AUTOIMMUNE ENCEPHALITIS

Dinda Hartami L, Devitra Rajendran

INTRODUCTION

Autoimmuneencephalitisisanimportantcauseofnew-
onsetalteredmentalstatus,thescopeofwhichhasonlyrecentlybeguntoberecognizedin
themedicalliterature.Despitethisincreasedrecognition,ithasyettobecomeanestablis
heddiagnosticconsiderationoutsideoflargetertiaryreferralcenters.Theterm“autoimm
uneencephalitis”generallyreferstoafamilyofcloselyrelateddiseaseprocessesthatshareov
erlappingclinicalfeaturesandneuroimagingfindingsbutareultimatelydifferentiatedb
ythespecificantibodysubtypesdrivingtheunderlyingimmunemediatedattackondiffe
rentCNSstructures.Thisantibody
mediatedattackonneuronalstructuresresultsinalocalizedinflammatoryresponse.1,2,3

These cases highlight several important discussion points. Perhaps most important
is that anti-NMDA-R encephalitis is an under recognized syndrome. With the advent of
antibody markers, this syndrome was confirmed in 20% of cases of encephalitis at one
tertiary referral center, and retrospectively diagnosed in 86% (6/7) of patients managed in
a single-center ICU with diagnosis “encephalitis of unknown origin” and compatible
clinical features.4,5,6

Encephalitis (brain inflammation) is often thought to be mediated by infections

(e.g. viral).With the advances in molecular diagnostics, new immunological markers
(antibodies) are being discovered in patients presenting with encephalitic syndromes.
Thus, research has evoked interest in the ‘immune theory’ of encephalitis. This group of
disorders appealing to clinicians because of the favourable response to immunotherapy
viz a viz infectious encephalitis where limited pharmacotherapy is available for most of
the viral agents.7,8,9

Various syndromes of autoimmune encephalitis have been described and many

more are expected with the advent of newer biomarkers. The clinical syndrome comprises
a complex of encephalopathy, cognitive disturbances, mood/personality changes, seizures
and movement disorders. Each of these can be the presenting manifestation, opening up a
 wide differential diagnosis, often delaying the diagnosis and therapy. Important clinical
clues to suspect autoimmune encephalitis are subacute onset, fluctuating course, mood
and behaviour changes, cognitive dysfunction, seizures, dyskinesiae and tremors.7

CLINICAL MANIFESTATION

Important clinical clues to suspect autoimmune encephalitis are subacute

onset, fluctuating course, mood and behaviour changes, cognitive dysfunction,
seizures, dyskinesiae and tremors. Diagnostic clues are summarized in Table 1.

Table 1: Clues for diagnosis of autoimmune encephalitis7

• Subacute onset of memory impairment (short-term memory loss),

encephalopthy or psychiatric symptoms
• At least 1 of the following:
• Focal neurological deficits
• Unexplained seizures
• CSF pleocytosis (white blood cell count >5 cells per mm3)
• MRI features suggestive of encephalitis
• Exclusion of alternative causes

The clinical presentation can be divided into following stages:7

1. Prodromal phase with infection; fever and headache

2. Early stage with psychosis, confusion, amnesia and dysphasia
3. Late stage (within 1–2 weeks) characterised by movement disorders (choreo-athetoid
movements, stereotypy), autonomic instability, encephalopathy with hypoventilation.
Some patients become mute and catatonic.

Other clinical presentations are:7

1. Autoimmune refractory epilepsy

2. Schizophrenia like symptoms
3. Demyelinating disorder
4. Patient with herpes simplex encephalitis with anti NMDA receptor antibodies
Table 2: Diagnostic clues: anti-NMDA receptor encephalitis7

1. Rapidly progressive following symptoms:

 Abnormal behaviour or cognitive dysfunction
 Decreased level of consciousness
 Speech dysfunction
 Seizures
 Movement disorder, especially oral dyskinesias
 Autonomic dysfunction or central hypoventilation
2. At least one of the following study results:
 Abnormal EEG (slowing, epileptiform activity or extreme delta
brush)
CSF pleocytosis or oligoclonal bands
3. Exclusion of other disorders
4. Accompanied by a systemic teratoma:
5. IgG anti-GluN1 antibodies (Definite)
RISK FACTORS

It is typical for patients with autoimmune encephalitis to have testing for various
infectious etiologies and they are fre-quently covered with antibiotic and/or antiviral
therapies (such as acyclovir) empirically as infectious causes are exclud-ed. Some of the
relevant risk factors for various causes of en-cephalitis are listed in Table 3 and the major
infections are listed in Table 4.10

Table 3. Risk factors for autoimmune and infectious encephalitis10

Risk factor Implications

Travel Consider infectious causes of encephalitis in visited region

HIV Opportunistic infections, risk depending on CD4 count

Transplantatio Opportunistic infections (CMV, VZV, HSV1, 6, 7); if recently transplanted,

n consider infection from donor

Consider lupus cerebritis, vasculitis

Systemic
autoimmunity

Consider specific paraneoplastic syndromes based on tumor, but also

Cancer lymphomatous/carcinomatous tumor involvement

Prior Consider relapse of initial encephalitis, secondary autoimmune causes, and (if
encephalitis immunosuppressed) opportunistic infections

Table 4. Infectious causes of encephalitis10

Pathogen Test Notes

HSV PCR A common cause in both healthy and immune-
compromised patients, with particular predilection for the
temporal lobes,
Specific anti-viral therapy may be life-saving,
Rare cases of secondary anti-NMDAR encephalitis
afterwards85
CMV PCR
VZV PCR
JE PCR Once a leading cause in East Asia, but declining due to vaccination
programs
Enterovirus PCR Other, non-polio, strains may also be neurotropic and it is a relatively
common cause of encephalitis
HHV6 PCR Important cause in transplant patients 1% of persons have
HHV-6 in their genome, so PCR test can be misleading
HHV7 PCR Rare cause in immune compromised patients 10-15% of
untreated patients have neurological symptoms
Neuroborreliosis Manifestations include meningitis, encephalitis, radiculitis, cranial
(Lyme disease) Serology neuritis, and pheripheral neuropathy
Widely distributed mosquito-born flavivirus
Most infections asymptomatic or minimally symptomatic
WNV (West PCR, Ensephalitis is the most common presentation, followed by
Nile) Serology meningitis and flaccid paralysis
Syphilis Serologies Most cases are sexually transmitter
Neurological symtoms may oocur years or decades after
exposure
Manifestations are protean
Latex
Cryptococcus agglution More often presents with meningitis in patients with AIDS
antigen test, and other immune-compromised states
culture CSF opening presssure may be marked elevated
Aspergillus Culture, biopsy Disseminated CNS aspergillosus is mostly in immune compromised
fumigatus (transplant
patients), and pathology usually involves basal ganglia and/or
thalami
Mucor May affect both immunocompromised and immune intact
Culture,biopsy persons
Anti-NMDAR-encephalitis

Anti-NMDAR-encephalitis is the most common autoimmune encephalitis in which Ig

G antibodies against the GluN1 subunit of the NMDA receptor are present. It can affect all
age groups, but is more common in children and young adults females.

Figure 1: Overview of the Antibody Targets in NMDAR, VGKC-complex, and

GAD-antibody-associated Encephalitis and their SynapticLocalizations 11

Table 5 summerizes the salient features of this group of conditions.7
AntiLGI1- encephalitis Anti
Anti-NMDAR CASPR2- Anti GABABR- Anti AMPAR-Ab
associated encephalitis
Encephalitis encephalitis encephalis.
Demographic Children and Older men, Median age Adult Median age 62 Middle aged
profile young males years women
Women 60 years
NMDAR (mainly
Antibody target NR1 VGKC-complex- VGKC-complex GABABR1 GluR1/2
subunit) Associated associated
LGI1 A CASPR2
Tumours are very rare.
Tumour Ovarian (or other) Thymomaprincipally, Thymoma and thymoma,
small-cell lung
Association teratomas in cancer. Lung lung, breast
≤50%
Responds well to Often
Response to early monophasic Can be treatment Responds to Responds to
immunotherapies
Immunotherapy and without need for responsive treatments treatments but
Early Continuing or have relapses common
tumour removal Immunosuppressi
but on spontaneous
nonparaneoplastic improvement, but
prognosis
cases can be confounded
chronic and tend
to by tumour when
Relapse present
Other EEG- extreme Frequent
charactristics delta 60% develop EMG- Myokymia coexisting
autoimmune
Brush hyponatremia diseases
 Complex and generalized seizures are reported in the majority of cases, distinguishing
anti-NMDA-R encephalitis from most causes of viral encephalitis and suggesting that
seizures are part of the natural history of this syndrome. Investigations should be requested
with the intent of confirming the diagnosis while excluding mimics (Table 6).

Tabel 6 Differential Diagnosis of Anti-NMDA-R Encephalitis

Distinguishing
Etiology Features

Physical
Examination Laboratory Markers Imaging

Infectious (e.g., bacterial - Fever - Positive CSF / serum cultures - CT: Hydrocephalus
- MRI: Temporal lobe
meningitis, HSV* - Nuchal rigidity - Specific antibody / antigen hyperintensity /
degeneration (HSV
encephalitis),
encephalitis, other viral, - Palpable purpura detection cortical
ribbon / basal
(Neisseria ganglia
prion disease) meningitidis) enhancement
(Creutzfeldt-Jakob
Disease)
†
Neoplastic (e.g., primary - Specific markers (PSA , CA- - CT / MRI: Space-
/ - Focal neurologic 125‡, occupying
secondary brain
neoplasm, Signs CEA§) lesion(s)
- Monoclonal proliferation on
central nervous system flow
cytometry,
lymphoma) immunohistochemistry
Metabolic (e.g., - Periventricular
Wernicke’s, - Abnormal eye - Decreased thiamine enhancement /
Hashimoto’s movements, - Anti-thyroid peroxidase / hemorrhage
encephalopathy) ataxic thyroglobulin (Wernicke’s)
gait (Wernicke’s) antibodies
- Diffuse cortical
‖ ¶
Autoimmune (e.g., - Systemic findings - Increased ESR / CRP changes, vessel wall
narrowing (with
vasculitis, systemic - Specific rheumatologic vessel-wall
lupus seromarkers imaging)
erythematous)
Algorithm 1 and 2 summarize the clinical and management aspects of immune encephalitis.7
 Treatment for suspected autoimmune encephalitis is often given empirically prior to
specific antibody test results. This may include steroids and/or IVIG. If a cell-
surface/synaptic antibody disorder is diagnosed, initial treatments may include IVIG,
plasmapheresis, and/or steroids. Steroids may be beneficial in a range of autoimmune
disorders but could potentially create problems with the diagnosis of certain disorders such as
CNS lymphoma. IVIG offers an important advantage of being unlikely to make infectious
encephalitis worse. Plasmapheresis is also unlikely to significantly worsen infectious
encephalitis.10

If a synaptic/cell-surface antibody is detected and the pa-tient has any significant

symptoms, first-line therapy should be given if it has not already been tried. In general,
prompt treatment, and escalation of treatment in patients who re-main ill, is associated with
better outcomes. Although there are not randomized treatment trials, protocols have been
proposed for anti-NMDAR encephalitis,1 and these ap-proaches have been applied to other
diseases in the cell-surface/synaptic autoantibody category. Our group often uses IV
solumedrol (1 gram daily for 3–5 days then a taper over several weeks) and IVIg (0.4
g/kg/day for 5 days). Other groups have advocated plasmapheresis instead of IVIg, and so far
there is not convincing evidence of superi-ority for either approach.10

If the patient remains significantly impaired after first-line therapy, second-line treatments
are typically used. Some groups might wait 2 weeks or longer to allow first-line ther apies
time to work, but our group often proceeds more quickly to second line therapy sooner is
patients who are very ill, for instance comatose patients with anti-NMDAR encephalitis.
Second line therapies include rituximab (often 375 mg/m2 weekly for 4 weeks) or
cyclophosphamide (750 mg/m2 IV monthly until improvement is noted), or both. Rituximab
is a monoclonal antibody targeting CD20, so plasmapheresis generally should not be done
after it is ad-ministered. Rituximab depletes CD19+/CD20+ B-cells, and circulating levels of
these cells typically become undetect-able for several months after treatment. Due to its
relatively favorable safety profile, rituximab is more often used as monotherapy in children.
Rituximab is thought to be gener-ally effective against neurological diseases where the auto-
antibodies are of the IgG4 subtype.12 Since IgG4 responses predominate in LGI1 and Caspr2
encephalitis this provides an additional theoretical support for using rituximab in those
diseases. Cyclophosphamide has several important toxicities, including a risk of infertility,
especially in young women who received repeated doses (The risk cumulatively increases,
potentially up to 40% after 12 doses). This risk be can reduced with use of a GnRH agonist in
women,12 or ad-dressed with egg/sperm collection.10

Anti-NMDAR encephalitis in children may present differ-ently than in adults.13 Children

are more likely to have ab-normal movements (chorea, incoordination) early in the dis-ease
course and also may have atypical motor symptoms such as ataxia or hemiparesis. Children
more often have sei-zures than adults. The classic symptoms of psychosis seen in adults are
less common, but behavioral regression is fre-quently noted. Patients may have prominent
speech difficul-ties. Treatment strategies are similar in children and adults, but physicians
may be more reluctant to use cyclophospha-mide, relying more on rituximab as a second line
treatment (As with adults, the optimal treatment strategies are not known). Responses to
treatment are similar in children and adults, with about half failing first line therapies.
Ovarian teratoma is lesslikely in female children before puberty, sotumors are uncommon in
young children.10

Patients with encephalitis may recover, completely or par-tially, and then experience
worsening symptoms. In autoim-mune encephalitis, relapse tends to follow a similar clinical
course to the initial attack. In anti-NMDAR encephalitis, these relapse tend to be milder than
the initial attack and manifest with confusion, worsening memory, personality change,
hallucinations or new seizures (In my experience, seizures in my cases of autoimmune
encephalitis remit with appropriate treatment, and new seizure should always raise concern
for relapse). The risk of relapse in anti-NMDAR en-cephalitis in approximately 12% over
two years (but contin-ues beyond that) and is highest in untreated patients, inter-mediate in
patients who had only first-line therapy, and lowest in patients treated with second-line
therapies.13 Re-lapsed patients are usually treated with second-line thera-pies, possibly after
first line therapies. These patients may be treated for longer periods of time with second line
thera-py, especially rituximab, but the optimal duration of treat-ment has not been
established. In other types of autoimmune encephalitis, the risk of relapse is less clearly
established. LGI1 antibodies and Caspr2 antibodies may associate with milder encephalitis,
compared with NMDAR antibodies, than is chronic or relapsing. Similar treatment strategies
may be used with these antibodies.
 CASE
PATIENT STATUS

Name : MM
Age : 12 years 1 month
Sex : Female
Address : Huta Bulu Dolok Pagaran
No. RM : 00.72.65.22
Admission : 22nd November 2017

HISTORY TAKING
Chief Complaint : Loss of consciousness
:
- This is experienced by patients since ± 5 hours before admission to hospital, decreased
awareness preceded by seizures. Seizures experienced by patient since 1 day before
entering the hospital, with frequency 2 times. The first seizure at 17.00 with a long spasm
of about 15 minutes, character of the seizure was whole body seizures with the hands and
feet stomping. The second seizure was experienced at 21:00 on the same day with a
duration of about 15 minutes and after the second seizure the patient was unconscious.
Seizures are preceded by fever.
- Headache is present in patient. History of headache was experienced by patient almost 3
weeks.
- Fever was found. History of fever was encountered since 1 months ago and the
temperature value is not constant (up and down). Fever falls with the use of antipiuretic.
Fever is not accompanied by chills.
- Shortness of breath is present in patient. Cough (-). History of cough was denied. Night
sweats (-), contact history with old cough sufferer (-).
- Nausea (-), vomiting (-), diarrhea (-).
- Decreased appetite is found. Weight loss is found ± 10 kg in 2 months.
- The history of urination is within normal limits.
- The history of defecation is within normal limits
- 2 weeks before came to H. Adam Malik Hospital, patient experienced loss of
consciousness and was brought to Tarutung Hospital. Patient experienced seizure whole
 body, rigid and about more than 15 minutes with frequency 3x/day with > 1 hour time
interval.

- During patient was at Tarutung Hospital, patient was diagnosed with status epilepticus.

Maternal pregnancy history : Patient is the second child and during pregnancy, mother is 25
Birth history
Immunization history
Previous medical history
Drug usage history
Feeding history
History of Growth and
Development
years old. Mother of the patient often control pregnancy to
midwife. History of fever, hypertension and diabetes during
pregnancy is denied. A history of taking drugs and herbs during
pregnancy is denied.
: Patients born normal assisted by the midwife. Patient born
with complete pregnancy months, immediately crying, and not
found blue. Weight at birth: 3000gr, Length at birth is
undefined.
: Not complete
: Epilepsy
: Ceftriaxone, Dexamethasone, Fenitoin
: - 0-4 month : Breast milk
- 6-8 bulan : Formula milk + milk porridge
- 8-12 bulan : Fomula milk + steamed porridge
- > 1 tahun : Formula milk + family rice
: - Crawling = Not clear
- Walking = 11 month
- Talking = 1 year

PHYSICAL EXAMINATION
Present status
Sensorium : Somnolen, GCS 8 (E2V2M4)
Blood pressure : 110/70 mmHg
Temp : 37,9 ̊C
HR : 108 x/I, reguler, murmur (-)
RR : 32x/I, reguler, ronkhi (-/-)
BB : 35 kg
TB : 150 cm
BB/U : 81,4%
TB/U : 98%
BB/TB : 81%
Impression : Malnutrition

Localization Status
Head
Eyes : Light Reflex (+/+), pupil isokor ukuran Ø 3mm/3mm, conjungtiva
palpebral inferior pale (-/-), sklera ikterik (-/-)
 E/N/M : Normal / NGT, O2 nasal canule / normal
Neck : Lymph nodes enlargement (-)
Toraks : Simetris fusiformis, retraction (-)
HR : 108 x/i, reguler, murmur (-)
RR : 32 x/i, reguler, ronkhi (-/-), wheezing (-/-)
Abdomen : Soepel, peristaltic (+) N, Hepar/Lien : impalpable
Ekstremity : Blood pressure : 110/70 mmHg, pulse : 108 x/i, reguler, warm extremities,
CRT < 3 seconds
Physiological reflexes : APR (+) N, KPR (+) N
Pathological reflexes : Babinski (-), Oppenheim (-), Chaddock (-)
Meningeal stimulus : Kaku Kuduk (-), Bruzindski I/II (-), Kernig Sign (-),
Lasegue(-)
Genitalia : Normal

LABORATORIUM ( Date: 22/11/2017 )

Complete Blood Result Reference
Hemoglobin : 13,4 g/dL (12 - 16)
Erythrocytes : 4,74 juta/µL (4,10 - 5,10)
Leukocytes : 18.790 /µL (4,000 – 11.000)
Hematocrit : 40% (36 – 47)
Platelets : 351.000 /µL (150.000 – 450.000)
Hitung Jenis
Neutrophils : 79,60 % (50.00 - 70.00)
Lymphocytes : 13,70 % (20.00 - 40.00)
Monocytes : 6,20 % (2.00 - 8.00)
Eosinophil : 0,10 % (1.00 - 3.00)
Basophils : 0,40 % (0.00 - 1.00)
Electrolyte
Calcium (Ca) : 8.20 mg/dL (8,4-10,2)
Sodium (Na) : 136 mEq/L (135 - 155)
Potassium (K) : 3,6 mEq/L (3,6 – 5,5)
Cloride (Cl) : 106 mEq/L (96 - 106)
DIFFERENTIAL DIAGNOSIS
 Autoimmune Encephalitis
 Meningoencephalitis
 Meningitis

CLINICAL DIAGNOSIS
 Autoimmune Encephalitis

MEDICATION
 IVFD NaCl o,9 % 30cc/jam
 Inj. Ceftriaxone 1,5 gram/12 jam/IV
 Inj. Fenitoin MD 90 mg/12 jam/IV
 Metilprednisolon 1 x 8 tab
 Haloperidol 1 x 0,5 mgs

PLANNING
 Complete blood, blood sugar level, electrolyte
 Urinalysis
 Kidney test
 Liver test
 EEG
 Blood culture
 Urine culture
 Lumbar puncture
 Head CT-scan
 PATIENT’S FOLLOW-UP

22-23 November 2017

S : Loss of consciousness (+), headache (+), fever (+), vomiting (-)
O : Consciousness:Somnolen, GCS 8 (E2V2M4), Temp: 38,0
Head : Eyes: RC +/+, pupil isokor, conj palp inf pale (-)/(-)
Ears: normal. Nose : NGT (+) O2 nasal canule (+) Mouth : normal
Neck: Stiff neck (-), lymph node enlargement (-),
Thorax : Simetris fusiformis, retraction (-)
HR: 124 x/minute, reguler, murmur (-)
RR: 22 x/minute, reguler, ronkhi (-/-)
Abdomen: Soepel, normal peristaltic (+), liver/ lien: impalpable
Ekstremity: Pulse: 124 x/minute, reguler, pressure/volume enough, CRT <3“
Physiology reflex: APR/KPR: (+)/(+)
Pathology reflex: Babinski (-), Chaddock (-), Oppenheim (-)
Meningeal reflex: stiff neck (-), Brudzinsky I/II (-/-)
Diagnosis: Autoimmune encephalitis
Treatment : Head elevation 30omidline position
O2 nasal canule 1 liter per menit
IVFD NaCl 0,9% 4 drops per minute (mikro)
Inj. Ceftriaxone 1,5g/12 hour/iv
Inj. Fenitoin MD 90mg/12 hour in NaCl 0.9% 20cc finish in 20 minute
Inj. Paracetamol350 mg/6 hour/iv

Planning/ - Lumbal puncture

- Blood culture

24-25 November 2017

S : Loss of consciousness (+), headache (+), fever (+), vomiting (-)
O : Consciousness : Sens: Somnolen, GCS 8 (E2V2M4), Temp: 38,0
Head: Eyes: RC +/+, pupil isokor, conj palp inf pale (-)/(-)
Ears: normal. Nose : NGT (+) O2 nasal canule (+)
Mouth : normal
 Neck: Stiff neck (-), lymph node enlargement (-),
Thorax : Simetris fusiformis, retraction (-)
HR: 124 x/minute, reguler, murmur (-)
RR: 22 x/minute, reguler, ronkhi (-/-)
Abdomen: Soepel, normal peristaltic (+), liver/ lien: impalpable
Ekstremity: Pulse: 124 x/minute, reguler, pressure/volume enough, CRT <3“
Physiology reflex: APR/KPR: (+)/(+)
Pathology reflex: Babinski (-), Chaddock (-), Oppenheim (-)
Meningeal reflex: Stiff neck (-),Brudzinsky I/II (-/-)
Diagnosis : Autoimmune encephalitis
Treatment : Head elevation 30omidline position
O2 nasal canule 1 liter per menit
IVFD NaCl 0,9% 4 tetes per menit(mikro)
Inj. Ceftriaxone 1,5g/12 hour/iv
Inj. Fenitoin MD 90mg/12 hour in NaCl 0.9% 20cc finish in 20 minute
Inj. Paracetamol350 mg/6 hour/iv

Planning/ - Head MRI with contras

26-28 NOVEMBER 2017

S : Loss of consciousness (+), headache (-), fever (-), vomiting (-)
O : Consciousness: Somnolen, GCS 8 (E2V2M4), Temp: 37,0
Head: Eyes: RC +/+, pupil isokor, conj palp inf pale (-)/(-)
Ears: normal. Nose : NGT (+) O2 nasal canule (+) Mouth : normal
Neck: Stiff neck (-), lymph node enlargement (-),
Thorax : Simetris fusiformis, retraction (-)
HR: 124 x/minute, reguler, murmur (-)
RR: 22 x/minute, reguler, ronkhi (-/-)
Abdomen: Soepel, peristaltik normal (+), liver/ lien: impalpable
Ekstremity: Pulse: 124 x/minute, reguler, pressure/volume enough, CRT <3“
Physiology reflex: APR/KPR: (+)/(+)
Pathology reflex: Babinski (-), Chaddock (-), Oppenheim (-)
Meningeal reflex: Kaku kuduk (-),Brudzinsky I/II (-/-)
Diagnosis : Autoimmune encephalitis
Treatment : Head elevation 30omidline positio
O2 nasal canule 1 liter per menit
IVFD NaCl 0,9% 4 drops per minute(mikro)
Inj. Ceftriaxone 1,5g/12 hour/iv
Inj. Fenitoin MD 90mg/12 hour in NaCl 0.9% 20cc finish in 20 minute
Inj. Paracetamol350 mg/6 hour/iv
29-30 November 2017
S : Loss of consciousness (+), headache (+), fever (+), vomiting (-)
O : Consciousness : Somnolen, GCS 8 (E2V2M4), Temp: 38,0
Head: Eyes: RC +/+, pupil isokor, conj palp inf pale (-)/(-)
Ears: normal. Nose : NGT (+) O2 nasal canule (+)
Mouth : normal
Neck: Stiff neck (-), lymph node enlargement (-),
Thorax : Simetris fusiformis, retraction (-)
HR: 124 x/minute, reguler, murmur (-)
RR: 22 x/minute, reguler, ronkhi (-/-)
Abdomen: Soepel, peristaltik normal (+), liver/ lien: impalpable
Ekstremity: Pulse: 124 x/minute, reguler, pressure/volume enough, CRT <3“
Physiology reflex: APR/KPR: (+)/(+)
Pathology reflex: Babinski (-), Chaddock (-), Oppenheim (-)
Meningeal reflex: Kaku kuduk (-),Brudzinsky I/II (-/-)
Diagnosis : Autoimmune encephalitis
Treatment : Head elevation 30omidline position
O2 nasal canule 1 liter per minute
IVFD NaCl 0,9% 4 drops per minute(mikro)
Inj. Ceftriaxone 1,5g/12 hour/iv
Inj. Fenitoin MD 90mg/12 hour in NaCl 0.9% 20cc finish in 20 minute
Inj. Paracetamol350 mg/6 hour/iv
Head MRI Report: SOL intracranial picture do not appeared

Meningoencephalitis do not appeared

Right mastoiditis
CASE PRESENTATION

DISCUSSION

Theory Case
Definitions In patient, we found memory loss and
Autoimmune encephalitis is treatable cause confusion with subacute onset (2 weeks).
of subacute onset memory loss and confusion
Clinicals Manifestations Clinicals Manifestations
 Focal Neurological deficits  Abnormal behaviour or cognitive
 Unexplained seizures dysfunction
 CSE pleocytosis (white blood cell  Decreases level of consciousness
count > 5 cells per m3.  Speech dysfunction
 MRI feature suggestive of  Oral dyskinesia
encephalitis  Autoimmune refractory epilepsy
 Exclusion of other disorders  Schizophrenia like symptoms
 Abnormal behaviour or cognitive  Abnormal EEG
dysfunction
 Decreases level of consciousness
 Speech dysfunction
 Movement disorders, especially oral
dyskinesia
 Autonomic dysfunction
 Autoimmune refractory epilepsy
 Schizophrenia like symptoms
 Patient with herpes simplex
encephalitis with anti NMDA
receptor antibodies
 Abnormal EEG
 IgG anti-GluN1 antibodies
Phase according to clinical manifestations Phase according to clinical manifestations
 Prodromal phase with infections;fever Late stage (with in 1-4 weeks)
and headache
  Early stage with psychosis, confusion,
amnesia and dysphasia
 Late stage (within 1-2 weeks)
characterised by movement disorders
(choreo-athetoid movements,
stereotypy), encephalopathy with
hypoventilation. Some patients
become mute and catatonic.
Etiology Etiology
 Infectious e.g., bacterial, meningitis,  Infection ( HSV encephalitis)
HSV encephalitis, other viral, prion
disease
 Neoplastic (e.g. primary/secondary
brain neoplasm, central nervous
system lymphoma)
 Metabolic (e.g., Wernicke’s,
Hashimoto’s encephalopathy
 Autoimmune (e.g. vasculitis, systemic
lupus erythematous)
Treatment Treatment
Acute treatment  IVFD NaCl o,9 % 30cc/jam
 IV Methylprednisolon (1gm daily for  Inj. Ceftriaxone 1,5 gram/12 jam/IV
5 days) or  Inj. Fenitoin MD 90 mg/12 jam/IV
 IVIg (0,4 mg/kg daily for 5 days) or  Metilprednisolon 1 x 8 tab
 Plasma exchange or  Haloperidol 1 x 0,5 mgs
If there is improvement:
Maintenance treatment
 Oral prednisolone taper over 4-6
months and consider
 Oral azathioprine or
 Oral mycophenolate mofetil or
 IV rituximab (Monitor with CD 19)
If there isn’t improvement:
  IV rituximab (375 mg/m2 weekly for
4 weeks). Or
 IV cyclophosphamide 1 gm IV
monthly for 6 months

Reference

1. Kelley B.P., Patel S.C., Marin H.L., Corrigan J.J., Mitsias P.D., and Griffith B.
Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked
Diagnosis. AJNR Am J Neuroradiol. 2017.
2. DalmauJ,RosenfeldMR.Autoimmuneencephalitisupdate.NeuroOncol 2014;16:771–78.
3. da Rocha AJ, Nunes RH, Maia AC Jr, et al. Recognizing autoim- mune-mediated
encephalitis in the differential diagnosis oflimbic disorders. AJNR Am J Neuroradiol
2015;36:2196 –205 .
4. Day GS, High SM, Cot B. Anti-NMDA-Receptor Encephalitis: Case Report and
Literature Review of an Under-Recognized Condition. J Gen Intern Med 26(7):811-6.
5. Davies G, Irani SR, Coltart C, et al. Anti-N-methyl-D-aspartate receptor antibodies: A
potentially treatable cause of encephalitis in the intensive care unit. Crit Care Med
2010;38:679-82.
6. Prüss H, Dalmau J, Harms L, et al. Retrospective analysis of NMDA receptor antibodies
in encephalitis of unknown origin. Neurology:75:1735-39.
7. Khadilkar S, Soni G, Patil S, Huchche A, Faldu H. Autoimmune Encephalitis: An
update. J Assoc Physicians India Vol 65 62-65.

8. Venkatesan A, Tunkel AR, Bloch KC, et al, for the International Encephalitis
Consortium. Case defi nitions, diagnostic algorithms, and priorities in encephalitis:
consensus statement of the international encephalitis consortium. Clin Infect Dis 2013;
57:1114– 28.
9. Kennedy PGE. Viral encephalitis: causes, differential diagnosis, and management
JNeurol Neurosurg Psychiatry 2004; 75:i10-i15.
10. Lancaster E. The Diagnosis and Treatment of Autoimmune Encephalitis. J Clin
Neurol 2016;12(1):1-13.
11. Bera KD, Vincent A, Irani SR. Autoimmune Encephalitis Antibody Targets and Their
Potential Pathogenicity in Immunotherapy-responsive Syndromes. US Neurology,
2013;9(1):55-60.
12. Huijbers MG, Querol LA, Niks EH, Plomp JJ, van der Maarel SM, Graus F, et al. The
expanding field of IgG4-mediated neurological autoimmune disorders. Eur J Neurol
2015;22:1151-1161.
13. Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, et al.
Treatment and prognostic factors for long-term out-come in patients with anti-NMDA
receptor encephalitis: an observa-tional cohort study. Lancet Neurol 2013;12:157-165.