What is Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)?
Central pontine myelinolysis (CPM) is a part of a condition known as osmotic demyelination syndrome (ODS). This condition involves damage to certain areas of the brain, specifically white matter regions in a part called the pons. This damage often happens after sudden correction of metabolic imbalances like low sodium in the body. In 1959, Adams and his team first identified CPM in a report of four patients who had trouble speaking/swallowing and loss of movement in all limbs. These first cases were associated with alcohol abuse and undernutrition. However, in the 1970s, it was discovered that CPM also had a link with rapidly correcting sodium levels. Since then, CPM has been reported in situations such as severe burns, liver transplantations, extreme cases of eating disorders, extreme morning sickness, and very high sugar levels. Symptoms of CPM typically start appearing a few days after quickly correcting low sodium levels. These symptoms can vary and can be as mild as confusion or as severe as a coma, potentially leading to death.
What Causes Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)?
Autopsies conducted by Adams and his team initially identified lesions of CPM as being symmetrical and consistently found in the same location. This led them to believe that it might be linked to a toxin or metabolic disorder. Moving ahead to 1976, Tomlinson reported the cases of two middle-aged women. These women didn’t have a history of alcohol addiction or malnutrition, but they had low sodium levels in their bodies.
When their sodium levels were corrected too quickly, they experienced sudden changes in their consciousness level and developed problems with muscle weakness and swallowing. Following these cases, Laureno and Kleinschmidt-DeMasters used animal experiments to confirm that the speed of sodium correction was indeed the problem.
Risk Factors and Frequency for Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)
The number of people affected by Central Pontine Myelinolysis (CPM) is unclear because it often goes undiagnosed. Research has suggested that 2.5% of patients admitted to intensive care units might have a related condition called osmotic demyelination syndrome. It is also known that about a quarter of patients with severe low sodium levels can develop neurological problems after their sodium level is corrected too quickly. This risk of complications can increase if the patient’s low sodium levels have been a long-term problem and are corrected rapidly within the first 48 hours.
The likelihood of getting CPM was also studied based on different factors such as age, sex, alcohol use disorder, and initial symptoms. However, none of these factors were found to significantly increase the chances of developing neurological issues. On the other hand, the incidence of CPM has been observed to increase in patients who have undergone a type of liver transplant known as ‘orthotopic liver transplantation’, usually within ten days post-transplantation.
Signs and Symptoms of Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)
Central pontine myelinolysis (CPM) is a condition that is more likely to affect people with certain health histories. Those at a higher risk include people who have experienced malnutrition, alcohol use disorder, chronic liver disease, and a condition in pregnancy known as hyperemesis gravidarum. It’s also more common in people who have a history of rapid sodium correction (greater than 0.5-1.0 mEq/L per hour). It’s particularly likely in people with chronic low sodium levels (for more than 48 hours), or those with severe low sodium levels (sodium levels less than 120 mEq/L).
The symptoms of CPM usually appear between 1 to 14 days after the correction of electrolyte levels. The symptoms indicate damage to the upper motor neurons and typically show up in two phases. Initially, people might have an episode of sudden brain dysfunction (acute encephalopathy) and seizures, which often improve back to normal as sodium levels are restored. However, these are often followed by a decline in health 3-5 days later.
- Difficulty swallowing (dysphagia)
- Difficulty speaking (dysarthria)
- Weakness in all four limbs (spastic quadriparesis)
- Weakness of the muscles that control swallowing and speech (pseudobulbar paralysis)
- Loss of full control of bodily movements (ataxia)
- Sluggishness, lack of energy (lethargy)
- Tremors
- Dizziness
- Abnormality of motor function (catatonia)
- In severe cases, being conscious but unable to move or communicate (locked-in-syndrome) and coma
Testing for Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)
When a doctor is trying to diagnose Central Pontine Myelinolysis (CPM), they will evaluate the patient’s clinical history and pay particular attention to laboratory tests, such as the rate of sodium correction. Imaging tests, like MRI, aren’t always necessary, but can be used to confirm the diagnosis if there’s any doubt.
An MRI can reveal some characteristic signs suggestive of CPM. For example, within the first 24 hours from the start of symptoms, the scan might show a restriction of diffusion, i.e., limited movement of water molecules, in the central part of the pons while sparing the outer part. As time progresses, these MRI images may display a “bat-wing” pattern in the central pons.
However, these telling signs on MRI might not be visible until up to two weeks after the onset of symptoms. So, even if the initial imaging tests come back negative, it doesn’t completely rule out CPM. If the doctor still suspects CPM based on clinical symptoms, they would recommend repeating the MRI after two weeks to confirm the diagnosis.
Treatment Options for Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)
Treatment for central pontine myelinolysis largely focuses on prevention. Research has helped set guidelines for how quickly sodium levels should be corrected in the body. The current advice suggests increasing sodium levels no more than 8-12 mEq/L each day. However, if someone’s sodium levels have been low for more than 48 hours or if it’s unknown how long they’ve been low, the increase should be slower, at 6-8 mEq/L per day.
In cases of serious low sodium (sodium <120 mEq/L) where neurological symptoms are present, a solution with 3% saline should be administered. If there are no neurological symptoms, the focus should be on slowly increasing sodium levels using intravenous fluids, again not exceeding 8-12 mEq/L daily. It's crucial to check sodium levels every 4-6 hours during this process. If sodium levels are very out of balance, checks should happen hourly.
Based on studies, the drug desmopressin has been tried and found effective for avoiding and reversing an overcorrection of low sodium. The studies even looked at using desmopressin as a preventive measure. They found that combining desmopressin with hypertonic saline resulted in fewer cases of sodium overcorrection. Typically, dosages of 1 to 2 mcg of desmopressin are administered under the skin or by injection – every 6-8 hours over 24 hours. Patients are also given intravenous hypertonic saline at specific rates 15 to 30 ml/hr.
If sodium levels have been corrected too quickly, a substance called D5W and desmopressin can be used to lower sodium levels back to the safe correction rate of 8-12 mEq/L. Desmopressin works by promoting water reabsorption in the kidneys. The drug is given at a dosage of 2 to 4 mcg, either under the skin or by injection. D5W is infused over 1 to 2 hours which should reduce sodium by around 2 mEq/L. This infusion continues until the desired sodium level is reached.
Treatment also includes supporting the patient, typically with breathing assistance, intensive physiotherapy and rehabilitation, and the use of anti-Parkinson’s disease drugs.
Other treatments for central pontine myelinolysis have been tested, but without randomized controlled trials, their effectiveness is not yet confirmed. Even so, some small case studies have resulted in favorable outcomes. For example, plasmapheresis has been seen to improve neurological symptoms. Similarly, a small number of studies suggest that certain steroids like dexamethasone could potentially reduce neurological impairment by affecting the blood-brain barrier, though more research is needed.
What else can Central Pontine Myelinolysis (Osmotic Demyelination Syndrome) be?
When trying to diagnose a condition called central pontine myelinolysis, doctors would consider the following conditions that may show similar symptoms:
- Hypertensive encephalopathy (a condition related to high blood pressure affecting the brain)
- Multiple sclerosis (a disease affecting the nervous system)
- Brainstem infarct (a stroke in the brainstem)
- Pontine neoplasms like astrocytomas (tumors in the brainstem)
- CNS lymphoma (a type of brain tumor)
- Brainstem metastasis (cancer that has spread to the brainstem)
- Progressive multifocal leukoencephalopathy (a rare brain disease)
- Acute autoimmune or infectious encephalitis (inflamed brain caused by infection or immune response)
- Mitochondrial encephalopathies (genetic disorders affecting the brain)
- CNS vasculitis (inflammation in the brain’s blood vessels)
It’s crucial for the doctor to carefully consider these conditions and perform the right tests to make a precise diagnosis.
What to expect with Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)
Central pontine myelinolysis was once considered almost always fatal, having a mortality rate between 90% to 100%. However, these numbers have significantly improved over time. Recent studies suggest that now about 94% of the patients survive. According to these studies, 25%-40% of patients fully recover without any lasting issues, while 25%-30% remain significantly affected.
Patients who have a particularly high risk for poor outcomes include those with extremely low sodium levels (less than 120 mEq/L), low potassium levels, and low Glasgow coma scale scores during their hospital stay. Those who underwent liver transplants and developed central pontine myelinolysis or osmotic demyelination syndrome were also found to have adverse outcomes, with a mortality rate of 63% at one year.
Interestingly, the patient’s clinical symptoms and radiological features were not found to play a significant role in determining their outcome. To improve the chances of a good outcome, it’s essential to identify those at high risk of developing CPM early, steer clear of rapidly correcting sodium levels too quickly, and swiftly diagnose the condition. In addition, preventing complications related to the condition such as pneumonia from inhaled food or drink, urinary tract infections, or blood clots in deep veins can also aid in a favorable outcome.
Possible Complications When Diagnosed with Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)
Central pontine myelinolysis, or CPM, can lead to various complications which can differ from person to person. These include several neurologic conditions such as locked-in syndrome, coma and, in the worst cases, death. It can also lead to other complications.
Secondary complications of CPM include:
- Venous thromboembolism, a blood clot that breaks loose and travels in the blood
- Aspiration pneumonia, a condition due to inhaling food, stomach acid or saliva into the lungs
- Ventilator dependence, where you might need a machine to help you breathe
- Muscle atrophy, which is the wasting away of muscles
- Urinary tract infections
- Decubitus ulcers, also known as bedsores or pressure sores
Preventing Central Pontine Myelinolysis (Osmotic Demyelination Syndrome)
As CPM, a certain medical condition, can have harmful complications, it’s important that patients are well-informed about the nature of the illness, treatment alternatives, and what to expect in the future. After leaving the hospital, patients should also have regular check-ups to monitor their progress and see how well they’re getting better.
