title: Hypothalamic digoxin-mediated model for subacute sclerosing panencephalitis.
abstract: The isoprenoid pathway including endogenous digoxin was assessed in subacute sclerosing panencephalitis (SSPE). This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The following parameters were measured in patients with SSPE and in individuals with right hemispheric, left hemispheric and bihemispheric dominance-(a) plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; (b) tryptophan/tyrosine catabolic patterns; (c) free-radical metabolism; (d) glycoconjugate metabolism; and (e) membrane composition and RBC membrane Na(+)-K(+) ATPase activity. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with SSPE and in those with right hemispheric dominance. In this group of patients: (a) the tryptophan catabolites were increased and the tyrosine catabolites reduced; (b) the dolichol and glycoconjugate levels were elevated; (c) lysosomal stability was reduced; (d) ubiquinone levels were low and free-radical levels increased; and (e) the membrane cholesterol:phospholipid ratios were increased and membrane glycoconjugates reduced. On the other hand, in patients with left hemispheric dominance the reverse patterns were obtained. The upregulated isoprenoid pathway and hypothalamic digoxin are involved in the pathogenesis of SSPE. SSPE occurs in right hemispheric chemically dominant individuals and a pathogenetic model for SSPE implicating hypothalamic digoxin is proposed.
authors.affiliation: Dept. of Neurology, Medical College, Trivandrum, Kerala, India.
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Kurup
authors.forename: Parameswara Achutha
authors.initials: PA
authors.lastname: Kurup
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004077:Digoxin / Q000378:metabolism*; D004286:Dolichols / Q000097:blood; D004292:Dominance, Cerebral; D004910:Erythrocyte Membrane / Q000201:enzymology; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism* / Q000503:physiopathology*; D008247:Lysosomes / Q000201:enzymology; D008274:Magnesium / Q000378:metabolism; D008297:Male; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013344:Subacute Sclerosing Panencephalitis / Q000097:blood* / Q000503:physiopathology*; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014451:Ubiquinone / Q000097:blood
chemical_list: D004286:Dolichols; D011106:Polyisoprenyl Phosphates; D014451:Ubiquinone; D014443:Tyrosine; D004077:Digoxin; D014364:Tryptophan; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium