Mx of neuropsychiatric lupus

Question 1

SLE

Answer 1

Systemic lupus erythematosus

Question 2

Predominance

Answer 2

9:1

Question 3

What are the treatments for lupus?

Answer 3

• hydroxychloroquine
• glucocorticoids
• steroid sparing agents
• rituximab
• cyclophosphamide

Question 4

What is an example of a glucocorticoid used to treat lupus?

Answer 4

Prednisolone

Question 5

When are glucocorticoids used to treat lupus?

Answer 5

During an acute flare 

Question 6

What are three steroid sparing agents used to treat lupus?

Answer 6

• mycophenolate (renal)
• azathioprine (during pregnancy)
• methotrexate (joint and skin)

Question 7

What are the treatments for severe disease?

Answer 7

Rituximab and cyclophosphamide

Rituximab is B cell depleting

Question 8

What are the EULAR/ ACR diagnostic criteria for SLE?

Answer 8

• ANA 1:10240
• fevers
• lymphopenic
• bilateral knee effusions
• probable lupus nephritis
• positive lupus anticoagulant
• positive Sm and RNP antibodies

Question 9

SLEDAI-2K

Answer 9

The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) is a measure of lupus severity

Question 10

What is the cut off for the SLEDAI-2K

Answer 10

3 or 4

Question 10

Two classifications of neuropsychiatric lupus symptoms

NPSLE: Neuropsychiatric Systemic Lupus Erythematosus

Answer 10

Central nervous system and peripheral nervous system

Question 11

CNS NPSLE symptoms

Answer 11

• aseptic meningitis
• stroke
• demyelinating syndrome
• headache
• movement disorder
• myelopathy
• seizure
• acute confusional state
• cognitive dysfunction
• mood disorder
• psychosis

Question 12

PNS NPSLE symptoms

Answer 12

• acute inflammatory demyelinating polyradiculoneuropathy
• autonomic disorders
• cranial neuropathy
• mononeuropathy
• myasthenia gravis
• plexopathy
• polyneuropathy

Question 13

What are the three key factors for npsle treatment?

Answer 13

1. immunosuppression
2. antipsychotics
3. time

Question 14

What is immunosupprive treatments for npsle?

Answer 14

• corticosteroids
• cyclophosphamide/ rituximab

Question 15

What are potential causes of npsle?

Answer 15

• direct inflammation of the CNS/ PNS
• damage from previous active lupus
• treatment (iatrogenic)
• concurrent psychiatric dx (related or unrelated to SLE)

Question 16

what is the prevalence of CNS symptoms in npsle

Answer 16

12-95%

Question 17

why are incidence/ prevalence of npsle symptoms so heterogenous?

Answer 17

• it is difficult to attribute symptoms to active lupus
• studies are poorly defined
• pathogenesis is poorly understood

Question 18

how frequently do SARDs patient report neuropsychiatric symptoms compared to controls

Answer 18

Self-reported lifetime prevalence (more than three times in life) of all symptoms were rated as significantly higher in patients compared to controls except for suicidal thoughts, delusions/ paranoia and seizures

Sloan et al. (2023)

Question 19

COVID-19 vaccination in autoimmune diseases (COVAD-2) study

Answer 19

Background
* A global register of more than 20,000 respondents
* Compared differences in physical functioning (PROMIS)
* Collected mx, comorbidities, disease activity, physical and mental health data
results
* factors associated with poor physical functioning including age, methotrexate use, diabetes, interstitial lung disease
* anxiety associated with poorer physical functioning
* hydroxychloroquine use associated with better physical functioning

Question 20

what is a possible seriological marker for npsle

Answer 20

anti-ribosomal p antibody

A meta-analysis showed that it was not a very specific marker

Question 21

what other conditions are positive for anti-ribosomal p antibody

Answer 21

• rash
• mouth ulcers
• other antibodies

Question 22

cerebrospinal fluid as a marker for npsle

Answer 22

• serum anti-ribosomal P, anti-NMDAR, and other antibodies did not differentiate between cns-npsle, pns-npsle, sle etc groups
• decreased levels six months later associated with decrease in disease activity rather than change in np symptoms
• only NMDAR antibodies in CSF characterstically different in cns-npsle and septic meningitis

Fragoso-loyo et al. (2008)

Question 23

potentional imaging targets as markers for npsle

Answer 23

• blood brain barrier (ideal)
• white matter changes

Question 24

blood brain barrier permeability as an imaging marker for npsle

Answer 24

dynamic contrast enhanced T1 weighted MRI shows increased hippocampal permeability in patients with SLE ## Footnote Chi et al. (2019) multiple T1 weighted MRI taken before during and after administering contrast

Question 25

white matter changes as an imaging marker for npsle

Answer 25

* dual echo and T1 weighted MRI frequently show white matter changes in SLE * derived T2 hyperintense lesional volume, number and probability * higher lesional volumes between hc and sle * higher lesional volume in npsle compared to non-npsle * higher lesion number in npsle vs non-npsle * sle associated with higher prevalence of lesions in the splenium of the corpus callosum, right superior longitudinal fasciculus and right corona radiata | Ramirez et al. (2021)

Question 25

potential histopathological markers for npsle

Answer 25

* aimed at characterizing the CD4 T cell populations present in the choroid plexus (CP) of MRL/MpJ-faslpr mice * chorotic plexus is the primary site of infiltration in classic lupus mouse models exhibiting a prominent neurobehavioural phenotype * results suggest that accumulation of CD4 TFH in the brain of MRL/MpJ-faslpr mice may contribute to the neuropsychiatric manifestations of SLE, and point to this T cell subset as a possible novel therapeutic candidate | Jain et al. (2018)