Extrapontine myelinolysis after correction of hyponatremia presenting as generalized tonic seizures

Central pontine myelinolysis and extrapontine myelinolysis are rare complications of rapid correction of chronic hyponatremia. Central pontine myelinolysis is more common and more predictable in presentation. Extrapontine myelinolysis' presenting symptoms vary and may be as general as lethargy or altered mood. We report experience with a patient who developed only extrapontine myelinolysis after rapid correction of severe hyponatremia associated with gastroenteritis. His presenting sign, generalized seizures, has not been previously reported. We summarize risk factors for myelinolysis, which may be more common than previously thought, as well as steps to minimize risk while managing vulnerable patients.     

No Association between Hyponatremia and Rhabdomyolysis in Rats

Background

Rhabdomyolysis is an uncommon complication of hyponatremia, reported previously only in case reports and small retrospective studies, and its underlying mechanism is controversial. Some studies support the hypothesis that the rapid correction of hyponatremia is responsible for rhabdomyolysis, whereas others emphasize the severity of the hyponatremia as a predisposing factor for rhabdomyolysis.

Objectives

To test the association between hyponatremia and rhabdomyolysis and to demonstrate a causal association.

Methods

Hyponatremia was induced by administration of water and desmopressin acetate in rats during 3 days, followed by its rapid correction, using animal models established for the evaluation of central pontine myelinolysis. The plasma creatine phosphokinase levels, a marker for rhabdomyolysis, were monitored, and hematoxylin and eosin sections of the quadriceps and gastrocnemius muscles were evaluated for signs of rhabdomyolysis.

Results

The induction of hyponatremia and its correction were accompanied by the previously reported neurological sequelae, including signs of central pontine myelinolysis. However, no increase in plasma creatine phosphokinase levels was found, and histopathological examination of the quadriceps and gastrocnemius muscles revealed no sign of rhabdomyolysis.

Conclusions

The present study, which is the first to test the association between hyponatremia and rhabdomyolysis in an animal model, does not support any causal association between hyponatremia and rhabdomyolysis. Thus, other factors might be necessary for an association between hyponatremia and rhabdomyolysis, such as genetic factors or convulsions that are known to be associated with both hyponatremia and rhabdomyolysis. Further research in this important physiologic and clinical question is needed.     

Osmotic demyelination and hypertonic dehydration in a 9-year-old girl: changes in cerebrospinal fluid myelin basic protein

A 9-year-old girl was admitted for the treatment of hyper-natremic dehydration. Her history was significant for psychogenic polydipsia, hyponatremia, and a renal concentrating defect. She presented with a 2-day history of altered mental status, ataxia, lethargy, fever, nausea, vomiting, and diarrhea. Meningitis was ruled out. Over the course of her illness, slow rehydration was maintained with a gradual decrease (10 mEq per 24 hours) of the serum sodium. Despite this care, she developed quadriparesis, and magnetic resonance imaging performed on day 6 of her illness was consistent with osmotic demyelination (central pontine myelinolysis). To rule out an excessively rapid correction of hypernatremia as the etiology of the problem, a myelin basic protein was measured in the cerebrospinal fluid that had been obtained on hospital day 1. The myelin basic protein was 649.50 ng/mL (normal, 0.07-4.10 ng/mL). The current literature is presented regarding the postulated pathogenesis of central pontine myelinolysis and suggested therapies, previous reports of central pontine myelinolysis in children are reviewed, and the potential role of myelin basic protein in its diagnosis is discussed.     

Alcohol and the central nervous system

Acute Wernicke-Korsakoff syndrome is an underdiagnosed cause of reversible coma in the alcoholic patient. Chronic toxic effects of ethanol include nutritional polyneuropathy, cerebellar degeneration, and diffuse cortical damage with resultant alcoholic dementia. The rapid correction of hyponatremia can result in the iatrogenic syndrome of central pontine myelinolysis.     

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

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 1H-nuclear 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 less than 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% NaCl 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 of the 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 of adequate concentrations of organic osmolytes may be relevant to the development of central pontine myelinolysis.     

脑桥中央髓鞘溶解症(附3例报告)

目的探讨脑桥中央髓鞘溶解症（CPM）的病因、临床特点、治疗及其预防措施。方法回顾性分析3例已确诊的CPM患者的诊断资料。结果3例患者均存在严重的基础病症,特别是严重的电解质紊乱（低钠血症）,过快纠正后出现球麻痹,四肢瘫痪;头颅磁共振成像（MRI）改变。经激素、脱水剂、B族维生素等治疗,均好转出院。结论营养不良或（和）电解质紊乱是CPM常见的基础疾病,纠正电解质紊乱不宜过快,头颅MRI对本病早期确诊意义较大,早期诊断适当治疗,预后良好。     

Central pontine myelinolysis

Central pontine myelinolysis (CPM), a neurologic disorder caused most frequently by rapid correction of hyponatremia, is characterized by demyelination that affects the central portion of the base of the pons. There are no inflammatory changes, and blood vessels are normal. Clinical features usually reflect damage to the descending motor tracts and include spastic tetraparesis, pseudobulbar paralysis, and the locked-in syndrome. Magnetic resonance imaging of the brain, the imaging procedure of choice, shows an area of prolonged T1 and T2 relaxation in the central pons, which may have a characteristic shape. Recovery varies, ranging from no improvement to substantial improvement. To avoid CPM, correction of serum sodium in patients with hyponatremia should not exceed 12 mEq/24 h. We describe a case of CPM in a hyponatremic patient who presented with a cerebellar syndrome with no pyramidal tract involvement and in whom the rate of correction of serum sodium was within the recommended limits.     

EXTRAPONTINE MYELINOLYSIS AFTER CORRECTION OF CHRONIC HYPONATRAEMIA WITH ISOTONIC SALINE

SUMMARY Rapid correction of severe chronic hyponatraemia with hypertonic saline can cause central pontine myelinolysis. Less well appreciated are the dangers of rapid correction with isotonic saline. A case is reported in which correction of severe hyponatraemia by 11 mmol/l in 24 hours with isotonic saline produced extensive extrapontine myelinolysis, one of the manifestations of the osmotic demyelination syndrome.     

Osmotic myelinolysis syndrome after treatment of severe deamino arginine vasopressin-associated hyponatraemia: pitfalls in emergency medicine

Hyponatraemia is among the more common electrolyte abnormalities encountered in the ED. Both the primary disturbance and its correction can result in life-threatening neurological sequelae. Osmotic myelinolysis syndrome is one such complication and is associated with the rapid correction of hyponatraemia. The present case report describes the mechanism of severe hyponatraemia in a patient taking deamino arginine vasopressin, and the subsequent development of both central pontine and extrapontine myelinolysis after rapid correction of sodium levels. Implications for the emergency management of such patients are discussed.     

Hyponatrémies en réanimation : actualités

Hyponatremia is a common hydroelectrolytic disturbance which can result from multiple origin, particularly iatrogenic. Usually, hyponatremia is related to hypotonia, inducing intracellular hyperhydration and swelling. The prevention of cellular swelling, especially in the brain, depends on the type of onset, acute or chronic, but also on other factors such as: female gender, young age, hypoxia... The management of hyponatremia is guided by the understanding of the pathophysiology and relies on routinely available data: patient’s history, clinical assessment of the extracellular fluid volume, routine blood and urine laboratory tests. The evaluation of clinical tolerance and of the type of onset are determinant in the therapeutic strategy. It is always more important to treat the symptoms rather than to correct laboratory values. Myelinolysis is a severe neurologic disorder that can occur after a rapid correction of chronic hyponatremia. According to recent preliminary data, myelinolysis could be reversed by reinducing hyponatremia but this point needs further research.     

A study of the pathogenesis and prevention of central pontine myelinolysis in a rat model

The development of central pontine myelinolysis was studied in rats. Severe hyponatraemia was induced using vasopressin tannate and 2.5% dextrose in water and then rapidly corrected with hypertonic saline alone, hypertonic saline and dexamethasone simultaneously, or hypertonic saline plus dexamethasone 24 h later. The permeability of the blood-brain barrier was evaluated using the extravasation of Evans blue dye and the expression of inducible nitric oxide synthase (iNOS) in the brain was examined using Western blot analysis. Histological sections were examined for demyelinating lesions. In rats receiving hypertonic saline alone, Evans blue dye content and expression of iNOS began to increase 6 and 3 h, respectively, after rapid correction of hyponatraemia and demyelinating lesions were seen. When dexamethasone was given simultaneously with hypertonic saline, these increases were inhibited and demyelinating lesions were absent. These effects were lost if dexamethasone injection was delayed. Disruption of the blood-brain barrier and increased iNOS expression may be involved in the pathogenesis of central pontine myelinolysis, and early treatment with dexamethasone may help prevent the development of central pontine myelinolysis.     

脑桥中央髓鞘溶解症的临床特征及其康复预后

目的研究脑桥中央髓鞘溶解症(CPM)的临床特征、康复和预后。方法回顾性分析并随访本院近10年确诊的CPM综合征患者20例,并与国外大型研究进行比较。结果与国外相比,国内应用垂体后叶素引起的渗透性髓鞘溶解综合征相对多见,并发脑桥外髓鞘溶解症(EPM)多见;主要在低钠血症快速纠正后2~10 d内出现迅速进展的皮质延髓束或皮质脊髓束症候群。康复治疗可以改善症状,但严重构音障碍者语言功能改善差。结论 CPM患者康复治疗有助于功能改善。应用垂体后叶素时注意监测电解质变化,低钠血症患者需严密监测、严格遵循补钠原则。     

Extrapontine myelinolysis caused by rapid correction of pituitrin-induced severe hyponatremia: A case report

BACKGROUND Severe hyponatremia is considered a rare complication of pituitrin,which is widely used for the treatment of pulmonary hemorrhage.However,the management of pituitrin-associated hyponatremia can be challenging because a rapid correction of hyponatremia may cause the development of osmotic demyelination syndrome,resulting in life-threatening neurological injuries.CASE SUMMARY A 20-year-old Chinese man with massive hemoptysis developed symptomatic hyponatremia(116 mmol/L)after therapy by a continuous intravenous drip of pituitrin.To normalize his serum sodium,a hypertonic saline infusion was applied for 3 d,and the pituitrin administration was stopped concurrently.Then,an overly rapid increase in serum sodium level(18 mmol/L in 24 h)was detected after treatment.One day later,the patient experienced a sudden onset of generalized tonic-clonic seizures,as well as subsequent dysarthria and dystonia.Magnetic resonance imaging revealed increased signal intensity in the bilateral symmetric basal ganglia on the T2-weighted images,compatible with a diagnosis of extrapontine myelinolysis.The patient received an intravenous administration of high-dose corticosteroids,rehabilitation,and neurotrophic therapy.Finally,his clinical abnormalities were vastly improved,and he was discharged with few residual symptoms.CONCLUSION Physicians should be fully aware that pituitrin can cause profound hyponatremia and its correction must be performed at a controlled rate to prevent the development of osmotic demyelination syndrome.     

Syndromes of excess antidiuretic hormone release

Hyponatremia, particularly that due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), is common in patients seen in the critical care setting. Because of aging-associated changes in the hormonal and renal systems involved in regulation of water and sodium balance, older persons are at higher risk than the young. The high prevalence of disease states and drug use in the elderly can affect water and sodium conservation and further contribute to the risk of hyponatremia in this population. The approach to management is dependent both on the severity of hyponatremia-related symptoms and the rapidity with which hyponatremia has developed. Careful monitoring of serum sodium during treatment is essential to produce prompt resolution of symptoms while avoiding the development of central pontine myelinolysis. Several therapeutic modalities are available for the longterm management of chronic hyponatremia.     

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

Organic 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 H2O. 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. After rapid correction of chronic hyponatremia, a topographic correlation between demyelination lesions and delayed accumulation of organic osmolytes exists.     

Etiology and management of hyponatremia in neurosurgical patients

Hyponatremia is the most common electrolyte disorder encountered in neurosurgical patients. The aggressive treatment of hyponatremia in this group is critical, as hyponatremia can lead to mental status changes, seizures, vasospasm, cerebral edema, and even death. When it occurs, it represents a failure of one of several homeostatic mechanisms that tightly regulate serum sodium. In these patients, hyponatremia is most commonly due to the syndrome of inappropriate antidiuretic hormone (SIADH) or cerebral salt wasting (CSW). It can be problematic to differentiate between these 2 as they share key features, including low serum sodium, low serum osmolality, a higher urine osmolality than serum osmolality, and an elevated urinary sodium concentration. Furthermore, distinctions between CSW and SIADH, namely extracellular fluid (ECF) volume and total sodium balance, are often difficult to establish. Syndrome of inappropriate antidiuretic hormone is characterized by a volume-expanded state, whereas CSW is characterized by a volume-contracted state. Determining the exact cause remains a clinical imperative as the treatment for each is different. The rate at which serum sodium is corrected must be attended to, as rapid shifts in serum sodium pose potential risk of cerebral pontine myelinolysis.     

Management of hyponatremia

Hyponatremia is an important electrolyte abnormality with the potential for significant morbidity and mortality. Common causes include medications and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Hyponatremia can be classified according to the volume status of the patient as hypovolemic, hypervolemic, or euvolemic. Hypervolemic hyponatremia may be caused by congestive heart failure, liver cirrhosis, and renal disease. Differentiating between euvolemia and hypovolemia can be clinically difficult, but a useful investigative aid is measurement of plasma osmolality. Hyponatremia with a high plasma osmolality is caused by hyperglycemia, while a normal plasma osmolality indicates pseudohyponatremia or the post-transurethral prostatic resection syndrome. The urinary sodium concentration helps in diagnosing patients with low plasma osmolality. High urinary sodium concentration in the presence of low plasma osmolality can be caused by renal disorders, endocrine deficiencies, reset osmostat syndrome, SIADH, and medications. Low urinary sodium concentration is caused by severe burns, gastrointestinal losses, and acute water overload. Management includes instituting immediate treatment in patients with acute severe hyponatremia because of the risk of cerebral edema and hyponatremic encephalopathy. In patients with chronic hyponatremia, fluid restriction is the mainstay of treatment, with demeclocycline therapy reserved for use in persistent cases. Rapid correction should be avoided to reduce the risk of central pontine myelinolysis. Loop diuretics are useful in managing edematous hyponatremic states and chronic SIADH. In all instances, identifying the cause of hyponatremia remains an integral part of the treatment plan.     

Myélinolyse centro- et extrapontine. Données actuelles et spécificités en réanimation

Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM), also known as the osmotic demyelination syndrome, are uncommon disorders, characterized by non-inflammatory demyelination involving the pons and other areas of the central nervous system. Usual predisposing factors are chronic alcoholism, malnutrition, and correction of hyponatremia. Clinical features are variable and depend on the involved brain regions. The usual CPM/EPM presentation includes tetraparesia, locked-in syndrome, abnormal movements, and psychiatric symptoms. Diagnosis is based on neuroimaging, especially magnetic resonance imaging, which shows typically hypointense lesions on T1-weighted sequences and hyperintense lesions on T2-weighted sequences. Supportive treatment is all that can be recommended. No specific treatment has been proven effective. Although earlier reports on CPM/EPM have shown very poor outcome, recent reports suggest better outcome with improved survival and recovery. However, no study has clearly identified any potential prognostic factors in CPM/EPM. Very few data are available for the most severely ill patients requiring mechanical ventilation. The uncertain benefits of aggressive and costly life-supporting treatments for these critically ill patients with severe comorbidities and neurologic impairment could have great influence on decision-making for the level of care. However, recovery is unpredictable on the basis of illness severity and decisions should not be influenced by the initial presentation since favorable outcome is possible.     

A Fatal Overdose of Arginine Hydrochloride

Abstract

Case Report: Arginine hydrochloride is used both diagnostically to test for growth hormone deficiency and therapeutically for treatment of metabolic alkalosis. We describe a 21-month-old girl who developed cardiopulmonary arrest following an accidental overdose of arginine hydrochloride. The patient developed acute metabolic acidosis and transient, but severe, hyponatremia. Thirty-six hours after successful resuscitation, she developed fatal central pontine and extrapontine myelinolysis. Unlike previous reports of arginine toxicity, our patient showed no evidence of hyperkalemia. This case illustrates a previously unreported mechanism of arginine hydrochloride toxicity.     

Pontine myelinolysis in a child with carbamate poisoning

Carbamate and organophosphate pesticides are widely used all over the world. Poisoning with these substances may produce both immediate and delayed neurotoxic effects. We report the case of a 4-year-old boy who was admitted to the Pediatric Department of the Second University of Naples for evaluation of stupor, lethargy, severe hypotonia, generalized weakness of his arms and legs, ataxia, dysmetria, miosis, excessive salivation and tearing. The pesticide carbaryl (1-naphthyl-N-methylcarbamate) was identified in blood and urine samples. On admission, magnetic resonance imaging (MRI) was unremarkable; on day 11, MRI showed central pontine myelinolysis. The demyelination improved after 4 months and disappeared after 2 years. Various underlying and concomitant diseases have been described in children with central pontine myelinolysis but, to our knowledge, the finding of pontine myelinolysis after carbamate poisoning has not yet been described.