Screen for excess FMR1 premutation alleles among males with parkinsonism

BACKGROUND: Individuals with fragile X-associated tremor/ataxia syndrome frequently have associated features of parkinsonism, often leading to an initial diagnosis of Parkinson disease or other parkinsonism spectrum disorders. Parkinson disease populations may thus include individuals who harbor premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. OBJECTIVE: To screen DNA samples (male) from an Italian Parkinson disease clinic for an excess of premutation expansions of the FMR1 gene. DESIGN: DNA samples obtained from 903 unrelated males through consecutive clinic visits were analyzed by an enhanced polymerase chain reaction method for detecting expanded CGG repeats. SETTING: Diagnostic assessments were performed at the Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy. Genotyping was conducted at the University of California Davis School of Medicine. PARTICIPANTS: A cohort of unrelated males with clinical features of parkinsonism. All but 12 males were of Italian origin, and all reported Caucasian ethnicity. MAIN OUTCOME MEASURE: CGG repeat number. RESULTS: Three premutation carriers (61, 69, and 80 CGG repeats) were identified (0.33%), which is not significantly higher than the frequency of premutation alleles in the general population. The outcome of the current study, the largest screen of individuals with parkinsonism to date, supports previous screens of smaller parkinsonism cohorts. CONCLUSION: Broad screening for premutation alleles in Parkinson disease populations is unlikely to be productive in the absence of additional clinical or family history data that suggest involvement of the FMR1 gene.     

123I]FP-CIT striatal binding in early Parkinson's disease patients with tremor vs. akinetic-rigid onset

We performed [123I]FP-CIT/SPECT in 20 drug-naive Parkinson's disease (PD) patients, 10 with unilateral akinesia/rigidity at onset (arPD) and 10 with additional tremor-at-rest (tPD), to evaluate whether resting tremor at onset is associated with differences in striatal dopamine transporter binding. Patients of the two cohorts were matched for age, disease duration (<3 years) and severity of non-tremor motor symptoms; 31 healthy participants served as controls. Mean striatal dopamine transporter binding reduction in PD patients vs. controls was 42% for arPD and 50% for tPD; mean ipsilateral striatum and caudate nucleus uptake values were lower by 12 and 24%, respectively, in tPD than arPD. We conclude that widespread degeneration of the nigrostriatal dopaminergic pathway might be necessary for the development of parkinsonian tremor-at-rest.     

Italian consensus on EULAR recommendations 2005 for the management of hip osteoarthritis

The recommendations for the management of osteoarthritis (OA) of the hip were proposed by EULAR in 2005. Among the most important objectives of the expert charged to provide these recommendations were their wide dissemination and implementation. Thus, the information generated can be used by each individual country to produce their own set of management guidelines and algorithms for treatment in primary care. According with that previously executed for the EU-LAR recommendation 2003 for the knee, the Italian Society of Rheumatology (SIR) has organised a Consensus on the EULAR recommendations 2005 for the management of hip OA. To obtain an acceptability as large as possible, the group of experts was composed by many physicians interested in the management of hip OA, including Orthopaedics, Rheumatologists, Physiatrists, and General Practitioners. Main aim of the Consensus was to analyse the acceptability and applicability of the recommendations according to own experience and local situations in the Italy. The results of this Consensus have demonstrated that a large majority of the EULAR recommendations are endorsed by the Italian experts. Furthermore, the final document of the Italian Consensus clearly indicated the need that the specialists involved in the management of hip OA strongly encourage the dissemination of the EULAR 2005 recommendations also in Italy.     

Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson's disease and depression: effect on quality of life.

We assessed the effect of 3-month treatment of sertraline (50 mg) or low-dose amitriptyline (25 mg) on depression and quality of life in 31 patients with Parkinson's disease in a prospective single-blind randomized study. Both drugs significantly reduced the Hamilton Depression Rating Scale (HDRS-17) score. Completion rate was 75% for sertraline (12 of 16) and 73% for amitriptyline (11 of 15). Responder rate (HDRS-17 score reduction >/= 50%) was 83.3% for sertraline and 72.7% for amitriptyline. Sertraline but not amitriptyline treatment determined a significant benefit on quality of life (PDQ-39 scale). We found no change in Unified Parkinson's Disease Rating Scale scores. However, the improvement in specific PDQ-39 subscores (mobility, activities of daily living, and stigma) suggests that depression affects patient self-perception of motor function and further emphasizes the need for its treatment.     

Adherence to antiparkinson medication in a multicenter European study

Two small studies reported suboptimal therapy adherence in Parkinson's disease. We conducted a larger multicenter European study to assess medicine‐taking behavior. Parkinson's disease patients taking dopaminergic therapy were enrolled in 8 centers in 5 countries, and disease severity and demographics recorded. Antiparkinson drug adherence was measured for 4 weeks using electronic monitoring bottles which record the date and time of cap opening (Aardex®, Switzerland). One hundred twelve patients, mean age 65 years (standard deviation (SD) 10), with Parkinson's disease for 7.7 (SD 8.2) years completed the study. Total median adherence (doses taken/doses prescribed) was 97.7% (interquartile range [IQ] 90.6–100), days adherence (correct dose days) was 86.2% (IQ 61.1–96.2) and timing adherence (doses taken at correct time intervals) was 24.4% (IQ 5.3–56.5). Fourteen patients (12.5%) took less than 80% of prescribed doses, which was defined as suboptimal adherence. Patients with satisfactory adherence took a median of 8 mg/day (IQ 0–33) less than their prescribed dose of levodopa (P = NS), while suboptimal adherence patients took a median of 481 mg/day (IQ 205–670) less than their prescribed dose (P = 0.0006). The Parkinson motor score was significantly higher in patients with suboptimal adherence at 29 (IQ 20–40), versus those with satisfactory adherence at 19 (IQ 13–26), P = 0.005. Once daily drugs had significantly better adherence when compared with drugs prescribed more frequently (P < 0.0001). Suboptimal therapy adherence is associated with significant deviation from prescribed levodopa doses, despite greater Parkinson's motor severity. Optimizing oral medication intake has a potential role in maximizing the therapy response in Parkinson's disease. © 2009 Movement Disorder Society     

Frontal dysfunction in early Parkinson's diseases

Recent studies have suggested that patients with Parkinson's disease (PD) share many of the behavioral deficits found following lesions to the pre-frontal cortex. We assessed the performance of a group of 22 mildly impaired, not-demented parkinsonians (I or II Hoehn & Yahr stage) in a test of classification and recall of pictures of familiar objects, which has been demonstrated to be sensitive to frontal damage in patients with unilateral cerebral excision. Parkinsonians utilized fewer categories than normal controls for object classification, while no significant difference was found in the immediate and delayed recall scores. These results support the contention that a subclinical dysfunction of frontal type may be present even in the early stages of PD. A subanalysis of the data suggests that this dysfunction could possibly be aggravated by anticholinergic drugs.     

Thin section MR study of the basal ganglia in the differential diagnosis between striatonigral degeneration and Parkinson disease

PURPOSE: Signal abnormalities within the putamen in MRI have been related to tissue degeneration in the striatonigral variant of multiple system atrophy (MSA-P). While previous work demonstrated the high specificity of these MR findings, sensitivity rates were unsatisfactory. We evaluated the specificity and sensitivity of an acquisition protocol using thin section MRI to differentiate MSA-P from Parkinson disease (PD). METHOD: Axial 3-mm-thick conventional T2 and proton density spin echo images at the level of basal ganglia were acquired at 1.5 T in 24 patients with MSA-P and 27 patients with PD. RESULTS: We found an abnormal putaminal T2 hypointensity in 21 of 24 MSA-P patients (87.5% sensitivity) and a proton density hyperintensity in 20 of 24 MSA-P patients (83.3% sensitivity). Three among 27 PD patients had an abnormal putaminal T2 hypointensity (88.8% specificity) and there were no proton density abnormalities (100% specificity). CONCLUSION: Our thin section conventional spin echo protocol showed a substantial increase in MR sensitivity compared with previous reports. We believe that a better depiction of even mild signs of degeneration in the putamen may allow a more widespread use of this technique in the differential diagnosis of parkinsonisms.