Update on diagnosis and treatment of acute ischemic stroke
CH. BAIRACTARIS, L. KARTSAKLIS

The purpose of this review is to provide an update on the pathophysiology, diagnosis and therapeutic strategies of Acute Ischemic Stroke (AIS).

World Health Organization (WHO) has defined stroke as a rapid progressive focal or global cerebral dysfunction that either lasts more than 24 hrs or becomes lethal.

On the basis of their etiology, strokes are divided into three subtypes that comprise 95% of all cases:

1. cardioembolic
2. major vessel atheromatosis and
3. small vessel disease.

The main pathophysiologic mechanism of ischemic stroke is atrery obstruction that results in the reduction of glucose and oxygen supply to the affected area.

When cerebral blood flow is lower than 50% of normal values, there is a disruption of molecule permeability through the synaptic membranes, resulting in a reduction of electrical activity at the damaged area, as well as energy depletion. Further cerebral blood flow reduction causes disturbance of membrane ionic balance and sets off a obain reaction sequence that eventually leads to cell death.

At the ininfarcted area there is a central core, a great loss of cerebral blood flow (CBF) occurs, and an external neighboring zone with decreased CBF compared to normal values, called ischemic penubra. CBF in ischemic penubra maintains energy metabolism and tissue viability for several hours.

It is evident that any drop in systemic arterial blood pressure affects the ischemic penubra, increasing the size of the infarcted area.

There is a detailed description of the cascade of events and the pathophysiologic mechanisms involved in this process both at the core of infarction and the ishemic penubra. These events reflect metabolic disorders, disturbance of transmembrane ion conduction, activation of intracellular inflammation mechanisms and transcription of nuclear early genes. The release of inflammatory molecules and the role of inflammation are thoroughly discussed.

Disorders of the anti-thrombotic and anti-inflammatory properties of the endothelium along with serious reduction of the endothelial plasminoge activation lead to further damage of the ischemic region after the revascularasation.

The therapeutic strategy should focus not only on the revascularisation of the occladed artery but also on neuroprotection and the prevention of further demage.

After an alysing the pathophysiologic mechanisms, we conclude that the therapeutic approach of acute ischemic stroke should target the ischemic penubra as soon as possible.

In the era of thrombolysis,“time is brain”: the sooner the therapy starts, the more brain tissue is rescued.

Computed Tomography (CT) is the imaging technique that should be used as soon as possible because of its high sensitivity in the recognition and evaluation of cerebral hemorrhage. There is a reference to its advantages and limitations in the evaluation of acute stroke.

Magnetic Resonnance imaging (MRI) gives detailed anatomic information on the infarcted areas. The use of GRE and other acquisi on techniques, such as diffusion (DWI) and perfusion (PWI), visualize the infarcted area much sooner than CT (within a few minutes).

Of great diagnostic value are also other imaging methods, such as classic or digital angiographies, Magnetic Resonance Angiography (MRA) and transcranial ultrasound, in combination with specific cardiologic evaluation(transthoracic or transnesophageal ultrasound, Holter examination).

Disorders of coagulation factors and other hematological disorders should always be investigated.

The use of r-TPA in the last decade established acute stroke as a medical emergency, which means that the pre-hospital patient requires special care.

For practical reasons, the therapeutic approach follows four steps:

1. Supporting vital functions, lowering high scrum glucose levels, lowering temperature, managing epileptic seizures and raised intracranial pressure.
2. Revascularising the ischemic cerebraltissue by using specific agents such as r-TPA or factors still under investigation (E6010, TKN0tPA).
3. Preventing the progression ofthrombosis by using antithrombotic therapy (heparin, heparinoids, aspirin and new antiplatelet and fibrinolytic agents).
4. Future therapeutic interventions include preventing the activation of endothelium inflammatory mechanisms, developing neuroprotecting agents and promoting self-repairing mechanisms. ngoing trials are discussed.

Since the only approved treatment for acute ischemic stroke is thrombolysis, common sense dictates that stroke should be treated as a medical emergency, bearing always in mind that “time is brain”.

Key words: Stroke, antiplatelet dryg, fibrinolytic elements, neuroprotective strategies.