Definition 

• Stroke is defined as sudden onset of a neurologic deficit from a vascular mechanism. 85% of strokes are ischemic and 15% are primary hemorrhages (Subarachnoid and Intraparenchymal). 
• Transient ischemic attacks (TIAs) are episodes of stroke symptoms that resolve rapidly, lasting fewer than 24 hours. 
• However, infarcts of the brain do occur in 15–50% of TIAs even though neurologic signs and symptoms completely resolve. Thus a newly proposed definition categorizes all patients with new brain infarct as having an ischemic stroke regardless of symptom duration. 

Mechanism of ischemic stroke 

• Thrombosis: Large vessel thrombosis, carotid artery thrombosis, carotid artery dissection 
• Cardioembolic: atrial fibrillation, atrial thrombus, dilated cardiomyopathy with ventricular thrombus, endocarditis, ASD, PFO, atrial myxoma 
• Hypercoagulable disease: Protein C deficiency, Protein S deficiency, Antithrombin III deficiency, Antiphospholipid syndrome, Factor V Leiden mutation , Systemic malignancy, Polycythemia vera, Lupus, Homocysteinemia, DIC, Oral contraceptives 
• Misc: cavernous venous sinus thrombosis, Vasculitis ( PAN, Wegener’s, Takayasu, Giant cell arteritis), SAH vasospasm, drugs like cocaine, eclampsia 
• Venous sinus thrombosis:  Occlusion of the dural venous sinuses, leading to venous outflow obstruction, venous hypertension and congestion, increased intracranial pressure, and intracerebral hemorrhage. 

Mechanism of Hemorrhagic stroke 

• Subarachnoid hemorrhage(SAH): Excluding head trauma, the most common cause of SAH is rupture of a saccular aneurysm. 
• Intracerebral hemorrhage: Hypertension and trauma are the most common causes. 

Symptoms & Signs 

• Cortical signs, suggesting large-vessel occlusion: Aphasia, visual field defect, gaze preference, neglect 
• Hemiparesis: Lower facial weakness, sparing the upper half of the face ,Slurred speech, Sensory changes, including neglect 
• Progressive decline in mental status and Coma 
• Posterior circulation symptoms: Dysmetria, ataxia, vertigo, diplopia, nausea, vomiting, hiccups, nystagmus 
• Transient monocular blindness (amaurosis fugax): Common presentation of embolic TIA, usually from internal carotid atherosclerotic lesion causing retinal ischemia. 

 

Stroke syndromes: Anterior circulation 

Middle cerebral artery (MCA) 

• Occlusion of the origin of the MCA 
  • Contralateral hemiplegia 
  • Contralateral hemianesthesia 
  • Contralateral homonymous hemianopia 
  • Gaze preference to ipsilateral side (resolves after 1 or 2 days) 
  • Dysarthria: common, due to facial weakness 
  • With dominant hemisphere involvement: global aphasia 
  • With nondominant hemisphere involvement: unilateral neglect, constructional apraxia, anosognosia (denial of the deficit) 
• Occlusion of inferior division 
  • Dominant hemisphere: receptive (Wernicke’s) aphasia (jargon speech with inability to comprehend written or spoken language), often with contralateral homonymous superior quadrantanopia 
  • Nondominant hemisphere: often subtle findings of hemineglect or spatial agnosia without weakness 
• Occlusion of lenticulostriate perforators that originate from the proximal MCA, without affecting flow within the MCA to more distal sites 
  • Produce classic lacunar stroke syndromes (see also below) 
  • Pure motor stroke, pure sensory stroke, ataxia-hemiparesis, clumsy hand-dysarthria 
  • Pure motor stroke or sensory motor stroke contralateral to lesion 
  • Ischemia within genu of internal capsule causes primarily facial weakness followed by arm and then leg weakness. 
  • Lacunar strokes of the globus pallidus and putamen: often few clinical symptoms; parkinsonism and hemiballismus possible, and may be delayed in onset from time of actual stroke 

Anterior cerebral artery (ACA) 

• Occlusion of proximal ACA 
  • Generally well tolerated because of collateral circulation 
  • Paralysis of contralateral foot and leg, typically without paresis of arm 
  • Cortical sensory loss over leg 
  • Contralateral grasp reflex, sucking reflex 
• Internal carotid artery 
  • Occlusion may go unnoticed with competent circle of Willis. 
  • If thrombus propagates into MCA, it produces symptoms of proximal MCA occlusion. 
• Occlusion of the origins of the ACA and MCA:Abulia or stupor occurs with hemiplegia, hemianesthesia, and aphasia or anosognosia. 

 

Stroke syndromes: posterior circulation 

Posterior cerebral artery (PCA) 

• Distal PCA supply, namely the visual cortex, is often spared by collateral flow from the posterior communicating artery. 
• Occlusion of perforators to the lateral midbrain 
  • Claude’s syndrome: ipsilateral third nerve palsy with contralateral hemiataxia 
  • Weber’s syndrome: ipsilateral third nerve palsy with contralateral hemiplegia 
• Alexia without agraphia 
• Loss of ability to read, with preserved ability to write, usually with a complete right homonymous hemianopia. 
• Other possible symptoms and signs: visual agnosia for faces, objects, mathematical symbols, and colors and anomia with paraphasic errors (amnestic aphasia) 

Vertebral artery and posterior inferior cerebellar artery (PICA) 

• Hemiparesis is not a feature of vertebral artery or PICA occlusion. 
• Occlusion of perforators off the vertebral or PICA that supply the lateral medulla 
• Lateral medullary (Wallenberg’s) syndrome: vertigo, loss of pain and temperature on the ipsilateral face and contralateral body (with preservation of vibration and joint position sense), diplopia, dysarthria, dysphagia, ipsilateral Horner’s syndrome 
• Vertebrobasilar insufficiency 
  • Atherosclerotic disease of the posterior circulation, combined with intermittent decreases in cardiac output (e.g., arrhythmias) can produce posterior circulation TIAs or strokes. 
  • Low-flow TIAs with syncope, vertigo, and alternating hemiplegia may occur when collateral circulation is insufficient, 1 vertebral artery is atretic or occluded, and an atherosclerotic lesion threatens the flow within the other vertebral artery 
• “Subclavian steal”: Exercise of ipsilateral arm increases demand on vertebral flow causing posterior circulation TIAs. 
• Subclavian stenosis must be proximal to the origin of the vertebral artery. 
• Increased demand in the upper extremity drives retrograde flow down the vertebral artery to supply the stenotic subclavian artery. 

Basilar artery and anterior inferior cerebellar artery (AICA) 

• Basilar artery occlusion 
• Can occur secondary to embolus from distant site or in situ thrombosis of ruptured atherosclerotic plaque in basilar artery 
• Typically results in life-threatening decreased level of consciousness, bilateral long tract signs, cranial neuropathies, and cerebellar dysfunction 
• “Locked-in” syndrome 
• If injury is restricted to the ventral pons, it can produce complete quadriplegia but completely normal consciousness. 
• Upper brainstem cranial nerve function is preserved, allowing communication with eye blinks. 
• Gaze paresis or internuclear ophthalmoplegia associated with ipsilateral hemiparesis may be only sign of bilateral brainstem ischemia; more often, unequivocal signs of bilateral pontine disease are present. 

Lacunar syndromes 

• As lacunar syndromes are caused by occlusion of small perforating arteries that supply deep subcortical structures, they do not have associated “cortical” signs such as aphasia, visual field deficits, gaze preference or neglect. 

Differential Diagnosis 

• The neurologic diseases that produce abrupt-onset, focal neurologic deficits include stroke, seizure, and migraine. 
• Metabolic encephalopathy, Drug overdose or intoxication, Vestibular vertigo 
• Hysterical conversion reaction 
• Wernicke’s encephalopathy 
• Bell’s palsy, Labyrinthitis, Multiple sclerosis 
• Hypertensive encephalopathy may mimic stroke like symptoms and tPA is infact contraindicated without controlling blood pressure. 

Diagnostic Approach 

• Diagnosis is based on history and physical examination. 
• Exact time of onset of symptoms to determine eligibility for thrombolysis 
• Complete Neurologic examination : Many scales are available that provide a structured, quantifiable neurologic examination. One of the most widely used and validated scales is the NIHSS, composed of 11 items adding up to a total score of 0 to 42 . Score >10 is considered as severe stroke. 
• Clinical examination also focuses on the peripheral and cervical vascular system. 
• Carotid auscultation for bruits 
• Blood pressure with comparison between arms 
• Heart (dysrhythmia, murmurs) 
• Extremities (peripheral emboli) 
• Retina for presence of papilledema 
• Appropriate laboratory studies to rule out metabolic causes or encephalopathy. 
• Once clinical diagnosis of stroke is made, brain imaging to determine if the cause is ischemia or hemorrhage. CT is more sensitive than routine MRI for acute bleeding and is preferred for acute stroke evaluation. 

Laboratory Tests 

• CBC,CMP, ESR, PT/PTT, appropriate coagulation studies,  Lipid profile, urinalysis, Tox screen, vasculitis panel.  Baseline EKG and troponins need to be checked as per AHA recommendations. 

Imaging 

• CT of the brain (noncontract):Infarct may not be reliably seen for 24–48 hours. 
• CTA: allows visualization of cervical and intracranial arteries, intracranial veins, and aortic arch. For patients in whom acute invasive treatment strategies (such as intraarterial thrombolysis or mechanical clot retrieval) are considered, urgent CT or magnetic resonance angiography is useful to identify the site of arterial occlusion 
• MRI of thebrain: DWI and FLAIR imaging is more sensitive for early brain infarction than standard MRI sequences or CT. 
• MRI perfusion studies with gadolinium contrast: Large regions of mismatch between perfusion and diffusion indicating salvageable tissue (ischemic penumbra) may better identify candidates for acute revascularization. 
• MRA: To evaluate patency of intracranial vessels and extra cranial carotid and vertebral vessels. Overestimates degree of stenosis as compared with conventional x-ray angiography 
• Cerebral angiography :“Gold standard” for evaluating atherosclerotic stenosis of cerebral arteries,  other intracranial and extracranial vessels. 
• ECHO for suspected cardiogenic source like endocarditis, atrial myxoma and patent foramen ovale 
• Carotid Ultrasound 
• Transcranial Doppler for assessment of middle, anterior, and posterior cerebral artery flow and of vertebrobasilar flow; commonly used to evaluate evolution of vasospasm following SAH 

Diagnostic Procedures 

• Electrocardiogram: Deep, symmetrical inverted T waves may be seen with SAH. Patients with acute stroke frequently has coronary occlusive disease and may have concomitant acute coronary syndrome. Also, the sympathetic surge in SAH may precipitate demand ischemia. 
• EEG, if seizures are suspected. 
• Lumbar puncture, if SAH is suspected 

Treatment Approach 

• Initial goal in the treatment of acute ischemic stroke is to reverse ongoing brain injury and to prevent secondary brain injury. 
• Initial medical stabilization: Airway, breathing, circulation 
• Assess for indications for thrombolysis or endovascular intervention and treat if indicated. 
• Alteplase (0.9 mg/kg, maximum 90 mg) remains the standard of care for eligible patients within 4.5 hours of symptom onset.
• Tenecteplase (0.25 mg/kg, maximum 25 mg) is recommended as an alternative to alteplase, particularly in patients eligible for mechanical thrombectomy
• If endovascular therapy is contemplated, a noninvasive intracranial vascular study (CTA or MRA) is strongly recommended during the initial imaging evaluation of the acute stroke patient but should not delay intravenous r-tPA if indicated. 
• Optimize cerebral perfusion of the surrounding ischemic penumbra. 
• “Permissive” hypertension treatment is common though incompletely studied 
• Anticoagulation (e.g., heparin) remains controversial. No evidence that heparin, oral anticoagulants, or thrombin inhibitors improve functional outcome when given in the acute phase of ischemic stroke. 
• Administer antiplatelet agents. 
• Closely monitor for mass effect from subsequent edema. Surgical decompression if needed (e.g., symptomatic swelling from cerebellar stroke) 
• Aggressively treat fever and hyperglycemia. 
• Minimize infection risks (e.g., aspiration pneumonia, urinary tract infection). 
• Provide prophylaxis for deep vein thrombosis. 
• Design rehabilitation plan. 
• Initiate secondary prevention strategies. 

 

Specific Treatments 

Medical support 

• Optimize cerebral perfusion in surrounding ischemic penumbra. 
• Permissive hypertension: The goal of permissive hypertension is to enhance collateral blood flow to the ischemic penumbra and thus prevent it from evolving into infarct. Antihypertensives of choice are labetalol and nicardipine. 
• Actively lower patient’s blood pressure gradually only in following scenarios: 
  1. Blood pressure > 185/110 mmHg and thrombolytic therapy is anticipated 
  2. Malignant hypertension, hypertensive encephalopathy, cerebral ischemia caused by aortic dissection, or compromise of other vital organ (e.g. active myocardial ischemia, hypertensive acute renal failure) 
  3. For active myocardial ischemia and significant cerebral ischemia, a β1-adrenergic blocker can provide cardiac protection without significantly lowering blood pressure. 
• Maintain intravascular volume with isotonic fluids to avoid hypovolemia, which may contribute to hypotension and worsening infarction. 
• Osmotic therapy with mannitol can be used in patients with symptomatic mass effect from edema in large infarcts. 
• Tight glucose control to less than 140. 
• There is no role for vasopressors to artificially raise MAP levels beyond the normal levels. 

Thrombolysis 

• With in 4.5 hours: Intravenous recombinant tissue plasminogen activator (tPA) remains the mainstay treatment within the initial 4.5 hours after symptom onset. NINDS Trial and ECASS III Trial

• The DWI-FLAIR mismatch on MRI has also been utilized to identify patients with unknown onset time who may benefit from thrombolysis, as shown in the WAKE-UP trial. I.e. When an ischemic lesion is visible on MRI diffusion weighted imaging (DWI) and not on fluid attenuated inversion recovery (FLAIR), the stroke is likely to have occurred within the prior 4.5 hours.
• 4.5 to 6 hours: IST 3 trial showed evidence supporting the use of alteplase up to 6 hours after stroke onset, particularly in patients over 80 years old.
• 4.5 to 9 hours: EXTEND trial showed that alteplase could improve functional outcomes when administered in this extended time window, especially if there is salvageable brain tissue identified by perfusion imaging
• Administration of tPA should not be delayed while awaiting the results of coagulation profile, unless patient is on anticoagulants or have strong suspicion to have bleeding diathesis. 
• If hypodensity on CT head involves more than 1/3rd of MCA territory, tPA must be held. 
• The dose of alteplase is 0.9mg/kg with a maximum dose of 90mg, given as 10% bolus and remainder over one hour. 
• tPA can sometime lead to life threatening angioedema 
• ​Contraindications 
  • CT scan showing hemorrhage and edema of more than one-third of MCA territory 
  • Sustained blood pressure > 185/110 despite treatment 
  • Platelets < 100,000; glucose < 50 or > 400 mg/dL 
  • Use of heparin within 48 hours and prolonged PTT or INR>1.7 
  • Rapidly improving or minor stroke symptoms 
  • Coma or stupor 
  • Prior stroke or head injury within 3 months; 
  • prior intracranial hemorrhage 
  • Major surgery in preceding 14 days i.e. 2 weeks 
  • GI bleeding in preceding 21 days i.e. 3 weeks 
  • Seizures at stroke onset 
  • Recent myocardial infarction in last 3 months 
  • Additional exclusion criteria for tPA between 3-4.5 hrs : Age>80 years, severe stroke with NIHSS>25, use of oral anticoagulants regardless of INR, previous stroke with diabetes, infarct size greater than 1/3rd of MCA territory 
• Avoid antithrombotic or anticoagulation treatment for 24 hours. 
• A follow up CT head is done after 24 hrs before initiating antiplatelet agents. 
• For decline in neurologic status or uncontrolled blood pressure, stop infusion, give 10 units of cryoprecipitate and 6 units of platelets, and reimage brain emergently. However, the utility of cryo and platelets after tPA bleed is not clear. 
• Risk of intracranial hemorrhage increases with: Large strokes , increasing time from onset of symptoms , dose of drug . 
• The incidence of intracranial hemorrhage after tPA is upto 7%. 
•  AcT trial showed tenecteplase was non inferior to alteplase. Tenecteplase offers potential advantages in terms of ease of administration and cost-effectiveness.

 

Endovascular options 

• Can be broadly divided into chemical dissolution of clots with locally delivered thrombolytic agents and clot retrieval or thrombectomy with mechanical devices or use of retrievable stent. 
• Endovascular thrombectomy is recommended for patients with LVO in the anterior circulation within 6 hours of symptom onset. However, it can be up to 24 hours in select patients with salvageable brain tissue, as demonstrated by the DAWN and DEFUSE 3 trials
• Patients who are eligible for IV tPA should recieve tPA even if they are being considered for endovascular therapies. 
• Stent retrieval: 5 RCTs on intra-arterial& stent assisted clot retriever (NNT of 5) 
• Criteria: 
  • Pre-stroke modified Rankin 0-1 (no deficits) 
  • tPA<4.5h since symptom onset 
  • ICA or prox MCA (M1) lesion 
  • Age ≥18 
  • NIHSS ≥6 
  • ASPECTS ≥ 6 
  • CT rating tool (early ischemia) to estimate risk of hemorrhagic transformation (low) 
  • W/in 6 hrs of symptom onset 
• Endovascular options, where available, can be considered for patients with: 
  • Acute ischemic stroke with contraindications to intravenous rtPA 
  • Typical time frame for intervention is within 6-8 hours of symptom onset, though window may be expanded by emerging perfusion studies which identify salvageable tissue 
  • Intraarterial thrombolysis can be considered in patients who have relative contraindication to tPA. The dose is much lower. However, SYNTHESIS study didn’t find any benefit to intra-arterial thrombolysis when compared to intravenous tPA. 
  • Intraarterial delivery of thrombolytics for MCA occlusion in patients presenting between 3 and 6 hours of symptom onset improves outcome. 
  • Mechanical embolectomy is considered for priximal large artery occlusion.  Can restore patency of occluded intracranial vessels within 8 hours of ischemic stroke symptoms 
  • Observing patients after intravenous r-tPA to assess for clinical response before pursuing endovascular therapy is not required to achieve beneficial outcomes and is not recommended. 
  • IV tPA vs localized tPA : In SYNTHESIS expansion study, patients with acute ischemic stroke were assigned within 4.5 hours to endovascular therapy (intraarterial thrombolysis with t-PA, mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Endovascular therapy was not superior to standard treatment with intravenous t-PA. Also, the incidence of ICH were the same around 6%. 
  • tPA vs tPA+ thrombectomy: In EXTEND-1A trial, in patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with a stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. Of note, both groups received intravenous tPA in this study. 
  • IV tPA vs IV tPA+ Intra arterial tPA: In MrCLEAN study, in patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was highly effective for emergency revascularization and functional independence.  All patients received systemic tPA before randomization. There were no difference in the rates of ICH. 
  • Other major landmark trials that showed benefit of thrombectomy after thrombolysis include ESCAPE , SWIFT PRIME , and REVASCAT .

Post-tPA and thrombectomy care

1. Hemodynamic management: AHA/Stroke guidelines recommend maintenance of BP ≤180/105 mmHg for the first 24 hours post-EVT.  BEST-II trial, a randomized controlled study, investigated the effects of intensive blood pressure lowering (target systolic BP 100-129 mm Hg) versus standard management (target systolic BP 130-180 mm Hg) in patients who achieved successful recanalization after thrombectomy. The results showed that intensive blood pressure lowering was associated with a lower rate of intracranial hemorrhage, but did not significantly improve functional outcomes at 90 days.
2. Neurological monitoring: Frequent assessments (e.g., every 15 minutes for 3 hours, then every 30 minutes for 3 hours) to detect any deterioration that could indicate complications such as intracranial hemorrhage.
3. Reperfusion management: Optimization of cerebral blood flow is essential, with monitoring for potential “no reflow” phenomenon in the microvasculature.
4. Complication surveillance: Vigilance for post-procedural complications, including access site bleeding, cerebral edema, and symptomatic intracranial hemorrhage, is maintained.
5. Early mobilization and rehabilitation: Protocols often include early mobilization and dysphagia screening to prevent complications and initiate rehabilitation.

Medical management

Antiplatelets 

• For minor ischemic stroke, Aspirin 325mg initial dose followed by 81 mg daily indefinitely along with Plavix 75 daily for 21-30 days – based on CHANCE and POINT Trials.
• For moderate to severe ischemic stroke, DAPT is not recommended in acute phase due to increased risk of bleeding.
• Also, in high risk patients especially with intracranial atherosclerosis, it is recommended to use dual antiplatelet therapy( ASA+Plavix) for the first 90 days followed by monotherapy. SAMMPRIS Trial
• For patients undergoing carotid endarterectomy or stenting, DAPT is typically recommended for 1-3 months post-procedure, followed by long-term single antiplatelet therapy
• If monotherapy is desired, Plavix or Aggrenox should be the first line agents rather than aspirin alone. CAPRIE trial showed that Plavix reduced the risk of vascular events better than aspirin. 
• Combination clopidogrel and aspirin ( In MATCH trial and CHARISMA trial, the combination was not any more effective than either drug alone but significantly increased bleeding complications. However, In CHANCE trial on Chinese population, there was significant stroke reduction in combination group for the first 90 days without increase in hemorrhage) . POINT Trial showed benefit of adding clopidogrel to aspirin in patients with minor stroke or high-risk TIA
• Combination aspirin and extended-release dipyridamole: In PROFESS trial , the combination was equally effective to Plavix in the secondary prevention of stroke. In ESPS-2 and ESPIRIT trial , the combination was more effective than aspirin alone. 
• Ticagrelor: SOCRATES study didn’t find it to be more effective than aspirin. THALES study found that addition of Ticagrelor to aspirin led to decreased stroke but more bleeding events.
• Prasugrel: TRITON-TIMI 38 trial showed increased risk of intracranial hemorrhage and should never be used for stroke.

 

Phosphodiesterase-3 inhibitors ( Cilostazol)

• CSPS 2 trial showed that cilostazol was non-inferior to aspirin for secondary stroke prevention and had a lower risk of hemorrhagic events.
• PICASSO trial compared cilostazol to aspirin in patients with prior ischemic stroke and a high risk of cerebral hemorrhage, finding a lower risk of hemorrhagic events with cilostazol

Anticoagulation 

• In small to moderate strokes, full dose anticoagulation can be started after 24 hrs. In large infarctions, it’s advisable to hold off anticoagulation for 2 weeks, given the risk of hemorrhagic transformation. 
• PREVAIL Study showed superiority of LMWH vs heparin for VTE prophylaxis. 
• Usefulness of urgent anticoagulation in patients with severe carotid stenosis and stroke is not well established. 
• The timing of anticoagulation after acute stroke:
  1. TIA: Start within 1 day
  2. Minor stroke: Start after 3 days
  3. Moderate stroke: Start after 6-7 days
  4. Major stroke: Start after 12-14 days
  5. This “1-3-6-12 day rule” is based on expert consensus, balancing the risk of early recurrent ischemic stroke against the risk of hemorrhagic transformation. ELAN Investigators
• ELAN Trial: Early anticoagulation (within 5 days) was not superior to later anticoagulation ( 12-14 days) in preventing recurrent stroke or systemic embolism at 30 days
• ARISTOTLE trial demonstrated the superiority of apixaban over warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation

Carotid endarterectomy 

• Benefits clear with symptomatic severe (>70%) carotid stenosis 
• Endovascular angioplasty/stenting is now evolving as an alternative to endarterectomy. 
• Emergent carotid endarterectomy in the setting of acute stroke is fraught with high risk and risk of restoke. 

PFO closure 

In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA ( CLOSURE I study) 

Neurosurgical intervention 

• Emergency surgical decompression should be considered if cerebellar edema increases intracranial pressure or causes brainstem compression. 
• Hemicraniectomy (craniotomy and temporary removal of part of the skull) 
• Special vigilance is warranted for patients with cerebellar infarction. Even small amounts of cerebellar edema can acutely increase intracranial pressure or directly compress the brainstem. Resulting brainstem compression can result in coma and respiratory arrest and require emergency surgical decompression. 

Complications:

Cerebral edema pathophysiology involves complex mechanisms that lead to increased brain water content. The primary types are cytotoxic, ionic, and vasogenic edema, which often coexist and evolve over time

 

Management of elevated ICP

1. Goals:
   • Maintain ICP below 22 mmHg. Normal ICP is 3-15.
   • Keep cerebral perfusion pressure (CPP) between 60-70 mmHg.
2. First-Tier Interventions:
3. • Head Elevation: Elevate the head to 30°.
   • Sedation: Use propofol (4-6 mg/kg/h).
   • Analgesia: Administer fentanyl (1-4 μg/kg/h).
   • Mechanical Ventilation: Target PaCO₂ of 35 mmHg.
   • Normothermia: Maintain normal body temperature.
   • Hyperosmolar Therapy: Use mannitol or hypertonic saline (3% saline boluses of 250-500 mL or continuous infusion at 0.5-1.5 mL/kg/h).
4. Second-Tier Therapies for Refractory Cases
5. • Barbiturate Coma: Induce coma to achieve burst suppression on continuous electroencephalography (EEG).
   • Therapeutic Hypothermia: Cool the body to 32-35°C.
   • Decompressive Craniectomy within 48 hours of stroke onset can significantly reduce mortality and improve functional outcomes in large MCA infarctions

Antiplatelet Timing After Hemorrhage

1. Minor hemorrhagic transformation: Antiplatelet therapy can generally be started or resumed as early as 24-48 hours after stroke onset, similar to patients without hemorrhagic transformation. PLoS One. 2014; 9(2): e89798
2. Major hemorrhagic transformation: Optimal timing remains uncertain, but most experts recommend waiting at least 7-14 days before initiating antiplatelet therapy. J Clin Med. 2023 Apr; 12(8): 2771

A study published in 2023 found that early resumption of antiplatelet therapy (within 30 days) after intracerebral hemorrhage was as safe as delayed resumption in terms of recurrent ICH risk. While this study focused on primary ICH rather than hemorrhagic transformation of ischemic stroke, it suggests that earlier antiplatelet initiation may be safer than previously thought in some cases.

 

PEARLS 

• Rankin score evaluates the functional independence after a stroke 
• As rapid evaluation and initiation of secondary prevention in TIA reduces subsequent stroke risk, patients with TIA should be either admitted or have urgent follow-up arranged in a clinic for patients with TIA. 
• As TIA is a clinical diagnosis, mimics such as seizure and migraine should be considered. 
• For patients who awake with neurologic deficits, the time of onset is considered to be the time at which they were last seen to be normal (e.g., typically the time at which they went to bed the previous night). 
• Cortical signs (language abnormalities, visual field deficits, gaze preference, neglect) suggest a large vessel occlusion and thus the likelihood of an embolic stroke. 
• Patients with progressive third nerve palsies (unilateral dilated pupil with limited medial and vertical gaze) should have urgent neuroimaging to evaluate for the possibility of mass effect from an expanding aneurysm of the posterior communicating artery. 
• Onset of diuresis with normal serum sodium levels in patients with SAH likely heralds the development of cerebral salt wasting and warrants frequent (e.g., at least twice daily) measurements of serum sodium. 
• The most common clinical signs of many of the common delayed complications of SAH (e.g., vasospasm, hydrocephalus, hyponatremia, infection) are drowsiness and altered mental status. 
• The presence or absence of cortical signs such as aphasia, visual field deficits, gaze preference, and neglect allow early identification of likely stroke type (embolic large-vessel stroke more likely when cortical signs are present, thrombotic small vessel stroke more likely when cortical signs are absent) and direct evaluation of likely etiology. 
• Major stroke guidelines, including those from the American Heart Association/American Stroke Association, do not recommend routine seizure prophylaxis for patients with acute ischemic stroke.