Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5573_Библиотеки_им_академика_М_И_Перельмана.pdf
456
B. Barlow et al.
head CT within 36h of stroke onset as sICH [15], while the European Cooperative
Acute Stroke Study (ECASS) and Safe Implementation of Thrombolysis in Stroke:
Monitoring Study (SITS-MOST) provide more stringent criteria of a worsening of
at least 4 points in the NIHSS score associated with hemorrhage within 36 h of
stroke onset [16, 92].
Regardless of denition, any acute change in neurologic status should prompt
clinical evaluation and consideration for emergent repeat head imaging to assess for
bleeding. Patients typically undergo scheduled hourly or every other hour neurologic exams in the rst 24h after stroke to rapidly identify new decits and prompt
further evaluation. The NINDS trial protocol mandated a routine 24-h head CT to
screen for hemorrhagic conversion, and while this practice has been questioned
[93], it provides a “cap” to the 24-h monitoring window when patients are most
likely to experience hemorrhagic conversion.
Treatment of hemorrhagic conversion should involve an assessment of the time
from thrombolysis administration (if administered) and if other factors that could
contribute to conversion (i.e., coagulopathy, antithrombotic therapy) are present.
The 2019 acute stroke guidelines and 2017 AHA/ASA scientic statement on hemorrhagic transformation after alteplase provide treatment recommendations for
patients who experience conversion [7, 91]. First, patients who experience minor,
asymptomatic hemorrhagic conversion (such as HI1 per the Heidelberg criteria)
may not require alterations in management. Patients with petechial hemorrhagic
conversion generally tolerate the initiation of antiplatelet agents, and petechial hemorrhage was not an exclusion criterion for the ELAN trial, which evaluated early
initiation of DOACs in stroke patients [69, 94]. In patients with sICH, deciding
whether to provide hemostatic therapy (“thrombolytic reversal”) should be based
primarily on the timing of thrombolytic administration. While the alteplase and
tenecteplase are terminally eliminated after 6 and 12h, respectively, the effect of
plasminogen activation persists for longer than the medications are present in circulation. Alteplase and tenecteplase exhibit both their intended pharmacologic action
and their potential toxicities (bleeding) indirectly (i.e., through activation of plasminogen to plasmin, where plasmin then dissolves brin into brin degradation
products); therefore, reversal should take into account both the pharmacokinetic
properties of the parent agents and the pharmacodynamic relationship between the
thrombolytic and the endogenous coagulation system. Fibrinogen, plasminogen,
and D-dimer concentrations have been used as surrogates for this relationship and
remain altered up to 24 h after thrombolytic administration [94, 95]. Therefore,
treating sICH that occurs within 24h of thrombolytic administration with hemostatic therapy may be reasonable to prevent hemorrhagic expansion.
Specic agents to consider when treating thrombolytic-associated sICH are summarized in Table17.9. Notably, none are direct reversal agents for the thrombolytic
agent itself per se but rather work to counteract the pharmacodynamic effect of
plasminogen activation. Additionally, dosing, monitoring, and considerations are
largely based on expert opinion, and no randomized controlled trials exist to guide
the selection of agents. Adjunctive agents, including prothrombin complex concentrate, vitamin K, fresh frozen plasma (FFP), platelet transfusion, or recombinant
17 Acute Ischemic Stroke
Table 17.9 Hemostatic therapy for sICH after thrombolysis administration [16, 56]
Agent Dosing Notes
Cryoprecipitate IV 10units 10units are expected to increase serum
Fibrinogen
concentrate (RiaSTAP,
Fibryga) IV
Tranexamic acid IV 10mg/kg (consider
Aminocaproic acid IV 4g infusion over 1h
40–70mg/kg
If baseline brinogen is
known, can calculate
dose:
Dose in mg/kg=(150
measured brinogen [mg/
dL])/1.7
empiric dosing of
1000mg)
followed by 1g/h for 8h
or until stable on repeat
imaging
brinogen by 50mg/dL
Consider repeating until serum brinogen
≥150mg/dL. Note: tenecteplase does not
signicantly affect serum brinogen
concentrations
Dosing extrapolated from recommendations
for congenital brinogen deciency
457
factor VIIa, can be considered in specic circumstances but generally do not have a
role in therapy for bleeding associated with thrombolytics. Despite this, treatment
with adjunct agents is common—in a multicenter cohort study of 128 patients who
experienced thrombolytic-associated sICH, 28.9% received a platelet transfusion,
20.3% received FFP, and 10.1% received vitamin K, PCC, or rFVIIa. None were
protective for in-hospital mortality or hematoma expansion, and platelet transfusion
was found to be associated with a higher rate of hematoma expansion (45.8 vs.
18.9%, p= 0.01) [96]. Lack of treatment with any product was common (38.2%
received no therapy), which may suggest confounding by indication, where more
severely ill patients received a higher intensity of therapy.
The role of cryoprecipitate or brinogen concentrate is to correct hypobrinogenemia, which is both a consequence of thrombolytic administration and a potential mediator of hemorrhagic conversion. Treatment typically targets a serum
brinogen concentration of ≥150mg/dL, but it is reasonable to treat even if brinogen concentrations are above this at baseline. Tenecteplase does not signicantly
affect serum brinogen concentrations, and thus repeat dosing to a target brinogen
concentration in patients who received tenecteplase may not be feasible [95]. Blood
banks often release pools of cryoprecipitate in batches of 10units, which is the basis
for the empiric dosing recommendation, but this may vary by institution. A cohort
study of 19 patients who received cryoprecipitate for thrombolysis-associated sICH
reported that the median dose was 5units, likely because this was the size of the pool
released by the institution’s blood blank. In this cohort, the median time to administration was 6.9h after alteplase administration, 74% of patients received concurrent
alternative blood products, and rates of thrombosis were low (5%). Hemostasis,
458
B. Barlow et al.
dened as stable ICH size on repeat head imaging within 24h of hemostatic therapy
administration, was observed in 4 of the 14 (29%) patients who had imaging available for evaluation [97]. A similar cohort of 24 patients who received brinogen
concentrate for thrombolysis-associated sICH received a median dose of brinogen
concentrate of 2215mg (mg/kg dose not reported) and reported a thrombosis rate of
12.5%. In this cohort, a higher rate of hemostasis was observed (77.2%) [98].
Support for the use of antibrinolytic agents to supplement treatment in
thrombolytic- associated sICH is mostly limited to case reports and series. Three
case reports describe effective hemostasis with tranexamic acid after thrombolysisassociated sICH, with doses ranging from 1000 to 1670mg [99–101]. TXA was
selected either because of patient preference not to receive blood products, hyperbrinolysis was identied on rotational thromboelastometry (ROTEM), or the patient
experienced a transfusion reaction to cryoprecipitate. Outcomes associated with
aminocaproic acid have been described in two case series by the same author group.
The rst is a cohort of 16 patients who received aminocaproic acid for thrombolysisassociated hemorrhage, of which 10 had received alteplase for stroke. Dosing varied, but the median bolus dose was 4g, and the median infusion dose was 1g/h for
5 h. Half of the included patients only received a single bolus. Of the included
patients who received alteplase for stroke and experienced sICH (7/10), 50% of
patients with evaluable repeat imaging (2/4) achieved hemostasis [102]. In a follow up series by the same authors evaluating cryoprecipitate (discussed above), receipt
of both cryoprecipitate and aminocaproic acid was associated with a 67% rate of
hemostasis compared to 8% for cryoprecipitate alone [97].
Other aspects of managing hemorrhagic conversion follow similar principles to
spontaneous ICH.It is reasonable to acutely control blood pressure and maintain
SBP less than 140 mm Hg, avoid fever, avoid hyperglycemia, and reverse other
potential coagulopathies. While secondary causes of ICH were excluded from key
trials evaluating these interventions in ICH [103], the principles likely apply to
hemorrhagic conversion as well.
17.6.2 Angioedema
An additional acute complication of acute ischemic stroke in patients treated with
intravenous thrombolysis is contralateral orolingual angioedema. Angioedema is
rare following thrombolysis, occurring in approximately 1–5% of treated patients,
but it can be life threatening if not identied early and managed appropriately [62].
The endogenous brinolytic system is directly involved in the activation and upregulation of the kallikrein-bradykinin system and has been implicated in the pathophysiology of hereditary angioedema (HAE) [104]. The introduction of recombinant
tissue plasminogen activator to serum thus accelerates the generation of bradykinin
and increases the risk of angioedema, as has been seen with alteplase and tenecteplase
treatment in patients with stroke [105, 106].
17 Acute Ischemic Stroke
459
Several factors notably increase the risk of angioedema in patients treated with
intravenous thrombolysis. Strokes localized to the right insulo-opercular area have
been associated with angioedema [106, 107], as has pre-stroke treatment with ACE
inhibitors [108]. A meta-analysis of 12 observational cohort studies identied that
patients on ACE inhibitors had more than a ve-times greater risk of developing
angioedema compared to patients not on ACE inhibitors (crude prevalence of 12.58
vs. 1.97%). This effect was distinct to ACE inhibitors, as rates of angioedema were
similar in patients taking angiotensin receptor blockers, beta-blockers, diuretics,
and calcium channel blockers [108]. Rates of angioedema appear to be similar
between alteplase and tenecteplase, although evidence evaluating this endpoint is
limited [109].
While angioedema following thrombolysis can be mild and self-limiting, the
need for urgent intubation and ultimately tracheostomy because of persistent angioedema has been reported [110]. Angioedema onset is typically rapid, within 1–2h
of thrombolysis administration in most cases [111]. If angioedema develops during
alteplase infusion, the infusion should be discontinued immediately.
The 2019 AHA/ASA guidelines for the management of acute ischemic stroke
provide a class 1B statement recommending preparedness for potential emergent
adverse events to thrombolysis, of which angioedema is specically listed [7].
Guideline-recommended management of thrombolysis-associated angioedema is
largely based on expert opinion and includes denitive securement of the airway if
needed, discontinuation of alteplase if infusion is still running, cessation of
angiotensin- converting enzyme (ACE) inhibitor therapy if currently ordered, and
treatment with intravenous corticosteroids, antihistamines (diphenhydramine and
famotidine), and nebulizers if needed. Therapies approved for HAE, such as icatibant or plasma-derived C1 esterase, are suggested, but it is unclear if these will be
effective in this population. Other therapies for angioedema, including fresh frozen
plasma (FFP), tranexamic acid (TXA), or ecallantide, are not mentioned and only
have case report-level evidence supporting their use for this indication. Therapy
recommendations are summarized in Table17.10.
17.6.3 Malignant Cerebral Edema
As neurons die after ischemic insult, they lose their ability to regulate electron gradients across cell membranes as the energy required to maintain sodium-potassium
ATP-ase pumps is no longer produced. Without electron gradients, water ows passively into neurons, causing progressive swelling and cytotoxic cerebral edema.
While some cerebral edema is present in nearly 25% of all strokes, “malignant”
cerebral edema (characterized by edema leading to mass effect and/or midline shift)
is less common, occurring in approximately 5% of patients and most commonly in
hemispheric MCA territory strokes [119]. Cerebral edema generally begins to
develop 24–48h after stroke onset, with incidence peaking at 3–5days [120], and
patients should be closely monitored for clinical signs of cerebral edema during this
460
Table 17.10 Therapies for thrombolysis-associated angioedema
Agent Dose Notes
First-line therapy
Methylprednisolone IV 125mg Can be scheduled every 6h if response is not immediate
Diphenhydramine IV 50mg Generally only needed once but can be scheduled every
Famotidine IV 20mg Generally only needed once but can be scheduled every
Second-line and rescue therapies
Epinephrine SC 0.3mg Generally avoided because of risk of posttreatment
Icatibant SC 30mg Approved for hereditary angioedema treatment; dose can
Plasma-derived C1
esterase inhibitor IV
(Ruconest, Berinert)
Ecallantide SC 30mg Approved for hereditary angioedema treatment. No
ranexamic acid IV 1000mg Theoretically benecial (inhibits bradykinin production).
T
20IU/kgApproved for hereditary angioedema treatment.
6–12h
12h
hypertension, but considered if not responding to
steroids and antihistamines
be repeated in 6h if insufcient response is noted.
Improvements have been observed in three case reports
and no response in one [112–115]
Improvements have been observed in one case report
[116]
published reports support its role for thrombolysisassociated angioedema
No published reports support its role for thrombolysisassociated angioedema, b
in ACEi-associated angioedema [117, 118]. Caution that
TXA may partially reverse the thrombolytic effect of
thrombolysis
ut cohort studies support its role
B. Barlow et al.
time period. Outcomes in the absence of surgical decompression are dismal; 78% of
patients in an early cohort of 55 patients who experienced malignant cerebral edema
died as a result of poststroke herniation [120]. Several factors, including younger
age, female sex, higher baseline NIHSS, early signs of ischemia and hyperdense
vessel sign on baseline head CT, and a history of diabetes, hypertension, atrial brillation, or heart failure, have been associated with increased odds of developing
malignant edema [119].
The management of patients who develop malignant cerebral edema after stroke is
summarized in a 2014 scientic statement from the American Heart Association and the
American Stroke Association and involves medical management of increased intracranial pressure and considerations for decompressive hemicraniectomy [121]. Strokes
involving the MCA territory and cerebellar hemispheres are at the highest risk of causing herniation and thus warrant the most aggressive management. Because of the low
quality of evidence with some signal for harm, both the 2014 malignant cerebral edema
recommendations and 2020 NCS cerebral edema guidelines recommend against the use
of prophylactic hyperosmolar agents in patients at risk of cerebral edema [121, 122].
Hyperosmolar therapy does have a role in patients who develop clinical or radiographic signs of mass effect with or without clinical herniation, however. If patients
17 Acute Ischemic Stroke
461
develop worsening levels of consciousness, signs of Cushing’s triad (bradycardia,
widening pulse pressure, irregular respirations), or changes in brainstem reexes,
urgent imaging should be obtained to assess for the development of edema and
hyperosmolar therapy should be considered. Bolus hyperosmolar therapy (sodium
chloride 3 or 23.4% or mannitol 20 or 25%) is preferable to continuous infusion in
the setting of acute increases in intracranial pressure, as boluses have been reported
to reverse clinical herniation [123]. There is insufcient evidence to support whether
hypertonic solutions should be given on an “as-needed” basis for clinical events or
if scheduled hyperosmolar therapy is ideal.
In cases of severe hemispheric cerebral edema, medical management with hyperosmolar therapy is insufcient to adequately treat increased intracranial pressure.
Hypertonic solutions establish an osmotic gradient across a healthy blood-brain barrier to cause a shift in water content out of brain tissue and out of the cranial vault and
also improve the rheological properties of red blood cells to improve perfusion to atrisk tissue. Because the blood-brain barrier is damaged in ischemic tissue, hypertonic
solutions mainly shrink the volume of non-infarcted tissue and may not impact the
volume of edema in the stroke bed. In one study of seven patients with hemispheric
strokes with midline shift who were administered 1.5g/kg of mannitol, brain volume
overall decreased by an average of 8.1mL (0.62%). The decrease was primarily in the
non-infarcted hemisphere, however, with an average decrease of 0.82% in the noninfarcted hemisphere vs. 0.0% in the infarcted hemisphere (p<0.05) [124].
If edema progresses, the denitive management involves decompressive
hemicraniectomy. Decompressive hemicraniectomy has been evaluated in nine
randomized controlled trials and has uniformly been found to be a lifesaving
procedure in patients with malignant cerebral edema. Trials generally randomized patients without substantial premorbid disability who presented with
strokes occupying 50–66% of the MCA or cerebellar vascular territory within
24–48 h of symptom onset associated with high baseline NIHSS scores and
alterations in levels of consciousness to surgical decompression or medical
management [125]. Across 526 randomized patients, surgical decompression
was associated with a signicant reduction in the risk of death at 6–12months
(OR 0.18, 95% CI 0.12–0.27) as well as death or disability (mRS >3) at
6–12months (OR 0.34, 95% CI 0.22–0.52), but rates of severe disability (mRS
5) were similar between arms (OR 0.73, 95% CI 0.36–1.44). While the number
of patients who experienced severe disability is higher in those who underwent
decompression, this is counterbalanced by the number of patients who survive
and are able to recover to lower levels of disability. Mortality is common in
patients managed with medical therapy alone (68.3%). Positive effects of
decompression are consistent between younger (<60years) and older (>60years)
patients and whether decompression occurred before or after 48h from symptom onset, although a trend towards improved outcomes with earlier decompression was noted [126]. While additional trials have been published since the
AHA/ASA recommendation, the 2014 recommendation provides a class I LOE
B recommendation for decompressive hemicraniectomy in patients <60years of
462
B. Barlow et al.
age with hemispheric infarctions who experience neurologic deterioration and a
class IIb LOE C recommendation for patients >60years of age.
Post-decompression, it is unclear what the role of hypertonic therapy is, as the
restrictive effect of the skull has been removed from the mass lesion. It may be reasonable to continue therapy post-decompression to prevent rebound edema.
Additional medical management considerations post-decompressive hemicraniectomy include seizure prophylaxis, as seizures occur in 25–36% of patients within a
week of decompression [127–129]. Prophylaxis with levetiracetam 500–1000mg
twice daily may be reasonable for 1week post-decompression, although evidence
supporting this is limited to retrospective observational data. It may also be reasonable to withhold antithrombotic secondary stroke prevention therapy for 2–7days
postoperatively, but it is unknown when the ideal time to resume antiplatelet or
anticoagulant therapy is after a hemicraniectomy.
17.7 Secondary Prevention
The risk of stroke recurrence is highest within the rst 30days post-event, a risk
which can be mitigated with appropriate secondary preventive measures. Secondary
prevention of stroke includes a comprehensive approach to risk factor modication,
stroke prevention, diet and lifestyle adjustment, and prevention of complications. A
simplied acronym to remember the key factors of secondary stroke prevention
includes the “ABCDEFGs.” A stands for antithrombotic therapy, either antiplatelet
or anticoagulant, which should be prescribed during the hospital stay. Patients with
atrial brillation should have an appropriate prescription for an oral anticoagulant,
with counseling provided to ensure that patients are aware of the signs and symptoms of recurrent stroke or bleeding events. As mentioned in the previous section on
antiplatelet therapy, candidates for DAPT should be sure that they are informed of
the appropriate duration of therapy (21 vs. 90days) to minimize the risk of adverse
sequelae from prolonged treatment. B stands for blood pressure control. Patients
with hypertension poststroke should be prescribed guideline-based antihypertensives, including an ACEi, ARB, or thiazide diuretic, which have been shown to
effectively lower BP and risk of recurrent stroke [13, 130]. The optimal blood pressure target for long-term management is <130/80mmHg [13]. C stands for smoking
cessation and cholesterol management with high-intensity statin therapy. Smoking
cessation is a critical factor in reducing the risk of stroke recurrence, as persistent
smoking after an initial event increased the risk of recurrent stroke 1.68-fold with
10–20 cigarettes a day which increases to 2.72in those who smoke more than 40
cigarettes daily [131]. Smoking cessation strategies can include nicotine replacement therapies (patch, gum, lozenges) or use of prescription-based treatments such
as varenicline or bupropion [132]. A meta-analysis of 11 randomized trials and 12
observational studies found that statins reduced the risk of recurrent stroke by
20–33% [133]. Patients should be discharged on a high-intensity statin (atorvastatin
40–80 mg, rosuvastatin 20–40 mg) with a target LDL <70 mg/dL [13]. Diet,
17
Acute Ischemic Stroke
463
exercise, u vaccination, and glucose control complete the DEFGs of secondary
stroke prevention management, all of which are important educational points for
patients upon discharge. Addressing barriers to adherence for medications and lifestyle should also be addressed to ensure the best possible outcomes for patients.
References
1. Tsao CW, Aday AW, Almarzooq ZI, etal. Heart disease and stroke statistics-2023 update: a
report from the American Heart Association. Circulation. 2023;147(8):e93–e621. https://doi.
org/10.1161/CIR.0000000000001123.
Pu L,
2.
3.
4.
5. Aroor S, Singh R, Goldstein LB.BE-FAST (balance, eyes, face, arm, speech, time): reduc-
6. Demel SL, Broderick JP.Basilar occlusion syndromes. Neurohospitalist. 2015;5(3):142–50.
7. Powers WJ, Rabinstein AA, Ackerson T, etal. Guidelines for the early management of patients
8. Eddelien HS, Butt JH, Christensen T, Danielsen AK, Kruuse C.Sex and age differences
9. Nicholls JK, Ince J, Minhas JS, Chung EML.Emerging detection techniques for large vessel
10. Jovin TG, Demchuk AM, Gupta R. Pathophysiology of acute ischemic stroke.
Wang L, Zhang R, Zhao T, Jiang Y, Han L. Projected global trends in ischemic
stroke incidence, deaths and disability-adjusted life years from 2020 to 2030. Stroke.
2023;54(5):1330–9. https://doi.org/10.1161/STROKEAHA.122.040073.
Zhao H, Pesa
Stroke. 2018;49(4):945–51. https://doi.org/10.1161/STROKEAHA.117.019307.
Huwez F
ing for detection of posterior circulation strokes. Int J Stroke. 2013;8(3):E3. https://doi.
org/10.1111/ijs.12008.
ing the proportion of strokes missed using the FAST mnemonic. Stroke. 2017;48(2):479–81.
https://doi.org/10.1161/STROKEAHA.116.015169.
https://doi.org/10.1177/1941874415583847.
with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management
of acute ischemic stroke a guideline for healthcare professionals from the American Heart
Association/American Stroke A. Stroke. 2019;50(49):e344–418. https://doi.org/10.1161/
STR.0000000000000211.
in patient-reported acute stroke symptoms. Front Neurol. 2022;13:846690. https://doi.
org/10.3389/fneur.2022.846690.
occlusion stroke: a scoping review. Front Neurol. 2022;12:780324. https://doi.org/10.3389/
fneur.2021.780324.
Continuum Lifelong Learning Neurol. 2008;14(6):28. https://doi.org/10.1212/01.
vento L, Coote S, etal. Ambulance clinical triage for acute stroke treatment.
, Casswell EJ.FAST-AV or FAST-AB tool improves the sensitivity of FAST screen-
Allen LM, Hasso AN, Handwerker J, Farid H.Sequence-specic MR Imaging ndings that
11.
are useful in dating ischemic stroke. Radiographics. 2012;32(5):1285–97; discussion 1297-9.
https://doi.org/10.1148/rg.325115760.
12. Adams HP, Bendixen BH, Kappelle LJ, etal. Classication of subtype of acute ischemic
stroke. Denitions for use in a multicenter clinical trial. TOAST.Trial of Org 10172in Acute
Stroke Treatment. Stroke. 1993;24(1):35–41. https://doi.org/10.1161/01.str.24.1.35.
13. Kleindorfer DO, Towghi A, Chaturvedi S, et al. 2021 guideline for the prevention of
stroke in patients with stroke and transient ischemic attack: a guideline from the American
Heart Association/American Stroke Association. Stroke. 2021;52(7):e364–467. https://doi.
org/10.1161/STR.0000000000000375.
14.
Tsi
vgoulis G, Katsanos AH, Sandset EC, etal. Thrombolysis for acute ischaemic stroke:
current status and future perspectives. Lancet Neurol. 2023;22(5):418–29. https://doi.
org/10.1016/S1474-
4422(22)00519- 1.
464
15. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.
Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581–8.
https://doi.org/10.1056/NEJM199512143332401.
16.
17.
18.
19.
20. Campbell BCV, Ma H, Ringleb PA, etal. Extending thrombolysis to 4·5-9 h and wake-up
21.
22.
23.
24.
25.
26. Goyal M, Menon BK, van Zwam WH, etal. Endovascular thrombectomy after large-vessel
27.
28.
29.
30.
31.
32. Tao C, Nogueira RG, Zhu Y, et al. Trial of endovascular treatment of acute basilar-artery
e W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after
Hack
acute ischemic stroke. N Engl J Med. 2008;359(13):1317–29. https://doi.org/10.1056/
NEJMoa0804656.
Emberson J, Lees KR, L
effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis
of individual patient data from randomised trials. Lancet. 2014;384(9958):1929–35. https://
doi.org/10.1016/S0140- 6736(14)60584- 5.
Charbonnier G, Bonnet L, Biondi
therapy in acute ischemic stroke. Front Neurol. 2021;11:11. https://doi.org/10.3389/
fneur.2020.629920.
Thomalla G, Simonsen CZ, Boutitie F
unknown time of onset. N Engl J Med. 2018;379(7):611–22. https://doi.org/10.1056/
NEJMoa1804355.
stroke using perfusion imaging: a systematic review and meta-analysis of individual patient
data. Lancet. 2019;394(10193):139–47. https://doi.org/10.1016/S0140- 6736(19)31053- 0.
Menon BK, Singh N, Sylaja PN.
Lancet. 2023;401(10377):618–9. https://doi.org/10.1016/S0140- 6736(22)02633- 2.
Thon JM, Heslin M, etal. Tenecteplase improves door-to-needle time in real-world acute
Hall J,
stroke treatment. Stroke. 2021;1(1):e000102. https://doi.org/10.1161/SVIN.121.000102.
obeissi H, Ghozy S, Turfe B, etal. Tenecteplase vs. alteplase for treatment of acute isch-
K
emic stroke: a systematic review and meta-analysis of randomized trials. Front Neurol.
2023;14:1102463. https://doi.org/10.3389/fneur.2023.1102463.
Kvistad CE, Næss H, Helleber
of acute ischaemic stroke in Norway (NOR-TEST 2, part a): a phase 3, randomised, openlabel, blinded endpoint, non-inferiority trial. Lancet Neurol. 2022;21(6):511–9.
org/10.1016/S1474-
Alamowitch S, Turc G, Palaiodimou L, etal. European Stroke Organisation (ESO) expedited
recommendation on tenecteplase for acute ischaemic stroke. Eur Stroke J. 2023;8(1):8–54.
https://doi.org/10.1177/23969873221150022.
ischaemic stroke: a meta-analysis of individual patient data from ve randomised trials.
Lancet. 2016;387(10029):1723–31. https://doi.org/10.1016/S0140-
Nogueira RG, Lutsep HL, Gupta R, et
cularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised
trial. Lancet. 2012;380(9849):1231–40. https://doi.org/10.1016/S0140-
Nogueira RG, Jadha
with a mismatch between decit and infarct. N Engl J Med. 2018;378(1):11–21. https://doi.
org/10.1056/NEJMoa1706442.
Albers GW
tion by perfusion imaging. N Engl J Med. 2018;378(8):708–18. https://doi.org/10.1056/
NEJMoa1713973.
Liu X, Dai Q,
vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial. Lancet
Neurol. 2020;19(2):115–22. https://doi.org/10.1016/S1474-
Langezaal LCM, v
stroke due to basilar-artery occlusion. N Engl J Med. 2021;384(20):1910–20. https://doi.
org/10.1056/NEJMoa2030297.
occlusion. N Engl J Med. 2022;387(15):1361–72. https://doi.org/10.1056/NEJMoa2206317.
, Marks MP, Kemp S, etal. Thrombectomy for stroke at 6 to 16 hours with selec-
yden P, etal. Effect of treatment delay, age, and stroke severity on the
A, Moulin T. Intracranial bleeding after reperfusion
, et al. MRI-guided thrombolysis for stroke with
Tenecteplase use in patients with acute ischaemic stroke.
g BH, etal. Tenecteplase versus alteplase for the management
4422(22)00124- 7.
6736(16)00163- X.
al. Trevo versus merci retrievers for thrombectomy revas-
v AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke
Ye R, et al. Endovascular treatment versus standard medical treatment for
4422(19)30395- 3.
an der Hoeven EJRJ, Mont’Alverne FJA, etal. Endovascular therapy for
B. Barlow et al.
https://doi.
6736(12)61299- 9.
cute Ischemic Stroke
17
A
33. Jovin TG, Li C, Wu L, et al. Trial of thrombectomy 6 to 24 hours after stroke due to
basilar-
artery occlusion. N Engl J Med. 2022;387(15):1373–84.
NEJMoa2207576.
34.
35.
36. Yoshimura S, Sakai N, Yamagami H, etal. Endovascular therapy for acute stroke with a
37.
38.
39.
40.
41. Yogendrakumar V, Churilov L, Guha P, et al. Tenecteplase treatment and thrombus char-
42.
43.
44.
45.
46.
47.
48.
49.
50.
A, Drumm B, D’Anna L, et al. Mechanical thrombectomy in acute basilar artery
Malik
stroke: a systematic review and meta-analysis of randomized controlled trials. BMC Neurol.
2022;22(1):415. https://doi.org/10.1186/s12883- 022- 02953- 2.
Bendszus M, Fiehler J, Subtil F
stroke with established large infarct: multicentre, open-label, randomised trial. Lancet.
2023;402(10414):1753–63. https://doi.org/10.1016/S0140- 6736(23)02032- 9.
large ischemic region. N Engl J Med. 2022;386(14):1303–13. https://doi.org/10.1056/
NEJMoa2118191.
gler JE, Qureshi MM, Nogueira RG, etal. Endovascular vs medical management for late
Sie
anterior large vessel occlusion with prestroke disability. Neurology. 2023;100(7):e751–63.
https://doi.org/10.1212/WNL.0000000000201543.
atel K, Taneja K, Shu L, et al. Anterior circulation thrombectomy in patients with low
P
national institutes of health stroke scale score: analysis of the national inpatient sample.
Stroke 2023 4(2):e000998. https://doi.org/10.1161/SVIN.123.000998.
ung EL, McTaggart RA, Baird GL, etal. Rethinking thrombolysis in cerebral infarction 2b.
T
Stroke. 2017;48(9):2488–93. https://doi.org/10.1161/STROKEAHA.117.017182.
ollenweber FA, Tiedt S, Alegiani A, et al. Functional outcome following stroke
W
Thrombectomy in clinical practice. Stroke. 2019;50(9):2500–6. https://doi.org/10.1161/
STROKEAHA.119.026005.
acteristics associated with early reperfusion: an EXTEND-IA TNK trials analysis. Stroke.
2023;54(3):706–14. https://doi.org/10.1161/STROKEAHA.122.041061.
PSS, Berkhemer OA, Lingsma HF, etal. Time to reperfusion and treatment effect for
Fransen
acute ischemic stroke: a randomized clinical trial. JAMA Neurol. 2016;73(2):190–6. https://
doi.org/10.1001/jamaneurol.2015.3886.
A, Millán M, San Román L, etal. Effect of intra-arterial alteplase vs placebo follow-
Renú
ing successful thrombectomy on functional outcomes in patients with large vessel occlusion
acute ischemic stroke: the CHOICE randomized clinical trial. JAMA. 2022;327(9):826–35.
https://doi.org/10.1001/jama.2022.1645.
AI, Suri MF, Shatla AA, etal. Intra-arterial recombinant tissue plasminogen activa-
Qureshi
tor for ischemic stroke: an accelerating dosing regimen. Neurosurgery. 2000;47(2):473–6.
discussion 477–9
giadis AL, Memon MZ, Shah QA, etal. Intra-arterial tenecteplase for treatment of acute
Geor
ischemic stroke: feasibility and comparative outcomes. J Neuroimaging. 2012;22(3):249–54.
https://doi.org/10.1111/j.1552-
Zhao ZA, Qiu J,
pass recanalization for acute ischemic strok
TNK trial. Front Neurol. 2023;14:1155269. https://doi.org/10.3389/fneur.2023.1155269.
y M, Lenck S, Degos V, et al. Cangrelor and stenting in acute ischemic stroke:
Elhoran
monocentric case series. Clin Neuroradiol. 2021;31(2):439–48. https://doi.org/10.1007/
s00062-
020- 00907- 0.
Holden DN, Entezami P
cangrelor utilizing platelet function testing in neuroendovascular patients. Pharmacotherapy.
2021;41(10):811–9. https://doi.org/10.1002/phar.2619.
Qureshi
adult patients presenting to the emergency department with stroke in the United States. Am J
Emerg Med. 2007;25(1):32–8. https://doi.org/10.1016/j.ajem.2006.07.008.
er B, Lu M, Morris DC, Mitsias PD, Lewandowski C, Chopp M.Blood pressure declines
Silv
and less favorable outcomes in the NINDS tPA stroke study. J Neurol Sci. 2008;271(1–2):61–7.
https://doi.org/10.1016/j.jns.2008.03.012.
Wang L, etal. Intra-arterial tenecteplase is safe and may improve the rst-
, Bush MC, etal. Characterization of antiplatelet response to low-dose
AI, Ezzeddine MA, Nasar A, etal. Prevalence of elevated blood pressure in 563,704
, et al. Endovascular thrombectomy for acute ischaemic
6569.2011.00628.x.
e with large-artery atherosclerosis: the BRETIS-
https://doi.org/10.1056/
465