La maladie de Parkinson :Actualités thérapeutiques

Parkinson's disease in a neurodegenerative disorder that affects as many as 1-2 % of persons aged 60 years and older. Parkinson's disease occurs infrequently under 40 years of age, with major genetic implication. Alpha-synuclein plays significant pathogenic role in Parkinson's disease. Therapeutic advances based on a synucleinrelated mechanism are now developed :Immunotherapy against alpha-synuclein for example. The diagnosis of Parkinson's disease remains mostly clinical. DatScan® may be helpful to distinguish parkinsonian syndrome and essential tremor. Current therapy is mainly based on a dopamine replacement strategy using the precursor levodopa (L-Dopa) and dopamine receptor agonists. Parkinson's is also associated with non-motor symptoms like sleep disorders, autonomic symptoms, neuropsychiatric symptoms. Advanced disease is associated with emergence of feature such as freezing, falling and neuropsychological dysfunction. Nonpharmacologic treatments like exercise are fundamental elements of patients' management .Motor complications and dyskinesia are common in advanced Parkinson's disease. Continuous administration of L-Dopa/carbidopa infusion in the jejunum provides more continuous dopaminergic drug delivery and stimulation and reduce motor complications. Fur ther other approach are developped like surgical procedures: Ex :High frequency stimulation of subthalamic nucleus, the more rational target for stimulation in Parkinson's disease.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Investigation "in vivo" du système dopaminergique présynaptique chez le rat sain et le rat rendu hémiparkinsonien

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Investigation "in vivo" du système dopaminergique présynaptique chez le rat sain et le rat rendu hémiparkinsonien

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Apport de la scintigraphie par 123I-FP-CIT (DaTSCAN™) au diagnostic différentiel des troubles du mouvement

The diagnosis of idiopathic Parkinson's disease (IPD) remains mostly clinical. Nevertheless, differentiating IPD from essential tremor or other parkinsonian syndromes solely by clinical examination can be challenging in some cases, especially in the early stage of the disease. The introduction of new isotopic functional imaging techniques, and more specifically the labelling of dopamine transporter derivatives, has improved the understanding and early detection of some diseases affecting the basal ganglia. Iodine-123-FP-CIT (DaTSCAN™), a (presynaptic) dopamine transporter analogue for nuclear medicine imaging, has recently been introduced for the non-invasive differential diagnosis between IPD and essential tremor or secondary (e.g. drug-related) parkinsonian syndromes. DaTSCAN™ scintigraphy has also demonstrated some usefulness in the evaluation of other neurodegenerative parkinsonian syndromes such as Lewy-body dementia or multiple system atrophy. For this latter however, the DaTSCAN™ has to be combined with a second scintigraphy, imaging the post-synaptic dopaminergic receptors, such as the D2-ligand 123I- iodobenzamide. Combining DaTSCAN™ scintigraphy to a functional study of the brain cortical activity using a brain perfusion scintigraphy or to the evaluation of the cardiac adrenergic system by means of a myocardial MIBG scintigraphy (a norepinephrine storage analogue) can also be helpful to refine the diagnosis. Our experience shows that a good collaboration between the neurologist specialized in movement disorders and the nuclear medicine physician is useful, if not mandatory, to optimize the diagnostic performances of DaTSCAN™ scintigraphy.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Levodopa-carbidopa intestinal gel in advanced Parkinson's: Final results of the GLORIA registry

Introduction This registry evaluated the 24-month safety and efficacy of levodopa-carbidopa intestinal gel (LCIG) treatment in advanced Parkinson's disease (PD) patients under routine clinical care. Methods Motor fluctuations, dyskinesia, non-motor symptoms, quality of life, and safety were evaluated. Observations were fully prospective for treatment-naïve patients (60% of patients) and partially retrospective for patients with ≤12 months of pre-treatment with LCIG (40% of patients). Hours of “On” and “Off” time were assessed with a modified version of the Unified Parkinson's Disease Rating Scale part IV items 32 and 39. Results Overall, 375 patients were enrolled by 75 movement disorder centers in 18 countries and 258 patients completed the registry. At 24 months LCIG treatment led to significant reductions from baseline in “Off” time (hours/day) (mean ± SD = −4.1 ± 3.5, P < 0.001), “On” time with dyskinesia (hours/day) (−1.1 ± 4.8, P = 0.006), Non-Motor Symptom Scale total (−16.7 ± 43.2, P < 0.001) and individual domains scores, and Parkinson's Disease Questionnaire-8 item total score (−7.1 ± 21.0, P < 0.001). Adverse events deemed to have a possible/probable causal relationship to treatment drug/device were reported in 194 (54%) patients; the most frequently reported were decreased weight (6.7%), device related infections (5.9%), device dislocations (4.8%), device issues (4.8%), and polyneuropathy (4.5%). Conclusions LCIG treatment led to sustained improvements in motor fluctuations, non-motor symptoms particularly sleep/fatigue, mood/cognition and gastrointestinal domains, as well as quality of life in advanced PD patients over 24 months. Safety events were consistent with the established safety profile of LCIG.0SCOPUS: ar.jinfo:eu-repo/semantics/publishe

FP-CIT SPECT in clinically inconclusive Parkinsonian syndrome during amiodarone treatment: A study with follow-up

ObjectiveS: To evaluate whether dopamine transport system imaging by FP-CIT single-photon emission computed tomography (SPECT) can be helpful to differentiate idiopathic Parkinsons disease (IPD) from secondary Parkinsonism induced by amiodarone. Methods: Twenty-two patients with Parkinsonism during amiodarone therapy were evaluated by clinical neurological examination and FP-CIT SPECT. Thereafter, amiodarone was discontinued whenever possible and antiparkinsonian treatment was modified, if required. Clinical neurological status was reevaluated within a year of the SPECT examination. Results: At baseline, clinical neurological examination was quite similar in all patients. No clinical symptom was able to clearly orientate the diagnosis toward IPD or drug-induced Parkinsonism. Using SPECT, the number of normal and abnormal patients was evenly distributed. In the abnormal SPECT group, amiodarone was modified in seven patients of whom six improved at follow-up. Antiparkinsonian treatment had been modified in all the patients. In the four cases with no amiodarone changes, clinical improvement was noted if antiparkinsonian treatment was optimized (three patients). In the 11 normal SPECT patients, amiodarone was modified in five patients. All patients ameliorated (two) or even normalized (three). In the six patients with normal SPECT in whom amiodarone had not been modified, symptoms remained stable despite the absence of antiparkinsonian treatment. Conclusion: In patients treated with amiodarone, IPD is sometimes clinically difficult to differentiate from drug-induced Parkinsonism. Using FP-CIT, a normal scan suggests drug-induced Parkinsonism, hence, there is no need for antiparkinsonian treatment and all possible attempts to reduce or preferably stop amiodarone. An abnormal scan, on the other hand, indicates IPD. In this case, treating IPD seems to have more impact on motor changes than modifying the antiarrhythmic drug. © 2010 Wolters Kluwer HealthSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Interobserver reproducibility of the interpretation of I-123 FP-CIT single-photon emission computed tomography

Objectives: I-123 ioflupane (FP-CIT) single-photon emission computed tomography is a recognized tool in the diagnosis of Parkinsonian syndromes. In practice, data interpretation relies on visual and semiquantitative analyses. Good interobserver reproducibility is a prerequisite before claiming the robustness of a technique. This study aimed at evaluating interobserver reproducibility of this approach. Methods: Thirty nuclear medicine physicians participated in the study. Data included FP-CIT images and semiquantitative measurements of 12 cases, covering a wide spectrum of scintigraphic patterns and for which a 'true' clinical diagnosis based on long-term follow-up was available. Interobserver agreement was defined, for each case, as the highest percentage reached among the three proposed answers with complete agreement arbitrarily set at 80% or more. Variability in an individual observer's sensitivity to assess data as normal, equivocal or abnormal was scored using a three-point scale. Results: Response rate was 99.7%. Among the three possible answers, 'normal' accounted for 41.2% of the total, 'abnormal' for 49.8% and 'equivocal' for 8.1%. The mean interobserver agreement was 76% (range: 37-100%), with complete agreement being reached only in five cases. The interpretation proposed by most observers accorded to clinical diagnosis in 75% of the cases. Abnormalities of the central nervous system were encountered in all the cases with disagreement between the observer's interpretation and clinical diagnoses. An important variability in the observers sensitivity was seen. Conclusion: In the particular setting of this preliminary study evaluating the reproducibility of FP-CIT single-photon emission computed tomography interpretation in a group of nuclear medicine physicians with various experiences, interobserver agreement was suboptimal. Collegial discussion and standardized interpretation criteria could contribute to an improved reproducibility. © 2010 Wolters Kluwer HealthSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Depression, anxiety and non-motor symptoms on initiation of intrajejunal levodopa/carbidopa therapy

In Parkinson’s disease (PD), clinical observations and some studies suggest that depression and anxiety are linked to motor fluctuations. We studied prospectively 10 patients with advanced PD just before initiation of intrajejunal levodopa/carbidopa therapy, and after 1 and 3 months of regular treatment. Motor symptoms, motor fluctuations, non-motor symptoms, quality of sleep, symptoms of depression and anxiety were evaluated with the appropriate scales. As expected, motor symptoms and motor fluctuations improved considerably. Non-motor symptoms, quality of sleep and depression also improved significantly. However, anxiety score remained unchanged during the study. Our data in a small numbers of patients indicate that all aspects of mental and psychic symptoms are not alleviated within a short period of reduction of motor fluctuations.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Hemibody tremor related to stroke.

BACKGROUND: Hemibody tremor is an uncommon manifestation of stroke. We describe a case investigated by both brain magnetic resonance imaging and positron emission tomography using [18F]fluorodeoxyglucose. CASE DESCRIPTION: Three months after a pure motor stroke, a 65-year-old man developed a right arm and leg tremor. The tremor was of large amplitude, intermittent at rest; its frequency was 5 to 6 Hz. Neither rigidity nor akinesia was detected, and administration of L-dopa was ineffective. Brain magnetic resonance imaging revealed an ischemic lesion in the left centrum semiovale and a left caudate lacunar infarction. We suspected that the resting unilateral tremor was related to this lacunar lesion. Positron emission tomography demonstrated glucose hypermetabolism in the left sensorimotor cortex. CONCLUSIONS: This case suggests that unilateral tremor may be related to a lacunar stroke in the caudate nucleus and may be accompanied by an increased glucose metabolism in the contralateral sensorimotor cortex.Case ReportsJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe