This document discusses autoimmune encephalitis, which occurs due to antibodies against neuronal proteins or synaptic receptors. It can comprise 5-10% of encephalitis cases. The most common type is anti-NMDAR encephalitis, which mainly affects females and presents in stages with psychiatric symptoms, decreased consciousness, and movements disorders. Diagnosis involves detecting antibodies in CSF or serum. Treatment is immunotherapy like steroids, IVIG, plasma exchange. Outcomes are generally good but some experience relapse or residual effects. It should be considered in the differential of acute encephalitis.

1. Dr. AmruthaVenkateswaran

2.  Autoimmune encephalitis- group of syndromes that
occur as a result of antibodies against-
- Neuronal cell protein
- Synaptic receptors
* Help in transmission, plasticity and excitability of
neurons

3.  Exact incidence not exactly known
 Studies show- comprises 5 to 10% of all encephalitic
syndromes
 May surpass viral encephalitis if close studies are
done

4.  Anti- N-Methyl D- Aspartic acid receptor
encephalitis (Anti NMDAR)
 Anti LG-1 Encephalitis
 CSAPR 2
 GABA –B
 AMPA encephalitis

5.  The antibodies target the NR1 subunit of the NMDA
receptor
 Second most common cause of autoimmune
encephalitis-
 Most common in females (80%), around 40% occurs
in less than 18 years of age.
 In older children and adoloscents, the disease
follows a predictable course

6.  First stage- Prodromal stage, mimics viral flu like
syndrome
 Second stage- Neuropsychiatric features,
behavioural changes- agitation, change in mood,
speech disturbances
 Third stage- decreased level of consciousness,
seizures, limb or oral dyskinesias, choreoathetoid
movements, and autonomic instability

7. NMDA Receptors- inhibitory
GABAnergic neurons and glutamergic
synapses
Increased extracellular glutamate
Fronto striatal syndrome- psychatric
manifestations
Complex movement disorders
Central Hypoventilation

8.  Toddlers and infants- present with complex
movement disorders and status epilepticus
 Often labelled as infantile tremor syndrome
* Often psychiatric disturbance missed due to their
young age.
• Cerebellar ataxia and hemiparesis
• On- Off phenomenon with response to the level of
consciousness

9.  Association with tumors- testicular and ovarian
teratomas
 Seen in more than 40% of females less than 12 years
 <15% in young boys

10.  EEG abnormal in most of the cases- 30% of adult
patients show a unique EEG pattern, called
“extreme delta brush” because of its resemblance
to the delta brush (beta-delta complexes) pattern in
premature infants.
 Brain MRI is abnormal in approximately 35% of
cases, nonspecific cortical and subcorticalT2
(FLAIR) signal abnormalities, transient cortical or
meningeal enhancement; nonspecific white matter
abnormalities. Lesions may also involve the spinal
cord producing symptoms of myelitis

11. EEG- Shows serrated appearance of delta
waves- due to overriding and fast beta activity
with slowing of theta waves

12. MRI BRAIN-T2 segment FLAIR bilateral temporal lobe
hyperintense signal
B- follow up shows decrease in intensity

13.  CSF- Abnormal in approximately 80% of cases,
showing moderate lymphocytic pleocytosis,
increased protein synthesis and oligoclonal bands.
 NMDAR antibodies in CSF or serum

14.  Mortality rate- 7%
 80% full recovery
 Slow recovery- can take 2 years, last to recover-
social interactions, language and executive
functions
 15% relapse- partial syndrome

15. Viral Encephalitis Acute onset, lesser psychosis
and dyskinesias, more
pleocytosis in csf
Relapsing post herpes simplex
encephalitis
4-6 weeks post treatment of
herpes simplex encephalitis-
true viral relapse (PCR +) or
Autoimmune (PCR-)
New onset psychosis Primary psychiatric disorder
Drugs/Toxins Ketamine, phencyclidine,
carbon monoxide.
Neuroleptic Malignant
Syndrome
episodes of rigidity,
hyperthermia, and autonomic
Instability, frequent
use of neuroleptics to control
the abnormal behavior

16. PEM- Paraneoplastic
encephalomyelitis
Personality changes,
disorientation, memory loss
Autoimmune post
streptococcal neurological
syndrome
PANDAS, PANS,CANS,
sydenham chorea,Tourette
syndrome
ADEM Confusion, ataxia, weakness
with visual blurring
Hashimoto’s encephalopathy Epilepsy, disorientation,
memory problems
Rasmussen’s encephalitis Mental deterioration,
seizures, hemiparesis

17.  Other D/D
- Limbic encephalitis
- Encephalitis lethargica
- Childhood disintegrative disorder/ late onset autism
- IEM
- Monoamine neurotransmitter disorders
- Demyelinating disorders
- CNS vasculitits

18.  Inflammatory process of the limbic system
including, the medial temporal lobes, amygdala,
and cingulate gyri.
 Antibodies against neuronal protein called leucine-
rich glioma inactivated 1 (LGI1), and a protein called
Caspr2 expressed in brain and myelinated nerves.
*This disorder was initially identified in 1968 as a
paraneoplastic syndrome associated with small-cell
lung cancer.

19.  Severe short-term memory loss
 Hyponatremia
 Seizures-
myoclonic-like movements (faciobrachial dystonic
seizures)
*Ophelia syndrome- association with Hodgkin’s
lymphoma
 Develop antibodies against mGluR5, a receptor
involved in learning and memory

20. A) T2 segment FLAIR in medial
temporal lobe
B) Improvement in density on
follow up
C) & D) generalized atrophy on
follow up after 9 months

21. T2 segment FLAIR seen in limbic encephalitis- closest D/D is
Herpes simplex Encephalitis which shows similar picture

22.  Other types can occur with antibodies against
intracellular antigens (eg, Hu, CRMP5, Ma2) or
against cell surface or synaptic proteins.
 InvolvesT cell immune mediated reactions
 Responds well to immunotherapy unlike the
conventional form

23.  Defined by the detection of thyroid peroxidase
(TPO) antibodies in patients with acute or subacute
encephalitis that responds to steroids.
 “Encephalopathy associated with autoimmune
thyroid disease” is considered more accurate- due
to normal thyroid function.
 Very vague symptoms- unclear course

24.  Stroke-like symptoms
 Tremor, myoclonus
 Transient aphasia
 Sleep and behaviour abnormalities
 Hallucinations, seizures and ataxia.
 EEG is usually abnormal
 MRI brain- normal
 CSF shows pleocytosis with elevated protein
 TPO antibodies should be viewed as a marker of
autoimmunity rather than a neurologic disease-specific or
pathogenic antibody.

25.  Relevant antibody-associated disorders, such as
GABA(B), LGI1, or NMDA receptor antibodies
 In some instances, plasma exchange or intravenous
immunoglobulin has been equally effective as
steroids.

26.  Inflammatory encephalopathy characterized by
progressive refractory partial seizures, cognitive
deterioration, and focal deficits that occur with
gradual atrophy of one hemisphere
 The disorder frequently presents in 6to 8year old
children, although adolescents and adults can be
affected.

27.  Mechanism still unclear
 Antibodies against the GluR3 subunit of the AMPA
receptor andT-cell mediated mechanisms triggered
by a viral infection.
 High dose methyl prednisolone
 Rituximab and intraventricular α-interferon
 ‘Functional hemispherectomy’- surgical
disconnection of the affected hemisphere.

28.  “Acute Encephalitis with Refractory Repetitive
Partial Seizures (AERRPS)”
 “Fever-Induced Refractory Epileptic
Encephalopathy Syndrome (FIRES),”
 “Devastating Epilepsy of School-aged Children
(DESC).”

29.  Presence of autoantibodies, but lack to response to
conventional treatment of autoimmune
encephalitis.
 Residual symptoms included cognitive impairment,
temporal lobe epilepsy, and mesial temporal
sclerosis.

30. ROHHAD
 Rapid onset obesity with hypothalamic dysfunction,
hypoventilation, and autonomic dysregulation seen
in children upto 2-4 years who are normal.
 Followed by episodes of hyperphagia, weight gain,
abnormal behaviour, autonomic dysfunction and
central hypoventilation
 Frequent association to neural crest tumors

31.  Basal ganglia encephalitis- patients with
predominant or isolated involvement of the basal
ganglia.
 Abnormal movements and neuropsychiatric
disease.
 Multiple etiologies, including metabolic, toxic,
genetic, and infectious processes, an immune-
mediated etiology has been postulated.
 Antibodies against the dopamine-2 receptor have
been identified

32.  Pseudomigraine syndrome with CSF pleocytosis
(PMP) or headache with neurologic deficits and
CSF lymphocytosis (HaNDL)- predominantly
affects young male adults with a family history of
migraine.
 Repeated episodes of severe headache with
transient neurologic deficits
 CSF- lymphocytosis with elevated protein
 MRI- normal
 EEG- background slowing activity

33. Ophthalmoplegic migraine (recurrent cranial
neuralgia)
 Recurrent bouts of head pain in addition to cranial
nerves III, IV, and/orVI involvement.
 MRI shows focal nerve thickening and contrast
enhancement
 D/D includes structural, neoplastic, traumatic,
metabolic, and infectious disorders.

34.  Occurs in children and adults although it probably
represents different diseases and pathogenic
mechanisms
 Syndrome usually develops in the 1st 2 yr of life
 50% have underlying neuroblastoma
 Child often presents with
Irritability, ataxia, myoclonus, tremor, and drooling of
saliva

35.  Typical features of opsoclonus characterized by
rapid, chaotic, multidirectional eye movements
without saccadic intervals
 CSF- antibodies against neuronal proteins
 Immunosuppressive treatment, including
corticosteroids, IVIG, rituximab, and
cyclophosphamide
 Relapses occur in 50% of the patients

36.  Subacute progressive ophthalmoplegia and ataxia
in addition to drowsiness or hyperreflexia.
 More frequent in adults
 Mimics GBS in younger children
 Serum GQ1b immunoglobulin G antibodies are
found in 66% of patients, with MRIT2 FLAIR
abnormality.
 Treated with steroids, IVIG, and/or plasma
exchange, and often have good outcome

37.  Idiopathic/ Post infectious
- CSF- no evidence of neuronal antibodies
- Show similar syndrome like anti NMDAR
encephalitis
 Patients usually have full recovery after treatment
with immunotherapy unlike opsoclonus- myoclonus
 d/d: listeria, enterovirus, primary CNS lymphoma

38.  Anti NMDAR
 Anti LG-1 Encephalitis
 CSAPR 2
 GABA –B
 AMPA encephalitis
Done in both serum and CSF

39.  No consensus guidelines
 Pulsed dose IV methyl prednisolone followed by
high dose oral steroids
( 30mg/kg/day upto 1 g/day) for 3 to 5 days followed by
1-2mg/kg/day of oral prednisolone
2g/kg of IV Ig for 2-5 days with plasma exchange
 Second line therapy- rituximab and
cyclophosphamide

40.  Absence of CSF pleocytosis does not rule
autoimmune encephalitis
 d/d:
- Viral encephalitis
- Mitochondrial disorders
- Leukodystrophy
 Should be investigated for new antibodies in serum
if CSFantibodies are negative.

41.  Should be considered as a differential for acute
encephalitis syndrome
 Presents with neuropsychiatric symptoms in older
children and with status epilepticus in younger
children and infants
 Treatable cause of acute encephalitis