Case based Pearls and Errors in diagnosing

AUTOIMMUNE ENCEPHALITIS AND RELATED SYNDROMES

Sarosh R Irani
Professor of Autoimmune Neurology
Head, Oxford Autoimmune Neurology Group; MRC Senior Clinical Fellow and
Honorary Consultant Neurologist
Nuffield Department of Clinical Neurosciences, University of Oxford
DISCLOSURES
Patents:
• LGI1/CASPR2/Contactin-2/VGKC-complex antibody discovery: Coinventor;
Royalties and licence
• Autoantibody detection: Coinventor
• Biomarkers to detect autoimmune relapses: Coinventor

Research support and/or Honoraria:

• UCB Pharma, Roche, Momenta, Brain, ONO pharmaceuticals and CSL
Behring
Case 1
• 73. Woman.
• 6 months dropping items from hands
• Falls – badly sprained ankle
• Separate rising epigastric sensations

• 2 months of memory and personality

changes
• Odd comments noticed
• “Slightly manic”
• MoCA = 24/30; recall poor
Other findings
• Physical examination
- frequent jerks
- L arm especially
- Ankle reflexes absent

• Normal bloods
• Normal MRI
• Normal CSF
• Mildly slow EEG
ARS

What is your favoured diagnosis?

1. Alzheimer’s disease

2. LGI1-anSbody encephaliSs

3. Frontotemporal lobar degeneraSon

4. NMDAR-anSbody encephaliSs

5. FuncSonal neurological disorder

 LGI1-antibody limbic encephalitis
• Later years
• Subacute onset – not ‘acute’

~40%
• Amnesia, disorientation,
~10%
emotionality
~99%
• Seizures ~20%
• Sleep disturbances ~40%

• Pain

• Hyponatraemia
 Faciobrachial dystonic seizures (FBDS)

• Adult-onset
• Arm and Face
• Frequent
• Brief
• Dystonic
Cognitive Impairment No Cognitive
• Stereotyped
(CI) Impairment (CI)

Irani et al 2011. Ann Neurol;

• LGI1-antibodies
Irani et al 2013 Brain;
Binks et al 2018 Brain;
Thompson et al 2018 Brain
Case 2
• 26. Woman.
• Recent bad break up with partner ; no past medical history

• “Lost her mind”

• Crying profusely – no clear trigger
• Wondering streets naked; shouting at film stars
• Aggression towards family

• Was working as full time accountant until 6 days ago

Upon hospital admission

• Very still

• Unusual tremor

• Appeared in distress

• Bizarre comments – unable to

formally assess cognition
ARS

What is your favoured diagnosis?

1. Primary psychiatric (Undifferentiated Psychosis)

2. NMDAR-antibody encephalitis

3. Recreational drug use

4. Functional neurological disorder

5. Non convulsive status epilepticus

 NMDAR-antibody encephalitis
Headache/fever & inftn (20%)
Psychiatric (77%)
Seizures (82%)
Hypersomnia (27%)
Cognitive dysfunction (91%)
Insomnia (34%)
Headache/fever: no inftn (45%)
Movement disorder (89%)
Fall in consciousness (45%)
Gaze deviation (14%)
Autonomic (72%)
-20 -10 0 10 20 30 40 50 60 70 80 90 100110120
Days since onset
Mixed psychiatric features precede
neurological manifestations

Al-Diwani et al 2019 Lancet Psych

What were the other clues? (& outcome)

• Young female

• Very abrupt onset

• Absence of psychiatric history

Case 3
• 45. Woman. January 2022 – single generalised seizure

• Hospitalised with confusion for 2 weeks

• Only partial improvement with residual disorientation and memory
disturbances

• Returned home without gaining independence

• 2 further possible focal seizures with automatisms
Imaging appearances

No Gd uptake
No diffusion restriction
Further findings
• Normal CSF and mild slowing on EEG
• Imaging: consistent with limbic encephaliYs
• NegaYve anYbodies: LGI1, NMDAR, CASPR2, GABABR, AMPAR
➡ Diagnosed with seronegaYve AE

• Very limited improvement despite steroids

• Memory problems staYc for 1 year

• note taking around home
• unable to leave home without being lost

• QuesYon in referral le_er: escalate therapy?

ARS

What is your favoured diagnosis?

1. Seronegative, treatment refractory AE

2. Seronegative AE with typical outcome

3. Seizure related oedema

4. Low grade glioma

5. Tumefactive MS
Why wasn’t this AE?
• Mostly immediate onset of all
features

• Static course thereafter,

without treatment

• Lack of improvement on
steroids
Case 4
• 36. Male.
• Painful spasms of right arm
• Occurring several Smes per day

• Can speak through them

• SomeSmes feels ‘dizzy’ during

• Mildly low mood for ~1 year

Examination and Investigations
• MMSE = 28/30
• HADS = D5A5

• Normal MRI / CSF

• Bloods normal but VGKC

antibody 580 pM (NR <100 pM)
ARS

What is your favoured diagnosis?

1. VGKC-antibody associated seizures

2. Faciobrachial dystonic seizures

3. Paroxysmal dystonia

4. Functional neurological disorder

5. Painful tonic spasms of multiple sclerosis

Please ignore VGKC(-complex)
antibody tests in isolation