EHLERS-DANLOS SYNDROME & DYSAUTONOMIA - … · EHLERS-DANLOS SYNDROME & DYSAUTONOMIA Presented By...
Transcript of EHLERS-DANLOS SYNDROME & DYSAUTONOMIA - … · EHLERS-DANLOS SYNDROME & DYSAUTONOMIA Presented By...
EHLERS-DANLOS
SYNDROME &
DYSAUTONOMIA
Presented By
Lauren Stiles, JD
President & Co-Founder
New York Institute of Technology
December 8, 2017
Most studies are on hEDS
hEDS patients have more autonomic symptoms
than other EDS types
49% of hEDS patients have POTS, 31% have OI,
20% have normal hemodynamics1
In hEDS, autonomic dysfunction is classified as:
mild (47%)
moderate (33%)
Severe (3.3%)2
HOW MANY PEOPLE WITH EDS
HAVE AUTONOMIC DYSFUNCTION?
1 Celletti, C., Camerota, F., Castori, M., et al., 2017. Orthostatic intolerance and postural orthostatic
tachycardia syndrome in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type:
Neurovegetative dysregulation or autonomic failure? BioMed Res Int., 9161865.
2 De Wandele, I., Rombaut, L., Leybaert, L., et al., 2014b. Dysautonomia and its underlying mechanisms
in the hypermobility type of Ehlers-Danlos syndrome. Semin Arthritis Rheum. 44(1) 93-100.
Chronic
Migraine
Reflex
Syncope
Interstitial
Cystitis
Complex
Regional Pain
Syndrome
POTS/OI
Fibromyalgia
Syndromic
(Possibly Disease Based?)Disease-Based
Dysautonomias
PeripheralCentral
Pure
Autonomic
Failure
Multiple
System Atrophy
Small Fiber
Neuropathies
Parkinson’s/
Lewy Body
Dementias
DiabetesMetabolic
MitochondrialGenetic
Inflammatory ImmuneAdapted from Chelimsky T, Robertson D, Chelimsky G.
Disorders of the autonomic nervous system. In Daroff:
Bradley’s Neurology in Clinical Practice. 6th ed. Philadelphia,
PA; Elsevier: chap 77.
Chronic
Fatigue
Syndrome
IBS/CIPO/
Gastroparesis
HR increase of ≥30bpm from supine to standing within
10 minutes (≥40bpm for ages 12-18)
In the absence of orthostatic hypotension (defined
as ≥20/10mmHg drop within 3 min. of standing)
Symptoms of orthostatic intolerance lasting ≥6
months
Symptoms exacerbated by standing and improved
with recumbency
Absence of other overt causes of orthostatic
symptoms or tachycardia
POTS: DIAGNOSTIC CRITERIA
Pronounced orthostatic
tachycardia
Palpitations
Shortness of breath
Lightheadedness/pre-syncope
Syncope (20-30% with
overlapping NCS)
GI motility (33% too fast, 33%
too slow)
Nausea
Bladder dysfunction (17%)
POTS SYMPTOMS
Sensitivity to heat/cold
Sensitivity to l ight/sounds
Migraines
Profound fatigue
Weakness
Tremulousness
Exercise intolerance
Dependent acrocyanosis
Flushing
Increased allergies
Acrocyanotic legs after a few minutes of standing
Prolonged blanching/delayed capillary refill
DEPENDENT ACROCYANOSIS
Common form of orthostatic intolerance
US estimates, 500K-3M
Newer estimates are in the higher range
For comparison…
MS: 400K US estimate
Parkinson’s: 1M US estimate
Mayo Clinic estimates 1 in 100 teens (~500K)
About half of all patients have onset in adulthood
EPIDEMIOLOGY OF POTS
POTS IS NOT A
“TEENAGE SYNDROME”
1 Stiles L, Ross A. Physician
Patient Interaction in Postural
Orthostatic Tachycardia
Syndrome. Dysautonomia
International. 2014.
ORTHOSTATIC PAIN
Orthostatic Headaches
Blood volume dysregulation
Chiari
CSF flow issues
CSF leak(s)
Check out Dr. Kinsella’s 2017 Conference Lecture on our Vimeo page:
www.vimeo.com/dysautonomia
POTS Controls P value
(n=65) (n=92)
Endometriosis 20% 5% .009
Uterine fibroids 25% 10% .015
Galactorrhea 9% 0% .004
Ovarian cysts 43% 13% <.001
Dysfunctional 14% 4% .042Bleeding
GYNECOLOGICAL
ABNORMALITIES IN POTS
Peggs KJ, Nguyen H, Enayat D, Keller NR, Al-Hendy A, Raj SR.
Gynecologic disorders and menstrual cycle lightheadedness in
postural tachycardia syndrome. Int J Gynaecol Obstet.
2012 Sept; 118(3): 242-246.
0 20 40 60 80
anxiety
stress from work/school/family
"all in your head"
depression
panic disorder
somatoform disorder
conversion disorder
munchausen's syndrome
factitious disorder
other mental/psychological illness
none of the above
Percent Total (%)
83% of POTS patients
given at least one psych
label prior to diagnosis
BEFORE your POTS diagnosis, were you ever told by a doctor that
your symptoms were due to the following diagnoses? Please
check all that apply:1
Other data suggests this is largely misdiagnosis…
Mayo 1992: Psychological domains similar amongst healthy
controls, CHF, COPD and POTS.
Vanderbilt 2009: POTS patients slightly less anxious than
general population, slight increase in mild depression .
Mayo 2016: mean mental composite score normal in
pediatric POTS.
When psychological comorbidity is present, it should be
addressed. Patients are often afraid to ask for help .
MISDIAGNOSIS
10g salt daily (3876mg sodium)
2-3L of hydrating fluids daily (avoid sugary drinks)
Medical compression stockings
Abdominal binders
Recumbent exercises
Good sleep habits
Learning about your illness can help you manage
symptoms better, and reduces fear of the unknown
Avoid heat, prolonged standing, hot showers, alcohol
Healthy diet
Cooling vests
POTS: NON-PHARMA TREATMENT
Avoid orthostatic stress during exercise until patient
builds up exercise tolerance, can take MONTHS/YEARS
Rowing,a recumbent bike, swimming, floor/core
Start SLOW and LOW
EDS - work with PT to stabilize & protect your joints
EXERCISE THERAPY
Vasoconstrictors
Midodrine
Octreotide
Droxidopa (Northera)
Phenylephrine (Sudafed PE)
Blood volume expansion
Fludrocortisone
Desmopressin
EPO
IV Saline
Beta blockers (less is more!)
Ivabradine
Mestinon
POTS: PHARMA TREATMENT
If mast cell dysfunction is
present:
H1/H2 blockers
Cromolyn (Gastrocrom)
Omalizumab (Xolair)
Ketotifen
Quercitin
Vitamin C
No FDA approved
treatment for POTS.
Maybe?
Assumption...
stretchy blood vessels due to EDS collagen probelms leads to
blood pooling, causing POTS
Reality.. .
No research documenting collagen deficits in hypermobile EDS
are causing stretchy blood vessels
No research showing that EDS/POTS patients have stretchier
blood vessels than non-EDS/POTS
Patients need answers backed by solid research that leads to
better treatments – we deserve more than assumptions!
IS EDS/POTS DIFFERENT
THAN NON-EDS/POTS?
AUTOIMMUNITY
SMALL FIBER NEUROPATHY
HYPOVOLEMIA
HYPERADRENERGIC STATE
HYPERTENSION
MAST CELL DYSFUNCTION
PEOPLE WITH EDS/POTS WHO RECOVER OR IMPROVE
“STRETCHY VEINS”
DON’T EXPLAIN…
Factors suggesting autoimmunity plays a role in POTS:
Female predominant condition (80-90% female)
50% have a post-viral onset
50% have small-fiber neuropathy
Increased rate of estrogen dependent co -morbidities
Mast cell abnormalities known to occur in early phases
of many autoimmune diseases
POTS & AUTOIMMUNITY
Dr. Francomano reported a high rate of autoimmunity
in her EDS patients in 2006, specifically:
RA/juvenile RA, lupus, Sjogren’s
12/72 consecutive EDS patients had one of these
autoimmune diseases.
7/72 had Raynaud’s, which is often seen in
autoimmune disorders.
“This raises the possibility that abnormalities of the
extracellular matrix might contribute to the
development of autoimmunity in the presence of other
genetic or environmental influences.”
EDS & AUTOIMMUNITY
Gustafson, Griswold, Burchett, Sherman, et al. Do abnormalities in the extracellular
matrix lead to autoimmune disorders? (2006) ASHG Annual Meeting; Program No. 608.
IRB approved structured online survey
3300 POTS patients, 400 variables
Patients from more than 15 countries
Largest POTS study to date – follow up surveys
in progress, plans to link to clinical data
THE BIG POTS SURVEY
2 Satish R. Raj MD MSCI, Lauren E. Stiles JD, Brett H Shaw MSc, Elizabeth A. Green MD, Cindy A. Dorminy MEd,
Cyndya A. Shibao MD MSCI, Luis E. Okamoto MD, Emily M. Garland PhD MSCI, Alfredo Gamboa MD MSCI, Andre
Diedrich MD PhD, Italo Biaggioni MD, David Robertson MD. The Face of Postural Tachycardia Syndrome (POTS): A
Cross-Sectional Community-Based Survey. Heart Rhythm 2016: 12 (5S):xx-xx (abstr) [in press].
Big POTS Survey results…
16% of all POTS patients report a confirmed
autoimmune disease.
18% of POTS patients also diagnosed with EDS report a
confirmed autoimmune disease.
Most commonly Hashimoto’s, Sjogren’s, lupus, celiac.
EDS, POTS & AUTOIMMUNITY
Initial 1993 description from Mayo suggested partial immune mediated neuropathy3
2012 Mayo Clinic: auto-immunoreactive IgGs to 40 different cardiac membrane proteins found in POTS 4
2014 Univ. of Oklahoma/Vanderbilt: 100% have adrenergic receptor antibodies (n=14),5 larger cohort in progress with EDS screening…
2014 Children’s Heart Institute: 15% of POTS subjects had significant expansion of double negative T cells, this correlated to the presence ofserum autoantibodies (n=60)6
POTS & AUTOIMMUNITY
VASOMOTOR NERVES & COLLAGEN
VIP
CD31
Col IV50 μm
• VIP-
Sympathetic
cholinergic
• CD31-
Vascular
marker
• Col IV-
Basement
membrane
Image courtesy of Dr. Roy Freeman, Harvard Medical School.
2015 SUNY Buffalo: 20% have comorbid autoimmune disease, 33% have commonly tested autoimmune markers (n=100 )7
2015 Mayo: 45% have thyroid and/or neural antibodies (n=33) compared to healthy controls (4.4%), 8 larger cohort in progress…
2015 Vanderbilt: increased IL -6, but normal CRP, in POTS9
2016 Stiles/Gudesblatt: 41% idiopathic dysautonomia patients with dry eyes or dry mouth have novel “early” Sjögren's antibodies SP-1, PSP, CA-6 (including 6 of 10 POTS patients in the study) (n=95)10
2016 UT Southwestern: Muscarinic receptor antibodies, 87.5% M1, 68.75% M2, 12.5% M3 (n=16), M1 & M2 statistically significant compared to 20 controls, M1 correlatedto cognitive impairment,11 larger cohort inprogress with EDS screening…
POTS & AUTOIMMUNITY
2016 Univ Oklahoma/Lund University: Swedish cohort
of 17 POTS, 7 VVS, and 11 healthy controls. All of the
POTS subjects had at least one type of adrenergic
receptor antibody (12 had beta-2, 11 had beta-1, 8 had
alpha-1). None of these antibodies were found in VVS
or controls.12
More research in progress...
POTS & AUTOIMMUNITY
AUTOIMMUNITY
SMALL FIBER NEUROPATHY
HYPOVOLEMIA
HYPERADRENERGIC STATE
HYPERTENSION
MAST CELL DYSFUNCTION
PEOPLE WHO RECOVER/IMPROVE
“STRETCHY VEINS”
DON’T EXPLAIN…
SMALL FIBER NEUROPATHY
Different types of small fiber nerves: sensory, sudomotor, vasomotor, etc.
Sudomotor dysfunction found in 65% of EDS patients
Sudomotor dysfunction found in 50% of all POTS patients
Vasomotor neuropathy/POTS research in progress at Harvard
Small fiber nerves help regulate blood vessel constriction
When nerves are damaged, blood vessels can’t constrict
“STRETCHY VEINS”
DON’T EXPLAIN…
AUTOIMMUNITY
SMALL FIBER NEUROPATHY
HYPOVOLEMIA
HYPERADRENERGIC STATE
HYPERTENSION
MAST CELL DYSFUNCTION
PEOPLE WHO RECOVER/IMPROVE
“STRETCHY VEINS”
DON’T EXPLAIN…
HYPOVOLEMIA
Almost all POTS patients have low blood volume
Plasma and red blood cells are equally low
Plasma volume controlled by aldosterone
Many other factors involved in regulating blood volume
Partial loss of sympathetic nerves in kidney suggested as
possible reason for low aldosterone (perhaps adrenergic
antibodies?)
Iron storage deficiency common in POTS
“STRETCHY VEINS”
DON’T EXPLAIN…
AUTOIMMUNITY
SMALL FIBER NEUROPATHY
HYPOVOLEMIA
HYPERADRENERGIC STATE
HYPERTENSION
MAST CELL DYSFUNCTION
PEOPLE WHO RECOVER/IMPROVE
“STRETCHY VEINS”
DON’T EXPLAIN…
HYPERADRENERGIC STATE
Almost all POTS patients have elevated plasma NE
Some more than others
Experts don’t agree on a definition for what constitutes
“hyperadrenergic” POTS
Causes of elevated plasma NE:
autonomic neuropathy
hypovolemia
anxiety
NET: mutations, epigenetic changes & mRNA variants
antibodies?
do stretchy veins contribute?
“STRETCHY VEINS”
DON’T EXPLAIN…
AUTOIMMUNITY
SMALL FIBER NEUROPATHY
HYPOVOLEMIA
HYPERADRENERGIC STATE
HYPERTENSION
MAST CELL DYSFUNCTION
PEOPLE WHO RECOVER/IMPROVE
“STRETCHY VEINS”
DON’T EXPLAIN…
HYPERTENSION IN POTS
During tilt testing:
1/3 of POTS patients drop BP (not to the point of OH)
1/3 of POTS patients maintain normal BP
1/3 of POTS patients increase BP
Some EDS/POTS patients increase BP on tilt
Some EDS/POTS patients experience hypertension even
sitting or laying down, or in response to stressors
“STRETCHY VEINS”
DON’T EXPLAIN…
AUTOIMMUNITY
SMALL FIBER NEUROPATHY
HYPOVOLEMIA
HYPERADRENERGIC STATE
HYPERTENSION
MAST CELL DYSFUNCTION
PEOPLE WHO RECOVER/IMPROVE
“STRETCHY VEINS”
DON’T EXPLAIN…
MAST CELL ACTIVATION SYNDROME
No clear answer on % overlap between POTS/EDS/MCAS
Vanderbilt 2005: first recognition of POTS/MCAS overlap
Mayo 2014: many POTS patients tested positive for at least one MCAS
biomarker
NIH 2014: approx. 40 families with hereditary tryptase mutations.
POTS/EDS/MCAS occur in some of these families.
associated with elevated baseline tryptase, which Mayo suggests is found in
less than 1 in 1000 POTS patients
likely just a risk factor, not the “cause” of “the trifecta of EDS/POTS/MCAS”
Univ. Toronto 2015: POTS, EDS, MCAS may frequently overlap
Prior research in Germany: andrenergic antibodies cause mast cells to
mature faster and degranulate more readily (these antibodies reported in
POTS)
More studies in progress…
“STRETCHY VEINS”
DON’T EXPLAIN…
AUTOIMMUNITY
SMALL FIBER NEUROPATHY
HYPOVOLEMIA
HYPERADRENERGIC STATE
HYPERTENSION
MAST CELL DYSFUNCTION
PEOPLE WHO RECOVER/IMPROVE
“STRETCHY VEINS”
DON’T EXPLAIN…
PEOPLE WHO RECOVER/IMPROVE
There are some people who have POTS/EDS who see
significant improvement in their POTS symptoms over time,
and some who considered themselves recovered from POTS.
Then still have EDS, so something else must have caused their
POTS.
One example: Very hypermobile adolescent female, athletic/active
Acute onset POTS after a cold
Homebound, almost bedridden
Diagnosed with EDS and POTS
Had the adrenergic antibodies (Univ Oklahoma)
Received IVIG as part of a research study
Antibodies reduced, POTS symptoms improved, but not 100%
She still has EDS
“STRETCHY VEINS”
DON’T EXPLAIN…
OUTCOMES IN ADOLESCENT POTS
19.2%
51.2%
15.7%
8.7%
3.5%
1.7%
Symptoms completely resolved
Symptoms persist, severity better
Remitting and relapsing
Symptoms persist, severity same
Symptoms persist, severity worse
Not reported
Adapted from: Bhatia R, Kizilbash SJ, Aherns SP,
Killian JM, Kimmes SA, Knoebel EE, Muppa P,
Weaver AL and Fischer PR. Outcomes of Adolescent-
Onset Postural Orthostatic Tachycardia Syndrome.
The Journal of Pediatrics. [Article in Press]. DOI:
dx.doi.org/10.1016/j.jpeds.2016.02.035.
Does Screening for Ehlers-Danlos Syndrome in Postural Tachycardia Syndrome Matter? Insights from a Cross-Sectional Community-Based Survey
Satish R. Raj MD MSCI1,3, Lauren E. Stiles JD2, Brett H. Shaw MSc1, Jessica Ng BSc1, Elizabeth A.
Green MD, Cyndya A. Shibao MD MSCI3, Luis E. Okamoto MD3, Emily M. Garland PhD MSCI3,
Alfredo Gamboa MD MSCI3, Andre Diedrich MD PhD3, Italo Biaggioni MD3 and David Robertson
MD3
1Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada; 2Dysautonomia International, East Moriches, NY, USA; 3Autonomic Dysfunction Center, Vanderbilt
University, Nashville, TN, USA
HEART RHYTHM SOCIETY 2017 ABSTRACT
STUDY AIM
To characterize the similarities
and differences between POTS
patients with and without EDS
SR Raj et al., Heart Rhythm Society Scientific Sessions, Chicago IL, May 2017
METHODS
• Cross-sectional, web-based survey
• “Diagnosis and Impact of POTS” study
• Vanderbilt IRB Approval
• Survey l inks posted to Dysautonomia International website &
social media channels
• Survey data collected July 2015 - October 2016
SR Raj et al., Heart Rhythm Society Scientific Sessions, Chicago IL, May 2017
RESULTS
• > 15 countries (primarily USA)
• Physician diagnosed POTS = 3389 patients
Female Male0
20
40
60
80
100
Perc
en
t (%
)
EDS No EDS0
20
40
60
80
100
Perc
en
t (%
)
Female vs. Male EDS vs. Non-EDS
SR Raj et al., Heart Rhythm Society Scientific Sessions, Chicago IL, May 2017
RESULTS – ORTHOSTATIC
No dif ferences in orthostatic symptom reporting between
POTS patients with and without EDS
Lighth
eadedness
Syncope
Tachycardia
Palpita
tions
Dyspnea0
20
40
60
80
100
Per
cent
(%)
EDSNo EDS
SR Raj et al., Heart Rhythm Society Scientific Sessions, Chicago IL, May 2017
RESULTS – SYMPTOMS ONSET
POTS patients with EDS
were less likely to report symptom onset after a triggering
event,
had a greater tendency to report dealing with POTS-like
symptoms for most of life
EDS No EDS0
20
40
60
80
100
Perc
en
t (%
)EDS No EDS
0
20
40
60
80
100
Perc
en
t (%
) p=0.009 p<0.001
Triggering Event Lifelong Symptoms
SR Raj et al., Heart Rhythm Society Scientific Sessions, Chicago IL, May 2017
RESULTS – GI
GI symptoms are reported significantly more often by
patients with EDS
EDSNo EDS
Constip
ation
Vomiti
ng
Stom
ach pain
Heart
burn/G
ERD
Dysphagia
0
20
40
60
80
100
Perc
en
t (%
) p=0.003
p<0.001
p<0.001p<0.001
p<0.001
SR Raj et al., Heart Rhythm Society Scientific Sessions, Chicago IL, May 2017
RESULTS – SENSORY
Sensory neuropathic symptoms reported significantly
more often in patients with EDS
EDSNo EDS
Skin b
urnin
g
Hand tinglin
g
Hand burn
ing
Hand num
bness
Cold h
ands0
20
40
60
80
100
Per
cen
t (%
)
p<0.001
p<0.001
p<0.001
p<0.001
p=0.001
SR Raj et al., Heart Rhythm Society Scientific Sessions, Chicago IL, May 2017
Sensory neuropathic symptoms reported significantly
more often in patients with EDS
EDSNo EDS
SR Raj et al., Heart Rhythm Society Scientific Sessions, Chicago IL, May 2017
RESULTS – SENSORY
Facial t
inglin
g
Facial n
umbness
Foot tin
gling
Foot num
bness
Cold fe
et0
20
40
60
80
100
Per
cen
t (%
)
p<0.001
p<0.001p<0.001
p<0.001p=0.001
BIG PICTURE
• There is a lot of neuropathy in EDS.
• We need detailed pathology studies to
know why.
Is the collagen in/around the nerve fibers impaired?
Are the nerves damaged by an inflammatory or
immune mediated process?
Some other reason?
• Why do EDS patients have
small fiber neuropathy?
CONNECT WITH US…
www.dysautonomiainternational.org
www.facebook.com/dysautonomiainternational
www.vimeo.com/dysautonomia
Twitter: @Dysautonomia
~ THANK YOU ~
3 . S c h o n d o r f R , L o w P A . I d i o p a t h i c p o s t u ra l o r t h o s ta t i c t a c h y c a r d i a s y n d r o m e : a n a t t e n u a t e d f o r m o f a c u t e p a n d y s a u t o n o m i a ? N e u r o l o g y . ( 1 9 9 3 ) 4 3 ( 1 ) ; 1 3 2 - 1 3 7 .
4 . W a n g X L , C h a i Q , C h a r l e s w o r t h M C , F i g u e r o a J J , e t a l . A u t o i m m u n e r e a c t i v e I g G s f r o m p a t i e n t s w i t h p o s t u r a l o r t h o s t a t i c t a c h y c a r d i a s y n d r o m e . P r o t e o m i c s C l i n . A p p l . ( 2 0 1 2 ) 6 ; 6 1 5- 6 2 5 .
5 . L i H , Y u X , L i l e s C , K h a n M , e t a l . A u t o i m m u n e B a s i s f o r P o s t u ra l T a c h y c a r d i a S y n d r o m e . J o u r A m e r H e a r t A s s n . ( 2 0 1 4 ) 3 ( 1 ) ; e 0 0 0 7 5 5 .
6 . A b d a l l a h H , P l a s s m e y e r M , R y h e r d M , A u s t i n L , e t a l . I m m u n o p h e n o t y p i c p r o f i l e s i n p a t i e n t s w i t h p o s t u r a l o r t h o s t a t i c t a c h y c a r d i a s y n d r o m e . C l i n A u t o n R e s . ( 2 0 1 4 ) 2 4 : 2 1 5 .
7 . B l i t s h t e y n S . A u t o i m m u n e m a r k e r s a n d a u t o i m m u n e d i s o r de r s i n p a t i e n t s w i t h p o s t u ra l t a c h y c a r d i a s y n d r o m e ( P O T S ) . L u p u s . ( 2 0 1 5 ) 0 ; 1 - 6 .
8 . S i n g e r W , K l e i n C J , L o w P A , L e n n o n V . A u t o a n t i bo d i e s i n t h e p o s t u r a l t a c h y c a r d i a s y n d ro m e . C l i n A u t o nR e s . ( 2 0 1 4 ) 2 4 : 2 1 4 .
9 . O a k a m o t o L E , R a j S R , G a m b o a A , S h i b a o C A , e t a l . S y m p a t h e t i c A c t i v a t i o n i s A s s o i c a t e d w i t h I n c r e a s e d I L - 6 , b u t n o t C R P i n t h e A b s e n c e o f O b e s i t y : L e s s o n s f r o m P o s t u r a l T a c h y c a r d i a S y n d r o m e a n d O b e s i t y . A M J P h y s i o l H e a t h C i r c P h y s i o l . ( 2 0 1 5 ) 3 0 9 ( 1 2 ) ; H 2 0 9 8 - 1 0 7 .
1 0 . A A N A n n u a l M e e t i n g a b s t r a c t p u b l i s h e d o n l i n e ( 2 0 1 6 ) : G u d e s b l a t t M , W i s s e m a n n K , S t i l e s L , X i a n S , e t a l . A u t o i m m u n i t y & A u t o n o m i c I m p a i r m e n t : P r e l i m i n a r y C h a r a c t e r i z a t i o n o f a C l i n i c a l S y n d ro m e w i t h S j ö g r e n ' s F e a t u re s A s s o c i a t e d w i t h N o v e l O r g a n S p e c i f i c A n t i b o d i e s . N e u r o l og y . ( 2 0 1 6 ) 7 8 ( M e e t i n g A b s t r a c t s ) ; P 5 . 1 0 8 .
1 1 . D u b e y D , H o p k i n s S , V e r n i n o S . M 1 a n d M 2 M u s c a r i n i c r e c e p to r a n t i b o d i e s a m o n g s t p a t i e n t s w i t h P o s t u r a l O r t h o s t a t i c T a c h y c a r d i a S y n d r o m e : p o t e n t i a l d i s e a s e b i o m a r k e r . J C l i n N e u r o m u s c u l D i s .( 2 0 1 6 ) 1 7 ( 3 ) .
1 2 . F e d e r o w s k i , L i , Y u , K o e l s c h , e t a l . A n t i a d r e n e r g i c a u t o i m m u n i t y i n p o s t u ra l t a c h y c a r d i a s y n d r o m e . E u r o p a c e . ( i n p r e s s ) .
POTS & AUTOIMMUNITY
CITATIONS