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. 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]
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]

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]

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.

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.

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

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.

Diagnostic Tests
Cerebral spinal fluid (CSF) probably is not necessary when the etiology and
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 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.

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.

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]

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]

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.

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.

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

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.

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 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.

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.