Thrombolysis without TPA aims to result to thrombus that is occluding the cerebral artery in patients with acute ischemic stroke. Intravenous thrombolysis has been available since 2002. Initially, it was indicated in patients with ischaemic stroke within three hours from onset. Many patients could not receive thrombolysis because they did not get a stroke referral center in time. Some years later in 2008, the treatment window was extended to 4.5 hours. Within this period of time, treatment without TPA is safe and improved patients prognosis. Approximately 15 percent of patients with ischemic stroke receive intravenous thrombolysis. However, intravenous rtPA cannot be given after this treatment window or in patients in whom the exact time of symptom onset is unknown such as patients who notice symptoms when waking up. It is also contraindicated if there's any medical situation that predisposes to risk of bleeding such as taking anti-coagulants with an INR above 1.7 or direct acting anticoagulants such as Delegate ran, Rivaroxaban, Apixaban or indoxiban, recent surgery or thrombocytopenia. It is important to remember that the earlier the treatment is given, the greater the benefits. The chance of recovery is increased three-fold if treatment is given within the first hour and a half from the start of symptoms, but only 1.5 volt if given after the first hour and a half. The procedure for administering intravenous thrombolysis consists of firstly, the patient must undergo neuro-imaging, usually a brain CT scan to rule out the presence of cerebral hemorrhage. Next, the contraindications must be reviewed to ensure that the treatment is given with maximum patient safety in mind. If thrombolysis is indicated, a dose of 0.9 milligrams per kilogram weight is given. It is given as an intravenous bolus of 10 percent of the total dose followed by an intravenous infusion over one hour. During this time, the clinical status of the patient must be monitored. It is important to maintain blood pressure below 185 over 105 during and after treatment to minimize the risk of hemorrhagic transformation of the cerebral infarct. The daughter needle time refers to the time elapsed from the patient's arrival at the hospital until the CT scan is performed. Contra-indications ruled out and treatment started. It should be as short as possible, ideally, under 30 minutes. Intravenous thrombolysis has a number of limitations that reduce its applicability and benefits. Firstly, the narrow window of treatment within 4.5 hours from the onset of symptoms means that many patients cannot receive treatment because they arrive at the stroke referral center after this time or because symptoms are noticed upon waking up and the exact time of onset is unknown. In addition, as mentioned before, certain medical situations countra indicate thrombolysis because of the increased risk of hemorrhage. The most serious and most feared complication is hemorrhagic transformation of the cerebral lymphocytes caused by reprofusion and the thrombolytic agent. This complication is uncommon, occurring in under 5 percent of the patients but it can be very serious. Lastly, in cases where the thrombus is large and located in one of the main cerebral arteries, treatment with intravenous RTPA has a very limited efficacy and dissolves the clotting only 30 percent of the cases. When the cause of ischemic stroke is occlusion of a large brain vessel, the most effective treatment for reestablishing cerebral blood flow is endovascular treatment. A catheter is introduced and advanced within the arteries towards the thrombus, which is then extracted with the use of several mechanical thrombectomy devices. Endovascular treatment allows recanalisation of the occluded artery to 80 percent of cases. Endovascular treatment is indicated in two situations. One, as an additional treatment to intravenous thrombolysis with rtPA in patients with large vessel occlusions and two, as a primary treatment in patients with large vessel occlusion and contra-indications for rtPA. Before opting for endavascular treatment, neuro-imaging is performed to establish the exact site of arterial occlusion and the status of the cerebral tissue to determine if it is salvageable and can be recovered or if the damage is completely irreversible. Initially, a non-contrast CT scan is done which can rule out if there's an established pain in fact, which would mean that the cerebral tissue was already irreversibly damaged and so re-profusion would not provide any benefits. Next, an angiographic study is done that allows us to identify the sites of the clot, ascertain if there's any blood flow to the affected area known as collateral circulation, and visualize the status of cervical arteries through which the catheter will pass. In some cases, more complex neuro-imaging techniques are performed such as multi-modal magnetic resonance or re-profusion CT. Cerebral perfusion studies offer precise information about the areas of the brain that are already dead, and the areas that are under hypo-perfusion conditions. These areas are at risk of developing into an infarct if cerebral blood flow is not re-established, but it's still salvageable if the clot is removed. The difference between these two areas is called mismatch, and is a condition to indicate the endovascular treatment. Endovascular treatment is performed in an angiography theater with the involvement of a multi-disciplinary team composed of interventional neuro radiologists, a vascular neurologist, and an anaesthetist and a team of nurses and technicians. The intervention is usually performed with the patient under sedation. But if the patients clinical status requires it or if they are agitated and their movements make the procedure difficult, general anaesthetic may be necessary. The catheter is normally introduced via the femoral artery until it reaches the site of the occlusion. Once positioned correctly, the extraction device is introduced. Often stent retrievers are used. These are stents that are deployed at the site of the thrombus and are then removed along with the thrombotic material. The aspiration systems and neuro devices undergoing development may also be used. In 80 percent of the cases, successful clot extraction and re-profusion of the affected brain tissue is achieved. There are different degrees of re-profusion according to whether it is complete or partial. The patient's recovery depends on the degree of re-profusion and the time elapsed from the onset of symptoms to recanalisation of the cerebral re-profusion. In 2015, the New England Journal of Medicine published five clinical trials on thrombectomy. The result of these five studies all coincided in demonstrating the benefit of endovascular treatment with mechanical thrombectomy in patients with acute stroke due to large interior vessel occlusion within six to eight hours from the onset of symptoms. Despite the methodological differences, these trials demonstrated that patients who received endovascular treatment had between a 15 and 25 percent greater likelihood of achieving functional independence, modified ranking score between zero and two at three months. One analysis performed with individual data from the five clinical trials found that the distribution of the ranking scale at three months was much more favorable in the group of patients treated with thrombectomy. The percentage of patients who were functionally independent was 46 percent in the endovascular group versus the 26 percent in the control group. In addition, it demonstrated that the benefit from endovascular treatment was observed for all patient subgroups, independently of the size the lesion or previous neuro-imaging, the sites of the occlusion, the severity of the stroke or patient age. The benefit of intravascular treatment was demonstrated initially in patients with acute stroke under six-eight hours from symptom onset. Recently, the time window has been extended up to 24 hours or in patients with a known time from onset if advanced neuroimaging is used. Dawn and Defuse-3trials, New England Journal of Medicine 2018. It should be noted that the benefit from endovascular treatment decreases as time from onset of symptoms increases. It is calculated that for every 30 minutes of delay to recanalisation, the patient loses one month of healthy life. For this reason, it is important to speed up the process at all points. Healthcare systems must establish transfer circuits from the emergency medical services and between hospitals that allow patients with stroke, with suspected large vessel occlusion to quickly get to a hospital that can offer endovascular treatment. In-hospital times must also be reduced as much as possible. In the next few years, health care professionals will need to be trained in endovascular techniques so that this treatment can be offered in more centers. In summary, the aim of re-profusion treatment is to re-establish cerebral blood flow in patients with ischaemic stroke using intravenous rtPA thrombolysis and endovascular treatment in cases of large vessel occlusion. Time is extremely important in stroke management. There is clear evidence that benefits from all re-profusion treatments, whether intravenous or endovascular, are greater when the treatment is started earlier.
