Targeted, expert neurological care for stroke patients in specialized stroke units and protocol-driven basic measures beforehand have led to a significant reduction in the late sequelae of stroke. Optimizing respiration and blood-pressure management are decisive elements in this chain of treatment. After cerebral hemorrhage has been excluded as the cause of the symptoms, and when there is definitive evidence of vascular occlusion, blood pressure values above the normal level of a maximum of 200–220 mmHg systolic are targeted. The patient’s temperature and blood glucose level have to be monitored and kept normal. Any form of excitement or agitation for the patient must be avoided, as the brain’s oxygen consumption increases by up to 50% due to stress-related neuronal activation. The primary goal of treatment for acute stroke is recanalization of the occluded cerebral vessel. Methods available included intravenous thrombolysis and endovascular, imaging-guided recanalization by interventional neuroradiologic methods. Treatment success is assessed at a clinical examination 3 months after the event, and the modified Rankin scale has become the internationally accepted standard for this (Table 1.4-2).
Table 1.4–2 Modified Rankin scale (mRS).
| 0 | No symptoms, no disability in daily living |
| 1 | No significant disability, despite some symptoms: able to carry out all usual tasks and activities. Slight neurological impairment possible |
| 2 | Slight disability: unable to carry out all previous activities, but able to look after own affairs without assistance. Clear neurological deficit |
| 3 | Moderate disability: requires some help, but able to walk unassisted. Clear neurological deficit |
| 4 | Moderately severe disability: unable to walk unassisted, unable to attend to own bodily needs without assistance. Limited mobility, limited communication |
| 5 | Severe disability: bedridden, incontinent, requires constant nursing care and attention. Barely any communication |
In some studies, death is scored as mRS 6.
1.4.5.1 Intravenous thrombolysis (IVT)
Thrombolytic agents were introduced for the treatment of stroke as early as the 1960s and 1970s. Patients were selected without any imaging procedures; the treatment was usually started too late, leading to very high rates of bleeding and mortality.
In the meantime, large studies totaling nearly 5000 patients have been carried out that have confirmed the efficacy of IVT within a time window of up to 4.5 hours after the onset of stroke. The National Institute of Neurological Disorders and Stroke (NINDS) study, published in 1995, included 624 patients with severe acute stroke (NIHSS 14). Within a 3-hour time window, half of the patients received a placebo and the other half were treated with intravenous administration of 0.9 mg rt-PA/kg body weight. A prior noncontrast CT examination excluded bleeding, but imaging evidence of a vascular occlusion was not required. No significant difference between the treatment group and the placebo group was observed within 24 hours. After 3 months, however, the patients treated with rt-PA showed a significantly better result than the placebo group (OR 1.7; 95% CI, 1.2 to 2.6; P = 0.008; number needed to treat: 7). Symptomatic intracerebral bleeding was observed in 6.4% of the treated patients, in comparison with 0.6% of the placebo patients. The publication of this study in 1995 led to approval in the United States for intravenous rt-PA administration at the above dosage within the 3-hour time window in the treatment of ischemic stroke.
Additional prospective, multicenter, and placebo-controlled studies in which the time window was extended to 6 hours achieved a significant improvement in the clinical outcome—the European Cooperative Acute Stroke Study (ECASS I and II) and the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) trial. Patients treated with IVT within up to 4.5 hours (ECASS III) were found after 3 months to have significantly better clinical findings—defined as mRS scores of 0 and 1— in comparison with the placebo group (52.4% vs. 45.2%, P = 0.04; n = 821). However, if mRS 2 is also included as a “good outcome,” the result is no longer significant, and the ECASS III study treated relatively mild cases of stroke (average NIHSS 9). The mortality rate also did not differ between the two groups, while symptomatic intracranial bleeding at 2.4% in the rt-PA group was very low, but significantly higher than in the control group (0.2%).
The disadvantage in the above studies is that no imaging documentation was available regarding the site of occlusion and the recanalization results. It is therefore clear that the studies must also have included patients in whom a vascular occlusion was not present or had already recanalized. The patients were therefore exposed to an unnecessary and indefensible risk of cerebral bleeding. Administering thrombolytic agents without positive CT, MRI, or angiographic evidence of vascular occlusion explaining the clinical symptoms is no longer acceptable given the currently available information.
When the initial findings and effect of intravenous treatment are documented with imaging or ultrasound methods, it is found that the efficacy of IVT declines with increasing vascular calibers. Adequate recanalization with IVT has been demonstrated using transcranial Doppler ultrasound 1 hour later in cases of occlusion of the internal carotid artery, middle cerebral artery, and anterior cerebral artery (carotid T occlusion) in 6% of cases, while recanalization of the main trunk of the middle cerebral artery (M1 occlusion) occurs in approximately 30% of cases and recanalization of branch occlusions (M2 occlusion) occurs in approximately 44% (Clotbust study). IVT-treated M1 occlusions that were reexamined using MRI after approximately 24 hours showed a persistent M1 occlusion in 30% of cases; minimal capillary recanalization was seen in 30% (TIMI 1); partial recanalization was found in 21% and complete recanalization (TIMI 3) in only 17%.
The advantage that IVT is rapidly and widely available stands in distinct contrast to the disadvantages of the low recanalization rate in large vessels, the associated bleeding complications, and the narrow time window of a maximum of 4.5 hours.
1.4.5.2 Endovascular stroke treatment
Local intra-arterial thrombolysis
Following pioneering studies by Zeumer, Mori, and Theron, it was the Prolyse in Acute Cerebral Thromboembolism (PROACT) I and II studies that subsequently confirmed the efficacy of intra-arterially administered prourokinase in the treatment of severe stroke (NIHSS 17). In both studies, angiographically documented occlusions of the middle cerebral artery were treated if it was possible to initiate the treatment within 6 hours of the start of symptoms. After documentation of the vascular occlusion, the treatment consisted of navigating a microcatheter into the M1 segment up to just in front of the occlusion. In 26 patients, 6 mg of prourokinase was injected locally for a period of up to 90 minutes, and in 14 patients only saline was injected (PROACT I). In the PROACT II trial, a maximum of 9 mg of prourokinase was injected for a maximum of 2 hours in front of the thrombus in 121 patients and the results were compared with 59 patients in whom only saline was injected as a placebo. Recanalization of the middle cerebral artery was observed in 66% of the patients who received intra-arterial thrombolysis, in comparison with 18% in the placebo group. After 3 months, only 25% of the patients in the placebo group had good clinical results (defined and measured as mRS 0–2), in comparison with 40% of those who were treated with prourokinase. The rate of symptomatic intracerebral bleeding among the patients who underwent thrombolysis was higher, at 10%, compared with the control group (2%).
Two other prospective studies have also confirmed the efficacy of local thrombolysis, although they were both ended prematurely. In the Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT), urokinase was injected into the thrombus rather than in front of it, and mechanical fragmentation of the thrombus was also allowed. A recanalization rate of 74% was achieved in this way. A clear positive trend for thrombolysis therapy was also noted clinically: 49.1% of the