More Than Sick of Salt

All Posts in Category: Ehlers-Danlos Syndrome

Ehlers-Danlos Syndrome

Ehlers-Danlos Syndrome (EDS) and Autonomic Dysfunction

Click here to download this post

Autonomic Nervous System Dysfunction in Ehlers-Danlos Syndrome

by Nicholas DePace MD, FACC, and Michael Edward Goldis DO, FACOI, MS, BS in Pharm

The autonomic nervous system (ANS) runs all background bodily functions that do not require a conscious thought process. Major consequences of autonomic dysfunction include abnormal and inappropriate blood volume and flow distribution to the body with gravitational pooling and difficulty returning blood to the heart.

Direct nerve dysfunction can affect pupil size and abnormal motility of the gastrointestinal (GI) tract, compensations which are adaptive mechanisms in the body’s attempt to compensate for autonomic dysfunction, which can cause adverse symptoms. There are 2 components: (1) the sympathetic nervous system, which releases predominantly norepinephrine and is the “accelerator” of the body; (2) the parasympathetic nervous system releases acetylcholine which is the “break” of the body.

The vagus nerve is the main component of the parasympathetic nervous system and is the longest nerve in the body. Because of its long distribution and size, it is susceptible to injury.

Impairment of blood flow to the brain, which is poor perfusion, leads to lightheadedness, tunnel vision, blackout vision, change in hearing, perception, complete loss of consciousness, syncope, presyncope, the need to lie down, giddiness, word-finding difficulties, and short term memory loss.

These occur in the standing position almost always or occasionally sitting, but not lying. These symptoms are known as orthostatic intolerance. Mental cloudiness and brain fog are described.

Lack of perfusion to the brain may precipitate migraines. Light intolerance, photophobia, bothersome sensation to loud noises, anxiety, insomnia, and depression may or may not reflect poor cerebral perfusion.

Ehlers Danlos Syndrome is often associated with GI motility and may be associated with mast cell activation. What the mast cells do is release histamine inflammatory mediators. This accounts for the overlapping features not EDS like abdominal pain and poor GI motility with foggy thinking.

There is an article in the New England Journal of Medicine that feels irritable bowel syndrome (IBS) is the result of a histamine abnormality. What the actual cause is controversial.

While some physicians believe there’s a component of autoimmunity, we believe there is an abnormal connective tissue in the veins precipitating the venous pooling phenomenon, there is poor cerebral perfusion, and Sympathetic overdrive leading to dysautonomia.

There may also be an anatomical component to the autonomic dysfunction when you consider the vagus nerve is a parasympathetic nerve and the most prominent and longest in the parasympathetic nervous system.

It is the 10th cranial nerve and arises from the brain stem located auth the junction between the cranium and the first cervical vertebrae, which is also at the base of the cerebellum.

Any craniocervical instability in this region or compression of the vagus nerve could potentially have profound effects on vagus nerve function. Craniocervical instability is common in EDS and needs flexion and extension radiographic images and proper measurements to clearly characterize it.

The vagus nerve exits from this location along with the ninth cranial nerve, the glossopharyngeal nerve, and the eleventh cranial nerve which is known as the spinal accessory nerve.

The vagus nerve then branches throughout most of the body. The vagus is both afferent sensory and efferent motor. This sensory fiber for the vagus takes information from the GI tract and runs it back to the brain, while the motor activity directs the bodily functions in many organs.

Some physicians describe the enteric nervous system as an organism “second brain” which can function completely in the absence of central nervous system input. The vagus nerve as well as the parasympathetic nervous system in general uses the neurotransmitter acetylcholine to transmit information from the presynaptic nerve termination to the end organ.

There can be abnormalities from the brain to the ganglia or from the end receptors where acetylcholine is released. There are about 30 neurotransmitters within the enteric nervous system which include more than 90% of the body’s serotonin and 50% of the body’s dopamine.

Read More

Autonomic Nervous System and EDS (Ehlers-Danlos Syndrome)

Click here to download this post

Dr. DePace, MD, FACC

49% of hypermobile EDS (Ehlers-Danlos Syndrome) patients have POTS (postural orthostatic tachycardia syndrome), 31% orthostatic intolerance and 20% have normal hemodynamics. We call this orthostatic intolerance and postural orthostatic intolerance  in joint hypermobility syndrome / Ehlers-Danlos  hypermobility type, neurovegetative dysregulation or autonomic failure. The autonomic dysregulation is moderate to severe in one-third of our hypermobile EDS patients.

Coat-hanger pain is common in orthostatic intolerance associated with EDS. Coat-hanger syndrome consists of pain at the back of the neck (paracervical) and base of the head (suboccipital) that worsens in the upright position. It is believed to be due to poor blood flow to the muscles of the upper back and neck. It is due to pooling of blood due to abnormal sympathetic nervous system response due to standing and abnormal vasoconstriction. Coat-hanger pain can be quite profound, especially in conjunction with all the other chronic pain seen in EDS patients due to joint hypermobility.

Orthostatic headaches are also seen in EDS due to blood vessel malformation called Chiari malformation, CSF (cerebral spinal fluid) flow issues and CSF leaks. This may collagen problems, leading to stretchy blood vessels in EDS leading to venous pooling. This hypothesis has not been proven; however it makes empiric sense.

Autonomic dysfunction has often been attributed to autoimmunity and many times autoimmune antibodies are not detected, and many believe that this is because they have not been discovered as of yet. Diseases like rheumatoid arthritis, lupus and Sjogren’s disease have been seen with EDS. Nearly 10% had Raynaud’s, which is often associated with autoimmune disorders. It is kissable that abnormalities in the extracellular matrix might contribute to development of autoimmunity in the presence of other genetic or environmental influences.

The most common autoimmune diseases associated with EDS and POTS are Hashimoto’s, Sjogren’s, lupus and celiac disease. However, POTS is not the only dysautonomia disorder that is seen in EDS patients.

Mast cell activation syndrome is often seen in patients who have autonomic dysfunction including POTS and EDS. POTS and mast cell activation syndrome may frequently overlap. POTS patients with EDS tend to report dealing with POTS-like symptoms for most of their life. GI (gastrointestinal) are reported significantly more often by patients with EDS. Sensory neuropathic symptoms have been reported significantly more often in patients with EDS with POTS, including skin burning, hand tingling, hand burning, hand numbness and cold hands. The neuropathy noted in EDS patients suggests that the collagen in and around the nerve fibers may be damaged or abnormal.

Small fiber neuropathy in hypermobile EDS patients likely cause the burning sensations, hypesthesia and allodynia. Small fiber neuropathy refers to dysfunction or damage to the A-Delta and C fibers which relay thermal and nociceptive or unpleasant information as well as mediating autonomic function. There is strong evidence for a peripheral neuropathic contribution to the pain syndrome in hypermobile disorders in addition to the known nociceptive and central sensitization components. This raises the question if there is a neurological cause of hypermobile EDS; the only EDS syndrome without a known genetic cause. Physicians should assess for small fiber pathology in hypermobile EDS patients and hypermobility spectrum disorder patients for sensory and autonomic impact. EDS patients show an overactivity of the resting parasympathetic nerve tone and a decreased sympathetic nerve reactivity to stimuli.


Read More
DePace Books Heart Repair Manual, Clinical and Mitochondrial Disorders

Autonomic Nervous System Dysfunction in Ehlers Danlos Syndrome

Click here to download this post

Dr. DePace, MD, FACC

Articulo-autonomic dysplasia is a unifying pathogenic mechanism in Ehlers-Danlos Syndrome (EDS) and related conditions in the clinical pattern termed arthritis-adrenalin disorder.

Increased neuromuscular symptoms in females may be related to surrounding muscle support and joint connective tissue in males, leading to decreased male severity.

The similar clinical profiles of joint, skeletal, and dysautonomia, regardless of age our EDS diagnosis suggests the operation of an articulo-autonomic dysplasia (AAD) cycle, where lax vessels and lower body pooling elicit a sympathetic response and autonomic imbalance, which in turn affect small nerve fibers and enhance connective tissue laxity.

The findings of AAD are more frequent in females but are paralleled by men.

These include undergoing back surgery, slow healing, bladder issues, hernias, valve regurgitation, gallbladder issues, hives and reactive skin, food and medicine intolerance, and hypothyroidism.

The greater flexibility and fragility of connective tissue in women is conveyed by measures ranging from the historical performance of hypermobility tricks to the physical performance of Beighton maneuvers.

Neuromuscular and dysautonomia symptoms more frequent in women include migraines, muscle aches, weakness, and atrophy, physically highlighting greater muscular development and support in men as a key factor in their reduced severity.

The role of surrounding muscle for joint connective tissue constraint and protection correlates with the benefits of physical therapy and exercise for the treatment of EDS.

Problems can include popping joints that may manifest as subluxations, polyarticular and symmetrical joint pain of knees, shoulders, and ankles with rare swelling and erythema, joint injuries in mostly ankles and knees, fractures most frequently in distal limbs, and disk degeneration or herniation.

Clumsiness from joint laxity, cumulative joint pain injury, and skeletal deformations like scoliosis, toeing in or out, and flat or high arches make the typical patient uncomfortable with sports and prone to inactivity.

Evidence of skin fragility is another hallmark of EDS with easy bruising, unusual scars, and early striae.

Most unnoticed unless questioned or documented is soft or elastic skin which can be pulled in 1-inch folds from their jaw liner mid-forearm on physical examination.

The common findings of migraines and daily headaches which may arise from blood vessel abnormalities like Chiari formation of crania-cervical stability leading to numbness, tingling and muscle aches can prompt fibromyalgia diagnosis.

Seizures may actually reflect syncope more than epilepsy and may be related to poor balance.

Bloating, stomach pain and nausea begin early in life and continue later with gall bladder dysfunction and are accentuated by mast cell activation disease that presents as eosinophilic esophagitis with frequent food intolerances.

It is common to misdiagnose the anxiety and tachycardia associated with Postural tachycardia syndrome (POTS) as a functional disease.

The bowel disorders and overlapping joint and autonomic symptoms seen in EDS often are confused with Crohn’s and Celiac disease with the various associated psychological aspects.

Genomic and immunological studies can help determine if the overlapping joint and autonomic symptoms have separate causes. It is also important to make sure there is not a vitamin D deficiency or hypothyroidism that can present as Hashimoto’s thyroiditis.

In addition to chronic fatigue, anxiety-tachycardia and POTS, we see brain fog – poor focus, and sleep disturbances.

This can be disabling and much more severe in females with the occasional extremely affected male and together with bowel issues, weight loss, hives and reactive skin, and reactive airway disease – shortness of breath.

Mild valvular regurgitation, mostly mitral prolapse in both sexes.

Findings related to Marfanoid habits include an angular build, arm span greater than height, and long fingers with consequent maneuvers like making the prayer sign behind the back. Deformations like neck kyphosis, scoliosis, and lordosis are much more frequent in females except for pectus and toeing-in mainly or out, a likely contributor to clumsiness.

Read More
Ehlers-Danlos Syndrome

Vascular Ehlers-Danlos Syndrome Part 2

Click here to download this post

Dr. DePace, MD, FACC


Note: This Post is a contuinuation of the September 13, 2022 post on Vascular EDS

EDS has different types. Type IV is known as Vascular EDS. Pregnancy increases the likelihood of uterine or vascular rupture in women suffering from EDS type IV particularly during the last 3 months. The highest risk of rupture is during labor. Uterine hemorrhage can also occur postpartum. Occasionally a hysterectomy has been needed. The value of a Cesarean section carried out before the onset of labor has not been proven. Some have proposed that a medication called desmopressin be used to control bleeding during delivery.

The tendency towards hemorrhage in Type IV EDS is due to the fragility of tissue and capillaries rather than something wrong with the blood. The problem is due a defect in the protein collagen that makes fibers in arterial and venous blood vessels. This defect is what accounts for tears or dissections. This is one reason why digestive perforations can occur frequently.

Pregnant women with vascular EDS should receive treatment at special clinics. Because it is genetic, once EDS type IV is identified, Genetic counseling is recommended. The transmission is autosomal dominant, which means you only need one parent to pass on the trait, however 50% can be spontaneous with no family history.

A conservative approach in the management of EDS type IV is usually recommended. Avoid intense physical activities, violent sports, contact sports and scuba diving. Avoid drugs that interfere with platelet function or coagulation, like anticoagulants or vitamin K antagonist. Arteriograms and endoscopies are usually relatively contraindicated in GI and uterine complications unless absolutely necessary.

Surgery may, however, may be required urgently to treat potentially fatal complications, especially with very large or expanding aneurisms, or in the case of dissections and in the case of hemorrhage. Special techniques need to be used and information on the use of stents to treat vascular complications of EDS type IV is insufficient. That being said, simple arterial repairs have been successfully carried out.

Read More
Vascular EDS

Vascular Ehlers-Danlos Syndrome

Click here to download this post

Dr. DePace, MD, FACC

Ehlers-Danlos Syndrome, Vascular Type

The vascular type of Ehlers-Danlos syndrome is predisposed to blood vessel and bowel rupture. Vascular EDS is not as common as hypermobile EDS, but important to recognize because of vascular complications.

Physical Characteristic Vascular Ehlers-Danlos Syndrome

The main presentation is hematoma (bruise or collection of blood) in a muscle. More serious and less common would be intracranial hemorrhage (bleeding in the skull).

Another serious complication, even less common, is arterial dissections (splitting of the wall of the blood vessel. Vascular EDS is not the only subtype of EDS  that presents with vascular complications. Hypermobile EDS is more common but rarely has vascular complications.

About 2% of non-vascular EDS have vascular complications.  The most common such problems include hematoma, then intracranial hemorrhage, arterial dissection, arterial aneurism,  GI bleeding, and operative hemorrhage or sporadic vascular complications.

In addition, venous complications such as varicose veins and deep vein thrombosis were reported. Referral for cardiovascular assessment and regular follow-up may be required.

Treatment for Vascular Ehlers-Danlos Syndrome

Therapeutic measures are limited to the treatment of symptoms in vascular EDS. There is only one evidence  based preventative medication called  Celiprolol, which reduces heart rate and pulsatile pressures if there is high blood pressure and can decrease continuous and pulsatile mechanical stress on collagen fiber within the arterial wall.

It should be emphasized that certain genetic determinants result in a shorter life expectancy. The goal is to delay the onset of complications.

Read More