Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.

ObjectiveTo investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for 2 major forms of motor neuron disorders: spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS).MethodsWe applied quantitative 3-point Dixon and semiquantitative T1-weighted and short tau inversion recovery (STIR) imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n = 21) and SBMA (n = 21), alongside healthy controls (n = 16). Acquired images were analyzed for the presence of fat infiltration or edema as well as specific patterns of muscle involvement. Quantitative MRI measurements were correlated with clinical measures of disease severity in ALS and SBMA.ResultsQuantitative imaging revealed significant fat infiltration in bulbar (p < 0.001) and limb muscles in SBMA compared to controls (thigh: p < 0.001; calf: p = 0.001), identifying a characteristic pattern of muscle involvement. In ALS, semiquantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Finally, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA.ConclusionsOur findings show that muscle MRI differentiates between SBMA and ALS and correlates with disease severity, supporting its use as a diagnostic tool and biomarker for disease progression. This highlights the clinical utility of muscle MRI in motor neuron disorders and contributes to establish objective outcome measures, which is crucial for the development of new drugs.

Purpose. Heme oxygenase-1 (HO-1) has been proposed to exert pharmacological benefits by its antioxidative and anti-inflammatory effects. HO-1 expression may be affected by the GT length polymorphism in the promoter region of the HO-1 gene. We investigated the inducibility of HO-1 by orally administered curcumin in healthy male subjects and its correlation with the GT length polymorphism. Methods. In an open label uncontrolled phase-1 pilot study, ten male subjects received 12 g of oral curcumin. To investigate the effects of the GT length polymorphism on the inducibility of HO-1, five subjects with homozygous short and five with homozygous long GT genotypes were studied. Plasma concentrations of curcumin, bilirubin, HO-1 mRNA, and protein expression in peripheral blood mononuclear cells (PBMCs) were analyzed over 48 hours. Results. At a detection limit of 1 µg/mL curcumin could not be detected in plasma of any subject. Compared to baseline, HO-1 mRNA and protein levels were not induced in PBMCs at any time point up to 48 hours. There was no correlation between any of the parameters and GT length polymorphism. Conclusions. Oral curcumin administration has low bioavailability and does not induce HO-1 on mRNA or protein level in PBMCs.

Objective: To investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for two major forms of motor neuron disorders, spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS). Methods: We applied quantitative 3-point Dixon and semi-quantitative T1-weighted and STIR imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n=21) and SBMA (n=21) patients, alongside healthy controls (n=16). Acquired images were analyzed for the presence of fat infiltration or edema as well as specific patterns of muscle involvement. Quantitative MRI measurements were correlated with clinical parameters of disease severity in ALS and SBMA. Results: Quantitative imaging revealed significant fat infiltration in bulbar (p<0.001) and limb muscles in SBMA compared to controls (thigh: p<0.001; calf: p=0.001), identifying a characteristic pattern of muscle involvement. In ALS, semi-quantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Lastly, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA. Conclusions: Our findings show that muscle MRI differentiates between SBMA and ALS and correlates with disease severity, supporting its use as a diagnostic tool and biomarker for disease progression. This highlights the clinical utility of muscle MRI in motor neuron disorders and contributes to establish objective outcome measures, which is crucial for the development of new drugs.

No abstract

The aim of this study was to evaluate associations between co-medications and survival of patients with amyotrophic lateral sclerosis (ALS). Prescription databases of the Austrian sickness funds covering more than 5 million people formed the basis of this study. ALS cases were deduced from riluzole prescriptions during the study period from January 1, 2008, to June 30, 2012. After adjusting for potential confounding factors associations between co-medications and ALS survival were analyzed. A total of 522 ALS patients could be identified during the study period. Sixteen of the most frequently used drug classes were considered for the survival analyses of which two were nominally associated with ALS survival. Proton pump inhibitors (PPI) were negatively correlated with survival (HR 1.34, 95 % CI 1.04-1.73) and centrally acting muscle relaxants (CAMR) showed a positive association (HR 0.56, 95 % CI 0.39-0.81). After correcting for multiple testing, the association between CAMR and ALS survival remained significant (p = 0.03). In conclusion, this is the first study systematically evaluating potential associations between commonly used drugs and ALS disease course. We report a positive association between CAMR use and survival, which may have derived from an indication bias representing the better prognosis of the upper motor neuron predominant disease variant. However, this is still interesting since it demonstrates the sensitivity of our study design to pick up survival effects. The use of large prescription registries could thus provide a valuable basis to find clues to underlying pathophysiological mechanisms in ALS.

Purpose: Perfusion magnetic resonance imaging (P-MRI) is part of the mismatch concept employed for therapy decisions in acute ischemic stroke. Using dynamic susceptibility contrast (DSC) MRI the time-to-maximum (Tmax) parameter is quite popular, but its inconsistently defined computation, arterial input function (AIF) selection, and the applied deconvolution method may introduce bias into the assessment. Alternatively, parameter free methods, namely, standardized time-to-peak (stdTTP), zf-score, and standardized-zf (stdZ) are also available, offering consistent calculation procedures without the need of an AIF or deconvolution.Methods: Tmax was compared to stdTTP, zf-, and stdZ to evaluate robustness of infarct volume estimation in 66 patients, using data from two different sites and MR systems (i.e., 1.5T vs. 3T; short TR (= 689 ms) vs. medium TR (= 1,390 ms); bolus dose 0.1 or 0.2 ml/kgBW, respectively).Results: Quality factors (QF) for Tmax were 0.54 ± 0.18 (sensitivity), 0.90 ± 0.06 (specificity), and 0.87 ± 0.05 (accuracy). Though not significantly different, best specificity (0.93 ± 0.05) and accuracy (0.90 ± 0.04) were found for stdTTP with a sensitivity of 0.56 ± 0.17. Other tested parameters performed not significantly worse than Tmax and stdTTP, but absolute values of QFs were slightly lower, except for zf showing the highest sensitivity (0.72 ± 0.16). Accordingly, in ROC-analysis testing the parameter performance to predict the final infarct volume, stdTTP and zf showed the best performance. The odds for stdTTP to obtain the best prediction of the final infarct size, was 6.42 times higher compared to all other parameters (odds-ratio test; p = 2.2*10–16).Conclusion: Based on our results, we suggest to reanalyze data from large cohort studies using the parameters presented here, particularly stdTTP and zf-score, to further increase consistency of perfusion assessment in acute ischemic stroke.

No abstract