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.     

Extrapontine myelinolysis with involvement of the hippocampus in three children with severe hypernatremia

Central pontine myelinolysis is a disorder of unknown etiology linked to overly aggressive correction of hyponatremia. In addition to the typical location of demyelination with preservation of neurons and axon cylinders in the basis pontis, similar lesions have been described in extrapontine locations. Central pontine myelinolysis and extrapontine myelinolysis usually occur together, and are identified at autopsy rather than in life because symptoms of extrapontine myelinolysis are often masked in the critically ill patient. Central pontine myelinolysis is described in children, usually in the clinical setting of hyponatremic dehydration. Extrapontine myelinolysis has not been described in children previously. We report three children with severe hypernatremia and extrapontine myelinolysis involving various combinations of thalamus, basal ganglia, external and extreme capsules, and cerebellar vermis. All three had additional involvement of the hippocampus seen on T2-weighted magnetic resonance imaging. None of the three had detectable pontine lesions. Clinical features of the three cases were dehydration in a 28-month-old girl, respiratory syncytial virus bronchiolitis in a 14-month-old girl, and acute respiratory failure due to anaphylaxis after consumption of walnuts in a 3-year-old boy. Peak sodium values in each child were 195, 168, and 177 mmol/L, respectively; each received aggressive treatment for hypernatremia. We believe this to be the first report of extrapontine myelinolysis in children, the first report of extrapontine myelinolysis without central pontine myelinolysis in children, and the first report in children of hippocampal formation involvement. The pathogenesis of the central and extrapontine myelinolysis complex in children is more complicated than previously believed, and might differ significantly from that of adults.     

脑桥中央和脑桥外髓鞘溶解症的临床分析和影像特点

目的:探讨脑桥中央和脑桥外髓鞘溶解症的临床及神经影像特点。方法:分析3例脑桥中央髓鞘溶解症和1例脑桥外髓鞘溶解症患者的临床特点,包括起病前诱因、临床表现、头颅MRI特点、治疗及预后情况。结果:4例患者均有慢性形成低钠血症后被快速纠正的病史,以意识改变、构音和吞咽困难、四肢瘫痪等为临床表现。3例脑桥中央髓鞘溶解症的MRI表现为脑桥部位对称性的T1加权低信号灶、T2加权高信号灶,呈环状分布;1例脑桥外髓鞘溶解症者在基底节区域有对称性的T1加权低信号、T2加权高信号病灶。4例患者总体预后良好。结论:提高髓鞘溶解症的认识对于本病的防治非常重要,缓慢纠正慢性形成的低钠血症是预防的关键。     

EXTENSIVE EXTRAPONTINE AND CENTRAL PONTINE MYELINOLYSIS ASSOCIATED WITH CORRECTION OF PROFOUND HYPONATRAEMIA

The relationship between correction of hyponatraemia and the development of central pontine myelinolysis (CPM) remains controversial. A case of CPM associated with extensive extrapontine demyelination is described. Profound hyponatraemia and its subsequent correction are documented. It is suggested that the extent of demyelination reflects the degree of hyponatraemia noted prior to correction, supporting current hypotheses regarding the role of hyponatraemia in CPM. This case is unusual in that other recognized risk factors for the development of CPM are absent.     

Central pontine myelinolysis associated with low potassium levels in alcoholism

Summary Two patients with chronic alcohol abuse and central pontine myelinolysis are described. One developed a Korsakoff syndrome 2 days before admission to our hospital and the other showed signs of a incipient delirium without Korsakoff syndrome. Diagnosis of incipient central pontine myelinolysis was based on acute brain-stem dysfunction, serum electrolyte disturbances, malnutrition with vitamin B₁ (thiamine), B₆ (pyridoxine) and B₁₂ (cyanocobalamine) deficiency in combination with typical neuroradiological findings. Hypokalaemia but no disturbance in serum sodium levels was found in both patients. After correction of hypokalaemia and vitamin deficiency the patients showed complete recovery of neurological and neuropsychological function. The findings are interpreted as suggesting that disturbances in serum potassium levels as well as rapid correction of hyponatraemia may be associated with pontine swelling and dysfunction which, if undetected, leads to central pontine myelinolysis.     

Parkinsonism and dystonia in central pontine and extrapontine myelinolysis

Parkinsonism as well as dystonic signs are rarely seen incentral pontine myelinolysis and extrapontine myelinolysis. A 51yearold woman developed central pontine myelinolysis and extrapontine myelinolysis with parkinsonism after severe vomiting which followed alcohol and drug intake, even though marked hyponatraemia had beencorrected gradually over six days. Parkinsonism resolved four monthsafter onset, but she then exhibited persistent retrocollis, spasmodicdysphonia, and focal dystonia of her left hand. Although the medicalliterature documents three similar patients, this patient is differentas dystonic symptoms only developed four months after parkinsoniansigns had resolved.

     

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 following correction of hyponatremia: MRI diagnosis

A 37-year-old woman with hepatic failure developed a locked-in syndrome after correction of a severe symptomatic hyponatremia. Magnetic resonance imaging showed a lesion involving the basis pontis and extending into the midbrain, consistent with central pontine myelinolysis. In this patient the rate of correction of hyponatremia was within the range considered sure by several authors, but factors such as hepatic encephalopathy, a single generalized seizure and correction of hyponatremia in 42 h with a change in serum sodium concentration of 34 mmol/l were present, and they could have been etiologically relevant. This case, like other recent reports, suggests new views about the pathogenesis of cerebral demyelinating lesions in patients with hyponatremia.     

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.     

Movement disorders as sequelae of central pontine myelinolysis: report of three cases.

In three survivors of central pontine myelinolysis, dystonia (in two patients) and rest tremor (in one) were sequelae. The onset of these movements occurred 3 weeks to 5 months after the initial presentation with central pontine myelinolysis. Magnetic resonance imaging revealed basal ganglia lesions suggestive of extra-pontine myelinolysis in all three patients. We propose that the movement disorders seen in our cases are clinical correlates of extra-pontine myelinolysis.     

Extrapontine myelinolysis in infancy: report of a case

Osmotic myelinolysis is a rare, acute, demyelinating process that involves the pons (central pontine myelinolysis) and other locations of the central nervous system (extrapontine myelinolysis). Central pontine myelinolysis is described in children, usually associated with rapid correction of hyponatremia. Other conditions, such as hypernatremia and hyperglycemia, have also been reported as being responsible for pontine myelinolysis. Extrapontine myelinolysis in childhood is very rare and presents in a wide variety of locations. We report a patient who developed extrapontine myelinolysis in the cerebellum during treatment of hyponatremic dehydration. This is the first case reported during infancy.     

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。     

Central pontine myelinolysis: delayed changes on neuroimaging.

The authors report two cases, a 44-year-old woman and a 6-year-old girl who had mental status changes and hyponatremia. Serum sodium levels in both of these cases were corrected quickly with further decline in their mental status, and the patients became quadriparetic. Magnetic resonance imaging (MRI) studies performed then did not reveal any abnormalities, whereas a repeat imaging study performed 10-14 days after the shift in serum sodium revealed evidence for central pontine myelinolysis and extrapontine demyelination. The clinical manifestations and distribution of lesions seen on the imaging studies demonstrated that the above presentation of neurologic illness is the result of hyponatremia and its correction. The authors conclude that imaging studies performed early during the illness may be unremarkable, but still a diagnosis of central pontine myelinolysis should be suspected and, most importantly, a repeat imaging study might be required in 10-14 days to establish the diagnosis of central pontine myelinolysis.     

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.     

Regressive dystonia and cerebellar ataxia: two unusual symptoms in central pontine myelinolysis

Two patients with central pontine myelinolysis who presented with dystonia are described. In one, it was associated with cerebellar ataxia which spontaneously improved. In the second, dystonia progressively disappeared 6 months later. In both cases magnetic resonance imaging (MRI) revealed characteristic pontine lesions. Extrapontine myelinolysis involving the putamen was also observed in one patient. Even when the basal ganglia seem to be spared on MRI, dystonia is probably due to their involvement by myelinolysis. Cerebellar ataxia may be related to peduncular or cerebellar lesions or both.     

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.     

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.     

Protective effect of steroids in electrolyte-induced demyelination

Electrolyte-induced demyelination (EID), an experimental model for central pontine myelinolysis was produced in rats by inducing hyponatremia followed by hypernatremia. There was a marked reduction in the number and size of lesions developing in animals that were bled repeatedly by tail transection during induction of the disease. Subsequently a similar protective effect was produced in animals by injecting a single dose of dexamethasone, one hour before the induction of hypernatremia. These findings suggest that steroids may be useful in preventing central pontine myelinolysis from developing in high risk patients requiring urgent correction of hyponatremia.     

Central pontine and extrapontine myelinolysis owing to disequilibrium syndrome

Neurologic disorders can be seen in patients with end-stage renal failure owing to complications of hemodialysis or peritoneal dialysis. The disequilibrium syndrome can be seen, usually soon after or toward the end of dialysis. We report a patient with central pontine and extrapontine myelinolysis owing to disequilibrium syndrome. The patient had depressed consciousness, agitation, tremor, stupor and hyperactive deep tendon reflexes toward the end of the second peritoneal dialysis. A brain computed tomographic (CT) scan showed hypodense lesions in pontine and extrapontine locations without radiocontrast medium enhancement After 2 days, the patient had only minimal memory deficits. A control brain CT scan 1 week later showed a decrease of the lesions in central pontine and extrapontine locations. Central pontine and extrapontine myelinolysis should be suspected and investigated in the acute neurologic disorders of dialysis patients.