Doris Newman, DO, FAAO Newman Osteopathic and Wellness [email protected] The Interstitium is m an ? FSACOFP Orlando, FL July 2018

Disclosures

Dr. Newman has nothing to disclose

Quote by A.T. Still, MD; Photo from presentation by Donald Hankinson, DO Tonight’s discussion includes

Fluid Dynamics: • New concepts about: • Fascia - Interstitium – submucousa • Fascia reconceived as a “fluid body” • Palpatory assessment of fluid or “Tide”

Midline: • Neurodevelopment process • Palpatory assessment of midline NEW CONCEPTS IN “FLUID-BODY” Early Osteopathic thoughts on treating the “fluid” of the body.

 A.T. Still, MD  William Garner Southerland, DO  The Philosophy and Mechanical  Teaching in the Science of Principles of Osteopathy, 1892 Osteopathy  “As blood and other fluids of life are  Edited by Ann Wales, DO as ponderable bodies of different adapted from AAO’s 1949 Yearbook consistencies,  “The potency of the cerebrospinal  and are moved through the system fluid Tide is the “highest known to construct, purify, vitalize, and element” furnish power necessary to keep the  “You can direct that Tide…” machinery in action,  “The CSF is in command and controls we must reason on the different  the Tide” powers necessary to move those bodies……”p59 Jane Carreiro, DO  An Osteopathic Approach to Children, 2nd ed, Elsevier  Page 136  Describes a typical strain  “A cone-shaped, rotational strain seen at the site of vacuum extracted infants.”

 Interpreted by many as a fluid-type motion  treated by identifying two ends of the strain and organizing the fluid strain along a midline;  the spiral becoming a linear flow distal to proximal Isn’t interstitium the same as fascia or ??

Interstitium Connective Tissue  A small area,  Fibrous type of body tissue, containing but few cells  space, or  Variety of functions  gap  Supports and connects internal organs  Forms bones and the walls of blood vessels  in the substance of an organ or tissue.  Attaches muscles to bones (tendons)  Mainly long fibers embedded in noncellular matter, the ground substance  The space between cells in  Fiber density and chemical content varies tissue  Soft and rubbery  Hard and rigid

 Can develop in any part of the body so the  See also connective tissue body uses connective tissue for repair (ie scar tissue)

https://medical- dictionary.thefreedictionary.com/connective+tissue Connective tissue…..further classified

 Supporting  A major constituent of which is or ground substance  Glycoproteins  Derived from the mesenchyme  Many classifications:  Matrix proportion – loose or dense  Arrangement of fibers – regular dense vs irregular dense  Fiber type – collagenous, elastic  Embedded cell types – adipose, lymphoid, hemopoietic  Degree of differentiation – mesenchymal, mucous

 Location – subcutaneous, periosteal, perichondria http://www.gstbody.com/important-  Appearance – areolar, granulation discovery-related-fascia/  Nature of matrix = cartilaginous, osseous, liquid (blood, )

https://medical-dictionary.thefreedictionary.com/connective+tissue Where does the term “Fascia” fit in?

 A term so vague in use that it signifies little more than assemblages of connective tissue large enough to be visible to the unaided eye

 Structure is highly variable

 Collagen fibers tend to be interwoven:  seldom compact, parallel orientation (tendons)

http://matrix-myofascial.abmp.com/what-is-  Takes many forms fascia-and-why-is-it-important  Surface or investing  Loose connective tissue  Provides a degree of mechanical isolation Gray’s Anatomy, 38th ed., page 782 Churchill*Livingstone  Fascia constitutes the loose packing of connective tissue around peripheral nerves, blood and lymph vessels as they pass between other structures, often linking them together as a neurovascular bundle  It forms a dense connective tissue layer investing some large vessels such as the common carotid tissue layer and femoral arteries  Fascia may be functionally significant aiding venous return by approximating large veins to pulsating arteries or could represent a primary tissue response to the pulsatile forces created by neighboring arteries  Superficial Fascia Functions:  As adipose between and muscles can decrease friction and  Provide increased mobility of skin  Contribute to thermal insultation  Constitutes a store of energy for metabolic use

https://learnmuscles.com/blog/2017/11/16/the-frictionless- skin-fascia-interface-with-underlying-bone-theory/ Subcutaneous tissue of the skin UKyOrtho “Strolling Under the Skin” on youtube Published on Aug 28, 2014 Basic Science https://www.youtube.com/watch?v=eW0lvOVKDxE Dr. Jean-Claude Guimberteau

THE “NEW ORGAN” DISCOVERY…… “Structure and Distribution of an Unrecognized Interstitium in Human Tissue”

 Open Access article Published: 27 March 2018  https://www.nature.com/articles/s41598-018-23062-6  Authors: Petros C. Benias, Rebecca G. Wells, Bridget Sackey-Aboagye, Heather Klavan, Jason Reidy, Darren Buonocore, Markus Miranda, Susan Kornacki, Michael Wayne, David L. Carr-Locke & Neil D. Theise  Scientific Reports Volume 8, Article number: 4947 (2018)  Icahn School of Medicine, Mount Sinai

 Illustrator: Jill Gregory’s blog, Mount Sinai Health Systems  https://www.ami.org/press/press-releases/2018/386- the-story-behind-my-viral-interstitium-illustration

 12 patients  IV fluorescein with direct in situ visualization at 60-70 micrometers deep  Confocal laser endomicroscopy (pCLE)  Submucosal reticular pattern  20 micrometers wide dark branching bands  Surrounding large flouorescein-filled polygonal spaces (fluid-filled)

 Which persisted upon immediate ex vivo pCLE visualizatioin

 Immediately froze the resected bile duct

 Samples were cut to an equal depth as the in vivo and ex vivo pCLE = 60 micrometers

 Perpendicular cuts to the lumen

 Flourescent microscopy

 The same reticular pattern was seen

Masson’s trichrome stain:  Blue collagenous bands separating open, formerly fluid- filled spaces

 Compared from samples of the same patient

Normally fixed specimen:  Described as a compacted and dense submucousa  Due to loss of the fluid and collapse of the collagen

 Additional microscopy and staining revealed

 Fluid filled spaces and collagen bundles  Lined by cells staining for CD34 (stem cells)  Submucous of multiple organs and tissues:  entire digestive tract,  urinary bladder,  peribronchial tissue,  fascia and stroma of arteries and veins of all sizes  epidermis

Continuity bw interstitium and lymph

 Then they further stained submucosa  Colonic (A-C)  gastric (D-F)  epidermal carcinomas (G-I)

 Observed the “tattooed” markers drain into respective lymph nodes Article Discussion:  “In sum, while typical descriptions of the interstitium suggest spaces between cells, we describe macroscopically visible spaces within tissues – dynamically compressible and distensible sinuses through which interstitial fluid flows around the body.”

 “A submucosa subjected to directional peristaltic flow is not the previously envisaged wall of dense connective tissue, but a potential conduit for movement of injurious agents, pro- fibrogenic signaling molecules, and tumor cells.”  Woosup Park, MD  Doximity.com

“New interest in the interstitium is like people suddenly obsessing about the stuffing in sofas.”

https://opmed.doximity.com/new-interest-in-the- interstitium-is-like-people-suddenly-obsessing-about- the-stuffing-in-sofas-308b1336a317 How many organs does the have?

 10 “systems” with  “Vital” organs = 5  (brain, , liver, lungs, kidneys)  Total organs = 78-80

 According to new research out of Mount Sinai Health Center  https://www.inverse.com/articl e/42886-interstitium- dscovered-new-organ-- lymph-system

 The interstitium may be the newest body organ https://ipfs.io/ipfs/QmXoypizjW3WknFiJnKLwHCnL72vedxjQkDD P1mXWo6uco/wiki/List_of_organs_of_the_human_body.html THE OSTEOPATHIC CONTEXT: So, what does it mean PALPATORILY? Two important concepts in Osteopathic Medicine are involved in this discussion:

Midline Fluid Flow Dynamics

 Developmentally  Fluid dynamics occur on a midline about  Midline of neurodevelopment a fulcrum in multiple axes (planes)  3 parts of the developing brain  Every joint, suture, extremity and organ, must align to develop has a midline (biomechanically and in appropriately the fluid body) that can be palpated  MOTOR and treated with OMT  SENSORY  Balancing of the membranes, ligaments or fluid occur when the physician holds  COGNITION the midline and allows the inherent  One fails, they are all at risk of mechanism to shift and change until the delay/failure motion is restored

DEVELOPMENT OF MIDLINE Concepts in Midline

Fluid dynamics organized along the midline

 Embryologic development is full of symmetry and each piece of the machine has a midline Neurodevelopment of Midline

Motor Milestone

Sensory Milestone

Cognitive Milestone Neurodevelopment of Midline

Motor Milestone

Sensory Milestone

Cognitive Milestone Motor Development

 Proceeds  cephalad to caudad and  proximal to distal

 Muscle tone dictates motor development process  Intrauterine  Birth  Infancy In motor control:

POSTURE primary

CONTROLLED MOVEMENT secondary

“Stability before Mobility” Gross Motor, Posture and Balance

 Posture is the ability of the  The maintenance of posture and balance body to control its position depends upon information in space against the forces from all three systems of the external world. 1. Vestibular (Shumway-Cook, 2. Visual Woollacott, 2000). 3. Somatosensory Sense of Balance  Posture is the product of an Sense of spatial integrated orchestration orientation between the sensory and Coordinated motor systems of the body. movement with balance

Vestibular System

 Auditory system  Eye movements  Trunk Muscles and proprioceptors  Sends signals to the CNS

 ORGANS:  Vestibular Organs Semicircular Canals Anterior Horizontal Posterior  Otolith organs Utriculus Sacculus

Extrapyramidal - Vestibular System

 Lateral vestibular nucleus mediate:  extensors of the legs  flexors of the arms/ upright stance Upright Stance  vestibulospinal reflex

 Medial and superior vestibular nuclei mediate:  vestibulo-ocular reflex Maintains eye fixation w/head turning

 Superior vestibular nucleus fibers terminate:  On motor neurons of cervical musculature  Influence neck position Stabilizes the head in space  vestibulocollic reflex Visual System

 The maintenance of posture and balance depends upon information from all three systems  Visually activated muscle 1. Vestibular synergies

2. Visual precedes 3. Somatosensory Sense of Balance Somatic sensory activated Sense of spatial systems orientation

Coordinated movement with balance

Visual System stimulates motor control

 3 days of age:  Newborns will orient their eyes to a visual stimulus and  Track it even though muscle synergies are too immature to support coordinated head movement

 2 months of age:  Early signs of postural control can be recognized  An infant lying on her back will turn her head to look at something  An infant lying on his stomach will begin to lift his head.  These are visually triggered activities.  3 month  Improved thoracic control but not lumbar control  6 months of age  Commando crawl with sinusoidal motions  Motor response from head, neck, torso  Hips and leg flexors are relaxed

ATNR involves motor, vestibular and visual activities

 Birth to 6 months  Must “turn off” or integrate to develop midline

 If persists can see problems with:  Handwriting skills  Reading  Laterality

 Midline development depends on neurological integration of primitive reflexes

STNR (6m-3yr) allows the quadruped position and reciprocation. The visual system is leading the neurological progress through the developmental milestones. Neurodevelopment of Midline

Motor Milestone

Sensory Milestone

Cognitive Milestone Somatosensory System

 Neurodevelopmental Milestones  Organs Muscles Joints Proprioceptive mechanoreceptors Motion – alignment, glide, flex, extends Skin Sensory nerves Receptive Fields Hypo or Hypertonia (ie motor issues) will alter proprioceptive information and biomechanical motion

 Children with spastic paraplegia have altered postural strategies secondary to biomechanical factors rather than neurological

Neurodevelopment of Midline

Motor Milestone

Sensory Milestone

Cognitive Milestone Three components of cognitive function

 Ability to attend (and record the function)  Sensory

 Ability to integrate (from the context of all other experiences)  Contextual

 Ability to interpret (the important of the response)  Derive meaning and respond Object Representation

Attention Spatial Position

Visual Motion Cortex Color

Use Name Cognitive awareness of shapes

• Attend • Integrate • Interpret Becomes awareness of language.

• Attend • Integrate • Interpret MIDLINE development can be affected by all 3

Motor Developmental Milestone

Sensory Developmental Milestone

Milestones of Cognitive Development Integrating MIDLINE and FLUID into your OMT practice.

 Identifying the flow  Slower than the cranial rhythm  Only about 4 cycles per minute

 More like a slow flowing brook Your job is to find the obstructions in the flow Midline Fluid Palpation  Location  Follows the primitive streak and remnant noto chord  Along the “line” of the nucleus pulposis  Deep and posterior in the body  Flow  Distal to proximal  Palpation  Supine patient  Physician seated head of bed  Hands flat and under the upper back  Thorax & Ribs Midline Fluid Palpation  In the areas of the ribcage

 Flow  Medial to lateral  Laterally from spine  Equal bilaterally

 Palpation  Hands under thorax  Seated at head of supine patient

Midline of the spine:  Mechanical axis passes through embryologic axis  primitive streak –  notochord –  nucleus pulposis

 PALPATION  Starting at the tip of the coccyx (“Henson’s node”) embryological origin of endpoint is located on the dorsal wall of the saphenous sinus. Henson’s Node @ Tip of Coccyx

Midline Fluid Palpation in the LEs

Flow:  Fluid flows from proximal to distal  Should line up with the “embryological origin” of the extremity = L3-L5 Palpation  Seated at the foot of the bed  Cradle both extremities in your hands  Do not grip or apply any force Midline Fluid Palpation in the UEs

Flow:  Fluid flows from proximal to distal  Should line up with the “embryological origin” of the extremity = C5-C8 Palpation  Seated at the side of the ext  Distally, grasp the patient’s hand and align your middle finger with his midline (C7)  Proximally, place your hand at the C5-C8 region Midline of Fluid Axes of the upper extremities It is sometimes necessary to treat the midline of a portion of the extremity first

Always finish with the midline of the entire extremity Distal Hand Position

May need to “get the wrist out of the treatment” initially. Midline Theory - Potency

 When balancing the mechanical and embryologic axis in an optimal setting, there is a “potency” (powerful movement) in two, sometimes in three waves.

 This “potency” is only noticeable when the axes harmonize itself.

 Treatment depends on interactions between patient and physician and is dependent on the own state, circumstances, situations.

Sutherland: “be still and know!” Amplified MRI (aMRI) human brain motion

“The brain moves slightly with each heartbeat, but these motions are tiny: on the order of ten to 180 micrometers, less than a width of a single human hair.” https://medicalxpress.com/news/ 2018-05-magnify-brain-motion- heartbeat.html

Original online source: Magnetic Resonance in Medicine, May 29.

Itamar Terem, Stanford University research assistant and first author