Central pontine myelinolysis

Definitions & Key takeaways

Central pontine myelinolysis (CPM) is a neurological disorder caused by the rapid correction of hyponatremia. CPM is a demyelinating disease that damages the insulation around nerve fibers (called myelin). This damage disrupts the conduction of nerve impulses, leading to neurologic deficits.

Symptoms of CPM include muscle weakness, difficulty swallowing, and problems with speech, vision, and balance. These symptoms often occur suddenly and progress rapidly. Death from respiratory failure can occur within days or weeks of onset.

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Introduction0:00–0:38

In central pontine myelinolysis, pontine refers to the pons of the brainstem, myelin refers to the fatty layer of insulation that wraps around neurons, and -lysis refers to destruction.
So, central pontine myelinolysis is the destruction of the myelin sheath around nerve cells that are in the pons. The main cause of destruction is rapid osmotic changes, meaning that a lot of water leaves the cells, and dries them out, causing them to die.
So the other name for central pontine myelinolysis is osmotic demyelination syndrome. Taking a look at the brain, the pons is part of the brainstem and it’s nestled between the midbrain and the medulla oblongata.

Physiology0:38–2:10

The pons itself has control centers that help manage the respiration rate and the depth of breathing while we’re awake and when we sleep.
So if you try to take a deep breath right now - that’s your pons in action! Neuron clusters or nuclei for cranial nerves V: trigeminal, VI: abducens, VII: facial, and VIII: vestibulocochlear are also housed in the pons.
Cranial nerve V allows you to feel things on your face and controls the muscles that help you chew, bite, and swallow. Cranial nerve VI allows your eyes to move side to side.
Cranial nerve VII helps with facial expressions - like making a weird face, and cranial nerve VIII helps with hearing. All of these nerves are made up of lots of individual neurons which capture signals from their dendrites, and pass those signals along through their axons.
In addition to the neurons, there are also supporting cells called oligodendrocytes and astrocytes. Oligodendrocytes physically wrap their fatty myelin-rich cell membranes around neuronal axons that are nearby to help action potentials move more quickly through them.
And astrocytes help repair damaged neurons. Neurons and oligodendrocytes are very sensitive to changes in the amount of water and electrolytes in themselves and their environment.

Pathology2:10–2:10

Pathology2:10–5:55

In other words, in the intracellular and extracellular compartment. And the pons is a part of the brain that’s particularly sensitive.
The cell membrane is permeable to water, but some substances called osmolytes cannot cross over as easily and are called semi-permeable.
Examples of osmolytes are electrolytes like potassium, sodium, and chloride, as well as organic substances like phosphorylated glucose - which makes the molecule more polar and prevents it from slipping through the membrane easily.
Intracellularly, there is high potassium and low sodium, while extracellularly, there is high sodium and low potassium. Normally, extracellular osmolality matches intracellular osmolality, meaning they are in equal balance of water and solute concentration.
When there’s a difference between the intracellular and extracellular osmolality, water flows towards the compartment with a higher osmolality to balance things out - and that’s osmosis - the process, not the company!
So, when neurons and oligodendrocytes are in an environment with a low sodium concentration, called hyponatremia, there is a lower osmolality outside the cell compared to inside the cell and water flows into the cells.
Hyponatremia might happen in a condition like syndrome of inappropriate diuretic hormone or SIADH, where the kidneys retain too much water.
Because the brain is restricted within the skull, brain swelling is significant because there’s no space to expand and the brain tissue gets compressed.
To avoid swelling up with too much water, neurons and oligodendrocytes have natural defense mechanisms. For example, let’s say that there’s a drop in extracellular osmolarity.
That change would first get sensed by channels on the cell membrane. In response, the cell would try to have fewer osmolytes, so that less water flows into the cell.
To do that, protein kinases would be inhibited from adding a phosphate group to substances like glucose, allowing glucose to more easily slip out of the cell.
In this way, the brain’s cells reduce the osmotic gradient. This process that can take about 48 hours to complete, and in the end, the cell is in complete equilibrium with the hyponatremic extracellular space.
Now, let’s say that the hyponatremia resolves, perhaps a person with SIADH is given an infusion of salt containing intravenous fluids.
In that situation, the balance is upset once again. This time, the extracellular component has too much sodium, and that creates an osmotic gradient that pulls water out of the cell.
Initially, the neurons and oligodendrocytes don’t have enough time to allow osmotically active substances to enter and reestablish balance.
With more osmolytes outside the cell, the water in the cell moves out. As a result, cells dehydrate, and that causes massive structural damage.
When oligodendrocytes and neurons get damaged, reactive astrocytes come to the site and form scar tissue made of glycoproteins to fill the empty space, a process called astrogliosis.
The proliferation of astrocytes at the injured site also signals the surrounding tissues to secrete proteins like laminin, fibronectin, and proteoglycans, which inhibit tissue regeneration.
When there’s enough damage to the pons, it can affect the function of the cranial nerve nuclei that are housed in the pons.

Symptoms5:55–6:29

Ultimately, central pontine myelinolysis can lead to impaired muscle movements in the head and neck causing dysarthria or an inability to speak normally, dysphagia or difficulty swallowing, and diplopia or double vision.
Classically, central pontine myelinolysis can cause “locked-in syndrome”, which is where there’s complete paralysis of most or all of the voluntary muscles in the body, while a person is completely conscious.
A bit like waking up and being completely paralyzed - a frightening thought. Central pontine myelinolysis can be diagnosed based on an MRI, which will show damage to the pons.

Diagnosis and treatment6:29–6:46

Typically there’s no way to reverse existing damage, but ongoing damage can be stopped by slowly and carefully correcting any electrolyte abnormalities.
All right, as a quick recap, central pontine myelinolysis, also known as osmotic demyelination syndrome, is the destruction of the myelin of nerve cells in the pons due to a rapid correction of hyponatremia.

Review6:46–7:06

It classically causes “locked-in syndrome” which is when person is conscious but unable to move any muscles.