glycogen and Ataxia

Congenital enzymopathic hyperlactacidemia results from a defect of utilisation of pyruvate either at the level of the pyruvate junction (pyruvate-carboxylase, pyruvate-dehydrogenase and Kreb's cycle), or at the level of the unidirectional enzymes on neo-glucogenesis and of neo-glycogenogenesis, e.g. glucose-6-phosphatase, phosphoenol-pyruvate-carboxykinase and glycogen synthetase. The enzymopathies which affect neoglucogenesis associate hyper-lactacidemia and fasting hypoglycemia and more or less marked hepatomegaly. Type I glycogenesis (von Gierke's disease) is the best known example. Enzymopathies which affect the pyruvate junction and the Krebs cycle, may be manifested in addition by: --either chronic neuropathies, e.g. Leigh's disease, recurrent ataxia, and moderate hyperalactacidemia,--or, as in congenital lactic acidoses, which have a rapid and severe prognosis with major hyperlactacidemia. Functional investigation, in particular, loading tests are of great value in orientation and justify the practice of tissue biopsy which permits the enzyme diagnosis. Recent, still unconfirmed knowledge of the pathogenesis of these diseases emphasizes the considerable importance of estimation of blood lactic acid in the investigation of metabolic acidoses of hereditary origin.

Topics: Acidosis; Ataxia; Brain Stem; Carbohydrate Metabolism, Inborn Errors; Citric Acid Cycle; Encephalomalacia; Fructose-1,6-Diphosphatase Deficiency; Glucose; Glycogen; Glycogen Storage Disease Type I; Glycogen Synthase; Humans; Infant; Infant, Newborn; Intellectual Disability; Lactates; Phosphoenolpyruvate Carboxykinase (GTP); Psychomotor Disorders; Pyruvate Carboxylase Deficiency Disease; Pyruvate Dehydrogenase Complex Deficiency Disease; Pyruvates

The causality of vascular and parenchymal damage to the central nervous system (CNS) was examined in rats with thiamine deficiency. Male Sprague-Dawley rats were divided into two groups; one was given a thiamine-deficient diet (TDD) and injected intraperitoneally with 10 micrograms/100 g bodyweight pyrithiamine (PT) in order to analyze morphometrically the topographical and sequential relationship between vascular and parenchymal changes and vasodilatation, and the other was given a TDD and 50 micrograms/100 g bodyweight PT in order to determine hemorrhagic sites using serial sections. Histological examination showed that spongiotic change occurred selectively in the inferior colliculus (100%) from day 19, and thereafter in the thalamus (95%), mammillary body (50%) and nuclei olivaris and vestibularis of the pons (25%), with or without hemorrhage. Simultaneously, glycogen accumulation was also observed in these regions at a frequency similar to that of hemorrhage. Ultrastructurally, however, hydropic swelling of astrocytic and neuronal processes without glycogen accumulation was observed as early as day 9 in the inferior colliculus, at which time an increase of glial fibrillary acidic protein-positive processes was also recognized. The superior colliculus was completely spared. From day 22 vasodilatation of the inferior colliculus occurred, concomitantly with bodyweight loss and neurological symptoms. Twenty-two examined hemorrhages, which occurred in the thalamus and inferior colliculus, were distributed along the arterioles or capillaries on the arterial side. In conclusion, the morphological CNS changes caused by thiamine deficiency with administration of low-dose PT in rats begin as hydropic swelling of neuronal and astrocytic processes, followed by hemorrhage and, thereafter, by vasodilation. The predilection for hemorrhage on the arterial side without parenchymal changes suggests that petechial hemorrhage is not simply secondary to parenchymal changes, but is due to hemodynamic change resulting from thiamine deficiency-induced vascular dysfunction.

Topics: Animals; Antimetabolites; Ataxia; Body Weight; Brain; Cerebral Hemorrhage; Glial Fibrillary Acidic Protein; Glycogen; Hypothermia; Immunohistochemistry; Inferior Colliculi; Male; Mammillary Bodies; Pyrithiamine; Rats; Rats, Sprague-Dawley; Seizures; Thalamus; Thiamine Deficiency; Vasodilation; Wernicke Encephalopathy

Topics: Animals; Ataxia; Cerebellar Nuclei; Extracellular Space; Genes, Lethal; Glycogen; Histocytochemistry; Medulla Oblongata; Microscopy, Electron; Neuroglia; Neurons; Pons; Rabbits; Time Factors

Topics: Animals; Ataxia; Brain Stem; Carbon Isotopes; Cerebral Cortex; Cytidine; Fatty Acids, Nonesterified; Glycerides; Glycogen; Inositol; Nucleotides; Phosphatidylinositols; Phosphotransferases; Rabbits; Transferases; Triglycerides

Topics: Animals; Ataxia; Brain; Carbohydrate Metabolism, Inborn Errors; Cerebellum; Glucose; Glycogen; Histocytochemistry; Lactates; Medulla Oblongata; Mesencephalon; Microscopy, Electron; Pons; Rabbits

Topics: Aged; Amyloid; Ataxia; Cerebellar Cortex; Glycogen; Humans; Male; Middle Aged; Myxedema; Neuroglia; Purkinje Cells; Spinal Cord