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Diana Driscoll, O.D. I disclose the following financial relationship: Other research support: Optos Plc.

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Presentation on theme: "Diana Driscoll, O.D. I disclose the following financial relationship: Other research support: Optos Plc."— Presentation transcript:

1 Diana Driscoll, O.D. I disclose the following financial relationship: Other research support: Optos Plc

2 Dr. Diana Driscoll Therapeutic Optometrist Special Interest in Disorders of Connective Tissue www.Prettyill.com

3 Ehlers-Danlos Syndrome (defective collagen resulting in loose joints, fragile and leaky vessels, permeable blood-brain-barrier) Autonomic dysfunction (“POTS”: Postural Orthostatic Tachycardia Syndrome), also known as dysautonomia Mast cell disease CCSVI (treated with angioplasty) One brain lesion, and developing symptoms of Multiple Sclerosis

4 Overlap between Ehlers-Danlos Syndrome (EDS) and Multiple Sclerosis (MS) More people with EDS go on to develop MS than in the general population. There is a 10-11 times increased prevalence of EDS in MS patients compared to the general population (“Ehlers-Danlos Syndrome and multiple sclerosis: a possible association” – PMID 18208891)

5 Clinical Trial (NCT01356134): “Vascular Fundus Changes in Patients With High Probability of Chronic Cerebrospinal Venous Insufficiency (CCSVI)” Could CCSVI cause a back-up of venous blood that could show up in the ocular fundus, not only given credence to CCSVI, but possibly acting as an inexpensive screening tool for potential CCSVI patients?

6 Normal fundus – note optic nerve, macula, arteries, veins, 2/3 A/V ratio is average, fairly smooth caliber, especially of veins.

7 Capillaries of the retina Central Retinal Vein Superior Ophthalmic Vein Cavernous Sinus Inferior & Superior Petrosal Sinuses Sigmoid Sinus Internal Jugular Vein

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11 Cavernous Sinus Engorgement of the cavernous sinus, applying pressure to some of these cranial nerves (intermittently) may be an indication of CCSVI (we’d see symptoms wax and wane).

12 Symptoms would include partial and intermittent paresis of an eye muscle, causing temporary diplopia, change in depth perception when looking at different angles, sinus or eye pain. Take paralysis of muscles and absence of sensation, and dial it back to partial, intermittent, episodic and even positional symptoms. May develop into a venous stasis retinopathy secondary to a low level cavernous sinus “thrombosis”. PMID: 15756573 “Cavernous sinus thrombosis elicited by a central retinal vein venous stasis retinopathy”

13 “ Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life” (NCT01367977) Retrospective analysis of head circumferences of EDS patients who developed dysautonomia later in life indicated that 100% of study participants had External Communicating Hydrocephalus in the first 15 months of life (prior to closure of the sutures of the skull).

14 Compared to % of normal, CDC 2008

15 Quick review of CSF dynamics Acetazolamide. What is missing?

16 Mast cell disease Causes leaky, weak, varicose vessels when they release: histamine, tryptase, prostaglandins, leukotrienes and cytokines. We know mast cells are related to M.S. “Elevated mast cell tryptase in cerebrospinal fluid of MS patients.” PMID: 7818259 “Mast cells, T cells, and inhibition by luteolin: implications for the pathogenesis and treatment of M.S.” PMID: 17713031 “Human mast cells stimulate activated T cells: implications for M.S.” PMID: 19076366

17 Abnormal mast cells in mast cell disease: Lungs, liver, GI tract (gluten intolerance, IBS anyone?), lymph nodes, skin, kidneys, eyes (granulomatous uveitis, pars planitis, incredible dryness and itching), and the BRAIN. Triggers for mast cell degranulation include: heat, exercise, hormones, positive or negative emotions or stress, certain foods, their colorings/flavorings, alcohol, caffeine, certain smells, etc. Tying it all together:

18 In brain: brain fog, dementia, changes in personality, bipolar presentation (my hypothesis), extreme fatigue. Change collagen 1 to collagen 3, causing varicosities and CCSVI. Mast cells love to hide out in the CHOROID PLEXUS Waste products accumulate around the brain due to poor drainage of venous blood and CSF (and increased production of CSF), thus stimulating the inflammatory cascade.

19 Result: Patients with slightly high levels of CSF and venous blood stagnation We’ve tied together: mast cell disease, reasons for CCSVI to occur and involve the conversion of collagen 1 to collagen 3; why BBB is leaky, what is happening to the arachnoid villi, the cause of granulomatous uveitis and pars planitis in M.S. patients, why M.S. symptoms can wax and wane, the cause of extreme fatigue and brain fog/dementia, G.I. symptoms, numerous other ocular symptoms; Cause of optic neuritis

20 Astrocytes: Intertwined with neurons, axons, myelin and brain capillaries During development, they induce endothelial cells to form tight junctions (BBB) Pro-inflammatory cytokines are produced by T-cells, astrocytes and microglial cells. After cytokine release, immune cells invade the brain and activate astrocytes, which results in apoptosis and gliosis. Compromise of BBB fluid in interstitial space vasogenic cerebral edema increase in ICP collapse in brain capillaries arrest of cerebral perfusion damage to astrocytes, damage to neurons and myelin

21 Final Considerations Should we screen M.S. patients for EDS (90% are never diagnosed). Consider a trial of acetazolamide to reduce ICP for symptom reduction. Consider acetazolamide prior to CCSVI angioplasty to allow influx of oxygenated blood into the brain, potentiating the effects of angioplasty. Consider mast cell disorders in M.S. patients. Because they may not have cutaneous signs, a trial with H1 and H2 inhibitors would be fast and inexpensive. Anyone who may have mast cell disorders need to be pretreated with H1 and H2 inhibitors, and perhaps PPI’s, Sodium Cromolyn, and low level steroids prior to angioplasty. Consider patient rest and avoidance of mast cell triggers as vital treatment protocol post-angioplasty, as the procedure itself may cause mast cell degranulation. Risk of anaphylaxis with general anesthesia and/or radiocontrast media with mast cell disorders (release of tryptase)

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23 For more information, all clinical trials, handouts, videos, please go to Pretty ill.com Thank you Diana Driscoll, O.D.


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