Biology of Brain Dysfunction

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.