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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 Therapeutic Optometrist
Dr. Diana Driscoll Therapeutic Optometrist Special Interest in Disorders of Connective Tissue

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 times increased prevalence of EDS in MS patients compared to the general population (“Ehlers-Danlos Syndrome and multiple sclerosis: a possible association” – PMID )

5 Clinical Trial (NCT ): “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 Internal Jugular Vein Capillaries of the retina Central Retinal Vein
Superior Ophthalmic Vein Cavernous Sinus Inferior & Superior Petrosal Sinuses Sigmoid Sinus Internal Jugular Vein

8 O.S. and O.D. 53 yr old female with CCSVI
Note tortuous and beaded vein in O.D. ; poor A/V ratio in both eyes Not unlike Dr. Simka’s research with OCT – one eye is worse.

9 Female, age 47, Same eye; note venous irregularity in caliber, stenosis, and see how narrow arteries are. Consider the perfusion coefficient – venous stenosis leading to inability to get oxygenated arterial blood into brain and retina?

10 42 yr old female – quite disabled
42 yr old female – quite disabled. Ignore large vitreous floater and fundus issues related to myopia. Small arteries and veins. 1) is this poor perfusion the reason so many CCSVI patients notice improved vision immediately upon angioplasty? 2) is this a stroke waiting to happen? 3) If this is what perfusion looks like in her fundi, what does perfusion look like in her brain?

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: “Cavernous sinus thrombosis elicited by a central retinal vein venous stasis retinopathy” IIIn: Oculomotor nerve: damage can cause the eye to go down and out, lid may droop (ptosis), pupil may be a bit larger on that side; IVn: Trochlear nerve: innervates the superior oblique – damage can make it more difficult to look down, and the patient may have vertical diplopia (double vision) V1n: Ophthalmic nerve. First branch of the trigeminal nerve. Sensory nerve of the cornea, ciliary body, and iris; to the lacrimal gland and conjunctiva; to the part of the mucous membrane of the nasal cavity; and to the skin of the eyelids, eyebrow, forehead and nose. V2n: Maxillary nerve: Second branch of the trigeminal nerve. It comprises the principal functions of sensation from the maxillary, nasal cavity, sinuses, the skin between the palpebral fissure and the mouth, the palate and subsequently that of the mid-face VIn: Abducens nerve: controls the lateral rectus – may have difficult turning the eye temporally. (SO4 LR6 All the Rest 3) Not a true “thrombosis”, but a “stenosis”. I experience pulsatile vision, especially in a.m. with conj injection that is not reversable with meds. I also notice intermittent and partial diplopia

13 “Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life” (NCT ) 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). Clinical trial with Ehlers-Danlos patients and how it may relate to Multiple Sclerosis Sense of pressure in your head? Occipital headache or neckache, radiating to the tops of your shoulders? Squishy ears/Eustachian tubes? Do you have autonomic dysfunction?

14 Compared to % of normal, CDC 2008
Hypothesis: “Benign External Hydrocephalus” is not benign at all. Many neurological symptoms in these patients, including delayed motor development, tremors, cataplexy, delayed speech, stuttering, etc. Do M.S. patients have a “low-level” of high ICP also? If not from birth, when and why did it start? What symptoms can it cause? Decreased cerebral blood flow secondary to the resulting cerebrovascular resistance when venous or CSF outflow is inhibited. Cerebral blood flow is equal to the cerebral perfusion pressure divided by the cerebrovascular resistance.

15 Quick review of CSF dynamics
Acetazolamide may have a place in MS tx: is used to treat ischemic strokes, which often causes brain swelling. Even TIA’s can cause brain swelling. How it has been helping patients with dysautonomia and Ehlers-Danlos (and how they often develop MS) 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: “Mast cells, T cells, and inhibition by luteolin: implications for the pathogenesis and treatment of M.S.” PMID: “Human mast cells stimulate activated T cells: implications for M.S.” PMID:

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 Change collagen 1 to collagen 3, causing varicosities and CCSVI.
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. Dr. Sclafani, Dr. Gabbiani. Thank you for pics. Choroid plexus mast cells degranulate, stimulating production of CSF. (Now we have increased production with poor drainage, and possible CCSVI with poor venous drainage).

19 what is happening to the arachnoid villi,
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 Arachnoid villi, which would normally help drain the CSF, are damaged not only by infection, viruses and viral antibodies, but by long term high CSF pressure. Due to the perfusion pressure, these patients have difficulty getting fresh, oxygenated blood into their brains.

20 Intertwined with neurons, axons, myelin and brain capillaries
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 Acetazolamide – can help reduce this cycle by decreasing fluid in the interstitial space, decreasing cerebral edema, decreasing ICP by decreasing CSF production (and is a mild diuretic), decrease cerebral perfusion.

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) New study – will likely use multiple centers Theory on cause and tx of optic neuritis Examples of mastocytosis causing change in collagen, cutis laxa Cutis laxa patients with idiopathic anaphylaxis Need change in criteria for mastocytosis Acetazolamide reduces brain edema (ex: in areas after a stroke). With constant alteration of CSF pressure, brain edema is possible. The Elephant Study Answering many objections to CCSVI: Cytokines influence HPA axis – as a hormone Venous sheathing – what I believe that is Why rapid rise in CSF causes transient flushing New proposed treatment for pars planitis and uveitis in M.S. patients

22 IR’s: if in doubt, always use what you KNOW works. 

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

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