Project description:BackgroundA heel rise task can be used to evaluate midfoot and ankle movement dysfunction in people with diabetes mellitus and peripheral neuropathy. Quantifying movement coordination during heel rise is important to better understand potentially detrimental movement strategies in people with foot pathologies; however, coordination and the impact of limited excursion on coordination is not well-understood in people with diabetes.MethodsSixty patients with diabetes mellitus and peripheral neuropathy, and 22 older and 25 younger controls performed single-limb heel rise task. Midfoot (forefoot relative to hindfoot) sagittal and ankle (hindfoot relative to shank) sagittal and frontal kinematics were measured and normalized to time (0 to 100%). Cross-correlation coefficients were calculated across individuals in each group. A graphical illustration was used to interpret the relationship of midfoot and ankle excursion and cross-correlation coefficient during heel rise.FindingsPeople with diabetes mellitus and peripheral neuropathy showed significantly lower midfoot and ankle cross-correlation coefficients during heel rise compared to older controls (p = 0.003-0.007). There was no difference in the midfoot and ankle cross-correlation coefficients during heel rise for the older and younger controls (p = 0.059-0.425). The graphic data illustrated a trend of greater excursion of two joints and a higher cross-correlation coefficient. Some individuals with lower excursion showed a high cross-correlation coefficient.InterpretationFoot pathologies, but not aging, impairs midfoot and ankle movement coordination during heel rise task. Investigating both movement coordination as well as joint excursion would better inform and characterize the dynamic movements of midfoot and ankle during heel rise task.
Project description:BackgroundMidfoot and ankle movement dysfunction in people with diabetes mellitus and peripheral neuropathy (DMPN) is associated with midfoot deformity and increased plantar pressures during gait. If midfoot and ankle motion during heel rise and push-off of gait have similar mechanics, heel rise performance could be a clinically feasible way to identify abnormal midfoot and ankle function during gait.Research questionIs midfoot and ankle joint motion during a heel rise associated with midfoot and ankle motion at push-off during gait in people with DMPN?MethodsSixty adults with DMPN completed double-limb heel rise, single-limb heel rise, and walking. A modified Oxford multi-segment foot model (forefoot, hindfoot, shank) was used to analyze midfoot (forefoot on hindfoot) and ankle (hindfoot on shank) sagittal angle during heel rise and gait. Pearson correlation was used to test the relationship between heel rise and gait kinematic variables (n = 60). Additionally, we classified 60 participants into two subgroups based on midfoot and ankle position at peak heel rise: midfoot and ankle dorsiflexed (dorsiflexed; n = 23) and midfoot and ankle plantarflexed (plantarflexed; n = 20). Movement trajectories of midfoot and ankle motion during single-limb heel rise and gait of the subgroups were examined.ResultsPeak double-limb heel rise and gait midfoot and ankle angles were significantly correlated (r = 0.49 and r = 0.40, respectively). Peak single-limb heel rise and gait midfoot and ankle angles were significantly correlated (r = 0.63 and r = 0.54, respectively). The dorsiflexed subgroup, identified by heel rise performance showed greater midfoot and ankle dorsiflexion during gait compared to the plantarflexed subgroup (mean difference between subgroups: midfoot 3°, ankle 3°).SignificancePeople with DMPN who fail to plantarflex the midfoot and ankle during heel rise have difficulty plantarflexing the midfoot and ankle during gait. Utilizing a heel rise task may help identify midfoot and ankle dysfunction associated with gait in people with DMPN.
Project description:BackgroundDiabetes mellitus related medial column foot deformity is a major contributor to ulceration and amputation. However, little is known about the relationship between medial column alignment and function and the integrity of the soft tissues that support and move the medial column. The purposes of this study were to determine the predictors of medial column alignment and function in people with diabetes and peripheral neuropathy.Methods23 participants with diabetes and neuropathy had radiographs, heel rise kinematics, magnetic resonance imaging and isokinetic muscle testing to measure: 1) medial column alignment (Meary's angle--the angle between the 1st metatarsal longitudinal axis and the talar head and neck), 2) medial column function (forefoot relative to hindfoot plantarflexion during heel rise), 3) intrinsic foot muscle and fat volume, ratio of posterior tibialis to flexor digitorum tendon volume, 4) plantar fascia function (Meary's angle change from toes flat to extended) and 5) plantarflexor peak torque. Predictors of medial column alignment and function were determined using simultaneous entry multiple regression.FindingsPosterior tibialis to flexor digitorum tendon volume ratio and intrinsic foot muscle volume were significant predictors of medial column alignment (P<.05), accounting for 44% of the variance. Intrinsic foot fat volume and plantarflexor peak torque were significant predictors of medial column function (P<.05), accounting for 37% of the variance.InterpretationDeterioration of medial column supporting structures predicted alignment and function. Prospective research is required to monitor alignment, structure, and function over time to inform early intervention strategies to prevent deformity, ulceration, and amputation.
Project description:BackgroundAnkle, hindfoot, and midfoot arthrodesis surgeries are standard procedures performed in orthopaedics to treat pain and functional disabilities. Although fusions can effectively improve pain and quality of life, nonunions remain a significant concern for surgeons. With the increased availability of computed tomography (CT), more surgeons rely on this modality for increased accuracy in determining whether a fusion was successful. The objective of this study was to report the rates of CT-confirmed fusion following ankle, hindfoot, or midfoot arthrodesis.MethodsA systematic review was performed using EMBASE, Medline, and Cochrane central register from January 2000 to March 2020. Inclusion criteria included studies with adults (<18 years) that received 1 or multiple fusions of the ankle, hindfoot, or midfoot. At least 75% of the study cohort must have been evaluated by CT postoperatively. Basic information was collected, including journal, author, year published, and level of evidence. Other specific information was collected, including patient risk factors, fusion site, surgical technique and fixation, adjuncts, union rates, criteria for successful fusion (%), and time of CT. Once data were collected, a descriptive and comparative analysis was performed.ResultsIncluded studies (26, n = 1300) had an overall CT-confirmed fusion rate of 78.7% (69.6-87.7). Individual joints had an overall fusion rate of 83.0% (73-92.9). The highest rate of union was in the talonavicular joint (TNJ).ConclusionThese values are lower than previous studies, which found the same procedures to have greater than 90% fusion rates. With these updated figures, as confirmed by CT, surgeons will have better information for clinical decision making and when having informed consent conversations.
Project description:Isolated midfoot and hindfoot Charcot reconstruction using internal fixation is increasingly a common procedure in multidisciplinary diabetic foot units, and the surgical techniques using internal fixation have well been described. However, about a third of Charcot deformities that require surgical limb salvage present with the involvement of midfoot and hindfoot. Surgical reconstruction of a combined hindfoot and midfoot deformity is an evolving technique and technically challenging. We present the surgical technique of deformity correction and stabilisation using internal fixation, developed by the senior author (VK), and present the outcomes. All patients that had undergone combined hindfoot and midfoot reconstruction to address a limb threatening deformity due to Charcot neuroarthropathy, performed by the senior author, with a minimum follow-up of 12 months, have been included in this study. The principles of surgical reconstruction included adequate pre-operative optimisation of the patient, sequential deformity correction and stabilisation of the hindfoot followed by midfoot using the principle of long-segment rigid internal fixation with optimal bone opposition. Standard post-operative regime, including offloading, has been used in all patients. A total of 34 patients (35 feet) had undergone combined midfoot and hindfoot Charcot reconstruction between January 2009 and December 2019. Active ulcers were noted in 13 feet at the time of the procedure. Eleven reconstructions were performed as two-stage procedures due to the presence of active infection. At a mean follow-up of 53 months, 11/13 ulcer healed, and 32 patients (33 feet) were full weightbearing in surgical shoes or a brace at the latest follow-up. Bone fusion was noted in 28 feet in the hindfoot region and 32 feet in the midfoot. Metal work failure was noted in 5 feet requiring removal in 3 feet. Revision procedures were required in 4 patients. Our newly described technique of combined hindfoot and midfoot Charcot has provided functional limb salvage in majority of presentations, with an acceptable level of complications, at a medium-term follow-up of 53 months.
Project description:We have generated mouse models of real CMT1B mutations in the gene encoding for myelin protein zero (P0). One of these mutants, P0S63del is retained in the ER where it elicits an unfolded protein response (UPR). Genetic ablation of the UPR factor CHOP restores the motor capacity in S63del mice. We used microarray to decipher the molecular mechanism undelying the P0S63del neuropathy and the rescue in S63del/Chop null nerves. Sciatic nerves were dissected from WT, S63del, Chop null and S63del/Chop null mice at three different time points: (i) postnatal day 5 (P5) when myelination has just started and only the primary effects of the presence of the mutant protein should be detected; (ii) P28, around the peak of myelination, when all the downstream targets of CHOP should be activated; and (iii) 4 months, to check for secondary effects of the disease and because this was the time-point when the motor and morphological rescue due to the ablation of CHOP were clearly detectable.
Project description:We have generated mouse models of real CMT1B mutations in the gene encoding for myelin protein zero (P0). One of these mutants, P0S63del is retained in the ER where it elicits an unfolded protein response (UPR). Genetic ablation of the UPR factor CHOP restores the motor capacity in S63del mice. We used microarray to decipher the molecular mechanism undelying the P0S63del neuropathy and the rescue in S63del/Chop null nerves.
Project description:Charcot-Marie-Tooth disease is the most common inherited peripheral neuropathy. Dominant mutations in the glycyl-tRNA synthetase (GARS) gene cause peripheral nerve degeneration and lead to CMT disease type 2D. The underlying mechanisms of mutations in GARS (GARSCMT2D ) in disease pathogenesis are not fully understood. In this study, we report that wild-type GARS binds the NAD+ -dependent deacetylase SIRT2 and inhibits its deacetylation activity, resulting in the acetylated α-tubulin, the major substrate of SIRT2. The catalytic domain of GARS tightly interacts with SIRT2, which is the most CMT2D mutation localization. However, CMT2D mutations in GARS cannot inhibit SIRT2 deacetylation, which leads to a decrease of acetylated α-tubulin. Genetic reduction of SIRT2 in the Drosophila model rescues the GARS-induced axonal CMT neuropathy and extends the life span. Our findings demonstrate the pathogenic role of SIRT2-dependent α-tubulin deacetylation in mutant GARS-induced neuropathies and provide new perspectives for targeting SIRT2 as a potential therapy against hereditary axonopathies.
Project description:PurposeMidfoot movement dysfunction, as measured by heel rise performance, is associated with midfoot deformity in people with diabetes and peripheral neuropathy. Understanding contributors of midfoot movement dysfunction may help clinicians understand deformity progression. The purpose of this study was to determine the factors associated with midfoot angle at peak heel rise.MethodsThe outcomes of fifty-eight participants with type 2 diabetes mellitus and peripheral neuropathy were analyzed. Midfoot (forefoot on hindfoot) sagittal kinematics during unilateral heel rise task were measured using 3-dimensional motion analysis. A multivariate linear regression model was used to predict midfoot sagittal movements at peak heel rise. Independent variables that were entered in the model were (in order of entry): age, body mass index, intrinsic foot muscle volume, and maximum available midfoot plantarflexion range of motion. Intrinsic foot muscle volume was obtained from magnetic resonance imaging and maximum available midfoot motion was measured during non-weightbearing plantarflexion using 3-dimensional motion analysis.ResultsBody mass index (R2 = 30.5%, p < 0.001) and maximum available midfoot plantarflexion range of motion (R2 = 10.9%, p = 0.001) were significant factors that accounted for 41.4% of variance of midfoot angle at peak heel rise, while age and intrinsic foot muscle volume were not significant predictors.ConclusionsGreater body mass index and less available midfoot plantarflexion range of motion were associated with greater midfoot movement dysfunction. These two significant predictors are potentially modifiable, suggesting possible improvements in midfoot movements with reduction in body weight and increasing midfoot plantarflexion range of motion. Health care professionals should consider patient's weight and joint motion when prescribing foot exercise(s) to prevent excessive midfoot collapse during weightbearing tasks.