Neuropsychiatry of Encephalitis Flashcards by Georgia Elouise

What are the two types of immune-mediated encephalitis?

▪️ Post-infectious
▪️ Autoimmune

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What is a paraneoplastic autoimmune encephalitis and how might it occur?

▪️ Associated with cancer
▪️ Immune response to cancer may initiate cross-reactivity with brain proteins

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Why might prevalence of autoimmune encephalitis be increasing?

▪️ Better recognition
▪️ Environmental factors
▪️ Development of new cancer immunotherapies

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How does HSV-1 encephalitis typically present?

▪️ 2-12 days latency
▪️ Predominantly in limbic lobes (limbic encephalitis)
▪️ Headache, fever, seizures, confusion
▪️ Essentially haemorrhagic

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Who is most at risk to HSV encephalitis?

▪️ Diabetic
▪️ Presence of malignant tumour
▪️ Immunocompromised
▪️ Deficits in toll-like receptor

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What psychiatric symptoms are commonly seen in the acute phase of HSV encephalitis?

▪️ Agitation
▪️ Confusion
▪️ Psychosis, especially hallucinations
▪️ Mania
▪️ Delirium
▪️ Confabulation
▪️ Catatonia

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What psychiatric symptoms are commonly seen in chronic HSV encephalitis?

▪️ Cognitive impairment, especially anterograde amnesia with variable retrograde
▪️ Executive/frontal dysfunction
▪️ Disinhibition
▪️ Aggression
▪️ Kluver-Bucy syndrome (hyperorality and hypersexuality)

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What is autoimmune antibody-associated encephalitis?

▪️ Autoantibodies target and bind to ion channels/receptors/associated proteins on neuronal cell surface
▪️ Typically downregulate function
▪️ Leading to often acute/subacute presentations such as cognitive impairment, seizures, or movement disorder

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What is the characteristic progression of acute encephalopathy seen with anti-NMDAR encephalitis?

Prodromal malaise/flu-like
Psychiatric (incl. sleep disturbance)
Movement disorder (incl. catatonia/dyskinesia)
Seizures
Autonomic dysfunction
Coma

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What is anti-NMDAR encephalitis commonly associated with?

Ovarian teratoma/malignancy

(Although decreasing now)

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What psychiatric symptoms are commonly seen in anti-NMDAR encephalitis?

▪️ Anxiety
▪️ Agitation
▪️ Psychosis (delusions, paranoia, hallucinations)
▪️ Catatonia
▪️ Echolalia

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What is the main investigation for identifying NMDAR encephalitis and what is usually found?

Lumbar puncture
▪️ 80% show abnormality
▪️ Typically increased white blood cells and oligoclonal bands (immunoglobulins)

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What imaging can you used to identify NMDA encephalitis and what might you find?

▪️ MRI - 33% abnormal, usually non-specific
▪️ EEG - 80-90% abnormal, usually slowing (‘extreme delta brush’)

(BUT important to differentiate encephalopathic EEG slowing from effects of psychiatric medication)

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What is the predominant feature or autoimmune (NMDAR) encephalitis?

Psychiatric/behavioural disturbance

(Is possible to get isolated presentation, particularly at relapse)

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What psychiatric disorder is the psychiatric phenotype of NMDAR encephalitis most similar to?

Schizophrenia/First episode psychosis

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What is the primary presenting symptom in most cases of NMDAR encephalitis in children?

Psychosis

(typically older children)

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How do anti-NMDAR antibodies causes disease?

▪️ Targets NMDA receptor and internalises it
▪️ Leads to fewer receptors at synapse = hypofunction

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Why do acute doses of ketamine produce symptoms similar to schizophrenia and NMDAR encephalitis?

It binds to NMDA receptors

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What are the two possible target proteins associated with voltage-gated potassium channel encephalitis?

▪️ LGI1
▪️ CASPR2

(DO NOT REQUEST VGKC ANTIBODIES)

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What is the main prodromal sign of LGI1 antibody disease?

Personality change

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What intrinsic risk factors may increase the risk of developing LGI1 antibody disease later in life?

▪️ Male gender
▪️ HLA (human leukocyte antigen)

Disease related to which antibody may present with sleep disorders such as REM and NREM parasomnia?

IgLON5

What is the issue with only testing for antibodies in people who appear encephalopathic?

Many identified cases of ‘isolated psychiatric’ presentations would be missed

BUT we can test everyone with psychiatric presentation?

How common is autoantibody-mediated psychosis?

NMDAR-Ab found in around 5% of FEP, indistinguishable from the others

Can we make diagnoses based off blood tests?

No!

What are the main onconeural antibodies associated with paraneoplastic immune-mediated encephalitis?

▪️ Anti-Yo ▪️ Anti-Hu ▪️ Anti-Ri ▪️ Anti-Ma ▪️ PCA-2

Why is it important to detect cases of psychosis with anti-neuronal antibodies?

So that we can treat them appropriately with immunotherapy or tumour removal

What is lymphocytic pleocytosis?

Abnormal increase in amount of lymphocytes in CSF (T and C WBCs)

What is rituximab?

A monoclonal antibody that targets CD20 on B cells, stopping the production of antibodies

What are the main problems with Graus criteria for autoimmune encephalitis?

▪️ Too focused on neurological signs and symptoms ▪️ 'Possible' criteria assumes EEG/MRI has been done - unclear which psychiatric patients to investigate ▪️ 'Definite' criteria is too liberal? - accept serum antibodies for diagnosis but they are common

How does the new Pollak criteria for autoimmune encephalitis differ from the Graus criteria?

▪️ Reduced emphasis on serum test - not enough for diagnosis ▪️ Primary focus on CSF analysis ▪️ Need abrupt onset alongside just one of the possible signs to be sent for a lumbar puncture (e.g., movement disorder, adverse response to antipsychotics, decreased consciousness etc)

What are the main symptoms of encephalitis lethargica?

▪️ Initial pharyngitis ▪️ Sleep disorder (hypersomnolence/sleep inversion/insomnia) ▪️ Basal ganglia signs (parkinsonism/dyskinesia/hyperkinetic) ▪️ Neuropsychiatric symptoms (e.g., psychosis)

What are the main forms of encephalitis lethargica?

▪️ Somnolent-ophthalmoplegic ▪️ Hyperkinetic ▪️ Parkinsonian ▪️ Psychotic

What are the most common chronic sequelae of encephalitis lethargica?

▪️ Parkinsonism ▪️ Compulsive behaviour ▪️ Psychosis ▪️ Catatonia

What antibodies have been associated with modern cases of encephalitis lethargica?

▪️ Basal ganglia antibodies ▪️ NMDAR/D2R antibodies

What is postviral autoimmune encephalitis?

Autoimmune encephalitis following initial viral encephalitis Most commonly NMDAR antibodies following HSVE

How does postviral autoimmune encephalitis typically present?

▪️ Choreoathetoid movement disorder in children ▪️ Cognitive dysfunction in adults ▪️ Seizures ▪️ Occasionally isolated psychiatric cases?

How might postviral encephalitis lead to autoimmune encephalitis?

▪️ Damage to limbic system exposes NMDA receptor epitopes which trigger a second immune response? ▪️ Molecular mimicry?

When is an onconeural antibody screen mandatory?

If a patient has a known cancer

How does risk of encephalitis change postpartum?

It increases - can mimic postpartum psychosis

What is Hashimoto's encephalopathy?

▪️ Encephalopathy of presumed autoimmune origin ▪️ Characterised by massively increased levels of anti-TPO/TG antibodies, not necessarily with thyroid disease ▪️ Responds rapidly to steroids

How do we treat psychiatric symptoms in encephalitis?

Focus on treating the causes (e.g., antivirals, antibiotics, immunotherapies)

What contraindications must you consider when treating psychiatric symptoms in encephalitis?

▪️ High dose steroids can precipitate mania and/or psychosis ▪️ Methotrexate and cyclophosphamide can cause mood changes ▪️ Immunosuppression leaves individual vulnerable to opportunistic infection

What treatments can you use for agitation and/or catatonia in encephalitis?

Benzodiazepines but may require very high dose

What should you avoid when treating psychotic symptoms in encephalitis?

Typical neuroleptics/antipsychotics because: ▪️ Increased risk of neuroleptic malignant syndrome (especially in NMDAR encephalitis) ▪️ Can reduce seizure thershold

What symptoms of autoimmune encephalitis are often the most persistent and why?

Psychiatric symptoms - symptom resolution often mimics symptom onset

What residual cognitive impairment may be apparent following NMDAR encephalitis?

▪️ Episodic memory ▪️ Processing speed ▪️ Executive function Often subtle!

What is the prognosis of cognitive impairment following LGI1 encephalitis?

Majority do not return to baseline cognition, particularly with memory deficits due to MTL/hippocampal atrophy

How likely is relapse following AE and how does it typically present?

Common! Most likely isolated psychiatric or cognitive symptoms

What autoantibodies are especially associated with persistent subacute encephalopathy?

LGI1 and CASPR2 (Low threshold for repeaT LP/MRI/EEG)

What factors may contribute to the worse long-term psychiatric outcomes seen in individuals following encephalitis?

▪️ Premorbid factors ▪️ Encephalitis-associated neuronal damage ▪️ Psychological impact of illness experience (e.g., ICU) ▪️ Quality of psychosocial support - over 30% don't return to work/school INCREASED SUICIDALITY = IMPORTANCE OF COMMUNITY PSYCHIATRIC FOLLOW-UP