Metabolic encephalopathy

Abstract

100 years ago, in the publication of the Croonian Lecture on Inborn Errors of Metabolism (Lancet 1908; 172: 1–7), AE Garrod wrote “the factors which confer upon us our predispositions to and immunities from the various mishaps which are spoken of as diseases, are inherent in our very chemical structure; and even in the molecular groupings which confer upon us our individualities and which went to the making of the chromosomes from which we sprang”. Since then, we have come a long way, and now the concept that cell functions are dependent on the biochemical regulation in different organs, and that this regulation is under genetic control, is taken for granted. The biochemical basis of brain functions and dysfunctions is important and knowledge of it is a crucial part in basic and clinical neurosciences. This book summarises a wealth of information on several neurological disorders from animal models to human conditions—from hypoglycaemic and hypoxic brain damage to vascular disorders; from seizure to hepatic, bilirubin, and uremic encephalopathy; from genetic myelin disorders to aminoacidopathies and galactosaemia; from inflammatory disorders of the CNS to toxic encephalopathies (from alcohol or lead); and, finally, from Alzheimer's disease to prion diseases. In all of these conditions, the main neuropathological and clinical abnormalities are described in terms of metabolic changes, which might, in different ways, influence the neuronal or glial cells and the neuroaxonal circuits as the nervous system cells have a selective vulnerability to the different biochemical dysfunctions. “The reasons for this cerebral specificity are largely unclear, but some studies show vastly different metabolism between brain regions: the cerebellum, for example, is biochemically different from adjacent areas.” Special attention is given to the pathogenetic aspects of the different symptoms in terms of neurochemical changes of cell metabolism and neurotransmitters, and of possible interference of treatment. This approach provides the book with a useful role for continuous education of general neurologists and for introducing neurological diseases to trainees in a modern way. Although most of the chapters give an extensive approach to selected disorders (usually a specific disease), the chapter dedicated to genetic leucodystrophies is less comprehensive, including only three examples: one due to a lysosomal dysfunction (Krabbe's disease), a second due to a peroxisomal dysfunction (adrenoleucodystrophy), and a third due to mitochondrial dysfunction (Canavan's diseases). The other many forms are excluded, some of which are more common. A chapter dedicated to myelination and myelin functions and dysfunctions, including multiple sclerosis, would complete the book in a future edition. In clinical practice, many of these metabolic encephal-opathies are generally poorly recognised. Therefore, this book helps to increase awareness of the importance of early diagnosis and treatment of these disorders, which can reduce the incidence of structural brain changes and morbidity. Published a century after Garrod's Croonian Lecture, Metabolic Encephalopathy stresses the primitive role of metabolic brain dysfunction as a basis of all the different neurological diseases. Moreover, this book suggests that increased knowledge of the biochemical basis of brain function is important for treatment and for further development of research into many neurological conditions.