Objective: Multiple sclerosis (MS) is characterized by demyelination centered around cerebral veins. Recent studies suggested this topographic pattern may be caused by venous congestion, a condition termed chronic cerebrospinal venous insufficiency (CCSVI). Published sonographic criteria of CCSVI include reflux in the deep cerebral veins and/or the internal jugular and vertebral veins (IJVs and VVs), stenosis of the IJVs, missing flow in IJVs and VVs, and inverse postural response of the cerebral venous drainage. Methods: We performed an extended extra- and transcranial color-coded sonography study including analysis of extracranial venous blood volume flow (BVF), cross-sectional areas, IJV flow analysis during Valsalva maneuver (VM), and CCSVI criteria. Fifty-six MS patients and 20 controls were studied. Results: Except for 1 patient, blood flow direction in the IJVs and VVs was normal in all subjects. In none of the subjects was IJV stenosis detected. IJV and VV BVF in both groups was equal in the supine body position. The decrease of total jugular BVF on turning into the upright position was less pronounced in patients (173 6 235 vs 362 6 150ml/min, p 1 criterion for CCSVI. Interpretation: Our results challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS. Future studies should elucidate the difference between patients and healthy subjects in BVF regulation. ANN NEUROL 2010;68:173–183

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.22085

No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis

Objective Medical compression stockings are a standard, non-invasive treatment option for all venous and lymphatic diseases. The aim of this consensus document is to provide up-to-date recommendations and evidence grading on the indications for treatment, based on evidence accumulated during the past decade, under the auspices of the International Compression Club. Methods A systematic literature review was conducted and, using PRISMA guidelines, 51 relevant publications were selected for an evidence-based analysis of an initial 2407 unrefined results. Key search terms included: 'acute', CEAP', 'chronic', 'compression stockings', 'compression therapy', 'lymph', 'lymphatic disease', 'vein' and 'venous disease'. Evidence extracted from the publications was graded initially by the panel members individually and then refined at the consensus meeting. Results Based on the current evidence, 25 recommendations for chronic and acute venous disorders were made. Of these, 24 recommendations were graded as: Grade 1A (n = 4), 1B (n = 13), 1C (n = 2), 2B (n = 4) and 2C (n = 1). The panel members found moderately robust evidence for medical compression stockings in patients with venous symptoms and prevention and treatment of venous oedema. Robust evidence was found for prevention and treatment of venous leg ulcers. Recommendations for stocking-use after great saphenous vein interventions were limited to the first post-interventional week. No randomised clinical trials are available that document a prophylactic effect of medical compression stockings on the progression of chronic venous disease (CVD). In acute deep vein thrombosis, immediate compression is recommended to reduce pain and swelling. Despite conflicting results from a recent study to prevent post-thrombotic syndrome, medical compression stockings are still recommended. In thromboprophylaxis, the role of stockings in addition to anticoagulation is limited. For the maintenance phase of lymphoedema management, compression stockings are the most important intervention. Conclusion The beneficial value of applying compression stockings in the treatment of venous and lymphatic disease is supported by this document, with 19/25 recommendations rated as Grade 1 evidence. For recommendations rated with Grade 2 level of evidence, further studies are needed.

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Indications for medical compression stockings in venous and lymphatic disorders: An evidence-based consensus statement:

Arterio-venous malformations (AVMs) are congenital vascular malformations (CVMs) that result from birth defects involving the vessels of both arterial and venous origins, resulting in direct communications between the different size vessels or a meshwork of primitive reticular networks of dysplastic minute vessels which have failed to mature to become 'capillary' vessels termed "nidus". These lesions are defined by shunting of high velocity, low resistance flow from the arterial vasculature into the venous system in a variety of fistulous conditions. A systematic classification system developed by various groups of experts (Hamburg classification, ISSVA classification, Schobinger classification, angiographic classification of AVMs,) has resulted in a better understanding of the biology and natural history of these lesions and improved management of CVMs and AVMs. The Hamburg classification, based on the embryological differentiation between extratruncular and truncular type of lesions, allows the determination of the potential of progression and recurrence of these lesions. The majority of all AVMs are extra-truncular lesions with persistent proliferative potential, whereas truncular AVM lesions are exceedingly rare. Regardless of the type, AV shunting may ultimately result in significant anatomical, pathophysiological and hemodynamic consequences. Therefore, despite their relative rarity (10-20% of all CVMs), AVMs remain the most challenging and potentially limb or life-threatening form of vascular anomalies. The initial diagnosis and assessment may be facilitated by non- to minimally invasive investigations such as duplex ultrasound, magnetic resonance imaging (MRI), MR angiography (MRA), computerized tomography (CT) and CT angiography (CTA). Arteriography remains the diagnostic gold standard, and is required for planning subsequent treatment. A multidisciplinary team approach should be utilized to integrate surgical and non-surgical interventions for optimum care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management.

Lymphoedema is a problem frequently encountered by professionals working in palliative care. This article reviews the evidence on the magnitude of the problem of lymphoedema in the general population and provides evidence on specific high risk groups within it. Prevalence is a good indicator of the burden of disease for chronic problems such as lymphoedema, as it indicates the numbers of patients who require care. Incidence is indicative of changes in the causes of lymphoedema and the success of any prevention programmes. Both are important means of assessing the current level of need and the potential for the changing needs in managing this condition. Problems exist in all studies in relation to precise definitions of lymphoedema, inconsistent measures to assess differential diagnosis and poorly defined populations. While there is some evidence of high rates in relation to breast cancer therapy, the total burden of lymphoedema in the general population is largely unknown.

Lymphoedema: estimating the size of the problem

We analyzed clinicopathologic and imaging features of chronic peripheral lymphedema to identify imaging findings indicative of its exact etiopathogenesis and to establish the optimal treatment strategy. One of the main problems of microsurgery for lymphedema is the discrepancy between the excellent technical possibilities and the subsequently insufficient reduction of the lymphedematous tissue fibrosis and sclerosis. Appropriate treatment based on pathologic studies and surgical outcome have not been adequately documented. Over the past 25 years, 676 patients with peripheral lymphedema have been treated with microsurgical lymphatic-venous anastomoses. Of these patients, 447 (66%) were available for long-term follow-up study. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Objectively, volume changes showed a significant improvement in 561 patients (83%), with an average reduction of 67% of the excess volume. Of the 447 patients followed, 380 (85%) have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was an 87% reduction in the incidence of cellulitis after microsurgery. Microsurgical lymphatic-venous anastomoses have a place in the treatment of peripheral lymphedema and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. Improved results can be expected with operations performed early, during the first stages of lymphedema.

Microsurgical techniques for lymphedema treatment: derivative lymphatic-venous microsurgery.

Correlates of the Ultrasonographic and Elastosonographic Parameters of the Plantar Fascia in Patients with Type 2 Diabetes

Summary A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Indeed, selecting an inappropriate study type, an error that cannot be corrected after the beginning of a study, results in flawed methodology. The results of clinical research studies enhance the repertoire of knowledge regarding a disease pathogenicity, an existing or newly discovered medication, surgical or diagnostic procedure or medical device. Medical research can be divided into primary and secondary research, where primary research involves conducting studies and collecting raw data, which is then analysed and evaluated in secondary research. The successful deployment of clinical research methodology depends upon several factors. These include the type of study, the objectives, the population, study design, methodology/techniques and the sampling and statistical procedures used. Among the different types of clinical studies, we can recognize descriptive or analytical studies, which can be further categorized in observational and experimental. Finally, also pre-clinical studies are of outmost importance, representing the steppingstone of clinical trials. It is therefore important to understand the types of method for clinical research. Thus, this review focused on various aspects of the methodology and describes the crucial steps of the conceptual and executive stages.

Methodology for clinical research

Summary Lymphedema is a chronic inflammatory disorder resulting from ineffective fluid uptake by the lymphatic system, and the effects are principally felt in the lower limbs. The condition is said to be primary when caused by genetic mutations and secondary when caused by injuries, infections, or surgery. Lymphedema, a worldwide pathology, does not have an effective therapy so far. Leukotriene B4 has recently been identified as a key molecule in lymphedema pathogenesis. Surgical, nonsurgical, and pharmacological treatments have been proposed; however, they do not cure the disease and only ameliorate the symptoms. Nutrition and nutritional status are extremely important in lymphedema physiopathology. Obesity is a comorbidity that exacerbates the risk for secondary lymphedema and constitutes a negative prognostic factor. Indeed, anti-inflammatory foods and their effects on the inflammatory state and on oxidative stress are now being investigated for their possible therapeutic role in lymphedema. Although no special diet has so far been proven to be very effective, specific dietary tips could help in alleviating the edematous state of patients with lymphedema. A few supplements have been tested for lymphedema treatment. Among them, GARLIVE® containing hydroxytyrosol, hesperidin, spermidine and vitamin A, exhibited promising effects in the animal model. Hydroxytyrosol, a polyphenol from olives, showed anti-inflammatory effects and reduced leukotriene B4 synthesis, thus holding promise as a potential natural candidate for lymphedema treatment.

S Michelini

Papers

Correlates of the Ultrasonographic and Elastosonographic Parameters of the Plantar Fascia in Patients with Type 2 Diabetes

Methodology for clinical research

Dietary supplements in lymphedema