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Thoms

Pearls Orthostatic tremor

Occurs in legs on standing

truncal and abdominal involvement are rare

may be enhanced by palpation  "thrill"

auscultation (continuous thumping" helicopter sign

surface emg - helicopter sign

high frequency 13-18 hz very characteristic on emg especially surface EMG

primary v secondary (orthostatic tremor +)

Pearls cavernous malformation

Diagnose with mri coupled with genetic testing

Most prevalent gene iskrit1/ccm1 esp among Hispanics

18 Japanese had mgc4607/ccm2 

Look for extra cns involvement esp eye ( retina) and cutaneous vascular malformations

Two Chinese families had ccm1 and mgc460/ccn2

Movementis

The 2022 International Conference

on

MOVEMENT and COGNITION

Sorbonne

PARIS

31.8.2022 – 2.9.2022

 

For Registration, Abstracts submission or questions:

www.movementis.com

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Contacts: office@movementis.com

 

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essential tremor devices

1.  Pen Again

2. CALA

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

PDF

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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

-----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.

Tenecteplase v altepalse

Campbell BCV et al. Tenecteplase versus altepalse before thrombectomy for ischemic stroke.  NEJM 378: 1573-1582.

Tenecteplase is more fibrin specific and has longer activity than alteplase.  101 patients were assigned to .25 mg/kgof tenecteplase and 101 to 0.9 mg/kg alteplase within 4.5 hours of onset.  . The primary outcome was repercussion of more than 50 percent of the involved ischemic territory or absent retrievable thrombus at time of angiography.  Secondary outcome was mRS at ninety days.  

Primary outcome was achieved in 22 % of tenecteplase patients, ten percent of altepalse patients p= 0.002, clinical difference of twelve percentage points.  sICH occurred in  1 percent of each group.  90 day mRS was also better , 2 v. 3 (p=0.04).  

EXTEND 1A, NIH sponsored trial.  

editorial  Baird AE. Paving the way for improved treatment of acute stroke with tenecteplase. NEJM  378:  1635-6.  

Notes that alteplase helps only a small portion of the patients with large clots, so time between tap and groin puncture is key.  Drug has a long half life, can be administed as a bolus,  doubled the rate of recanalization and averted the need for some thrombectomies. This is a second phase two trial and a phase 3 trial is needed.

In a study of patients with mild stroke who were not expected to proceed to thrombectomy,  superiority of tenecteplase at a dose of .4 mg/kg  v. alteplase was NOT shown.    Additional ongoing trials including TASTE and ATTEST2  have not reported.  Campbell also did NOT show a decrease between thrombolysis and thrombectomy in tenecteplase treated patients in another trial.

Management of antiphospholipid syndrome-- pearls

from Garcia D. and Erkan D. Diagnosis and management of the antiphospholipid syndrome. NEJM 378; 2010:2021.  

1.  Ten percent of healthy blood donors are positive for apl  antibodies and one percent are positive for lupus anticoagulant; however after one year, only one percent remain positive, so rechecking titers is key. Its rare for a truly healthy person to  remain positive. Transient apl is common during infections.

2.  Prevalence by underlying condition of persisting moderate to high risk apl antibody profiles:  SLE, 20-30 percent;  women with pregnancy complications, six percent;  patients with venous thrombosis, ten percent;  MI, 11 percent; patients less than fifty with stroke, 17 percent.  

3.  Clinical presentation pearls: among pregnant women, most occur after ten weeks of pregnancy (those in earlier period more likely have genetic anomalies causing miscarriage).  Patients with venous thromboembolism most likely have lower extremity or pulmonary emboli.  

4.  Other clinical features include pulmonary hypertension, livedo reticularis, thrombocytopenia, hemolytic anemia, acute or chronic renal vascular lesions, and moderate or severe cognitive impairment.  

5.  Other lab features to note:  LA test best correlates with clinical events, but may be misleading among patients on warfarin or DOACs.  For ELISA, moderate to high titers ( greater than 40 GPL or 99th percentile of cal or anti B2GP1correlate better with outcomes than lower titers; IgG is more strongly associated with bad clinical events than IgA.  

6. Treating traditional risk factors and avoiding estrogen  is very important.

7.  Anticoagulation for primary prevention or use of aspirin for primary prevention is still controversial.  For patients with persistent apl syndrome and provoked thrombosis, eg. by surgery, or for those with impersistent apl ab's, the benefit of prolonged anticoagulation is "less certain."  

8. Treatment of "warfarin failures" is not known, but options include high intensity warfarin to INO 3-4, addition of aspirin or plaquenil or statin, use of a different anticoagulant such as a  LMWH or a combination.  There is insufficient evidence about DOACs.  

9. Catastrophic apl syndrome includes ARF, ARDS and adrenal hemorrhage.  Diagnosis is definite with involvement of three or more organs and a persistently positive test.  Early treatment with anticoagulants, steroids, IVIG and PLEX is indicated.  

10. Treatment in pregnancy is with low quality evidence, use of low dose aspirin and LMWH,  

if platelets are more than 50 K, no acute therapy

if platelets are more than 20 K, first line is steroids and IVIG not splenectomy

for warm mediated HA steroids are used first

ARF with thrombotic microangiopathy is usually treated with PLEX

Valve disease with high risk use ASA or warfarin for high risk vegetations

APS criteria-- once clinical event (venous or arterial) and/or fetal loss after ten weeks and/or 3 sequential miscarriages before 10 weeks  AND either present LA, ACL ab, or antiB2glycoprotein

Rivaroxabin for stroke prevention after embolic stroke of undetermined source

Hart RG. Rivaroxabin for stroke prevention after embolic stroke of undetermined source.  NEJM; 378: 2191-2201.  

Study tested  15 MG rivaroxaban v. 100 mg of aspirin with presumed embolic but undetermined source, with no arterial stenosis,lacunae or identified cardioembolic source.7213 patients were enrolled at 459 sites. Study was halted at eleven months with non superiority. Primary outcome was recurrent ischemic or hemorrhage stroke and primary safety measure was bleeding.   Recurrent stroke was 4.7 percent is both groups.  Bleeding occurred in 1.8 percent of rivaroxaban group, 0.7 percent of aspirin group ( p<0 .001="" a="" and="" bleeding.="" div="" effective="" had="" higher="" more="" nbsp="" not="" of="" onclusion:="" rate="" rivaroxaban="" was="">

NAVIGATE ESUS trial-- New approach rivaroxaban inhibition of factor Xa in a global trial versus aspirin to prevent embolism in embolic stroke of undetermined source.

The primary outcome of any stroke or systemic embolism slightly and non significantly favored rivaroxaban (5.1 v. 4.8 percent) There were hemorrhagic strokes in 0.4 v. 0.1 in respective groups (statistically significant but low effect size).  

Atrial fibrillation was not excluded prior to randomization.  About 12 percent of patients with cryptogenic stroke have undiagnosed atrial fibrillation.  PFO's were excluded. 

Comment-- Study is conclusive for unselected group, but what about for selected group with an educated guess of etiology? That could happen through selection of patients with certain ECHO characteristics , for example  left atrial hypertrophy or intracranial stenosis.  While one may argue that would be overkill to do the study, in the prior negative warfarin studies (WASID) patients never maintained their INR's within range..  

Power was very high to determine outcome.  Risk of stroke in first 11 months was about five percent.  

Risk of stroke after a TIA

Amarenco P., et al.  Five year risk of stroke after TIA or Minor ischemic stroke. NEJM; 378: 2182-2190.

Methods: TIA registry from 2009-2011, 21 countries, 4789 patients.  Outcome was composite ischemic brain or heart or death.  

results rate of stroke,coronary syndrome or death was 6.4 percent in the first year, 6.4 percent infers 2-5.  ABCD2 score predicted a higher rate of stroke if score was greater than or equal to 4.  The presence of a brain lesion on imaging was not important. 

POINT trial

Johnston SC et al. Clopidogrel and aspirin in acute ischemic stroke and high risk TIA.  NEJM; 379:215-225  

Gotta, JC.  Antiplatelet therapy after ischemic stroke or TIA. NEJM 379:291 (editorial)

Chinese trial (CHANCE) previously showed a benefit of dual anti platelets in a Chinese population for a short period after stroke.  This study was a  RCT 1:1 of minor ischemic stroke  (NIHSS of 3 or less) or high risk TIA (ABCD2>4) to receive clopidorel loading dose (600 mg on day one, then 75 mg per day) plus aspirin 50-325 mg po daily (dual anti platelets or DAP), v. aspirin alone.  Primary outcome was the risk of composite ischemic events (Stroke, MI, or CV death). 4881 patients at 269 sites internationally.  After 84 percent enrollment, the trial was halted when trial showed less major ischemic events AND higher risk of major hemorrhage at 90 days than mono therapy.  The effect size was fairly small, with 6.5 % risk in DAP, 5.0 % in aspirin alone.  Major hemorrhage occurred in 0.9 % of DAP, 0.4 percent of aspirin alone. This was a ninety day trial.  

Commment- basic math shows 1.5 percent less major ischemic events, 0.5 percent more major hemorrhage with DAP.  Previously Chinese trial (CHANCE) showed 32 % decreased stroke recurrence with DAP and no increased hemorrhages.

James Grotta- Most of the prevented events were ischemic strokes arguably the most important outcome after TIA/minor stroke.  Most of the bleeding were systemic, nonfatal,nonintracranial hemorrhages.  Most of the benefit occurred int he first week, most of the hemorrhages occurred later.  DAP should be confined to a limited time, eg. the first three weeks.  

Candidates for neuroprotective trials

1. Hypothermia
2. Caspace inhibitors (none tried yet due to irreversibility)
3. Hypoxic preconditioning (how would this study be done?)
4. Magnesium antiexcitotoxin, inhibits inflammation, reduces infarct volume six hours late
5. Minocycline
6. Enlimomab
7. FK506
8.

Clinical trials: DEDAS

DEDAS dose escalation study of desmoteplase in acute ischemic stroke -- twin study to DIAS. phase 2 trial for safety and efficacy among patients with P/D mismatch on mRI 3-9 hours after onset of acute ischemic stroke. (Tony Furlan). 39 patients, doses 90 and 125 ug/kg, NIHSS baseline 4-20. There were no sICH cases Reperfusion occurred in 37.5 %, including 18 % of lower dose patients and 53% of higher dose patients. Good outcome occurred in 25 % of placebo, 28 % of lower dose patients, and

Clinical trials LIFE

Losartan v. atenolol-- looked at hypertensive stroke patients with LVH. Losartan prevented morbidity and mortalityin the group, but the effects were small.

CONTINUUM STROKE PREVENTION risk factors, AF

This next series of posts designates pearls taken from Continuum education series and designed to assist preparation for vascular neurology boards. Again, many commonly understood ideas won't be blogged, only those on the fringe or confused commonly need to be blogged, so the posts may seen disjointed, but it has a purpose.

Nonmodifiable risk factors for stroke: age (doubles per decade after 55), sex (24-30% greater in men), race (2.4 fold increase for African Americans, 2 fold in Hispanics, increased in Chinese), and heredity (1.9 fold with positive family history).


Modifiable risk factors

Hypertension affects 50 million people in US, and population-attributable risk for stroke is 40 % depending on age group. In Framingham, htn > 160/95 had an age adjusted relative risk of stroke of 3.1 for men, 2.9 for women (Kannel 1970). Isolated systolic htn is also a risk factor. Dutch study showed similar. Linear relationship of stroke to bp occurs down to 115/75. JNC created a category of "prehypertension." Its defined as 120-139/80-89. These should be treated.

Atrial fibrillation
Prevalence of stroke in age>65 is 6 %. Attributable risk increases with age. In Framingham the relative risk was 20 x in patients with valvular disease + AF and 5 x in patients with AF alone. (Wolf et al 1991), which is independent of age hypertension, and other cardiac abnormalities. SPAF (Stroke in AFIB) trials clarified. SPAF studied nonvalvular afib only. SPAF I randomized to placebo, ASA or warfarin. Placebo stroke risk was 6 % per year. High risk patients were those with htn, chf, prior stroke or tia, systemic emboli, or women over 75, or LV dysfunction or increase left atrial size. SPAF III found low risk patients as defined above had stroke risk of 2 % per year on ASA and a disabling stroke risk of .8% per year. Patients with htn who were moderate risk had intermediate risk (3.6 per year). Framingham derived study based on new AF not treated with warfarin created a risk stratification model to predict 5 year risk of stroke. from JAMA 2003:
Assign points for different conditions
age <59>Points Five year risk,%

0-1 5
2-3 6
4 7
5 8
6-7 9
8 11
9 12
10 13
11 14
12 16
13 18
14 19
15 21
16 24
17 26
18 28
19 31
20 34
21 37
22 41
23 44
24 48
25 51
26 55
27 59
28 63
29 67
30 71
31 75

African Americans have less atrial fibrillation

Von Willebrand's disease and other bleeding disorders

VWD

Ristocetin induces platelet activity and is used to diagnose von Willebrand's disease, which is most common inherited bleeding/coagulability disorder. Reduced levels of platelet aggregation are seen in vwd in association with ristocetin antibiotic presence.

type 1, 3 -- quantitative defect of VWF
type 2- qualitative defect of VWF

Rx: desmopressin or plasma concentrates c Factor VII and VWF

Bernard Soulier- May Hegglin's anomaly, gray platelet syndrome, inherited giant platelet disorder with thrombocytopenia and bleeding

Hemohilia A-- deficient factor VIII (more common)
Hemophilia B (deficient factor IX ) Christmas disease

spot sign

DVT prophylaxis in cerebral hemorhage

Zubkov AY, Wijdicks EFM Reviews in Neurological Diseases 2009; 6:21-25.

DVT occurs in 55 % of patients with acuts stroke and 5 % of early deaths in this group. Clinically apparent DVT occurs in 1.8 to 5 % of patients with ischemic stroke, subclinical in 28-73 %. In ICH, risk is similar; 15.9 % had DVT at 10 days among those wearing stockings. LE doppler is insensitive (misses many cases). 30 % of patients with PE do not show signs of lower extremity DVT. ACCP (2004) suggested mechanical means to prevent DVT, discouraged LMWH, and left heparin at discretion of practitioner. A meta-analysis in 2000 showed 45 % RR among neurosurgical patients receiving heparin. Only one RCT done shows 85 % reduction in DVT in heparinized patients (J Neurosurg 1978).

Statins enhance collateralization in acute stroke

Ovbiagele B Saver JL, Starkman S et al. Neurology 2007; 68: 2129-2131.

Mendelsohn maneuver for stroke

The Mendelsohn maneuver is taught by having the patient place


their fingers lightly over the thyroid cartilage and then trying to

swallow. When the thyroid cartilage reaches the top part of its

elevation during the swallow the patient is supposed to try to keep it

in this position for a second or two. The crycopharyngeus upper

esophageal sphincter is stretched by this excursion and is mechanically

opened. There may also be some reflex inhibition of the sphincter, but

the benefit is probably mostly mechanical. Logeman's book on dysphagia

has a much better description.

PFO business NEJM September 14,2017

article 1-  Farb A, Ibrahim BG, Zuckerman BD. Patent foramen ovale after cryptogenic stroke --assessing the evidence for closure  NEJM 2017: 377: 11 pp. 2006-2009.

article 2- Mas J-l, Derumeaux G, Guillon B, et al.  Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke.  NEJM 2017: 377: 11 pp.1011-1021.  663 patients were randomized 1:1:1.  Average ROPE score was 7, selected group had large shunt without ASA or with ASA, or had a mild to moderate shunt and ASA.
<60 .="" 1-4="" 12-15="" 29="" 2="" 5.4="" 5.9="" 8-11="" at="" atrial="" be="" cause="" chol.="" complications="" cryptogenic="" developed="" did="" dm="" fibrillation="" five="" followup="" found="" four="" had="" high="" htn="" ie="" including="" mean="" nbsp="" no="" not="" number="" one="" or="" other="" over="" p="" percent="" prevent="" procedure.="" recur="" smokers="" stroke="" that="" to="" transient="" treat="" twenty.="" unsuccessful="" usually="" was="" were="" years.="" years:="" years="">
<60 .="" 1-4="" 12-15="" 29="" 2="" 5.4="" 5.9="" 8-11="" at="" atrial="" be="" cause="" chol.="" complications="" cryptogenic="" developed="" did="" dm="" fibrillation="" five="" followup="" found="" four="" had="" high="" htn="" ie="" including="" mean="" nbsp="" no="" not="" number="" one="" or="" other="" over="" p="" percent="" prevent="" procedure.="" recur="" smokers="" stroke="" that="" to="" transient="" treat="" twenty.="" unsuccessful="" usually="" was="" were="" years.="" years:="" years="">
Article 3:  Saver, JL, Carroll JD, Thaler DE et al.  Long term outcomes of patent foramen ovale closure or medical therapy after stroke.   NEJM 2017: 377: 11 pp.1022-1032. They studied 960 patients with PFO and cryptogenic stroke ages 19-60; extension trial of previously reported NEGATIVE RESPECT trial at two years.  Subjects had to have TEE confirmed PFO with exclusion of large artery arteriopathy, lacune, known cardioembolic source, dissection, APL AB'sASCOD or other known cause of stroke.ASCOD method was used to determineAbout one third had hypertension, 7-8 percent smoked, 6-8 percent had DM.  In stroke v. medical therapy, there were 0.58 percent and 1.07 events per 100 patient years

<60 .="" 1-4="" 12-15="" 29="" 2="" 5.4="" 5.9="" 8-11="" at="" atrial="" be="" cause="" chol.="" complications="" cryptogenic="" developed="" did="" dm="" fibrillation="" five="" followup="" found="" four="" had="" high="" htn="" ie="" including="" mean="" nbsp="" no="" not="" number="" one="" or="" other="" over="" p="" percent="" prevent="" procedure.="" recur="" smokers="" stroke="" that="" to="" transient="" treat="" twenty.="" unsuccessful="" usually="" was="" were="" years.="" years:="" years="">
<60 .="" 1-4="" 12-15="" 29="" 2="" 5.4="" 5.9="" 8-11="" at="" atrial="" be="" cause="" chol.="" complications="" cryptogenic="" developed="" did="" dm="" fibrillation="" five="" followup="" found="" four="" had="" high="" htn="" ie="" including="" mean="" nbsp="" no="" not="" number="" one="" or="" other="" over="" p="" percent="" prevent="" procedure.="" recur="" smokers="" stroke="" that="" to="" transient="" treat="" twenty.="" unsuccessful="" usually="" was="" were="" years.="" years:="" years="">
<60 .="" 1-4="" 12-15="" 29="" 2="" 5.4="" 5.9="" 8-11="" at="" atrial="" be="" cause="" chol.="" complications="" cryptogenic="" developed="" did="" dm="" fibrillation="" five="" followup="" found="" four="" had="" high="" htn="" ie="" including="" mean="" nbsp="" no="" not="" number="" one="" or="" other="" over="" p="" percent="" prevent="" procedure.="" recur="" smokers="" stroke="" that="" to="" transient="" treat="" twenty.="" unsuccessful="" usually="" was="" were="" years.="" years:="" years="">Article Four  Sandergaard L, Kasner SE, Rhodes JF. et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke.  NEJM 2017: 377: 11 pp. 1033-42.  International trial studied PFO closure + antiplatelet to antiplatelet therapy only.  664 patients were enrolled.  Median followup was 3.2 years.  1.6 percent had serious device related complications and 6.6 percent had postprocedure atrial fibrillation.  Subjects needed to be less than 60,  and OTHER causes of stroke had to be ruled out as above to be enrolled. They all had imaging of arteries of head and neck and aortic arch.Holter monitoring not required.  ASA was only assessed at timeof closure.  Clinically known infarcts were reduced but silent infarcts were not.There was a 1.4 v 5.4 percent difference in amount of new strokes.

Editorial, Ropper A. Tipping point for PFO.  Notes importance of cardiac criteria (large shunt, presence of ASA) as well as clinical criteria (ROPE score).  A large PFO is defined as a more than thirty microbubbles in three cardiac cycles; a large ASA is septum primum excursion more than 10 mm.

my editorial notes  Statistical benefit is undeniable in patients under 60, with a RoPE score of seven or more, with an ASA, with cryptogenic stroke after full evaluation.  Parsing those patients with partial  combinations of features will still be challenging.  Clinical degree of benefit is small number with NTT around 20 and the amount of side effects around five percent.  Questions going forward, include: can one screen for right to left shunt with TCD rather than TEE; more precise criteria involving clinical and cardiac features of PFO.  Also, what amount of cardiac eval for atrial fibrillation needs to be done in cryptogenic patients prior to closing. In studies, 30 days was enough, but other studies suggest a need for much longer monitoring in which case, if positive, the strokes are not cryptogenic.
<60 .="" 1-4="" 12-15="" 29="" 2="" 5.4="" 5.9="" 8-11="" at="" atrial="" be="" cause="" chol.="" complications="" cryptogenic="" developed="" did="" dm="" fibrillation="" five="" followup="" found="" four="" had="" high="" htn="" ie="" including="" mean="" nbsp="" no="" not="" number="" one="" or="" other="" over="" p="" percent="" prevent="" procedure.="" recur="" smokers="" stroke="" that="" to="" transient="" treat="" twenty.="" unsuccessful="" usually="" was="" were="" years.="" years:="" years="">

Risk factors for seizures after alteplase administration

Based on the ENCHANTED trial, risk  factors for seizures included being male, having a fever, or severe impairment.  Having a seizure predicted poor outcome

Xu Y, Hackett ML, et al.  Neurol Clin Prac 2017; 7: 324-332

Aberrant ICA pearls

Krings T, Geibprasert S, Cruz JP, et al.  Neurovascular Anatomy in Interventional Neuroradiology: A Case based approach. New York, Thieme, 2015. pp. 13-16.

 

1.  In ICA agenesis, APhA reconstitutes in horizontal petrous segment to form "distal ICA" and tympanic artery entering skull through Jacobsen's canal. 

 

2. Symptoms may be absent, or include pulsatile tinnitus, conductive hearing loss,  or a pulsatile retrotympanic mass. 

 

3. It can mimic glomus tumor, otosclerosis or AVM.  A temporal bone CT can help differentiate as aberrant ICA can show absent vertical segment of carotid canal, and lateral swing called line of Lapowyker beyond vestibular line

 

4.  Persistent stapedial artery exists in 0.5 percent of population and can present as pulsatile mass in middle ear cavity with or without pulsatile tinnitus.  Its associated with absent foramen spinosum.  It appears as a vessel  from petrous ICA supplying the MMA.

 

Pearls about aberrant subclavian artery

Krings T, Geibprasert S, Cruz JP, et al.  Neurovascular Anatomy in Interventional Neuroradiology: A Case based approach. New York, Thieme, 2015. pp. 6-9

 

1.  Its usually a remnant of distal right dorsal aorta distal to left subclavian artery, crossing midline to irrigate right upper extremity

 

2.  Diverticulum of Komerell, an outpouching of right dorsal aorta, arises as it crosses the  esophagus that occasionally compresses the esophagus and causes dysphagia "dysphagia lusoria", nonspecific thoracic pain, compression of trachea with dyspnea, or arteriotracheal or arterioesophageal fistulas wityh hematemesis or hemoptysis (very rare).  Even rarer is subclavian steal of ARSA

 

3. It can be inferred from anterior displacement of esophagus in mediastinum

 

4.  May need to intervene through the left vertebral artery which can be difficult 

Pioglitzaone after ischemic stroke

Kernan WN, Viscoli CM, Furie KL et al.  Pioglitazone after ischemic stroke or transient ischemic attack. NEJM 2016; 374:1321-31  and editorial Semenkovich CF.  Insulin resistance and along, strange trip. NEJM; 2016: 374:14-15.

 

Study shows that the drug pioglitozone  for secondary prevention in stroke/TIA is effective.  N=3876 pts v. placebo,  patients with no history of diabetes but with insulin resistance, who were given drug had less diabetes develop, more weight gain, edema and fracture, and less MI/CVA at mean 4.8 years.  Effect magnitude was fairly small, with primary outcome in 9.0 percent (175 patients) in active drug group and 11.8 % (228 patients) in placebo group. Patients on pioglitazone were more likely than placebo patients to stop drug due to side effects.

 

This is also known as the IRIS trial (insulin resistance after stroke).   

 

Editorial speculates patient selection is important to avoid side effects and profiling should include PPAR-y genes.

sammpris study risk factors for stroke w pct

Waters MF et al.  Factors associated with recurrent ischemic stroke in the Medical Group of the SAMMPRIS trial  JAMA Neurology 73:3 2016 pp.308-315

Endpoint: stroke or death within 30 days, stroke in appropriate arterial territory after 30 days.

Overall, risk of a primary endpoint was half of what was expected based on WASID or other studies.The highest risk features are prior stroke in the territory of the stenotic artery, stroke as the qualifying event, and absent statin use at time of enrollment. TRENDS occurred based on risk of higher degree of stenosis and presence of diabetes mellitus.  In WASID, degree of stenosis stratified risk with more risk with higher degree of artery stenosis.   The risk in WASID of stroke was 18 % in 70-79 %, but 31 % in 80-89%.  The groups were not analyzed separately in WASID, above is post hoc.  In Sammpris, only patients 70-99 % were enrolled, and the risk was 19 % with greater than 80 % stenosis, and 12 % with 70-79 % stenosis.  

For diabetics in Sammpris, diabetics reached an endpoint at a rate of 18 % v. 10 % for nondiabetics.  

By artery, the intracranial carotid had a risk of an endpoint of 23 %.  The VA and BA wer 9.3 and (.5 % respectively.  By gender, risk for women was 20.1 per cent, 10.7 % for men.

The risk factors for periprocedural stroke had little overlap, the main ones being in that arm being older age, nonsmoking status, diabetes and BA stenosis.

Patients in medical group with TIA alone had LOW risk at one and two years of 5.6 and 7 % respectively.

Exercise during followup was the most important determinant of outcome in the medical arm.  

Overall the risk of the medical arm in SAMMPRIS was 15 percent at 32 months.

Screening for neuro "clearance" before CABG PEARLS

based on a lecture at ISC 2016 Los Angelos

by Michael Mullen  U Penn

1.  Patient risk factors for perioperative stroke:  (odds ratio):  prior stroke (3.55), PVD, DM AND HTN (EACH around 1.3),  female (1.6).  If divided into early and late stroke, risk factors (odds ratios) for early stroke are prior stroke (11.6), female (6.9), ascending aorta atherosclerosis (2.0), time on bypass (1.1).  Delayed stroke : history of stroke (27.6), diabetes (2.8), female (2.4), low CO and AF (1.7_)  ascending aorta atherosclerosis (1.4)

2. Timing of surgery and risk of stroke after a prior stroke:  (odds ratio). No prior stroke (1.), any prior stroke, any mechanism (4.0);  < 3 monthds prior (14); 3-6 mo prior (4.9); 6-12 mo prior , 3.0; > 12 months prior(2.5).  Sweet spot is 9 months

3.  Carotid screening:  1. not recommended for noncasrdiac surgery   2.  For cardiac surgery scren high risk patients:  >65, left main disease, peripheral vascular disease, history of prior stroke or TIA, carotid bruit based on guidelines ACCF/AHA for CABG (2011) by Hillis et al,  and by Brott et al, on Extracranial caroitd disease.  Published in Circulation.

4.  Risk of stroke with carotid disease: metanalysis(2011) Li et al, JAMA Neurology, 2009.  Low stroke risk in unilateral, asymptomatic carotid stenosis suggests revascularization is not necessary.  Odds ratio for stroke in such patients is (2.0).  However, suggest maintaining arterial perfusion pressure in such patients.

5. In patients with bilateral 50-99 % stenosis, unilateral 50-99 + contralateral occlusion, asymptomatic, odds ratio is (6.5).   Among these patients its reasonable to consider revascularizing one side.

6.  How to sequence procedures: Staged CEA-CABG, combined CEA-CABG

or staged CAS- CABG.  Main risk of staged CEA-CABG is MI, of combined CEA-CABG is stroke.  If CABG is urgent, do a combined CEA-CABG.  If not urgent do staghed CAS-CABG.

White matter hyperintensity patterns

in cerebral amyloid angiopathy and hypertensive arteriopathy.  Neurology; 2016; 86: 505-511.  Authors Charidmou A, Boulouis G, Haley K, et al.

 

Authors studied 319 patients with cerebral amyloid angioapthy and 137 with hypertensive arteriopathy for different patterns of white matter hyperintensity in the two diseases. 

 

Results showed that the presence of multiple subcortical spots was higher in the CAA group, and the peribasal ganglia WMH pattern was more prevalent in the HA group.  Multiple spots was associated with presence of cortical cerebral microbleeds.

The risk of symptomatic carotid stenosis:the

future is not what it used to be.  Chaturvedi S, Rothwell PM.  Neurology 2016; 86-494-495 (editorial) and refers to

 

Johannson E, Cuadrado -Gida E, Hayden D., et al.  Recurrent stroke in symptomatic carotid stenosis awaiting revascularizatio: a pooled analysis. Neurology 2016; 86: 498-504  and to

 

Shahidi S. , Owen Falkenberg A, Hjerpsted U et al.  Urgent best medical therapy may obviate the need for urgent surgery in patients with symptomatic carotid stenosis.

 

Idea: Best medical therapy of today, "second generation medical therapy" including statins, dual antiplatelets, and optimal BP control was not used in NASCET trials in the 1990s.  Therefore, the studies are obsolete and need to be repeated.

 

The two studies mentioned above give opposite suggestions.  Johannson et al. studied patients from three European centers with 50-99% stenosis and recent stroke or tia, and found in 227 suitable patients, a pooled risk risk of ipsilateral stroke of 11.5 % at 14 days and 18.8 % at 90 days, with less risk as usual for retinal ischemia.  A single center in Denmark studied patients with severe carotid stenosis, symptomatic, awaiting CEA with 21st century modern best medical therapy  and found that the rate of events in patients fell from 29 to 2.5 % , with events being TIA's. 

 

They also suggest that the risk in patients with asympromatic stenosis has fallen with "optimal medical therapy" (see Marquardt L, Geraghty OC, Mehta Z et al.  Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective population based study. Stroke 2010; 41: e 11-e17  and Spence JD, Coates V, Li H et al.  Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis.  ArchNeurol 2010; 67: 180-1`86.

AHA / ASA Scientific statement re exclusion/inclusion criteria for alteplase

 

Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al.  AHA/ASA Scientific statement  for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/ American Stroke Association.  Stroke 2016; 47:  1-61.

The above article was previously circulated .  It is not a practice parameter.   It functions as an FAQ / legal cover/ resource for many uncommon scenarios for stroke alerts.  It is not ORMC policy to abide by it.  However, it does summarize existing evidence well, and assigns a grade to the quality of the evidence (class/level of evidence) grades that have become popular. I am re-presenting it in tabular form so it is available during stroke alerts, if needed. 

Please circulate to any/all additional members of the team involved in stroke care that might wish to see it.  Thanks

Daniel Jacobs, MD, FAAN

Director , Orlando Health  Comprehensive Stroke Center

 

Zero to -3 hour window

Not an exclusion

1.  Age > 80

2.  severe stroke

3.  mild / rapidly improving but still disabling stroke

4.  coagulation studies not returned but no clinical suspicion of bleeding disorder 

warfarin use if INR is lower than OR EQUAL to 1.7

5. MI within three months if the MI was nSTEMI, or STEMI affecting the right or inferior myocardium

6.  GI/GU bleed more than 21 days ago

7.  History of cerebral microbleeds

8.  Unruptured cerebral aneurysm (unless a giant aneurysm)

9.  Intracranial extraaxial neoplasm

10. End stage renal disease with normal PTT

11.  Seizure at stroke onset  unless deficits are suspected to be due to postictal phenomenon

12.  Suspected extracranial cervical arterial dissection

13.  Lumbar puncture within 7 days

14. Post cerebral or cardiac catheterization related acute stroke

15.  Absent person to consent for an otherwise eligible patient

16.  Single or dual antiplatelet therapy

17.  Cocaine or other drug use as a possible cause of stroke

alteplase can be considered if benefits outweigh risks

1.  pregnancy esp moderate to severe deficit

2.  history of bleeding diathesis including renal or hepatic disease (consider on a case by case basis)

3.  use of NOAC's (novel anticoagulants) > 48 hours if renal dysfunction is present,may assess with lab (PT, PTT, platelet count, ecarin clotting time, thrombin time, or direct factor Xa activity) 

4.  Major surgery within 14 days- with careful selection and weighing the risk of hemorrhage at the site

5. Major trauma within 14 days on a case by case basis

6.  MI affecting the left anterior myocardium

7. Pericarditis with severe deficit after consulting a cardiologist

8. LV or LA thrombus with severe stroke likely to cause severe disability

9. History of recent stroke within three months

10.  Uncontrolled severe HTN > 185/110 unless it can be lowered safely in a stable fasion and monitored and kept low for 24 hours.

11. Dementia considering premorbid function, patient and family wishes and goals of therapy

12.  Current malignancy if no other contraindications and reasonable life expectancy (> 6 months)

13.  Preexisting major disability considering premorbid function, family wishes and goals of therapy

14.  Diabetic hemorrhagic retinopathy weighing and presenting risks of visual loss against stroke deficit

15.  Vaginal bleeding including menstruation that is monitored for 24 hour period; if anemia is present consider consulting GYN first

16.  Cardiac myxoma and large severe deficit; same for papillary fibroelastoma

Absolute exclusion, uncertain benefit or no evidence favoring

1.  acute intracranial hemorrhage on CT scan

2.  warfarin use with INR > 1.7

3.  therapeutic or prophylactic low molecular weight heparin dose within 24 hours

 or use of NOAC's (novel anticoagulants) within 48 hours  unless lab parameters as appropriate are assessed

4.  Major head trauma within three months

5.  Posttraumatic infarction that occurs in the hospital

6. Pericarditis with mild deficit

7.  LA or LV thrombus with expected mild or moderate disability

8.  Infective endocarditis

9.  Intracranial or intraspinal surgery within three months

10. Major GI or GU bleed within 21 days

11.  Arterial puncture of a noncompressible site within 7 days (eg. subclavian artery)

12. History of intracranial hemorrhage

13. Unruptured cerebral giant aneurysm

14.  Unruptured untreated cerebral AVM's unless benefit outweighs the heightened risk

15.  Intracranial neoplasm intraaxial

16.   End stage renal disease with elevated PTT

17.  Blood glucose initially < 50 or > 400 unless corrected

18.  Large area of hypoattenuation on initial CT scan

19.  Clinical suspicion of subarachnoid hemorrhage

20.  Suspected aortic arch dissection

21.  Suspected intracranial dissection

22.  Stroke due to sickle cell disease

Extended window:  Three to 4.5 hours

Not an exclusion

1.  Age > 80

2.  On warfarin with INR < 1.7

3.  Prior stroke and diabetes

alteplase can be considered if benefits outweigh risks

Absolute exclusion, uncertain benefit or no evidence favoring

1.  NIHSS > 25

2.  Wake up stroke with time last normal > 4.5 hours

3.  Use of neuroimaging to select patients with last time normal > 4.5 hours