Multiparametric cerebellar imaging and clinical phenotype in childhood ataxia telangiectasia.

BACKGROUND: Ataxia Telangiectasia (A-T) is an inherited multisystem disorder with cerebellar neurodegeneration. The relationships between imaging metrics of cerebellar health and neurological function across childhood in A-T are unknown, but may be important for determining timing and impact of therapeutic interventions. PURPOSE: To test the hypothesis that abnormalities of cerebellar structure, physiology and cellular health occur in childhood A-T and correlate with neurological disability, we performed multiparametric cerebellar MRI and establish associations with disease status in childhood A-T. METHODS: Prospective cross-sectional observational study. 22 young people (9 females / 13 males, age 6.6-17.8 years) with A-T and 24 matched healthy controls underwent 3-Tesla MRI with volumetric, diffusion and proton spectroscopic acquisitions. Participants with A-T underwent structured neurological assessment, and expression / activity of ataxia-telangiectasia mutated (ATM) kinase were recorded. RESULTS: Ataxia-telangiectasia participants had cerebellar volume loss (fractional total cerebellar volume: 5.3% vs 8.7%, P < 0.0005, fractional 4th ventricular volumes: 0.19% vs 0.13%, P < 0.0005), that progressed with age (fractional cerebellar volumes, r = -0.66, P = 0.001), different from the control group (t = -4.88, P < 0.0005). The relationship between cerebellar volume and age was similar for A-T participants with absent ATM kinase production and those producing non-functioning ATM kinase. Markers of cerebellar white matter injury were elevated in ataxia-telangiectasia vs controls (apparent diffusion coefficient: 0.89 × 10-3 mm2 s-1 vs 0.69 × 10-3 mm2 s-1, p < 0.0005) and correlated (age-corrected) with neurometabolite ratios indicating impaired neuronal viability (N-acetylaspartate:creatine r = -0.70, P < 0.001); gliosis (inositol:creatine r = 0.50, P = 0.018; combined glutamine/glutamate:creatine r = -0.55, P = 0.008) and increased myelin turnover (choline:creatine r = 0.68, P < 0.001). Fractional 4th ventricular volume was the only variable retained in the regression model predicting neurological function (adjusted r2 = 0.29, P = 0.015). CONCLUSIONS: Quantitative MRI demonstrates cerebellar abnormalities in children with A-T, providing non-invasive measures of progressive cerebellar injury and markers reflecting neurological status. These MRI metrics may be of value in determining timing and impact of interventions aimed at altering the natural history of A-T.

Initial fixation and cyclic loading stability of knotless suture anchors for rotator cuff repair.

This study evaluated the resistance to gapping and the mode of failure for 2 knotless suture anchor systems used for rotator cuff repair compared with the performance of a conventional titanium anchor system. Eight matched pairs of fresh-frozen humeri were dissected free of all soft tissues and scanned to measure bone mineral density (BMD). The suture anchor systems tested were the TwinFix 5.0 Titanium (Smith & Nephew, Andover, MA), Bioknotless RC (DePuy Mitek, Norwood, MA), and Magnum (Opus Medical, San Juan Capistrano, CA), and each was inserted into each humerus. Cyclic, tensile loading was applied through the suture loop for 5000 cycles, or until failure, by using a servohydraulic testing machine. Gapping distances, defined as increasing elongation of the bone/anchor/suture system, were continuously measured. Total cycles to failure and mechanism of failure were documented. Mean initial (first cycle) and final (last cycle) gapping distances were 3.81 mm and 5.36 mm for the TwinFix 5.0, 4.02 mm and 5.34 mm for the Bioknotless RC, and 3.56 mm and 4.98 mm for the Magnum anchors. No significant difference was detected among mean gap openings (P > .05). However, the Bioknotless RC had more early failures (5) than the other 2 implants (1 each), approaching significance (P = .07). Trials of the Bioknotless RC that did not fail early were found to have significantly less gap opening than the other 2 systems for both initial (1.89 mm vs 3.82 mm for the TwinFix 5.0 and 3.56 mm for the Magnum) and final (2.00 mm vs 4.68 mm for the TwinFix 5.0 and 4.24 mm for the Magnum) gap opening. BMD was a significant predictor of initial (P = .029) and final (P = .008) gap opening, whereas the site of anchor insertion was a significant predictor of final displacement. The Opus Magnum was comparable with a conventional suture anchor, but the Mitek Bioknotless RC showed a trend toward early failure. Biomechanical analysis of knotless suture anchor systems can demonstrate trends among implants in an experimental setting. Knowledge of these trends could influence implant selection.