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International audience; Objective: To explore associations between changes of lower extremity function (LEF) parameters over a 5-year period and diffusion tensor imaging (DTI) parameters of white matter tracts among community-dwelling older adults.Design: A secondary analysis on image and physical function data collected from the Multidomain Alzheimer's Preventive Trial (MAPT).Participants: 208 older adults (aged 75 ± 4 years, with spontaneous memory complaint or limited instrumental daily living activity or slow gait speed, 60% female) of the MAPT-magnetic resonance imaging (MRI) ancillary study. The time interval between a participant's enrolment and MRI scan was on average 110 ± 97 days.Measurements: Forty-eight white matter tracts (WMTs) were measured. LEF parameters (measured after the MRI scan) were assessed as the short physical performance battery (SPPB) score, gait speed, and chair stands time over a 5-year period. Mixed-effects models were performed to explore the associations between baseline DTI values and the progression of LEF parameters. Bonferroni correction was applied for multiple comparison correction.Results: The progression of LEF was associated with 35 baseline DTI parameters from 24 WMTs. Higher baseline DTI parameter values were related to more decreases in SPPB score and gait speed, and greater increases in chair stands time. Bilateral uncinate fasciculus was associated with all LEF parameters. Other WMTs in cingulum, cerebral and cerebellar peduncle, internal capsule, and corpus callosum also showed close connections with LEF changes.Conclusions: Our findings show that DTI parameters of some WMTs are associated with the 5-year decline in LEF, suggesting that alterations in WMT integrity (evaluated by DTI parameters) might be used to explore potential causes of impaired mobility in older adults when no clear explanations can be found.

International audience; Following a long period dominated by random fasciocutaneous flaps or muscle flaps, solutions to cover the lower limb have been largely diversified by the advent of so-called "perforator" flaps. Extended knowledge of vascular anatomy has propagated the development of this innovative procedure, in the objective of reducing morbidity. The existence of close to 400 perforator vessels in the body makes it possible to offer new flap perspectives for many defects, which were sometimes previously impossible to manage before except by free flap. For us, perforator flaps have become the current first-line solutions for small to medium size loss of substances. Understanding of vascular physiology and surgical experience are essential in choosing indications, detecting perforators, and modeling flaps to be optimally positioned in the reconstructive decisional algorithm. New skills are needed to master this type of reconstruction and limit failures, which implies a learning curve not only for flap design, perforator detection and surgical procedure, but also for monitoring and management of complications. In this manuscript, we outline the concepts and principles of the majority of the pedicled perforator flaps available for coverage of the lower limb, based on experience of more than 400 perforator flaps suitable for this localization.

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

International audience; BACKGROUND: Lower extremity peripheral artery disease is the third leading cause of atherosclerotic cardiovascular morbidity, following coronary artery disease and stroke. This study provides the first comparison of the prevalence of peripheral artery disease between high-income countries (HIC) and low-income or middle-income countries (LMIC), establishes the primary risk factors for peripheral artery disease in these settings, and estimates the number of people living with peripheral artery disease regionally and globally. METHODS: We did a systematic review of the literature on the prevalence of peripheral artery disease in which we searched for community-based studies since 1997 that defined peripheral artery disease as an ankle brachial index (ABI) lower than or equal to 0*90. We used epidemiological modelling to define age-specific and sex-specific prevalence rates in HIC and in LMIC and combined them with UN population numbers for 2000 and 2010 to estimate the global prevalence of peripheral artery disease. Within a subset of studies, we did meta-analyses of odds ratios (ORs) associated with 15 putative risk factors for peripheral artery disease to estimate their effect size in HIC and LMIC. We then used the risk factors to predict peripheral artery disease numbers in eight WHO regions (three HIC and five LMIC). FINDINGS: 34 studies satisfied the inclusion criteria, 22 from HIC and 12 from LMIC, including 112,027 participants, of which 9347 had peripheral artery disease. Sex-specific prevalence rates increased with age and were broadly similar in HIC and LMIC and in men and women. The prevalence in HIC at age 45-49 years was 5*28% (95% CI 3*38-8*17%) in women and 5*41% (3*41-8*49%) in men, and at age 85-89 years, it was 18*38% (11*16-28*76%) in women and 18*83% (12*03-28*25%) in men. Prevalence in men was lower in LMIC than in HIC (2*89% [2*04-4*07%] at 45-49 years and 14*94% [9*58-22*56%] at 85-89 years). In LMIC, rates were higher in women than in men, especially at younger ages (6*31% [4*86-8*15%] of women aged 45-49 years). Smoking was an important risk factor in both HIC and LMIC, with meta-OR for current smoking of 2*72 (95% CI 2*39-3*09) in HIC and 1*42 (1*25-1*62) in LMIC, followed by diabetes (1*88 [1*66-2*14] vs 1*47 [1*29-1*68]), hypertension (1*55 [1*42-1*71] vs 1*36 [1*24-1*50]), and hypercholesterolaemia (1*19 [1*07-1*33] vs 1*14 [1*03-1*25]). Globally, 202 million people were living with peripheral artery disease in 2010, 69*7% of them in LMIC, including 54*8 million in southeast Asia and 45*9 million in the western Pacific Region. During the preceding decade the number of individuals with peripheral artery disease increased by 28*7% in LMIC and 13*1% in HIC. INTERPRETATION: In the 21st century, peripheral artery disease has become a global problem. Governments, non-governmental organisations, and the private sector in LMIC need to address the social and economic consequences, and assess the best strategies for optimum treatment and prevention of this disease. FUNDING: Peripheral Arterial Disease Research Coalition (Europe).

International audience; OBJECTIVES: To assess the current 'real-world' management of hospitalised patients with lower-extremity peripheral artery disease (LE-PAD) and to assess the 1-year outcome. DESIGN, MATERIALS AND METHODS: The prospective and multicentre registry COhorte des Patients ARTériopathes (COPART) recruited consecutive patients from the departments of vascular medicine of three academic hospitals in Southwestern France. RESULTS: Among the 940 patients, 27.4% had intermittent claudication (IC), 9.3% ischaemic rest pain, 54.3% ulceration or gangrene and 9.3% acute limb ischaemia (ALI). Patients with IC were younger and more likely to be men, with a history of smoking (89.5%) and chronic obstructive pulmonary disease (17%). Among those with IC, 8.9% had bypass surgery and 41.5% were treated with percutaneous angioplasty. Those with tissue loss had higher rates of cardiovascular disease (CVD) risk factors and co-morbidities. At entry to the study, the level of control of the CVD risk factors was poor. The 1-year mortality rate was of 5.7% in patients with IC, 23.1% in patients with ischaemic rest pain, 28.7% in patients with tissue loss and 23% in those with ALI. Compliance with evidence-based medicine and pharmacological treatment was sub-optimal. CONCLUSION: This registry underscores the differences in patient profiles in the daily clinical setting, compared to those enrolled in several trials.

Objective We aimed at determining whether a negative single complete compression ultrasonography (CUS) of the lower limbs veins is a safe and accurate diagnostic method to rule out the diagnosis of deep venous thrombosis in pregnant and early postpartum women. Design Hospital-based retrospective study. Setting The gynaecology and vascular ultrasound units of three general hospitals in western France. Patients We identified from the hospitals databases all pregnant or up to three months postpartum women who underwent CUS for a suspicion of deep venous thrombosis between January 2002 and December 2004. Methods Questionnaires were sent to all women with a negative CUS. Their medical records were also checked. Main outcome measures We assessed the three-month thromboembolic risk and its 95% percent confidence interval in women left untreated on the basis of a negative single complete CUS of the lower limbs. Results During the study period, 162 pregnant or postpartum women underwent CUS for a suspicion of deep venous thrombosis. It was positive in 44 (27%). The 118 women who had a negative CUS were sent the questionnaire. Information about the three-month follow-up was found for 107 patients (91%). None of them experienced a thromboembolic event during follow-up: 0.0% (95% CI: 0.0–3.6). Conclusions Single complete CUS of lower limbs veins appears to be a safe method to rule out the diagnosis of deep venous thrombosis in pregnant or early postpartum women. This has to be confirmed by a prospective management study with a formal follow-up.

Opinion/Feedback Amputation of a limb is always perceived as a catastrophe. The principles underlying creation of a stump adapted to modern prosthetic fittings must be fully understood and the patient managed by a multidisciplinary team. In paediatric patients, preserving residual limb length is a crucial point that should be assessed according to the expected growth potential. Advances in prosthetic fittings have led to changes in the overall concept of socket design, which seeks to achieve three objectives: to maximise the weight-bearing surface area, to eliminate friction of the skin on the socket, and to eliminate lever-arm effects. The introduction on the market of new materials has contributed substantially to advances in prosthetic fittings. These advances require the use of new criteria for stump quality and optimisation, which exert a considerable influence on prosthesis function. Prosthetic fitting and specific management of psychological and social problems are provided during an inpatient stay in a physical medicine department, by a team of physicians, other healthcare professionals, social workers, and educators. Three-dimensional imaging and gait analysis provide valuable information. Amputation of a limb is always perceived as a catastrophe. The principles underlying creation of a stump adapted to modern prosthetic fittings must be fully understood and the patient managed by a multidisciplinary team. In paediatric patients, preserving residual limb length is a crucial point that should be assessed according to the expected growth potential. Advances in prosthetic fittings have led to changes in the overall concept of socket design, which seeks to achieve three objectives: to maximise the weight-bearing surface area, to eliminate friction of the skin on the socket, and to eliminate lever-arm effects. The introduction on the market of new materials has contributed substantially to advances in prosthetic fittings. These advances require the use of new criteria for stump quality and optimisation, which exert a considerable influence on prosthesis function. Prosthetic fitting and specific management of psychological and social problems are provided during an inpatient stay in a physical medicine department, by a team of physicians, other healthcare professionals, social workers, and educators. Three-dimensional imaging and gait analysis provide valuable information.

International audience; OBJECTIVE: To assess the safety of using single complete compression ultrasonography in pregnant and postpartum women to rule out deep vein thrombosis. DESIGN: Prospective outcome study. SETTING: Two tertiary care centres and 18 private practices specialising in vascular medicine in France and Switzerland. PARTICIPANTS: 226 pregnant and postpartum women referred for suspected deep vein thrombosis. METHODS: A single proximal and distal compression ultrasonography was performed. All women with a negative complete compression ultrasonography result did not receive anticoagulant therapy and were followed up for a three month period. MAIN OUTCOME MEASURES: Symptoms of venous thromboembolism, second compression ultrasonography or chest imaging, a thromboembolic event, and anticoagulant treatment. RESULTS: 16 women were excluded, mainly because of associated suspected pulmonary embolism. Deep vein thrombosis was diagnosed in 22 out of the 210 included women (10.5%). 10 patients received full dose anticoagulation despite a negative test result during follow-up. Of the 177 patients without deep vein thrombosis and who did not receive full dose anticoagulant therapy, two (1.1%, 95% confidence interval 0.3% to 4.0%) had an objectively confirmed deep vein thrombosis during follow-up. CONCLUSIONS: The rate of venous thromboembolic events after single complete compression ultrasonography in pregnant and postpartum women seems to be within the range of that observed in studies in the non-pregnant population. These data suggest that a negative single complete compression ultrasonography result may safely exclude the diagnosis of deep vein thrombosis in this setting. TRIAL REGISTRATION: clinicaltrials.gov NCT00740454.

International audience; Using self-report of race/ethnicity, African Americans consistently have a higher prevalence of peripheral artery disease (PAD) compared to other ethnic groups. We aimed to determine the associations between estimated genetic admixture and PAD among African and Hispanic Americans. We studied the association between genetic ancestry and PAD among 1417 African and Hispanic American participants in the Multi-Ethnic Study of Atherosclerosis who were genotyped for ancestry informative markers (AIMs). PAD was defined as an ankle-brachial index (ABI) < 0.90. The overall prevalence of PAD among the 712 self-identified African American subjects was 15.2% and 4.6% among the 705 self-identified Hispanic Americans. A one standard deviation increment in European ancestry was associated with non-significant reductions in the odds for PAD among African (OR: 0.96 [95% CI: 0.78-1.18]) and Hispanic Americans (0.84 [0.58-1.23]), while the same increment in Native American ancestry was significantly associated with a lower odds of PAD in Hispanic Americans (0.56 [0.36-0.96]). Adjustment for demographic variables, field center, cardiovascular disease (CVD) risk factors and inflammatory markers strengthened the odds for European ancestry among African (0.85 [0.66-1.10]) and Hispanic Americans (0.68 [0.41-1.11]). The magnitude of the association for Native American ancestry among Hispanic Americans did not materially change (0.56 [0.29-1.09]). In conclusion, a higher percent Native American ancestry in Hispanics is associated with a lower odds of PAD while in both Hispanics and African Americans, greater European ancestry does not appear to be associated with lower odds for PAD.

International audience; OBJECTIVES: To assess the added benefit of scanning lower limbs in addition to the usual whole-body positron emission tomography/computed tomography (PET/CT) scan in patients with no known or suspected primary or metastatic melanoma involving the lower limbs. MATERIALS AND METHODS: This is a retrospective study of 122 consecutive patients [174 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) PET/CT] who underwent FDG PET/CT for staging of melanoma at different time points in the course of the disease from October 2005 to February 2009 at the Brest University Hospital. Reports of whole-body PET/CT scans including lower limbs were reviewed. PET/CT abnormalities on the lower extremities were tabulated by location and correlated with pathology, other imaging studies and at least a 6-month clinical follow-up. The usefulness of lower limbs acquisition in clinical management was evaluated according to imagery findings. RESULTS: Among the 174 consecutive PET/CT scans performed in 122 patients, 33 scans in 28 patients highlighted abnormal FDG uptakes considered as equivocal or suggestive of malignancy in the lower limbs. In 28 cases, uptakes were located at once in the lower limbs and in the rest of the body (lung, liver, mediastinal and sub-diaphragmatic lymph nodes, adrenal glands, bone) corresponding to disseminated disease. In five cases, PET/CT uptakes were located only in lower limbs; each pathological uptake corresponded to benign lesions. Lower limbs findings never impacted clinical and therapeutic decision. CONCLUSION: Lower limbs additional PET/CT acquisition seems to offer poor additional benefit with none unexpected lesion detected and routine skull base to upper thigh images might be sufficient for this subset of patients.

International audience; Computed tomography (CT) is widely used in diagnostic strategies for suspected pulmonary embolism (PE). As single-slice computed tomography has a limited sensitivity of about 70%, it has to be used in association with lower limbs veins compression ultrasonography (CUS). To improve the test, it has been proposed to add lower extremity CT venography to visualise lower limbs veins. Diagnostic performances of CT venous angiography and CUS have never been compared and there is no published well conducted study suggesting that adding CT venous angiography is useful. Recent studies have confirmed that CUS is no more mandatory when using the recent sensitive multi-slice computed tomography. These data limit the potential use of CT venography of the lower limbs veins in patients with suspected PE.

International audience; The aim of this study is to identify the kinetic principal components involved in one-leg running vertical jumps, as well as the potential differences between specialists from different sports. The sample was composed of 25 regional skilled athletes who play different jumping sports (volleyball players, handball players, basketball players, high jumpers and novices), who performed a running one-leg jump. A principal component analysis was performed on the data obtained from the 200 tested jumps in order to identify the principal components summarizing the six variables extracted from the force-time curve. Two principal components including six variables accounted for 78 % of the variance in jump height. Running one-leg vertical jump performance was predicted by a temporal component (that brings together impulse time, eccentric time and vertical displacement of the center of mass) and a force component (who brings together relative peak of force and power, and rate of force development). A comparison made among athletes revealed a temporal-prevailing profile for volleyball players, and a force-dominant profile for Fosbury high jumpers. Novices showed an ineffective utilization of the force component, while handball and basketball players showed heterogeneous and neutral component profiles. Participants will use a jumping strategy in which variables related to either the magnitude or timing of force production will be closely coupled; athletes from different sporting backgrounds will use a jumping strategy that reflects the inherent demands of their chosen sport.

International audience; BACKGROUND: Thromboprophylaxis in elderly patients, including post-acute care patients, is at variance with scientific evidence. The purpose of this study was to determine whether a multifaceted intervention was followed by a decrease in deep venous thrombosis (DVT). METHODS: A prospective preintervention-postintervention study was conducted in 1373 patients (preintervention phase, n = 709; postintervention phase, n = 664), aged 65 years or older, enrolled in 33 hospital-based post-acute care facilities in France. An evidence-based guideline addressing pharmacologic and mechanical prophylaxis was implemented through a multifaceted intervention. The main outcome measure was any DVT diagnosed at routine comprehensive ultrasonography performed by registered angiologists. RESULTS: A DVT was found in 91 patients (12.8%) in the preintervention phase and in 52 patients (7.8%) in the postintervention phase (P = .002). The decrease in DVT involved the calf (7.1% vs 3.6%; P = .005) and the proximal venous segments (5.8% vs 4.2%; P = .18) and remained significant after adjusting for risk factors (adjusted odds ratio of any DVT, 0.58; 95% confidence interval, 0.39-0.86). Pharmacologic prophylaxis with either low-molecular-weight heparin at the high-risk dose, unfractionated heparin, and vitamin K antagonist was similar in the 2 study groups, whereas patients in the postintervention group were more likely to use graduated compression stockings (27.4% vs 34.6%; P = .004) and less likely to receive low-molecular-weight heparin at the low-risk dose (24.7% vs 18.5%; P = .006), which was not recommended by our guideline. CONCLUSIONS: A multifaceted intervention addressing venous thromboembolism prophylaxis in post-acute care patients can be followed by a significant decrease in the rate of any DVT in elderly patients. More active interventions are needed to enforce compliance with evidence-based guidelines.

International audience; PURPOSE OF REVIEW: Minimally invasive diagnostic strategies for pulmonary embolism are in constant evolution, integrating new diagnostic tools along with the better use of clinical information. RECENT FINDINGS: In the past year, several reports have provided more data on the value of clinical signs and symptoms for diagnosing pulmonary embolism and improved clinical prediction rules for pulmonary embolism. Among the diagnostic tools, the use of multislice computed tomography of the chest received further validation, whereas the yield of bedside tests, such as the D-dimer test or alveolar dead-space measurement, have been further investigated. Furthermore, data linking good outcomes with appropriate diagnostic strategies in patients with suspected pulmonary embolism were reported this year for the first time. SUMMARY: These new data allow a more evidence-based and cost-effective approach to patients with suspected non-massive pulmonary embolism. Multislice computed tomography is replacing other imaging tests. More research should be performed on the role of lower limb venous compression ultrasonography, and on how to select patients in whom pulmonary embolism should be suspected and investigated.

SummaryThe presence of a clot – even asymptomatic – in the proximal lower limb veins of a patient with clinically suspected pulmonary embolism (PE) provides evidence for venous thromboembolism and indicates anticoagulant therapy in such patients. We aimed at assessing the diagnostic performance of compression ultrasonography as compared to multi-slice computed tomography (MSCT) for the diagnosis of PE. We analyzed data from a large outcome management study that included consecutive outpatients referred to the emergency ward with clinically suspected PE. All high clinical probability patients, and all non-high clinical probability patients with a positive D-dimer test underwent both MSCT and CUS. Of the 756 included patients, 232 had PE ruled out on the basis of a negative D-dimer test, and 524 patients underwent both MSCT and CUS. PE was found in 187 out of the 511 patients witha conclusive MSCT. The sensitivity of CUS for the presence of PE on MSCT was 39% (95% confidence interval: 32 to 46%), and its specificity was 99% (95% CI:97 to 100%). Positive and negative likelihood ratios were 42.2 (95% CI: 13.5 to 131.9) and 0.6 (95% CI: 0.5 to 0.7), respectively. We conclude from that large study of unselected patients that CUS has high specificity but low sensitivity, for the diagnosis of PE at MSCT in suspected patients. It allows ruling in the diagnosis of PE without further invasive and/or expensive testing in suspected patients.

International audience; In order to show the value of CT angiography in the pretherapeutic assessment of lower leg ischemia, we studied 93 CT angiographies in 85 patients. Two groups were defined according to the level of revascularization: 52 angioscanner were made prior to suprainguinal revascularization and 41 prior to infrainguinal reconstruction. Two decision attitudes were chosen by two different physicians, a radiologist and vascular surgeon, members of the same team. The attitudes where then compared in order to evaluate the value of CT angiography. The first attitude was a pragmatic strategy based on the images as interpreted by the first physician and on the intraoperative information including surgical treatment and, if necessary, angiography. This indicates that the results of this attitude cover the performed revascularizations. The second attitude determined a virtual strategy and was chosen by the second physician a posteriori, based solely on the medical file with the same CT angiography images. These two strategies were compared in order to assess the agreement on the level of the lesion and the choice of revascularization. In 84 CT angiographies (90.3%), the analysis of the lesions and the choice of lesions to be treated were identical. In 9.6% of scans the strategies were not comparable because the lesions were interpreted differently or the scans were difficult to read. The sensitivity of CT angiography in detecting lesions and guiding the therapeutic strategy was 96% and its positive predictive value was 93%. Follow-up was reported according to the life-table method to assess the overall outcome and the results in both groups. The overall survival rate at 12 months for 85 patients was 90%. Secondary patency rates at 12 months in the group of patients who underwent a suprainguinal and infrainguinal revascularization were 98% and 71% respectively. Overall limb salvage at 12 months was 94%. In this setting, CT angiography allowed us to select adequate treatment in the majority of cases. These results obtained after a strategy based on CT angiography images are comparable with the results as published in the literature after the strategy based on conventional angiography.

International audience; The flexion or flexor reflex (FR) recorded in the lower limbs in humans (LLFR) is a widely investigated neurophysiological tool. It is a polysynaptic and multisegmental spinal response that produces a withdrawal of the stimulated limb and resembles (having several features in common) the hind-paw FR in animals. The FR, in both animals and humans, is mediated by a complex circuitry modulated at spinal and supraspinal level. At rest, the LLFR (usually obtained by stimulating the sural/tibial nerve and by recording from the biceps femoris/tibial anterior muscle) appears as a double burst composed of an early, inconstantly present component, called the RII reflex, and a late, larger and stable component, called the RIII reflex. Numerous studies have shown that the afferents mediating the RII reflex are conveyed by large-diameter, low-threshold, non-nociceptive A-beta fibers, and those mediating the RIII reflex by small-diameter, high-threshold nociceptive A-delta fibers. However, several afferents, including nociceptive and non-nociceptive fibers from skin and muscles, have been found to contribute to LLFR activation. Since the threshold of the RIII reflex has been shown to correspond to the pain threshold and the size of the reflex to be related to the level of pain perception, it has been suggested that the RIII reflex might constitute a useful tool to investigate pain processing at spinal and supraspinal level, pharmacological modulation and pathological pain conditions. As stated in EFNS guidelines, the RIII reflex is the most widely used of all the nociceptive reflexes, and appears to be the most reliable in the assessment of treatment efficacy. However, the RIII reflex use in the clinical evaluation of neuropathic pain is still limited. In addition to its nocifensive function, the LLFR seems to be linked to posture and locomotion. This may be explained by the fact that its neuronal circuitry, made up of a complex pool of interneurons, is interposed in motor control and, during movements, receives both peripheral afferents (flexion reflex afferents, FRAs) and descending commands, forming a multisensorial feedback mechanism and projecting the output to motoneurons. LLFR excitability, mediated by this complex circuitry, is finely modulated in a state- and phase-dependent manner, rather as we observe in the FR in animal models. Several studies have demonstrated that LLFR excitability may be influenced by numerous physiological conditions (menstrual cycle, stress, attention, sleep and so on) and pathological states (spinal lesions, spasticity, Wallenberg's syndrome, fibromyalgia, headaches and so on). Finally, the LLFR is modulated by several drugs and neurotransmitters. In summary, study of the LLFR in humans has proved to be an interesting functional window onto the spinal and supraspinal mechanisms of pain processing and onto the spinal neural control mechanisms operating during posture and locomotion.