Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis

What is acute disseminated encephalomyelitis?
Acute disseminated encephalomyelitis (ADEM) is a rare neurological disorder. It affects children more than adults, but can affect anyone.

What are the symptoms of acute disseminated encephalomyelitis?
More than half of patients have an illness, usually an infection, two to four weeks before developing ADEM. Most of these illnesses are viral or bacterial, often no more than an upper respiratory tract infection. In children with ADEM, prolonged and severe headaches occur. In addition, the patient develops fevers during the ADEM course.
Along with this pattern, the patients usually get neurological symptoms which may include:
  • confusion, drowsiness, and even coma
  • unsteadiness and falling
  • visual blurring or double vision (occasionally)
  • trouble swallowing
  • weakness of the arms or legs
In adults with ADEM, motor (movement) and sensory (tingling, numbness) symptoms tend to be more common. Overall, what triggers a diagnosis of ADEM is a rapidly developing illness with neurological symptoms, often with fever and headache, usually following an upper respiratory tract infection, and which has significant MRI and spinal fluid findings consistent with ADEM.

What causes ADEM?

The cause of ADEM is not clear but in more than half of the cases, symptoms appear following a viral or bacterial infection, usually a sore throat or cough and very rarely following vaccination. ADEM is thought to be an autoimmune condition where the body’s immune system mistakenly identifies its own healthy cells and tissues as foreign and mounts an attack against them. This attack results in inflammation.  Most cases of ADEM begin about 7 to 14 days after an infection or up to three months following a vaccination. In some cases of ADEM, no preceding event is identified.

Pathology

Thought to occur from a cross reactivity in immunity to viral antigens triggering a subsequent autoimmune attack on the CNS.
The pathological hallmark is perivenular inflammation with limited ‘‘sleeves of demyelination", which is also a feature of multiple sclerosis. However, multiple sclerosis typically present confluent sheets of macrophage infiltration mixed with reactive astrocytes in completely demyelinated regions

How is ADEM different from MS?

  • In most but not all cases, ADEM occurs only once, while patients with MS have further, repeated attacks of inflammation in their brains and spinal cords.
  • In most cases, ADEM patients do not develop new scars on a repeat MRI scan whereas MS patients typically experience new scars on their follow-up MRI scans.
  • Typical symptoms of ADEM such as fever, headache and confusion, vomiting, and seizures are not usually seen in people with MS, although they can be seen in pediatric MS onset especially in patients younger than 11 years.
  • Sometimes the pattern of MRI abnormalities helps differentiate these two disorders.
  • Most patients with MS are treated with ongoing medication to prevent attacks. Patients with ADEM do not require such medication.
  • ADEM occurs more frequently in males; MS more frequently in females.
  • ADEM is more common in children; MS is more common in adults.
  • ADEM occurs more frequently in winter and spring; MS has no seasonal variation.

Radiographic features

Appearances vary from small punctate lesions to tumefactive regions, which have less mass effect than one would expect for their size, distributed in the supratentorial or infratentorial white matter. Compared to multiple sclerosis, involvement of thecallososeptal interface is unusual. Lesions are usually bilateral but asymmetrical. Involvement of cerebral cortex, subcortical grey matter, especially the thalami, and thebrainstem is not very common, but if present are helpful in distinguishing frommultiple sclerosis .
In addition to lesions involving grey matter, especially in the setting of post-streptococcal pharyngitis, antibodies to basal ganglia can also develop resulting in more diffuse involvement 
Spinal cord may show confluent intramedullary lesions with variable enhancement.
CT
The lesions are usually indistinct regions of low density within the white matter and may demonstrate ring enhancement.
MRI
MRI is far more sensitive than CT:
·         T2: demonstrates regions of high signal, with surrounding oedema typically situated in subcortical locations; the thalami and brainstem can also be involved
·         T1 C+ (Gd): punctate, ring or arc enhancement (open ring sign) is often demonstrated along the leading edge of inflammation; absence of enhancement does not exclude the diagnosis
·         DWI: there can be peripheral restricted diffusion; the center of the lesion, although high on T2 and low on T1 does not have increased restriction on DWI (c.f. cerebral abscess); nor does it demonstrate absent signal on DWI as one would expect from a cyst, this is due to increase in extracellular water in the region of demyelination
Magnetization transfer may help distinguish ADEM from MS, in that normal appearing brain (on T2 weighted images) has normal magnetization transfer ratio (MTR) and normal diffusivity, whereas in MS both measurements are significantly decreased 

What are the causes and/or risk factors associated with acute disseminated encephalomyelitis?

We know that ADEM usually follows an infection of some kind. In 50 percent to 75 percent of cases, the beginning of the disease is preceded by a viral or bacterial infection, usually a sore throat or cough (upper respiratory tract infection). Many different bacteria, viruses and other infections have been related to ADEM, but the disease does not appear to be caused by any one infectious agent. Most cases of ADEM begin about 7 to 14 days after the infection.
On occasion, ADEM occurs after a vaccination. This is rare overall, but when it happens, it usually occurs after the measles, mumps, and rubella vaccination. In these cases, ADEM may occur up to three months after the vaccination.
ADEM appears to be an immune reaction to the infection. In this reaction, the immune system, instead of fighting off the infection, causes inflammation in the central nervous system. Inflammation is defined as the body's complex biological response to harmful stimuli, such as infectious agents, damaged cells, or irritants. Inflammation is a protective attempt to remove the injurious stimuli and initiate the healing process. In the case of ADEM, the immune response is also responsible for demyelination, a process in which the myelin that covers many nerve fibers is stripped off.

How is acute disseminated encephalomyelitis treated?

ADEM is a rare disease, and so there are no well-designed clinical trials comparing one treatment with placebo, or one treatment with another. Everything we know about treatment in ADEM comes from small published series of cases, and there are no guidelines for treatment of ADEM yet.
At this time, intravenous methyl-prednisolone (for instance, Solu-Medrol®) or other steroid medications are the front-line treatment for ADEM. Usually these medications are given over a five- to seven-day course, followed by a tapering dose of oral steroids. The aim is to reduce inflammation and speed recovery from the disease.
Patients on steroids need to be monitored for increased blood glucose, low potassium, and sleep disturbance. There may be mood changes (irritability, crying, anxiety) when people are on steroid therapy. Other short-term complications of steroid therapy include weight gain, flushed cheeks, facial swelling, and a metallic taste (when using IV Solu-Medrol).
If a patient does not respond to IV methylprednisolone, the next line of treatment may be intravenous immune globulin (IVIG). This is an intravenous treatment using a blood product which has been shown to reduce the activity in certain immune diseases, including ADEM. Treatment is usually given for a few hours daily over five days for ADEM. IVIG has the same risks as any blood product (allergic reaction, infection); it also sometimes causes shortness of breath due to fluid overload. Rarely, patients lack an antibody important to the system and may react more strongly to IVIG.
Another approach to treatment is a process called plasmapheresis. This is a treatment in which the blood is circulated through a machine that withdraws components of the immune system from the circulation, reducing immune activity. It is usually a process which takes a few hours and is done every other day for 10 to 14 days, often as part of a hospital stay. It may require the placement of a central venous catheter to allow for blood to be removed from the system rapidly. Risks of plasmapheresis include discomfort from taking blood, sometimes a tendency to bleed due to a reduction in platelets, and infections.



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