Osteopathy Journals and Research by Darren Chandler

 

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  1. Anatomy of the extraocular muscle

    There are seven extraocular muscles.

    • Four rectus muscles:
    1. Medial rectus muscle. 

    Attachments: common tendinous ring* & dural sheath of the optic nerve --> sclera. Action: adducts eye.

    2. Lateral rectus muscle.

    Attachments: common tendinous ring* > greater wing of sphenoid --> sclera. Action: abducts eye

    3. Superior rectus muscle.

    Attachments: common tendinous ring* & dural sheath of optic nerve --> upper part of the sclera. Action: elevates and adducts cornea. Also medially rotates.

    4. Inferior rectus muscle.

    Attachments: common tendinous ring* --> sclera. Action depression > adduction & lateral rotation cornea. Depresses lower eyelid.

    *: The common tendinous ring is a fibrous ring that surrounds the optic canal and part of the superior orbital fissure at the apex of the orbit. It gives origin to the four recti muscles.

    The optic nerve and opthalamic artery enter the orbit via the optic canal lying within the tendinous ring.

    • Two oblique muscles:
    1. Superior oblique muscle.

    Attachments: body of sphenoid & tendinous attachment of superior rectus --> trochlea --> sclera. Action: elevates posterior part of eyeball and depresses anterior part of eyeball < in adducted position. Abducts eye and intorts eyeball.

    2. Inferior oblique muscle.

    Attachments: orbital surface of the maxilla --> sclera. Action: depresses the posterior part of the eyeball and elevates the anterior part of the eyeball < in adducted position. Abducts and extorts the eye.

    Wright (1999) describes the intervening connective tissue between the superior rectus and medial rectus muscles that envelopes the superior oblique tendon as the intermuscular septum.

    Robertson (1983) identified an intermuscular fascial septum between the sheaths of the inferior oblique and the lateral and inferior recti. This fascia forms a sling for the inferior oblique sheath and helps to maintain its line of action.

    • Levator palpebrae superioris.

    Attachments: lesser wing sphenoid --> anterior surface tarsus, (--> orbicularis oculi) skin of upper eyelid & conjunctiva (via the common sheath of fascia between levator palpebrae superioris and superior rectus).

    Aponeurosis of the levator palpebrae superioris attaches medially to the medial palpebral ligament & laterally to the orbital tubercle of the zygomatic bone (Standring 2015).

    Action: primarily responsible for eyelid elevation.

    Ettl et al (1996) identified the connective tissue system of the levator palpebrae superioris muscle as consisting of:

    i. Network of radial septa connecting the fascial sheath of the levator palpebrae superioris with the periorbit of the orbital roof.

    ii. Septa surrounding the sheath of the levator palpebrae superioris.

    iii. Superior transverse ligament (Whitnall's ligament).

    iv. Common sheath of fascia between the levator palpebrae superioris superiorly and the superior rectus muscle inferiorly. The anterior band-like component of this common sheath of fascia is called transverse superior fascial expansion of the superior rectus muscle and levator palpebrae superioris. Extending between these two muscles the sheath attaches on to the conjunctiva.

    The transverse superior fascial expansion of the superior rectus muscle and levator palpebrae superioris:

    i. Mainly extends from the connective tissue of the trochlea --> fascia of the lacrimal gland.

    ii. Sends connective tissue attachments to the medial and lateral rectus muscle.

    iii. Blends with Tenon's capsule.

    iv. Send expansions inferiorly to insert into the connective tissue of the medial and lateral rectus muscle.

    v. Blends with the superolateral intermuscular septum (? the lateral rectus-superior rectus muscle band, Nam et al 2019). 

    The relationship of Tenon’s capsule to the common sheath of the levator palpebrae superioris/superior rectus, superior transverse ligament is discussed in the section ‘Tenon’s capsule’.

    Myofascial continuity from the neck to the eye

    There is a direct myofascial link whereby tension in the posterior superficial cervical fascia pulls on and stimulates mechanoreceptors in Muller’s (supratarsal) muscle via the occipitofontalis and levator palpebrae superioris (Bordoni & Zanier, 2014). Muller's (supratarsal) muscle is the smooth muscle fibers of the levator palpebrae superioris attached to the medial and lateral rectus muscle pulley (refer 'Tenon's capsule') (Kakizaki et al 2010).

    To extend the myofascial chain from the superficial cervical fascia to the Levator Palpebrae Superioris further the Levator Palpebrae Superioris and superior rectus muscle is connected with Tenon’s capsule. As well as forming a fascial sleeve for the extraocular muscles Tenon’s capsule surrounds the optic nerve where it terminates in the eye, blending with the meningeal tissue. 

    Could it be that tension in the fascial area in the upper cervical spine affects the movement of the eyeball, altering the visual field and posture, or causing dysfunction related to the fascial traction on the optic nerve, with resultant alteration in the ocular reflexes? (Bordoni Zanier 2014).

    Tenon’s capsule

    Tenon’s capsule is a thin fascial sheath (fascia bulbi) that envelopes the eyeball from the optic nerve to the corneoscleral junction. The optic nerve and the extraocular muscles pass through Tenon's capsule. The fascia that makes up Tenon's capsule blends with the meningeal tissue of the optic nerve as well as the extraocular muscles.

    The extraocular muscles pierce Tenon’s capsule (fascia bulbi). This fascia reflects back as a sleeve or tubular sheath around each muscle. The muscles pass straight through this sheath to insert on to the sclera of the eye.

    This fascial tubular sheath encircling each rectus muscle creates a pulley (Nam et al 2019). These pulleys function to constrain each extraocular muscle and maintain its position in relation to its insertion. Kono et al (2005) found each rectus pulley coupled to:

    • Orbital wall: attaching to the orbital wall as check ligaments the fascia provides a firm attachment for the muscle.
    • Tenon’s capsule: Tenon's capsule, the fascia bulbi, reflects back from the eyeball as a tubular fascial sleeve that forms the pulley. The rectus muscles pass through this fascial sleeve to attach on to the sclera.
    • Adjacent extraocular muscles: the outer (orbital) muscle fibers of the rectus muscles are meant to attach on to this fascial pulley from Tenon's capsule. However McClung et al (2006) could find no muscle fibers leaving the rectus muscles to attach on to the pulley. These authors suggest the collagen expansions from the rectus muscles that are meant to attach on to the pulleys instead form the check ligaments. 

    The individual fascial tubular sheaths of the four recti merge to form a fascial ring (Standring 2015)

    These pulleys posses smooth muscle fibers under parasympathetic innervation. This gives the pulleys dynamic neural control.

    Nam et al (2019) found suspensory bands of connective tissue running between these pulleys extending from:

    • Medial rectus muscle pulley to the inferior rectus muscle pulley.
    • Medial rectus muscle pulley to the superior rectus muscle pulley.
    • Lateral rectus muscle pulley to superior rectus muscle pulley.

    Fascial expansions from Tenon’s capsule that forms the muscular fascia:

    • Fascial expansions from the medial rectus: attaches to the lacrimal bone. Forms the medial check ligament. Limits the actions of the medial rectus muscle.
    • Fascial expansions from the lateral rectus: attaches to the zygomatic bone. Forms the lateral check ligament. Limits the action of the lateral rectus muscle.
    • Inferior rectus: blends with the sheath of the inferior oblique. This thickened fused sheath has an expansion into the lower eyelid. Here it is augmented by some of the fibers of the orbicularis oculi where it attaches to the inferior tarsus as the inferior tarsus muscle.

    Not only are the check ligaments formed from the expansion of Tenon’s capsule that form the muscular fascia but McClung et al (2006) found the check ligaments attached on to the outer layer of the rectus muscles. These authors suggest the projections from the rectus muscles attaching onto the pulley on MRI images are in fact the collagen bundles of the check ligament.

    The suspensory ligament of the eye (Lockwood’s ligament) extends from the medial to the lateral check ligaments stretching below the eyeball. It encloses the inferior oblique and inferior rectus muscles.

    Other fascial extension of Tenon’s capsule are:

    • Superior transverse ligament (Whitnall's ligament): medial and lateral transverse expansions attach on to the orbit.
    • The relations of the transverse superior fascial expansion of the superior rectus muscle and levator palpebrae superioris to Tenon’s capsule is discussed in anatomy of the extraocular muscles.

    Function of the muscle pulleys

    Refer to 'Tenon's capsule' for the anatomy of the muscle pulleys. 

    The paths of the extraocular muscles through the orbit is constrained by connective tissue pulleys formed from Tenon's capusle. The normal pulley positions are necessary to maintain each extraocular muscle in its proper location with respect to its insertion, simplifying neural control of eye movement and balancing the forces of antagonist extraocular muscles.

    Conversely, abnormal pulley positions destabilize control of eye movements by both changing the direction of the extraocular muscle force applied to the globe and unbalancing the forces of the abnormally placed extraocular muscle with its antagonist (Clark 2015).

    These pulleys shift position during contraction and relaxation of the extraocular muscles. This dynamically changes the biomechanics of force transfer from the tendon onto the globe.

    Clark (2015) found normal pulley positions are important in facilitating neural control of eye movements. Abnormal pulley positions introduce unbalanced muscle forces within the orbit that destabilize neural control of eye position and help create incomitant strabismus (Clark 2015).

    Trochlea 

    The trochlea of the superior oblique is a pulley-like structure in the eye. Anatomically this is different from the pulleys from the other extraocular muscles. The tendon of the superior oblique muscle passes through it. 

    The trochlea is a cartilaginous "U" shaped structure attached to the periosteum that overlies the trochlear fossa of the frontal bone in the superior nasal quadrant of the orbit.

    Within the trochlea, a connective tissue wraps around the superior oblique tendon in an onion-skin configuration (Wright 1999).

    Kikuta et al (2019) found the relationship of the supratrochlear nerve and the trochlea was classified into three types:

    • Type I: the supratrochlear nerve passes lateral to the trochlea. 52.6% of cases.
    • Type II: the supratrochlear nerve passes through the trochlea. 42.1% of cases.
    • Type III: the supratrochlear nerve passed medial to the trochlea. 3.4% of cases.

    Hypertrophy of the superior oblique muscle where it passes through the trochlea has the potential to entrap the supratrochlear nerve (type II).

    Sandford-Smith (1975) found a stenosing tenosynovitis of the superior oblique is characterised by hypertrophy of the tendon where it changes direction in the trochlea.

    This author found these changes were demonstrable by tenderness on gentle palpation using the ball of the thumb over the trochlea and just posterior to it while the patient was actively elevating and depressing the eye in adduction.

    A swelling, if present, could be felt just posterior to the trochlea in a depression, which moved forwards to abut against the trochlea in attempted elevation.

    Cachinero-Torre et al (2017) attributed disorders in the trochlear region as causing orbital pain.

    Anatomy of the supratrochlear (V1) and supraorbital (V1) nerves

    Trigeminal nerve --> opthalamic nerve --> enters the posterior orbit at the superior orbital fissure --> opthalamic nerve divides into three branches. One of the branches the frontal nerve runs between the levator palpebrae superioris and the periosteum (Hagan et al 2016). Terminal branches of the frontal nerve are: (lateral branch) supraorbital nerve & (medial branch) supratrochlear nerves.

    Supraorbital nerve

    Passes through the supraorbital notch (or foramen). Sensory innervation to the skin of the forehead (reaching as far as the temporal and parietal areas) and the extraocular muscles (Cachinero-Torre 2017). Probably provides the postganglionic sympathetic fibers which innervate the sweet glands of the supraorbital area (Haladaj et al 2019).

    Just after exiting the supraorbital notch, the supraorbital nerve: superficial branch passes over the frontalis muscle. Innervates skin over the forehead. Deep branch: runs deep to the corrugator supercilii and frontalis muscles and across the lateral forehead between the galea aponeurotica and the pericranium. Innervates the frontoparietal scalp.

    For causes of disorders of the supraorbital nerve refer to 'Extraocular muscles and headaches and migraines'.

    Supratrochlear nerve

    Kikuta et al (2019) found the relationship of the supratrochlear nerve and the trochlea was classified into three types:

    • Type I: the supratrochlear nerve passes lateral to the trochlea. 52.6% of cases.
    • Type II: the supratrochlear nerve passes through the trochlea. 42.1% of cases.
    • Type III: the supratrochlear nerve passed medial to the trochlea. 3.4% of cases.

    The supratrochlear nerve passes through the frontal notch (or, very rarely, foramen). Sensory innervation to the bridge of the nose, medial part of the upper eyelid, and medial forehead.

    For causes of disorders of the supratrochlear nerve refer to 'Extraocular muscles and headaches and migraines'

    Extraocular muscles and headaches and migraines

    The relationship between the extraocular muscles and headaches and migraines has been well established (Fernández-de-Las-Peñas 2006). The pathology associated with these extraocular muscles includes:

    • Trapped nerves.
    • Myofascial trigger points.

    Trapped nerves

    • Supratrochlear nerve.

    Kikuta et al (2019) found the supratrochlear nerve can pass through the trochlea in 42.1% of cases.

    Sandford-Smith (1975) found a stenosing tenosynovitis of the superior oblique muscle is characterised by hypertrophy of the tendon where it changes direction in the trochlea. This could potentially cause an entrapment of the supratrochlear nerve at this location.

    Diagnosis of this condition was through palpation using the ball of the thumb over the trochlea and just posterior to it while the patient was actively elevating and depressing the eye in adduction.

    A positive finding was (i) tenderness and (ii) a swelling, if present, just posterior to the trochlea in the depression which moved forwards to abut against the trochlea in attempted elevation.

    Cachinero-Torre et al (2017) attributed disorders in the trochlear region as causing orbital pain.

    Extraocular sites of supratrochlear compression are the corrugator muscle (Janis et al 2013) and a periosteal or fascial band along the supraorbital rim (Hagan et al 2016).

    Myofascial trigger points

    Cachinero-Torre et al (2017) found trigger points produced from:

    • Overuse i.e. gazing for a long time in inappropriate conditions e.g. computer screens.
    • Disorders in the trochlear region.
    • Mechanosensitivity in the supraorbital nerve: (i) supraorbital notch/foramen (including the fascial band of the notch). (ii) Glabellar myofascial complex (including the corrugator muscle) (Janis et al 2013 & Fallucco et al 2012):

    Lateral rectus

    Symptoms: deep ache located at the supraorbital region or the homolateral forehead (Fernandez-de-Las Penas et al 2009).

    Examination: pressure is applied to the anatomical projection of the lateral rectus, in the lateral corner of the orbit, for 20 seconds. Maintaining the pressure, the subject sustains a medial gaze to stretch the muscle (Cachinero-Torre et al 2017).

    Superior oblique muscle

    Symptoms: a deep ache is located at the retro-orbital region, sometimes extending to the supraorbital region or the ipsilateral forehead (Fernandez de la Penas et al 2005 & 2006).

    Inferior oblique muscle

    In some instances, the nerve to the inferior oblique muscle (inferior branch of the oculomotor nerve) may pierce the inferior rectus muscle (Haladal 2019). Could tightness in the inferior rectus muscle sensitise this nerve and cause trigger points in the inferior oblique muscle?

    Levator palpebrae superioris

    The levator palpebrae superior is innervated by the superior division of the oculomotor nerve. Some of those nerve fibers continue their course either around the medial border of the superior rectus or pierce it to innervate the overlying levator palpebrae superioris muscle (Haladal 2019). Could tightness in the superior rectus cause trigger points in the levator palpebrae superioris?

    References 

    BROWN'S SYNDROME: DIAGNOSIS AND MANAGEMENT BY Kenneth W Wright (1999) 

    Myofascial disorders in the trochlear region in unilateral migraine: a possible initiating or perpetuating factor (2006). Fernández-de-Las-Peñas CCuadrado MLGerwin RDPareja JA.

    Referred pain from the trochlear region in tension-type headache: a myofascial trigger point from the superior oblique muscle. Fernandez de las Peñas CCuadrado MLGerwin RDPareja JA.

    Referred pain elicited by manual exploration of the lateral rectus muscle in chronic tension-type headache (2009). Fernández-de-Las-Peñas CCuadrado MLGerwin RDPareja JA.

    The intermuscular septum of the inferior oblique muscle: revised concepts (1983). Robertson I.

    Normal Anatomy and Anomalies of the Rectus Extraocular Muscles in Human: A Review of the Recent Data and Findings (2019). Robert HaÅ‚adaj

    Supraorbital Rim Syndrome: Definition, Surgical Treatment, and Outcomes for Frontal Headache (2016). Robert R. Hagan, Michael A. Fallucco, Jeffrey E. Janis

    Relationship of the Lateral Rectus Muscle, the Supraorbital Nerve, and Binocular Coordination with Episodic Tension-Type Headaches Frequently Associated with Visual Effort (2017) Anxo Cachinero-Torre, Bele´n Dıaz-Pulido, and Angel As unsolo-del-Barco.

    Clinical and symptomatological reflections: the fascial system (2014). Bruno Bordoni and Emiliano Zanier

    Müller's muscle: a component of the peribulbar smooth muscle network. (2010). Kakizaki H, Takahashi Y, Nakano T, Asamoto K, Ikeda H, Selva D, Leibovitch I.

    Anatomical Variations of the Supraorbital and Supratrochlear Nerves: Their Intraorbital Course and Relation to the Supraorbital Margin (2019). Robert HaÅ‚adaj, MichaÅ‚ Polguj and MirosÅ‚aw Topol

    Detailed Anatomy of the Lateral Rectus Muscle-Superior Rectus Muscle Band (2019). Yong Seok Nam, Yooyeon Park, In-Beom Kim, and Sun Young Shin

    Extraocular Connective Tissues: A Role in Human Eye Movements? (2006). J. Ross McClungBrian L. AllmanDiana M. DimitrovaStephen J. Goldberg

    The Role of Extraocular Muscle Pulleys in Incomitant Non-Paralytic Strabismus (2015). Robert A. Clark

    Superior oblique tendon sheath syndrome (1975). J. H. SANDFORD-SMITH

    Anatomy of the supratrochlear nerve: implications for the surgical treatment of migraine headaches (2013). Janis JE, Hatef DA, Hagan R, Schaub T, Liu JH, Thakar H, Bolden KM, Heller JB, Kurkjian TJ.

    The anatomical morphology of the supraorbital notch: clinical relevance to the surgical treatment of migraine headaches (2012). Fallucco M, Janis JE, Hagan RR.

    Gray’s Anatomy 41st edition (2015). Standring S. 

  2. Introduction

    There is increasing insight into the role of the production and absorption of CSF and interstitial fluids into the lymphatic system.

    This in part attributed to the developmental understanding of the g-lymphatic system. More interesting from an osteopaths perspective is the interplay of this system with other physiological systems and biomechanics.

    Traditionally the cranium has been viewed as a rigid box, unyielding, and enclosing the brain and all its fluids. When studied in relation to the body’s physiology, the movement of these fluids is at least partially dependent upon the systemic functioning of the body. 

    This is true of fluid movement all over the body. However from a mechanical perspective the fluids in the head and brain are placed under unique circumstances as they are encased in the relatively unyielding cranium. Because the casing of the head doesn’t move much if a lot of fluid was to flow into and out of the head in an uncoordinated manner intracranial pressure would dangerously rise and drop. If the skull lacked any compliance to accommodate these fluctuations in pressure from the ebb and flow of fluid into and out of the cranium there could be the potential of physiological discord. For this reason a degree of cranial compliance (Seimetz et al 2012) is essential to help maintain a controled fluctuation of intracranial pressure. This is the basis of the Monro-Kellie hypothesis.

    Brief introduction to the g-lymphatic system 

    The g-lymphatic system is discussed in more detail under 'g-lymphatic system'. This is a brief introduction to the concepts of this system. Essentially the g-lymphatic system delivers CSF into the brain where it mixes with the interstitial fluid (ISF). This mix of CSF-ISF then returns to and gets drained away by the lymphatic system.

    • CSF gets pumped along arterial perivascular pathways into the brain parenchyma.
    • This creates a mix of ISF-CSF in the brain parenchyma that gets drained away along venous perivascular pathways.
    • The ISF-CSF mix then gets emptied into the subarachnoid space. From here it gets drains into the lymphatic vessels of (i) perineural spaces of the cranial nerves and (ii) the lymphatics of the dural venous sinuses (superior sagittal sinus, transverse sinus & sigmoid sinus), diploic veins (Tsutsumi et al 2014) and middle meningeal artery.
    • These lymphatic vessels inturn drain into the deep cervical lymphatic vessels and nodes.

    Production and drainage of the CSF - EXCLUDING the g-lymphatic system

    Production of CSF

    Traditionally the CSF is thought to be solely produced from the choroid plexus in the ventricles of the brain.

    Miyajima and Arai (2015) reviewed the literature on CSF being produced by the capillaries in the CNS. It seems to be a concept that has kept reoccurring over the last 100 years and has been widely reported in other mammals. Bulat & Klarica (2011) attributed the mechanism of the capillaries in producing CSF to the filtering out of water across the walls of arterial capillaries. This process sieves out the plasma osmolytes. Whilst this is typically a mechanism of producing ISF Yiming et al (2017) found 20% of all CSF originates from the brain's ISF.

    The intimate relationship of the ISF and CSF is discussed further in the g-lymphatic system.

    Movement of CSF from the ventricles --> subarachnoid spaces

    The CSF moves through the ventricles ending in the fourth ventricle. At the fourth ventricle the CSF passes through three small foramina into the subarachnoid spaces. These foramina are the two lateral apertures (of Luschka) and one median aperture (of Magendie). The subarachnoid space is formed between the outer arachnoid mater and inner pia mater.

    As well as exiting the fourth ventricle via its apertures CSF also exits the ventricles by the parenchymal (cerebral) capillaries. These capillaries directly absorbs CSF from the ventricular walls into the brain parenchyma (Miyajima & Arai 2015).

    In the spinal canal the capillaries absorbs CSF into the subarachnoid space. Arachnoid granulations have been shown to exist in the spinal subarachnoid space (Miyajima & Arai 2015).

    Movement of CSF from the subarachnoid spaces --> veins & lymphatics

    The CSF moves through the subarachnoid spaces accumulating in the subarachnoid cisterns. These cisterns are dilations of the subarachnoid space where the arachnoid mater and pia mater are not in close approximation. These cisterns are all interconnected and transmit cranial nerves and intracranial vessels.

    Flanagan (2015) found the cisterns strategically located to provide extra protection and buoyancy for the brain, especially the brainstem due to its location above the base of the skull and foramen magnum.

    For example:

    • The lower cisterns e.g. cisterna magna, premedullary, and prepontine cisterns, help to prevent the cerebellum from sinking into the foramen magnum. This prevents cerebellar tonsillar ectopia similar to Chiari malformations.
    • Cisterna magna may function as a shock absorber against the pulsatile CSF pressure waves emanating from within the brain. These pressure waves are determined by fluctuating CSF volume and pressure in the cranial vault. This loss of buffering capacity of the cisterna magna can shift pressure to the central canal. This increase in pulsatility in the central canal could lead to a syrinx formation.

    Increase in CSF volume in the cisterns compromises their compliance and reduces their shock absorbing function. This may cause potentially destructive increases in not only CSF but also arterial pulsatility and pressure waves surrounding the brainstem. This can cause or contribute to atrophy of the brainstem.

    A similar action can be attributed to the veins in the subarachnoid space. A loss of compliance in the veins decreases their buffering capacity. Consequently, high pulsatile arterial pressure waves can be transmitted from the subarachnoid space to the delicate tissues of the brain parenchyma, as well as the walls of the ventricles.

    Movement of CSF from the subarachnoid spaces --> dural venous sinus

    Projections from the arachnoid mater, the arachnoid villi, protrude into the dura mater and dural venous sinuses (as well as the diploic veins, Tsutsumi et al 2014). This allows absorbtion of the CSF into the dural venous sinuses (superior sagittal sinus, transverse sinus & sigmoid sinus) and possibly their lymphatic vessels (refer movement of CSF from the subarachnoid space --> lymphatics).

    Movement of CSF from the subarachnoid spaces --> lymphatics

    1. Lymphatics in the perineural space

    As the cranial nerves cross the subarachnoid space the lymphatics in the perineural spaces drain the CSF into the nasal mucosa and deep lymph nodes in the neck.

    2. Dural lymphatics (refer movement of the CSF from the subarachnoid spaces --> dural venous sinuses)

    The arachnoid villi projects into the dura mater and the dural venous sinuses as well as the diploic veins. This not only allows absorbtion of the CSF into the venous sinuses (superior sagittal sinus, transverse sinus & sigmoid sinus) but also possibly their lymphatic vessels (Simon & Iliff 2016).

    Tsutsumi et al (2019) found a vein between the olfactory fossa and nasal vestibule. This vein drained into the lower limit of the superior sagittal sinus. They proposed this maybe an extracranial route of cerebrospinal fluid drainage.

    The lymphatic system in absorbing CSF

    The main drainage route of CSF is into the lymphatic circulation. Some CSF can be drained from the Arachnoid Villi and granulations into the walls of the venous sinus and diploe veins (Lachkar et al 2019). However Miyajima and Arai (2015) attributed absorbtion of CSF into the venous sinuses as a secondary pathway when there is an increased CSF hydrostatic pressure.

    These authors concluded this as the arachnoid villi do not exist prenatally in humans but occur postpartum, increasing in number with age. In some mammals it is estimated that at least 50% of CSF drains into the lymphatics but the proportion in humans is still unknown. These lymphatic pathways include:

    1. Nasal lymphatics: via the cribriform plate of the ethmoid, channels connect the subarachnoid space with lymphatic vessels in the nasal mucosa (Engelhardt 2016). Engelhardt et al (2016) found in the mouse lymphatic drainage along the sagittal sinus continued through the cribiform plate into the nasal mucosa. In human studies Visanji et al (2017) found dural lymphatics in the sagittal sinus.

    2. Dural lymphatics: Benveniste et al (2019) described lymphatic vesels along the venous sinuses (e.g. superior sagittal sinus, transverse sinus, sigmoid sinus) and middle meningeal artery. CSF runs in the subarachnoid spaces. Dilations in this space (subarachnoid cisterns) are filled with CSF. The subarachnoid cisterns directly associated with the dural sinuses, for example quadrigeminal cistern with the great cerebral vein, could give access to sinus-associated lymphatic vessles (Simon & Iliff 2016).

    3. Lymphatic vessels around the perineural spaces of the cranial nerves I, II, V, VIII (acoustic), X, XII (Koh et al 2005). The cranial nerves are bathed in CSF as they pass through the subarachnoid space and subarachnoid cisterns. The olfactory nerve (CNI) exits the skull via the cribriform plate into the nasal mucosa draining into the deep cervical lymph nodes. Although the eye doesn’t contain any lymphatics Hasuo and colleagues proposed CSF drainage from the subarachnoid space of the optic nerve through arachnoid granulations into the orbital connective tissue from which lymphatics were believed to transfer the fluid to the cervical lymph nodes.

    4. Engelhardt et al (2016) identified lymphatic drainage along spinal nerve roots.

    g-lymphatic system

    The g-lymphatic system both integrates and adds a new component to this model. It comes into play after the CSF has left the ventricles to enter the subarachnoid spaces:

    Movement of the CSF from the subarachnoid spaces --> periarterial spaces

    Benveniste et al (2019) identified CSF being driven from the subarachnoid space to the periarterial spaces. This was driven from pressure gradients derived from arterial pulsations (bulk flow).

    Movement of CSF from the periarterial spaces --> interstitial fluid spaces

    CSF is propelled from the periarterial compartments into the interstitial fluid spaces. The interstitial spaces is the space between the neural cells and capillaries and is filled with interstitial fluid. This fluid facilitates communication between the nerves in the brain.

    This movement of CSF from the periarterial spaces to the interstitial fluid spaces is facilitated by aquaporin 4 (AQP4). These are water channels on the perivascular endfeet of astrocytes (O'Donnell et al 2015). Brinker et al (2014) found AQP4 allowed for a continuous to and fro flow of bi-directional fluid exchange.

    In the interstitial fluid spaces the CSF and ISF mix 

    Movement of CSF-ISF mix from the interstitial fluid spaces --> perivenous spaces

    CSF-ISF fluid mixed with interstitial waste solutes is subsequently transported towards the perivenous spaces of the larger central veins. 

    Movement of CSF-ISF from the perivenous spaces --> subarachnoid spaces:

    Once transported along the perivenous spaces the CSF-ISF mix drains into the subarachnoid spaces (and cisterns).

    This creates a continuous space from the brain parenchyma along the perivascular pathways to the subarachnoid spaces.

    Movement of CSF-ISF from the subarachnoid spaces --> lymphatics

    Once in the subarachnoid space the CSF-ISF mix drains into the lymphatic circulation as identified previously. However there is another potential route of spread into the lymphatics of the dural sinuses.

    Simon & Iliff (2015) found the drainage of interstitial solutes along perivenous routes conceivably provides direct access to the most distal segments of these sinus-associated lymphatic structures. For example, the internal cerebral veins merge to form the Great Vein of Galen, which in turn joins the inferior sagittal sinus to form the straight sinus. Therefore could the perivenous flow through the internal cerebral vein eventually give access to the lymphatic vessels of the inferior sagittal and straight sinus?

    Movement of the g-lymphatic system

    Lee et al (2015) experimented on rats and mice to identify different influences that affect movement of the g-lymphatic system. Some of the mechanical influences may differ for humans due to the dimensional differences. These authors found the movement of the g-lymphatic system to be dependent upon:

    • Sleep. During sleep the brain's interstitial space volume expands by 60% (Xie etal 2013). This expansion lowers the overall resistance to periarterial inflow of CSF into the brain parenchyma. Inturn this increases CSF-ISF exchange and drainage along perivenous spaces and ultimately the lymphatic vessels.
    • Body position. The most effective positions for encouraging the g-lymphatic system is firstly lying in a right lateral position, then supine and lastly prone.

    This could give an evolutionary explanation as to why the most popular sleep posture is in a lateral position as it optimizes waste removal during sleep.

    • Arterial pulsatility. Arterial pulsatility drives g-lymphatic influx. Greitz et al (1992) found an influx of arterial blood leads to an outflow of CSF.

    • Movement of the brain. In systole the arteries expand. This expansion creates a piston like effect squashing the CSF out of the brain and into the spinal cord (Greitz et al 1992). This venting of CSF into the spinal cord during systole may explain the funnel-shaped movement of the brain as if it were being pulled down by the spinal cord (Greitz et al 1992).

    • Forced inspiration. Forced inspiration leads to an increase venous flow out of the head and an increase CSF flow into the head. This upward movement of CSF on inspiration was noted from the middle thoracic spine all the way up to aqueduct in the ventricular system (Kulaczewski et al 2017).

    • Increased intracranial pressure decreases CSF production (Miyajima and Arai 2015).

    • Body position (CSF influx): there is a reduced CSF influx into the brain in the prone position. But conversley an increase influx into the spinal cord.

    • Body position (CSF efflux): Lee et al (2015) tested the effect of body position on CSF efflux pathways of CNVIII (auditory nerve–cochlea complex), CNX (point of exit of the vagus), superior sagittal sinus and the periarterial space along the internal carotid arteries.  

    The vagus nerve is the most prominent CSF efflux pathway compared with the other routes.

    The only route affected by body position was along the internal carotid artery. Here efflux was more pronounced in rats when in a prone position compared with a right lateral position.

    Reciprocal movement of CSF into the brain and spinal cord

    There seems to be a reciprocal relationship with CSF flow into the brain and spinal cord. This reciprocal relationship seems to be dependent on posture, arterial pulsations and respiration. 

    Body posture

    Lee et al (2015) found being in the prone position reduces influx of CSF into the head, slows the influx of CSF in the g-lymphatic system and increases an efflux of CSF along the internal carotid artery pathway. In contrast being prone increases CSF flow to the spinal cord.

    Arterial pulsations

    In systole the arteries expand. Greitz et al (1992) found this expansion created a piston like effect squashing the CSF out of the brain and into the spinal cord. These authors attributed this venting of CSF into the spinal cord to creating the funnel-shaped movement of the brain as if it were being pulled down by the spinal cord.

    Respiration

    Forced inspiration leads to an increase venous flow out of the head and an increase CSF flow into the head. This upward movement of CSF on inspiration was noted from the middle thoracic spine all the way up to aqueduct in the ventricular system (Kulaczewski et al 2017).

    Neurological and physiological influences on g-lymphatic transport

    Lee et al (2015) asked why does g-lymphatic transport improve when placing anesthetized rats in the right lateral position and get worse when prone.

    They concluded the answer is likely a function of complex physiological adjustments to different head and body positions inducing a stretch on different nerves and vessels. 

    When prone the slight thoracic compression of venous return volume decreases stroke volume, with little impact on the heart rate. In other words less coming in the heart = less coming out the heart. This reduction in stroke volume will reduce arterial pulsatility, which is an important driver of g-lymphatic influx.

    Also it would be expected that overall sympathetic tone in the prone position would be higher as a natural response to the decrease in cardiac stroke volume from compression of venous return. Conversely sympathetic tone lowers when lying in the right rather than in the left lateral position. The sympathetic nervous system effects the g-lymphatic system.

    The effect of norepinephrine in inhibiting g-lymphatic influx is though to be because norepinephrine triggers rapid changes in neural activity that can reduce interstitial space volume (Xie et al 2013). This constriction increases the overall resistance to the periarterial inflow of CSF into the brain parenchyma.

    Not only does lowering sympathetic tone increase the efficiency of the g-lymphatic system but so does stimulating the vagus nerve (Cheng et al 2019).

    Whilst acknowledging the limitations of their research these authors proposed the effects of vagal nerve stimulation maybe partially or completely independent of systemic cardio and respiratory responses and more dependent upon (1) regionalized brain reflexes. For example the synaptic connections of the vagus nerve to the facial nerve which inturn innervates the cerebral artery. (2) Altering the neurotransmitter and metabolite content of CSF which could possibly interact with the astrocytic endfeet lining the paravascular spaces. 

    Lee et al (2015) thought the effect of body position may also effect systemic lymphatic circulation via the effects on the autonomic nervous system. They attributed the prone position to increasing sympathetic tone to the lymphatic vessels which would slow g-lymphatic transport. Conversely right sidelying reduces sympathetic tone concomitantly with an increase in vagal tone which speeds up g-lymphatic transport. However Le & Sloan (2016) found norepinephrine significantly increased lymph flow. 

    One other possible reason for the advantage of the right lateral position is that the heart is positioned higher when lying on the right side.

    This slight elevation of the heart facilitates the pumping of blood and with greater venous return may increase cardiac stroke volume; also, the sympathetic tone is reduced, reducing norepinephrine which improves g-lymphatic influx.

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