Sudden neuropathological deaths: An autopsy study

Introduction

Autopsy practice varies from country to country. In India, all unnatural deaths (accidents/suicides/homicides) are investigated and a medico-legal autopsy is conducted. But very often, natural deaths form the basis of medico-legal investigations if they have occurred suddenly in an apparently healthy person under suspicious circumstances. ¹ In certain cases of sudden death where the treating physician is convinced that the death is natural, there is no suspicion of foul play and the cause of death is certain, the physician certifies the cause of death, and such deaths are not investigated. If there is suspicion of foul play, the case is registered as an unnatural death, and a medico-legal autopsy will be conducted. In certain deaths due to natural diseases where the treating physician is keen to know the extent of the suspected pathology, the consent of the next of kin is obtained, and an autopsy is conducted by pathologists. Such cases are not investigated by the police or magistrate. Hence, sudden natural deaths are underreported in India by forensic medicine practitioners.

Death is said to be sudden or unexpected when a person not known to have been suffering from any dangerous disease, injury or poisoning is found dead or dies within 24 hours after the onset of terminal illness (World Health Organization). Natural death means the death is caused entirely by the disease, and the trauma or poison did not play any role in bringing about the death. The practicing forensic pathologist is likely to encounter cases where either the cause of death or a major contribution to the cause of death is underlying damage to or disease of the central nervous system (CNS). ² Hence, one should be well versed with the routine neuropathological conditions encountered in day-to-day practice.

Neuropathologies constitutes about 10–18% of sudden natural deaths. The neuropathological causes for sudden natural deaths include cerebral haemorrhage, cerebellar haemorrhage, pontine haemorrhage, cerebral thrombosis and embolism, brain tumour, meningitis, carotid artery thrombosis, brain abscess, epilepsy, and so on. ³ In such deaths, it is a difficult task for the forensic experts or medical officer to establish the cause of death. In every case, a thorough history of the illness, duration of emerging signs and symptoms, any reports from the treating hospital, in addition to a meticulous autopsy (including biochemical analysis, histopathological examination, microbiological examination and chemical analysis), play a vital role in solving the puzzle of sudden death. Despite the availability of potent antibiotics, the mortality rate due to acute bacterial meningitis remains significantly high in India and other developing countries. ¹ The spectrum of causes of death attributed to meningitis ranges from systemic (e.g. septic shock) to severe neurological complication (e.g. brain oedema, hydrocephalus, cerebrovascular involvement and intractable seizure). ⁴

It has been estimated that as many as 15% of patients with spontaneous subarachnoid haemorrhage (SAH) die before reaching the nearest hospital. ⁵ SAH as a cause of death in autopsies where death occurred before reaching medical attention has not changed over the years. ⁶ SAH can cause virtually instantaneous death, even though the mechanism is obscure. The majority of the natural causes of SAH are spontaneous in nature. SAH comprises 1–7% of all strokes; therefore, it is a significant cause of morbidity and mortality, especially in the elderly. ⁷

Most large intracerebral haematomas occur in middle-aged men with hypertension or in the elderly. ⁸ Tumours of the CNS are among the rare causes of sudden and unexpected deaths. ⁹

Material and methods

The Department of Forensic Medicine at the MS Ramaiah Medico-Legal Institute provides a post-mortem examination service for northern Bangalore, a metropolitan city in southern India. A 10-year (January 2003 to December 2012) retrospective study was conducted in the department, where a total of 7520 medico-legal autopsy reports were reviewed. All the sudden natural deaths were included, in which, after meticulous medico-legal autopsy and chemical analysis, the cause of death was attributed to neuropathology. This resulted in 291 cases of sudden natural death, out of which 43 cases were due to neuropathology. Natural deaths amongst unknown cases were excluded, as there were no proper data available. Descriptive statistics for the qualitative type of data were summarized using frequency and percentage.

Results and discussion

During the study period, from January 2003 to December 2012, 7520 medico-legal autopsies were conducted, of which sudden natural deaths accounted for 291 cases (3.9% of total unnatural deaths). Of these, neuropathology constituted the cause of death in 43 cases (0.57% of total autopsies and 14.8% of total sudden natural deaths). Similar findings have been noted in various studies, where neuropathology constituted 10–18% of sudden natural deaths. ³ This is in contrast to a study conducted in Jamaica, where sudden natural deaths constituted 51.3% of medico-legal autopsies. ¹⁰ This is because not as many natural deaths are investigated in India compared to Jamaica. In Jamaica, there are both a non-coroner’s autopsy and a coroner’s autopsy, which are similar to the pathological autopsy and medico-legal autopsy in India. The cases were equally distributed over the entire study period from 2003 to 2012, except in 2008 and 2009 during when nine cases were observed each year.

Of the 43 cases (Table 1), 69.7% were male and 30.3% were female, since most of the cases were caused by stroke and SAH, and men carry higher risk factors such as smoking, hypertension, diabetes and so on. Other reasons for the higher incidence in males were because they are generally working outdoor and are subjected to more strenuous work (physical exertion) and mental stress which could cause a sudden rise in blood pressure and hence rupture of pre-existing undiagnosed aneurysms and stroke. The role of physical or emotional stress – for example, minor assault or a verbal argument – when someone dies from a natural disease process shortly after the event is not an uncommon medico-legal problem. Such deaths most frequently result from SAH or intracerebral haemorrhage or cardiac disease, with death possibly occurring as a consequence of a rise in blood pressure as a result of the stress. ⁸ In an autopsy study of SAH, it was observed that 55.3% were female and 44.7% were male. ⁷

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Table 1.

Distribution of cases based on age and sex.

Sl No	Age group (years)	Total		Males		Females
1	0–9	0	0%	0	0%	0	0%
2	10–19	3	7.0%	2	4.7%	1	2.2%
3	20–29	6	14.0%	4	9.3%	2	4.7%
4	30–39	5	16.4%	3	7.0%	2	4.7%
5	40–49	8	18.5%	6	13.8%	2	4.7%
6	50–59	10	23.4%	7	16.4%	3	7.0%
7	≥60	11	25.5%	8	18.5%	3	7.0%
	Total	43	100%	30	69.7%	13	30.3%

Most cases (25.5%) belonged to the ≥60 years age group, followed by the 50–59 years age group (23.4%), with eight cases (18.5%) belonging to 40–49 years age group. The number of cases increased with age. This could be attributed to the higher incidence of stroke and spontaneous SAH in the elderly. No cases were reported in the 0–9 years age group. Only three cases (7%) belonged to 10–19 years age group (two were due to meningitis, and other one was due to epilepsy).

SAH was the most common type of sudden neuropathological death (21 cases), comprising half of all cases (Figures 1–3). This high number of SAH deaths encountered could be because all sudden unexplained death in epilepsy (SUDEP) and the majority of deaths due to stroke are certified by the treating physician, and thus are not routinely autopsied. The second most common type of death was stroke (excluding SAH; Figure 4) constituting 30.2% of the cases. It was observed that there was no sex differences in cases due to tumours and infection, since these cases were independent of the risk factors. The mechanism of death in cases of tumours was sudden haemorrhage into the midbrain and brainstem leading to sudden death because of the effect of pressure on the vital centres located in that region. Out of 21 cases of SAH, 16 were males and 5 were females (4:1), and among 13 cases of stroke, only three were females (4:1). Hamman found that 8% of all patients who had died suddenly had some sort of cerebral hemorrhage. ¹¹ OPEN IN VIEWER

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Figure 2.

Ruptured berry aneurysm present at the junction of anterior cerebral and anterior communicating artery causing subarachnoid haemorrhage (spontaneous).

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Figure 3.

Diffuse Subarachnoid haemorrhage (spontaneous) present over base of the brain.

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Figure 4.

Deep seated non-traumatic intra cerebral haemorrhage present in the region of basal ganglia.

SAH and stroke were commonly seen in middle-aged and elderly individuals, whereas meningitis and tumours were found in the 10–39 years age group. SAH constituted 7.2% and stroke about 4.5% of sudden natural deaths (Table 2). In most cases of SAH, the haemorrhage was diffuse and mainly in the basal region. In 14 cases, it was due to the rupture of a saccular aneurysm, in one case due to arterio-venous malformation and in six cases the exact site of the bleed could not be identified. Amongst the 14 cases of aneurismal rupture, it was observed that six were in the posterior circulation of the Circle of Willis and eight in the anterior circulation. In eight cases of SAH, the haemorrhage also extended into the ventricles.

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Table 2.

Distribution of cases based on the pattern.

Sl no	Pattern	Males	Females	Total no. cases	Percentage
1	Stroke	10	3	13	30.2%
2	Sub arachnoid haemorrhage	16	5	21	48.8%
3	Infection	3	3	6	14%
4	Tumours	1	1	2	4.7%
5	Epilepsy	1	0	1	2.3%
	Total	31	12	43	100%

In one study, it was observed that in 27 of 33 cases, the ruptured aneurysms arose in the anterior circulation of the Circle of Willis, and in only six cases was a ruptured posterior circulation aneurysm responsible for death. ⁸ Studies have shown that 8–10% of deaths from a ruptured intracranial saccular aneurysm occur suddenly, before reaching hospital.^12–14 In discussion, particular emphasis was placed on the exceptionally high fatality rate in patients with ruptured saccular aneurysms arising from the posterior circulation of the Circle of Willis. A few hospital-based studies have also suggested a somewhat higher mortality after the rupture of posterior circulation saccular aneurysms,^15,16 whereas others have failed to detect any differences in the outcome.^17–20

Out of six cases, five were due to acute bacterial meningitis, and the remaining case was due to the spontaneous rupture of a cerebral abscess. Four cases had longstanding suppurative ear discharge before succumbing to sudden death. In the remaining two cases, there were no significant symptoms, except fever and headache which were symptomatically treated at the tertiary level health-care centre on an outpatient basis.

In India, the treating physician usually certifies the death in cases of status epilepticus. Thus, an autopsy is not conducted routinely in such cases. In the single case of status epilepticus where an autopsy was conducted, the treating family physician was not on duty, and the deceased was brought to our hospital and registered as an unnatural death. He was a known epileptic on irregular medication, and he had had a continuous seizure lasting for about 8–10 minutes. At autopsy, there were findings consistent with a seizure, that is, bruising of the tongue, pulmonary oedema, petechial haemorrhages in the mucous membranes and so on. Thus, the death was ascribed to status epilepticus.

Tumours constituted 6.9% of sudden CNS deaths, accounting for 1% of total sudden natural deaths. Both the cases of tumours were undiagnosed astrocytoma, which presented as a haemorrhage into the brainstem, leading to sudden death.

Intracranial tumours are said to account for 8% of non-traumatic intracerebral haemorrhage, and in about half, it may be the first manifestation.^21,22

It was observed that the incidence of tumours was between 0.17% and 0.54% in several series of forensic autopsy studies.^23,24

Twenty individuals were on medication for hypertension and 14 were diabetic. The majority of cases who died due to stroke or SAH had either hypertension or diabetes or both. Eight individuals had a cardiac illness such as ischemic heart disease, valvular heart disease and so on in addition to hypertension (Table 3).

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Table 3.

Distribution of cases based on history.

Sl No	History	Cases
1	Diabetes mellitus	14
2	Hypertension	20
3	Previous heart disease	8

In a similar study, cerebrovascular accidents were the most common cause of death, and hypertension was associated with majority of the cases (78.1%). ¹⁰

Conclusion

Neuropathology is one of the major causes of sudden natural deaths. The forensic pathologist plays a crucial role in ascertaining the cause of death in such cases. In every case, a thorough history of the illness, the duration of emerging signs and symptoms, any reports from the treating hospital, in addition to a meticulous autopsy, play a vital role in solving the puzzle of sudden death. The results of our study can be summarized as follows:

Neuropathological deaths constituted 0.57% of total unnatural deaths and 14.8% of sudden natural deaths.