Molecular pathogenesis of subarachnoid haemorrhage

Subarachnoid haemorrhage (SAH) results from leakage of blood into the subarachnoid space and carries high morbidity and mortality. However, there is limited understanding to date, of the risk factors, cellular, intermediate biochemical and genetic traits predisposing to SAH. Nevertheless, in conjunction with improved methods of diagnostic imaging and less invasive approaches to preventing aneurysmal rupture, there may be utility in gaining a better understanding of the pathogenesis and in identifying pre-disease markers. Additionally, it is not impossible that drugs of value (e.g. matrix or endothelial modifiers) could become available. Several different clinical subtypes can be recognised, distinguished by arterial or venous involvement, presence of unruptured arterial aneurysms, and apparently "sporadic" and "familial" occurrences. Epidemiological risk factors include alcohol consumption and smoking: hypertension is a risk factor for rupture. About 10% seem to reflect strong family history and this subset may be particularly illuminating with respect to the molecular pathogenesis. Haemodynamic stress and poor vascular structure may be the main mechanisms of pathogenesis. The epidemiological and statistical evidence for familial megaphenic genes and modifier genes is reviewed. This review focuses on the pathogenesis, as opposed to inflammatory response to SAH. It sets in context the roles of specific genes and their protein products, such as polycystin (PKD1), fibrillin (FBN1), collagen III (COL3A1), elastin (ELN), collagen IV, protease inhibitor or alpha1-antitrypsin (PI) and proteases. These considerations illustrate the shortfalls in current knowledge, the needs of future biochemical and cellular research and their potential implications for future prevention of this often fatal condition.     

Smoking and subarachnoid haemorrhage.

A retrospective study of 208 patients with ruptured cerebral aneurysms showed a highly significant excess of cigarette smokers among both men and women compared with the expected incidence. Results suggested that continued smoking increases the risk of suffering a subarachnoid haemorrhage (SAH) by a factor of 3.9 for men and 3.7 for women. Other factors besides smoking must affect the genesis of aneurysmal SAH since it is found in non-smokers, but continued cigarette smoking appears to increase substantially the risk of aneurysmal SAH occurring.     

Recovery after subarachnoid haemorrhage.

OBJECTIVE--To determine the implications of subarachnoid haemorrhage for quality of life and aftercare. DESIGN--Prospective follow up study of patients surviving subarachnoid haemorrhage over one year (at discharge, three months, and one year) by examination of cognitive functions (a test battery) and changes in everyday life (semistructured interview). SETTING--Regional neurosurgical unit at a tertiary referral centre. PATIENTS--100 Patients with subarachnoid haemorrhage; 17 were lost during the study because of ineligibility (further surgery, previous head injury, relevant psychiatric history, and cultural differences), loss of contact, and non-compliance; a further 13 patients who developed a neurological deficit were considered separately. MAIN OUTCOME MEASURE--Performance on cognitive test battery and reported changes in quality of life. RESULTS--At discharge patients with and without neurological deficit scored below established norms with most tests, but by three months the difference had resolved in patients without deficit. Reduced quality of life attributable to subarachnoid haemorrhage at one year mainly included less energy (seven patients), adverse emotional changes (five), early retirement, affected social life, and domestic tension (three each). None reported reduced capacity for work. CONCLUSIONS--Patients surviving subarachnoid haemorrhage without neurological symptoms have a good prognosis and should be encouraged to return to a normal lifestyle within about three months.     

Acute myocardial infarction complicating subarachnoid haemorrhage

An acute myocardial infarction is a rare complication of a subarachnoid haemorrhage. The combination of these two conditions imposes important treatment dilemmas. We describe two patients with this combination of life-threatening conditions. Patient 1 was treated with emergency percutaneous coronary intervention followed by clipping of the anterior communicating artery aneurysm. Six months after discharge the patient's memory and orientation had almost completely recovered. Patient 2 was treated with aspirin until coiling of the aneurysm could be performed. After successful coiling low-molecular-weight heparin was added. One week later the patient died due to a free wall rupture. (Neth Heart J 2009;17:284–7.)     

Oral contraceptives and fatal subarachnoid haemorrhage.

A case-control study was conducted of the deaths from subarachnoid haemorrhage (SAH) in women aged 15-44 in England and Wales in 1976. There was a small excess of oral contraceptive use by the women who died from SAH compared with their generally healthy practice-matched controls; this was not, however, statistically significant. Out of 134 women who died from SAH, 34 had a history of hypertension compared with only six of their controls. Renal disease and pre-eclamptic toxaemia were more commonly associated with hypertension in the dead women than in controls. No change in the annual mortality from SAH has been observed in the past 20 years such as might have been expected if the risks were high. Although current or past use of oral contraceptives may have increased the blood pressure and risk of SAH in a few women, the most important factor in determining this risk was hypertension. SAH should thus probably not be regarded as serious cause for concern in healthy non-hypertensive women using oral contraceptives.     

Lumbar puncture in spontaneous subarachnoid haemorrhage.

Seventy-four patients with proved spontaneous subarachnoid haemorrhage were studied. Sixty-four underwent computed tomography and 55 underwent lumbar puncture. Seven cases deteriorated dramatically after lumbar puncture, six of these showing evidence of cerebral dislocation on further investigation. Four of the seven had not undergone computed tomography and three underwent computed tomography after lumbar puncture. Computed tomography of the brain could determine patients at risk of coning. It is suggested that computed tomography is the investigation of choice after spontaneous subarachnoid haemorrhage and that lumbar puncture, if still then necessary, should be avoided until computed tomography has been undertaken.