encephalitis-acute disseminated encephalomyelitis...

Encephalitis - Acute disseminated

Encephalomyelitis

(ADEM)

Dr. Christian Korff

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ENCEPHALITIS-ADEMENCEPHALITIS-ADEM

DEFINITIONS

ENCEPHALITIS

Inflammation of the brain parenchyma

Histopathological diagnosis (inflammation,

oedema, neuronal cell death)

ENCEPHALOMYELITIS

Inflammatory process involving the brain and

spinal cord parenchyma

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MECHANISMS

ADEM

• Scattered, focal or multifocal (disseminated)

areas of inflammation and demyelination

• Subcortical and deep cortical white matter

• Gray matter involvement may be seen as well

(particularly in the thalamus)

• Autoimmune + genetic predisposition?

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• The encephalitis Working Group recognizes that certain clinical and neurodiagnosticfeatures may also be suggestive of acute encephalitis, allowing for a clinical diagnosis in the absence of tissue histopathology.

• It is this clinical diagnosis that is expected to be employed in the vast majority of situations utilizing these definitions.

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Clinical diagnosis

Brain dysfunction+

Clinical demonstration of inflammatory process

Clinical diagnosis

Brain dysfunction

• Cortical• Subcortical• Both

• Diffuse

– Consciousness, cognition,

behavior

• Focal

– Focal neurological deficits

• Both

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Clinical diagnosis

Inflammatory process

• Fever (> or = 38.0°C)• CSF pleocytosis

• Suggestive MRI and EEG features

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EPIDEMIOLOGY

ENCEPHALITIS (overall)

� Incidence : 0.08/100’000 (hospitalbased)-7.4/100’000 (population based)

� Geographical repartition : widespread, germs vary

� Children are at higher risk than adults

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EPIDEMIOLOGY

ADEM

� Incidence : 0.07/100’000 children /

year – 0.64/100’000 persons / year

� Geographical repartition : widespread

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ETIOLOGY

ENCEPHALITIS

Infectious

Metabolic

Autoimmune

Toxic

Neoplastic

…

Unknown: 70%!

ADEM

Post-infectious

Post-immunizations

…

Unknown: 26%!(Tenembaum, 2002)

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PROGNOSIS

ENCEPHALITIS

� High risk of

neurological

sequelae

� High mortality with

certain germs: up to

33% with HSV1

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ADEM

� Usually excellent

� Minor sequeleae in

10-30% of patients

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ENCEPHALITIS ETIOLOGY: AUTOIMMUNE

Various autoantibodies have been involved:

Glutamatergic NMDA- or AMPA-receptors

Voltage-gated potassium channels

GABAa and GABAb receptors

Glutamic acid decarboxylase

Folate receptors

…

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ADEM ETIOLOGY: IMMUNIZATIONS

Japanese encephalitis

Yellow fever

Measles

Influenza

Smallpox

Anthrax

…

• “The only epidemiologically and pathologically

proven association of an antecedent event is

with antirabies vaccination using the Semple

rabies vaccine (a vaccine derived from

sheep/mouse brains); such association has not

been observed with modern formulations of

rabies vaccine » Sejvar, 2007

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ADEM ETIOLOGY: IMMUNIZATIONS

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ENCEPHALITIS

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ADEM

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ENCEPHALITIS ADEM

+ -

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• ADEM is distinguished from acute encephalitis

by

– (a) a predominance of demyelinating, rather than

cytotoxic injury

– (b) a temporal association with a specific inciting

immunogenic challenge

• Infection

• immunization

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• Autoimmune encephalitis, behavioral changes

and movement disorder

IMG_0281.MOV

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NMDA-R

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NMDA-R

Blood: NMDA-R autoantibodies

CSF: NMDA-R autoantibodies, oligoclonal

distribution type 2 (intrathecal synthesis)

Treatments: iv methylprednisolone, iv

Immunoglobulins, plasma exchanges, rituximab

• Evolution:

– At 2 months of follow-up: no sequelae!

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NMDA-R

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ENCEPHALITIS + ADEM

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LUMBAR PUNCTURE:


ENCEPHALITIS + ADEM

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LUMBAR PUNCTURE:


ENCEPHALITIS ADEM

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= Iliac crest = L4

LUMBAR PUNCTURE: TECHNICAL ASPECTS

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ENCEPHALITIS + ADEM

• EEG signs compatible with encephalitis

– Diffuse, multifocal or focal epileptiform activity, or slowing

– Absent organisation and variability

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Herpes viruses are predominantly (but not specifically) attracted by

temporal lobes

ENCEPHALITIS (HSV) ADEM

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EEG

Laoprasert, Atlas of pediatric EEG, 2011

• High signal intensity in T2, diffusion-weighted and FLAIR sequences

• Low signal intensity in T1 sequences

• Edema, cytotoxic changes, and hemorrhage suggest a viral etiology

• ADEM suggestive locations:– Periventricular white matter(50%), basal ganglia (50%), brainstem /

cerebellum / spinal cord (30-50% each)

• MRI may also be normal in both situations

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Early MRI features suggestive of encephalitis

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ENCEPHALITISS. pneumoniae

DWI sequenceT1 sequence T2 sequence

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ADEM

FLAIR sequences

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Level 1 diagnostic certainty


ENCEPHALITIS

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ENCEPHALITIS

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ENCEPHALITIS

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EXCLUSION CRITERIA

ENCEPHALITIS

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ADEM

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ADEMLevel 2 diagnostic certainty

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ADEMLevel 3 diagnostic certainty

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ADEM

EXCLUSION CRITERIA

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TREATMENT (proposal)

• acyclovir, 30 mg/kg/day

+

• iv methylprednisolone, 20-30 mg/kg/day,

3-5 days

If unresponsive

• iv immunoglobulins, 2g/kg (total dose),

over 2-5 days

• plasma exchanges


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REFERENCES

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Thank you

Dr Christian Korff

encephalitis-acute disseminated encephalomyelitis...

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