Wednesday, January 20, 2016
Sunday, January 03, 2016
Saturday, August 22, 2015
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
(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
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"
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.
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.
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
Acute ischemic stroke
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
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.
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.
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
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).
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
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.
Friday, April 24, 2015
Wednesday, April 01, 2015
Sunday, March 29, 2015
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
Thursday, February 05, 2015
The Safety of Intravenous Thrombolysis for Ischemic Stroke in Patients With Pre-Existing Cerebral Aneurysms
A Case Series and Review of the Literature
- 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.
- 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 email@example.com
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
Sunday, December 07, 2014
Tuesday, December 02, 2014
No history of
cortical infarct 1
total score -- add sum of parts
cut score used in many articles is 7
source Neurology 2013 au Thaler
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.
Sunday, November 30, 2014
2. Clinical: hemiparesis, hemianopia, cortical blindness; seizures, dementia, migraine, muscle weakness,
4. May be relapsing remitting
5. High lactic/abn muscle biopsy
6. AVOID statins and Depakote
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
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.
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.
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
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
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
Thursday, November 13, 2014
Monday, October 20, 2014
Odds ratio and population attributable risk of 10 factors estimated to acount for 90 % of ischemic stroke risk
Additional points for cardiac surgery-- evidence based
RISK OF HEMORRHAGE