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).

REVASCAT

206 patients with acute ischemic stroke
•
PROBE design
•
NIHSS ≥ 6
•
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.

 

Results:
•
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

 

COMMENT-- ALLOWED GROIN PUNCTURE UP TO 8 HOURS BUT DID NOT ANALYZE THAT GROUP, REQUIRED ASPECTS > 7, AGE UP TO 85 

EXTEND 1A

•
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.

 

COMMENT---ENDOVASCULAR THERAPY 'WAS INITIATED' AT 3.5 HOURS

 

SWIFT PRIME

•
Purpose:
–
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.
•
Methods:
–
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
•
ASPECTS <6
•
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)

 

Results:
•
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).

 

Results:
•
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.

 

COMMENT

used cta AND ct-p AND ASPECTS SCORE

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.

 

Results:
•
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

 

COMMENT- MAY SUPPORT NOT INTERVENING AFTER SIX HOURS

 

ONSET TO GROIN PUNCTURE 4.3 HOURS

ONSET TO REPERFUSION 5.3 HOURS

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.

 

 

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.

 

Abstract
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.

ESCAPE, SWIFT PRIME and EXTEND -1A tirals

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. 

 

 

 

 

Safety of IV tpa with aneurysms

Stroke. 2012; 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. Nancy J. Edwards, MD;
2. Hooman Kamel, MD;
3. 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 nancy.edwards@ucsfmedctr.org

Abstract

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.

Disclaimer--
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.

Effects of Golden 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

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 in this 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.IgA mediated, also get renal deposits

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 more than 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.

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

Age
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

DJ

MELAS pearls

maternal , mitochondrial dna a3243g

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


MRI parietal-occipital, parietal temporal acute strokes
MRS lactate peak
CSF increased lactate, pyruvate and amino acids
depletes NAD+, NADH+
increases anaerobic metabolism
increases lactic acidosis

progressive strokes and vision loss before age 40
presents in childhood
dx muscle biopsy ragged red fibers on Gomori stain

Rx CoQ
carnitine
L-Arginine
B vitamins
AED's but not depakote

HERNS (RVCL)

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

Features
Vision and memory loss
Seizures
Hemiparesis
Apraxia
Dysarthria
dysautonomia
AUT DOM

Onset in fourth decade
Death in five to ten years

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

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

Small white matter lesions may resemble MS

Caused by mutations of TREX1 genE
Inherited as aut dome frame shift mutation that encodes dna exonuclease

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). Patients with PCK have increased risk of aneurysm, but their first degree relatives only have 9 percent risk

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 alteplace 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.

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

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.

11

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

 

Introduction

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. 

 

Results

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.

 

DJ

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 

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

 

Notes

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

systematic

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

RISK OF HEMORRHAGE

 

-- 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

OR

NIHSS>17 plus AF

Duration of dual antiplatelet therapy after implantation of drug eluting stents

Park et al. NEJM 2010; 362: 1374-82. 
Conclusion
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.

vitatops study

http://ac.els-cdn.com/S1474442210701873/1-s2.0-S1474442210701873-main.pdf?_tid=c39f01f0-f232-11e3-9c1b-00000aacb361&acdnat=1402578739_e5b1b16c09ddc46f739cdc8e3ecf08fb

 

b vitamins and folic acid was safe but not more effective than placebo to prevent strokes

Fingolimod and atrial fibrillation

Rolf et al.  Paroxysmal atrial fibrillation after initiation of fingolimod for multiple sclerosis treatment

 

42 year old male had PAF on initiation, resolution on withdrawal of, recurrence on reinitiation and reresolution permanently on discontinuation of fingolimod.  Extensive cardiac testing was negative.   This is different than the bradycardia that is known to occur with fingolimod which requires initiation with cardiac monitoring. 

 

Authors note that fingolimod is an agonist of S1P-R1,2,3 in cardiovascuklar system.  In atrial myocytes, binding of the receptors causes activation of the potassium channels leading to an inward K current and decreased firing rate.  Therefore drug causes bradycardia or AV conduction blockade.  There is in animal models, S1P induced reperfusion tachyarrythmias. 

IV thrombolysis and renal disease

Neurology 2013; 81: 1780-8.

Studied 4780 ivt treated patients, of whom 25.5 % had a low GFR below 60 mL/min.  Low GFR was significantly associated with poor 3 month outcome  death and sICH; lower GFR "might be a better risk indicator than age" and a decrease by 10 mL/min/1.73 m@ has a similar impact on death or SIC as one point on the NIHSS

IV tpa is safe in Chagas disease related strokes

Neurology 2013;81:1773-5.  Out of a series of 240 patients in Brazil, 24 (13.8%) had positive serologic testing for Chagas disease.  They more likely had heart failure and higher NIHSS but did NOT have more symptomatic intracranial hemorrhage or in hospital death than patients without.  Conclusion:  Chagas disease diagnosis does not preclude use of tpa.
editor note: does not apply to those with known Chagas disease vasculitis, and a small number was studied, and positive serology is different than having severe disease

AHA guidelines for stroke prevention in women

http://stroke.ahajournals.org/content/early/2014/02/06/01.str.0000442009.06663.48

Syndrome of the trephined

Skin "sinks" weeks to months after a craniectomy.  It can have minor or major presentations, rarely coma, and be relieved with placing patient in trendelenberg position and using a titanium mesh.  

Abcd2

Abcd2 and stroke risk

Cardiac papillary fibroelastoma: A comprehensive

 

Cardiac papillary fibroelastoma: A comprehensive

analysis of 725 cases

Ramesh M. Gowda, MD,a Ijaz A. Khan, MD, FACP, FACC,b Chandra K. Nair, MD, FACP, FACC,b

Nirav J. Mehta, MD,b Balendu C. Vasavada, MD, FACC,a and Terrence J. Sacchi, MD, FACCa Omaha, Neb, and

Brooklyn, NY

 

(Am Heart J 2003;146:404–10.)

 

Seven hundred twenty-five cases of CPF were identified. Males comprised 55% of

patients. Highest prevalence was in the 8th decade of life. The valvular surface was the predominant locations of tumor.

The most commonly involved valve was the aortic valve, followed by the mitral valve. The left ventricle was the predominant

nonvalvular site involved. No clear risk factor for development of CPF has been reported. Size of the tumor varied

from 2 mm to 70 mm. Clinically, CPFs have presented with transient ischemic attack, stroke, myocardial infarction, sudden

death, heart failure, presyncope, syncope, pulmonary embolism, blindness, and peripheral embolism. Tumor mobility

was the only independent predictor of CPF-related death or nonfatal embolization. Symptomatic patients should be

treated surgically because the successful complete resection of CPF is curative and the long-term postoperative prognosis

is excellent. The symptomatic patients who are not surgical candidates could be offered long-term oral anticoagulation,

although no randomized controlled data are available on its efficacy. Asymptomatic patients could be treated surgically if

the tumor is mobile, as the tumor mobility is the independent predictor of death or nonfatal embolization. Asymptomatic

patients with nonmobile CPF could be followed-up closely with periodic clinical evaluation and echocardiography, and

receive surgical intervention when symptoms develop or the tumor becomes mobile.

 

Additional pearls from this review:

 

1. 

Cardiac

papillary fibroelastomas (CPF), the second most

common primary cardiac tumors, are benign endocardial

papillomas predominantly affecting the cardiac

valves, and account for three fourths of all cardiac valvular

tumors. They consist of a small, highly papillary,

pedunculated and avascular tumor, covered by a single

layer of endothelium, containing variable amounts of

fine elastic fibrils arranged in whorls in a hyaline

stroma.

2.

Although CPF are rare and histologically benign

tumors, they may result in life-threatening complications,

such as stroke, acute valve dysfunction, embolism,

and sudden death.

3.

The most common clinical presentation was of transient

ischemic attack or stroke (n 120 patients). The

other manifestations were angina (n 49 patients),

myocardial infarction (n 28 patients), sudden death

(n 21 patients), heart failure (n 24 patients), presyncope

or syncope (n 12 patients), pulmonary

embolism (n 3 patients), blindness (n 7 patients),

mesenteric ischemia (n 2 patients), peripheral emboli

(n 3 patients), and renal infarction (n 1 patient).

In patients with mitral valve tumors, stroke was

the most common clinical presentation, but in patients

with aortic valve tumors, sudden death and myocardial

infarction were the 2 most common presentations. In

a large number of patients, tumors were identified as

incidental findings at autopsy (n 209 patients) or at

surgery for other cardiac reasons (n 9 patients).

4.

The major immunophenotypic

difference between CPF and cardiac myxoma was the

frequent presence of muscle-specific actin in the stellate

cells of the stroma in cardiac myxoma but not in

CPF.

5. 

Because most CPF are located in the left heart (95%),

systemic embolism in particular is frequent. In a majority

of CPF cases with embolism, the cerebral arteries,

including retinal arteries, are affected, and transient

ischemic attack, stroke, and sudden visual loss have

been reported

6.

The classic

diastolic tumor plop, which is heard in one third of

patients with atrial myxoma, has not been described

with CPF, except in 1 case where a tricuspid valve

CPF was associated with a tumor plop.46

7. Diferential diagnostic analysis:

Cardiac myxoma

is a predominant left atrial tumor, and is usually attached

to the atrial septum by a stalk. Histologically,

myxoma differs from CPF by presence of polygonal

 

myxoma cells and blood vessels within papillae.125

The papillae of CPF are devoid of blood vessels. Calretinin

staining may be a useful way to distinguish between

myxoma and CPF.218 Cardiac fibroma, which is

a separate entity, frequently demonstrates calcification

and cystic degeneration. Cardiac rhabdomyomas are

predominant myocardial neoplasms seen in infants and

children.214 Metastatic tumors of the heart are more

frequent than the primary tumors.1 Unlike CPF, malignant

tumors commonly involve the pericardium and

myocardium, and are usually accompanied by systemic

symptoms. However, with both primary and metastatic

tumors, the clinical course may be complicated by emboli.

Ljevak J, Mismas A, Bazina A, et al.
An infrequent type of stroke with an unusual cause and successful therapy: basilar artery occlusion caused by a cardiac papillary fibroelastoma recanalized 12 hours after onset [In Process Citation]
Intern Med (Japan), 2013, 52(2) p277-9

 

take home points: Again, BA can be recanalized later than other vessels; this tumor type is very sensitive to lysis

Etiology and treatment of ischaemic stroke in patients with (sup)-thalassemia major.

Eur J Neurol 2011 Dec;18(12):1426-8    (ISSN: 1468-1331)

 

BACKGROUND AND PURPOSE: Although hypercoagulability-induced thromboembolism is generally accepted as cause of cerebral ischaemia in thalassemic patients, cardiogenic embolism has been recently suggested as another possible stroke etiology. METHODS: We present four adult (sup)-thalassemia major patients with manifest cardiac involvement who suffered territorial strokes. RESULTS: In the presence of siderotoxic cardiomyopathy and arrhythmia, we assumed cardiogenic embolism as etiology of stroke and initiated oral anticoagulation as preventive medication. Two of our patients were the first (sup)-thalassemia major patients who underwent successful thrombolysis with rtPA. CONCLUSIONS: Cardioembolism seems to be the cause of stroke in cases of (sup)-thalassemia major. Thrombolysis can be applied in the setting of acute brain ischaemia in such high risk patients. [ 2011 The Author(s). European Journal of Neurology 2011 EFNS.].

 

Comment:  Take home points

1.  Thal cases can be cardioembolic not just hypercoagulable and may benefit from anticoagulation

2.  Thrombolysis might help in some cases

anticoagulation in acute stroke

Lancet Neurology 2013 published a metaanalysis of studies showing no benefit of anticoagulation in acute stroke.  However, like Freddy Krueger, the debate will not die.  Below is an excerpt from the editorial by Hart et al.  that lays out some of the remaining points of contention.

A meta-analysis of 24 trials involving 23 748 patients with acute stroke found that early anticoagulation compared with no anticoagulation reduced recurrent ischaemic stroke and venous thromboembolism at the cost of increased intracranial and extracranial haemorrhage, with no overall reduction in death or disability.² Consequently, guidelines for stroke management now recommend that anticoagulants should not be used for the management of acute stroke caused by common cerebrovascular disorders (including atrial fibrillation).³ Nonetheless, the question remains: are there acute stroke patients at high risk of thrombotic events and low risk of bleeding who might yet benefit from early anticoagulant therapy?

In this issue of The Lancet Neurology, William Whiteley and colleagues⁴ report the results of a pooled individual patient-level analysis of the five largest randomised trials that have tested heparins in patients with acute ischaemic stroke. The authors developed risk prediction models to identify acute stroke patients The analyses by Whiteley and colleagues provide no support for the use of anticoagulants in the management of patients with acute stroke, but the results must be interpreted with caution. First, despite careful efforts by the investigators to derive the best risk-prediction models, they were only modestly predictive of thromboembolic and bleeding events (C-statistics in the order of 0·6), thereby reducing the quality of the evidence and limiting the strength of the conclusions. Second, the conclusion must necessarily be restricted to the subgroups common to the trial databases; for example, the presence of large artery atherosclerosis was not considered.⁵ Third, uncertainty remains regarding the role of heparins in patients with uncommon conditions resulting in acute brain ischaemia. These include patients with acute cerebral venous thrombosis, small-to-moderate brain infarcts due to cerebral arterial dissection, aseptic embolism from prosthetic cardiac valves, mobile left ventricular thrombi, and aortic arch plaque with protruding overlying thrombi.

The balance between risks and benefits of heparins also remains unclear for patients with acute transient ischaemic attack or minor ischaemic strokes who were poorly represented in the randomised trials. These patients have a low risk of secondary haemorrhagic transformation because they do not have substantial areas of acute brain necrosis. A randomised trial that assessed the combination of clopidogrel plus aspirin in patients with acute transient ischaemic attack found a benefit of the intensive antiplatelet therapy,⁶ and other trials testing dual antiplatelet therapy in patients with acute ischaemic attack or minor ischaemic stroke are ongoing.⁷ Whether early anticoagulation provides benefit for these patients needs to be assessed.

Recently introduced novel oral anticoagulants that selectively target thrombin (dabigatran etexilate) or factor Xa (rivaroxaban, apixaban) are attractive candidates for acute stroke treatment because they work rapidly (within 2–3 h) after oral administration. The most important advantage of the novel oral anticoagulants over warfarin is the sharply decreased risk of intracerebral haemorrhage seen during long-term treatment in patients with atrial fibrillation.⁸ If the novel oral agents are associated with a similarly low risk of secondary brain haemorrhage after acute stroke, the balance between risks and benefits of early anticoagulation might be altered in favour of treatment, making this a priority for future research.

Despite multiple randomised trials testing heparins in patients with acute ischaemic stroke, and also the rigorous efforts by Whiteley and colleagues to identify subsets of patients defined by thromboembolic and bleeding risk that might benefit from early anticoagulation, the value of this approach has not been established for any patient group.⁴ However, promising early data with the use of combined antiplatelet therapy and the emergence of novel oral anticoagulants with a rapid onset of action and low risk of intracranial haemorrhage means that anticoagulant therapies for patients with acute brain ischaemia remains a fruitful area for future clinical research.