Brain repair for Parkinson's disease:is the answer in the matrix?

正Two hundred years after James Parkinson first described the cardinal motor symptoms of the disorder that would later bear his name,there is still an irrefutable need for a therapy that targets the underlying pathophysiology of the disease and not solely its symptoms.Parkinson’s disease(PD)is classically characterised by Lewy body formation and a relatively selective degeneration of nigrostriatal dopaminergic     

Low‐frequency deep brain stimulation for Parkinson's disease: Great expectation or false hope?

The long‐term efficacy of subthalamic deep brain stimulation for Parkinson's disease is not always retained, and many patients lose the improvement achieved during the “second honeymoon” following surgery. Deep brain stimulation is a versatile tool, as stimulation parameters may undergo a fine‐tuning depending on clinical needs. Among them, frequency is the parameter that leads to more complex scenarios because there is no generalizable relationship between its modulation and the overall clinical response, which also depends on the specific considered sign. High‐frequency stimulation (>100 Hz) has shown to be effective in improving most parkinsonian signs, particularly the levodopa‐responsive ones. However, its effect on axial signs (such as balance, gait, speech, or swallowing) may not be sustained, minimal, or even detrimental. For these reasons, several studies have explored the effectiveness of low‐frequency stimulation (generally 60 or 80 Hz). Methods, results, and especially interpretations of these studies are quite variable. Although the use of low‐frequency stimulation certainly opens new avenues in the field of deep brain stimulation, after having gathered all the available evidence in patients with subthalamic implants, our conclusion is that it might be clinically useful mainly when it lessens the detrimental effects of high‐frequency stimulation. © 2016 International Parkinson and Movement Disorder Society     

Nursing and multidisciplinary interventions for Parkinson's disease: what is the evidence?

This paper reports the interim results of an ongoing systematic review of the available evidence for the effectiveness of nursing care for people with Parkinson's disease (PD). Five clinical and four health-economic evaluations suggest that the clinical and cost effectiveness of nursing care for PD remain inconclusive. This is in contrast to clinical experience and may be due to issues related to study designs, study interventions, and the outcome measures used. More studies are needed and may benefit from considering specific interventions evaluated using outcome measures that are valid and responsive representations of their expected outcomes.     

Pharmacogenomics in Parkinson's disease: which perspective for developing a personalized medicine?

<正>Every disease treatment is ideally finalized to prevent symptom occurrence,to stop or slow down the progression of disease,to alleviate complications already present and consequently to improve the quality of life for each patient.Unfortunately,in Parkinson’s disease(PD)a treatment able to completely cure the disease is not so far available.Indeed,until now,the current therapies only allow to control the disease symptoms,     

Dynamic psychotherapy or dialectical behavioral therapy-- which is better for borderline personality disorder?

Clinical dilemma: A 20-year-old female patient, diagnosed as suffering from borderline personality disorder, is referred to your clinic. Her disorder is characterized by unstable personal relationships, impulsivity, suicidal behavior, emotional instability and pan-anxiety. After initiation of pharmacological treatment which you have chosen, you meet with her parents who ask you which is better for their daughter dynamic-analytic psychotherapy or dialectical behavioral therapy.     

Switching dopamine agonists in advanced Parkinson's disease: is rapid titration preferable to slow?

BACKGROUND: New dopamine agonists are available, but no study has examined safe and effective ways to switch from one agonist to another. OBJECTIVE: To compare rapid- versus slow-titration schedules for starting a new dopamine agonist in patients already on chronic agonist therapy for Parkinson's disease. METHODS: Sixteen patients on stable carbidopa/levodopa and a dopamine agonist (bromocriptine or pergolide) switched to pramipexole using a conversion calculation of 1:1 for pergolide dose and 10:1 for bromocriptine dose. Patients were randomized to two titration schedules-either slow titration, following the package insert and taking up to 8 weeks to reach their equivalent dosage (8 patients), or rapid titration, receiving the full converted dose the day after stopping the former agonist (8 patients) with subsequent weekly dose adjustments. Using a blinded observer, the primary outcome variable was the time required to a Unified Parkinson's Disease Rating Scale (UPDRS) motor score superior to baseline without increased adverse effects. RESULTS: Both groups showed equivalent and statistically significant improvement after switching to the new agonist. The mean time to reach a UPDRS score that was superior to baseline without increased adverse effects was significantly shorter in the rapid-titration group (mean 2.1 weeks versus 5.3 weeks). Furthermore, with slow titration two patients experienced enhanced parkinsonian serious adverse effects requiring hospitalization (two falls with fractures). CONCLUSION: The switchover from one agonist to another can be safely and successfully accomplished with a rapid titration based on an equivalency dose calculation.     

Controversy: is Parkinson's disease a single disease entity? Yes

Parkinson's disease (PD) is a common, and in principle, sporadic, neurodegenerative disorder that occurs in adults. Pathological studies have revealed that in PD, nerve cell loss and Lewy bodies (LB) are distributed widely in the nervous system. Moreover, molecular pathology has made remarkable advances over the last several years, after the identification of alpha-synuclein gene abnormality in familial PD. Extensive pathological findings support the idea that PD is a single disease entity and that there are no cases of PD in which neurodegeneration occurs only in the substantia nigra and in which there are no LBs.     

How useful is (123I) beta-CIT SPECT in the diagnosis of Parkinson's disease?

Because clinical features of parkinsonism can occur in other forms of parkinsonian syndromes in addition to Parkinson's disease, neuroimaging may have a role in determining true disease status. Iodine-123 ((123)I) (2beta-carboxymethoxy-3beta-[4-iodophenyl] tropane) or ((123)I) beta-CIT is a recently developed diagnostic biomarker of Parkinson's disease that provides in vivo information about nigrostriatal degeneration. In clinical trials, beta-CIT single photon emission computed tomography (SPECT) has been shown to be a highly sensitive diagnostic tool in differentiating clinically probable Parkinson's disease from normal subjects and essential tremor patients. As a tool for differentiating Parkinson's disease from atypical parkinsonian syndromes, ((123)I) beta-CIT SPECT may have more limited use because of more extensive postsynaptic pathology in the latter. Differentiating among various parkinsonian syndromes may be improved by methodological refinements, a combined strategy of imaging presynaptic and postsynaptic sites, or by metabolic imaging.     

Dopamine agonists: the treatment for Parkinson's disease in the XXI century?

Levodopa combined with a peripheral dopa-decarboxylase inhibitor (DCI) has been considered the therapy of choice for Parkinson's disease (PD). Levodopa is nearly always effective, but has a high incidence of adverse effects with long term use, including response fluctuations (on/off phenomena) and dyskinesias. Dopaminergic agonists, acting directly at the receptor level, would be able to decrease the incidence of these motor complications.In progressive neurodegenerative diseases, such as PD, modification of the rate of disease progression (often referred to as neuroprotection) is currently a highly debated topic. Increased oxidative stress is thought to be involved in nigral cell death, that is characteristic of PD. This oxidative stress may be further exacerbated by levodopa therapy. These mechanisms have been proven in vitro and animal models, but it's relevance in humans remains speculative.Based on the considerations above, the emerging therapeutic strategies for PD advocate early use of dopamine agonists in the treatment of PD. A number of recent well-controlled studies have proven the efficacy of dopamine agonists used as monotherapy. Moreover, as predicted by animal studies, on the long term, dopaminergic agonists induce significantly less motor complications than levodopa.In the last 2years, three new dopamine agonists have been launched, including ropinirole, pramipexole and cabergoline. These new agonists have been added, as therapeutical options to well-established drugs, like pergolide, bromocriptine or talipexole. The recently launched compounds have proven efficacy in monotherapy and as adjunctive therapy to levodopa. Unfortunately, only a very limited amount of comparative data among the different agonists is available. Pergolide has proven to be a superior drug to bromocriptine as adjunctive therapy to levodopa in a significant number of studies and is considered the gold standard dopamine agonist. Nevertheless, none of the recently launched compounds has compared itself against pergolide.A comparison of monotherapy trials is difficult, because of differences in design and populations. In a recently completed trial pergolide was statistically significantly better than placebo in all the efficacy parameters tested, with 57% of pergolide treated patients improving over 30% in the motor section of the UPDRS, as compared to 17% in the placebo arm. Interestingly, these results were obtained in the absence of any other antiparkinsonian drug during the trial. Recent monotherapy trials done with ropinirole and pramipexole achieved also significant improvements as monotherapy, but in these cases selegeline, a drug that causes a symptomatic improvement in PD, was allowed as co-medications during the trial. Not all trials used the same efficacy measures, i.e. monotherapy trials with pergolide and ropinirole used a "responder" based analysis (responder were all patients that improved 30% or more on the motor section of UPDRS), as well as a baseline to endpoint improvement in motor scores. Pramipexole monotherapy trials used only the latter approach, which is clinically less powerful than a responder analysis.Even with the difficulties mentioned above, all the recent trials with dopamine agonists have proven that these drugs are a useful symptomatic long term treatment for PD with or without levodopa and that the early use of dopamine agonists reduces the incidence of motor complications as compared to levodopa.