Monday, March 23, 2009
Monday, March 09, 2009
Neuroflo device in acute ischemic stroke AAN abstract
[P02.087] A Novel Treatment in the Management of Acute Ischemic Stroke
Mohamed M. Ibrahim, Maher Saqqur, Arabesque Parker, Monica Saini, Dulka Manawadu, Ken Butcher, Derek Emery, Ashfaq Shuaib, Edmonton, AB, Canada
OBJECTIVE: Role of Transcranial Doppler (TCD) monitoring in acute stroke patients treated with NeuroFlo
device . BACKGROUND: The NeuroFlo device has been implemented as an experimental tool for potential interventional treatment in non- IV rt-PA responder patients with acute ischemic stroke. The presumed mechanism of action is enhancement of blood flow diversion to cerebral collaterals to minimise infarct volume and improve clinical outcomes. DESIGN/METHODS: Patients presenting to our ER with acute ischemic stroke, who did not show significant improvement after thrombolysis were screened; after an informed consent, they were enrolled in the Feasibility and Safety of NeuroFlo in Stroke Patients Receiving rt-PA. An intra-aortic balloon was inflated after completion of the rtPA infusion, resulting in the partial occlusion of abdominal Aorta for 45 minutes. TCD was performed at baseline, at the end of IV rt-PA treatment, before and during balloon inflation. RESULTS: We enrolled 9 cases, 4 patients did not had TCD study, of the remaining 5 patients 3 patients had MCA occlusion and 2 Terminal ICA occlusion. Three patients had good long term outcome Modified Rankin Scale (MRS) at 90 days were 1, zero and Zero respectively. There TCD during balloon inflation revealed: 1- Enhancing flow at the occlusion site (mean flow velocity increased from 18 to 24, 8 to 22 and 14 to 46 cm/sec) 2- Two patients had anterior cross filing developed through anterior communicating artery (ACom). 3- Enhancing flow through contralateral MCA (MFV 108 to 177 cm/sec) and ips ACA flow (MFV 22 to 81 cm/sec) in one patient. Two patients had poor outcome (MRS at 90 days 
3) both had no enhancing flow during balloon inflation. CONCLUSIONS/RELEVANCE: NeuroFlo
device might provide a new treatment for acute stroke patients beyond the 3 hours window by enhancing the flow at the occlusion site and opening up collateral flow.
Category - Cerebrovascular Disease - Acute Stroke Therapy
Mohamed M. Ibrahim, Maher Saqqur, Arabesque Parker, Monica Saini, Dulka Manawadu, Ken Butcher, Derek Emery, Ashfaq Shuaib, Edmonton, AB, Canada
OBJECTIVE: Role of Transcranial Doppler (TCD) monitoring in acute stroke patients treated with NeuroFlo
device . BACKGROUND: The NeuroFlo device has been implemented as an experimental tool for potential interventional treatment in non- IV rt-PA responder patients with acute ischemic stroke. The presumed mechanism of action is enhancement of blood flow diversion to cerebral collaterals to minimise infarct volume and improve clinical outcomes. DESIGN/METHODS: Patients presenting to our ER with acute ischemic stroke, who did not show significant improvement after thrombolysis were screened; after an informed consent, they were enrolled in the Feasibility and Safety of NeuroFlo in Stroke Patients Receiving rt-PA. An intra-aortic balloon was inflated after completion of the rtPA infusion, resulting in the partial occlusion of abdominal Aorta for 45 minutes. TCD was performed at baseline, at the end of IV rt-PA treatment, before and during balloon inflation. RESULTS: We enrolled 9 cases, 4 patients did not had TCD study, of the remaining 5 patients 3 patients had MCA occlusion and 2 Terminal ICA occlusion. Three patients had good long term outcome Modified Rankin Scale (MRS) at 90 days were 1, zero and Zero respectively. There TCD during balloon inflation revealed: 1- Enhancing flow at the occlusion site (mean flow velocity increased from 18 to 24, 8 to 22 and 14 to 46 cm/sec) 2- Two patients had anterior cross filing developed through anterior communicating artery (ACom). 3- Enhancing flow through contralateral MCA (MFV 108 to 177 cm/sec) and ips ACA flow (MFV 22 to 81 cm/sec) in one patient. Two patients had poor outcome (MRS at 90 days 3) both had no enhancing flow during balloon inflation. CONCLUSIONS/RELEVANCE: NeuroFlo device might provide a new treatment for acute stroke patients beyond the 3 hours window by enhancing the flow at the occlusion site and opening up collateral flow. Category - Cerebrovascular Disease - Acute Stroke Therapy
negative effect of alteplase on stroke patients with CHF AAN abstract
[P02.083] Clinical Outcomes of Patients with Congestive Heart Failure Who Receive Thrombolytic Therapy for Acute Ischemic Stroke
Kachikwu Illoh, Miriam Morales, Tamara Humphrey, Alexander Katcheves, Nneka Ifejika, Francisco Fuentes, Mc Lean, VA, Houston, TX
OBJECTIVE: To determine whether thrombolytic therapy improved outcome among patients with CHF presenting with AIS. BACKGROUND: Patients with severe congestive heart failure (CHF) often have impaired cerebral perfusion. They have poor clinical outcomes on presenting with acute ischemic stroke (AIS). In these patients, it is likely that prompt thrombolysis would stem further decline in an already compromised cerebral perfusion state. Whether thrombolytic therapy improves the outcome in these patients is unclear. DESIGN/METHODS: In a cohort study with retrospective review of records from a prospectively collected database, we included AIS patients who were consecutively admitted to the stroke service of a large tertiary care center. Poor clinical outcome was defined as a modified Rankin score (mRS) of greater than 3. We examined the characteristics of AIS patients with history of CHF by their thrombolytic therapy status and compared their clinical outcomes with non-CHF patients. RESULTS: A total of 2,180 AIS patients with a mean age of 65 (SD, 15) years and 53% females were enrolled. Of the entire cohort, 26% (576/2180) received intravenous thrombolytic therapy, and 9% (196/2180) had history of CHF. The in-hospital mortality overall was 6% (129/2081); among CHF patients mortality was 8%. Of the 196 CHF patients, 66 (34%) got thrombolytic therapy. Yet, the CHF patients who received thrombolytic therapy did not achieve better mortality outcome compared to those not receiving the treatment (9% versus 8%, P = 0.786). Likewise, there was no difference in functional outcome between CHF patients who got thrombolytic therapy and CHF patients without the treatment (mRS >3; 49% versus 50%; P = 1.000). CONCLUSIONS/RELEVANCE: In patients with history of CHF who presented with AIS, thrombolytic therapy was not associated with an improvement in their clinical outcome. This finding needs further exploration in larger studies as more aggressive management of CHF may be required to augment thro mbolytic therapy.
Category - Cerebrovascular Disease - Acute Stroke Therapy
Tuesday, April 28, 2009 11:30 AM
Kachikwu Illoh, Miriam Morales, Tamara Humphrey, Alexander Katcheves, Nneka Ifejika, Francisco Fuentes, Mc Lean, VA, Houston, TX
OBJECTIVE: To determine whether thrombolytic therapy improved outcome among patients with CHF presenting with AIS. BACKGROUND: Patients with severe congestive heart failure (CHF) often have impaired cerebral perfusion. They have poor clinical outcomes on presenting with acute ischemic stroke (AIS). In these patients, it is likely that prompt thrombolysis would stem further decline in an already compromised cerebral perfusion state. Whether thrombolytic therapy improves the outcome in these patients is unclear. DESIGN/METHODS: In a cohort study with retrospective review of records from a prospectively collected database, we included AIS patients who were consecutively admitted to the stroke service of a large tertiary care center. Poor clinical outcome was defined as a modified Rankin score (mRS) of greater than 3. We examined the characteristics of AIS patients with history of CHF by their thrombolytic therapy status and compared their clinical outcomes with non-CHF patients. RESULTS: A total of 2,180 AIS patients with a mean age of 65 (SD, 15) years and 53% females were enrolled. Of the entire cohort, 26% (576/2180) received intravenous thrombolytic therapy, and 9% (196/2180) had history of CHF. The in-hospital mortality overall was 6% (129/2081); among CHF patients mortality was 8%. Of the 196 CHF patients, 66 (34%) got thrombolytic therapy. Yet, the CHF patients who received thrombolytic therapy did not achieve better mortality outcome compared to those not receiving the treatment (9% versus 8%, P = 0.786). Likewise, there was no difference in functional outcome between CHF patients who got thrombolytic therapy and CHF patients without the treatment (mRS >3; 49% versus 50%; P = 1.000). CONCLUSIONS/RELEVANCE: In patients with history of CHF who presented with AIS, thrombolytic therapy was not associated with an improvement in their clinical outcome. This finding needs further exploration in larger studies as more aggressive management of CHF may be required to augment thro mbolytic therapy.
Category - Cerebrovascular Disease - Acute Stroke Therapy
Tuesday, April 28, 2009 11:30 AM
alteplase and malignancy at AAN
[P02.082] Outcomes of Patients with Malignancy Treated with Thrombolytics
Ramy El Khoury, Miriam M. Morales, Oleg Chernyshev, Anitha Abraham, M. Rick Sline, Indrani Acosta, Vivek Misra, Andrew Barreto, Sean Savitz, Kachikwu Illoh, James Grotta, Nicole R. Gonzales, Bellaire, TX, Mc Lean, VA, Houston, TX
OBJECTIVE: Treating patients with a history of cancer for ischemic strokes with thrombolytics may not alter patient's outcome. BACKGROUND: Very limited literature discusses the outcome of patients with malignancy treated with thrombolytics for ischemic stroke. The purpose of our research is to describe our experience in treating patients who have malignancy with thrombolysis. DESIGN/METHODS: We conducted a retrospective case-control study comparing the outcomes of patients receiving thrombolysis with a history of or active cancer (cancer positive, CP) compared with a control group (cancer negative, CN) matched for age and baseline NIHSS. Primary outcome measure was symptomatic intracerebral hemorrhage (sICH). Secondary outcome measures included good outcome (discharge modified Rankin Scale (mRS) <3), and good discharge disposition (discharge home or in-patient rehabilitation). RESULTS: From 2003-2008, 679 patients were treated with thrombolytics (IV, IV/IA, or IA only). Of these, 60 patients were CP with a mean age 73 (SD, 13) years and 120 CN patients were matched for age and baseline NIHSS. Baseline median NIHSS was 12 in both groups with similar ranges (p=0.835). There were no significant differences among baseline characteristics between the two groups. The most common malignancies were prostate 27% and breast 22%. There was no significant difference among 24 hour post-tPA NIHSS, good outcomes, length of stay, sICH, or good disposition. CONCLUSIONS/RELEVANCE: Our data demonstrates that patients with malignancy (or a history of) who receive thrombolysis have outcomes similar to CN patients and do not appear to be at increased risk of sICH. It also suggests that the presence or history of malignancy should not preclude thrombolysis if the patient is otherwise a thrombolytic candidate.
Category - Cerebrovascular Disease - Acute Stroke Therapy
Tuesday, April 28, 2009 11:30 AM
Ramy El Khoury, Miriam M. Morales, Oleg Chernyshev, Anitha Abraham, M. Rick Sline, Indrani Acosta, Vivek Misra, Andrew Barreto, Sean Savitz, Kachikwu Illoh, James Grotta, Nicole R. Gonzales, Bellaire, TX, Mc Lean, VA, Houston, TX
OBJECTIVE: Treating patients with a history of cancer for ischemic strokes with thrombolytics may not alter patient's outcome. BACKGROUND: Very limited literature discusses the outcome of patients with malignancy treated with thrombolytics for ischemic stroke. The purpose of our research is to describe our experience in treating patients who have malignancy with thrombolysis. DESIGN/METHODS: We conducted a retrospective case-control study comparing the outcomes of patients receiving thrombolysis with a history of or active cancer (cancer positive, CP) compared with a control group (cancer negative, CN) matched for age and baseline NIHSS. Primary outcome measure was symptomatic intracerebral hemorrhage (sICH). Secondary outcome measures included good outcome (discharge modified Rankin Scale (mRS) <3), and good discharge disposition (discharge home or in-patient rehabilitation). RESULTS: From 2003-2008, 679 patients were treated with thrombolytics (IV, IV/IA, or IA only). Of these, 60 patients were CP with a mean age 73 (SD, 13) years and 120 CN patients were matched for age and baseline NIHSS. Baseline median NIHSS was 12 in both groups with similar ranges (p=0.835). There were no significant differences among baseline characteristics between the two groups. The most common malignancies were prostate 27% and breast 22%. There was no significant difference among 24 hour post-tPA NIHSS, good outcomes, length of stay, sICH, or good disposition. CONCLUSIONS/RELEVANCE: Our data demonstrates that patients with malignancy (or a history of) who receive thrombolysis have outcomes similar to CN patients and do not appear to be at increased risk of sICH. It also suggests that the presence or history of malignancy should not preclude thrombolysis if the patient is otherwise a thrombolytic candidate.
Category - Cerebrovascular Disease - Acute Stroke Therapy
Tuesday, April 28, 2009 11:30 AM
AAN venous anomaly and malignant MCA infarction
[P02.080] Ipsilateral Cerebral Venous Outflow Obstruction Is Associated with Life-Threatening Brain Edema of Middle Cerebral Artery Infarction
Wengui Yu, Joanna Rives, Babu Welch, Jonathan White, Duke Samson, Dallas, TX
OBJECTIVE: The aim of this study was to investigate the role of cerebral venous anomaly in the development of life-threatening brain edema after middle cerebral artery (MCA) infarction. BACKGROUND: Approximately 35% of the patients with complete MCA infarction develop life-threatening brain edema and herniation. Although infarct size was the major determinant, its predictive value was only moderate. DESIGN/METHODS: This is a retrospective study of consecutive patients with complete MCA infarction who were admitted to our Neurointensive Care Unit from January 2007 to October 2008. Patient demographics and clinical features were reviewed. Brain edema on serial CT or MRI scans and cerebral venous anatomy on CTA or digital subtraction angiography were evaluated. Functional outcome at discharge was estimated using modified Rankin scales. RESULTS: A total of 14 patients were identified to have complete MCA infarction and cerebral venography. Four patients (25.6%) were found to have ipsilateral cerebral venous anomaly, including transverse sinus atresia (1), hypoplasia (2), and previous surgical ligation of internal jugular vein (1). All of them had fatal brain edema. The severity and timing of maximal edema were correlated with the degree of cerebral venous outflow obstruction. They all refused surgery and died from transtentorial herniation. The remaining 10 patients had symmetric or ipsilateral dominant cerebral venous drainage. Only one of them developed life-threatening edema possibly due to poor collateral circulation and bilateral carotid stenosis. He underwent decompressive surgery and recovered with moderate left hemiparesis. Patient age, sex, co-morbidity, carotid artery occlusion, or infarct size was not independently associated with life-threatening edema. CONCLUSIONS/RELEVANCE: Our preliminary results suggest that ipsilateral cerebral venous outflow obstruction is independently associated with life-threatening brain edema after MCA infarction and may be an indication for early decompressive craniectomy.
Category - Cerebrovascular Disease - Acute Stroke Therapy
Wengui Yu, Joanna Rives, Babu Welch, Jonathan White, Duke Samson, Dallas, TX
OBJECTIVE: The aim of this study was to investigate the role of cerebral venous anomaly in the development of life-threatening brain edema after middle cerebral artery (MCA) infarction. BACKGROUND: Approximately 35% of the patients with complete MCA infarction develop life-threatening brain edema and herniation. Although infarct size was the major determinant, its predictive value was only moderate. DESIGN/METHODS: This is a retrospective study of consecutive patients with complete MCA infarction who were admitted to our Neurointensive Care Unit from January 2007 to October 2008. Patient demographics and clinical features were reviewed. Brain edema on serial CT or MRI scans and cerebral venous anatomy on CTA or digital subtraction angiography were evaluated. Functional outcome at discharge was estimated using modified Rankin scales. RESULTS: A total of 14 patients were identified to have complete MCA infarction and cerebral venography. Four patients (25.6%) were found to have ipsilateral cerebral venous anomaly, including transverse sinus atresia (1), hypoplasia (2), and previous surgical ligation of internal jugular vein (1). All of them had fatal brain edema. The severity and timing of maximal edema were correlated with the degree of cerebral venous outflow obstruction. They all refused surgery and died from transtentorial herniation. The remaining 10 patients had symmetric or ipsilateral dominant cerebral venous drainage. Only one of them developed life-threatening edema possibly due to poor collateral circulation and bilateral carotid stenosis. He underwent decompressive surgery and recovered with moderate left hemiparesis. Patient age, sex, co-morbidity, carotid artery occlusion, or infarct size was not independently associated with life-threatening edema. CONCLUSIONS/RELEVANCE: Our preliminary results suggest that ipsilateral cerebral venous outflow obstruction is independently associated with life-threatening brain edema after MCA infarction and may be an indication for early decompressive craniectomy.
Category - Cerebrovascular Disease - Acute Stroke Therapy
Sunday, March 08, 2009
HHT and stroke (aka Osler Weber Rendu s)
Felix S et al., Neurology 2008; 71: 2012-2013.
Hereditary hemorrhagic telangiectasia (HHT) is a rare aut dom disease caused by one of 2 mutations, designated HHT1 and HHT2. The mutations are in the ENG and ALK1 genes. Diagnosis required 3 of the following 4: spontaneous epistaxis, cutaneous telangiectasias. av malformations of the interior organs and positive family history. Complications are anemia, portal hypertension, hypoxemia, brain abscess and stroke.
Authors of a case report demonstrate occurrence of a stroke after embolization of the pulmonary artery venous malformation. Authors note the need to check platelet function prior to using antiplatelet drugs in patients with HHT for prevention before endovascular procedures.
MRI may show lots of tiny hemorrhages.
Recommendation is to screen relatives
notes
avm rupture can cause paradoxical pulmonary fistula
conjunctival
lung liver gi and brain
stroke is due to paradoxical emboli across the PAVM
rarely due to anemia, hypoxia or air emboli
PAVM are most concerning if larger than 2 cm
signs and symptoms
epistaxis long precedes telangiectasias
Dyspnea is second most common symptoms
Hemoptysis is third most
others clubbing cyanosis,GI bleeds in the over 58, less often chest pain and syncope
can auscultate a murmur over the PAVM in about half
Neurologic symptoms are present in about half including confusion, syncope, paresis, headache and vertigo especially
Migraines 43 percent
TIA 37 percent
stroke 18 percent
brain abscess in 9 percent
seizure 8 percent
more with advancing age
Hereditary hemorrhagic telangiectasia (HHT) is a rare aut dom disease caused by one of 2 mutations, designated HHT1 and HHT2. The mutations are in the ENG and ALK1 genes. Diagnosis required 3 of the following 4: spontaneous epistaxis, cutaneous telangiectasias. av malformations of the interior organs and positive family history. Complications are anemia, portal hypertension, hypoxemia, brain abscess and stroke.
Authors of a case report demonstrate occurrence of a stroke after embolization of the pulmonary artery venous malformation. Authors note the need to check platelet function prior to using antiplatelet drugs in patients with HHT for prevention before endovascular procedures.
MRI may show lots of tiny hemorrhages.
Recommendation is to screen relatives
notes
avm rupture can cause paradoxical pulmonary fistula
conjunctival
lung liver gi and brain
stroke is due to paradoxical emboli across the PAVM
rarely due to anemia, hypoxia or air emboli
PAVM are most concerning if larger than 2 cm
signs and symptoms
epistaxis long precedes telangiectasias
Dyspnea is second most common symptoms
Hemoptysis is third most
others clubbing cyanosis,GI bleeds in the over 58, less often chest pain and syncope
can auscultate a murmur over the PAVM in about half
Neurologic symptoms are present in about half including confusion, syncope, paresis, headache and vertigo especially
Migraines 43 percent
TIA 37 percent
stroke 18 percent
brain abscess in 9 percent
seizure 8 percent
more with advancing age
AHA abstract of note: Relationship of BNP level to cardiac thromus in patients with CVA and AF
Presentation Number:
ASA P12
Publishing Title:
Brain Natriuretic Polypeptide is a Marker Associated with Cardiac Thrombus in Stroke Patients
with Atrial Fibrillation
Author Block:
Yoko Okada
, Ehime hospital, Toon, Japan; Kensaku Shibazaki, Kazumi Kimura, Noriko Matsumoto, Yasuyuki
Iguchi, Kawasaki Medical Sch, Kurashiki, Japan
Abstract Body:
Background and purpose
Brain natriuretic peptide (BNP) is used as a biological marker of heart diseases. 8-10% of acute stroke patients
with atrial fibrillation (AF) have cardiac thrombus (CTh), which is considered as a high risk of stroke recurrence.
We investigated whether high BNP levels could be a biological marker of CTh in acute stroke patients with AF.
=0 A
Methods
Between November 2006 and June 2008, acute ischemic stroke patients with AF within 7 days of stroke onset
who underwent transesophageal echocardiography (TEE) were enrolled. We measured BNP using rapidly assay
(SHIONOSPOT® BNP) on TEE examination. Patients were divided into two groups according to the absence and
presence of CTh (Negative and Positive groups). We compared clinical characteristics including age, gender,
previous ischemic stroke, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score on
admission, and BNP level between the two groups. Moreover, the factors associated with CTh were investigated
by multivariate logistic regression model.
Results
67 patients (male 40; mean age, 76.5±11.1 years) were enrolled. 17 (25.4%) patients had CTh. Hypertension
(88.2% vs. 58.0%, p= 0.037) was higher in the Positive group than in the Negative group. There were no
significant differences between the Positive group and Negative group in age (76.5±9.5 vs. 76.4±11.7, p=0.730),
female (58.8% vs. 34.0%, p=0.072), previous ischemic stroke (23.5% vs. 30.0%, p=0.760), diabetes mellitus
(35.3% vs. 20.0%, p=0.201), hyperlipidemia (17.6% vs. 14.0%, p=0.706), smoking (41.2% vs. 52.0%, p=0.441),
and NIHSS score on admission (9.8±8.3 vs. 7.0±7.8, p=0.237). The mean±SD BNP level was significantly higher
in the Positive group than in the Negative group (307.3±270.6 vs. 146.5±119.0 pg/ml, p=0.024). The optimal cutoff
level, sensitivity, and specificity of BNP levels to distinguish the Positive group from the Negative group were
145.0 pg/ml, 70.6% and 64.0%, respectively. Multivariate logistic regression analysis demonstrated that plasma
BNP level of >145.0 pg/ml (odds ratio, 4.61; 95%CI, 1.29 to 16.51, p=0.019) was independent factor associated
with CTh.
Conclusions
BNP is a marker associated with CTh in stroke patients with AF.
Saturday, March 07, 2009
risk factors for arterial dissection
tobacco use,
HTN, OCPs, migraines , MTHFR genotype, alpha 1 antitripsin deficiency,
hyperhomocysteinemia, ADPKD, Ehlers-Danlos (vascular type), TRAUMA
HTN, OCPs, migraines , MTHFR genotype, alpha 1 antitripsin deficiency,
hyperhomocysteinemia, ADPKD, Ehlers-Danlos (vascular type), TRAUMA
Thursday, March 05, 2009
More on statins and stroke
Coull BM, Johnston SC Statins: not just for the faint of heart. (editorial) Neurology 2009; 72: 684-685.
Nice discussion of statins and stroke.
"Ironclad" evidence of reduction of cvd and cva in patients treated with HMGCOA.
Chaturverdi et al. compared 2000+ patients over 65 with those under 65 in posthoc analysis of SPARCL data. They found rr of stroke in elderly group was reduced by 10 %, and in the younger group by 26 %; only the second was statistically significant. However, with reduced sample sizes the two groups were not different (go figure, ask a math guy).
For atorvastatin, there was a 1.5 % reduction in second stroke at 5 years, giving a NNT of 327 for STROKE in elderly. However, for all heart disease and stroke the reduction was 4.1 % with a NNT of 120 per year, which was highly significant and probably cost effective. No one knows if simvastatin is better but it is cheaper. Authors urge use of a HIGH DOSE statin.
Nice discussion of statins and stroke.
"Ironclad" evidence of reduction of cvd and cva in patients treated with HMGCOA.
Chaturverdi et al. compared 2000+ patients over 65 with those under 65 in posthoc analysis of SPARCL data. They found rr of stroke in elderly group was reduced by 10 %, and in the younger group by 26 %; only the second was statistically significant. However, with reduced sample sizes the two groups were not different (go figure, ask a math guy).
For atorvastatin, there was a 1.5 % reduction in second stroke at 5 years, giving a NNT of 327 for STROKE in elderly. However, for all heart disease and stroke the reduction was 4.1 % with a NNT of 120 per year, which was highly significant and probably cost effective. No one knows if simvastatin is better but it is cheaper. Authors urge use of a HIGH DOSE statin.
Monday, March 02, 2009
Inflammatory bowel disease
Strokes occur in one percent
Elevated fibrinogen, decreased protein S or increased clotting factors usually are implicated.Other causes include increased homocysteine due to B12 deficiency, or optic neuropathy, or vasculitis.
Elevated fibrinogen, decreased protein S or increased clotting factors usually are implicated.Other causes include increased homocysteine due to B12 deficiency, or optic neuropathy, or vasculitis.
Cogan's syndrome
is caused by a vasculitis similar to PAN, causing bilateral deafness (often simultaneous), uveitis and blindness secondary to retinal ischemia. Fever, chills, weight loss, thrombocytopenia, and abnormal CSF also occur. Treatment is with immunosuppressive drugs.
interstitial keratitis- granular corneal infiltration
SN hearing loss
aortitis with aortic insufficiency
some need AVR
Pearls: Infectious stroke
1. For most infections, CSF exam is the tipoff
2. In syphilitic meningovascular disease, a branch of the MCA or aorta may be involved
3. HIV itself, coexisting syphilis or NBTE , fungal or zoster infections occur in HIV infected patients.
4. Zoster stroke in MCA distribution occurs several weeks after cutaneous zoster infection. Steroids are critical, and antiplatelet drugs also are used.
5. Cysticercosis has stroke in about ten percent, usually lacunes, CSF may be helpful, and treatment is with albendazole, praziquental, and steroids or occassionally surgery.
6. Mucormycosis has typical and dramatic presentation, but it can include cavernous sinus thrombosis with ICA occlusion and stroke. Signs of include bilateral exopthalmos, proptosis, chemosis, ocular impairments and visual loss.
7. Cat scratch disease due to bartonella can cause an arteritis and stroke
Moya moya disease pearls
Review article NEJM 2009; 360:1226-1237
1. There are many disease associations esp SCD, NF1, irradiation, and Down's syndrome, and less commonly cardiac anomaly, renal artery stenosis, giant cervicofacial hemangioma and hyperthyroidism.
2. It occurs throughout the world but especially in northeast Asia, 10x frequency as in N America
3. In Japan the responsible gene is 17q25. Other genetic association is RNF 213 autosomal dominant AD
4. The disease is more fulminant in children ; can be triggered by exertion, crying, hyperventilation, dehydration, or anaesthesia, presumably related to decreased CO2 tension in a compensated and fragile system.
5. Ischemic stroke is more common in children and adults, but hemorrhagic stroke occurs much more frequently in adults than in children
6. Headache, often refractory, occurs in two thirds, and may resolve within a year of revascularization surgery
7. Choreiform movement disorders in children occassionally resolve with revascularization surgery
8. Morning glory disc is associated and should prompt a consideration of the diagnosis
http://images.google.com/imgres?imgurl=http://www.nature.com/eye/journal/v21/n10/images/6702851f7.jpg&imgrefurl=http://www.nature.com/eye/journal/v21/n10/fig_tab/6702851f7.html&usg=__ycWmZRS6FxhD_gWU8YhCPzJQ1v8=&h=306&w=390&sz=112&hl=en&start=2&sig2=ybxbCPAci2WQ5GHSHYrFqQ&tbnid=oCbcKU1tcEBAIM:&tbnh=97&tbnw=123&prev=/images%3Fq%3Dmorning%2Bglory%2Bdisc%26gbv%3D2%26hl%3Den&ei=OGPJSY_1M5usMvW3wdYD
9. Pathology is smooth muscle proliferation and caspace dependent apoptosis. Some walls are stressed with microaneurysms which can explain hemorrhage.
10. EC IC bypass may be indicated in some . This is because the disease is inexorably progressive without surgical treatment and standard medical treatment does not work. Metaanalysis studies suggest treatment can halt progression.
11. Suzuki.Takaku developed a grading system for arterial changes
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=119568&Ausgabe=235294&ProduktNr=224273&filename=119568.pdf
10. Cessation of smoking and birth control pills is indicated
11. "Ivy sign" radiographically may be seen in 70 % and resolve with bypass, consists of leptomeningeal enhancement with pial engorgement going into cortex. This is seen on FLAIR and post contrast images and resembles ivy creeping up on stone.
morning glory disc
1. There are many disease associations esp SCD, NF1, irradiation, and Down's syndrome, and less commonly cardiac anomaly, renal artery stenosis, giant cervicofacial hemangioma and hyperthyroidism.
2. It occurs throughout the world but especially in northeast Asia, 10x frequency as in N America
3. In Japan the responsible gene is 17q25. Other genetic association is RNF 213 autosomal dominant AD
4. The disease is more fulminant in children ; can be triggered by exertion, crying, hyperventilation, dehydration, or anaesthesia, presumably related to decreased CO2 tension in a compensated and fragile system.
5. Ischemic stroke is more common in children and adults, but hemorrhagic stroke occurs much more frequently in adults than in children
6. Headache, often refractory, occurs in two thirds, and may resolve within a year of revascularization surgery
7. Choreiform movement disorders in children occassionally resolve with revascularization surgery
8. Morning glory disc is associated and should prompt a consideration of the diagnosis
http://images.google.com/imgres?imgurl=http://www.nature.com/eye/journal/v21/n10/images/6702851f7.jpg&imgrefurl=http://www.nature.com/eye/journal/v21/n10/fig_tab/6702851f7.html&usg=__ycWmZRS6FxhD_gWU8YhCPzJQ1v8=&h=306&w=390&sz=112&hl=en&start=2&sig2=ybxbCPAci2WQ5GHSHYrFqQ&tbnid=oCbcKU1tcEBAIM:&tbnh=97&tbnw=123&prev=/images%3Fq%3Dmorning%2Bglory%2Bdisc%26gbv%3D2%26hl%3Den&ei=OGPJSY_1M5usMvW3wdYD
9. Pathology is smooth muscle proliferation and caspace dependent apoptosis. Some walls are stressed with microaneurysms which can explain hemorrhage.
10. EC IC bypass may be indicated in some . This is because the disease is inexorably progressive without surgical treatment and standard medical treatment does not work. Metaanalysis studies suggest treatment can halt progression.
11. Suzuki.Takaku developed a grading system for arterial changes
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=119568&Ausgabe=235294&ProduktNr=224273&filename=119568.pdf
10. Cessation of smoking and birth control pills is indicated
11. "Ivy sign" radiographically may be seen in 70 % and resolve with bypass, consists of leptomeningeal enhancement with pial engorgement going into cortex. This is seen on FLAIR and post contrast images and resembles ivy creeping up on stone.
morning glory disc
Buerger disease
Signs and symptoms include
1. Digital ischemia leading to ulceration
2. Claudication of the upper and lower limbs
3. Superficial thrombophlebitis
History-- heavy tobacco use, three fourths are young or middle aged men
Rarely strokes occur
Treatment is smoking cessation, possibly antiplatelets
Pearls on fibromuscular dysplasia
1. Predominance of women
2. Associations: young adults, Ollier's disease, saccular aneurysms
3. String of beads, long tapered segment, and false aneurysm may be found radiographically
4. Usual location is 1.5 cm above bifurcation although other sites may be implicated
5. Complications include dissection or vasospasm due to angiography
6. Half may develop TIA or stroke
7. Other signs include asymptomatic bruit, pulsatile tinnitus
8. Overall prognosis is relatively benign with less recurrent strokes than with atheromatous disease
9.HTN
10, usually extracranial, due to abnormal Media. middle portion of artery familial or sporadic SAH
11. Renal aa involved
2. Associations: young adults, Ollier's disease, saccular aneurysms
3. String of beads, long tapered segment, and false aneurysm may be found radiographically
4. Usual location is 1.5 cm above bifurcation although other sites may be implicated
5. Complications include dissection or vasospasm due to angiography
6. Half may develop TIA or stroke
7. Other signs include asymptomatic bruit, pulsatile tinnitus
8. Overall prognosis is relatively benign with less recurrent strokes than with atheromatous disease
9.HTN
10, usually extracranial, due to abnormal Media. middle portion of artery familial or sporadic SAH
11. Renal aa involved
Causes of dilated or other cardiomyopathy
1. Ischemic heart disease
2. Post partum
3. Chronic alcohol use
4. Viral illness
5. Mitochondrial disease (Melas, Merrf)
6. Myotonic, limb girdle and scapuloperoneal dystrophy
7. Primary oxalosis leads to calcification and heart embolus
2. Post partum
3. Chronic alcohol use
4. Viral illness
5. Mitochondrial disease (Melas, Merrf)
6. Myotonic, limb girdle and scapuloperoneal dystrophy
7. Primary oxalosis leads to calcification and heart embolus
Atrial myxoma
Presentation is obstructive, constitutional syndromes and stroke. Obstruction presents with sudden decreased cardiac output, even death with obstruction of mitral orifice. The usual sign is a murmur with a change in posture. Constitutional signs include low grade fever, arthralgias, skin eruptions and fleeting neurological signs. Elevated sed rate and abnormal serum proteins may lead to a misdiagnosis of lupus. One third will have neurological symptoms, including stroke, that can be the presenting sign of the illness. EKG shows nonspecific signs. Tumor embolus can act as a nidus for intracranial aneurysm formation. Rarely, a fibroelastic or malignant tumor of the heart can cause a stroke. Surgical resection is indicated. Anticoagulation does not work.
Libman Saks endocarditis pearls
1. Associated with Lupus and apl
2. Changes may be detectable on cardiac imaging
3. MV disease with apl's can lead to micro brain infarction (multiple) in PAN
4. Sneddon's syndrome has livedo reticularis, apl's and digital ischemia
Pearls on NBTE
1. Uncommon condition, but one third develop strokes
2. May be multiple and hemorragic
3. Mental status changes are common
4. DIC associations include thrombocytopenia, decreased fibrinogen, elevated FDP, increased d-dimer
5. Vegetations usually affect mitral and aortic valves
6. Vegetations may be too small to see on cardiac imaging
7. Treatment includes anticoagulation for DIC and treatment of malignancy
8. Associations include adenoca (pancreas, lung, ovary,bowel); DM, pregnancy, surgery, AIDS, dehydration.
9. Due to underlying condition, prognosis is poor.
Atrial fibrillation pearls
1. AF increases the stroke risk by 5-6 times
2. In presence of heart disease AF increases stroke risk 15 times
3. 10 % of stroke patients will be found to have AF
4. Europeans found 14 % silent stroke rate in AF patients.
5. In Oxfordshire, 30 day mortality for stroke with AF is 23 %, 8 % without
6. Presence of AF increases health spending 15-29 times
7. Lone AF depends on age, risk of 0.5 % ages 50-59, 9 % ages 80-89
8. Risk is higher in patients with HTN, DM, elderly and prior stroke
9. Presence of murmur or any heart disease precludes a diagnosis of lone AF
10. TEE may not be needed if clinical neurologic symptoms prove need for anticoagulation
11. Warfarin may lower risk of stroke in susceptible patients by 80%
12. Anticoagulate for 3-4 weeks before and after cardioversion, consider a TEE before
Aortic dissection pearls
1. Presents with chest or back pain, may be stroke if proximal enough
2. Thrombolysis is dangerous in this setting
3. Syphilis is a classic etiology that is currently likely overrated,but other causes are Marfan's or atherosclerosis
4. Also consider with unstable vital signs, hypotension, unequal pulses, or widened aortic silhouette on chest x ray
5. Surgical treatment (replacement of the aorta) is performed but the results are poor overall.
6. Warfarin is used but some believe it can lead to cholesterol embolization and purple toe syndrome
7. Antiplatelet agents might be the best treatment although that is not proved.
2. Thrombolysis is dangerous in this setting
3. Syphilis is a classic etiology that is currently likely overrated,but other causes are Marfan's or atherosclerosis
4. Also consider with unstable vital signs, hypotension, unequal pulses, or widened aortic silhouette on chest x ray
5. Surgical treatment (replacement of the aorta) is performed but the results are poor overall.
6. Warfarin is used but some believe it can lead to cholesterol embolization and purple toe syndrome
7. Antiplatelet agents might be the best treatment although that is not proved.
Sunday, March 01, 2009
Unusual carotid syndromes
JP Mohr chapter, Barnett book.
Opticocerebral syndrome (combined) is very rare, less than .5% in Bogousslavsky's series.
TMB-- usually does not occur with finding of cholesterol emboli (hollenhorst plaques).
CRAO has associated carotid appropriate pathology 50-70 % of time. TIA's are common
Ischemic optic neuropathy-- findings include RAPD, neovascularization. (rebeosis iridis) , secondary glaucoma, proliferative retinopathy, microaneurysms, flame shaped hemorrhages, venous stasis, optic atrophy.
Migraine variant= Raeder syndrome= pericarotid syndrome--facial pain and ipsilateral oculosympathetic effect.
Opticocerebral syndrome (combined) is very rare, less than .5% in Bogousslavsky's series.
TMB-- usually does not occur with finding of cholesterol emboli (hollenhorst plaques).
CRAO has associated carotid appropriate pathology 50-70 % of time. TIA's are common
Ischemic optic neuropathy-- findings include RAPD, neovascularization. (rebeosis iridis) , secondary glaucoma, proliferative retinopathy, microaneurysms, flame shaped hemorrhages, venous stasis, optic atrophy.
Migraine variant= Raeder syndrome= pericarotid syndrome--facial pain and ipsilateral oculosympathetic effect.
Notes on Thrombolytic systems
from text of barnett et al. c 9 Keyt et al.
t-PA inhibits conversion of plasminogen to plasmin, and plasmin , and fibrin clot, which is formed by the action of thrombin on fibrinogen, is dissolved by plasmin. Plasmin also feedback activates t-PA and enhances conversion into double chain form. Activation of system leads to a cascade leading to production of thrombin.
Arterial and venous clot are morphologically different (red v. white clot) but difference is more quantitative than qualitative. t-PA works much better on fibrin rich clots than on platelet rich white clots.
SAFETY antiplatelet drugs
SUMMARY
• Antiplatelet drugs (aspirin, dipyridamole,
clopidogrel), given in single- or dualagent
regimens, are the treatment of
choice for secondary prevention in
ischemic NCS
• Choice of single- or dual-agent therapy
depends upon calculation of safety risk
relative to preventive efficacy
• Key safety concerns are hemorrhage
(aspirin + clopidogrel), GI effects (all antiplatelet
agents) and headache (dipyridamole)
• ESPS-2: Dual therapy with aspirin + ER
dipyridamole significantly improved prevention in
patients with a history of TIA or stroke, without
excess risk of bleeding, compared with aspirin
alone
• ESPRIT: In patients with a history of TIA or minor
stroke, aspirin + dipyridamole resulted in fewer
cardio- or cerebrovascular endpoint events,
including first ischemic stroke, compared with
aspirin alone, with fewer major bleeding
complications; dipyridamole-related headache
was a notable cause of study withdrawal
• MATCH: Adding aspirin to clopidogrel did not
significantly reduce risk of major vascular events
(including stroke) in patients with stroke/TIA
history, but did significantly increase risk of lifethreatening,
major, and minor bleeding
• CHARISMA: In a broader patient population than
MATCH (with multiple atherothrombotic risk
factors or symptomatic, documented vascular
disease), vascular events were not significantly
reduced, but moderate bleeding was
significantly increased, with the combination of
aspirin + clopidogrel compared with aspirin
alone
• Based on available evidence, AHA guidelines
advise the practicing physician to prescribe:
• Aspirin
• The combination of aspirin and ER
dipyridamole or clopidogrel monotherapy for
survivors of stroke or TIA
• Aspirin + ER dipyridamole over aspirin alone
to avoid routine use of dual therapy with aspirin
+ clopidogrel because of excess bleeding risk
• The complex histories of many poststroke and
post-TIA patients require an individual approach,
considering the need for anticoagulation, use of
aspirin + clopidogrel post-PCI, bleeding risks,
and the potentials for drug allergy, resistance,
and intolerance
ACTIVE and SPS3
ACTIVE
Another important study underway is ACTIVE
(Atrial fibrillation Clopidogrel Trial with Irbesartan
for Vascular Events). This multicenter trial plans
to enroll a total of 14,000 patients with AF and
at least 1 risk factor for stroke, including but not
limited to prior stroke or TIA.7
ACTIVE comprises 3 component trials—ACTIVE
W, ACTIVE A, and ACTIVE I. ACTIVE W is a
randomized, open, noninferiority trial comparing
oral anticoagulation therapy (target
international normalized ratio [INR] of 2 to 3)
with aspirin (75 to 100 mg/day) + clopidogrel
(75 mg/day).7 ACTIVE A, which included
patients ineligible for randomization to anticoagulation,
is a double-blind comparison of
clopidogrel + aspirin with aspirin alone.7
Patients participating in ACTIVE W or A could
be enrolled in ACTIVE I, a partial factorial,
double-blind trial in which irbesartan
(300 mg/day) or placebo is added to the
regimen of ACTIVE W or A.7
Planned follow-up is 3 years (mean).7 For
ACTIVE W and A, the primary outcome is the
composite of first occurrence of stroke,
non–central nervous system (non-CNS) systemic
embolism, myocardial infarction (MI), or
vascular death, with major bleeding as a
secondary outcome.7 ACTIVE I has 2-part
primary outcomes of stroke, MI, and vascular
death with and without hospitalization for
heart failure.7
Although ACTIVE A and I remain ongoing,16
ACTIVE W was recently terminated prematurely
because of “clear evidence of superiority of
anticoagulation therapy” compared with aspirin
+ clopidogrel.16 Oral anticoagulation provided
more effective prevention of the primary endpoint
events (P=.0003) and of stroke (P=.001;
Figure 2).16 Minor bleeding was more common
with aspirin + clopidogrel (P=.0009), with
major bleeding similar between the groups;
total incidence of hemorrhage was significantly
greater with aspirin + clopidogrel than with
SPS3
SPS3
Small subcortical strokes (S3), also known as
lacunar or small-vessel strokes, account for
about 25% of brain infarctions and are associated
with vascular dementia. These strokes are
especially frequent in younger and minority
populations, and patients with symptomatic S3
strokes have a recurrent stroke rate of 8%.8
Secondary Prevention of Small Subcortical
ASA = aspirin; ER-DP = extended-release dipyridamole; C = clopidogrel; T =telmisartan;
W = warfarin (or, in ACTIVE, the available vitamin K antagonist anticoagulant); I = irbesartan; S = simvastatin
TABLE 1
Brief Summary of Studies
STUDY PROJECTED N POPULATION DESIGN/COMPARISON PRIMARY OUTCOME
PRoFESS1,4,
10,11,12,13,15,17
20,333 Recent ischemic stroke
history
Randomized, double-blind, multicenter
2x2 factorial
ASA + ER-DP vs C; T in half of population
Time to second stroke
ACTIVE7,8,10,17 14,000 AF history with ³1 risk
factor for stroke (including
prior stroke/TIA)
All ACTIVE trials are multicenter
ACTIVE W (completed): randomized, open,
noninferiority trial W vs ASA + C
ACTIVE A: double-blind ASA + C vs ASA
ACTIVE I: partial factorial, double-blind
Irbesartan (I) or placebo added to regimen
of ACTIVE W or A
Composite of first
occurrence of stroke,
non-CNS systematic
embolism, MI, vascular
death (ACTIVE I
eliminates non-CNS
systemic embolism and
adds hospitalization for
heart failure
SPS324 2500 Small subcortical
stroke history
Factorial, multicenter
ASA + C vs ASA; hypertensive subset receives
usual or aggressive BP reduction therapy
Stroke prevention
CASTIA10,19-22 2400 Acute ischemic stroke/TIA
(first 24 h)
Randomized
ASA + C vs ASA
Composite of stroke,
new MRI-documented
infarction, MI,
vascular death
FASTER20,23 500 (pilot)
7500 (total)
Acute ischemic stroke/TIA
(first 24 h)
Randomized, double-blind, multicenter
2x2 factorial
4 arms of study:
ASA alone; ASA + C;
ASA + S; ASA + C + S
Recurrent stroke
ARCH9,17,25 1500 Atherosclerosis of
aortic arch
Recent (<6 months)
cerebral or peripheral
embolic event)
Open, randomized, multicenter
W vs ASA + C
Composite of recurrent
stroke, acute MI,
peripheral embolism,
vascular death
Strokes (SPS3) is a 45-center, randomized
trial that will assess stroke prevention (primary
endpoint) and cognition (secondary endpoint)
in a planned cohort of 2500 patients with a
history of S3.8,10,17 A factorial design will
compare aspirin + placebo vs aspirin +
clopidogrel; hypertensive patients in these
2 groups will also receive either usual blood
pressure control (to a target of 130-149
mmHg systolic BP) or intensive control (to a
target of <130 mmHg systolic BP).8 Mean
follow-up will be 3 years.8 SPS3 will provide
data on the stroke prevention with aspirin +
clopidogrel in a population with cerebrovascular
manifestations of atherothrombosis.18
Another important study underway is ACTIVE
(Atrial fibrillation Clopidogrel Trial with Irbesartan
for Vascular Events). This multicenter trial plans
to enroll a total of 14,000 patients with AF and
at least 1 risk factor for stroke, including but not
limited to prior stroke or TIA.7
ACTIVE comprises 3 component trials—ACTIVE
W, ACTIVE A, and ACTIVE I. ACTIVE W is a
randomized, open, noninferiority trial comparing
oral anticoagulation therapy (target
international normalized ratio [INR] of 2 to 3)
with aspirin (75 to 100 mg/day) + clopidogrel
(75 mg/day).7 ACTIVE A, which included
patients ineligible for randomization to anticoagulation,
is a double-blind comparison of
clopidogrel + aspirin with aspirin alone.7
Patients participating in ACTIVE W or A could
be enrolled in ACTIVE I, a partial factorial,
double-blind trial in which irbesartan
(300 mg/day) or placebo is added to the
regimen of ACTIVE W or A.7
Planned follow-up is 3 years (mean).7 For
ACTIVE W and A, the primary outcome is the
composite of first occurrence of stroke,
non–central nervous system (non-CNS) systemic
embolism, myocardial infarction (MI), or
vascular death, with major bleeding as a
secondary outcome.7 ACTIVE I has 2-part
primary outcomes of stroke, MI, and vascular
death with and without hospitalization for
heart failure.7
Although ACTIVE A and I remain ongoing,16
ACTIVE W was recently terminated prematurely
because of “clear evidence of superiority of
anticoagulation therapy” compared with aspirin
+ clopidogrel.16 Oral anticoagulation provided
more effective prevention of the primary endpoint
events (P=.0003) and of stroke (P=.001;
Figure 2).16 Minor bleeding was more common
with aspirin + clopidogrel (P=.0009), with
major bleeding similar between the groups;
total incidence of hemorrhage was significantly
greater with aspirin + clopidogrel than with
SPS3
SPS3
Small subcortical strokes (S3), also known as
lacunar or small-vessel strokes, account for
about 25% of brain infarctions and are associated
with vascular dementia. These strokes are
especially frequent in younger and minority
populations, and patients with symptomatic S3
strokes have a recurrent stroke rate of 8%.8
Secondary Prevention of Small Subcortical
ASA = aspirin; ER-DP = extended-release dipyridamole; C = clopidogrel; T =telmisartan;
W = warfarin (or, in ACTIVE, the available vitamin K antagonist anticoagulant); I = irbesartan; S = simvastatin
TABLE 1
Brief Summary of Studies
STUDY PROJECTED N POPULATION DESIGN/COMPARISON PRIMARY OUTCOME
PRoFESS1,4,
10,11,12,13,15,17
20,333 Recent ischemic stroke
history
Randomized, double-blind, multicenter
2x2 factorial
ASA + ER-DP vs C; T in half of population
Time to second stroke
ACTIVE7,8,10,17 14,000 AF history with ³1 risk
factor for stroke (including
prior stroke/TIA)
All ACTIVE trials are multicenter
ACTIVE W (completed): randomized, open,
noninferiority trial W vs ASA + C
ACTIVE A: double-blind ASA + C vs ASA
ACTIVE I: partial factorial, double-blind
Irbesartan (I) or placebo added to regimen
of ACTIVE W or A
Composite of first
occurrence of stroke,
non-CNS systematic
embolism, MI, vascular
death (ACTIVE I
eliminates non-CNS
systemic embolism and
adds hospitalization for
heart failure
SPS324 2500 Small subcortical
stroke history
Factorial, multicenter
ASA + C vs ASA; hypertensive subset receives
usual or aggressive BP reduction therapy
Stroke prevention
CASTIA10,19-22 2400 Acute ischemic stroke/TIA
(first 24 h)
Randomized
ASA + C vs ASA
Composite of stroke,
new MRI-documented
infarction, MI,
vascular death
FASTER20,23 500 (pilot)
7500 (total)
Acute ischemic stroke/TIA
(first 24 h)
Randomized, double-blind, multicenter
2x2 factorial
4 arms of study:
ASA alone; ASA + C;
ASA + S; ASA + C + S
Recurrent stroke
ARCH9,17,25 1500 Atherosclerosis of
aortic arch
Recent (<6 months)
cerebral or peripheral
embolic event)
Open, randomized, multicenter
W vs ASA + C
Composite of recurrent
stroke, acute MI,
peripheral embolism,
vascular death
Strokes (SPS3) is a 45-center, randomized
trial that will assess stroke prevention (primary
endpoint) and cognition (secondary endpoint)
in a planned cohort of 2500 patients with a
history of S3.8,10,17 A factorial design will
compare aspirin + placebo vs aspirin +
clopidogrel; hypertensive patients in these
2 groups will also receive either usual blood
pressure control (to a target of 130-149
mmHg systolic BP) or intensive control (to a
target of <130 mmHg systolic BP).8 Mean
follow-up will be 3 years.8 SPS3 will provide
data on the stroke prevention with aspirin +
clopidogrel in a population with cerebrovascular
manifestations of atherothrombosis.18
CaSTIA, fASTER AND ARCH
CASTIA
Can acute antiplatelet treatment make a
difference in stroke recurrence? Clopidogrel
in Acute Stroke and TIA (CASTIA) will randomize
a projected 2400 patients with
acute, minor ischemic stroke or TIA within
the first 24 hours of symptom onset; all
patients will be treated with aspirin,
75 mg/day, and will also receive either
placebo or clopidogrel at an initial loading
dose of 300 mg/day followed by maintenance
at 75 mg/day.10,19,20 Primary
composite outcome will include stroke, new
infarction documented by MRI, MI, and
vascular death at 90 days of follow-up.19,20
FASTER
The preventive benefits of acute care are
also the subject of FASTER (Fast Assessment
of Stroke and Transient ischemic attack
to prevent Early Recurrence).21,22 This randomized,
double-blind trial is expected to
enroll 500 stroke/TIA patients at 19 centers
in a pilot phase, eventually enrolling
7500 patients if the pilot proves feasibility.19-23
FASTER will use a 2x2 factorial design: in the
first 24 hours after stroke/TIA, all patients will
be treated with aspirin, and randomized to
placebo or clopidogrel (300 mg/day load,
followed by 75 mg/day) and to placebo or
simvastatin 40 mg/day.19-22 This creates
4 possible treatment arms: aspirin alone,
aspirin + clopidogrel, aspirin + simvastatin,
and aspirin + clopidogrel + simvastatin.23
Eligible patients will not be candidates for
acute thrombolytic therapy.21,22 Patients will
be treated for 1 month, and follow-up will be
90 days.19-22 The primary outcome measure
is recurrent stroke.19,20 Results of FASTER’s
pilot program are anticipated soon,19,20 and
will provide some indication of the utility of
dual antiplatelet therapy, with or without a
statin for short-term stroke prevention.
ARCH
Aortic arch atheroma is a significant risk
factor for ischemic stroke.9 To date, there
has been no evidence regarding the choice
of preventive strategies for recurrent stroke
in this population.9 ARCH (Aortic Arch
Related Cerebral Hazard) is an open,
randomized trial with a projected enrollment
of 1500 patients at 15 centers, enrolling
patients with atherosclerosis of the aortic
arch and a recent (less than 6 months)
cerebral or peripheral embolic event.9,17 The
study will compare oral anticoagulation with
warfarin (target INR, 2-3) vs aspirin 75 to
325 mg/day + clopidogrel 75 mg/day.9 The
primary outcome is a composite of recurrent
stroke, acute MI, peripheral embolism, or
vascular death.9 ARCH will be the first trial to
assess prevention of secondary stroke in
this subpopulation.9
Esprit and Charisma
2006 European Stroke Conference in Brussels,
include results from the European/Australian Stroke
Prevention in Reversible Ischemia Trial (ESPRIT),
which assessed the incremental efficacy of aspirin
+ ER dipyridamole over aspirin alone. Data also
included results from a substudy of patients
enrolled in CHARISMA who experienced stroke
during study treatment with aspirin + clopidogrel
or aspirin alone.
SPIRIT—the Stroke Prevention in Reversible
Ischemia Trial.1 The objective of SPIRIT (n=1316)
was to compare the efficacy and safety of oral
anticoagulation (to an international normalized ratio
[INR] 3.0 to 4.5) vs low-dose aspirin (30 mg/d) for
secondary prevention of cardio- and cerebrovascular
events after TIA or minor stroke.8 SPIRIT
reported an excess of primary outcome events—
vascular death, nonfatal stroke, nonfatal MI, or
nonfatal major bleeding complication—in the group
treated with oral anticoagulation.8 This excess was
predominantly due to a high rate of bleeding
complications, which increased by a factor of 1.43
with each 0.5-unit increase in INR; this high
incidence of anticoagulant-related bleeding
resulted in early termination of SPIRIT at only 17%
of its expected number of observed patient-years.
BLOGGER COMMENT- Overdosed warfarin, underdoses ASA
SUMMARY
n Current secondary event–prevention guidelines
from the AHA recommend intervention
with antiplatelet agents in patients who have
suffered NCS or TIA; however, questions
remain about which regimen is optimal
n Although oral anticoagulation therapy is a
mainstay for treatment of patients with
cardiogenic cerebral embolism, it has not
shown sufficient efficacy in NCS to justify the
substantial risk of bleeding complications. In
CHARISMA, clopidogrel + aspirin tended to
increase moderate-to-severe bleeding risk
compared with aspirin alone. In ESPRIT, while
major bleeding was less frequent with aspirin
+ dipyridamole than with aspirin alone,
investigators thought this may have been a
chance effect
n New data presented at ESC 2006 provide
further evidence on optimization of antiplatelet
therapy. These data come from 2 clinical
studies (ESPRIT and the CHARISMA Stroke
Substudy)
n The objective of ESPRIT was to determine if
aspirin + ER dipyridamole provided greater
preventive benefit than aspirin alone; this
result was documented in the earlier ESPS-2
trial, but there was some uncertainty about
the result, owing to conflicting findings in
other studies
n Results from ESPRIT confirm that aspirin +
dipyridamole is more effective than aspirin
alone in the prevention of vascular events
following NCS or TIA
n ESPRIT also confirmed that there is no
significant increase in bleeding events with
aspirin + dipyridamole vs aspirin alone
Antiplatelet agents, plaque, misc for stroke
1. Mechanism of injury is plaque rupture that causes platelet activation, exposure of platelets to VWF that tethers and causes to adhere other platelets to site. Platelet granules release alpah granules and fibrinogen and ADP that causes more platelet activation. Platelet also derives thromboxane A2 and thrombin. Also get G2 protein receptor, platelet shape change (round to discoid with extending filaments) increased cAMP intracellularly, P2Y1 receptor causes an ADP mediated increased cytosolic calcium, P2Y12 receptor potentiates granule secretion, recruitment of platelets and aggregation.
2. ASA blocks thromboxane A 2 mediated path. Plavix blocks P2Y12 receptor. Dipyridamole increases ic cAMP deterring platelet activation and is vasodilatory due to secondary inhibition of phosphodiesterase (PDE). It blocks ADP nucleic acid uptake in dose dependent manner.
3. Acetylcyclic acid inhibits cyclooxygenase 1 (Cox 1) aka PGH synthase. Inhibition of Cox 1 is irreversible for 8-10 day lifetime of platelets. However, thrmobotic potential exists with 20 % Cox 1 activity so daily ASA is advised. Low doses may be effective because platelets in portal circulation are extensively exposed before degradation (hepatic metabolism, renal excretion).
4 As a vasodilator, dipyridamole should be used cautiously in patients with CAD or hypotension. It lasts half day (extended form) is conjugated to glucuronic acid and excreted via bile into feces.
5. Clopidogrel must be metabolized into an unknown active metabolite by liver.Actions affect dense granule secretion, fibrinogen activity, and coag rate, and TXA2 function. Affects thrombus size and duration but NOT platelet shape. Affects platelet irreversibly. Typically effects are seen within 2 hours, with steady state 40-60 % inhibition at 2-3 days (steady state).
2. ASA blocks thromboxane A 2 mediated path. Plavix blocks P2Y12 receptor. Dipyridamole increases ic cAMP deterring platelet activation and is vasodilatory due to secondary inhibition of phosphodiesterase (PDE). It blocks ADP nucleic acid uptake in dose dependent manner.
3. Acetylcyclic acid inhibits cyclooxygenase 1 (Cox 1) aka PGH synthase. Inhibition of Cox 1 is irreversible for 8-10 day lifetime of platelets. However, thrmobotic potential exists with 20 % Cox 1 activity so daily ASA is advised. Low doses may be effective because platelets in portal circulation are extensively exposed before degradation (hepatic metabolism, renal excretion).
4 As a vasodilator, dipyridamole should be used cautiously in patients with CAD or hypotension. It lasts half day (extended form) is conjugated to glucuronic acid and excreted via bile into feces.
5. Clopidogrel must be metabolized into an unknown active metabolite by liver.Actions affect dense granule secretion, fibrinogen activity, and coag rate, and TXA2 function. Affects thrombus size and duration but NOT platelet shape. Affects platelet irreversibly. Typically effects are seen within 2 hours, with steady state 40-60 % inhibition at 2-3 days (steady state).
Subscribe to:
Posts (Atom)