Stroke management

Stroke indications

Treatment	Indication	Study
Thrombectomy + thrombolysis	◦ Prestroke modified Rankin Score (mRS) of <3 ◦ Anterior circulation ◦ Age ≥18 years ◦ NIHSS score ≥6 ◦ ASPECTS ≥6 ◦ Mismatch ratio and ischemic core volume > 1.8 ◦ Timing < 24 hrs ◦ Intracranial haemorrhage has been excluded	MR CLEAN Hermes DAWN DEFUSE 3
CEA-symptomatic	◦ Recent stroke/TIA ◦ Carotid stenosis >70% stenosis ◦ Earlier the better (<2 weeks)	NASCET ECST
CEA-Asymptomatic	◦ Carotid stenosis >60% stenosis	ACAS ACST
CAS-Symptomatic	◦ CEA better only offer CAS if CEA cannot be performed	ICSS
CAS-Asymptomatic	◦ Similar to CEA	SAPPHIRE ACST ACT CREST SPACE 2
CAS Intracranial symptomatic	Don’t do	SAMPPRIS
ECIC Bypass - Intracranial symptomatic	Don’t do	JET COSS
ECIC Bypass - Moyamoya	History of infarct/hemorrhage/progressive disease	JAM MarioTeo
Decompressive craniectomy for Malignant MCA infarct	<60 age NIHSS >15, 1a>0 CT >50% MCA area, DWI >145mls Prestroke mRS <=1 Surgery within 48 hrs of referral (72 hrs from onset)	HAMLET DECIMAL DESTINY

Management

Admit to ICU

Frequent VS with cranial checks (hrly for 12 hrs, then if stable, q 2 hrs)

Monitor cardiac rhythm

History/physical exam: include a stroke scale (preferably NIHSS (p. 1348))

Higher NIHSS scores indicates more deficit and correlate with more proximal vascular lesions (larger vessel occlusion causes more widespread deficit)

NIHSS should be administered to any patient with a suspected stroke to aid decision-making and prognostication (as well as monitor progression).

Total scores range from 0-42 with higher values representing more severe infarcts:

> 25 Very severe neurological impairment;
15-24 Severe impairment;
5-14 Moderately severe impairment;
< 5 Mild impairment.

Prognostication

Increase in 1 point of NIHSS score decreases the likelihood of an excellent outcome by 17%
A 2-point (or greater) increase on the NIHSS administered serially indicates stroke progression.

an initial score of 7 has become an important cut-off point since patients with NIHSS 7 or more demonstrated a worsening rate of 65.9%,
those with NIHSS < 7 demonstrated a worsening rate of 14.8% and were almost twice as likely to be functionally normal at 48 h (45% back to normal).

Likelihood of intracranial haemorrhage if

NIHSS > 20 was 17%
NIHSS < 20 was 3% in those

Outcome

NIHSS < 5 most strongly associated with D/C home,
NIHSS 6-13 most strongly associated with D/C to rehab
NIHSS > 13 most strongly associated with D/C to nursing facility

Onset or last known well (LKW) time

Scale	Finding
1a. Level of consciousness (LOC)	ㅤ
0	Alert; keenly responsive
1	Not alert, but arousable by minor stimulation to obey, answer, or respond
2	Not alert, requires repeated stimulation to attend, or is obtunded and requires strong painful stimulation to make movements (not stereotyped)
3	Comatose: responds only with reflex motor (posturing) or autonomic effects, or totally unresponsive, flaccid and areflexic
1b. Level of consciousness questions	Patient is asked the month and their age.
0	Answers both questions correctly (must be exact; no credit for being close)
1	Answers one question correctly or cannot answer due to ET tube, orotracheal trauma, severe dysarthria, language barrier, or other non-aphasia issues
2	Answers neither question correctly, or is aphasic, stuporous, or does not comprehend the questions
1c. Level of consciousness commands	Patient is asked to open and close their eyes and grip/release the non-paretic hand. Substitutions allowed for inability to use hands. Demonstration may be used if no response to commands.
0	Performs both tasks correctly
1	Performs one task correctly
2	Performs neither task correctly
2. Best gaze	Test only horizontal eye movement. Use motion to attract attention of aphasic patients.
0	Normal horizontal movements
1	Partial gaze palsy or isolated cranial nerve III, IV, or VI paresis
2	Forced deviation or total gaze paresis not overcome by oculocephalic maneuver
3. Visual	Test visual fields (upper and lower quadrants) via confrontation. May be normal if patient looks towards stimulus. Use threat perception if comprehension limits testing.
0	No visual field deficit
1	Partial hemianopia or extinction to double-sided simultaneous stimulation
2	Complete hemianopia
3	Bilateral hemianopia (blind, including cortical blindness)
4. Facial palsy	Ask patient (or pantomime) to show their teeth, or raise eyebrows and close eyes. Use painful stimulus and grade grimace response in poorly responsive or non-comprehending patients.
0	Normal symmetrical movement
1	Minor paralysis (flattened nasolabial fold, asymmetry on smiling)
2	Partial paralysis (total or near-total paralysis of lower face)
3	Complete paralysis of one or both sides (absent facial movement in upper and lower face)
5. Motor Arm (5a = left, 5b = right)	Instruct patient to hold the arms outstretched, palms down (at 90° if sitting, or 45° if supine). If consciousness or comprehension impaired, cue patient by actively lifting arms into position while verbally instructing patient to maintain position.
0	No drift (holds arm at 90° or 45° for full 10 seconds)
1	Drift (holds limbs at 90° or 45° position, but drifts before full 10 seconds but does not hit bed or other support)
2	Some effort against gravity (cannot get to or hold initial position, drifts down to bed)
3	No effort against gravity, limb falls
4	No movement
9	Amputation or joint fusion: explain
6. Motor leg (6a = left, 6b = right)	While supine, instruct patient to maintain the non-paretic leg at 30°. If consciousness or comprehension impaired, cue patient by actively lifting leg into position while verbally instructing patient to maintain position. Then repeat in paretic leg.
0	No drift (holds leg at 30° full 5 seconds)
1	Drift (leg falls before 5 seconds, but does not hit bed)
2	Some effort against gravity (leg falls to bed by 5 seconds)
3	No effort against gravity (leg falls to bed immediately)
4	No movement
9	Amputation or joint fusion: explain
7. Limb ataxia	Looking for unilateral cerebellar lesion. Finger-nose-finger and heel-knee-shin tests are performed on both sides. Ataxia is scored only if clearly out of proportion to weakness. Ataxia is absent in the patient who cannot comprehend or is paralyzed.
0	Absent
1	Present in one limb
2	Present in two limbs
9	Amputation or joint fusion: explain
8. Sensory	Test with pin. When consciousness or comprehension impaired, score sensation normal unless deficit clearly recognized (e.g. clear-cut asymmetry of grimace or withdrawal). Only hemisensory losses attributed to stroke are counted as abnormal.
0	Normal, no sensory loss
1	Mild to moderate sensory loss (pinprick dull or less sharp on the affected side, or loss of superficial pain to pinprick but patient aware of being touched)
2	Severe to total (patient unaware of being touched in the face, arm, and leg)
9. Best language	In addition to judging comprehension of commands in the preceding neurologic exam, the patient is asked to describe a standard picture, to name common items, and to read and interpret standard text. The intubated patient should be asked to write: - You know how. - Down to earth. - I got home from work. - Near the table in the dining room. - They heard him speak on the radio last night.
0	Normal, no aphasia
1	Mild to moderate aphasia (some loss of fluency, word finding errors, naming errors, paraphasias, and/or impairment of communication by either comprehension or expression disability)
2	Severe aphasia (great need for inference, questioning, and guessing by listener; limited range of information can be exchanged)
3	Mute or global aphasia (no usable speech or auditory comprehension) or patient in coma (item 1a = 3)
10. Dysarthria	Patient may be graded based on information already gleaned during evaluation. If patient is thought to be normal, have them read (or repeat) the standard text shown in this box. - MAMA - TIP-TOP - FIFTY-FIFTY - THANKS - HUCKLEBERRY - BASEBALL PLAYER - CATERPILLAR
0	Normal speech
1	Mild to moderate (slurs some words, can be understood with some difficulty)
2	Severe (unintelligible slurred speech in the absence of, or out of proportion to any dysphasia, or is mute/anarthric)
0	Intubated or other physical barrier
11. Extinction and inattention (formerly neglect)	Sufficient information to identify neglect may already be gleaned during evaluation. If the patient has severe visual loss preventing visual DSSS, and the cutaneous stimuli are normal, the score is normal. Scored as abnormal only if present.
0	Normal, no sensory loss
1	Visual, tactile, auditory, spatial, or personal inattention or extinction to DSSS in one of the sensory modalities
2	Profound hemi-inattention or hemi-inattention to more than one modality. Does not recognize own hand or orients to only one side of space.
A. Distal motor function (not part of NIHSS) (a = left arm, b = right)	Patient’s hand is held up at the forearm by the examiner and is asked to extend the fingers as much as possible. If the patient cannot do so, the examiner does it for them. Do not repeat the command.
0	Normal (no finger flexion after 5 seconds)
1	At least some extension after 5 seconds (any finger movement is scored)
2	No voluntary extension after 5 seconds

Prevention

Anti-lipid therapy

NICE:

Immediate initiation of statin treatment is not recommended in people with acute stroke
Continue statin treatment in people with acute stroke who are already receiving statins.

Antiplatelet therapy

Aspirin

Given with 24-48hrs after onset
160-300mg
If IV tPA is given delay aspirin 24 hrs later

Patients with minor stroke: dual antiplatelet therapy (ASA+ clopidogrel) for 21 days starting ≤24 hrs can reduce secondary stroke for up to 90 days

IV tirofiban & eptifibatide:

Efficacy is not established pending further clinical trials

Abciximab & other glycoprotein IIb/IIIa receptor antagonists

Not recommended (potential harm)

Ticagrelor

Not recommended over ASA in the acute treatment of minor stroke (no benefit)

Maintain O2 saturation >94%

If sat >94% no need O2

Noncontrast brain CT: the usual initial diagnostic tool of choice (image in ≤20 mins)

To rule out: hemorrhage (SAH, ICH, EDH, SDH), mass (tumor, abscess…)
To calculate ASPECTS (Alberta stroke program early CT score)

To identify candidates for thrombectomy

Treat CHF and arrhythmias.

MI or myocardial ischemia may present with neuro deficit

Blood glucose:

NICE: Maintain a blood glucose concentration between 4 and 11 mmol/litre in people with acute stroke
Essential lab to obtain in case IV tPA is indicated
Avoid hyperglycemia in the 1st 24 hours after AIS (worse outome).
Goal: blood sugar 140– 180mg/dL (5.3-10 nmol/L)

Rationale: hyperglycemia may extend ischemic zone (penumbra)

Avoid hypoglycemia < 60mg/dL
Hyperglycemia and hypoglycemia may mimic AIS and should be treated if identified (tPA is not indicated for nonvascular conditions) (no benefit)

Antiepeliptics

Not recommended prophylactically

Osmotic therapy

Mannitol 50 to 100 gm IV over 20minutes or 3% saline
For clinical deterioration from cerebral edema associated with AIS

Temp

Dx and Tx fever >38 °C:
Hypothermia use is not well-established and should only be employed within trials

General

The benefit of drug-induced hypertension is not well-established in AIS
Keep within normal limits
Blood pressure should not be lowered in the acute phase unless there are complications e.g. Hypertensive encephalopathy

Avoid hypotensin and hypovolemia: SBP< 110 or DBP< 70:

IVF: 250 cc NS over 1 hr, then 500 cc over 4 hrs, then 500 cc over 8 hrs
If fluid ineffective or contraindicated: consider pressors

HTN in stroke

General

HTN may actually be needed to maintain CBF in the face of elevated ICP, and it usually resolves spontaneously.
Therefore treat HTN cautiously and slowly to avoid rapid reduction and overshooting the target.
Avoid treating mild HTN.
Indications to treat HTN emergently include:

Acute LV failure (rare)
Acute aortic dissection (rare)
Acute hypertensive renal failure (rare)
Neurologic complications of HTN

Hypertensive encephalopathy
Conversion of a large pale (ischemic) infarct into a hemorrhagic infarct
Patients with ICH; some HTN is needed to maintain CBF

Hypertension treatment algorithm

Guidelines for Lower Limits of Treatment Endpoints for HTN in Strokes

ㅤ	No Prior History of HTN	Prior History of HTN
Do not lower SBP below	160–170 mm Hg	180–185 mm Hg
Do not lower DBP below	95–105 mm Hg	105–110 mm Hg

If DBP> 140 (malignant hypertension): ≈ 20–30% reduction is desirable.

Cardene infusion or IV labetalol are agents of choice;
Arterial-line monitor recommended;
Sympatholytics (e.g. trimethaphan) contraindicated (they reduce CBF)

SBP> 230 or DBP 120–140×20 mins:

Labetalol (unless contraindicated): start at 10mg slow IVP over 2 mins, then double q 10min (20, 40, 80, then 160mg slow IVP) until controlled or total of 300mg given.
Maintenance: effective dose (from above) q 6–8 hrs PRN SBP>180 or DBP>110

SBP 180–230 or DBP 105–120:

Defer emergency treatment unless there is evidence of LV failure or if readings persist × 60mins
Oral labetalol (p.139) (unless contraindicated) dosed as follows:

For SBP >210 or DBP> 110: 300mg PO BID
For SBP 180–210 or DBP 100–110: 200mg PO BID

If labetalol contraindicated: nicardipine (p.139)

IF want to start IV tPA:

Control HTN before giving IV-tPA
Maintain above BP targets for 24 hours after tPA

Other meds

Corticosteroids

Not recommended for cerebral oedema
Can cause harm

Laxatives

Avoid diuretics

Emergency surgery indication

Herniation from subdural hematoma

Suboccipital craniectomy for progressive neurologic deterioration due to brainstem compression from cerebellar haemorrhage or infarction

Decompressive craniectomy for malignant MCA territory stroke (see below)

Carotid endarterectomy for high grade carotid stenosis ipsilateral to fluctuating neuro deficit; see Emergency carotid endarterectomy (p. 1364)

Potential thrombolysis case:

If the patient presents within 4.5 hours of onset of focal symptoms, thrombolysis referral may be appropriate – see Acute Stroke 1 Guideline.
If the patient presents >4.5 hours, follow local protocol for stroke admissions.

General: (NHS GGC)

Temperature:

Keep within normal limits
If >37.5ºC look for evidence of infection and send blood / urine / sputum culture as appropriate.

O2 saturation and treat hypoxaemia if necessary
BM

Keep within normal limits

Rhythm check - atrial fibrillation may be present
Cholesterol lowering

If serum cholesterol is > 3.5 mmol/l patients should be commenced on a statin.
Many physicians will delay treatment until after at least 48 h due to conflicting evidence from retrospective subgroup analyses of the SPARCL and HPS studies which showed that while high dose statins significantly reduce the risk of recurrent ischemic stroke, they may be associated with a higher rate of haemorrhage.

A later prospective study using routine statin doses does not support this hypothesis, but physicians have remained cautious.

Antiplatelet therapy

Withhold antiplatelet / antithrombotic medication until CT scan excludes haemorrhage.
Aspirin

300 mg orally or rectally should be given as soon as possible if a hemorrhagic stroke has been excluded
For 2 weeks then stop

Clopidogrel

Recommended as first-line for secondary prevention in people who have had an ischemic stroke
Aspirin plus MR dipyridamole is recommended only if clopidogrel is contraindicated or not tolerated, and MR dipyridamole alone is recommended if both aspirin and clopidogrel are contraindicated or not tolerated.

Anticoagulation

Prophylactic dose

The use of aspirin and/or low dose heparin/LMHW for venous thromboembolism (VTE) prophylaxis can be considered within 24 h of symptom onset.

Treatment dose

In the absence of intracerebral haemorrhages or haemorrhagic transformation of infarcts, NICE/AHA/ASA guidelines recommend starting anticoagulation at 14 days after the onset of stroke in those at high risk (e.g. atrial fibrillation).
14 days because

Risk of further ischemic strokes between days 7 and 14 is significantly reduced from 4.9 to 3% with early anticoagulation
BUT the risk of symptomatic intracerebral haemorrhage was also significantly increased from 0.7% to 2.5%.

Moderate-large areas of cerebral infarction are subject to the risk of haemorrhagic transformation within the acute period (< 14 days).

Start Apixaban 5mg BD from 2 weeks point

Scoring system

CHA2DS2-Vasc score

Goal estimate the risk of embolic stroke in patients with AF and assist with deciding on whether or not to anti-coagulate a patient.

Score	Decision
0	No treatment
1	Consider anticoagulation in males
≥ 2	Offer anticoagulation

HAS-BLED scoring

Goal: estimate the risk of major bleeding for patients on anticoagulation for AF
There are no formal rules on how we act on the HAS-BLED score although a score of >= 3 indicates a “high risk” (4-6%) of major bleeding such as

Intracranial haemorrhage
Bleeding requiring hospitalization
Haemoglobin decrease > 2 g/l, or bleeding requiring transfusion.

ABCD2 score

Goal: risk stratifies patients presenting in the outpatient setting with suspected TIA

Score	Stroke risk	2 day stroke risk
0-3	Low	1.0%
4-5	Moderate	4.1%
6-7	High	8.1%

ABCD2 score >=4

Started on aspirin (300 mg daily) immediately

If the diagnosis if confirmed, After 14 days of aspirin, clopidogrel is recommended first-line long term therapy in TIA (aspirin + dipyridamole should be given to patients who cannot tolerate clopidogrel).
In the US, TIA is more commonly managed with 325 mg aspirin with a goal of performing carotid endarterectomy within 24 h of presentation

Specialist assessment and investigation (ECG, TTE, carotid duplex scan, MRI) within 24 h of onset of symptoms,
Start measures for secondary prevention started based on individual risk factors.
People with crescendo TIAs (two or more episodes in a week) should be treated as being at high risk of stroke, even though they may have an ABCD2 score of 3 or below.

ABCD2 score is <=3

Specialist assessment within 1 week of symptom onset is advised, including decision on brain imaging if vascular territory or pathology is uncertain.

Medical management of structure

Goal: prompt restoration of blood supply by recanalization of the occluded vessel to rescue the penumbra.

Avoid hypotension, hyperthermia, and ensure strict glycaemic control.

Patients should undergo workup and treatment for etiological factors.

Prevention of penumbral infarction drives stroke management.

Minimal standard of care involves appropriate and timely triage of stroke patients, administration of IV tPA for all eligible patients.

Deviation from standard practice drives medical solicitors.

Treatment options

Up to 4.5 hours: IV tPA
If no improvement and patient in relatively good grade (e.g., NIHSS 8-10), then candidate for IA tPA or mechanical embolectomy.

If 6-8 hours: IA tPA or embolectomy

If >8 hours: Advisable to get a perfusion imaging to assess penumbra.

If >1/3 of MCA territory infarcted, then mechanical embolectomy is contraindicated.

If too large cannot thrombectomy can cause haemorrhagic transformation

Considerations for thrombolytic therapy

Varies depending on local practice/guidelines:

ICH, suspected SAH, known aneurysms/AVM, bleeding tendency
SBP >185 or DBP >110 despite IV labetalol or nicardipine infusion.
Recent major surgery, GI haemorrhage, seizures at time of stroke, arterial puncture in non-compressible site, MI pericarditis, extremes of blood glucose levels.

Dose of tPA:

NINDS protocol: 0.9 mg/kg IV bolus over 1 min followed by 0.81 mg/kg infusion over 60 minutes (maximum of 90 mg).

Hold all anti-coagulants and anti-platelets for 24 hours.

Patient now has some improvement in right side power but blood pressure remains high 230/120

Hypertension in stroke patients

Hypertension is needed to maintain cerebral blood flow (CBF) in acute stroke management and often resolves spontaneously.

Cautious management is required to avoid rapid or overshooting of the target.

Indications for aggressive blood pressure (BP) management:

Acute left ventricular failure (LVF)
Aortic dissection
Hypertensive renal failure (all rare)
Neurological complications of hypertension (HTN)

Antihypertensive drugs of choice:

Labetalol: Safe in pregnancy, bradycardia is a side effect.

Nicardipine: Calcium channel blocker.

Sodium nitroprusside: Contraindicated in high cardiac output failure.

Sympatholytic (e.g., Trimethaphan): Contraindicated in stroke as they reduce cerebral blood flow (CBF).

Anti-platelets Vs Anticoagulation

Aspirin 325mg improves outcomes if given within 48 hours.

Although heparin is widely used after stroke, there is no evidence to suggest improved outcomes nor dual antiplatelet.

Temperature control

Fever is an independent predictor of poor outcome in stroke patients.

Despite evidence that fever worsens outcomes, there is no proof that correcting it to normothermia improves prognosis.

Patient had an episode of right sided focal motor seizure with secondary generalization, what is next.

ICH following thrombolytic therapy

Factors associated with increased risk for symptomatic ICH:

Higher NIHSS score (more severe strokes are more likely to have ICH)

Pre-treatment CT showing mass effect

Larger infarct size

Elevated blood sugar

Stop tPA, obtain CT if not done

Bleeding profile

6–8 units of cryoprecipitate

6–8 units of platelets

Patient dropped to flexing what is next?

If EVD is needed consider recombinant factor VIIa 40–80 mg/kg immediately (for time-buying purposes).

Other factors:

Glucose control: hyperglycaemia spreads the penumbra, could be a stress response as well.

Avoid overhydration: aim for 30% haematocrit.

BP management if systolic <110: give saline bolus 250ml over 1 hour, then 500ml/4hrs.

Laxatives.

If EVD is needed for tPA associated ICH/HCP: consider VIIa 40–80 mg/kg.

Steroids for steroid sensitive vasculitis.

Hyper-osmolar therapy to buy time.

These times are applicable to anterior circulation strokes. Posterior circulation occlusions may be treated more aggressively.

(a) IV tPA: give to essentially all candidates within 4.5 hours of onset (NICE)
(b) 3–4.5 hrs: IV tPA reasonable but not studied in same patient population
(c) thrombectomy candidates: NIHHS score ≥ 6; ASPECTS ≥ 6; Large vessel occlusion (LVO); Puncture ≤ 6 hrs from onset (NICE), within 6-24hrs of wake up strokes
(d) Thrombectomy 6–16 hrs in candidates who meet other DAWN or DEFUSE-3 (p.1356) eligibility
(e) Thrombectomy 16–24 hrs in candidates with anterior circulation LVO who meet other DAWN eligibility criteria

Thrombolysis

Indicated

Clinical diagnosis of ischemic stroke causing measurable neurologic deficit

Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal or at neurologic baseline
Onset <4.5 hrs (4.5 hrs within last well)

At 4.5 hrs the risk and CI line crosses

Age ≥18 years

Intracranial haemorrhage has been excluded

Contraindication

Patient history

Ischemic stroke or severe head trauma in the previous three months
Previous intracranial haemorrhage
Intra-axial intracranial neoplasm
Gastrointestinal malignancy
Gastrointestinal haemorrhage in the previous 21 days
Intracranial or intraspinal surgery within the prior three months

Clinical

Symptoms suggestive of subarachnoid haemorrhage
Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg)
Active internal bleeding
Presentation consistent with infective endocarditis
Stroke known or suspected to be associated with aortic arch dissection
Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic'

Hematologic

Platelet count <100,000/mm3*
Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds*
Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE)
Current use (ie, last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays

Head CT

Evidence of haemorrhage
Extensive regions of obvious hypodensity consistent with irreversible injury

Recanalization rates

4.4% for distal internal carotid artery occlusion,

4% for basilar artery occlusions

30% for M1 and M2 segment occlusions.

NNT to get one person to functionally independent

1 in 10 if <3 hrs

1 in 20 if <4.5 hrs

IV tPA (tissue plasminogen ativator, alteplase)

Within 4.5 hours of onset when thrombectomy not being done immediately or for patients that are not thrombectomy candidates

Goal: “door-to-needle” (DTN) time ≤60 minutes

Future trials

ATTEST-2 Trial

Alteplase vs Tenecteplase
Tenecteplase 8x more potent in dissolving clot

Combined: IV tPA a thrombectomy

NICE: Thrombectomy + IV thrombolysis

Last known to be well up < 24 hours previously (including wake‑up strokes

Who have acute ischaemic stroke and confirmed occlusion of the proximal posterior circulation (that is, basilar or posterior cerebral artery) demonstrated by CTA or MRA AND

If there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion or diffusion-weighted MRI sequences showing limited infarct core volume

Thrombectomy within 6 hours with or without alteplase versus alteplase or standard medical care

Outcomes	No of Participants (studies) Follow up	Quality of the evidence (GRADE)	Relative effect (95% CI)	Anticipated absolute effects: Risk with Control	Anticipated absolute effects: Risk difference with Thrombectomy plus medical management (95% CI)
Mortality at 90 days	1334 (6 studies)	MODERATE 1 due to imprecision	RR 0.9 (0.7 to 1.16)	157 per 1000	16 fewer per 1000 (from 47 fewer to 25 more)
Modified Rankin scale (0 - 2) - 90 days	1324 (6 studies)	MODERATE 2 due to risk of bias	RR 1.47 (1.28 to 1.68)	377 per 1000	177 more per 1000 (from 106 more to 256 more)
Modified Rankin scale ordinal shift at 90 days	1324 (6 studies)	MODERATE 2 due to risk of bias	OR 1.78 (1.47 to 2.16)	Control rate not reported	ㅤ
Symptomatic intracerebral haemorrhage at 90 days	1312 (6 studies)	LOW 1 due to imprecision	RR 0.98 (0.6 to 1.6)	44 per 1000	1 fewer per 1000 (from 18 fewer to 26 more)
Intracerebral haemorrhage	65 (1 study)	LOW 1 due to imprecision	RR 0.97 (0.21 to 4.45)	94 per 1000	3 fewer per 1000 (from 74 fewer to 324 more)
Any serious adverse event at 90 days	800 (3 studies)	MODERATE 1 due to imprecision	RR 1.08 (0.92 to 1.28)	423 per 1000	34 more per 1000 (from 34 fewer to 118 more)
EQ-5D at 90 days Scores range from -0.33 to 1, with higher scores indicating a better quality of life	260 (1 study)	MODERATE 2 due to risk of bias	ㅤ	The mean EQ-5D in the control group was 0.515	The mean EQ-5D at 90 days in the intervention groups was 0.02 higher (0.08 lower to 0.11 higher)

Might be optimal therapy (unless contraindicated) due to

2 million neurons die each minute

Lysis can be given whilst waiting for Angio suite

Transfer to suitable center

5% of thrombus will lyse by time of procedure

Summary

Initial trials of endovascular therapy versus IV rtPA alone (e.g. MERCI, IMS III, SYNTHESIS Expansion, MR RESCUE trials) failed to definitively demonstrate superiority of mechanical embolectomy—possibly due to use of first generation stent retrievers with poor recanalization rates, and limited availability of advanced imaging to confirm vessel occlusion and identify prenumbral pattern/infarct core

Current evidence shows that CAStent confers a higher post-procedural morbidity vs best MM and Carotid endarterectomy (CEA)

CAStent has a lower risk of procedural Ml and local complications.

Similar long-term protection against ipsilateral stroke / restenosis.

CAStent consideration for certain select patients.

Thrombectomy: Mechanical clot retrieval

Indication

Mechanical thrombectomy:

Large vessel occlusion

ICA
MCA
Bassilar

Prestroke modified Rankin Score (mRS) of <3
Causative occlusion of ICA or M1 segment of MCA
Age ≥18 years
NIHSS score ≥6
ASPECTS ≥6
Mismatch ratio and ischemic core volume 1.8

See below (DEFUSE and DAWN)

Timing

≤6 hours of onset

MR CLEAN

Acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe
Intra-arterial treatment had better mRS

HERMES (meta-analysis of MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, EXTEND IA)

The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2·6.
Recanalization rates 58-88%

All trials meta-analysis:

Endovascular treatment, in particular thrombectomy as an add-on to intravenous rt-PA, provides beneficial functional outcomes after ischaemic stroke secondary to occlusion of anterior large vessels, without increased detrimental effects compared with medical care alone

>6hrs

DAWN & DEFUSE-3 are the only randomized controlled trials that showed benefit of mechanical thrombectomy > 6 hours from onset

Issues with this is you need to scan a lot of people before you find one that is suitable for thrombectomy >6hrs

Other trials

Wider range of good outcome % in MT

May reflect impact of additional brain imaging selection criteria used to select patients with greater volume of salvageable tissue (EXTEND-IA, SWIFT-PRIME, ESCAPE, DAWN, DEFUSE-3)

5 trials without selection bias show good outcomes in 11-16% - lower but consistent.

Overall NNT of <3 for an improved functional outcome.

6–16 hours onset

Anterior circulation who meet other DAWN or DEFUSE-3 eligibility criteria.

DEFUSE-3

Initial infarct volume (ischemic core) of less than 70 ml,
A ratio of volume of ischemic tissue to initial infarct volume of 1.8 or more
An absolute volume of potentially reversible ischemia (penumbra) of 15 ml or more.

Size of the penumbra was estimated from the volume of tissue for which there was delayed arrival of an injected tracer agent (time to maximum of the residue function [Tmax]) exceeding 6 seconds

DAWN

Patients had to have a mismatch between the severity of the clinical deficit and the infarct volume, which was defined according to the following criteria:

Group A

>= 80 years of age,
NIHSS score >= 10
Infarct volume < 21 ml

Group B

< 80 years of age,
NIHSS score <= 10
Infarct volume < 31 ml

Group C

< 80 years of age,
NIHSS score >= 20
Infarct volume 31 - 51 ml

16–24 hours

Anterior circulation LVO who meet other DAWN eligibility criteria.

DAWN

Patients had to have a mismatch between the severity of the clinical deficit and the infarct volume, which was defined according to the following criteria:

Group A

>= 80 years of age,
NIHSS score >= 10
Infarct volume < 21 ml

Group B

< 80 years of age,
NIHSS score <= 10
Infarct volume < 31 ml

Group C

< 80 years of age,
NIHSS score >= 20
Infarct volume 31 - 51 ml

Goal

Reperfusion to a Modified treatment in cerebral ischemia scale (mTICI) 2b/3 angiographic result and to minimize the time to treatment in order to maximize the chances of good functional outcome.

Grade	Description
0	No perfusion
1	Antegrade perfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion
2a	Antegrade perfusion of <50% of the ischemic territory of the occluded target artery (e.g. in 1 major division of the MCA & its territory)
2b	Antegrade perfusion of >50% of the ischemic territory of the occluded target artery (e.g. in 2 major divisions of the MCA & their territories)
3	Complete antegrade reperfusion of the ischemic territory of the occluded target artery, with absence of visualized occlusion in all distal branches

Thrombectomy- Outcomes

NNT 4-6 for independence

NNT 2.6 to shift mRS by I

Comparable rates of ICH to thrombolysis alone

Benefits reduces by 5% each hour delay

50% at 3 hours
40% at 6 hours
33% at 8 hours

Level IA evidence that modern-device mechanism thrombectomy achieves significant higher re-canalization rates (and better clinical outcome) than TPA alone for LVO stroke.

11-36% absolute increase in patients recovering from AIS to be independant in ADLs.

Areas of uncertainty

Post circulation Large vessel obstruction

Mainly Basilar thrombus only in practice
NICE: Benefits uncertain, but mechanical thrombectomy may be reasonable for

Carefully selected patients with causative occlusion of M2 or M3 segment of MCA, or anterior cerebral, vertebral, basilar or posterior cerebral arteries
Or prestroke mRS> 1, ASPECTS < 6 and causative occlusion of ICA or M1 segment; however, additional randomized trials are needed
When treatment can be initiated (groin puncture) ≤6 hours after onset

Evidence

BASICS study group (European): No difference EVT vs medical therapy
BEST (Worldwide): No difference EVT vs medical therapy

Distal occlusions

The more distal the risky it is as there is less control of instruments

Mild stroke (NIHSS <6) with confirmed LVO

GA vs LA

MR CLEAN: 37.8% used GA

Intra-arterial tPA thrombolysis

Evidence

Only one patient in MR CLEAN used intra-arterial tPA

Intracranial carotid artery stenting/angioplasty

Angioplasty by itself has high chance re-occlusion within 24 hrs

Indication for end stenting

Symptomatic patient with

High bifurcation
Symptomatic restenosis
Post radiotherapy stenosis

Contraindications

Complete occlusion.
Major disabling stroke on ipsilateral side
Intracranial tumour / hemorrhage
Unstable plaque / thick calcification at stenosis
Extreme vessel tortuosity

Evidence

Yeo 2024 Meta analysis

PTAS has greater peri- and post (first 30 days)-procedural stroke and death risk over best medical therapy in patients with symptomatic ICAS (RR = 2.22)

SAMMPRIS RCT (2011), N=451

Aggressive medical management was superior to PTAS

30-day rate of stroke or death was

14.7% in the PTAS group
5.8% in the medical-management group

The risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected

Secondary prevention

Management

Antithrombotics:

Aspirin 300 mg OD for two weeks

STOP aspirin at two weeks

START apixaban 5 mg BD

Blood pressure lowering

Increase ACE inhibitor dose aiming for SBP<130 mm Hg

Cholesterol lowering

Continue statin

Avoid driving: needs driving assessment in due course

Large vessel occlusions

Scope of the Problem

Common: 30-40% of all ischemic stroke

Severe: 5x higher mortality, 3-fold reduction in good outcome

Respond poorly to intravenous thrombolytic (tPA)

Only 1/3 will work with IV TPA 2/3 will not work

Conclusion

Surgical management of stroke

Embolic stroke - Thrombectomy

Ischaemic stroke - Endarterectomy

Haemodynamic stroke

Revascularisation

CAS vs CEA

Three large European trials

EVA-3S (endarterectomy vs angioplasty in patients with symptomatic severe carotid stenosis)
SPACE (stent-protected angioplasty vs carotid endarterectomy)
ICSS (International carotid stenting study)

Overall higher procedural risk of stroke with CAS than with CEA.

Risk of stroke or death within 30 days after procedure 7.7% (CAS) vs 4.4% (CEA)

CREST (North American Carotid Revascularization Endarterectomy vs Stenting Trial) (1321 pts with symptomatic stenosis)

Results were consistent with European trials

Multicenter prospective substudy of ICSS found 50% of CAS pts (vs 17% of CEA) had new, mainly asymptomatic ischemic lesions on DWI after Rx.

Consistent with a systematic review of nonrandomized studies showing an average of 37% CAS patient with new DWI lesions vs 10% of CEA patients.

CREST also showed lower procedural risk of MI in CAS cohorts.

Cranial nerve palsies (CAS 0.3% vs CEA 5.5%)

Groin haematoma (CAS 0.9% vs CEA 2.7%)

CEA superior to CAS in patients aged >70 years.

Less favourable vascular anatomy
Higher atherosclerotic burden

Increased risk of dislodging emboli

Increased white matter damage on baseline CT or MRI

Small emboli (which are more common with CAS) more likely to result in stroke symptoms due to lower CVS reserve.

Pooled data from NASCET and ESCT shows surgery more effective when performed within first 2 weeks after ischaemic event.

Very few data available showing safety of CAS at early stages after stroke

Data from pooled analysis of European trials suggests that the increase in stroke risk after CAS is greatest when treated within 7 days of symptoms.