclinical models, the field is now entering a new phase where the functionality and safety of these products will need to stand the test in clinical trials. If successful, these new products can have the potential to provide patients with a one-time administered treatment which may alleviate them from daily symptomatic dopaminergic medication.

Therapeutic benefit of TH-engineered mesenchymal stem cells for Parkinson's disease

2005 ◽  
Vol 15 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Lingling Lu ◽  
Chunli Zhao ◽  
Yujun Liu ◽  
Xiaohong Sun ◽  
Chunli Duan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Benefit

scholarly journals Influence of Dopaminergic Medication on Conditioned Pain Modulation in Parkinson's Disease Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135287 ◽  
Author(s):  
Wiebke Grashorn ◽  
Odette Schunke ◽  
Carsten Buhmann ◽  
Katarina Forkmann ◽  
Sabrina Diedrich ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Dopaminergic Medication

P2-36. Short-interval intracortical inhibition and facilitation in Parkinson’s disease

2013 ◽  
Vol 124 (8) ◽  
pp. e36
Author(s):  
Yuichiro Shirota ◽  
Yasuo Terao ◽  
Shinya Ohminami ◽  
Ryosuke Tsutsumi ◽  
Yoshikazu Ugawa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Short Interval ◽  
Intracortical Inhibition ◽  
Intracortical Inhibition And Facilitation

scholarly journals Lung Function Testing On and Off Dopaminergic Medication in Parkinson's Disease Patients With and Without Dysphagia

2015 ◽  
Vol 3 (2) ◽  
pp. 146-150 ◽  
Author(s):  
Tareq Sawan ◽  
Mary Louise Harris ◽  
Christopher Kobylecki ◽  
Laura Baijens ◽  
Michel van Hooren ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lung Function ◽  
Lung Function Testing ◽  
Dopaminergic Medication ◽  
Function Testing

scholarly journals Differential dopaminergic modulation of spontaneous cortico-subthalamic activity in Parkinson’s disease

2020 ◽  
Author(s):  
Abhinav Sharma ◽  
Diego Vidaurre ◽  
Jan Vesper ◽  
Alfons Schnitzler ◽  
Esther Florin
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Beta Activity ◽  
Beta Band ◽  
Time Resolved ◽  
Functional Roles ◽  
Dopaminergic Medication ◽  
Physiological Processes ◽  
Motor Network ◽  
Theta Frequency

AbstractPathological oscillations including elevated beta activity in the subthalamic nucleus (STN) and between STN and cortical areas are a hallmark of neural activity in Parkinson’s disease (PD). Oscillations also play an important role in normal physiological processes and serve distinct functional roles at different points in time. We characterised the effect of dopaminergic medication on oscillatory whole-brain networks in PD in a time-resolved manner by employing a hidden Markov model on combined STN local field potentials and magnetoencephalography (MEG) recordings from 17 PD patients. Dopaminergic medication led to communication within the medial and orbitofrontal cortex in the delta/theta frequency range. This is in line with deteriorated frontal executive functioning as a side effect of dopamine treatment in Parkinson’s disease. In addition, dopamine caused the beta band activity to switch from an STN-mediated motor network to a frontoparietal-mediated one. In contrast, dopamine did not modify locally-originating STN oscillations in PD. STN–STN synchrony emerged both on and off medication. By providing electrophysiological evidence for the differential effects of dopaminergic medication on the discovered networks, our findings open further avenues for electrical and pharmacological interventions in PD.

scholarly journals A survey into the influence of dopaminergic drug exposure on ‘sense of presence’ symptoms in patients with parkinson's disease

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S279-S280
Author(s):  
Emma Padfield ◽  
Hannah Potticary ◽  
Tim Segal
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Regression Analysis ◽  
Drug Exposure ◽  
Drug Dosage ◽  
Equivalent Dose ◽  
Dopaminergic Medication ◽  
Dopaminergic Drug ◽  
Sense Of Presence ◽  
The Relationship

AimsThe first objective was to estimate prevalence of sense of presence (SoP) experiences in patients with Parkinson's Disease (PD), including whether onset was prior to or after commencing dopaminergic medication. The second objective was to explore the relationship between frequency of SoP experiences and dopaminergic drug, drug dosage and length of drug exposure. The experimental hypothesis was that SoP symptoms in PD would present more frequently in patients treated longer and with higher dopaminergic drug doses.BackgroundPD is a debilitating neurodegenerative disorder. Psychiatric symptoms are common and associated with impaired quality of life and higher treatment costs. PD psychosis often starts with ‘minor hallucinations’, the most common being a false ‘sense of presence’ (SoP), the vivid sensation that someone else is nearby when nobody is there. SoP symptoms typically do not cause significant distress but may act as a prognostic marker for future severe psychosis and may prompt alteration of treatment or reduction in dopaminergic drug dosage. This study aimed to extend prior research by characterizing SoP further and investigating the link with dopaminergic medication.MethodThis was a retrospective, cross-sectional study. Twenty-one patients diagnosed with PD completed a questionnaire to identify presence of SoP symptoms, duration of symptoms, timing of onset related to dopaminergic treatment and the frequency of symptoms in relation to current levodopa equivalent dose (LED). Descriptive frequencies were compared using a two-tailed t-test. Multiple regression analysis was conducted to assess the relationship between frequency of SP experiences, levodopa equivalent dose and length of drug exposure.ResultSixteen of twenty-one patients reported experiencing SoP symptoms. Patients who had not experienced SoP symptoms had a significantly lower LED than those who had experienced these symptoms. There were no other significant differences between the groups. No statistical significance was shown on regression analysis; however our study was not adequately powered for the regression analysis as the number of participants was too low.ConclusionThis study confirms that SoP symptoms are common among patients with PD and supports a correlation between the total daily equivalent dose of levodopa and SoP symptoms. It does not provide evidence for a temporal relationship between onset of SoP symptoms and duration of dopaminergic treatment. The study was insufficiently powered and a larger study is required to investigate further.

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