eMedicine Specialties > Neurology > Neurotoxicology

Central Pontine Myelinolysis

Christopher Luzzio, MD, Clinical Assistant Professor, Department of Neurology, University of Wisconsin at Madison
Contributor Information and Disclosures

Updated: Jan 16, 2007

Introduction

Background

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.

Contemporary physicians recognize that CPM occurs inconsistently as a complication of severe and prolonged hyponatremia, particularly when corrected too rapidly. Standard of care requires judicious treatment of electrolyte disturbances to reduce the incidence of osmotic myelinolysis.

Pathophysiology

CPM is concentrated, frequently symmetric, noninflammatory demyelination within the central basis pontis. In at least 10% of patients with CPM, 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.

Frequency

United States

The exact incidence of CPM is unknown. A study by Singh et al demonstrated that CPM 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.

Mortality/Morbidity

See Follow-up .

Race

No reports exist of CPM in African Americans.

Sex

CPM occurs more frequently in females than in males.

Clinical

History

A typical case of CPM can unfold as follows:

• 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.
• Brain MRI reveals intense symmetric demyelination in the brain stem pons.

Physical

• The most consistent examination findings are those of pseudobulbar palsy and spastic quadriplegia caused by demyelination of corticospinal and corticobulbar tracts within the pons.
• Delirium is extremely common.
• The volume of demyelination within the pons is variable. 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.
  • 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.
  • Lesions within the pons cause horizontal gaze paralysis.
  • Vertical ophthalmoparesis is caused by demyelination extending through the mid brain.
  • 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.

Causes

Conditions predisposing patients to CPM include alcoholism, liver disease, malnutrition, and hyponatremia.

• Risk factors for CPM 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 CPM. Thus, other less obvious risk factors probably exist.
• Patients with an acute episode of hyponatremia that is treated promptly are unlikely to develop CPM.
• CPM reportedly occurs occasionally in patients who are treated for hypernatremia.
• CPM may complicate liver transplantation surgery.
  • Consider CPM when confusion and/or weakness complicate the liver transplant patient's postoperative recovery.
  • The author provided consultation for a liver transplant patient who developed CPM and critical illness neuromyopathy. The typical exam findings for CPM 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 CPM.
• CPM also has occurred concurrently with Wilson disease and neoplasia.

References

• Alcohol (Ethanol) Related Neuropathy
• Brainstem Gliomas
• Cerebellar Hemorrhage
• Complex Partial Seizures
• Diffuse Sclerosis
• Intracranial Hemorrhage
• Lacunar Syndromes
• Leptomeningeal Carcinomatosis
• Multiple Sclerosis
• Subarachnoid Hemorrhage
• Uremic Encephalopathy