Central pontine myelinolysis
Encyclopedia
Central pontine myelinolysis is 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. The term "osmotic demyelination syndrome" is similar to "central pontine myelinolysis", but also includes areas outside the pons.
Central pontine myelinolysis is 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 hyponatraemia who have made intracellular adaptations to the prevailing hypotonicity. Hyponatremia should be corrected at a rate of no more than 8-10 mmol/L of sodium per day to prevent central pontine myelinolysis.
, betaine, and glutamine
. In hyponatremia the levels of these osmolytes fall, preventing entry of free-water into cells. The reverse is true for hypernatremia. So rapid correction of sodium in hyponatremia would cause the extracellular fluid to be relatively hypertonic. Free water would then move out of the cells. This leads to a central pontine myelinolysis, manifesting as the paralysis.
The demyelination of the axon
s (nerve fibers in the brain) damages them.
In the context of chronic
low plasma sodium, the brain's cells (neurons and glia) adapt by taking in a small amount of water; the net effect is to move water out of the interstitium and equilibrate (or nearly so) the intracellular and extracellular tonicities. The chronic hyponatremia is thus compensated.
With correction of the hyponatremia with intravenous fluids, the intra- and extra-cellular tonicities are again changed, this time in the opposite direction. With the use of intravenous hypertonic saline, the correction can be too quick, not allowing enough time for the brain's cells to adjust to the new tonicity. With a rise in extracellular tonicity, the cells compensate by losing a small amount of water. This loss will continue until the intra- and extra-cellular tonicities are equal. If hypertonic therapy continues or is too rapid, the extracellular tonicity will continue to drive water out of the brain's cells, leading to cellular dysfunction and the condition of central pontine myelinolysis.
Rapid correction of hypernatremia causes water to move into cells, leading to multiple cerebral hemorrhages, equally catastrophic as osmotic demyelination.
).
It has been observed following hematopoietic stem cell transplantation.
patients can be affected by:
It can be associated with hyperemesis gravidarum
.
Imaging by MRI
demonstrates an area of high signal return on T2 weighted images.
, 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.
Alcoholic patients should receive vitamin supplementation and a formal evaluation of their nutritional status.
Once demyelination has begun, there is no 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. Animal studies suggest inositol
reduces the severity of osmotic demyelination syndrome if given prior to rapid correction of chronic hyponatraemia. Further study is required prior to its application in humans for this indication.
to signs of severe brain damage, such as spastic quadriparesis and locked-in syndrome
. 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.
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
in the brainstem, more precisely in the area termed the pons
Pons
The pons is a structure located on the brain stem, named after the Latin word for "bridge" or the 16th-century Italian anatomist and surgeon Costanzo Varolio . It is superior to the medulla oblongata, inferior to the midbrain, and ventral to the cerebellum. In humans and other bipeds this means it...
, predominately of iatrogenic
Iatrogenesis
Iatrogenesis, or an iatrogenic artifact is an inadvertent adverse effect or complication resulting from medical treatment or advice, including that of psychologists, therapists, pharmacists, nurses, physicians and dentists...
etiology. It is characterized by acute paralysis, dysphagia
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
(difficulty swallowing), and dysarthria
Dysarthria
Dysarthria is a motor speech disorder resulting from neurological injury of the motor component of the motor-speech system and is characterized by poor articulation of phonemes...
(difficulty speaking), and other neurological symptoms.
It can also occur outside the pons. The term "osmotic demyelination syndrome" is similar to "central pontine myelinolysis", but also includes areas outside the pons.
Central pontine myelinolysis is a complication of treatment of patients with profound, life-threatening hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
(low sodium). It occurs as a consequence of a rapid rise in serum tonicity following treatment in individuals with chronic, severe hyponatraemia who have made intracellular adaptations to the prevailing hypotonicity. Hyponatremia should be corrected at a rate of no more than 8-10 mmol/L of sodium per day to prevent central pontine myelinolysis.
Pathophysiology
The currently accepted theory states that the brain cells adjust their osmolarities by changing levels of certain osmolytes like inositolInositol
Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol...
, betaine, and glutamine
Glutamine
Glutamine is one of the 20 amino acids encoded by the standard genetic code. It is not recognized as an essential amino acid but may become conditionally essential in certain situations, including intensive athletic training or certain gastrointestinal disorders...
. In hyponatremia the levels of these osmolytes fall, preventing entry of free-water into cells. The reverse is true for hypernatremia. So rapid correction of sodium in hyponatremia would cause the extracellular fluid to be relatively hypertonic. Free water would then move out of the cells. This leads to a central pontine myelinolysis, manifesting as the paralysis.
The demyelination of the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s (nerve fibers in the brain) damages them.
In the context of chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
low plasma sodium, the brain's cells (neurons and glia) adapt by taking in a small amount of water; the net effect is to move water out of the interstitium and equilibrate (or nearly so) the intracellular and extracellular tonicities. The chronic hyponatremia is thus compensated.
With correction of the hyponatremia with intravenous fluids, the intra- and extra-cellular tonicities are again changed, this time in the opposite direction. With the use of intravenous hypertonic saline, the correction can be too quick, not allowing enough time for the brain's cells to adjust to the new tonicity. With a rise in extracellular tonicity, the cells compensate by losing a small amount of water. This loss will continue until the intra- and extra-cellular tonicities are equal. If hypertonic therapy continues or is too rapid, the extracellular tonicity will continue to drive water out of the brain's cells, leading to cellular dysfunction and the condition of central pontine myelinolysis.
Rapid correction of hypernatremia causes water to move into cells, leading to multiple cerebral hemorrhages, equally catastrophic as osmotic demyelination.
Causes
The most common cause is the rapid correction of low blood sodium levels (hyponatremiaHyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
).
It has been observed following hematopoietic stem cell transplantation.
patients can be affected by:
- underlying severe liver disease
- liver transplant patients
- severe burns
- malnutrition
- anorexia
- severe electrolyte disorders
- AIDS
It can be associated with hyperemesis gravidarum
Hyperemesis gravidarum
Hyperemesis gravidarum is a severe form of morning sickness, with "unrelenting, excessive pregnancy-related nausea and/or vomiting that prevents adequate intake of food and fluids." Hyperemesis is considered a rare complication of pregnancy but, because nausea and vomiting during pregnancy exist...
.
Diagnosis
It can be difficult to identify using conventional imaging techniques.Imaging by MRI
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
demonstrates an area of high signal return on T2 weighted images.
Symptoms
Frequently observed symptoms in this disorder are acute para- or quadraparesis, dysphagiaDysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
, dysarthria
Dysarthria
Dysarthria is a motor speech disorder resulting from neurological injury of the motor component of the motor-speech system and is characterized by poor articulation of phonemes...
, diplopia
Diplopia
Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...
, loss of consciousness
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, and other neurological symptoms associated with brainstem damage. The patient may experience locked-in syndrome
Locked-In syndrome
Locked-in syndrome is a condition in which a patient is aware and awake but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for the eyes. Total locked-in syndrome is a version of locked-in syndrome where the eyes are paralyzed as...
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.
Prevention and treatment
To prevent CPM via the most common cause, overly rapid correction of hyponatremia, the hyponatremia should be corrected at a rate not in excess of 10 mmol/L/24hr or 0.5 mEq/L/Hr; thus diligently avoiding hypernatremia. 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.
Once demyelination has begun, there is no specific treatment. Care is supportive, with the goal of preventing complications like aspiration pneumonia
Aspiration pneumonia
Aspiration pneumonia is bronchopneumonia that develops due to the entrance of foreign materials into the bronchial tree, usually oral or gastric contents...
or deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
. Alcoholics are usually given vitamins to correct for other deficiencies.
Research has led to improved outcomes. Animal studies suggest inositol
Inositol
Inositol or cyclohexane-1,2,3,4,5,6-hexol is a chemical compound with formula 6126 or 6, a sixfold alcohol of cyclohexane. It exists in nine possible stereoisomers, of which the most prominent form, widely occurring in nature, is cis-1,2,3,5-trans-4,6-cyclohexanehexol, or myo-inositol...
reduces the severity of osmotic demyelination syndrome if given prior to rapid correction of chronic hyponatraemia. Further study is required prior to its application in humans for this indication.
Prognosis
The prognosis is overall poor. 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. Permanent disabilities range from minor tremors and ataxiaAtaxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
to signs of severe brain damage, such as spastic quadriparesis and locked-in syndrome
Locked-In syndrome
Locked-in syndrome is a condition in which a patient is aware and awake but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for the eyes. Total locked-in syndrome is a version of locked-in syndrome where the eyes are paralyzed as...
. 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.
External links
- MedPix Images of Osmotic Myelinolysis