What Is Acute Disseminated Encephalomyelitis?

It started off as what you thought was just a common cold, and then you realised that this was something different. Your arms felt weak and heavy, you struggled to think straight, and eventually, you could barely see. 

This sounds like something out of a horror movie; however, unfortunately, it is a potential reality for those who experience the rare neurological condition acute disseminating encephalomyelitis (ADEM). 

To learn more about this disease, including how those who are affected are cared for, please continue reading this article.

Overview

Acute disseminating encephalomyelitis, or ADEM as it is sometimes known, is a neurological condition that involves the body attacking the central nervous system (the brain and spinal cord) as a reaction to an infection or, in rare cases, to a vaccination.^1,2,3

This disease is the consequence of an inappropriate response of your immune system to an insult and leads to inflammation of the central nervous system combined with damage to a major component of nervous tissue, myelin.^1,2,3

Myelin is a vital structural and functional element within the central nervous system that coats and protects the nerves and allows effective nervous electrical signalling to take place throughout your brain, spinal cord, and nerves.² 

Acute disseminated encephalomyelitis typically affects children and young adults, and in most cases, they will only experience a single episode (monophasic).^1,2,3 However, rarely, they may also experience either:

1. Repeated episodes that recur following a period of remission and affect new locations (multiphasic disease)²
2. The same area undergoing repeated damage following what was believed to be an effective course of treatment (recurrent disseminating encephalomyelitis)²

Although the consequences of this disease have the potential to be catastrophic, the majority of people respond positively after prompt diagnosis and treatment.^{1, 2}

However, in rare instances, some people may present with the highly aggressive variant, acute haemorrhagic leukoencephalitis, a fulminant type of demyelinating disease that is known for its risk of severe complications and mortality.^1,4

Causes of acute disseminating encephalomyelitis 

Acute disseminating encephalomyelitis is often linked to an infectious event or a vaccination. However, in a minority, 26% of people, there is no obvious link to either.^1,2,3

People generally tend to present with symptoms within 2 days to four weeks following such an event. The occurrence of the triggering event can usually be identified during the taking of a thorough medical history.² 

Even if you often find yourself ill with coughs and colds, this information may help establish a potential triggering infectious event for ADEM. 

ADEM has been linked to infections of both a viral or bacterial nature, with some specific offending organisms being linked to more severe presentations of the disease.^1,2,4

Risk factors for acute disseminated encephalomyelitis 

Risk factors for acute disseminating encephalomyelitis include:

• Age less than 10 years^1,2,4
• Being assigned male at birth^1,2
• Infection with influenza, measles, mumps, rubella, varicella-zoster, Epstein Barr virus, herpes simplex virus, influenza virus, enterovirus, cytomegalovirus (CMV), hepatitis A, coxsackievirus, Mycoplasma pneumoniae, Borrelia burgdorferi, Leptospira, beta-haemolytic Streptococcus or undetermined upper respiratory infection^1,2,3,4
• Vaccination for hepatitis B, pertussis, diphtheria, measles, mumps, rubella, pneumococcus, varicella (chickenpox/shingles), influenza, smallpox, poliomyelitis, human papillomavirus (HPV), rabies vaccine and Japanese B encephalitis^1,2,3,4
• The season – you are more likely to contract ADEM in spring or winter^1,2

Signs and symptoms of acute disseminated encephalomyelitis

Symptoms of acute disseminating encephalomyelitis involve a group of non-specific, ’general illness’ symptoms in combination with those which are related specifically to the neurological nature of the disease.

General symptoms include:

• Fever
• Feeling sick or being sick 
• Headache 
• Tiredness^1,2,3

Neurological symptoms include:

• Changes to vision due to damage to the optic nerve 
• Nerve pain 
• Changes in sensations (numbness or tingling)
• Changes to coordination or movement 
• Changes in behaviour, mood, or level of consciousness
• Muscle weakness 
• Seizures^1,2,3,5

Symptoms often present suddenly and vary in degree, having the potential to be either mild and of minimal concern or severe enough to prompt admission to the hospital.  

Diagnosis of acute disseminating encephalomyelitis

Diagnosis of acute disseminating encephalomyelitis may prove difficult because its presentation shares similarities with several other neurological conditions, such as multiple sclerosis (MS) or neuromyelitis optica (NMO).^1,2,3

However, the use of the following diagnostic tests should enable these differential diagnoses to be excluded:  

• Lumbar Puncture – this involves the collection of cerebrospinal fluid (CSF) from the spinal canal. This fluid is then analysed for the presence of a number of markers to assist in diagnosis.^1,2,3

For example, testing for markers of bacterial and viral infection will help to exclude symptoms being caused by an infection within the central nervous system if their presence is absent. Such infection markers may include the presence of white blood cells, bacterial colonies developing during microbiological culturing (to see whether bacteria grow from the fluid) or a positive viral PCR (similar technology to that is used for COVID-19 testing). If these tests are negative, it can permit the elimination of an infective cause for the encephalitis/meningitis.² 

As part of the analysis of CSF, the fluid may also be tested for the presence of oligoclonal bands (OCB).2 This marker can help differentiate between ADEM and multiple sclerosis (MS).2 In MS, these are raised dramatically and act as a very important marker in its diagnosis, whereas in ADEM, although you may see increases in this marker, it is less common, and its levels may be only slightly raised ²

• Blood tests – certain blood tests may also be used to assist in the diagnosis of ADEM, for example, a test for the presence of myelin oligodendrocyte glycoprotein (MOG) antibodies.^1,2,3 This marker can be used to determine whether damage to myelin has occurred.^1,2,6,7 These antibodies are commonly present in ADEM but not in MS so they act as a means of excluding the latter disease.^2,6,7

Similarly, also testing blood for the presence of aquaporin 4 (AQP4) antibodies can be used to exclude the condition neuromyelitis optica, which presents with similar symptoms to ADEM.^2,8

• Magnetic resonance imaging (MRI) of the brain / spinal cord – use of this imaging technique can help to identify abnormalities in the structure of the central nervous system.^1,2,6,9,11 

Specifically, with acute disseminated encephalomyelitis, there will often be widespread lesions within the brain in both white and grey matter.^2,6,9,10,11 Unlike MS, these will usually have poorly defined borders and shapes, and typically, the locality of these lesions tends to be different from MS. ^{(2,6,9,10,11)} Additionally, when there is the involvement of the spinal cord, these lesions may be of different sizes and affect contrasting portions of the spinal cord.^2,6,9,11

• Biopsy – although not typically used as a diagnostic technique, analyses of tissue biopsies often prove that the areas affected in ADEM are ‘perivenous’, meaning that the damage specifically affects the area’s surrounding veins.¹² This is not the case in MS, and consequently, some believe that this is the ‘gold standard’ of evidence to confirm a diagnosis of ADEM¹² 

Management and treatment of acute disseminated encephalomyelitis

Treatment should be started as soon as possible to minimise any potential lasting effects of the condition.^1,9 Management of ADEM may include symptomatic support with the use of medicines to prevent disease complications such as seizures or nerve pain that may occur.^2,9 However, the most commonly used options for the treatment of ADEM include:

Corticosteroids – these medicines work by reducing the inflammation associated with the disease and aim to minimise the damage to nerves and the central nervous system by suppressing the exaggerated immune response seen in ADEM.^1,2,3,9 Typically, you will be given the steroid methylprednisolone via a drip in your arm (Intravenously) to assist the steroid in quickly getting into your body and ensure its rapid and potent effect. It is often given as a short course over several days, during which you will be closely observed for your response to treatment.^1,2,3,9 Depending on this, you may then also receive longer-term steroids in the form of a tablet to ensure your recovery and prevent damage from recurring in the early stages of your illness ⁹ 

Plasmapheresis – plasma exchange, or ‘PLEX’ as it may be known, is another method used in treating acute disseminated encephalomyelitis.^1,2,3,9,13 It involves the removal of the patient’s blood into a machine which separates plasma (a component of blood) from the other constituents of blood.^1,2,3,9,13 The machine then replaces the plasma with a fresh fluid substitute and then pumps this back into your body along with the other non-plasma blood components.^9,13 By filtering and removing the plasma, any toxins responsible for the disease symptoms found within the plasma are removed, thereby preventing further nerve damage from occurring.^9,13 This procedure needs specialist staff to carry it out because of the training required to operate the equipment. Also, it is essential to gain ‘central venous access’ (i.e. via the jugular vein in your neck) to perform this procedure.¹⁴ This must, therefore, be carried out within a hospital setting and normally takes place over a number of days ^9,13,14 

Intravenous immunoglobulin – this treatment option involves administering immunoglobulin by injection into your bloodstream.^1,2,3,9 Immunoglobulin is a blood product taken from healthy blood donors and contains a number of important antibodies.^1,15,16 This treatment works by neutralising the effect of the damaging antibodies seen in ADEM within the blood and acts to normalise the response to insult, thereby reducing the nerve damage caused by the immune system.^1,9,16 There have also been some suggestions about the potential for immunoglobulin therapy to cause the repair of myelin, but this has yet to be confirmed as a fact.¹⁶ In the context of your treatment program, immunoglobulin therapy may only be reserved for cases that do not effectively respond to the initial treatment with either high-dose steroids or plasma exchange as above ^1,2,9 

Rehabilitation – although this may not necessarily be a part of the initial treatment for ADEM, rehabilitation forms a crucial part of your care and will allow for the best recovery to be made in the long run.^1,9 Several healthcare professionals will be involved to help you set goals, with the ultimate aim of you being able to return to living a normal life   

Complications of acute disseminating encephalomyelitis

Complications may include those related to the disease itself, as well as those that may be associated with the treatments outlined above. Fortunately, complications related to the disease itself are usually responsive to effective treatment, and the majority of people should gradually make a full recovery from the symptoms associated with ADEM.^2,9 However, an unfortunate few may be left with lasting complications such as muscle spasticity or weakness, movement and coordination problems, changes to memory, attention or mood or even continued nerve pain.^2,9,17,18

Complications related to treatments will be specific to the type of treatment received. Some potential complications to be aware of include:

• Bleeding from major veins when trying to carry out plasma exchange^13,14
• Disturbance of the body’s electrolyte balance through the use of plasma exchange¹³
• Infection from the catheter required to perform plasma exchange^13,14
• A pneumothorax is where air unintentionally enters the space surrounding the lung^13,14
• Infusion-related reactions (such as a severe allergic reaction) upon administration of immunoglobulin^15,16
• Transmission of viral infections during immunoglobulin administration^15,16
• Blood clots caused by the venous catheter used for plasma exchange or, in rare instances, caused by immunoglobulin therapy^13,14,15,16
• Steroid-related side effects such as increased infection risk, bleeding in the stomach, reduced bone strength and, in rare cases, psychosis or dramatic changes in behaviour^1,19

These risks will be weighed up by your medical team, and steps will be taken to try and reduce the chances of these occurring. Although some therapies may present with serious adverse effects, these are often rare, and within the context of ADEM, if you are not treated effectively, the disease itself has the potential to cause lasting damage to your health.^2,9,17,18

Summary

Although ADEM may present as an explosively sudden, debilitating disease, the majority of cases can be managed successfully, allowing a near-complete recovery. Because this rare disease often presents in tandem with feeling generally unwell, this poses difficulty in making an early diagnosis. However, by using various specific diagnostic tests, expert neurology teams should be able to exclude other diseases and initiate treatment in good time. 

Treatment options each possess their own advantages and disadvantages, therefore it is important that options are explored thoroughly with your medical team to offer you the best chance of recovery.