Central Pontine Myelinolysis CPM

Central pontine myelinolysis (CPM), also known as Osmotic demyelination syndrome or Central pontine demyelination, is a neurological disease caused by severe damage of the myelin sheath of nerve cells in the brainstem, more precisely in the area termed the pons, predominately of iatrogenic etiology. It is characterized by acute paralysis, dysphagia (difficulty swallowing), and dysarthria (difficulty speaking), and other neurological symptoms.

It can also occur outside the pons.[1] The term "osmotic demyelination syndrome" is similar to "central pontine myelinolysis", but also includes areas outside the pons.[2]

Central pontine myelinolysis presents most commonly as a complication of treatment of patients with profound, life-threatening hyponatremia (low sodium). It occurs as a consequence of a rapid rise in serum tonicity following treatment in individuals with chronic, severe hyponatremia who have made intracellular adaptations to the prevailing hypotonicity.[3] Hyponatremia should be corrected at a rate of no more than 8-12 mmol/L of sodium per day to prevent central pontine myelinolysis.[3]

Although less common, it may also present in patients with a history of chronic alcoholism or other conditions related to decreased liver function. In these cases, the condition is often unrelated to correction of sodium or electrolyte imbalance.

Pathophysiology 

The currently accepted theory states that the brain cells adjust their osmolarities by changing levels of certain osmolytes like inositol, betaine, and glutamine in response to varying serum osmolality. In the context of chronic low plasma sodium (hyponatremia), the brain compensates by decreasing the levels of these osmolytes within the cells, so that they can remain relatively isotonic with their surroundings and not absorb too much fluid. The reverse is true in hypernatremia, in which the cells increase their intracellular osmolytes so as not to lose too much fluid to the extracellular space.

With correction of the hyponatremia with intravenous fluids, the extracellular tonicity increases, followed by an increase in intracellular tonicity. When the correction is too rapid, not enough time is allowed for the brain's cells to adjust to the new tonicity, namely by increasing the intracellular osmoles mentioned earlier. If the serum sodium levels rise too rapidly, the increased extracellular tonicity will continue to drive water out of the brain's cells. This can lead to cellular dysfunction and the condition of central pontine myelinolysis, where the myelin sheath surrounding the nerve axons becomes damaged in the part of the brain called the pons.,[4][5]

Causes 

Loss of myelinated fibers at the basis pontis in the brainstem (Luxol-Fast blue stain)

The most common cause is the too rapid correction of low blood sodium levels (hyponatremia).[6]

It has also been known to occur in patients suffering withdrawal symptoms of chronic alcoholism.[7] In these instances, occurrence may be entirely unrelated to hyponatremia or rapid correction of hyponatremia.

It has been observed following hematopoietic stem cell transplantation.[8]

CPM may also occur in patients affected by

severe liver disease

liver transplant[9][10][11]

alcoholism

severe burns[12][13]

malnutrition

anorexia[14][15][16]

severe electrolyte disorders

AIDS

hyperemesis gravidarum[17][18]

hyponatremia due to Peritoneal Dialysis

Wernicke encephalopathy[19]

Diagnosis 

It can be difficult to identify using conventional imaging techniques. It presents more prominently on MRI than on CT, often taking several weeks after acute onset of symptoms before it becomes identifiable. Imaging by MRI demonstrates an area of high signal return on T2 weighted images.

Symptoms 

T2 weighted magnetic resonance scan image showing bilaterally symmetrical hyperintensities in Caudate nucleus (small, thin arrow), Putamen (long arrow), with sparing of Globus Pallidus (broad arrow), suggestive of Extrapontine myelinolysis.

Clinical presentation of CPM is heterogeneous and depend on the regions of the brain involved. Observable immediate precursors may include seizures, disturbed consciousness, gait changes, and decrease or cessation of respiratory function.[20][21]

Frequently observed symptoms in this disorder are acute para- or quadraparesis, dysphagia, dysarthria, diplopia, loss of consciousness, and other neurological symptoms associated with brainstem damage. The patient may experience locked-in syndrome where cognitive function is intact, but all muscles are paralyzed with the exception of eye blinking. These result from a rapid myelinolysis of the corticobulbar and corticospinal tracts in the brainstem.[22]

Prevention and treatment 

To prevent CPM from its most common cause, overly rapid reversal of hyponatremia, the hyponatremia should be corrected at a rate not exceeding 10 mmol/L/24 h or 0.5 mEq/L/h; or 18 m/Eq/L/48hrs; thus avoiding hypernatremia.[3] Details concerning the etiology and correction of electrolyte disorders are discussed extensively in general medicine texts. Alcoholic patients should receive vitamin supplementation and a formal evaluation of their nutritional status.[23][24]

Once demyelination of the pons has begun, there is no cure or specific treatment. Care is supportive, with the goal of preventing complications like aspiration pneumonia or deep vein thrombosis. Alcoholics are usually given vitamins to correct for other deficiencies.

Research has led to improved outcomes.[25] Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia.[26] Further study is required before using inositol in humans for this purpose.

Prognosis 

The prognosis is overall poor. However, recent data indicate that the prognosis of critically ill patients may even be better than what is generally considered,[27] despite severe initial clinical manifestations and a tendency by the intensivists to underestimate a possible favorable evolution.[28] While some patients die, most survive and of the survivors, approximately one-third recover; one-third are disabled but are able to live independently; one-third are severely disabled.[29] Permanent disabilities range from minor tremors and ataxia to signs of severe brain damage, such as spastic quadriparesis and locked-in syndrome.[30] Some improvements may be seen over the course of the first several months after the condition stabilizes.

The extent of recovery depends on how many axons were damaged.[4]

References 

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