Case record... Acute disseminated encephalomyelitis

1. CASE OF THE WEEK
PROFESSOR YASSER METWALLY
CLINICAL PICTURE
CLINICAL PICTURE
A 18 years old female patient presented clinically with disturbed level of consciousness, recurrent grand mal fits, bilateral
optic neuritis and meningeal irritation signs. The patient gradually improved during hospital stay and was discharged two
weeks following admission after almost full recovery.
RADIOLOGICAL FINDINGS
RADIOLOGICAL FINDINGS
Figure 1. Acute disseminated encephalomyelitis (ADEM). Postcontrast MRI T1 images showings scattered hypointense
rounded and oval lesions, mostly situated at the junction of deep cortical gray and subcortical white matter. The
immediate periventricular region is spared. Lesions are mostly larger than MS lesions and did not show contrast
enhancement. Some lesions are seen encroaching upon the cortical grey matter. In general lesions did not have marked
mass effect.

2. Figure 2. Acute disseminated encephalomyelitis (ADEM). Postcontrast MRI T1 images showings scattered hypointense
rounded and oval lesions, mostly situated at the junction of deep cortical gray and subcortical white matter. The
immediate periventricular region is spared. Lesions are mostly larger than MS lesions and did not show contrast
enhancement. Some lesions are seen encroaching upon the cortical grey matter. In general lesions did not have marked
mass effect.
Figure 3. A case of acute
disseminated encephalomyelitis.
Notice that the multifocal cortical /
subcortical hyperintense foci are
sparing the periventricular region,
and this is the classic pattern in
ADEM. The foci, although of large
size they have mild mass effect.

3. Figure 4. Acute disseminated encephalomyelitis (ADEM). Notice that the multifocal cortical / subcortical lesions are
sparing the periventricular region. The ADEM lesions are hypointense on MRI T1 images and hyperintense on MRI T2
and FLAIR images. ADEM lesions, though large, exert mild mass effect.
Figure 5. Acute disseminated encephalomyelitis
(ADEM). Notice that the multifocal cortical /
subcortical lesions are sparing the periventricular
region. The ADEM lesions are hypointense on MRI T1
images and hyperintense on MRI T2 and FLAIR
images. ADEM lesions, though large, exert mild mass
effect.
DIAGNOSIS:
DIAGNOSIS: ACUTE DISSEMINATED ENCEPHALOMYELITIS (ADEM)

4. DISCUSSION
DISCUSSION
Acute disseminated encephalomyelitis (ADEM) presents as an acute-onset neurological dysfunction following a triggering
event such as an infection or vaccination. Patients present with polysymptomatic neurological dysfunction, and imaging
shows multifocal white matter lesions in the brain and spinal cord. Clinical evaluation, magnetic resonance imaging, and
cerebrospinal fluid study are most useful in establishing the diagnosis and ruling out important differential diagnoses.
Corticosteroids are the mainstay of treatment and the role of other modalities of treatment, such as plasma exchange and
intravenous immunoglobulin, require further study. Prognosis is generally good. The recently proposed consensus
definitions are likely to facilitate delineation of ADEM from other acquired demyelinating disorders.
Acute disseminated encephalomyelitis (ADEM) has evolved considerably since the first case description of a patient with
post-measles neurological dysfunction by Lucas in 1790. [1] Histopathologic and immunologic studies have provided
considerable insight into the mechanism of the disease, and the advent of magnetic resonance imaging (MRI) has
facilitated early diagnosis. With the recent introduction of consensus definitions, it is now established as a well-delineated
entity. ADEM is a monophasic, inflammatory demyelinating disorder of the central nervous system (CNS). Clinical
examination reveals polysymptomatic neurological involvement and imaging shows multifocal demyelinating lesions in the
brain and spinal cord. It is an immune-mediated disorder that usually follows infections or vaccinations. [2,3] Though
previously described as an illness with poor prognosis, recent studies have demonstrated improved outcomes following the
introduction of effective immunomodulation. [4,5,6,7] This article will focus on the recent trends in the diagnosis and
management of ADEM.
 Epidemiology
The incidence of ADEM has been estimated to be 0.4 per 100,000 population per year [8] and it may represent 30% of all
childhood encephalitic illnesses. [9] ADEM more commonly affects children and young adults, probably because of
exposure to frequent vaccinations and exanthematous and upper respiratory tract infections in this age-group.
[6,7,10,11,12,66] The mean age of onset in children ranges from 5 to 8 years. [6,12,13] ADEM generally does not show a
predilection for any one sex, though two recent studies have shown a male predominance among the victims. [13,14]
ADEM occurs throughout the year, but there is a significant increase in incidence during winter and spring. [6,7]
 Triggering Events
ADEM typically follows an antigenic challenge, such as infection or vaccination, which activates the immune system.
Exanthematous fevers such as measles, mumps, and rubella are the usual triggering infections. Recently, there has been a
distinct change in the trend and, in regions with extensive immunization coverage, nonspecific upper respiratory tract
infections are the most common triggering events. [11] However, ADEM following vaccine-preventable diseases is still
prevalent in Egypt. [15] The association with infection may be difficult to establish and only 70% of ADEM patients report
a triggering event. Though extensive microbiological investigations have led to the inclusion of a wide spectrum of
infections in the list of those alleged to cause ADEM [Table - 1], they may fail to identify a cause in the majority of cases.
[6,7,10]
Table 1. Infections alleged to cause ADEM
Viral Measles, Mumps, Varicella, Rubella, Influenza, A,B Hepatitis, A,B Coxsackie, Epstein-Barr, Dengue [16]
and HIV [17]
Bacterial Mycoplasma pneumoniae, Borrelia burgdorferi, Mycobacterium tuberculosis, Brucella, Chlamydia,
Legionella, Salmonella typhi, and Leptospira, Campylobacter, Streptococcus pyogenes
Vaccination Rabies, Measles, Rubella, Smallpox, Diphtheria, Mumps, Tetanus, antitoxin, Pertussis, Japanese
encephalitis, Polio, Hepatitis B, Influenza, and Meningococcal A, and C
Drugs Gold, Arsenical compounds, Sulfonamides, streptomycin/PAS
Miscellaneous Allogenic bone marrow transplantation [19], Heart-lung transplantation [19] Herbal extracts [20],
Ventriculo-atrial shunts, [21] Stings, Leprosy type I reaction
Post-immunization ADEM occurs most frequently following measles, rubella, or mumps vaccination. Many vaccines have
been implicated in the causation of ADEM [Table - 1]. In countries where neural tissue-based vaccines are still used,
antirabies immunization with either BPL (betapropionolactone inactivated) or Semple (phenol inactivated) vaccines are
important causes for ADEM. [4]
 Clinical Features
The spectrum of neurological symptoms and signs in ADEM is broad, reflecting widespread central and peripheral
nervous system (PNS) involvement. There may be a prodrome consisting of fever, headache, vomiting, and malaise.

5. Neurological dysfunction generally occurs within 3-6 weeks of the triggering event and may appear abruptly or may
progress over several days. [6,7] Generally, ADEM is a monophasic illness and its severity may range from mild disease,
with headache, subtle drowsiness, and irritability, to fulminant disease characterized by coma, decerebration, and
respiratory failure. The distribution of the lesions in the nervous system determines the clinical presentation, and the
commonest features are altered sensorium, pyramidal dysfunction, cerebellar ataxia, optic neuritis, and/or myelitis.
Retention of urine, urinary frequency, urgency, or incontinence may occur during the acute stage and lower urinary tract
dysfunction may persist even after disappearance of other neurological deficits. [23] Seizures are not uncommon and may
be of focal or generalized type . [24] There may be additional features such as fever, headache, and meningismus, with the
disease mimicking meningitis. Children under 3 years generally present only with encephalopathy, probably because they
have immature myelin. [2,7]
ADEM may have various atypical presentations. Behavioral disturbances may occasionally be the sole symptom. Presence
of flaccidity and areflexia in an otherwise typical case of ADEM betrays additional PNS involvement, which is most
commonly at the level of the spinal roots; [25] this picture is frequently seen in antirabies vaccination-related ADEM. [4]
Combined CNS and PNS demyelination may suggest the possibility of shared pathological epitopes. [26] There is evidence
to suggest that central (ADEM) and peripheral (acute and chronic inflammatory demyelinating polyradiculoneuropathy)
demyelinating disorders represent two ends of a spectrum and overlap of clinical features may occur. [27] Extrapyramidal
manifestations such as chorea and dystonia are rare but may be prominent in ADEM following group A streptococcal
infection. [28] Occasional patients may present with focal deficits, clinical features of raised intracranial pressure, and
imaging results suggesting a mass lesion. Such a presentation of ADEM, tumefactive demyelination , may be mistaken for
neoplasm till histopathology establishes the diagnosis. The pattern of neurological dysfunction may be influenced by the
type of triggering event. For example, post-mumps demyelination commonly presents as myelitis, post-varicella
demyelination has cerebellar ataxia as its hallmark, and rubella-associated ADEM often has an explosive onset of
symptoms, seizures and mild pyramidal dysfunction. [29] Acute hemorrhagic leukoencephalitis (AHLE) and acute
necrotizing hemorrhagic leukoencephalitis (ANHLE) of Weston Hurst represent the hyperacute, fulminant form of
postinfectious demyelination [2] [Table - 2].
Table 2. ADEM versus Acute hemorrhagic leukoencephalitis (AHLE)
Feature ADEM AHLE
Age group Children Young adult
Triggering events Viral exanthema, respiratory tract infection, respiratory tract infection
vaccination
Onset Acute Hyperacute, fulminant
Blood picture Normal Leukocytosis
ESR/acute phase Normal Elevated
reactant
Urine Normal Proteinuria
CSF cellularity Mononuclear Neutrophils, red blood cells
Neuroimaging Multifocal white matter lesions Large lesions, mass effect, hemorrhage, necrosis
Pathology Periventricular demyelination, inflammation Fibrinoid necrosis, hemorrhage, necrosis,
demyelination
Prognosis Good Bad
 Consensus Definition for ADEM
Clinical research in ADEM has always been hampered by the lack of a uniform case definition, resulting in heterogeneous,
incomparable study populations. The recent introduction of consensus definitions for children by the International
Pediatric MS Study Group is likely to facilitate the differentiation of monophasic ADEM from other acquired
demyelinating conditions [Table - 3]. [30] According to the consensus definition patients should have an acute or subacute
onset of the first clinical event of multifocal CNS affection, characterized by polysymptomatic neurological dysfunction.
Encephalopathy is an essential clinical feature; it is defined as either behavioral changes, alteration in consciousness, or
both. MRI brain must show focal or multifocal lesions greater than 1-2 cm in size, which must be predominantly in the
white matter, though it may also be present in the grey matter such as the basal ganglia or thalamus. In addition, the spinal
cord may show confluent lesions. The clinical event must have a presumed inflammatory or demyelinating basis, without
other etiologies. It should be followed by improvement, either clinically or on MRI, though there may be residual deficits.
New or fluctuating symptoms and signs or MRI findings within three months of the initial event are considered part of the
initial acute event.
Table 3. Monophasic ADEM and other acquired demyelinating conditions
Monophasic multifocal disease

6.  Acute disseminated encephalomyelitis
 Acute hemorrhagic leukoencephalitis
Clinically isolated syndromes
 Transverse myelitis
 Optic neuritis
 Cerebellitis
 Brain stem dysfunction
Multiphasic and recurrent acute disseminated encephalomyelitis
 Is ADEM always a monophasic disease?
Though ADEM is classically described as a monophasic illness, a biphasic temporal profile has been documented in 0-20%
of patients. [6,7,13,14] Such patients do not proceed to develop multiple sclerosis (MS). [7] It is now possible to define
patients of ADEM who develop relapses, i.e., multiphasic or recurrent ADEM. [30] A new clinical event should have
occurred that meets the case definition of ADEM. The new event should occur three or more months after the initial
episode. The event should occur when the patient is not on steroids and at least one month after completion of therapy. In
multiphasic ADEM , clinical examination and MRI should demonstrate involvement of new areas of the CNS during the
relapse. In recurrent ADEM , clinical findings and MRI should suggest involvement of the same areas that had been
involved in the initial ADEM episode.
 Investigations
 Cerebrospinal fluid
Cerebrospinal fluid (CSF) should be analyzed to exclude the differential diagnoses of ADEM, especially the CNS
infections. CSF is abnormal in nearly three-fourth of ADEM patients and is characterized by pleocytosis, elevated proteins,
and normal sugar values. [6,7] Cellular response is usually lymphocytic and counts are moderately elevated. Intrathecal
oligoclonal immunoglobulin synthesis is rare and usually disappears after clinical recovery. [7,13]
 Electrophysiology
Generalized slowing is the most common finding in electroencephalography and is nonspecific. Patients with spinal cord,
brain stem, or optic nerve involvement may have abnormal somatosensory, brain stem auditory, or visual evoked
potentials, respectively. [2]
 Imaging
Computed tomography (CT) may demonstrate hypodense lesions in the white matter and basal ganglia. However, initial
CT imaging may be normal in 40% of cases, as lesions may appear only 5-14 days after the onset of clinical signs. [2,31,66]
MRI forms the cornerstone for diagnosis of ADEM and is more sensitive than CT in detecting lesions. Abnormalities are
best appreciated in T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences as patchy, multifocal, poorly
marginated lesions of increased signal intensity. White matter lesions are usually asymmetric and most frequently situated
subcortically, in the cerebellum, brain stem, and spinal cord. [32,33] Thalamic and basal ganglia lesions are seen in nearly
one-third of cases and may be symmetric. Corpus callosum may be affected when involvement is extensive. [3] The spinal
cord becomes swollen and may show increased signal intensities, most commonly in the thoracic region. Enhancement
after contrast administration is variable and occurs in acute lesions due to disruption of the blood-brain barrier. [32,33]
Lesions may show complete ring, incomplete ring ('open-ring sign'), nodular, gyral, or spotty patterns of enhancement.
[33,34] Tumefactive demyelination appears as a large white matter lesion with mass effect. Though clinically a monophasic
illness, new lesions may appear serially over several weeks and hence, may appear to be of varying ages on MRI. [33]
Occasionally, initial MR images may be normal and lesions may appear in images repeated later in the course of the
disease or even during the stage of clinical improvement. [35] Though lesions generally resolve with treatment,
hyperintensities may persist in MRI long after clinical recovery and is due to astrocytic hyperplasia, gliosis, or cystic
changes. [36,37] Resolution of MRI abnormalities within six months of the demyelinating episode favors the diagnosis of
ADEM. [38]

7. Figure 6. Acute disseminated encephalomyelitis. Notice the
contrast enhancement which is characteristic of acute lesions.
Also notice that many lesions are situated at the junction of
deep cortical gray and subcortical white matter which is
characteristic of ADEM
Figure 7. In acute disseminated
encephalomyelitis tumefactive
demyelination appears as a large white
matter lesion with mass effect.
 Newer modalities
Quantitative proton MR spectroscopic imaging has shown low N-acetylaspartate (NAA) and high lactate levels in acute
lesions, which normalize after recovery. [39] Further studies are required to assess the role of MR imaging techniques such
as magnetization transfer and diffusion tensor imaging in detecting early or small lesions. [40] Abnormalities in 99m Tc-
HMPAO SPECT appear as areas of hypoperfusion, which are more extensive than the abnormalities seen in MRI and may
parallel the time course of the disease more accurately. [41] Notably, in patients with residual cognitive deficits, SPECT
with acetazolamide is able to detect persistent abnormalities from areas where lesions had apparently resolved on MRI.
[42,43]
 Pathogenesis
 Immunology
The lesions of ADEM are due to autoimmune-mediated inflammation of the CNS, and the absence of viral or bacterial
antigens in the CNS is nearly universal. [5,7] T-cells have been shown to play an important role, possibly through
molecular mimicry or by nonspecific activation of autoreactive T-cell clones. [3] Interleukin-6 may be associated with
proliferation of B-lymphocytes and immunoglobulin G synthesis. [44] Anti-basal ganglia antibodies have been
demonstrated in children with classical features of ADEM following streptococcal infection. [28] A complex interplay
between cytokines and adhesion molecules is responsible for the cellular events of inflammatory encephalomyelitis and
oligodendrocyte death. An association has been established between ADEM and certain class II HLA alleles, indicating

8. that genetic factors may play a role in immunoregulation and progression from infection/vaccination to ADEM. [29,66]
 Pathology
Histopathology studies have demonstrated perivenous cuffing with inflammatory cells, especially lymphocytes and
macrophages, and loss of myelin. Most of the changes are seen in white matter. However, grey matter also shows changes,
including chromatolysis and neuronal loss, especially in the thalami, deep cortical lamina, and hypothalamus. The
meninges may also show inflammatory reaction. [2,45]
Figure 8. Histopathology studies In ADEM have demonstrated
perivenous cuffing with inflammatory cells, especially
lymphocytes and macrophages, and loss of myelin
 Differential Diagnosis
In the absence of specific biological markers, the diagnosis of ADEM is based upon clinical and imaging features. Clinical
evaluation, neuroimaging, and blood and CSF analysis can help to distinguish ADEM from other conditions. [46] Herpes
simplex encephalitis commonly presents with abnormal behavior and focal/secondary generalized seizures, which are more
frequent and difficult to treat than in ADEM. MRI, EEG, and CSF polymerase chain reaction for Herpes simplex virus
help in confirmation of the diagnosis. Japanese encephalitis presents with acute encephalopathy. MRI may show bilateral
thalamic lesions, akin to ADEM. History, EEG findings, and CSF evidence of antibodies to the virus are useful for
differentiation. Other infections such as bacterial meningitis and brain abscess can be ruled out by relevant investigations
such as imaging and lumbar puncture. Complicated tuberculous meningitis may sometimes mimic ADEM and can be
excluded if CSF sugar is normal and cultures are sterile.
Neuromyelitis optica is characterized by optic neuritis and myelitis, with spinal lesions extending over three or more
segments, features that may also be seen in ADEM. It may be distinguished from ADEM by the relative paucity of white
matter lesions in MRI of the brain and presence of antibodies to aquaporin 4 (NMO-IgG). [47] Patients with Behcet's
disease may present with multifocal neurological signs due to brain and spinal cord involvement. Clinical and imaging
features may resemble ADEM, and the history of recurrent mucocutaneous ulcers of the mouth and genitalia will be
essential to establish the diagnosis. Antiphospholipid antibody syndrome may also mimic the clinical and MRI features of
ADEM and should be ruled out by measuring the specific antibodies. Immune-mediated disorders such as systemic lupus
erythematosus, Sjögren syndrome, and sarcoidosis may present with neurological dysfunction and multifocal white matter
changes and can be diagnosed by history and relevant blood tests. Susac's syndrome may present with subacute
encephalopathy, with MRI of the brain showing multiple white matter lesions; however, it can be differentiated from
ADEM based on additional features such as the presence of headache, visual impairment due to retinal artery branch
occlusion, sensorineural hearing loss, and specific involvement of central corpus callosum in MRI. [48,66] The diagnosis of
recurrent ADEM should be made only after excluding other lesions such as arteriovenous malformations, neoplasms, and
vasculitis.

9. Metabolic leukoencephalopathies such as metachromatic leukodystrophy (MLD), adrenoleukodystrophy, and MELAS
(mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) may mimic childhood ADEM.
Leukodystrophies may have a stepladder clinical course, with the exacerbations associated with febrile illnesses. History
may reveal prior neurological dysfunction. MRI may show symmetric, confluent white matter lesions, hallmarks of
inherited rather than acquired leukoencephalopathies. Specific investigations such as serum aryl sulfatase for MLD and
very long-chain fatty acids (VLCFA) levels for adrenoleukodystrophy will confirm the diagnosis. The clinical features of
mitochondrial cytopathies such as MELAS may be similar to that of ADEM and lesions seen on MRI may be transient.
Serum and CSF lactate levels may be elevated during the acute episode and MR spectroscopic imaging may show elevated
lactate in the affected tissues.
 ADEM or multiple sclerosis?
In a patient presenting with neurological dysfunction and MRI showing multiple white matter lesions, the most important
differential diagnosis is MS. Distinguishing between ADEM and MS is a diagnostic challenge and has important
therapeutic and prognostic implications. There are several clinical, imaging, and laboratory parameters that may be useful
to distinguish between the two [Table - 4]. CSF electrophoresis has shown a significant reduction in the beta-1 globulin
fraction in patients with MS as compared to those with ADEM and this may be a potential CSF marker. [49] Features that
strongly favor ADEM include a history of preceding infection, polysymptomatic neurological dysfunction, encephalopathy,
grey matter involvement on MRI, and absence of oligoclonal bands in CSF. [6,7] Often, distinction between these two
conditions cannot be made with certainty and follow-up with serial MRI may be necessary to establish the diagnosis.
[3,36,66]
Table 4. Differences between ADEM and multiple sclerosis
Feature ADEM MS
Onset Abrupt Subacute
Triggering events Preceding infection or vaccination in 70 Uncommon
% of cases
Age group More common in children More common in young adult
Temporal profile Monophasic, rarely relapsing Relapsing
Clinical features
Altered sensorium More common Rare
Seizures More common Rare
Neurological deficit Multifocal Usually single deficit
Optic neuritis Bilateral Unilateral
Myelitis Complete, transverse myelitis Partial myelopathy
Lower motor neuron signs More common Rare
Headache More common Rare
Meningismus More common Rare
Neuroimaging findings
Distribution of the lesions Bilateral extensive lesions Scattered asymmetric lesions
White matter lesions Confluent, ill-defined periventricular and Well-defined, with periventricular
subcortical white matter lesions preponderance
Corpus callosum lesions Rare Common
Grey matter involvement Thalamic and basal ganglionic lesions are Uncommon
common
Edema and mass effect May be present Uncommon
Follow-up MRI No new lesions New lesions with dissemination in time
and place
Cerebrospinal fluid
Cell count Mild to moderate pleocytosis Normal to mild pleocytosis
Protein Increased Normal
Oligoclonal bands Uncommon, transient Common and persistent
Mortality 10-25 Uncommon
 Treatment

10. Public health initiatives are important for minimizing exposure to the triggering events of ADEM. These include
implementing effective vaccination programs and avoiding vaccines containing neural tissues or enveloped viruses. [2]
Early initiation of antibiotics for infections may not prevent the immune trigger that culminates in ADEM. [50] Treatment
of ADEM involves immunomodulation that aims to counter autoimmune-mediated inflammation. Though spontaneous
resolution has been described, recovery is usually incomplete and hence patients presenting in the acute stage with
significant, progressive neurological deficits should receive treatment. [51] In view of the rarity of ADEM, treatment
regimes for children and adults are based on anecdotal reports and lack validation by randomized controlled trials. High-
dose corticosteroids have become the first line of management and are associated with rapid recovery when given early in
the disease. [6,7,13,14,52] Earlier studies used ACTH, but nowadays either intravenous methylprednisolone (10-30
mg/kg/day, up to maximum of 1 gm/day) or dexamethasone (1 mg/kg/day) for 3 to 5 days are being used. [6,7,13,14] Full
recovery was reported in 50-80% of patients. Methylprednisolone treated patients have significantly better outcome with
respect to disability compared to those treated with dexamethasone. [13] In addition to immunosuppression, steroids also
have anti-inflammatory and antiedema actions, and the immediate improvement following administration of steroids is
likely to be due to reduction in cerebral edema. [53] Oral corticosteroids are continued and gradually tapered over six
weeks to minimize the risk of recurrence. [7] The role of corticosteroids in patients presenting late in the course of the
disease is questionable. [54] Vaccinations should be avoided during the first six months after recovery. [7]
Plasma exchange is another therapeutic modality, and its role in the management of demyelinating disorders that are
nonresponsive to corticosteroids has been established in one randomized control trial. [55] In most studies, 1-1.4 plasma
volumes were exchanged by continuous flow centrifugation and 70% of volume was replaced by 5% serum albumin, fresh-
frozen plasma, or hydroxyethyl starch. Patients received 2-20 exchanges, depending on the severity of illness and clinical
response. It is likely to be effective in patients of ADEM not responding to corticosteroids, especially when given early in
the course of the disease. [56,57] Intravenous immunoglobulin is yet another option and the results so far are impressive,
especially in corticosteroid nonresponders. In most studies, 0.4 gm/kg/day was given over 5 days and improvement was
noted within 2 to 3 days. [58,59,60] However, in most reported cases, patients had received prior corticosteroids and the
delayed effects of these drugs could not be ruled out as the reason for the improvement. At present, the evidence is
insufficient to design a treatment algorithm for ADEM. However, based on the available reports, plasma exchange and
intravenous immunoglobulin are likely to be second-line therapies when corticosteroids fail. The relative efficacies of the
two have not been evaluated. The choice of second-line therapy should be individualized, depending upon the type of CNS
involvement, complications, and comorbidities. For example, autonomic dysfunction and hypotension would preclude the
use of plasma exchange. Anecdotal reports suggest that intravenous immunoglobulin may be more effective in patients
with who also have PNS involvement [25] and plasma exchange in patients with tumefactive demyelination. [61]
Combination therapy with methylprednisolone and immunoglobulin has been reported to be successful in atypical cases of
ADEM. [62] Cyclophosphamide [52] and hypothermia [63] have been successfully tried in fulminant ADEM.
Hemicraniectomy has been reported to be lifesaving in patients with massive life-threatening cerebral edema refractory to
conventional medical management. [64,65]
 Outcome
ADEM is usually a monophasic illness lasting 2-4 weeks. [2] However recovery may continue for weeks or months. While
earlier studies reported mortality of 20% and significant morbidity amongst survivors, recent reports suggest excellent
outcomes, especially in children. [7,10,13,14] Visual impairment, weakness, lower urinary tract dysfunction, cognitive
impairment, and behavioral changes may persist at follow-up. [7,13,23] Children thought to have made a full recovery may
show subtle neurocognitive and behavioral changes on formal assessment, though these may be less severe than the
changes seen in children with MS. [43] Patients having progressive neurological dysfunction , altered sensorium, and
seizures have poor long-term outcomes. [24]
SUMMARY
SUMMARY
ADEM presents as an acute onset neurological dysfunction following infection or vaccination. Clinical evaluation, MRI,
and CSF study are most useful to establish the diagnosis and rule out important differential diagnoses. The recently
proposed consensus definitions are likely to facilitate delineation of ADEM from other acquired demyelinating disorders.
Corticosteroids are the most important treatment modality, while the role of other agents requires further study. Prognosis
is generally good.

11.  Addendum
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