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Review

Oxidative injury in epilepsy: potential for antioxidant therapy?

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Pages 541-553 | Published online: 10 Jan 2014

References

  • Brodie MJ, Dichter MA. Antiepileptic drugs. N. Engl. Med 334, 168–175 (1996).
  • Schwartzkroin PA. Basic mechanisms of epileptogenesis. In: The Treatment of Epilepsy: Principles and Practice. Wyllie E (Ed.). Williams & Wilkins, MD, USA, 106–121 (1997).
  • Babb TL, Pretorius JK. Pathological substrates of epilepsy. In: The Treatment of Epilepsy: Principles and Practice. Wyllie E (Ed.). Williams & Wilkins, MD, USA, 106–121 (1997).
  • Johnston MV. Neurotransmitters and Epilepsy. In: The Treatment of Epilepsy: Principles and Practice. Wyllie E (Ed.). Williams & Wilkins, MD, USA, 122–138 (1997).
  • Meldrum BS. Identification and preclinical testing of novel antiepileptic compounds. Epilepsia 38, S7—S15 (1997).
  • Biervert C, Schroeder BC, Kubisch C et al A potassium channel mutation in neonatal human epilepsy. Science 279, 403–406 (1998).
  • Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants and the degenerative diseases of aging. Proc. Natl Acad. Li. USA 90, 7915–7922 (1993).
  • Marnett LJ, Hurd H, Hollstein MC, Esterbauer DE, Ames BN. Naturally occurring carbonyl compounds are mutagens in Salmonella tester strain TA104. Mutat. Res. 148, 25–34 (1985).
  • Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation and impairment of antioxidant enzymes in aging. Experiment. Biol. Med. 227, 671–682 (2002).
  • •Provides a synopsis of current thinking on the role played by oxidative injury in aging.
  • Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 59, 527–605 (1979).
  • Ratan RR, Murphy TH, Baraban JM. Oxidative stress induces apoptosis in embryonic cortical neurons. j Neurochem. 62, 376–379 (1994).
  • Whittemore ER, Loo DT, Cotman CW. Exposure to hydrogen peroxide induces cell death via apoptosis in cultured rat cortical neurons. Neuromport5, 1485–1488 (1994).
  • Geller HM, Cheng KY, Goldsmith NK et al. Oxidative stress mediates neuronal DNA damage and apoptosis in response to cytosine arabinoside. j Neurochem. 78, 265–275 (2001).
  • Greenlund LJ, Deckwerth TL, Johnson EM. Superoxide dismutase delays neuronal apoptosis: a role of reactive oxygen species in programmed neuronal death. Neumn 14, 303–315 (1995).
  • Stoian I, Oros AA, Moldoveanu E. Apoptosis and free radicals. Biochem. Mal Med. 59, 93–97 (1996).
  • Chan PH, Chu L, Chen SF, Carlson EJ, Epstein CJ. Reduced neurotoxicity in transgenic mice overexpressing human copper—zinc—superoxide dismutase. Stroke 21\(Suppl. 11), 80–82 (1990).
  • Martin KR Barrett JC. Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signalling versus high-dose toxicity. Hum. ET. Toxicol. 21, 71–75 (2002).
  • Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB I 10, 709–720 (1996).
  • Hensley K, Robinson KA, Gabbita SP, Salsman S, Floyd RA. Reactive oxygen species, cell signalling and cell injury. Free Radic. Biol. Med. 28, 1456–1462 (2000).
  • Crow JP, Ischiropoulos H. Detection and quantification of nitrotyrosine residues in proteins: in vivo marker of peroxynitrite. Method Enzymol 269, 185–194 (1996).
  • Ischiropoulos H, Gow A, Thom SR, Kooy NW Royall JA, Crow JR Detection of reactive nitrogen species using 2,7-dichlorodihydrofluorescein and dihydrorhodamine 123. Methods Etzzymol. 301, 367–373 (1999).
  • Buss H, Chan TP, Sluis KB, Domigan NM, Winterbourn CC. Protein carbonyl measurement by a sensitive ELISA method. Free Radic. Biol. Med. 23, 361–366 (1997).
  • Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ II. A series of prostaglandin F2-like compounds are produced in vivo in humans by a noncyclooxygenase, free radical-catalyzed mechanism. Proc. Natl Acad. Li. USA 87, 9383–9387 (1990).
  • Delanty N, Reilly M, Pratico D, Fitzgerald DJ, Lawson JA, Fitzgerald GA. 8-Epi PGF2 a: specific analysis of an isoeicosanoid as an index of oxidant stress in vivo. BE J. Clin. Pharmacol 42, 15–19 (1996).
  • Helbock HJ, Beckman KB, Ames BN. 8- Hydroxydeoxyguanosine and 8-hydroxyguanine as biomarkers of oxidative DNA damage. Methods Etzzymol 300, 156–166 (1999).
  • Halliwell B, Gutteridge J. Free Radicals in Biology and Medicine. Third Edition. Oxford University Press, Oxford, UK.
  • ••Currendt the best reference text on free radical pathobiology.
  • Beal MF, Ferrante RJ, Browne SE, Matthews RT, Kowall NW, Brown RII Jr.Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann. Neural 42, 644–654 (1997).
  • Przedborski S, Donaldson DM, Murphy PL etal. Blood superoxide dismutase, catalase and glutathione peroxidase activities in familial and sporadic amyotrophic lateral sclerosis. Neumdegeneration 5, 57–64 (1996).
  • Przedborski S, Donaldson D, Jakowec M et al. Brain superoxide dismutase, catalase and glutathione peroxidase activities in amyotrophic lateral sclerosis. Ann. Neural. 39, 158–165 (1996).
  • Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid - peptide-associated free radical oxidative stress. Free Radic. Biol. Med. 32, 1050–1060 (2002).
  • Markesbery WR, Carney JM. Oxidative alterations in Alzheimer's disease. Brain Athol 9, 133–146 (1999).
  • Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Eng" J. Med. 320, 915–924 (1989).
  • Salonen JT, Yla-Herttuala S, Yamamoto R et al Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 339, 883–887 (1992).
  • Pulsinelli W Pathophysiology of acute ischaemic stroke. Lancet 339, 533–536 (1992).
  • Hall ED, McCall JM, Means ED. Therapeutic potential of the lazaroids (21-aminosteroids) in acute central nervous system trauma, ischaemia and subarachnoid hemorrhage Adv. Pharmacol. 28, 221–268 (1994).
  • Browne SE, Bowling AC, MacGarvey U et al Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann. Neural 41, 646–653 (1997).
  • Sian J, Dexter DT, Lees AJ, Daniel S, Jenner P, Marsden CD. Glutathione-related enzymes in brain in Parkinson's disease. Ann. Neural 36, 356–361 (1994).
  • Jenner P, Dexter DT, Sian J, Schapira AH, Marsden CD. Oxidative stress as a cause of nigral cell death in Parkinson's disease and incidental Lewy body disease. The Royal
  • •• Kings and Queens Parkinson's disease Research Group. Ann. Neural. 32, S82—S87 (1992).
  • Gotoda T, Arita M, Arai H et al Adult- onset spinocerebellar dysfunction caused by a mutation in the gene for the a-tocopherol-transfer protein. N Engl. Med. 16,1313–1318 (1995).
  • Yokota T, Shiojiri T, Gotoda T et al Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the a-tocopherol transfer protein gene. Ann. Neural. 41,826-832 (1997).
  • Shohami E, Gati I, Beit-Yannai E, Trembovler V, Kohen R. Closed head injury in the rat induces whole body oxidative stress: overall reducing antioxidant profile. I Neurotrauma 16, 365–376 (1999).
  • Marshall LF, Maas AI, Marshall SB et al A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury. Neurosurg. 89,519–525 (1998).
  • Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, Marshall LE Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two Phase III clinical trials. The Selfotel Investigators.' Neurosurg. 91,737-743 (1999).
  • Geromel V, Darin N, Chretien D et al. Coenzyme Q (10) and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Mal Genet. Metab. 77,21-30 (2002).
  • Wei YH, Lee HC. Mitochondrial DNA mutations and oxidative stress in mitochondrial diseases. Adv. Clin. Chem. 37,83–128 (2003).
  • Delanty N, Dichter MA. Oxidative injury in the nervous system. Acta Neural. Land. 98,145–153 (1998).
  • Jenner P. Oxidative damage in neurodegenerative disease. Lancet 344, 796–798 (1994).
  • Avshalumov MV, Rice ME. NMDA receptor activation mediates hydrogen peroxide-induced pathophysiology in rat hippocampal slices. I Neurophysiol 87, 2896–2903 (2002). Outlines the direct evidence that free radical exposure can directly lead to neuronal hyperexcitability.
  • Frantseva MV, Perez Velazquez JL, Carlen PL. Changes in membrane and synaptic properties of thalamocortical circuitry caused by hydrogen peroxide. Neurophysiol 80,1317–1326 (1998).
  • Mailly F, Mann P, Israel M, Glowinski J, Premont J. Increase in external glutamate and NMDA receptor activation contribute to H202-induced neuronal apoptosis. Neurochem. 73,1181-1188 (1999).
  • Sah R, Schwartz-Bloom RD. Optical imaging reveals elevated intracellular chloride in hippocampal pyramidal neurons after oxidative stress. I Neurosci. 19, 9209–9217 (1999).
  • Sah R, Galeffi F, Ahrens R, Jordan G, Schwartz-Bloom RD. Modulation of the GABA(A)-gated chloride channel by reactive oxygen species. I Neurochem. 80, 383–391 (2002).
  • Fattman CL, Schaefer LM, Oury TD. Extracellular superoxide dismutase in biology and medicine. Free Radic. Biol. Med. 35,236–256 (2003).
  • Shaw CA, Bains JS. Synergistic versus antagonistic actions of glutamate and glutathione: the role of excitotoxicity and oxidative stress in neuronal disease. Cell Mal Biol. 48,127–136 (2002).
  • Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res. Rev. 25,335–358 (1997).
  • Delanty N, Dichter MA. Antioxidant therapy in neurologic disease. Arch. Neural 57,1265–1270 (2000).
  • Muntwyler J, Hennekens CH, Manson JE, Buring JE, Gaziano JM. Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Arch. Intern Med. 162,1472–1476 (2002).
  • Gaziano JM, Manson JE, Buring JE, Hennekens CH Dietary antioxidants and cardiovascular disease Ann. NY Acacl Sci. 669,249–258 (1992).
  • Gridley G, McLaughlin JK, Block G, Blot WJ, Gluch M, Fraumeni JF Jr. Vitamin supplement use and reduced risk of oral and pharyngeal cancer. Am. I Epidemial 135,1083–1092 (1992).
  • Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and mortality among a sample of the United States population. Epidemiology3, 194–202 (1992).
  • Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl. Med. 328,1444–1449 (1993).
  • Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl. Med. 328,1450–1456 (1993).
  • Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek poulation. N Engl. I Med. 348, 2599–2608 (2003).
  • Schmid-Elsaesser R, Zausinger S, Hungerhuber E, Plesnila N, Baethmann A, Reulen HJ. Superior neuroprotective efficacy of a novel antioxidant (U-101033E) with improved blood—brain barrier permeability in focal cerebral ischaemia. Stroke 28,2018-2024 (1997).
  • Andrus PK, Fleck TJ, Oostveen JA, Hall ED. Neuroprotective effects of the novel brain-penetrating pyrrolopyrimidine antioxidants U-101033E and U-104067F against postischaemic degeneration of nigrostriatal neurons. I Neurosci Res. 47,650–654 (1997).
  • Cowers WR. Epilepsy and Other Chronic Convulsive Disorders: Their Cases, Symptoms and Treatment William Wood, NY, USA, 225 (1881).
  • Murthy VN. Synaptic plasticity: step-wise strengthening. CUI7: Bia 8, R650—R653 (1998).
  • Triggs WJ, Willmore U. In vivo lipid peroxidation in rat brain following intracortical Fe2+ injection. I Neurochem. 42,976–980 (1984).
  • Willmore LJ, Triggs WJ. Effect of phenytoin and corticosteroids on seizures and lipid peroxidation in experimental posttraumatic epilepsy. I Neurosurg. 60, 467–472 (1984).
  • •Demonstrates that lipid peroxidation is a key factor in the iron chloride animal model of epileptogenesis. Also highlights the lack of effect of phenytoin on lipid peroxidation and lack of effect in preventing the development of post-traumatic epilepsy.
  • Willmore LJ, Rubin JJ. Formation of malonaldehyde and focal brain oedema induced by subpial injection of FeC12 into rat isocortex. Brain Res. 246,113–119 (1982).
  • •Demonstrates the role of oxidative injury in the iron chloride animal model of epileptogenesis.
  • Willmore LJ, Hiramatsu M, Kochi H, Mori A. Formation of superoxide radicals after FeC13 injection into rat isocortex. Brain Res. 277,393–396 (1983).
  • Willmore LJ, Triggs WJ, Gray JD. The role of iron-induced hippocampal peroxidation in acute epileptogenesis. Brain Res. 382, 422–426 (1986).
  • Singh R, Pathak DN. Lipid peroxidation and glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and glucose-6-phosphate dehydrogenase activities in FeC13-induced epileptogenic foci in the rat brain. Epilepsia 31,15–26 (1990).
  • Kabuto H, Yokoi I, Habu H, Willmore LJ, Mori A, Ogawa N. Reduction in nitric oxide synthase activity with development of an epileptogenic focus induced by ferric chloride in the rat brain. Epilepsy Res. 25, 65–68 (1996).
  • Willmore LJ, Triggs WJ. Iron-induced lipid peroxidation and brain injury responses. Int. Dev. Neurosci. 9,175–180 (1991).
  • Ciliffi M, Gentilini G, Franchi-Micheli S, Zilletti L. Lipid peroxidation induced in vivo by iron-carbohydrate complex in the rat brain cortex. Neurochem. Res. 16,43–49 (1991).
  • Frantseva MV, Velazquez JL, Hwang PA, Carlen PL. Free radical production correlates with cell death in an in vitro model of epilepsy. Etc: j Neurosci. 12, 1431–1439 (2000).
  • Layton ME, Pazdernik TL. Reactive oxidant species in piriform cortex extracellular fluid during seizures induced by systemic kainic acid in rats. J. Mal Neurosci. 13,63–68 (1999).
  • Frantseva MV, Perez Velazquez JL, Tsoraklidis G et al Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 97,431–435 (2000).
  • Kovacs R, Schuchmann S, Gabriel S, Kann O, Kardos J, Heinemann U. Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. .1. Neurophysiol 88,2909–2918 (2002).
  • Milatovic D, Zivin M, Gupta RC, Dettbarn WD. Alterations in cytochrome c oxidase activity and energy metabolites in response to kainic acid-induced status epilepticus. Brain Res. 912,67–78 (2001).
  • Kurekci AE, Alpay F, Tanindi S et al Plasma trace element, plasma glutathione peroxidase and superoxide dismutase levels in epileptic children receiving antiepileptic drug therapy. Epilepsia 36,600–604 (1995).
  • Yuksel A, Cengiz M, Seven M, Ulutin T Erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children with valproate and carbamazepine monotherapy. j Basic Gun. Physiol Pharmacol 11, 73–81 (2000).
  • Cengiz M, Yuksel A, Seven M. The effects of carbamazepine and valproic acid on the erythrocyte glutathione, glutathione peroxidase, superoxide dismutase and serum lipid peroxidation in epileptic children. Pharmacol Res. 41,423–425 (2000).
  • Sudha K, Rao AV, Rao A. Oxidative stress and antioxidants in epilepsy. Gun. Chim. Acta. 303,19–24 (2001).
  • Turkdogan D, Toplan S, Karakoc Y. Lipid peroxidation and antioxidative enzyme activities in childhood epilepsy. j Child Neural 17,673–676 (2002).
  • Verrotti A, Basciani F, Trotta D, Pomilio MP, Morgese G, Chiarelli F. Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy. Epilepsy Res. 48,71–75 (2002).
  • Yokoi I, Toma J, Liu J, Kabuto H, Mori A. Adenosines scavenged hydroxyl radicals and prevented posttraumatic epilepsy. Free Radic. Biol. Med. 19,473–479 (1995).
  • Kabuto H, Yokoi I, Ogawa N. Melatonin inhibits iron-induced epileptic discharges in a green tea extract containing ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E. Epilepsia 39, 237–243 (1998).
  • Yoneda T, Hiramatsu M, Sakamoto M, Togasaki K, Komatsu M, Yamaguchi K. Antioxidant effects of catechin'. Biochem. MoL Biol. Int. 35,995–1008 (1995).
  • Komatsu M, Hiramatsu M. The efficacy of an antioxidant cocktail on lipid peroxide level and superoxide dismutase activity in aged rat brain and DNA damage in iron-induced epileptogenic foci. Toxicology148, 143–148 (2000).
  • Ramaekers VT, Calomme M, Vanden Berghe D, Makropoulos W Selenium deficiency triggering intractable seizures. Neuropediatric525, 217–223 (1994).
  • Savaskan NE, Brauer AU, Kuhbacher M et al. Selenium deficiency increases susceptibility to glutamate-induced excitotoxicity. EASE a J. 17,112–114 (2003).
  • Willmore LJ, Rubin JJ. Antiperoxidant pretreatment and iron-induced epileptiform discharges in the rat: EEG and histopathologic studies. Neurology 31, 63–69 (1981).
  • ••Outlines the effects of vitamin E in animalmodels of epileptogenesis.
  • Willmore LJ, Rubin JJ. Effects of antiperoxidants on FeC12-induced lipid peroxidation and focal oedema in rat brain. Exp. Neural 83,62–70 (1984).
  • Levy SL, Burnham WM, Bishai A, Hwang PA. The anticonvulsant effects of vitamin E: a further evaluation. Can. j Neural Li. 19,201–203 (1992).
  • Frantseva MV, Velazquez JL, Hwang PA, Carlen PL. Free radical production correlates with cell death in an in vitro model of epilepsy. Eur. j Neurosci 12, 1431–1439 (2000).
  • Levy SL, Burnham WM, Hwang PA. An evaluation of the anticonvulsant effects of vitamin E. Epilepsy Res. 6,12–17 (1990).
  • Oztas B, Kilic S, Dural E, Ispir T Influence of antioxidants on the blood—brain barrier permeability during epileptic seizures. Neumsci. Res. 66,674–678 (2001).
  • Kaya M, Cimen V, Kalayci R et al, and a-tocopherol attenuate blood—brain barrier breakdown in pentylenetetrazole-induced epileptic seizures in acute hyperglycaemic rats. Pharmacol Res. 45,129–133 (2002).
  • Komatsu M, Hiramatsu M, Willmore U. Zonisamide reduces the increase in 8-hydroxy-2'-deoxyguanosine levels formed during iron-induced epileptogenesis in the brains of rats. 43ikpsia 41,1091–1094 (2000).
  • •Highlights the potential intrinsic antioxidative properties of the novel anticonvulsant zonisamide.
  • Bialer M, Johannessen SI, Kupfeberg HJ et al Progress report on new antiepileptic drugs: a summary of the sixth Eilat conference (EILAT VI). Epilepsy Res, 51, 31–71 (2002).
  • Isoherranen N, Yagen B, Bialer M. New CNS-active drugs which are second-generation valproic acid: can they lead to the development of a magic bullet? CUI7: Opin. Neural 16,203–211 (2003).
  • ••Outlines advances and future directions indevelopment of novel anticonvulsants with specific antioxidant properties, particularly the second-generation valproate derivatives.
  • Bazan NG, Birkle DL, Tang W, Reddy TS. The accumulation of free arachidonic acid, diacylglycerols, prostaglandins and lipoxygenase reaction products in the brain during experimental epilepsy. Adv. Neural 44,879–902 (1986).
  • Labiner DM. DP-VPA. D-Pharm. Curr. Opin. Invest. Drugs 3,921–923 (2002).
  • Dawson IQ, Duncan A. Ascorbic acid and long-term anticonvulsant therapy in children. Br. Nutt: 33,315–318 (1975).
  • Ogunmekan AO. Predicting serum vitamin E concentrations from the age of normal and anticonvulsant drug-treated epileptic children using regression equations. Epilepsia 20,295–301 (1979).
  • Kataoka K, Kanamori N, Oishi M, Yarnaji A, Tagawa T, Mimaki T Vitamin E status in pediatric patients receiving antiepileptic drugs. Ebv Phannacol Then 14,96–101 (1989).
  • Ogunmekan AO. Relationship between age and vitamin E level in epileptic and normal children. Ainj Gun. Nutt: 32,2269–2271 (1979).
  • Ogunmekan AO. Plasma vitamin E levels in normal children and in epileptic children with and without anticonvulsant drug therapy. Trap. Geogr Med 37,175–177 (1985).
  • Krause KH, Bonjour JP, Berlit P, Kynast G, Schmidt-Gayk H, Schellenberg B. Effect of long-term treatment with antiepileptic drugs on the vitamin status. Drug- Nutt: Interact. 5,317–343 (1988).
  • ••Provides a comprehensive investigationinto the nutritional antioxidant status of patients with epilepsy on anticonvulsant therapy.
  • Ogunmelcan AO, Hwang PA. A randomised, double-blind, placebo-controlled, clinical trial of D-a-tocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children. 43ilEpsia 30,84–89 (1989).
  • ••First study to report evidence for clinicalefficacy of supplemental vitamin E therapy in children with refractory epilepsy. The study followed a substantial body of animal data suggesting that vitamin E and other nutritional antioxidants can reduce both oxidative injury and seizure frequency in various animal models of epileptogenesis.
  • Raju GB, Behari M, Prasad K, Ahuja GK. Randomised, double-blind, placebo-controlled, clinical trial of D-a-tocopherol (vitamin E) as add-on therapy in uncontrolled epilepsy. Epilepsia 35, 368–372 (1994).
  • ••Quelled the optimism resulting fromOgunmekan's study by reporting a lack of benefit in adults with refractory epilepsy receiving vitamin E supplements.
  • Gutteridge JM, Westermarck T, Santavuori P. Iron and oxygen radicals in tissue damage: implications for the neuronal ceroid lipofuscinoses. Acta Neural. Land. 68,365-370 (1983).
  • Marklund SL, Santavuori P, Westermarck T Superoxide dismutase, catalase and glutathione peroxidase in infantile, late infantile and juvenile neuronal ceroid lipofuscinosis. Clin. Chirn. Acta. 116, 191–8 (1981).
  • Marklund SL, Heiskala H, Westermarck T, Santavuori P Superoxide dismutase isoenzymes in cerebrospinal fluid and plasma from patients with neuronal ceroid-lipofuscinoses. Clin Sci 71,57–60 (1986).
  • •Outlines studies on neuronal ceroid lipofuscinoses patients searching for primary defect(s) in antioxidant defence mechanisms.
  • Johansson E, Lindh U, Westermarck T, Heiskala H, Santavuori P Altered elemental profiles in neuronal ceroid lipofuscinosis. Trace Bern. Dectrolytes Health Dis. 4, 139–142 (1990).
  • Kieseier BC, Wisniewski KE, Schuller- Levis G, Park E, Goebel IIf I. Normalsuperoxide radical production in the neuronal ceroid-lipofuscinoses. Neuropediatrics27, 202–203 (1996).
  • Westermarck T, Aberg L, Santavuori P, Antila E, Edlund P, Atroshi E Evaluation of the possible role of coenzyme Q10 and vitamin E in juvenile neuronal ceroid-lipofuscinosis (NCO. Mal Aspects Med 18, S259—S262 (1997).
  • Santavuori P, Westermarck T Antioxidant therapy in neuronal ceroid-lipofuscinosis. Med Biol. 62,152–153 (1984).
  • •Is of historic importance as the authors describe some benefit conferred by antioxidant therapy in for progressive myoclonic epilepsy of the Unverricht-Lundborg type (PME-UL).
  • Santavuori P, Heiskala H, Westermarck T, Sainio K, Moren R. Experience over 17 years with antioxidant treatment in Spielmeyer-Sjogren disease. Am J. Med. Genet. (Suppl. 5), 265–274 (1988).
  • Maertens P, Dyken P, Graf W, Pippenger C, Chronister R, Shah A. Free radicals, anticonvulsants and the neuronal ceroid-lipofuscinoses. Am. J. Med. Genet. 57, 225–228 (1995).
  • Ben-Menachem E, Kyllerman M, Marklund S. Superoxide dismutase and glutathione peroxidase function in progressive myoclonic epilepsies. Epilepsy Res. 40,33–39 (2000).
  • Hurd RVV, Wilder BJ, Helveston WR, Uthman BM. Treatment of four siblings with progressive myoclonus epilepsy of the Unverricht-Lundborg type with N-acetylcysteine. Neurology47, 1264–1268 (1996).
  • ••Reports a beneficial effect onN-acetylcysteine in PME-UL.
  • Ben-Menachem E, Kyllerman M, Marklund S. Superoxide dismutase and glutathione peroxidase function in progressive myoclonus epilepsies. Epilepsy Res. 40,33–39 (2000).
  • Selwa LM. N-acetylcysteine therapy for Unverricht-Lundborg disease. Neurology 52,426–427 (1999).
  • Edwards MJ, Hargreaves IP, Heales SJ et al N-acetylcysteine and Unverricht-Lundborg disease: variable response and possible side effects. Neurology59, 1447–1449 (2002).

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