Neuroinflammation is also emerging as an important factor in disease initiation and progression and is Significance research is underway on improving brain lymphatic drainage in neurodegenerative, neurovascular and neuroinflammatory diseases. Prog Neurobiol 2018, 163-164, 118-143, doi:10.1016/j.pneurobio.2017.08.007. 2: Chen, J., et al. (2021 The lymphatic drainage system of the CNS plays a role in lymphatic drainage, immunity, and neuroinflammation

systematic finding, we also found another regular phenomenon: a dense network of neurites that stained for neurofilament thymic epithelial cells (TEC) restricted to the corticomedullary junction of the thymus showed similar neurofilament

There's nothing quite so satisfying as reading a well written paper which summarises everything interesting that we know about the lymph system. In this regard, the recent paper by Weber et al (1) is a good read for anyone fascinated by lymphatics, regardless of academic ability. Personally I can't help but make connections with the descriptions given, and what I know about lymphatic physiology and the effects of MLD. It's also very affirming when new understandings in lymphology, support the basic tenets and mechanisms of MLD. "...the lymphatic system in health and disease has become a hot topic in vascular research." Firstly, the authors give us a summary of recent discoveries that have sparked increased interest in research on lymphatics, and describe the 'positive feedback loop' that is the chronic progression of lymphoedema. Samples of lymph collector vessels were studied to determine the histopathological changes affecting the lymph vessels in lymphoedema. There are some excellent images and descriptions showing how the vessels become fibrosed, sclerosed and eventually completely obliterated in advanced disease. The main aim of the article is to highlight the potential and considerations in surgical procedures such as lympho-venous anastomosis (LVA). However, I will review the histological results with relevance to the stage of lymphoedema and to highlight how important it is to start MLD* as soon as possible when there is lymphatic overload. Normal lymphatic anatomy In the section on normal anatomy of the lymph vessels we are given reference images of healthy lymph vessels showing the layers of endothelium and smooth muscle. I read with interest the role of mast cells in regulating lymphatic vascular function. I've always know they were involved in regulating inflammation, but I hadn't realised how closely they were located to the initial lymph vessels or the role they play in vessel permeability and contractility. Likewise I've been teaching how the vasa vasorum supply the smooth muscle in the blood vessel walls, so of course the lymphatic smooth muscle needs them too, and the paper has a great image of these lymph collector vasa vasorum. Next comes a description of the development and maintenance of valves, which fits with previous reports on the influence of lymph flow in valve formation, direction, and health. Read my previous post on lymph flow and valves. And this is where I start to connect the dots with MLD*, and why it is so very important in the early stages of lymphatic dysfunction - valve health depends on it! Shear-stress activated mechanisms are responsible for formation and maintenance of the valves and the endothelial cell junctions. So much of this tallies with our primary goal in performing MLD, which is to stimulate lymphatic pumping and increase lymph flow*. To achieve this we apply very precise stretching forces across and along the lymph collector vessels. We've always been focussed on how this affects lymph-motoricity, but it may also be beneficial in maintaining valve function and endothelial integrity in lymphatic disease. Read more posts on the importance of gentle shear forces including in tissue repair. Lymph vessel changes in lymphoedema As with the connective tissue changes, early changes in lymph vessels are happening before the lymphoedema itself becomes apparent. When the lymph pathway is obstructed by something like lymph node removal, the supplying vessels become dilated and the walls become thin and leaky. This is the stage where we have the best - and in fact any chance at all - of assisting the system to recover full function. MLD* improves lymph flow and if applied early enough can increase the formation of new lymph vessels in the damaged area. This reinforces recommendations that MLD be applied as early as possible once lymph vessels have been damaged in any way. The next stage in the damaged lymph vessels correlates to the middle stages of lymphoedema, which are typified by fat and fibre induration in the connective tissues. Similar changes occur in the vessel walls. Under a high lymph load the smooth muscle layers thicken which reduces the size of the lumen (the inside of the vessel). Normally there 1-3 layers of smooth muscle in the vessel wall, but in this intermediate stage of disease there can be up to 10 layers as the system tries to compensate for the obstruction in lymph flow. Collagen is deposited under the endothelium and in the advanced stages the vessels become sclerosed and cease to work at all. The role of MLD in lymph vessel health and recovery Can these changes in lymph vessel pathology be reversed? This paper doesn't offer any answers as to the potential for disease reversal, other than the observation that Interrupting this viscous cycle seems imperative. Clinically we know that MLD improves lymph flow*, which is essential in maintaining vessel health and at least slowing disease progression. MLD will have the best effect in the early or mild stages of disease. Since the pathological changes to the vessels and connective tissue are happing before there is any visible swelling, MLD should be applied before any obvious swelling appears. There is a small window of opportunity after surgical damage to re-establish lymph flow across the scar and MLD should be used as soon as possible to maximise this repair process. Read more on the effects of MLD. Once fibrosis and fatty changes have begun it is much more difficult to reverse these connective tissue change, so likely more difficult to reverse pathological changes in the vessels too. In the advanced stages we are left with trying to prevent progression and manage symptoms. So the main message remains the same, MLD should be applied as soon as there is any lymphatic damage, be it from lymph node removal or other surgery, radiation damage, traumatic injury or obesity (which is the fastest growing cause of lymphoedema globally). Since inflammation is both an initiator and promoter of lymph vessel disease, improving lymph flow and clearing these molecules from the tissue is still one of the best mechanism we have for slowing lymphoedema progression. I don't know of a better way to do this without drugs, than to apply MLD, which has been shown to reduce inflammation systemically*. Read more on inflammation and MLD. * Effects of MLD on lymphatic pumping apply only to the Vodder method of MLD, these effects are not shown in lymphatic effleurage techniques, read more on these differences here. 1) Elisabetta Weber MA, Eugenio Bertelli, Guido Gabriele, Paolo Gennaro, and Virginia Barone. Lymphatic Collecting Vessels in Health and Disease: A Review of Histopathological Modifications in Lymphedema. Lymphatic research and biology 2022; 20: 468-477. DOI: 10.1089/lrb.2021.0090. https://www.liebertpub.com/doi/epdf/10.1089/lrb.2021.0090 Lymphatic Collecting Vessels in Health and Disease: A Review of Histopathological Modifications in Lymphedema Abstract Secondary lymphedema of the extremities affects millions of people in the world as a common side effect of oncological treatments with heavy impact on every day life of patients and on the health care system. One of the surgical techniques for lymphedema treatment is the creation of a local connection between lymphatic vessels and veins, facilitating drainage of lymphatic fluid into the circulatory system. Successful results, however, rely on using a functional vessel for the anastomosis, and vessel function, in turn, depends on its structure. The structure of lymphatic collecting vessels changes with the progression of lymphedema. They appear initially dilated by excess interstitial fluid entered at capillary level. The number of lymphatic smooth muscle cells in their media then increases in the attempt to overcome the impaired drainage. When lymphatic muscle cells hyperplasia occurs at the expenses of the lumen, vessel patency decreases hampering lymph flow. Finally, collagen fiber accumulation leads to complete occlusion of the lumen rendering the vessel unfit to conduct lymph. Different types of vessels may coexist in the same patient but usually the distal part of the limb contains less affected vessels that are more likely to perform efficient lymphatic–venular anastomosis. Here we review the structure of the lymphatic collecting vessels in health and in lymphedema, focusing on the histopathological changes of the lymphatic vessel wall based on the observations on segments of the vessels used for lymphatic–venular anastomoses.

An area of great excitement in lymphatic research - and I think great confusion - is the ‘new discovery’ of ‘lymph vessels’ in the brain. The idea of functioning lymph vessels inside the brain is fascinating, as is every new discovery in lymphology, but the research doesn't exactly show this. The evidence for lymphatic endothelium in the dural spaces is exciting, but is it vastly different to what we have been teaching in Vodder Courses for the last 20 years? and will it change the way we perform clinically? No and no. But it does offer an opportunity to review what we know about fluid and waste removal and the passage of immune cells through the cerebral spaces. The paper that started all the hype was published in Nature in 2015 and stated that the authors had found “...... functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system.” Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523:337. Delving a little deeper into the paper we find that this work has been done in murine models (mice), not humans, so care should be taken not to immediately assume that humans will be the same. What was found are vessels in the dural spaces which appear to have the characteristics of initial lymph vessels and that these vessels are connected to lymph pathways in the deep cervical system. The endothelial cells form in tubules with a lumen but there is no smooth muscles and no valves, Image of a mouse brain showing evidence of lymphatic endothelial cells lining the dural sinuses This adds an extra layer of detail to what we already know about removal of the lymph obligatory load (LOL) from the cerebral spinal fluid (CFS). We already know that the LOL, which includes circulating immune cells and waste products such as the amyloids responsible for Alzheimer’s disease, are removed through the subarachnoid sheath via ‘arachnoid granulations’. Dyes and tracers used to image this pathway show pathways through the deep cervical lymphatics, the perineural sheaths of olfactory, optic nerves and spinal nerves and in suboccipital lymph nodes. The new findings suggest that there is a formed, lymphatic endothelium along the dural sinuses of mice, which resemble initial lymph vessels. If these vessels are also present in human they may add a connecting piece in the puzzle of how the LOL is transported from the subarachnoid sheath to the external collecting lymphatics. Does this influence the way we perform MLD for drainage of the cerebral spaces as we do after stroke etc? Not at all! Clearing proximal pathways via the cervical lymph nodes and drainage of the soft palate to clear the olfactory pathway are still the best technique to reduce cerebral oedema. New lymphatic discoveries are always welcome – and there is so much still to discover! For MLD therapists, this is one of the less startling discoveries of late, partly because it doesn’t really add anything to our clinical practice. Diagram of cerebral drainage pathways from the 1997 Textbook of Dr. Vodder’s Manual Lymph Drainage by former Vodder School Medical Director, Dr Ingrid Kurz. Volume 2: Therapy 4th Edition, Haug Publishers #MLD #braindrainage #CFS #cerebrallymphatics

Neurodegeneration and the glymphatic system. oedema, and drainage of all the deep cavities of the head using MLD is an effective way to reduce the neuro-inflammatory Read more about MLD and neuroinflammation 2. Age and stress. indicate that the Special Techniques for respiratory drainage and all those ways we have to reduce neuroinflammation

Central sympathetic neurons synapse with peripheral SNS neurons in the Sympathetic ganglia and can transfer

metabolic waste products and toxins from the brain, including those associated with dementia and other neurodegenerative can lead to reduced clearance of these toxic proteins, contributing to their buildup and subsequent neuronal Sleep disturbances, which are common in neurodegenerative diseases are a vicious cycle where impaired Understanding the role of the glymphatic system in neurodegenerative diseases opens up new avenues for But does MLD actually increase the clearance of abnormal protein aggregates in neurodegenerative diseases

We need more research on how MLD could be used in treatment or prevention of several neurological conditions

A distressing and elusive neurological disorder which causes skin changes, vascular malfunctions and particularly vulnerable to developing CRPS, but any surgery or traumatic injury can cause the persistent neurological

Neurological Problems One of the few manual treatments to directly drain the cerebral space, MLD* for

International Journal of Neuroscience, 119(8), 1105-1117. doi:10.1080/00207450902834884 Abstract This