Central pontine myelinolysis following rapid correction of hyponatremia

Laureno, Robert

doi:10.1002/ana.410130303

Cited by 228 publications

(81 citation statements)

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“…With the exception of glycine, amino acids and their derivatives are highest in the cerebrum and cerebellum, I) \ (9) and plasma osmolality (29). The concentrations of glycine in the brainstem decrease significantly with hyponatremia and increase after rapid correction of the hyponatremia, thus, they play a major role on the osmoregulation in the brainstem.…”

Section: Resultsmentioning

confidence: 99%

“…Sterns et al (5) reported that neurological complications occur more frequently in hyponatremic patients with a higher correction rate of serum sodium. In experimental animals, including rats (6,7), rabbits (8), and dogs (9), rapid correction of hyponatremia has been shown persistently resulting in demyelinative lesions. However, not all investigators agree on the association of rapid correction of hyponatremia with CPM.…”

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confidence: 99%

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Role of organic osmolytes in myelinolysis. A topographic study in rats after rapid correction of hyponatremia.

Lien¹

1995

J. Clin. Invest.

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IntroductionOrganic osmolytes have been implicated in the pathogenesis of myelinolysis because some of them are accumulated slowly during correction of chronic hyponatremia. I investigated whether there was a topographic correlation between demyelinative lesions and the regional changes of organic osmolytes after rapid correction of chronic hyponatremia.In normal female Sprague-Dawley rats, concentrations of glutamate, glutamine, taurine, and betaine were highest in the cerebral cortex and decreased toward the brain stem. Conversely, glycine level was highest in the brainstem, and decreased toward the cortex. Myoinositol, glycerophosphorylcholine, glycerophosphorylethanolamine, and creatine were distributed more evenly. In chronic hyponatremic rats (plasma Na 110±4 meq/liter), organic osmolytes decreased globally with the total loss ranging from 13 (medulla) to 24 (cerebellum) mmol/kg H20. After rapid correction with intraperitoneal injection of hypertonic saline, the recovery of the loss of organic osmolytes was 48% in the cerebral cortex, cerebellum, and medulla oblongata, 44% in pons, but only 17% in midbrain and 36% in striatum. Histopathology of the brain was examined in nine rats 2-7 d after correction of hyponatremia. Large demyelinative lesions were seen persistently in the midbrain and striatum, and smaller lesions in cerebrum, cerebellum, and pons were found less frequently. This is the first report of regional distribution of brain organic osmolytes. (9), rapid correction of hyponatremia has been shown persistently resulting in demyelinative lesions. However, not all investigators agree on the association of rapid correction of hyponatremia with CPM. In a large autopsy series of CPM, it was found that hyponatremic patients only accounted for a small fraction (10). It is clear that rapid correction of hyponatremia is not the sole cause of CPM. Other factors such as alcoholism, malnutrition, chronic liver diseases, malignancy, severe burns, and potassium depletion are also important (1,(11)(12)(13).In this study, I investigated the role of organic osmolytes in the pathogenesis of myelinolysis in rats after rapid correction of hyponatremia. Organic osmolytes are important solutes which are accumulated in, or released from, cells during the adaptation process to the increase or decrease in surrounding osmolality. The major organic osmolytes in the brain are glutamate, glutamine, taurine, creatine/phosphocreatine, and myonositol (14-17). We have previously shown that after rapid correction of chronic hyponatremia, the reaccumulation of brain organic osmolytes in rats is outpaced by the reaccumulation of brain Na and Cl, and speculated that the delayed increase of organic osmolytes may be relevant to the development of myelinolysis (18). CPM and extrapontine myelinolysis in humans are anatomical site-specific lesions as described earlier (1, 2). The topographic distribution of demyelinative lesions induced by rapid correction of hyponatremia in rats was studied by 7). They demonstrated that after ...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Role of organic osmolytes in myelinolysis. A topographic study in rats after rapid correction of hyponatremia.

Lien¹

1995

J. Clin. Invest.

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“…*P < 0.05 compared to slow correction rate development of neurological complications after liver transplantation is more closely associated with the correction rate of hyponatremia rather than hyponatremia. The risks of rapid correction of hyponatremia itself and its associations with osmotic demyelination syndrome have been demonstrated in animal models (Kleinschmidt-DeMasters and Norenberg 1981;Laureno 1983;Verbalis and Martinez 1991), and the risk of rapid correction is currently emphasized in clinical practice. Rapid correction rate was associated with neurological sequelae in patients with severe hyponatremia (Sterns et al 1994).…”

Section: Discussionmentioning

confidence: 99%

Rapid Correction Rate of Hyponatremia as an Independent Risk Factor for Neurological Complication Following Liver Transplantation

Lee

et al. 2013

Tohoku J. Exp. Med.

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Hyponatremia is prevalent before liver transplantation and generally corrected immediately after transplantation. However, the clinical significance of correction rate of hyponatremia is not well investigated. The prognostic impact of pre-transplant serum sodium concentrations and post-transplant correction rate of hyponatremia were assessed. A total of 512 patients who received orthotopic liver transplants were enrolled. The correction rate of hyponatremia (delta sodium, ΔNa) was calculated based on the data collected during the first 48 hours following liver transplantation. Outcomes, including in-hospital mortality, delirium, neurological complications, acute kidney injury, and infections, were compared according to the serum sodium levels (sNa < 125, 125-135, and ≥ 135 mmol/L), and the risk factors for in-hospital mortality and neurological complications were analyzed using multivariate logistic regression methods. Patients with severe hyponatremia (sNa < 125 mmol/L) had higher rates of in-hospital mortality (9.6%, P = 0.010), delirium (54.8%, P = 0.003), neurological complications (24.7%, P = 0.003), and acute kidney injury (57.5%, P = 0.005). In multivariate analysis, serum sodium levels (OR = 0.975, P = 0.402) and delta sodium (OR = 1.097, P = 0.066) were not independent risk factors for in-hospital mortality. However, delta sodium (OR = 1.093, P = 0.003) and fast correction rate of hyponatremia (ΔNa ≥ 12 mmol/ L/24h, OR = 3.397, P = 0.023) were significantly associated with post-transplant neurological complications. Pre-transplantation hyponatremia was not independently associated with clinical outcomes. However, rapid correction of hyponatremia is an independent risk factor for the development of post-transplant neurological complications.

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“…Clinical and experimental observations have suggested that rapid correction of severe chronic hyponatremia (serum Na < 120 meq/liter) is associated with the development of central pontine myelinolysis (13)(14)(15)(16)(17)(18). Verbalis and Drutarosky have demonstrated that chronic hyponatremia induced by the combination of minipump infusion of DDAVP and feeding of a liquid diet is well tolerated by rats (20).…”

Section: Discussionmentioning

confidence: 99%

“…Animal studies have definitively shown that symmetrical demyelinating lesions of the central nervous system occur after hypertonic infusion for correction of severe chronic hyponatremia (15)(16)(17)(18). Slow correction of hyponatremia, however, does not appear to be associated with this neurological lesion either clinically or experimentally (13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Study of brain electrolytes and organic osmolytes during correction of chronic hyponatremia. Implications for the pathogenesis of central pontine myelinolysis.

Lien¹,

Shapiro²,

Chan³

1991

J. Clin. Invest.

253

122

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Osmotic injury induced by rapid correction of severe chronic hyponatremia has been implicated in the development of central pontine myelinolysis. Organic osmolytes known previously as "idiogenic osmoles" accumulate intracellularly to protect cells from osmotic injury. We investigated the changes of these organic osmolytes as well as electrolytes in the brain during the induction and correction of chronic hyponatremia. Using 'Hnuclear magnetic resonance spectroscopy and HPLC, we found that in rats with chronic hyponatremia (3 d, serum sodium = 109±3 meq/liter), brain concentrations of myoinositol (41%), glycerophosphorylcholine (45%), phosphocreatine/creatine (60%), glutamate (53%), glutamine (45%), and taurine (37%) were all significantly decreased compared with control values (percentage control value shown, all P < 0.01). The contribution of measured organic osmolytes and electrolytes to the total brain osmolality change was 23 and 72%, respectively. With rapid correction by 5% NaCI infusion, significant brain dehydration and elevation of brain Na and Cl levels above the normal range occurred at 24 h. These changes were not seen with slow correction by water deprivation. Reaccumulation of most organic osmolytes except glycerophosphorylcholine is delayed during the correction of hyponatremia and is independent ofthe correction rate of serum sodium. It is concluded that: most of the change of brain osmolality in chronic hyponatremia can be accounted by the changes in organic osmolytes and brain electrolytes; and rapid correction of hyponatremia is associated with an overshoot of brain sodium and chloride levels along with a low organic osmolyte level. The high cerebral ion concentrations in the absence ofadequate concentrations oforganic osmolytes may be relevant to the development of central pontine myelinolysis. (J. Clin. Invest. 1991. 88:303-309.)

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Central pontine myelinolysis following rapid correction of hyponatremia

Cited by 228 publications

References 29 publications

Role of organic osmolytes in myelinolysis. A topographic study in rats after rapid correction of hyponatremia.

Role of organic osmolytes in myelinolysis. A topographic study in rats after rapid correction of hyponatremia.

Rapid Correction Rate of Hyponatremia as an Independent Risk Factor for Neurological Complication Following Liver Transplantation

Study of brain electrolytes and organic osmolytes during correction of chronic hyponatremia. Implications for the pathogenesis of central pontine myelinolysis.

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