Lymphedema Therapy Source

  

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Can MLD Slow Cognitive Decline? (Part 2)

Last month we learned the brain has lymphatic vessels in the outer meningeal layer (the dura mater). Fluid inside the brain (cerebral spinal fluid) mixes with interstitial fluid in the innermost meningeal layer (the pia mater) before draining to the outer dura mater & its lymphatic vessels. When things go awry, dementia enters the picture. How does this occur?

The Glymphatic System

Along the blood vessels in the brain are cells called astrocytes. Astrocytes are a type of glial cell (a specialized WBC that are helpers or support cells for neurons & coat neurons with myelin).1 They come from monocytes & reside in the CNS.

Astrocytes & microglial cells (another type of glial cell in the CNS) aid in nutrition, but they also help with immunity, waste clearance & maintaining homeostasis (just like the lymph system does). The perivascular channels containing these cells were named the “glymphatic system” because of their similarity to lymphatic system function.2,3,4

perivascular channels

The Cause of Dementia & Other Neurological Conditions

Previously, amyloid plaques were thought to be the cause of Alzheimer’s. Instead, they’re likely a by-product of the glymphatic system drainage disruption. More recent research is finding impairment in the glymphatic drainage is the likely cause of many neurological conditions, including dementia & Alzheimer’s (a form of dementia), by allowing a buildup of harmful waste to occur in the brain.  There seem to be two primary culprits.

The Culprits

One culprit is faulty clearance of the fibrillar form of the beta-amyloid protein (an imbalance in the production & clearing of the peptide that comes from the processed amyloid protein, in particular).5,6 Another culprit is faulty clearance of the phosphorylated tau protein.7,8

The Stars of the CNS

Glial cells found in the brain (astrocytes, oligodendrocytes & microglia) can be considered the stars of the CNS because of their important role in preventing inflammation & their job of coating neurons with myelin.9 Myelin is the fatty sheath that surrounds & protects nerve fibers. It allows nerve impulses to travel quickly & efficiently.

diagram showing myelin sheath

Brain inflammation (such as faulty clearance of substances mentioned above) causes this myelin sheath to break down, leading to the symptoms experienced in neurological diseases.10 How could MLD help? Find out in part 3.

References
1 https://my.clevelandclinic.org/health/body/23273-autonomic-nervous-system
2 https://www.nih.gov/news-events/nih-research-matters/new-brain-cleaning-system-discovered
3 https://www.researchgate.net/figure/Outline-of-the-glymphatic-system-This-figure-illustrates-that-perivascular-clearance_fig1_322688508
4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636982/#:~:text=The%20glymphatic%20system%20is%20a,from%20the%20
central%20nervous%20system
5 https://www.medicalnewstoday.com/articles/if-amyloid-accumulation-is-part-of-normal-aging-what-causes-alzheimers#:~:text=The%20researchers%20showed%20that%20the,journal%20of%20the%20Alzheimer’s%20Association
6 https://www.ncbi.nlm.nih.gov/books/NBK459119/
7 Garland EF, Hartnell IJ, Boche D. Microglia and Astrocyte Function and Communication: What Do We Know in Humans?. Front Neurosci. 2022;16:824888. Published 2022 Feb 16. doi:10.3389/fnins.2022.824888 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888691/)
8 https://www.nih.gov/news-events/nih-research-matters/lymphatic-vessels-discovered-central-nervous-system#:~:text=The%20lymphatic%20system%20carries%20white,was%20termed%20the%20glymphatic%20system
9 https://my.clevelandclinic.org/health/body/23273-autonomic-nervous-system
10 https://my.clevelandclinic.org/health/body/22974-myelin-sheath

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Why Would Treatment Not Work (Part 2)

Reason 2 – Inadequate Treatment

In part 1, we looked at one reason CDT may not work. In part 2, we’ll look at the important components of lymphedema treatment.

Complete Decongestive Therapy (CDT) involves (4) pillars of treatment:

1. Manual lymph drainage (MLD)
2. Multilayer compression bandaging
3. Skin Care
4. Exercise

If one of these is lacking (particularly 1, 2 & 4), a patient will not maximize their potential. Let’s look at each of these individually.

Manual Lymph Drainage

The purpose of MLD is to remove the protein in the interstitial tissue space. (The protein accumulation is due to damage of the lymphatic system – from a birth defect or a secondary cause.) Bandaging without MLD might squeeze the “water” from the tissue space, but it won’t remove the protein (neither will diuretics). That’s a specific function of MLD. And if protein attracts water, what will the result be? More swelling.

I’ve recently read & heard that there isn’t proof that MLD works. But there is research to back the efficacy of MLD.

  • In a 2017 study published in the Lymphatic Research and Biology Journal, near-infrared imaging was used to track a dye (indocyanine green) in nine healthy participants before & after a 15-minute period of MLD followed by a compression garment for 10 minutes applied to the arm. Images were taken at the forearm & elbow. There was a statistically significant improvement in the movement of lymph fluid & the speed of transport. At baseline, lymph transport speed was 6.7 millimeters per second (mm/s). This increased to 13.3 mm/s after MLD! Speed increased by 10.5 mm/s after use of a compression garment.3
  • Another study published in 2011 also used near-infrared imaging to assess the speed of lymph contractile function before & after MLD. Results showed lymph transport speed increased by 23% in symptomatic limbs (ones with lymphedema) & 25% in asymptomatic limbs (ones without lymphedema).4

Characteristics of MLD include a gentle, 2-way stretch of the skin (approximately 1 stretch per second8) that create a “pulling & shear force.”12 If too much pressure is applied, anchoring filaments of the initial lymphatic vessels close to the skin’s surface may be damaged. If MLD strokes are performed too fast or too firm, lymphangions may spasm.8  Frequency of MLD should be daily in Phase I (the decongestion phase).1 If MLD is not administered correctly or with less frequency than recommended, results will show it.

Multilayer compression bandaging

Compression is an essential part of CDT. According to Foldi’s Textbook,1 a study from the European Journal of Cancer assessed the outcome of MLD in breast cancer-related lymphedema. The study found that MLD reduces limb volume & dermal (skin) thickness in the upper arm.5 In contrast, the 9th edition of the Munich Cancer Center manual reported a deterioration in arms of women with lymphedema who received lymph drainage but did not wear compression sleeves.

The International Lymphoedema Framework publishes a best practice guideline for compression.6 The upper body guideline states, “The application of a compression garment results in constant pressure on the skin when the limb is at rest (resting pressure). When the muscles contract, expand and then relax (e.g. during exercise), they transiently press against the resisting garment and so the tissue pressure in the limb increases temporarily.” This pressure increase “compresses the adjacent dermal lymphatics and because the collecting and larger lymphatics are valved, these vessels pump passively so that lymph flows up the arm without the lymphatics having to contract.” In other words, the resistance provided by compression increases tissue pressure &, as a result, lymph movement.

Other benefits of compression include softening of fibrotic tissue & improving the venous pump function.10 Foldi states, “In lymphedema, one should always use the maximum compression that is tolerated by the patient.”7 (A 2016 study found 84 mmHg compression stopped lymphatic flow.8 This is extremely high pressure. Compression seldom goes above ~46 mmHg in lymphedema garments & limb size should be considered. Smaller circumferences like fingers & arms will not tolerate the same compression that legs might.)

Compression is an important component of CDT. If it is lacking in the treatment phase or maintenance phase, there will not be sufficient volume reduction or containment. If compression bandages are removed between sessions, refilling will occur. And if bandages are not applied correctly, there can be adverse consequences such as increased swelling or pressure wounds.

Skin Care

Good hygiene & using acidic products more like the skin’s natural pH level will reduce itching & improve skin texture. These will also help mitigate potential infections due to a compromised skin barrier.

Exercise

When the body is at rest, only a minor amount of lymph is formed.12 Movement is key to lymph creation. Exercise engages the muscle pump. Singing, deep breathing & laughing are excellent ways to engage the diaphragm & compress the most important lymph vessel in the body (the thoracic duct).11 Exercising with compression increases tissue pressure (& so lymph movement) & softens fibrosis in extremities (helping to reduce volume).

In summary, all aspects of CDT are important components. If one is overlooked or administered inadequately, CDT may fail at worst or results may be subpar at best.

References
1 Foldi, M, Foldi, E. (2006). Foldi’s Textbook of Lymphology (2nd ed.), p. 272. Germany: Urban and Fisher. Foldi, M., & Foldi, E. (2012). Foldi’s Textbook of Lymphology (3rd ed.). Urban and Fisher.
2 https://www.lympho.org/publications
3 Lopera C, Worsley PR, Bader DL, Fenlon D. Investigating the Short-Term Effects of Manual Lymphatic Drainage and Compression Garment Therapies on Lymphatic Function Using Near-Infrared Imaging. Lymphat Res Biol. 2017;15(3):235-240. doi:10.1089/lrb.2017.0001
4 Tan IC, Maus EA, Rasmussen JC, et al. Assessment of lymphatic contractile function after manual lymphatic drainage using near-infrared fluorescence imaging. Arch Phys Med Rehabil. 2011;92(5):756-764.e1. doi:10.1016/j.apmr.2010.12.027
5 Williams AF, Vadgama A, Franks PJ, Mortimer PS. A randomized controlled crossover study of manual lymphatic drainage therapy in women with breast cancer-related lymphoedema. Eur J Cancer Care (Engl). 2002;11(4):254-261. doi:10.1046/j.1365-2354.2002.00312.x
6 Moffatt, CJ, et al. International Lymphedema Framework. (p. 13)
7 Foldi, M, Foldi, E. (2006). Foldi’s Textbook of Lymphology (2nd ed.), p. 273. Germany: Urban and Fisher. Foldi, M., & Foldi, E. (2012). Foldi’s Textbook of Lymphology (3rd ed.). Urban and Fisher.
8 Foldi, M, Foldi, E. (2006). Foldi’s Textbook of Lymphology (2nd ed.), p. 526. Germany: Urban and Fisher. Foldi, M., & Foldi, E. (2012). Foldi’s Textbook of Lymphology (3rd ed.). Urban and Fisher.
9 Belgrado JP, Vandermeeren L, Vankerckhove S, et al. Near-Infrared Fluorescence Lymphatic Imaging to Reconsider Occlusion Pressure of Superficial Lymphatic Collectors in Upper Extremities of Healthy Volunteers. Lymphat Res Biol. 2016;14(2):70-77. doi:10.1089/lrb.2015.0040
10 Foldi, M, Foldi, E. (2006). Foldi’s Textbook of Lymphology (2nd ed.), p. 568-569. Germany: Urban and Fisher. Foldi, M., & Foldi, E. (2012). Foldi’s Textbook of Lymphology (3rd ed.). Urban and Fisher.
11 Shields, J. (1992). Lymphology, v25, n4, Dec. 1992, p. 147* & Foldi, M, Foldi, E. (2006). Foldi’s Textbook of Lymphology (2nd ed.), p. 550. Germany: Urban and Fisher. Foldi, M., & Foldi, E. (2012). Foldi’s Textbook of Lymphology (3rd ed.). Urban and Fisher.
12 Foldi, M, Foldi, E. (2006). Foldi’s Textbook of Lymphology (2nd ed.), p. 198. Germany: Urban and Fisher. Foldi, M., & Foldi, E. (2012). Foldi’s Textbook of Lymphology (3rd ed.). Urban and Fisher.
* https://lymphaticyoga.net/deep-breathing-and-the-lymphatic-system/ cites Dr. Shields as saying, “Deep diaphragmatic breathing stimulates the cleansing of the lymph system by creating a vacuum effect which pulls the lymph through the bloodstream.” I cannot find this statement in the cited article posted by the author. (https://journals.uair.arizona.edu/index.php/lymph/article/view/17643/17366)

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Contraindications to MLD

One of the more popular posts I’ve written is about contraindications to treatment (time when treatment should not be done). Lymphedema treatment includes manual lymph drainage (MLD), multi-layer short-stretch bandaging, skin care and exercise. Both MLD & bandaging have specific precautions.1

General Precautions

The general precautions for MLD include:
– Active infection (caused by pathogens)
– Untreated cardiac failure
– Renal failure

There’s a relative contraindication for MLD:
– Malignant lymphedema (active cancer is causing the swelling)

Specific Precautions

But there are also specific precautions for MLD depending on where it is performed on the body. A sequence for MLD typically starts at the neck where the fluid drains. It doesn’t matter if swelling is in the legs, arms, head or elsewhere. But not all people will be appropriate for a neck sequence due to specific contraindications. For example, if someone has a cardiac arrhythmia related to an atrioventricular block or “AV-block” (referring to a block of the AV node in the heart’s electrical system). Doing a neck sequence could potentially stimulate the vagus nerve and cause cardiac arrest.

AV node

Understanding General Precautions (Active Infection)

So why are the general precautions a concern? In the case of an active infection caused by a pathogen (like bacteria in a cellulitis infection), performing MLD may cause the infection to spread. Fascinatingly, even though arterial & lymphatic flow increases during inflammation, in local inflammation, lymph vessels near the site of infection constrict. Thisprevents bacteria from escaping and entering the rest of the circulation.  In performing MLD, this spasm could be relaxed, allowing normal flow to resume. The bacteria might then be allowed to move into the rest of the body & the infection could become systemic (i.e. sepsis).

(Untreated Heart Failure)

In the case of untreated heart failure, the concern is increasing pressure. The pressure in the veins returning blood to the heart near each collar bone (clavicle) is usually low. This is where lymphatic fluid returns to the body’s blood circulation. In untreated heart failure, the pressure is increased in these veins. Stimulating lymph flow with MLD would only add more fluid to a congested area and further increase the pressure. This can contribute to heart damage.

venous angle (top right illustration)

(Kidney Failure)

In the case of kidney failure, there is swelling in the body (often the lower part of the body). MLD would increase the amount of fluid returning to the heart and subsequently to the kidneys, increasing the fluid they must filter. This could overtax them. But the main reason MLD is not performed is because it would be of no use (if swelling being treated is due to kidney failure). That’s because kidney-caused swelling is edema, not lymphedema. The lymph vessels are already working as hard as they can to help get rid of the excess fluid. MLD speeds up lymphatic flow but beyond its normal high-working speed.

(Active Cancer)

In the case of cancer, MLD is a relative precaution. Meaning, there’s some room for discernment. The primary reason for avoiding MLD in the case of cancer is the potential to spread the cancer cells. (Cancer spreads through one of two ways: blood or lymph flow.) However, according to Foldi, molecular biology showed metastasis formation is an active process controlled by the cancer cells themselves. For example, cancer cells secrete a protein called vascular endothelial growth factor C (VEGF-C). 2 This is responsible for creating new lymphatic vessels within and around a tumor from existing ones (lymphangiogenesis). Nonetheless, many therapists prefer to avoid the area of the tumor to avoid any potential accusation of / or potential of hastening cancer cell transportation.

It’s also important to know if a patient is receiving adequate cancer treatment and that the cancer is responding. One note: Some suggest avoiding MLD for 2-3 days after chemo to allow the drug(s) to remain in the body and do their job. Others suggest proceeding with MLD to help distribute the chemo throughout the body and to use gloves to prevent transmission of chemo through the skin to the therapist. I would tend to side with the former group (avoid MLD – at least in the area of the body directly affected by the tumor1). But it’s important to check with the oncologist before providing any treatment.

References
1 Foldi, M, Foldi, E. (2006). Foldi’s Textbook of Lymphology (2nd ed.), p. 275-276. Germany: Urban and Fisher. Foldi, M., & Foldi, E. (2012). Foldi’s Textbook of Lymphology (3rd ed.). Urban and Fisher.
2 Yan, H., Zhang, C., Wang, Z. et al. CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis. Sci Rep 7, 7442 (2017). https://doi.org/10.1038/s41598-017-06637-7

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