**3. Current stroke management in the clinical setting: the first step after the stroke**

Early diagnosis of stroke is a predictor for better clinical outcomes [30]; therefore, its confirmation is a pressing matter for the treatment to begin as soon as possible from the recognition of symptoms onset [31]. Currently, different strategies for acute ischemic stroke are being used in the clinical setting and are part of the AHA/ASA clinical practice guidelines [32].

The differential diagnosis for stroke includes transient ischemic attacks, seizure, syncope, migraine, and brain tumors [33]. To establish a correct and timely diagnosis and to determine the best course of action, the clinician must rely on laboratory testing [34] (blood glucose is usually high, total cholesterol, LDL, HDL, AST, CPK-MB), and although the gold standard for diagnosis is a cerebral angiography, clinicians try to avoid it by choosing different methods such as imaging testing, including the first-line non-contrast CT scans, CT angiography, MRI, and MRI angiography [32, 35, 36]. In the earliest stages of acute stroke, CT scans are less useful for ischemic stroke diagnosis but can rule out hemorrhagic stroke [36]. Other clinical tests such as EKG, EEG, and the National Institutes of Health Stroke Scale (NIHSS) help establish differential diagnosis and treatment plan [35].

Specific and timely reperfusion treatment is essential to determine the course of the clinical outcome and to improve survival. Once the ischemic etiology has been established, and the patient is stable, treatment should start promptly. Currently, two major therapeutic strategies are being used to treat cerebral ischemia to allow for recanalization and reperfusion. The treatment of choice will depend on time to treatment and etiology of the injury; these therapies are thrombolysis using pharmacological agents and mechanical thrombectomy [35, 37–39].

At present and still after decades, the FDA only approves the use of recombinant tissue plasminogen activator (rTPA), also known as alteplase, as the sole pharmacological option for recanalization [35, 39]. Alteplase initiates local fibrinolysis when administered intravenously by hydrolyzing the peptide bond in plasminogen to form plasmin [40]. The standard IV dosage is 0.9 mg/kg for 60 min, with a 10% bolus over 1 min within 4.5 h of AIS onset [31].

Although alteplase is the only drug available for thrombolysis, most stroke sufferers do not receive this drug as treatment. There usually is a delay in

#### *Available Therapeutics after a Stroke: Current and Promising Options DOI: http://dx.doi.org/10.5772/intechopen.91282*

chemokines [25]. The production and release of these molecules promote the bloodbrain barrier (BBB) rupturing, thus causing peripheral leukocyte invasion into the

Microglial cells are then activated in the non-perfused region of the brain parenchyma [27], microglial cells acquire phagocytic characteristics and a predominantly pro-inflammatory phenotype (M1), which in turn increases the release of interleukin-6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), NO molecules, and prostanoids [28]. Peripheral immune cells such as neutrophils, B lymphocytes, T lymphocytes, and NK are recruited into the injured tissue, this event is thought to contribute both beneficially by inducing the release of antiinflammatory cytokines and growth factors, and negatively by increasing the lesion through a sustained release of proinflammatory cytokines and free radicals [29]. Within the process of the ischemic cascade, three points are identified that could classify as strategic to restore neuroprotection (ionic imbalance, excitotoxicity, and inflammation); nonetheless, most neuroprotective drugs act in many of the phases of the ischemic cascade, which is why they cannot be classified into a single step of

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

**3. Current stroke management in the clinical setting: the first**

(NIHSS) help establish differential diagnosis and treatment plan [35].

macological agents and mechanical thrombectomy [35, 37–39].

bolus over 1 min within 4.5 h of AIS onset [31].

**282**

Early diagnosis of stroke is a predictor for better clinical outcomes [30]; therefore, its confirmation is a pressing matter for the treatment to begin as soon as possible from the recognition of symptoms onset [31]. Currently, different strategies for acute ischemic stroke are being used in the clinical setting and are part of

The differential diagnosis for stroke includes transient ischemic attacks, seizure, syncope, migraine, and brain tumors [33]. To establish a correct and timely diagnosis and to determine the best course of action, the clinician must rely on laboratory testing [34] (blood glucose is usually high, total cholesterol, LDL, HDL, AST, CPK-MB), and although the gold standard for diagnosis is a cerebral angiography, clinicians try to avoid it by choosing different methods such as imaging testing, including the first-line non-contrast CT scans, CT angiography, MRI, and MRI angiography [32, 35, 36]. In the earliest stages of acute stroke, CT scans are less useful for ischemic stroke diagnosis but can rule out hemorrhagic stroke [36]. Other clinical tests such as EKG, EEG, and the National Institutes of Health Stroke Scale

Specific and timely reperfusion treatment is essential to determine the course of the clinical outcome and to improve survival. Once the ischemic etiology has been established, and the patient is stable, treatment should start promptly. Currently, two major therapeutic strategies are being used to treat cerebral ischemia to allow for recanalization and reperfusion. The treatment of choice will depend on time to treatment and etiology of the injury; these therapies are thrombolysis using phar-

At present and still after decades, the FDA only approves the use of recombinant tissue plasminogen activator (rTPA), also known as alteplase, as the sole pharmacological option for recanalization [35, 39]. Alteplase initiates local fibrinolysis when administered intravenously by hydrolyzing the peptide bond in plasminogen to form plasmin [40]. The standard IV dosage is 0.9 mg/kg for 60 min, with a 10%

Although alteplase is the only drug available for thrombolysis, most stroke

sufferers do not receive this drug as treatment. There usually is a delay in

injured brain parenchyma [26].

neuroprotection.

**step after the stroke**

the AHA/ASA clinical practice guidelines [32].

recognition of the symptoms and the time window in which rTPA must be administered is from 3 to 4.5 h from onset of symptoms, and benefits diminish over time [39, 41], which is why the new AHA/ASA guidelines recommend not waiting for clinical improvement before administration [32]. Also, not all patients are eligible, since candidates must be ≤80 years of age, without diabetes or stroke history, with an NIHSS score ≤ 25, not currently taking oral anticoagulation, and without radiologic evidence of ischemic injury involving more than one-third of the MCA territory [42].

Complications that are associated with its use are limited: BBB integrity alterations, and hemorrhagic transformation, granting that other studies have shown it to be well tolerated by patients using warfarin or other anticoagulants [38], in controversy with the new AHA/ASA guidelines that suggest it should not be administered if the patient received heparin 24 h before [32, 35, 43]. Other drugs are also available, such as aspirin, which must be delivered within 24–48 h after stroke onset. Although the guidelines emphasize that it should not be used to replace mechanical thrombectomy or IV alteplase, aspirin continues to be the choice for secondary prophylaxis [32, 44], even when the 2018 guidelines find no benefit from its use for the treatment of an ongoing AIS [32].

Furthermore, the FDA approves of endovascular treatments, which are reported to have a time window of up to 8 hours from the onset of symptoms [38].

For patients with large vessel occlusion, less responsive to rTPA, intra-arterial therapy is recommended, since it leads to higher recanalization rates by being able to infuse the drug directly into the occluded area or the clot itself [35, 45]. About 10% of patients with AIS fall into this category, but only a few centers can perform endovascular procedures in proper conditions [46].

Also, endovascular mechanical thrombectomy using contact aspiration (CA) [47], which has been described before [48], and stent retrievers (SR), especially those of new generations [49], for clot rupturing and aspiration has shown significant benefits in large vessel occlusion [50] regarding clinical outcomes and lower complication rates [49]. Notwithstanding, CA alone, without the use of a SR, is associated with a greater need for rescue treatment, and thus, worse outcomes [51]; the SR might also increase the risk for hemorrhagic transformation and neurological deficit [52].

Increased costs of endovascular treatments, as well as their complexity and need for trained personnel, cause patients to have less access to them. Therefore, exploring new pharmacological therapies should be continued.
