EDS Comorbidities

➤BRAIN:
📍Symptoms - Dizziness, Lightheadedness, Headaches, Migraine, Cognitive difficulties (viz. socialization, tiredness, laziness, lacked attention, anxiety, depression, panic disorder, memory loss or lapses), Chiari Malformation Type I (CMI) (viz. Severe neck and head pain; Balance problems and dizziness; Visual disturbances, such as blurred or double vision; Loss of muscle strength, especially in the upper body; Hypersensitivity to bright lights; Loss of pain and temperature sensation in the upper torso and arms; Spasticity and abnormal muscle contractions; Pressure-like headaches at back of skull; Neck and shoulder pain; Blurred or double vision or Black out spells)

📝Management Analysis - The Craniocervical Instability (CCI) is a medical condition involving excessive movement between the skull and top vertebrae (C0-C1-C2), often caused by ligament laxity. It causes severe neck pain, headaches, vertigo, and neurological symptoms due to brainstem or vascular compression.

The CCI clinical analysis are done as –

• • • • Supine MRI (sMRI) – It is the standard imaging method where the person lies flat and still on a table that moves inside a cylindrical scanner. The machine captures detailed images of internal structures, helping to evaluate the spine, joints, or soft tissues.

• • • • Upright MRI (uMRI) – This imaging technique is preferred for CCI diagnosis, as it allows for assessment of the cervical spine under the weight of the head, which reveals instability that may not be visible in a supine MRI.

            The upright MRI provides images under weight-bearing circumstances, demonstrating how gravity can affect the body. This capability is particularly useful for diagnosing conditions involving back pain that worsens when standing or sitting but eases when lying down. By imaging the spine under the body's natural weight, it can detect issues like spinal compression or joint instability that can be missed in a traditional supine MRI. The upright MRI offers more precise diagnostics. It also allows patients to be scanned in positions that mimic or trigger pain patterns, providing a clearer understanding of patients’ symptoms. It can rotate patients from a vertical to a horizontal orientation, enabling both weight-bearing and supine scans in one session.  

• • • • Direct-Motion X-ray (DMX) – DMX is a real-time X-ray that shows the movement of the cervical spine, helping to detect abnormal motion between the atlas and axis. DMX is a fluoroscopic X-ray video that captures spine in real-time motion of ligaments recording 30 frames per second as one gently moves the neck. The DMX shows -

1. Vertebral movement in flexion, extension, rotation, and lateral bending

2. Abnormal motion between vertebrae

3. Alar and transverse ligament laxity

4. Upper cervical instability that causes neurological symptoms

DMX is the better option if you:

1. Have neurological symptoms with normal brain scans

2. Feel worse with head movement or posture changes

3. Have suspected C0–C1–C2 instability

4. Are planning regenerative therapy like PRP or stem cells

5. Have symptoms like dizziness, light sensitivity, or brain fog that worsen during activity

6. Have failed upright MRI or standard MRI with no diagnosis

Upright MRI may be helpful for observing disc position under gravity, but it simply 

cannot detect instability during motion. 

• • Flexion-Extension MRI & CT Scans: These scans are taken while the patient flexes and extends their neck, allowing doctors to assess how the cervical spine moves under different conditions.

The treatment of CCI in EDS patients can range from conservative management (Refer: EDS Exercises and Functional Rehabilitation) to surgical intervention, depending on the severity of the condition. If EDS / HSD CCI or NECK issues had not been diagnosed early and delayed for many years than only EDS / HSD leads to severe instability, and surgery is needed which is normally 5% of EDS / HSD population. The most common surgical procedure for CCI in EDS / HSD patients is occipito-cervical fusion (OCF), which stabilizes the skull and upper cervical vertebrae with titanium rods and screws. Bone grafts are used to encourage fusion of the bones, which prevents further movement and relieves pressure on the brainstem and spinal cord. Normally, CCI exercises with the help of neurologic physical therapist and medication leads to betterment.

➤DENTAL:
📍Symptoms - Dental issues (viz. high cusps and deep fissures of premolars and molars, shortened or abnormally shaped roots with stones in the pulp of crowns, enamel hypoplasia, gum recession, gum fragility, frequent cavities, tooth discoloration), pain radiating into teeth or pain when chewing the food, perform clenching of your teeth at night, high or narrow palate, dental crowding, ectopic eruption, and short roots [9, 10],  and  Temporomandibular Joint (TMJ) (viz. symptoms ranging from mild discomfort to severe jaw dysfunction, jaw clicking or popping, difficulty with movement, jaw of facial pain, ear fullness or partial dislocation). 

➤EARS:
📍Symptoms - pain in ears, ringing in ears (viz. sounds related to the ocean, ringing, buzzing, clicking, hissing or whooshing) and reduced volume or clarity of sound. 

➤EYES:
📍Symptoms - high power and high myopia (nearsightedness), Strabismus (viz. squint or eye misalignment), dry eye, thin corneas, light sensitivity, blue sclera (the white of the eye appears blue), microcornea (small cornea), corneal surface irregularities, binocular vision dysfunction, retinal detachment, subconjunctival hemorrhage, eyes drooping, dermatochalasis, eyelid heaviness, keratoconus, corneal ruptures, corneal ulceration

➤FACE:
📍Symptoms - Facial asymmetry.

➤FIBROMYALGIA:
📍Symptoms - Headaches, Jaw and facial pain due to temporomandibular joint (TMJ) disorders, Irritable bowel syndrome, Anxiety and Depression.

📝Management Analysis - The Fibromyalgia is a pain-processing disorder, more precisely a chronic disorder characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive difficulties. It’s more common in women. It’s mainly due to the way our brain and spinal cord process painful and nonpainful signals which increases the overall sensitivity to pain. Stress can make your symptoms worse or cause them to flare up more often. It could also increase your chances of developing depression.

The management analysis towards Fibromyalgia are -   

• High-dose thiamine (vitamin B1) - High-dose thiamine (vitamin B1) supplementation (600–1800 mg/day) may improve fibromyalgia symptoms like chronic pain, fatigue, and brain fog by correcting metabolic abnormalities and mitochondrial dysfunction. Evidence from small, preliminary studies suggests this therapy can significantly reduce fatigue and pain, likely by overcoming a dysfunction in transporting thiamine into the mitochondria.

The Vitamin B1 (Thiamine) Protocol for Fibromyalgia and Chronic Fatigue Syndrome can be done as -

Vitamin B1 300-500 mg tablets - Let’s use 400 mg as an example, you will need to adjust your protocol according to what strength you find available.

• 1-400 mg tablet once daily for 3 days (400mg),

• Then, 2-400 mg tablets once daily for 3 days (800mg)

• Then, 3-400 mg tablets once daily for 3 days (1200mg)

• Then, 4-400 mg tablets once daily for 3 days (1600mg)

• Then, 5-400 mg tablets once daily for 3 days (2000mg)

Gradually increase your tablets until you get to 2000-2100 mg. You may notice you felt better at 1600 mg than the 2000 mg. At that point, go back to the dose where you felt your best. If it does not help, it will not help to go higher, and you may discontinue the protocol.

Vitamin B1 is water soluble, and therefore, nontoxic. It will not harm you or your organs. It is totally safe.

• Medicines – They are -

  • • Antidepressants (Duloxetine, Milnacipran, Amitriptyline)

    • Anti-seizure drugs (Pregabalin, Gabapentin), and Muscle relaxants (Cyclobenzaprine, Tizanidine).

• Neuro-modulation – Peripheral nerve stimulation with a transcutaneous electrical nerve stimulation (TENS) unit, applied at high intensity over multiple sessions, has been shown to improve pain and fatigue in fibromyalgia patients. Additionally, transcranial magnetic stimulation and transcranial direct current stimulation have been found to reduce pain perception and fatigue in those with fibromyalgia.

• Massage therapy – A regular gentle massage therapy has been shown to be beneficial in managing fibromyalgia symptoms.

➤GASTRO-INTESTINAL (GI):

📍Symptoms - stomach blotting, constipation, sound coming from stomach, diarrhea, acid reflux, nausea, difficulty in swallowing (viz. dysphagia), pain in swallowing food or liquid (viz. odynophagia), discomfort or pain anywhere in abdomen, GERD–Gastroesophageal reflux disease, irritable bowel syndrome (IBS) (viz. Dysmotility, Visceral hypersensitivity, severe infections, food intolerance, fibromyalgia) and gastroparesis.

📝Management Analysis - The understanding of GASTRO-INTESTINAL (GI) is crucial and beneficial for effective management of any GI issues. The key important things to understand are - 

🫵Simply say “NO” to ENDOSCOPY / COLONOSCOPY - Most people with EDS / HSD along with MCAS have some degree of GI symptoms — bloating, nausea, pain, early fullness, diarrhea, constipation. Because of that, they’re often told they need an endoscopy right away. But an endoscopy usually has low yield, and high risks — especially for patients with MCAS and hypermobile EDS — are higher than most realize. Before jumping straight to endoscopy, it’s better to go with some noninvasive testing first — things like fecal calprotectin (says about real inflammation in gut), celiac serologies (screening for antibodies in the blood), H.pylori breath test (detects bacteria linked to Gastroenteritis, ulcers and long term stomach issues), pancreatic stool elastase (food digestion properly mainly fats) and other blood or stool tests that help clarify what we’re really dealing with?

➤HEART:
📍Symptoms - variable heart rate, heart burn (viz. burning pain), fluctuating BP, brain fog (viz. memory problems, difficulty focusing or concentrating, and confusion), dysautonomia (viz. fast heart rate, low blood pressure, Dizziness / lightheadedness, sound or light sensitivity), POTS (viz. heart rate and BP are not regulated effectively, palpitations, dizziness, temperature dysregulation, fainting) and fragile blood vessels. 

POTS means -

• Postural: related to the position of your body

• Orthostatic: related to standing upright

• Tachycardia: increased heart rate

• Syndrome: a group of symptoms 

POTS five subtypes are -

• Neuropathic POTS is a term used to describe POTS associated with damage to the small fiber nerves (small-fiber neuropathy). The features in neuropathic POTS, it involves -

o   Lower blood pressure and higher heart rate when standing

o   A rapid heart rate increase by ≥ 30bpm upon standing

o   Blood pooling in the lower extremities

o   Dizziness and fatigue

o   Leg discomfort, including burning or tingling sensations

o   Loss of sweating in extremities

o   Cyanosis in the feet (turning a bluish color when standing / warm) or low Venous return

o   More common after viral infection

 The treatments which can be tried are –

o   Midodrine

o   Pyridostigmine

o  Graded compression garments, including abdominal compression of 40 mmHg and leg compression of 20-30 mmHg.

• Hyperadrenergic / Adernal POTS is a term used to describe POTS associated with elevated levels of the stress hormone norepinephrine (mainly released by nerves). The features in Hyperadrenergic / Adernal POTS, it involves -

o   Increase blood pressure (≥10 mmHg) when standing

o   Higher heart rate (≥ 30bpm)  when standing

o   Excessive sweating and tremors

o   Increased anxiety and palpitations

o   More heart palpitations (viz. where you feel like that your heart skips a beat or you feel like your heart is beating out of your chest)

o   High resting heart rate (even while sitting)

o   Headaches, Migraine

o   Nausea / Vomiting

o   Increased urinary output after being upright

o   The most common comorbidity here is Mast Cell Activation Syndrome (MCAS)

The treatments which can be tried are –

o   Clonidine

o   Beta Blockers 

• Hypovolemic POTS is a term used to describe POTS associated with abnormally low levels of blood (hypovolemia). The features in hypovolemia POTS, it involves -

o   Severe fatigue and dizziness (especially in heat or when dehydrated)

o   Weakness 

o   Nausea and frequent headaches

o   Poor or decreased tolerance to exercise or upright activity

 The treatments which can be tried are –

o   Fludrocortisone / Florinef

o   Desmopressin

o   Erythropoietin

o   IV Fluids / PICC line

o   Increased salt (6-10 g) and fluids (2-3 L) to increase blood volume

o  Compression garments with at least 20-30 mm Hg pressure, including leg stockings and a pair of biker-style shorts

• Secondary POTS is a term used to describe POTS associated with another condition known to potentially cause autonomic neuropathy, such as diabetes, Lyme disease, or autoimmune disorders such as lupus or Sjögren’s syndrome.    

• Mixed Type POTS is a term used to describe features having mixed POTS subtypes.

• Deconditioning POTS features involves -

o   Exercise intolerance

o   Gradual loss of physical strength

Refractory POTS - When standard treatments fail with every single conventional medication and lifestyle mechanism being practised without finding relief, POTS is classified as refractory POTS. Please refer below after MANAGEMENT ANALYSIS for Refractory POTS (rPOTS) treatment.  

📝Management Analysis - The understanding of POTS specific subtype is  crucial and beneficial for effective management of POTS. Also, an understanding of any overlap of POTS sub types in an individual is highly important.

➤MAST CELL ACTIVATION SYNDROME (MCAS):
A type of white blood cell, found in the connective tissue throughout the body, found in every organ system including the brain, it’s part of the body’s immune response, it’s part of the body’s inflammatory response. The body’s 1st responders to perceived dangers and threats. 

📍Symptoms - They are -
1. GI symptoms — Bloating, nausea, pain, early fullness, diarrhea, constipation.

2. Pain, Inflammation, bladder irritation, and neurologic flares. 

3. Brain fog, fatigue, and migraines 

4. Neuro inflammation - The relationship between mast cells and the nervous system is bi-directional which means that mast cells influence neural function and neurons modulate mast cell activity. Mast cells are present and communicate in the Central Nervous System (CNS) which is the brain and spinal cord, and in the Peripheral Nervous System (PNS) which is the network of nerves that extends throughout the body, connecting the CNS to the rest of the body including muscles and organs. 

5. Additives present in medicine does trigger reactions that makes it feel like every medication is the problem 

📝Management Analysis - The understanding of MAST CELL ACTIVATION SYNDROME (MCAS) is crucial and beneficial for effective management of MCAS. The key important things to understand are -
1. Low Histamine Diet
2. Medication - H1 Antihistamine, H2 Antihistamine and Mast Cell Stabilizers. Please refer "EDS - Medicines | Supplements | Complementary Therapy | Management Treatments | Diet" section. Please do consult SPECIALISTS like "Allergists, Immunologists, Hematologists, Dermatologist, Gastroenterologist" in having proper medication.

3. GLP-1 (Glucagon-Like Peptide-1) treatment

4. Vagus Nerve – In MCAS, the vagus nerve influence is especially important. Dysfunction in the vagus nerve can lead to increased histamine production and other inflammatory mediators, contributing to symptoms such as digestive problems, anxiety, and sensitivity to cold. The vagus nerve significantly influences mast cell activity through mechanisms that include direct stimulation and modulation of inflammatory responses, emphasizing the importance of this interaction for overall health and disease management.

                                           The vagus nerve plays a significant role in modulating mast cell activity. Vagus nerve stimulation has shown to regulate mast cell degranulation, which can alleviate damage to the BBB (blood-brain barrier) and intestinal barrier following ischemic stroke. This modulation is part of the micro biota-gut-brain axis, indicating a complex interaction between the nervous system and the immune system. The vagus nerve can influence mast cell behavior through the parasympathetic nervous system which is crucial for controlling inflammation and maintaining mast cell activity within a balanced state. This system helps to calm the body, allowing for rest and digestion, and is essential for managing the inflammatory response.

5. Environment, Food and Lifestyle - By having ambient environmental factors (Temperature 10°C - 20°C, Air Quality Index (AQI) < 100, Moderate Humidity, Avoiding public gatherings), food (as mentioned in DIET section) and life style (No anxiety, no depression and no stress). 

➤NECK:
📍Symptoms - neck pain, forward head posture postural issue (viz. every inch the head moves forward, the load on the neck increases and results into pain), heavy head or bobblehead (viz. head feeling too heavy for the body to support) and craniocervical instability (CCI). 

➤NEURO:
📍Symptoms - regular body pain or chronic, widespread pain, fatigueness, allergic conditions, lower back pain, pain in legs, emotional dysregulation (viz. difficulties in managing the intensity, duration, or expression of emotions or obsessive-compulsive disorder or negative feeling,  muscle pain and stiffness , fibromyalgia (viz. pain and tenderness throughout your body), MCAS (Mast Cell Activation Syndrome) and reactive hypoglycemia (viz. blood sugar (glucose) level is lower than the standard range that occurs most often post meal or physical activity or hot weather or  showering). 

➤NOSE:
📍Symptoms - thin nose, tongue touch the tip of your nose. 

➤ORTHO:
📍Symptoms - joints dislocations or recurrent joint dislocations (viz. displacement of a bone from its natural position in the joint), sub-laxation (viz. significant structural displacement), difficulty in sitting still, shoulder Instability (viz. frequent dislocations due to ligament laxity), elbow instability (viz. joint hypermobility leads to subluxations), wrist instability (viz. frequent sprains and difficulty with gripping), thumb and finger joint Issues (viz. hyperextension and instability in fingers and thumb), thoracic outlet syndrome (viz. nerve compression causing arm pain and numbness), costochondritis (viz. inflammation of the cartilage connecting the ribs to the sternum, causing chest pain), slipping rib syndrome (viz. instability of the lower ribs causes pain, clicking, and nerve impingement.), spinal instability and scoliosis (viz. scoliosis and spinal instability cause back pain and deformity), sacroiliac joint dysfunction (viz. instability or misalignment of the sacroiliac joints, which connect the pelvis to the spine), hip dysplasia and instability (viz. loose hip joints cause dislocations and early arthritis), hip micro-instability (viz. subtle instability in the hip joint causing pain), knee instability (viz. knee joint laxity leading to patellar dislocations), shin splints (medial tibial stress syndrome) (viz. pain along the inner edge of the shinbone, often due to overuse or biomechanical abnormalities), ankle instability (viz. frequent sprains due to ligament laxity), foot issues (flat feet, bunions) (viz. flat feet and bunions causing pain and gait issues) and fascia-related issues (viz. loose or weak fascia leading to instability and pain). 

➤PHERIPHERAL NERVE:
📍Symptoms - peripheral nerve compression (viz. nerve compression due to joint instability, such as carpal tunnel or tarsal tunnel syndromes).

➤RESPIRATORY:
📍Symptoms - shortness of breath (viz. dyspnea), being given an inhaler by doctor to help in breathing, resistance in having local anesthesia, noisy breathing, difficulty with deep inhalation, inspiratory thoracic pain, chest tightness, and breathlessness with exertion. 

➤SKIN:
📍Symptoms - easy bruising, fragile or thin skin (viz. blisters and tears easily), soft and hyper extensible skin (viz. it extends easily and snaps back after release), increased bleeding and delayed wound healing, angioedema (viz. swelling in the face, lips, tongue, hands, feet, or genitals). 

➤THROAT:
📍Symptoms - Throat pain (viz. voice problems (dysphonia) such as hoarseness, loss of voice, or creaky/dry vocal quality; speaking problem; muscles become weak or uncoordinated over time), hypothyroidism (viz. thyroid gland doesn’t make or release enough hormone into your bloodstream),  chronic sore throats, sinus infections, vocal cord dysfunction.

➤URO-GENITAL:
📍Symptoms - pelvic issues, prolapse, endometriosis, adenomyosis, dysmenorrhea (painful periods), dyspareunia (painful intercourse),  menorrhagia (heavy periods) and pain or urge to urinate.