central pontine myelinolysis
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Central pontine myelinolysis is a neurological condition involving severe damage to the
myelin sheath Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be l ...
of
nerve cells A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
in the ''
pons The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of Va ...
'' (an area of the brainstem). It is predominately
iatrogenic Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. "Iatrogenic", ''Merriam-Webster.com'', Merriam-Webster, Inc., accessed 27 ...
(treatment-induced), and is characterized by acute paralysis,
dysphagia Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or liq ...
(difficulty swallowing),
dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectively ...
(difficulty speaking), and other neurological symptoms. Central pontine myelinolysis was first described as a disorder in 1959. The original paper described four cases with fatal outcomes, and the findings on autopsy. The disease was described as a disease of
alcoholics Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomina ...
and
malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
. 'Central pontine' indicated the site of the lesion and 'myelinolysis' was used to emphasise that myelin was affected. The authors intentionally avoided the term 'demyelination' to describe the condition, in order to differentiate this condition from multiple sclerosis and other neuroinflammatory disorders. Since this original description, demyelination in other areas of the central nervous system associated with osmotic stress has been described outside the pons (extrapontine). Osmotic demyelination syndrome is the term used for both central pontine myelinolysis and extrapontine myelinolysis. Central pontine myelinolysis, and osmotic demyelination syndrome, present most commonly as a complication of treatment of patients with profound
hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135  mmol/L (135  mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be a ...
(low
sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...
), which can result from a varied spectrum of conditions, based on different mechanisms. It occurs as a consequence of a rapid rise in serum
tonicity In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane-im ...
following treatment in individuals with chronic, severe hyponatremia who have made intracellular adaptations to the prevailing hypotonicity.


Signs and symptoms

Symptoms depend on the regions of the brain involved. Prior to its onset, patients may present with the neurological signs and symptoms of hyponatraemic encephalopathy such as nausea and vomiting, confusion, headache and seizures. These symptoms may resolve with normalisation of the serum sodium concentration. Three to five days later, a second phase of neurological manifestations occurs correlating with the onset of myelinolysis. Observable immediate precursors may include seizures, disturbed consciousness, gait changes, and decrease or cessation of respiratory function. The classical clinical presentation is the progressive development of spastic
quadriparesis Tetraplegia, also known as quadriplegia, is defined as the dysfunction or loss of motor and/or sensory function in the cervical area of the spinal cord. A loss of motor function can present as either weakness or paralysis leading to partial or t ...
,
pseudobulbar palsy Pseudobulbar palsy is a medical condition characterized by the inability to control facial movements (such as chewing and speaking) and caused by a variety of neurological disorders. Patients experience difficulty chewing and swallowing, have in ...
, and emotional lability (
pseudobulbar affect Pseudobulbar affect (PBA), or emotional incontinence, is a type of emotional disturbance characterized by uncontrollable episodes of crying, laughing, anger or other emotional displays. PBA occurs secondary to a neurologic disorder or brain i ...
), with other more variable neurological features associated with brainstem damage. These result from a rapid myelinolysis of the
corticobulbar In neuroanatomy, the corticobulbar (or corticonuclear) tract is a two-neuron white matter motor pathway connecting the motor cortex in the cerebral cortex to the medullary pyramids, which are part of the brainstem's medulla oblongata (also called ...
and
corticospinal The pyramidal tracts include both the corticobulbar tract and the corticospinal tract. These are aggregations of efferent nerve fibers from the upper motor neurons that travel from the cerebral cortex and terminate either in the brainstem (''co ...
tracts in the brainstem. In about ten per cent of people with central pontine myelinolysis, extrapontine myelinolysis is also found. In these cases symptoms of
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
may be generated.


Causes

The most common cause is overly-rapid correction of low blood sodium levels (
hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135  mmol/L (135  mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be a ...
). Apart from rapid correction of hyponatraemia, there are case reports of central pontine myelinolysis in association with hypokalaemia, anorexia nervosa when feeding is started, patients undergoing dialysis and burn victims. There is a case report of central pontine myelinolysis occurring in the context of refeeding syndrome, in the absence of hyponatremia. It has also been known to occur in patients suffering withdrawal symptoms of chronic
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
. In these instances, occurrence may be entirely unrelated to hyponatremia or rapid correction of hyponatremia. It could affect patients who take some prescription medicines that are able to cross the blood-brain barrier and cause abnormal thirst reception - in this scenario the central pontine myelinolysis is caused by
polydipsia Polydipsia is excessive thirst or excess drinking.Porth, C. M. (1990). ''Pathophysiology: Concepts of altered health states''. Philadelphia: J.B. Lippincott Company. The word derives from the Greek () "very thirsty", which is derived from (, "mu ...
leading to low blood sodium levels (hyponatremia). In
schizophrenic Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdr ...
patients with psychogenic polydipsia, inadequate thirst reception leads to excessive water intake, severely diluting serum sodium. With this excessive thirst combined with psychotic symptoms, brain damage such as central pontine myelinolysis may result from hyperosmolarity caused by excess intake of fluids, (
primary polydipsia Primary polydipsia and psychogenic polydipsia are forms of polydipsia characterised by excessive fluid intake in the absence of physiological stimuli to drink. Psychogenic polydipsia which is caused by psychiatric disorders, often schizophrenia, i ...
) although this is difficult to determine because such patients are often
institutionalised In sociology, institutionalisation (or institutionalization) is the process of embedding some conception (for example a belief, norm, social role, particular value or mode of behavior) within an organization, social system, or society as a who ...
and have a long history of mental health conditions. It has been observed following
hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
. Central pontine myelinolysis may also occur in patients prone to hyponatremia affected by: * Severe liver disease (e.g.,
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
) * Liver transplant *
Alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
*
Hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
* People with serum sodium <105 mEq/L * Severe burns *
Malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues ...
*
Anorexia nervosa Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gr ...
* Severe electrolyte disorders *
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
* hyperemesis gravidarum * Hyponatremia due to
peritoneal dialysis Peritoneal dialysis (PD) is a type of dialysis which uses the peritoneum in a person's abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. It is used to remove excess fluid, correct electrolyte pro ...
*
Wernicke encephalopathy Wernicke encephalopathy (WE), also Wernicke's encephalopathy, or wet brain is the presence of neurological symptoms caused by biochemical lesions of the central nervous system after exhaustion of B-vitamin reserves, in particular thiamine (vit ...


Pathophysiology

The currently accepted theory states that the brain cells adjust their osmolarities by changing levels of certain osmolytes like inositol,
betaine A betaine () in chemistry is any neutral chemical compound with a positively charged cationic functional group, such as a quaternary ammonium or phosphonium cation (generally: onium ions) that bears no hydrogen atom and with a negatively charge ...
, and
glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...
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 central pontine myelinolysis.


Diagnosis

It can be diagnosed clinically in the appropriate context, but may be difficult to confirm radiologically using conventional imaging techniques. Changes are more prominent on MRI than on CT, but often take days or weeks after acute symptom onset to develop. Imaging by
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
typically demonstrates areas of hyperintensity on T2-weighted images.


Treatment

To minimise the risk of this condition developing 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 mEq/L/48hrs; thus avoiding demyelination. No large clinical trials have been performed to examine the efficacy of therapeutic re-lowering of serum sodium, or other interventions sometimes advocated such as steroids or plasma exchange. Alcoholic patients should receive vitamin supplementation and a formal evaluation of their nutritional status. Once osmotic demyelination has begun, there is no cure or specific treatment. Care is mainly supportive. Alcoholics are usually given vitamins to correct for other deficiencies. The favourable factors contributing to the good outcome in central pontine myelinolysis without hyponatremia were: concurrent treatment of all electrolyte disturbances, early intensive care unit involvement at the advent of respiratory complications, early introduction of feeding including thiamine supplements with close monitoring of the electrolyte changes and input. Research has led to improved outcomes. Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia. Further study is required before using inositol in humans for this purpose.


Prognosis

Though traditionally the prognosis is considered poor, a good functional recovery is possible. All patients at risk of developing refeeding syndrome should have their electrolytes closely monitored, including sodium, potassium, magnesium, glucose and phosphate. Recent data indicate that the prognosis of critically ill patients may even be better than what is generally considered, despite severe initial clinical manifestations and a tendency by the intensivists to underestimate a possible favorable evolution. 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
ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
to signs of severe brain damage, such as spastic quadriparesis and
locked-in syndrome Locked-in syndrome (LIS), also known as pseudocoma, is a condition in which a patient is aware but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for vertical eye movements and bli ...
. Some improvements may be seen over the course of the first several months after the condition stabilizes. The degree of recovery depends on the extent of the original axonal damage.


References


External links


MedPix
Images of Osmotic Myelinolysis {{Demyelinating diseases of CNS Demyelinating diseases of CNS Electrolyte disturbances