Central Pontine Myelinolysis

Updated: Nov 17, 2015
  • Author: Christopher Luzzio, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Overview

Overview

Adams et al described central pontine myelinolysis (CPM) as a unique clinical entity. They published their findings in 1958, observing that patients who suffered from alcoholism or malnutrition developed spastic quadriplegia, pseudobulbar palsy, and varying degrees of encephalopathy or coma from acute, noninflammatory demyelination that centered within the basis pontis. [1]

Physicians currently recognize that central pontine myelinolysis occurs inconsistently as a complication of severe and prolonged hyponatremia, particularly when corrected too rapidly. [2] Standard of care requires judicious treatment of electrolyte disturbances to reduce the incidence of osmotic myelinolysis. [3]

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Pathophysiology

Central pontine myelinolysis is a concentrated, frequently symmetric, noninflammatory demyelination within the central basis pontis. In at least 10% of patients with central pontine myelinolysis, demyelination also occurs in extrapontine regions, including the mid brain, thalamus, basal nuclei, and cerebellum. The exact mechanism that strips the myelin sheath is unknown.

One theory proposes that in regions of compact interdigitation of white and gray matter, cellular edema, which is caused by fluctuating osmotic forces, results in compression of fiber tracts and induces demyelination. Prolonged hyponatremia followed by rapid sodium correction results in edema. During the period of hyponatremia, the concentration of intracellular charged protein moieties is altered; reversal cannot parallel a rapid correction of electrolyte status. The term osmotic myelinolysis is more appropriate than central pontine myelinolysis for demyelination occurring in extrapontine regions after the correction of hyponatremia. [4, 5, 6, 7]

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Causes

Conditions predisposing patients to central pontine myelinolysis include alcoholism, liver disease, malnutrition, and hyponatremia.

Risk factors for central pontine myelinolysis in the hyponatremic patient include the following:

  • Serum sodium of less than 120 mEq/L for more than 48 hours
  • Aggressive IV fluid therapy with hypertonic saline solutions
  • Development of hypernatremia during treatment

Many patients who have hyponatremia that is corrected rapidly do not develop central pontine myelinolysis. Thus, other less obvious risk factors probably exist. Central pontine myelinolysis reportedly occurs occasionally in patients who are treated for hypernatremia.

Central pontine myelinolysis may complicate liver transplantation surgery. [8] Consider central pontine myelinolysis when confusion and/or weakness complicate the liver transplant patient's postoperative recovery. The author provided consultation for a liver transplant patient who developed central pontine myelinolysis and critical illness neuromyopathy. The typical exam findings for central pontine myelinolysis were masked by peripheral nerve and muscle disease. MRI studies provided conclusive evidence for brain stem demyelination.

Burn patients with a prolonged period of serum hyperosmolality are prone to developing central pontine myelinolysis. Central pontine myelinolysis also has occurred concurrently with Wilson disease and neoplasia.

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Epidemiology

The exact incidence of central pontine myelinolysis is unknown. A study by Singh et al demonstrated that central pontine myelinolysis was present in 29% of postmortem examinations of liver transplant patients. Two thirds of these patients had serum sodium fluctuations of only ± 15-20 mEq/L. [9] Central pontine myelinolysis occurs more frequently in females than in males.

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Prognosis

Death is common. Maximum recovery from central pontine myelinolysis may require several months. Chronic neurologic deficits range from locked-in syndrome to spastic quadriparesis. Patients with extrapontine lesions may exhibit tremor and ataxia.

Possible complications include those associated with severe central nervous system injury and reduced activity, such as the following:

  • Ventilator dependency
  • Aspiration pneumonia
  • Venous thrombosis
  • Pulmonary embolism
  • Contractures
  • Muscle wasting
  • Decubitus ulcers
  • Urinary tract infections
  • Depression
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History and Physical Examination

Severe hyponatremia is diagnosed in a person who presents to the emergency department with delirium. Electrolyte disturbances frequently cause encephalopathy. IV fluid therapy is administered, and serum sodium is normal by the next day. The patient's mental status improves, and he or she is more alert, but this is followed by neurologic deterioration 48-72 hours later.

Key features of the neurologic exam include confusion, horizontal gaze paralysis, and spastic quadriplegia. Increased limb tone, limb weakness, hyperactive reflexes, and Babinski sign are typical features of spastic quadriplegia or lesions that involve upper motor neurons or the corticospinal tracts. Brain MRI reveals intense symmetric demyelination in the brain stem pons. [10, 11]

The most consistent examination findings are those of pseudobulbar palsy and spastic quadriplegia caused by demyelination of corticospinal and corticobulbar tracts within the pons. The volume of demyelination within the pons is variable. [12] The loss of myelin can occur in adjacent brainstem areas and in more distal supratentorial locations. Thus, a diverse spectrum of examination findings and long-term disabilities are found.

Pseudobulbar palsy is characterized by head and neck weakness, dysphagia, and dysarthria. Lesions within the pons cause horizontal gaze paralysis. Vertical ophthalmoparesis is caused by demyelination extending through the mid brain.

Delirium is extremely common. Coma or delirium results from lesions in the pontine tegmentum and/or thalamus. Abnormalities in sensory modalities usually are not observed.

A large basis pontis lesion may cause a locked-in syndrome, which includes paralysis of lower cranial nerves and limb musculature. Vertical eye movements, blinking, breathing, and alertness may remain intact in these patients.

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Diagnostic Tests

Cerebral spinal fluid (CSF) probably is not necessary when the etiology and diagnosis are obvious. CSF studies may demonstrate increased opening pressure, elevated protein, or mononuclear pleocytosis.

MRI is the imaging modality of choice (see the image below). According to one study, serial brain imaging is of value because a substantial proportion of patients have normal findings on initial MRI. [13] Typically, T2-weighted MRI images demonstrate hyperintense or bright areas where demyelination has occurred and has been caused by relatively increased water content in those regions. MRI or CT imaging of the brain stem may not reveal an obvious anatomic disturbance. A thorough neurologic exam therefore is indispensable. [14]

T2-weighted MRI scan of the brain demonstrating pa T2-weighted MRI scan of the brain demonstrating patchy areas of signal change within the pons that are consistent with demyelination or central pontine myelinolysis. Courtesy of Dr Andrew Waclawik, Department of Neurology, University of Wisconsin, Madison.

Electroencephalography in central pontine myelinolysis may demonstrate diffuse bihemispheric slowing. Brainstem-evoked potentials may reveal abnormalities when neuroimaging is unrevealing.

Relative preservation of axons and surrounding neurons within areas of demyelination and an associated reduction in oligodendroglia is present.

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Treatment & Management

Treatment is supportive only. Correction rate is controversial (for more information on treatment, see the Medscape Reference article on hyponatremia). Diligently avoid hypernatremia. It is advised to study details concerning the etiology and correction of electrolyte disorders.

Patients with alcoholism should receive vitamin supplementation. Formally evaluate their nutritional status.

Once medically stable, the patient should be evaluated by a neurorehabilitation specialist and, if appropriate, transferred for further inpatient recovery-oriented therapy.

Consultations

Patients who survive central pontine myelinolysis likely require extensive and prolonged neurorehabilitation. Incorporate occupational, physical, speech, and language therapists early in the care of such patients. Swallowing studies are necessary to evaluate for dysphagia and determine the risk for aspiration pneumonia.

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