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Disease Progression Rate (disease + progression_rate)
Selected AbstractsDistinct Brain Volume Changes Correlating with Clinical Stage, Disease Progression Rate, Mutation Size, and Age at Onset Prediction as Early Biomarkers of Brain Atrophy in Huntington's DiseaseCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 1 2009Ferdinando Squitieri Searching brain and peripheral biomarkers is a requisite to cure Huntington's disease (HD). To search for markers indicating the rate of brain neurodegenerative changes in the various disease stages, we quantified changes in brain atrophy in subjects with HD. We analyzed the cross-sectional and longitudinal rate of brain atrophy, quantitatively measured by fully-automated multiparametric magnetic resonance imaging, as fractional gray matter (GM, determining brain cortex volume), white matter (WM, measuring the volume of axonal fibers), and corresponding cerebral spinal fluid (CSF, a measure of global brain atrophy), in 94 gene-positive subjects with presymptomatic to advanced HD, and age-matched healthy controls. Each of the three brain compartments we studied (WM, GM, and CSF) had a diverse role and their time courses differed in the development of HD. GM volume decreased early in life. Its decrease was associated with decreased serum brain-derived-neurotrophic-factor and started even many years before onset symptoms, then decreased slowly in a nonlinear manner during the various symptomatic HD stages. WM volume loss also began in the presymptomatic stage of HD a few years before manifest symptoms appear, rapidly decreasing near to the zone-of-onset. Finally, the CSF volume increase began many years before age at onset. Its volume measured in presymptomatic subjects contributed to improve the CAG-based model of age at onset prediction. The progressive CSF increase depended on CAG mutation size and continued linearly until the last stages of HD, perhaps representing the best marker of progression rate and severity in HD (R2= 0.25, P < 0.0001). [source] Gender differences in patients with Parkinson's disease treated with subthalamic deep brain stimulationMOVEMENT DISORDERS, Issue 8 2007Ettore Accolla MD Abstract We investigated gender-differences in clinical phenomenology and response to deep brain stimulation (DBS) of the subthalamic nucleus (STN) in a group of patients with advanced Parkinson's disease (PD). Thirty-eight consecutive patients with PD (22 men and 16 women), bilaterally implanted for DBS of the STN, were evaluated 1 month before and 11 to 14 months after surgery. Gender differences in severity of the disease (HY and UPDRS), ability in the activities of daily living (ADL, UPDRS II), tremor and rigidity (UPDRS III), bradykinesia (UPDRS III and hand tapping test), levodopa-induced dyskinesias (LIDs, UPDRS IV), and levodopa equivalent daily dosage (LEDD) were analyzed before and after intervention. We found a predominantly male population, with no gender-related differences in age at onset, disease progression rate, or severity of disease. Nevertheless, women had more severe LIDs than men, only before the intervention. Bradykinesia was significantly less responsive to any kind of treatment (pharmacologic and neurosurgical) in women than in men. Finally, although STN-DBS induced similar total benefits in both genders, postoperative assessment suggested that the ADL improved more in women than in men. Women and men with advanced PD appear to differ in some clinical features and in response to dopaminergic and STN-DBS treatment. © 2007 Movement Disorder Society [source] Reduced angiotensin II levels in the cerebrospinal fluid of patients with amyotrophic lateral sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009M. Kawajiri Background,,, Recent studies suggest that angiotensin II, a major substrate in the renin,angiotensin system, protects neurons through stimulation of its type 2 receptors. However, quite a few clinical studies of angiotensin II levels have shown their relation to disease severity in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Aims of the study,,, To clarify the significance of angiotensin II in ALS. Methods,,, We assayed angiotensin II concentrations in cerebrospinal fluid (CSF) samples from 23 patients with ALS, nine patients with spinocerebellar degeneration (SCD) and 24 control individuals. We evaluated the disability levels of patients with ALS using the Revised ALS Functional Rating Scale (ALSFRS-R) and calculated the disease progression rate (DPR). Results,,, CSF angiotensin II levels were significantly lower in the ALS group compared with that in the control group (P = 0.00864), and showed a significant positive correlation with scores on the ALSFRS-R, and a significant negative correlation with the DPR. Conclusions,,, In the present study, we reveal for the first time that angiotensin II levels in the CSF from patients with ALS are significantly reduced and significantly associated with disease severity and progression rate. These findings suggest that reduced levels of intrathecal angiotensin II may play a role in ALS. [source] Evidence for prolonged clinical benefit from initial combination antiretroviral therapy: Delta extended follow-upHIV MEDICINE, Issue 3 2001Delta Coordinating Committee Background The findings from therapeutic trials in HIV infection with surrogate endpoints based on laboratory markers are only partially relevant for clinical decisions on treatment. Although the collection of clinical follow-up data from such a trial would be relatively straightforward, this rarely occurs. An important reason for this may be the perception that such data have little value because the number of participants remaining on their original allocated therapy has usually fallen substantially. Methods Delta was an international, multicentre trial in which 3207 HIV infected individuals were randomly allocated to treatment with zidovudine (ZDV) alone, ZDV combined with didanosine (ddI) or ZDV combined with zalcitabine (ddC). Although the trial closed in September 1995, information on vital status, AIDS events, treatment changes and CD4 counts was still collected every 12 months until at least March 1997. This has allowed analyses of the longer term clinical effect of treatment. Results The median follow-up to date of death or last known vital status was 43 months (10th percentile 18 months; 90th percentile 55 months). The proportion of participants remaining on their allocated treatment fell steadily over time; by 4 years after trial entry, 3% remained on ZDV, 20% on ZDV + ddI and 21% on ZDV + ddC. Changes mainly involved the stopping, addition or switching of a nucleoside reverse transcriptase inhibitor (NRTIs). There was little use of protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) before the third year of the trial. Between the third and fourth years, regimens included a drug from one of these classes for approximately 17% of person-time in all treatment groups. Relative to ZDV monotherapy, the beneficial effects of combination therapy on mortality and disease progression rates increased significantly with time since randomization. The maximum effects on mortality were observed between 2 and 3 years, with a 48% reduction for ZDV + ddI and a 26% reduction for ZDV + ddC. These rates were observed when the original allocated treatment was received 42% and 47% of the time in the ZDV + ddI and ZDV + ddC groups, respectively. The mean CD4 count remained significantly higher (approximately 50 cells/,L) in the combination therapy groups 4 years after randomization, suggesting a projection of a clinical benefit beyond this time point. Conclusions The sustained clinical effect of the initial allocation to combination therapy, particularly ZDV + ddI, was remarkable in light of the convergence of drug regimens actually received across the three treatment groups. Interpretation of this finding is not straightforward. One of the possible explanations is that the effectiveness of ddI and ddC is diminished if first used later in infection or with greater prior exposure to ZDV, although the data do not clearly support either hypothesis. This analysis highlights the value of long-term clinical follow-up of therapeutic trials in HIV infection, which should be considered in the planning of all new studies. [source] | ||||||||||