Mutations in FGF14, which encodes intracellular fibroblast growth factor 14 (iFGF14), have been linked to spinocerebellar ataxia (SCA27). In addition, mice lacking Fgf14 (Fgf14 Ϫ/Ϫ ) exhibit an ataxia phenotype resembling SCA27, accompanied by marked changes in the excitability of cerebellar granule and Purkinje neurons. It is not known, however, whether these phenotypes result from defects in neuronal development or if they reflect a physiological requirement for iFGF14 in the adult cerebellum. Here, we demonstrate that the acute and selective Fgf14-targeted short hairpin RNA (shRNA)-mediated in vivo "knock-down" of iFGF14 in adult Purkinje neurons attenuates spontaneous and evoked action potential firing without measurably affecting the expression or localization of voltage-gated Na ϩ (Nav) channels at Purkinje neuron axon initial segments. The selective shRNA-mediated in vivo "knock-down" of iFGF14 in adult Purkinje neurons also impairs motor coordination and balance. Repetitive firing can be restored in Fgf14-targeted shRNA-expressing Purkinje neurons, as well as in Fgf14 Ϫ/Ϫ Purkinje neurons, by prior membrane hyperpolarization, suggesting that the iFGF14-mediated regulation of the excitability of mature Purkinje neurons depends on membrane potential. Further experiments revealed that the loss of iFGF14 results in a marked hyperpolarizing shift in the voltage dependence of steady-state inactivation of the Nav currents in adult Purkinje neurons. We also show here that expressing iFGF14 selectively in adult Fgf14 Ϫ/Ϫ Purkinje neurons rescues spontaneous firing and improves motor performance. Together, these results demonstrate that iFGF14 is required for spontaneous and evoked action potential firing in adult Purkinje neurons, thereby controlling the output of these cells and the regulation of motor coordination and balance.
Purpose Distal femur morphology has been shown to inluence knee joint kinematics and may afect rotatory knee laxity. The purpose of this study was to determine the relationship between rotatory knee laxity and distal femoral morphology in patients with complete anterior cruciate ligament (ACL) rupture. It was hypothesized that increased posterior femoral condylar depth on standard lateral radiographs, quantiied as the "lateral femoral condyle ratio" would correlate with increased rotatory knee laxity, measured by a quantitative pivot shift test. Methods Consecutive patients who underwent ACL reconstruction from 2014 to 2016 were retrospectively reviewed. A standardized pivot shift test was performed preoperatively on both knees and quantiied using tablet technology. Using standard lateral radiographs of the knee, the ratio of posterior condylar distance over total condylar distance was deined as the lateral femoral condyle ratio. Results Data sets were obtained for 57 patients. The mean anterior translation of the lateral knee compartment during a quantitative pivot shift test was found to be 4.0 ± 2.4 mm and 1.3 ± 0.9 mm for the injured and uninjured knees, respectively. The mean lateral femoral condyle ratio on X-ray was 63.2 ± 4.5%. There were signiicant correlations between the lateral femoral condyle ratio and the absolute quantitative (ρ = 0.370, p < 0.05) and side-to-side diferences in anterior translation of the lateral knee compartment (ρ = 0.419, p < 0.05).
ConclusionThe most important inding from this study is that increased posterior femoral condylar depth, quantiied as a lateral femoral condyle ratio, is associated with increased rotatory knee laxity in ACL-deicient patients. This suggests that distal femur morphology may inluence rotatory knee laxity. This study may assist clinicians in evaluating ACL injuries and identifying patients at greater risk for persistent increased rotatory knee laxity after ACL reconstruction. Level of evidence III.
Increased LTPS and MTPS are independent risk factors for graft failure following ACL reconstruction regardless whether tunnel position is anatomic or non-anatomic. This information may be helpful to clinicians when considering slope correction in selected revision ACL reconstruction procedures.
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