Diana Driscoll, O.D.
I disclose the following financial
relationship: Other research
support:
Optos Plc
Dr. Diana Driscoll
Therapeutic Optometrist
Special Interest in Disorders of
Connective Tissue
www.Prettyill.com
•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
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)
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?
Normal fundus – note optic nerve, macula, arteries,
veins, 2/3 A/V ratio is average, fairly smooth caliber,
especially of veins.
Capillaries of the retina
Central Retinal Vein
Superior Ophthalmic Vein
Cavernous Sinus
Inferior & Superior Petrosal Sinuses
Sigmoid Sinus
Internal Jugular Vein
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).
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”
“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).
Compared to % of normal, CDC 2008
100
90
80
70
60
50
head circum
40
weight
30
length
20
10
0
Quick review of CSF dynamics
Acetazolamide.
What is missing?
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
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:
• 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.
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
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
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)
For more information, all clinical trials,
handouts, videos, please go to
Prettyill.com
Thank you
Diana Driscoll, O.D.