Cardiac MRI - NEJM: tPA - - 3-4.5hr - - NEJM: tPA in 3 to 4.5 hour window - ">- 3-4.5hr data - - Call 911 - - TeleSTROKE - - MERCI - - ABCD2 - - Acute Ischemic Stroke - - IV Tx - - BP Control - - SAH - - ICH - - AHA Stroke Guidelines -

STROKE TOPICS

tPA

ICH

SAH

MRA

CTA

tPA must be given within 180 minutes of symptom onset

tPA Protocol

Establish onset time

When was pt. last normal?

180 minute time window

PT: 15 or less

CT: No bleed

close BP Monitoring

0.9 mg/kg

Max. dose = 90 mg

Blood Pressure Control is of critical importance during tPA infusion

Advanced Neuroimaging Techniques Enhance Stroke Diagnosis and Treatment.

CT Angiography using 64 slice scanners and 3D reconstruction software can be of great importance in rapidly and accurately diagnosing a major MCA occlusion:.

	3D reconstruction showing an acute right MCA occlusion; study was acquired with a 64 slice CT scanner
Non-contrast CT exam must be done first to exclude ICH	MR Angiography is an additional tool that can be combined post tPA treatment to assess the efficacy of thrombolytic therapy

After completing tPA infusion, close monitoring in an ICU setting is important to closely control blood pressure and to monitor for any neurologic chnage

Transient Ischemic Attack : The ABCD2 Scoring System Age > 60? BP > 140/90 mmHg at initial evaluation? Clinical Features of the TIA? (unilateral weakness: +2) Duration of Symptoms? (>60 min: +2)? Diabetes Mellitus?

NINDS Study on tPA for Acute Stroke: Link to original NEJM article on tPA for Acute Ischemic Stroke

MGH Protocol for Acute Ischemic Stroke Link to MGH Protocol for Acute Ischemic Stroke

MGH Protocol for IV tPA Link to MGH Protocol for IV tPA

MGH Protocol for BP Management for Thrombolysis Link to MGH Protocol for BP Control

MGH Protocol for Sub-Arachnoid Hemorrhage Link to MGH Protocol for SAH

MGH Protocol for Intra-Cerebral Hemorrhage Link to MGH Protocol for ICH

AHA Stroke Guideline Data Bank Link to AHA Stroke Guidelines

Advances in Intracerebral Hemorrhage Management Link to ICH Management review article

Advances in Care of Intracerebral Hemorrhage Link to ICH Management review article -Mayo Proceedings

CHADS2 Score for Atrial Fibrillation Related Stroke Risk Link to CHADS2 (score/Adjusted Stroke Rate : 0/1.9, 1/2.8, 2/4.0, 3/5.9, 4/8.5, 5/12.5,, 6/18.2)

ICH Score : Infratentoral/>80 years/Intra-Ventricular Extension/ICH Volume > 30cc/ Depressed Glasgow (5 to 12 = 1 and 3 to 4 = 2 points) Link to ICH Scoring System to Assess 30 Day Mortaltiy Risk (score/30 Day mortality Rate : 0/0%, 1/13%, 2/26%, 3/72%, 4/97%, 5+/100%)

Required Educational Material for 8-1 Stroke Unit Staff Medical Complications in a Comprehensive Stroke Unit and an Early Supported Discharge Service

ECMC Application for Designation as a Primary Stroke Center
1. Item One 2. Item Two 3. Item Three 4. Item Four 5. Item Five 6. Item Six 7. Item Seven 8. Item Eight 9. Item Nine 10. Item Ten
11. Item Eleven 12. Item Twelve 13. Item Thirteen 14. Item Fourteen 15. Item Fifteen 16. Item Sixteen 17. Item Seventeen 18. Item Eighteen 19. Item Nineteen 20. Item Twenty
21. Item Twenty One 22. Item Twenty Two 23. Item Twenty Three 24. Item Twenty Four 25. Item Twenty Five 26. Item Twenty Six 27. Item Twenty Seven 28. Item Twenty Eight 29. Item Twenty Nine 30. Item Thirty 31. Item Thirty One 32. Item Thirty Two

Sagital Brain Vasculature 1 Sagital Brain Vasculature 2 Sagital Brain Vasculature 3

STROKE is the number two cause of death worldwide, and number three in the United States.

Learn more about stroke with free on-line CME

AHA: Ischemic Stroke American Heart Association(Journal Articles : STROKE)

AHA: Hemorrhagic Stroke American Heart Association(Journal Articles : STROKE)

ICH Intracerebral Hemorrhage

Neurologic Emergencies - Educational Foundation (FERNE) FERNE.org

Post-Stroke Care: Stop DVT

GI bleed risk with antithrombotic therapy GI Bleed Risk Factors

Medscape Links to Free Stroke CME Multiple CME courses

NIH Stroke Scale American Heart Association link

Secondary Stroke Prevention 1.25 CME for Stroke

Reperfusion Therapy for Ischemic Stroke: An Update Thrombolytic Therapy

National Stroke Association Links to two audio webcast programs on stroke

2007 Guidelines for the Early Management of Adults With Ischemic Stroke Link to Stroke vol 38, page 1655 - 1711:

2006 Guidelines for Primary Prevention of Ischemic Stroke Link to Stroke vol 37, page 1583:

Case Example : Massive Left MCA infarction

The dynamic CT perfusion scan shown above illustrates a complete occlusion of the left middle cerebral artery. This type of infarction has a greater than 80% mortality

Case Example:3D Surface Rendering of CT angiography after Right MCA Stroke

Case Example : PET imaging of brain metabolism after stroke

Case Example : tPA lysis of MCA thrombus

Case Example : 3D surface rendering of CT angiography data reveals a large, partially calcified cerebral aneursym:

As noted by Wiebers et.al. in their study of 4060 patients (of whom 1692 did not have aneurysmal repair), 5 year cumulative rupture rates for patients who did not have a history of subarachnoid haemorrhage with aneurysms located in internal carotid artery, anterior communicating or anterior cerebral artery, or middle cerebral artery were 0%, 2.6%, 14.5%, and 40% for aneurysms less than 7 mm , 7-12 mm, 13-24 mm, and 25 mm or greater, respectively, compared with rates of 2.5%, 14.5%, 18.4%, and 50%, respectively, for the same size categories involving posterior circulation and posterior communicating artery aneurysms.

Unruptured Anterior Circulation Aneurysms <7mm have a extremely low 5 year Rupture Rate See data on 1037 AC/MC/IC and 210 Caverous Carotid Cases

911Stroke.info

Case Example : Complete Sagittal Sinus Occlusion

The above case illustrates one of four venous sinus occlusion cases that were successfully treated by Drs. Meyer and Beale: Successful treatment of four young adults with cerebral-vein thrombosis was achieved by retrograde venous infusion of urokinase directly into the clot, with good outcomes in all. Two of these four patients presented with seizures, subcortical hemorrhagic changes, and rapid neurologic deterioration due to extensive thrombosis of the superior sagittal sinus. The condition of a third patient developed more slowly, with thrombosis of only the anterior half of the sinus; in a fourth patient, the deep cerebral veins were involved. In all four patients, remarkable sustained clinical and radiologic improvement was found with slow local urokinase infusions given for as long as 30 hours (please see New England J. Medicine, Volume 345:1777-1778 )

Difficult Issues in Stroke Care: TIA in Association with Atrial Fibrillation (Heparin as a bridge to Coumadin?)

Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: This review concluded "... For patients with AF of known duration < 48 h, we suggest cardioversion without anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or low molecular weight heparin at presentation (Grade 2C)" : free full text link to CHEST 2004

Successful Use of tPA in Acute Stroke :

Strict Adherance to Protocol

To be eligible for the NINDS tPA study, patients had to have had: an ischemic stroke with a clearly defined time of onset, a deficit measurable on the NIHSS, and a base-line computed tomographic (CT) scan of the brain that showed no evidence of intracranial hemorrhage. Patients did not undergo randomization if they had had another stroke or serious head trauma within the preceding 3 months; had undergone major surgery within 14 days; had a history of intracranial hemorrhage; had a systolic blood pressure above 185 mm Hg or diastolic blood pressure above 110 mm Hg; had rapidly improving or minor symptoms; had symptoms suggestive of subarachnoid hemorrhage; had gastrointestinal hemorrhage or urinary tract hemorrhage within the previous 21 days; had arterial puncture at a noncompressible site within the previous 7 days; or had a seizure at the onset of stroke. Patients who were taking anticoagulants or who had received heparin within the 48 hours preceding the onset of stroke and had an elevated partial-thromboplastin time were excluded, as were those with prothrombin times greater than 15 seconds, platelet counts below 100,000 per cubic millimeter, or glucose concentrations below 50 mg per deciliter (2.7 mmol per liter) or above 400 mg per deciliter (22.2 mmol per liter). Patients were also excluded if aggressive treatment was required to reduce their blood pressure to the specified limits. Patients received placebo or alteplase (Activase, Genentech, South San Francisco), a recombinant t-PA, in a dose of 0.9 mg per kilogram of body weight (maximum, 90 mg), 10 percent of which was given as a bolus followed by delivery of the remaining 90 percent as a constant infusion over a period of 60 minutes.

tPA ContraIndication Summary

Pre-Treatment Guidelines BLOOD PRESSURE MANAGEMENT - Labetalol can be used:

tPA Dose EXACT BODY WEIGHT NEEDED:

During and After tPA GUIDELINES:

Follow-up after tPA GUIDELINES:

The Erie County Medical Center NIHSS Quick Assesment Tool:

A visual aid to determine NIHSS (NIH Stroke Scale)

Predicting Hemorrhagic transformation: Preliminary Results in 8 Patients Prediction of subsequent hemorrhage in acute ischemic stroke using permeability CT imaging and a distributed parameter tracer kinetic model by Bisdas et.al. J Neuroradiol. 2007 Mar 22; [Epub ahead of print] This study showed: "The applied statistics for comparing the ischemic voxels with the contralateral healthy tissue showed significantly higher permeability-surface product (PS)... in the ischemic voxels" admission perfusion surveys of eight patients with HT of the initial infarct without thrombolysis

Brain Blood Vessel Anatomy: Corrosion Cast Lateral View

Stroke Web Site Link : Click Here-> Teaching Web Site on Stroke by Wikipedia

Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. For patients with symptomatic carotid stenosis of 60% or more, the rates of death and stroke at 1 and 6 months were lower with endarterectomy than with stenting

Transgenic Histochemical Technique to localize BRAIN ENDOTHELIAL CAPILLARY CLAUDIN 5 RELATED TIGHT JUNCTURES : The Blood-Brain Barrier reporter gene: GFAP(adapted by Dr. Meyer from: GENSAT Data Base)

Electron Micrograph of BRAIN ENDOTHELIAL CAPILLARY CELL JUNCTURE : The Blood-Brain Barrier micrograph by D.W. Vaughan, from : Chan-Palay Text

Electron Micrograph CEREBRAL CORTEX ENDOTHELIAL CAPILLARY CELL from : Chan-Palay Text

CT Angiography Using the 64 Slice CT Scanner
3D CTA

MR Diffusion and MR Angiography MRA Neck Vessels

Trans-Cranial Doppler TCD Waveform

For a link to a whole brain atlas, please see: Brain Atlas

AHA Get With The Guidelines for Stroke : American Heart Association
Management of the Acute Ischemic Stroke: For a recent review on this topic, please see : American Family Physician

Acute ICH and Recombinant Activated Factor 7
For the multi-center NEJM article on treating ICH with Recombinant Activated Factor 7, please see : NEJM Article by Mayer et.al.

New ABCD Scoring for risk of stroke after TIA Lancet 2005 article

INTERNET STROKE CENTER LINK
The Internet Stroke Center - a valuable resource

Aneurysm Case Review : Click Here-> Teaching Case: A 45-year-old patient presented with sudden onset severe headache

Stroke Literature Update: full text links

CT and ACUTE STROKE : For acute stroke patients, a large study found that 65.2% received imaging within 1 hour of ED arrival : Click Here-> Time to CT from ER arrival

REHAB & STROKE 30.7% of a large group of stroke patients studied had received outpatient stroke rehabilitation after leaving the hospital : Click Here-> REHAB

2005 STROKE EPIDEMIOLOGY : Click Here-> stroke map

2005 CHILDREN WITH STROKE : As noted by Jordan and Hillis : stroke is among the top ten causes of death in childhood and that nearly half of pediatric strokes are hemorrhagic : Click Here-> stroke map

MRI : As noted by Dr Julio A Chalela and co-authors, Relative to the final clinical diagnosis, MRI had a sensitivity of 83% (181 of 217; 78-88%) and CT of 26% (56 of 217; 20-32%) for the diagnosis of any acute stroke: Click Here-> MRI

REVIEW OF CYTOKINES As reviewed by Dr. Wang and colleagues, Intracellular inflammatory signaling pathways such as nuclear factor kappa beta and mitogen-activated protein kinases, and mediators produced by inflammatory cells such as cytokines, chemokines, reactive oxygen species and arachidonic acid metabolites play important roles in Stroke pathophysiology : Click Here-> CYTOKINES

DEPRESSION : As noted by Caeiro,et.al. : ...Depression was present in almost one-half of the acute stroke patients and was related to previous mood disorder but not not to stroke type or location. Apathy/loss of interest was the predominant clinical feature.. : Click Here-> DEPRESSION

DNA REPAIR GENES : Dutra and colleagues studied two common polymorphisms in the DNA repair gene, XRCC1, C26304T and G28152A, in 134 well characterized patients with non lacunar ischemic strokes, and found that a major gene effect of the T allele of the C26304T polymorphism modulating the cerebral response to ischemia in non lacunar ischemic stroke : Click Here-> DNA REPAIR GENES

INFLAMMATORY MARKERS: As noted by Sacco and colleagues, levels of hsCRP are higher in stroke patients than in stroke-free subjects. Levels of inflammatory biomarkers associated with atherosclerosis, including hsCRP, appear to be stable for at least 28 days after first ischemic stroke.: Click Here-> CRP

NEUROGENESIS: As there has been evidence for injury-induced human neurogenesis has been presented previously in Huntingtons disease and Alzheimers disease, the authors Jin et.al. report similar immunofluorsecent marker evidence for stroke-induced neurogenesis in human brain from brain biopsy specimens of stroke patients : Click Here-> NEUROGENESIS

PROSTAGLANDINS : Matsuo et.al. demonstrate the induction of microsomal PGE synthase 1 (mPGES-1), an inducible terminal enzyme for PGE2 synthesis, in neurons, microglia, and endothelial cells in the cerebral cortex after transient focal ischemia , and believe that mPGES-1 may be a critical determinant of postischemic neurological dysfunctions and a valuable therapeutic target for treatment of human stroke : Click Here-> PROSTAGLANDINS

CHOLESTEROL AND ICH: Ebrahim et.al. noted that increased risk of haemorrhagic stroke is confined to people with low concentrations of blood cholesterol and markers of high alcohol consumption and that Lowering cholesterol is unlikely to increase the risk of haemorrhagic stroke, even in a population with a high incidence of haemorrhagic stroke : Click Here-> ICH & CHOLESTEROL

Current Protocol for ACUTE STROKE EVALUATION Immediate Evaluation to include CT Angiography

Current Literature on CAROTID STENTING (full text links below)

AHA Science Advisory - Carotid Stenting and Angioplasty

AHA Science Advisory - Carotid Stenting and Angioplasty in Journal Stroke '98

Letter to Editor on CAS

Short Term Outcome: ambulatory patients

distal balloon protection

cost benefit analysis

embolic protection in 442 cases

Anti-platelet Tx with CAS

TCD with CAS

Distal protection devices : 100 cases

CRP and CAS risk

No new brain lesions

Who benefits from CAS?

Tirofiban IA

For more information, please contact : Dr. Mike Meyer, Professor of Clinical Neurology and Nuclear Medicine, Erie County Medical Center Chief of Neurology and Stroke Services, Attending Neurologist for SUNY Dept Neurology and Jacobs Neurological Institute, SUNY Buffalo (Contact information: ECMC Dept. Neurology, 462 Grider Street, Buffalo, NY tel 716-898-3638)