Acute Disseminated Encephalomyelitis Case File

Acute Disseminated Encephalomyelitis Case File

Eugene C. Toy, MD, Ericka Simpson, MD, Pedro Mancias, MD, Erin E. Furr-Stimming, MD

CASE 25

A 20-year-old college student presents with a 2-day history of headache, nausea, confusion, weakness in both legs, and urinary incontinence. He had a viral illness 3 weeks earlier, but his symptoms had resolved and he was otherwise healthy. His roommate called 911, and he was taken to the emergency department. On examination, the patient was lethargic, and his speech was slurred. His vitals were stable, he was afebrile, and his general examination was normal. Neurologic evaluation was significant for weakness in his lower extremities. He was able to stand, but his gait was unsteady and he required assistance with walking. His reflexes were diffusely increased, and he had upgoing toes bilaterally. He additionally had a subjective sensory level at the level of his navel. The patient was admitted for evaluation and management.

▶ What is the most likely diagnosis?

▶ What is the prognosis for this condition?

▶ What is the next step in therapy?

ANSWERS TO CASE 25:

Acute Disseminated Encephalomyelitis                                                    

Summary: A 20-year-old man has developed multiple neurologic symptoms 3 weeks after the resolution of a viral illness. He complains of headache and had symptoms of spinal cord compromise (ie, weakness in lower extremities, urinary incontinence, sensory level).

• Most likely diagnosis: Acute disseminated encephalomyelitis (ADEM).
• Prognosis: Fairly good.
• Next step in therapy: Consider intravenous corticosteroids, plasmapheresis, and intravenous immunoglobulin.

ANALYSIS

Objectives

1. Understand the differential diagnosis of ADEM.
2. Understand the evaluation for ADEM.
3. Understand the prognosis of ADEM.
4. Understand when and how to treat ADEM.

Considerations

ADEM is a monophasic, demyelinating illness associated with multiple neurologic symptoms secondary to involvement of the brainstem, spinal cord, optic nerves, cerebrum, and/or cerebellum. ADEM usually follows infection or vaccination, especially in children. One-quarter of patients with ADEM will develop multiple sclerosis (MS), often causing difficulty differentiating the first attack of MS from ADEM. However, ADEM is usually uniphasic and has a favorable long-term prognosis.

APPROACH TO:

Acute Disseminated Encephalomyelitis                                        

DEFINITIONS

ACUTE DISSEMINATED ENCEPHALOMYELITIS (ADEM): ADEM is an acute, uniphasic syndrome caused by an immune-mediated inflammatory demyelination. It often is associated with recent vaccination or viral illness.

ACUTE NECROTIZING HEMORRHAGIC ENCEPHALOMYELITIS (ANHE):

ANHE is a hyperacute form of ADEM with similar symptoms and etiology. It can rapidly progress to coma and death.

CLINICAL APPROACH

Etiologies and Clinical Presentation

ADEM can occur as a postinfectious complication in 1:400 to 1:2000 patients with measles, 1:600 patients with mumps, 1:10,000 patients with varicella, and 1:20,000 rubella patients. It is a postvaccination complication in 1:63 to 1:300,000 patients following vaccinia (smallpox vaccine) and can also occur following other immunizations, including diphtheria (tetanus), pertussis, and rubella.

ADEM is a monophasic illness characterized by multiple neurologic signs and symptoms reflecting compromise of the brainstem, spinal cord, cerebrum, optic nerves, and cerebellum. The symptoms appear suddenly 1 to 3 weeks following the infection and can include headache, nausea, vomiting, and confusion. It may progress to obtundation and coma. The etiopathogenesis of ADEM is multifactorial. In a subset of patients who are genetically susceptible to these disorders, the immune system is triggered to react to myelin by an environmental trigger, either by a vaccine or by a virus, and that sets up a cascade of events that causes ADEM.

In addition to the above-noted symptoms of ADEM, patients can have hemiparesis, hemisensory compromise, ataxia, optic neuritis, transverse myelitis, seizures, myoclonus, and memory loss. When ADEM follows mumps, the disease usually presents with cerebellar ataxia.

ADEM is likely a T-cell–mediated autoimmune disease targeting myelin/oligodendrocyte antigens, including myelin basic protein. Viral infection may lead to ADEM by causing downregulation of CD4+ suppressor T cells and activation of myelin-reactive T-helper cells.

Neuropathology of ADEM consists of perivenular inflammatory myelinopathy, with engorgement of veins in the white matter of the brain. There is perivascular edema with significant mononuclear infiltration, primarily lymphocytes and macrophages. The primary finding is perivenular demyelination with relative sparing of axons.

The diagnosis of ADEM primarily focuses on the clinical presentation of a uniphasic illness with multifocal central nervous system (CNS) involvement and encephalopathy. The most challenging aspect of its diagnosis is in distinguishing it from a first attack of MS. Clinically, the encephalopathy distinguishes ADEM from typical MS. Cerebrospinal fluid (CSF) findings can be abnormal but are not specific for ADEM (eg, mononuclear pleocytosis, mildly elevated protein), although oligoclonal bands, which are found in MS, should be absent. Magnetic resonance imaging (MRI) of the brain reveals hyperintense white matter T2-weighted signals and enhancement on T1-weighted images. The lesions vary in size because of the significant associated edema. The lesions described are rather extensive, poorly defined, and more often located in the peripheral subcortical cerebral white matter. Lesions in the thalami are more often described in ADEM than MS and can be a useful finding that suggests ADEM. Conversely, periventricular lesions are less common in ADEM than in MS.

The differential diagnosis of ADEM is the same as that noted in Case 24 for MS. The fact that ADEM is monophasic, whereas MS is usually not, and the clear time frame of feeling well for several weeks following a viral illness, respectively, help differentiate ADEM from MS and an acute viral episode.

The prognosis of ADEM is fairly good. However, approximately one-quarter (up to one-third) of these patients will subsequently relapse following the acute illness. If relapse occurs, the physician should suspect MS.

TREATMENT

If there is any suspicion of encephalitis, empiric acyclovir should be started until an infectious cause such as herpes simplex virus encephalitis is excluded. Immune suppression is the main treatment for ADEM. High-dose steroids can be used to shorten the duration of illness, and patients who do not respond to steroids can be treated with intravenous immunoglobulin (IVIg) or plasmapheresis. In severe cases, it is important to maintain vital functions, maintain fluid and electrolyte balance, and avoid pneumonia, urinary infection, and decubitus ulcers.

CASE CORRELATION

• See also Case 24 (Multiple Sclerosis)

COMPREHENSION QUESTIONS

25.1 Select the combination of signs and symptoms that best help to distinguish ADEM from a first attack MS.

A. Oligoclonal bands in CSF, recurrent symptoms, positive vaccination history

B. Positive vaccination history, lesions of the thalami, mental confusion

C. Pleocytosis in CSF, recurrent symptoms, positive vaccination history

D. Recent viral exposure, mental confusion, late ataxia

25.2 A 43-year-old woman is diagnosed with acute lower extremity weakness caused by ADEM. Which of the following is the best therapy for this condition?

A. Interferon 1b

B. Corticosteroid therapy

C. Amantadine

D. Immunoglobulin therapy

25.3 A 33-year-old man presents to his physician with complaints of weakness in both of his legs and urinary incontinence of 2 days’ duration. Approximately 2 weeks previously, he had a “flu-like” illness. Which of the following is most likely to be present?

A. Sensorineural hearing loss

B. Ataxia

C. Facial nerve palsy

D. Tinnitus

ANSWERS

25.1 B. In the absence of a biological marker, the distinction between ADEM and MS cannot be made with certainty at the time of first presentation. However, certain features are more indicative of ADEM, including a viral prodrome or recent vaccination exposure, early-onset ataxia, high lesion load on MRI, involvement of the deep gray matter, especially thalami, and absence of

oligoclonal bands.

25.2 B. Corticosteroids can help to reduce the duration and severity of symptoms in patients with ADEM. Intravenous gamma globulin therapy remains controversial, although it has been used. Standard of care for patients with MS are immune-modulating agents Food and Drug Administration (FDA) approved for MS, such as interferon beta-1b therapy. Amantadine is an antiviral agent helpful for influenza and also has slight therapeutic value for Parkinson disease A and for MS.

25.3 B. This patient has a typical presentation of ADEM. While ADEM patients can have hemiparesis, hemisensory compromise, ataxia, optic neuritis, transverse myelitis, seizures, myoclonus, and memory loss, sensorineural hearing loss, facial nerve paralysis, and tinnitus are not a complication of the disease.

    CLINICAL PEARLS    

▶ Acute disseminated encephalomyelitis (ADEM) is a “rare disease” affecting less than 200,000 people in the US population. ▶ The etiopathogenesis of ADEM is multifactorial and may include genetic susceptibility and environmental triggers (ie, vaccine or virus). ▶ Although ADEM is generally thought of as a monophasic disease, episodes of recurrent ADEM have been described, which are usually triggered by infections. It is possible that episodes of recurrent ADEM are multiple episodes of MS, and one should tailor management accordingly. ▶ In the absence of a biological marker, differentiation of ADEM from the initial presentation of MS may not be possible.

REFERENCES

Minagar A, Sheremata WA. Acute disseminated encephalomyelitis. In: Evans RW, ed. Saunders Manual of Neurologic Practice. Philadelphia, PA: Saunders/Elsevier; 2003:241-243. 

Sadiq SA. Multiple sclerosis. In: Rowland LP, ed. Merritt’s Neurology. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:941-961. 

Wingerchuk DM. Acute disseminated encephalomyelitis, transverse myelitis, and neuromyelitis optica. Continuum (Minneap Minn). 2013;19(4):944-967.

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