Pediatric acute disseminated encephalomyelitis (ADEM)

What is pediatric acute disseminated encephalomyelitis (ADEM)?

ADEM is a condition defined by inflammation within the brain that can be accompanied by spinal cord or optic nerve involvement. In ADEM, portions of the immune system leave the bloodstream and enter the brain causing damage. In the central nervous system, there are specialized cells called neurons. These cells connect to each other via long extensions, similar to the wiring of a house.

These “wires” are called axons. The axons are covered by a protective coating called myelin. The inflammation of ADEM causes loss of the protective myelin and this damage is known as demyelination. This is commonly a monophasic (one time only) event, but can be the presenting sign of a systemic, recurring condition.

What are the different types of pediatric acute disseminated encephalomyelitis (ADEM)?

Most ADEM involves inflammation that causes loss of the protective myelin around axons in the central nervous system (brain, spinal cord and optic nerves). A rare, severe form of ADEM, called acute hemorrhagic leukoencephalitis (also known as Weston-Hurst syndrome or Hurst disease), is accompanied by bleeding in the brain.

What are the signs and symptoms of pediatric acute disseminated encephalomyelitis (ADEM)?

The signs and symptoms of ADEM are based on which part of the nervous system is affected. By definition, all ADEM patients have brain involvement and many will have spinal cord or optic nerve involvement as well.

Typical symptoms of ADEM can include mental changes, numbness, weakness, difficulty with balance, difficulty with walking, vision loss, double vision, headache and bowel/bladder changes. Each patient can have different symptoms based on where the inflammation occurs. In severe forms of ADEM, patients can become unresponsive or comatose. 

After the initial acute stage, patients generally recover well. Most patients make complete or near complete recoveries, but some can be left with deficits. Patients often require physical therapy (PT), occupational therapy (OT) and speech/language therapy to aid in their recovery.

Furthermore, our center has studied the longer-term cognitive impacts of ADEM and found it necessary to monitor children’s memory and academic function. Some young children make an apparent recovery in terms of their school functioning but begin to have academic challenges during later grades. Careful monitoring by a neuropsychologist is important for identifying any cognitive difficulties that an ADEM patient may experience over the years after their initial event.

How is pediatric acute disseminated encephalomyelitis (ADEM) diagnosed?

• Children presenting with neurologic deficits consistent with ADEM will undergo a physical exam and a variety of tests that will include an MRI of the brain, spinal cord and optic nerves.

• A lumbar puncture is often performed to obtain a cerebrospinal fluid sample.

• Finally, blood work is performed to identify potential causes of ADEM. In rare circumstances, a brain biopsy may be needed in order to confirm a diagnosis of ADEM or rule out other potential conditions.

What are the causes of pediatric acute disseminated encephalomyelitis (ADEM)?

Most ADEM is thought to be post infectious. This means that a patient experiences an infection somewhere in their body (such as a respiratory or gastrointestinal illness) and then recovers.

Scientists theorize that the infection triggers an immune response to clear the body of the pathogen which then goes on to cause damage in the brain by mistake. This process is referred to as molecular mimicry. Under the theory of molecular mimicry, there is some protein in the infection that resembles a protein in the brain. After clearing the infection, the immune system goes on to survey the whole body and attacks the brain in error. 

Some ADEM is caused by a systemic autoimmune condition that leads to a persistent alteration of the immune system. For example, some patients develop autoantibodies to the aquaporin 4 protein or the myelin oligodendroglial glycoprotein (MOG) protein. Patients with these antibodies are at risk for future inflammatory events.

Rarely, children who present with ADEM can go on to have attacks over time that fulfill the criteria for relapsing remitting multiple sclerosis.

How is pediatric acute disseminated encephalomyelitis (ADEM) treated?

ADEM is treated in a variety of ways including treatment to address the acute inflammatory stages and supportive therapy and interventions to improve recovery. Acute anti-inflammatory therapies include high doses of steroids, plasma exchange (PLEX), intravenous immunoglobulin (IVIG), and sometimes medications such as cyclophosphamide (Cytoxan®) or methotrexate. Steroids work by reducing the number of inflammatory cells in the brain. They can be administered by IV or orally. Most children tolerate steroids well, but some may experience mood changes, appetite changes, difficulty sleeping or irritability. Rarely, patients can experience infection or bone abnormalities. 

• Plasma exchange (PLEX) - A therapy that requires special IV access and a portable machine that cleans the blood of inflammatory proteins. A patient’s blood is circulated through the machine and proteins such as antibodies are removed. A therapy session takes about 90 minutes and is usually well-tolerated. A patient usually receives five to seven treatments to complete a PLEX course. 

• Intravenous immunoglobulin (IVIG) - An infusible therapy that has been used extensively in pediatrics. IVIG is a collection of antibodies collected from blood donors and pooled together. When infused into patients, the antibodies are thought to cause a reduction or blocking of the patient’s abnormal immune response. 

• Other medications - When patients are not responding to steroids, PLEX or IVIG, medications such as cyclophosphamide or methotrexate are used. These medications cause more profound immune suppression and should be used by centers that have experience in prescribing these medications.

• Therapy - After the acute therapy, patients will often require rehabilitation and symptom management. This can include physical therapy (PT), occupational therapy (OT), speech/language therapy, swallow therapy and management of bladder dysfunction. Rarely, patients may experience neuropathic pain that requires treatment.

• Psychology support/therapy - In addition to evaluation by a neuropsychologist for cognitive, emotional, and/or behavioral problems, patients may also require psychosocial support or therapy to manage the behavioral and emotional impacts of ADEM.