Dysautonomia and POTS
In this article Ross Hauser, MD discusses:
- Dysautonomia – problems of or dysfunction of the autonomic nervous system. It’s symptoms such as lightheadedness, palpitations and tremulousness during standing. Postural Orthostatic Tachycardia Syndrome (POTS)- a type of dysautonomia; and the connection between dysautonomia/POTS with Ehler-Danlos Syndrome and Joint Hypermobility Syndrome.
The autonomic nervous system (ANS) is made up of nerves that control the automatic functions throughout the body. It is the master regulator, controlling heart rate, blood pressure, temperature, respiration, sweating, digestion and other vital functions. These systems operate without consciously thinking about them, because the ANS provides the connection between them and the brain.
The ANS is made up of two subsystems: the sympathetic autonomic nervous system (SANS) and the parasympathetic autonomic nervous system (PANS). Most organs are directed by both the sympathetic and parasympathetic systems. The SANS is usually more of a stimulatory system, increasing heart rate and blood pressure when necessary.
Where the PANS, generally slows bodily processes, such as reducing heart rate and blood pressure. There are certainly exceptions. Digestion and urination, for instance are stimulated by the PANS and slowed by the SANS. The SANS triggers emergency responses or the “fight or flight” responses to prepare for stressful situations and controls the body’s response to stress. The PANS conserves energy and restores tissues for ordinary functions, helping to return the body’s equilibrium to the resting state.
Dysautonomia refers to problems of or dysfunction of the autonomic nervous system. Since the ANS regulates automatic or involuntary bodily functions, such as controlling the activities of organs, glands, smooth muscles and cardiac muscles, when the ANS malfunctions, the organs it regulates malfunction. For this reason, when individuals suffer from dysautonomia, they often exhibit numerous maladies and symptoms.
Orthostatic intolerance is a common problem in autonomic dysfunction and presents with lightheadedness, palpitations and tremulousness during standing. When in the upright posture other symptoms include visual changes, discomfort in the head or neck, throbbing of the head, poor concentration, tiredness, weakness and occasionally fainting. Many of the symptoms are relieved by lying down.
Other symptoms of dysautonomia include exercise intolerance, due to an inability to alter heart rate and regulate the cardiovascular system. Excessive or insufficient sweating is a problem due to problems regulating temperature. Slow digestion causes nausea, loss of appetite, bloating, diarrhea or constipation, and difficulty swallowing. Urinary problems can include difficulty starting urination, incontinence, and incomplete emptying of the bladder. Problems with vision include blurry vision or the failure of the pupils to react quickly enough to changes in light. And the list goes on…Fatigue, abnormal breathing patterns, dyspnea, vertigo, syncope, gait problems, hypoglycemia, “anxiety,” insomnia/non-restorative sleep and peripheral paresthesias. Any or all of these symptoms may be present in varying degrees of severity.
Postural Orthostatic Tachycardia Syndrome (POTS)
Often more simply referred to as postural tachycardia syndrome, POTS, is the most common form of dysautonomia and is characterized by orthostatic intolerance, with or without associated orthostatic hypotention, and excessive autonomic excitation. Symptoms manifest with the body’s inability to make the necessary adjustments to counteract gravity when standing up.
- Excessive heart rate increments upon standing is the defining symptom of POTS and is characterized by a marked rise of 30 beats per minute or greater within 10 minutes of standing from supine, or greater than 120 bpm while upright.
- Tachycardia is often accompanied by a mild decrease in blood pressure. Sympathetic overactivity causes the tachycardia, mild hypotension, with brain and other organ hypoperfusion causing a host of other symptoms.
POTS symptoms may range from mild and occasional complaints to severely incapacitating disease. Sufferers are commonly misdiagnosed as having chronic anxiety or panic disorder or chronic fatigue syndrome.1
There are a multitude of other symptoms that often accompany this syndrome including pre-syncope, syncope, dizziness, palpitations, headache, fatigue, bladder, and gastrointestinal (GI) symptoms.2
POTS sufferers often present with numerous musculoskeletal conditions, as POTS is frequently associated with hypermobile conditions such as Ehlers-Danlos Syndrome.3
The clinician should take into consideration the association between these conditions when diagnosing and treating those with this syndrome. “Presentation and association of autonomic diseases such as POTS, with other disorders may be so varied and subtle that clinicians may fail to recognize autonomic disturbance as an individual clinical entity within the disease and therefore appropriate management remains inadequate. Joint hypermobility disorder, along with postural orthostatic tachycardia syndrome and dysautonomia are increasingly being recognized as an associated clinical entity.”3
Dysautonomia, Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome
There is a strong connection between Joint Hypermobility Syndrome (JHS) and autonomic nervous system dysfunction. In fact, significant dysautonomia is observed in JHS patients with symptoms such as syncope and pre-syncope, orthostatic intolerance, palpitations, chest discomfort, fatigue, and heat intolerance. These symptoms are significantly more common among hypermobile patients. In one study, orthostatic hypotension, postural orthostatic tachycardia syndrome, and uncategorized orthostatic intolerance were found in over three-quarters of the hypermobile patients in comparison to one tenth in the controls.4
Joint hypermobility is a condition where there is an increased range of joint movement due to a variant of collagen. This condition affects close to 20% of the general population, and is more common in females. JHS is a chronically disabling disorder manifested as widespread pain, fatigue, multiple soft tissue lesions and fragility of skin and supportive connective tissues, along with the aforementioned autonomic dysfunctions.
Ehlers-Danlos Syndrome (EDS) involves the presence of joint hypermobility as well as other musculoskeletal and extra-articular connective tissue difficulties.
The term “Ehlers-Danlos Syndrome” (EDS) groups together an increasing number of heritable connective tissue disorders mainly featuring joint hypermobility and related complications, with skin, joints, blood vessels and internal organs variably affected. EDS-hypermobility type (EDS-HT), which is one of the most common variants, is still a clinical diagnosis based on subtle and likely unspecific features, and shows a nearly complete phenotypic overlap with Joint Hypermobility Syndrome (JHS), a heritable rheumatologic condition defined by the Brighton criteria. Some classify both Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome-HT as the same condition; however, the question whether EDS-HT and JHS are also identical at the molecular level is still a matter of debate.
The definition of Ehlers-Danlos Syndrome (EDS) continues to change because of the expanding spectrum of heritable connective tissue disorders sharing the variable triad of (i) generalized joint hypermobility and related osteoarticular complications, (ii) dermal dysplasia extending from minor changes of skin texture to clinically relevant skin fragility and defective scarring, and (iii) vascular and internal organ fragility with proneness to traumatic injuries and spontaneous ruptures, dissections and prolapses. 5,6,7
Dysautonomia in JHS/EDS-HT, often presents with orthostatic tachycardia syndrome and/or orthostatic intolerance, and seems to relate to increased sympathetic activity at rest and reduced sympathetic reactivity to stimuli.5,7
Overall, hypermobile patients tend to have higher mean autonomic dysfunction and orthostatic intolerance than non-hypermobile patients. Symptoms of autonomic dysfunction are not only higher in hypermobile patients, but also correlate strongly with the degree of hypermobility. Symptoms have been noted to change in female hypermobile patients with POTS, who report increased dizziness during menses, and improved orthostatic tolerance during the mid-luteal phase of the menstrual cycle. Estrogen affects blood volume as well as the renin-angiotensin-aldosterone system, and during the mid-luteal phase estrogen and progesterone are higher and may upregulate the renal-adrenal hormones.6
Autonomic abnormalities in patients with joint hypermobility are typically manifested as POTS. In the UK, 90% of POTS patients in a clinic for autonomic dysfunction also had Joint Hypermobility Syndrome. In another study of 48 patients with Joint Hypermobility Syndrome who fulfilled the 1998 Brighton criteria, 78% suffered from orthostatic hypotension, POTS and uncategorized orthostatic intolerance compared to only 10% of healthy controls. 6
In a study of 61 patients with Ehlers-Danlos Syndrome, 38% met the criteria for POTS. Furthermore, in patients under the age of 25, 72% were affected. “The presence of POTS was associated with a reduction in quality of life, including inability to maintain gainful employment or attend school.”7
“The lower the sympathetic reserves, the more exaggerated the sympathetic response to even minor stresses. The over-response often triggers an overcorrection, then an over-response. The lower the sympathetic activity is, the greater heart variability, or the more exhausted an EDS patient gets, the more “depleted” their energy reserves get, the more exaggerated heart rate fluctuations will be. The more heart rate fluctuates, the more disrupted sleep (and daytime activities) get. The more energy is wasted on autonomic fluctuations during the day, and the more disrupted sleep gets, the more exhausted one gets—a nasty vicious cycle.”16
Why is POTS/Dysautonomia So Predominant in Those with EDS and JHS?
The common hypothesis is the abnormal connective tissue in the dependent blood vessels permitting the veins to distend excessively in response to ordinary hydrostatic pressures, leading to peripheral vascular pooling and its hemodynamic and symptomatic consequences such as orthostatic intolerance. “Simply put, this connective tissue abnormally allows excessive amounts of blood to pool in these patient’s lower limbs when they stand.”8
Neuropathy, connective tissue laxity, and vasoactive medication are also thought to play a probable role in the development of dysautonomia.9 Any autonomic nervous system disruption may be part of a larger disease process, as dysautonomia commonly presents secondary to diabetes mellitus, amyloidosis, autoimmune neuropathies, heavy metal intoxication, cancer, central nervous system diseases, and more. Another important cause of dysautonomia is joint instability.
EDS, JHS, Dysautonomia and Joint Instability
Ligaments are bands of dense connective tissue bundles made up of collagenous fibers. Individuals with EDS and JHS have multiple joints that are unstable because of laxity of ligaments and tendons due to collagen variants. Let’s take a look first at the instability and laxity of ligaments this collagen disorder causes in the neck. “Investigating an occipitoatlantoaxial instability is relevant during the assessment of patients with occipital or postural/orthostatic headache, and/or additional unexplained neurological symptoms.”5
Instability and hypermobility in the neck
When the capsular ligaments of the neck become elongated, exhibit laxity and cause excessive movement of the cervical vertebrae, a few things occur:
1) At the upper cervical spine instability (C0-C2), this can cause a number of symptoms including, but not limited to, nerve irritation and vertebrobasilar insufficiency with associated vertigo, tinnitus, dizziness, facial pain, arm pain, and migraine headaches.
2) In the lower cervical spine (C3-C7), this can cause muscle spasms, crepitation, and/or paresthesia in addition to chronic neck pain.
In either case, the presence of excessive motion between two adjacent cervical vertebrae cause these associated symptoms similar to those described in dysautonomia.
Iatridou et al. found “poor static balance following challenge of the vestibular system, which may be justified by vestibular deficiency and/or insufficient proprioceptive capabilities of the neck. Impairments of dynamic balance in individuals with JHS may be attributed to proprioceptive deficits, which can alter feedforward and feedback mechanisms.”10
The occipito-atlanto-axial complex also has a unique anatomical relationship with the vertebral arteries. In the lower cervical spine, the vertebral arteries lie in a relatively straight-forward course as they travel through the transverse foramina from C3-C6.
However, in the upper cervical spine the arteries assume a more serpentine-like course. This pathway creates extra space which allows for normal head rotation without compromising vertebral artery blood flow. Considering the position of the vertebral arteries in the canals of the transverse processes in the cervical vertebrae, it is possible to see how head positioning and excessive movement can alter vertebral arterial flow. Proper blood flow in the vertebral arteries is crucial because these arteries travel up to form the basilar artery at the brainstem and provide circulation to the posterior half of the brain. When this blood supply is insufficient, vertebrobasilar insufficiency (VBI) can develop and cause symptoms, such as neck pain, headaches/migraines, dizziness, drop attacks, vertigo, difficulty swallowing and/or speaking, and auditory and visual disturbances. VBI usually can also arise when there is intermittent vertebral artery occlusion induced by extreme rotation or extension of the head.11 Once again, these symptoms sound quite familiar!!
“De Wandele, et al found that, although affective distress and decreased physical activity are often suggested as possible causes for dysautonomia, their testing did not support this, but rather supported the hypothesis that joint hypermobility and neuropathy may play a role in the development of autonomic symptoms.”12
C1 and C2 are held in proper position by the transverse and alar ligaments-helping to protect the spinal cord, brain stem, and nervous system from excess movement in the upper cervical spine. When the ligaments are lax and elongated from hypermobility, this protective barrier is inefficient. Cervical instability can provoke irritation of both the vertebral and sympathetic nerves. Damage to ligaments and ensuing irritation to the surrounding nerve endings may alter the firing patterns from these nerve endings, which may cause increased activation of the sympathetic nervous system.13 Researchers have determined that even minor damage to ligaments and/or other musculoskeletal tissues can cause an over-stimulation of the sympathetic nervous system resulting in dysautonomic symptoms. One of the first doctors to recognize symptoms of dysautonomia in relation to joint instability was Dr. George S. Hackett, MD, who found that ligament relaxation (or laxity) activated the autonomic nervous system.14 Dr. Hackett found that in correcting the underlying joint instability by treating injured ligaments with Prolotherapy, not only did the local pain resolve, but so did the dysautonomia.
Treatment for Musculoskeletal Pain in EDS and JHS
We’ve concentrated on cervical instability; however, we know that EDS and JHS entail multi-joint laxity. Sympathetic nerves reside in the spinal cord from T1 of the thoracic spine to L2 of the lumbar spine. Any ligamentous injury here could also stimulate the SNS.15 Sympathetic stimulation can occur from any ligament or tendon injury or elongation. If a ligament remains in this state of injury, with the sympathetic system firing chronically, we can see how dysfunction of the autonomic nervous system could occur.
Fortunately, Prolotherapy is a treatment for chronic musculoskeletal injuries, neck pain, underlying joint instability and ligament laxity. It offers great results for individuals with EDS and JHS. The use of comprehensive Hackett-Hemwall Prolotherapy provides great hope to those with hypermobility because it is designed to successfully treat the ligament and tendon laxity that accompanies EDS and JHS, which can also cause the aforementioned dysautonomia. Prolotherapy is also a therapy capable of treating the multiple joint involvement in EDS and JHS cases. Ligament laxity predisposes to injury, and Prolotherapy can repair the injured joint(s). Muscles spasm when the joint is injured or unstable. Prolotherapy stabilizes the joint and stops the spasms. Myofascial trigger points develop in response to joint laxity, along with the activation of the ANS. Prolotherapy will tighten the ligaments and tendons, stopping those triggers. The joint laxity may also allow for extra movement which may cause nerve impingement and neuropathic pain. Prolotherapy can stabilize the unstable joint, eliminating the excessive movement as well as the impingement and pain. Prolotherapy is safe and relatively non-invasive as well as efficacious in relieving joint pain and instability. Treating the joint instability stabilizes the hypermobile joints and can resolve pain as well as symptoms of autonomic connection.
Treating patients with EDS, JHS and dysautonomia is multidimensional. Keeping stress to a minimum is of extreme importance. As is getting quality sleep! Fatigue can even be a direct result of autonomic dysfunction, e.g. increased parasympathetic activity.16
Circulation needs to be addressed, such as adequate salt and fluid intake, support hose, elevation of legs, and medication to maximize effective circulatory volume. Beta blockers may also be considered.
In addition to Prolotherapy…“Improving sleep, reducing pain, optimizing circulation, and minimizing daytime stresses helps to replenish autonomic reserves, which in turn improves daytime autonomic stability and improves sleep, which in turn improves daytime function, which in turn improves circadian rhythms and sleep.”16
Hypermobile joints in JHS and EDS individuals can be stabilized with Prolotherapy and autonomic dysfunction can be reduced with Prolotherapy, lifestyle changes, stress reduction, improved sleep and when necessary, medications.
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16. Pocinki AG. Is dysautonomia associated with Hypermobility? Clinical Autonomic Dysfunction in Ehlers-Danlos Syndrome. http://www.ednf.org/2014-physicians-conference