distal branches of ICA

branches

meningohypophyseal trunk
inferior hypophyseal artery

supraclinoid segment
 c4
ophthalmic artery
superior hypophyseal a
posterior communicating
anterior choroidal

HEPARIN INDUCED THROMBOCYTOPENIA (HIT)

Antibodies v. factor 4 platelets complexes
10 x more common with heparin than with LMWH
20-50 percent get arterial or venous thrombosis
platelet count is less than fifty percent normal
may use a direct thrombin inhibitor eg. argabotran

basic science notes
heparin and LMWH are indirect thrombin inhibitors as they do not act on fibrin bound thrombin.  By contrast, the direct inhibitors (hirudin, argabotran, bivalirudin) inactivate fibrin bound thrombin.

At an injury site, F VIIa (extrinsic pathway) and tissue factor are activated.  Thrombus propagates when F IXa binds to cofactor VIIIa (intrinsic pathway) and forms a complex that binds F X.  Xa binds Va to form prothrombinase that converts prothrombin to thrombin.  XI promotes Xa, final step is conversion of fibrinogen to fibrin

Statins on vessels basic science

Increase synthesis, decrease degradation of LDL receptors on heptatocytes
-LFT's increase in one percent
- tissue factor is PRO coagulant in enthothelial surface as is Va, F VIII
-heparin and prostacyclin are anticoagulants in endothelium, also NO, enodog tpa, heparin like substance

RE: pfo Studies

I have included 2 articles :

 

Transcranial Doppler to detect right‐to‐left shunt in cryptogenic acute ischemic stroke

Paola Palazzo, ^{1 , 2} Pierre Ingrand, ³ Pierre Agius, ⁴ Rafik Belhadj Chaidi, ⁵ and Jean‐Philippe Neau ¹

^{I include this for your review because it is 2019,  because all the patients were done brachial, and because the references are very well done.  It does not address the femoral route}

Sensitivity of brachial versus femoral vein injection of agitated saline to detect right‐to‐left shunts with Transcranial Doppler

Rubine Gevorgyan MD

Alice Perlowski MD

Michael Shenoda MD

M. Khalid Mojadidi MD

Harsh Agrawal MD

Jonathan M. Tobis MD

First published: 09 January 2014

https://doi.org/10.1002/ccd.25391

Cited by: 4

Conflict of interest: Nothing to report.

Read the full text

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Abstract

Background

Transcranial Doppler (TCD) can detect a right‐to‐left shunt (RLS) with high sensitivity but has a 5% chance of a false negative study. TCD is usually performed with injection of agitated saline into an arm vein. We compared the sensitivity of TCD performed from the brachial versus femoral veins.

Methods

Patients presenting to the cardiac catheterization laboratory for percutaneous closure of a patent foramen ovale (PFO) were enrolled. Power M‐mode Transcranial Doppler (Terumo 150 PMD) was conducted. After injection of a mixture of 8 cc of agitated saline, 0.5 cc of air, and 1 cc of blood into the brachial vein, embolic tracks were counted over the middle cerebral arteries. The degree of RLS was evaluated by TCD at rest, and with Valsalva at 40 mmHg aided by visual feedback with a manometer device. The test was repeated using femoral venous injections.

Results

Sixty five patients were enrolled, mean age 52, 43% male. TCD grades were significantly higher with femoral injections compared to brachial injections at rest (p<0.0001), and with the Valsalva maneuver (p<0.0001). The presence of a RLS was confirmed by intracardiac echocardiography (ICE) during cardiac catheterization in 62 (95.4%) patients.

Conclusion

The sensitivity of TCD for detection of RLS is increased when agitated saline injections are performed through the femoral vein. In patients with a high clinical suspicion for RLS, low TCD grades obtained with traditional brachial venous access should be interpreted with caution. When possible, a repeat study using femoral venous access may be considered. © 2014 Wiley Periodicals, Inc.

I have included this second article from 2014 as responsive to your note.

cTCD by brachial  injection has a 93% sensitivity and a 97% specificity.   I am not sure how much better "2X as good" is.  The introduction of a 1.5%-8% complication rate with a femoral catheter and the added cost may be justified under some circumstances.

The assumption is that the TIA or CVA is, in fact, cryptogenic,( that it has has been fully evaluated with Holter monitor, coag studies etc)     In this circumstance, negative TEE in which satisfactory valsalva has been noted along with a negative good quality cTCD for RLS leaves the circumstance to appear to be truly cryptogenic. 

The benefit of transcutanious PFO closure has always been clear to me, but the proof of benefit over ASA does require some statistical yoga.  This leaves the clear option of treating a truly cryptogenic group with ASA.  The number of spots on the MRI might help decide

I wonder if those relatively rare circumstances might be best resolved with a cardiac cath. ( especially if events are recurrent on ASA)  PVL can certainly participate in a f/u cTCD with femoral catheter.   We are not set up to do it in the PVL

-----Original Message-----
From: djacobs272 <djacobs272@aol.com>
To: adam.waldman <adam.waldman@orlandohealth.com>; mmenkin <mmenkin@aol.com>; ca.rosado <ca.rosado@gmail.com>; dhj1.strokenotes <dhj1.strokenotes@blogger.com>
Sent: Wed, Apr 24, 2019 9:39 am
Subject: pfo Studies

from Thaler DE and Cramer SC Paradoxical embolism in stroke in  Caplan LR, Biller J. Uncommon Causes of Stroke

"The choice of vein used to introduce echocardiographic contrast influences the sensitivity for PFO detection. Blood entering the right atrium via the inferior vena cava is directed towards the interatrial septum where PFOs are located whereas blood from the superior vena cava tends to be directed towards the tricuspid valve. Studies have been consistent in finding a 2.5-fold increase in diagnostic sensitivity when the contrast medium is injected via the femoral rather than the antecubital vein (Gin et al., 1993; Hamann et al., 1998).

Caplan, Louis R.; Biller, José. Uncommon Causes of Stroke (pp. 565-567). Cambridge University Press. Kindle Edition.

full citations for above:

Gin, K., Huckell, V., and Pollick, C. 1993. Femoral vein delivery of contrast medium enhances transthoracic echocardiographic detection of patent foramen ovale. J Am Coll Cardiol, 22, 1994– 2000.

Hamann, G., Schatzer-Klotz, D., Frohlig, G., et al. 1998. Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale. Neurology, 50, 1423– 8.

ALL MY TAKE

I ASSUME ONE HUNDRED PERCENT OF OUR STUDIES BOTH TCD AND TEE BUBBLE ARE DONE THROUGH ARM VEIN BUT RHEOLOGY SHOWS FEMORAL VEIN IS 2.5 X AS GOOD.  PERHAPS WE COULD CONSIDER DOING THESE STUDIES FEMORRALLY SECOND LINE IN CHALLENGING PATIENTS SUCH AS WE HAVE HAD LATELY?  LOOK FORWARD TO EVERYONE'S THOUGHTS

DJ

Re: pfo Studies

I have included 2 articles :

Transcranial Doppler to detect right‐to‐left shunt in cryptogenic acute ischemic stroke

Paola Palazzo, ^{1 , 2} Pierre Ingrand, ³ Pierre Agius, ⁴ Rafik Belhadj Chaidi, ⁵ and Jean‐Philippe Neau ¹

^{I include this for your review because it is 2019,  because all the patients were done brachial, and because the references are very well done.  It does not address the femoral route}

Sensitivity of brachial versus femoral vein injection of agitated saline to detect right‐to‐left shunts with Transcranial Doppler

Rubine Gevorgyan MD

Alice Perlowski MD

Michael Shenoda MD

M. Khalid Mojadidi MD

Harsh Agrawal MD

Jonathan M. Tobis MD

First published: 09 January 2014

https://doi.org/10.1002/ccd.25391

Cited by: 4

Conflict of interest: Nothing to report.

Read the full text

PDF

Tools

Share

Abstract

Background

Transcranial Doppler (TCD) can detect a right‐to‐left shunt (RLS) with high sensitivity but has a 5% chance of a false negative study. TCD is usually performed with injection of agitated saline into an arm vein. We compared the sensitivity of TCD performed from the brachial versus femoral veins.

Methods

Patients presenting to the cardiac catheterization laboratory for percutaneous closure of a patent foramen ovale (PFO) were enrolled. Power M‐mode Transcranial Doppler (Terumo 150 PMD) was conducted. After injection of a mixture of 8 cc of agitated saline, 0.5 cc of air, and 1 cc of blood into the brachial vein, embolic tracks were counted over the middle cerebral arteries. The degree of RLS was evaluated by TCD at rest, and with Valsalva at 40 mmHg aided by visual feedback with a manometer device. The test was repeated using femoral venous injections.

Results

Sixty five patients were enrolled, mean age 52, 43% male. TCD grades were significantly higher with femoral injections compared to brachial injections at rest (p<0.0001), and with the Valsalva maneuver (p<0.0001). The presence of a RLS was confirmed by intracardiac echocardiography (ICE) during cardiac catheterization in 62 (95.4%) patients.

Conclusion

The sensitivity of TCD for detection of RLS is increased when agitated saline injections are performed through the femoral vein. In patients with a high clinical suspicion for RLS, low TCD grades obtained with traditional brachial venous access should be interpreted with caution. When possible, a repeat study using femoral venous access may be considered. © 2014 Wiley Periodicals, Inc.

I have included this second article from 2014 as responsive to your note.

cTCD by brachial  injection has a 93% sensitivity and a 97% specificity.   I am not sure how much better "2X as good" is.  The introduction of a 1.5%-8% complication rate with a femoral catheter and the added cost may be justified under some circumstances.

The assumption is that the TIA or CVA is, in fact, cryptogenic,( that it has has been fully evaluated with Holter monitor, coag studies etc)     In this circumstance, negative TEE in which satisfactory valsalva has been noted along with a negative good quality cTCD for RLS leaves the circumstance to appear to be truly cryptogenic. 

The benefit of transcutanious PFO closure has always been clear to me, but the proof of benefit over ASA does require some statistical yoga.  This leaves the clear option of treating a truly cryptogenic group with ASA.  The number of spots on the MRI might help decide

I wonder if those relatively rare circumstances might be best resolved with a cardiac cath. ( especially if events are recurrent on ASA)  PVL can certainly participate in a f/u cTCD with femoral catheter.   We are not set up to do it in the PVL

pfo Studies

from Thaler DE and Cramer SC Paradoxical embolism in stroke in  Caplan LR, Biller J. Uncommon Causes of Stroke

"The choice of vein used to introduce echocardiographic contrast influences the sensitivity for PFO detection. Blood entering the right atrium via the inferior vena cava is directed towards the interatrial septum where PFOs are located whereas blood from the superior vena cava tends to be directed towards the tricuspid valve. Studies have been consistent in finding a 2.5-fold increase in diagnostic sensitivity when the contrast medium is injected via the femoral rather than the antecubital vein (Gin et al., 1993; Hamann et al., 1998).

Caplan, Louis R.; Biller, José. Uncommon Causes of Stroke (pp. 565-567). Cambridge University Press. Kindle Edition.

full citations for above:

Gin, K., Huckell, V., and Pollick, C. 1993. Femoral vein delivery of contrast medium enhances transthoracic echocardiographic detection of patent foramen ovale. J Am Coll Cardiol, 22, 1994– 2000.

Hamann, G., Schatzer-Klotz, D., Frohlig, G., et al. 1998. Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale. Neurology, 50, 1423– 8.

ALL MY TAKE

I ASSUME ONE HUNDRED PERCENT OF OUR STUDIES BOTH TCD AND TEE BUBBLE ARE DONE THROUGH ARM VEIN BUT RHEOLOGY SHOWS FEMORAL VEIN IS 2.5 X AS GOOD.  PERHAPS WE COULD CONSIDER DOING THESE STUDIES FEMORRALLY SECOND LINE IN CHALLENGING PATIENTS SUCH AS WE HAVE HAD LATELY?  LOOK FORWARD TO EVERYONE'S THOUGHTS

DJ

 

High risk cardiac embolism

Atrial fibrillation
mechanical valve
LAA thrombus
Anterior wall MI
endocarditis
aortic sclerosis
dilated cardiomyopathy
PFO/ASA
atrial flutter
aortic dissection
atrial myxoma

diffuse meningocerebral angiomatosis

older adults
livedo reticularis
dementia
seiozures
brain infarcts
demyelination

Protein C and warfarin, tests and Factor V Leiden mutation

warfarin decreases protein C level, so can't measure it if they are on warfarin

Activated protein C resistance is SCREENING TOOL  for Factor V Leiden mutation
APCR is also caused by: pregnancy, contraceptives, cancer, APL's,  so its sensitive but not specific for Factor V Leiden mutation.  APCR is NOT associated with protein C deficiency or AT 3 deficiency.

Factor V causes a 2-10 x risk of lifetime clots, venous not arterial.  High in Europeans, lower in Asians and African Americans. Its AUT DOMINANT. Anticoagulate if present and multiple events or if one severe event. PT G20210A gene mutation also confers only a venous risk.  Additive risk with contraceptives and with each other

Warfarin also causes a rapid fall in Factor VII (extrinsic pathway). Heparin decreases skin necrosis

essential thrombocytosis

no Philadelphia chromosome
aspirin helps esp if erythromelalgia is present

Polycythemia vera

+ Phil chromosome
Increased Hct
HA
vertigo
vision changes
seizures
"ruddy " complexion

Signs
retinal engorgement
papilledema

Rx
phlebotomy
hydroxyurea
steroids

Measuring extrinsic, intrinsic and common pathways

PT measures extrinsic and common pathways, is sensitive to low levels of Factors 7,10, tissue factor

intrinsic pathway - includes factors 8,9,11,12 also prekallikrein
PTT is elevated if deficient factors 8,9, also SLE, heparin tx
PTT is low in hypercoagulable state

Common pathway includes Factors V, X, prothrombin and fibrinogen

VWB disease- VWF depends on ristocetin induced aggluctination, decreased Factor 8, False positive occurs in inflammation, pregnancy, estrogen therapy

Vitamin K dependent factors decreased by coumadin include : extrinsic
prothrombinm F VII, F X   but not VIII,XI, XII

Long QT interval

Associations sudden death, syncope, presyncope
classic Torsades de pointe
Rapid V TACH above or below line EKG
med causes :  amiodarone, disopyramide, procainamide, quinidine, Haldol, sotalol, methadone, emycin

Aortic dissection

chest pain
syncope
Horner's

Association- may result from coarctation(coarctation also causes fusiform aneurysm)
IN men gtr than  50 due to HTN
if less than 50 due to Marfan's or to pregnancy

PFO pearls

fossa ovalis of septum in in right atrium.  Limbus with horseshoe shaped valve ovalis.  Ostium primum- fetal
ostium secondum opens

PFO prevalence 40-60 % in patients with migraine + aura

Wolff Parkinson White WPW syndrome

atrial tachycardia and accessory pathways
decreased PR interval
Delta wave in QRS complex
Avoid CCB's and beta blockers

Lip (a) and stroke risk

increased in women and in African Americans
correlates with LDL
is an independent predictor of stroke  and vascular death in older men

predictors of hemorrhage in AVM

Increased age
hemorrhagic presentation
deep location
exclusive deep venous drainage

NOT
headache
seizure
gender
size
aneurysm on nodal vessels

Malaria

encephalopathy
preceding petechial rash
rarely presents as stroke
don't give steroids.

APMPPE acute posterior mulitofocal placoid pigment epitheliopathy

chorioretinal disease of the young with strokes and aseptic meningitis

white dot syndromes
associated with TB and many other infections and associations
retinal abnormalities after return of vision
rare CNS involvement
rapid bilateral central vision either simultaneously or sequentially
choroidal vasculitis

Eye findings
anterior and posterior uveitis
papillities
RAPD
serous detachment, edema, hemorrhages and episcleritis
CRVO
revascularization
antecedent vaccinations
41 percent have prodromic flu
association with Harada disease
MS like disease
pseudotumor

male = female but more men get CNS complications that include

aseptic meningitis
lymphocytic pleocytosis and increased protein

territorial strokes esp PCA but also MCA and deep
PACNS
granulomatous angiitis
treat with steroids

Spinal hematoma due to coagulation issues

Back pain
radiculopathy
get an MRI

spinal cord stroke

most common type ASA
PSA is rare
artery of Adamkiewicz from right 30 percent and joins the ASA

hypereosinophilia syndrome

spectrum

stroke
encephalopathy
multifocal motor neuropathy

first stage asymptomatic
second stage development of thrombi
third stage myocardial fibrosis

Dural AVF of brain

Most common
transverse and sigmoid sinus

Aneurysm of cavernous sinus

diplopia
facial pain
headache
decreased acuity
VI n paresis is more common than II n paresis

in contrast supraclinoid aneurysm causes bitemporal anopias

Wyburn Mason syndrome

large tortuous arteries and veins
racemose retina

affects one eye
retinal , facial, oral and intracranial AVM
intracranial avm usually is ipsilateral optic nerve temporal lobe and middle and posterior fossae
nonhereditary
believed to derive from seventh week mesoderm
retinal AVM are often stable but 25 percent of time are not and cause complications
orbital AVM correlate with proptosis and with intracranial avm's
oral maxillofacial AVM can result in feared bleeding especially after dental extraction or from nose without warning or provocation

Signs and symptoms include

HA
cephalic bruit
HH and HP

ddx:
Sturge Weber--
von Hippel Lindau

Von Hippel Lindau

hemangiomablastoma in brain, cord, and retina
cysts kidneys liver and pancreas
70 percent develop clear cell CA kidney

Autosomal dominant deletions/mutations in tumor suppressor gene 3p25

Churg Strauss

allergic rhinitis
nasal polyps
asthma
eosinophilia
increased IgE

Cerebral amyloid angiopathy genetic forms

Annual bleed risk ten percent.

Dutch type

Icelandic type (young)

Named stroke syndromes

Benedicts' syndrome-- lesion in midbrain ventral and tegmentum affecting CTS,IIIn, red nucleus, cerebellothalamic fibers leads to contralateral weakness, facial weakness, ipsilateral abducens, chorea

Millard Gubler-- medial pons affects VI n, and CST get ipsilateral VI n. paresis and contralateral HP

Foville's -- dorsal pons  , above with extension into tegmentum, affects PPRF get ipsilateral facial paresis, conjugate gaze paresis also

Weber's-  medial midbrain.  ipsilateral IIIn and cerebral peduncle with HP

Claude's-  midbrain and dorsal tegmentum-- ipsilateral IIIn, red nucleus  HP + ataxia contralateral (pupil dilated, and eye is down and out)

Raymond Cestan s-- ventral pons-  CST + MLF produces INO, contralateral HP and loss adduction side of lesion

Hemiplegic migraine mimicking stroke

Usually + auras then headache
gene mutation of P/Q VGCC CAC NA1A on chromosome 19p13 that encodes pore forming subunit of P/Q type VDCO's Men=women

menkes syndrome

ATP7a  X linked

small and large vessel disease

growth failure
hypotonia
blue sclerae
seizures
brittle hair

Malignant atrophic papulosis

young adults
skin lesions
GI symptoms
infarcts and hemorrhages

Kawasaki syndrome

mucocutaneous lymph node syndrome

affects skin and mucous membranes of kids and young adults

Clinical

fever then skin lesions
conjunctivitis
lymphadenopathy
stroke- ischemic, SAH, MI

Intracranial hemorrhage in infants

ruptured subependymal vessels in germinal matrix in premature infants
Half occur in first day of life, 90 percent in first four days

Subdural hemorrhage
symptoms change in level of consciousness, seizures, tough to see on CT or differentiate from cerebellar hemorrhage treat conservatively or surgically.

CVT neonates have more involvement than adults of straight sinus or deep venous system

Periventricular leukomalacia

associated with prematurity
occurs in one third of CP patients under 1000 grams
one fourth of those have secondary minor hemorrhages
44 percent have spastic diplegia

Neonates with strokes hypercoagulable associations

59 percent have one or more prothrombotic risk factors esp. increased lipoprotein (a) (45/125, then Factor V leiden  (32/125) or protein S deficiency (one patient) which is much more rare

1:4000 term babies have strokes usually MCA left more than right due to flow with PDA Patent ductus arteriosus

half are normal later in infancy

Stroke mortality is dramatically higher in neonates with high death rate especially for ICH

Catheters cause 80 percent of deep vein thrombosis in newborns, 60 percent inolder children.  Noncatheter associated arterial thrombosis is rare

Alternating hemiplegia of childhood

sporadic
may start at 2-18 months
poor prognosis
mental retardation and choreoathetosis associated
symptoms regress with sleep
a benign older form exists

Aneurysms in babies

rare
less than one percent of all SAH
Usually present with SAH
more commonly occur at MCA whereas GIANT aneurysms are more common in posterior circulation

AVM vein of Galen

features

high output heart failure due to shunting

may lead to hydrocephalus
AVM's are number one cause of hydrocephalus in children
nonalternating hemicranial pain
bruits occur in more than half

Carotid endarterectomy complications and contraindications

complications-- should be less than six percent

include

transient cranial neuropathy of nerves VII, X, and XII
MI and stroke

contraindications

large or disabling stroke
contralateral laryngeal palsy

few aspirin studies in stroke with a few of take away points

Dutch trial 1991  30 mg aspirin was as good as 283 mg
CAST  aspirin was better than placebo
MATCH   aspirin plus Plavix had little increased benefit but more bleeding
CHANCE trial  Chinese trial favored dual antiplatelet drugs for 90 days
IST trial 1997-- aspirin in first 48 hours led to better outcome
CAPRIE trial clopidogrel was superior to aspirin IF peripheral vascular disease is present otherwise they are same
CHARISMA trial  Dual antiplatelet treatment is dangerous for primary prevention
ESPS 2  Aggrenox was superior to aspirin alone.
PROFESS trial 2007  Aggrenox v. Plavix showed no difference between the two

intracranial dissection

in pediatrics, sixty percent are in anterior circulation and only those recurred.  In posterior circulation, most occur near C1-2 level.

Ehlers Danlos type 4- vascular type VED

features

Col3a1 gene codes for type 3 procollagen
autosomal dominant
arterial dissection and rupture
risk of SMT
thin translucent skin
typical facies
porencephaly

may NOT have hyperelastic skin
diagnose with death during childbirth, hemorrhage after minor trauma or surgery, bowel rupture
median survival 51
Aneurysms are common in VED but VED is not common in aneurysms. No 1 vessel is ICA
Complications of catheterization as high as 67 percent with 17 percent mortality
CCF are common as are dissections of many vessels

Tangier disease

features


autosomal dominant
low HDL, apo1
decreased LDL
mildly increased TG
mutations in binding cassette transporter A1 (ABDA1)
abnormal reverse cholesterol transport
orange tonsils
peripheral neuropathy
cerebrovascular and cardiovascular disease.

Causes of stroke in pediatric populations

CARDIOEMBOLIC

atrial fibrillation
myxoma
infective endocarditis
PFO
fat emboli

CEREBRAL VENOUS THROMBOSIS

orbital infection
cavernous sinus thrombosis
leukemia

CVT presents with seizures and acute illness
especially affects SSS and lateral more than straight sinus

Distribution

42 % ICH
32 % SAH
17 % ischemic stroke

Alagille syndrome

autosomal dominant
arteriodysplastic syndrome with multiorgan involvement
mutation in Jagged 1 gene, ligand for notch receptor.

clinical
peculiar facies
chronic cholestasis
buttery vertebral arch
polycystic kidneys

usually affects GI/cardiovascular/pulmonary
stroke can occur
reports of aneurysmal SAH and moya moya

PHACE syndrome

PHACE POSTERIOR FOSSA MALFORMATION HEMANGIOMAS, ARTERIAL ANOMALIES AND COARCTATION OF AORTA, OTHER CARDIAC DEFECTS AND EYE DEFECTS,

clinical
posterior fossa malformations
MASSIVE facial hemangiomas
arterial cerebrovascular disease, eye abnormalities

Associations: Dandy Walker cyst
women more than men
stroke
moya moya
sternal clefting
supraumbilical abdominal raphe may occur
coarctation and other cardiac deficits

Lemierre's syndrome

postanginal sepsis. This is a rare complication of pharyngeal infection with FUSOBACTERIUM NECROPHORUM.  a gram negative rod occurring in immunocompromised kids or adults.  It may involve meningitis, cerebral venous thrombosis, stroke, subdural emyema, ICA stenosis.  Patients given antibiotics and surgery usually survive.