Observations on the symptomatology and pathogenesis of hepatic coma.
1. The literature describing the neurological manifestations of hepatic coma is reviewed.

2. The neurological signs observed in 18 cases of hepatic coma are described. The full picture consisted of personality changes, mania, and coma, with dilated pupils, choreifonn movements of the arms, tome grasping, and sometimes lead-pipe or cogwheel rigidity; absent abdominal reflexes, increased knee-jerks, ankle clonus, and extensor plantar responses. In some cases there was either spasticity or lead-pipe rigidity of the legs. During the early phase of coma the patients sometimes adopted a characteristic posture, with the legs tightly drawn up to the abdominal wall. Cranial nerve palsies were a rare accompaniment, and convulsions were not observed. All these changes were more prominent in children than in adults.

3. A number of theories to account for such changes have been advanced at various times. It is here suggested that hypoglycaemia may precipitate convulsions, but is not otherwise directly associated with the production of symptoms. The possibility of an intestinal toxin passing through a damaged liver to enter the general circulation is discarded; so also is the theory that acetylcholine accumulates in the blood as a result of a fall in the plasma-cholinesterase. Reference is made to experimental work which suggests that the products of autolysis of the liver parenchyma, which have a high aminoacid content, are toxic. It is possible that these products, entering the circulation, account for the phase of excitement observed in acute liver failure.

4. The theory is put forward that the disturbed pattern of blood aminoacids, which occurs as the result of both acute and chronic liver failure, may be toxic' to the brain. Experimental work in animals which supports this theory is briefly referred to. It is suggested that the variable clinical picture of hepatic coma is almost certainly of biochemical origin, and may be directly related to the variable pattern of the blood aminoacids.

5. The part played by glutamic acid metabolism in the central nervous system is described. It is suggested that in some cases interference may have occurred in the utilization of t.hia substance, with a consequent breakdown in the ammonia-binding mechanism of the brain. There may also have been a