Autoimmune encephalitis a term used in children presenting with neurological syndrome associated with serum and/ or cerebrospinal fluid antibodies directed against ion channels, receptors and associated proteins. It comprises group of clinical syndrome that can occur at all ages but preferentially affect younger adult and children. Auto antibodies against: Neuronal cell surface protein Synaptic receptors involved in transmission ,plasticity ,excitability. Triggers: Tumors, Post viral infections, Post vaccination. Autoimmune encephalitis includes ADEM Anti NMDAR encephalitis Encephalitis a/w GABA R antibodies NMOSD Opsoclonus-myoclonus & cerebellar - brainstem encephalitis Bickerstaff encephalitis Hashimoto encephalitis Rasmussen encephalitis Basal ganglia encephalitis CLIPPERS ROHHAD. ADEM is MC cause of autoimmune encephalitis in children and adolescents. Acute onset of polyfocal neurological deficit accompanied by encephalopathy and changes compatible with demyelination on MRI brain.

1. AUTOIMMUNE
ENCEPHALITIS
SPEAKER – DR CHAYANIKA MISHRA

2. INTRODUCTION:
◦ Autoimmune encephalitis a term used in children presenting with neurological syndrome associated
with serum and/ or cerebrospinal fluid antibodies directed against ion channels, receptors and
associated proteins.
◦ It comprises group of clinical syndrome that can occur at all ages but preferentially affect younger
adult and children.
◦ Auto antibodies against:
1. Neuronal cell surface protein
2. Synaptic receptors involved in transmission ,plasticity ,excitability.
◦ Triggers:
1. Tumors
2. Post viral infections
3. Post vaccination

3. AUTOIMMUNE ENCEPHALITIS IN CHILDREN
◦ ADEM
◦ Anti NMDAR encephalitis
◦ Encephalitis a/w GABA R antibodies
◦ NMOSD
◦ Opsoclonus-myoclonus & cerebellar - brainstem encephalitis
◦ Bickerstaff encephalitis
◦ Hashimoto encephalitis
◦ Rasmussen encephalitis
◦ Basal ganglia encephalitis
◦ CLIPPERS
◦ ROHHAD

4. ADEM:
◦ MC cause of autoimmune encephalitis in children and adolescents.
◦ Acute onset of polyfocal neurological deficit accompanied by encephalopathy and
changes compatible with demyelination on MRI brain.

5. EPIDEMIOLOGY:
◦ It can occur at any age most cases reported 5-8 yrs, slight male predominance.
◦ Usually it is monophasic, if recurrence occur 3 month or longer after the first episode termed as
MDEM (Multiphasic Disseminated Encephalo-Myelitis).
◦ 50% ADEM MOG (Myelin Oligodendrocyte Glycoprotein) Ab +, almost all case of MDEM MOG Ab +.
◦ ADEM can be followed by demyelination in a new location & if MOG-Ab negative - MS
◦ ADEM f/b relapse in specific location like
Optic nerve -ADEM-ON
◦ Optic nerve and spinal cord- NMOSD . Both frequently a/w MOG-Ab positive.

6. PATHOGENESIS:
Molecular
mimicry
• Post infectious
• Influenzae
• EBV
• CMV
• Varicella
• Enterovirus
• Measles, mumps, rubella
• HSV
• Mycoplasma pneumoniae
• Post vaccination
• Rabies
• Smallpox
• Measles
• Mumps
• Rubella
• JE-B
• DPT
• Influenzae

7. CLINICAL MANIFESTATION:
◦ Initial symptoms include- lethargy ,fever ,headache ,vomiting ,meningeal sign and seizure.
◦ Encephalopathy:
1. Is hallmark
2. Ranging from change in behaviour , persistent irritability to coma.
◦ Focal neurological deficit:
1. Difficult to ascertain in obtunded or very young child ,
2. Common neurological signs- visual loss, ataxia, motor and sensory deficit, bowel bladder dysfunction
if spinal cord demyelination occurs.
◦ It is usually rapidly progressive over days may need ICU admission particularly when
1. Brain stem dysfunction
2. Raised ICT.

8. DIAGNOSIS:
Clinical
CSF • Often normal, pleocytosis with lymphocytic or
monocytic predominance.
• Proteins can be elevated but true OCB rare.
• MOG AB +ve
Serum • MOG Ab +ve
EEG • Generalised slowing, but focal slowing or epileptiform
discharge may present.
MRI (Imaging study of choice) • B/L large multifocal sometimes confluent edematous
mass like lesions with variable enhancement within
white & gray matter.
• Typically appears to be of similar age.
• Repeat MRI after 3- 12 months – improvement or
complete resolution.
CT Scan • Normal/Hypodense lesions

9. MRI brain:

10. Treatment:
Symptomatic treatment
• Empirical antibiotics and antivirals should be considered when infective evaluations are pending
High dose steroids
• IV methylprednisolone- 20-30 mg/kg for 5 days (max. 1000mg/day)
• Followed by oral prednisolone 1-2 mg/kg/day over 4-6 weeks (max. 40-60 mg/day)
For refractory or severe cases
Others options
• IVIG – 2 gm/kg over 2-5 days
• Plasmapheresis- 5-7 exchange every other days

11. Prognosis:
◦ Most children experiences full motor recovery.
◦ But residual defect may be seen- cognitive deficit & behavioural changes.
Differential diagnosis:
◦ Multiple sclerosis
◦ Leukodystrophy
◦ Vasculitis
◦ Tumor
◦ Ab associated disorder

13. Anti NMDAR Encephalitis:
(N-Methyl D-Asparatate Receptor)
◦ Second MCC of AE.
◦ Female > Male ( < 12 years Male > Female)
◦ Underlying teratoma (40% of female >12 yrs ovarian teratoma)
◦ Pathogens:
1. Mycoplasma pneumoniae
2. HSV-1
3. HHV-6
4. Enterovirus
5. Influenzae
HSV Encephalitis
(Ab against GluN
1 subunit of
NMDAR)
2-12 weeks after
treatment
completion
Relapse of
symptoms-
Choreoathetosis
post HSV
Encephalitis

14. Pathogenesis
• IgG Ab target the Glu N1 subunit of
NMDA receptor

15. Clinical features:
Usually evolve in stages
Prodormal symptoms
• Viral illness like
fever, headache.
Psychiatric
manifestation
• Rapidly progressive
anxiety
• Mood disturbances
• Catatonia
• Bizzare behaviour
• Memory deficit
• Language
disintegration
• Insomnia
After few days to weeks
• Decreased level of
consciousness
• Seizure
• Limb or oral
dyskinesia
• Choreoathetoid
movements
• Autonomic
instability (tachy-
brady, fluctuation of
BP, hypoventilation,
hyperthermia,
sialorrhea)
In Teenagers & young adults:

16. In toddlers & infants:
Psychiatric manifestation- may
be missed
• Irritability
• New onset temper tantrum
• Agitation
• Aggression
• Reduced speech
• Mutism
• Autistic like regression
After few days to weeks
• Decreased level of
consciousness
• Seizure
• Limb or oral dyskinesia
• Choreoathetoid movements
• Autonomic instability- less
sever
• Some children may develop
cerebellar ataxia &
hemiparesis

17. Diagnosis:
Clinical
CSF Moderate lymphocytic pleocytosis
Increased protein synthesis & OCB ( less frequent)
NMDAR Ab – 100% sensitivity
Serum NMDAR Ab-85% sensitivity
EEG Focal or diffuse slow activity in delta & theta range
Characteristic- Extreme delta brush
MRI Brain Abnormal in 35%
T2 FLAIR – cortical and subcortical signal abnormality
MRI/USG Abdomen & Pelvis R/O teratoma

18. Extreme delta brush on EEG

19. Treatment:
◦ Symptomatic
management
◦ Tumor Removal
◦ Immunotherapy
First line
• Steroid, IVIg or Plasma exchange
50% treatment
failure
• Rituximab
• May used in combination or after 1st line therapy
If no response
• Cyclophosphamide

20. Prognosis:
Mortality Rate- 7%
Recovery (substantially/fully)- 80%
• May take as long as 2 years after symptoms onset
• Last symptoms to improve social interaction, language, executive function
Relapse- 15%
Milder than initial episodes, response well to immunotherapy
Efficacy of chronic immunosuppressant (azathioprine,MMF) in preventing relapse is unknown

21. D/D of NMDAR AE
DIFFERENTIAL DIAGNOSIS Differentiating features
Viral Encephalitis CSF findings, psychosis, dyskinesia -less
New onset psychosis No neurological manifestations
Neuroleptic malignant syndrome Dyskinesia, catatonia - absent
Relapsing post HSV encephalitis Viral PCR, response to acyclovir, progression of
necrotic changes on MRI
Drug/Toxins Ketamine, phencyclidine (dopamine agonist)
Systemic rheumatic disease Involvement of other organs (skin, joint, kidney,
blood vessels, blood forming cells)
CNS vasculitis FLAIR T2 MRI- Ischemia & microhemorrhages
Acquired demyelinating disease ADEM & NMOSD

22. Encephalitis with Ab against GABA-A
Receptor:
◦ Rare AE, that can affect children.
◦ In adults may occur with thymoma.
◦ Present with status epilepticus, refractory seizure.
◦ MRI (T2/FLAIR) brain shows- multifocal hyperintense abnormality.
◦ Treatment- Immunotherapy & removal of tumor.

23. Ophelia Syndrome
◦ Occur in a/w Hodgkin lymphoma.
◦ Predominantly affect young adults, teenager & children.
◦ Some develops Ab against mGluR5 receptor involved in learning & memory.
◦ Management:
1. Removal of tumor
2. Immunotherapy

24. Hashimoto Encephalopathy:
◦ Steroid responsive encephalopathy with autoimmuno-thyroiditis.
◦ Detection of TPO Ab in patients with acute/subacute encephalitis.
◦ Detection of TPO Ab is a marker of autoimmunity rather than a disease specific marker.
◦ So testing of more relevant Ab like NMDAR Ab should be done.

25. Bickerstaff Encephalitis:
◦ Rapid progression (<4wks) of
1. B/L external ophthalmoplegia
2. Ataxia
3. Decreased level of consciousness
◦ Mostly affect adults, but children of 3 yrs old have been identified.
◦ Serum GQ1b IgG Ab found in 66% cases.
◦ May develop hyporeflexia and overlap with MFS.
◦ MRI T2 signal abnormality (30%)- Brainstem, thalamus & cerebellum.
◦ Good response to immunotherapy.

26. Rasmussen encephalitis:
◦ Inflamatory encephalopathy c/b
1. Refracory focal seizures
2. Cognitive deterioration
3. Focal neurological deficit.
◦ Frequently affect children 6-8 yr old but
adolescents &adults can be affected.
Etiology:
◦ Unknown.
◦ Theories proposed are neuronal antibody &
T- cell mechanisms - triggered by viral
infection.
MRI Brain- Cerebral hemiatrophy

27. Management of Rasmussen encephalitis:
1. High dose steroid, IVIG or plasma exchange.
2. Rituximab & intraventricular Gamma interferon effective in isolated cases.
3. Tacrolimus- better outcome of neurological function & slower progression of cerebral atrophy
but no effect on seizure control.
4. Adalimumab( monoclonal antibody against TNF-alpha) shows seizure control &preservation of
cognitive function in 50% cases.
5. Most effective treatment for controlling seizure is functional hemispherectomy i.e. surgical
disconnection of affected hemisphere.

28. Autoimmune limbic encephalitis:
◦ Inflamatory process of the limbic system including medial temporal lobe, amygdala, cingulate gyrus.
◦ Most commonly found in adults.
◦ Some patients there is underlying tumor i.e. leukemia, ganglioneuroblastoma, neuroblastoma, small cell
carcinoma of ovary.
◦ Autoantibodies are-
1. VGKCs /LGI1(Leucine rich glioma inactivated 1)
2. Caspr2 antibodies

29. MRI of limbic encephalitis

30. Opsoclonus-myoclonus and other type of brainstem-
cerebellar encephalitis:
◦ In children- 50% have underlying NEUROBLASTOMA.
◦ In teenagers and young adults underlying TERATOMA usually in ovaries.
◦ Initially present with- irritability, ataxia, falling, myoclonus, tremor and drooling.
◦ Later- hypotonia, Opsoclonus c/b rapid, chaotic, multidirectional eye movement without saccadic interval.
◦ Immunotherapy improves abnormal eye movement but residual behavioral, language, cognitive problems
persists.
◦ Delay in treatment appears to be a/w poor outcome , therefore in case of neuroblastoma removal of the
tumor should not delay the start of immunotherapy.

31. CLIPPERS:
◦ Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids
◦ Pontine predominant encephalomyelitis
◦ Usually present with episodic diplopia and facial parasthesia.
◦ MRI Brain – symmetric curvilinear gadolinium enhancement around the pons & extend variably into
medulla, cerebellum, midbrain and spinal cord.
◦ Responds to high dose of steroids , may worsen during steroid tapering, requiring chronic steroid.
Brainstem & spinal cord
dysfunction

32. ROHHAD:
◦ Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation & Autonomic Dysregulation.
◦ An autoimmune or
paraneoplastic etiology.
◦ Response to immunotherapy
in few patients.
Children having
normal
development till
2-4 yrs
Rapid onset of
hyperphagia,
weight gain,
abnormal
behaviour
• Social disinhibition,
impulsivity, lethargy,
outburst of euphoria &
laughing
Autonomic
dysfunction &
central
hypoventilation
• Abnormal pupillary
responses, thermal
dysregulation, GI
dysmotility

33. NMOSD
◦ Typical involvement of optic nerve & spinal cord.
◦ Encephalopathy in the form of diencephalic or area postrema syndromes.
◦ Can have AQP4 or MOG Ab. Some are seronegative.
◦ Involvement of brain areas rich in AQP4 (periaqueductal gray matter, hypothalamus, optic nerve
and central involvement of the spinal cord).
◦ High risk of relapses and long term disability.
◦ Requires chronic immunotherapy.
◦ Patients with MOG Ab have better outcome than those with AQP4 Ab or seronegative cases.