lupus neuropsiquiatria
DESCRIPTION
Leonor A. Barile-Fabris, MD, PhD Professor of Rheumatologo Chair, Rheumatology Department Centro Médico Nacional Siglo XXI Mexico City, MexicoTRANSCRIPT
![Page 1: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/1.jpg)
The 10th International Congress on SLEBuenos Aires, Argentina
Neuro-psychiatric SLE
Leonor A. Barile-Fabris, MD, PhD Professor of Rheumatology
Chair, Rheumatology Department Centro Médico Nacional Siglo XXI
Mexico City, Mexico
![Page 2: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/2.jpg)
Key points
NP manifestations have been increasingly recognized.
Both attribution and diagnosis remain clinical challenges.
Selection of optimum treatment is complex due to scarce and heterogeneous clinical data.
![Page 3: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/3.jpg)
Key issues in SLE patients with neuropsychiatric manifestations
EULAR Task force on SLE- Evidence and expert-based answers
• Who is at risk to develop NPSLE?
• Is NPSLE common?
• When to suspect NPSLE?
• How can I attribute a NP event to SLE?
• How do I treat NPSLE?
Bertisas GK.Nat Rev Rheumatol.2010:6;1-10
![Page 4: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/4.jpg)
Key points
NP symptoms are present in approximately 20 to 50% of SLE patients, frequently within the first 2 years.
These symptoms are primarily associated with a poor HRQoL and an increase in functional impairment, leading to unemployment in some cases.
Mild manifestations are common and include headache, anxiety, depression, and cognitive deficit. These, however, are not normally related to the disease.
Source: Bertisas GK. Nat Rev. Rheumatol. 2010:6;1-10.
![Page 5: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/5.jpg)
Neuropsychiatric SLE – General statements
1. When do they occur?
-May precede, coincide, or follow the diagnosis of SLE but commonly (40-50%) occur within the first year after SLE diagnosis,
-Usually (50-60%) in the presence of generalized disease activity (B).
2. Cumulative incidence of neuropsychiatric manifestations:
- common (10-20%): cerebrovascular disease, seizures
- relatively uncommon (3-10%): severe cognitive dysfunction, major depression, acute confusional state and peripheral nervous disorders
- rare (<3%): psychosis, myelitis, chorea, cranial neuropathies, aseptic meningitis (B)
EULAR Recommendations for the Management of Neuropsychiatric SLE
eular
Bertisas GK. Ann Rheum Dis: 69.2074-82
![Page 6: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/6.jpg)
NP events at the time of diagnosis
Hanly JG. Ann Rheum Dis 2101;3:529-35.
![Page 7: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/7.jpg)
NP Manifestations in 88 SLE patients at the Centro Médico Nacional “La Raza”, Mexico City
Manifestation Number
Seizures 32
Delirium 21
Stroke 15
Pheripheral neuropathy 12
Optic neuritis 10
Transverse myelitis 4
Barile et al. Lupus 1988;7:S 107
![Page 8: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/8.jpg)
Seizures 99 30.9
Headeache 54 16.8
Psychosis 49 15.3
Delirium 47 14.6
Stroke 34 10.6
Sensitive neuropathy 33 10.3
Motor neuropathy 31 9.6
Coma 10 3.13
Aseptic meningitis 7 2.19
Transverse myelitis 7 1.7
Chorea 5 1.5
Ataxia 4 1.2
Pseudo tumor cerebri 2 0.63
Organic brain syndrome 2 0.63
GLADEL
Barile et al. Lupus 1998 (Suppl);7:53
![Page 9: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/9.jpg)
Differing prevalences in LSE
Highly heterogeneous clinical manifestations.Some are not specific or “subclinical”.Manifestations may be present despite the
absence of other disease activity signs.Attribution is difficult to establish.There might be differences between inception
and survival cohorts.
![Page 10: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/10.jpg)
Bertisas GK.Nat Rev Rheumatol.2010:6;1-10
![Page 11: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/11.jpg)
Bertisas GK.Nat Rev Rheumatol.2010:6;1-10
![Page 12: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/12.jpg)
Neuropsychiatric SLE – General statements
4. Diagnostic work-up
a) In SLE patients with new or unexplained symptoms or signs suggestive of neuropsychiatric disease, initial diagnostic work-up should be similar to that in non-SLE patients presenting with the same manifestations (D).
b) Depending upon the manifestation, this may include lumbar puncture and CSF analysis (primarily to exclude CNS infection), EEG, neuropsychological assessment of cognitive function, nerve conduction studies, and neuro-imaging (MRI) to assess brain structure and function (D).
c) The recommended MRI protocol (brain and spinal cord) includes conventional MRI sequences (T1/T2 FLAIR), diffusion-weighted imaging (DWI), and gadolinium-enhanced T1 sequences (B).
EULAR Recommendations for the Management of Neuropsychiatric SLE
eular
Bertisas GK. Ann Rheum Dis: 69.2074-82
![Page 13: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/13.jpg)
MRI white-matter lesions in NPSLE
• ↑ signal in Τ2 / FLAIR
• Localized in subcortical and periventricular white matter and frontal-parietal lobe (70–80%)
• Prevalence 50–60% of all patients with NPSLE …but 18–40% of non-NPSLE
…no correlation with a particular NP syndrome
• Cerebral atrophy, number and size of WML and cerebral infarcts correlate with severity of cognitive dysfunction
In young SLE patients new MRI WMLs (especially if ≥5, ≥6-8mm, and bilateral may suggest active NPSLE
![Page 14: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/14.jpg)
Case 1
2007 SLE: Arthritis, cutaneous involvement, serologic criteria.
ANA 1:280 C4 3 C3 55
2009 Arthritis, skin.
2010 Arthritis, Raynaud, digital vasculitis.
Methilprdnisolone 3grIV Cy single dose
Abril 2010Anxiety, insomnia, mood disorders.CAT and MRI: Normal. CSF:NormalSteroidal psicoisis Ketiapine 200mg, Prednisone 35mg, Sertraline 50mg MMF 2 gr /d.
2011 SLEDAI 0 (low complement levels) slow prednisone tappering and MMF.
Regional hospital : MMF 500mg d.
![Page 15: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/15.jpg)
24/02/13:Seizures.Increased reflexes.DFH Levertiracetam, Metilprednisolone 3 gr.
03/03/13:Seizures.Increased reflexes.DFH Levertiracetam, Metilprednisolone 3 gr.Abnormal movements.Topiramate and lumbar puncture.
06/03/13:Anxiety-depression disorder.
Case 1 (Readmission)
![Page 16: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/16.jpg)
IRM
![Page 17: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/17.jpg)
Identifying differential diagnosis
Embolic infarct.Opportunistic infection.Brain abscess.NP SLE.Brain tumor.
![Page 18: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/18.jpg)
MRI Diagnosis
Radiology: Infarcts (embolus), cortical, in two different territories, restricted diffusion, low ADC.
Neurology: Opportunistic infection (toxoplasmosis) vs. brain abscess (headache, fever, seizures).
![Page 19: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/19.jpg)
Cardioembolic infarct
NP SLE
Abscess
Tumor
CSF:Cels 0, RC 10, C 100%.Prot25.2 mg/dl, Gluc42 mg/dl, Cl 127 mEq/L. ANA (-), C3 y C4 0, Anti DNA 8.9, aCL 2.0
Gramm (-).Cultive (-)
Brain gammagram Taliium 201 and Gallium 67: normal.
.
IV Cy.
Case 1: results
TE echocardiogram: Normal
![Page 20: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/20.jpg)
MRI in NP SLE
Multiple white matter lesions.Cerebral infarction.Cerebral hemorrhage.Venous sinus thrombosis.Atrophic changes.Spinal cord disease.
Lupus 2003;12:891
![Page 21: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/21.jpg)
![Page 22: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/22.jpg)
![Page 23: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/23.jpg)
![Page 24: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/24.jpg)
Saggital T1 image: Clot in the Stright sinus
![Page 25: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/25.jpg)
![Page 26: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/26.jpg)
Take-home messages,case 1
There is not such thing as a typical MRI in neurolupus.
Differential diagnosis comprises a wide range of causes.
![Page 27: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/27.jpg)
![Page 28: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/28.jpg)
![Page 29: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/29.jpg)
Prognosis and treatment
![Page 30: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/30.jpg)
Prognosis
Poor prognosis factors:• Caucasians?• Active disease• aRO, LA, IgG aCl.
Rheumatology 2004; 43:1555-1560.
![Page 31: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/31.jpg)
Prognosis in 2 referral hospitals in Mexico City
71%
29%
improvement no response
![Page 32: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/32.jpg)
Poor prognosis, cont’d.
Male gender.neuroSLICC ≥1 p = 0.0001.↑antiDNA p= 0.21.Low complement levels p= 0.05.↑ESR p= 0.036.
![Page 33: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/33.jpg)
Poor prognosis factors
Consolidation analysis:
Normal ESR and complement: 85.7% improved.Low complement and high ESR : 69.2% worsened.P= 0.001
![Page 34: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/34.jpg)
Treatment
Barile L. Reumatol Clin. 2005;1 Supl 2: S42-5
![Page 35: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/35.jpg)
5. Therapy
a) Corticosteroids and immunosuppressive therapy are indicated for neuropsychiatric manifestations felt to reflect an immune/inflammatory process (acute confusional state, aseptic meningitis, myelitis, cranial and peripheral neuropathies, and psychosis) following exclusion of non-SLE related causes (A, D).
b) Anti-platelet/anti-coagulation therapy is indicated when manifestations are related to anti-phospholipid antibodies, particularly in thrombotic cerebrovascular disease (A, D).
c) The use of symptomatic therapies (e.g. anticonvulsants, antidepressants) and the treatment of aggravating factors (e.g. infection, hypertension and metabolic abnormalities) should also be considered (D).
d) Anti-platelet agents may be considered for primary prevention in SLE patients with persistently positive, moderate or high, anti-phospholipid antibody titers (D).
EULAR Recommendations for the Management of Neuropsychiatric SLE
eular
Neuropsychiatric SLE – General statements
![Page 36: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/36.jpg)
• Induction Metilprednisolone (MP) 1 g/d for 3 d.
• MP 1 g/d por 3 d, monthly for 4 m, then bimonthly for 6 m, and subsequently every 3 m for 1 y.
or
• Ciclophosphamide (Cy) 0.75 g/m2 bs monthly for 1 y, and every 3 m for another y.
Ann Rheum Dis 2005;64:620–625.
![Page 37: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/37.jpg)
![Page 38: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/38.jpg)
Allocation
![Page 39: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/39.jpg)
Median monthly values of visual analogue scale ratings for changes in muscular strenght in NP and TM patients
0= No changes from basal conditions; 10= the best possible improvement
P=0.04
![Page 40: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/40.jpg)
MPDCFM
Seizures
![Page 41: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/41.jpg)
Average prednisone intake/ day
![Page 42: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/42.jpg)
Response to treatment
Response MPD CY
Failure 7 1
Improvement 11 18
p
<0.003
<0.05
![Page 43: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/43.jpg)
Trevisani et al Cochrane 2008
![Page 44: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/44.jpg)
Case: Female, 62 years old.
2001: Optic Neuritis in right eye.2010: Non Hodgkin lymphoma, QxTx RxRx. May 2010: Optic Neuritis in left eye.Hypotiroidism. ANA 1:640 H, lymphopenia,
leukopenia, Neurolupus: Pdn 50mg/d and Mycophenolate.
Oct 3 2010: Hyperstetic sensitive level C5 and T7, medular discharges, hyporeflexia.
![Page 45: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/45.jpg)
Oct 3 2010: Hyperstetic sensitive level C5 and T7, medular discharges, hyporeflexia.
MRI: Hyper intensity with T1 enhancement, suggestive of longitudinal myelopathyFrom C2 to T12 with high activity in neuro-imaging
![Page 46: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/46.jpg)
![Page 47: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/47.jpg)
![Page 48: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/48.jpg)
Selecting treatment
• IV MP• Oral prednisone and high dose MMF• IV Cy• Plasmaphereis• IV MP and IV Cy• Others?
![Page 49: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/49.jpg)
MP 5 gPdn 50 mg/d
Partial improvement in sensitivity. Paraplegia. Acute confusional syndrome. Delirium. IV Cy 700mg.
Currently: 6 pulses Partial recovery Sensitivity fully recovered Motor capacity 30% recovery
![Page 50: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/50.jpg)
Take-home messages: Case 2
Despite published evidence, response to treatment even within the same clinical manifestation may be heterogeneous.
Transverse myelopathy has a better prognosis than longitudinal myelopathy.
![Page 51: Lupus neuropsiquiatria](https://reader034.vdocuments.us/reader034/viewer/2022042623/5455c773af7959b53e8b8777/html5/thumbnails/51.jpg)
Final considerations
There are different clinical subgroups in neurolupus.
Etiopathogenic mechanisms might be different, but they all seem to be related to vascular endothelium.
NP SLE has a profound impact in prognosis, HRQoL and damage.