Sinemet scientific update |
|
 |
|
2010 Jun 11. [Epub ahead of print]
de Oliveira MM, Conti CF, Valbuza JS, de Carvalho LB, do Prado GF.
Department of Emergency Medicine and Evidence Based Medicine (UNIFESP), Universidade Federal de São Paulo, São Paulo, Brazil.
The pharmacological treatment for uremic restless legs syndrome: Evidence-based review.
Restless legs syndrome (RLS) is a common and often misdiagnosed entity among the general population and it may be more common among dialysis patients, with an estimated prevalence of 6.6 to 21.5%. The treatment for uremic RLS has been controversial and therefore a systematic synthesis of the evidence is needed in order to evaluate the effectiveness and safety of treatments for uremic RLS. This was a systematic review of randomized or quasi-randomized double-blind trials on treatments for uremic RLS. The outcomes considered were relief of RLS symptoms marked on a validated scale, subjective sleep quality, sleep quality measured using night polysomnography and actigraphy, quality of life measured subjectively, and adverse events associated with these treatments. Six eligible clinical trials were included. The results from subjective analyses in these studies were divergent, although objective analyses in one trial showed that there was a statistically significant improvement in periodic leg movement while asleep in the treatment group. No combined analysis (meta-analysis) was performed. The most common adverse event seen was gastrointestinal symptoms. Only a few therapeutic trials on patients with uremia with RLS have been published, and there is insufficient scientific evidence to favor any specific therapeutic regimen for uremic-associated RLS. Therapy using levodopa, dopaminergic agonists, anticonvulsants, and clonidine tend to be effective, but further studies are needed. (c) 2010 Movement Disorder Society.
2010 Jun 9. [Epub ahead of print]
Zaidel A, Spivak A, Grieb B, Bergman H, Israel Z.
1 The Interdisciplinary Centre for Neural Computation, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Subthalamic span of {beta} oscillations predicts deep brain stimulation efficacy for patients with Parkinson's disease.
The significance of oscillations that characterize the subthalamic nucleus in Parkinson's disease is still under debate. Here, we analysed the spectral and spatial characteristics of 314 microelectrode trajectories from 128 patients undergoing subthalamic nucleus deep brain stimulation surgery for Parkinson's disease. We correlated the subthalamic nucleus pathophysiology with the outcome of surgery, as evaluated by the third section of the Unified Parkinson's Disease Rating Scale (motor score), which was subdivided into tremor, rigidity, limb-bradykinesia and axial-bradykinesia subscores. beta-oscillatory activity (13-30 Hz) comprised a continuous stretch within the subthalamic nucleus, and was limited to a distinctly-bounded dorsolateral oscillatory region. Although less consistent and more sporadic, low-frequency (3-7 Hz) power was also increased in the dorsolateral oscillatory region. In contrast, the more ventral subthalamic nucleus was characterized by consistently reduced beta and increased gamma (30-100 Hz) activity. Neuronal responses to passive arm movement (analysed by their alignment to goniometer tracing of the joints' angular displacement) were significantly more common in the dorsolateral oscillatory region than the ventral subthalamic nucleus region (62 versus 25% of sites tested respectively, P < 0.01). The length of the dorsolateral oscillatory region recorded in the macroelectrode-implanted trajectory predicted a favourable response to subthalamic nucleus deep brain stimulation (R = 0.67, P < 0.0001). This correlation was also evident for improvement in the specific symptom subscores of rigidity, limb-bradykinesia and axial-bradykinesia (P < 0.05). Similarly, increased subthalamic nucleus beta power was associated with postoperative improvement. In contrast, the preoperative response to levodopa did not correlate with dorsolateral oscillatory region length (P = 0.33), however, it did tend to be associated with increased beta (and decreased low frequency) subthalamic nucleus power. Finally, the active macroelectrode contact, independently selected by optimal clinical outcome, coincided with the dorsolateral oscillatory region centre. On average, the location of the active contact was not significantly different from the dorsolateral oscillatory region centre (P = 0.10), but was significantly different from the subthalamic nucleus centre (P < 0.0001). We conclude that the spatial extent of the dorsolateral oscillatory region, which overlaps the motor territories of the subthalamic nucleus, predicts the outcome of subthalamic nucleus deep brain stimulation. Thus the frequency and spatial characteristics of the subthalamic nucleus trajectory may be used for deep brain stimulation outcome optimization.
2010 May;93(5):529-40.
Nunta-Aree S, Sitthinamsuwan B, Boonyapisit K, Pisarnpong A.
Division of Neurosurgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. sisna@mahidol.ac.th
SW2-year outcomes of subthalamic deep brain stimulation for idiopathic Parkinson's disease.
BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the recent surgical treatment of choice for patients with idiopathic Parkinson's disease (PD) complicated by motor fluctuation and disabling dyskinesia. OBJECTIVE: To study 2 years clinical outcomes, changes of medication and complications following STN-DBS in patients with advanced PD. MATERIAL AND METHOD: Twenty-seven patients with 2-year follow-up and complete data were enrolled for retrospective evaluation of Unified Parkinson's Disease Rating Scale (UPDRS) and levodopa equivalent dose (LED). Postoperative UPDRS at 6-month, 1-year and 2-years were compared with the preoperative corresponding UPDRS. Postoperative LED at 2 years was compared with the preoperative baseline. Statistical analysis was performed with paired t-test. Additionally, 62 patients with STN-DBS were enrolled for evaluation of treatment complications. RESULTS: Of 27 patients with complete 2-years follow-up, preoperative dopamine challenge test showed 50.6% improvement of motor score (UPDRS axis III). Mentation, behavior and mood (UPDRS axis I) were not significantly improved in each subscore, but significantly improved in the total score. Marked improvement of activities of daily living (UPDRS axis II) and complications of therapy (UPDRS IV) was found. Two-year postoperative motor score (UPDRS axis III) during "off medication-on stimulator" showed progressive and dramatic improvement by mean of 59.83%. The present study also revealed significant improvement of motor score (UPDRS axis III) during "on medication-on stimulator" in some items. A significant 33.4% reduction of LED was noted. Of 62 patients with bilateral STN-DBS, there was 1 asymptomatic intracerebral hemorrhage (0.8% per side), 2 speech difficulty (3.2%), 1 transient confusion (1.6%), 2 transient hypomania (3.2%), 1 stimulation induced hemiballism (1.6%), 1 wound infection (1.6%) and 1 lead malposition (0.8% per side). CONCLUSION: STN-DBS is a safe and effective treatment for PD complicated by motor fluctuation or dyskinesia. The operative outcomes show long-term improvement of activities of daily living, motor function and reduction of medication and drug-related complications.
2010 May 28. [Epub ahead of print]
Bermejo PE, Ruiz-Huete C, Anciones B.
Servicio de Neurología, Hospital Universitario Puerta de Hierro, Calle Manuel de Falla, 1. 28222, Majadahonda, Madrid, Spain, pedro.bermejo.v@gmail.com.
Zonisamide in managing impulse control disorders in Parkinson's disease.
Impulse control disorders (ICDs) are a set of behaviours that take place in a subgroup of patients with Parkinson's disease (PD). Although reduction or switch of dopamine agonists or decrease of levodopa are the common treatment, this does not always improve the compulsive behaviour. Zonisamide (ZNS) has proved effective for motor symptoms in PD and it may be also useful in the field of ICDs. The aim of our study is to evaluate the safety and efficacy of ZNS in PD patients with ICDs who did not improve following a reduction of either levodopa or dopamine agonists. Fifteen patients were initiated on 25 mg/day ZNS dosage, which was titrated to 200 mg/day, as tolerated. Severity of the behaviours was assessed by means of the Clinical Global Impression and the Barratt Impulsiveness Scale, while motor impairment was assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS). Demographic data, medication dose, treatment duration and adverse events were also collected and analyzed. There was a marked reduction in the severity of impulsive behaviours and global impulsiveness (mean change from baseline -5.8 to -4.8, respectively). UPDRS changed only marginally. ZNS was generally well tolerated. Our study suggests that ZNS may be effective for ICDs in PD. The lack of studies with other medications to treat these behaviours in PD and the potential beneficial effects of ZNS for motor complications make this drug important in the treatment of the disease.
2010 May 15;25(7):838-45.
Dissanayaka NN, Sellbach A, Matheson S, O'Sullivan JD, Silburn PA, Byrne GJ, Marsh R, Mellick GD.
Neurology Research Centre, Royal Brisbane and Women's Hospital, Brisbane, Australia. n.dissanayaka@griffith.edu.au
Anxiety disorders in Parkinson's disease: prevalence and risk factors.
Anxiety disorders are common in Parkinson's disease (PD) patients, yet are poorly studied. We examined the prevalence of anxiety disorders in PD, investigated the association between anxiety, and presentation and progression of PD, and studied for the first time the contribution of putative risk factors for anxiety in PD. A case-series of 79 PD patients recruited from neurology out-patient clinics was examined for anxiety disorders using the DSM-IV criteria. The Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr Staging of PD were employed to understand the relationship between anxiety disorders, and the clinical presentation and severity of PD. A validated survey assessed putative risk factors for anxiety in PD. Twenty-five percent of PD patients were diagnosed with anxiety. Panic disorder, generalised anxiety disorder and social phobia were prevalent anxiety disorders. Comorbid depression with anxiety was observed (14%). The severity but not the duration of PD was positively related to anxiety. PD patients with postural instability and gait dysfunction symptom clustering were more likely to experience anxiety than tremor-dominant patients. While levodopa dosage had no relationship to anxiety, experience of dyskinesias or on/off fluctuations increased the risk. Lateralisation of PD had no association with anxiety. Anxiety disorders decreased with age and young onset PD patients were more likely to experience anxiety than the late onset subjects. Anxiety adds to the complexity of PD, lowering patients' quality of life. Future research can be directed to identify reactive and organic nature of anxiety in PD. (c) 2010 Movement Disorder Society.
2009 Dec;15 Suppl 3:S6-12.
Wolters ECh.
Neuroscience Campus Amsterdam, Dept. of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Non-motor extranigral signs and symptoms in Parkinson's disease.
Clinical symptoms in Parkinson's disease (PD) comprise both motor and non-motor symptoms. In this disease, synucleinopathic-induced, nigral dopamine deficiency-related dysfunction of the basal ganglia is held responsible for the characteristic levodopa-responsive motor signs and symptoms (bradykinesia, hypokinesia, rigidity), known as parkinsonism and essential for clinical diagnosis in PD, as well as subtle motivational and cognitive dysfunctions. Some motor symptoms, such as tremor and postural instability, and most non-motor symptoms, however, are not fully levodopa-responsive, and suggested to manifest extranigral pathology. These symptoms include autonomic, sleep, sensory and neuropsychiatric symptoms, which in some cases may precede the first signs of motor parkinsonism, closely correlating with the progression of Lewy body pathology in PD. The recognition and treatment of these mostly under-recognized and under-treated symptoms is important, as these symptoms might have more impact on the quality of life in PD patients as compared to motor parkinsonism. On top of this, recognition of these manifestations in the prodromal phase of motor PD is critical to early diagnosis and treatment, as disease-modifying drugs, once identified, should be initiated as soon as possible, preferably in this premotor phase of the disease. On top of this, (non)motor extranigral symptoms in PD might also be of iatrogenic origin, whether directly as indirectly. During conventional, oral, dopaminomimetic treatment, the progressive loss of striatal dopaminergic nerve endings with the loss of cerebral dopamine storage capacity, renders the cerebral dopamine level fully dependent of the plasma levodopa levels, thus changing dopaminergic receptor stimulation from continuous to a more pulsatile pattern. Supposedly due to this process, neuroplastic changes in (sub)cortical dopaminergic pathways might cause therapeutic response fluctuations: motor and nonmotor fluctuations with anxiety- and panic-attacks and/or mood swings, dyskinesias and punding. Finally, dopaminomimetic pharmacotherapy may also induce extranigral non-motor drug-related direct adverse effects, such as impulse control disorders. In this article, non-motor signs and symptoms of extranigral PD-related pathology will be discussed, as well as the (suggested) criteria for diagnosis and treatment. Of course, also the recognition of the signs and symptoms of the prodromal (premotor) phase, suggestive for the presence of the PD, will be discussed. Iatrogenic non-motor symptoms, though, will not be further discussed.
2009 Dec;15 Suppl 3:S17-21.
Hauser RA.
University of South Florida, Department of Neurology, Tampa, FL 33606, USA.
New considerations in the medical management of early Parkinson's disease: impact of recent clinical trials on treatment strategy.
The best approach to medical management of early Parkinson's disease remains controversial. Recent studies suggest that early use of MAO-B inhibitors may improve long-term outcome. Long-term follow-up to a delayed-start rasagiline study indicated that patients who were treated with rasagiline from the start did better through 5.5-6 years of treatment (with all PD medications) than patients who began rasagiline after a delay of 6 months. In a long-term selegiline study, patients randomized to treatment with selegiline did better over 7 years than patients randomized to treatment with placebo. Dopamine agonists provide moderate symptomatic benefit, delay the need for levodopa, and delay the emergence of motor complications, especially dyskinesia. Long-term studies have not demonstrated a clear overall benefit to introducing a dopamine agonist prior to levodopa in general PD populations, but treatment regimens tend to become increasingly similar over time, most studies have had high drop-out rates, and there may be subsets of patients who experience greater benefit with this strategy. Levodopa remains the most efficacious oral medication for the treatment of motor signs of PD but is associated with the development of motor complications. Long-acting levodopa formulations are now under development and it will be important to determine whether they cause fewer motor complications than standard levodopa. The current approach to treatment of early PD depends in part on individual patient factors including age, severity of motor signs, presence of cognitive dysfunction, and other co-morbidities.
2009 Dec;45(4):621-30.
Berends HI, Nijlant JM, Movig KL, Van Putten MJ, Jannink MJ, Ijzerman MJ.
Roessingh Research and Development, Enschede, The Netherlands.
The clinical use of drugs influencing neurotransmitters in the brain to promote motor recovery after stroke; a Cochrane systematic review.
The objective of this review was to compare and to discuss the results of studies that investigated the ability of drugs to improve motor recovery after stroke by influencing dopamine, norepinephrine, or serotonin concentrations in the brain. A systematic literature search up to January 2009 was conducted in MEDLINE, Pubmed, EMBASE and in the database of the Cochrane Stroke Group Trial Register. In addition, the literature reference lists of the relevant publications were checked. The literature search was conducted in order to identify randomized controlled trials focusing on the effects of drugs on motor recovery after stroke. In order to structure the data, motor recovery was sub-divided into motor control and motor function. The methodological quality of the studies was also assessed. Six studies, investigating the effects of 7 different kinds of drugs were included. Methodological scores varied between 10 and 14 (max 19). Motor control was not influenced by any of the drugs. Motor function improved in patients treated with methylphenidate, trazodone, and nortriptyline. Results for fluoxetine and levodopa were contradicting. There is insufficient evidence to conclude that neuromodulating drugs targeting serotonin, norepinephrine, or dopamine influence motor recovery after stroke.
2009;2009:969752. Epub 2009 Sep 9.
Müller T.
Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088 Berlin, Germany.
Possible treatment concepts for the levodopa-related hyperhomocysteinemia.
The saga of harmful levodopa (LD) in the treatment of Parkinson's disease (PD) resulted from outcomes of animal-and cell culture studies and the clinical observation of motor complication related to the short half life of LD. Further aspects of LD long term application, the LD associated homocysteine increase and its emerging consequences on progression, and onset of neuropsychiatric symptoms and of vascular disease are only partially considered. Therapeutic approaches for this LD-mediated neurotoxic homocysteine increase are vitamin supplementation or LD application with an inhibitor of catechol-O-methyltransferase (COMT). However, forcing central dopamine metabolism further down the methylation path by central blocking of COMT and MAO-B may reduce oxidative stress and homocysteine levels. But it may also increase N-methylation of tetrahydroisoquinolines to neurotoxic N-methylated tetrahydroisoquinolines. These compounds were observed in cerebrospinal fluid and plasma of long term LD-treated PD patients. Therefore LD application with peripheral COMT inhibition may be safer.
2009 Dec;29(12):1452-67.
Chen JJ, Swope DM, Dashtipour K, Lyons KE.
Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Loma Linda University, Loma Linda, California 92350, USA.
Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson's disease.
Rotigotine is a highly lipophilic dopamine-receptor agonist and the first transdermally delivered agent to demonstrate efficacy and safety as monotherapy in early Parkinson's disease and to reduce "off" hours in levodopa-treated patients with advanced Parkinson's disease. The rotigotine pharmacophore is nonergolinic and demonstrates high affinity for dopamine D(2) and D(3) receptors. With once-daily application, the patch matrix provides continuous, nonfluctuating plasma drug levels at steady state, resulting in continuous and steady plasma and brain levels and striatal dopamine-receptor stimulation. In early Parkinson's disease, doses of rotigotine up to 8 mg/24 hours demonstrate comparable efficacy to ropinirole (at doses up to 12 mg/day); in advanced Parkinson's disease, doses of rotigotine up to 16 mg/24 hours demonstrate comparable efficacy and tolerability to pramipexole (at doses up to 4.5 mg/day). In the registration trials for early and advanced Parkinson's disease, the adverse effects most commonly observed with rotigotine were minor application site reactions, dizziness, nausea, and somnolence. Doses of transdermal rotigotine can be titrated to a maintenance dose within 2-3 weeks, and the once-daily regimen minimizes complexity of therapy. The transdermal delivery system is also an advantage when nonoral administration is desired, and the 24-hour, continuous, nonfluctuating drug levels can improve early morning and nocturnal symptoms of Parkinson's disease. Thus, transdermally delivered rotigotine is a clinically innovative and useful addition to the dopamine-receptor agonist class. This review summarizes the key pharmacologic and clinical data for rotigotine and provides a focused clinical context for its use in early-to-advanced Parkinson's disease, as well as a brief summary for its role in restless legs syndrome.
2008 Dec;29 Suppl 5:S380-2.
Canesi M, Zecchinelli AL, Pezzoli G, Antonini A.
Parkinson Institute, Istituti Clinici di Perfezionamento, Via Bignami 1, 20126, Milan, Italy.
Clinical experience of tolcapone in advanced Parkinson's disease.
We are reporting our clinical experience in 66 patients with advanced Parkinson's disease (PD) who were switched to tolcapone because of persisting off periods despite treatment with entacapone (according to the European Agency for the Evaluation of Medicinal products: EMEA). We used UPDRS II-III-IV in "on" state to monitor tolcapone effectiveness at 6 and 12 months. We found significant reductions in mean off-time duration (UPDRS item 39) and levodopa dose at follow up. Eleven patients dropped out (17%) during the first month of treatment, 2 (3%) because liver enzymes exceeded normal limit. Amongst patients who continued tolcapone, 30/55 (54%) reported "off-time" reduction > or =25% (UPDRS-39 decrement > or =1 point). Our findings indicate that tolcapone widens the levodopa therapeutic window, even in patients who have not benefited from entacapone. We suggest that tolcapone is indicated before patients are referred for more invasive procedures.
2008 Dec;64 Suppl 2:S47-55.
Schapira AH, Olanow CW.
University Department of Clinical Neuroscience, Institute of Neurology, London, United Kingdom.
Drug selection and timing of initiation of treatment in early Parkinson's disease.
There is increasing evidence to challenge the traditional view that the initiation of drug treatment in Parkinson's disease (PD) should be delayed until the patient has significant disability such as to affect work or social function. Firstly, to delay treatment sentences the patient to protracted impairment of quality of life that could be improved by therapy. Secondly, there is evidence to support the notion that earlier rather than later initiation of treatment leads to better long term motor benefit. The selection of which drug to begin must be tailored to the patient's individual characteristics and circumstances. Monoamine oxidase B inhibitors result in a mild improvement in motor function compared to dopamine agonists or levodopa. They are well tolerated, easy to use once a day drugs and there is evidence that early use of Rasagiline improves motor outcome. Dopamine agonists lead to a substantial improvement in motor function and are, or will shortly be, available as once a day drugs. They are generally well tolerated but can be associated with exacerbating confusion or hallucinations and with behavioral changes. Levodopa is the most potent of the dopaminergic drugs. It is routinely combined with a dopa decarboxylase inhibitor and can also be used with a catecholo-o-methyl transferase inhibitor for enhanced absorption. The most important limiting factor for the use of levodopa is the emergence of motor complications. These are related to a number of factors including the dose of levodopa and the duration of its use.
2008 Dec;66(4):800-4.
Godeiro-Junior C, Felício AC, Barsottini OG, Aguiar PM, Silva SM, Borges V, Ferraz HB.
Movement Disorders Unit, Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo SP, Brazil. cleciojunior@yahoo.com.br
Clinical features of dystonia in atypical parkinsonism.
BACKGROUND: The association between Dystonia and Parkinson's disease (PD) has been well described especially for foot and hand dystonia. There is however few data on dystonic postures in patients with atypical parkinsonism. OBJECTIVE: To evaluate the frequency and pattern of dystonia in a group of patients with atypical parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP, and corticobasal degeneration - CBD) and to investigate whether dystonia could be the first presenting symptom at disease onset in those patients. METHOD: A total of 38 medical charts were reviewed (n=23/MSA group; n=7/CBD group; n=8/PSP group) and data values were described as means/standard deviations. The variables evaluated were sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopatherapy, Hoehn &Yahr -scale >3 after three years of disease, and magnetic resonance imaging findings. RESULTS: The overall frequency of dystonia in our sample was 50% with 30.4% (n=7) in the MSA group, 62.5% (n=5) in the PSP group, and 100% (n=8) in the CBD group. In none of these patients, dystonia was the first complaint. Several types of dystonia were found: camptocormia, retrocollis, anterocollis, blepharoespasm, oromandibular, and foot/hand dystonia. CONCLUSION: In our series, dystonia was a common feature in atypical parkinsonism (overall frequency of 50%) and it was part of the natural history although not the first symptom at disease onset. Neuroimaging abnormalities are not necessarily related to focal dystonia, and levodopa therapy did not influence the pattern of dystonia in our group of patients.
2008;22 Suppl 1:S33-40.
Mazzone P, Sposato S, Insola A, Dilazzaro V, Scarnati E.
Functional and Stereotactic Neurosurgery, CTO, ASL RMC, Rome, Italy. stereomaz@libero.it
Stereotactic surgery of nucleus tegmenti pedunculopontine [corrected].
The nucleus tegmenti pedunculopontine (PPTg) is a new target for deep brain stimulation (DBS) in Parkinson's disease (PD), in particular for ameliorating postural abnormalities and gait disturbances. The objective of the study is to describe the pre-operative planning, the surgical procedures and results of the DBS of PPTg in humans. Thirteen patients were considered. The surgical approach evolved from the traditional 'indirect' method based on stereotactic ventriculography (5 patients) to a more recent 'direct' method, based on both a digital elaboration of axial stereotactic CT scan and on the 'direct' visual 3D representation of the PPTg (8 patients). No major complication occurred. The direct approach allowed to eliminate the major sources of variability caused by the use of the traditional stereotactic approach. The DBS of PPTg induced a significant amelioration of the following clinical symptoms: gait disturbances, freezing on, speech and arising from the chair. These symptoms are usually not improved by levodopa treatment. The implantation of PPTg proved safe and effective in the treatment of levodopa resistant PD patients. The classic determination of stereotactic coordinates, through a proportional system based on ventriculography, utilising as landmark the CA-CP line and the top of the thalamus, and stereotactic atlases, can hardly be applied to brainstem surgery. The 'direct' method, based on both a digital elaboration of axial stereotactic CT scan and, on the 'direct' visualisation of brainstem borders as well as on the 3D representation of the PPTg, permits a better adaptation to individual anatomic features.
2008;44(1):26-35. Epub 2008 Jul 20.
Lee JY, Han JH, Kim HJ, Jeon BS, Kim DG, Paek SH.
Department of Neurosurgery, Cancer Research Institute, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
STN DBS of Advanced Parkinson's Disease Experienced in a Specialized Monitoring Unit with a Prospective Protocol.
OBJECTIVE: In the evaluation of patients with Parkinson's disease (PD), most neurologists only see their patients during a limited period of their fluctuating 24-hour-a-day lives. This study aimed to assess the short-term outcome of STN stimulation for patients with advanced PD evaluated in a 24-hour monitoring unit for movement disorder (MUMD) using a prospective protocol. METHODS: Forty-two patients with advanced PD consecutively treated with bilateral STN stimulation using multi-channel microelectrode recording were included in this study. All patients were evaluated using a 24-hour MUMD with a video recording/editing system and were evaluated with a prospective protocol of the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr Staging, Schwab and England Activities of Daily Living, levodopa equivalent daily dose (LEDD), Short Form-36 Health Survey, and neuropsychological tests. Magnetic resonance (MR) images of the brain were performed prior to and six months after surgery. RESULTS: All patients were evaluated at three and six months after surgery. There was a rapid and significant improvement of the motor symptoms, especially in tremor and rigidity, after STN stimulation with low morbidity. Dyskinesia was markedly decreased with much lowered LEDD values by 50% after STN stimulation. 1.5T MR images were safely taken according to the manufacturer's guidelines at six months after surgery without any adverse effects in 41 patients treated with STN stimulations. CONCLUSION: Evaluations in a 24-hour monitoring unit could reduce the dose of medication efficiently to an optimal level with patients'comfort and improve the clinical symptoms in harmony with STN stimulation.
2007;13 Suppl 3:S446-9.
Antonini A.
Parkinson Institute, Istituti Clinici di Perfezionamento Milano, Italy. angelo3000@yahoo.com
New strategies in motor parkinsonism.
A satisfactory motor control can be achieved for many years in Parkinson's disease (PD). Clinical management is more complex when disease progresses and occurrence of motor fluctuations and dyskinesias negatively impacts on patients' quality of life. Mobility depends increasingly on levodopa peripheral bioavailability. Medical strategies consist of raising the number of levodopa administrations and the association with COMT inhibitors, entacapone or the more potent tolcapone. MAO-B inhibitors rasagiline or selegiline can be also added. When these options fail, achievement of motor control requires more complex therapeutic strategies: continuous infusion of dopaminergic drugs or neuromodulation with deep brain stimulation (DBS). Apomorphine is a dopamine agonist that can provide motor benefit similar to dopamine, but its use is limited by compliance, local skin reactions at the site of injection and risk of psychiatric adverse events, particularly when round-the-clock administration is used. DBS of the subthalamic nucleus is very effective but feasible only for a small number of patients mostly because of age constraints. Continuous duodenal infusion of levodopa/carbidopa allows replacement of oral therapy resulting in marked improvement of quality of life and activities of daily living. Interestingly, this procedure produces a satisfactory therapeutic response that is paralleled by a reduction in dyskinesia severity.
2007;13 Suppl 3:S421-4.
Stoessl AJ.
Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, 2221 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5. jstoessl@interchange.ubc.ca
Positron emission tomography in premotor Parkinson's disease.
Functional imaging can be used to detect preclinical evidence of dopamine deficiency in people deemed to be at increased risk of Parkinson's disease (PD) based on genetic or environmental risk, or because they have clinical features such as REM sleep behaviour disorder that may be a harbinger of PD. Positron emission tomography (PET) using [11C]dihydrotetrabenazine to label the vesicular monoamine transporter type 2 (VMAT2), a variety of 11C- or 18F-labeled ligands for the membrane dopamine transporter (DAT), or 6-[18F]fluoro-L-dopa (FD), which assesses uptake and decarboxylation of levodopa as well as vesicular storage of radiolabeled dopamine, can all be used, and all provide comparable, but somewhat different information. DAT binding using either PET or SPECT appears to be the most sensitive marker of dopamine denervation, while FD uptake is subject to compensatory upregulation and its reduction may more closely herald the onset of clinical disease. Alterations in glucose metabolism and in dopamine release also occur in the asymptomatic hemisphere of subjects with unilateral PD. An interesting potential application of PET is the determination of non-dopaminergic abnormalities that correlate with the presence of clinically apparent pre-motor symptoms of PD.
2007 Sep;2(3):234-43.
Khor SP, Hsu A.
Clinical Pharmacokinetics and Pharmacodynamics, IMPAX Laboratories, Inc. Hayward, CA, USA.
The pharmacokinetics and pharmacodynamics of levodopa in the treatment of Parkinson's disease.
Levodopa, a prodrug of dopamine, remains to be one of the main drugs in the treatment of Parkinson's disease. All current levodopa products are formulated with aromatic amino acid decarboxylase inhibitors such as carbidopa or benserazide to prevent the metabolism of levodopa in the gastrointestinal tract and systemic circulation. Levodopa pharmacokinetic profiles remain unchanged after multiple doses, and are similar between healthy volunteers and patients and among patients at different stages of disease. Entacapone inhibits the metabolism of levodopa therefore increases the area under the plasma concentration-time profile of levodopa; however, it may decrease the initial absorption rate of levodopa in some patients probably due to competitive absorption. Food appears to affect the absorption of levodopa, but its effects vary with formulations. The results of positron emission tomography study suggest that a high protein diet may compete with the uptake of levodopa into the brain, therefore, may result in reduced levodopa effects. Since infusion studies demonstrated that it is beneficial to maintain stable plasma concentrations of levodopa, controlled-release formulations have been designed to provide prolonged absorption of levodopa. However, subsequent pharmacokinetic and pharmacodynamic studies demonstrated that a threshold concentration of levodopa appears to be necessary to switch patients "on". Once patients are turned "on", the duration of levodopa effects may be correlated with plasma concentration of levodopa. As such, more recent studies have demonstrated significant clinical benefits such as shorter time to "on" and longer duration of "on" when combining the immediate- and controlled-release levodopa products as compared to controlled-release levodopa products. Given these findings, it is important for physicians to understand the relationship between the pharmacokinetics and pharmacodynamics of levodopa in order to provide dosage regimens that meet patient needs. The pharmacokinetics and pharmacodynamics data of levodopa reported in the literature are reviewed here.
2007 Jun;3(3):467-74.
Lecht S, Haroutiunian S, Hoffman A, Lazarovici P.
Rasagiline - a novel MAO B inhibitor in Parkinson's disease therapy.
Parkinson's disease (PD) is a progressive neurodegenerative, dopamine deficiency disorder. The main therapeutic strategies for PD treatment relies on dopamine precursors (levodopa), inhibition of dopamine metabolism (monoamine oxidase [MAO] B and catechol-O-methyl transferase inhibitors), and dopamine receptor agonists. Recently, a novel selective and irreversible MAO B propargylamine inhibitor rasagiline (N-propargyl-1-R-aminoindan, Azilect((R))) was approved for PD therapy. In contrast to selegiline, the prototype of MAO B inhibitors, rasagiline is not metabolized to potentially toxic amphetamine metabolites. The oral bioavailability of rasagiline is 35%, it reaches T(max) after 0.5-1 hours and its half-life is 1.5-3.5 hours. Rasagiline undergoes extensive hepatic metabolism primarily by cytochrome P450 type 1A2 (CYP1A2). Rasagiline is initiated at 1 mg once-daily dosage as monotherapy in early PD patients and at 0.5-1 mg once-daily as adjunctive to levodopa in advanced PD patients. Rasagiline treatment was not associated with "cheese effect" and up to 20 mg per day was well tolerated. In PD patients with hepatic impairment, rasagiline dosage should be carefully adjusted. Rasagiline should not be administered with other MAO inhibitors and co-administration with certain antidepressants and opioids should be avoided. Although further clinical evidence is needed on the neuroprotective effects of rasagiline in PD patients, this drug provides an additional tool for PD therapy.
2007 Nov;61(5):E1024-9; discussion E1029-30.
Tsai ST, Lin SH, Lin SZ, Chen JY, Lee CW, Chen SY.
Department of Neurosurgery, Division of Functional Neuroscience, Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
Neuropsychological effects after chronic subthalamic stimulation and the topography of the nucleus in Parkinson's disease.
OBJECTIVE: The neuropsychological effects of chronic subthalamic nucleus (STN)-deep brain stimulation (DBS) as a treatment for Parkinson's disease are variable. Whether these side effects result from the target per se or current diffusion into neighboring structures is uncertain. In this study, the relationship between clinical outcomes and coordinates of active contact are analyzed and compared between patients with and without neuropsychological sequelae. METHODS: Thirty-eight Parkinsonian patients who underwent bilateral STN-DBS were enrolled in this retrospective cohort study. They were followed for at least 12 months. During the follow-up period, they were divided into two groups for comparison; Group A included patients with neuropsychological side effects and Group B was composed of patients without neuropsychological side effects. The position of the active contact of the electrode was defined with postoperative magnetic resonance imaging scans according to the midcommissural line. Active contact coordinates and clinical outcomes were compared for the two groups. RESULTS: Among the 38 Parkinsonian patients who underwent STN-DBS, eight patients who had neuropsychological side effects were assigned to Group A; the other 30 patients were assigned to Group B. In Groups A and B, the mean follow-up periods were 13.9 and 12.1 months, respectively, the Unified Parkinson's Disease Rating Scale motor score was improved by 53.4 and 45.2% (P = 0.24), respectively, and the levodopa equivalent daily dosage was decreased by 68.4 and 46.4% (P = 0.16), respectively. The mean coordinates of active contact in both Groups A and B were x = 10.1 and 10.5 mm, respectively, y = -2.8 and -3.9 mm, respectively, and z = -6.3 and -6.2 mm, respectively, relative to the midcommissural point. A significant difference was observed on the y axis (P = 0.01). CONCLUSION: When taking spatial influence into consideration, the neuropsychological effects of chronic STN-DBS were related to a significant anteriorly located active contact within the ventral STN in this preliminary study. This might suggest the existence of topography of STN in patients with Parkinson's disease concerning limbic and associative circuits.
J Psychiatr Res. 2005 May;39(3):241-250.
Mohr C, Krummenacher P, Landis T, Sandor PS, Fathi M, Brugger P.
Department of Neurology, Functional Brain Mapping Laboratory, University Hospital Geneva, Rue Micheli-du-Crest 24, 1211 Geneva 14, Switzerland; Rehabilitation Clinic, University Hospital Geneva, Geneva, Switzerland; Department of Neurology, Universit
Psychometric schizotypy modulates levodopa effects on lateralized lexical decision performance.
Emergence of psychotic thought has been related to a breakdown in left-hemisphere language dominance. Dopamine (DA) is implicated in both psychotic pathology and modulation of the semantic system. The present study explored whether controlled DA administration modulates basic language functions: (1) in general and/or (2) as a function of schizophrenia-associated thought. Forty healthy men performed a tachistoscopic lexical decision task. Participants' performance was also analyzed as a function of their positive (magical ideation, MI) and negative (physical anhedonia, PHYSAN) schizotypal features. Half of the subjects received 200 mg levodopa, the other half a placebo. Our findings showed that pharmacological treatment per se did not influence task performance, but influenced laterality patterns as a function of participants' schizotypal features. In the placebo, but not in the levodopa group, right hemisphere language contribution increased as a function of increasing MI scores. In the levodopa, but not in the placebo group, superior left hemisphere lexical decision performance was related to increasing PHYSAN scores. The findings from both substance groups suggest that in the healthy brain, a DA agonist restores left-hemispheric dominance for language by reducing right-hemispheric contribution with respect to a positive schizotypal trait and by increasing left-hemispheric specialization with respect to a negative schizotypal trait. We conjecture that the healthy brain compensates through intact neurochemical mechanisms an increased DA concentration, in particular for persons with elevated positive psychotic-like features.
J Commun Disord. 2005 May-Jun;38(3):187-96.
De Letter M, Santens P, Borsel JV.
Department of Oto-Rhino-Laryngology, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
The effects of levodopa on word intelligibility in Parkinson's disease.
Dysarthria is a common manifestation in patients with idiopathic Parkinson's disease. This study investigated the effects of levodopa on intelligibility in patients with Parkinson's disease. Ten participants were tested during on- and off-states using the Yorkston and Beukelman intelligibility test (1980). Intelligibility as scored by a panel of speech therapists was significantly improved in the on-condition. No correlation was found, however, between intelligibility and overall severity of the disease or severity of the motor problems. EDUCATIONAL OUTCOMES:: As a result of this activity the participant will be able to discuss the effects of levodopa on intelligibility in patients with Parkinson's disease.
J Psychiatr Res. 2005 May;39(3):241-250.
Mohr C, Krummenacher P, Landis T, Sandor PS, Fathi M, Brugger P.
Department of Neurology, Functional Brain Mapping Laboratory, University Hospital Geneva, Rue Micheli-du-Crest 24, 1211 Geneva 14, Switzerland; Rehabilitation Clinic, University Hospital Geneva, Geneva, Switzerland; Department of Neurology, Universit
Psychometric schizotypy modulates levodopa effects on lateralized lexical decision performance.
Emergence of psychotic thought has been related to a breakdown in left-hemisphere language dominance. Dopamine (DA) is implicated in both psychotic pathology and modulation of the semantic system. The present study explored whether controlled DA administration modulates basic language functions: (1) in general and/or (2) as a function of schizophrenia-associated thought. Forty healthy men performed a tachistoscopic lexical decision task. Participants' performance was also analyzed as a function of their positive (magical ideation, MI) and negative (physical anhedonia, PHYSAN) schizotypal features. Half of the subjects received 200 mg levodopa, the other half a placebo. Our findings showed that pharmacological treatment per se did not influence task performance, but influenced laterality patterns as a function of participants' schizotypal features. In the placebo, but not in the levodopa group, right hemisphere language contribution increased as a function of increasing MI scores. In the levodopa, but not in the placebo group, superior left hemisphere lexical decision performance was related to increasing PHYSAN scores. The findings from both substance groups suggest that in the healthy brain, a DA agonist restores left-hemispheric dominance for language by reducing right-hemispheric contribution with respect to a positive schizotypal trait and by increasing left-hemispheric specialization with respect to a negative schizotypal trait. We conjecture that the healthy brain compensates through intact neurochemical mechanisms an increased DA concentration, in particular for persons with elevated positive psychotic-like features.
Mov Disord. 2005 Feb 22.
Moller JC, Oertel WH, Koster J, Pezzoli G, Provinciali L.
Department of Neurology, Philipps-University Marburg, Germany.
Long-term efficacy and safety of pramipexole in advanced Parkinson's disease: Results from a European Multicenter Trial.
A double-blind, placebo-controlled study with a subsequent open-label phase was conducted in 354 patients with Parkinson's disease (PD) and motor fluctuations under individually adjusted therapy with levodopa. During the double-blind phase 174 patients received pramipexole and 180 placebo. In agreement with previous studies, pramipexole treatment improved UPDRS sum scores of parts II and III by 30% and off times by approximately 2.5 hours per day. Differences between the treatment groups became significant at a daily dose of 0.75 mg of pramipexole dihydrochloride. We, furthermore, performed post hoc analyses with respect to resting tremor and depression. Patients with pronounced resting tremor derived a clear benefit from pramipexole treatment compared with placebo. In addition, pramipexole significantly improved the subitems motivation/initiative and depression in a subpopulation with increased Unified Parkinson's Disease Rating Scale I scores at the time of inclusion. There were 262 patients who were subsequently enrolled into the open-label study featuring a maximum duration of up to 57 months. Statistical analysis revealed good long-term efficacy and tolerability of pramipexole. Overall, only a low prevalence of somnolence was found. In summary, this study provides additional level I evidence of the usefulness of pramipexole, suggests a particular tremorlytic and a possible antidepressant action of this compound, and addresses for the first time its efficacy and safety during long-term administration in advanced PD. (c) 2005 Movement Disorder Society.
Prescrire Int. 2005 Apr;14(76):51-4.
Levodopa + carbidopa + entacapone. Entacapone: a second look: new preparations. Parkinson's disease: a modest effect.
(1) If patients with Parkinson's disease treated with levodopa develop end-of-dose motor fluctuations, the standard therapy is to add bromocriptine, a dopamine receptor agonist, to their ongoing treatment. (2) Evaluation data available in 1999 on entacapone, a catechol-o-methyltransferase (COMT) inhibitor, failed to show whether the balance of benefits versus harm was at least equivalent to that of bromocriptine. (3) Entacapone is now also available as a triple fixed-dose combination with levodopa + carbidopa. (4) Three double-blind trials have compared triple combinations of levodopa + carbidopa (or benserazide) + entacapone with levodopa + carbidopa (or benserazide) + placebo. Two of these trials showed an increase of about 1 hour in "on" phases during the day, together with a small reduction in the daily dose of levodopa. These results are consistent with earlier studies. (5) Entacapone has still not been compared with a dopamine agonist. (6) The fixed-dose combination of levodopa + carbidopa + entacapone has been compared with unfixed combinations in two unblinded trials only. (7) These two trials showed that efficacy was similar whether entacapone was used separately or included in a fixed-dose combination with levodopa + carbidopa. The only relevant trial (a non randomised cross-over trial) failed to show patient preference for the fixed-dose combination. (8) In France, a short-acting combination of levodopa and carbidopa is available, with a dose ratio of 10:1. This compares to a ratio of 4:1 for levodopa and carbidopa in the fixed-dose combination of levodopa + carbidopa + entacapone. The dose of carbidopa is therefore higher for a given dose of levodopa, provoking more dyskinesias and nausea. (9) Entacapone can cause drowsiness. Cases of cholestatic hepatitis have also been reported. Risks of liver toxicity, rhabdomyolysis and neuroleptic malignant syndrome remain to be determined. (10) In practice, bromocriptine remains the first-choice for adjunctive therapy when levodopa becomes ineffective.
Neurologia. 2005 May;20(4):180-8.
Castro A, Valldeoriola F, Linazasoro G, Rodriguez-Oroz M, Stochi F, Marin C, Rodriguez M, Vaamonde J, Jenner P, Alvarez L, Pavon N, Macias R, Luquin M, Hernandez B, Grandas F, Gimenez-Roldan S, Tolosa E, Obeso J.
Servicio de Neurologia. Hospital Xeral de Galicia. Santiago de Compostela.
[Optimization of use of levodopa in Parkinson's disease: role of levodopa-carbidopa-entacapone combination.][Article in Spanish]
Levodopa remains the mainstay treatment for Parkinson's disease (PD). Chronic treatment is associated with motor complications (MC) that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible. We here review recent data regarding the mechanism of action of levodopa and its application in clinical practice on the light of the marketing of the combination levodopa-carbidopa- entacapone. Accumulated evidence indicates that MC are mainly the consequence of disease severity governing the degree of dopaminergic depletion and the <> dopaminergic stimulation provided by levodopa short plasma half-life. There is no in vivo or clinical evidence of a relevant neurotoxic effect of levodopa. In fact, the recent ELLDOPA study may suggest a neuroprotective effect. Entacapone reduces homocysteine plasma levels which could provide a mechanism to reduce cell death in PD. Currently, the combination levodopa-carbidopa-entacapone is particularly indicated for the treatment of <> fluctuations. Experimental evidence suggests that early treatment with levodopa-carbidopa-entacapone may substantially ameliorate the incidence of MC. Such a clinical study in <> patients is underway. At present, the combination levodopa-carbidopaentacapone is indicated when levodopa is judged necessary. Neurologia 2005;20(4):180-188.
Sinemet description...
|
|
Drug category:Antiparkinson agents
 Sinemet scientific update
Buy here
|
|
My Basket