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Management > Autoimmunity and Mental Health > Flashcards

Autoimmunity and Mental Health Flashcards

1
Q

Who is wagner-Jauregg

A

1st psychiatrist of 3 ever to win a noblel prize for malarial therapy in treating dementia paralytica in 1927

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2
Q

What are the mulitple organisms implicated in schizophrenia, bipolar, autism and OCD?

A

herpes viruses (HSV, CMV, EBV), influenza, toxoplasma more

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3
Q

What is the role of the microbial cells?

A

secrete neurotransmitters (serotonin, GABA), influence immune response, metabolise nutrients, affect brain development and function (not understood how)

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4
Q

2016 there were _____ syphilis diagnoses a ____ increase in previous year and ____ rise on 2012

A

5,920 syphilis diagnoses, 12%, 97%

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5
Q

How does rogues gallery: syphilis mainly occur?

A

men who have sex with men

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6
Q

What are the 4 stages of disease?

A

Primary: ulcer or chancre at site of inoculation
Secondary (4-10 wks): early generalised lesions in skin and mucous membranes
Latent: asymptomatic
Tertiary: vascular, cardiac, CNS problems

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7
Q

What are early and late stage neurosyphilis examples

A

Early: acute meningitis, meningovascular
Late: tabes dorsalis, general paresis of the insane (GPI)

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8
Q

What are the psychiatric symptoms of spyhilis?

A

General paresis/dementia paralytica
Personality change
Disinhibition
Grandiosity/mania (less common)
Simple dementing form (more common)
Depressive, paranoid and neurasthenic forms all described
Dementia progresses, with seizures and paralysis, until death 4-5 years after diagnosis.

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9
Q

Who is susceptible to toxoplasma?

A

Devastating infection in neonates and immunosuppresed people (e.g. in HIV)

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10
Q

What psychiatric symptoms is toxoplasma associated with

A

Appears to associate with impulsive behaviour in humans
Increased risk of suicide/self harm/automobile accidents
Associated with increased risk of schizophrenia and possibly other psychiatric disorders
Evidence for association w/ bipolar disorder, anxiety disorders, addictions

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11
Q

What does toxoplasma infection cause (in animals?)

A

production of brain reactive antibodies and perturbation of dopamine function in animals.

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12
Q

The first stage of lyme disease is…. with what symptoms?

A

Localized infection (2-30 days)
Any of the following, none of which are always present
Rash at site of bite: Classically ‘Erythema Migrans’
Lymphadenopathy
Systemic symptoms: Fever, chills, fatigue, muscle/joints aches

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13
Q

The second stage of lyme disease is…. with what symptoms?

A

. Early disseminated infection (Days - months):
Neurological: facial palsy/other cranial nerve lesions, meningitis, radiculoneuritis (shingles-like pain without rash over area of pain)
Musculoskeletal: ongoing myalgia & arthralgia +/-itis
Cardiovascular: conduction abnormalities - rare
Ocular & Hepatic features: v. rare

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14
Q

What are other clinical features of lyme disease?

A
  1. Encephalopathy: memory & concentration problems. Cytokine mediated response to systemic infection?
  2. Arthritis: of large joints, esp a ‘boggy’ & not particularly painful knee. Rarer in UK acquired infection.

And rarely……

  1. Late encephalomyelitis: spastic paraparesis, broader/more severe cognitive impairment, cranial neuropathy, bladder dysfunction & dysarthria
  2. Acrodermatitis chronica atrophicans: late skin complication – often occurs with peripheral neuropathy
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15
Q

What is herpes virus?

A

Large family of dsDNA viruses: includes HSV-1, HSV-2, HHV-6, CMV, EBV, VZV
Can establish latency in sensory ganglion neurons (HSV-1 + 2, VZV) or in lymphocytes (EBV) or other cell types.
Neurotropic; can cause encephalitis in rare cases
Often sexually transmitted
Very widespread infections: often >90% prevalence

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16
Q

What are the psychiatric associations of herpes viruses?

A

Well-replicated association with cognitive impairment in schizophrenia and BPAD and HSV-1
CBV/EBV infection frequently reported before CFS/ME
Postmortem evidence of HSV-1 in Alzheimer’s disease brains

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17
Q

What is influenza?

A

Seasonal influenza A viruses (H3N2 and H1N1) circulate within the population, causing yearly epidemics.

Pandemic viruses are the result of cross-species transmission, after which they adapt to humans and spread worldwide.
1918 H1N1 ‘Spanish flu’
1957 H2N2 ‘Asian flu’
1968 ‘Hong Kong flu’
2009 H1N1 ‘Mexican flu’ or ‘swine flu’.
Acute infection can present with encephalitis, but v rare.

18
Q

Influenza and increased risk of

A

schizophrenia (esp first half of pregnancy), BPAD

19
Q

Influenza led to what model

A

Maternal Immune Activation (MIA) model

+Molecular mimicry: multiple peptide homologies with various brain proteins (inc NMDAR)

20
Q

What genes are implicated in psychosis?

A

MHC genes, other immune SNPs

21
Q

What are inflammatory markers of the blood/CSF?

A

C-reactive protein, cytokines

22
Q

Schizophrenia is associated with a ____ risk for autoimmune disease

A

55%
highest relative risk autoimmune hepatitis (5.4-5.6)
only negative relative risk is rheumatoid arthritis

23
Q

What is encephalitis and the types?

A

Inflammation of the brain
infectious encephalitis, unknown and immune mediated encephalitis (post-infectious, autoimmune encephalitis)

24
Q

What are the causes of infective encephalitis?

A

Viral: HSV-1, HSV-2, HIV, measles, influenza VZV, CMV, EBV, HHV-6, HHV-7, poliovirus, rabies virus, dengue, West Nile, Zika, JC virus
Bacterial: syphilis, borrelia (Lyme disease), Mycobacterium tuberculosis
Protozoal: malaria, toxoplasma, human African trypanosomiasis (sleeping sickness)
Rickettsial: Q fever
Fungal: cryptococcus, aspergillosis, candidiasis

25
Q

What are the causes of noninfective encephalitis?

A

Autoimmune
Paraneoplastic: Hu, Ma, ampiphysin, CV2
Non-paraneoplastic: NMDAR, LGI1, CASPR2, DPPX, IgLON5
Systemic lupus erythematosus
ADEM

26
Q

What are the two unknown encephalitis?

A

Encephalitis lethargica
Rasmussen’s encephalitis

27
Q

autoantibodies bind to and cause

A

ion channels, receptors, associated proteins on neuronal cell surface
cognitive, seizures, movement disorders (respond to immunotherapy)

28
Q

What do Anti NMDAR antibodies do?

A

target the receptor, internalize it cause NMDA receptor hypofunction

29
Q

What is encephalitis lethargica?

A

Pharyngitis followed by sleep disorder (somnolence/sleep inversion/insomnia), basal ganglia signs (esp parkinsonism/dyskinesias) and neuropsychiatric symptoms
Main forms:
Somnolent-ophthalmoplegic
Hyperkinetic
Parkinsonian
Psychotic
40% recovery, 40% residual deficits, 20% death

30
Q

What are the chronic sequelae of encephalitis lethargica?

A

Parkinsonism
Compulsive behaviour
Psychosis
Catatonia

31
Q

Significant association with ASD observed in families with

A

with hypothyroidism, type 1 diabetes, rheumatoid arthritis, and psoriasis.

32
Q

Children born to mothers with autoimmune disease ____ more likely to develop ASD

A

34%

33
Q

Increased ASD risk associated with what polymorphisms?

A

HLA and complement

34
Q

What antibodies are observed in maternal sera?

A

37 and 73-kDa antibodies (antigen remains unidentified)

35
Q

Rare study of what antibodies attributable to autistic regression/childhood disintegrative disorder

A

Anti-NMDAR antibodies

36
Q

CASPR2 antibodies common in

A

mothers of children with NDDs and possibly ASD: maternal-fetal transfer in animals recapitulates a neurodevelopmental phenotype

37
Q

In bipolar what antibodies correlate with manic episodes in Dickinson study

A

NMDAR antibody

38
Q

What are the potential mechanisms of neuropsychiatric sequelae of COVID_19?

A

Direct effects of (likely) neurotropic virus via BBB or neuronal transport
Immune response: cytokine storm and/or later autoimmunity (antibody mediated) OR vasculopathy/vasculitis

39
Q

What are the chronic disabling symptoms of longcovid?

A

‘Mild’ initial infection: not hospitalized

Chronic disabling symptoms
Fatigue, headache, brain fog
Breathlessness, chest pains/tightness
Paraesthesias/pains other sensorimotor
GI/Derm/other (inc anxiety depression)
Pyrexia
Other……

Symptoms often dismissed/not taken seriously, esp if no positive (or negative) Ag or Ab test

Seen mostly in primary care, but increasingly in secondary care

40
Q

Do vaccines cause psychiatric disease?

A

NO!

Management (4 decks)

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