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Metabolic Brain Disease

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01.03.2010 | Original Paper

Central pontine myelinolysis: historical and mechanistic considerations

verfasst von: Michael D. Norenberg

Erschienen in: Metabolic Brain Disease | Ausgabe 1/2010

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Abstract

Central pontine myelinolysis (CPM) is a demyelinating condition affecting not only the pontine base, but also involving other brain areas. It usually occurs on a background of chronic systemic illness, and is commonly observed in individuals with alcoholism, malnutrition and liver disease. Studies carried out 25–30 years ago established that the principal etiological factor was the rapid correction of hyponatremia resulting in osmotic stress. This article reviews progress achieved since that time on its pathogenesis, focusing on the role of organic osmolytes, the blood–brain, barrier, endothelial cells, myelinotoxic factors triggered by osmotic stress, and the role of various factors that predispose to the development of CPM. These advances show great promise in providing novel therapeutic options for the management of patients afflicted with CPM.

Adams JH (1962) Central pontine myelinolysis. In: Jacob H (ed) IV International Congress of Neuropathology, vol 3. Georg Thieme Verlag, Stuttgart, pp 303–308

Adams RD, Victor M, Mancall EL (1959) Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. AMA Arch Neurol Psychiat 81:154–172

Adler S, Verbalis JG, Williams D (1995) Effect of rapid correction of hyponatremia on the blood–brain barrier of rats. Brain Res 679:135–143PubMed

Aleu FP, Terry RD (1963) Central pontine myelinolysis. Arch Path 76:140–146PubMed

Alfieri RR, Cavazzoni A, Petronini PG, Bonelli MA, Caccamo AE, Borghetti AF, Wheeler KP (2002) Compatible osmolytes modulate the response of porcine endothelial cells to hypertonicity and protect them from apoptosis. J Physiol 540:499–508PubMed

Ashrafian H, Davey P (2001) A review of the causes of central pontine myelinosis: yet another apoptotic illness? Eur J Neurol 8:103–109PubMed

Ayus JC, Krothapalli RK, Armstrong DL (1985) Rapid correction of severe hyponatremia in the rat: histopathological changes in the brain. Am J Physiol Renal Fluid Electrolyte Physiol 248:F711–F719

Baker EA, Tian Y, Adler S, Verbalis JG (2000) Blood–brain barrier disruption and complement activation in the brain following rapid correction of chronic hyponatremia. Exp Neurol 165:221–230PubMed

Bluml S, Zuckerman E, Tan J, Ross BD (1998) Proton-decoupled 31P magnetic resonance spectroscopy reveals osmotic and metabolic disturbances in human hepatic encephalopathy. J Neurochem 71:1564–1576PubMedCrossRef

Bonham CA, Dominguez EA, Fukui MB, Paterson DL, Pankey GA, Wagener MM, Fung JJ, Singh N (1998) Central nervous system lesions in liver transplant recipients: prospective assessment of indications for biopsy and implications for management. Transplantation 66:1596–1604PubMed

Boon AP, Carey MP, Adams DH, Buckels J, McMaster P (1991) Central pontine myelinolysis in liver transplantation. J Clin Pathol 44:909–914PubMed

Brightman MW, Hori M, Rapoport SI, Reese TS, Westergaard E (1973) Osmotic opening of tight junctions in cerebral endothelium. J Comp Neurol 152:317–325PubMed

Brown WD (2000) Osmotic demyelination disorders: central pontine and extrapontine myelinolysis. Curr Opin Neurol 13:691–697PubMed

Burcar PJ, Norenberg MD, Yarnell PR (1977) Hyponatremia and central pontine myelinolysis. Neurology 27:223–226PubMed

Burg MB, Ferraris JD (2008) Intracellular organic osmolytes: function and regulation. J Biol Chem 283:7309–7313PubMed

Burg MB, Ferraris JD, Dmitrieva NI (2007) Cellular response to hyperosmotic stresses. Physiol Rev 87:1441–1474PubMed

Cammer W, Bloom BR, Norton WT, Gordon S (1978) Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages: a possible mechanism of inflammatory demyelination. Proc Natl Acad Sci USA 75:1554–1558PubMed

Chason JL, Landers JW, Gonzalez JE (1964) Central pontine myelinolysis. J Neurol Neurosurg Psychiat 27:317–325PubMed

Córdoba J, Gottstein J, Blei AT (1996) Glutamine, myo-inositol, and organic brain osmolytes after portacaval anastomosis in the rat: implications for ammonia-induced brain edema. Hepatology 24:919–923PubMed

Cyong JC, Witkin SS, Rieger B, Barbarese E, Good RA, Day NK (1982) Antibody-independent complement activation by myelin via the classical complement pathway. J Exp Med 155:587–598PubMed

De Broucker T, Rueff B, Hammel P, Hadengue A (1989) Hypophosphoremia: a possible cause of central pontine myelinolysis. Presse Med 18:1166PubMed

DeLuca GC, Nagy Z, Esiri MM, Davey P (2002) Evidence for a role for apoptosis in central pontine myelinolysis. Acta Neuropathol 103:590–598PubMed

Estol CJ, Faris AA, Martinez AJ, Ahdab-Barmada M (1989) Central pontine myelinosis after liver transplantation. Neurology 39:493–498PubMed

Feigin I, Budzilovich GN (1978) The role of edema in diffuse sclerosis and other leukoencephalopathies. J Neuropathol Exp Neurol 37:326–357PubMed

Feigin I, Budzilovich G, Weinberg S, Ogata U (1973) Degeneration of white matter in hypoxia, acidosis and edema. J Neuropathol Exp Neurol 32:125–143PubMed

Ferreiro JA, Robert MA, Townsend J, Vinters HV (1992) Neuropathologic findings after liver transplantation. Acta Neuropathol 84:1–14PubMed

Ghidoni P, Di Bella C, Masini T, Paone G, Matturri L (1994) Central pontine and extrapontine myelinolysis after orthotopic liver transplantation. Transplant Proc 26:3602–3603PubMed

Goebel HH, Zur PH (1972) Central pontine myelinolysis. A clinical and pathological study of 10 cases. Brain 95:495–504PubMed

Goebel HH, Zur PH (1976) Central pontine myelinolysis. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 28. North Holland Publishing Co, Amsterdam, pp 285–316

Goldman JE, Horoupian DS (1981) Demyelination of the lateral geniculate nucleus in central pontine myelinolysis. Ann Neurol 9:185–189PubMed

Gupta RK, Saraswat VA, Poptani H, Dhiman RK, Kohli A, Gujral RB, Naik SR (1993) Magnetic resonance imaging and localized in vivo proton spectroscopy in patients with fulminant hepatic failure. Amer J Gastroenterol 88:670–674

Häussinger D, Laubenberger J, Vom Dahl S, Ernst T, Bayer S, Langer M, Gerok W, Hennig J (1994) Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy. Gastroenterology 107:1475–1480PubMed

Hedley-Whyte E, Hsu DW (1986) Effect of dexamethasone on blood–brain barrier in the normal mouse. Ann Neurol 19:373–377PubMed

Heng AE, Vacher P, Aublet-Cuvelier B, Garcier JM, Sapin V, Deteix P, Souweine B (2007) Centropontine myelinolysis after correction of hyponatremia: role of associated hypokalemia. Clin Nephrol 67:345–351PubMed

Hoheisel D, Nitz T, Franke H, Wegener J, Hakvoort A, Tilling T, Galla HJ (1998) Hydrocortisone reinforces the blood–brain barrier properties in a serum free cell culture system. Biochem Biophys Res Commun 244:312–316PubMed

Illowsky BP, Laureno R (1987) Encephalopathy and myelinolysis after rapid correction of hyponatraemia. Brain 110:855–867PubMed

Isaacks RE, Bender AS, Kim CY, Prieto NM, Norenberg MD (1994) Osmotic regulation of myo-inositol uptake in primary astrocyte cultures. Neurochem Res 19:331–338PubMed

Isaacks RE, Bender AS, Kim CY, Shi YF, Norenberg MD (1999a) Effect of ammonia and methionine sulfoximine on myo-inositol transport in cultured astrocytes. Neurochem Res 24:51–59PubMed

Isaacks RE, Bender AS, Kim CY, Shi YF, Norenberg MD (1999b) Effect of osmolality and anion channel inhibitors on myo-inositol efflux in cultured astrocytes. J Neurosci Res 57:866–871PubMed

Karp BI, Laureno R (2000) Central pontine and extrapontine myelinolysis after correction of hyponatremia. Neurologist 6:255–266

Ke QH, Liang TB, Yu J, Zheng SS (2006) A study of the pathogenesis and prevention of central pontine myelinolysis in a rat model. J Int Med Res 34:264–271PubMed

Kepes JJ, Reece CA, Oxley DK (1965) Central pontine myelinolysis in a 7-year-old boy. J Neurol Neurosurg Psychiat 28:39–47PubMed

Klavins JV (1963) Central pontine myelinolysis. J Neuropathol Exp Neurol 22:302–317PubMed

Kleinschmidt-DeMasters BK, Norenberg MD (1981) Rapid correction of hyponatremia causes demyelination: relation to central pontine myelinolysis. Science 211:1068–1070PubMed

Kleinschmidt-DeMasters BK, Rojiani AM, Filley CM (2006) Central and extrapontine myelinolysis: then...and now. J Neuropathol Exp Neurol 65:1–11PubMed

Kreis R, Ross BD, Farrow NA, Ackerman Z (1992) Metabolic disorders of the brain in chronic hepatic encephalopathy detected with H-1 MR spectroscopy. Radiology 182:19–27PubMed

Lampl C, Yazdi K (2002) Central pontine myelinolysis. Eur Neurol 47:3–10PubMed

Laureno R (1980) Experimental pontine and extrapontine myelinolysis. Ann Neurol 8:117

Laureno R (1983) Central pontine myelinolysis following rapid correction of hyponatremia. Ann Neurol 13:232–242PubMed

Leslie KO, Robertson AS, Norenberg MD (1980) Central pontine myelinolysis: an osmotic gradient hypothesis. J Neuropathol Exp Neurol 39:370

Lien Y-HH (1995) Role of organic osmolytes in myelinolysis. A topographic study in rats after rapid correction of hyponatremia. J Clin Invest 95:1579–1586PubMed

Lien Y-HH, Shapiro JI, Chan L (1991) Study of brain electrolytes and organic osmolytes during correction of chronic hyponatremia. Implications for the pathogenesis of central pontine myelinolysis. J Clin Invest 88:303–309PubMed

Liu JS, Zhao ML, Brosnan CF, Lee SC (2001) Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. Am J Pathol 158:2057–2066PubMed

Lohr JW (1994) Osmotic demyelination syndrome following correction of hyponatremia: association with hypokalemia. Am J Med 96:408–413PubMed

Lubrich B, Spleiss O, Gebicke-Haerter PJ, Van Calker D (2000) Differential expression, activity and regulation of the sodium/myo-inositol cotransporter in astrocyte cultures from different regions of the rat brain. Neuropharmacology 39:680–690PubMed

Ludwin SK (1997) The pathobiology of the oligodendrocyte. J Neuropathol Exp Neurol 56:111–124PubMed

Martin RJ (2004) Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiat 75(Suppl 3):iii22–iii28

McKee AC, Winkelman MD, Banker BQ (1988) Central pontine myelinolysis in severely burned patients: relationship to serum hyperosmolality. Neurology 38:1211–1217PubMed

Messert B, Orrison WW, Hawkins MJ, Quaglieri CE (1979) Central pontine myelinolysis. Considerations on etiology, diagnosis, and treatment. Neurology 29:147–160PubMed

Michell AW, Burn DJ, Reading PJ (2003) Central pontine myelinolysis temporally related to hypophosphataemia. J Neurol Neurosurg Psychiat 74:820PubMed

Monteiro L (1971) La myelinolyse du centre du pont dans cadre d’un nouveau syndrome histopathologique de topographie systematisee. J Neurol Sci 13:293–314PubMed

Murase T, Sugimura Y, Takefuji S, Oiso Y, Murata Y (2006) Mechanisms and therapy of osmotic demyelination. Am J Med 119:S69–S73PubMed

Neuwelt EA, Barnett PA, Bigner DD, Frenkel EP (1982) Effects of adrenal cortical steroids and osmotic blood–brain barrier opening on methotrexate delivery to gliomas in the rodent: the factor of the blood–brain barrier. Proc Natl Acad Sci USA 79:4420–4423PubMed

Norenberg MD (1981) Ultrastructural observations in electrolyte-induced myelinolysis. J Neuropathol Exp Neurol 40:319

Norenberg MD (1983) A hypothesis of osmotic endothelial injury. A pathogenetic mechanism in central pontine myelinolysis. Arch Neurol 40:66–69PubMed

Norenberg MD (1984) Treatment of hyponatremia: the case for a more conservative approach. In: Narins RG (ed) Controversies in nephrology and hypertension. Churchill Livingstone, New York, pp 379–391

Norenberg MD, Bell KP (1982) Plasminogen activator and steroids in electrolyte-induced myelinolysis. Proc Int Cong Neuropathol 9:76

Norenberg MD, Papendick RE (1984) Chronicity of hyponatremia as a factor in experimental myelinolysis. Ann Neurol 15:544–547PubMed

Norenberg MD, Leslie KO, Robertson AS (1982) Association between rise in serum sodium and central pontine myelinolysis. Ann Neurol 11:128–135PubMed

Oh MS, Choi KC, Uribarri J, Sher J, Rao C, Carroll HJ (1990) Prevention of myelinolysis in rats by dexamethasone or colchicine. Amer J Nephrol 10:158–161

Okeda R (1974) Centrale pontine Myelinolyse. Pathogetische Aspekte aufgrund morphometrischer Untersuchungen des Brückenfusses. Acta Neuropathol 27:233–246PubMed

Powers JM, McKeever PE (1976) Central pontine myelinolysis. An ultrastructural and elemental study. J Neurol Sci 29:65–81PubMed

Pujol J, Kulisevsky J, Moreno A, Deus J, Alonso J, Balanzó J, Martí-Vilalta JL, Capdevila A (1996) Neurospectroscopic alterations and globus pallidus hyperintensity as related magnetic resonance markers of reversible hepatic encephalopathy. Neurology 47:1526–1530PubMed

Qadir F, Hasan A, Masood M (2005) Extra pontine myelinolysis associated with hypophosphatemia. J Pakistan Med Assoc 55:254–256

Rapoport SI (1976) Blood–brain barrier in physiology and medicine. Raven, New York

Reynolds TB (1980) Water, electrolyte, and acid-base disorders in liver disease. In: Maxwell MH, Kleeman CR (eds) Clinical disorders of fluid and electrolyte metabolism. McGraw-Hill, New York, pp 1251–1261

Riggs JE, Schochet SS Jr (1989) Osmotic stress, osmotic myelinolysis, and oligodendrocyte topography. Arch Pathol Lab Med 113:1386–1388PubMed

Rojiani AM, Prineas JW, Cho ES (1987) Protective effect of steroids in electrolyte-induced demyelination. J Neuropathol Exp Neurol 46:495–504PubMed

Rojiani AM, Prineas JW, Cho E-S (1994a) Electrolyte-induced demyelination in rats—I. Role of the blood-barrier and edema. Acta Neuropathol 88:287–292PubMed

Rojiani AM, Cho E-S, Sharer L, Prineas JW (1994b) Electrolyte-induced demyelination in rats—II. Ultrastructural evolution. Acta Neuropathol 88:293–299PubMed

Rosenberg GA, Dencoff JE, Correa N Jr, Reiners M, Ford CC (1996) Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood–brain barrier injury. Neurology 46:1626–1632PubMed

Rosman NP, Kakulas BA, Richardson EP Jr (1966) Central pontine myelinolysis in a child with leukemia. Arch Neurol 14:273–820PubMed

Schneck SA, Burks JS, Yarnell PR (1978) Antemortem diagnosis of central pontine myelinolysis. Neurology 28:389

Scolding NJ, Morgan BP, Houston A, Campbell AK, Linington C, Compston DA (1989) Normal rat serum cytotoxicity against syngeneic oligodendrocytes. Complement activation and attack in the absence of anti-myelin antibodies. J Neurol Sci 89:289–300PubMed

Shurtliff LF, Ajax ET, Englert E Jr, D’Agostino AN (1966) Central pontine myelinolysis and cirrhosis of the liver. A report of four cases. Am J Clin Pathol 46:239–244PubMed

Silver SM, Schroeder BM, Sterns RH, Rojiani AM (2006) Myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats. J Neuropathol Exp Neurol 65:37–44PubMed

Simka M (2009) Blood brain barrier compromise with endothelial inflammation may lead to autoimmune loss of myelin during multiple sclerosis. Curr Neurovasc Res 6:132–139PubMed

Singh N, Yu VL, Gayowski T (1994) Central nervous system lesions in adult liver transplant recipients: clinical review with implications for management. Medicine 73:110–118PubMed

Sinton CM, Fitch TE, Petty F, Haley RW (2000) Stressful manipulations that elevate corticosterone reduce blood–brain barrier permeability to pyridostigmine in the rat. Toxicol Appl Pharmacol 165:99–105PubMed

Soupart A, Penninckx R, Stenuit A, Decaux G (2000) Azotemia (48 h) decreases the risk of brain damage in rats after correction of chronic hyponatremia. Brain Res 852:167–172PubMed

Soupart A, Silver S, Schroeder B, Sterns R, Decaux G (2002) Rapid (24-h) reaccumulation of brain organic osmolytes (particularly myo-inositol) in azotemic rats after correction of chronic hyponatremia. J Am Soc Nephrol 13:1433–1441PubMed

Starzl TE, Schneck SA, Mazzoni G, Aldrete JA, Porter KA, Schroter GP, Koep LJ, Putnam CW (1978) Acute neurological complications after liver transplantation with particular reference to intraoperative cerebral air embolus. Ann Surg 187:236–240PubMed

Sterns RH, Silver S, Kleinschmidt-DeMasters BK, Rojiani AM (2007) Current perspectives in the management of hyponatremia: prevention of CPM. Expert Rev Neurotherap 7:1791–1797

Strange K (1992) Regulation of solute and water balance and cell volume in the central nervous system. J Am Soc Nephrol 3:12–27PubMed

Strange K (1993) Maintenance of cell volume in the central nervous system. Pediatr Nephrol 7:689–697PubMed

Sugimura Y, Murase T, Takefuji S, Hayasaka S, Takagishi Y, Oiso Y, Murata Y (2005) Protective effect of dexamethasone on osmotic-induced demyelination in rats. Exp Neurol 192:178–183PubMed

Thurston JH, Hauhart RE, Nelson JS (1987) Adaptive decreases in amino acids (taurine in particular), creatine, and electrolytes prevent cerebral edema in chronically hyponatremic mice: rapid correction (experimental model of central pontine myelinolysis) causes dehydration and shrinkage of brain. Metab Brain Dis 2:223–241PubMed

Todd AS (1972) Endothelium and fibrinolysis. Atherosclerosis 15:137–140PubMed

Tomlinson BE, Pierides AM, Bradley WG (1976) Central pontine myelinolysis. Two cases with associated electrolyte disturbance. Quart J Med 45:373–386PubMed

Vadeboncoeur N, Segura M, Al Numani D, Vanier G, Gottschalk M (2003) Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2. FEMS Immunol Med Microbiol 35:49–58PubMed

Vanguri P, Koski CL, Silverman B, Shin ML (1982) Complement activation by isolated myelin: activation of the classical pathway in the absence of myelin-specific antibodies. Proc Natl Acad Sci USA 79:3290–3294PubMed

Verbalis JG, Gullans SR (1991) Hyponatremia causes large sustained reductions in brain content of multiple organic osmolytes in rats. Brain Res 567:274–282PubMed

Verbalis JG, Gullans SR (1993) Rapid correction of hyponatremia produces differential effects on brain osmolyte and electrolyte reaccumulation in rats. Brain Res 606:19–27PubMed

Verbalis JG, Martinez AJ (1991) Neurological and neuropathological sequelae of correction of chronic hyponatremia. Kidney Int 39:1274–1282PubMed

Verma S, Nakaoke R, Dohgu S, Banks WA (2006) Release of cytokines by brain endothelial cells: a polarized response to lipopolysaccharide. Brain Behavior Immun 20:449–455

Wing MG, Zajicek J, Seilly DJ, Compston DA, Lachmann PJ (1992) Oligodendrocytes lack glycolipid anchored proteins which protect them against complement lysis. Restoration of resistance to lysis by incorporation of CD59. Immunology 76:140–145PubMed

Wren DR, Noble M (1989) Oligodendrocytes and oligodendrocyte/type-2 astrocyte progenitor cells of adult rats are specifically susceptible to the lytic effects of complement in absence of antibody. Proc Natl Acad Sci USA 86:9025–9029PubMed

Wright DG, Laureno R, Victor M (1979) Pontine and extrapontine myelinolysis. Brain 102:361–385PubMed

Wszolek ZK, McComb RD, Pfeiffer RF, Steg RE, Wood RP, Shaw BW Jr, Markin RS (1989) Pontine and extrapontine myelinolysis following liver transplantation: relationship to serum sodium. Transplantation 48:1006–1012PubMed

Titel: Central pontine myelinolysis: historical and mechanistic considerations
verfasst von: Michael D. Norenberg
Publikationsdatum: 01.03.2010
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 1/2010
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-010-9175-0

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