Hemorrhagic stroke accounts for about 15% of all strokes but is associated with a disproportionate degree of morbidity. Studies have indicated that inflammatory processes may be involved in exacerbating brain injury after the hemorrhagic even (Hua y, J. Nuerosurg. 200, 1016-1022).
There are two main types of hemorrhagic strokes: (1) intracerebral hemorrhage and 2. subarachnoid hermorrhage.
Intracerebral Hemorrhage (ICH)
Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke carrying a mortality rate of 30-50% which has not improved over the last two decades. Moreover, ICH imparts some form of disability in close to 90 of its survivors.
Risk Factors: The most common etiology of ICH is hypertension.
Complications: include haematoma expansion (HE), perihaematomal oedema (PHE), intraventricular extension of haemorrhage (IVH) with hydrocephalus, seizures, venous thromboembolic events (VTE), hyperglycaemia, increased blood pressure (BP), fever, and infections. Complications such as HE, IVH with obstructive hydrocephalus, and hyperglycaemia are major predictors of increased ealry mortality and adverse outcome during the hyperactue phase of ICH.
Etiology:
1. Role of complement system:
(i) Inhibitors of C3 and C5: Complement C3 is an important factor causing brain damage following ICH in mice. However, another study reported that neurological deficits and brain edema were worse in complement C5 deficient mice. These differing results indicate that different complement factors have different effects on brain injury after ICH, that is, either beneficial or harmful. C5 deficient mice fail to form C5a fragments and member attack complex (MAC), but complement C3 deficient mice fail to form C3a, C3b, C5a and MAC (Yang, “the role of complement C3 in intracerebral hemorrhage-induced brain injury” J. Cerebral Blood Flow & Metabolism (2006), 26, 1490-1495).
Lambris (US13/059482) discloses complement inhibotrs which reduce or prevent C3a and C5a formation, thereby treating intracerebral hemorrhage. In a preferred embodiment, the inhibitor is a C3 inhibitor which not only prevents the formation of C5a but also C3a. Examples of C3 inhibitors used are compstatin or their analogs.
(ii) inhibitors of C3aR and C5aR: Lambris (US13/059482) discloses that inhibitors of C3aR and C5aR improved recovery (reduced brain edema and imprvoed nuerological outcome) in a mouse model for ICH.
Treatment: Treatment options for ICH are mostly supportive. Elevation of the head to 20-30 degrees and avoidance of pain and fever could minimize any rise in ICP. Medical measures such as hyperventilation and the use of analgesia, sedatives, and osmotic diuretics are designed to lower ICP before placement of an ICP monitor or any definitive neurosurgical intervention such as craniotomy or ventriculostomy.
Subarachnoid Hemorrhage
A subarachnoid hemorrhage is bleeding into the space (subarachnoid space) between the inner lyaer (pia mater) and middle layer (arachnoid mater) of the tissue covering the brain (meninges). The most common cause is rupture of an anuerysm (bulge) in an artery. Usually, rupture of an artery causes a sudden, severe headache, often followed by a brief loss of consciesness. Computed tomography, sometimes a spinal tap and angiography are done to confirm the diagnosis. Drugs are used to relieve headache and to control blood presure and surgery is done to stop the bleeding.