Effectiveness of Curcuma longa Extract for the Treatment of Symptoms and Effusion-Synovitis of Knee Osteoarthritis : A Randomized Trial.

BACKGROUND: Current pharmacologic therapies for patients with osteoarthritis are suboptimal. OBJECTIVE: To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis. DESIGN: Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224). SETTING: Single-center study with patients from southern Tasmania, Australia. PARTICIPANTS: 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis. INTERVENTION: 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks. MEASUREMENTS: The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks. RESULTS: CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related. LIMITATION: Modest sample size and short duration. CONCLUSION: CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings. PRIMARY FUNDING SOURCE: University of Tasmania and Natural Remedies Private Limited.

Understanding the impact of bilateral brain injury in children with unilateral cerebral palsy.

The presence of bilateral brain injury in patients with unilateral cerebral palsy (CP) may impact neuroplasticity in the ipsilateral hemisphere; however, this pattern of injury is typically under-analyzed due to the lack of methods robust to severe injury. In this study, injury-robust methods have been applied to structural brain magnetic resonance imaging (MRI) data of a cohort of 91 children with unilateral CP (37 with unilateral and 54 with bilateral brain injury, 4-17 years) and 44 typically developing controls (5-17 years), to determine how brain structure is associated with concurrent motor function, and if these associations differ between patients with unilateral or bilateral injury. Regression models were used to associate these measures with two clinical scores of hand function, with patient age, gender, brain injury laterality, and interaction effects included. Significant associations with brain structure and motor function were observed (Pearson's r = .494-.716), implicating several regions of the motor pathway, and demonstrating an accurate prediction of hand function from MRI, regardless of the extent of brain injury. Reduced brain volumes were observed in patients with bilateral injury, including volumes of the thalamus and corpus callosum splenium, compared to those with unilateral injury, and the healthy controls. Increases in cortical thickness in several cortical regions were observed in cohorts with unilateral and bilateral injury compared to controls, potentially suggesting neuroplasticity might be occurring in the inferior frontal gyrus and the precuneus. These findings identify prospective useful target regions for transcranial magnetic stimulation intervention.

Cerebral quantitative susceptibility mapping predicts amyloid-ß-related cognitive decline.

See Derry and Kent (doi:10.1093/awx167) for a scientific commentary on this article.The large variance in cognitive deterioration in subjects who test positive for amyloid-ß by positron emission tomography indicates that convergent pathologies, such as iron accumulation, might combine with amyloid-ß to accelerate Alzheimer's disease progression. Here, we applied quantitative susceptibility mapping, a relatively new magnetic resonance imaging method sensitive to tissue iron, to assess the relationship between iron, amyloid-ß load, and cognitive decline in 117 subjects who underwent baseline magnetic resonance imaging and amyloid-ß positron emission tomography from the Australian Imaging, Biomarkers and Lifestyle study (AIBL). Cognitive function data were collected every 18 months for up to 6 years from 100 volunteers who were either cognitively normal (n = 64) or diagnosed with mild cognitive impairment (n = 17) or Alzheimer's disease (n = 19). Among participants with amyloid pathology (n = 45), higher hippocampal quantitative susceptibility mapping levels predicted accelerated deterioration in composite cognition tests for episodic memory [ß(standard error) = -0.169 (0.034), P = 9.2 × 10-7], executive function [ß(standard error) = -0.139 (0.048), P = 0.004), and attention [ß(standard error) = -0.074 (0.029), P = 0.012]. Deteriorating performance in a composite of language tests was predicted by higher quantitative susceptibility mapping levels in temporal lobe [ß(standard error) = -0.104 (0.05), P = 0.036] and frontal lobe [ß(standard error) = -0.154 (0.055), P = 0.006]. These findings indicate that brain iron might combine with amyloid-ß to accelerate clinical progression and that quantitative susceptibility mapping could be used in combination with amyloid-ß positron emission tomography to stratify individuals at risk of decline.

PREMM: preterm early massage by the mother: protocol of a randomised controlled trial of massage therapy in very preterm infants.

BACKGROUND: Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety. The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants. Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels.  Effects on maternal mood, anxiety and mother-infant attachment will also be measured. METHODS/DESIGN: A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32 weeks and 6 days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12 months and 24 months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments. DISCUSSION: Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massage on neurodevelopment. An early intervention such as massage that is relatively easy to administer and could alter the trajectory of preterm infant brain development, holds potential to improve neurodevelopmental outcomes in this vulnerable population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12612000335897 . Date registered: 22/3/2012.

Extent of altered white matter in unilateral and bilateral periventricular white matter lesions in children with unilateral cerebral palsy.

AIMS: To investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function. METHODS AND PROCEDURES: Diffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test). OUTCOMES AND RESULTS: Children with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups. CONCLUSIONS AND IMPLICATIONS: Periventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction.