Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction

Central pontine myelinolysis and extrapontine myelinolysis are rare demyelinating diseases of the central nervous system. These diseases are related frequently to rapid correction of hyponatremia. They have also been described in association with other underlying conditions such as alcoholism and malnutrition. In the present study, we report a case of central pontine and extrapontine myelinolysis with acute hepatic dysfunction. The patient had no apparent evidence of hyponatremia and no history of alcohol abuse. On admission, the patient was lethargic; dysphagia, dysarthria, and quadriplegia were noted. Laboratory examination showed significantly increased transaminase without hyponatremia. Magnetic resonance imaging revealed abnormal signal intensities in the pons and thalamus. Consciousness level and clinical symptoms improved gradually within a week. We suggest that acute hepatic dysfunction may play an important role in the development of central pontine myelinolysis and extrapontine myelinolysis.     

A patient using ziprasidone with polydipsia, seizure, hyponatremia and rhabdomyolysis

We aimed to report a case with rhabdomyolysis related to hyponatremia and/or its correction. A 32–year–old male schizophrenic patient on ziprasidone treatment was admitted to the hospital following a seizure. Patient had primary polydipsia and secondarily developed hyponatremia. After the correction of hyponatremia, due to the high liver enzyme levels, he was diagnosed as rhabdomyolysis. Although the role of antipsychotics in this situation is speculative, development of rhabdomyolysis related to hyponatremia and/or its correction should not be underestimated and should be assesed throughly.     

Central pontine myelinolysis following ‘slow’ correction of hyponatremia

Two patients with central pontine myelinolysis are described for the peculiar mode of development. Both patients were in chronic renal failure and admitted in a stuporous state due to hyponatremia. Both developed central pontine myelinolysis during the hospital stay following slow and judicious correction of hyponatremia. The role of chronicity of hyponatremia prior to its correction, in the genesis of central pontine myelinolysis, particularly in the patients who have chronic debilitating illness, septicemia or malnutrition, is highlighted.     

Pontine myelinolysis and delayed encephalopathy following the rapid correction of acute hyponatremia

We describe a case of pontine myelinolysis associated with hyponatremia and hyperammonemia resulting from bladder irrigation during a transurethral prostatic resection. Following the procedure the patient exhibited seizurelike activity. He underwent rapid correction of the hyponatremia, he initially recovered but developed encephalopathy 19 days later. Magnetic resonance images showed symmetrical lesions in the white matter of the cerebellar peduncles. A relatively small pontine lesion was also noted. The patient later recovered. This case demonstrates that myelinolysis associated with rapid correction of hyponatremia may be greater in the cerebellar peduncles than in the central pons.     

Rapid correction of hyponatremia produces differential effects on brain osmolyte and electrolyte reaccumulation in rats

Studies from these and other laboratories have shown that hyponatremia causes marked depletion of both electrolytes and organic osmolytes from the brain. The present studies evaluated brain reaccumulation of both classes of solute after correction of chronic hyponatremia. Hyponatremia was induced by subcutaneoys infusions of 1-deamino-[8-D-arginine]-vasopressin (dDAVP) in rats fed a balanced liquid diet. After 14 days of sustained hyponatremia the dDAVP minipumps were removed causing rapid correction of plasma sodium concentrations from104±1mmol/l to139±1mmol/l in 24 h. Water and solute contents were measured in brain extracts both before and for 5 days after correction of the hyponatremia, and compared to values in normonatremic rats maintained on the same diet for 14 days. Our results demonstrate that electrolytes, particularly Na⁺ and Cl⁻, reaccumulate rapidly in the brain, resulting in a significant overshoot above normal control brain Na⁺ and Cl⁻ contents as early as 24 h after correction. In contrast, organic osmolyte reaccumulation occurs more slowly, requiring 5 or more days for a return to normal control brain contents in most cases. A prominent exception to this pattern was glutamate, which also returned rapidly to normal brain contents within 24 h similar to the electrolytes. Quantitative analysis of brain water and solute contents after correction of hyponatremia indicated that the reaccumulation of electrolytes and organic osmolytes was sufficient to account for the changes in brain volume that occurred. Electrolytes accounted for 91–96% of the brain volume regulation during the first 24–48 h after correction of hyponatremia, but over longer periods of time organic osmolytes replaced some of the initial electrolyte gains and accounted for approximately one-third of the observed volume regulation by 5 days after correction of hyponatremia. These results therefore demonstrate markedly dissimilar patterns of reaccumulation of different classes of solutes in brain tissue following correction of chronic hyponatremia, which may be of significance for the pathological brain demyelination often seen under these conditions.     

Myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats

ABSTRACT: When chronic hyponatremia is rapidly corrected, reaccumulation of brain organic osmolytes is delayed and brain cell shrinkage occurs, leading to the osmotic demyelination syndrome (ODS). We hypothesized that treatment with myoinositol, a major organic osmolyte, could prevent ODS. Severe hyponatremia was induced in adult male rats by administration of arginine vasopressin and intravenous infusion of dextrose and water. Sixty-four hours after induction of hyponatremia, all animals underwent rapid correction of hyponatremia with infusion of hypertonic saline over 4 hours, increasing the serum sodium from 105 to 135 mM; half of the animals were also given myoinositol intravenously beginning 20 minutes before correction and continuing for 28 hours. Serum sodium concentrations were equivalent in both groups at all time points. At 7 days, 7 of 8 animals that received myoinositol survived compared with one of the 9 control animals (p < 0.01). In a second study, sodium was reduced to 106 mM over 64 hours in 24 animals and then corrected by 20 mM over 4 hours with concomitant loading and infusion of either mannitol (control) or myoinositol. Animals were killed 96 hours after correction of hyponatremia was begun. Myoinositol-treated animals had significantly fewer demyelinating lesions than mannitol (2.25 +/- 1.1 versus 6.42 +/- 1.4 lesions/brain, p < 0.03). We conclude that myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats.     

Guillain-Barrè syndrome and inadequate antidiuretic hormone secretion syndrome

Several neurologic disorders including Guillain-Barré syndrome (GBS) are associated with hyponatremia. Hyponatremia and its overly fast correction have major implications to the course of the underlying neurologic disease. We report a case of GBS complicated by hyponatremia secondary to the development of inadequate antidiuretic hormone secretion syndrome. Differential diagnosis, pathophysiology, and therapeutic approach of hyponatremia in association with GBS are discussed.     

Hyponatremic encephalopathy--some experimental and clinical findings

Hyponatremia is a common electrolyte disturbance occurring in a broad spectrum of patients, from asymptomatic to critically ill. The disease is defined as a decrease in serum sodium concentration to a level below 136 mmol per liter. The brain damage from hyponatremia can be associated with either hyponatremic encephalopathy or improper therapy of symptomatic hyponatremia both in patients and in experimental models of hyponatremia in rats. This review covers the clinical symptoms of hyponatremia as well as the consequences of its correction. It also summarises the effects of experimental hyponatremia associated with vasopressin on some aspects of cerebral blood flow regulation and the morphology of cerebral tissue.     

Effect of rapid correction of hyponatremia on the blood-brain barrier of rats

Brain demyelination sometimes follows rapid correction of hyponatremia, especially if the hyponatremia is chronic. During correction brain water decreases and the brain shrinks. The present study examined whether such shrinkage might be sufficient to disrupt the tight junctions of the blood-brain barrier. Barrier intactness was evaluated using magnetic resonance imaging and intravenous gadolinium contrast administration. Hypertonic saline infusion rapidly increased the plasma sodium concentration and caused barrier disruption more frequently in chronic than in acute hyponatremic rats. Similar increases in plasma sodium concentration did not disrupt the barrier in normonatremic rats. The disruption appeared to be due to altered plasma osmolality since infusion of hypertonic mannitol, which raised plasma osmolality without changing the plasma sodium concentration, disrupted the barrier in hyponatremic but not normonatremic rats. Moreover, the osmotic threshold for barrier disruption was lowest in chronic hyponatremia, intermediate in acute hyponatremia, and highest in normonatremia. The greater susceptibility to osmotic disruption in chronic hyponatremia suggests that blood-brain barrier disruption may play a significant role in causing the demyelination sometimes found following too rapid correction of hyponatremia, possibly through exposure of oligodendrocytes to plasma macromolecules such as complement.     

Blood-brain barrier disruption and complement activation in the brain following rapid correction of chronic hyponatremia

In previous studies we developed a rat model in which demyelination is reproducibly produced following rapid correction of chronic hyponatremia and demonstrated that the development of demyelination in this model is strongly associated with NMR indices of blood-brain barrier (BBB) disruption. Because complement is toxic to oligodendrocytes, we evaluated the hypothesis that BBB disruption precipitated by correction of hypoosmolality is followed by an influx of complement into the brain, which then contributes to the demyelination that occurs under these conditions. We studied four groups of rats with immunocytochemical analysis using primary antibodies to IgG and the C3d split-fragment of activated complement: (1) normal rats; (2) rats in which hyponatremia was maintained for 7 days; (3) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 20 h prior to perfusion; and (4) chronically hyponatremic rats in which the plasma [Na(+)] was rapidly corrected with hypertonic saline administration 5 days prior to perfusion. In normonatremic and uncorrected hyponatremic rats only background staining was observed in areas lacking a BBB and in blood vessel walls, whereas marked increases in IgG and C3d staining were seen in the brains of rats both 20 h and 5 days after rapid correction of hyponatremia. The staining intensity was significantly correlated with the degree of neurological impairment. These results provide evidence for functional BBB disruption following rapid correction of hyponatremia and support the hypothesis that complement activation may be involved in the pathogenesis of osmotic demyelination.     

脑桥外髓鞘溶解症的临床特点（附1例报道及文献分析）

目的 提高临床医生对脑桥外髓鞘溶解症（extrapontine myelinolysis,EPM）的病因、临床及影像学特点的认识。方法回顾性分析本科收治的1例EPM的临床资料。结果本例患者中年女性,在治疗咯血过程中出现重度低钠血症,病后1周发现血钠为109mmol／L,给予迅速补钠后渐出现精神行为异常,并进行性加重,头颅MRI示双侧豆状核、尾状核、丘脑对称性异常信号。经积极治疗后疗效不佳,随访6个月病情无恢复。结论EPM是少见的中枢神经系统髓鞘溶解性疾病,目前认为与过快纠正低钠血症相关,本病重在预防,一旦发生则预后不良,提醒临床医生注意补钠速度以防发生EPM。     

Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: a prospective magnetic resonance imaging study

The rate at which profound hyponatremia should be corrected is the focus of a recent clinical debate. We prospectively studied neurological outcomes with serial magnetic resonance imaging in 13 hyponatremic subjects with serum sodium concentrations of less than 115 mmol/L (mean initial serum sodium concentration, 103.7; range, 93-113 mmol/L). All subjects were corrected to mildly hyponatremic levels at 24 hours and ultimately underwent an increase in serum sodium concentration of 25 mmol/L without development of hypernatremia. Magnetic resonance imaging revealed the development of pontine lesions in 3 patients. The correction rate of hyponatremia over the first 24 hours was significantly faster in patients with pontine lesions (mean +/- SD, 1.25 +/- 0.4 mmol/(L . hr) versus 0.74 +/- 0.3 mmol/(L . hr); p less than 0.05). Initial sodium concentration was also significantly lower in the pontine lesion group (97.3 +/- 6.7 vs 105.6 +/- 5.2 mmol/L, p less than 0.05). We conclude that the correction rate of hyponatremia plays a significant role in the pathogenesis of pontine lesions in individuals with profound hyponatremia who undergo large increases in sodium concentration as a result of severe initial hyponatremia.     

Catatonia associated with hyponatremia treated with electroconvulsive therapy

ABSTRACT: Catatonia has been reported to occur in various brain pathologies and systemic conditions. We present a case of catatonia associated with hyponatremia treated with a course of electroconvulsive therapy. A 48-year-old woman presented with catatonia and, upon investigation, was found to have persistent/recurrent hyponatremia. Upon investigation also, she was found to have adrenal insufficiency. Her symptoms of catatonia did not respond to correction of hyponatremia, a course of lorazepam, after which she was treated with ECT, with which her catatonia improved.     

Osmotic myelinolysis in a normonatremic patient

Osmotic demyelination syndrome is usually associated with hyponatremia or rapid correction of this condition. The prognosis is usually fatal. We treated a 34-year-old chronic renal failure patient who did not have hyponatremia but developed severe pontine myelinolysis demonstrated with MRI. Serial MRI revealed gradual reduction of the lesions over 2 months. This case demonstrates that osmotic demyelination syndrome is not always associated with hyponatremia, and that, although the prognosis is usually poor, some patients recover.     

Cortical Laminar Necrosis Caused by Rapidly Corrected Hyponatremia

Cortical laminar necrosis (CLN) is radiologically characterized by hyperintense cortical lesions on unenhanced T1-weighted images. Hypoxia is the representative cause of CLN; however, the rapid correction of hyponatremia has also been suggested as another possible cause. We present a patient who developed CLN and a permanent neurologic sequel following the rapid correction of hyponatremia without hypoxic insult, and discuss the characteristics of CLN lesions in view of osmotic demyelination syndrome based on magnetic resonance (MR) image findings.     

Cerebral correlates of hyponatremia

Hyponatremia, defined as a serum sodium concentration ([Na⁺]) less than 135 mEq/L, is commonly caused by elevated levels of the hormone arginine vasopressin (AVP), which causes water retention. The principal organ affected by disease-related morbidity is the brain. The neurologic complications associated with hyponatremia are attributable to cerebral edema and increased intracranial pressure, caused by the osmotically driven movement of water from the extracellular compartment into brain cells. Although neurologic symptoms induced by hyponatremia are limited by an adaptive brain mechanism known as “regulatory volume decrease,” an overly rapid correction of serum [Na⁺] before the reversal of this adaptive response can also produce neurologic damage. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a frequent cause of hyponatremia related to central nervous system disorders, neurosurgery, or the use of psychoactive drugs. Fluid restriction is the standard of care for patients with SIADH who are asymptomatic or who have only mild symptoms but patients with severe or symptomatic hyponatremia require more aggressive therapy. Infusion of hypertonic saline is the usual approach to the treatment of symptomatic hyponatremia, but patients require frequent monitoring. Pharmacologic agents such as demeclocycline and lithium may be effective in some patients but are associated with undesirable adverse events. The AVP-receptor antagonists are a new therapeutic class for the treatment of hyponatremia. The first agent in this class approved for the treatment of euvolemic hyponatremia in hospitalized patients is conivaptan. Two other agents, tolvaptan and lixivaptan, are being evaluated in patients with euvolemic and hypervolemic hyponatremia. The AVP-receptor antagonists block the effects of elevated AVP and promote aquaresis, the electrolytesparing excretion of water, resulting in the correction of serum [Na⁺]. These agents may also have intrinsic neuroprotective effects.     

Parkinsonism after correction of hyponatremia with radiological central pontine myelinolysis and changes in the basal ganglia.

Parkinsonism has been rarely described following central pontine and extrapontine myelinolysis. We report a case of parkinsonism developing following rapid correction of hyponatremia with radiological evidence of central pontine myelinolysis and changes in the basal ganglia. A 56-year-old man developed drooling and bilateral hand tremors 3 weeks after correction of hyponatremia from 103 to 125 mmol/L over 14 h. He had a prominent 6 Hz resting tremor which worsened with action and mild cogwheel rigidity. Magnetic resonance imaging (MRI) showed changes consistent with central pontine myelinolysis and increased signal on T1-weighted images in the putamen bilaterally. His tremor responded well to L-dopa therapy. There have been several other cases of parkinsonism developing after central pontine/extrapontine myelinolysis. Increased signal in the basal ganglia on T1-weighted images has been described in another case of central pontine myelinolysis imaged about the same time after sodium correction as our case.     

Protective effect of dexamethasone on osmotic-induced demyelination in rats

Central pontine myelinolysis (CPM) is a serious demyelination disease commonly associated with the rapid correction of hyponatremia. Although its pathogenesis remains unclear, the disruption of the blood-brain barrier (BBB) as a consequence of a rapid increase in serum sodium concentration is considered to play a critical role. Since glucocorticoids are known to influence BBB permeability and prevent its disruption as a result of hypertension or hyperosmolarity, we investigated whether dexamethasone (DEX) could protect against osmotic demyelination in an animal model of CPM. Hyponatremia was induced in rats by liquid diet feeding and dDAVP infusion. Seven days later, the animals' hyponatremia was rapidly corrected by injecting a bolus of hypertonic saline intraperitoneally. Rats subjected to this treatment displayed serious neurological impairment and 77% died within 5 days of rapid correction of their hyponatremia; demyelinative lesions were observed in various brain regions in these animals. On the other hand, rats that were treated with DEX (2 mg/kg, 0 and 6 h after hypertonic saline injection) exhibited minimal neurological impairment and all were alive after 5 days. Demyelinative lesions were rarely seen in the brains of DEX-treated rats. A marked extravasation of endogenous IgG was observed in the demyelinative lesions in the brains of rats that did not receive DEX, indicating disruption of the BBB, but was not observed in DEX-treated rats. Furthermore, Evans blue injection revealed a significant reduction in staining in the brains of DEX-treated rats (P < 0.05). These results indicate that early DEX treatment can prevent the BBB disruption that is caused by the rapid correction of hyponatremia and its associative demyelinative changes, and suggest that DEX might be effective in preventing CPM.     

Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia.

Central pontine myelinolysis is usually associated with hyponatremia or rapid correction of this condition. In general, this neurological disorder has a fatal prognosis. We observed a 30-year-old woman with a history of chronic alcohol abuse but without evidence of hyponatremia, who developed severe pontine central myelinolysis. The initial magnetic resonance (MR)-imaging showed a marked lesion in the central pontine area, sequential MR-imaging revealed progressive reduction of this defect over the following months. This reduction was accompanied by excellent clinical recovery. This case report demonstrates that central pontine myelinolysis is not always associated with hyponatremia and illustrates that, although in general the prognosis is bad, some patients may recover with improvement of the abnormalities on the MR-images.     

Encephalopathies caused by electrolyte disorders

Some of the most common reasons for metabolic neurologic disturbances in the setting of a general hospital are frequently encountered electrolyte and related osmolality disorders. Hyperosmolality is usually related to hypernatremia and/or hyperglycemia. Identifying the cause and carefully calculating the water deficit is crucial to appropriate management. Hyponatremia may be hypertonic, isotonic, or hypotonic. When hypotonic, it may be hypervolemic, euvolemic, or hypovolemic in nature. Determining the precise nature of the hyponatremia allows the clinician to focus the therapy appropriately. The rate of development of hyponatremia is crucial to safe and appropriate treatment. In acutely developing hyponatremia, hypertonic saline is required, whereas in slowly developing hyponatremia, water restriction and slow correction is required to avoid the syndrome of osmotic demyelination. Disorders of potassium metabolism are also common electrolyte disorders seen in the general hospital. Appropriate diagnosis and management of hyperkalemia and hypokalemia are also discussed.