Friday, November 24, 2017

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="">

Monday, September 04, 2017

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

Monday, September 12, 2016

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 

Friday, July 15, 2016

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.

Sunday, May 15, 2016

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.

Sunday, March 20, 2016

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.

Tuesday, February 23, 2016

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.

Wednesday, January 20, 2016

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

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

Sunday, January 03, 2016

Alteplase in strokes with NIHSS>25

Mazya MV, Lees KR, Collas D, et al.  IV thrombolysis in very severe and severe acute ischemic stroke. Results from the SITS/ISTR registry.  Neurology 2015; 85:20898-2106 (also editorial).
Authors study a large number of patients with severe strokes and find that iv alteplase does not affect their chances of developing a hemorrhage.  There also was no difference in treatment benefit compared to those with lower NIHSS scores.

Saturday, August 22, 2015

low dose v standard dose altephase in acute ischemic stroke

Journal Stroke


Korean authors


Background and Purpose—The low-dose (0.6 mg/kg) alteplase strategy to treat acute ischemic stroke patients became widespread in East Asian countries, without rigorous testing against standard-dose (0.9 mg/kg) alteplase treatment. Our aim was to investigate the comparative effectiveness and safety of the low-dose versus standard-dose intravenous alteplase strategy.

Methods—A total of 1526 acute ischemic stroke patients who qualified for intravenous alteplase and treated within 4.5 hours were identified from a prospective, multicenter, and nationwide stroke registry database. Primary outcomes were a modified Rankin scale score of 0 to 1 at 3 months after stroke and occurrence of symptomatic hemorrhagic transformation. Inverse probability of low-dose alteplase weighting by propensity scores was used to remove baseline imbalances between the 2 groups, and variation among centers were also accounted using generalized linear mixed models with a random intercept.

Results—Low-dose intravenous alteplase was given to 450 patients (29.5%) and standard-dose intravenous alteplase to 1076 patients (70.5%). Low-dose alteplase treatment was comparable to standard-dose therapy according to the following adjusted outcomes and odds ratios (95% confidence intervals): modified Rankin scale score 0 to 1 at 3 months and 0.95 (0.68–1.32); modified Rankin scale 0 to 2 at 3 months and 0.84 (0.62–1.15); symptomatic hemorrhagic transformation and 1.05 (0.65–1.70); and 3-month mortality and 0.54 (0.35–0.83). The associations were unchanged when the analysis was limited to those without endovascular recanalization.

Conclusions—The low-dose alteplase strategy was comparable to the standard-dose treatment in terms of the effectiveness and safety.

Thursday, July 02, 2015

New guidelines for endovascular therapy with emphasis on Class I level a

New Class I level A recommendations for endovascular therapy
(1) pre-stroke modified Rankin Score (mRS 0-1)
(2) acute ischemic stroke receiving IV rtPA within 4.5 hours of onset according to guidelines from professional medical societies,
(3) causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1),
(4) age 18 years and over,
(5) National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater,
(6) Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of6 or greater, and
(7) treatment can be initiated (groin puncture) within 6 hours of symptom onset
"If endovascular therapy is contemplated, a noninvasive intracranial vascular study is strongly recommended during the initial imaging evaluation of the acute stroke patient but should not delay IV rtPA if indicated. For patients who qualify for IV rtPA according to guidelines from professional medical societies, initiating IV rtPA before non-invasive vascular imaging is recommended for patients who have not had non-invasive vascular imaging as part of their initial imaging assessment for stroke. Non-invasive intracranial vascular imaging should then be obtained as quickly as possible"  (Class I, Level A recommendation)
"Regional systems of stroke care should be developed. These should consist of consisting of:
Health care facilities that provide initial emergency care including administration of IV rtPA, including PSCs, CSCs and other facilities
Centers capable of performing endovascular stroke treatment with comprehensive peri-procedural care, including CSC and other health care facilities, to which rapid transport can be arranged when appropriate"
Class 1 Level A evidence
When treatment is initiated beyond 6 hours from symptom onset, the benefits of endovascular therapy are uncertain for patients with acute ischemic stroke who have causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1).Additional randomized trial data are needed
"It might be reasonable to favor conscious sedation over general anesthesia during endovascular therapy for acute ischemic stroke. However, the ultimate selection of anesthetic technique during endovascular therapy for acute ischemic stroke should be individualized based on patient risk factors, tolerance of the procedure, and other clinical characteristics. Randomized trial data are needed.  (RATES ONLY LEVEL 2B, CLASS C RECOMMENDATION)" (Dr. Tsappidi previously outlined case for anesthesia and our policy is that the interventionist can decide whether to use).


206 patients with acute ischemic stroke

PROBE design


Intracranial ICA or M1 occlusion by CTA, MRA or DSA.

Patients who had received IV rtPA were eligible if there was no significant neurological improvement (criteria specified in the protocol) at 30 minutes post initiation of the infusion and vascular imaging at this time confirmed an eligible occlusion.

Groin puncture had to be possible within 8 hours of stroke onset.

There were exclusion criteria for coagulopathies. The main exclusion criteria on imaging were ASPECTS <7 on NECT or <6 on DWI-MRI. After the enrollment of 160 patients, the inclusion criteria were modified to include patients up to the age of 85 years (initially 80 years was maximum allowed) with an ASPECTS >8.

Only 95% confidence intervals were reported.

The primary outcome analysis showed a common odds ratio of improvement in the distribution of the modified Rankin scale score (shift analysis) favoring endovascular treatment (adjusted odds ratio 1.7, 95% CI 1.05 to 2.8).

The proportion of patients with a mRS of 0-2 at 90 days was 43.7% in the intervention group and 28.2% in the control group (adjusted odds ratio 2.1, 95% CI 1.1 to 4.0).

There were no significant differences in death or sICH.

Ninety-five per cent of those in the endovascular group underwent thrombectomy.

TICI 2b/3 recanalization was observed in 66% of the endovascular group.

Across the pre-specified subgroups, there were no significant interactions according to NIHSS score, vessel-occlusion site, baseline ASPECTS score, administration of IV rtPA, age or time of randomization, although for the latter dichotomized at 4.5 hours, the p-value for interaction was 0.9 with the later group doing worse. No data are given for those who underwent groin puncture after 6 hours


Seventy participants who were eligible using "standard criteria" to receive IV rtPA within 4.5 hours of stroke onset were randomized in a PROBE design to receive either IV rtPA only or IV rtPA plus endovascular therapy with a stent retriever.

Groin puncture had to be within 6 hours and endovascular treatment had to be completed within 8 hours after stroke onset.

CT or MRI had to be performed before commencing IV rtPA. Occlusion of the ICA or of M1 or M2 on CT angiography was required. In addition, CT or MRI perfusion imaging had to show (a) mismatch ratio of greater than 1.2, and (b) absolute mismatch volume of greater than 10 mL, and (c) infarct core lesion volume of less than 70mL based on specialized software

Exclusion criteria for coagulopathies as in SWIFT-PRIME

The co-primary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the NIHSS or a score of 0 or 1 at day 3). The mRS at 90 days was a secondary outcome.
Results Interim Analysis:

Trial halted showed that stopping criteria had been met.

Occlusion sites: ICA 31%, MCA 54%

Percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular group than in the IV rtPA group.

Outcomes: Endovascular therapy, initiated at a median of 210 (IQR 166-251, IQR) minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, p=0.002).

More patients achieved functional independence in the endovascular group (mRS 0-2, 71% vs. 40%; p=0.01).

There were no significant differences in rates of death or sICH.

Recanalization to TICI2b/3 was achieved in 86% of patients in the endovascular group at a median of 248 (IQR 204-277) minutes after stroke onset.



To determine if patients experiencing an acute ischemic stroke due to large vessel occlusion, treated with combined IV tPA and Solitaire FR within 6 hours of symptom onset, have less stroke-related disability than those patients treated with IV tPA alone.


Global, multicenter, prospective, randomized, open, blinded endpoint (PROBE) IDE Study

Intervention: IV rtPA with Solitaire FR Device

Control: IV rtPA alone

39 enrolling centers
Inclusion Criteria

Acute ischemic stroke

Age 18-80

Pre-stroke mRS<1


Baseline NIHSS 8-29 at time of randomization

Initiation of IV rtPA within 4.5 hours of onset of stroke

CTA or MRA confirmation of large vessel occlusion in ICA, M1 segment of MCA or carotid terminus

Endovascular treatment can be initiated within 6 hours of onset of stroke symptoms and within 90 minutes from CTA/MRA to groin puncture
If CTA or MRA was part of local standard of care, it was performed at initial evaluation prior to commencing IV rtPA; if not, it was performed after review of the initial imaging and signing of informed consent.

Initially, CT perfusion or multimodal MRI was required and enrollment was restricted to patients with the target mismatch profile (as assessed by specialized software) and defined as: the ischemic core lesion measured 50 mL or less, the volume of tissue with a time to maximum delay of more than 10 seconds was 100 mL or less, and the mismatch volume was at least 15 mL and the mismatch ratio was more than 1.8.

Midway through the trial, the inclusion criteria were modified to accommodate sites with limited perfusion imaging capability. Sites with perfusion imaging were encouraged to continue to use the target mismatch criteria. Sites without perfusion imaging used ASPECTS scores (ASPECTS > 6 was required)

196 patients were randomized after IV rtPA up to 6 hours from onset to groin puncture to Solitaire IA therapy or control.

Two primary outcomes (shift analysis): mRS at 90 days (p < 0.001) and increased proportion with mRS 0-2 at 90 days -60% in the endovascular group and 35% in the rtPA alone group (risk ration 1.70, 95% CI, 1.23-2.33)

No differences in death or symptomatic ICH (sICH)

TICI 2b/3 recanalization: = 88% in the endovascular group.

escape TRIAL

PROBE two-arm superiority trial of 316 patients with acute ischemic disabling stroke, NIHSS > 5, capable of being randomized up to 12 hours after onset.

CT/CTA, NECT and CTA (multiphase): door to imaging <25 minutes

Small infarct core (ASPECTS = 6-10 or CTP)

Occluded proximal artery in anterior circulation, MCA -M1 or 2 or more M2, moderate to good collaterals(filling of 50% of the pial MCA on CTA)

1:1 randomization of 58 patients who received IV rtPA within 4.5 hours

Receive guideline-based care alone or guideline-based care plus endovascular treatment with the use of available thrombectomy devices. The use of retrievable stents and suction through a balloon guide catheter during thrombus retrieval was also recommended.

The primary outcome was the odds ratio that the intervention would lead to lower scores on the mRS at 90 days (shift analysis).

Interim analysis after the O'Brien Fleming stopping boundary was crossed.

Primary Outcome: The adjusted odds ratio (indicating the odds of improvement of 1 point on the mRS) was 3.1 (95% CI, 2.0 to 4.7) favoring endovascular intervention.

The difference in proportion of patients with a mRS of 0-2 at 90 days was 53% in favor of the intervention group versus 23.7% in the control group (p<0.001).

Retrievable stents were used in 86.1% who underwent an endovascular procedure.

TICI 2b/3 recanalization was observed in 72.4% in the endovascular group.

The number randomized after 6 hours was too small to reach any conclusions regarding intervention beyond 6 hours.

MR Clean results

A PROBE, two-arm, superiority trial that studied 500 patients with acute ischemic stroke caused by an proximal intracranial occlusion in the anterior circulation [distal intracranial carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery (A1 or A2)] established by computed tomographic angiography (CTA), magnetic resonance angiography (MRA), or digital-subtraction angiography (DSA), and a score of 2 or higher on the NIHSS

Initiation of endovascular treatment within 6 hours of stroke onset had to be possible.

Patients who were eligible in agreement with national guidelines received IV rtPA. Those with a non-favorable response were eligible for inclusion.

Randomized 1:1 (usual care, IA treatment plus usual care)

Occlusion site: M1 (64%), ICA + M1 (27%)

Onset to groin puncture: 260 (210-313 IQR) minutes

Stent retriever used in: 81.5%

TICI 2b/3 revascularization in 59%; Stroke to reperfusion time: 322 (279-394 IQR) minutes

The treatment effect was estimated as an odds ratio, adjusted for pre-specified prognostic factors, that IA treatment would lead to lower mRS at 90 days, as compared with usual care alone (shift analysis)

Outcome:Absolute difference of 13.5% (95% CI, 1.21 to 2.30) in achieving mRS 0-2 in favor of the intervention group

This difference became non-significant if reperfusion was delayed > 6.2 hours

Tuesday, May 19, 2015

The earlier tpa is given, the better GWTG evidence

Saver JL, Fonarow GC, Smith EE. et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke.  JAMA 2013; 309; 2480-2488. 

Authors used real world data based on GWTG registry, covering 54,353 patients treated between 2003-2012 at 1395 institutions, and analysed in fifteen minute increments for treatment effects.  Across the ninety minute increments (0-90, 91-180, 181-270 minutes) there was no difference in hospital characteristics such as treatment time or volume, treatment rates, or designation as a stroke center.  Patients treated in first ninety minutes had higher NIHSS scores (mean 12) than those treated in the 181-270 time frame  (mean 9.0).  Nonetheless, faster treatment . 

Findings based on fifteen minute increments showed less mortality  for each 15 minute increment (0.96 OR), and increased odds of independent ambulation at discharge (or 1.03 per 15 minute increment). 

IST 3 -- benefits of tpa in elderly at greater than three hours

Sandercock P, Wardlaw JM, Lindley RI, et al.  The benefits and harms of  intravenous thrombolysis with recombinant tissue plasminogen activator within six hours of acute ischaemic stroke(the third international stroke trial IST 3); a randomized control trial.  Lancet 2012; 379: 2352-2363.
Study looked at tpa among patients without clear indication or contraindication to tpa, in a European study.  Due to approval initially in Europe for age < 79  and use within 3 hours of onset, this study was in effect for those >79, and those outside 3 hours, in Europe.  Study looked at tpa + usual care v. usual care. 156 sites enrolled 2025 patients.   53 % were > 79, 72 % were treated after 3 hours after stroke onset but thin six hours.  There was no significant difference in the dichotomized outcome, the initial primary measure, but by shift analsysi of the Oxford Handicap scores, TPA improved the odds of a one level improvement in the outcome.  sICH occurred in 7 % v. 1 % of the control group. 
In the subset treated within 3 hours, the primary dichotomized outcome occurred more with tpa than with the control group (OR 1.64) 

Wardlaw JM, Murray V, Berge E. et al.  Recombinant tissue plasminogen activator  for acute ischaemic stroke: an updfated systematic review and metanalysis.  Lancet 2012; 309: 2480-2488.

An updated metaanalysis of tpa trials that included IST 3 showed that ivv tpa given within 3 hours of stroke improved the odds of a good functional outcome (OR 1.53)

Large percent of posterior circulation strokes missed by acute MRI; however tpa does not usually resolve diffusion deficits on MRI

Hotter B, Kufner A, Malzahn U. et al.  Validity of negative high resolution diffusion weighted imaging in transient cerebrovascular events.  Stroke 2013; 44:2598-2600
151 patients with suspected stroke and negative DWI in first twenty four hours , 63 underwent followup MRI showing stroke in seven (11%).  5/7 had at least one point on NIHSS. 
Oppenheim C, Stanescu R, Dormont D, et al.  False negative diffusion weighted MR findings in acute ischemic stroke.  AJNR 2000; 21: 1434-1440
older study showing miss rate of about 20 %
Schellinger PD, Bryan RN, Caplan LR et al.  Evidence -based guideline: the role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology; 2010; 75:177-185.
guideline from AAN cautioning that sensitivity of MRI to diagnose stroke is imperfect.

Albach FN, Brunecker P, Usnich T, et al.  Complete early reversal of diffusion weighted imaging hyperintensities after ischemic stroke is mainly limited to small embolic lesions.  Stroke 2013; 44:1043-1048

Authors studied 153 patients with an average NIHSS of 4 who received tpa; and underwent MRI on admission and in subsequent week.  97/611 (16%) of MRI diffusion hyperintensities resolved, but only 2 % of patients had ALL of their diffusion abnormalities resolve after receiving tpa.

Sunday, March 29, 2015

renal function and tpa

IV thrombolysis and renal function.

Gensicke H1, Zinkstok SM, Roos YB, Seiffge DJ, Ringleb P, Artto V, Putaala J, Haapaniemi E, Leys D, Bordet R, Michel P, Odier C, Berrouschot J, Arnold M, Heldner MR, Zini A, Bigliardi G, Padjen V, Peters N, Pezzini A, Schindler C, Sarikaya H, Bonati LH, Tatlisumak T, Lyrer PA, Nederkoorn PJ, Engelter ST.
OBJECTIVE: To investigate the association of renal impairment on functional outcome and complications in stroke patients treated with IV thrombolysis (IVT).

METHODS: In this observational study, we compared the estimated glomerular filtration rate (GFR) with poor 3-month outcome (modified Rankin Scale scores 3-6), death, and symptomatic intracranial hemorrhage (sICH) based on the criteria of the European Cooperative Acute Stroke Study II trial. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients without IVT treatment served as a comparison group.

RESULTS: Among 4,780 IVT-treated patients, 1,217 (25.5%) had a low GFR (<60 mL/min/1.73 m(2)). A GFR decrease by 10 mL/min/1.73 m(2) increased the risk of poor outcome (OR [95% CI]): (ORunadjusted 1.20 [1.17-1.24]; ORadjusted 1.05 [1.01-1.09]), death (ORunadjusted 1.33 [1.28-1.38]; ORadjusted 1.18 [1.11-1.249]), and sICH (ORunadjusted 1.15 [1.01-1.22]; ORadjusted 1.11 [1.04-1.20]). Low GFR was independently associated with poor 3-month outcome (ORadjusted 1.32 [1.10-1.58]), death (ORadjusted 1.73 [1.39-2.14]), and sICH (ORadjusted 1.64 [1.21-2.23]) compared with normal GFR (60-120 mL/min/1.73 m(2)). Low GFR (ORadjusted 1.64 [1.21-2.23]) and stroke severity (ORadjusted 1.05 [1.03-1.07]) independently determined sICH. Compared with patients who did not receive IVT, treatment with IVT in patients with low GFR was associated with poor outcome (ORadjusted 1.79 [1.41-2.25]), and with favorable outcome in those with normal GFR (ORadjusted 0.77 [0.63-0.94]).

CONCLUSION: Renal function significantly modified outcome and complication rates in IVT-treated stroke patients. Lower GFR might be a better risk indicator for sICH than age. A decrease of GFR by 10 mL/min/1.73 m(2) seems to have a similar impact on the risk of death or sICH as a 1-point-higher NIH Stroke Scale score measuring stroke severity.

Thursday, March 26, 2015


ESCAPE trial  (" Endovascular treatment for small core and anterior circulation proximal occlusion with emphasis on minimizing CT to recanalization times")
120 patients with proximal anterior circulation occlusion were randomized to alteplase v. alteplase + embolectomy.  Study was stopped early due to positive results.  Outcome measure was mrs at 90 days.  The study used CT and CT-A and multiphase CT angiogram. mrs of 0-2 was achieved in 53 % v. 29.2 % (p<0.001).
SWIFT PRIME ("Solitaire with the intention for thrombectomy as primary endocascular treatment"). 98 patienrs were randomized in each arm within 4.5 hours to tpa and 6 hours of symptom onset to Solitaire.  Outcome was mrs 0-2 at 90 days 60.2 % with endovascular treatment v. 35.5 % without (p= 0.0002)
For every 100 patients treated, 39 would have a better outcome with endovascular than with just tpa, and an additional 25 % would reach functional independence. Study was led by Dr. Saver.  He notes that whether to perform the procedure after six hours is not answered.
For MRS of 0, 17 % of patients achieved who got alteplase + procedure v. 8.6 % of alteplase only
For MRS of 1, 25.5 % v. 10.8 % 
For MRS of 2, numbers wwere 17.3 % v. 17.2 %
Overall good outcome occurred in 60.1 % of patients with embolectomy v. 35.5 % of patients with T-pa alone.
EXTEND 1A: ("Extending the time for thrombolysis in emergency neurological deficits-intraarterial").  35 patients were randomized to tpa alone, 33 to embolectomy but only 27 underwent embolectomy.  37 % of tpa patients achieved early reperfusion v. 100 % of embolectomy patients (p<0.0001).  37 % of patients on tpa achieved early neurological recovery v. 80 % of patients receiving embolectomy (p=0.0002).  They used the Solitaire stent and a 4.5 hour tpa window.  Endovascular was initiated within 210 minutes after onset of stroke.  Study was led by Dr. Bruce Campbell in Austrailia. 

Thursday, February 05, 2015

Stroke.43: 412-416

The Safety of Intravenous Thrombolysis for Ischemic Stroke in Patients With Pre-Existing Cerebral Aneurysms

A Case Series and Review of the Literature

  1. S. Andrew Josephson, MD
+ Author Affiliations
  1. From the Department of Neurology (N.J.E., S.A.J.), University of California San Francisco, San Francisco, CA; and the Department of Neurology and Neuroscience (H.K.), Weill Cornell Medical College, New York, NY.
  1. Correspondence to Nancy J. Edwards, MD, University of California San Francisco, Neurovascular Service, 505 Parnassus Avenue, Box 0114, San Francisco, CA 94143-0114. E-mail


Background and Purpose—Unruptured cerebral aneurysms are currently considered a contraindication to intravenous tissue-type plasminogen activator for acute ischemic stroke. This is due to a theoretical increase in the risk of hemorrhage from aneurysm rupture, although it is unknown whether this risk is a significant one. We sought to determine the safety of intravenous tissue-type plasminogen activator administration in a cohort of patients with pre-existing aneurysms.
Methods—We reviewed the medical records of patients treated for acute ischemic stroke with intravenous tissue-type plasminogen activator during an 11-year period at 2 academic medical centers. We identified a subset of patients with unruptured cerebral aneurysms present on prethrombolysis vascular imaging. Our outcomes of interest were any intracranial hemorrhage, symptomatic intracranial hemorrhage, and subarachnoid hemorrhage. Fisher exact test was used to compare the rates of hemorrhage among patients with and without aneurysms.
Results—We identified 236 eligible patients, of whom 22 had unruptured cerebral aneurysms. The rate of intracranial hemorrhage among patients with aneurysms (14%; 95% CI, 3%–35%) did not significantly differ from the rate among patients without aneurysms (19%; 95% CI, 14%–25%). None of the patients with aneurysms developed symptomatic intracranial hemorrhage (0%; 95% CI, 0%–15%) compared with 10 of 214 patients without aneurysms (5%; 95% CI, 2%–8%). Similar proportions of patients developed subarachnoid hemorrhage (5%; 95% CI, 0%–23% versus 6%; 95% CI, 3%–10%).
Conclusions—Our findings suggest that intravenous tissue-type plasminogen activator for acute ischemic stroke is safe to administer in patients with pre-existing cerebral aneurysms because the risk of aneurysm rupture and symptomatic intracranial hemorrhage is low.

Please note these are people who were incidentally found to have aneurysms on screening.  There is no guideline to say that managing patients with tpa is safe or valid.

Tuesday, January 13, 2015

Effects of Glden Hour Thrombolysis

Ebinger M, Kunz Am Wendt M et al  Effects of golden hour thrombolysis: a prehospital acute neurological treatment and optimizatyion of medical care in stroke (Phantom S ) Study.  JAMA Neurol 2015; 72: 25-30 with accompaning editorial
German study with stroke emergency mobile units, ie ambulances with CT scanner, POC lab, and telemedicine connection.  It also is staffed with a neurologist.
Rates of thrombolysis in golden hour 22 v. 32 % with deployment of STEMO, rate of golden hour thrombolysis is higher and were more likely to be discharged home with no increased risks to patient. The future?
Comment-- watch what happens in Germany and try to apply it to the United States
Our ambulances have cited short drive times to OH

Sunday, December 07, 2014

Pearls on strokes associated with hematologic diseases

This is based on an OLD article by Martin Samuels, so newer drugs for condition are not included
Samuels MA, Thalinger K.  Cerebrovascular manifestations of selected hematologic diseases.  Seminars in Neurology 11:4 1991.
1.  Anemia-- examine the EYE.  First sign is pallor, then spindle shaped retinal hemorrages with cotton wool spots. 
2.  Blood transfusions can trigger stroke in patients with Beta thallasemia (cites Logothetis J. et al. Neurology 1972;22:294-304.
3. In thrombocytopenia, intracranial hemorrhages occurs as small ring shaped hemorrhages in the gray and white matter due to capillary bleeding.Subdural, subarachnoid and epidural hemorrhages are rare inthis condition.  Peripheral nerve and spinal cord hemorrhage also are rare.
4. In thrombotic thrombocytic purpura (TTP), consists of triad of thrombotic purpura, hemolytic anemia and neurologic manifestations.  Fever and renal disease are "invariably" present.  Diagnosis depends on tissue of skin, lymph node, bone marrow or spleen that show hyalinization of arterioles and platelet thrombi with small foci of parenchymal necrosis and petecchiae."Gray matter" symptoms include headache, confusion, aphasia, hemiparesis,visual changes, dysarthria, seizures, coma, vertigo. Exchange transfusion helps dramatically. Other treatments are heparin, steroids, splenectomy.
5.  In hemolytic uremic syndrome, similar to TTP, caused by immune deposits, exchange transfusion can result in dramatic improvement.  FFP without albumen also helps. 
6.  Henoch-Schoenlein purpura (anaphylactoid purpura) is characterized by serosanguineous effusions into subcutaneous, submucous, and subserous tissues, esp in young adults.  Treatment is supportive.  ICH and SAH occur rarely.
7.  Ischemic strokes occur in 15-32 percent of patients with polycythemia vera.  The annual incidence of TIA/ stroke is 4-5 percent even in those treated with phlebotomy.  Conversely, risk of stroke is rare in secondary polycythmia.  For example, someone with congenitally cyanotic heart disease and Hct of 60 has very low risk, none occurred in a small series cited with> 200 patient years of followup.
8.  Hyperviscosity syndrome is a major cause of stroke in patients with myeloma.  Clinical presentation is stupor, coma, drowsiness, inattention,delirium.  Fundoscopic changes include "sausage veins,"  retinal hemorrhages and exudates.  Focal events can occur in Waldenstrom's macroglobulinemia.  Plasma exchange can dramatically improve symptoms due to heavy proteins.

Tuesday, December 02, 2014

PFO and attributable risk with RoPE score

                        cryptogenic stroke, CS (n= 3,023)                                           
RoPE score          No patients   Prevalence PFO   PFO attributable   
0-3                         613               23(19-26)             0                          
4                            511               35(31-39)             38 (25-48)              
5                            516               34 (30-38)            34 (21-45)             
6                            482               47(42-51)             62 (54-68)         
7                            434               54(49-59)             72 (66-76)            
8                            287               67(62-73)             84 (79-87)         
9-10                       180                73(66-79)             88(83-91)         
                       cryptogenic stroke (CS) with PFO (N=1,324)
                            No CS+PFO    est 2 yr TIA/CVA (Kaplan-Meier) 
0-3                         108                20(12-28)
4                            148                12(6-18)
5                            186                  7 (6-18)
6                            236                  8 (4-12)
7                            263                  6 (2-10)
8                            233                  6 (2-10)
9-10                       150                   2(0-4)

attributable risk PFO based on Bayes' theorem

derivation of data used to make RoPE database

RoPE score for PFO

RoPE score for PFO (Risk of Paradoxical Embolus)

Characteristic    Points

No history of
DM                         1
stroke/TIA              1
HTN                       1
nonsmoker             1
cortical infarct        1

18-29                      5
30-39                      4
40-49                      3
50-59                      2
60-69                      1

total score  -- add sum of parts
cut score used in many articles is 7

source Neurology 2013 au Thaler

RoPE score, PFO and CS

Thaler DE, Ruthazer R, Weimar C., et al.  Recurrent stroke predictors differ in medically treated patients with pathogenic v. other PFO's.  Neurology 2014; 83: 221-226.
The RoPE score, "Risk of Paradoxical Embolism" score estimates the probability that a PFO discovered in a cryptogenic stroke (CS) patient is incidental or pathogenic, based on Bayes theorem.  Patients with high RoPE score (younger, no vascular risk factors, and a superficial infarct) are more likely to have pathogenic PFO's while patients with low RoPE scores (older, vascular risk factors) are probably incidental.  Authors hypothesized that predictors of recurrent stroke should differ among high and low RoPE score patients and PFO characteristics should be les important in low RoPE score individuals. 
Risk factors for recurrence with 1-2.2 yrs of followup  included LOW RoPE scores (one year followup, 7 v. 4 %; two year followup 10 v. 5 %) with 4/5 recurrences being in low score subgroup 
Patients with TIA had more recurrent events (HR 1.69) but there was no interaction with RoPE score.
Variable associated with risk in low RoPE group include older age, those treated with antiplatelet drugs after initial event.

Variables associated with recurrence in highRoPE score group include history of stroke or TIA, hypermobile interatrial septum, and a small shunt, but not shunt at rest. 
Comment of blogger
The article confirms / validates the RoPE score to some extent.  However, the point of closure is to prevent lifetime risk of paradoxical embolus, not 2 year risk.  As such, I am skeptical of the claim that risk of recurrence is lower in high RoPE score group

Sunday, November 30, 2014

MELAS pearls

1. Onset before 40
2. Clinical: hemiparesis, hemianopia, cortical blindness; seizures, dementia, migraine, muscle weakness,
3. Associated
Short stature
Hearing loss
Recurrent vomiting
4. May be relapsing remitting
5. High lactic/abn muscle biopsy
6. AVOID statins and Depakote


Retinal vasculopathy with cerebral leukodystrophy aka cerebroretinal vasculopathy sysndrome aka hereditary endotheliopathy, retinopathy, nephropathy and stroke.

Vision and memory loss

Onset in fourth decade
Death in five to ten years

Retinopathy is neovascularization of disc, retinal hemorrhage a and macular edema.

Half patients have tumor like lesion with cortical sparing resembling malignancy.

Small white matter lesions may resemble MS

Caused by mutations o. TREX1 gene

Inherited as aut dom

Retinopathy may respond to bevacizumab

CARASIL pearls

1.  Onset decades 3 to 5
2.  Premature alopecia occurs in teen years
3.  Cervical and lumbar spondylitis occurs in 2d and 3d decades
4.  Mutations in A serine peptides 1 on chromosome 10 q is implicated

Cadasil pearls

1. Strokes are subcortical many with classic lacunae syndromes
2. False negative genetic tests should prompt skin biopsy for granular osmiophic material in the vascular basal lsmina which is a specific finding
3. MRI finding occur in anterior temporal poles (o'Sullivan sign seen in 90 percent) but also extreme capsule and corpus callosum also are distinctive
4.  Other MRI findings are microbleeds and brain atrophy
5.  80 plus NOTCH3 mutations are identified
6.  Migraine with aura occurs in 30 percent, often in 3rd decade long before strokes

Unruptured aneurysm pearls

1. High risk patients who require screening are those with at least two first degree relatives with aneurysm or autosomal dominant polycystic kidney disease

2. Risk factors include age, female gender, family history

3. Risk of rupture in positive family history patients is 17 x higher than in predicted based on size and location in observational studies (Familial Intracranial Aneurysm study).

4. Associated diseases are Marfan syndrome, Ehler Danlos syndrome type IV, aortic coarctation, FMD, and autosomal dominant PCK (12.4 percent).

5. Modifiable risk factors for aneurysm growth include smoking, alcohol abuse and hypertension

6. MCA bifurcation aneurysms are more readily accessible to surgery.

Pearls pediatric stroke

1. Stroke may present with seizures in newborns and even older kids

2. Paroxysmal or stuttering episodes ppt by HV is typical for Moyà Moyà

3. In newborn, consider maternal factors (HTN, DM), perinatal factors, neonatal factors (congenital heart disease, dehydration, infection), and PLACENTAL vasculopathy

4. ACCP recommends against the use of altplace in pediatric stroke outside clinical trials

5. In Toronto, UFH is used for AIS regardless of mechanism

6. The syndrome of transient cerebral arteriopathy of childhood is a well defined unilateral focal arteriopathy presumably of inflammatory origin. Features include irregular stenosis at carotid T junction. Varicella angiopathy is similar and borrelia and bartonella are also reported. Treatment may include antithrombotics, high dose pulse steroids with long taper, and acyclovir. differential includes Moyà Moyà and dissection of the carotid.

Hypercoagulable misc

1. Homocystinuria, anti phospholipid syndrome, and thrombin deficiency are some of the only syndromes associated with arterial thrombosis

2. The most common acquired thrombophilia is the apl syndrome

3. Seven percent of the white population carries the prothrombin gene mutation but it's rare in black and Asian populations

4. Inherited protein S deficiency autosomal dominant and heterozygous; homozygous is incompatible with life.

5. Protein C deficiency can be due to meningococcemia, liver disease, DIC, ARDS, methotrexate, 5FU, and cyclophosphamide.

Saturday, November 29, 2014

Pearls on factor V (Leiden) mutation

1. By far the most common genetic risk factor for thrombophilia

2. Mechanism: increases thrombin production

3. Prevalence varies widely by ethnicity: 5.3 percent in whites, 2.2 percent in Hispanics, 1.3 percent in native Americans, 1.2 percent in African Americans, 0.5 percent in Asian Americans.

4. Five to ten percent of heterozygous carriers in their lifetimes; a sevenfold risk over non carriers but homozygous have an 80 fold risk.

5. 90 to 95 percent of patients with protein C resistance have a point mutation of factor V506Q.

6. Other causes of increased protein C resistance include smoking, oral contraceptives, pregnancy, HRT use, cancer, and anti phospholipid syndrome

7. Syndrome is convincingly linked to venous but not arterial thrombotic events

8. Testing in nonwhite populations is low yield

9. Testing in ischemic stroke in absence of a right to left shunt is low yield

10. In presence of a right to left shunt screening for Dvt with leg ultrasound and pelvic venography is useful

Tuesday, November 25, 2014

thrombolysis and aneurysms

Post-Thrombolysis Hemorrhage Risk of Unruptured Intracranial Aneurysms; Chen F, Yan S, Jin X, Lin C, Cao J; European Neurology 73 (1-2), 37-43 (Nov 2014)

Background/Aims: It has been questioned whether patients with unruptured intracranial aneurysms (IAs) are at a greater risk for the development of intracerebral hemorrhage (ICH) following thrombolytic therapy. We thus performed a meta-analysis to better quantify the risk of post-thrombolysis ICH in patients with acute ischemic stroke and incidental IAs. Methods: We searched PubMed, Web of Science and EMBASE for studies assessing ICH risk in patients with acute ischemic stroke treated with thrombolysis, in relation to the presence of pretreatment IAs. A fixed-effects model meta-analysis was performed. Results: We identified four studies totaling 707 participants receiving intravenous thrombolysis. The prevalence of unruptured IAs was 6.8%. Pooled analysis demonstrates relative risk (RR) for the presence of unruptured IAs and the development of any ICH to be 1.204 (95% CI 0.709-2.043; p = 0.492; I(2) = 0.0%). The RR for sICH is 1.645 (95% CI 0.453-5.970; p = 0.449; I(2) = 28.1%). Conclusion: Intravenous thrombolysis was safe among patients with acute ischemic stroke and incidental unruptured IAs. Future prospective studies with much larger sample sizes are required to clarify the significance of the association between pre-existing unruptured IAs and the development of post-thrombolysis ICH. © 2014 S. Karger AG, Basel.


Friday, November 14, 2014

Subarachnoid hemorhage and growth hormone treatment in childhood

Poidvin A, et al.  GH treatment for childhood short stature and risk of stroke in early adulthood. Neurology; 2013; 83: 780-6.
6874 children with idiopathic GH deficiency or short stature who stated GH treatment had  rate of hemorrhage from 3.5 to 7.0 compared registry rates. from 1985-96 
Editorial (Ichord R) outlines ramifications on screening adults exposed to GH and counselling kids considering GH about risks, which are small but not negligible.

Small strokes causing severe vertigo. Frequency of false negative MRI's and

nonlacunar mechanisms.
Tehrani ASS, Kattah JC, Mantokoudis G, et al. Neurololgy 2014; 83: 169=173
Out of acute vestibular syndrome (AVS)  25 % have stroke
80 % of patients with stroke have isolated dizziness/vertigo and 20 % have focal neurologic signs
35 % of strokes are missed, often with negative MRI's. 
Out of 190 high risk  AVS presentations, 105 strokes
15  "small strokes" who underwent repeat imaging and found lesion < 10 mm in axial diameter
Location of stroke: lateral medulla (60 %)
Etiology Many dissections of vertebral artery, less commonly small vessel, cardiac embolus 
"HINTS PLUS" with the plus being a "hearing battery" bedside finger rub picks up the AICA strokes more accurately than MRI
My comment-
Lateral medullary infarctions have expected neurologic signs and symptoms that may be missed by physicians who do not know what to look for.  These include decreased gag/phonation, and crossed sensory symptoms (loss of st tract on one foot, dorsal column function on the other) that will pick up many or most of those. I would guess that in AVS with HINTS plus hearing eval plus careful gag/sensory exam some if not most of the strokes could be diagnosed clinically and localized accurately.  MRI is a poor test in this disease, but diagnosis is possible.

Thursday, November 13, 2014

Blood pressure variability after thrombolysis: prognostic signficance

Delgado-Mederos E, Ribo M, Rovira A, et al.  Prognostic significance of blood pressure variability after thrombolysis in acute stroke.  Neurology 2008; 71: 552=558.
80 stroke patients were prospectively studies who had MCA occlusion treated with t-pa.Multiple BP measurements were obtained.  Recanalization was assessed with TCD at six hours.  NIHSS was done at baseline and 24 hours, MRS at 3 months. 
55 % were recanalized.  Both SBP and DBP variability were highly associated with DWI growth (done before and 36 hours after thrombolysis) and outcome, but only in patients who failed to recanalize
Notes-- There was a significant decline in overall SBP and DBP in recanalized but not unrecanalized patients. However BP variability was the only factor corresponding to DWI growth.  Authors speculate that treating the swings is as important as treating the outlying numbers.
Blogger comment-- this observational study is interesting but not powerful enough to be determinant 

Monday, October 20, 2014

Infarction in the anterior choroidal artery territory: clinical progression and prognosis factors

Chausson N, et al.  JSCD; 2014; 23:8: 2012-7.
Authors describe the phenotypes of  anterior choroidal stroke in heretofore unappreciated ways.  They prospectively enrolled patients with AChA disease
*One hundred patients were found out of 1234 total (8.1 %) who had AChA strokes
*  Main risk factors found were hypertension and (79 %) and diabetes (31 %). 
*  88 % had "lacunar" (motor syndrome in 51, sensorimotor in 23, ataxic hemiparesis in 14, isolated ataxia in 4, other 7)
*  only four patients had hemianopia
*  cardioembolic and atherothrombotic causes wee rare
*  3 % mortality but 26 % poor outcomes, invariably due to residual motor deficit and/or spasticity
* Progressive strokes were seen in 46, and 16 with fluctuations, wiht progressions over a mean of 56 hours and being almost exclusively motor
* Use of iv tpa did nto help prevent progression (tpa was used in 12/46 progressors and 9/54 nonprogressors)
* predictor of poor outcome was those who reached an NIHSS of 6 or greater, clinical progression, and infarct size > 15 mm
* Progression was nearly always due to infarct expansion on DWI
* Authors suggest new treatments are needed for this disease.

Recurrence in Intracranial atherosclerotic disease (ICAD): a stenosis based analysis

Gouvela a, et al.  JSCD, 2014: 23:8:2080-4.
Authors confirmed prior work showing extremely high recurrence rate of stroke in this type of disease:  12.3 per 100 patient years, with mean time to recurrence being 1.7 months among symptomatic intracranial stenosis (SIS) and 0.88 per 100 patient years among asymptomatic intracranial stenosis (AIS). 
They investigated 1302 patients retrospectively, with 218 strokes in 158 patients, of which 77 were symptomatic and 141 asymptomatic.  Patients with AIS were older, had more AF
blogger note-- interesting article that splits ICAD ina new way, to AIS and SIS that has very different clinical outcomes.

Odds ratio and population attributable risk of 10 factors estimated to acount for 90 % of ischemic stroke risk

Risk factor            OR              PAR    (confidence intervals available elsewhere)
hypertension          2.64            34.6
current smoking     2.09            18.9
waist to hip ratio    1.65             26.5
Diet risk score       1.35             18.8
Regular exercise    0.69             28.5
Diabetes mellitus   1.36             5.0
ETOH (> 30/mo)     1.51             3.8
Stress/depression   1.30            4.6
Cardiac causes       2.38            6.7
ratio apo B/A1        1.89             24.9
Spouses of smokers have double risk of stroke.  Much benefit of cessation occurs in first 6 months.  Cessation leads to return to baseline risk within five years.
Fives risk factors  related to lifestyle and risk
1. Absent current smoking
2. 30 + minutes per day of exercise
3. healthy diet
4.  moderate ETOh consumption
5.  BMI < 25
If all five risk factors are favorable,   RR is -.2, PAR is -53.
Cretan Mediterranean diet is the best one; those randomized to it had 70 % less CV events within 27 months
This diet contains more fat esp olive oil.  Its much lower in meat and dairy products and uses fruit as desert. It has high levels of canola nad olive oil, high fruit/vegetable/lentils/beans and nuts.  Avoid trans fats and egg yolks; meat every other day.
Ottawa Model of Smoking Cessation
Identify smoking status-- have you used any form of tobacco in the past six months? The past seven days?
Document-- smoking history (pack years); previous quit attempts, time to first cigarette
Advise--- "There is nothing more important that cessation. We can help you with that"
Pharmacotherapy-- readily available medicine, prescribed appropriately
Followup-- FP; telephone calls; community resources.

ACC/AHA Guisdelines for postcardiac surgery atrial fibrillation; and CABG in general

* patients with pre-existing AF receiving antiarrhythmics or rate controlling agents should be continued ont hese in postop period.
*  Oral beta blocker is recommended to prevent post op AF in patients undergoing cardiac surgery-- unless contraindicated
*  An AV nodal blocking agent is recommended for postop rate control in patients who develop postop AF
* Preop amiodarone decreases the incidence of AF in patients undergoing cardiac surgery  and represents appropriate prophylactic therapy for patients at high risk of AF
*  Its reasonable to restore sinus rhythm pharmacologically or through cardioversion among patients who develop postoperative AF
*  It is reasonable to administer anti-arrhytmics to maintain SR in patients with postop refractory or recurrent AF
*  Antithrombotic medication is reasonable to administer in patients who develop postop AF
*  Prophylactic sotalol may be considered in high risk patients. 

Additional points for cardiac surgery-- evidence based
*Matching preop and postop BP may reduce the risk of perioperative stroke or death  III/B
* Preop statins reduce the perioperative stroke risk in cardiac surgery  IB/A
*  Antiplatelet therapy eg ASA reduces the postop stroke risk without increasing the risk of bleeding complications  Ia/A
*  Discontinuing warfarin or antiplatelet agents in anticipation of surgery increases the risk of perioperative stroke, with the highest risk in patients with CAD

Benefit of CEA in different conditions

Degree of stensois         Studies        Recc           Risk reduction
Symptomatic stenosis
   70-99%                       NASCET     CEA LEVEL A       16.5 % at two years
   >60 %                         ECST               "                     11.6 % at 3 years
   50-69 %                       NASCET           "                    10.1 % at 5 years
Asymptomatic stenosis
>60 %                            ACAS, ACST     "                     6.3 % at five years

-- some literature favors early surgery for patients without early ICH on CT scans
-- of those who hemorrhaged, hemorhhage occured 3-6 days after surgery when patients were improving or ambulatory.  They occurred in 6/900 patients studied
-- Dosick et al. reported 9.5 % restroke incidence with six week waiting period before CEA
--In NASCET 4.9 % of 103 patients  (5 patients) had restroke within 30 days of trial entry if treated medically
-- In a variety of studies patients operated within 3 weeks had 3 % stroke risk, those operated beyong 3 weeks had a 5.3 % stroke risk

Timing of tpa; outcomes

0-90 minites  odds ratio for favorable outcome at 3 months based on 4 point decline of NIHSS is 2.11
90-180 minutes-- odds ratio is 1.69
In NINDS trials, poor outcomes as defined by MRS >3 at 24 hours were predicted by NIHSS>22
NIHSS>17 plus AF

Thursday, October 09, 2014

Duration of dual antiplatelet therapy after implantation of drug eluting stents

Park et al. NEJM 2010; 362: 1374-82. 
use of dual antiplatelet therapy more than 12 months among patients who received drug eluting stents was not significantly more effective than aspirin monotherapy. 

Lenient v. strict rate control in patients with atrial fibrillation

Gelder et al.  NEJM 2010; 362: 1363-73

study of 614 patients showed that among patients with permanent AF, lenient rate control is as effective as strict rate control and is easier to achieve.