Basic Principles

Basic Principles

CHAPTER 26

26

26.1 Sudden, Unexpected Death 525 26.1.1 Definition 525

26.1.2 Epidemiology 526 26.1.3 Classification 526

26.1.3.1 Neuronal-Mediated Death 526 26.1.3.2 Death Associated

with Vascular Diseases 527 26.1.3.3 Death Associated

with Inflammatory Diseases 527

26.2 Further Cerebral Diseases of Forensic Significance 527

Bibliography 528

References 528

It is not the intention of the present chapter to pres- ent clinical neuropathology in all of its complexity.

Instead the focus will be mainly on sudden and un-

and/or functional disturbances of the CNS in adults.

Similar naturally occurring processes in children are discussed elsewhere (pp. 451 ff). Cerebral dis-

expected death or resulting from initially survived external violence such as impact or intoxication are additionally treated here. Because the neuropatholo- gist is often confronted with such disorders in con- nection with forensic questions, they are relevant to the topic of the present volume. Diseases of the latter type can lead to death due to generalized ce- rebral or extracerebral processes or events. Typical chronic or acute neurological disease processes that do not lead directly to death, i.e. multiple sclerosis will be shortly discussed, but the usual spectrum of neurological diseases whose pathology is the subject of textbooks on clinical neuropathology, will not be described here.

26.1

Sudden, Unexpected Death

26.1.1 Definition

Sudden, unexpected death is a death that occurs in persons in apparently good health or after rapid worsening of a minor illness. Mason (1995) defines it as follows as “an unexpected death following so rapidly from the onset of symptoms that the cause of death could not be certified with confidence by a medical practitioner familiar with the patient.” Black and Graham (2001, 2002) have discussed the differ- ent uses of the terms “sudden” and “unexpected”

death. What interval between the onset of symptoms and death can be described as “sudden?” The World Health Organization accepts a maximal interval of 24 h (Knight 1996). This is regarded as being too long by some authors who prefer a much shorter interval of “within a few hours of apparently good health”

(Simpson 1947) or of “one hour” (Knight 1996).

The definition applied in a given instance is de- pendent to a large part on the circumstances of the particular case. If one is seeking information for in- surance purposes as to the statistical risk of an acute death occurring during hospitalization (Shafer et al.

1990), different criteria will apply than if informa- tion is being sought for purely forensic-diagnostic reasons. Shafer and his team (1990) prefer applying an operational classification for a neurology service by using specific predictors developed and validated for such a service.

The definition we use places less weight on the time interval than on the “surprise effect” (Berg and Fricke 1992), i.e., “sudden” is used in the sense that any death with a very rapid onset is unexpected. An

”unexpected” death, by contrast, can occur slowly

over a prolonged period of time, the victim being dis-

covered dead to everyone’s “surprise” at a time when

the death is not expected. Hecht and Löffler (1984)

speak therefore of the “expectation improbability.”

526 PART VI: Clinical Neuropathology

Though the terms “unexpected death” and “un- explained death” are partly synonymously used, the term “unexplained” needs a further clarification.

“Unexplained” does not designate cases that remain unexplained after full postmortem examination, but cases that are unexplained at the time of death, i.e., before autopsy and final analyses have been com- pleted.

26.1.2 Epidemiology

The first (very early) epidemiological study was done by Kuller (1966; Kuller et al. 1967) while the most ex- tensive study was carried out by Janssen and Naeve (1975). In their study of 40,444 deaths they found that 22,321 (55.2%) could be classified as unexpected deaths from natural (non-traumatic) causes. This finding agrees with that of a smaller study of about 1,000 cases which also reported about 50% of the deaths to have been acute and unexpected (Berg and Fricke 1992). If the cause of death is assigned to the principle organ system involved, all studies [as sum- marized by Berg and Fricke (1992)] found the heart and circulatory system to predominate (40−70% of cases), with the central nervous system following far behind (4−24% of cases).

Among the CNS diseases that are most likely to lead acutely and unexpectedly to death, epilepsy is listed as being absolutely predominant by the afore- mentioned Glasgow studies (Black and Graham 2001, 2002), followed by spontaneous subarachnoid hemorrhage. A somewhat older study (Shafer et al.

1990), which assumes an interval of 30 days between onset of symptoms and death, reported the following diseases, necessary medical measures, and/or symp- toms, to be associated with acute death:

1. AIDS with central nervous system involvement 2. Intubation in or out of the emergency room 3. “Found on floor” at age >64 years

4. Coma with structural lesion on cranial CT or lat- eralizing exam if CT not done

5. Stroke with hemiplegia

6. Stroke with loss of consciousness

7. Subarachnoid hemorrhage, not induced by exter- nal violence

8. Status epilepticus

9. Intracranial hemorrhage, any cause, any size 10. Cancer primary to CNS or metastatic to brain or

cord or cauda equina 11. Deep coma of any cause 12. Bacterial meningitis 13. Severe quadriplegia

26.1.3 Classification

We have already referred above to the following dif- ferentiation:

1. Sudden death from intracranial diseases

2. Sudden death with an accompanying cerebral disease in cases of generalized and/or extracere- bral processes

This differentiation should be compared with anoth- er classification referred to elsewhere (Oehmichen and Gerling 1992).

26.1.3.1

Neuronal-Mediated Death

Neuronal-mediated deaths have already been dis- cussed elsewhere in this volume, including Chap. 2.

The cortical regions are known to have a direct effect on the hypothalamic nuclei, while in the hypothala- mus and pituitary gland regulation occurs at the neu- rohormonal and immunological level [see Adinolfi (1991) among others]. Feedback mechanisms are also able to directly influence the cortex. This func- tional network allows the thesis that an acute death can also result from cerebral-somatic and cerebral- psychological causes (Angell 1985; Williams 1990;

Pedal et al. 1996; Kernbach-Wighton et al. 2003).

The burgeoning field of neurocardiology, the study of brain−heart interactions (Cechetto 1994), has been of great assistance in our understanding of sudden death. It is clear that autonomic control of the heart rate and rhythm extends above the spinal, brain stem, and hypothalamic axis (Cechetto and Saper 1987; Cechetto and Chen 1990), and that the highest level of autonomic control is the cerebral cortex (Ya- sui et al. 1991; Butcher and Cechetto 1995). Studies of cardiac chronotropic sites in the posterior insular cortex, for example, have shown tachycardia repre- sented rostrally and bradycardia caudally (Oppen- heimer and Cechetto 1990). Cortical stimulation can produce lethal cardiac arrhythmias (Oppenheimer et al. 1991). Cerebrogenic cardiac arrhythmias and their role in sudden death have been reviewed (Op- penheimer et al. 1990). Cerebral arrhythmogenesis is a topic most germane to the medicolegal pathologist faced with a paucity of anatomical findings to ex- plain asphyxial, hypoxic, athletic or epileptic deaths, or deaths where there is brain disease on first glance insufficient to explain death.

We know from sudden death in athletes, sudden

death in epileptic patients (SUDEP), sympathetic dy-

adic death in the elderly (where death of one spouse

is followed shortly by the death of the other), cardiac

arrest in subarachnoid hemorrhage and from the

inevitable heart stoppage in respirator brain (brain

CHAPTER 26: Basic Principles 527

death) (Auer and Sutherland 2002), that coronary occlusion or other heart structural abnormality is not necessary for the heart to stop. Cases of delayed death 4 days after hanging (Hausmann and Betz 1997) or 2−3 days after CO poisoning (Opeskin and Drummer 1994) can be considered neurocardiac death. Brain disease or brain injury must act via a final common pathway of either heart stoppage or cessation of breathing in order to cause death. These forms of death seen with antecedent brain injury, or with overstimulation of the heart caused by the brain, attest to the powerful trophic influence of the brain on the heart for its continued normal rhyth- micity and long-term function.

But we must state: a neurocardiac death as de- scribed above will never occur in healthy young pa- tients other than highly exertional athletes. The pre- requisite will be a primary cardiac pathology (ath- letes, elderly) or a primary brain pathology (epilepsy, subarachnoid hemorrhage, brain damage caused by hanging or CO poisoning).

Moreover we know of centrally induced pulmo-

sult of mechanical brain injury (MBI) in the form of so-called neurogenic edema of the lung (Graf and Rossi 1975). An acute central respiratory arrest is regularly seen after herniation secondary to an in- tracranial space-occupying process or compression of the respiratory center. The swallowing reflex can be disturbed by injury of the CNS: individuals under the influence of alcohol or toxic agents, or with trau- matic or age-related cerebral atrophy are particularly at risk of asphyxia due to aspiration of vomitus into the respiratory tract or from alimentary bolus (Mal- lach and Oehmichen 1982).

26.1.3.2

Death Associated with Vascular Diseases

Vascular diseases will be discussed below. Here only the following will be mentioned:

Luminal stenosis or luminal occlusion and/or re- duced or arrested perfusion can lead via local or gen- eralized O2 deficiency to an acute and unexpected central regulation failure, in the sense of hypoxia or ischemia. A typical example of sudden, unexpected death is massive intracranial bleeding, which can lead via an acute space-occupying process to her- niation. Rapid tumor growth accompanied by tumor hemorrhage in primary neurogenic tumors − more often however in metastases − can quickly result in a space-occupying event, even if the tumor had pre- viously produced no neurological deficits. Tumors especially prone to bleeding include oligodendro- glioma, glioblastoma, metastatic melanoma, and the rarer choriocarcinoma. Hypoxia and bleeding can have many causes. According to the Harvard Study (Mohr et al. 1978), predominant among brain ves-

sel diseases are thrombosis (53%), embolism (31%), intracerebral bleeding of unknown cause (10%), and subarachnoid bleeding due to aneurysm or angioma (6%).

26.1.3.3

Death Associated with Inflammatory Diseases Inflammation of the CNS is usually accompanied by systemic clinical and pronounced somatic, neuro- logical or psychopathological symptoms, which usu- ally require emergency medical or clinical treatment before death. Despite this fact, inflammation of the CNS is often a diagnosis, sometimes even surprising and unexpected, that is first made at autopsy.

For death to be unexpected under these condi- tions there must be an absence of prior symptoms, a misunderstanding of the true nature of the illness, or poor observation by others. Inflammation can lead to acute death in infants or children, in isolated elderly persons, the homeless, alcoholics, and drug addicts.

26.2

Further Cerebral Diseases of Forensic Significance

There are numerous types of death that, while not being sudden or unexpected, must still be diagnosed and assessed by the forensic neuropathologist:

▬

Delayed (secondary) death resulting from injury or intoxication

▬

Deaths, the causes of which cannot be explained clinically or by autopsy alone

▬

Deaths due to neglect and/or failure of medical treatment

We will not present the entire spectrum of such dis- eases and their sequelae here, but limit our com- ments to the following two disease groups:

1. Nutritional and metabolic insults 2. Degenerative diseases of the elderly

In both groups the same questions must be addressed by the forensic scientist:

1. Which disease of the CNS is present (diagnosis)?

2. Is there a causal connection between the disease and the death?

3. Could the disease have been prevented under dis- tinct conditions?

4. Was the death itself preventable?

Since a large percentage of the diseases are accompa-

nied by dramatic psychopathological changes, the fo-

rensic neuropathologist must often answer a number

of other questions as an expert witness; for example,

528 PART VI: Clinical Neuropathology

was the deceased able to act or to think clearly, i.e., legal capacity for the last will, to decide, etc. Since the number of such cases is on the increase both in the clinic setting and in the context of forensic autopsy, an interpretation of the neuropathological findings in terms of cerebral (intellectual) function appears to be unavoidable (Stewart et al 2004).

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