1916 



IIKDHikiK nl PHYSIOLOGY 



NKrkOI'HYSIOI.OGY III 



common genetic fault? Diets low in phenylalanine 

 sources do appear to have a salutory effect on the 

 condition (g). When the diet is given to some affected 

 children, then- is a substantial improvement in mood, 

 behavior, motor activity and responses to other people. 

 When phenylalanine is again given to such children, 

 these improvements are reversed. Beyond this degree 

 of improvement the mental retardation has not been 

 reversed by diet or other therapy. It is quite possible 

 that the synthesis of normal molecular constituents 

 in the developing nerve cells is abnormal from early 

 fetal or embryonal life. The answer to the puzzle may 

 come when a newborn infant who excretes phenyl- 

 pyruvate is put on a low phenylalanine diet at once. 

 Thus far phenylketonuria has not been present in 

 any individual who has not also been mentally 

 defective. 



. ludiogenit Seizures 



In a number of rodents, violent convulsions may 

 occur when the animals hear loud, high-pitched 

 noises (15). The convulsions are often quickly lethal. 

 Although this behavior is superficially similar in the 

 various animals, and a recognized genetic process 

 lies at the root of many, the mechanism of expression 

 differs. Various environmental factors, such as dietary 

 constituents, drugs and infections, also influence the 

 degree of susceptibility to the seizures. One inbred 

 strain of mice known as DBA 2 has been studied 

 extensively. In these animals the period of suscepti- 

 bility to lethal sonogenic convulsions is virtually 

 limited to the postnatal age of 24 to 45 da\s. The 

 genetic situation is that of a dominant, apparently 

 single factor which in more than 80 per cent of cases 

 expresses itself through a response to the sound range 

 usually employed experimentally. A high-pitched 

 sound, such as an air blast or a door-bell, precipitates 

 the onset of rapid running movements, then tonic, 

 clonic .md spasmodic convulsions. Depending on the 

 noise (and on the individual) death or recovery 

 results; the fatal reaction may occur in less than 



((ii sec. A number of anticpileptic drugs, glutamate 

 for example, can raise the threshold for seizures or 

 actually prevent them, while other compounds lower 

 the threshold. 



The liioclicmic.il disturbance responsible in DBA 

 mice has been related to an abnormality of phos 

 phorylation in the forebrain, probably not in the 

 brain stem (1). Compared with .1 control strain "l 

 mice .11 age 30 days, oxidative phosphorylation in 

 brain homogenates ol ;o-day-old DBA mice is sub- 



stantially reduced, and adenosinctriphosphatase is 

 significantly lower than normal. These and some 

 related indicators of a 'defective' phosphorylative 

 system are present up to about 45 days of age when 

 they are gradually replaced by normal values. The 

 investigators interpret the findings as indicating that 

 the lower threshold for convulsive excitation of the 

 DBA mouse brain is caused by a relative lack of 

 energy-synthesizing processes which normally keep 

 functional activity under restraint. 



The chief point of interest about audiogenic seizures 

 in these mice is that they seem to illustrate how an 

 ontogenetic delay in maturation of one part of the 

 metabolic machinery — the formation of certain 

 enzymes in the brain itself — can place the organism 

 in a specifically precarious neurophysiolosjic position 

 in relation to its environment. The condition may be 

 viewed as a 'transient' inborn error of metabolism. 

 The month-old mouse is in a stage of transition to an 

 adult pattern of highly oxygen-dependent brain 

 metabolism which normally results from an har- 

 monious and synchronous maturation of molecular 

 events. How many analogous situations there may 

 be among vertebrates where asynchronous timing of 

 developmental metabolic processes leads to transient 

 imbalances and temporary neurophysiologic dis- 

 turbances can onlv be sjuessed. 



NEOPLASTIC DEVELOPMENT 



A number of developmental disorders express 

 themselves in the form of abnormal growths or frank 

 neoplasms early in life, often being present at birth. 

 Vascular malformations and hemangiomas are among 

 the commonest, functional changes being referable 

 to the part of the nervous system involved by the 

 vascular growth or second. nib affected by impaired 

 blood supply. Tuberous sclerosis is .1 rare example of a 

 semineoplastic malformative process involving the 

 brain. The occurrence of similar gliomas in identical 

 twins at the same lime, although rare, suggests that a 

 developmental disturbance might underlie some ol 

 these growths. 



Retinoblastoma 



This rare tumor composed of embryonal neural 

 cells may develop in the retina in infants or young 

 adults 1 171. Although usually fatal, some tumors are 

 apparently self-limiting, dying out before they spread 

 hi metastasize. The disease is due to a dominant gene 



