charcot fusion

INTRODUCTION: Arthrodesis is an expensive procedure that is less applicable in developing countries. In this case report we reported a case of diabetic charcot neuroartropathy (CN) with primary ankle arthrodesis technique with a fibular strut graft which is considered cheaper and has a higher union rate. CASE DESCRIPTION: A 47 years old female with complaints of pain in her right ankle after falling down the stairs with foot inverted one month before admission...

BACKGROUND AND AIMS: Mitofusin 1 (MFN1) and MFN2 are outer mitochondrial membrane fusogenic proteins regulating mitochondrial network morphology. MFN2 mutations cause Charcot-Marie-Tooth type 2A (CMT2A), an axonal neuropathy characterized by mitochondrial fusion defects, which in the case of a GTPase domain mutant, were rescued following wild type MFN1/2 (MFN1/2WT ) overexpression. In this study, we compared the therapeutic efficiency between MFN1WT and MFN2WT overexpression in correcting mitochondrial defects induced by the novel MFN2K357T mutation located in the highly conserved R3 region...

BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) with Charcot arthropathy is a rare combination in orthopaedic clinical practice. The experience dealing with such patients is limited. Here with this case of approximately 10 years follow-up, we wish to shed light on the choices of strategies of surgeries and alerting clinicians with post-surgery complications. The possible underlying reasons for the recurrent Charcot arthropathies as well as strategies for peri-operative management for such surgical cases are also discussed...

The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFβ4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells (SCs), which might be one of the downstream effector in CMT1A...

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral polyneuropathy in humans, and its subtypes are linked to mutations in dozens of different genes, including the gene coding for ganglioside-induced differentiation-associated protein 1 (GDAP1). The main GDAP1-linked CMT subtypes are the demyelinating CMT4A and the axonal CMT2K. Over a hundred different missense CMT mutations in the GDAP1 gene have been reported. However, despite implications for mitochondrial fission and fusion, cytoskeletal interactions, and response to reactive oxygen species, the etiology of GDAP1-linked CMT is poorly understood at the protein level...

Acetylated microtubules play key roles in the regulation of mitochondria dynamics. It has however remained unknown if the machinery controlling mitochondria dynamics functionally interacts with the alpha-tubulin acetylation cycle. Mitofusin-2 (MFN2), a large GTPase residing in the mitochondrial outer membrane and mutated in Charcot-Marie-Tooth type 2 disease (CMT2A), is a regulator of mitochondrial fusion, transport and tethering with the endoplasmic reticulum. The role of MFN2 in regulating mitochondrial transport has however remained elusive...

Charcot neuroarthropathy (CNA) is a disabling and progressive disease that affects the bones and joints of the foot. Successful Charcot reconstruction focuses on restoring anatomic alignment, obtaining multiple joint arthrodesis, selecting stable fixation, preserving foot length, and creating a foot suitable for community ambulation in supportive shoegear. Intramedullary fixation arthrodesis of the medial and lateral columns has been previously reported to produce improvement in midfoot Charcot reconstruction...

Hindfoot osteoarthritis (OA) or deformity involving the ankle and subtalar joint is a disabling condition. Tibiotalocalcaneal (TTC) fusion is an effective salvage option in pathologies where total ankle replacement is contraindicated. The purpose of this study is to compare the union rate of the ankle joint in proximal static versus dynamically locked retrograde intramedullary nail fixation for tibiotalocalcaneal arthrodesis. An institutional review board-approved comprehensive chart and radiographic review was performed...

Charcot-Marie-Tooth disease type 2A (CMT2A), the most common inherited peripheral axonal neuropathy, is associated with more than 100 dominant mutations, including R94Q as the most abundant mutation in the Mitofusin2 (MFN2) gene. CMT2A is characterized by progressive motor and sensory loss, color-vision defects, and progressive loss of visual acuity. We used a well-established transgenic mouse model of CMT2A with R94Q mutation on MFN2 gene ( MFN2 R94Q ) to investigate the functional and morphological changes in retina...

BACKGROUND: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells...

OBJECTIVES: Inherited defects of the neuromuscular junction (NMJ) comprise an increasingly diverse range of diseases. Several recently identified genes highlight the overlap between peripheral neuropathies and congenital myasthenic syndromes (CMS). The beta-2 adrenergic receptor agonist salbutamol has been shown to provide symptomatic benefit in CMS, while improving structural defects at the NMJ. Based on these findings, we identified cases of motor neuropathy with NMJ dysfunction and assessed the effect of salbutamol on motor function...

Mitochondria are essential for the health and viability of both motor and sensory neurons and their axons. Processes that disrupt their normal distribution and transport along axons will likely cause peripheral neuropathies. Similarly, mutations in mtDNA or nuclear encoded genes result in neuropathies that either stand alone or are part of multisystem disorders. This chapter focuses on the more common genetic forms and characteristic clinical phenotypes of "mitochondrial" peripheral neuropathies. We also explain how these various mitochondrial abnormalities cause peripheral neuropathy...

[This retracts the article DOI: 10.7759/cureus.28036.].

Phenotypic variations in Charcot-Marie-Tooth disease type 2A (CMT2A) result from the many mutations in the mitochondrial fusion protein, mitofusin 2 (MFN2). While the GTPase domain mutations of MFN2 lack the ability to hydrolyze GTP and complete mitochondrial fusion, the mechanism of dysfunction in HR1 domain mutations has yet to be explored. Using Mfn1 / Mfn2 double null cells and Mfn2 knock out (KO) fibroblasts, we measured the ability of this variant protein to change conformations and hydrolyze GTP. We found that a mutation in the HR1 domain (M376A) of MFN2 results in conformational change dysfunction while maintaining GTPase ability...

Mitochondria are energy-converting organelles that shift between fusion and fission states in order to perform a variety of essential functions. Disruption of these dynamics is detrimental to cellular health and is associated with a range of human diseases. Mitofusin 2 is an essential large GTPase protein that orchestrates fusion of outer mitochondria membranes, and mutations in the encoding gene are causative for Charcot-Marie-Tooth disease. In order to gain further insights into the function of this crucial protein, we have performed large-scale yeast two-hybrid screening to identify interactors of the orthologous protein in Caenorhabditis elegans (FZO-1) ...

Mitofusin (MFN) 1 and MFN2 are dynamin GTPase family mitochondrial proteins that mediate mitochondrial fusion requiring MFN conformational shifts, formation of macromolecular complexes on and between mitochondria, and GTP hydrolysis. Damaging MFN2 mutations cause an untreatable, largely pediatric progressive peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease type 2A. We used small molecule allosteric mitofusin activators that promote MFN conformations favoring fusion to interrogate the effects of MFN2 conformation and GTPase activity on MFN2-mediated mitochondrial fusion and motility in vitro...

BACKGROUND: Tibiotalocalcaneal (TTC) arthrodesis is considered a salvage procedure for either complex deformity or arthritis about the hindfoot, and can be performed via fibula-resection (FR) or fibula-sparing (FS) approaches. The primary aim of this study was to investigate differences in outcomes in FR versus FS TTC arthrodeses. METHODS: This was a retrospective cohort study reviewing outcomes of TTC arthrodesis at a single institution. Patients who underwent a TTC arthrodesis from 2005 to 2017 and had minimum two-year follow-up were included...

Hindfoot and ankle Charcot neuroarthropathy is a challenging condition to treat, specifically with segmental bone defects secondary to avascular necrosis or infection. Several techniques exist alongside continued challenges of nonunion and complication rates. The authors assert that combining distal tibial distraction osteogenesis with external fixation in tibiocalcaneal or tibiotalocalcaneal arthrodesis should be considered an effective method for management of complex Charcot neuroarthropathy conditions of the ankle...

Introduction The treatment for severe fixed hindfoot osteoarthritis secondary to Charcot-Marie-Tooth disease (CMT) is tibiotalocalcaneal (TTC) arthrodesis. In our centre, we have noticed a disproportionate rate of periprosthetic fractures in CMT patients following TTC arthrodesis with retrograde hindfoot nailing. The aim of this study was to test this hypothesis by evaluating our local cohort of TTC arthrodesis with retrograde hindfoot nailing. Methods A retrospective review of patients who had TTC arthrodesis with intramedullary nailing was conducted over a seven-year period...

Dominant mutations in ubiquitously expressed Mitofusin 2 gene (MFN2) cause Charcot-Marie-Tooth type 2A (CMT2A; OMIM 609260), an inherited sensory-motor neuropathy that affects peripheral nerve axons. Mitofusin 2 protein has been found to take part in mitochondrial fusion, mitochondria-endoplasmic reticulum tethering, mitochondrial trafficking along axons, mitochondrial quality control, and various types of cancer, in which MFN2 has been indicated as a tumor suppressor gene. Discordant data on the mitochondrial altered phenotypes in patient-derived fibroblasts harboring MFN2 mutations and in animal models have been reported...