Ischemic stroke


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Ischemic stroke

  1. 1. ISCHEMIC STROKEEpidemiology, Classification, Risk Factors, Etiopathogenesis and Investigations Dr. Tushar Patil, MD Senior Resident, Department of Neurology King George’s Medical University, Lucknow, India
  2. 2. WHO Definition of Stroke“Rapidly developing clinical signs of focal (or global)disturbance of cerebral function, with symptoms lasting24 hours or longer or leading to death, with no apparentcause other than of vascular origin[1].” By this definition ,TIA, which lasts <24 hours, and patients with strokesymptoms caused by subdural hemorrhage, tumors, poisoning, or trauma areexcluded.1.WHO MONICA Project Investigators. The World Health Organization MONICA Project (Monitoring trends and determinants incardiovascular disease). J Clin Epidemiol 41, 105-114. 1988
  3. 3. Epidemiology
  4. 4. Global Epidemiology of Stroke• Annually, 15 million worldwide suffer a stroke-5 million die and 5 million are permanently disabled [2]• WHO estimates a stroke occurs every 5 seconds [3]• Stroke related disability is the sixth most common cause of reduced DALYs[2]• Accounts for 10% of all deaths worldwide[2]2.Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of Ischemic and Hemorrhagic Stroke: Incidence,Prevalence, Mortality, and Risk Factors. Neurol Clin. 2008 Nov;26(4):871-95, vii.3.Donnan GA, Fisher M, Macleod M, et al. Stroke. Lancet 2008;371(9624):1612–23.
  5. 5. Global Epidemiology of Stroke• Globally, stroke is the second leading cause of death [4]• In the United States, a stroke occurs approximately every 40 seconds; that translates into 2160 strokes per day.[2]• 1 out of 16 Americans dies as a consequence of stroke [5].• Total cost of stroke has been estimated at $65.5 billion in 2008.4.Bogousslavsky J, Aarli J, Kimura J. Stroke: time for a global campaign? Cerebrovasc Dis 2003;16(2):111–3.5. Rosamond W, Flegal K, Furie K, et al. Heart disease and stroke statisticsd2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2008;117(4):e25–146.
  6. 6. Global Epidemiology of StrokeIncidence:• Varies from 240 per 100,000 in Dijon, France to 600 per 100,000 in Novosibirsk, Russia [3]• Framingham Heart Study (FHS) estimates for 1990 to 2004 was 5.3 in men and 5.1 in women[6]Prevalence:• Varies from 1.6% to 6% [5]Recurrence of Stroke:• 2% at 7 days, 4% at 30 days,12% at 1 year, and 29% at 5 years after initial cerebral ischemia [7].Case fatality and mortality:• Rochester Epidemiologic Project: Risk for death after first ischemic strok 7% at 7 days, 14% at 30 days, 27% at 1 year, and 53% at 5 years [7].6. Carandang R, Seshadri S, Beuser A, et al. Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years. JAMA 2006;296(24):2939–46.7. Petty GW, Brown RD Jr, Whisnant JP, et al. Survival and recurrence after first cerebral infarction: a population-based study in Rochester, Minnesota, 1975 through 1989. Neurology 1998;50(1):208–16.
  7. 7. Stroke in IndiaStroke Morbidity and Mortality in India• Prevalence 55.6 per 100,000 all ages (Dalal 2007)• 0.63 million deaths (WHO 2005)• 1.44-1.64 million cases of new acute strokes every year (WHO 2005, Murthy 2007)• 6,398,000 DALYs (WHO 2009)• 12% of strokes occur in the population aged <40 years (Shah + Mathur 2006)• 28-30 day case fatality ranges from 18-41% (Dalal et al 2008, Das et al 2007)
  8. 8. Stroke in India• Prevalence : 84-262/100,000 in rural and 334-424/100,000 in urban areas.(WHO 2008)• Incidence : 89/100,000 in 2005, projected to to 91/100,000 in 2015 and 98/100,000 in 2030. (Ezzati et al 2004)• Accounted for 0.9% to 4.5% of total medical admissions and 9.2%-30% of admission to neurological wards. (Bharucha+Kuruvilla 1998)
  9. 9. Classification
  10. 10. Classification of StrokeIschemic Stroke — three subtypes:• Thrombosis : In situ obstruction of an artery.• Embolism : Particles of debris originating elsewhere that block arterial access to a particular brain region.• Systemic hypoperfusion : More general circulatory problem, manifesting itself in the brain and perhaps other organs.Hemorrhagic Stroke due to intracerebral hemorrhage or subarachnoid hemorrhage Data compiled by AHA show that strokes due to ischemia, intracerebral hemorrhage and subarachnoid hemorrhage are 87%, 10%, and 3 %respectively[8]8. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation 2011; 123:e18.
  11. 11. Classification of Stroke
  12. 12. Classification of Stroke SubtypesTOAST Classification [9]1. Large-artery atherosclerosis (embolus/thrombosis)*2. Cardioembolism (high-risk/medium-risk)*3. Small-vessel occlusion (lacune)*4. Stroke of other determined etiology*5. Stroke of undetermined etiology a. Two or more causes identified b. Negative evaluation c. Incomplete evaluation*Possible or probable depending on results of ancillary studies.9. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 Jan;24(1):35-41.
  13. 13. Classification of Stroke SubtypesStroke Data Bank Subtype (NINDS) Classification [10] Derived from the Harvard Stroke Registry classification, the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank recognised -1. Atherothrombosis2. Tandem arterial pathology3. Cardiac Embolism4. Lacune5. Unusual Cause6. Infarction of undetermined cause7. Parenchymatous haemorrhage8. Subarachnoid Hemorrhage10. Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG. Classification of stroke subtypes. Cerebrovasc Dis. 2009;27(5):493-501. Epub 2009 Apr 3.
  14. 14. The Oxford Community Stroke Project classification (OCSP/ Bamford / Oxford classification) Based on symptoms -1.Total anterior circulation stroke (TAC)2. Partial anterior circulation stroke (PAC)3.Lacunar stroke (LAC)4. Posterior circulation stroke (POC)The type of stroke is then coded by adding a final letter to the above:• I – for infarct (e.g. TACI)• H – for haemorrhage (e.g. TACH)• S – for syndrome; intermediate pathogenesis, prior to imaging (e.g. TACS) These four entities predict the extent of the stroke, the area of the brain affected, the underlying cause, and the prognosis.11. Bamford J, Sandercock PA, Dennis MS, Burn J, Warlow CP: Classification and natural history of clinically identifiable subtypes of brain infarction. Lancet 1991; 337: 1521– 1526.
  15. 15. SSS-TOAST Classification1. Large artery atherosclerosis (Evident/Possible/Probable)2. Cardio-aortic embolism (Evident/Possible/Probable)3. Other causes (Evident/Possible/Probable)4. Undetermined causes (Unknown/ Cryptogenic embolism/ Other cryptogenic/ Incomplete evaluation/ Unclassified)12. Ay, H, Benner, T, Arsava, EM. A computerized algorithm for etiologic classification of ischemic stroke: the Causative Classification of Stroke System. Stroke 2007; 38:2979 .
  16. 16. Causative Classification System (CCS)Automated version of the SSS-TOAST (Arsava et al,Neurology 75 October 5, 2010) (
  17. 17. Etiopathology
  18. 18. Etiology of Ischemic Stroke A. Thrombosis Large intracranial Large extracranial vessels vessels • Atherosclerosis • Atherosclerosis • Dissection • Dissection • Takayasu arteritis • Arteritis/vasculitis • Giant cell arteritis • Noninflammatory • Fibromuscular vasculopathy dysplasia • Moyamoya syndrome • VasoconstrictionSmall vessel disease• Lipohyalinosis ( due to hypertension) and fibrinoid degeneration• Atheroma formation at their origin or in the parent large artery
  19. 19. B.Cardioaortic embolic stroke1. Cardiac sources definite - 2. Cardiac sources possible antithrombotic therapy generally Mitral annular calcification usedLeft atrial thrombus Patent foramen ovaleLeft ventricular thrombus Atrial septal aneurysmAtrial fibrillation Atrial septal aneurysm withSustained atrial flutter patent foramen ovaleRecent myocardial infarction (within 1 Left ventricular aneurysm month) without thrombusRheumatic mitral or aortic valve disease Isolated left atrial smoke (noBioprosthetic and mechanical heart valve mitral stenosis or atrialChronic myocardial infarction with fibrillation) ejection fraction <28 percent Mitral valve strandsSymptomatic heart failure with ejection fraction <30 percentDilated cardiomyopathy 3. Cardiac sources definite - anticoagulation hazardous Bacterial endocarditis Atrial myxoma 4. Ascending aortic atheromatous disease
  20. 20. C. Systemic hypoperfusionD. Blood disordersSickle cell anemiaPolycythemia veraEssential thrombocytosisHeparin induced thrombocytopeniaProtein C or S deficiency, acquired or congenitalProthrombin gene mutationFactor V Leiden (resistance to activated protein C)Antithrombin III deficiencyAntiphospholipid syndromeHyperhomocysteinemia
  21. 21. Risk Factors for Ischemic Stroke
  22. 22. Emerging Risk Factors• Lipoprotein (a)• Lipoprotein-associated phospholipase A2• C-reactive protein (CRP)• High-sensitivity C-reactive protein (Hs-CRP)• Serum Uric Acid*• The CD40/CD40 ligand (CD40L) dyadRebbeca A. Grysiewicz, Neurol Clin 26 (2008) 871–895* Patil TB et al. Serum Uric Acid Levels in Acute Ischemic Stroke:A Study of 100 Patients. J Neurol Res • 2011;1(5):193-200
  23. 23. Risk factors for stroke among the Indian populationThree transitions that contributed to emergence of stroke epidemic in India: Demographic, lifestyle and socioeconomic. (Dalal et al 2007, Pandian et al 2007, Gupta et al 2008)• Demographic shift - Increased life expectancy• Lifestyle shift - Food consumption and less physical activity• Socio economic shift - Rise in living standards by an urban elite who adopt western lifestyles. (Reddy 2004)
  24. 24. Stroke prevalence studies in India (Gupta et al 2008)
  25. 25. Pathophysiology of Ischemic StrokeCEREBRAL AUTOREGULATION• CBF (Cerebral blood flow) determined resistance within cerebral blood vessels• CBF is maintained at constant level despite variations in perfusion pressure.• Smooth muscle contract when CPP increases and relax when CPP drops.• Nitric oxide also plays a role in autoregulation.• Occurs within a mean arterial pressure 60 - 150 mmHg.• Outside this range, CBF increases or decreases with CPP• Ischemia at low and edema at high CPP
  26. 26. Normal cerebral autoregulation and itsdisturbance during acute ischemic stroke
  27. 27. Effects of decreased cerebral blood flow on vital brain functions
  28. 28. Cerebral autoregulation during stroke• Impaired during ischemic stroke .• As CPP falls, blood vessels dilate to increase CBF. Reduced CPP beyond compensation reduces CBF.• Neuronal electrical failure at 16 to 18 mL/100 g per minute• Failure of membrane ion homeostasis at 10 to 12 mL/100 g per minute.• This marks threshold for infarct .• In hypertensive individuals, autoregulation has adapted to occur at higher arterial pressures.• Reduction of blood pressure to normal levels could actually exacerbate the derangement.
  29. 29. Consequences of reduction in blood flow during stroke• Brain contains little or no energy stores and relies on blood for their delivery.• During stroke, reduction of blood flow to brain results in a deprivation of glucose and oxygen .• Region directly surrounding vessel is most affected.• Central core irreversibly damaged and necrosis if ischemia is long enough. (Infarct)• Cells which receive oxygen and glucose by diffusion from collaterals are viable. (Penumbra)
  30. 30. Mechanisms of ischemic cell injury and death• Depletion of ATP• Changes in ionic concentrations of sodium, potassium, and calcium• Increased lactate• Oxygen free radicals• Intracellular accumulation of water, Activation of proteolytic processes• Excitatory glutamate at synapses---- NMDA) receptor---- depolarization----calcium influx• Nitric oxide• Inflammatory pathway• Necrosis and apoptosis
  31. 31. Investigations in Ischemic Stroke
  32. 32. Vital signsBlood pressure• MAP usually elevated in acute stroke.• Represents response to maintain brain perfusion.• Decision to treat requires balance between severe increases in blood pressure, and decline in neurologic functioning with decreased BP.Breathing• Raised ICP (ICH/vertebrobasilar ischemia/ bihemispheric ischemia) - decreased respiratory drive /muscular airway obstruction.• Hypoventilation (increase in PCO2) - cerebral vasodilation -further elevates ICP.• Intubation- to restore adequate ventilation and protect airway.• Especially in vomiting with increased ICPFever• Worsens brain ischemia•
  33. 33. History and Physical ExaminationDistinguish between stroke and stroke mimics• Migraine• Head trauma• Brain tumor• Todds palsy (paresis, aphasia, neglect, etc. after a seizure episode)• Functional deficit (conversion reaction)• Systemic infection• Toxic-metabolic disturbances (hypoglycemia, acute renal failure, hepatic insufficiency, exogenous drug intoxication)(Ask for use of insulin/OHA/ seizure disorder/ drug overdose or abuse/ medications/ recent trauma/hysteria.)
  34. 34. Clinical Course: Embolic strokes Occur suddenly; deficits maximal at onset & Rapid recoveryMultiple embolic events with different clinical symptoms (initially weakness, followed byparesthesias).
  35. 35. Clinical Course: Thrombotic StrokeSymptoms fluctuate; Stepwise / stuttering progression & some periods of improvement
  36. 36. Clinical Course: Lacunar Stroke• Symptoms develop over short time, hours or at most few days• large artery-related ischemia can evolve over longer period.• stuttering course may ensue
  37. 37. Clinical course : Intracerebral hemorrhage • Does not improve during the early period• Rapid downhill course• Progresses in minutes/ few hours• Aneurysmal SAH develops in an instant. Focal brain dysfunction is less common.
  38. 38. Physical examination• Absent pulses (inferior extremity, radial, or carotid) - favors atherosclerosis with thrombosis• Sudden onset of cold, blue limb- favors embolism.• Occlusion of common carotid artery in the neck neck with bruit -occlusive extracranial disease• Temporal arteritis- temporal arteries irregular and with dilatation, tender, pulseless• Cardiac findings(especially atrial fibrillation, murmurs,cardiac enlargement) - favor cardiac-origin embolism.• Carotid artery occlusion –iris speckled, ipsilateral pupil dilated and poorly reactive, retinal ischemia• Fundus - cholesterol crystal, white platelet-fibrin, or red clot emboli. Subhyaloid hemorrhage in brain or subarachnoid hemorrhage.
  39. 39. What Is a Minimal Diagnostic Evaluation?• Blood pressure• H/o chronic blood pressure- lowering treatment• Tobacco smoking (current or stopped within the previous 6 months)• Diabetes mellitus• Weight, Height, Waist circumference• Physical exercise versus sedentary lifestyle• Family h/o vascular disease• H/o coronary intervention, acute coronary syndrome or myocardial infarction, atrial fibrillation.
  40. 40. • Noncontrast brain CT or brain MRI• Electrocardiogram• Complete blood count including platelets• Cardiac enzymes and troponin• Electrolytes, urea nitrogen, creatinine• Serum glucose• Prothrombin time and international normalized ratio (INR), Partial thromboplastin time• Oxygen saturation• Lipid profile• Assessment of extracranial arteries (Carotid ultrasound examination or MRA/ CT angiography/X-ray angiography).• Assessment of intracranial arteries (Transcranial Doppler/ MRA/CT angiography/or X-ray angiography/high-resolution MRI).
  41. 41. Appropriate in selected patients• Liver function tests• Toxicology screen• Blood alcohol level• Pregnancy test in women of child-bearing potential• Arterial blood gas if hypoxia is suspected• Lumbar puncture if subarachnoid hemorrhage is suspected and head CT scan is negative for blood• Electroencephalogram if seizures are suspected
  42. 42. Algorithm for imaging management of acute stroke patients (Kunst & Schaefer, 2011) Radiol Clin N Am 49 (2011) 1e26
  43. 43. Computed Tomography• Most frequently used modality• First-line imaging study in suspected stroke patients• Exquisite sensitivity for the detection of blood.• Overt processes must be excluded (tumor, subdural or epidural hematoma, subarachnoid hemorrhage, and lobar hemorrhage.)• Sensitivity of standard noncontrast CT for brain ischemia increases after 24 hours.• Early ischemia - 2 hrs from stroke onset, although they may appear much later- known as Early Ischemic Changes (EIC).
  44. 44. Loss of grey white matter differentiaton
  45. 45. Obscuration of the lentiform nucleus• Because the lenticulostriate branches of the MCA are end-vessels, the lentiform nucleus is prone to early irreversible damage after proximal MCA occlusion.
  46. 46. Cortical sulcal effacement.
  47. 47. Insular ribbon sign• Hypoattenuation of the insular cortex in the early stage of MCA occlusion can be explained by its watershed position far from the collateral supply of both the ACA & PCA, thus leading to early irreversible damage.
  48. 48. Hyperattenuation of large vessel• MCA occluded by a fresh thrombus appears hyper- attenuating relative to the normal C/L MCA at NCCT (Hyperdense MCA sign)• Thrombosis of more peripheral branches of the MCA may also be suspected on the basis of hyper-attenuating “dots” (MCA Dot sign)• Highly specific (100%) but less sensitive(30%).
  49. 49. Alberta Stroke Programme Early CT Score (ASPECTS)• It was developed to provide a simple and reliable method of assessing ischemic changes on head CT scan .• To identify acute stroke patients unlikely to make an independent recovery despite thrombolytic treatment .• It is mainly useful for evaluating MCA territory stroke. ASPECTS Study Group. Alberta Stroke Programme Early CT Score. Lancet 2000; 355:1670.
  50. 50. The ASPECTS value is calculated from two standardaxial CT cuts; 1. At the level of the thalamus and basal ganglia, 2. Just rostral to the basal ganglia
  51. 51. How to Calculate Aspects Score ?• The score divides the middle cerebral artery (MCA) territory into 10 regions of interest.• 3 points - Subcortical structures (1 each for caudate, LN, IC)• 7 points – Allotted to MCA cortex 3 points - M1. M2, M3 regions (Axial CT cut at BG level) 1 points - insular cortex 3 points - M4, M5, and M6 regions (CT cut just rostral to BG)• 1 point is subtracted for an area showing EIC, such as focal swelling or parenchymal hypoattenuation, for each of the defined regions.• Therefore, a normal CT scan has an ASPECTS value 10 points.
  52. 52. Utility of ASPECTS• ASPECTS was inversely correlated with stroke severity.• The median ASPECTS value was 8; a value of < 7 was associated with a sharp increase in dependence and death at three months.• Baseline ASPECTS in MCA strokes within 3 hr correlate inversely with the severity of the NIH stroke scale (NIHSS) score and with functional outcome. ASPECTS Study Group. Alberta Stroke Programme Early CT Score. Lancet 2000; 355:1670.
  53. 53. Limitations of ASPECTS• ASPECTS is not applicable to Lacunar stroke, Brainstem stroke, or Any stroke outside of the MCA territory
  54. 54. Other CT Imaging• Utility of CT contrast dye• CT angiography• CT perfusion imaging
  55. 55. Role Of MR Imaging• MRI has been shown to be more sensitive in detection of acute infarct as compared to CT, detecting almost 80% of the infarcts within initial 24hrs.• With the emergence of newer techniques like DWI, PWI, it is possible to identify the tissue at risk, salvageable by thrombolytic therapy.• Additional advantage of MRI include;• Ability to detect small lacunar infarcts and brainstem infarcts• Identification of stroke mimics.
  56. 56. MR- Imaging Protocol in Ischemic Stroke• Imaging protocols for acute ischemic stroke usually include• T1- and T2-weighted fast spin echo images,• FLAIR sequences, and• DWI with ADC maps.• T2 – weighted Gradient echo (GRE)
  57. 57. Acute Stage (T1,T2WI) (Upto 7 days)• Prolongation of T1 & T2 relaxation time d/t increased tissue water.• Hypointense on T1, Hyperintense on T2.• T2 signal start increasing after 8 hrs. Seen in 90% 24 hrs• In initial 24 hrs, these changes are more apparent in gray matter, especially deep gray matter structures (thalamus, BG)• Increase in vasogenic edema l/t gyral swelling, sulcal effacement (T1,T2) Peaks on day 3-4• Typical pattern of progressive enhancement• Initial 5-7 days = arterial wall enhancement without parenchymal enhancement• f/b gyral parenchymal enhancement after 7 days.
  58. 58. Subacute Infarction (T1, T2WI) (1-8 weeks)• Edema, mass effect resolves.• Parenchymal enhancement persists.• Relatively subtle T2 changes seen initially become obvious with marked hyperintensity on T2WI
  59. 59. Chronic Infarct (T1,T2WI)• Considered to begin when the integrity of the BBB is restored, edema has resolved, and most of the resorption of necrotic tissue is complete.• Usually occurs by 6 weeks.• Focal atrophy, widening of sulci.• Secondary findings seen in the chronic phases of cerebral infarction can include morphologic & signal intensity changes seen in the areas remote from the infarct, which represent Wallerian degeneration
  60. 60. FLAIR Imaging• FLAIR has been particularly helpful for the detection of infarction than T2- weighted imaging in the evaluation of strokes in periventricular and cortical regions.• It shows occluded vessels or vessels with reduced blood flow as hyperintense.• Limitations• Less sensitive than DWI in Hyperacute infarcton• Lack of specificity for acute hemorrhage.
  61. 61. Diffusion-Weighted Imaging (DWI)• Principle: In stroke, cytotoxic edema → movement of water molecules into the IC compartment → Restricted movement of water molecules → Appears as Hyperintense signal on DWI• DWI hyperintensity appears within minutes and becomes obvious in 24-48 hrs. It starts waning in 7-10 days. It may disappear after few weeks.• DWI does not change until CBF drops below 15 to 20 mL/100 g/min . (Stroke 1992;23: 1602–1612.)• However, since DWI contains some T2-weighing, some lesions which appear hyperintense on T2 may also appear hyperintense on DWI.
  62. 62. Apparent Diffusion Co-efficient (ADC)• DWI is also subject to signal alteration from gross patient motion, tissue vibration, and cardiac-related motions, and so the term apparent diffusion coefficient (ADC) has been coined.• ADC values• low within hours after the stroke continue to decline for the next few days.• Remain reduced for first 4 to 5 days after stroke• Pseudonormalization between 7 -10 days• After this the ADC subsequently rises in the lesion (i.e., the ADC map shows hyperintensity) beyond 10 days• This pattern is altered in case of reperfusion.• There is a significant amount of heterogeneity in the ADC values within the infarct area & has prognostic value for hemorrhagic transformation.
  63. 63. Perfusion-Weighted Imaging (PWI)• Perfusion imaging done using bolus dose of a paramagnetic contrast agent.• Magnetic susceptibility contrast agents such as dysprosium-diethylene triamine pentaacetic acid (DTPA)-bis(methylamide) or gadolinium-DTPA induce a T2* shortening and produce a signal loss in perfused tissue.• These agents remain in the intravascular space when the BBB is intact, inducing a local magnetic field gradient in the capillary bed.• A transient increase in signal is observed as the agent moves out into the tissue .
  64. 64. DWI-PWI Mismatch• Several studies have shown that the perfusion deficit (measured as a prolonged MTT or TTP delay) is initially larger in the acute setting .• It appears that in 70% to 80% of patients imaged within the first 6 hours of stroke, measured PWI deficits > DWI deficit.
  65. 65. Evolution Of Infarct with PWI deficit> DWI deficitA - 1 hourB - 3 days post-ictus
  66. 66. Ultrasound MethodsCarotid and vertebral duplexColor flow guided duplex ultrasound is well established as a noninvasive examination to evaluate extracranial atherosclerotic disease.Transcranial Doppler• Uses low frequency (2 MHz) pulsed sound to penetrate bony windows and visualize intracranial vessels of the circle of Willis.• Noninvasive means of assessing the patency of intracranial vessels.• Able to detect intracranial stenosis, identify collateral pathways, detect emboli on a real-time basis, and monitor reperfusion after thrombolysis• Major drawbacks include examiner-dependence, poor patient windows , and low sensitivity in the vertebrobasilar system.Combined duplex and TCD —High utility when performed by skilled ultrasonographers, although the available data come mainly from small studies.
  67. 67. Specific etiologies• Suspicion of endocarditis - emergent hemocultures and echocardiography• Suspicion of aortic dissection- emergent thoracic CT or TEE• Suspicion of cerebral artery dissection – ultrasound/ MRA / X- ray angiography/ fat-saturated MRI : hematoma in arterial wall.• A late work-up can be normal due to resolution of hematoma
  68. 68. When and How to Evaluate Cardiac Cavities and Wall?• Suspicion of intracardiac thrombus• Possibility of intracardiac mass• Search for endocarditis, either bacterial or nonbacterial• Search for akinetic or aneurismal ventricle• Prosthetic valve or clinical suspicion of valvular disease• Search for endomyocardial fibrosis;• Transthoracic and transesophageal 2D echo/cardiac CT MRI.
  69. 69. When Should TEE Be Performed?• Need to assess the right and left atrial cavities• Searching for an atrial septal aneurysm• Need to assess the thoracic aorta• In addition to TEE, a cardiac CT or MRI can help.
  70. 70. When and How Should a Coronary Artery Disease be Considered?• High risk of CAD –h/o chest pain, diabetes, or documented atherosclerosis cerebral arteries• Exercise T1-201 or dipyridamole myocardial scintigraphy• CT coronary angiography is still under evaluation• X-ray coronary angiography indicated with positive myocardial scintigraphy or in patients with ACS.
  71. 71. How Precise Should the Search for Atrial Arrhythmia Be?• Continuous monitoring during the acute phase of stroke using a monitor• Remote telemetry is helpful when available• Holter recording in patients with palpitations• Assessment of atrial vulnerability should only be investigational.
  72. 72. For Whom Should a Complete Evaluation of Hemostasis Be Performed?• Family h/o thrombophilia;• Young patients with stroke of unknown cause• Suspected cancer-related thrombophilia;• Associated deep vein thrombosis or pulmonary embolism (mainly if repeated and erratic events);• Recurrent brain embolism with AF and INR in therapeutic range.• Clinical findings that suggest systemic lupus erythematosus or the antiphospholipid antibody syndromeObtaining antiphospholipid antibody:• A history of lupus or symptoms compatible with lupus• Features such as miscarriages, venous thrombosis, or migraine headaches• Cryptogenic stroke or TIA at a young age
  73. 73. Suggested diagnostic laboratory evaluation in children and young adults who have acute arterial ischemic stroke (Bernard & Goldenberg,2010)• Complete blood count• Comprehensive metabolic panel (including hepatic indices)• ESR• CRP• Antinuclear antibody screen• Urine toxicology screen• Urine b-hCG (in postmenarchal woman)• Metabolic disease screening (if suspected by clinical presentation) {Includes blood lactate concentration, blood pyruvate concentration, serum carnitine concentration, urine organic acids profile, and serum amino acids profile}• Mitochondrial DNA mutational analyses (if suspected by clinical presentation)Bernard TJ, Goldenberg NA. Pediatric Arterial Ischemic Stroke. Hematol Oncol Clin N Am 24 (2010) 167–180
  74. 74. Contd…..• Thrombophilia panel {protein C activity, free protein S antigen or protein S activity, antithrombin activity, factor VIII activity, factor V Leiden mutation, prothrombin 20,210 mutation, homocysteine concentration (methylenetetrahydrofolate reductase mutations), antiphospholipid antibody evaluation (lupus anticoagulant testing eg, dilute Russell’s viper venom time or StaClot-LA, anticardiolipin IgG and IgM levels, anti–b2- glycoprotein I IgG and IgM levels), and lipoprotein(a) concentration.}• Disseminated intravascular coagulation screen (prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer)
  75. 75. Contd…..• Viral evaluation (if suspected by clinical presentation or if cerebral arteriopathy is demonstrated){ blood titers of VZV, HSV, Epstein-Barr virus (EBV), enterovirus, and parvovirus; blood viral culture; CSF viral culture; CSF VZV, HSV, EBV, enterovirus, and parvovirus testing by polymerase chain reaction (PCR); Helicobacter pylori testing; and enteroviral PCR from oral and rectal swabs.}• measurements of thrombotic factors in the neonate should be delayed until 3 months of age to obtain reliable results.
  76. 76. Stroke in pregnancy• Preeclampsia and Eclampsia• Reversible Cerebral Vasoconstriction Syndrome• Cerebral venous and sinus thrombosis• Choriocarcinoma• Peripartum Cardiomyopathy• Congenital and Rheumatic Heart disease• Amniotic Fluid Embolism• Paradoxic Embolism• General causes of stroke in young women(carotid and vertebral artery dissection, cardiac arrhythmias, heart valve disease, cerebral vasculitis, arteriovenous malformations, migraine, moyamoya disease, and sickle cell anemia.)Tettenborn B. Neurol Clin 30 (2012) 913–924
  77. 77. Safety of Brain Imaging During PregnancyCT• Fetal exposure to ionizing radiation from CT of the maternalhead is extremely low.• risk of birth defects by radiation limited to embryogenesis in first few weeks.• radiation <5 rad not associated increased fetal anomalies / pregnancy loss.• CT head gives a fetal exposure of < 1 rad• can be safely performed , especially if hemorrhage is suspected• Iodine contrast given crosses placenta and may depress fetal and neonatal thyroid function• Neonatal thyroid function should be checked
  78. 78. MRI• safer and more useful in pregnancy.• National Radiologic Protection Board arbitrarily advises against MRI in first trimester.• More recent data suggest that MRI is safe in any trimester of pregnancy.• Available safety data are for 1.5-T MRI. MRI safety for 3-T system remains unknown.• Gadolinium-based contrast (GBC) studies may be useful for neck MR angiograms.• No agreement on safety of GBC in pregnancy.• Animal models have shown growth retardation by GBC• no controlled human studies have confirmed.• GBC is considered as a category C substance
  79. 79. Vasulitides that may cause / mimic Stroke• Primary (isolated) angiitis of the CNS• Wegener’s granulomatosis• Microscopic polyangiitis• Classical polyarteritis nodosa• Churg–Strauss syndrome• Temporal arteritis• Takayasu’s arteritis• Henoch-Schonlein purpura• Kawasaki disease• systemic lupus erythematosus (SLE)• Sarcoidosis• Seropositive rheumatoid disease• systemic sclerosis, Sjogren’s syndrome and mixed connective tissue disease• Cryoglobulinaemia• Behçet’s disease• VZV Vasculopathy• Malignancy and cerebral vasculitis• Drug-induced cerebral vasculitis
  80. 80. Summary• WHO estimates a stroke occurs every 5 seconds• Also contributes to mortality and morbidity in India• Many classification systems for stroke subtypes are available ,of which CCS modification of TOAST is most recent.• There are modifiable , nonmodifiable and emerging risk factors for ischemic stroke.• Impaired cerebral autoregulation and excitotoxicity, oxidative stress contribute to brain injury in schemic stroke.• A quick clinical evaluation and NCCT are vital• MRI , MR/CT angiography and doppler studies for detailed analysis• Cardiac evaluation for suspected heart disease• Hematological work up for suspected hypercoagulable state• work up for stroke in specific population like pregnant females, neonates, children, young adults, vascultis and malignancy
  81. 81. OU !! ANKYTH