Parkinson's Disease Rating Scale Motor Scores Research Articles

Is the cingulate island sign a marker for early dementia conversion in Parkinson's disease?

To investigate whether the cingulate island sign (CIS) ratio (i.e., the ratio of regional uptake in the posterior cingulate cortex relative to the precuneus and cuneus on cerebral perfusion scans) is associated with early dementia conversion in Parkinson's disease (PD). We enrolled 226 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase 18 F-FP-CIT PET scans. Patients with PD were classified into three groups according to the CIS ratio on early-phase 18 F-FP-CIT PET images: a PD group with CIS or high CIS ratios (PD-CIS; n = 96), a PD group with inverse CIS or low CIS ratios (PD-iCIS; n = 40), and a PD group consisting of the remaining patients with normal CIS ratios (PD-nCIS; n = 90). We compared the risk of dementia conversion within a 5-year time point between the groups. There were no significant differences in age, sex, education, or baseline cognitive function between the PD groups. The PD-CIS group had higher Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and more severely decreased dopamine transporter availability in the putamen. The PD-iCIS group had a smaller hippocampal volume compared with the other groups. The risk of dementia conversion in the PD-CIS group did not differ from that in the PD-iCIS and PD-nCIS groups. Meanwhile, the PD-iCIS group had a higher risk of dementia conversion than the PD-nCIS group. The results of this study suggest that inverse CIS, rather than CIS, is relevant to early dementia conversion in patients with PD.

CircEPS15, as a sponge of MIR24-3p ameliorates neuronal damage in Parkinson disease through boosting PINK1-PRKN-mediated mitophagy

ABSTRACT Despite growing evidence that has declared the importance of circRNAs in neurodegenerative diseases, the clinical significance of circRNAs in dopaminergic (DA) neuronal degeneration in the pathogenesis of Parkinson disease (PD) remains unclear. Here, we performed rRNA-depleted RNA sequencing and detected more than 10,000 circRNAs in the plasma samples of PD patients. In consideration of ROC and the correlation between Hohen-Yahr stage (H-Y stage) and Unified Parkinson Disease Rating Scale-motor score (UPDRS) of 40 PD patients, circEPS15 was selected for further research. Low expression of circEPS15 was found in PD patients and there was a negative positive correlation between the circEPS15 level and severity of PD motor symptoms, while overexpression of circEPS15 protected DA neurons against neurotoxin-induced PD-like neurodegeneration in vitro and in vivo. Mechanistically, circEPS15 acted as a MIR24-3p sponge to promote the stable expression of target gene PINK1, thus enhancing PINK1-PRKN-dependent mitophagy to eliminate damaged mitochondria and maintain mitochondrial homeostasis. Thus, circEPS15 rescued DA neuronal degeneration through the MIR24-3p-PINK1 axis-mediated improvement of mitochondrial function. This study reveals that circEPS15 exerts a critical role in participating in PD pathogenesis, and may give us an insight into the novel avenue to develop potential biomarkers and therapeutic targets for PD. Abbreviations: AAV: adeno-associated virus; DA: dopaminergic; FISH: fluorescence in situ hybridizations; HPLC: high-performance liquid chromatography; H-Y stage: Hohen-Yahr stage; LDH: lactate dehydrogenase; MMP: mitochondrial membrane potential; MPTP/p: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid; NC: negative control; PD: Parkinson disease; PINK1: PTEN induced kinase 1; PBS: phosphate-buffered saline; ROS: reactive oxygen species; SNpc: substantia nigra pars compacta; TEM: transmission electron microscopy; UPDRS: Unified Parkinson’s Disease Rating Scale-motor score

Association between freezing of gait and bone mineral density in patients with Parkinson's disease.

Parkinson's disease (PD) patients are at risk for developing bone health problems, and freezing of gait (FOG) in PD is associated with a high risk of falling and fracture. This study aimed to determine the association between FOG and bone mineral density (BMD) in patients with PD. We included 148 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q), and BMD was measured by dual-energy X-ray absorptiometry. Of 148 PD patients, 102 (68.9%) had FOG. PD patients with FOG were older and had longer disease duration, higher levodopa equivalent dose, higher modified Hoehn and Yahr stage, higher Unified PD Rating Scale motor score, higher FOG-Q score, higher total Non-Motor Symptom Scale score, and lower BMD scores in the femoral neck area than those without FOG. Pearson correlation analysis revealed that age, sex, body mass index, and age at onset were significantly correlated with areal BMDs in all areas. FOG-Q scores correlated negatively with areal BMDs in the total hip area and femoral neck, but not with areal BMD in the lumbar spine. Multivariate regression analysis showed that FOG-Q score was significantly correlated with areal BMD in the femoral neck, but not with areal BMDs in the lumbar spine or total hip. FOG in PD patients correlates significantly with BMD in the femoral neck area. Therefore, PD patients with FOG should be screened for osteoporosis.

Cost-Effectiveness Analysis of Deep Brain Stimulation for Parkinson Disease in Taiwan

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective therapy for Parkinson disease (PD). However, cost-effectiveness analysis is required because most patients are older adults and decision makers must therefore consider whether the long-term effectiveness outweighs the initial cost. A Markov decision model was constructed on the basis of a societal perspective. The Hoehn and Yahr scale and Unified PD Rating Scale motor score were used in the polytomous logistic regression model. Markov Chain Monte Carlo simulation was used to initiate the probabilistic cost-effectiveness analysis. The life-year gained (LYG) in the STN-DBS group and medication group was, respectively, 2.937 and 2.632 years at the 3-year follow-up and 7.417 and 5.971 years at the 10-year follow-up. The quality-adjusted life-year (QALY) gained in the STN-DBS and medication groups was, respectively, 1.739 and 1.220 at the 3-year follow-up and 4.189 and 2.88 at the 10-year follow-up. The incremental cost-effectiveness ratio of STN-DBS compared with medication was $147,065 per LYG and $123,436 per QALY gained at the 3-year follow-up and $36,833 and $69,033 at the 10-year follow-up, respectively. STN-DBS is an optimal strategy when the willingness to pay is $150,000 per LYG and over $90,000 per QALY gained in 3 years and when the willingness to pay is over $38,000 per LYG and over $41,000 per QALY gained in 10 years. This study provided data comparing STN-DBS and medical treatment for PD with respect to LYG and QALY gained. STN-DBS was more cost-effective in terms of LYG and QALY gained according to the current gross domestic product of Taiwan.

Comparison of Awake vs. Asleep Surgery for Subthalamic Deep Brain Stimulation in Parkinson’s Disease

Deep brain stimulation (DBS) surgery for Parkinson's disease (PD) is usually performed as awake surgery allowing sufficient intraoperative testing. Recently, outcomes after asleep surgery have been assumed comparable. However, direct comparisons between awake and asleep surgery are scarce. To investigate the difference between awake and asleep surgery comparing motor and nonmotor outcome after subthalamic nucleus (STN)-DBS in a large single center PD population. Ninety-six patients were retrospectively matched pairwise (48 asleep and 48 awake) and compared regarding improvement of Unified PD Rating Scale Motor Score (UPDRS-III), cognitive function, Levodopa-equivalent-daily-dose (LEDD), stimulation amplitudes, side effects, surgery duration, and complication rates. Routine testing took place at three months and one year postoperatively. Chronic DBS effects (UPDRS-III without medication and with stimulation on [OFF/ON]) significantly improved UPDRS-III only after awake surgery at three months and in both groups one year postoperatively. Acute effects (percentage UPDRS-III reduction after activation of stimulation) were also significantly better after awake surgery at three months but not at one year compared to asleep surgery. UPDRS-III subitems "freezing" and "speech" were significantly worse after asleep surgery at three months and one year, respectively. LEDD was significantly lower after awake surgery only one week postoperatively. The other measures did not differ between groups. Overall motor function improved faster in the awake surgery group, but the difference ceased after one year. However, axial subitems were worse in the asleep surgery group suggesting that worsening of axial symptoms was risked improving overall motor function. Awake surgery still seems advantageous for STN-DBS in PD, although asleep surgery may be considered with lower threshold in patients not suitable for awake surgery.

Novel Approach to Stem Cell Therapy in Parkinson's Disease.

In this commentary we discuss International Stem Cell Corporation's (ISCO's) approach to developing a pluripotent stem cell based treatment for Parkinson's disease (PD). In 2016, ISCO received approval to conduct the world's first clinical study of a pluripotent stem cell based therapy for PD. The Australian regulatory agency Therapeutic Goods Administration (TGA) and the Melbourne Health's Human Research Ethics Committee (HREC) independently reviewed ISCO's extensive preclinical data and granted approval for the evaluation of a novel human parthenogenetic derived neural stem cell (NSC) line, ISC-hpNSC, in a PD phase 1 clinical trial ( ClinicalTrials.gov NCT02452723). This is a single-center, open label, dose escalating 12-month study with a 5-year follow-up evaluating a number of objective and patient-reported safety and efficacy measures. A total of 6 years of safety and efficacy data will be collected from each patient. Twelve participants are recruited in this study with four participants per single dose cohort of 30, 50, and 70 million ISC-hpNSC. The grafts are placed bilaterally in the caudate nucleus, putamen, and substantia nigra by magnetic resonance imaging-guided stereotactic surgery. Participants are 30-70 years old with idiopathic PD ≤13 years duration and unified PD rating scale motor score (Part III) in the "OFF" state ≤49. This trial is fully funded by ISCO with no economic involvement from the patients. It is worth noting that ISCO underwent an exhaustive review process and successfully answered the very comprehensive, detailed, and specific questions posed by the TGA and HREC. The regulatory/ethic review process is based on applying scientific and clinical expertise to decision-making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines or novel therapies.

A Comprehensive Approach to Care in Parkinson's Disease Adds Quality to the Current Gold Standard.

Providing high-quality care for patients with Parkinson's disease (PD) involves addressing both motor and nonmotor features. We describe the implementation and evaluation of a 2-day, interdisciplinary Comprehensive Care Clinic (CCC) for patients with PD. Patients who attended the CCC between January 2010 and July 2013 were matched by sex and age with patients who were evaluated in specialist care during the same time frame. Provider documentation of the American Academy of Neurology (AAN) quality measures for PD and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were compared between specialist and CCC visits at baseline and at 12 months. Ninety-five patients participated in the CCC (60% men; 75% white; mean age, 68 years; age range, 38-97 years). Of these, 29 patients were matched to specialist care patients based on the availability of 12-month follow-up data. Both groups were similar with respect to race, marital status, years with PD, and baseline UPDRS motor scores. On average, patients who received CCC care met 10 of 10 AAN quality measures, whereas those who received specialist care met only 5 of 10 quality measures (P < 0.001) over 12 months. At 12-months, there were no significant differences in UPDRS motor scores between the groups (P = 0.5). According to the AAN quality measures, the CCC provided higher quality care than the gold standard of specialty care. A randomized controlled trial of the CCC model is warranted to determine its impact on patient-centered outcomes and to assess whether the standard model of care should be altered.

Neuroprotection of Granulocyte Colony-Stimulating Factor for Early Stage Parkinson's Disease

Parkinson's disease (PD) is a slowly progressive neurodegenerative disease. Both medical and surgical choices provide symptomatic treatment. Granulocyte colony-stimulating factor (G-CSF), a conventional treatment for hematological diseases, has demonstrated its effectiveness in acute and chronic neurological diseases through its anti-inflammatory and antiapoptosis mechanisms. Based on previous in vitro and in vivo studies, we administered a lower dose (3.3 μg/kg) G-CSF injection for 5 days and six courses for 1 year in early-stage PD patients as a phase I trial. The four PD patient's mean unified PD rating scale motor scores in medication off status remained stable from 23 before the first G-CSF injection to 22 during the 2-year follow-up. 3,4-Dihydroxy-6-18F-fluoro-L-phenylalanine (18F-DOPA) positron emission tomography (PET) studies also revealed an annual 3.5% decrease in radiotracer uptake over the caudate nucleus and 7% in the putamen, both slower than those of previous reports of PD. Adverse effects included transient muscular–skeletal pain, nausea, vomiting, and elevated liver enzymes. Based on this preliminary report, G-CSF seems to alleviate disease deterioration for early stage PD patients. The effectiveness of G-CSF was possibly due to its amelioration of progressive dopaminergic neuron degeneration.

Long-term risk of falls in an incident Parkinson's disease cohort: the Norwegian ParkWest study.

The objective of this study is to examine the frequency, development, concomitants, and risk factors of falls in a population-based incident Parkinson's disease (PD) cohort. One hundred eighty-one drug-naïve patients with incident PD and 173 normal controls recruited from the Norwegian ParkWest study were prospectively monitored over 7years. Information on falls was obtained biannually from patients, and at baseline and after 1, 3, 5, and 7years of follow-up in control subjects. Generalized estimating equation models for correlated data were applied to investigate concomitant features of falls and risk factors for incident falls during 7years of follow-up in PD. Overall, 64.1% of patients reported falling during the study period. The 7-year cumulative incidence of falls in non-falling patients at baseline (n=153) was 57.5%, with a relative risk to controls of at least 3.1 (95% confidence interval 1.5-6.3; p<0.002). Significant concomitants of falls in patients during the study period were higher age, Unified PD Rating Scale motor score, postural instability and gait difficulties (PIGD) phenotype, dementia, and follow-up time. Higher age at baseline, PIGD phenotype at 1-year visit, and follow-up time were independent risk factors for incident falls during follow-up. Nearly two-thirds of patients in the general PD population experience falls within 7 years of diagnosis, representing a more than threefold increased risk compared to age- and gender-matched controls. Patients with higher age at baseline and early PIGD have the greatest risk of falling and may, therefore, be the prime target of specialized assessment and treatment interventions.

Rapid assessment of gait and speech after subthalamic deep brain stimulation.

Background:Describe a rapid assessment for patients with idiopathic Parkinson's disease (PD) and deep brain stimulation of the subthalamic nucleus reporting worsening speech and/or gait problems.Methods:We retrospectively reviewed 29 patients that had improvement in gait and/or speech within 30 min after turning stimulation off. Clinical data analyzed include unified PD rating scale motor scores and stimulation parameters before and after adjusting stimulation. All patients received electrode efficacy and side effect threshold testing. Stimulation parameters were adjusted to maximize efficacy, avoid side effects, and maximize battery longevity.Results:Turning stimulation off revealed reversible speech and/or gait stimulation side effects within 30 min. Focusing on six factors revealed stimulation modifications that improved motor symptoms, eliminated stimulation side effects, and reduced battery drain. Primary stimulation parameters modified were cathode selection and pulse width reduction.Conclusions:Stimulation-induced side effects impacting gait and speech can be identified within 30 min. A systematic evaluation can distinguish disease progression from reversible stimulation side effects and improve motor outcomes over the long term.

Amplitude of low-frequency oscillations in Parkinson's disease: a 2-year longitudinal resting-state functional magnetic resonance imaging study.

Background:Neuroimaging studies have found that functional changes exist in patients with Parkinson's disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.Methods:Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.Results:Compared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in the UPDRS motor score (r = 0.61, P < 0.05, uncorrected).Conclusions:The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease's progression in patients with PD.

Non-motor symptoms in an Indian cohort of Parkinson's disease patients and correlation of progression of non-motor symptoms with motor worsening.

To document the frequency and prevalence of non-motor symptoms (NMS) in an Indian cohort of Parkinson's disease (PD) patients. To validate the non-motor score scale (NMSS) in an Indian cohort of PD patients for recording NMS of the disease, to study the prevalence and frequency of NMS in Indian PD patients using the NMSS, and to compare the progression of NMS with motor worsening. Conclusion and Results: This was a cross-sectional, single-center, open-label, one point in time evaluation study conducted from 2009 to 2011. It validated the NMSS scale in an Indian population. The study has profiled the prevalence and pattern of NMS in an Indian cohort of PD patients. Comparison of NMS scale scores with the Unified PD Rating Scale motor scores demonstrated a correlation between non-motor and motor symptoms in the disease progression, particularly of manifestations related to the cognitive decline, memory disturbances, urinary incontinence and smell.

Subjective cognitive decline predicts future deterioration in cognitively normal patients with Parkinson's disease

Increasing evidence suggests that subjective cognitive decline (SCD) is a potential predictor of future cognitive decline or dementia. We investigated whether SCD in patients with Parkinson's disease (PD) is a predictor of future cognitive decline. Forty-six cognitively normal patients with PD were selected using comprehensive neuropsychological tests, and classified depending on the presence (PD-SCD+, n = 25) or absence of SCD (PD-SCD−, n = 21). After a mean follow-up of 2.4 years, we repeated the cognitive assessments with the same subjects. The clinical characteristics and cognitive performance of the 2 groups did not differ at baseline. At the follow-up assessment, 11 patients in the PD-SCD+ group (44.0%) and 2 in the PD-SCD− group (9.5%) were diagnosed with mild cognitive impairment (MCI), and the PD-SCD+ patients showed more rapid decline in semantic fluency and visuospatial memory tasks than those in the PD-SCD− group. A multivariate logistic regression analysis showed that presence of SCD (odds ratio, 8.378; 95% confidential interval, 1.472–47.683, p = 0.017) and higher Unified PD Rating Scale motor score of 20 or more (odds ratio, 4.539; 95% confidential interval, 1.004–20.528; p = 0.049) were risk factors for incident MCI. Present results demonstrate that SCD in cognitively normal patients with PD is an independent risk factor for incident MCI and acts as a predictor for future cognitive decline.

The influence of motor and cognitive impairment upon visually-guided saccades in Parkinson's disease

Studies of saccades in Parkinson's disease (PD) have seldom examined the influence of cognitive status, ranging from normal cognition, through mild cognitive impairment, to dementia. In a large and heterogeneous sample, we examined how motor and cognitive impairment was reflected in the performance of reflexive, visually-guided saccades. We examined 163 people with PD and 47 similar-aged controls. Ninety three of the PD group had normal cognition (PDN), 48 had mild cognitive impairment (PD-MCI), and 22 had dementia (PDD). Pseudo-random targets (amplitudes of 5, 10, 15 and 20deg and inter-stimulus-intervals ranging from 550 to 1800ms) were shown in 108 mixed randomised trials, incorporating gap, step, and overlap onset conditions. Analyses were conducted using multi-level regression modeling. Participants were first assessed by continuous measures (Unified PD Rating Scale motor score and the Montreal Cognitive Assessment). Prolonged latency was significantly related to both motor and cognitive impairment, with the cognitive effect being compounded by increasing age. Decreased saccade amplitude, meanwhile, was primarily related to motor impairment. When assessed by discrete cognitive categories, all of the PD groups showed reduced saccadic amplitude relative to controls. Saccadic latencies, meanwhile, were abnormally prolonged only in the PD-MCI and PDD groups (the control and PDN groups were similar to each other). Latency in the overlap task was particularly sensitive to increasing motor and cognitive impairment. We conclude that reflexive saccades in PD are subtly decreased in amplitude even early in the disease process. Prolonged saccade latency, meanwhile, tends to occur later in the disease process, in the presence of more substantial motor and cognitive impairment, and greater age. The progressive impairment of reflexive saccades, and the differential onset of amplitude and latency impairments, may make them a useful objective tool for assessing disease status.

Autonomic and cognitive functions in Parkinson's disease (PD)

We performed this study to evaluate the relationship between the stages of PD and autonomic dysfunction, and to find an association between the autonomic dysfunction and cognitive impairment in PD. Sixty-three patients who met the criteria of the United Kingdom PD Society Brain Bank were enrolled prospectively. Clinical stages were using the Hoehn and Yahr (H&Y) staging and unified PD rating scale motor scores. Cognitive functions were evaluated using the mini-mental state examination (MMSE) and the modified MMSE (3MS) test. The scale for outcome in PD-autonomic (SCOPA-AUT) was used to evaluate autonomic symptoms. Severities of autonomic dysfunction were classified using the composite autonomic scoring scale (CASS). Fifty-four of the 63 patients (86%) had shown abnormalities on CASS. H&Y stages correlated with SCOPA-AUT ( p < 0.05) and 3MS and MMSE scores ( p < 0.05). H&Y stages were positively related with autonomic dysfunction, heart rate ratios during deep breathing and the quantitative sudomotor axon reflex test (QSART) scores. Autonomic dysfunction may be present from disease onset, whereas the rate of cognitive decline increases with disease progression. We recommend that both qualitative and quantitative autonomic evaluation from the early stage of disease and regular cognitive screening with disease progression might be useful to facilitate optimal management in PD.

Clinical and cerebral activity changes induced by subthalamic nucleus stimulation in advanced Parkinson's disease: A prospective case-control study

Background High-frequency stimulation of the subthalamic nucleus (STN-DBS) improves motor symptoms in advanced Parkinson's disease (PD), but the mechanisms are still unclear. Functional imaging evidenced pathological overactivity in motor cortical areas in advanced PD that can be normalized by effective therapies. Patients and methods We studied resting state cerebral blood flow pre-operatively and 12 months after surgery in 40 patients with advanced PD using ECD-SPECT. SPECT scans were also acquired 1 year apart in 21 matched PD controls who did not undergo surgery. Statistical analysis was performed using statistical parametric mapping (SPM2) software. In addition, we correlated brain perfusion changes after surgery with clinical improvement, assessed using the unified PD rating scale motor score (UPDRS-III). Results Patients showed marked motor improvement and medication reduction after surgery. Stimulated PD patients revealed bilateral rCBF decrements in motor cortical areas and prefrontal cortex bilaterally compared to pre-surgical condition as well as versus PD controls ( p < .01 FDR corrected). Perfusion increases were found in cerebellum, temporal and occipital lobes. Clinical improvement was associated with perfusion decrements in primary motor and premotor cortices. Conclusions Effective STN-DBS is associated with neuronal activity changes in brain regions implicated in movement programming and performance. We hypothesize that clinical benefit might be associated with stimulation-induced normalization of the abnormal overactivity within the cortico-basal ganglia-thalamo-cortical motor loop in advanced PD.

Continued efficacy and safety of subcutaneous apomorphine in patients with advanced Parkinson's disease

The study purpose was to assess the efficacy of intermittent subcutaneous apomorphine (APO) as acute therapy for off episodes in advanced Parkinson's disease (PD) patients who had previously received APO for ⩾3 months. Patients ( n = 62 ) were randomized to receive double-blind treatment with APO at their typically effective dose (TED; APO), APO at their TED+0.2 mL (2.0 mg; APO+2), placebo at volume equal to their TED (PL), or placebo at volume equal to their TED+0.2 mL (PL+2), for a single off episode. Significantly greater improvement in mean Unified PD rating scale motor scores was seen with pooled APO versus pooled placebo 20 min after administration (−24.2 vs. −7.4; p < 0.0001 ); the difference was also significant at 10 min ( p < 0.0001 ). Overall adverse event incidence did not significantly differ between pooled APO and pooled PL. This study supports the long-term use of intermittent APO as effective acute therapy for off episodes in advanced PD patients.

The long-duration action of levodopa may be due to a postsynaptic effect.

A single dose of levodopa (L-DOPA) reduces motor disability in Parkinson's disease (PD) for a few hours, a short-duration effect. However, there are suggestions that L-DOPA may also produce a long-duration benefit of some days. In the present study, we examined the long-duration action of L-DOPA by observing the time taken to achieve maximum stable benefit after starting a constant dose of sinemet-CR (sinemet-CR) (200 g L-DOPA/50 mg carbidopa) twice daily in nine newly diagnosed patients, and the time taken to deteriorate back to baseline after stopping treatment. A single dose of sinemet-CR (200 mg L-DOPA/50 mg carbidopa) had little obvious short-duration action on the Unified PD Rating Scale (UPDRS) motor scores in the majority of patients, either before starting chronic sinemet-CR therapy (200 mg L-DOPA/50 mg carbidopa, b.i.d.) or after chronic treatment. However, all patients gradually improved on chronic sinemet-CR therapy, taking 9.3 +/- 1.8 days to achieve maximum response. On stopping chronic sinemet-CR treatment, it took 6.8 +/- 3.0 days for the same patients to deteriorate back to baseline motor disability. In similar experiments, the time taken to deteriorate back to baseline after stopping treatment with the directly acting dopamine agonist ropinirole (9-21 mg daily) in eight other de novo patients with PD was found to be 6.2 +/- 1.7 days. The long-duration effect of L-DOPA and ropinirole may, therefore, be due to some slowly evolving postsynaptic pharmacodynamic change in the central nervous system (CNS). Loss of this long-duration action may be responsible for the emergence of motor fluctuations on chronic L-DOPA therapy.