Compartments of the crural fascia: clinically relevant ultrasound, anatomical and histological findings.

PURPOSE: Compartment syndrome is a surgical emergency that can occur in any part of the body and can cause cell necrosis when maintained over time. The resulting defects can affect the nerves, muscle cells, bone tissue, and other connective tissues inside the compartment, and fasciotomy has to be performed. The anatomical and histological characteristics of the leg make acute, chronic, and exertional compartment syndrome more likely in this limb. For these reasons, knowledge of the ultrasound, anatomical, and histological features of the crural fascia can help in the treatment of leg compartment syndrome. METHODS: Twenty-one cryopreserved lower limbs from adult cadavers and from one 29-week-old fetus were obtained from the dissection room. They were examined by ultrasound and a subsequent anatomical dissection and microscopy to study the crural fascia and its relationship with the different muscles. Anthropometric measurements were taken of the distances from the head of the fibula and lateral malleolus to the origin of the tibialis anterior muscle in the crural fascia, the exit of the superficial fibular nerve, and the fascia covering the deep posterior muscles of the leg. RESULTS: The crural fascia has very important clinical relationships, which can be identified by ultrasound, as the origin of the tibialis anterior muscle at 16.25 cm from the head of the fibula and the exit of the superficial fibular nerve that crosses this fascia at 21.25 cm from the head of the fibula. Furthermore, the presence of a septum that fixes the deep posterior muscles of the leg and the vessels and nerve can be seen by ultrasound and can explain the possible development of a posterior compartmental syndrome of the leg. Awareness of these features will help to keep these structures safe during the surgical treatment of compartment syndrome. CONCLUSION: The ultrasound study allows identification of anatomical structures in the leg and, thus, avoids damage to them during surgery for compartmental syndromes.

Compartments of the antebrachial fascia of the forearm: clinically relevant ultrasound, anatomical and histological findings.

PURPOSE: Acute compartment syndrome is defined as a limb-threatening condition caused by bleeding or oedema in a closed muscle compartment surrounded by fascia or bone. It is most commonly encountered in the forearm, which has three compartments: posterior, anterior and lateral. These are surrounded and closed in by the antebrachial fascia, formed by dense connective tissue that facilities their study on ultrasound and is key to fasciotomy treatment. The purpose of this study was to broaden existing ultrasound, anatomical and histological knowledge of the fascia of the forearm to facilitate their identification on ultrasound, with possible clinical and therapeutic applications. METHODS: The study was performed in 50 cryopreserved upper limbs from adult cadavers from the dissection room of the Faculty of Medicine and Health Sciences. They were examined on ultrasound and subsequent anatomical dissection and microscopy to study the fascia and its relationship with different muscles of the forearm compartments. RESULTS: Distinct anatomical relationships were observed on ultrasound and dissection between the fascia and the extensor carpi ulnaris, extensor digiti minimi, and anconeus muscle in the posterior compartment, and the flexor carpi radialis and flexor carpi ulnaris in the anterior compartment. They were isolated by the antebrachial fascia and had distinct relationships with the neurovascular structures. CONCLUSION: These results demonstrate that high-definition ultrasound enables us to locate the antebrachial fascia and particular muscles with a distinct relationship with neurovascular structures. This helps better identify these structures, facilitating diagnosis of any pathology in the area, with potential therapeutic and clinical applications.

Don't forget the jumper's knee in the young sportsman: evaluation of patellar tendinopathy with a high frequency ultrasound probe.

Patellar tendinopathy, or Jumper's knee, is a painful knee condition caused by inflammation of the patella tendon. This condition is most frequently observed in subjects who play sports that require repetitive regular jumping. Jumper's knee is frequently misdiagnosed as a minor injury and many athletes, like our patient, keep on training and competing and either tend to ignore the injury or attempt to treat it themselves. However, jumper's knee is a serious condition that requires a correct and timely diagnosis, which often necessitates ultrasound investigation in order to start the most appropriate treatment.

Joint disease in haemophilia: Pathophysiology, pain and imaging.

Haemarthroses cause major morbidity in patients with haemophilia. Blood has devastating effects on all joint components, resulting in synovitis, osteochondral degeneration and ultimately end-stage haemophilic arthropathy. Key players in this process are iron and inflammation. Preventing joint bleeds is of utmost importance to maintain joint health as targeted therapies directed against blood-induced inflammation and iron-mediated processes are lacking. Joint bleeds result in acute pain as well as chronic pain due to synovitis or arthropathy. Acute pain originates from nociceptors activated by tissue damage. In chronic inflammation, central and peripheral sensitization of nociceptors might occur resulting in chronic pain. This also triggers a series of brain disorders such as emotional fear, anxiety, mood depression and impairment of cognitive functions. Treatment of haemophilia-related pain not only consists of analgesics, but also of exercise, education and in selected cases antidepressants and anticonvulsants. For objective assessment of joint structural outcome and detecting earlier changes of haemophilic arthropathy, both ultrasound (US) and magnetic resonance (MR) imaging have shown valuable. Both can be considered equally able to reveal signs of disease activity. MR imaging is able to visualize haemosiderin deposition and is more comprehensive in depicting osteochondral changes. Disadvantages of MR imaging are the duration of the examination, evaluation of a single joint at a time, costs and may require sedation, and it may need intraarticular contrast injection to depict initial osteochondral changes with accuracy. As such, US is a more useful screening tool and can be used for repeated follow-up examinations.

Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab.

BACKGROUND: Clinical responses to ipilimumab are variable in terms of onset, magnitude and duration. Upfront identification of patients who are more likely or unlikely to benefit from treatment is a major need. PATIENTS AND METHODS: Prospectively collected data from 720 advanced melanoma patients treated with ipilimumab 3 mg/kg within the Italian expanded access program were analyzed. The derived neutrophil-to-lymphocyte ratio (dNLR) was calculated from baseline peripheral blood cell counts, and receiver operating characteristic curve was used to evaluate the best cutoff for this marker. Patients were stratified according to dichotomized baseline absolute neutrophil counts (ANC), dNLR and their combination. The prognostic values of ANC and dNLR for survival were assessed using multivariate Cox proportional hazard models. A subgroup analysis including LDH in the models was also carried out. RESULTS: The median follow-up was 16.5 months. The optimal cutoff for dNLR was 3. Baseline ANC and dNLR were significantly associated with the outcome of ipilimumab-treated melanoma patients, in terms of disease progression and death (P < 0.0001 for all). Furthermore, for each elevated variable, prognosis worsened. Patients with both ANC ≥ 7500 and dNLR ≥ 3 had a significantly and independently increased risk of death [hazard ratio(HR) = 5.76; 95% confidence interval (CI) 4.29-7.75] and of progression (HR = 4.10; 95% CI 3.08-5.46) compared with patients with both lower ANC and dNLR. Patients with one of the two factors elevated displayed an intermediate risk of progression and death. The 1- and 2-year survival rates were 2% and 0%, respectively, for patients with ANC ≥ 7500 and dNLR ≥ 3, and 43% and 24%, respectively, for patients with both lower ANC and dNLR. CONCLUSIONS: Although these findings need to be confirmed and validated, we suggest that a neutrophil-based index may help risk-group stratification and assist disease-management strategies. Furthermore, the potential predictive value of this index for response to ipilimumab should be investigated in randomized clinical trials.

Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients.

BACKGROUND: Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit. METHODS: A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg(-1) ipilimumab, and 27 patients treated with 10 mg kg(-1) ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors. RESULTS: In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22-0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13-0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients. CONCLUSION: Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.

Sonoelastographic Findings of Carpal Tunnel Injection.

PURPOSE: The objectives of this study were to compare sonoelastographic color findings of the perineural area between carpal tunnel syndrome patients and healthy volunteers, and to analyze elastographic findings in that area before and immediately after intracarpal tunnel injection in carpal tunnel syndrome patients. MATERIALS AND METHODS: We studied both hands of 15 healthy volunteers (7 men, 8 women; mean age: 60.1 years, range: 41 - 88 years) and 72 hands from 70 patients with symptomatic carpal tunnel syndrome (24 men, 46 women; mean age: 54.2 years, range: 24 - 83 years). Sonoelastographic color distribution was assessed in the perineural area between the median nerve and adjacent flexor tendons. The color elastograms were graded using the following system: Grade 1 as red (softest), grade 2 as yellow (soft), grade 3 as green (hard), grade 4 as blue (hardest). The patients were treated with corticosteroid injection and were reassessed with sonoelastography immediately after the injection. RESULTS: The median color grading in the perineural area of carpal tunnel syndrome patients was grade 3 (3.1 ±â€Š0.3, mean ±â€Š95 % Cl), which was stiffer than that of healthy volunteers (grade 1, 1.9 ±â€Š0.4) (p < 0.0001). Immediately after injection, the diffusion of the injected fluid was observed as having a softer appearance (grade 1, 1.4 ±â€Š0.2) (p < 0.0001). CONCLUSION: The perineural area surrounding the median nerve in carpal tunnel syndrome patients was stiffer than that in healthy volunteers. Diffusion of the injected fluid in the carpal tunnel was seen as a softer finding after injection in real time using sonoelastography.

Managing haemophilia for life: 4th Haemophilia Global Summit.

The 4th Haemophilia Global Summit was held in Potsdam, Germany, in September 2013 and brought together an international faculty of haemophilia experts and delegates from multidisciplinary backgrounds. The programme was designed by an independent Scientific Steering Committee of haemophilia experts and explored global perspectives in haemophilia care, discussing practical approaches to the optimal management of haemophilia now and in the future. The topics outlined in this supplement were selected by the Scientific Steering Committee for their relevance and potential to influence haemophilia care globally. In this supplement from the meeting, Jan Astermark reviews current understanding of risk factors for the development of inhibitory antibodies and discusses whether this risk can be modulated and minimized. Factors key to the improvement of joint health in people with haemophilia are explored, with Carlo Martinoli and Víctor Jiménez-Yuste discussing the utility of ultrasound for the early detection of haemophilic arthropathy. Other aspects of care necessary for the prevention and management of joint disease in people with haemophilia are outlined by Thomas Hilberg and Sébastian Lobet, who highlight the therapeutic benefits of physiotherapy and sports therapy. Riitta Lassila and Carlo-Federico Perno describe current knowledge surrounding the risk of transmission of infectious agents via clotting factor concentrates. Finally, different types of extended half-life technology are evaluated by Mike Laffan, with a focus on the practicalities and challenges associated with these products.

Contribution of ultrasound in the assessment of nerve diseases.

BACKGROUND AND PURPOSE: Recently, ultrasound (US) has been used to assess the peripheral nervous system; however, there is no real study about its possible significant role in routine practice. Our study aims to assess the contribution of US as a routine tool in a neurophysiological laboratory. METHODS: The study assesses 130 patients who presented clinical suspicion of peripheral nerve diseases, excluding motor neuron disease, radiculopathy, hereditary and acquired polyneuropathy. All patients were clinically, neurophysiologically and sonographically assessed in the same session by the same neurologist/neurophysiologist. To avoid interpretation bias, two independent and blinded clinicians, different than the examiners performing electrodiagnosis and US, reviewed clinical, neurophysiological and US findings (also data about follow-up, when available) and classified the contribution of US as follows: Contributive (US had influence on the diagnostic and therapeutic strategies), Confirming (US confirmed the clinical and neurophysiological diagnosis), Non-Confirming (US findings were normal) and Incorrect (US findings led to incorrect diagnosis). RESULTS: US impacted, namely modified the diagnostic and therapeutic path in 42.3% of cases (55 patients); US had a confirmatory role in 40% (52 patients); US did not confirm clinical and neurophysiological diagnosis in 17.7% (23 cases); no incorrect US findings were observed. CONCLUSION: US complements neurophysiological assessment even in routine practice, and this confirms the increasing interest in US for a multidimensional evaluation of peripheral nerve system diseases.

Musculoskeletal complications of acromegaly: what radiologists should know about early manifestations.

The purpose of this article is to summarise the early musculoskeletal complications of acromegaly. Some of the early signs of acromegaly may be evaluated by the musculoskeletal radiologist. In the early stage of disease, peripheral nerve enlargement associated with carpal tunnel syndrome or cubital tunnel syndrome and thickening of retinacula, such as A1 pulley in trigger finger, represent the features that may be seen by radiologists and are worthy of an endocrinological evaluation. Due to the insidious nature of the disease, the diagnosis of acromegaly is significantly delayed. Few and nonspecific symptoms characterise the initial phases of the disease, and therefore, most patients will have generally consulted many specialists (most frequently musculoskeletal radiologists) before an adequate endocrinological assessment is performed. For this reason, initial clinical signs are much more important than symptoms for an early diagnosis of acromegaly. The first and most important therapeutic approach to acromegaly is early diagnosis, whereas the therapeutic goals are to eliminate morbidity and reduce mortality to the expected age- and sex-adjusted rates and prevent the development of systemic complications. Musculoskeletal radiologists should be aware that these features may be early manifestations of acromegaly. When both radiological and clinical abnormalities are present, an endocrinological workup is useful to diagnose the disease in an early phase.

A reappraisal of intra-articular corticosteroid therapy in juvenile idiopathic arthritis.

Intraarticular corticosteroid (IAC) injection is a safe and rapidly effective treatment for synovitis in children with juvenile idiopathic arthritis (JIA). This procedure can be performed in an ambulatory care setting using local anaesthesia, with or without conscious sedation. Younger children, or those candidate to multiple injections, require general anaesthesia. Triamcinolone hexacetonide is the optimal corticosteroid preparation. However, for smaller joints or joints that are not easy to assess clinically, use of a more soluble corticosteroid drug is advised. Imaging guidance may facilitate accurate placement of the needle within the joint space. Use of ultrasound for this purpose has gained increasing popularity in the recent years. IAC injections are used most frequently to treat oligoarthritis, but the strategy of performing multiple IAC injections to induce disease remission, while simultaneously initiating therapy with second-line or biologic agents, has been proposed also for children with polyarticular JIA. However, the current place of IAC therapy in the management of children with JIA is uncertain due to the lack of controlled studies. Furthermore, it is still unknown whether this therapy has a disease-modifying effect over the long-term. This review summarises the present information about the use of IAC therapy in children with JIA.

Endoneural abscess of common popliteal nerve as first clinical manifestation of leprosy: the first reported case in history in a low-incidence country.

A migrant from Palestine came to our attention for weakness of dorsiflexion of the left foot and hypoesthesia of the homolateral common peroneal nerve territory. Skin biopsies from skin lesions in the hypoesthetic area were not diagnostic. Radiological investigation showed focal nerve enlargement with a possible focal lesion. At this time, and given the uncertainty of the diagnosis, we had to choose between medical therapy with steroid and a surgical exploration of the nerve. We decided for the latter option. Intraoperatively, we found a focal round enlargement of the nerve. Epineurotomy was performed at that level, revealing a round caseous granulomatous mass that was excised. Microbiological examination revealed presence of Mycobacterium Leprae allowing diagnosis of leprosy. Medical therapy was then started, leading to resolution of clinical symptoms. Endoneural lepromatous abscesses are uncommon lesions that should be suspected in patients presenting with peripheral nerve dysfunction with anamnesis of travel in leprosy endemic regions or contacts with people from endemic regions with or even without skin lesions. Detection of endoneural abscesses is of critical importance because prompt surgical excision in conjunction with medical therapy leads to improvement of symptoms and permits correct diagnosis. In times of large human migrations from leprosy endemic areas, knowledge of this uncommon presentation of leprosy and its management will help lead to the best management of these patients.

Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with outcome of patients treated with BRAF inhibitors.

PURPOSE: The aim of this study is to verify if baseline hematological markers, in patients with advanced melanoma receiving BRAF inhibitor (BRAFi)-based therapies, are independently associated with progression free survival (PFS) and overall survival (OS). METHODS: We retrospectively analyzed 90 patients with metastatic melanoma harboring BRAF V600 mutation, who received treatment with either BRAFi alone or combined with a MEK inhibitor (MEKi) at the recommended dosages. Study population included 28 women and 62 men. Median age was 53 years. Seventy-three (82%) patients presented with M1c disease, 49 (56%) had elevated LDH and 54 (60%) had three or more metastatic sites. RESULTS: The median PFS was 9.1 and 3.5 months, respectively, for patients with baseline NLR < 5 and NLR ≥ 5, while median OS was 17.2 and 5.5 months, respectively, for patients with NLR < 5 and NLR ≥ 5. Multivariate analysis confirmed that baseline NLR < 5 was significantly associated with half risk of relapse (HR = 0.49; 95% CI = 0.28-0.85; p = 0.01) and half risk of death (HR = 0.46; 95% CI = 0.23-0.76; p = 0.004), independent of age, sex, stage, LDH > 2xULN, previous treatments, concomitant use of steroids and type of therapy. In patients with LDH ≥ ULN, NLR < 5 remained significantly and independently associated with improved PFS (HR = 0.28; 95% CI = 0.13-0.62; p = 0.002,) and OS (HR = 0.23; 95% CI = 0.10-0.55; p = 0.001). CONCLUSIONS: These biomarkers are easily reproducible, affordable and costless and NLR could help to identify patients who have the best benefit from BRAF inhibitors.

Anatomical causes of compression of the sciatic nerve in the pelvis. Piriform syndrome. / Causas anatómicas de compresión del nervio ciático en la pelvis. Síndrome piriforme.

OBJECTIVE: The piriformis syndrome is one of the etiologies of pelvic pain due to the sciatic nerve's entrapment by the piriformis muscle. Nowadays this syndrome might be difficult to be diagnosed. The aim of this study is to know the prevalence of anatomic variations in our population that may contribute to the appearance of piriformis syndrome. Furthermore, anthropometric measurements of the piriformis muscle and the sciatic nerve procedures are studied for a possible application in the gluteal region. MATERIAL AND METHOD: The study was carried out in 59 pelvis of 32 cryopreserved bodies. The anatomical variations of piriformis and sciatic nerve founded were described following the Beaton and Anson's classification. Anthropometric measurements of both structures with reference to the greater trochanter of the femur were performed. RESULTS: The sciatic nerve and the piriformis had an anatomical variation in a 28.13%. The most frequent variation found was tipus II (21.64%) and tipus III (6.49%).Insertion most frequently observed was an independent piriformis tendon inserted into the trochanteric fossa with 53.85%. CONCLUSION: The anatomic variations' incidence in the population studied indicates that those have to be evaluated as a differential diagnosis of gluteal region pain due to the symptoms and signs resemblance with the vertebral disc pathology involving nerve root injury. In addition, anatomical knowledge of this region can be useful for the interpretation of imaging techniques, especially when ultrasound-guided injections are performed.

Carpal tunnel syndrome: ultrasound, neurophysiology, clinical and patient-oriented assessment.

OBJECTIVE: The aim of this study is twofold. First, to assess the relationships between the cross-sectional area (CSA) of the median nerve (MN) calculated at ultrasound (US) and: (1) patient's perception of his/her symptoms and hand function; (2) clinical severity of CTS; (3) neurophysiological classification; (4) hand distribution of symptoms. Second, to assess the sensitivity of ultrasonography (US) and neurophysiology in the diagnosis of CTS using clinical measures as gold standard. METHODS: We performed a prospective study by using multidimensional assessment: clinical (Historic and Objective scale, Hi-Ob), neurophysiological, patient-oriented measures (Boston Carpal Tunnel Questionnaire, BCTQ) and high-resolution US. The dominant hands of 54 consecutive patients who were referred to our neurophysiologic laboratory with clinical signs of CTS (43 females, mean age 53.3, range 30-80, SD: 13.1) were examined. RESULTS: A statistically significant correlation was found between the CSA of the MN at wrist and (1) hand function (according to BCTQ, r=0.35, p=0.01), (2) clinical scale (Hi-Ob scale, r=0.51, p<0.00007), (3) neurophysiologic classification (r=0.80, p<0.0000001), and (4) hand distribution of symptoms (p=0.017). Neurophysiology showed higher sensitivity than US but in one of 3 cases with normal neurophysiological results, US showed data suggestive of CTS. CONCLUSIONS: A positive correlation exists between US findings and all the conventional measures of CTS severity. The sensitivity of the combination of US and neurophysiology is higher than the sensitivity of neurophysiology or US alone. US is a useful complementary tool for CTS assessment. SIGNIFICANCE: Information on the contribution of US in CTS and the interpretation of severity measurements in CTS.

Contribution of ultrasound in a neurophysiological lab in diagnosing nerve impairment: A one-year systematic assessment.

OBJECTIVE: To evaluate the usefulness of a combination of electromyography (EMG) and ultrasound (US) assessments in diagnosing nerve trunk involvement. We hypothesised that in some cases, when the clinical or neurophysiological picture is unclear, the simultaneous study of the peripheral nervous system through both US and EMG may provide pathologic information not obtainable through EMG alone, and this may influence therapeutic decisions. METHODS: In 2005, we performed a prospective study in 77 consecutive patients with involvement of a single nerve trunk, using a combination of EMG and US in the same session. We divided the diagnostic contribution of US into four categories: diagnostic, confirming, inconclusive and misdiagnostic. RESULTS: In about a quarter of the patients, US provided results confirming the clinical neurophysiological diagnosis. In another quarter of the cases, US was very helpful in modifying diagnosis and therapy. In most of these cases, the contribution of US was important for the detection of tumors or cysts, thus showing the cause of nerve involvement. In half of the cases the US results were inconclusive, and in one case US was misdiagnostic. CONCLUSIONS: The combination of EMG and US performed in the same session (or in collaboration with an ultrasound examiner) may be useful for diagnosis and determination of appropriate therapy. SIGNIFICANCE: Diagnosis of mononeuropathies is improved through a combined functional and morphological evaluation of the nerve by using EMG and US.

Dabrafenib in metastatic melanoma: a monocentric 'real life' experience.

Dabrafenib is a potent BRAF-kinase inhibitor. Its activity was evaluated on 40 consecutive metastatic melanoma patients (pts) harboring the V600BRAF mutations. Dabrafenib was administered orally at the dosage of 150 mg b.i.d. daily. ORR was 82%, with 7% CR, 62% PR, 13% SD and 18% PD. The median PFS and OS were seven and 17 months, respectively (median follow-up: 8.5 months). Increased risk of progression was found in pts with elevated LDH, ECOG PS >1 and more than two metastatic sites. Grade 3-4 adverse events were recorded in 4 pts. In this retrospective analysis, Dabrafenib confirmed its role as the standard clinical option in metastatic melanoma pts.