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1.  Predictors of Barefoot Plantar Pressure during Walking in Patients with Diabetes, Peripheral Neuropathy and a History of Ulceration 
PLoS ONE  2015;10(2):e0117443.
Objective
Elevated dynamic plantar foot pressures significantly increase the risk of foot ulceration in diabetes mellitus. The aim was to determine which factors predict plantar pressures in a population of diabetic patients who are at high-risk of foot ulceration.
Methods
Patients with diabetes, peripheral neuropathy and a history of ulceration were eligible for inclusion in this cross sectional study. Demographic data, foot structure and function, and disease-related factors were recorded and used as potential predictor variables in the analyses. Barefoot peak pressures during walking were calculated for the heel, midfoot, forefoot, lesser toes, and hallux regions. Potential predictors were investigated using multivariate linear regression analyses. 167 participants with mean age of 63 years contributed 329 feet to the analyses.
Results
The regression models were able to predict between 6% (heel) and 41% (midfoot) of the variation in peak plantar pressures. The largest contributing factor in the heel model was glycosylated haemoglobin concentration, in the midfoot Charcot deformity, in the forefoot prominent metatarsal heads, in the lesser toes hammer toe deformity and in the hallux previous ulceration. Variables with local effects (e.g. foot deformity) were stronger predictors of plantar pressure than global features (e.g. body mass, age, gender, or diabetes duration).
Conclusion
The presence of local deformity was the largest contributing factor to barefoot dynamic plantar pressure in high-risk diabetic patients and should therefore be adequately managed to reduce plantar pressure and ulcer risk. However, a significant amount of variance is unexplained by the models, which advocates the quantitative measurement of plantar pressures in the clinical risk assessment of the patient.
doi:10.1371/journal.pone.0117443
PMCID: PMC4315609  PMID: 25647421
2.  Increased osteoclastic activity in acute Charcot’s osteoarthopathy: the role of receptor activator of nuclear factor-kappaB ligand 
Diabetologia  2008;51(6):1035-1040.
Aims/hypothesis
Our aims were to compare osteoclastic activity between patients with acute Charcot’s osteoarthropathy and diabetic and healthy controls, and to determine the effect of the receptor activator of nuclear factor-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG).
Methods
Peripheral blood monocytes isolated from nine diabetic Charcot patients, eight diabetic control and eight healthy control participants were cultured in the presence of macrophage-colony stimulating factor (M-CSF) alone, M-CSF and RANKL, and also M-CSF and RANKL with excess concentrations of OPG. Osteoclast formation was assessed by expression of tartrate-resistant acid phosphatase on glass coverslips and resorption on dentine slices.
Results
In cultures with M-CSF, there was a significant increase in osteoclast formation in Charcot patients compared with healthy and diabetic control participants (p = 0.008). A significant increase in bone resorption was also seen in the former, compared with healthy and diabetic control participants (p < 0.0001). The addition of RANKL to the cultures with M-CSF led to marked increase in osteoclastic resorption in Charcot (from 0.264 ± 0.06% to 41.6 ± 8.1%, p < 0.0001) and diabetic control (0.000 ± 0.00% to 14.2 ± 16.5%, p < 0.0001) patients, and also in healthy control participants (0.004 ± 0.01% to 10.5 ± 1.9%, p < 0.0001). Although the addition of OPG to cultures with M-CSF and RANKL led to a marked reduction of resorption in Charcot patients (41.6 ± 8.1% to 5.9 ± 2.4%, p = 0.001), this suppression was not as complete as in diabetic control patients (14.2 ± 16.5% to 0.45 ± 0.31%, p = 0.001) and in healthy control participants (from 10.5 ± 1.9% to 0.00 ± 0.00%, p < 0.0001).
Conclusions/interpretation
These results indicate that RANKL-mediated osteoclastic resorption occurs in acute Charcot’s osteoarthropathy. However, the incomplete inhibition of RANKL after addition of OPG also suggests the existence of a RANKL-independent pathway.
doi:10.1007/s00125-008-0992-1
PMCID: PMC2362134  PMID: 18389210
Charcot’s osteoarthropathy; OPG; Osteoclasts; Osteolysis; RANKL; Resorption
3.  Infrared Thermal Imaging for Automated Detection of Diabetic Foot Complications 
Background
Although thermal imaging can be a valuable technology in the prevention and management of diabetic foot disease, it is not yet widely used in clinical practice. Technological advancement in infrared imaging increases its application range. The aim was to explore the first steps in the applicability of high-resolution infrared thermal imaging for noninvasive automated detection of signs of diabetic foot disease.
Methods
The plantar foot surfaces of 15 diabetes patients were imaged with an infrared camera (resolution, 1.2 mm/pixel): 5 patients had no visible signs of foot complications, 5 patients had local complications (e.g., abundant callus or neuropathic ulcer), and 5 patients had diffuse complications (e.g., Charcot foot, infected ulcer, or critical ischemia). Foot temperature was calculated as mean temperature across pixels for the whole foot and for specified regions of interest (ROIs).
Results
No differences in mean temperature >1.5 °C between the ipsilateral and the contralateral foot were found in patients without complications. In patients with local complications, mean temperatures of the ipsilateral and the contralateral foot were similar, but temperature at the ROI was >2 °C higher compared with the corresponding region in the contralateral foot and to the mean of the whole ipsilateral foot. In patients with diffuse complications, mean temperature differences of >3 °C between ipsilateral and contralateral foot were found.
Conclusions
With an algorithm based on parameters that can be captured and analyzed with a high-resolution infrared camera and a computer, it is possible to detect signs of diabetic foot disease and to discriminate between no, local, or diffuse diabetic foot complications. As such, an intelligent telemedicine monitoring system for noninvasive automated detection of signs of diabetic foot disease is one step closer. Future studies are essential to confirm and extend these promising early findings.
PMCID: PMC3876354  PMID: 24124937
automatic detection; diabetic foot; infrared imaging; prevention; telemedicine; thermography
4.  Neuropathic midfoot deformity: associations with ankle and subtalar joint motion 
Background
Neuropathic deformities impair foot and ankle joint mobility, often leading to abnormal stresses and impact forces. The purpose of our study was to determine differences in radiographic measures of hind foot alignment and ankle joint and subtalar joint motion in participants with and without neuropathic midfoot deformities and to determine the relationships between radiographic measures of hind foot alignment to ankle and subtalar joint motion in participants with and without neuropathic midfoot deformities.
Methods
Sixty participants were studied in three groups. Forty participants had diabetes mellitus (DM) and peripheral neuropathy (PN) with 20 participants having neuropathic midfoot deformity due to Charcot neuroarthropathy (CN), while 20 participants did not have deformity. Participants with diabetes and neuropathy with and without deformity were compared to 20 young control participants without DM, PN or deformity. Talar declination and calcaneal inclination angles were assessed on lateral view weight bearing radiograph. Ankle dorsiflexion, plantar flexion and subtalar inversion and eversion were assessed by goniometry.
Results
Talar declination angle averaged 34±9, 26±4 and 23±3 degrees in participants with deformity, without deformity and young control participants, respectively (p< 0.010). Calcaneal inclination angle averaged 11±10, 18±9 and 21±4 degrees, respectively (p< 0.010). Ankle plantar flexion motion averaged 23±11, 38±10 and 47±7 degrees (p<0.010). The association between talar declination and calcaneal inclination angles with ankle plantar flexion range of motion is strongest in participants with neuropathic midfoot deformity. Participants with talonavicular and calcaneocuboid dislocations result in the most severe restrictions in ankle joint plantar flexion and subtalar joint inversion motions.
Conclusions
An increasing talar declination angle and decreasing calcaneal inclination angle is associated with decreases in ankle joint plantar flexion motion in individuals with neuropathic midfoot deformity due to CN that may contribute to excessive stresses and ultimately plantar ulceration of the midfoot.
doi:10.1186/1757-1146-6-11
PMCID: PMC3616933  PMID: 23531372
Foot alignment; Deformity; Ankle and foot joint goniometry; Limited joint mobility
5.  A Prospective Study of Calcaneal Bone Mineral Density in Acute Charcot Osteoarthropathy 
Diabetes Care  2010;33(10):2254-2256.
OBJECTIVE
To measure prospectively bone mineral density (BMD) of the Charcot and non-Charcot foot in 36 diabetic patients presenting with acute Charcot osteoarthropathy.
RESEARCH DESIGN AND METHODS
Calcaneal BMD was measured with quantitative ultrasound at presentation, at 3 months of casting, and at the time of the clinical resolution.
RESULTS
BMD of the Charcot foot was significantly reduced compared with BMD of the non-Charcot foot at presentation (P = 0.001), at 3 months of casting (P < 0.001), and at the time of clinical resolution (P < 0.001). Overall, from the time of presentation to the time of resolution there was a significant fall of BMD of the Charcot foot (P < 0.001) but not of the non-Charcot foot (P = 0.439).
CONCLUSIONS
Although the Charcot foot was treated with casting until clinical resolution, there was a significant fall of BMD only from presentation up until 3 months of casting.
doi:10.2337/dc10-0636
PMCID: PMC2945169  PMID: 20628091
6.  Comparative analysis of uniplanar external fixator and retrograde intramedullary nailing for ankle arthrodesis in diabetic Charcot's neuroarthropathy 
Indian Journal of Orthopaedics  2011;45(4):359-364.
Background:
Charcot's neuroarthropathy of ankle leads to instability, destruction of the joint with significant morbidity that may require an amputation. Aim of surgical treatment is to achieve painless stable plantigrade foot through arthrodesis. Achieving surgical arthrodesis in Charcot's neuroarthropathy has a high failure rate. This is a retrospective nonrandomized comparative study assessing the outcomes of tibio-talar arthrodesis for Charcot's neuroarthropathy treated by uniplanar external fixation assisted by external immobilization or retrograde intramedullary interlocked nailing.
Materials and Methods:
Records of the authors′ institution were reviewed to identify those patients who had undergone ankle fusion for diabetic neuroarthropathy from January 1998 to December 2008. A total of11 patients (six males and five females) with a mean age of 56 year and diabetes of a mean duration of 15.4 years with ankle tibio-talar arthrodesis using retrograde nailing or external fixator for Charcot's neuroarthropathy were enrolled for the analysis. Neuropathy was clinically diagnosed, documented and substantiated using the monofilament test. All procedures were performed in Eichenholz stage II/III.Six patients were treated with uniplanar external fixator, while the remaining five underwent retrograde intramedullary interlocking nail. The outcomes were measured for union radiologically, development of complications and clinical follow-up, according to digital archiving systems and old case notes.
Results:
All five (100%) patients treated by intramedullary nailing achieved radiological union on an average follow-up of 16 weeks. The external fixation group had significantly higher rate of complications with one amputation, four non unions (66.7%) and a delayed union which went on to full osseous union.
Conclusion:
The retrograde intramedullary nailing for tibio-talar arthrodesis in Charcot's neuroarthropathy yielded significantly better outcomes as compared to the use of uniplanar external fixator.
doi:10.4103/0019-5413.82343
PMCID: PMC3134023  PMID: 21772631
Charcot's diabetic neuropathy; retrograde intramedullary nailing; tibio-talar arthrodesis; uniplanar external fixator
7.  Pedal bone density, strength, orientation, and plantar loads preceding incipient metatarsal fracture after Charcot neuroarthropathy: 2 case reports 
Study Design
Case reports
Background
Charcot neuroarthropathy (CN) is a progressive, non-infective, inflammatory destruction of bones and joints leading to foot deformities and plantar ulceration. Though individuals with CN typically have low areal bone mineral density (aBMD), little is known regarding changes in volumetric bone mineral density (vBMD), bone geometry, joint mal-alignment, and biomechanical loads preceding fracture.
Case Description
Two females, aged 45 and 54 years at the onset of an acute non-fracture CN event, received regular physical therapy with wound care and total contact casting. Both enrolled in a larger research study that included plantar pressure assessment and quantitative computed tomography (QCT) at enrollment and 3, 6, and 12 months later. The women sustained mid-diaphyseal fifth metatarsal fracture 10–11 months after enrollment. QCT image analysis techniques were used to measure vBMD; bone geometric indices reflecting strength in compression, bending, and cortical buckling; and 3-dimensional bone-to-bone orientation angles reflecting foot deformity.
Outcomes
Fifth metatarsal mid-diaphyseal vBMD decreased during off-loading treatment from 0 to 3 months, then increased to above baseline levels by 6 months. All geometric strength indices improved from baseline through 6 months. Plantar loading in the lateral midfoot increased preceding fracture, concomitant with alterations in bone orientation angles which suggest progressive development of metatarsus adductus and equinovarus foot deformity.
Discussion
Fractures may occur when bone strength decreases or when biomechanical loading increases. Incipient fracture was preceded by increased loading in the lateral midfoot, but not by reductions in vBMD or geometric strength indices, suggesting that loading played a greater role in fracture. Moreover, the progression of foot deformities may be causally linked to the increased plantar loading.
Level of evidence
Therapy, level 4
doi:10.2519/jospt.2013.4443
PMCID: PMC3959983  PMID: 24256173
Diabetes; foot; plantar ulcers; fracture
8.  Effect of selected exercises on in-shoe plantar pressures in people with diabetes and peripheral neuropathy 
Foot (Edinburgh, Scotland)  2012;22(3):130-134.
BACKGROUND
In people with diabetes and peripheral neuropathy (DM+PN), injury risk is not clearly known for weight bearing (WB) vs. non-weight bearing (NWB) exercise. In-shoe peak plantar pressures (PPP) often are used as a surrogate indicator of injury to the insensitive foot.
OBJECTIVE
Compare PPPs in people with DM+PN during selected WB and NWB exercises.
METHODS
15 subjects with DM+PN participated. PPPs were recorded for the forefoot, midfoot, and heel during level walking and compared to; WB exercises - treadmill walking, heel and toe raises, sit to stands, stair climbing, single leg standing; and NWB exercises - stationary bicycling, balance ball exercise and plantar flexion exercise.
RESULTS
Compared to level walking; mean forefoot PPP during treadmill walking was 13% higher, but this difference was eliminated when walking speed was used as a covariate. Mean PPPs were similar or substantially lower for other exercises, except for higher forefoot PPP with heel raise exercises.
CONCLUSIONS
Slow progression and regular monitoring of insensitive feet are recommended for all exercises, but especially for heel raises, and increases in walking speed. The remaining WB and NWB exercises pose no greater risk to the insensitive foot due to increases in PPP compared to level walking.
doi:10.1016/j.foot.2012.05.001
PMCID: PMC3434274  PMID: 22677098
Diabetes; Peripheral Neuropathy; Plantar pressure; Exercise
9.  Mortality Risk of Charcot Arthropathy Compared With That of Diabetic Foot Ulcer and Diabetes Alone 
Diabetes Care  2009;32(5):816-821.
OBJECTIVE
The purpose of this study was to compare mortality risks of patients with Charcot arthropathy with those of patients with diabetic foot ulcer and those of patients with diabetes alone (no ulcer or Charcot arthropathy).
RESEARCH DESIGN AND METHODS
A retrospective cohort of 1,050 patients with incident Charcot arthropathy in 2003 in a large health care system was compared with patients with foot ulcer and those with diabetes alone. Mortality was determined during a 5-year follow-up period. Patients with Charcot arthropathy were matched to individuals in the other two groups using propensity score matching based on patient age, sex, race, marital status, diabetes duration, and diabetes control.
RESULTS
During follow-up, 28.0% of the sample died; 18.8% with diabetes alone and 37.0% with foot ulcer died compared with 28.3% with Charcot arthropathy. Multivariable Cox regression shows that, compared with Charcot arthropathy, foot ulcer was associated with 35% higher mortality risk (hazard ratio 1.35 [95% CI 1.18–1.54]) and diabetes alone with 23% lower risk (0.77 [0.66–0.90]). Of the patients with Charcot arthropathy, 63% experienced foot ulceration before or after the onset of the Charcot arthropathy. Stratified analyses suggest that Charcot arthropathy is associated with a significantly increased mortality risk independent of foot ulcer and other comorbidities.
CONCLUSIONS
Charcot arthropathy was significantly associated with higher mortality risk than diabetes alone and with lower risk than foot ulcer. Patients with foot ulcers tended to have a higher prevalence of peripheral vascular disease and macrovascular diseases than patients with Charcot arthropathy. This finding may explain the difference in mortality risks between the two groups.
doi:10.2337/dc08-1695
PMCID: PMC2671113  PMID: 19196882
10.  The Effect of Zoledronic Acid on the Clinical Resolution of Charcot Neuroarthropathy 
Diabetes Care  2011;34(7):1514-1516.
OBJECTIVE
To investigate the clinical efficacy of zoledronic acid in patients with diabetes and acute Charcot neuroarthropathy.
RESEARCH DESIGN AND METHODS
Thirty-nine consecutive patients were randomly assigned to placebo or three intravenous infusions of 4 mg zoledronic acid. The primary outcome was clinical resolution of acute Charcot neuroarthropathy determined by total immobilization time (casting plus orthosis).
RESULTS
At baseline, there was no significant difference between the randomly assigned groups with respect to Charcot disease activity or other baseline values. In the zoledronic acid group, the median time for total immobilization was 27 weeks (range 10–62), and in the placebo group it was 20 weeks (20–52) (P = 0.02).
CONCLUSIONS
Zoledronic acid had no beneficial effect on the clinical resolution of acute Charcot neuroarthropathy in terms of total immobilization time. It is possible that it may prolong the time to clinical resolution of Charcot neuroarthropathy.
doi:10.2337/dc11-0396
PMCID: PMC3120211  PMID: 21593295
11.  Impact of Charcot neuroarthropathy on metatarsal bone mineral density and geometric strength indices 
Bone  2012;52(1):407-413.
Charcot neuroarthropathy (CN), an inflammatory condition characterized by rapid and progressive destruction of pedal bones and joints, often leads to deformity and ulceration in individuals with diabetes mellitus (DM) and peripheral neuropathy (PN). Repetitive, unperceived joint trauma may trigger initial CN damage, causing a proinflammatory cascade that can result in osteolysis and contribute to subsequent neuropathic fracture. We aimed to characterize osteolytic changes related to development and progression of CN by measuring bone mineral density (BMD) and geometric strength indices using volumetric quantitative computed tomography. Twenty individuals with DM+PN were compared to twenty age-, sex-, and race-matched individuals with DM+PN and acute CN. We hypothesized that individuals with acute CN would have decreased BMD and decreased total area, cortical area, minimum section modulus, and cortical thickness in the diaphysis of the second and fifth metatarsals. Results showed BMD was lower in both involved and uninvolved feet of CN participants compared to DM+PN participants, with greater reductions in involved CN feet compared to uninvolved CN feet. There was a non-significant increase in total area and cortical area in the CN metatarsals, which helps explain the finding of similar minimum section modulus in DM+PN and CN subjects despite the CN group’s significantly lower BMD. Larger cortical area and section modulus are typically considered signs of greater bone strength due to higher resistance to compressive and bending loads, respectively. In CN metatarsals, however, these findings may reflect periosteal woven bone apposition, i.e., a hypertrophic response to injury rather than increased fracture resistance. Future research using these techniques will aid further understanding of the inflammation-mediated bony changes associated with development and progression of CN and other diseases.
doi:10.1016/j.bone.2012.10.028
PMCID: PMC3515650  PMID: 23117208
Charcot neuroarthropathy; bone mineral density; computed tomography; diabetes mellitus; peripheral neuropathy
12.  Pressure pain perception in the diabetic Charcot foot: facts and hypotheses 
Diabetic Foot & Ankle  2013;4:10.3402/dfa.v4i0.20981.
Background
Reduced traumatic and posttraumatic (nociceptive) pain is a key feature of diabetic neuropathy. Underlying condition is a gradual degeneration of endings of pain nerves (A-delta fibers and C-fibers), which operate as receivers of noxious stimuli (nociceptors). Hence, the absence of A-delta fiber mediated sharp pain (“first” pain), and of C-fiber mediated dull pain (“second” pain). However, patients with diabetic neuropathy and acute Charcot foot often experience deep dull aching in the Charcot foot while walking on it.
Aim
To create a unifying hypothesis on the kind of pain in an acute Charcot foot.
Result
Absence of punctuate (pinprick) pain perception at the sole of a Charcot foot, as was shown recently, likely corresponds to vanished intraepidermal A-delta fiber endings. C-fiber nociceptors are reduced, according to histopathology studies. Both types of fibers contribute to posttraumatic hyperalgesia at the skin level, as studies show. Their deficiencies likely impact on posttraumatic hyperalgesia at the skin level and, probably, also at the skeletal level.
Conclusion
It is hypothesised that deep dull aching in an acute diabetic Charcot foot may represent faulty posttraumatic hyperalgesia involving cutaneous and skeletal tissues.
doi:10.3402/dfa.v4i0.20981
PMCID: PMC3661900  PMID: 23705057
pain perception; diabetic neuropathy; Charcot neuroarthropathy
13.  Etiology, pathophysiology and classifications of the diabetic Charcot foot 
Diabetic Foot & Ankle  2013;4:10.3402/dfa.v4i0.20872.
In people with diabetes mellitus, the Charcot foot is a specific manifestation of peripheral neuropathy that may involve autonomic neuropathy with high blood flow to the foot, leading to increased bone resorption. It may also involve peripheral somatic polyneuropathy with loss of protective sensation and high risk of unrecognized acute or chronic minor trauma. In both cases, there is excess local inflammatory response to foot injury, resulting in local osteoporosis. In the Charcot foot, the acute and chronic phases have been described. The former is characterized by local erythema, edema, and marked temperature elevation, while pain is not a prominent symptom. In the latter, signs of inflammation gradually recede and deformities may develop, increasing the risk of foot ulceration. The most common anatomical classification describes five patterns, according to the localization of bone and joint pathology. This review article aims to provide a brief overview of the diabetic Charcot foot in terms of etiology, pathophysiology, and classification.
doi:10.3402/dfa.v4i0.20872
PMCID: PMC3661901  PMID: 23705058
Charcot foot; classification; diabetes mellitus; diabetic foot; neuropathy; osteoarthropathy
14.  Neuroarthropathy of the hip following spinal cord injury 
Indian Journal of Orthopaedics  2011;45(1):87-90.
We present the case of a 33-year-old male who sustained a burst fracture D12 vertebrae with spinal cord injury (ASIA impairment scale A) and a right mid-diaphysial femoral shaft fracture around 1.5 years back. The patient reported 1.5 years later with a swelling over the right buttock. Arthrotomy revealed serous fluid and fragmented bone debris. The biopsy showed a normal bony architecture with no evidence of infection and malignant cells. Hence, a diagnosis of Charcot’s hip was made. Charcot’s neuroarthropathy of the feet is a well-recognized entity in the setting of insensate feet resulting from causes such as diabetes or spina bifida. Although Charcot’s disease of the hips has been described, it is uncommon in association with spinal cord injury, syphilis and even with the use of epidural injection. The present case highlights the fact that neuroarthropathy of the hip can occur in isolation in the setting of a spinal cord injury, and this can lead to considerable morbidity.
doi:10.4103/0019-5413.73665
PMCID: PMC3004089  PMID: 21221231
Charcot’s hip; neuroarthropathy; spinal cord injury
15.  Syringomyelia with Chiari I Malformation Presenting as Hip Charcot Arthropathy: A Case Report and Literature Review 
Neuroarthropathy (neuropathic osteoarthropathy), also known as Charcot joint, is a condition characterized by a progressive articular surface destruction in the setting of impaired nociceptive and proprioceptive innervation of the involved joint. It is seen most commonly in the foot and ankle secondary to peripheral neuropathy associated with diabetes mellitus. Cases of hip (Charcot) neuroarthropathy are rare and almost exclusively reported in patients with neurosyphilis (tabes dorsalis). We report a case of a 36-year-old man who presented to the emergency department complaining of right hip pain. On physical examination, pain and thermal sensory deficits were noted in the upper torso with a cape-like distribution, as well as signs of an upper motor neuron lesion in the left upper and lower extremities. A magnetic resonance imaging study (MRI) of the right hip showed evidence of early articular surface destruction and periarticular edema consistent with hip Charcot arthropathy. An MRI of the spine revealed an Arnold-Chiari type I malformation with extensive syringohydromyelia of the cervical and thoracic spine.
doi:10.1155/2015/487931
PMCID: PMC4322850
16.  Effects of low-dye taping on plantar pressure pre and post exercise: an exploratory study 
Background
Low-Dye taping is used for excessive pronation at the subtalar joint of the foot. Previous research has focused on the tape's immediate effect on plantar pressure. Its effectiveness following exercise has not been investigated. Peak plantar pressure distribution provides an indirect representation of subtalar joint kinematics. The objectives of the study were 1) To determine the effects of Low-Dye taping on peak plantar pressure immediately post-application. 2) To determine whether any initial effects are maintained following exercise.
Methods
12 asymptomatic subjects participated; each being screened for excessive pronation (navicular drop > 10 mm). Plantar pressure data was recorded, using the F-scan, at four intervals during the testing session: un-taped, baseline-taped, post-exercise session 1, and post-exercise session 2. Each exercise session consisted of a 10-minute walk at a normal pace. The foot was divided into 6 regions during data analysis. Repeated-measures analysis of variance (ANOVA) was used to assess regional pressure variations across the four testing conditions.
Results
Reduced lateral forefoot peak plantar pressure was the only significant difference immediately post tape application (p = 0.039). This effect was lost after 10 minutes of exercise (p = 0.036). Each exercise session resulted in significantly higher medial forefoot peak pressure compared to un-taped; (p = 0.015) and (p = 0.014) respectively, and baseline-taped; (p = 0.036) and (p = 0.015) respectively. Medial and lateral rearfoot values had also increased after the second session (p = 0.004), following their non-significant reduction at baseline-taped. A trend towards a medial-to-lateral shift in pressure present in the midfoot immediately following tape application was still present after 20 minutes of exercise.
Conclusion
Low-Dye tape's initial effect of reduced lateral forefoot peak plantar pressure was lost after a 10-minute walk. However, the tape continued to have an effect on the medial forefoot after 20 minutes of exercise. Further studies with larger sample sizes are required to examine the important finding of the anti-pronatory trend present in the midfoot.
doi:10.1186/1471-2474-10-40
PMCID: PMC2676256  PMID: 19383160
17.  Proinflammatory Modulation of the Surface and Cytokine Phenotype of Monocytes in Patients With Acute Charcot Foot 
Diabetes Care  2009;33(2):350-355.
OBJECTIVE
Despite increased information on the importance of an inappropriate inflammatory response in the acute Charcot process, there has been no previous attempt to define the specific pathways that mediate its pathogenesis. Here, the role played by monocytes was analyzed.
RESEARCH DESIGN AND METHODS
The immune phenotype of peripheral monocytes was studied by fluorescence-activated cell sorter analysis comparing patients with acute Charcot (n = 10) in both the active and recovered phase, diabetic patients with neuropathy (with or without osteomyelitis), and normal control subjects.
RESULTS
When compared with diabetic control subjects and healthy subjects, monocytes from acute Charcot patients showed a proinflammatory immune phenotype characterized by increased production of proinflammatory cytokines, reduced secretion of anti-inflammatory cytokines, increased expression of surface costimulatory molecules, and increased resistance to serum withdrawal-induced apoptosis. In addition, the pattern of circulating cytokines confirmed activation of proinflammatory cytokines. No modulation of the monocyte phenotype was documented in diabetic control subjects and healthy subjects, thus indicating that the proinflammatory alterations of monocytes are specific and causative of acute Charcot.
CONCLUSIONS
Together, these data provide evidence for the role of proinflammatory changes in the immune phenotype of monocytes in the pathogenesis of acute Charcot. These alterations may explain the abnormally intense and prolonged inflammatory response that characterizes this disorder and may represent a potential therapeutic target for specific pharmacological interventions.
doi:10.2337/dc09-1141
PMCID: PMC2809281  PMID: 19880584
18.  Mortality Associated With Acute Charcot Foot and Neuropathic Foot Ulceration 
Diabetes Care  2010;33(5):1086-1089.
OBJECTIVE
To compare the mortality of patients with an acute Charcot foot with a matched population with uninfected neuropathic foot ulcers (NFUs).
RESEARCH DESIGN AND METHODS
Data were extracted from a specialist departmental database, supplemented by hospital records. The findings were compared with the results of earlier populations with Charcot foot and uninfected NFUs managed from 1980. Finally, the results of all patients with acute Charcot foot and all control subjects managed between 1980 and 2007 were compared with normative mortality data for the U.K. population.
RESULTS
A total of 70 patients presented with an acute Charcot foot (mean age 57.4 ± 12.0 years; 48 male [68.6%]) between 2001 and 2007; there were 66 matched control subjects. By 1 October 2008, 13 (eight male; 18.6%) patients with a Charcot foot had died, after a median of 2.1 years (interquartile range 1.1–3.3). Twenty-two (20 male; 33.3%) control subjects had also died after a median of 1.3 years (0.6–2.5). There was no difference in survival between the two groups (log-rank P > 0.05). Median survival of all 117 patients with acute Charcot foot managed between 1980 and 2007 was 7.88 years (4.0–15.4) and was not significantly different from the control NFU patients (8.43 years [3.4–15.8]). When compared with normative U.K. population data, life expectancy in the two groups was reduced by 14.4 and 13.9 years, respectively.
CONCLUSIONS
These data confirm that the mortality in patients presenting to our unit with either an acute Charcot foot and an uninfected neuropathic ulcer was unexpectedly high.
doi:10.2337/dc09-1428
PMCID: PMC2858181  PMID: 20185744
19.  Correlation between Plantar Foot Temperature and Diabetic Neuropathy: A Case Study by Using an Infrared Thermal Imaging Technique 
Background
Diabetic neuropathy consists of multiple clinical manifestations of which loss of sensation is most prominent. High temperatures under the foot coupled with reduced or complete loss of sensation can predispose the patient to foot ulceration. The aim of this study was to look at the correlation between plantar foot temperature and diabetic neuropathy using a noninvasive infrared thermal imaging technique.
Methods
Infrared thermal imaging, a remote and noncontact experimental tool, was used to study the plantar foot temperatures of 112 subjects with type 2 diabetes selected from a tertiary diabetes centre in South India.
Results
Patients with diabetic neuropathy (defined as vibration perception threshold (VPT) values on biothesiometry greater than 20 V) had a higher foot temperature (32–35 °C) compared to patients without neuropathy (27–30 °C). Diabetic subjects with neuropathy also had higher mean foot temperature (MFT) (p = .001) compared to non-neuropathic subjects. MFT also showed a positive correlation with right great toe (r = 0.301, p = .001) and left great toe VPT values (r = 0.292, p = .002). However, there was no correlation between glycated hemoglobin and MFT.
Conclusion
Infrared thermal imaging may be used as an additional tool for evaluation of high risk diabetic feet.
PMCID: PMC3005049  PMID: 21129334
diabetic neuropathy; infrared thermal imaging; mean foot temperature; serum cholesterol; type 2 diabetes
20.  An overview of conservative treatment options for diabetic Charcot foot neuroarthropathy 
Diabetic Foot & Ankle  2011;2:10.3402/dfa.v2i0.6418.
Conservative management of Charcot foot neuroarthropathy remains efficacious for certain clinical scenarios. Treatment of the patient should take into account the stage of the Charcot neuroarthopathy, site(s) of involvement, presence or absence of ulceration, presence or absence of infection, overall medical status, and level of compliance. The authors present an overview of evidence-based non-operative treatment for diabetic Charcot neuroarthropathy with an emphasis on the most recent developments in therapy.
doi:10.3402/dfa.v2i0.6418
PMCID: PMC3284343  PMID: 22396831
diabetic foot; osteomyelitis; Charcot neuroarthropathy; ulcer; bone stimulation
21.  Radiographic and functional results in the treatment of early stages of Charcot neuroarthropathy with a walker boot and immediate weight bearing 
Diabetic Foot & Ankle  2013;4:10.3402/dfa.v4i0.22487.
Background
One of the most common gold standards for the treatment of Charcot neuroarthropathy (CN) in the early Eichenholtz stages I and II is immobilization with the total contact casting and lower limb offloading. However, the total amount of offloading is still debatable.
Objectives
This study evaluates the clinical and radiographic findings in the treatment of early stages of CN (Eichenholtz stages I and II) with a walker boot and immediate total weight-bearing status.
Methods
Twenty-two patients with type 2 diabetes mellitus (DM) and CN of Eichenholtz stages I and II were selected for non-operative treatment. All patients were educated about their condition, and full weight bearing was allowed as tolerated. Patients were monitored on a fortnightly basis in the earlier stages, with clinical examination, temperature measurement, and standardized weight-bearing radiographs. Their American Orthopedic Foot and Ankle Society (AOFAS) scores were determined before and after the treatment protocol.
Results
No cutaneous ulcerations or infections were observed in the evaluated cases. The mean measured angles at the beginning and end of the study, although showing relative increase, did not present a statistically significant difference (p > 0.05). Mean AOFAS scores showed a statistically significant improvement by the end of the study (p < 0.005).
Conclusion
The treatment of early stages of CN (Eichenholtz stages I and II) with emphasis on walker boot and immediate weight bearing has shown a good functional outcome, non-progressive deformity on radiographic assessment, and promising results as a safe treatment option.
doi:10.3402/dfa.v4i0.22487
PMCID: PMC3813827  PMID: 24179634
Charcot neuroarthropathy; classification; ulceration; diabetes; weight bearing
22.  Plantar Foot Surface Temperatures with Use of Insoles 
Purpose-
Patients with diabetes are often prescribed foot orthoses to help prevent foot ulcer formation. Orthotics are used to redistribute normal and shear stress. Shear stresses are not easily measurable and considered to be responsible for skin breakdown. Local elevation of skin temperature has been implicated as an early sign of impending ulceration especially in regions of high shear stress. The purpose of this study was to measure the effects of commonly prescribed insole materials on local changes in plantar foot temperature during normal gait.
Methods-
Six commonly used foot orthosis materials were tested using the Thermo Trace™ infrared thermometer to measure foot temperature. Ten healthy adult volunteers without any history of diabetes or abnormal sensation participated in the study. During each trial the subject walked on a treadmill with the test material in the dominant foot's shoe, for six minutes at a speed of four miles per hour and rested for six minutes between trials. Four locations on the foot (hallux, first and fifth metatarsal heads, and heel) and the contralateral bicep temperatures were measured at 0, 1, 3, 5 minutes during the rest period. The order of material and skin location testing was randomized.
Results-
Significant differences were found between baseline temperatures and foot temperatures for all materials. However, no differences were found between materials for any location on the foot.
Conclusion-
Previous studies have attempted to characterize materials based on laboratory and clinical testing, while other studies have attempted to characterize the effect of pressure on skin temperature. However, no study has previously attempted to characterize foot orthosis materials based on foot temperatures. This study compared foot temperatures of healthy adults based on the material tested. Although this study was unable to distinguish between materials based on foot temperatures, it was able to show a rise in foot temperature with any material used. This study demonstrates a need to a larger study on a population with diabetes.
PMCID: PMC1888418  PMID: 15296210
23.  Lower-Extremity Amputation Risk After Charcot Arthropathy and Diabetic Foot Ulcer 
Diabetes Care  2009;33(1):98-100.
OBJECTIVE
To compare risks of lower-extremity amputation between patients with Charcot arthropathy and those with diabetic foot ulcers.
RESEARCH DESIGN AND METHODS
A retrospective cohort of patients with incident Charcot arthropathy or diabetic foot ulcers in 2003 was followed for 5 years for any major and minor amputations in the lower extremities.
RESULTS
After a mean follow-up of 37 ± 20 and 43 ± 18 months, the Charcot and ulcer groups had 4.1 and 4.7 amputations per 100 person-years, respectively. Among patients <65 years old at the end of follow-up, amputation risk relative to patients with Charcot alone was 7 times higher for patients with ulcer alone and 12 times higher for patients with Charcot and ulcer.
CONCLUSIONS
Charcot arthropathy by itself does not pose a serious amputation risk, but ulcer complication multiplicatively increases the risk. Early surgical intervention for Charcot patients in the absence of deformity or ulceration may not be advisable.
doi:10.2337/dc09-1497
PMCID: PMC2797995  PMID: 19825822
24.  Ataxia and other data reviewed in Charcot-Marie-Tooth and Refsum's disease. 
The author reports his experience on Refsum's disease and that gained after personally examining in detail 64 patients with Charcot-Marie-Tooth disease over the past ten years. The "cerebellar" inco-ordination in Charcot-Marie-Tooth disease (with or without distal wasting) and in Refsum's disease is analysed. Some variations in the motor and sensory neuropathy of Charcot-Marie-Tooth disease and Refsum's disease are discussed. The adequacy of motor conduction velocity in genetically distinguishing types of the above mentioned familial peripheral neuropathies is reviewed. Data on the neuropathy assessed by modern techniques of three original patients of Roussy and Levy (1926) are given. The possibility of extensor plantar responses in patients with Charcot-Marie-Tooth and Refsum's disease without structural lesion of the pyramidal tract is pointed out. The existence of the association between Friedreich's ataxia and Charcot-Marie-Tooth disease is criticised. It is emphasised that spinocerebellar degeneration (other than Friedreich's ataxia) presenting with distal limb weakness and wasting and sensory impairment may mimic Charcot-Marie-Tooth disease.
PMCID: PMC491688  PMID: 6186770
25.  Plantar Foot Pressures After the Augmented Low Dye Taping Technique 
Journal of Athletic Training  2007;42(3):374-380.
Context: Taping and orthoses are frequently applied to control excessive foot pronation to treat or prevent musculoskeletal pain and injury of the lower limb. The mechanism(s) by which these devices bring about their clinical effects are at best speculative and require systematic evaluation.
Objective: To determine the initial effect of the augmented low Dye taping technique (ALD) on plantar foot pressures during walking and jogging.
Design: Within-subjects, repeated-measures randomized control trial.
Setting: Gait research laboratory.
Patients or Other Participants: Fifteen women and 7 men with an average age of 28.0 ± 7.4 years who were asymptomatic.
Intervention(s): Participants walked and jogged along a 12-m walkway before and after the application of ALD. The untaped side served as the control.
Main Outcome Measure(s): Peak and mean maximum plantar pressure data were calculated for the medial and lateral areas of the rear and midfoot and the medial, central, and lateral forefoot areas. Thus, a 3-factor model was tested: condition (ALD, control) × time (preapplication, postapplication) × area (medial and lateral rearfoot and midfoot and medial, central, and lateral forefoot).
Results: Significant 3-way interactions were present for both peak and mean maximum plantar pressure during walking (F 6,126 = 9.55, P = .006 and F 6,126 = 11.36, P = .003, respectively) and jogging (F 6,126 = 5.76, P = .026 and F 6,126 = 4.56, P = .045, respectively) tasks. The ALD predominantly increased plantar pressures in the lateral midfoot during walking and jogging. In addition, tape reduced mean maximum pressure at the medial forefoot and at the medial rearfoot during walking.
Conclusions: The ALD, which has previously been shown to reduce excessive pronation, produced significant increases in lateral midfoot plantar pressures, thereby providing additional information to be considered when the mechanism(s) of action of such a treatment are modeled.
PMCID: PMC1978458  PMID: 18059993
pronation; gait

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