Extrapontine myelinolysis in a pediatric case of diabetic ketoacidosis and cerebral edema

Central pontine and extrapontine myelinolysis are characterized by symmetric demyelination following rapid shifts in serum osmolality, although in extrapontine myelinolysis, demyelination is confined to the supratentorial compartment. We present a case of extrapontine myelinolysis in a 17-year-old female that occurred in the setting of diabetic ketoacidosis, cerebral edema, mannitol therapy, and meningitis. The rate of correction of this patient's glucose and electrolyte levels was within well-accepted limits. Extrapontine myelinolysis is rare in pediatric patients: there are only 12 reports of extrapontine myelinolysis in children under age 20 years and no pediatric cases of extrapontine myelinolysis or central pontine myelinolysis associated with diabetic ketoacidosis. We review the published cases of extrapontine myelinolysis and examine the underlying etiologies and electrolyte disturbances that characterize these cases. This case expands the list of conditions in which extrapontine myelinolysis occurs to include pediatric patients with complicated diabetic ketoacidosis, emphasizing the importance of sudden osmolar shifts in the genesis of this disorder.     

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。     

Lateral pontine and extrapontine myelinolysis associated with hypernatremia and hyperglycemia

Efforts to understand and prevent pontine and extrapontine myelinolysis have focused on the correction of hyponatremia, but controversy persists. We report a woman who presented in hyperosmolar diabetic coma with hypernatremia (169 mEq/l) and hyperglycemia (954 mg/dl). Plasma sodium rapidly increased to 188 mEq/l before gradually returning to normal. She remained obtunded and died 21 days later. Autopsy showed widespread, symmetrical demyelination involving the subcortical white matter, corpus callosum, anterior commissure, extreme, external, and internal capsules, fornix, thalamus, cerebellum, and lateral pons. The central pons and lateral geniculate nuclei were uninvolved. This case illustrates that lateral pontine and extrapontine myelinolysis can be associated with hypernatremia and hyperosmolality. In both hypo- and hypernatremic states, the significant event may be an increase in serum sodium or serum osmolality of sufficient rapidity and magnitude.     

Central pontine and extrapontine myelinolysis: report of an autopsied case and review of the literature

An autopsied case of central pontine and extrapontine myelinolysis in a 16-year-old diabetic girl is described. Due to dehydration she was treated vigorously with daily intravenous isotonic saline, from the first day of hospitalization. In the first three days the serum sodium level increased by more than 30 mEq/l when compared with the initial level. By the next days the serum sodium level, after a mild drop, rose again and was maintained above normal range for a further 12 days. On the sixth day of this new and sustained serum sodium increase, the patient presented progressive neurological manifestations that remained until her death, characterized by mutism, inability to eat, to move her head, trunk, and members and, in addition, retention of respiratory secretions. The neuropathological examination showed massive central pontine myelinolysis and similar myelinolytic lesions in the subcortical white matter of the temporal lobe, the right optic tract, the external and extreme capsules to the right, the main mammillary tract and the subcortical white matter of the left cerebellar hemisphere. The review of the literature on central pontine and extrapontine myelinolysis shows that the present case is the 30th of such condition. The clinical picture and the etiopathogenesis of central pontine and extrapontine myelinolysis are commented upon. It is suggested, as possible causative factors, the persistent and rapid correction of serum sodium concentration as well as its fluctuation in patients with hyponatremia and/or dehydration.     

Overlapping features of extrapontine myelinolysis and acquired chronic (non-Wilsonian) hepatocerebral degeneration

Central pontine myelinolysis (CPM, osmotic demyelination syndrome) and acquired chronic hepatocerebral degeneration (ACHD) both occur in patients with liver failure, but are not thought to be caused by similar etiopathogenic mechanisms despite the fact that occasional patients exhibit both disorders. In our autopsy practice we have recently encountered three patients with the pontine lesions of acute or subacute osmotic demyelination syndrome, coupled with superimposed non-Wilsonian ACHD. All three patients had well-documented rapid elevations in serum sodium proximate to their demise, as well as terminal liver failure. A close intermingling and juxtaposition of lesions with severe demyelination and macrophage breakdown [thought to represent extrapontine myelinolysis (EPM)] to those with vacuolization of myelin but no cellular reaction or myelin loss (ACHD) was noted within some of the same anatomic areas. Particular overlap was seen in lesions at the cerebral cortical gray–white junction and in pencil fibers of the striatum. In these areas it was difficult to be certain whether the lesions were due to EPM or ACHD. We concluded that there was a synergism between the two disorders and raise the possibility that there may be factors common to both disorders that lead to similar anatomic sites for involvement.Presented (in abstract format) at XVIth International Congress of Neuropathology, San Francisco, Sept 10–15, 2006.     

Cerebellar peduncular myelinolysis in a patient receiving hemodialysis

Here, we report the observation of extrapontine lesions, in addition to the pontine lesions previously documented in a diagnosed case of hemodialysis-associated osmotic demyelination syndrome due to end-stage renal disease. The patient exhibited lesions on bilateral middle cerebellar peduncles, and had been receiving regular hemodialysis as treatment for end-stage renal disease. He presented with progressive gait disturbance and postural instability. Accompanying symptoms included peduncular hallucinations and mild cognitive dysfunction. Brain MRI revealed high signal intensity in the area of bilateral cerebellar peduncles on the diffusion and T2-weighted images, with a decreased signal intensity noted on the ADC map. The ataxic form of osmotic myelinolysis syndrome is quite rare. The involvement of the cerebellar peduncles in extrapontine myelinolysis in a patient with end stage renal disease has not, to our knowledge, been previously reported. Here, we describe the MRI findings and clinical features associated with this unique case, and include a review of the relevant literature.     

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.     

Reversible central pontine and extrapontine myelinolysis in a 16-year-old girl

A rare case of an osmotic demyelination syndrome in a 16-year-old girl is presented. MRI in the acute stage revealed a focal abnormal signal within the basis pontis and both caudate nuclei and putamina. Two years later brain lesions had disappeared on T1- and T2-weighted imaging, indicating that central pontine and extrapontine myelinolysis may be completely reversible. Received: 4 July 2000     

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.     

The corticobasal syndrome triggered by central pontine myelinolysis

Single case reports have described movement disorders including parkinsonism, dystonia and chorea, but not corticobasal syndrome as a consequence of central pontine and extrapontine myelinolysis. We report a case of a 61-year-old woman who developed progressive asymmetric parkinsonism with ideomotor apraxia and cortical sensory deficits following central pontine myelinolysis.     

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.     

Current perspectives in the management of hyponatremia: prevention of CPM

Central pontine myelinolysis represents a relatively contemporary neurologic entity in which an imbalance of water relative to alterations in the body's electrolyte levels induces characteristic demyelination in the central part of the basis pontis as well as extrapontine sites. The clinical scenario is typically one of chronic hyponatremia followed by a rapid correction to normonatremic or hypernatremic levels. This seemingly innocuous series of events can result in fatal consequences. Better understanding of the pathophysiology of this disorder provides avenues for clinical management, including use of steroids and organic osmoles, such as myoinositol. More recently, the introduction of a newer class of pharmacologic agents - the vasopressin receptor antagonists, known as vaptans, which induce an excretion of increased amounts of water without altered sodium or potassium excretion - is of particular interest. This review addresses classic approaches to the management of this disorder along with a discussion of newer pharmacologic agents that may become important therapeutic interventions in the clinical management of the osmotic myelinolysis syndrome.     

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 case report of central pontine and extrapontine myelinolysis which occurred during pregnancy and was accompanied by choreic movement

A 25-year-old female in the 17th week of pregnancy was diagnosed by MRI as having central pontine and extrapontine myelinolysis. Serial observations with MR showed gradual disappearance of the lesions in the pons and striatum. Improvement of the symptoms took place shortly before disappearance of the lesions on MRI pictures. The initial symptoms were consciousness disturbance, cranial nerve palsy and tetraparesis. Before the latter disappeared seven months after occurrence of the disease, all other symptoms gradually improved. They were followed by delayed appearance of choreic movements, which was still remaining one year after discharge. It is rare for a pregnant woman to be attacked by central pontine myelinolysis. Moreover, very few symptoms caused by such extrapontine lesions have so far been reported. Also, a review of the relevant literature by the authors found no other case showing choreic movements. This report is of an extremely rare case of central pontine and extrapontine myelinolysis which occurred during pregnancy and is accompanied by choreic movements.     

Delayed onset movement disorders as a complication of central pontine myelinolysis

This report describes a case of central pontine myelinolysis occurring after a rapid correction of profound hyponatremia. Delayed-onset generalized dystonia and choreoathetosis then appeared. A small pontine myelinolysis was demonstrated by magnetic resonance images, but striatal myelinolysis could not be established. Aspects of movement disorders associated with the osmotic demyelination syndrome are briefly reviewed and discussed.     

Central pontine and extrapontine myelinolysis: a report of 58 cases

In 58 cases with central pontine myelinolysis (CPM) and/or extrapontine myelinolysis, systematic examination of the central nervous system was performed. The demyelinating disease occurred in three subtypes: (1) CPM, in which the lesion was confined to the pons, (2) CPM combined with extrapontine myelinolysis and (3) exclusively extrapontine myelinolysis. Type (1) was found in 27 cases, (2) in 18 cases and (3) in 13 cases. Cerebellum and lateral geniculate body were the most frequently affected extrapontine regions. One case with an extreme extension of the lesions is described in detail. Extrapontine lesions seem to be more frequent and widespread than has been hitherto reported in the literature.     

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。     

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.     

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.