Biology of Brain Dysfunction, Softcover reprint of the original 1st ed. 1973
Volume 1

The growth of neurochemistry, molecular biology, and biochemical genetics has led to a burgeoning of new information relevant to the pathogenesis of brain dysfunction. This explosion of exciting new information is crying out for collation and meaningful synthesis. In its totality, it defies systematic summa­ tion, and, of course, no one author can cope. Thus invitations for contributions were given to various experts in areas which are under active investigation, of current neurological interest, and pregnant. Although this project is relatively comprehensive, by dint of size, other topics might have been included; the selection was solely my responsibility. I believe systematic summation a virtual impossibility-indeed, hardly worth the effort. The attempt to assemble all of the sections involved in a large treatise with multiple authors inevitably results in untoward delays due to the difference in the rate at which various authors work. Therefore, the following strategy has been adopted: multiple small volumes and a relatively flexible format, with publication in order of receipt and as soon as enough chapters are assembled to make publication practical and economical. In this way, the time lag between the ideas and their emergence in print is the shortest.

1 Genetic Disorders of Mucopolysaccharide Metabolism.- I. Introduction.- II. Classification of the Disorders.- A. Mucopolysaccharidosis I—the Hurler Syndrome.- B. Mucopolysaccharidosis II—the Hunter Syndrome.- C. Mucopolysaccharidosis III—the Sanfilippo Syndrome.- D. Mucopolysaccharidosis IV—the Morquio Syndrome.- E. Mucopolysaccharidosis V—the Scheie Syndrome.- F. Mucopolysaccharidosis VI—the Maroteaux-Lamy Syndrome.- G. Other Mucopolysaccharide Disorders.- III. Genetics.- IV. Chemical Pathology.- A. Storage.- B. Excretion of Mucopolysaccharides.- V. Chemistry of the Sulfated Mucopolysaccharides.- VI. The Biochemical Defect.- VII. Some Practical Applications of Recent Biochemical Findings.- VIII. Summary.- Note Added in Proof.- References.- 2 Galactosemia: Biochemistry, Genetics, Pathophysiology, and Developmental Aspects.- I. Introduction.- A. Evolutionary and Developmental Aspects.- B. Galactose Uptake.- II. Galactose Metabolism.- A. Galactokinase.- B. Galactose-1-Phosphate Uridylyl Transferase.- C. UDP-Galactose-4-Epimerase.- D. UDP-Glucose Pyrophosphorylase.- E. UDP-Glucose Dehydrogenase.- F. UDP-Galactose Galactosyl Transferase.- G. Galactose Dehydrogenase.- H. Galactose Reductase.- III. Hereditary Enzymatic Deficiencies in Galactose Metabolism.- A. Galactokinase Deficiency.- B. Galactose-1-Phosphate Uridylyl Transferase Deficiency.- C. Pedigree Studies.- D. Variations in Galactosemia.- E. Detection of Galactosemia.- IV. The Pathophysiology of Galactosemia.- A. Accumulation of Galactitol in Tissues.- B. Biochemical Basis for the Pathophysiology of Galactose-1-Phosphate Accumulation.- V. Treatment.- A. Dietary Control.- B. Outcome of Treatment.- References.- 3 Cytogenetic Aspects of Brain Dysfunction.- I. Introduction.- II. Incidence of Human Chromosome Anomalies.- III. Syndromes Related to Autosomal Abnormalities.- A. Numerical Aberrations.- B. Structural Aberrations.- IV. Syndromes Related to Sex Chromosome Abnormalities.- A. XXY—Klinefelter’s Syndrome.- B. XXXXY Syndrome.- C. XXX, XXXX, and XXXXX Females.- D. XYY and XXYY Males.- E. X0—Turner’s Syndrome.- V. Syndromes Related to Chromosome Breakages.- VI. Detection of Individuals with Abnormal Chromosomes.- VII. Prenatal Diagnosis of Chromosomal Abnormalities.- VIII. Concluding Remarks.- References.- 4 Disorders of Glucose Metabolism in Brain Dysfunction.- I. Introduction.- II. Systemic Disorders of Glucose Metabolism.- A. Hypoglycemia.- B. Systemic Disorders of Glucose Metabolism in Mental Disease.- III. Newer Concepts of Cerebral Glucose Metabolism in Vivo.- A. Human Subjects Studied with Arteriovenous Technique.- B. Animal Experiments on Metabolic Compartmentation in Brain.- C. Comments and Summary.- IV. Disorders of Glucose Metabolism in Brain.- A. Arteriovenous Studies with Chronic Mental Patients.- B. Convulsive Agents.- C. Hepatic Encephalopathy and Coma.- D. Hypoxia, Anoxia, and Hypocarbia.- E. Cerebral Vascular Disease and Cerebral Arteriosclerosis.- F. Other Conditions Causing Disorders in Cerebral Glucose Metabolism.- G. Comments and Summary.- References.- 5 Effects of Viral Infections on the Brain.- I. Introduction.- II. Methods.- A. Histological Techniques.- B. Histochemical Techniques.- C. Immunofluorescent Methods.- D. Electron Microscopy.- E. Cell and Tissue Culture Methods.- F. Virological Techniques.- G. Biochemical Methods.- H. Immunological Methods.- III. Pathways of Viral Spread.- A. Spread of Viruses to the Brain.- B. Dissemination of Viruses Within the Brain.- IV. Cellular Response to Viral Infection.- A. Susceptibility of Brain Cells to Viral Infection.- B. Cytopathic Effects.- C. Cell Proliferation.- D. Malignant Transformation.- E. Cellular Changes Resembling the Effect of Aging.- F. Infection of Cells Without Morphological Changes.- G. Inflammatory Reaction.- V. Biochemical Changes.- A. Nucleic Acids, Proteins, and Lipids.- B. Interferon.- VI. Immunological Reactions.- A. Formation of Humoral Antibodies.- B. Delayed-Type Hypersensitivity.- C. Autoimmune Response.- VII. Pathogenesis of Viral Diseases of the Brain.- A. Acute Infections.- B. Slow Infections.- C. Latent Infections.- D. Chronic Infections.- VIII. Conclusion.- References.- 6 Disorders of Cerebrospinal Fluid and Brain Extracellular Fluid.- I. Introduction.- II. Anatomical Considerations.- A. Cerebrospinal Fluid Compartment.- B. Brain Extracellular Fluid Compartment.- C. Further Physiological Considerations.- III. Pathophysiological Aspects of Cerebrospinal Fluid.- A. Appearance.- B. Cellular Elements.- C. Pressure.- D. Proteins and Amino Acids.- E. Glucose.- F. Lipids.- G. Enzymes.- H. Monoamines.- I. Miscellaneous.- IV. Pathophysiological Aspects of Brain Extracellular Fluid.- A. General Considerations.- B. Acid-Base.- C. Lactic Acid.- D. Sodium.- E. Potassium.- F. Chloride.- G. Calcium.- H. Magnesium.- I. Osmolality.- References.- 7 Disorders of Nucleic Acid Metabolism.- I. Disorders of Purine Metabolism.- A. The Lesch-Nyhan Syndrome.- B. Overproduction Hyperuricemia with Partial Deficiency of HGPRT.- C. Other Hyperuricemic Disorders Presenting in Childhood in Which HGPRT Is Normal.- D. Gout.- E. Xanthinuria.- II. Disorders of Pyrimidine Metabolism.- A. Orotic Aciduria.- References.- 8 Effects of Malnutrition on Brain Development.- I. Introduction.- II. General Considerations Involved in Cellular Growth.- III. Normal Cellular Growth of the Brain.- IV. Nutritional Effects on Cellular Growth of the Brain.- V. Prenatal Malnutrition.- VI. Summary.- References.- 9 Pathophysiology of Anoxic Brain Damage.- I. Introduction.- II. Normal Oxidative Metabolism in the Brain.- III. Work Performed by the CNS Cells.- IV. Supply of Oxygen to the Brain Cells.- V. Supply and Metabolism of Substrates.- A. Glycolysis.- B. The Tricarboxylic Acid Cycle.- C. The Electron Transport Chain.- D. Rate of Control of TCA Reactions and Electron Transport.- E. Relations to Amino Acid Metabolism.- F. CO2 Fixation in the Brain.- VI. Energy Flow and Energy State.- A. Tissue Acid-Base Metabolism.- B. The Energy Charge Potential.- VII. Measurements of Energy States and Metabolite Levels.- VIII. Types of Cerebral Hypoxia and Anoxia.- A. Hypoxemia.- B. Reduced Oxygen-Carrying Capacity.- C. Ischemia.- IX. Cerebral Changes in Anoxia and Hypoxia.- A. Acute, Total Anoxia.- B. Subtotal Anoxia.- X. Cerebral Changes in Ischemia.- A. Total Ischemia.- B. Regional Metabolic Changes.- C. Changes in Intracellular pH.- D. Revival after Complete Ischemia.- E. Subtotal Brain Ischemia.- XI. Factors Modifying the Response to Anoxia.- A. Age.- B. Temperature.- C. Anesthesia.- References.- 10 Effects of Deficiencies of Folic Acid and Vitamin B12 on Central Nervous System Function and Development.- I. Introduction.- II. Biochemical Roles of Coenzyme Forms of Folic Acid and Vitamin B12.- III. Central Nervous System Damage Due to Folic Acid Deficiency.- A. Developmental Damage to Fetus Related to Use by Mother of Antifolates.- B. Developmental Damage to Newborn Related to Congenital Defects in Folate Absorption or Utilization.- C. Functional Damage to Adults Related to Nutritional Folate Deficiency.- D. Anticonvulsants and Folate Deficiency—Folic Acid Alleged Undesirable for Epileptic Patients.- E. Severe Neurological Damage in Adults Associated with Intrathecal Methotrexate Therapy.- IV. Central Nervous System Damage Due to Vitamin B12 Deficiency.- A. Developmental Damage to Newborn Related to Congenital Defects in Vitamin B12 Utilization.- B. Structural and Functional Damage Due to Nutritional Vitamin B12 Deficiency at Any Age.- References.