Acute disseminated encephalomyelitis

Definitions & Key takeaways

Acute disseminated encephalomyelitis (ADEM), also called post-infectious encephalomyelitis, is a rare but serious neurologic disorder in which nerves in the brain and spinal cord become demyelinated due to an inflammation that takes place after a course of an infection.

The cause of ADEM is not well understood, but it is believed to be autoimmune-related. Symptoms come on suddenly and include headache, fever, difficulty speaking or understanding speech, weakness or paralysis of an arm or leg, double vision, seizures, and coma.

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Introduction0:00–0:34

In acute disseminated encephalomyelitis or ADEM, acute means that the disease evolves rapidly, disseminated refers to the fact that there are multiple sites involved, encephalo- refers to the brain, myelo- refers to the spinal cord, and -itis refers to inflammation.
So acute disseminated encephalomyelitis is an autoimmune disease of the central nervous system, where there’s sudden inflammation and demyelination at multiple sites of the brain and spinal cord.

Physiology0:34–1:55

The central nervous system consists of the brain and the spinal cord. Grossly, the central nervous system can be divided into two main areas: the grey matter, which is made up of neuron cell bodies, and the white matter, which is made up of projections from the neuron cell bodies known as axons and dendrites.
The dendrites receive electrical impulses from other neurons; the neuron cell body has all of the neuron’s main organelles like the nucleus; and finally the axons transmit electrical impulses to the dendrites of the next neuron in the series.
Some axons are surrounded by a fatty protective sheath called myelin that helps increase the speed at which electrical impulses are sent.
This myelin is produced by oligodendrocytes, which are a group of cells that support neurons. Now, the brain is protected by harmful things in the blood by the blood brain barrier, which only lets certain molecules and cells through.
For immune cells like T and B cells that means having the right ligand or surface molecule to get through the blood brain barrier, this is kind of like having a VIP pass to get into an exclusive club.
Once a T cell makes its way in, it can get activated by something it encounters. Once the T-cell gets activated, it changes the blood brain barrier cells to express more receptors, and this allows immune cells to more easily bind and get in, kind of like bribing the bouncer to let a lot of people in.

Pathology1:55–4:28

In the case of acute disseminated encephalomyelitis, T-cells are activated by myelin. Acute disseminated encephalomyelitis is a type IV hypersensitivity reaction, or cell-mediated hypersensitivity.
And this means that those myelin specific T-cells release cytokines like IL-1, IL-6, TNF-alpha, and interferon-gamma, and together dilate the blood vessels which allows more immune cells to get in, as well as directly cause damage to the oligodendrocytes.
They cytokines also attract B-cells and macrophages as part of the inflammatory reaction. Those B-cells begin to make antibodies that mark the myelin sheath proteins, and then the macrophages use those antibody markers to engulf and destroy the oligodendrocytes, leading to demyelination at multiple locations throughout the brain and spinal cord.
Now, all of this is extremely similar to another disease called multiple sclerosis. The big difference between them is that acute disseminated encephalomyelitis usually occurs as a single event of demyelination in a child, whereas multiple sclerosis is progressive disease with recurrent bouts of demyelination that occurs in young adults.
The underlying trigger for acute disseminated encephalomyelitis is still unclear, but because some pathogens have proteins that are similar to oligodendrocytes proteins, one mechanism may be molecular mimicry.
That’s when the cells of our immune system generate a response against pathogenic proteins, and then mistakenly attack similar proteins expressed by our own cells.
A variety of viral infections are thought to be associated with acute disseminated encephalomyelitis, including influenza, measles, mumps, rubella, and various human herpes viruses.
There are also bacterial infections associated with acute disseminated encephalomyelitis like Mycoplasma pneumoniae and beta-hemolytic Streptococci.
It’s worth noting that these pathogens are relatively common in the environment, but that acute disseminated encephalomyelitis is quite rare.
That’s because the disease only seems to manifest in a person with a particular genetic predisposition and the right environmental trigger.
It is also thought that, in very rare situations, acute disseminated encephalomyelitis might be triggered by certain vaccines, but this topic is still highly debated.

Symptoms4:28–5:02

Symptoms of acute disseminated encephalomyelitis have a sudden onset, and usually begin one to three weeks after being exposed to the trigger.
Since acute disseminated encephalomyelitis is associated to a systemic inflammation, most individuals present fever, headache, nausea and vomiting.
Then, demyelination breaks down the communication between neurons, leading to visual problems, seizures, weakness, irritability, confusion, drowsiness, and even coma.

Diagnosis5:02–5:34

Acute disseminated encephalomyelitis is typically suspected when a child develops the typical symptoms after infection or vaccination.
The diagnosis is supported by an MRI, which shows multiple central nervous system lesions. Also a lumbar puncture can be done, since in the cerebrospinal fluid there might be high levels of antibodies, which indicates an autoimmune process.
Finally a visual evoked potential can be helpful as well, which measures the nervous system’s response to visual stimuli.

Treatment5:34–6:12

Treatment for acute disseminated encephalomyelitis includes corticosteroids, and they should be given rapidly to reduce the inflammation of the central nervous system.
Other treatments include intravenous immunoglobulin therapy to bind and neutralize the autoantibodies, or cyclophosphamide, which is a cell cycle inhibitor.
Occasionally, more severe cases may be treated with plasma exchange, or plasmapheresis, which is when plasma proteins like antibodies are removed, and replaced with plasma from a healthy donor.
The majority of individuals recover fully a few months after treatment, but some have a residual disability. All right, as a quick recap, acute disseminated encephalomyelitis is a rare autoimmune disease with demyelination at multiple sites of the central nervous system.

Review6:12–6:45

It generally occurs as a single event and it usually affects children. Symptoms depend on where the demyelination occurs, but can include visual problems, seizures, weakness, irritability, confusion, and even coma.
Most cases have full recovery, but some retain residual disability, and a small minority do not survive.