Neuroscience II 1.02 Acute Ischemic Stroke PDF

NEUROSCIENCE II 1.02: Acute Ischemic Stroke OVERVIEW I. Introduction V. Neuroimaging A. History of Stroke A. Role of Neuroimaging B. Current State of Stroke Care in B. Brain Atta...

NEUROSCIENCE II 1.02: Acute Ischemic Stroke OVERVIEW I. Introduction V. Neuroimaging A. History of Stroke A. Role of Neuroimaging B. Current State of Stroke Care in B. Brain Attack Team and the Philippines Neuroimaging C. Main Principles of Acute Stroke C. Early signs of Ischemia on a CT Care Scan D. Stroke Subtypes D. Diagnostics E. Guidelines for Managing E. Neuroimaging Clues to Stroke Patients with AIS Etiology II. Acute Ischemic Stroke F. Neuroimaging Algorithm A. Definition G. Other Diagnostics B. Four Phases of AIS Treatment VI. Emergency Treatment III. Pre-hospital Phase (Prehospital A. Evolution of AIS Care Stroke Management) B. Goals of AIS A. Stroke Recognition C. Intravenous Thrombolysis B. Emergency Medical Service D. Mechanical Thrombectomy Systems VII. General Supportive Care C. Mimics vs Misses A. Collateral Flow D. Telemedicine B. General Supportive Measures E. Brain Attack Code VIII. Treatment of Acute Complications IV. Hyperacute Phase A. Addressing Complications A. Four Steps for Therapeutic B. Brain Swelling in AIS Figure 1. Acute Stroke Care Decision Making in Hyperacute IX. Secondary Prevention Stroke A. Secondary Stroke Prevention D. STROKE SUBTYPES B. Brain Attack Algorithm Ischemic stroke (85%) C. Brain Attack Team ○ Atherothrombotic cerebrovascular disease (20%) D. Emergency Room Evaluation ○ Lacunar (25%) History Taking Stroke Scales ○ Cryptogenic (30%) ○ Cardioembolic (20%) I. INTRODUCTION Hemorrhagic stroke (15%) A. HISTORY OF STROKE ○ Intracerebral hemorrhage (70%) Hippocrates ○ Subarachnoid hemorrhage (30%) ○ First recognized stroke over 2400 years ago In the Philippines, stroke cases mostly consist of 50% ischemic and 50% ○ Stroke was called apoplexy meaning ‘struck down by violence’ in Greek hemorrhagic. Johann Jakob Wepfer (Mid-1600s) ○ Found that patients who died with apoplexy had bleeding in E. GUIDELINES FOR MANAGING PATIENTS WITH AIS the brain This guideline is a comprehensive guideline to AIS management from ○ Also discovered that a blockage in one of the brain’s blood symptom onset in the prehospital setting through 2 weeks post-stroke. vessels could cause apoplexy William Cole (1635-1716) Applying Classification of Recommendations and Level of Evidence ○ First to use the term ‘stroke’ to denote apoplexy in English medical Guidelines are not a commandment of a legal decree. writing ○ Only a resource and a roadmap Rudolf Ludwig Karl Virchow (1821-1902) Class of recommendations (COR) ○ Introduced the following terms: ○ Estimates the magnitude and certainty of benefit in proportion to risk Apoplexia sanguinea - hemorrhagic apoplexy of the brain; cerebral E.g. Class I (Strong): Benefit >>> Risk hemorrhage Applicable to most patients under most circumstances Apoplexia ischaemica - ischemic apoplexy; cerebral softening; Level of Evidence (LOE) cerebral infarct, caused by embolism ○ Rates the type, quantity, and consistency of data from clinical trials and Created the terms ‘thrombosis’ and ‘embolism’ other sources No approved therapy for acute ischemic stroke until early 1996 ○ Before 1996, journal articles investigated whether there is still a need to II. ACUTE ISCHEMIC STROKE admit stroke patients or whether stroke patients still need to be seen by A. DEFINITION a neurologist when there is no treatment yet Acute Ischemic Stroke ○ Stroke is a subspecialty in neurology. ○ Time critical ○ Certain treatment modalities are time-bound B. CURRENT STATE OF STROKE IN THE PHILIPPINES ○ Early management is key to optimizing outcomes Stroke remains the leading cause of disability and death in the Philippines ○ New evidence has produced major changes in treatment The DOH institutionalized a national policy framework for preventing and managing stroke. However, government financing coverage remains limited. B. FOUR PHASES OF AIS TREATMENT Stroke medicine access program (MAP) was launched in 2016 Table 1. Four Phases of Treatment of Acute Stroke Patients ○ 1000 vials of rtPA (alteplase) subsidized to selected government Primary Objective and Therapeutic hospitals in the country. Phases of Treatment Focus ○ DOH discontinued the program due to lack of neuroimaging machines and organized system of care to support the provision of the medicine From Reduce risk of death and disability Stroke diagnostics and treatment facilities are more concentrated in urban Pre-hospital symptom through diagnosis, hospital choice, settings, mostly in private hospitals, where out-of-pocket expenditures Phase onset to and impact of time-to-treatment. prevail hospital door No unified stroke registry Reduce risk of death and disability by ○ The Philippine Neurological Association established a stroke registry in Door to first absolute focus on recanalization of Hyperacute Phase 2020, but it is still not implemented nationwide. It only involves 11 hour artery or reduction of swelling due to major centers in the Philippines bleeding 1-24 hours Reduce risk of death by neurological C. MAIN PRINCIPLES OF ACUTE STROKE CARE Acute Phase after screening and close monitoring of 1. Achieve timely recanalization of the occluded artery and reperfusion of the admission cardiac and respiratory systems ischemic tissue Reduce risk of death by close 24-72 hours 2. Optimize collateral flow monitoring of cardiac and respiratory Post-acute Phase after 3. Avoid secondary brain injury systems and prevention of recurrent admission stroke Page 1 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke III. PRE-HOSPITAL PHASE (PREHOSPITAL STROKE MANAGEMENT) A. STROKE RECOGNITION Recognize stroke immediately for prompt admission and treatment because some treatments are time-bound The BE FAST acronym serves as an adequate guide in determining if there is a stroke The difference of stroke from other diseases is the suddenness of symptoms. It is characterized by a sudden onset of focal neurological deficits. Table 2. BE FAST Acronym for Stroke Recognition STROKE RECOGNITION B Balance Loss of balance; headache or dizziness E Eyes Blurred vision/ double vision/ vision changes F Face One side of the face is drooping A Arms Arm or leg weakness Figure 3. Spoke and Hub model via Telemedicine for stroke management S Speech Speech difficulty/ slurred speech In other countries, mobile stroke units are used. These are like ambulances T Time Time to call for an ambulance immediately with a CT scan inside which are used to identify infarcts or bleeds, thereby being able to decide to give alteplase or not right then and there. B. EMERGENCY MEDICAL SERVICE SYSTEMS Choose the right hospital: For patients who have BEFAST symptoms, we take them to Acute Stroke Ready Hospitals (ASRH). These hospitals have an In the emergency room, instead of BE FAST, they use the ROSIER scale organized stroke team and can provide the imaging, laboratory, and (Recognition of Stroke in the Emergency Room). medication needed. ○ ASRH are both private and public (e.g. SLMC can treat stroke patients *TG Note: Doc said ROSIER is only nice to know. from doortime within 1 hour, while EAMC despite the numerous patients can be treated within 1-2 hours. *TG Note: From Doc: Assignment, get to know the Acute Stroke Ready Hospitals (ASRH) near your area, your parents’, your family and friends’ Do not delay. There is a (false) notion that if a patient has a stroke, he should rest first to lower his blood pressure, receive a massage, or take medications such as aspirin. This is wrong, because there is NO first aid for stroke. We just need to bring the patient to ASRHs. ○ The more time we waste, the more we disqualify them from treatment modalities ○ As med students, we can check for oxygen saturation, blood pressure, IV access, glucose test, and pre-admit patients to leave as little as possible to be done after hospital arrival. However, this should not delay going to the hospital. E. BRAIN ATTACK CODE Usually, in the hospitals, the triage nurse looks at the patient first and recognizes if it is a probable stroke. They then call the attention of the emergency medicine doctor. The emergency medicine doctor then calls the Brain Attack Code. IV. HYPERACUTE PHASE Goal of hyperacute phase: reduce the risk of death and disability by focusing on the recanalization of artery and reduction of swelling Table 3. Hyperacute stroke decision making 4 Steps for Therapeutic Decision Making in Hyperacute Stroke Figure 2. ROSIER scale Diagnosis of ischemic stroke is done C. MIMICS VS MISSES 1 Diagnosis CLINICALLY and NOT on CT imaging We have to be careful because a lot can mimic stroke such as alcohol Imaging is used to exclude bleeding intoxication, cerebral infection, metabolic disorders, neuropathy (Bell’s palsy), because the treatment modalities for brain tumors, migraine, seizures and post-seizures states, Todd’s paralysis, 2 Exclude bleeding ischemic stroke is contraindicated if hypoglycemia, epidural hematoma, drug overdose / toxicity, hypertensive there is bleeding encephalopathy 3 Assess severity ○ What sets the difference between stroke and these diseases would be good history taking. Stroke is a primarily clinical diagnosis. 4 Identify contraindication What we are more afraid of are “misses” wherein the patient is already having a stroke but we missed it. This is because it limits the treatment we Time is Brain can offer. Although alteplase can be administered up to 4.5 hours after symptom onset, with each passing second, more brain cells die, leading to worsened D. TELEMEDICINE outcomes Up until recently, we have been using telemedicine for stroke especially in Every second counts! places without neurologists or anyone knowledgeable how to use rTPAs As seen in Figure 3, we employ a spoke and hub model wherein there is a Table 4. Brain loss in stroke central area with a neurologist and computer (hub) and then small medical 1.2 billion neurons lost Stroke centers and health clinics, etc. with internet connection (spokes) which can 830 billion synapses lost Hour do history taking and PE using the telemedicine platform. per ○ If they are okay, patients are brought to the hub for procedures (e.g. 1.9 million neurons lost Minute thrombolysis, surgery, etc.) 8.7 hours of accelerated aging Second Page 2 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke Table 7. Brain Attack Team Neurology/ Neurosurgery/ Stroke ECS/ Ward Residents Consultant Radiology Consultant Stroke Fellow ED Nurse Neurology & Neurosurgery Lab Technologist Residents Endovascular Consultant Stroke Nurse Clinical Pathologist Phlebotomist House Manager ECS Officer Clinical Pharmacist There is evidence that the presence of a brain attack team have improved patient outcomes Table 8. AHA recommendations for hospital stroke teams Recommendations COR LOE Figure 4. Door-to-needle time Table 5. Door-to-needle time An organized protocol for the emergency Goal: Door-to-needle time of ≤60 minutes 1 I B-NR evaluation of stroke patients is recommended Suspected stroke patient arrives at emergency 1 0 minutes department Designation of an acute stroke team that includes Once the patient has arrived, they must be evaluated physicians, nurses, and 2 ≤10 minutes by a physician within 10 minutes (first encounter). This 2 laboratory/radiology personnel are recommended. I B-NR physician will call the brain attack code. Patients with stroke should have a careful clinical The brain attack team must arrive within 15 minutes assessment, including neurological examination 3 ≤15 minutes after the door time Multicomponent quality improvement initiatives, In 25 minutes, the patient has to be imaged (Head CT which include ED education and multidisciplinary 4 ≤25 minutes or MRI scan) 3 teams with access to neurological expertise, are I A The result of the imaging scan must be available recommended to safely increase IV fibrinolytic 5 ≤45 minutes treatment within 45 minutes Decision of administering IV alteplase must be made It is recommended that stroke systems of care be 6 ≤60 minutes developed so that the fibrinolytic-eligible patients in under an hour The team is very particular with the time limits because a timer is started 4 and mechanical thrombectomy-eligible patients I A once the brain attack team is called. They audit the recorded time in order to receive treatment in the fastest onset-to-treatment pinpoint where the delay/problem is and improve the response to stroke time ○ Making a more efficient stroke response system is a team effort which Establishing and monitoring target time goals for includes the elevator staff, imaging staff, etc. Emergency Department door-to-treatment IV 5 I B-NR fibrinolysis can be beneficial in order to monitor A. BRAIN ATTACK ALGORITHM and enhance system performance When to Activate Brain Attack Algorithm Suspect acute stroke when an individual suddenly presents with the Table 9. Timeline of AIS Management following signs and symptoms within 6 hours of onset: Timeline Action ○ Weakness on one side of the body 10 minutes from ○ Numbness of one side of the body Evaluation by physician arrival or sooner ○ Slurring of speech ≤15 minutes Stroke or neurologic expertise contacted ○ Difficulty in understanding speech or loss of speech ○ Doubling of vision or loss of vision, particularly in one eye ≤20 minutes NCCT or MRI ○ Dizziness associated with loss of balance ≤45 minutes Interpretation of neuroimaging ○ Severe and unusual headache (worst headache of your life) ≤60 minutes Initiation of IV alteplase Airway, Breathing, and Oxygenation Immediate Stabilization Table 6. AHA/ASA 2019 Recommendation on airway, breathing, and oxygenation In immediate stabilization, the following steps are done simultaneously Recommendations COR LOE Assess CBA’s (hook the patient to a cardiac monitor and pulse oximeter), vital signs Airway support and ventilatory assistance are Provide supplemental oxygen to maintain O2 sat >94% recommended for the treatment of patients with Obtain IV access and blood samples 1 acute stroke who have decreased consciousness I C-EO Check CBG and correct hypo- or hyperglycemia or who have bulbar dysfunction that causes Obtain 12-lead ECG compromise of the airway Perform neurological screening assessment Supplemental oxygenation should be provided to Activate Brain Attack Team 2 I C-LD maintain oxygen saturation >94% C. EMERGENCY ROOM EVALUATION Supplemental oxygen is not recommended in non III. No Immediate Actions by the BAT 3 B-R Immediate neurologic assessment (done within 15 minutes) hypoxic patients with AIS Benefit ○ Review patient history Oxygen is not given in non hypoxic patients with AIS ○ Establish the symptom onset (ictus) ○ It is only given to maintain an oxygen saturation of >94% ○ Perform NIHSS and other neurologic assessments ○ Order emergent Cranial CT-scan or MRI B. BRAIN ATTACK TEAM CODE (BAT CODE) Initiate brain imaging (done within 25 minutes) Once the BAT code is sounded, the team follows a strict timetable based on ○ CT/MRI with or without angiography the National Institute of Neurological Disorder and Stroke (NINDS) Timeline for Thrombolysis History Taking Immediate response ensures rapid diagnosis, exclusion of mimickers, and Essential in the diagnosis of stroke initiation of time-bound therapies like thrombolysis, as well as neurosurgical ○ Stroke diagnosis is done clinically and not through imaging or endovascular interventions Should focus on the following (but not limited to): A BAT code must be activated instead of just telling random staff that there ○ Ictus - time the patient was last known well or seen normal is a stroke patient because the whole team of different departments must be Surrogate marker to determine if eligible for rtPA or thrombectomy informed immediately and thereby be more organized to facilitate early ○ Nature and severity of symptoms recognition and prompt medical response for suspected stroke patients ○ Progression of symptoms ○ History of previous strokes or other CV diseases Page 3 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke ○ History of vascular risk factors (HTN, DM, heart disease) Table 12. 4 P’s to assess in neuroimaging ○ Medication history, particularly blood thinners 4 P’s Description ○ History of recent surgery or bleeding Parenchyma Brain ○ Any other comorbidities Pipes Vessels History taking is important because it must be investigated if the patient has Perfusion Assess if the perfusion received is good. contraindications for alteplase The underlying principle in stroke care i.e., in ischemic The details above must be established immediately stroke, is to assess the presence of a penumbra to be The rest of the history (smoking, alcohol drinking, drug use, family history, saved. patient history) can be completed while the patient is transported to the Ex. If a patient had a stroke 2 weeks ago, and there’s no imaging rooms, while waiting for the imaging results or after the patient is Penumbra penumbra with only an ischemic core, then there’s no stabilized sense in saving. ○ In this case, rehab should be done instead. Stroke Scales ○ Can’t do anything about the stroke Standardized severity scales to quantify neurologic deficit ○ Facilitate communication ○ Identify patients for acute treatments Table 13. Recommendations for neuroimaging ○ Monitor for improvement or worsening conditions Recommendations COR LOE All patients with suspected acute stroke should NATIONAL INSTITUTE OF HEALTH STROKE SCALE (NIHSS) receive emergency brain imaging evaluation Preferred severity scale as it is rapid, accurate, reliable, and can be (whether CT scan or MRI) on first arrival to a performed by a broad spectrum of providers hospital before initiating any specific therapy to 11 item analysis, with a score from 0 (no symptoms) to 42 (worst score) 1 I A treat AIS. The scores are based only on the patient’s responses and not on the : The role of CT scan is to exclude bleeds. observer’s interpretations Bleeds can be seen right away in CT scans but Can be done in 10 minutes or less by trained staff not infarcts. Table 10. 11 Item NIHSS Systems should be established so that brain Level of Consciousness Leg Motor Drift imaging studies can be performed as quickly as 2 I B-NR possible in patients who may be candidates for IV Horizontal extraocular movements Sensation fibrinolysis, mechanical thrombectomy, or both. Visual fields Language/Aphasia Noncontrast computed tomography (NCCT) is Facial Palsy Dysarthria 3 effective to exclude ICH before IV alteplase I A Arm Motor Drift Extinction/Inattention administration. Magnetic resonance imaging (MRI) is effective to Leg Motor Drift 4 I B-NR exclude ICH before IV alteplase administration. Classifies stroke as mild, moderate, and severe CTA with CTP or MR angiography (MRA) with ○ Can also predict the size of the stroke diffusion-weighted MRI (DW-MRI) with or More sensitive for anterior circulation stroke 5 I A without MR perfusion is recommended for certain ○ Posterior circulation strokes have lower scores even if they are large in patients. size COR - Class of Recommendation; LOE - Level of Evidence, CTA - Computed tomography Highlights the importance of history taking more than the use of a angiography, CTP - CT perfusion scale Table 11. Recommendations for using Stroke Scales B. BRAIN ATTACK TEAM AND NEUROIMAGING Recommendations COR LOE BAT (brain attack) patients are given priority in the CT-MRI department – The use of a stroke severity rating scale, preferably I I B-NR d/t the importance of time. the NIHSS, is recommended ○ Kahit may nakapila or schedule na, uunahin pa rin ang BAT patient since it’s an emergency. CHECKPOINT ○ The radiology department should know/ agree with that since may made-delay na patient. 1. What does BEFAST stand for? Either a non-contract CT or multimodal MR-DWI with or w/o MRA is 2. What is the preferred severity scale as it is reliable, rapid, accurate, and can be performed by a broad spectrum of providers? recommended. 3. What are the four steps in therapeutic decision making in hyperacute stroke? Scheduled procedures are deferred for the BAT patients. Ongoing imaging procedures, especially those employing contrats and/or Answers: 1. Balance, Eyes, Face, Arms, Speech, Time; 2. NIHSS; 3. Diagnosis, Exclude bleeding, Assess severity, Identify contraindications sedation, are completed before accommodating BAT patients C. EARLY SIGNS OF ISCHEMIA ON CT SCAN V. NEUROIMAGING The goal is to differentiate an infarct from a bleed: A. ROLE OF NEUROIMAGING Stroke is a clinical diagnosis but the type of stroke will depend on the neuroimaging. Do not treat stroke (e.g., give aspirin) without neuroimaging; order a cranial CT scan at least. Role of neuroimaging: ○ Diagnosis Infarct vs. bleed Vessel involved Etiology TIming ○ Prognosis (or prognostic aid) Figure 5. (L-R): A - hypodensity d/t infarct, B - hyperdensity d/t a bleed Ex. If a patient has a large bleed, the percentage for surviving is less. In the early first few hours of stroke, the infarct can’t be seen right away. ○ Treatment selection ○ There is a bleed but no infarct, and the CT scan would appear normal. “What needs to be assessed?” → remember the 4 P’s: *TG Note: The ff. section was given as an assignment. Most of the information was lifted from Radiology Assistant. Page 4 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke Table 14. Early signs of ischemia on CT scan EARLY SIGNS OF ISCHEMIA ON CT SCAN Hypoattenuating Obscuration of the Loss of sulci or Insular ribbon sign Dense MCA sign brain tissue lentiform nucleus Sulcal effacement Figure 6. Hypoattenuation Figure 7. (↗) Obscuration of LN, (*) Figure 8. (↖) Insular ribbon sign Figure 9.(↖) Dense MCA sign Figure 10. Sulcal effacement Insular ribbon sign Highly specific for “Blurred basal ganglia” Hypodensity & swelling of Result of a thrombus or Loss of precise delineation of irreversible ischemic brain One of the earliest & most the insular cortex embolus in the MCA the sulci accompanied by loss damage if detected w/n the frequently seen signs in MCA Indicative & subtle early sign of gray-white differentiation first 6 hours infarction of infarction in the territory of secondary to localized mass Ischemia on CT can be seen ○ Lentiform nucleus: the MCA effect [Kumar & Nagesh, 2018] Putamen + globus Very sensitive to ischemia as d/t cytotoxic edema that pallidus [Blumenfeld, 2010] it is the furthest removed develops from ion-pump The basal ganglia are almost from collateral flow failure always involved in MCA Needs to be differentiated (↑) Hypoattenuating brain from herpes encephalitis infarction. tissue in the right Refer to Figure 7: hemisphere suggesting a ○ Comparing the L & R probable MCA infarction insula, the L (↑) is more edematous & less clearly [delineated]. Dense MCA sign Hyperdense sign *B: Middle cerebral artery is thrombosed. *Image has no contrast but the MCA can be seen because of a blockage in that area. MCA becomes dense, which can indicate a stroke. *TG note. Some parts in this section were inaudible. To preserve accuracy, kindly visit the recording, around 29:53-30:22 to review. Figure 11. Dense MCA Sign (B, leftmost D. DIAGNOSTICS Table 15. Diagnostics. See Appendix for bigger images COMPUTER TOMOGRAPHY (CT) SCAN CT Angiography (CTA) CT Perfusion (CTP) ASPECTS Score Figure 12. (L-R): CTA uses contrast. Note that in the reconstruction at the R, the MCA is no longer there. (A) Figure 13. CT perfusion (B) Figure 14. ASPECTS score (C) When to request for CTA/ MRA: The only imaging study that can tell if there is still a Alberta Stroke Programme Early CT Score Useful in: penumbra to be saved Gives a clue on how big the stroke is ○ Evaluation of the etiology of the stroke → ○ Remember, [in stroke care], it is the penumbra Looks at 10 structures in the brain: direct correct management that matters. ○ M1-M6 ○ Looking for macrovascular causes of ICH CT perfusion looks at the ff. factors: ○ Caudate (C) or SAH e.g., aneurysm, AVM, AVF, and etc. ○ Cerebral blood flow (CBF) ○ Insular ribbon (I) in bleeds ○ Cerebral blood volume (CBV) ○ Internal capsule (IC) ○ Detection of large vessel occlusion (LVO), ○ Mean transit time (MTT) ○ Lentiform nucleus (L) intracranial stenosis, and etc. in infarcts Disadvantages: Deduct 1 point if there is swelling, loss of gray-white Important since LVO will warrant a ○ Expensive & time consuming matter differentiation, etc. different treatment ○ Not all radiologists can read CTP right away Perfect score: 10 (normal CT scan) ○ Requires a software which is not always available Lowest score: 0 (“infarct na lahat”) in all CT scans, thus it is not always done ○ Can prognosticate & disqualify patients from certain In giving medicine, time is used as a surrogate. treatment modalities ○ It has been shown that at 4.5 hours, there is still a ○ If everything’s an [ischemic] core already, then penumbra that can be saved. there’s nothing to save (i.e., no penumbra). ○ But the “final say” would really depend on whether ○ Conversely, if puro penumbra pa then there is a a penumbra can still be detected. basis to save. ○ Ex. It’s been 5 hours (so, > 4.5) since the stroke, Score interpretation: but CTP showed a difference, and there’s still a ○ 8-10 small core penumbra; alteplase can still be given. ○ 6-7 moderate core ○ 0-5 large core Page 5 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke MAGNETIC RESONANCE IMAGING (MRI) More sensitive & more specific than CT within the first few hours after onset of stroke ○ In CT scan, the only goal is to detect/ exclude a bleed since infarcts cannot be detected. ○ In MRIs, an infarct may be detected as early as 30 minutes from stroke consult. Role of MRI → Rule out mimickers Good for looking at the posterior circulation ○ In CT scan, there are many bony prominences around the brainstem, so it’s more difficult to appreciate the posterior circulation. Figure 15: ○ CT scan looks normal as if there’s no stroke, since it’s still early, but the MRI reveals a large stroke. ○ Thus, to see infarcts, do an MRI since lesions can be detected as early as 30 minutes. In MRIs, it is also possible to age or look at how old a stroke is since it employs different sequences (see below). Figure 15. Top (A, B, C): CT scan (early stroke). Bottom (D, E, F): MRI DWI & ADC T2 & FLAIR GRE & SWI Refer to Figures 16-19: Refer to Figure 20: Also refer to Figure 20: The first 2 sequences looked at Useless – shows a stroke 4, 4.5, or 5 hrs. from GRE & SWI show if there’s a bleed. Both sequences look at restricted symptom onset Used to exclude [bleeds] diffusion. ○ Cannot exactly tell when but it’s between these ○ If the patient is bleeding, do not give Acute stroke appears times r-tPA. ○ White in DWI Minsan ‘yan ‘yung ginagawang measurement kasi ‘di ○ Dark in ADC nila masabi or no one knows the history, but if there ○ *DWI & ADC should match. are no changes in the T2 & FLAIR – it’s still acute If it reverses (i.e., dark in DWI & white and alteplase can be given. in ADC), the infarct is already chronic Sometimes, the hx is wrong or the px says that it’s (“lumang stroke”) as seen in Figure 19.. only been an hour since the symptoms started, but ○ No need to give alteplase or MRI (T2 and FLAIR) would reveal changes in the perform thrombectomy same areas as DWI & ADC, which suggest an old ○ Ex. patient had a stroke 5-10 years stroke (“matagal na”) or poor collaterals. ago ○ In this case, refrain from giving alteplase since there’s no more penumbra. Figures 16-18. Examples of DWI & ADC showing Acute Stroke: Sequences Figure 16. Figure 17. Figure 18. Figure 19. Chronic infarct (Dark in DWI, White in ADC) Figure 20. ADC, FLAIR, T2, GRE, SWI Page 6 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke Figure 21. Lesion on DWI is not seen on FLAIR Figure 22. Lesion on DWI is also seen on FLAIR Lesions may be seen in DWI but not in FLAIR Comparison of DWI & FLAIR may be useful in determining which patients may still benefit from tPA when the ictus is unknown ○ Underlying principle: presence of penumbra. Patient selection is on the basis of evidence for threatened but salvageable tissue (Figure 23) In Figure 21, the lesion is seen in DWI but not in FLAIR → presence of penumbra → tPA may be given In Figure 22 the lesion is seen both in DWI and FLAIR → no penumbra → tPA will not be given DWI & FLAIR The same principle is used in cases of “Wake up strokes” when the patient wakes up mismatch with symptoms and the ictus is unknown. ○ For example: A patient slept at 10 PM and woke up at 6 AM with stroke Figure 23. Principle behind DWI-FLAIR mismatch symptoms. From this information, you may think that they are already disqualified from tPA and thrombectomy since 8 hours have passed and the ictus is unknown. ○ However, if the MRI reveals a DWI and FLAIR mismatch, it could be assumed that the stroke has not been around for longer than 4-5 hours*. Instead of doing a CT-perfusion, this may be used as a surrogate in determining if a patient can still qualify for tPA. Table 16. Recommendations for tPA administration based on DWI-FLAIR mismatch Recommendations COR LOE In patients with AIS who awake with stroke symptoms or have unclear time of onset > 4.5 hours from last I known well or baseline stat, MRI to identify diffusion-positive FLAIR-negative lesions can be useful for selecting II-a B-R those who can benefit from IV alteplase administration within 4.5 hours of stroke symptoms recognition *TG Note: In the 2026 trans, it was written as 4-6 hours ; however, Doc Juangco says 4-5 hours in the lecture. The latter is used for this example. The table for recommendation for tPA administration based on DWI-FLAIR mismatch was not discussed and was thus added only for completion. For more radiologic images of DWI-FLAIR mismatch, please refer to Appendix 6 MR angiography is much like CT angiography except an MRA image may be produced without the use of contrast and may thus be used in patients with high creatinine MR Angiography Figure 24. MRA showing impaired flow (L) & cut-offs (R) KEY POINTS: CT scan vs. MRI + r-tPA administration CT Scan vs MRI r-tPA administration CT scan = only goal is to detect/ exclude bleeds Underlying principle is the presence of penumbra ○ Modalities: DWI & FLAIR mismatch CT Angiography → to evaluate etiology ○ The lesion is seen in DWI but not in FLAIR → presence of penumbra → tPA may ↪ Bleeds - macrovascular causes (e.g., aneurysm, AVM, etc.) be given ↪ Infarct - LVO No DWI & FLAIR mismatch CT Perfusion → CBF, CBV, MTT ○ The lesion is seen both in DWI and FLAIR → no penumbra → tPA will not be MRI = used to detect infarcts (esp. w/n the first few hours) given ○ More sensitive & specific than CT scan within the first few hours of stroke (as early as 30 mins.) ○ Used to r/o mimickers & is better for the posterior circulation ○ The location of the stroke as seen in the MRI can give an idea which vessel is involved (eg: whether it’s a large or small vessel). Please refer to Appendix 7 for examples. ○ Sequences: DWI & ADC, T2 & FLAIR, GRE & SWI For acute stroke: DWI & ADC = Clue is 2nd letter ↪ W = white, D = Dark If it reverses → chronic already ADC - Apparent diffusion coefficient , T2 - Transverse relaxation time, FLAIR - Fluid attenuated inversion recovery, GRE - Gradient echo sequences, SWI - Susceptibility weighted imaging Page 7 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke Table 17. Neuroimaging clues to Stroke Etiology E. NEUROIMAGING CLUES TO STROKE ETIOLOGY Type of Infarct Definition Pictures Involves large vessels Large Territorial Infarct Usually caused by an embolic source Figure 25. Large territorial infarcts Multiple Small Embolic May be due to emboli formed in the heart and then Infarcts “showers” into the brain Figure 26. Cardioembolic infarct Involves small arteries (eg: penetrating arteries found deep in the brain parenchyma) Small vessel Disease / Usually caused by a thrombotic source Lacunar Stroke Behaves differently from other types of stroke Figure 27 Lacunar stroke in the pons Involves areas in between the distribution of major vessels (i.e in between ACA-MCA or MCA-PCA) Usually caused by a decrease in flow (eg: decrease in blood flowing through the ICA) Figure 28. Watershed strokes Watershed Infarct* Figure 29. Upper cyan: ACA-MCA watershed ; Lower Cyan: MCA-PCA watershed ; Yellow: internal watersheds Page 8 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke Due to an occlusion of a vein The appearance of venous strokes is different on imaging Venous Stroke because their distribution in the brain is different from that of arteries Figure 30. Cerebral venous sinus thrombosis Old stroke [not discussed] Figure 31. CT scan showing an old stroke *TG Note: Doc Juangco mentioned that there is a difference between Internal Watershed and External Watershed but asked us to find the difference on our own. [Adams and Victor’s Ch. 33 p. 815] When the circulation of one carotid artery has been incompletely compromised, reducing blood flow in the middle and exterior cerebral territories on that side, the zone of maximal ischemia lies between the two vascular territories (cortical watershed) or, alternatively, in the deep portions of the hemisphere between the territories of the lenticulostriate branches and the penetrating vessels from the convexity (internal or deep watershed). F. NEUROIMAGING ALGORITHM cardiopulmonary events Other diagnostic tests: ○ CBC with platelets ○ PT and PTT ○ Creatinine ○ Chest X-Ray, Urinalysis VI. Emergency Treatment A. EVOLUTION OF ACUTE ISCHEMIC STROKE (AIS) CARE 1996: Treatment for stroke began and became the earliest study on alteplase ○ NINDS trials (1995): alteplase approved for the first 3 hrs ○ WAKE-UP trials (2018): allowed use up to 4.5 hrs After 2015: Thrombectomy trials came out positive ○ Approved as a treatment for large vessel occlusions Figure 32. Neuroimaging algorithm The primary goal of imaging is to identify if there is bleeding or not, which is in turn used for risk-stratification *TG Note: The algorithm was not discussed in detail G. OTHER DIAGNOSTIC TESTS Figure 33. Evolution of acute ischemic stroke (AIS) care over two decades B. GOALS OF AIS Table 18. Goals in Acute Ischemic Stroke (AIS) Other diagnostic testing should be individualized Other diagnostic tests must NOT delay the imaging and the entire process Goals Strategies Critical NOT to delay initiation of IV alteplase Medical: Thrombolysis Recanalization ○ Only assessment of blood glucose must precede IV alteplase Endovascular: Thrombectomy Blood glucose is the most important among the other diagnostic tests Prevent Neurological Acute Stroke Unit/ ICU admission because both HYPER and HYPO glycemia can present with focal neurologic Worsening, Antithrombotics deficit Early Recurrence, & Complications Supportive Treatment ○ “For some reason, kahit na metabolic siya, focal [deficit] yung Save Ischemic Tissue Neuroprotection lumalabas” -Doc Juangco One strategy does not disqualify from the others ○ As such, if the patient is confirmed to only be hypoglycemic, there is no There are different indications for each strategy need to undergo CT scan ○ Ex. If px is indicated for thrombectomy and thrombolysis, they will be Baseline ECG and troponins are recommended, but should NOT delay given both treatment Stroke patients, unlike other patients, remain admitted in the hospital after Utility of chest radiographs is uncertain treatment for monitoring as problems like worsening or recurrence may occur ○ Cohort study comparing AIS patients with and without CXR showed after recanalization longer door-to-needle (DTN) time in those with a CXR ; no difference in Page 9 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke Recanalization and Reperfusion *TG Note: The information Doc discussed was lifted from a paper, which you can access Recanalization: degree of reopening of the occluded artery here. The figures included in his slides can be viewed in the Appendix. ○ Blood vessel is opened to remove the clot ○ First thing to do Intravenous (IV) Thrombolysis or IV rTPA Administration of Alteplase Reperfusion: the degree of flow reaching the previously Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 min, with 10% of the dose given as a bolus over 1 min. *TG Note: According to Doc, we have to review his lecture last year in Pharma regarding stroke and alteplase as they will be included in the exams. ○ The rest of the dose is given over the next 60 minutes Admit the patient to an intensive care or stroke unit for monitoring. If the patient develops severe headache, acute hypertension, nausea, or C. INTRAVENOUS THROMBOLYSIS vomiting or has a worsening neurological examination, discontinue the IV rTPA (Alteplase) infusion (if IV alteplase is being administered) and obtain emergency head CT scan. Alteplase is given to stroke patients Measure BP and perform neurological assessments every 15 min during IV Alteplase is beneficial regardless of age & stroke severity and after IV alteplase infusion for 2 h, then every 30 min for 6 h, then hourly Eligibility criteria have evolved over time until 24 h after IV alteplase treatment. ○ If a patient or representative is not available for consent, justifiable to Increase the frequency of BP measurements if SBP is >180 mm Hg or if proceed without consent in an otherwise eligible patient DBP is >105 mm Hg; administer antihypertensive medications to maintain Eligibility Checklist and Order Sheet BP at or below these levels Inclusion Criteria Delay placement of nasogastric tubes, indwelling bladder catheters, or 1. Age ≥ 19 years old intra-arterial pressure catheters if the patient can be safely managed ○ Studies based on adults, no studies yet on children, though rTPA still without them. administered in pediatric stroke[2026 Trans] Obtain a follow-up CT or MRI scan at 24 h after IV alteplase before 2. Clinical diagnosis of ischemic stroke which causes a measurable neurologic starting anticoagulants or antiplatelet agents. deficit ○ Patient should manifest with symptoms and have deficits before Clinical Practice Guidelines on the Management of AIS alteplase is administered Some people are advocating for the use of 0.6 mg/kg alteplase instead of 0.9 mg/kg because of a non-randomized Japanese study and a randomized control trial that tested 3. Time of onset is well established this value ○ Alteplase must be given within 4.5 hrs after onset ○ Advantage: Allows the usage of only 1 vial (equivalent to 50 mL) of alteplase and ○ If there is evidence that penumbra is present, alteplase can be given conserve resources despite the onset being ＞4.5 hrs already ○ If a 60 kg patient uses 0.9 mg/kg of alteplase, 54 mL will be administered in total thus 2 vials will be consumed as opposed to 0.6 mg/kg which will result to 36 mL Exclusion Criteria only ○ 1 vial ranges from PHP 30,000-40,000 while in SLCM it costs around PHP 70,000-80,000 No evidence of reaching the threshold for non-inferiority and that the 0.6 mg/kg alteplase can overcome the 0.9 mg/kg. *TG Note: Doc may be pertaining to this study in 2020 regarding the use of 0.6 mg/kg IV alteplase. The “Sweet Spot” Not all patients improve even if they receive alteplase ○ Some have a “sweet spot” who have a favorable outcome from alteplase but there are those who will not respond even if it was administered on time ○ There are also some who will bleed, which we do not want Figure 34. Exclusion criteria for IV rTPA administration *TG Note: Since there are a lot of exclusion criteria, Doc asked us to be familiar with them. He will not be asking specific values during the exam so just know the criteria generally. In previous studies, it was mentioned that alteplase has many contraindications ○ The European Stroke Organisation (ESO) uses alteplase even up until 9 hrs If there is penumbra to be seen, as this indicates that there is tissue that can still be saved ○ Alteplase can be also used for the elderly and those with prior disabilities Figure 36. Patient profiles used to determine benefit from rTPA. Based on the green boxes, giving alteplase will result to a favorable outcome on those with: ○ Time of onset: 30% of infarcted Isolated petechiae petechiae in minimal mass area with definite in infarcted tissue infarcted tissue effect occupying mass effect (IV without mass effect without mass effect 1, NIHSS < 6, ASPECTS < 6, causative occlusion of ICA or M1 → Case #2 treatment can be initiated w/in 6 hrs Patient: 63F, NIHSS 11, atrial fibrillation ○ Previously in aspirin and clopidogrel Case Reports Case #1 Patient: 56F, 2h 42m from ictus, NIHSS 5 Figure 43. Case 2 DSA Lab Tests ○ DSA: (Fig. 43) Blockage on MCA Good collaterals (small vessels) ↪ Reason why it did not progress to NIHSS 20+ Management ○ IV rtPA was NOT given Due to patient’s bleeding parameters Figure 40. Case 1 MRI Figure 44. Case 2 Thrombectomy. Left: Before. Right: After Figure 41. Case 1 MRA. LEFT: MRA of Px. RIGHT: Normal MRA reference ○ Thrombectomy Lab Tests Fig 44 (Right): Perfusion after clot removal ○ Lab values: Normal Day 1 post-procedure: NIHSS 3 ○ MRI: Very small stroke (Fig. 40) Discharged after 7 days Restricted diffusion at left internal capsule[2026 trans] ↪ Improved to NIHSS 0 ○ MRA: Left MCA not visible (Fig. 41) Management Recommendation for Thrombectomy (6-24 Hours) ○ IV rtPA was given DEFUSE 3 and DAWN Trials (2017) Inclusion criteria was met ○ Recommends thrombectomy as long as: NIHSS 17 after administration (paralyzed, dysarthric, aphasic) Perfusion studies are performed ↪ Stroke was in progression There is a penumbra to be saved ↪ rtPA did not work with LVO ○ Full AHA/ASA Recommendation for Thrombectomy at 6-24 hrs (Appendix) Page 12 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke Basilar Artery (BA) Thrombectomy A. COLLATERAL FLOW Initial studies (BASICS, BEST) showed disappointing results Establishing and improving collateral flow is done regardless of TPA administration and MT ○ Helps lessen the amount of dead tissue ○ Responsible for keeping the ischemic penumbra viable ○ Provides enough flow to prevent critical ischemia and infarction but not sufficient flow to maintain normal cellular functions ○ Often tenuous and can sustain viability only for limited time ○ Can be protected by general supportive measures B. GENERAL SUPPORTIVE MEASURES Airway, breathing and oxygenation Supplemental oxygen should be provided to maintain oxygen saturation >98% Support and ventilatory assistance are recommended for those with decreased consciousness or with bulbar dysfunction causing airway compromise. Figure 45. mRS Scores in (Top) ATTENTION and (Bottom) BAOCHE Trials Blood Pressure Fig. 45: ATTENTION and BAOCHE Trial (2022) Blood pressure should be fixed; for the few days, permissive hypertension is ○ Showed improved mRS scores in intervention population allowed Not as good compared to anterior circulation blocks ○ We do not know what ‘permissive’ is and how long Society of Vascular and Interventional Neurology (SVIN) ○ Observational studies are variable ○ Recommendation to do thrombectomy in basilar artery occlusion ○ No clear date on fluid choice, volume, or duration (Appendix) BP with alteplase, however targets: ○ BP 94% indicated by the Organized to facilitate early recognition and prompt medical response for suspected stroke patients Brain Attack different Should be educated on acute stroke recognition, diagnosis, management, referral, and treatment (i.e. fibrinolytic treatment) color – this is not Team Should follow a strict timetable on AIS management under Neuroimaging) Assess CBA’s Provide supplemental oxygen to maintain O2 sat >94% Immediate Obtain IV access and blood samples Stabilization Check CBG and correct hypo- or hyperglycemia Obtain 12-lead ECG Perform neurologic screening assessment EMERGENCY ROOM EVALUATION Immediate neurologic assessment (done within 15 minutes) ○ Review patient history Immediate ○ Establish symptom onset (ictus) Actions By The ○ Perform NIHSS and other neurologic assessments Bat ○ Order emergent Cranial CT-scan or MRI Initiate brain imaging (done within 25 minutes) ○ CT/MRI with or without angiography Essential in the diagnosis of stroke History-Taking Should focus on the following: ○ Ictus - time the patient was last known well or seen normal Page 17 of 21 | CRUZ  NEURO II 1.02 Acute Ischemic Stroke ○ Nature and severity of symptoms ○ Progression of symptoms ○ History of previous strokes or other CV diseases ○ History of vascular risk factors (HTN, DM, heart disease) ○ Medication history, particularly blood thinners ○ History of recent surgery or bleeding ○ Any other serious comorbidities National Institute of Health Stroke Scale (NIHSS) Preferred severity scale as it is rapid, accurate, reliable, and can be performed by a broad spectrum of providers Stroke Scales 11 item analysis, with a score from 0 to 42, scores are based only on the patient’s responses More sensitive for anterior circulation stroke EMERGENCY TREATMENT 1996: Treatment for stroke began and became the earliest study on alteplase Evolution After 2015: Thrombectomy was approved as a treatment for large vessel occlusions Goals Strategies Medical: Thrombolysis Recanalization Endovascular: Thrombectomy AIS CARE Goals Acute Stroke Unit/ ICU admission Prevent Neurological Antithrombotics Worsening, Early Recurrence, and Complications Supportive Treatment Save Ischemic Tissue Neuroprotection Recanalization Recanalization: the degree of reopening of the occluded artery & Reperfusion Reperfusion: the degree of flow reaching the previously Beneficial regardless of age and stroke severity Inclusion Criteria Exclusion Criteria Age ≥ 19 years old Clinical diagnosis of ischemic stroke which causes a measurable neurologic deficit Evidence of intracranial hemorrhage on pretreatment CT or MRI Time of onset is well established Evidence of multilobar infarction (> 1/3 cerebral hemisphere) on CT Clinical presentation suggestive of subarachnoid hemorrhage (SAH), even with normal Administration of Alteplase CT Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 min, with 10% of the dose Significant head trauma or prior stroke within 3 months given as a bolus over 1 min. History of previous intracranial hemorrhage (ICH) Admit the patient to an intensive care or stroke unit for monitoring. Known arteriovenous malformation If the patient develops severe headache, acute hypertension, nausea, or Arterial or lumbar puncture at a non-compressible site within 7 days vomiting or has a worsening neurological examination, discontinue the Recent intracranial or spinal surgery infusion and obtain emergency head CT scan. History of gastrointestinal malignancy or gastrointestinal bleeding within the first 21 Measure BP and perform neurological assessments days ○ Every 15 min during and after IV alteplase infusion for 2 h, Known bleeding diathesis, including but not limited to: ○ Then every 30 min for 6 h, ○ Platelet count < 100,000/mm3 ○ Then hourly until 24 h after IV alteplase treatment. ○ Patient has received heparin within 48 hours and has an elevated aPTT (greater than Increase the frequency of BP measurements if SBP is >180 mm Hg or if DBP is