A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group (http://www.emsa-sg.org), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson’s disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.     

Hydrocarbon exposure and Parkinson's disease

BACKGROUND: Single cases of parkinsonism have been associated with hydrocarbon solvents. OBJECTIVE: To determine whether exposure to hydrocarbon solvents is related to PD. METHODS: Cohort study of 990 patients with PD according to Core Assessment Program for Intracerebral Transplantations (CAPIT) criteria, selected from 1455 consecutive subjects presenting at a referral center; case-control study assessing Unified PD Rating Scale scores (motor score as primary endpoint) in all subjects with positive history of hydrocarbon solvent exposure (n = 188), matched for duration of disease and gender to 188 subjects selected from the remaining 802 with a negative history. Two subgroups in the case-control study included the following: 1) response to apomorphine (n = 26); 2) brain MRI (n = 15). PET imaging (n = 9) was compared with that of historic controls. RESULTS: Exposed patients were younger (61.0 +/- 9.4 versus 64.7 +/- 9.4 years, p = 0.002), predominantly male (76.4% versus 45.2%, p = 0.0001), less educated (8.4 +/- 4.2 versus 10.1 +/- 4.4 years, p = 0.0001), and younger at onset of disease (55.2 +/- 9.8 versus 58.6 +/- 10 years, p = 0.014). Exposure to hydrocarbon solvents directly correlated to disease severity (r = 0. 311) and inversely correlated to latency period (r = -0.252). Nine blue-collar occupations accounted for 91.1% of exposures. CONCLUSIONS: Occupations involving the use of hydrocarbon solvents are a risk factor for earlier onset of symptoms of PD and more severe disease throughout its course. Hydrocarbon solvents may be involved in the etiopathogenesis of PD, which does not have a major genetic component.     

MR imaging of the superior profile of the midbrain: differential diagnosis between progressive supranuclear palsy and Parkinson disease

BACKGROUND AND PURPOSE: Quantitative evaluation of midbrain atrophy may be useful in differentiating progressive supranulear palsy (PSP) from Parkinson disease (PD); however, this finding is not specific of PSP, and quantitative measurements are not always practical. We determined whether an abnormal superior midbrain profile (flat or concave aspect) is a more practical diagnostic parameter for PSP. METHODS: MR imaging studies of 25 patients with PSP and 27 with PD were reviewed by means of five parameters: midbrain superior profile on midsagittal T1-weighted images, midbrain atrophy, tegmental abnormal T2 hyperintensity, abnormal T2 putaminal hypointensity or hyperintensity on axial proton density-weighted images. We also measured the anteroposterior diameter of the midbrain on axial T2-weighted sections at the level of the superior colliculus. RESULTS: The finding of an abnormal superior profile of the midbrain had 68% sensitivity and 88.8% specificity. Midbrain atrophy had 68% sensitivity and 77.7% specificity. Tegmental T2 hyperintensity had 100% specificity but poor sensitivity (28%). Only 14.8% of patients with PD and 24% of those with PSP had abnormal putaminal T2 hypointensity; none had proton-density hyperintensity. With PSP, the average midbrain diameter was smaller than that with PD, but an important overlap was observed. Reader discordance was lower for the midbrain superior profile sign (eight of 52 cases); this was similar for tegmental hyperintensity (nine of 52 cases) and higher for midbrain atrophy (16 of 52 cases). CONCLUSION: An abnormal superior profile of the midbrain facilitates the distinction of PSP from PD and may support the clinical differential diagnosis of parkinsonism.     

Predictive variables for malignant transformation in 452 patients with asymptomatic IgM monoclonal gammopathy

The natural history of asymptomatic IgM monoclonal gammopathies (MG) and variables predicting evolution to symptomatic lymphoproliferative disorders were investigated in 452 patients diagnosed from 1975 to 2001. Univariate and multivariate Cox models were used to identify possible predictors of disease progression. At a median follow-up of 49 months (range, 12 to 233), 41 cases (9.1%) evolved to symptomatic Waldenstrom's macroglobulinemia (n = 36), non-Hodgkin's lymphoma (n = 2), B-cell chronic lymphocytic leukemia (n = 1), IgM multiple myeloma (n = 1), and primary amyloidosis (n = 1); the median interval from diagnosis was 53 months (range, 12 to 154). The cumulative probabilities of transformation into a symptomatic lymphoproliferative disease at 5 and 10 years were 8% (95% confidence interval [CI], 6% to 12%) and 21% (95% CI, 16% to 29%), respectively. At univariate analysis, monoclonal component size and hemoglobin level as continuous parameters, lymphocytosis (>4 x 10(9)/L), bone marrow lymphoplasmacytoid infiltration (>10%), erythrocyte sedimentation rate (>40 mm/h), and detectable Bence Jones proteinuria were significantly related with evolution probability. At multivariate analysis, paraprotein level (P <.0001), hemoglobin level (P <.05), and lymphocytosis (P <.0001) independently predicted malignant evolution (P <.0001). In conclusion, patients with asymptomatic IgM-MG showing hematological features predictive of progression should be carefully monitored in view of an early treatment of the disease.     

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 ≥25% (UPDRS-39 decrement ≥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.     

Fluorocytometric analysis of anti-HLA class 2 autoantibodies in patients with lupus nephritis

Systemic lupus erythematosus (SLE) patients are known to produce a variety of autoantibodies (AAb), some of which may be directed against immunocompetent cells. Anti-B cell autoimmunity may encompass reactivity against HLA-class 2 molecules, which are also expressed on kidney tissue. We studied 15 patients with moderate to severe renal involvement and 5 lupus patients with no clinical renal disease, in order to detect the presence of anti-HLA class 2 AAb. Flow cytometry was employed in an inhibitory assay using patient sera, autologous cells and two anti-class 2 monoclonals, to establish the specificity of anti-B cell AAb. Seven out of 15 nephritis patients had detectable anti-class 2 AAb with an epitopic heterogeneity, as demonstrated by different degrees of inhibition on the binding of non-overlapping monoclonals. The specificity of the reaction was confirmed by the lack of inhibition of non-class 2 antibody binding. The presence of such AAb was not correlated with disease activity but with the presence of a diffuse proliferative glomerulonephritis on renal biopsy. Anti-class 2 AAb may be a marker of SLE diffuse proliferative nephritis.     

The contribution of nurses in integrated primary cares for chronic obstructive pulmonary disease outpatient: first results from an ongoing trial in a health district in northern Italy

The study assesses the role and impact of nursing in an ongoing trial of integrated primary cares, carried out in a health district in northern Italy, started in 2004. The goals were to establish a joint collaboration with general practitioners (GP), in order to improve the follow-up of chronic patients. As a first stage, the trial focuses on COPD (chronic obstructive pulmonary disease), diabetes mellitus, hypertension, cardiovascular failure and patients following anticoagulant therapy. The district??s project covers up to 60,000 patients treated by the team of GPs and nurses. Benefits for users are represented by easier access to cares, dedicated projects for chronic disease, follow-up, health education and multidisciplinary work. This first reports presents the questionnaire data according to patients?? satisfaction and the results achieved so far on COPD patients: 101.6% of COPD patients followed by teams have had at least 1 spirometry/year (vs. 43.2% of all the COPD affected??regional data) Hospital admissions are lower according to people attending a COPD integrated program and it is getting lower in time (health district??s rate: 0.125% in 2005?C0.115% in 2007; regional data).