Acute Levodopa Challenge Test Research Articles

Improvement by Medication Less than Expected in Parkinson's Disease: Blinded Evaluation of Levodopa Response.

The latest Movement Disorder Society (MDS) diagnostic criteria require a good and sustained response to medication to get a diagnosis of Parkinson's disease, PD. The aim of this study was to evaluate levodopa response in a group of patients with probable PD, diagnosed by movement disorder specialists. An acute levodopa challenge test (LDCT) was performed after pausing the dopaminergic medication for 6 half-times. The motor part of the Unified Parkinson's Disease Rating Scale was performed in the OFF-state and after LDCT (ON). A good effect was defined as >30% improvement. A video-protocol was used to secure standardized motor examination with blinded assessments of the UPDRS-III OFF and ON. An age-matched group of control subjects (CS) was included but did not go through LDCT. All participants were evaluated with Montreal Cognitive Assessment (MoCA) and Beck's Depression Inventory (BDI). In the statistical analysis, 37 patients were included. Twenty-one patients showed an improvement ≤30%, while 16 patients showed an improvement >30%. LDCT showed an overall mean improvement of 27.3% of motor UPDRS. In 43.2%, there was a discrepancy between the effect seen with the LDCT and the patients' self-perceived medicine evaluation. Patients with PD had a significantly lower MoCA score and more depressive symptoms compared to CS. We showed an acute effect of levodopa using LDCT that was around 30% improvement. While it lends support to the use of this limit in the MDS diagnostic criteria, an acute effect of less than 30% should be considered acceptable in some patients. Our study highlights a discrepancy in the objective measure of medicine effect on motor symptoms and the patient's subjective evaluation.

Kinect-based objective assessment of the acute levodopa challenge test in parkinsonism: a feasibility study.

The acute levodopa challenge test (ALCT) is an important and valuable examination but there are still some shortcomings with it. We aimed to objectively assess ALCT based on a depth camera and filter out the best indicators. Fifty-nine individuals with parkinsonism completed ALCT and the improvement rate (IR, which indicates the change in value before and after levodopa administration) of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was calculated. The kinematic features of the patients' movements in both the OFF and ON states were collected with an Azure Kinect depth camera. The IR of MDS-UPDRS III was significantly correlated with the IRs of many kinematic features forarising from a chair, pronation-supination movements of the hand, finger tapping, toe tapping, leg agility, and gait (rs = - 0.277 ~ - 0.672, P < 0.05). Moderate to high discriminative values were found in the selected features in identifying a clinically significant response to levodopa with sensitivity, specificity, and area under the curve (AUC) in the range of 50-100%, 47.22%-97.22%, and 0.673-0.915, respectively. The resulting classifier combining kinematic features of toe tapping showed an excellent performance with an AUC of 0.966 (95% CI = 0.922-1.000, P < 0.001). The optimal cut-off value was 21.24% with sensitivity and specificity of 94.44% and 87.18%, respectively. This study demonstrated the feasibility of measuring the effect of levodopa and objectively assessing ALCT based on kinematic data derived from an Azure Kinect-based system.

Effect of acute levodopa challenge test on cerebral blood flow in Parkinson's disease with the supine-to-standing transcranial Doppler test

BackgroundLevodopa, a common drug that improves symptoms of Parkinson's disease (PD), can induce a reduction in blood pressure (BP); however, the effect of levodopa on cerebral blood flow (CBF) remains unclear. ObjectivesTo observe the changes in BP and CBF during active standing before and after the acute levodopa challenge test (ALCT) and analyse the influencing factors of CBF in patients with PD. MethodsBP and CBF velocity were simultaneously recorded by continuous beat-to-beat non-invasive BP monitoring and transcranial Doppler at supine and orthostatic positions twice, before and after ALCT. The patients were divided into two groups according to those with increased and decreased CBF at baseline after ALCT to analyse the influencing factors. ResultsWe examined 64 patients with PD (59.2 ± 11.6 years, 33 males). BP decreased at all timepoints after ALCT, while there was no significant change in the magnitude of the drop in BP induced by standing. CBF was reduced after ALCT, especially within 15 s to 1 min of standing (15 s: 48.95 ± 13.50 vs. 44.93 ± 13.26, p < 0.001; 30 s: 52.46 ± 12.06 vs. 50.11 ± 12.56, p = 0.033; 1 min: 52.19 ± 11.83 vs. 50.17 ± 13.21, p = 0.044). Lower body mass index (β = −0.280, p = 0.027) was an independent factor associated with CBF reduction after ALCT. ConclusionsAdditional attention should be paid to changes in CBF and BP within 1 min after standing in patients with PD taking levodopa, especially in those with low bodyweight.

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.

Integrated PET/MRI With 11C-CFT and 18F-FDG for levodopa response difference in Parkinson’s disease

AimParkinson's disease is one of the most common neurodegenerative diseases. Excellent levodopa responsiveness has been proposed as a characteristic supporting feature in substantiating the PD diagnosis. However, a small portion of clinically established PD patients shows poor levodopa response. This study aims to investigate brain function alterations of PD patients with poor levodopa responsiveness by PET/MRI. MethodA total of 46 PD patients were recruited. They all completed 11C-CFT PET/MRI scans and the acute levodopa challenge test. Among these 46 PD patients, 42 participants further underwent 18F-FDG PET/MRI scans. Clinical variables regarding demographic data, disease features and cognition scales were also collected. Based on the improvement rate of UPDRS‐III, PD patients were divided into non-responders (improvement rate < 33 %) and responders (improvement rate ≥ 33 %). Statistical parametric zapping was performed to analyze molecular imaging. Dopaminergic uptake and metabolism of 70 brain regions were converted to quantitative values and expressed as standard uptake value (SUV). SUV was further normalized by the cerebellum. The resulting SUV ratios and clinical variables were then compared by SPSS. ResultsThe difference between levodopa non-responders (n = 17) and responders (n = 29) in the UPDRS III baseline was statistically significant and the former had a lower UPDRS III baseline (19 (10, 32), p＜0.05). In contrast, no statistical difference between these two groups was found in age, gender, disease duration, cognition, motor subtype and Hoehn-Yahr stage. Dopaminergic uptake differences between levodopa non-responders (n = 17) and responders (n = 29) were shown in the left inferior frontal cortex (1.00 ± 0.09 vs 1.07 ± 0.08, p < 0.05 and FDR < 0.2), the right posterior cingulum (1.10 ± 0.10 vs 1.20 ± 0.13, p < 0.05 and FDR < 0.2) and the right insula (1.21 ± 0.12 vs 1.30 ± 0.10, p < 0.05 and FDR < 0.2). The metabolic alterations between levodopa non-responders (n = 16) and responders (n = 26) were shown in the right supplementary motor area (1.30 (1.18, 1.39) vs 1.41 (1.31, 1.53), p < 0.05 and FDR < 0.2), right precuneus (1.37 ± 0.10 vs 1.47 ± 0.18, p < 0.05 and FDR < 0.2), right parietal cortex (1.14 ± 0.15 vs 1.27 ± 0.21, p < 0.05 and FDR < 0.2), right supramarginal gyrus (1.16 (1.12, 1.26) vs 1.25 (1.14, 1.46), p < 0.05 and FDR < 0.2), right postcentral gyrus (1.15 (1.08, 1.32) vs 1.24 (1.17, 1.39), p < 0.05 and FDR < 0.2), medulla (0.75 ± 0.07 vs 0.80 ± 0.07, p < 0.05 and FDR < 0.2), right rolandic operculum (1.25 (1.18, 1.32) vs 1.33 (1.25, 1.50), p < 0.05 and FDR < 0.2), right olfactory (0.95 (0.91, 1.01) vs 1.01 (0.95, 1.15), p < 0.05 and FDR < 0.2), the right insula (1.15 (1.06, 1.22) vs 1.21 (1.12, 1.35), p < 0.05 and FDR < 0.2) and the left cerebellum crus (0.96 (0.91, 1.01) vs 0.92 (0.86, 0.96), p < 0.05 and FDR < 0.2). ConclusionsPD patients with poor response to levodopa showed less severe impairment of baseline motor symptoms, more severe dopaminergic deficits in the left inferior frontal, right posterior cingulate cortex and the right insula, and lower metabolism in the right supplementary motor area, right precuneus, right parietal cortex, right supramarginal gyrus, right postcentral gyrus, medulla, right rolandic operculum, right olfactory, the right insula and higher metabolism in the left cerebellum crus.

Clinical characteristics and reaction to dopaminergic treatment of drug-naïve patients with Parkinson's disease in central China: A cross sectional study

BackgroundThe symptoms of early Parkinson's disease (PD) are complex and hidden. The aim of this study is to explore and summarize the characteristics of the symptoms of drug naïve patients with PD. Objectivesand Methods Drug-naïve patients with PD and age-matched healthy controls were recruited from the outpatient clinic of Wuhan Union Hospital. The motor and non-motor symptoms were evaluated for further analysis using Unified Parkinson's Disease Rating Scale (UPDRS) I, II, and III; Sniffin’ Sticks Screening 12 test; Mini-Mental State Exam (MMSE); Montreal Cognitive Assessment (MoCA); Hamilton Anxiety Scale (HAMA); and Hamilton Depression Scale (HAMD) scores. The acute levodopa challenge test (ALCT) was adopted to assess the reaction to dopaminergic treatment. ResultsWe recruited 80 drug-naïve patients with PD and 40 age-matched healthy controls (HCs). Approximately 53.7% of the patients were females. The mean onset age was 59.96 ± 10.40 years. The mean UPDRS I, II, and III were 2.01 ± 1.90, 6.18 ± 3.68, and 26.13 ± 12.09, respectively. Compared with HCs, PD patients had lower scores in MMSE and MoCA; and higher scores in HAMA and HAMD (p < 0.05). In ALCT, 54 patients showed good responses to levodopa while 26 patients did not. The mean improvement rate of UPDRS III was 34.09% at 120 min. ConclusionThe motor symptoms of patients with early PD were mild but virous. They also suffered from different non-motor symptoms. In ALCT, about two thirds of patients (54/80) with early PD showed good response to levodopa. Among four aspects of motor symptoms, bradykinesia reacted best to ALCT, while axial symptoms were the worst.

Levodopa responsiveness and white matter alterations in Parkinson's disease: A DTI-based study and brain network analysis: A cross-sectional study.

Patients with Parkinson's disease (PD) present various responsiveness to levodopa, but the cause of such differences in levodopa responsiveness is unclear.Previous studies related the damage of brain white matter (WM) to levodopa responsiveness in PD patients, but no study investigated the relationship between the structural brain network change in PD patients and their levodopa responsiveness. PD patients were recruited and evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS). Each patient received a diffusion tensor imaging (DTI) scan and an acute levodopa challenge test. The improvement rate of UPDRS-III was calculated. PD patients were grouped into irresponsive group (improvement rate<30%) and responsive group (improvement rate ≥ 30%). Tract-based spatial statistics (TBSS), deterministic tracing (DT), region of interest (ROI) analysis, and automatic fiber identification (AFQ) analyses were performed.The structural brain network was also constructed and the topological parameters were calculated. Fifty-four PD patients were included. TBSS identified significant differences in fractional anisotropy (FA) values in the corpus callosum and other regions of the brain. DT and ROI analysis of the corpus callosum found a significant difference in FA between the two groups. Graph theory analysis showed statistical differences in global efficiency, local efficiency, and characteristic path length. PD patients with poor responsiveness to levodopa had WM damage in multiple brain areas, especially the corpus callosum, which might cause disruption of information integration of the structural brain network.

Early motor response to dopamine replacement therapy in Parkinson's disease patients carrying GBA variants

BackgroundMutations in the glucocerebrosidase (GBA) gene represent the most common genetic risk factor for Parkinson's Disease (PD) and are associated with a more aggressive motor phenotype at late stages. However, the motor response at early stages of disease remains understudied. MethodsRetrospective study of PD patients that underwent next-generation sequencing panel tests for PD-related genes. We extracted demographic data and the MDS-UPDRS III response to an acute levodopa challenge (LDC), the best ON score, and the levodopa equivalent daily dose (LEDD) during the first six months after the LDC and initiation of DRT. We compared the response of GBA-PD patients to that of patients without pathogenic variants or rearrangements in other PD related genes (sporadic PD). Results13 GBA-PD and 48 sporadic PD patients were identified. Baseline MDS-UPDRS III score (24.6 ± 9.6 vs. 21.8 ± 9.3. p = 0.4), response to LDC (39.2% ± 7.9% vs. 32.7% ± 13.4%; p = 0.1), best ON score (36.9% ± 39.5% vs. 41.6% ± 20.8%; p = 0.6) and LEDD (188 mg ± 100 mg vs. 261.8 mg ± 164.8 mg; p = 0.2) during the first six months after initiation of DRT were not different between GBA-PD and sporadic PD patients. ConclusionsAt early disease stages of GBA-PD, the motor response to acute levodopa challenge test and the initial response to DRT are similar to that of patients with sporadic PD. Although limited by small sample size, these preliminary findings should be confirmed by future prospective larger studies.

Levodopa responsiveness in Parkinson’s disease patients and white matter alterations in diffusion tensor imaging: a cross-sectional tract-based spatial statistics study

This study aimed to investigate the relationship between levodopa responsiveness and white matter alterations in Parkinson's disease patients using diffusion tensor imaging (DTI). Twenty-six recruited Parkinson's disease patients were evaluated using the Mini-Mental State Examination, Hoehn and Yahr scale (H&Y) and Unified Parkinson's Disease Rating Scale (UPDRS). Each patient underwent a DTI scan and an acute levodopa challenge test. The improvement rate of UPDRS-III was calculated, Parkinson's disease patients were grouped into a responsive group (improvement rate ≥30%) and a nonresponsive group (improvement rate <30%). The differences in fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity between the two groups were measured using tract-based spatial statistics. There was no difference in demographic features or baseline evaluations between groups. The UPDRS-III score after the challenge was higher in the nonresponsive group than that in the responsive group. Compared to the responsive group, patients in the nonresponsive group exhibited decreased fractional anisotropy in the corpus callosum; cingulum; left corona radiata; left internal capsule; left middle frontal gyrus; left superior longitudinal fasciculus and right somatosensory cortex. Mean diffusivity and radial diffusivity were increased in wide-ranging areas in the nonresponsive group. No difference was observed in axial diffusivity. White matter alterations in the abovementioned areas may affect the function of the dopaminergic network and thus may be associated with the levodopa response in Parkinson's disease patients. Further studies are needed to analyze the specific mechanism and pathological changes underlying these effects.

Laboratory-Supported Multiple System Atrophy beyond Autonomic Function Testing and Imaging: A Systematic Review by the MoDiMSA Study Group.

Neuroimaging has been used to support a diagnosis of possible multiple system atrophy (MSA). Only blood pressure changes upon standing are included in the second consensus criteria but other autonomic function tests (AFT) are also useful to diagnose widespread and progressive autonomic failure typical of MSA. Additional diagnostic tools are of interest to improve accuracy of MSA diagnosis. To assess the utility of diagnostic tools beyond brain imaging and AFT in enhancing a laboratory-supported diagnosis of MSA to support the upcoming revision of the consensus criteria. The International Parkinson and Movement Disorders Society MSA Study Group (MoDiMSA) performed a systematic review of original papers on biomarkers, sleep studies, genetic, neuroendocrine, neurophysiological, neuropsychological and other tests including olfactory testing and acute levodopa challenge test published before August 2019. Evaluation of history of levodopa responsiveness and olfaction is useful in patients in whom MSA-parkinsonian subtype is suspected. Neuropsychological testing is useful to exclude dementia at time of diagnosis. Applicability of sphincter EMG is limited. When MSA-cerebellar subtype is suspected, a screening for the common causes of adult-onset progressive ataxia is useful, including spinocerebellar ataxias in selected patients. Diagnosing stridor and REM sleep behavior disorder is useful in both MSA subtypes. However, none of these tools are validated in large longitudinal cohorts of postmortem confirmed MSA cases. Despite limited evidence, additional laboratory work-up of patients with possible MSA beyond imaging and AFT should be considered to optimize the clinical diagnostic accuracy.

Gait Analysis of Old Individuals with Mild Parkinsonian Signs and Those Individuals' Gait Performance Benefits Little from Levodopa.

Background and PurposeGait analysis and the effects of levodopa on the gait characteristics in Mild parkinsonian signs (MPS) are rarely published. The present research aimed to (1) analyze the gait characteristics in MPS; (2) explore the effects of levodopa on the gait performance of MPS.MethodsWe enrolled 22 inpatients with MPS and 20 healthy control subjects (HC) from Nanjing Brain Hospital. The Unified Parkinson’s Disease Rating Scale was used to evaluate motor symptoms. Acute levodopa challenge test was performed to explore the effects of levodopa on the gait performance of MPS. The instrumented stand and walk test was conducted for each participant and the JiBuEn gait analysis system was used to collect gait data.ResultsFor spatiotemporal parameters: Compared with HC, the state before taking levodopa/benserazide in MPS group (meds-off) demonstrated a decrease in stride length (SL) (p≤0.001), an increase in SL variability (p≤0.001), and swing phase time variability (p=0.016). Compared with meds-off, the state after 1 hour of taking levodopa/benserazide in MPS group (meds-on) exhibited an increase in SL (p≤0.001), a decrease in SL variability (p≤0.001). For kinematic parameters: Compared with HC, meds-off demonstrated a decrease in heel strike angle (p=0.008), range of motion (ROM) of knee joint (p=0.011) and ROM of hip joint (p=0.007). Compared with meds-off, meds-on exhibited an increase in HS (p≤0.001). Bradykinesia and rigidity scores were significantly correlated with gait parameters.ConclusionAlthough the clinical symptoms of the MPS group are mild, their gait damage is obvious and they exhibited a decreased SL and joints movement, and a more variable gait pattern. Levodopa had little effect on the gait performance of those individuals.

Predicting Long-Term Outcome of Patients of Early Parkinsonism with Acute Levodopa Challenge Test.

The aim of this study was to evaluate the sensitivity and specificity of various outcomes of acute levodopa challenge test (ALCT) namely improvement of motor function, development of dyskinesia and intolerance; to predict the diagnosis of idiopathic Parkinson's disease (IPD) or Parkinson-plus syndrome; to predict levodopa responsiveness and levodopa-induced dyskinesia (LID) during long-term therapy. ALCT was performed on 89 patients with parkinsonism of <2 years and were followed up for 18 months. Improvement of UPDRSm by ≥30% was considered positive. The test was positive in 37 (43.5%) and negative in 48 (56.5%) of 85 patients completing it. Of the 75 patients completing 18 months' follow-up 34 (45.3%) were diagnosed as IPD. A positive ALCT predicted a clinical diagnosis of IPD with sensitivity and specificity of 97.4% and 70.7% respectively. The predictive value of ALCT for long-term levodopa responsiveness was less than predicting a diagnosis of IPD. While appearance of dyskinesia during ALCT had a low predictive value for future LID (sensitivity 14.3%), it had high predictive value for a diagnosis of multisystem atrophy (MSA) (91% specificity and 37.5% sensitivity). The appearance of symptoms of levodopa intolerance (SLI) during ALCT could predict a clinical diagnosis of MSA with high specificity (95.5%) and moderate sensitivity (50%). Levodopa responsiveness during ALCT was useful in predicting a diagnosis of IPD but not long-term response to levodopa. The development of dyskinesia during ALCT could not correctly predict LID, but could predict a diagnosis of MSA. The appearance of SLI during ALCT could also predict MSA correctly.

Levodopa challenge test: indications, protocol, and guide.

A drug challenge test in Parkinson's disease, such as the levodopa challenge test (LCT), is an easy and generally safe procedure, which has been used by clinicians for various indications. The results of the test have significant implications in the management of patients, from preoperative evaluation for deep brain stimulation to providing the basis for medication adjustments to address motor or non-motor fluctuations and dyskinesias. This paper reviews the different indications and protocols commonly used in an acute LCT. Potential complications of the procedure and an overview of levodopa responsiveness and unresponsiveness are also discussed.

Wearable Sensors Measure Ankle Joint Changes of Patients with Parkinson's Disease before and after Acute Levodopa Challenge.

Background Previous studies found levodopa could improve the activity of the ankle joints of patients with Parkinson's disease (PD). But ankle joint movement is composed of four motion ranges. The specific changes of four motion ranges in PD remain unknown. Objective The purpose of this study was to decompose the complex ankle joint movement, measure ankle joint changes before and after the acute levodopa challenge test (ALCT), and investigate the effects of these parameters on gait performance. Methods 29 PD patients and 30 healthy control subjects (HC) completed the Instrumented Stand and Walk (ISAW) test and gait parameters were collected by the JiBuEn gait analysis system. The percentage of improvement of gait data and the UPDRS III in the on-drug condition (ON) were determined with respect to the off-drug condition (OFF). Results We observed a reduction in the heel strike angle (HS), 3-plantarflexion (3-PF) angle, and 4-dorsiflexion (4-DF) angle of ankle joints. We did not find significant difference in the toe-off angle (TO), 1-plantarflexion (1-PF) angle, and 2-dorsiflexion (2-DF) angle among three groups. Stride length improvement rate was significantly correlated with HS (rs = 0.616, P < 0.001) and 3-PF (rs = 0.639, P < 0.001) improvement rates. The improvement in the sum of rigidity items (UPDRS motor subsection item 22) was also correlated with HS (rs = 0.389, P=0.037) and 3-PF (rs = 0.373, P=0.046) improvement rates. Conclusions Exogenous levodopa supplementation can significantly reduce the rigidity of patients with PD, improve their 3-PF and 4-DF of ankle joint kinematic parameters, and ultimately enhance their gait.

Measurement of Step Angle for Quantifying the Gait Impairment of Parkinson's Disease by Wearable Sensors: Controlled Study.

BackgroundGait impairments including shuffling gait and hesitation are common in people with Parkinson’s disease (PD), and have been linked to increased fall risk and freezing of gait. Nowadays the gait metrics mostly focus on the spatiotemporal characteristics of gait, but less is known of the angular characteristics of the gait, which may provide helpful information pertaining to the functional status and effects of the treatment in PD.ObjectiveThis study aimed to quantify the angles of steps during walking, and explore if this novel step angle metric is associated with the severity of PD and the effects of the treatment including the acute levodopa challenge test (ALCT) and deep brain stimulation (DBS).MethodsA total of 18 participants with PD completed the walking test before and after the ALCT, and 25 participants with PD completed the test with the DBS on and off. The walking test was implemented under two conditions: walking normally at a preferred speed (single task) and walking while performing a cognitive serial subtraction task (dual task). A total of 17 age-matched participants without PD also completed this walking test. The angular velocity was measured using wearable sensors on each ankle, and three gait angular metrics were obtained, that is mean step angle, initial step angle, and last step angle. The conventional gait metrics (ie, step time and step number) were also calculated.ResultsThe results showed that compared to the control, the following three step angle metrics were significantly smaller in those with PD: mean step angle (F1,48=69.75, P<.001, partial eta-square=0.59), initial step angle (F1,48=15.56, P<.001, partial eta-square=0.25), and last step angle (F1,48=61.99, P<.001, partial eta-square=0.56). Within the PD cohort, both the ALCT and DBS induced greater mean step angles (ACLT: F1,38=5.77, P=.02, partial eta-square=0.13; DBS: F1,52=8.53, P=.005, partial eta-square=0.14) and last step angles (ACLT: F1,38=10, P=.003, partial eta-square=0.21; DBS: F1,52=4.96, P=.003, partial eta-square=0.09), but no significant changes were observed in step time and number after the treatments. Additionally, these step angles were correlated with the Unified Parkinson's Disease Rating Scale, Part III score: mean step angle (single task: r=–0.60, P<.001; dual task: r=–0.52, P<.001), initial step angle (single task: r=–0.35, P=.006; dual task: r=–0.35, P=.01), and last step angle (single task: r=–0.43, P=.001; dual task: r=–0.41, P=.002).ConclusionsThis pilot study demonstrated that the gait angular characteristics, as quantified by the step angles, were sensitive to the disease severity of PD and, more importantly, can capture the effects of treatments on the gait, while the traditional metrics cannot. This indicates that these metrics may serve as novel markers to help the assessment of gait in those with PD as well as the rehabilitation of this vulnerable cohort.

Symptoms of Levodopa Intolerance During Acute Levodopa Challenge Test: Predictor of MSA in Early Years of Parkinsonism (P3.8-008)

Symptoms of Levodopa Intolerance During Acute Levodopa Challenge Test: Predictor of MSA in Early Years of Parkinsonism (P3.8-008)

Acute Levodopa Challenge Test in Patients with de novo Parkinson's Disease: Data from the DeNoPa Cohort.

The precise clinical diagnosis of Parkinson's disease (PD) can be difficult in the early stages. Diagnostic criteria include the response of key motor features to levodopa as a supportive prospective criterion. Data are sparse on the diagnostic value of the acute levodopa challenge test (LDCT) in patients with de novo PD. The objective of this study was to validate the LDCT as a tool in the early clinical diagnosis of PD. We performed the standardized LDCT with 250 mg levodopa in the prospective longitudinal cohort study "DeNoPa," comprising 159 patients with de novo PD, and carried out longitudinal clinical follow-up for 24 months. Motor assessments at baseline using the motor part (part III) of the Unified Parkinson's Disease Rating Scale before and 1 hr after drug administration were documented. The optimal cutoff score on the LDCT was calculated using the Youden index. Clinical reassessment of 144 patients who returned for follow-up confirmed the diagnosis of PD in 120 patients (83%). In 24 patients (17%), the initial diagnoses were revised and classified as other neurologic disorders. The optimal cutoff at 33% improvement of motor symptoms on the part 3 of the Unified Parkinson's Disease Rating Scale during the LDCT reached a sensitivity of 70% a specificity of 71%. The positive and negative predictive values were 92% and 32%, respectively. Sensitivity (91%), specificity (79%), and positive/negative (96%/63%) predictive values improved with the addition of further clinical information (urinary incontinence, fainting, asymmetric tremor, and amount of further drug-intake). The LDCT is a reliable tool in the early diagnosis of PD. The accuracy of this test can be further improved by additional, easy-to-acquire clinical information provided by patients. © 2017 International Parkinson and Movement Disorder Society.

Frailty phenotype and the role of levodopa challenge test in geriatric inpatients with mild parkinsonian signs.

Deficiency in dopaminergic system function may be one of the hypothetical reasons of the frailty syndrome but its role still remains unclear. The aim of our study was to assess the frailty phenotype prevalence in geriatric inpatients with mild parkinsonian signs (MPS) and to investigate levodopa test in the frail patients with MPS. We examined 118 participants: 90 with MPS and 28 in control group (without MPS). The frailty syndrome presence was evaluated by the Fried criteria. Deficiency in dopaminergic system function was assessed by one of the modifications of an acute levodopa challenge test (LCT): in MPS group every patient was examined by performing Up and Go Test and also Step Test before and 3h after taking 125mg of Madopar (levodopa+benserazide). Sixty-nine study subjects (58%) met criteria for frailty. Fifty-five participants in MPS group (61.1% of MPS group) and fourteen (50%) in control group. All of the patients that scored positive in walk speed criterion of frailty were frail. When all MPS patients were considered, the number of components scored positive for frailty was directly related to the walk speed (r=-0.70, p<0.0001). In MPS group LCT scores were significantly higher for frailty patients compared to non-frailty (p=0.0027). When all MPS patients were considered, the number of components scored positive for frailty was directly related LCT score (r=0.37, p=0.0004). There was a relationship between LCT and walk speed (r=-0.31, p=0.0032). Our observations provide new information about the relationship between frailty and MPS, suggest the need for increased awareness of frailty in MPS patients and conversely. Our study provides data for a discussion on pathophysiological background of the frailty syndrome (FS), emphasizing the theories of the important impact of dopaminergic system deficit and encourages further research on the role of LCT in measuring it.

Subjective Perceived Motor Improvement after Acute Levodopa Challenge in Parkinson’s Disease

Previous studies found a poor association between parkinsonian patient's reported subjective improvement after commencing dopaminergic treatment and improvements in objective measures of motor impairment by clinician. To compare PD patient's subjective perceived motor improvement after acute levodopa challenge test with objective motor improvement assessed by the clinician using the UPDRS part III. To analyze clinical characteristics, i.e. age, disease duration, cognitive performance or severity of axial features, that may have influenced patient's perception. Fifty-seven consecutive PD patients (23 women, 34 men; mean age, 63.4±7.7 years) (Hoehn and Yahr off score, 2.5±0.7; mean disease duration, 11.4±4.1 years) completed the acute levodopa challenge. The percentage of improvement in motor disability, i.e. objective motor improvement, was determined with respect to the off-drug condition. Bland & Altman visual analysis reveals a high degree of correlation between objective and subjective perceived motor improvement. Both the axial sub-scores in the off- and on-state (respectively, P = 0.006 and P = 0.024) and the presence of peak-dose dyskinesia (P = 0.043) significantly influence the difference between objective and subjective perceived motor improvement. This is the first study reporting on how PD patients assessed their motor improvement after acute levodopa challenge. These findings suggest a strong correlation between objective motor improvement assessed by the clinician using the UPDRS part III and subjective perceived motor improvement reported by the patient.

Do patients with late-stage Parkinson's disease still respond to levodopa?

BackgroundLate-stage Parkinson’ disease (PD) is dominated by loss of autonomy due to motor and non-motor symptoms which can be marginally corrected by medications adjustments. However, controversy exists on the mechanisms underlying the apparent decrease of benefit from levodopa. ObjectiveTo study the response to levodopa in late-stage PD (LSPD). Methods20 LSPD patients (Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 in MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (DBS) underwent an acute levodopa challenge test. MDS-UPDRS-III and the modified Abnormal Involuntary Movement Scale were evaluated in off and after administration of a supra-maximal levodopa dose. ResultsLSPD patients had a median age of 78.8 (IQR: 73.5–82) and median disease duration of 14 years (IQR: 10-19.75). DBS patients had a median age of 66 (IQR: 61-72) and median disease duration of 18 years (IQR: 15-22). LSPD and DBS patients' MDS-UPDRS-III score improved 11.3% and 37% after levodopa, respectively. Rest tremor showed the largest improvement, while axial signs did not improve in LSPD. However, the magnitude of levodopa response significantly correlated with dyskinesias severity in LSPD patients. One third of LSPD and 9% of DBS patients reported moderate drowsiness. ConclusionsLSPD patients show a slight response to a supra-maximal levodopa dose, which is greater if dyskinesia are present, but it is frequently associated with adverse effects. A decrease in levodopa response is a potential marker of disease progression in LSPD.