Dr Graham Exelby January 2024
Many of the typical symptoms associated with Postural Orthostatic Tachycardia Syndrome (POTS,) irrespective of the cause, can be traced to a set of mechanical “drivers” aggravated by other inflammatory causes and DNA predisposition.
To summarize the clinic findings in POTS, there are a series of vascular compression syndromes that we have found in all POTS (over 350). Head and neck vascular and mechanical pathology underpins 85% of POTS and drives symptoms, with impaired venous, arterial and lymphatic flow in the head and neck, and consequent vascular flow changes in the brainstem and brain proper. These appear responsible for Intracranial Hypertension, Intracranial Hypotension with CSF leaks, and Intracranial Vascular Pressure Dysfunction.
Jugular outlet syndrome (JOS) , (Venous Eagle, or Styloidogenic Jugular Venous Compression Syndrome) is very common finding in our POTS vascular compression studies with very high level of correlation where the Internal Jugular Vein (s) is compressed between the transverse process of the first cervical vertebra and the stylohyoid ligament, with varying levels of compression. The preliminary studies suggest that Venous Thoracic outlet Syndrome accompanies these, with a strong correlation between VTOS, JOS and cervical spine pathology.
While case studies have found changes in head and neck vascular and musculoskeletal function in most POTS, there are many with intra-abdominal compression areas. Increasingly there is a high incidence of Median Arcuate Ligament Syndrome (MALS), Superior Mesenteric Artery Syndrome (SMA) as well as the Nutcracker and May-Thurner Syndromes presenting as POTS. This concurs with the increased incidence noted between pre-Covid and post-Covid patient numbers.
We cannot as yet ascertain if these “rare diseases, especially MALS and SMA” signify the microglial -induced small fibre neuropathic central sensitization, or a change in collagen or both. Improved radiological methods may also be a significant factor. As we have no way to confirm these, so this remains a series of comparative observations.
The “mechanical and hydraulic” causes we have found in clinic are described as
Thoracic Outlet Syndrome (TOS). Arterial TOS can have direct effects on cerebral circulation. Venous TOS is clinically and functionally directly related to JOS and cervical spine dysfunction, generally from poor posture and trauma – Thoracic Outlet Syndrome
Jugular Outlet Syndrome (JOS) where the Internal Jugular Vein (s) is compressed between the transverse process of the first cervical vertebra and the stylohyoid ligament. Jugular Outlet Syndrome is intricately linked to the Thoracic Outlet Syndrome and upper cervical pathology.
Internal Jugular Vein Stenosis (IJVS) and Internal Jugular Vein Obstruction (IJVO)- (23)(24)(25) collectively with Jugular Outlet Syndrome, both affect venous outflow from the brain,(26) but the jugular dilation of the Internal Jugular Vein potentially affects the vagus, carotid baroreceptors, cervical sympathetic chain and jugular nerve.
Collectively the JOS and IJVS has been referred to as chronic cerebrospinal venous insufficiency (CCSVI). (23) Dynamic scanning of the Subclavian and Internal Jugular veins in a small preliminary study of 15 patients has shown the Internal Jugular Vein to dilate as the arms are elevated, and when neck flexion is added, obstruction to Internal Jugular Vein flow has been shown, the IJV flow return slow to return. As this has been accompanied by POTS symptoms, this requires formal studies to confirm the importance of this finding, and to differentiate the relative importance of each facet.
Loss of cervical lordosis/ flexion kyphosis – potentially impacting on Vertebral Artery flow as found by Bulut (27), Vertebral Vein and surrounding lymphatics- Cervical Spine Abnormality, Ehlers-Danlos Syndrome and Vertebral Vascular and Lymphatic Dysfunction.
All the above are likely to cause lymphatic obstruction as these in particular surround the Internal Jugular and Vertebral Veins. This impaired lymphatic flow potentially creates “backpressure” in the Glymphatic System which is affected by genetic predisposition, sleep disorder, and most importantly Covid infections. Glymphatic System
The combination of these changes is described in Intracranial Hypertension, Intracranial Hypotension, CSF Leaks and Craniovascular Pressure Change
In the abdomen the primary ones involve the Coeliac axis (MALS and SMA), Renal Vein Compression with gonadal vein reflux (Nutcracker Syndrome) with pelvic congestion, and May-Thurner Syndrome involving the iliac veins.
Recent advances in radiology has shown a high incidence of left renal vein compression associated with Superior Mesenteric Artery Syndrome (SMA), providing a potential explanation for intra-abdominal venous (and spinal vein plexus) dysfunction in SMA, previously unable to be explained.
The venous congestion potentially involves the Azygous and spinal vein systems- Intra-abdominal Vascular Compression Syndromes Bowdino, Owens and Shaw (64) describe that in 3% of people, the retroperitoneal venous vessels, such as lumbar or hemiazygos vessels, drain into the right renal vein before it enters the inferior vena cava.
The Azygous system of veins, which includes the hemiazygous and accessory hemiazygous veins provide an alternative blood flow from the lower half of the body to the superior vena cava was recognized by Nicolaides et al as significant in their work on venous outflow abnormalities and Multiple Sclerosis (28) and explored by Scholbach.(29)
This, and its association with the vertebral venous system has a place in POTS pathogenesis, but as yet this has not been fully elucidated. Symptoms occasionally can only be explained by dysfunctional azygous flow, but again we have no evidence to confirm this. Case study 2 describes the physical responses to clipping of the Axygous veins in operation.- Cervical Spine Abnormality, Ehlers-Danlos Syndrome and Vertebral Vascular Dysfunction, Intra-Abdominal Vascular Compression Syndromes
Jugular Outlet Syndrome
Cegas et al (21) describe that “in recent years, the theory of brain venous congestion has been proposed. The main brain venous drainage is attained through the sinuses that end in the internal jugular vein (IJV). This vessel starts off at the base of the skull, is the continuation of the lateral sinus, and drains into the subclavian vein at the end of its cervical portion. The mesial (towards the midline) temporal area of the brain drains through the basal vein of Rosenthal, internal cerebral vein, vein of Galen, straight sinus, transverse sinus, and lateral sinus. The IJV has a single valve just proximal to its end in the subclavian vein.”
Larsen (19) describes compression of the internal jugular veins, especially in patients who have a poor secondary-drainage system (via the vertebral, suboccipital, cavernous and pterygoid plexuses), may result in cerebral venous hypertension, with or without raised cerebrospinal fluid levels.
Research from Ozen et al (20) showed that normal drainage volumes in the internal jugular veins is between 700-1200 mililiters per minute, although Larsen found that drainage must be quite low before serious symptoms occur, usually as low as 300mL/min. But fatigue and headache can be seen as high as 500mL/min, especially in patients whose optimal drainage rate is high (this is impossible to know in advance).
Ozen describes “As venous hypertension raises, a raise in CSF pressure will also tend to occur. But, it can be hard to identify, because as several researchers have shown CSF leaks, as chronic elevation in CSF tends to cause secondary CSF leaks which causes a quite diffuse and equivocal constellation of symptoms as well as imaging findings that may seem paradoxical.”(20)
To understand what is happening we need to look firstly at the Eagle Syndrome and the anatomy of this region. The classical Eagle Syndrome was first described in 1937 by Dr Walt Eagle and usually involves the Carotid artery, although this is not the case in our findings, with most pathology coming from the venous compression.
Anatomy of the Eagle Syndrome
The styloid process is a cylindrical, slender, needle-like projection of varying lengths averaging 2 to 3 cm. The styloid process projects from the inferior part of the petrous temporal bone and offers attachment to the stylohyoid ligament and the stylohyoid, stylopharyngeus, and styloglossus muscles. Through these structures, the styloid process facilitates the movement of the tongue, pharynx, larynx, hyoid bone, and mandible. (3)
Figure 1: Location of Stenoses in Internal Jugular Vein
Red arrow: Stenosis between Stylohyoid and transverse process of C1, Blue arrow: Location of the Jugular Valve
Source: Rashid et al, Results of Numerical Modeling of Blood Flow in the Internal Jugular Vein Exhibiting Different Types of Strictures.
The styloid process is attached to the temporal bone and runs through two angles, downward then medially toward the pharynx. The cartilage extremity is prolonged by a fibrous band, the stylohyoid ligament, inserting on the lesser horn of the hyoid bone.(3) It is this fibrous band, the stylohyoid ligament, and calcification in this ligament that has figured so prominently in our current scanning.
Figure 2: The Mouth, Extrinsic muscles of the tongue; Left side, Dorsum of Tongue, Styloglossus, Hyoglossus, Genioglossus, Geniohyoideus, Stylopharyngeus, Thyroid cartilage
Source: Gray's Anatomy Plates. From: Anatomy, Head and Neck, Styloid Process
2023, StatPearls Publishing LLC.
Significant vessels and nerves surround the styloid process. The internal jugular vein, internal carotid artery, and glossopharyngeal nerve (CN IX), vagus nerve (CN X), and accessory nerve (CN XI) lie medial to the styloid process. The occipital artery and hypoglossal nerve (CN XII) run along its lateral side.(3)
Eagle Syndrome
Approximately 4% of the general population have an elongated styloid process. Although the majority of these individuals are asymptomatic, a small percentage of those with an elongated styloid process show symptoms and can present with one of two types of Eagle syndrome. The first type, classic Eagle syndrome or stylohyoid syndrome, presents as a sharp pain in the neck or the ear that extends to the maxilla, face, and oral cavity. The pain might appear exaggerated with the rotation of the head, chewing, swallowing, extending the tongue, or yawning. It might also be associated with a foreign body sensation in the pharynx, tinnitus, or vertigo. (3)
Symptoms of classic Eagle syndrome are due to the irritation or possible entrapment of the nearby cranial nerves (CN V, VII, IX, or X). The second type of Eagle syndrome is known as “stylocarotid artery syndrome”, which occurs when the styloid process impinges upon the internal or external carotid artery and the nerve plexus accompanying them. It presents as pharyngeal pain, eye pain, or parietal cephalgia, resembling a migraine or a cluster headache. Compression of the internal carotid artery might present with symptoms of internal carotid vascular insufficiency such as weakness, visual changes, or syncope exacerbated with head movement. The elongated styloid process might also pose the risk of carotid artery dissection leading to a transient ischemic attack or stroke.(3)
Figure 3: Eagle Syndrome
Source: Eagle Syndrome. Exodontia.info. https://exodontia.info/eagle-syndrome/
Eagle Syndrome has 2 main sub-types, with the third, the venous type only recently recognized.
Type 1 is from impingement of cranial nerves V, VII,IX and X. Symptoms include:
Facial pain turning the head
Dysphagia (difficulty swallowing), and sometimes pain
Sensation of foreign body
Pain extending the tongue
Change in voice
Sensation of hypersalivation
Tinnitus or ear pain (otalgia) (5)
Type 2 from Carotid Artery impingement:
Mechanical compression- visual symptoms, syncope carotid dissection
Sympathetic plexus symptoms from nerves running along the arteries- eye pain and parietal pain
Intracranial hypertension associated with an Eagle syndrome (18)
headaches, typically behind the eyes, may be worse in mornings, or when coughing or straining
visual changes, blurred vision, transient visual changes- grey-outs, black-outs, or blur-outs lasting 5 to 15 seconds, aggravated by postural change (10)
Diplopia
Loss of peripheral vision
Tinnitus, typically in time with heart rate (pulse-synchronous)
Nausea,
Vomiting,
Eye pain
Jugular Outlet Syndrome (Jugular Venous Compression Syndrome)
The first study demonstrating Jugular venous Compression was published in 2012 by Dashti et al (8) considering it an Eagle syndrome subtype. An elongated styloid process occurs in 4–28% of the population and is more common in women. Jayaraman et al (8) found that the right and left sides are equally affected, but the incidence of the left side is more common (right 24.1% vs left 30.6%).
Farina et al (7) showed that venous compression occurs because the jugular vein wall, which is thinner than that of the artery and devoid of smooth muscle and elastic fibres, is more likely to be compressed by extrinsic structures in the upper neck, such as the transverse process of C1 and styloid process.
This causes jugular vein compression and causes venous flow congestion, which predisposes to thrombosis. Several comorbidities have been found, including intracranial hypertension and a high-pressure gradient due to stenosis, thrombosis of the transverse sigmoid sinus, and perimesencephalic subarachnoid haemorrhage.(7)
Zhao et al (1) in 2018 described Jugular Venous Compression Syndrome as a cause of headache and Idiopathic Intracranial Hypertension, and demonstrated the effectiveness of surgical intervention in their small series, and reinforced by other researchers. (6) Ding et al (2) felt that this was caused by cervical spondylosis. They described symptoms of:
Head noise (77%)
Tinnitus (69%)
Insomnia (67%)
Dizzyness (54%)
Hearing impairment (47%)
Headaches (39%)
Visual impairment (34%)
Dry eyes (34%)
Neck discomfort (30%)
\Vertigo (19%)
Anxiety or depression (19%)
Memory impairment (10%)
Nausea/vomiting (8%)
Other researchers have confirmed the symptoms, Zhou et al (4) described pulsatile tinnitus as well as previously reported symptoms, and also described that the head noise and tinnitus suggested altered blood flow in the Internal Jugular Vein. They described increased MRI cerebral hyperintensities which I believe reflects the increased vascular and lymphatic backpressure and increased paravascular spaces.
Furthermore they suggested that prolonged elevated intracranial pressure can lead to thickening of the venous vessel wall and endothelial dysfunction, which is a plausible explanation for the cerebral hyperperfusion seen in SPECT study of POTS patients.
Kjetil Larsen describes “Impingement of the 9-12th nerves can also occur at this interval. Glossopharyngeal neuralgia is perhaps one of the more common ones, resulting in pain in the throat that worsens with head flexion and neck retraction. Vagal impingement can also occur, causing problems such as globus hystericus, dysphagia, vomiting, gagging, dystonia, gastroparesis and more. Impingement of the accessory nerve can cause cervical dystonia, Impingement of the hypoglossal nerve can cause burning tongue syndrome but also oromandibular dystonia.” (12)
SPECT scans of POTS patients
SPECT scans of brain of POTS patients demonstrate a mix of cerebral hyperperfusion and around 50% have brainstem hypoperfusion.
Figure 4: Cerebral Hyperperfusion in POTS
Source: courtesy Mermaid Molecular Imaging
Figure 5: Cerebral Hyperperfusion with Brainstem Hypoperfusion
Source: courtesy Mermaid Molecular Imaging
Brainstem hypoperfusion has been a subject of investigation for many years particularly in CFS. In 1995, Costa, Tannock and Brostoff (31) confirmed this in all ME/CFS patients with no psychiatric history, and compared to depressed patients with CFS, the perfusion was less. Griffith University has been addressing this for many years, and their results I believe confirm this study.
Collaborative discussions regarding the hyperperfusion seen in the SPECT scans felt that this was from “endotheliitis” from craniovascular flow changes, especially involving the Internal Jugular Vein occlusion, although the research from Guedj et al (32) hypothesizing glutamate/astrocyte dysfunction (in Long Covid patients using brain SPECT scans) need to be added to the possible causes for the perfusion abnormalities. Complicating this is the likely reduced blood flow in the brainstem, from a combination of impaired arterial flow from the neck- Katz (30) and Bulut (27), and sympathetic activation affecting arterial vasoconstriction.
Lymphatic Obstruction at Stylohyoid
Figure 6: Deep Cervical Lymph nodes, Principal gland of tongue, Supraomohyoid gland, Central trunk, Interrupting nodule, Trunks from margin of tongue, Submental gland, Vessels from apex, Vessels from margin of tongue, Vessels from root of tongue
Source: Gray's Anatomy plates
StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK574498/
Patients with Jugular Outlet Syndrome also have a high probability of lymphatic obstruction at the stylohyoid, compounding the obstruction in the vertebral system and at the subclavicular/ internal jugular junction/ venous angle. This potentially increases CSF pressures (conventionally regarded ICH), a well as increased craniovascular pressure due to venous outlet congestion. This lymphatic compression can be sometimes seen in clinical examinations, but I can find no suitable radiology to confirm this.
Relationship of JOS with Intracranial Hypertension
Michael Wall from University of Iowa describes the symptoms of Idiopathic Intracranial Hypertension: (11)
headache (94%)
transient visual obscurations or blurring (68%)
pulse synchronous tinnitus or "whooshing noise" in the ear (58%)
pain behind the eye (44%)
double vision (38%)
visual loss (30%)
pain with eye movement (22%)
In his paper on Intracranial Hypertension, Larsen describes: “A variable degree of intracranial hypertension (ICH) is a common affliction amongst patients with chronic fatigue syndrome, vestibular dysfunction, chronic headache or migraine, and [pulsatile] tinnitus. Yet, the majority of these patients remain undiagnosed and continue to suffer. The main reason for this, is that the body may quite subtly demonstrate intracranial hypertension on imaging studies, despite often obvious clinical symptoms.” (13)
“Blood clots in the cerebral venous drainage system, also called dural sinus thrombosis, is a known potential cause of intracranial hypertension and even hydrocephalus. However, in many circumstances, clots in the venous system may not severely affect CSF pressures, but may still greatly impair cerebral blood drainage and thus increase the craniovascular pressures despite the CSF pressures being normal or borderline.”
”Mechanical stenosis (narrowing) of the venous sinuses, especially the transverse venous sinuses is yet another phenomenon causing great confusion. Literature has suggested that up to 50% of sinuses may be “idiopathically stenosed”.(13)
Detailed in -Intracranial Hypertension, CFS Leaks, Intracranial Hypotension and Craniovascular Pressure Change
Figure 7: Cerebral Venous Sinuses
Source: Larsen,K. Intracranial Hypertension: Beyond CSF. Diagnosis and treatment. 2020. MSK Neurology. https://mskneurology.com/intracranial-hypertension-beyond-csf-diagnosis-and-treatment/
CSF versus craniovascular pressures
Larsen describes: “Almost all diagnostic measures in the detection of intracranial hypertension are based on CSF pressure markers, which is very unreliable.” “Most of chronic intracranial hypertension sufferers develop secondary CSF leaks through minor (secondary) dural defects or through defects (again, secondary to pressure increase) in the maxillary, ethmoid, frontal, sphenoid or mastoid sinuses. This makes the patient drip CSF and thus the CSF pressures will reduce to where it is borderline high or at the high end of normal ranges.” (13)
“Venous stenosis has been shown to highly associated with intracranial hypertension, as is elevated dural sinus pressures by catheter manometry (De Simone, Advancement in idiopathic intracranial hypertension pathogenesis: focus on sinus venous stenosis, 2010 (14)). Although not commonly understood, chronic craniovenous drainage insufficiency will result in both elevations of CSF pressures as well as craniovascular pressures. This is why CSF shunting a patient with intracranial hypertension will not have curative effect if it is venogenic, ie. if it is originating from chronic venous insufficiency, but it may be curative if the patient suffers from obstructive hydrocephalus, for example.” (13)
“If the patient has an underlying venous pathology that is not being detected, the patient may or may not develop significant indicators of elevated CSF. For example, stenosis or thrombosis of the superior sagittal sinus, which is the main drainage pathway for CSF, will almost inevitably result in papilledema and elevated lumbar punctures, as well as possible hydrocephalus.
However, if one transverse sinus is obstructed, especially the hypoplastic one, this may not be enough of a problem to cause significant CSF drainage impairment, but will certainly reduce blood drainage in that hemisphere and therefore increase the likelihood of symptoms due to consequent vascular congestion on that side.” Larsen states (13) “Craniovenous drainage deficiency, indicated by stenosed segments identified upon MR or CT venography, will to a variable degree increase the intracranial blood pressures, regardless of whether or not the CSF pressures appear normal.” (13)
These studies do not consider the accompanying lymphatic obstruction at the same obstruction points, but again this is currently unable to be proven. There is simply no research available to confirm what is a strong clinical finding in many POTS patients, mostly as the CSF cannot be effectively imaged.
JOS, TOS, IJVS and Craniocervical Instability
Ahn et al (14) described right and left internal jugular vein stenosis to be common in patients with neurogenic TOS symptoms. Treatment of internal jugular vein stenosis could potentially benefit these patients, and the implications of these findings warrant further study.
Larsen described “Facet joint misalignment has been associated with craniocervical instability . Sagittal plane misalignment of the atlanto-axial or occipito-atlantal facet joints will suggest some degree of dysfunction of the upper cervical spine. These misalignments are usually not enough to cause frank compression of the brainstem.”
“The facetal misalignment, rather than necessarily requiring surgery due to pathological instability, will result in jugular outlet syndrome (Larsen 2021; unpublished). Posterior slippage of the occipital facet on the C1 will result in resituating of the jugular foramen and styloid process vs. the lateral mass of the C1. This will often cause bilateral, severe obstruction of craniovenous outflow and can also cause compression of the 9th to 12th cranial nerves. The potential sequelae of jugular outlet syndrome are numerous and depends on severity as well as the angulation of the styloid process.”
Internal Jugular Vein Stenosis (IJVS)
Although recognized as a separate entity, IJVS is being found frequently as JOS is being evaluated. The Jugular Outlet Syndrome (JOS) revolves primarily around compression of the Internal Jugular Vein (IJV) by C1 transverse process against the stylohyoid ligament, which simply puts backpressure back into the cerebral circulation.
This is compounded when there is compression at the thoracic outlet venous angle and in these the IJVs dilate affecting structures in the carotid sheath, the jugular and vagus nerves and potentially the baroreceptors in the carotids, Internal Jugular Vein Stenosis (IJVS). More proximally the glossophayngeus and vagus can be affected at the stylohoid with consequent symptoms eg swallowing.
The combination of these compression areas has the potential for marked cerebrovascular pressure abnormality as well as autonomic instability.
Figure 8,9: Anatomy of distal Internal Jugular Vein
Henry Vandyke Carter and one more author - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below) Bartleby.com: Gray's Anatomy
Figure 10: Internal Jugular Vein Dilation -Spectral CT reconstruction showing obstruction at distal IJV
Source: Dr Zane Sherif, Mermaid Beach Radiology
Figure 11: Axial View of Internal Jugular vein Dilation
Source: Dr Zane Sherif, Mermaid Beach Radiology
Figure 12: Stenosed Valve in Internal Jugular Vein – with venous dilation above. This requires Dynamic Ultrasonography to differentiate valve insufficiency from simple obstruction from CT scanning position (and volume of contrast)
Source: Dr Zane Sherif, Mermaid Beach Radiology
Figure 13: Carotid Sheath
Source: Wikipedia. Carotid Sheath https://en.wikipedia.org/wiki/Carotid_sheath
Figure 14: The Carotid Space
Illustration demonstrating the contents and configuration of the left carotid space, including cranial nerves glossopharyngeus (IX), vagus (X), accessory (XI), and (XII hypoglossal) with proximity of the Cervical Sympathetic Chain
Source: Chengazi, H.U., Bhatt, A.A. Pathology of the carotid space. Insights Imaging 10, 21 (2019). https://doi.org/10.1186/s13244-019-0704-z
Internal Jugular Vein Outflow Dysfunction- Stenosis and Obstruction and relationship to Vertebral Venous Obstruction
Larsen (19) describes how compression of the internal jugular veins, especially in patients who have a poor secondary-drainage system (via the vertebral, suboccipital, cavernous and pterygoid plexuses), may result in cerebral venous hypertension, with or without raised cerebrospinal fluid levels. Venous hypertension will slow the arterial to venous transfer at the capillaries due to venous side congestion and may thus also affect arterial resting pressures.
Research from Ozen et al (20) showed that normal drainage volumes in the internal jugular veins is between 700-1200 mL/ min, although Larsen found that drainage must be quite low before serious symptoms occur, usually as low as 300mL/min. But Larsen (19) described “fatigue and headache can be seen as high as 500mL/min, especially in patients whose optimal drainage rate is high (this is impossible to know in advance).”
Ozen describes “As venous hypertension raises, a raise in CSF pressure will also tend to occur. But, it can be hard to identify, because as several researchers have shown CSF leaks, chronic elevation in CSF tends to cause secondary CSF leaks which causes a quite diffuse and equivocal constellation of symptoms as well as imaging findings that may seem paradoxical.”(20)
Kosugi et al (33) described “.The condylar veins (anterior, lateral, and posterior) and the anterior condylar confluence (ACC), which is located extracranially in front of the aperture of hypoglossal canal, represent the most important connections between the intracranial cerebral venous circulation and the VVS, and have been suggested to contribute to the main outflow tract for encephalic drainage in the upright position.”
Figure 15: Summary of the positional changes in craniocervical venous structure between supine and upright posture.
Source: Kosugi,K et al Posture-Induced Changes in the Vessels of the Head and Neck: Evaluation using conventional Supine CT and Upright CT. Nature (Scientific reports) 2020. https://www.nature.com/articles/s41598-020-73658-0
Kosugi et al (33), using CT angiography, showed that “in a supine position, the internal jugular veins (IJVs) are the primary venous drain for the brain. Several studies have recently reported that the jugular veins are collapsed and the main venous outflow from the brain occurs via the vertebral venous systems (VVS) in an upright position. The vertebral venous system contains veins, venous plexuses, and venous sinuses that course along the entire length of the spine, and it is regarded as a unique, large capacity, valveless plexiform venous network in which the flow is bidirectional, and plays a role in the main venous outflow or large-capacity venous reservoir in an upright posture.”
Larsen (19) believes, as confirmed in our studies, that contrary to common belief, craniovenous outlet insufficiency is a common disorder. Frydrychowski et al (36) demonstrated that bilateral jugular vein compression leads to a hyperkinetic cerebral circulation and direct transmission of pulse pressure into the brain microcirculation.
Jayaraman et al (35) showed that up to 70% of patients undergoing angiographies demonstrated concurrent venous outlet obstruction at the skull base, either uni or bilateral. Ding et al (2) found that 75% of patients with cervical spondylosis also had internal jugular venous stenosis at the skull base. Fifty percent of the stenotic vessels were compressed by the transverse process of C1, and 45% by the transverse process of C1 combined with the styloid process. The transverse process of C1 compression was more common in unilateral Internal Jugular Vein Syndrome while the transverse process of C1 combined with the styloid process compression had a higher propensity to occur in bilateral form.
The Jugular Outlet Syndrome (JOS) revolves primarily around compression of the Internal Jugular Vein (IJV) by C1 transverse process against the stylohyoid ligament, which simply puts backpressure back into the cerebral circulation. Commonly, this is a postural problem and can be treated by postural correctives in most circumstances.
Normal flow and valve sizes
Research from Ozen et al (20) showed that normal drainage volumes in the internal jugular veins is between 700-1200 mL/min, although Larsen (19) found that drainage must be quite low before serious symptoms occur, usually as low as 300mL/min. But fatigue and headache can be seen as high as 500mL/min, especially in patients whose optimal drainage rate is high (this is impossible to know in advance).
Ranges of “normal” in IJV diameters have a wide variation, both from one dominant side to the other, and between studies. Heffner and Andreos (39) describe the CT diameters of internal jugular vein on average: 8.7 mm in the upper neck, 10.8 mm in the middle neck, and 12.5 mm in the lower neck, while Tartière et al (40) using CT: The diameter of the right IJV :17 ± 5 mm [median: 17 mm, range: 13 to 20 mm] and left IVJ:14 ± 5 mm [median: 13 mm, range: 10 to 16 mm], with a cross-sectional area in right: 181 ± 111 mm2 [median: 160 mm2, range: 108 to 235 mm2] and left: 120 ± 81 mm2 [median: 102 mm2, range: 63 to 168 mm2].
So for practical purposes measuring in the low neck a range of 10 to 20mm may be normal. With the follow-up dynamic ultrasound assessments, most were associated with obstruction at the region of the valve, and appeared to be directly related to the presence of a venous thoracic outlet syndrome. As such we felt it needed more formal studies to confirm these findings, although we found no real evidence in our small study of valve stenosis.
At the distal end of the Internal Jugular Vein, Lewis (41) proposed that IJV valve insufficiency can cause venous congestion in the mesial temporal lobe area, inducing the episodes of amnesia, and Chung et al (42) found intracranial venous reflux in a group of patients with TGA.
It is clearly very difficult to separate the 2 entities, JOS and IVJS, and should be considered as both separately and together as Internal Jugular Vein Outflow Dysfunction.
Dynamic ultrasound scanning does appear to be the preferred investigation (43)(44)(45), but in the POTS patients with multiple pathology, the Spectral CTA/CTV has provided a very useful tool to assess the various vascular compression areas underpinning POTS. It is limited primarily by being a supine scan, so dynamic ultrasonography is a necessary component to look at each affected region.
When IVJ dilation is found below the stylohyoid and above the valve in the IVJ, ultrasound may be required to differentiate between IVJ Stenosis and IVJ Obstruction from arm positioning (and relevant to symptoms in normal day to day life) as well as competency of the IJV valve. There are other clues that may be present eg large external jugular veins or other collaterals in the neck. POTS patients usually have characteristic high rates of symptoms with arms elevated, but in each, the origin of the symptoms needs to be evaluated.
Hypotheses: Effects of Dilation of IVJ on surrounding structures
In Internal Jugular Vein Obstruction (IJVO) there is usually compression at the thoracic outlet venous angle, the junction of the Internal Jugular and Subclavian Veins while in Internal Jugular Vein Stenosis (IJVS), there is stenosis of the valve at the IJV/ subclavian junction. Others may not have a valve, and others show reflux of blood back into the intracranial system.
More proximally the glossopharyngeal and vagus nerves can be affected at the stylohoid with consequent symptoms eg swallowing. Both IJVO and IJVS have a very strong association with the Thoracic Outlet Syndrome (TOS). We hypothesize that the Arterial TOS may be the underlying cause of the fibrosis that occurs in the IJV valve, while the “lesser” VTOS varieties, that are typically ignored, provide intermittent occlusion and intermittent symptoms.
As we as yet are not seeing significant numbers of IJVS we hypothesize that it is the VTOS that causes the baroreceptor signalling as described by Geddes et al (46), the IJV dilating with arms elevated. I have no doubt this is a “normal” occurrence, and it is the sensitization that is responsible for the exaggerated autonomic responses.
In all subjects so far assessed in this particular cohort, the upper cervical spine appears to play a major component, whether by arterial, venous, lymphatic or neural dysfunction, and we have found multiple areas of dysfunction, typically VTOS + varying levels of JOS + loss of cervical lordosis or flexion kyphosis, exaggerated in Ehlers-Danlos Syndrome and intra-abdominal vascular compression syndromes, most commonly the Nutcracker and May-Thurner Syndromes. Previously unrecognized I believe, we have found a high correlation of Left Renal Vein Compression accompanying duodenal compression in SMA Syndromes, thus providing a link again into the paraspinal and azygous venous systems.
These findings where blood shunted into the valveless para-spinal veins increases the pressure in throughout the whole spinal venous system and reaffirms the vascular findings by Scholbach.(29)-discussed in Intra-abdominal Vascular Compression Syndromes
Figure 16. Vertebral Venous Plexus
Figure 17. Enlarged Paraspinal Veins from Left Renal Vein Compression (Nutcracker)
Source: Dr Zane Sherif. Mermaid Beach Radiology
Figure 18. Compression of Left Renal Vein between Superior Mesenteric Artery and Aorta
Source: Dr Zane Sherif. Mermaid Beach Radiology
Figure 19. Compression of Left Renal Vein and Duodenum in Superior Mesenteric Artery Syndrome (SMA)
Source: Dr Zane Sherif. Mermaid Beach Radiology
As the IVJ dilates in the carotid sheath, it potentially affects structures in the carotid sheath, the jugular and vagus nerves and potentially the carotid arteries and baroreceptors in the carotids. The Cervical Sympathetic Chain and ganglia lie in close proximity and are potentially vulnerable. The work by Geddes et al (46) describing heart rate and blood pressure oscillations with heads-up tilting, demonstrating these to be from baroreflex signalling modulating sympathetic and parasympathetic signalling, and simulating neuropathic and hyperadrenergic POTS makes this a reasonable hypothesis in the hyperadrenergic POTS.
We also believe the accompanying lymphatic obstruction when the Internal Jugular and the Vertebral Veins are compressed with subsequent impaired lymphatic flow and this backpressure is at least in part responsible for the increased CSF pressure in Intracranial Hypertension, and this with secondary effects on the HPA axis.
Figure 20. Anatomy of the Cervical Sympathetic Chain
Source: Pileggi et al. Stellate ganglion block combined with intra-arterial treatment: a “one-stop shop” for cerebral vasospasm after aneurysmal subarachnoid haemorrhage—a pilot study.(38)
The superior cervical ganglion is the largest of the cervical ganglia and most often appears embedded within soft tissue anterior to the transverse processes of the C2-C3 vertebrae, where it is vulnerable in migraine with C2/3 malrotation.
Figure 21. Cervical Sympathetic Trunk and relationship to cervical vertebrae and arteries
Anterior view of the neck where the cervical sympathetic trunk lies. Muscles and veins have been removed to show the ganglia of the cervical sympathetic trunk and their relationship to the cervical vertebrae and the vertebral and carotid arteries.
Source: Bombardieri et al. https://neurosurgery.directory/2022/12/31/cervical-sympathetic-nerve-block-for-cerebral-vasospasm/
The stellate ganglion is a fusiform or bilobed structure located anterior to the transverse process at the level of the C6 vertebra, superior to the subclavian artery & the posterior aspect of the pleura, and posterior to the vertebral vasculature. The vulnerability of this ganglion in Thoracic Outlet Syndrome can be seen with the use of a Stellate Ganglion Block to confirm Neurogenic Thoracic Outlet Syndrome. Thoracic Outlet Syndrome
Figure 22: Thoracic Outlet Syndrome showing venous compression of subclavian vein (VTOS)
Source: Venous Thoracic Outlet Syndrome. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/22317-venous-thoracic-outlet-syndrome
Figure 23: Path of Vagus Nerve in the neck
When viewed with the contents of the Carotid Sheath, the vulnerability of the vagus is shown
Source: Marjot, J.
Lymphatic Obstruction in the Head and Neck
Figure 24: Entry of Lymphatic duct into Subclavian Vein
Source: Tewfik,T. Thoracic Duct Anatomy. https://emedicine.medscape.com/article/1970145-overview
Lymphatic obstruction in the head and neck, and occasionally on the chest wall, is often obvious in POTS, but even when not so, the intimate relationship of the lymphatic channels to the Internal Jugulars and Vertebral arteries and veins ensures there is associated lymphatic obstruction, whether at the stylohyoid, venous angle or the upper cervical spine. Simple measures can help- walking in soft wet sand, neck posturing, lymphatic therapy and possibly ultrasonic treatment -things currently being assessed.
Figure 25: Deep Cervical Lymph nodes, Principal gland of tongue, Supraomohyoid gland, Central trunk, Interrupting nodule, Trunks from margin of tongue, Submental gland, Vessels from apex, Vessels from margin of tongue, Vessels from root of tongue. Again showing vulnerability to compression in the Carotid Sheath
Source: Gray's Anatomy plates
StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK574498/
Symptoms of Internal Jugular Vein Outflow Dysfunction
A decade ago a number of studies on IJV flow disturbances were undertaken looking at possible treatments for various neurological disorders especially MS. The majority of clinical trials of various endovascular treatments focussed on the abnormal valves with balloon angioplasty and stenting failed overall to have much impact.(48) Rashid et al (48) used computer modelling to suggest that an impaired outflow from the brain through the internal jugular veins is likely to be primarily caused by the upper jugular compression (Jugular Outlet Syndrome).
Chronic Cerebrospinal Venous Insufficiency (CCSVI) was discovered in 2010 by Italian Vascular Surgeon Paolo Zamboni, where he found up to 91% of patients with Multiple Sclerosis (MS), the veins that drain blood from the brain and spine were blocked, stopping normal blood flow out of the brain and spine, presumably causing an increase in venous pressure inside of the brain. In 2017 his treatments that had been developed were proven ceased after failures that I suspect lay in the belief that each had a single source, whereas in a similar way that POTS usually have multiple “drivers” to explain their symptoms. The findings by Zamboni (28) reflect what has been found in the majority of POTS patients, irrespective of what has activated their POTS.
Ding et al (49) studied cerebral arterial stenosis and venous stenosis in the clinical setting. Chronic cerebrospinal venous insufficiency (CCSVI) has also been confirmed to contribute to neurological deficits and impose a significant impact on cerebral arterial circulation.
Zhou et al (47) and Li et al (50) in relatively small studies described symptoms of Internal Jugular Venous Outflow Disturbance to include: tinnitus (60.5%), tinnitus cerebri (67.6%), headache (48.8%), dizziness (32.6%), visual disorders (39.5%), (including diplopia and blurred vision (20), hearing impairment (39.5%), neck discomfort (39.5%), sleep disturbance (60.5%), anxiety or depression (37.5%) and subjective memory decline (30.2%).
Li (51) and Cegas (21) confirmed Transient Global Amnesia, and Li (18) the high frequency hearing loss and head noise.
Cegas et al (45), studying transient global amnesia (TGA) found flow disturbances in the mesial temporal lobes thought to be secondary to venous congestion, providing clues to the persistent hyperperfused brains seen on Spect scanning. Ultrasound evaluation of the internal jugular vein (IJV) demonstrated a high prevalence of valvular insufficiency with a 79% correlation in these amnesia patients, the right side was affected more often than the left side, and 26.8% of the patients had bilateral incompetence.
Ding et al (52) described IJVS to be associated with several CNS diseases, notably transient monocular blindness, Ménière’s disease, Alzheimer's disease, idiopathic intracranial hypertension, and multiple sclerosis, as well as less specific symptoms of headache, head noise, tinnitus and visual impairment.
Ding et al (2) included eye soreness, eye dryness, visual distortion, visual loss, visual field defects and impaired visual acuity. Dysphrenia (stuttering or stammering) has also been attributed to this. But as we dissect the more complex nature of IJVS, many of these symptoms are neck or autonomic-related, and it appears both neck-related vascular impairment and IJVS need to be present to complete the nature of the condition. As with Zamboni, I believe too much was attributed to one problem.
Currently, it is suspected that these neurological pathologies are associated with autonomic-driven vascular flow changes and abnormal functioning of the glymphatic system, which primarily depends on a temporary decrease of the cortical blood flow, followed by a wave of inflow of the cerebrospinal fluid from the spinal canal to the cranial cavity. -The Glymphatic System.
Intracranial Hypertension and Chronic Fatigue Syndrome
We hypothesize that these vascular compression areas are intricately associated with Intracranial Hypertension (and Hypotension) and Chronic Fatigue Syndrome. The commonality of the mixture of impaired venous and lymphatic flow appears to reflect simple hydraulic dysfunction from mechanical causes, which when combined with inflammatory, autonomic and genetic causes, reflects POTS pathophysiology. The description of “pressure” associated with brain fog in POTS we believe is a vital part of understanding the pathology in that patient.
Higgins et al (53) described the cardinal symptoms of each - fatigue and headache - are common in the other and their multiple other symptoms are frequently seen in both. The single discriminating factor is raised intracranial pressure, evidenced in IIH usually by the sign of papilloedema, regarded as responsible for the visual symptoms which can lead to blindness. They hypothesised that IIH, and an undetermined proportion of chronic fatigue cases are all manifestations of the same disorder of intracranial pressure across a spectrum of disease severity, in which this subset of chronic fatigue syndrome would represent the most common and least severe and IIH the least common and most extreme.” This hypothesis, and the findings of Larsen (13) mirrors what we are finding in clinic in large numbers and is discussed in Intracranial Hypertension, CFS Leaks, Intracranial Hypotension and Craniovascular Pressure Change
Higgins (53) describes when discussing Intracranial Hypertension and CFS having the same pathogenesis, that “Symptoms will vary. Not every person will have headaches, vision issues, or any of the less common side effects of high pressure. Assumption otherwise is the reason many cases are misdiagnosed.”
Headache- Pressure headaches are often described as throbbing or bursting and are exacerbated by any factors that further increase ICP such as coughing, sneezing, recumbency or exertion. Classically the headache of raised ICP is worse in the morning, and may not be relieved by analgesics. There are often migraine characteristics eg light and sound sensitivity, and may occur in more than one area. It may be worse with eye movement.
Vision symptoms - can cause rapid or progressive vision changes. may include gray spots, dots, floaters, or dim-outs in one or both eyes, blurred vision, or double vision.
Tinnitus, especially pulse-synchronous
Altered mental state
Nausea and vomiting
Dizzyness
Neck pain and stiffness
Other common symptoms described in both ICH and CFS:
Fatigue
Low mood
Poor memory
Inability to concentrate
Muscle and joint pains
The ”Empty Sella,” Glymphatic Dysfunction and HPA Axis- Is lymphatic obstruction the primary factor responsible for the Intracranial Hypertension?
The sella (turcica) is a where the pituitary gland is located,a saddle-shaped notch in the bone at the base of the skull. An empty sella, or empty pituitary fossa, refers to the appearance of the sella turcica, when the pituitary gland appears shrunken or invisible and CSF fills the space instead.(63) It is often disregarded as an incidental finding of no clinical significance, but there exists a well-established association with Idiopathic Intracranial Hypertension. (63)
Readily recognized causes include causes include brain trauma, tumours, hydrocephalus, meningitis, strokes, abscesses, intracranial haemorrhage and some metabolic disorders.
It is also well known that severely increased cerebral pressure can cause compression and flattening of the pituitary gland, potentially leading to pituitary hormone deficiency, termed “empty sella syndrome.”(63)(34) Hulens et al (34) describe increased intracranial pressure causing hormonal disturbances in Fibromyalgia Syndrome and Chronic Fatigue Syndrome from compressive effects of the cerebrospinal fluid on the pituitary gland, impeding the blood flow in the pituitary gland and the pituitary stalk. Subsequent disturbances in the interactions between the hypothalamus, pituitary gland, and adrenal glands (the hypothalamo-pituitary-adrenal (HPA) axis) in FMS and CFS may result in abnormal hormone production.
The findings of this review by Hulens (34) provide further support for the hypothesis that moderately or intermittently increased cerebrospinal fluid pressure from a mix of mechanical, hydraulic and autonomic dysfunction is involved in the pathogenesis of POTS as well as FMS and CFS and should stimulate further research into the aetiopathogenesis of these conditions
Obstruction to the lymphatics that surround the Internal Jugular and Vertebral Veins we believe creates lymphatic/CSF “backpressure” in the Glymphatic System which is affected by genetic predisposition, sleep disorder, and most importantly, Covid infections. With Covid infections causing impaired glymphatic function,(possibly by impaired astrocyte/glutamate function) and venous flow changes in the dural sinuses, it is not surprising that fatigue and brain fog as well as other metabolic and hormonal disturbances that characterize POTS and Long Covid may be at least be partially explained.
We theorize that the accompanying lymphatic obstruction when the Internal Jugular and the Vertebral Veins are compressed with subsequent impaired lymphatic flow and this backpressure is at least in part responsible for the increased CSF pressure in Intracranial Hypertension, and this with secondary effects on the HPA axis.
Figure 26: Empty Sella
The pituitary gland shrinks or is flattened.
Case courtesy of Chris O'Donnell, <a href="https://radiopaedia.org/?lang=gb">Radiopaedia.org</a>. From the case <a href="https://radiopaedia.org/cases/20261?lang=gb">rID: 20261</a>
Abnormal valves
Silva et al (54) and Zamboni, Nicolaides et al (23) found valves usually present at the termination of the IJV just before its junction with the subclavian vein in 87% of normal individuals, but in no other segments, and is the only valve between the heart and the brain, so if the IJVV is damaged or becomes incompetent, increase in intrapleural pressure could result in raised intracranial pressure. They did find a number of different types of anomaly affecting flow.
Raut (55) confirmed the “valve in the internal jugular vein (IJV) generally is observed in 90% of the population. It usually is situated at a mean distance of 9 mm (0-26 mm) proximal to the confluence of the internal jugular veins and subclavian into the brachiocephalic vein. The leaflet of the valve normally is bicuspid (77%-98%), but rarely is it tricuspid (0%-7%) or unicuspid (1.4%-16%). Being the only valve between the brain and the heart, it is important in preventing backward flow of venous blood.” A competent IJV valve is considered to protect the brain from rising intrathoracic pressure during positive-pressure ventilation and coughing, especially in patients with compromised cerebral perfusion.
Zamboni, Nicolaides et al (23): found 5 main patterns of distribution of significant (>50%) venous stenoses have been found in large venographic series of patients with MS.
Single jugular lesion (30–36%): a significant stenosis in one of the two IJVs with a compensatory enlargement of the contralateral IJV.
Double jugular lesion (14–56%): bilateral stenoses of IJVs, with normal AZ venous system.
Double lesion (23%) involving one of the IJVs and the proximal AZ vein.
Triple lesion (3–38%): significant stenosis of both IJVs and the proximal AZ vein.
Multilevel involvement of the Azygous and lumbar venous system (18%). Stenosis of IJVs observed in approximately half of these patients causing additional obstruction. The potential role of the Azygous system is being investigated.
Other causes of IJVS
Li et al (56), and Zamboni, Nicolaides (23) described other currently recognized causes of extrinsic compression are the digastric muscle, lymph nodes, arteries, sternocleidomastoid muscle and thoracic outlet syndrome, lymph nodes, sternocleidomastoid muscle, and thoracic outlet syndrome. They found abnormalities may occur congenitally, as in patients with ICA dysplasia and fibromuscular dysplasia. Li et al (18) described two patients with bilateral IJVS caused by compression from the adjacent abnormal tortuous ICA. All types of hypertension, aneurysm, ectasia, and atherosclerosis may contribute to the tortuosity of the ICA.
The Baroreflex
The baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms that helps to maintain blood pressure nearly constant. Triggering of baroreceptors is thought to be an integral part of the autonomic hyperactivity found in POTS.
Figure 27: The Baroreflex
“Baroreflex activation is distinct from vagal stimulation. It works through an afferent limb which has the double effect of stimulating vagal output and attenuating global sympathetic outflow.”
Hypothesis: Potential effect of IJV dilatation on autonomic responses and excess parasympathetic activity in POTS
The baroreflex utilizes baroreceptors found chiefly in the walls of the aortic arch and carotid sinuses which provide a rapid negative-feedback loop: elevated blood pressure reflexively causes a decrease in heart rate and blood pressure. When blood pressure decreases, baroreflex activation also decreases, which allows heart rate to increase and blood pressure to rise. The baroreflex can start working within fractions of a second. Thus, baroreflex adjustments are key factors in dealing with postural hypotension, the tendency for blood pressure to decrease because of gravity when the person stands up. (57)
Geddes et al (46) describe heart rate and blood pressure oscillations with heads-up tilting, demonstrating these to be from baroreflex signalling modulating sympathetic and parasympathetic signalling, simulating neuropathic and hyperadrenergic POTS.(46) Baroreceptors and mechanoreceptors respond to changes in pressure or stretch in blood vessels within the aortic arch and carotid sinus. The baroreceptors of the aortic arch transmit signals via the vagus nerve to the solitary nucleus of the medulla. The baroreceptors of the carotid sinus, where the common carotids bifurcate, transmit signals via the glossopharyngeal nerve to the solitary nucleus of the medulla.(46)
Dilatation of the internal jugular vein in the carotid sheath thus has the potential to be a major “driver” through direct pressure on the carotid baroreceptors.
Changes in blood pressure are mediated by the parasympathetic and the sympathetic branches of the autonomic nervous system. Sympathetic activation raises blood pressure by increasing heart rate and contractility, as well as increasing arterial vasoconstriction. Conversely, parasympathetic activation leads to a reduced heart rate (bradycardia) and reduced cardiac contractility, which reduces cardiac output and blood pressure. The baroreflex can produce a rapid and profound decrease in blood pressure by inhibiting the sympathetic branch while activating the parasympathetic branch.
Conversely, the baroreflex can also elevate blood pressure by inhibiting the parasympathetic branch while activating the sympathetic branch. (57)
The importance of this linking to the inflammatory triggering can be seen in the work by Yang et al (59) in their study on famotidine activating the vagal inflammatory reflex to attenuate the cytokine storm providing a tantalising look at the role of the vagus in POTS and Long Covid symptoms.
Activation of the vagus nerve is frequently implicated in POTS. It is almost impossible to prove its presence, and there are no reliable tests to perform for this. Using heart rate variability, you can often differentiate sympathetic overactivity from parasympathetic overactivity -Case studies in POTS. Clinically the vagal activity can originate from intra-abdominal “drivers” such as Nutcracker, May-Thurner and rarer intra-abdominal causes affecting a vagal pathway (case study 1), or from the head and neck.
Vagal neuropathy is sometimes seen in the Thoracic Outlet Syndrome/Jugular Outlet Syndrome/ impaired cervical lordosis and flexion kyphosis. The vagal nerves pass between the anterior scalene and clavicular head of the sternocleidomastoid muscles, and in Jugular Outlet Syndrome it can be impinged between the C1 transverse process and the stylohoid process. Clinically, symptoms here include hoarseness, voice changes and dry cough.
The vagus is also closely related to the Internal Jugular Vein, the Carotid artery (with the associated baroreceptors in the Carotid bulb) in the carotid sheath. While the vagus is within the carotid sheath, it gives off the superior cardiac nerve and is associated with parasympathetic fibres and impact on cardiac function.(60) With the Jugular nerve and Cervical Sympathetic Chain in close proximity, all are potentially affected by the dilation of the Internal Jugular Vein, which we have visualized in dynamic ultrasounds to assess IJV flow. This has a close association with the Subclavian vein compression found in the Venous Thoracic Outlet, and providing a second anatomical position for potential vagal dysfunction. This was a small study but sufficient to warrant formal studies, as it is very likely to link the chaotic autonomic dysfunction seen on Heart Rate Variability studies.
POTS is characterized by autonomic dysfunction, as seen in heart rate variability studies.
The effects of IJVS and subsequent dilatation on physiological reflexes can be very complex and multi-faceted. As part of our hypotheses, we believe the dilated IJV, occurring as the arm is elevated, potentially triggers the baroreceptor reflex by direct compression of the baroreceptors in the Carotid Artery walls, as part of sympathetic overactivity, as described by Geddes et al (46). We believe it requires an exaggerated response as a result of microglial- activated “sensitization,” to become symptomatic.
Complicating this includes the irritation of the cervical sympathetic chain from entrapment in the thoracic outlet producing Raynaud’s symptoms (62), chest pain, neck and throat tightness as examples.(61)
The carotid baroreceptors are sensitive to stretch and changes in arterial pressure, typically to maintain cerebral perfusion and overall systemic blood pressure, but when the central sensitization is severe (as seen in all POTS) it is a strong theoretical observation that even change in physical height eg driving up hills, can activate these.
Conversely while the primary receptors for the Bezold-Jarisch reflex (BJR) are in the ventricles, it is a possibility that a significant (exaggerated, and mediated by the increased microglial sensitization) change in systolic blood pressure could influence this reflex, so that baroreceptor-mediated vasodilatation could decrease ventricular filling, stimulating the BJR leading to further vasodilatation and bradycardia.
It is known that when the jugular vein is compressed, causing a decrease in venous return to the heart it can lead to activation of the vagus nerve through the Bezold-Jarisch reflex. IJVO should in principle, produce the same response, with baroreceptors then signalling to the brainstem, specifically the nucleus tractus solitarius, which is involved in regulating autonomic functions. The reflex pathways are not yet established, although the underlying “mechanical and hydraulic” causes are becoming more apparent as we assess each POTS patient carefully.
Management
There is little published literature on the Internal Jugular Vein Stenosis treatment other than surgery, and medical treatment has centred around anti-coagulation. Zhou et al (43) Fifteen consecutive patients with suspected Intracranial hypertension and isolated IJV stenosis. The stenotic IJV was corrected with stenting. Headache disappeared in 14 out of 15 patients, visual impairments were recovered in 10 of 12, and tinnitus resolved in 10 out of 11 patients.
Management of Eagle syndrome can be conservative or surgical, depending on severity. However, initial conservative management is recommended. In a full Eagle Syndrome, conservative management may consist of steroid or long-acting anaesthetic injections at the inferior portion of the tonsillar fossa or the lesser cornu of the hyoid bone for symptomatic relief, in a similar way to injections for plantar fasciitis, to reduce the inflammatory process. In the calcified stylohyoid ligaments, surgical management can be through an extra-oral transcervical approach or an intra-oral transpharyngeal approach.(3)
Larsen (12) maintains that Jugular outlet syndrome, a result of craniocervical instability, postural problems or spondylosis can be resolved without fusion surgery in most circumstances. The aim is to decompress the jugular outlet, which with the TOS and loss of cervical lordosis is very much a structural problem.
The TOS, JOS and IJVS are intimately related, and researchers eg Kjetil Larsen (12) are adamant that neck pathology is the primary culprit, so management based around relieving “pressure” at the Jugular Foramen and correcting abnormal neck shape (and most importantly the “drivers” such as bad posture, prolonged computer use, and supporting the hypermobile necks in EDS. Indeed clinically it appears that vertebral vascular (and lymphatic) dysfunction is a requirement for POTS to be symptomatic (excluding intra-abdominal compression syndromes.)
Subclavian arterial compression can cause direct increased arterial flow as it is compressed. Researchers (Larsen) maintain that venous obstruction also increases intracranial pressure. There seems little doubt this is correct, but it will require new dynamic flow studies to assess the exact mechanism.
The lymphatic obstruction is often obvious, but even when not so, the intimate relationship of the lymphatic channels to the Internal Jugulars and Vertebral arteries and veins ensures there is associated lymphatic obstruction. Simple measures can help- walking in soft wet sand, neck posturing, lymphatic therapy and possibly ultrasonic treatment -things currently being assessed.
Management in the clinic has largely been with reducing the sensitization and controlling the mechanical drivers, usually with lifestyle, posture, neck and thoracic outlet physiotherapy -as this has been showing considerable symptomatic improvements in patients, methods are being evaluated by a team of physical therapists.
Conclusion
The management of patients with JOS/TOS/neck pathology holds significant promise in POTS, but it does require knowledge of all the other “drivers” which also need to be addressed. At present, the focus initially is on conservative management of the associated cervical spine dysfunction.
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