Symptomatic hyponatraemia: can myelinolysis be prevented by treatment?

The treatment of hyponatraemia is controversial because of the risk of causing central or extrapontine myelinolysis (EPM). Rapid correction with hypertonic saline to a low normal sodium level has its proponents; others feel that slow correction to below normal sodium values is preventative. Most investigators feel that overcorrection should be avoided. It is not known whether the magnitude of serum sodium change is more important than the actual rate of correction. We present three patients with hyponatraemia ranging from 103 to 105 mmol/l who were corrected slowly with normal saline, corrected quickly with hypertonic saline, or rapidly overcorrected with hypertonic saline. All became comatose and died; all had EPM with or without central pontine myelinolysis (CPM). The rate of correction, the solution used, or the magnitude of correction did not seem to protect against demyelination. In a review of 67 reported CPM cases since 1983, no patients documented as having CPM or EPM by radiological studies or necropsy were treated with water restriction only. A group of 27 hyponatraemic patients treated only with water restriction and 35 with diuretic cessation alone did not develop CPM or EPM. This may be a reasonable approach to patients with symptomatic hyponatraemia and normal renal function.     

A review of the causes of central pontine myelinosis: yet another apoptotic illness?

One of the well recognized stimuli for central pontine myelinosis (CPM) is the rapid correction of chronic hyponatraemia. Conventionally this has been perceived to lead to pontine glial cell swelling through osmosis and eventually to cell death. However, although a purely osmotic argument has been central to any patho-physiological understanding of CPM, there are deficiencies in this approach that do not account for why certain individuals develop CPM with relatively mild osmotic insults. Here we review the varying aetiologies of CPM and propose a novel hypothesis for CPM causation by suggesting that individuals predisposed to CPM have inadequate energy provision as well as other factors that result in a pro-apoptotic drive, which renders them susceptible to brain injury from diverse causes. In CPM, the precipitant of brain injury appears to be osmotic stress. Furthermore, this model suggests a number of therapeutic interventions that may prevent or at least mitigate the consequences of CPM.     

Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa

A 31-year-old man was admitted to hospital with of anorexia, binge eating, and self induced vomiting. On admission, he showed a pronounced low weight and disturbance of the body image and was diagnosed as having anorexia nervosa. In addition, electrolyte abnormalities, mainly hypokalaemia, and increased serum renin and aldosterone concentrations were recorded, suggesting pseudo-Bartter syndrome as a complication. Under frequent monitoring of the serum potassium and sodium concentrations, serum electrolytes were gradually corrected, but brain magnetic resonance imaging revealed reversible central pontine myelinolysis (CPM). Although attention has been mainly paid to the association of CPM with rapid correction of hyponatraemia and abnormal osmolality, this case report strongly suggested the involvement of hypokalaemia in the pathogenesis of CPM.     

Central pontine myelinolysis

Central pontine myelinolysis (CPM) was initially associated with alcoholism. Subsequently other factors, including rapid reversal of hyponatraemia and extreme serum hypoosmolality associated with severe burns, have been identified as other important factors in its pathogenesis. Extra-pontine lesions have also been described. CPM may be found at autopsy, either having been overlooked during life or as an incidental finding. Its precise incidence is not known but the ability to diagnose it during life has been helped by modern neuroimaging, particularly magnetic resonance imaging (MRI) of the brain stem. In the past the prognosis for CPM was thought to be invariably fatal. It is clear now that with the greater general awareness of the disorder and the ability to diagnose it during life that some degree of recovery is possible. However, the number who do recover and the degree of recovery is not known. We report a 40-year-old man who developed CPM presenting with quadriparesis and inability to speak and swallow. There were risk factors for CPM and the diagnosis was confirmed by MRI scanning. He made a complete recovery although he remains ataxic. We are reporting this case as we believe it is important to make clinicians aware of the potential for recovery of CPM. While no specific treatment has been shown to influence the degree and rate of recovery of the demyelination, the fact that the quadriplegia and bulbar paralysis can recover fully is of considerable importance. In particular, it means that when the diagnosis is made, complete and vigorous nursing and medical care is warranted.     

Brain-stem auditory evoked responses in diagnosis of central pontine myelinolysis

Summary Central pontine myelinolysis (CPM) developed in association with acute adrenocortical insufficiency during correction of severe hyponatraemia in a 58-year-old woman. Repeated CT scanning and NMR imaging were normal from the onset of the illness. Electroencephalography and brainstem auditory evoked responses showed abnormalities consistent with a brain-stem lesion, which resolved as the patient made a gradual but incomplete recovery. Our observations illustrate the value of electrophysiological monitoring in CPM and support the proposed association between this condition and the rapid correction of an electrolyte imbalance.     

Central pontine myelinolysis.

Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with demyelination of other areas of the central nervous system (CNS). The term 'osmotic demyelinization syndrome' is used for pontine and extrapontine myelinolysis. In this paper, we are concerned with CPM although the extrapontine one is based on the same pathogenesis. Both share the diagnostic methods, and their prevention and therapy are the same. The etiology and pathogenesis of this disorder are unclear and will be discussed. However, almost all cases of CPM are related to severe diseases. Chronic alcoholism is still the most common underlying condition of CPM patients. In the literature, 174 cases of CPM have been reported in alcoholics since 1986, which is equivalent to an incidence of 39.4%. Likewise, 95 cases of CPM following the correction of hyponatremia have been documented since 1986 (21.5%). The role of hyponatremia and its correction will be outlined in the discussion of the pathogenesis of CPM. The third largest group of CPM cases are liver transplant patients (17.4%), with the development of CPM being attributed to the immunosuppressive agent cyclosporine in particular. Depending on the involvement of other CNS structures, the clinical picture can vary considerably. The large-scale introduction of magnetic resonance imaging has increasingly facilitated the antemortem diagnosis of CPM, although the radiological findings lag behind and do not necessarily correlate with the clinical picture. As yet, there is no specific therapy of choice. A number of therapeutic approaches have been tested and although they have not been compared with regard to their rate of success, they have all led to a substantial improvement in the prognosis of CPM.     

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.     

Central pontine myelinolysis in AIDS

Central pontine myelinolysis (CPM) is an uncommon complication in sick patients with severe underlying disorders such as chronic alcoholism, malignancy, malnutrition and hyponatraemia. We report two patients with advanced HIV infection who developed CPM. In one case the diagnosis was not suspected in life, in the other the diagnosis was made just before death, on the basis of magnetic resonance (MR) imaging appearances. At post mortem there was a close correlation between the MR abnormalities and the anatomic changes in the pons. Received: 6 March 1998 / Revised, accepted: 11 May 1998     

渗透性脱髓鞘综合征的临床分析

摘 要： 目的了解渗透性脱髓鞘综合征（ODS）的发病机制、诊断、治疗和预防方法。方法报告11例ODS患者，并结合文献进行分析。结果10例患者有明显低钠血症；发病诱因包括药源性3例，营养不良3例，肝移植术后、脑挫裂伤、垂体微腺瘤、糖尿病肾病和妊娠剧吐各1例。存在严重呕吐或进食量极少的患者7例。神经系统表现包括不同程度意识障碍，假性球麻痹，四肢瘫痪，眼球活动障碍，闭锁综合征，精神症状，震颤或手足徐动等不自主运动，肌张力齿轮样增高等帕金森样症状等。头颅MRI显示桥脑或双侧豆状核、尾状核头、丘脑等桥外部位脱髓鞘。单纯CPM 3例，单纯EPM 2例，CPM合并EPM 6例。治疗后10例好转，1例病情获稳定。结论ODS的发病与脑内渗透压平衡失调有关，各种原因引起的低钠血症及其快速纠正容易诱发，临床表现可为单纯CPM、EPM或二者合并存在。随着头颅MRI的应用，可使该病早期诊断，其预后明显改善。避免快速纠正低钠血症是预防的主要措施。     

Rare association of central pontine myelinolysis with infantile tremor syndrome

Central pontine myelinolysis (CPM) is an acute demyelination within the central basis pontis. Though exact mechanism is not known it is seen commonly with rapid correction of hyponatremia and also with pontine ischemia or infarction, demyelinating diseases, pontine neoplasm and different metabolic diseases. We report a rare association of CPM in a patient of Infantile Tremor Syndrom (ITS). ITS is a syndrome of tremor, mental and physical retardation, pigmentary changes of hair and skin and anemia in malnourished children. Though first reported in Indian subcontinent many identical cases were reported from around the world. Our case is a 15 month old child with generalized tremor, mild hepatosplenomegaly with features of grade II malnutrition including skin and hair changes. All the signs and symtoms of tremor improved after treatment with the World Health Organization (WHO) protocol for protein energy malnutrition (PEM) and administration of propranolol without any side effects.     

Akinetic-rigid syndrome due to extrapontine and pontine myelinolysis following appropriate correction of hyponatraemia

Extrapontine myelinolysis in association with the more common central pontine variety is increasingly reported. Although typically associated with rapid correction of hyponatraemia, myelinolysis is also seen when sodium correction occurs at recommended rates. We present a 60-year-old man who developed hyponatraemia and hypokalaemia due to repeated vomiting. An acute symmetric akinetic-rigid syndrome followed correction of hyponatraemia, performed in line with current guidelines. There were no clinical features of pontine involvement even though a typical lesion was seen on MRI. Bilateral putaminal and caudate lesions were seen. He recovered well with only symptomatic treatment. Myelinolysis can present with features of extrapontine involvement with the pontine lesions remaining asymptomatic. Current guidelines for the correction of hyponatraemia do not prevent development of myelinolysis in all instances. In contrast to the generally expected poor outcome in this condition, patients do make a good recovery with symptomatic treatment and good nursing care.     

渗透性脱髓鞘综合征

渗透性脱髓鞘综合征是由于慢性低钠血症患者,予以迅速补钠,改变低渗状态,造成有毒损害。渗透性脱髓鞘综合征的临床表现有脑桥中央髓鞘溶解症、脑桥外髓鞘溶解症。本文复习了渗透性脱髓鞘综合征的临床、病因和病理并作介绍。     

Centropontine myelinolysis related to refeeding syndrome in an adolescent suffering from anorexia nervosa

Centropontine myelinolysis (CPM) is a rare neurologic disorder defined by symmetric demyelination in the central pons, mostly due to alcoholism, malnutrition, or water-electrolyte abnormalities. We report an unusual case of CPM likely due to hypophosphatemia, related to a refeeding syndrome in the context of mental anorexia. A 15-year-old girl with mental anorexia presented with hypophosphatemia in the following days of enteral refeeding, and then suffered from confusion, neurological signs, and typical MRI lesions of CPM. Hypophosphoremia may be considered as a causative agent in CPM related to refeeding syndrome. This clinical observation also highlights the importance of recognizing patients at high risk of refeeding syndrome to initiate a balanced nutrition with careful monitoring.     

Central pontine and extra-pontine myelinolysis in an alcoholic patient without hydro-electrolyte disturbances: case report

Central pontine myelinolysis (CPM) and extra-pontine myelinolysis (EPM) are different presentations of a demyelinating disorder of the brain more commonly associated with rapid correction of hyponatremia, spastic tetraparesia and pseudo-bulbar palsy. There are in the literature a few cases of CPM/EPM in patients without electrolyte disturbances. We report the case of a 39 year-old man with severe alcoholism, who presented with spastic tetraparesis and palsy of several cranial nerves, associated with lesions in the magnetic resonance compatible with CPM/EPM. The patient had a good follow-up after pulse therapy with corticosteroids.     

Mild central pontine myelinolysis: a frequently undetected syndrome

Summary Over a period of 1 year we diagnosed central pontine myelinolysis (CPM) in five patients all of whom survived, two of them with complete functional recovery despite extensive lesions on cranial computerized tomography and magnetic resonance imaging.Diagnosis was based upon the combination of an acute brainstem dysfunction with typical neuroradiological features; a history of chronic alcoholism or a preceding hyponatremia may serve as a diagnostic hint.The spectrum of symptoms ranged from severe tetraplegia and cranial nerve palsies to latent signs of pyramidal tract lesions and discrete ocular motor abnormalities. In two patients pontine and extrapontine manifestations of demyelination were confirmed neuroradiologically; in one patient a solely extrapontine manifestation was present.Thus it is reasonable that: (1) the incidence of comparatively mild forms of CPM as well as extrapontine manifestations are more frequent than hitherto assumed, (2) the clinical outcome of the syndrome is better than expected from earlier fatal case reports and is quite independent of the extent of the lesion as it appears with brain imaging methods.     

Central pontine myelinolysis in severely burned patients: relationship to serum hyperosmolality

The rapid correction or over-correction of hyponatremia is believed by many to be the crucial factor in the causation of central pontine myelinolysis (CPM). Over a 17-year period we found CPM in 10 (7%) of the 139 burn patients examined postmortem but in only 10 (0.28%) of the 3,528 patients in the general autopsy population (p less than 0.001). Each of the burn patients with CPM had suffered a prolonged, nonterminal episode of extreme serum hyperosmolality, whereas most burn patients without CPM had not suffered such an episode. The histologic age of the lesions correlated with the duration of time between the hyperosmolar episode and death. Hypernatremia, hyperglycemia, and azotemia, alone or combined, accounted for the hyperosmolality. No single electrolyte or metabolic derangement was essential, as in at least one burn patient with CPM the serum sodium, glucose, or blood urea nitrogen was normal during the hyperosmolar episode. Hyponatremia was not present in any burn patient with CPM. We conclude that severely burned patients, like alcoholics, are especially susceptible to CPM, and that in burn patients with CPM there is a striking association with serum hyperosmolality. The data also suggest that the rapid correction of hyponatremia exerts its effects by causing an osmotic shift and not because of any specific property of the sodium ion.     

Demyelination of the lateral geniculate nucleus in central pontine myelinolysis

Postmortem examination of the central nervous system in 6 of 9 patients with central pontine myelinolysis (CPM) revealed demyelination in the lateral geniculate nucleus (LGN). Histologically, the geniculate lesions consisted of myelin swelling and disintegration, largely in the central part of the nucleus, with preservation of axons and neuronal perikarya. The pathological changes resembled those found in the basis pontis in CPM.     

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.     

渗透性脱髓鞘综合征的临床和影像学研究(附四例报道)

目的 探讨渗透性脱髓鞘综合征的临床和神经影像特点.方法 对4例渗透性脱髓鞘综合征患者的临床演变过程、CSF、头颅CT和MRI、EEG动态变化特点、治疗及预后进行分析.结果 4例患者均存在低钠血症,纠正后出现精神意识改变、构音和吞咽困难、四肢瘫痪、肌张力障碍等症状,临床过程有双相性.EEG出现一过性的重度异常.头颅CT及CSF均未见异常.MRI特征性影像晚于临床表现10 d以后出现,4例患者首次MRI均为阴性,7～13 d后复查才显示病灶.MRI示4例患者均存在脑桥外髓鞘溶解症病灶,T1WI加权低信号,T2WI加权高信号,对称性地累及双侧尾状核、豆状核、丘脑、脑岛叶皮质、海马头部等部位,其中3例同时存在脑桥中央髓鞘溶解症改变,呈脑桥基底部位对称性T1低、T2高信号的蝶形病灶;Flair加权异常信号更清楚.3例有好转或痊愈,其中1例遗留明显肌张力障碍.结论 渗透性脱髓鞘综合征与慢性低钠血症有关,合并低血钾、低血氯时可能更易发生.治疗时应尽量避免过快纠正,临床病程具有双相性.MRI的特征性改变出现较迟,复查MRI是非常必要的.     

渗透性脱髓鞘综合征的临床和影像学研究(附四例报道)

目的 探讨渗透性脱髓鞘综合征的临床和神经影像特点.方法 对4例渗透性脱髓鞘综合征患者的临床演变过程、CSF、头颅CT和MRI、EEG动态变化特点、治疗及预后进行分析.结果 4例患者均存在低钠血症,纠正后出现精神意识改变、构音和吞咽困难、四肢瘫痪、肌张力障碍等症状,临床过程有双相性.EEG出现一过性的重度异常.头颅CT及CSF均未见异常.MRI特征性影像晚于临床表现10 d以后出现,4例患者首次MRI均为阴性,7～13 d后复查才显示病灶.MRI示4例患者均存在脑桥外髓鞘溶解症病灶,T1WI加权低信号,T2WI加权高信号,对称性地累及双侧尾状核、豆状核、丘脑、脑岛叶皮质、海马头部等部位,其中3例同时存在脑桥中央髓鞘溶解症改变,呈脑桥基底部位对称性T1低、T2高信号的蝶形病灶;Flair加权异常信号更清楚.3例有好转或痊愈,其中1例遗留明显肌张力障碍.结论 渗透性脱髓鞘综合征与慢性低钠血症有关,合并低血钾、低血氯时可能更易发生.治疗时应尽量避免过快纠正,临床病程具有双相性.MRI的特征性改变出现较迟,复查MRI是非常必要的.