Acute Disseminated Encephalomeylitis (ADEM)
Brighton Collaboration Case Definition (Level 1)

Focal or multifocal findings referable to the central nervous system, including one or more of the following:

  • Encephalopathy
  • Focal cortical signs (including but not limited to: aphasia, alexia, agraphia, cortical blindness)
  • Cranial nerve abnormality/abnormalities
  • Visual field defect/defects
  • Presence of primitive reflexes (Babinski's sign, glabellar reflex, snout/sucking reflex)
  • Motor weakness (either diffuse or focal)
  • Sensory abnormalities
  • Altered deep tendon reflexes (hypo- or hyperreflexia, asymmetry of reflexes)
  • Cerebellar dysfunction (including ataxia, dysmetria, cerebellar nystagmus)

Magnetic resonance imaging (MRI) findings displaying diffuse or multifocal white matter lesions on T2-weighted, diffusion-weighted (DWI), or fluid-attenuated inversion recovery (FLAIR) sequences (± gadolinium enhancement on T1 sequences).

Acute Disseminated Encephalomeylitis (ADEM) Discussion

Acute disseminated encephalomyelitis (ADEM) is a monophasic inflammatory disease that often occurs after a viral infection or rarely after vaccinations. The inflammatory process causes an acute widespread multifocal demyelinating condition which can affect both the brain and the spinal cord. The proposed pathogenesis is that myelin autoantigens, such as myelin basic protein, share antigenic determinants with those of an infecting pathogen. Antiviral antibodies or a cell-mediated response to the pathogen cross reacts with the myelin autoantigens, resulting in ADEM.

The neurologic signs are variable, multifocal and depend upon the location of the CNS lesions. Motor deficits, impaired consciousness, cranial nerve abnormalities, including optic neuritis with vision impairment, gaze paresis, facial weakness, sensory deficits, and swallowing difficulties occurred frequently. Systemic symptoms like fever, malaise, myalgias, headache, nausea and vomiting can precede the neurological symptoms. Seizures may occur in the acute hemorrhagic form of ADEM. Optic neuritis is often bilateral and transverse myelitis is often complete.

Evidence of inflammation is commonly found in the cerebral spinal fluid. Lymphocytic pleocytosis (up to 1000/mm3) can be seen. Polymorphonuclear leucocytosis may be seen initially. Increased protein concentration is found in the majority of patients. Glucose content is usually normal. Rarely oligoclonal bands can be seen in patients with ADEM. However the CSF can also be normal in some patients. Therefore, neuroimaging is helpful to support the diagnosis of ADEM.

Both computed tomography scanning and magnetic resonance imaging have been widely used in patients suspected of having ADEM. MRI is generally regarded as the superior technique, because, as CT scans can be normal during the initial phase of the disease. Multiple patchy areas of increased signal intensity may be seen on conventional T2 weighted MRI images and fluid-attenuated inversion recovery sequence in the subcortical white matter. Lesions are typically bilateral but asymmetric and tend to be poorly marginated. Almost all patients have multiple characteristic lesions of demyelination in the deep and subcortical white matter. Grey matter, such as basal ganglia, thalami and brainstem may also be affected.

In the past, ADEM commonly followed such childhood infections as measles and chickenpox. However, ADEM in developed countries is now seen most frequently after non-specific viral illnesses. The viruses that have been associated with the disorder include rubella, influenza, Epstein-Barr, coxsackie, coronavirus, HIV, herpes simples, cytomegalovirus, and West Nile virus.

ADEM has a broad differential diagnosis. ADEM, multiple sclerosis, viral encephalitis and vasculitis share similar CSF profile, and similar MRI findings though not necessarily the same clinical course. ADEM tends to present with a more acute, widespread MRI lesions and typically all lesions are of the same age. Viral encephalitis, subcortical arteriosclerotic leukoencephalopathy, neuro-sarcoidosis, progressive multifocal leukoencephalopathy, HIV encephalitis, subacute sclerosing panencephalitis, mitochondrial encephalopathy, and leukodystrophies are also on the differential though the incidence is low.

The lumbar puncture is essential to the ADEM workup. Titers for various bacteria, viruses, or other agents can assist in distinguishing ADEM from various forms of infectious meningoencephalitis.

The immune profile is also helpful in distinguishing ADEM from MS. The IgG index or oligoclonal bands are positive in more than two thirds of all first clinically recognized MS bouts and in 90-98% of individuals who have experienced multiple MS bouts. One or more of these studies is positive in no more than 10% of ADEM cases.

Acute Disseminated Encephalomeylitis (ADEM) Treatment

Treatment of ADEM attempts to suppress a presumed aberrant immune response to an infectious agent or a vaccination and so ADEM is often treated with high-dose intravenous corticosteroids. One common protocol is 20 mg/kg/d of methylprednisolone (maximum dose of 1 g/d) for 3-5 days.

Approximately two thirds of the patients who are treated early with steroids have cessation of further progression of their symptoms, reduction in the duration of neurological symptoms, and a decrease in the severity of long term sequelae.

However, when steroids fail, intravenous immune globulin (IVIG) or plasmapheresis have been reported to improve symptoms and speed recovery. IVIG is believed to treat conditions associated with inflammation and immune dysregulation by neutralizing circulating myelin antibodies, by down-regulating proinflammatory cytokines, blocking Fc receptors on macrophages, suppressing inducer T and B cells and augmenting suppressor T cells, and by blocking the complement cascade. A total of 2 g/kg of IVIG for 2-3 days is recommended. IVIG may be preferable when meningoencephalitis cannot be excluded. IVIG is easier to administer and has fewer complications than plasma exchange. The cost and efficacy of the two treatments are comparable. There is no convincing evidence that treatment with the combination of intravenous corticosteroids and IVIG confers any advantage.

To reduce the risk of potential anaphylaxis, it is recommended to check serum IgA level before infusing IVIG. Infusions may increase risk of thromboembolic events, migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 days postinfusion). There is increased risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, and preexisting kidney disease.

Acute Disseminated Encephalomeylitis (ADEM) Case Example

20 year old white male was in his usual state of good health until the day prior to presentation, 2 weeks post-vaccination, when he noticed a bilateral, ascending, circumferential numbness in his lower extremities. His symptoms progressed within 24 hours to lower extremity muscle weakness causing difficulty with walking and standing and an inability to urinate. On physical exam there was decreased sensation to pin prick and light touch to the mid-chest, and lower extremity weakness (left > right and distal > proximal). Reflexes 3+/4 at the bicep, triceps and patella, 2+/4 at ankles with 3-4 beat clonus. Patient had sluggish pupils and absent corneal reflexes. There was no diplopia, loss of vision, dysphagia, or dysarthria. Within hours, the patient developed acute shortness of breath and was intubated. There were no recent upper respiratory tract infections, diarrhea, rashes, animal or insect bites.

MRI of brain, C-spine and T-spine showed multifocal diffuse T2 hyperintensity throughout brain and spinal cord. Cerebral spinal fluid had 27WBC, 40RBC, protein of 113, and glucose of 80.