In the complete absence of blood flow, neuronal death occurs within 2–3 minutes from the exhaustion of energy stores. However, in most strokes, there is a salvageable penumbra (tissue at risk) that retains viability for a period of time through suboptimal perfusion from collaterals. Local cerebral edema from the stroke results in a compromise of these collaterals and progression of the ischemic penumbra to infarction if the flow is not restored and maintained. Prevention of this secondary neuronal injury drives the treatment of stroke and has led to the creation of designated Primary Stroke Centers that offer appropriate and timely triage and treatment of all potential stroke patients.
Entries from the 2018 AHA guidelines 1) are indicated by the corresponding level of the recommendation.
1. admit to ICU
2. frequent VS with crani checks (q 1 hr × 12 hrs, then if stable, q 2 hrs)
3. monitor cardiac rhythm
4. activity: bed rest
b) ★only blood glucose determination must precede initiation of IV tPA in all patients (Level I)
c) usefulness of CXR in the absence of cardiovascular indications is unclear, and should not delay IV tPA (LevelI I)
d) baseline EKG & cardiac troponins are recommended but should not delay IV tPA(LevelI).
EKG changes occur in 5–10% of AIS; acute MIs in 2–3%
e) “special”(when appropriate): RPR(to rule out neurosyphilis), ESR(to rule out giant cell arteritis), hepatic profile, cardiac (lipid) profile
f) at 24 hrs: CBC, platelet count, cardiac (lipid) profile, EKG
a) provide supplemental O2 to maintain O2 saturation > 94% (Level I)
b) airway support and ventilator for decreased level of consciousness or for bulbar dysfunction that compromises the patient’s ability to protect their airway (Level I)
c) supplemental O2 is not recommended in nonhypoxic patients (no benefit)
d) hyperbaric oxygen is not recommended except for air embolism (no benefit)
7. diet: NPO
8. nursing care
a) indwelling foley(urinary)catheter if consciousness impaired or if unable to use urinal or bedpan; intermittent catheterization q 4–6 hrs PRN no void if Foley not used
b) accurate’s&O’s;notify M.D.for urine output <20 cc/hr×2hrs by Foley,or<160ccin8hrs if no Foley
a) avoid hyperglycemia in the 1st 24hours after AIS(worse outcome).Goal:blood sugar 140–180 mg/dL (Level II)
rationale: hyperglycemia may extend the ischemic zone (penumbra)
b) avoid hypoglycemia < 60 mg/dL (Level I)
c) hyperglycemia and hypoglycemia may mimic AIS and should be treated if identified (tPA is not indicated for nonvascular conditions) (no benefit)
10. IV fluids:NS or 1/2N Sat 75–125cc/hr for most patients(to eliminate dehydration if present)
a) avoid glucose
b) avoid overhydration in cases ofICH, CHF, or SBP>180
a) treat recurrent seizures the same as for other neurologic conditions(LevelI)
b) prophylactic seizure medication is not recommended(no benefit)
12. treat CHF and arrhythmias.MI or myocardial ischemia maypresentwithneurodeficit 13. bloodpressure(BP)management: a) forpatientswithHTNwhoareotherwisecandidatesforIVtPA:carefullylowerSBP to < 185 mm Hg, and DBP to < 110 before giving IV-tPA (Level I1), and maintain < 180/105 for 24 hours after tPA (Level I1) otherwise, for general management, see Hypertension in stroke patients below b) avoidhypotensinandhypovolemia(LevelI1):nospecificsprovided.Suggestion:forpatients presenting with SBP < 110 or DBP < 70: ● unless contraindicated (viz.: ICH, cerebellar infarct, or decreased cardiac output) give 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 c) the benefit of drug-induced hypertension is not well-established in AIS (Level II1) 14. osmotictherapy(mannitol50to100gmIVover20minutesor3%saline):forclinicaldeteriora- tion from cerebral edema associated with AIS (Level II1) 15. patienttemperature: a) fever>38°C:identifyandtreatthesource,useantipyreticsasneeded(LevelI1) b) inducedhypothermia:useisnotwell-establishedandshouldonlybeemployedwithin approved clinical trials (Level II1) 16. othermedications a) corticosteroids(includingdexamethasone) ● ✖ not recommended for cerebral edema and/or increased ICP complicating stroke (poten- tial harm1) ● exceptions: steroid responsive vasculitis, e.g. giant cell arteritis (temporal arteritis), dem- onstration of associated brain tumor b) stoolsoftener
● noncontrast brain CT: the usual initial diagnostic tool of choice (image in ≤ 20 mins)
● thrombectomy is the standard of care for eligible patients: cerebral ischemia (including infarct) caused by LVO of the ICA or M1 segment of the MCA, 1) when it can be initiated within 6 hours of symptom onset or 2) if perfusion studies identify viable tissue 6–24 hours from onset
○ 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
Current guidelines for the treatment of acute ischemic stroke are mainly based on the time between symptom onset and initiation of treatment. This time is unknown in patients with wake-up stroke (WUS).
It is inadequately treated in the USA and worldwide due to a lengthy history of neuroprotective drug failures in clinical trials.
The rapid development of a neuroprotective or cytoprotective compound would allow future stroke victims to receive a treatment to reduce disabilities and further promote recovery of function.
A opinion article reviews in detail the enormous costs associated with developing a small molecule to treat stroke, as well as providing a timely overview of the cell-death time-course and relationship to the ischemic cascade. Distinct temporal patterns of cell-death of neurovascular unit components provide opportunities to intervene and optimize new cytoprotective strategies. However, adequate research funding is mandatory to allow stroke researchers to develop and test their novel therapeutic approach to treat stroke victims 2).
Research has reported how excitatory amino acids act as the major excitatory neurotransmitters in the cerebral cortex and hippocampus. Furthermore, other therapeutic targets such as free radical scavenger strategies and the anti-inflammatory neuroprotective strategy have been evaluated with conflicting data in animal models and human subjects with acute ischemic stroke. Whereas promising combinations of neuroprotection and neurorecovery, such as citicoline, albumin and cerebrolysin have been tested with findings worthy of further evaluation in larger randomized clinical trials. Understanding the complexities of the ischemic cascade is essential to developing pharmacological targets for acute ischemic stroke in neuroprotective or flow restoration therapeutic strategies 3).
Therapeutic hypothermia is increasingly recognized as having a tissue-protective function and positively influencing neurological outcome, especially in cases of ischemia caused by cardiac arrest or hypoxic-ischemic encephalopathy in newborns. Yet, many aspects of hypothermia as a treatment for ischemic stroke remain unknown. Large-scale studies examining the effects of hypothermia on stroke are currently underway 4).
Brain ischemia and treatment are one of the important topics in neurological science. Free oxygen radicals and inflammation formed after ischemia are accepted as the most important causes of damage. Currently, there are studies on many chemopreventive agents to prevent cerebral ischemia damage. The aim of Aras et al is to research the preventive effect of the active ingredient in genistein There is currently no promising pharmacotherapy aside from intravenous or intra-arterial thrombolysis. Yet because of the narrow therapeutic time window involved, thrombolytic application is very restricted in clinical settings. Accumulating data suggest that non-pharmaceutical therapies for stroke might provide new opportunities for stroke treatment 5).
Progression of focal stroke symptoms still constitutes a serious clinical problem for which heparin has insufficient effectiveness in clinical practice. New therapies, ideally preventive, are needed 6).
After cerebral ischemia, revascularization in the ischemic boundary zone provides nutritive blood flow as well as various growth factors to promote the survival and activity of neurons and neural progenitor cells. Enhancement of angiogenesis and the resulting improvement of cerebral microcirculation are key restorative mechanisms and represent an important therapeutic strategy for ischemic stroke.
Improvements in acute ischemic stroke (AIS) outcomes have been achieved with intravenous thrombolytics (IVT) and intra-arterial thrombolytics vs supportive medical therapy. Given its ease of administration, noninvasiveness, and most validated efficacy, IVT is the standard of care in AIS patients without contraindications to systemic fibrinolysis. However, patients with large-vessel occlusions respond poorly to IVT. Recent trials designed to select this population for randomization to IVT vs IVT with adjunctive endovascular therapy have not shown improvement in clinical outcomes with endovascular therapy. This could be due to the lack of utilization of modern thrombectomy devices such as Penumbra aspiration devices, Solitaire stent-trievers, or Trevo stent-trievers, which have shown the best recanalization results. Continued improvement in the techniques with using these devices as well as randomized controlled trials using them is warranted 8).
With the emergence of new technologies in imaging, thrombolysis and endovascular intervention, the treatment modalities of acute ischemic stroke will enter a new era 9).
Within 3 h from symptom onset, the existence of FLAIR-positive lesions on pretreatment MRI is significantly associated with an increased bleeding risk due to systemic thrombolysis. Therefore, considering FLAIR-positive lesions on baseline MRI might guide treatment decisions in ischemic stroke 10).