Stroke management

an updated account on management of TIA, Ischemic and hemorrhagic stroke in Sri Lanka. This is based on American Stroke Association and NICE guidelines.

1. STROKE MANAGEMENT DR KTD Priyadarshani Registrar in emergency medicine Teaching hospital- Peradeniya

2. outline General management Transient ischemic attacks Ischemic stroke Hemorrhagic stroke Intracranial hypertension and herniation

3. Definition The World Health Organization defines stroke as rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin ( 40 yrs ago ) ICD 11 Updated definition- the acute focal neurological signs, of presumed vascular origin, lasting longer than 24 hours or causing death , but subtypes (ischemic or hemorrhagic) has not been determined by neuroimaging or other techniques. 11% of all deaths Significant cause of morbidity

4. Classification Ischemic (85%) - due to an interruption of blood supply, or  Hemorrhagic- due to rupture of a cerebral artery.  Unable to distinguish between a hemorrhagic and ischemic stroke until imaging obtained

5. General management

6. Initial prehospital evaluation History and physical examination Determine LKW ABCs Glucose check Stroke severity screen exam Obtain IV access and blood for IX Contact stroke center and pre hospital notification

7. Stroke patients are dispatched at the highest level of care available in the shortest time possible.  Time between the receipt of the call and dispatch of the EMSS team is <90 s.  EMSS response time is <8  min (time elapsed from the call receipt to arrival on the scene by the equipped and staffed ambulance).  The on-scene time is <15  min (barring extenuating circumstances such as extrication difficulties). 

8. Emergency Department Evaluation Activate stroke code system Vital signs Maintain oxygen saturation >94% Determine time of onset/ LKW Determine NIHSS score CT/CTA Medication list (Anticoagulants) IV access (18G) IX- CBS, FBC with platelets, PT/INR, PTT and beta HCG, ECG

9. NIHSS score reproducibly and quantifiably assess a patient’s stroke symptoms. Scores range from 0 (no deficit) to 42

10. Nihss - limitations Limited use in in scoring brainstem strokes estimating the severity of a right hemispheric stroke. In the 2007 AHA/ASA guidelines, an NIHSS of 4 was a threshold to treat AIS with thrombolytics, but in the 2018 guidelines, a low score is not an absolute contraindication and potential risks should be weighed against anticipated benefits.

11. Iv fluid Hypovolemia may exacerbate ischemic brain edema and increase stress on the myocardium.  Stroke patients should receive maintenance isotonic intravenous fluids in the form of normal saline.  The utilization of plasma volume expanders has not demonstrated benefit.

12. TRANSIENT ISCHEMIC ATTACK

13. DIAGNOSIS The diagnosis of TIA is based on the new onset of focal neurological symptoms and signs that are explainable by a vascular disease (e.g., arterial occlusion of a single or group of arteries adequately explain the patient’s signs and symptoms), and the resolution of these signs and symptoms within 24  h (most TIAs resolve in a much shorter period of time). However, up to one-third of TIAs have demonstrable injury on DW- MRI. Condition should be treated with a similar sense of urgency as unstable angina

14. etiology Thromboembolic Spasm (cocaine) Dissection Hemodynamic, subclavian steal syndrome

15. Abcd2 score Risk greater with frequent TIAs cerebral vs ocular events Severe carotid stenosis Age over 60 Diabetes Symptoms longer than 10 min Weakness Impairment of speech Carotid are more liable than vertebral basilar to be followed by stroke

16. Rosier score Sensitivity 93% Specificity 83%

17. Low risk TIA (abcd2 0-3) Start antithrombotic agent ASA 81–300  mg/ day, clopidogrel 75 mg/day ASA 25 mg/extended release dipyridamole 200 mg twice daily Start high intensity statin atorvastatin 40–80 mg/ day rosuvastatin 20–40  mg or equivalent Consider moderate intensity statins (atorvastatin 10–20  mg, rosuvastatin 5–10  mg, simvastatin 20–40  mg, pravastatin 40–80  mg) in patients >75 years old.  

18. Encourage smoking cessation Outpatient workup in 1–2  days Imaging ( USS Carotid , CTA, MRA) Consider transthoracic echocardiogram If electrocardiogram (ECG) or rhythm strip shows atrial fibrillation , consider starting anticoagulation (oral anticoagulant or low molecular weight heparin) or ASA Consider 30 day ambulatory cardiac monitor - to detect intermittent atrial fibrillation

19. High‑Risk TIA ( ABCD2 scores >3) Hospital admission (crescendo attacks, symptomatic carotid stenosis, cardiac source of emboli, hypercoagulable state) Permissive hypertension is encouraged (not to exceed 220/120  mmHg), and BP should be gradually lowered over 24–48  h In a high-risk TIA (ABCD2 score ≥4), the CHANCE trial demonstrated that dual antiplatelet therapy using a combination of Clopidogrel (initial dose of 300  mg followed by 75  mg/day) and Aspirin 81  mg/day for 21  days followed by Clopidogrel 75 mg/day for 90 days was superior to aspirin alone in reducing the risk of stroke

20. the POINT trial from USA showed that combined use of Clopidogrel at a loading dose of 600 mg once followed by 75 mg/day for 90 days plus Aspirin 50–325 mg/ day for first 21 days was superior to aspirin 50–325 mg/ day for 90  days. The SAMMPRIS trial showed that in patients with TIA from stenosis of a major intracranial artery (70–99%), medical management with aspirin 325  mg/day and Clopidogrel 75  mg/day with aggressive medical management of primary risk factors was superior to combined medical therapy and intracranial stenting group. 

21. Progress trial 2001 (Perindopril pROtection aGainst REcurrent Stroke Study) showed Rx  with ACEI & thiazide → larger ↓BP and ↓CVA than with perindopril alone. Consider these two agents routinely if history of prevention CVA or TIA, whether HT or normotensive.

22. Surgical or endovascular measures Carotid revascularization- 70-99% - surgery when perioperative morbidity and mortality risk <6% 50-69%- moderate benefit <50%- no surgery Closure of PFO and right to left shunt 18-60 yrs , cryptogenic stroke or TIA, NO uncontrolled DM, HT, or specific indication for long term anticoagulation

23. Clinical pearls in tia mx a brief episode of neurological dysfunction caused by focal brain or retinal ischemia. A substantial risk of stroke exists in the early period after TIA . ABCD2 score is the recommended risk stratification tool for TIA. Early specialist assessment and modification of risk factors (diabetes, AF, hypertension, hypercholesterolemia, and smoking) reduces the risk of subsequent stroke. Aspirin should be started immediately unless there are contraindications.

24. Patients who have a TIA affecting the anterior circulation, and who are potentially fit for surgery, should have carotid imaging Patients with crescendo TIA (two or more TIAs in a week) should have specialist assessment within 24 hours of symptom onset. Patients who are discharged from the ED should be advised that they cannot drive for at least one month . They may resume driving after this period if clinical recovery is satisfactory.

25. ISCHEMIC STROKE

26. etiology

27. In a young patient, consider:  V asculitis T hrombophilia SAH V enous-sinus thrombosis or  C arotid artery dissection (e.g. via near-strangling or fibromuscular dysplasia).

28. 1 st hour Activate stroke code system Vital signs Supplemental oxygen to maintain spO2 >94% Determine LKW & NIHSS CT Medication list IV access and blood for IX- CBS, CBC with platelets, PT/INR, APTT, ECG

29. LKW<3 h: IV thrombolysis   If a patient is deemed a candidate for thrombolysis and there is no reason to suspect abnormal laboratory test results, thrombolytics should be administered without waiting for these laboratory test values to prevent further delay.  If the patient’s coagulation and platelet count results are abnormal (INR>1.7 or PT is abnormally elevated, platelet count <100,000 mm3 ) , then thrombolytics should be discontinued.

30. One relative contraindication is “clearing neurological deficit.” If a patient has plateaued or still has significant stroke symptoms without contraindication, treatment with thrombolysis should proceed as it would otherwise. Also, some patients will present with stuttering symptoms. If symptoms completely resolve, clinicians should reset the clock to start a new thrombolysis candidacy window; if there are still symptoms—however mild—the time of onset remains unchanged. Patients with stuttering symptoms tend to be at high risk for extending their vascular occlusions. 

31. IV alteplase 2 peripheral IV lines Calculate actual body weight 0.9 mg/kg (max 90mg) 10% given in bolus over 1 st minute Rest given over 1 hour infusion Stop immediately if neurological deterioration Improves chance of recovery without significant disability at 90 days from 26% to 39% if given with in 3 hrs

32. BP CONTROL If the patient is a potential thrombolysis candidate, interventions to control BP should be initiated immediately. Target BP goal for patients eligible for IV tPA is <185/110  mmHg , and once IV  tPA is initiated, BP must be maintained below 180/105  mmHg for 24  h after administration of IV  tPA to limit the risk of intracranial hemorrhage. 

33. DURING THROMBOLYSIS BP and neurological assessment every 15  min for the first 2 h after starting alteplase , every 30 min for the next 6 h, hourly for the next 16 h . While the half-life of alteplase is approximately 5 min , and only 20% of the medication is still present and active at 10 min after completion of the infusion, PT and activated partial thromboplastin time (APTT) are prolonged and fibrinogen levels are decreased for 24 h or more. 

34. Risk of ICH after IV tPA 50% or greater mortality rate. This is often accompanied by a marked rise in blood pressure (BP); however, a marked rise or fall in BP alone may signal an ICH.

35. Deterioration during or after IV tPA (24H) Stop alteplase infusion Obtain a non-contrast head CT scan STAT  Obtain CBC, PT, PTT, INR, fibrinogen level, type and cross-match  Vital signs every 15  min (neurological assessment for signs of increased intracranial pressure). Assess GCS/pupil response. Treat BP and use noninvasive interventions to lower intracranial pressure (ICP) (raise the head of bed, neck midline)  Supportive therapy , including management of BP, ICP, cerebral perfusion pressure (CPP), temperature, and glucose should be performed. 

36. Cryoprecipitate (contains fibrinogen ): 10 units infused over 10–30  min; administer additional dose for fibrinogen level <150  mg/dl. fibrinogen concentrate has been used to replenish the fibrinogen levels. The initial dose is 2 gm of IV fibrinogen followed by further dosing based on fibrinogen levels. prothrombin complex concentrate (25– 50 U/kg) and fresh frozen plasma (12 ml/kg) may be as an adjunctive therapy to normalize the INR. Antifibrinolytics Tranexamic acid 1000  mg (10–15  mg/kg) IV or ε- aminocaproic acid 4–5  g IV over 1  h , followed by 1  g IV until bleeding is controlled. One bag of single donor platelets or 6–8 bags of random donor platelets may also be transfused. Consult neurosurgery .   For small, asymptomatic, hemorrhagic conversion, conservative medical management may be considered after weighing the risks and benefits of reversal agents. 

37. Intra arterial thrombectomy If the patient has an LVO —e.g., proximal (M1) MCA, intracranial internal carotid artery (ICA), basilar or vertebral artery—or suspected LVO and the patient is within 6  h of LKW time , mechanical thrombectomy treatment should be considered. If the patient is a candidate for IV thrombolytics, it should be administered expeditiously, regardless of endovascular procedure candidacy. 

38. Endovascular Treatment ( lkw 6-24 hrs ) Based on the results of the DAWN and DEFUSE 3 trials , it is recommended that in patients presenting with an AIS within 6–24  h of LKW time who have an LVO in the anterior circulation, obtaining a CTP, DWI— MRI+MRI perfusion is recommended to aid in selection of patients for mechanical thrombectomy who meet the eligibility criteria. 

39. Admission/ Transfer Keep glucose 140–180  mg/ dL ; Hyperglycemia is associated with worsen outcomes and increased risk of ICH following AIS. Administer IV fluids, preferably isotonic saline , at 1.5 ml/kg/h initially, with a goal of euvolemic.  Continue bedside cardiac monitoring principally to detect paroxysmal atrial fibrillation and should continue for at least 72 h after admission. 

40.  Treat fever sources with appropriate antibiotics or therapies while preventing fever with antipyretics . If thrombolytic was administered, avoid indwelling urinary catheter, nasogastric tubes, and IA catheters for 4  h, and do not give anticoagulant/antiplatelet therapy for 24 h . Urinary catheters should in general be avoided unless absolutely needed.  While elevation of the head of bed is recommended for decreasing the risk of aspiration pneumonia, it was not found to make any difference in disability outcome of the stroke injury.  Patients should be nil per oral (NPO ) until evaluated for swallowing difficulties by a speech therapist Early mobilization and active rehabilitation

41. CLINICAL PEARLS IN AIS MX LKW in wake-up stroke is time patient went to bed. In cases of stuttering symptoms, the clock is reset only if patient is 100% back to baseline. With patients on direct oral anticoagulation, determine the last time the patient took their medication. Low NIHSS is not a contraindication to thrombolysis . Observing patients after thrombolysis for response is not required prior to mechanical thrombectomy. Consider short-term dual antiplatelet therapy in patients with TIA and ischemic stroke.

42. HEMORHAGIC STROKE

43. Definition Spontaneous bleeding into the parenchyma of the brain

44. etiology Hemorrhagic stroke generally occurs in small arteries or arterioles Chronic hypertension (~60% of cases)- basal ganglia, pons, thalamus, cerebellum Cerebral amyloid angiopathy (CAA)- lobar distribution Coagulopathy (warfarin, antiplatelet meds) Vascular anomalies (AVM, cavernous malformation) Sympathomimetic drugs (cocaine, methamphetamine) infarcts into which secondary hemorrhage has occurred Central nervous system bleeds (hypertension, head injury, aneurysm rupture). 

45. Ich- the golden hour Airway compromise Herniation and brain(stem) compression Hematoma expansion Elevated intracranial pressure Secondary brain injury Seizures Fever Hyperglycemia

46. 1 st hour History – medical hx , medications, social HX FBC with platelet count, PT, INR, APTT NCCT Brain- hematoma size, location, IVH GCS Calculate ICH Score

47. ICH score Each point increase in the ICH score is associated with an increased risk of mortality and a decreased likelihood of good functional outcome. It should not be used for prognosis; use it as a method for communicating disease severity

48. 1 st hour - Interventions Coagulopathy reversal (goal INR <1.4) Blood pressure lowering (goal SBP 140-180) Clevidipine /nicardipine drip Avoid nitroprusside Surgical hematoma evacuation Airway/ ventilation management

49. COAGULOPATHY REVERSAL MEDICATION REVERSAL UFH Protamine antiplatelets Consider DDAVP (0.4 mcg/kg) single IV dose • Platelets NOT recommend unless undergoing neurosurgical procedure Factor Xa inhibitors Rivaroxaban Apixaban LMWH Andexanet alfa • Consider activated charcoal (50 gm) if last oral dose was within 2h • PCC or FEIBA if Andexanet alfa not available • Protamine for LMWH given < 8 hrs for partial reversal Direct Thrombin Inhibitors Idarucizumab Activated charcoal (50 gm) if last oral dose was within 2h PCC or FEIBA if Idarucizumab not available

50. surgery location Surgery urgently Cerebellar ICH Declining neuro exam Size > 3cm Compressive effects brainstem Hydrocephalus Supratentorial ICH ICH causing mass effects/ herniation in severely affected but salvageable patient and as a life saving measure Still defining role of minimally invasive aspiration techniques

51. External ventricular drainage EVD recommended in GCS <8 Large mass effect hydrocephalus

52. Clinical pearls in ich mX Hematoma expansion occurs within first 6-12 hours in up to 40% of patients. Spot sign on contrast CT and BAT score on noncontract CT can help identify patients at risk for hematoma expansion. Admission to a NCCU is associated with improved ICH outcomes. Lower SBP to 140-180 mmHg with the specific target determined by patient- related factors. Urgent coagulopathy reversal is important to minimize hematoma expansion.

53. Current recommendations do not endorse routine seizure prophylaxis . Use short course in patients with lobar ICH and those undergoing surgical hematoma evacuation ERICH study- Levetiracetam used as prophylaxis was not associated with poor outcome at 3 months If level of consciousness is out of proportion to imaging, consider subclinical seizures.

54. INTRA CRANIAL HYPERTENSION AND HERNIATION

55. INTRACRANIAL COMPARTMENTS

56. INCREASED ICP ICP pressure & volume curve Compliance – (∆V/∆P) High compliance – (a) Low compliance – (b) Elastance - ∆P/∆V Elevated ICP: ICP > 22 mmHg sustained for > 5 min Cerebral PERFUSION pressure = MAP - ICP

57. Herniation syndromes

58. CLINICAL SIGNS AND SYMPTOMS EARLY LATE Headache Changes in level of consciousness or reduction in GCS or FOUR score >2 points Irritability, Seizure Ipsilateral change in pupillary size, shape and light responsiveness Vomiting Contralesionally hemiparesis (new or worsening) Photophobia, nystagmus, diplopia Contralesionally change in pupillary size and ipsilesional hemiparesis ( Kernohan’s phenomenon) Lethargy Cushing's triad

59. Icp monitoring

60. Icp waveform ICP waveform P1 - (Percussion wave) thought to reflect arterial pulsation P2 - (Tidal wave) thought to reflect degree of intracranial compliance P3 - ( Dichrotic wave) thought to reflect aortic valve closure ICP wave form analysis When P2 > P1 , suggests that brain has poor compliance / at risk for impending herniation

61. Hyperosmolar therapy Mannitol IV 0.5-1 g/kg bolus through peripheral IV line over 5-15 min repeated every 4-6 hrs Decide on repeat dosing with osmolar gap No therapeutic benefit if osmolar gap >20 mOsm /kg HTS 2-23.4% >7.5% in central line Serum Na every 4-6 hrs Na target <160 mEq /L

62. SEDATION AND ANALGESIA Propofol reduce CMRO2 and cerebral blood volume Bolus 1-2 mg/kg or infusion PENTOBARBITAL (bolus 5-15 mg/kg over 30 min- 2h, maintenance infusion of 1-4 mg/kg/ hr )

63. Surgical Decompression For those failing medical management: Review decompressive surgical options with neurosurgery Evacuation of mass lesion decompression craniectomy Placing an EVD

64. Additional Neuromonitoring Brain tissue oxygenation Cerebral micro dialysis Transcranial doppler-derived CBF

65. References American stroke association guidelines NICE guidelines Current medical diagnosis and treatment 2022

66. QUESTIONS?

67. Thank you!