Background and Aim: Some cases with aneurysmal subarachnoid hemorrhage (SAH) never reach the medical centre alive and they are not included in most studies of SAH. To explain the clinical profile of sudden death from aneurysmal SAH, we examined the epidemiology and clinicopathologic characteristics of patients with aneurysmal SAH who never reached medical attention or died within first 24 hours of the onset of first symptoms.
Materials and Methods: Using the autopsy records in Legal Medicine Organization of Tehran, we identified all cadavers who were diagnosed with aneurysmal SAH between 2001 and 2005.
Results: There were 85 women and 60 men with a mean age of 50 years. Twenty patients (14%) died without reaching medical care and 58 (40%) died within first 24 hours of the onset of first symptoms. The remnant had died after 24 hours to 28 days of hospitalization. In comparing patients with sudden death versus remnant, the main variables were the frequency of posterior circulation aneurysms that was found in 59% compared with 19.4% in those who had died after 24 hours, intraventricular hemorrhage 53.8% versus 19.4%, and pulmonary edema 92.3% versus 34.3% (P = 0.01).
Conclusion: In our population, the frequency of sudden death from aneurysmal SAH has not changed during the last 5 years. The typical clinical profile of sudden death in SAH includes intraventricular hemorrhage, pulmonary edema, and a ruptured posterior circulation aneurysm. Intracerebral hemorrhage is rarely connected to sudden death from aneurysmal SAH.
Nontraumatic subarachnoid hemorrhage (SAH) is a neurologic emergency characterized by the extravasations of blood into the spaces covering the central nervous system that are filled with cerebrospinal fluid. The leading cause of nontraumatic SAH is rupture of an intracranial aneurysm, which accounts for about 80% of cases and has a high rate of death and complications.1–3 Intracranial aneurysms are common.4–9 Autopsy studies have shown that the overall frequency in the general population ranges from 0.2% to 9.9% (mean frequency, approximately 5%),8,9 suggesting that 3 to 3.5 million persons in the Iran have or will have intracranial aneurysms.
Intracranial aneurysms are acquired lesions that are most commonly located at the branching points of the major arteries passing through the subarachnoid space at the base of the brain (Figures 1, 2).
A SAH because of the rupture of an intracranial aneurysm is a devastating event associated with high rates of morbidity and mortality. In the developed countries, approximately 12% of patients die before receiving medical attention,10,11 40% of hospitalized patients die within one month after the event,10,12–16 and more than one-third of those who survive have major neurologic deficits.10,12–16
Some cases with aneurysmal SAH never reach the medical centre alive and they are not included in most studies of SAH. To clarify the clinical profile of sudden death from aneurysmal SAH, we design a study for evaluation of this subject in our community.
MATERIALS AND METHODS
This is a noninterventional prospective study on the basis of data from the autopsy of cadavers referred to Tehran Legal Medicine Organization with diagnosed SAH due to the rupture of an intracranial aneurysm. We also studied medical records of these patients and performed an interview with their relatives. Data were obtained for all cadavers examined in Legal Medicine Organization of Tehran with diagnosis of SAH because of the rupture of an intracranial aneurysm between 2001 and 2005. We divided all patients into 2 categories, sudden death and no sudden death. Sudden death was defined as any death that occurred 24 hours or less from the onset of the first symptoms of an aneurismal SAH, and no sudden death included patients who had died after 24 hours from the onset of the first symptoms of an aneurismal SAH. Variables such as age, sex, duration from initiation of disease until death, medical attention, manifestation of disease, type, location, amount, source of bleeding, and also risk factors which are all investigated with autopsy, interview with relatives and studying clinical records for both groups and compared with together. Hospital records, autopsy protocols, and death certificates were abstracted to obtain diagnostic evidence of the cause of death and an accurate time course of the terminal event. The statistical software package SPSS was used for the calculations.
The study population was comprised of 145 patients (85 female and 60 male) were referred to legal medicine organization of Tehran from January 2001 to December 2005 and cause of their death was nontraumatic SAH caused by rupture of an intracranial aneurysm. Fifty-nine percent of deceased was female. M/F ratio was 0.7 and the average age was 50 ± 6.6 years, ranging from 19 to 72 years (Figure 3).
Of 145 patients, 20 (14%) had died before they receive any medical attention and 58 patients (40%) had died in first 24 hours after hospitalization (43 female and 35 male). Thus 78 (54%) of them were sudden death, in compare with 39 patients (27%) who had died within 2 weeks and 28 patients (19%) after 2 weeks. We divided deceased into 2 groups, group A included 78 cases with sudden death (who never reached the hospital alive and patients that had received medical attentions and died in the first 24 hours) and group B included 67 (43 female and 25 male) cases with no sudden death (who had died after 24 hours till 28 days). The chief manifestation of the onset of disease was a sudden onset of severe headache (78% of cases of sudden death), followed by loss of consciousness. Nausea, vomiting, diminished level of consciousness, bilateral lower-extremity weakness, abulia, third nerve palsy, and sixth-nerve palsy were other manifestations that were seen mainly among who admitted in the hospital and alive more than 24 hours. There was a history of hypertension in 44 (56.4%) patients group A and in 43 (64.2%) of patients group B. Thirty-six of deceased (46.2%) in the group A and 21 (31.3%) in the group B were cigarette smoker. Familial history of nontraumatic SAH reported for 9% deceased in both groups. Nothing of decedents had notice as the case of intracranial aneurysm but 43 of them (24 in group A and 19 in group B) were known as ischemic heart disease. Of 145 patients, 29 (19 in group A and 10 in group B) had a history of headache and were under treatment as migraine or tension headache. Alcohol consumption reported by 13 of 145 (9%) patients (7 in group A and 6 in group B).
Autopsies were performed in all cases. At autopsy, there was SAH in all cases of both groups, but in the cases with sudden death (group A), intraventricular hemorrhage was present in 42 patients (53.8%) and 72 patients (92.3%) had acute pulmonary edema. In comparing patients in the group B, intraventricular hemorrhage was present in 13 patients (19.4%) and 23 patients (34.3%) had acute pulmonary edema (P = 0.01).
Intracerebral hemorrhage was present in 12 (15.4%) of cases group A and 9 (13.4%) of cases group B. Posterior circulation aneurysms were found in 46 (59%) of cases with sudden death (group A), compared with 13 (19.4%) in group B (P = 0.01).
Anterior circulation aneurysms were found in 28 (35.9%) of patients group A and 47 (70.1%) of patients group B and we could not find the definite source of hemorrhage in the remnant cases. Arteriosclerosis was present in most of patients (79.3%) of all (78.2% in group A and 80.6% in group B) (P = 0.01).
Summary of results were shown in Table 1.
Sudden death is commonly defined as any death that occurs less than 24 hours after the onset of clinical symptoms and is not attributable to trauma or known preexisting illness. The most frequent cause is cardiovascular disease, specifically coronary artery disease. It has been reported to be responsible for between 50% and 90% of all sudden deaths.17–24 SAH as a result of the rupture of an intracranial aneurysm is one of the other causes of sudden death. In the developed countries, approximately 12% of patients die before receiving medical attention.10,11
We know that significant cardiac involvement can occur in patients with acute intracranial hemorrhage, particularly in those with SAH. These patients may present with electrocardiography abnormalities that were previously thought to be benign. However, many die of cardiovascular sequelae, which suggest more serious cardiac problems. SAH frequently results in myocardial necrosis with release of cardiac enzymes. Historically, this necrosis has been attributed to coronary artery disease, coronary vasospasm, or oxygen supply-demand mismatch.
Pulmonary edema and cardiac injury are well-known complications of SAH. Cardiac injury after SAH is a neural mediated process. Massive release of catecholamines, probably because of hypothalamic ischemic stress, results in specific myocardial lesions and hydrostatic pressure injury to the pulmonary capillaries causing neurogenic pulmonary edema. Catastrophic neurogenic pulmonary edema and cardiac failure may present simultaneously or in isolation. They represent the severe end of a clinical spectrum of respiratory and cardiac impairment, which results in hypoxia and hypotension—major detrimental factors influencing outcome in acute brain injury.
In addition to the problems caused by the bleeding, 3 delayed neurologic complications can occur after SAH which are as follows:
Rebleeding refers to a second rupture of the brain aneurysm. Without surgery, rebleeding occurs in about 20% of patients in the first 2 weeks after the initial SAH, with a period of highest risk 48 hours after the initial event. After this initial time period the probability of rebleeding steadily declines. There is a 50% mortality associated with rebleeding.
Cerebral vasospasm refers to narrowing of arteries of the brain because of spasm of the vessels. If this is severe, delayed cerebral ischemia can occur, leading to a stroke or even death. Vasospasm has been described as a sustained arterial contraction unresponsive to vasodilator drugs. This condition is commonly classified as either angiographic or clinical. Angiographic vasospasm refers to visible narrowing of the dye column in an artery, as shown on cerebral angiograms. Clinical vasospasm is the functional manifestation of cerebral ischemia produced by this arterial narrowing. Of 10 patients, 7 with aneurysmal SAH developed vasospasm, and of these 7 people, 3 developed symptomatic cerebral ischemia.
Hydrocephalus refers to excessive accumulation of the fluid that surrounds the brain (cerebrospinal fluid) caused by clogging and blockage of the normal outflow pathways by blood. This can result in lethargy, confusion, and a dangerous increase in the pressure inside the skull.
The literature contains some confusing and at times contradictory conclusions concerning the timing of sudden death from stroke. Secher-Hansen25 found that 100 of 130 patients who died suddenly from SAH in a forensic series died instantaneously. In a series of 250 medicolegal cases of SAH from intracranial aneurysm, Freytag26 found that 60% of patients had “no survival” and another 29% died within 24 hours.
We believe that all sudden deaths caused by aneurismal SAH in our community during the period between 2001 and 2005 have been identified, but we know that all the patients who die after 24 hours of hospitalization no refer to Legal Medicine Organization and our study had a significant number of missed cases in patients who had died with no sudden death. Thus our finding about characteristics of sudden death by ruptured an intracranial aneurysm will be more reliable, but in cases with no sudden death this data is not included all patients in our community. In all of our 145 cases, autopsy was done. We believe that, in all cases, the autopsy findings and clinical evidence were clear enough that we could be confident of the diagnosis.
We found that most patients (86%) with SAH survived to reach medical attention, but a great number of them (40%) will die within first 24 hours. The frequency of sudden death from aneurysmal SAH has not changed during the last 5 years.
All of the patients in our study had SAH as the terminal event. In the cases with sudden death, they were significantly severed than those in the no sudden death group. The typical clinical profile of sudden death in SAH included intraventricular hemorrhage, pulmonary edema, and a ruptured posterior circulation aneurysm. Intracerebral hemorrhage was uncommonly associated with sudden death from aneurysmal SAH. The main preventable risk factors included hypertension and smoking.
This research was done on Iranian cadavers in Legal Medicine Organization. Legal Medicine Organization of Iran with more than 1.5 million clinical forensic referrals and 50,000 autopsies per year is an appropriate field for such research and training.27–32
The authors thank the legal medicine practitioners and staff at Tehran's Legal Medicine Organization who assisted with this study.
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