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Levodopa Therapy (levodopa + therapy)
Selected AbstractsEarly versus delayed initiation of entacapone in levodopa-treated patients with Parkinson's disease: a long-term, retrospective analysisEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2009H. Nissinen Background:, We analysed data from three clinical trials in Parkinson's disease (PD) patients with wearing-off to determine whether early enhancement of levodopa therapy with entacapone can lead to better long-term outcomes than delayed entacapone treatment. Methods:,Post-hoc analysis of pooled data from three randomized, double-blind, placebo-controlled studies and their long-term, open-label extension phases. In all three studies, patients on levodopa/dopa-decarboxylase inhibitor (DDCI) were first randomized to entacapone (,early-start' group) or placebo (,delayed-start' group) for the initial 6-month double-blind phase, after which all patients received open-label levodopa/DDCI and entacapone treatment for up to 5 years. Results:, A total of 488 PD patients with wearing-off were included in the analysis. A statistically significant benefit of early initiation of levodopa/DDCI and entacapone was found, with an improvement in Unified Parkinson's Disease Rating Scale Part III (motor) score of ,1.66 (95% confidence intervals [,3.01, ,0.31]) points compared with the delayed-start treatment group (P < 0.05). Levodopa/DDCI and entacapone therapy was well tolerated. There was no excess of dyskinesia in the early-start group. Conclusions:, These data suggest that early rather than delayed addition of entacapone to levodopa/DDCI in PD patients with wearing-off provides a modest clinical benefit over levodopa/DDCI that is maintained for up to 5 years. [source] Quantitation of non-motor symptoms in Parkinson's diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 2008K. Ray Chaudhuri Background:, Disabling non-motor symptoms (NMS) associated with Parkinson's disease (PD), such as dementia and loss of balance, do not respond well to levodopa therapy and can lead to eventual death in patients with the disease. In 2006, a multidisciplinary group of experts and patient representatives developed an NMS screening questionnaire (NMSQuest) and a unified Non-Motor Symptoms Scale (NMSS) to address the need for simple identification and comprehensive assessment of NMS in patients with PD. Methods and Results:, An international pilot study of 96 healthy controls and 123 patients with various stages of treated and untreated PD was conducted to demonstrate that the NMSQuest is a feasible, valid, and accepted tool. Conclusion:, The majority of patients and caregivers felt that the questionnaire was clear and relevant to their daily lives. Data from 242 PD patients with no dementia were analysed in a pilot study on the clinimetric validation of NMSS. Similar to the NMSQuest study, the NMSS study revealed a significant correlation between progression of PD and increasing NMS burden. These studies suggest that the NMSQuest accurately detects the NMS, and that the NMSS closely correlates with quality of life for PD patients. [source] Sleep disruption, daytime somnolence and ,sleep attacks' in Parkinson's disease: a clinical survey in PD patients and age-matched healthy volunteersEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2006J. J. Ferreira Recent case reports of ,sleep attacks' (SA) in patients with Parkinson's disease (PD) generated concerns about drug-induced daytime somnolence in this population. However, there are nearly no comparative data on sleep and vigilance problems between PD patients and normal controls. We performed a cross-sectional survey in PD patients and age-matched controls using a structured questionnaire on PD history, treatments, co-morbidity, activities of daily living, habits, exercise, sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence, episodes of SA and the circumstances in which such episodes occurred. Daytime somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174 controls were included. The same proportion of PD patients (27%) and controls (32%) reported episodes of SA, but these were more frequent in PD patients and occurred more frequently during situations requiring attention (10.8% vs. 1.7%, p<10,3). More PD patients had abnormal daytime somnolence (ESS) and poor sleeping quality (PSQI). The most consistent factor associated with SA was the duration of levodopa therapy and the predictive value of an abnormal ESS score was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at night are more frequent in PD patients than in normals. However, SA are reported in both groups, although less frequently in the normals during activities that requires attention. [source] The symptomatic treatment of multiple system atrophyEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2002C. Colosimo Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined aetiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar and pyramidal signs. Despite the lack of any effective therapy to reverse this condition, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the statement that patients with MSA are non or poorly levodopa-responsive is misleading. Clinical and pathologically proven series document about 40,60% levodopa efficacy in patients with MSA presenting with predominant parkinsonian features. Unfortunately, other antiparkinsonian compounds (dopamine agonists, amantadine) are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient's history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed in the laboratory with additional tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A variety of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment and physiological diurnal changes and by using other non-pharmacological strategies. The treatment of the very common genito-urinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients. [source] The effect of stage of Parkinson's disease at the onset of levodopa therapy on development of motor complicationsEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2002V. S. Kosti The aim of this study was to ascertain whether the stage of Parkinson's disease (PD) (according to the Hoehn and Yahr staging system) would affect the length of time between the introduction of levodopa therapy and appearance of levodopa-associated motor complications. Forty patients with clinically definite PD were studied. In all, clinical and therapeutic data were collected from the time of diagnosis to the time of levodopa-associated motor complications (i.e. dyskinesia, motor fluctuations). In 17 patients, levodopa could be started in Hoehn and Yahr stage I (H&Y-I; 16.2 months after the onset of PD), whilst in 13 patients levodopa could be started in H&Y-II (19.6 months after the onset of the disease) and in 10 in H&Y-III (45.1 months after the onset of PD). Cox proportional hazard regression model shows that the PD patients in whom the initial levodopa treatment was introduced at stage III develop both dyskinesias and motor fluctuations significantly earlier than the patients whose levodopa started in stage I and II of PD. The median interval to develop dyskinesias was 66, 72 and 24 months for patients in whom levodopa was introduced in stage I, II and III, respectively. These values were 64, 55 and 14 months for motor fluctuations. These findings add to the clinical arguments that favour an essential role of severity of PD at levodopa initiation as a risk factor for the development of levodopa-associated motor complications. [source] Nigrostriatal denervation does not affect glutamate transporter mRNA expression but subsequent levodopa treatment selectively increases GLT1 mRNA and protein expression in the rat striatumJOURNAL OF NEUROCHEMISTRY, Issue 4 2001J.-C. Liévens There is growing evidence that the loss of the nigrostriatal dopaminergic neurones induces an overactivity of the corticostriatal glutamatergic pathway which seems to be central to the physiopathology of parkinsonism. Moreover, glutamatergic mechanisms involving NMDA receptors have been shown to interfere with the therapeutical action of levodopa. Given the key role played by uptake processes in glutamate neurotransmission, this study examined the effects of nigrostriatal deafferentation and of levodopa treatment on the striatal expression of the glutamate transporters GLT1, GLAST and EAAC1 in the rat. No significant changes in striatal mRNA levels of these transporters were detected after either levodopa treatment (100 mg/kg; i.p., twice a day for 21 days) or unilateral lesion of the nigrostriatal pathway by intranigral 6-hydroxydopamine injection. In contrast, animals with the lesion subsequently treated with levodopa showed a selective increase (36%) in GLT1 mRNA levels in the denervated striatum versus controls. These animals also showed increased GLT1 protein expression, as assessed by immunostaining and western blotting. These data provide the first evidence that levodopa therapy may interfere with striatal glutamate transmission through change in expression of the primarily glial glutamate transporter GLT1. We further suggest that levodopa-induced GLT1 overexpression may represent a compensatory mechanism preventing neurotoxic accumulation of endogenous glutamate. [source] Nicotine and Parkinson's disease: Implications for therapyMOVEMENT DISORDERS, Issue 12 2008Maryka Quik PhD Abstract Accumulating evidence suggests that nicotine, a drug that stimulates nicotinic acetylcholine receptors, may be of therapeutic value in Parkinson's disease. Beneficial effects may be several-fold. One of these is a protective action against nigrostriatal damage. This possibility stems from the results of epidemiological studies that consistently demonstrate an inverse correlation between tobacco use and Parkinson's disease. This reduced incidence of Parkinson's disease has been attributed to the nicotine in tobacco products, at least in part, based on experimental work showing a protective effect of nicotine against toxic insults. Second, several studies suggest a symptomatic effect of nicotine in Parkinson's disease, although effects are small and somewhat variable. Third, recent data in nonhuman primates show that nicotine attenuates levodopa-induced dyskinesias, a debilitating side effect that develops in the majority of patients on levodopa therapy. Collectively, these observations suggest that nicotine or CNS selective nicotinic receptor ligands hold promise for Parkinson's disease therapy to reduce disease progression, improve symptoms, and/or decrease levodopa-induced dyskinesias. © 2007 Movement Disorder Society [source] The history of dopamine and levodopa in the treatment of Parkinson's disease,MOVEMENT DISORDERS, Issue S3 2008Stanley Fahn MD Abstract The discoveries of dopamine as a neurotransmitter in the brain, its depletion in patients with Parkinson disease, and its replacement with levodopa therapy were major revolutionary events in the rise to effective therapy for patients with this disorder. This review describes these events and the persons who carried out these accomplishments. Their impact went beyond a single clinical entity of parkinsonism, for it opened up the beginning of a much better understanding of the role of dopamine in other neurologic movement disorders and also in many psychiatric diseases. © 2008 Movement Disorder Society [source] Levodopa-related motor complications,Phenomenology,MOVEMENT DISORDERS, Issue S3 2008Susan H. Fox MRCP (UK) Abstract Long term levodopa therapy in Parkinson's disease (PD) results in a range of problems. These include fluctuations in FD symptoms termed motor fluctuations, as well as non-motor symptoms, termed non-motor fluctuations. Here we review the phenomenology and methods of assessing these levodopa-related complications. © 2008 Movement Disorder Society [source] Continuous dopaminergic stimulation: Is it the answer to the motor complications of Levodopa?MOVEMENT DISORDERS, Issue 1 2007John G. Nutt MD Abstract Continuous dopaminergic stimulation (CDS) is a treatment strategy hypothesized to avoid or reduce the motor complications of long-term levodopa therapy, motor fluctuations, and dyskinesia, by preventing or reversing sensitization induced by pulsatile dopaminergic stimulation. The CDS hypothesis is itself based on several hypotheses. First, tonic dopaminergic stimulation is physiological. Second, sensitization is undesirable and should be reversed. Third, reduction of off time and dyskinesia can be induced simultaneously. Finally, clinical studies substantiate the CDS hypothesis. The evidence for these hypotheses is reviewed, and the need for randomized clinical trials that rigorously test the CDS hypothesis is emphasized. © 2006 Movement Disorder Society [source] High dose levodopa therapy is not toxic in multiple system atrophy: Experimental evidenceMOVEMENT DISORDERS, Issue 7 2007Nadia Stefanova MD Abstract Levodopa is generally regarded the first choice therapy for parkinsonism associated with multiple system atrophy (MSA-P). However, MSA-P patients often show a poor or unsustained levodopa response which inflicts high dose therapy. This is generally attributed to progressive striatal degeneration with loss of dopamine receptors. Experimental evidence suggests that dopaminergic stimulation may accelerate the striatal disease process in MSA, possibly by pro-oxidative mechanisms. Intact nigrostriatal dopamine release augments striatal lesion size in the unilateral nigral and striatal double lesion rat model of MSA-P. Further, neuronal vulnerability to exogenous oxidative stress is increased in a transgenic MSA mouse model with oligodendroglial ,-synuclein inclusions. The aim of the present study was to analyze whether high dose levodopa delivery in the transgenic MSA model is associated with neurotoxicity exacerbated by the presence of oligodendroglial ,-synuclein inclusion pathology. Control and transgenic MSA mice underwent pulsatile treatment with either vehicle, low or high dose levodopa for a period of 1 month. Behavioral and neuropathological indices failed to show evidence for neurotoxic effects of high-dose levodopa in this ,-synuclein transgenic MSA model. These findings support the idea that high dose levodopa therapy in MSA is not detrimental to the underlying neuropathological process. © 2007 Movement Disorder Society [source] Malignant melanoma in early Parkinson's disease: The DATATOP trialMOVEMENT DISORDERS, Issue 5 2007Radu Constantinescu MD Abstract The available epidemiological data on the incidence of malignant melanoma in Parkinson's disease are contradictory. The role of levodopa therapy in this context has been debated. We identified all known cases of malignant melanoma (N = 5) in the DATATOP clinical trial cohort and compared that to published expected values (N = 1.5) for a standard healthy population. The standardized event ratio was 3.3 (95% confidence interval, 1.1,7.8), indicating that incidence of malignant melanoma was higher than expected. We found no association between levodopa therapy and the incidence of melanoma. © 2007 Movement Disorder Society [source] Neuroprotective therapy in Parkinson's disease and motor complications: A search for a pathogenesis-targeted, disease-modifying strategyMOVEMENT DISORDERS, Issue S11 2005C. Warren Olanow MD, FRCPC Abstract The introduction of levodopa in the late 1960s represented a landmark in the therapy of Parkinson's disease (PD). However, motor complications of chronic levodopa therapy have emerged as a major limitation of this otherwise effective therapy. Advancing medical and surgical treatment of these complications has been the main objective of clinical trials during the past few decades. In addition, basic research has focused on better understanding of the mechanisms of motor complications and how to prevent them. Slowing or delaying the progression of the disease delays the need for levodopa therapy; therefore, neuroprotective strategies may play an important role in preventing the onset and reducing the severity of levodopa-related adverse effects. In this introductory review, we present the rationale for current and experimental therapies designed to favorably modify the progression of PD. If implemented early in the course of the disease, such treatments, if found effective, may not only alter the natural progression of the disease but may also delay or minimize motor and nonmotor complications associated with levodopa. © 2005 Movement Disorder Society [source] Amantadine for levodopa-induced choreic dyskinesia in compound heterozygotes for GCH1 mutationsMOVEMENT DISORDERS, Issue 10 2004Yoshiaki Furukawa MD Abstract Amantadine suppressed severe levodopa-induced choreic dyskinesia, which developed at initiation of levodopa therapy, in two siblings manifesting dystonia with motor delay phenotype of GTP cyclohydrolase I deficiency caused by compound heterozygous GCH1 mutations. Our finding suggests a beneficial effect of amantadine on this type of dyskinesia frequently observed in relatively severe dopamine-deficient metabolic disorders. © 2004 Movement Disorder Society [source] Presynaptic parkinsonism in multiple system atrophy mimicking Parkinson's disease: A clinicopathological case studyMOVEMENT DISORDERS, Issue 4 2002José Berciano PhD Abstract We describe the clinicopathological findings in a patient aged 63 years at death who, at age 55 years, developed levodopa-responsive parkinsonism with no atypical features. A diagnosis of idiopathic Parkinson's disease (PD) was made. During the clinical course, fluctuations and dyskinesias appeared. Eight years after onset, he was successfully treated with subthalamic nucleus stimulation but died 3 weeks postoperatively from pulmonary embolus. Brain autopsy showed marked neuronal loss and gliosis in the substantia nigra and locus coeruleus, and, to a much lesser extent, in the basis pontis, inferior olivary nuclei, and cerebellar cortex. Striatum was normal. There were numerous oligodendroglial and neuronal cytoplasmic inclusions and neuropil threads, the highest density being localized in the pons and cerebellar white matter. No Lewy bodies were observed. We conclude that nigral, presynaptic parkinsonism may occur in multiple system atrophy, which even in the long run can be indistinguishable from PD. Putaminal preservation accounts for good response to both levodopa therapy and subthalamic nucleus stimulation. © 2002 Movement Disorder Society [source] Reaction time is not impaired by stimulation of the ventral-intermediate nucleus of the thalamus (Vim) in patients with tremorMOVEMENT DISORDERS, Issue 3 2002Didier Flament PhD Abstract We studied the effect of high-frequency electrical stimulation of the ventral-intermediate nucleus of the thalamus (Vim) in four patients implanted with chronic stimulators to determine whether this procedure adversely affects reaction time to a proprioceptive stimulus. Two patients had undergone this surgery for treatment of tremor resulting from Parkinson's disease insufficiently responsive to levodopa therapy and two patients for treatment of essential tremor. Reaction times to auditory, visual, cutaneous, and proprioceptive stimuli were tested in a simple motor task requiring flexion of the elbow joint to a visual target in response to each stimulus. Reaction times were tested postoperatively with and without the stimulator turned on. We found that reaction time for all stimulus modalities was not increased when the stimulator was turned on; in fact, reaction times were, on average, slightly shorter during stimulation, but this difference was not statistically significant. We conclude that transmission of somatosensory inputs, necessary for initiating voluntary movement, from the periphery to the cortex is not significantly impaired by stimulation of the ventral-intermediate nucleus of the thalamus in patients with pathological tremor. © 2002 Movement Disorder Society [source] Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson diseaseANNALS OF NEUROLOGY, Issue 1 2010Cory Toth MD Objective Peripheral neuropathy (PN) is thought to be coincidental in patients with idiopathic Parkinson disease (IPD). We sought to examine the prevalence of PN in a population of IPD patients and a potential relationship to levodopa use and fasting methylmalonic acid (MMA) levels. Methods In a prospective cohort study, IPD patients randomly selected from a comprehensive database were compared to control subjects regarding the presence and severity of PN using clinical and electrophysiological measures. IPD severity was determined using the Unified Parkinson's Disease Rating Scale (UPDRS). We determined the relation of levodopa use with serum levels of cobalamin, MMA, and homocysteine (Hcy). We also explored the association between presence and severity of PN and age, duration of IPD, cumulative levodopa dosing, cobalamin, MMA, and Hcy levels. Results Fifty-eight randomly selected IPD patients were compared to 58 age- and sex-matched controls. PN was present in 55% of IPD patients and 9% of controls. Patients with IPD had greater prevalence of PN and fasting MMA/Hcy levels than controls. IPD patients with PN were older and exhibited higher UPDRS scores, fasting MMA/Hcy levels, and cumulative levodopa exposure. PN severity in IPD subjects positively correlated with both levodopa exposure and MMA levels. Interpretation IPD patients have a higher prevalence of PN than controls. Although causality is not established, levodopa exposure is associated with MMA elevation and sensorimotor neuropathy in IPD patients. Cobalamin replacement concurrent with levodopa therapy should be considered to protect against development of PN in IPD patients. ANN NEUROL 2010;67:28,36 [source] Dopamine-dependent motor learning: Insight into levodopa's long-duration responseANNALS OF NEUROLOGY, Issue 5 2010Jeff A. Beeler PhD Objective Dopamine (DA) is critical for motor performance, motor learning, and corticostriatal plasticity. The relationship between motor performance and learning, and the role of DA in the mediation of them, however, remain unclear. Methods To examine this question, we took advantage of PITx3-deficient mice (aphakia mice), in which DA in the dorsal striatum is reduced by 90%. PITx3-deficient mice do not display obvious motor deficits in their home cage, but are impaired in motor tasks that require new motor skills. We used the accelerating rotarod as a motor learning task. Results We show that the deficiency in motor skill learning in PITx3(,/,) is dramatic and can be rescued with levodopa treatment. In addition, cessation of levodopa treatment after acquisition of the motor skill does not result in an immediate drop in performance. Instead, there is a gradual decline of performance that lasts for a few days, which is not related to levodopa pharmacokinetics. We show that this gradual decline is dependent on the retesting experience. Interpretation This observation resembles the long-duration response to levodopa therapy in its slow buildup of improvement after the initiation of therapy and gradual degradation. We hypothesize that motor learning may play a significant, underappreciated role in the symptomatology of Parkinson disease as well as in the therapeutic effects of levodopa. We suggest that the important, yet enigmatic long-duration response to chronic levodopa treatment is a manifestation of rescued motor learning. ANN NEUROL 2010;67:639,647 [source] | ||||||||||