Levodopa Intake Research Articles

Prosody matters: Preserved prominence marking strategies in people with Parkinson's disease independent of motor status.

While many studies focus on segmental variation in Parkinsonian speech, little is known about prosodic modulations reflecting the ability to adapt to communicative demands in people with Parkinson's disease (PwPD). This type of prosodic modulation is important for social interaction, and it involves modifications in speech melody (intonational level) and articulation of consonants and vowels (segmental level). The present study investigates phonetic cues of prosodic modulations with respect to different focus structures in mild dysarthric PwPD as a function of levodopa. Acoustic and kinematic speech parameters of 25 PwPD were assessed in two motor conditions. Speech production data from PwPD were collected before (medication-OFF) and after levodopa intake (medication-ON) by means of 3-D electromagnetic articulography. On the acoustic level, intensity, pitch, and syllable durations were analyzed. On the kinematic level, movement duration and amplitude were investigated. Spatio-temporal modulations of speech parameters were examined and compared across three different prosodic focus structures (out-of-focus, broad focus, contrastive focus) to display varying speech demands. Overall, levodopa had beneficial effects on motor performance, speech loudness, and pitch modulation. Acoustic syllable durations and kinematic movement durations did not change, revealing no systematic effects of motor status on the temporal domain. In contrast, there were spatial modulations of the oral articulators: tongue tip movements were smaller and lower lip movements were larger in amplitude under levodopa, reflecting a more agile and efficient articulatory movement under levodopa. Thus, respiratory-phonatory functions and consonant production improved, while syllable duration and tongue body kinematics did not change. Interestingly, prominence marking strategies were comparable between the medication conditions under investigation, and in fact, appear to be preserved in mild dysarthric PwPD.

Treating Idiopathic Parkinson’s Disease with Bonoesikpungjigyeong-tang : A Case Study on “Delayed On” and “Wearing Off” Phenomena after Long-term Levodopa Intake

A 69-year-old female diagnosed with idiopathic Parkinson’s disease and treated with anti-Parkinsonian medications, including levodopa, for 7 years presented with complaints of wearing-off phenomenon and delayed onset of medication efficacy, resulting in postural instability and feeling of severe exhaustion. The patient underwent a 50-day course of treatment with Bonoesikpungjigyeong-tang formula. The effects of the treatment were evaluated by recording the average time to onset of medication efficacy, the average time to medication wearing-off, and discomfort due to wearing-off phenomenon. Postural instability was assessed using the Numeric Rating Scale (NRS). The patient’s overall quality of life was assessed using the EQ-5D-3L. After 50 days of treatment, the average time to onset of medication efficacy decreased, and the average time to medication wearing-off increased. Discomfort due to wearing-off phenomenon and postural instability decreased. This case suggests that Bonoesikpungjigyeong-tang might be an alternative for improving discomfort caused by long-term levodopa intake.

Exploring Cardiovascular Autonomic Function before and after Chronic Deep Brain Stimulation in Parkinson's Disease.

Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic failure and levodopa treatment. To evaluate the effect of chronic STN-DBS, levodopa, and their combination on cardiovascular autonomic functions in PD. We performed cardiovascular reflex tests (CRTs) before and 6-months after STN-DBS surgery in 20 PD patients (pre-DBS vs. post-DBS). CRTs were executed without and with medication (med-OFF vs. med-ON). CRT results and occurrence of neurogenic orthostatic hypotension (OH) did not differ between pre- and post-DBS studies in med-OFF condition. After levodopa intake, the BP decrease during HUTT was significantly greater compared to med-OFF, both at pre-DBS and post-DBS evaluation. Levodopa-induced OH was documented in 25% and 5% of patients in pre-DBS/med-ON and post-DBS/med-ON study. Chronic stimulation did not influence cardiovascular responses, while levodopa exerts a relevant hypotensive effect. The proportion of patients presenting levodopa-induced OH decreases after STN-DBS surgery.

3D Kinematics Quantifies Gait Response to Levodopa earlier and to a more Comprehensive Extent than the MDS-Unified Parkinson's Disease Rating Scale in Patients with Motor Complications.

Quantitative 3D movement analysis using inertial measurement units (IMUs) allows for a more detailed characterization of motor patterns than clinical assessment alone. It is essential to discriminate between gait features that are responsive or unresponsive to current therapies to better understand the underlying pathophysiological basis and identify potential therapeutic strategies. This study aims to characterize the responsiveness and temporal evolution of different gait subcomponents in Parkinson's disease (PD) patients in their OFF and various ON states following levodopa administration, utilizing both wearable sensors and the gold-standard MDS-UPDRS motor part III. Seventeen PD patients were assessed while wearing a full-body set of 15 IMUs in their OFF state and at 20-minute intervals following the administration of a supra-threshold levodopa dose. Gait was reconstructed using a biomechanical model of the human body to quantify how each feature was modulated. Comparisons with non-PD control subjects were conducted in parallel. Significant motor changes were observed in both the upper and lower limbs according to the MDS-UPDRS III, 40 minutes after levodopa intake. IMU-assisted 3D kinematics detected significant motor alterations as early as 20 minutes after levodopa administration, particularly in upper limbs metrics. Although all "pace-domain" gait features showed significant improvement in the Best-ON state, most rhythmicity, asymmetry, and variability features did not. IMUs are capable of detecting motor alterations earlier and in a more comprehensive manner than the MDS-UPDRS III. The upper limbs respond more rapidly to levodopa, possibly reflecting distinct thresholds to levodopa across striatal regions.

The effect of dopaminergic treatment on whole body kinematics explored through network theory

Three-dimensional motion analysis represents a quantitative approach to assess spatio-temporal and kinematic changes in health and disease. However, these parameters provide only segmental information, discarding minor changes of complex whole body kinematics characterizing physiological and/or pathological conditions. We aimed to assess how levodopa intake affects the whole body, analyzing the kinematic interactions during gait in Parkinson’s disease (PD) through network theory which assess the relationships between elements of a system. To this end, we analysed gait data of 23 people with PD applying network theory to the acceleration kinematic data of 21 markers placed on participants’ body landmarks. We obtained a matrix of kinematic interactions (i.e., the kinectome) for each participant, before and after the levodopa intake, we performed a topological analysis to evaluate the large-scale interactions among body elements, and a multilinear regression analysis to verify whether the kinectome’s topology could predict the clinical variations induced by levodopa. We found that, following levodopa intake, patients with PD showed less trunk and head synchronization (p-head = 0.048; p-7th cervical vertebrae = 0.032; p-10th thoracic vertebrae = 0.006) and an improved upper-lower limbs synchronization (elbows right, p = 0.002; left, p = 0.005), (wrists right, p = 0.003; left, p = 0.002; knees right, p = 0.003; left, p = 0.039) proportional to the UPDRS-III scores. These results may be attributable to the reduction of rigidity, following pharmacological treatment.

Effect of dopaminergic therapy on lacrimation in Parkinson's disease

The prevalence of dry eye syndrome (DES) in Parkinson's disease (PD) reaches 87% and leads to impaired quality of life in many patients.Objective: to evaluate the lacrimal function and the effect of dopaminergic therapy in patients with PD.Material and methods: 43 patients with stage II–III PD according to Hoehn and Yahr (H&Y) receiving therapy with levodopa (n=17), amantadines (n=13) and dopamine receptor agonists (ADR) (n=28) were assessed using Schirmer's test (to estimate tear flow), sialometry, Unified Parkinson's Disease Rating Scale (UPDRSI-IV), Schwab and England Activities of Daily Living scale (Sch&En), the Parkinson’s Disease Questionnaire Summary Index (PDQ-39), the Mini Mental State Examination Scale (MMSE), the Non-Motor Symptom Questionnaire (NMSQ), the American Urological Association Symptom Scale (AUA), the Gastrointestinal Symptom Rating Scale (GSRS), the Bristol Stool Form Scale (BSFS).Results. Lacrimal insufficiency was found in 49% of patients. It occurred more frequently (χ2=9.546; p=0.003) in patients taking amantadine and correlated with the daily dose of amantadine (r-S=-0.359). It did not depend on the intake of ADR and levodopa and their doses but correlated with the UPDRS-IV score (r-S= -0.463), namely with the presence and duration of OFF-periods. Lacrimal insufficiency correlated with the Sch&En score (r-S=0.321) and non-motor parameters: UPDRSI (r-S =-0.302), NMSQ (r-S=-0.435), constipation domain of the GSRS (r-S=-0.362), BSFS (r-S=0.363). It was not related to age, gender, stage and duration of PD, motor symptoms of parkinsonism (assessed during the ON-phase) and was not related to salivation (although it was reduced in 39.5% of patients).Conclusion. Lacrimal insufficiency is observed in half of patients with stage II–III PD; it is related to the presence and duration of OFF-periods, the severity of other autonomic disorders and the use of amantadines, suggesting the role of dopamine dysregulation, neurodegeneration of autonomic centers and anticholinergic therapy in the development of DES in PD.

Objective assessment of the effects of opicapone in Parkinson’s disease through kinematic analysis

BackgroundOpicapone (OPC) is a third-generation, selective peripheral COMT inhibitor that improves peripheral L-DOPA bioavailability and reduces OFF time and end-of-dose motor fluctuations in Parkinson’s disease (PD) patients.ObjectivesIn this study, we objectively assessed the effects of adding OPC to L-DOPA on bradykinesia in PD through kinematic analysis of finger movements.MethodsWe enrolled 20 treated patients with PD and motor fluctuations. Patients underwent two experimental sessions (L-DOPA, L-DOPA + OPC), separated by at least 1 week. In each session, patients were clinically evaluated and underwent kinematic movement analysis of repetitive finger movements at four time points: (i) before their usual morning dose of L-DOPA (T0), (ii) 30 min (T1), (iii) 1 h and 30 min (T2), and (iv) 3 h and 30 min after the L-DOPA intake (T3).ResultsMovement velocity and amplitude of finger movements were higher in PD patients during the session with OPC compared to the session without OPC at all the time points tested. Importantly, the variability of finger movement velocity and amplitude across T0–T3 was significantly lower in the L-DOPA + OPC than L-DOPA session.ConclusionsThis study is the first objective assessment of the effects of adding OPC to L-DOPA on bradykinesia in patients with PD and motor fluctuations. OPC, in addition to the standard dopaminergic therapy, leads to significant improvements in bradykinesia during clinically relevant periods associated with peripheral L-DOPA dynamics, i.e., the OFF state in the morning, delayed-ON, and wearing-OFF periods.

Advanced Analysis of Electrodermal Activity Measures to Detect the Onset of ON State in Parkinson’s Disease

Background: Electrodermal activity (EDA) serves as a prominent biosignal for assessing sympathetic activation across various scenarios. Prior research has suggested a connection between EDA and fluctuations in Parkinson’s disease (PD), but its precise utility in reliably detecting these fluctuations has remained unexplored. This study aims to evaluate the efficacy of both basic and advanced analyses of EDA changes in identifying the transition to the ON state following dopaminergic medication administration in individuals with PD. Methods: In this observational study, 19 individuals with PD were enrolled. EDA was continuously recorded using the Empatica E4 device, worn on the wrist, during the transition from the OFF state to the ON state following levodopa intake. The raw EDA signal underwent preprocessing and evaluation through three distinct approaches. A logistic regression model was constructed to assess the significance of variables predicting the ON/OFF state, and support vector machine (SVM) models along with various Neural Network (NN) configurations were developed for accurate state prediction. Results: Differences were identified between the ON and OFF states in both the time and frequency domains, as well as through the utilization of convex optimization techniques. SVM and NN models demonstrated highly promising results in effectively distinguishing between the OFF and ON states. Conclusions: Evaluating sympathetic activation changes via EDA measures holds substantial promise for detecting non-motor fluctuations in PD. The SVM algorithm, in particular, yields precise outcomes for predicting these non-motor fluctuation states.

Acute effect of levodopa on orthostatic hypotension and its association with motor responsiveness in Parkinson's disease: Results of acute levodopa challenge test

ObjectiveLevodopa administration can induce or worsen orthostatic hypotension (OH) in patients with Parkinson's disease (PD). Understanding of acute OH post levodopa (AOHPL) is important for rational drug use in PD patients. Primary objective of this study was to investigate the incidence of AOHPL in PD patients. The secondary objectives were a) hemodynamic character of AOHPL; b) risk factors of AOHPL; c) relationship between motor responsiveness and blood pressure (BP) change. Methods490 PD inpatients underwent acute levodopa challenge test (LCT). Supine-to-standing test (STS) was done 4 times during LCT, including before levodopa and every hour post levodopa intake within 3 h. Patients were classified into two groups, AOHPL and non-AOHPL. A comprehensive set of clinical features scales was assessed, including both motor (e.g., motor response, wearing-off) and nonmotor symptoms (e.g., autonomic dysfunction, neuropsychology). Results33.1% PD patients had OH before drug, 50.8% the same subjects had AOHPL during levodopa effectiveness. PD patients who had better response to levodopa likely to have lower standing mean artery pressure (MAP) and severer systolic BP drop after levodopa intake. BP increased when the motor performance worsened and vice versa. Beneficial response was a risk factors of AOHPL (OR = 1.624, P = 0.017). ConclusionsAOHPL was very common in PD patients. We suggested that PD patients with risk factors should monitor hemodynamic change during LCT to avoid AOHPL following the introduction or increase of oral levodopa. The fluctuations of BP were complicated and multifactorial, likely caused by the process of PD and levodopa both.

A study on the correlations between acoustic speech variables and bradykinesia in advanced Parkinson's disease.

Very few studies have assessed the presence of a possible correlation between speech variables and limb bradykinesia in patients with Parkinson's disease (PD). The objective of this study was to find correlations between different speech variables and upper extremity bradykinesia under different medication conditions in advanced PD patients. Retrospective data were collected from a cohort of advanced PD patients before and after an acute levodopa challenge. Each patient was assessed with a perceptual-acoustic analysis of speech, which included several quantitative parameters [i.e., maximum phonation time (MPT) and intensity (dB)]; the Unified Parkinson's Disease Rating Scale (UPDRS) (total scores, subscores, and items); and a timed test (a tapping test for 20 s) to quantify upper extremity bradykinesia. Pearson's correlation coefficient was applied to find correlations between the different speech variables and the tapping rate. A total of 53 PD patients [men: 34; disease duration: 10.66 (SD 4.37) years; age at PD onset: 49.81 years (SD 6.12)] were included. Levodopa intake increased the MPT of sustained phonation (p < 0.01), but it reduced the speech rate (p = 0.05). In the defined-OFF condition, MPT of sustained phonation positively correlated with both bilateral mean (p = 0.044, r-value:0.299) and left (p = 0.033, r-value:0.314) tapping. In the defined-ON condition, the MPT correlated positively with bilateral mean tapping (p = 0.003), left tapping (p = 0.003), and right tapping (p = 0.008). This study confirms the presence of correlations between speech acoustic variables and upper extremity bradykinesia in advanced PD patients. These findings suggest common pathophysiological mechanisms.

The vicious circle between homocysteine, methyl group-donating vitamins and chronic levodopa intake in Parkinson's disease.

A biomarker for declined methylation capacity is elevation of homocysteine levels. They increase the risk for onset of vascular disease and contribute to progression of chronic neurodegeneration and aging. This narrative review discusses associations between homocysteine, consumption of methyl group-donating vitamins and impact on disease-generating mechanisms in levodopa-treated patients with Parkinson's disease. We conclude to recommend levodopa-treated patients to substitute themselves with methyl group-donating vitamins. This is harmless in terms of application of folic acid, methylcobalamin or hydroxocobalamin. Moreover, we suggest a crucial discussion on the value of the various popular hypotheses on Parkinson's disease-generating mechanisms. Findings from studies with acute levodopa exposure describe oxidative stress generation and impaired methylation capacity, which causes gene dysfunction. Their repeated occurrences contribute to onset of mitochondrial dysfunction, iron enrichment and pathologic protein accumulation in the long term. Current research underestimates these epigenetic, metabolic consequences of chronic levodopa application. Supplementary treatment strategies are recommended to avoid levodopa-related side effects.

Prognostic factors of unilateral prelemniscal radiations radiofrequency lesions: A surgical technique for the treatment of Parkinson’s disease motor symptoms

ObjectiveA group of patients with Parkinson's disease (PD) were managed with unilateral prelemniscal radiation radiofrequency lesions (U-Raprl). The current study aims to evaluate prognostic factors that could influence clinical response. MethodsPatients previously diagnosed with PD managed with U-Raprl were included in the study, classifying them into two groups according to their percentage of clinical response (</≥ 50%) at 5 years of follow-up in relation to the part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III), analyzing the possible factors associated with their response (age, evolution of PD, Hoehn and Yahr scale (HYS), and levodopa dose). To show differences between groups before and after the intervention, a T-test was performed, and a Mann-Whitney U test was carried out to determine differences between the response groups, added to an effect size calculation using a Cohen's d (α = 0.05, and β = 0.20). ResultsThirty-four patients were included, where the most prevalent symptoms were tremor and rigidity, with 52.9% percentage of males, 59.3 ± 6.4 mean age, and 7.4 ± 2.1 of mean evolution of PD. Analysis shows differences between groups (p < 0.05) according to the HYS, UPDRS, and levodopa intake, after the intervention. The analysis of the groups according to their response showed differences between the HYS (p < 0.01, ∆ > 1.5), Age (p < 0.0001, ∆ = 2.38), Evolution (p < 0.0001, ∆ = 2.38), and post-operative UPDRS (p < 0.01, ∆ = 1.38). The qualitative analysis of the distribution regarding the responder group shows that those patients with an age under 58 years, an evolution fewer than 7 years, and a preoperative HYS score smaller than 2, showed a response ≥ 50% according to the UPDRS-III in all cases. ConclusionU-Raprl is a highly effective procedure with a 5-year persistence of improvement. The most relevant prognostic factors to consider for a clinical response according to UPDRS-III greater than 50% are age under 58 years, less than 7 years of PD evolution, and HYS less or equal to 3.

A “new” role of amantadines in COVID-19 in patients with Parkinson’s disease: results of own comparative study

Amantadine has begun to be used as a possible alternative in COVID-19 therapy to mitigate its effects. There is anecdotal evidence that patients with Parkinson's disease (PD) treated with amantadine and who test positive for COVID-19 often do not develop clinical manifestations of COVID-19. Objective : to compare the clinical course of COVID-19 in patients with PD who took or did not take amantadine sulfate. Patients and methods . A prospective continuous study included 142 patients with PD who were treated in Republican Clinical Diagnostic Center for Extrapyramidal Pathology and Botulinum Therapy in Kazan from October 2021 to January 2022. Patients filled out a proprietary internally developed questionnaire. Results and discussion . Out of 142 individuals with PD COVID-19 occurred in 77 (54.2%), of which 52.0% had a mild course, 39.0% had a moderate course, 2.6% had a severe course, and in 6.5% the severity of the disease has not been established. Deterioration after COVID-19 infection was noted by 36% of patients: the appearance or increase in motor fluctuations (41%), increased tremor, stiffness or slowness (31%), the appearance of "exhaustion" of the effect of a single dose of levodopa (13%), the appearance or increased dyskinesia (21%), hallucinations (3.5%). Patients taking amantadine sulfate had PD much longer (11.5±5.62 years versus 5.12±3.24 years) and had a more pronounced (III–IV) stage of the disease. These patients were more likely to experience mild COVID-19 (in 60.87% of cases), in contrast to patients not receiving amantadine sulfate (only in 48.15% of cases). There was no correlation between the severity of COVID-19 and levodopa intake. Conclusion . The results of the study showed that patients with PD taking amantadine sulfate are more likely to have a mild course of COVID-19.

A quantitative systems pharmacology model for simulating OFF-Time in augmentation trials for Parkinson's disease: application to preladenant.

The clinical impact of therapeutic interventions in Parkinson's disease is often measured as a reduction in OFF-time when the beneficial effects of the standard-of-care L-DOPA formulations wanes off. We investigated the pharmacodynamic interactions of augmentation therapy to standard-of-care using a quantitative systems pharmacology (QSP) model of the basal ganglia motor circuit, essentially a computer model of neuronal firing in the different subregions with anatomically informed connectivity, cell-specific expression of 17 different G-protein coupled receptors and corresponding coupling to voltage-gated ion channel effector proteins based on experimentally observed intracellular signaling. The calculated beta/gamma (b/g) power spectrum of the local field potentials in the subthalamic nucleus was previously calibrated on the clinically relevant Unified Parkinson's Disease Rating Scale (UPDRS). When combining this QSP model with PK modeling of different formulations of L-DOPA, we calculated the b/g fluctuations over a 16h awake period and used a weighted distance from a specific threshold to determine the cumulative liability of OFF-Time. Prediction of OFF-time with clinical observations of different L-DOPA formulations showed a significant correlation. Simulations show that augmentation with the adenosine A2A antagonist preladenant reduces OFF-time with 6min for carbidopa/levodopa 950mg 5-times daily to 37min for 100mg L-DOPA - 3 or 5 times daily. Exploring delays between preladenant and L-DOPA intake did not improve the outcome. Hypothetical A2A antagonists with an ideal PK and pharmacology profile can achieve OFF-Time reductions ranging from 9.5min with DuoDopa to 55min with low dose L-DOPA formulations. Combination of the QSP model with PK modeling can predict the anticipated OFF-Time reduction of novel A2A antagonists with standard of care. With the large number of GPCR in the model, this combination can support both the design of clinical trials with new therapeutic agents and the optimization of combination therapy in clinical practice.

Central Aortic Pressure and Arterial Stiffness in Parkinson's Disease: A Comparative Study.

Background Cardiovascular autonomic dysfunction, which leads to hemodynamic disorders, is commonly observed in patients with Parkinson's disease (PD). Central aortic pressure (CAP) is the systolic blood pressure (SBP) at the root of the aorta. In young people, CAP is lower than peripheral arterial blood pressure. In older people, the difference between CAP and peripheral arterial blood pressure decreases depending on the extent of arterial stiffness (AS). In patients with AS, CAP increases. CAP is thus regarded as an indicator of AS. Objective To compare CAP and other hemodynamic parameters for AS between patients with Parkinson's disease and control group. We also aimed to evaluate changes in these hemodynamic parameters after the levodopa (LD) intake. Methods We included 82 patients with PD and 76 healthy controls. Age, sex, disease duration, disease subtype, Hoehn–Yahr stage (H&Y), and nonmotor symptoms (NMS) were documented. TensioMed Software v.3.0.0.1 was used to measure CAP, peripheral arterial blood pressure, pulse pressure (PP), heart rate (HR), mean arterial pressure (MAP), augmentation index (AI), pulse wave velocity, and ejection time. All patients were being treated with LD, and measurements were performed 1 h before and 1 h after LD intake. Results Baseline peripheral arterial blood pressure and CAP values were significantly higher in the PD group than in the control group (p < 0.001 and p=0.02, respectively). Most cardiac hemodynamic parameters, including peripheral arterial blood pressure and CAP, decreased significantly (p < 0.02 and p < 0.001, respectively) after LD intake in the PD group. Disease subtype, duration, and severity did not affect any of the hemodynamic parameters. When NMS were evaluated, patients with psychosis and dementia showed higher baseline parameters. Conclusion Loss of postganglionic noradrenergic innervation is well-known with PD. Several cardiac hemodynamic parameters were affected, suggesting cardiac autonomic dysfunction in these patients. The data obtained were independent of disease severity, duration, and subtype. After LD intake, most of these parameters decreased, which might have a positive effect on the vascular burden.

Dopamine dysregulation syndrome after prescription of dopamine agonists: a case report

IntroductionWe present the case of a 65-year-old woman with multiple and chronic psychosomatic symptoms. Due to motor impairments she was diagnosed in 2009 with Parkinson’s Disease (PD) by the neurology department and empirical treatment with levodopa was prescribed. However, the patient increased her levodopa intake by three times the recommended dose. The patient presented many adverse effects, including psychotic symptoms, that were interrupted after the levodopa intake was ended during a two month internament in a psychiatric unit. Dopamine dysregulation syndrome (DDS) is a condition in which patients with PD increase their levodopa intake without an objective worsening of motor symptoms. Higher-than-prescribed doses are taken by patients who develop tolerance and dependence to dopaminergic agonists.ObjectivesTo analyse the prevalence of DDS, its diagnosis and treatment as well as the identification of risk factors.MethodsA case report is presented alongside a review of the relevant literature regarding DDS.ResultsThe available evidence suggests that the main risk factors for DDS are a history of mood disorders and behavioural disorders, but more studies are needed. Given that DDS is considered a rare adverse effect, physicians usually overlook voluntary dose increase by patients.ConclusionsDDS, even though uncommon, has severe adverse effects such as dependence and acute psychosis. Before prescription of dopamine agonists, individual risk factors (such as psychiatric comorbidities or history of substance abuse) should be assessed. Also, patients and families should be informed and trained in alarm signs detection. Further studies would be justified to determine DDS prevalence, early diagnosis and treatment.DisclosureNo significant relationships.

Sensitivity to gait improvement after levodopa intake in Parkinson's disease: A comparison study among synthetic kinematic indices.

The synthetic indices are widely used to describe balance and stability during gait. Some of these are employed to describe the gait features in Parkinson's disease (PD). However, the results are sometimes inconsistent, and the same indices are rarely used to compare the individuals affected by PD before and after levodopa intake (OFF and ON condition, respectively). Our aim was to investigate which synthetic measure among Harmonic Ratio, Jerk Ratio, Golden Ratio and Trunk Displacement Index is representative of gait stability and harmony, and which of these are more sensitive to the variations between OFF and ON condition. We found that all indices, except the Jerk Ratio, significantly improve after levodopa. Only the improvement of the Trunk Displacement Index showed a direct correlation with the motor improvement measured through the clinical scale UPDRS-III (Unified Parkinson's Disease Rating Scale-part III). In conclusion, we suggest that the synthetic indices can be useful to detect motor changes induced by, but not all of them clearly correlate with the clinical changes achieved with the levodopa administration. In our analysis, only the Trunk Displacement Index was able to show a clear relationship with the PD clinical motor improvement.

Short-term effect of dopaminergic medication on speech in early-stage Parkinson\u2019s disease

The effect of dopaminergic medication on speech has rarely been examined in early-stage Parkinson’s disease (PD) and the respective literature is inconclusive and limited by inappropriate design with lack of PD control group. The study aims to examine the short-term effect of dopaminergic medication on speech in PD using patients with good motor responsiveness to levodopa challenge compared to a control group of PD patients with poor motor responsiveness. A total of 60 early-stage PD patients were investigated before (OFF) and after (ON) acute levodopa challenge and compared to 30 age-matched healthy controls. PD patients were categorised into two clinical subgroups (PD responders vs. PD nonresponders) according to the comparison of their motor performance based on movement disorder society-unified Parkinson’s disease rating scale, part III. Seven distinctive parameters of hypokinetic dysarthria were examined using quantitative acoustic analysis. We observed increased monopitch (p > 0.01), aggravated monoloudness (p > 0.05) and longer duration of stop consonants (p > 0.05) in PD compared to healthy controls, confirming the presence of hypokinetic dysarthria in early PD. No speech alterations from OFF to ON state were revealed in any of the two PD groups and speech dimensions investigated including monopitch, monoloudness, imprecise consonants, harsh voice, slow sequential motion rates, articulation rate, or inappropriate silences, although a subgroup of PD responders manifested obvious improvement in motor function after levodopa intake (p > 0.001). Since the short-term usage of levodopa does not easily affect voice and speech performance in PD, speech assessment may provide a medication state-independent motor biomarker of PD.

One-Carbon Metabolism in Alzheimer's Disease and Parkinson's Disease Brain Tissue.

Disruptions in one-carbon metabolism and elevated homocysteine have been previously implicated in the development of dementia associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Moreover, a PD diagnosis itself carries substantial risk for the development of dementia. This is the first study that explores alterations in one-carbon metabolism in AD and PD directly in the human brain frontal cortex, the primary center of cognition. Applying targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS), we analyzed post-mortem samples obtained from 136 subjects (35 AD, 65 PD, 36 controls). We found changes in one-carbon metabolites that indicate inefficient activation of cystathionine β-synthase (CBS) in AD and PD subjects with dementia, the latter seemingly accompanied by a restricted re-methylation flow. Levodopa–carbidopa is known to reduce available vitamin B6, which would explain the hindered CBS activity. We present evidence of temporary non-protein-bound homocysteine accumulation upon levodopa intake in the brain of PD subjects with dementia but not in non-demented PD subjects. Importantly, this homocysteine elevation is not related to levodopa dosage, disease progression, or histopathological markers but exclusively to the dementia status. We hypothesize that this levodopa-induced effect is a direct cause of dementia in PD in susceptible subjects with reduced re-methylation capacity. Furthermore, we show that betaine best correlates with cognitive score even among PD subjects alone and discuss nutritional recommendations to improve one-carbon metabolism function.

ANOTHER FACE OF PARKINSON’S DISEASE: PERIPHERAL INVOLVEMENT

BACKGROUND AND AIM: Parkinson’s disease (PD) was initially seen as a neurodegenerative process of the basal ganglia but clinical and pathological evidence revealed its strong systemic as well as peripheral nervous system involvement. The current review aims to present the recent data in the association of polyneuropathy (PN) and PD. METHODS: We performed a systematic literature search in the most important international databases. We report the results of most recent studies in a narrative way. RESULTS: Several recent studies have shown the presence of PN as a small fiber disease in the early stages of PD. Also there seems to be a link between acquired axonal neuropathy and chronic Levo-Dopa intake. We present the possible pathogenesis of this association, also a summary of the evaluation of PN in PD patients and the main management approaches. CONCLUSION: The association of PN in PD patients is an important phenomenon that significantly decreases their quality of life, underlining the value of clinical and paraclinical assessment the all stages of the disease.