Pressure pain perception at the injured foot: the impact of diabetic neuropathy.

BACKGROUND: At feet with painless diabetic neuropathy (PDN) and a healed fracture (quiescent Charcot-foot), cutaneous pressure pain perception threshold (CPPPT) is elevated beyond the range of measurement, whereas deep pressure pain perception threshold (DPPPT) may be normal. It is unknown, how these thresholds behave under the conditions of a foot injury. We therefore measured CPPPT and DPPPT in the vicinity of a unilateral active foot injury. PATIENTS AND METHODS: 18 diabetic patients with PDN and plantar injury, partly involving the skeleton (Wagner grade I-II ulcer), 10 non-neuropathic subjects with acute painful skeletal injury (sprain, fracture) and 20 healthy control subjects without foot injury were studied. CPPPT was measured using calibrated monofilaments, and DPPPT was measured by Algometer II® over muscle and joint. RESULTS: Compared to control subjects, non-neuropathic acutely injured (and contralateral) feet displayed lowered CPPPT and DPPPT. Conversely, ulcerated and contralateral feet with PDN displayed unmeasurably elevated thresholds in 100% (CPPPT), 72% (DPPPT over joint), and 28% (DPPPT over muscle) of patients, respectively. CONCLUSION: In the vicinity of an active foot injury, physiologic hyperalgesia was demonstrated in the non-neuropathic subjects, but not in the patients with PDN in whom neglect of foot trauma is, therefore, common.

Pressure pain thresholds at the diabetic Charcot-foot: an exploratory study.

OBJECTIVE: Painless mechanical trauma is believed to induce neuroosteoarthropathy at the neuropathic foot in diabetes (diabetic Charcot-foot). To investigate pressure nociception at the diabetic foot, we measured the pain perception thresholds for deep pressure (DPPPT, using Algometer II®) and cutaneous pressure (CPPPT, using calibrated monofilaments). METHODS: In 24 diabetic patients with painless neuropathy (11 with a chronic, inactive Charcot-foot and a history of foot ulcer, and 13 control patients who never had an ulcer), and in 20 healthy subjects, CPPPT (at palmar and plantar digital skinfolds) and DPPPT (over musculus abductor pollicis, musculus hallucis longus, and over metacarpophalangeal and metatarsophalangeal joints) was measured. RESULTS: At the hands, DPPPT and CPPPT were similar in patients and healthy subjects. At the feet, CPPPT was above the upper safety limit of measurement (512 mN) in 2/20 healthy subjects, and in 11/11 Charcot patients compared to 6/13 neuropathic controls (p=0.005). At the feet, median DPPPT was similar in all groups. In Charcot patients only, DPPPT was higher over metatarsophalangeal joint than over m. hallucis longus (p=0.048). CONCLUSION: Perception thresholds for cutaneous pressure pain, but not for deep pressure pain, may be extremely elevated at the diabetic neuropathic foot, and particularly at the Charcot-foot.

Weight-bearing intensity produces charcot deformity in injured neuropathic feet in diabetes.

UNLABELLED: The purpose of the study was to investigate the relationship between the intensity of unrestrained weight bearing after a non-fracture injury (e.g. sprain), and the development of osteoarthropathic deformities of the foot (Charcot foot) in patients with diabetic neuropathy. METHODS: 34 diabetic patients (14 Type 1, 20 Type 2) with foot bone injuries were studied in retrospect. At onset of injury symptoms (e.g. foot swelling), 32 of 34 feet displayed unremarkable X-ray, but pathologic MR imaging (e.g. bone marrow edema along the Lisfranc and/or the Chopart joint). Cumulative load forces after the onset of symptoms until treatment by total contact cast (TCC) were estimated using the product of body weight and number of weeks of ambulation (kg x week) as a surrogate. Feet were classified in 3 groups according to the degree of foot deformities found at the start of treatment with TCC: Feet without deformities (group A, n=16), feet with minor deformities (partially reduced plantar arch (group B, n=6) and feet with major deformities (collapsed plantar arch, group C, n=12) RESULTS: Feet in group A had been exposed to 262 (95% CI 135-390) kg x week, compared to 974 (95% CI 342-1606) in group B, and to 2348 (95% CI 1265-3430) kg x week in group C (p<0.05 between groups), indicative of a dose-response relationship between weight-bearing and progressive foot deformities. Destruction along the Lisfranc joint was observed in 2/16 feet in group A, versus 18/18 feet in group B and C combined (p<0.001). In group A, the undeformed feet were healed without major deformities (except for 2 non-compliant patients), whereas in group B and C feet remained as deformed as they were at TCC application. CONCLUSION: Unrestrained weight-bearing of injured foot bones and joints of more than 400 kg x week (equivalent to 8 weeks of normal walking by a person of 50 kg body weight) prompts Charcot deformities, with disintegration of the Lisfranc joint. Early off-loading by TCC treatment allows healing without deformities.

"Silent" bone stress injuries in the feet of diabetic patients with polyneuropathy: a report on 12 cases.

BACKGROUND: Bone stress injuries are rarely being diagnosed in patients with sensory neuropathy, most likely because they may be silent in terms of pain. Load-related pain is considered a key feature of any bone stress injury, a symptom, which may be partially or completely absent in subjects with sensory neuropathy (loss of protective sensation). We evaluated the clinical course of bone stress injuries in insensitive feet in diabetic patients with polyneuropathy. METHODS: We investigated 12 consecutive diabetic patients with bone stress injuries of the foot (bone marrow edema, bone bruise and microtrabecular fractures, on magnetic resonance imaging MRI), which were undetectable on plain X-ray. All patients suffered from diabetic polyneuropathy, none of them had an active foot ulcer. RESULTS: The patients presented with a swollen foot, which was only mildly painful and did not prevent them from walking. Complaints were related to the swelling, which increased during load-bearing. In seven cases, a traumatic event preceding the onset of symptoms could be ascertained. MRI disclosed stress injuries in 2.5 (1-8) [median (range)] bones per foot. In 11 patients, treatment was started immediately by off-loading with total contact cast for 17 (8-52) weeks, followed by gradual increase in weight bearing. One patient unfortunately received off-loading treatment only after deforming fractures had developed. All bone injuries healed uneventuelly in eight patients, and with residual mild osteoarthrosis in three patients without gross deformities. However, the untreated patient developed severe Charcot foot deformity. CONCLUSIONS: In diabetic patients with polyneuropathy, symptoms of bone stress injuries of the foot are atypical, in that there is load-related swelling rather than load-related pain. Immediate diagnosis, and treatment with off-loading, leads to a restitutio ad integrum like in non-neuropathic patients. Delayed cessation of overuse, however, may cause irreversible joint and bone damage (Charcot foot).

Evaluation of the diabetic charcot foot by MR imaging or plain radiography--an observational study.

Magnetic resonance (MR) images and concomitant plain radiographs of 26 Charcot feet of different stages (stage 0 to III) were reviewed in retrospect for discordant findings. Bone and joint abnormalities were evaluated qualitatively, and quantitatively guided by the AO integral classification of injuries of the foot. MR images revealed traumatic bone and joint injuries (bone oedema, occult fractures, and joint effusion) already in stage 0, when X-ray still showed normal bone and joint anatomy (p = 0.02). Moreover, MR images revealed bone oedema, joint effusion and soft tissue oedema in addition to fractures and calluses in stage I (bone dissolution), stage II (bone coalescence), and stage III (bone remodeling), i.e., in stages with overt radiographic pathology. According to this observational study, MR imaging, in addition to radiography, provides important information as to the extent and the natural course of bone injury in the diabetic Charcot foot. MR imaging, thus, may improve disease staging, as well as treatment monitoring.

Charcot foot in diabetes: farewell to the neurotrophic theory.

Neuropathic osteoarthropathy is characterised by relatively painless swelling together with extensive damage in bones and joints, predominantly in the feet and ankles. The uncontrolled natural course of the condition leads to gross foot deformity, skin pressure ulceration, spreading infections, and sometimes amputation. Jean-Martin Charcot in 1883 described "Charcot foot" named after him in patients with tabes dorsalis insensitivity. Charcot believed that intrinsic bone weakness was the underlying condition, and was caused by neurogenic deficiencies in bone nutrition. His followers believed such dystrophy to be mediated by sympathetic denervation of the bone vasculature (neurotrophic, or neurovascular theory). Attempts to prove this theory were futile. A neurogenic circulatory disorder potentially relevant to bone nutrition could not be identified. Nowadays, Charcot foot is mostly seen in diabetic neuropathy, which has replaced syphilis as a frequent cause of peripheral nerve dysfunction. Recent studies in the diabetic Charcot foot and bone turnover indicate that the neurotrophic theory is a myth. The assumption of bone resorption due to sympathetic denervation proved to be false--sympathetic activity increases osteoclastic activity and thereby bone loss (sympathomimetic bone resorption). Except for the transient, inflammatory stage of the diabetic Charcot foot, there is no evidence of relevant osteoporosis or demineralisation of the foot skeleton in diabetes.

The diabetic charcot foot: MRI discloses bone stress injury as trigger mechanism of neuroarthropathy.

It is generally accepted that traumatic bone injury contributes to the clinical picture of neuroarthropathy of the foot in diabetes, i.e., of the diabetic Charcot foot. While radiology is capable of visualizing only advanced bone injuries, like complete fractures, magnetic resonance imaging (MRI) discloses bone injuries that precede complete fractures (stress bone injuries). In diabetic polyneuropathy, stress bone injuries are silent in terms of pain, due to the lack of pain sensation. At the foot, their clinical appearance is characterized by inflammatory swelling with little or no pain. The present paper reviews the contribution of MRI to the detection of bone injuries in what is called stage 0 Charcot foot, with emphasis on the bearings for the treatment strategy.

Progression of diabetic retinopathy during improved metabolic control may be treated with reduced insulin dosage and/or somatostatin analogue administration -- a case report.

It is well known that intensified insulin treatment of poorly controlled type 1 diabetic patients may worsen an existing diabetic retinopathy (DR). This observation has been explained by an insulin-induced stimulation of the GH/IGF-I axis. Here, we report on three cases, where the progression of DR during intensified metabolic control was treated with manipulation of insulin therapy and/or by administration of octreotide. Serum concentrations of IGF-I, IGFBP-3, insulin, cystatin C, creatinine, endogenous creatinine clearance and HbA1c-levels were assessed by routine laboratory methods; serum IGF-I bioactivity was estimated by a highly specific kinase receptor activation assay. Visual acuity and retinopathy stage was assessed by established clinical methods including fluorescein angiography. After glycaemic control was improved by intensified insulin therapy, serum IGF-I levels acutely increased. Subsequently, DR progressed to an advanced stage ("florid retinopathy"), with macular edema, and proliferation of new vessels (in two cases). Immediate reduction of insulin dosage and administration of octreotide lowered serum total IGF-I levels (and IGF-I bioactivity as measured in one patient). Subsequently, macular edema resolved partly, and visual acuity improved, allowing laser photocoagulation to be performed. In conclusion, in poorly controlled type 1 diabetic patients, intensified insulin therapy is able to cause florid DR with acute macular edema. These sight-threatening changes may improve by short-term reduction of insulin dosage or by administration of octreotide, and we speculate that this may be related to down-regulation of (serum) IGF-I.

The perils of procrastination: effects of early vs. delayed detection and treatment of incipient Charcot fracture.

BACKGROUND: At the onset of acute diabetic Charcot foot, therapeutic intervention may be delayed because plain X-rays may not show fractures. AIM OF THE STUDY: To assess the clinical course of acute Charcot foot in 24 patients without evidence of definite fractures on the first X-ray after onset of symptoms, who were referred to the foot clinic for diagnosis and treatment either early or delayed, i.e. before or after definite fractures were detectable on repeat X-rays. PATIENTS AND METHODS: Eleven patients were referred early (incipient Charcot foot, case group), and 13 patients were referred delayed (overt Charcot foot, control group). In the foot clinic, both groups were immediately treated with off-loading and total contact casting. After the healing process of the Charcot foot was complete, the extent of fractures and subsequent deformities were evaluated. RESULTS: Based on X-rays at the onset of symptoms, in 19 of the 24 patients the condition had been misdiagnosed prior to referral (in 11 patients as sprain injury). Additional imaging techniques (MRI, CT scan or bone scintigraphy) had been performed in 10 patients prior to referral. While these techniques had been used more frequently in the cases vs. the controls (P=0.012), misdiagnosis was less frequent in the cases vs. the controls (P=0.013). Only one out of 11 case patients developed extended foot fractures and severe deformity, vs. 12 out of 13 control patients (P<0.001). CONCLUSION: Early detection of incipient Charcot foot is facilitated by imaging techniques other than plain X-rays. Immediate off-loading of incipient Charcot foot appears to minimize fractures and incapacitating deformities.

New insights into the pathogenesis of diabetic retinopathy--hormonal rather than metabolic factors are important.

Diabetic retinopathy has traditionally been viewed as a metabolite-driven, occlusive vasculopathy that affects both retinal microvascular haemodynamics and stricture; analogies to cholesterol-driven occlusive atherosclerosis of the macrovascular circulation were drawn. However this paradigm may no longer be appropriate. Recent evidence suggests that diabetic retinopathy from the beginning is the consequence of a complex hormonal dysfunction, which is related to insulin-dependent up- and downregulation of growth factors, to which metabolic, haemodynamic, endocrine, paracrine, and autocrine mechanisms contribute.

[Diabetic foot disease--a review of pathogenesis, treatment and prevention of diabetic podopathy]. / Der diabeteskranke Fuss--Pathogenese, Behandlung und Prävention der diabetischen Podopathie.

An update is presented of the pathogenesis, treatment and prevention of diabetic podopathy. Although the underlying conditions, polyneuropathy and peripheral ischaemic vessel disease presently cannot be cured, their complications, i.e. foot ulcers, foot gangrene and foot fractures in most cases can nowadays be treated successfully without major amputations.

Outcome of critical foot ischaemia in longstanding diabetic patients: a retrospective cohort study in a specialised tertiary care centre.

BACKGROUND: We sought to establish risk factors predicting the outcome of foot lesions in longstanding diabetic patients with critical foot ischaemia (CFI). PATIENTS AND METHODS: We investigated retrospectively 98 consecutive diabetic patients with ischaemic foot lesions. The patients (mean age 70 years, duration of diabetes 21 years) were jointly cared for by specialised diabetologists and vascular surgeons; 75 patients were treated by arterial revascularisation. RESULTS: Good outcome (lesions healing) was observed in 53 patients (54%). Bad outcome was observed in 45 patients: not healing lesions (n = 5), major amputation (n = 19), and death in relation to the foot lesion (n = 21). Patients with good and bad outcome did not differ regarding age, sex, smoking status, type, duration and treatment of diabetes mellitus, presence of neuropathy, coronary heart disease, stroke, previous amputations, current revascularization, and localization of the foot lesion. The risk of bad outcome was increased 8.9 times in patients on dialysis for end-stage renal disease; 7.0 times if surgical complications were present; and 5.4 times with C-reactive protein (CRP) above the second quintile (cut-off value 8 mg/dl). CONCLUSION: Management of longstanding diabetic patients with ischaemic foot lesions leaves room for improvement. Dialysis treatment, elevated CRP levels and surgical complications were strongly predictive of non-healing lesions, major amputation and death.

Reversion of 'early worsening' of diabetic retinopathy by deliberate restoration of poor metabolic control.

Acutely lowering long-standing severe hyperglycaemia can trigger progression ('early worsening') of diabetic retinopathy, most likely by up-regulation of the circulating insulin-like growth factor 1 (IGF-1). This condition, also called 'florid retinopathy', rarely responds to standard laser coagulation treatment. In this retrospective report, 2 young patients with type 2 diabetes are described, in whom deliberate restoration of poor diabetes control reduced the serum IGF-1 levels and improved 'early worsened' diabetic retinopathy.

Effectiveness of a new brand of stock 'diabetic' shoes to protect against diabetic foot ulcer relapse. A prospective cohort study.

AIMS: Diabetic patients with podopathy (diabetic foot syndrome) may need protective footwear, be it customized or industrially produced stock 'diabetic' shoes (SDS). The effectiveness of each type of 'diabetic' shoe needs to be proven clinically, e.g. in terms of prevention of foot ulceration. The following study assesses a new German SDS, the LucRo shoe, which consists of rocker-shaped walking sole, a standardized shock absorption insole, and soft uppers without stiff toe-caps. The LucRo SDS has been registered as a Medicinal Product according to the European Community Guideline 93/42/EC. PATIENTS AND METHODS: A total of 92 high-risk diabetic patients (mean age 63 years, duration of diabetes 13 years) with healed foot ulcer were recruited prospectively over 31 months; 87 patients suffered from polyneuropathy, 24 patients had peripheral ischaemic vessel disease. One group of patients (n = 60) received the LucRo SDS and wore them, while the remaining patients (n = 32) did not receive the SDS and were forced to use their normal footwear. This allocation reflects the haphazard reimbursement policies of the individual patients' health insurance, and is in accordance with the current German legislation. The patients were followed up for up to 42 months until the first foot ulcer relapse, or the end of the study. RESULTS: There were no differences between the groups concerning age, sex, type and duration of diabetes, prevalence of polyneuropathy and peripheral ischaemic vessel disease, frequency of foot care and mortality rate. The first year annual rate of foot ulcer relapse was significantly different between the groups: 60% without SDS vs. 15% with SDS. The overall cumulative ulcer-free survival was significantly greater with SDS (P < 0.0001, log rank test). CONCLUSION: The LucRo stock 'diabetic' shoe appears effective in the prevention of foot re-ulceration in high-risk patients with diabetic podopathy.