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in whom much of the cerebrum is not fully developed, is much less obvious than one in an older child Moreover, as the disease evolves, the clinical manifestations are always in uenced by the ongoing maturation of the untouched elements in the nervous system These interactions may give the impression of regression of attained neurologic function, lack of progress of development (developmental delay), or even improvement in function that is attributable to continuing maturation of the normal parts of the nervous system The separation of metabolic-genetic from degenerative diseases (accorded a separate chapter) may disquiet the reader, for there are many overlaps between the two groups The current division is tenable only until such time as all the degenerative diseases will have been shown to have a comprehensible pathogenesis Because of the overriding importance of the age factor and the tendency of certain pathologic processes to appear in particular epochs of life, it has seemed to the authors logical to group the inherited metabolic diseases not according to their major syndromes of expression, as we have done in other parts of the book, but in relation to the periods of life at which they are most likely to be encountered: the neonatal period, infancy (1 to 12 months), early childhood (1 to 4 years), late childhood, adolescence, and adult life Only in the last two age periods do we return to the more clinically useful syndromic ordering of diseases In adopting this chronological subdivision, we realize that certain hereditary metabolic defects that most typically manifest themselves at a particular period in life are not necessarily con ned to that epoch and may appear, sometimes in variant form, at a later stage Such variations are noted at appropriate points in the discussion

In the face of such clinical information, one should obtain appropriate biochemical analyses of blood, urine, and cerebrospinal uid (CSF); magnetic resonance imaging (MRI) of the brain; and, in certain instances, chromosome-genetic studies In addition to the investigation of symptomatic individuals, the array of available genetic and biochemical tests has made practical the mass screening of newborns for inborn metabolic defects Innovative tests have also led to the discovery of a number of previously unknown diseases and have clari ed the basic biochemistry of old ones As a consequence, the neurologist s role is changing No longer must he wait until a disease of the nervous system has declared itself by conventional symptoms and signs, by which time the underlying lesion may have become irreversible Now it is possible to nd patients who, though asymptomatic, are at risk and to introduce dietary and other measures that may prevent injury to the nervous system This is especially important to families who have already had an affected infant To assume this new responsibility intelligently requires some knowledge of genetics, biochemical screening methods, and public health measures The many clinical syndromes by which these inborn errors of metabolism declare themselves vary in accordance with the nature of the biochemical defect and the stage of maturation of the nervous system at which these metabolic alterations become apparent In phenylketonuria, for example, there is a speci c effect on the cerebral white matter, mainly during the period of active myelination; once the stages of myelinogenesis are complete, the biochemical abnormality becomes relatively harmless Even more important from the neurologist s point of view is the level of function that has been achieved by the developing nervous system when the disease strikes A derangement of function in a neonate or infant,

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A small number of progressive metabolic diseases become evident in the rst few days of life The importance of these diseases relates not to their frequency (they constitute only a small fraction of diseases that compromise nervous system function in the neonate) but to the fact that they must be recognized promptly if the infant is to be prevented from dying or from suffering a lifelong severe mental de ciency This inherent threat introduces an element of urgency into neonatal neurology Recognition of these diseases is also important for purposes of family and prenatal testing Two approaches to the neonatal metabolic disorders are possible one, to screen every newborn, using a battery of biochemical tests of blood and urine, and the other, to undertake in the days following birth a detailed neurologic assessment that will detect the earliest signs of these diseases Unfortunately, not all the biochemical tests have been simpli ed to the point where they can be adapted to a mass screening program, and many of the commonly used clinical tests at this age have yet to be validated as markers of disease Moreover, many of the biochemical tests are costly, and practical issues such as cost-effectiveness insinuate themselves, to the distress of the pediatrician The recent introduction of tandem mass spectrometry for the evaluation of blood and urine has allayed some of the latter concerns

Dr Watson Windows 9x and Windows 2000/XP include a utility called Dr Watson, which can help you pinpoint the causes of errors in running applications When an error occurs or when the program is initiated by the user, Dr Watson takes a snapshot of the system s current configuration (see Figure 10-3) This information includes all currently running applications and tasks as well as currently loaded device and user drivers Also included is a Diagnosis tab, where Dr Watson will indicate error information such as which program experienced the error, which program caused the error, and which memory address was the site of the error The Dr Watson snapshot can be saved as a log file so that you can refer to it at a later time Dr Watson does not run automatically when you start Windows, so when an error occurs, you must initiate the utility right away to get an accurate record of the system s configuration Note that some applications start the Dr Watson utility automatically when you run them Once Dr Watson is running, it will continue to monitor application performance and can automatically inform you when an error occurs Follow the steps in Exercise 10-2 to start Dr Watson, take a system snapshot, and log the details in Windows 98

Returned sum of values: 140

As pointed out in Chap 28, the neonate s nervous system functions essentially at a brainstem-spinal level The pallidum and visuo-

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