Acute disseminated encephalomyelitis (ADEM)
Acute disseminated encephalomyelitis (ADEM) as the name would suggest, is featured by a monophasic acute inflammation and demyelination of white matter typically following a recent (1-2 weeks prior) viral infection or vaccination 4,6. Grey matter, especially that of the basal ganglia, is also often involved, albeit to a lesser extent, as is the spinal cord.
Typically, ADEM presents in children or adolescents (usually younger than 15 years of age). However, cases have been reported in all ages 12. Winter and spring seasonal peaks in the presentation have been observed in some studies, supporting the infectious aetiology of ADEM 9.
Less than 5% of all ADEM cases follow an immunisation 8.
Unlike many other demyelinating diseases (e.g. multiple sclerosis (MS) or neuromyelitis optica (NMO)), there is no female predilection for ADEM; if anything, there is slight male predominance 12.
ADEM is usually a monophasic illness, although, within the episode, individual lesions may be of varying stages of evolution, with different lesions maturing over a number of weeks 4. In 10% of cases, relapse within the first three months is encountered 12.
Unlike MS, symptoms are more systemic rather than focal and include fever, headache, decreased level of consciousness varying from lethargy to coma, seizure, and multifocal neurologic symptoms such as hemiparesis, cranial nerve palsies, and movement disorders; behavioural changes like depression, delusions, and psychosis may dominate the symptoms 3.
ADEM is thought to occur from a cross-reactivity in immunity to viral antigens, triggering a subsequent autoimmune attack on the CNS. In approximately half of confirmed cases, Anti-MOG (myelin oligodendrocyte glycoprotein) immunoglobulin G antibodies can be identified 12.
The pathological hallmark is perivenular inflammation with limited ‘‘sleeves of demyelination", which is also a feature of multiple sclerosis. However, multiple sclerosis typically presents confluent sheets of macrophage infiltration mixed with reactive astrocytes in completely demyelinated regions 9.
- cerebrospinal fluid pleocytosis 12
- cerebrospinal fluid may show an increase in myelin basic protein
- anti-MOG antibodies 12
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 the callososeptal interface is unusual. Lesions are usually bilateral but asymmetrical. Involvement of cerebral cortex, subcortical grey matter - especially the thalami - and the brainstem is not very common, but if present are helpful in distinguishing from multiple sclerosis 4,12.
In addition to lesions involving grey matter, antibodies to basal ganglia can also develop, especially in the setting of post-streptococcal pharyngitis, resulting in more diffuse involvement 11,12.
The spinal cord may show confluent intramedullary lesions with variable enhancement, but these are only seen in approximately one third of cases 12.
The lesions are usually indistinct regions of low density within the white matter and may demonstrate ring enhancement.
MRI is far more sensitive than CT and demonstrates lesions characteristic of demyelination:
- 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 peripherally 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 3.
Treatment and prognosis
Treatment typically consists of methylprednisolone, with immunoglobulin and cyclophosphamide reserved for patients refractory to steroids 4.
Complete recovery within one month is the most common outcome (50-60%), with sequelae (most commonly seizures) seen in a significant proportion of cases (20-30%).
In a small proportion (reported figures range form 10 to 20% 12) the course is more fulminant, frequently resulting in death. In such cases, the lesion may demonstrate haemorrhage and the condition are then known as acute haemorrhagic leukoencephalitis (Hurst disease) 12.
Relapsing forms of ADEM are certainly described (relapsing disseminated encephalomyelitis (RDEM) and multiphasic disseminated encephalomyelitis (MDEM)), although the demarcation between these and relapsing-remitting multiple sclerosis is contentious.
When the diagnosis of ADEM is made, progression to MS is not uncommon, reported in up to 35% of cases 4. As fever and infection are well known triggers for MS, it is perhaps not surprising that a history of recent infection is identified in clinically isolated syndrome (CIS).
General imaging differential considerations include:
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- 4. Hynson JL, Kornberg AJ, Coleman LT et-al. Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology. 2001;56 (10): 1308-12. Neurology (full text) - Pubmed citation
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- 8. Lee YJ. Acute disseminated encephalomyelitis in children: differential diagnosis from multiple sclerosis on the basis of clinical course. Korean J Pediatr. 2011;54 (6): 234-40. doi:10.3345/kjp.2011.54.6.234 - Free text at pubmed - Pubmed citation
- 9. Young NP, Weinshenker BG, Lucchinetti CF. Acute disseminated encephalomyelitis: current understanding and controversies. Semin Neurol. 2008;28 (1): 84-94. doi:10.1055/s-2007-1019130 - Pubmed citation
- 10. Wang PN, Fuh JL, Liu HC et-al. Acute disseminated encephalomyelitis in middle-aged or elderly patients. Eur. Neurol. 1996;36 (4): 219-23. Pubmed citation
- 11. Dale RC, Church AJ, Cardoso F et-al. Poststreptococcal acute disseminated encephalomyelitis with basal ganglia involvement and auto-reactive antibasal ganglia antibodies. Ann. Neurol. 2001;50 (5): 588-95. Pubmed citation
- 12. Sarbu N, Shih RY, Jones RV et-al. White Matter Diseases with Radiologic-Pathologic Correlation. Radiographics. 2016;36 (5): 1426-47. doi:10.1148/rg.2016160031 - Pubmed citation
- primary demyelinating disorders
- clinically isolated syndrome (CIS)
- radiologically isolated syndrome (RIS)
- multiple sclerosis (MS)
- neuromyelitis optica (NMO) (Devic disease)
- acute disseminated encephalomyelitis (ADEM) and acute haemorrhagic encephalomyelitis (AHEM)
- tumefactive demyelinating lesions
- transverse myelitis
- chronic inflammatory demyelinating polyneuropathy (CIDP)
- Guillain-Barre Syndrome (GBS)
- primary demyelinating disorders