Brain stem death

Cerebral oedema (swelling of brain leading to brain stem death due to fluid overload) and hyponatraemia (lowered sodium concentration)... 

Royal College of Physicians Working Party (1995) Criteria for the diagnosis of brain stem death. Working party review. J R Coll Phys 29 381-382... 

Motor neuron disease is characterized clinically by weakness, muscle atrophy and spasticity. This illness, often termed Lou Gehrig s disease in the United States, is the most common adult-onset form of MND with a prevalence of approximately 2-3 per 100,000 people [1-3,10, 25, 28]. Each year in the United States, in excess of 5,000 people are diagnosed with ALS. In parts of the United Kingdom, 1 in =500 deaths are attributed to some form of MND. The principal clinical signs of ALS include progressive limb weakness, which may be symmetrical or asymmetrical atrophy of appendicular, bulbar and respiratory muscles and spasticity [1,2,26,28]. The paralysis/muscle atrophy and spasticity are the result of degeneration of motor neurons in the spinal cord/brain stem and motor cortex respectively. The onset of this illness is typically in the fifth or sixth decade of life affected individuals usually... 

In view of the advances in nnderstanding the canse of death in cells, it is somewhat ironic that we understand so little as to what causes death in otherwise healthy humans as they become old (i.e. death due to senescence). In fact, in the UK it is now not permissible to write old age or a similar phrase on a death certificate. The most likely cause of death in humans under most circumstances, is, as indicated above, failure of the vital centres in the brain, e.g. the cells in the brain stem. A suggestion for the cause of death in old age is the progressive decrease in cardiac output with age. Nonetheless, under normal conditions, even a lower cardiac output will not compromise the function of the brain. However, a mild trauma, mild stress or mild infection requires an increase in cardiac output (to support the biochemical changes described in Chapter 18). If this required increase can no longer be attained by the heart in an elderly person, the provision of blood to the brain could be insufficient for this organ. The part of the brain that maintains the essential functions of the body, that is, the brain stem, may be the first to be affected, so that the control of the contraction of the heart or breathing... 

IV. Stage of medullary depression This deep stage of anesthesia includes severe depression of the CNS, including the vasomotor center in the medulla, as well as the respiratory center in the brain stem. Without circulatory and respiratory support, death rapidly ensues. 

Despite these significant advances and an overall pattern of clinical acceptability and low toxicity in animals, recent studies of arteether 6 have uncovered an unsettling neurotoxicity in animals leading to death at higher than therapeutic doses.9,10 This toxicity, a lethal degeneration of the brain stem, has resulted in a reexamination of these antimalarial drugs, particularly structure-activity relationships (SAR) as directed toward potency, oral administration, and neurotoxicity. 

Cicutoxin is concentrated in the roots but also may be found in aboveground parts. A mouthful of the root may be sufficient to kill an adult. Death results from status epilepticus, possibly caused by excessive stimulation of cholinergic receptors in the basal ganglia or brain stem. 

ALS was first described by the French neurologist Chariot in 1869. The disease involves rapid loss of motor neurons in the cortex, brain stem, and spinal cord death usually follows 3-5 years after diagnosis. ALS is more commonly referred to as Lou Gehrig s disease because it struck down the New York Yankees immortal at the peak of his baseball career. ALS usually occurs in a sporadic form but in rare cases there is a familial factor this provided the first clues to the molecular basis for ALS. 

The neonate is at risk for kemicterus if the serum unconjugated bilirubin level is higher than 17 mg/dL. Kemicterus is characterized by yellow staining of clusters of neuronal cell bodies in the basal ganglia, cerebellum, and brain stem, leading to motor and cognitive deficits or death. Immaturity and f)erhaps hypoxia make the blood-brain barrier permeable to bilirubin and contribute to the likelihood of kemictems. The biochemical basis of bilirubin encephalopathy is due to many causes inhibition of RNA and protein synthesis, carbohydrate metabolism (both cAMP-mediated and Ca " -activated), phospholipid-dependent protein kinases, enzymes involved in the electron transport system, and impaired nerve conduction. 

---