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.     

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.     

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.     

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.     

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 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.     

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.     

Changes of auditory brainstem responses in electrolyte-induced myelinolysis in rats. Role of hyponatremia and hypernatremia

Electrolyte-induced myelinolysis was produced in rats to evaluate electrophysiological derangement in the brainstem. Auditory brainstem responses (ABRs) were used to assess the brainstem function. Rats treated with hypertonic saline for 2 days had normal interpeak latencies in ABRs. Rats treated with vasopressin-induced hyponatremia alone and those with hypertonic saline after 3 days of hyponatremia had significantly prolonged interpeak latencies between waves II-III and III-IV in ABRs. These prolongations indicate electrophysiological derangement of the upper pons and mesencephalon in hyponatremic rats as well as in rats with hyponatremia followed by hypernatremic myelinolysis. In view of these data, hyponatremia may be a prerequisite for electrolyte-induced myelinolysis and electrolyte derangements such as hyponatremia, and rapidly correcting hypernatremia may be the cause of electrolyte-induced myelinolysis in rats.     

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.     

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.     

Chronicity of hyponatremia as a factor in experimental myelinolysis

A recent analysis of hyponatremic patients disclosed that those who were chronically hyponatremic prior to rapid correction subsequently developed central pontine myelinolysis. To test the view that chronicity of hyponatremia is a factor in myelinolysis, we studied a group of rats that were hyponatremic for 1 day and compared it with another group of animals maintained in a hyponatremic state for 3 days prior to the administration of hypertonic saline solution. The 3-day hyponatremic rats developed more numerous and more severe demyelinative lesions than the 1-day rats. The findings support the view that duration of hyponatremia is a factor in myelinolysis and that the electrolyte disturbance of chronically hyponatremic patients should be corrected cautiously and relatively slowly.     

Behavioral manifestations of central pontine myelinolysis

A young woman with a clinical history and magnetic resonance imaging scan consistent with central pontine myelinolysis came to medical attention because of prominent behavioral symptoms. Marked clinical recovery occurred despite persistent radiologic abnormalities. Rapid correction of hyponatremia was probably related to the development of the central pontine myelinolysis. A normal computed tomographic scan and the absence of brain-stem signs delayed accurate diagnosis.     

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 rapid correction of hyponatremia

Central pontine and extrapontine myelinolysis was experimentally produced in dogs by the rapid correction of severe, sustained, vasopressin-induced hyponatremia. Hyponatremia alone or slowly corrected hyponatremia did not produce the disease. Affected dogs showed rigid quadriparesis. The central pons, lateral aspects of the thalamus and adjacent internal capsules, deep layers of cerebral cortex and subjacent white matter, cerebellum, and other regions were symmetrically involved. Myelin and oligodendroglia were affected out of proportion to axons and neurons. Thus, the clinical features, the distribution of the lesions, and their histological features closely resemble the human disease. These experiments document an electrolyte manipulation that can cause permanent neuropathological lesions. Taken with the available clinical data on human patients, the experimental results indicate that human myelinolysis may be due to a rapid increase in serum sodium from previously low levels, and that rapid normalization of severe, sustained hyponatremia should therefore be avoided.     

Hemiparesis apparently due to central pontine myelinolysis following hyponatremia

A 63-year-old woman was in an acute confusional state accompanied by rapidly progressive left hemiparesis, dysphagia, and dysarthria two weeks after an episode of diuretic-induced hyponatremia. High-resolution computed tomographic scanning disclosed a circumferential hypodense pontine lesion compatible with the diagnosis of central pontine myelinolysis. Although the patient improved clinically within six weeks, the computed tomographic abnormalities remained unchanged.     

A case of central pontine and extra-pontine myelinolysis demonstrated by magnetic resonance imaging]

A 74-year-old woman was admitted because of disturbed consciousness due to iatrogenic hyponatremia. At admission, her serum level of sodium was 88 mEq/l. The hyponatremia was carefully corrected with physiologic saline for three days at a rate of 0.75 mEq/h until the serum sodium concentration of 135 mEq/l was achieved. Her neurologic state gradually improved to respond to painful stimuli with her left hand during the first week of treatment, but further improvement was not noted after that. On the 16th hospital day, seizure developed on her face and left upper extremity. Although abnormal lesions were not detected by MRI of the brain at admission, those performed on the 15th hospital day revealed multiple uncommon lesions with Tl and Gd enhanced images. On Tl images areas of low signal intensity were found in the central pons and left putamen, which were more clearly demonstrated by Gd enhanced MRI images. These lesions were considered to be consistent with central pontine and extra-pontine myelinolysis (CPEM). In addition, a part of the right temporal cortex was enhanced clearly by Gd-DTPA, which was also thought to be an extra-pontine myelinolysis. These lesions were responsible for the development of neurological signs due to CPEM. To our knowledge, this is the first case in which a lesion in the cerebral cortex was revealed as an extra-pontine myelinolysis by Gd enhanced MRI images. Gd enhanced MRI is useful for detecting the extra-pontine myelinolysis as well as central pontine myelinolysis.     

Coping strategies,cognitive impairment,psychological variables and their relationship with quality of life in multiple sclerosis

We report clinical, radiological and pathological findings in a patient with central pontine and extrapontine myelinolysis. The patient was a 61-year-old woman who had a radical mastectomy for breast cancer. Based on clinical evidence, acute hyponatremia had set in only a few days before onset of symptoms. The patient’s disease progressed in two stages and became more severe during slow hyponatremia correction after 9 days from onset. Diffusion MRI provided early evidence of neurological lesions. In spite of a therapeutic attempt, the patient died unexpectedly 18 days after onset of her neurological disease due to massive pulmonary embolism. Histologically, our findings confirmed that the major features of central pontine myelinolysis in the acute stage are demyelination, the presence of large amounts of macrophages with no lymphocytic inflammatory reaction, and moderate astrocytosis. It is interesting to note that a monotypic immunological reaction persisted 19 days after radiological demonstration of parenchymal alterations.     

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.     

"Man-in-the-barrel" syndrome as delayed manifestation of extrapontine and central pontine myelinolysis: beneficial effect of intravenous immunoglobulin

"Man-in-the-barrel" syndrome has been rarely described following osmotic myelinolysis. We report a case of a 45-year-old woman admitted with septicemia and severe hyponatremia. She presented with a "man-in-the-barrel" syndrome which developed more than 10 days after rapid correction of the hyponatremia. There was radiological evidence of central pontine and extrapontine myelinolysis. Three days after completing a course of intravenous immunoglobulin therapy (0.4 g/kg body weight/day for 5 days) there was considerable improvement (Expanded Disability Status Scale score improved 30%). This case, reported for its peculiar mode of development, unusual presentation and challenging therapeutic response to intravenous immunoglobulin, highlights the enigmatic and unpredictable aspects of osmotic myelinolysis.     

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

We describe a patient with severe hyponatremia (serum sodium 94 mmol/L) who developed encephalopathy and decorticate posturing after a 29 mmol/L rise in serum sodium concentration during the first 24 hours of correction. High-resolution computed tomography of the pons was normal during the first, second, and twelfth weeks of the illness. Subsequent magnetic resonance imaging revealed a pontine lesion consistent with central pontine myelinolysis.