Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...
Lupus neuropsiquiatria
1. The 10th International Congress on SLE
Buenos 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
2. 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.
3. 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
4. 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.
5. EULAR Recommendations for the
Management of Neuropsychiatric SLE
eular
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)
Bertisas GK. Ann Rheum Dis: 69.2074-82
6. NP events at the time of diagnosis
Hanly JG. Ann Rheum Dis
2101;3:529-35.
7. 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
9. 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.
12. EULAR Recommendations for the Management of Neuropsychiatric
SLE
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).
Bertisas GK. Ann Rheum Dis: 69.2074-82
eular
13. 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
14. Case 1
2007
SLE: Arthritis, cutaneous involvement, serologic
criteria.
2009
Arthritis, skin.
2010
ANA 1:280
C4 3 C3 55
Arthritis, Raynaud, digital vasculitis.
Abril 2010
2011
Methilprdnisolone 3gr
IV Cy single dose
Anxiety, insomnia, mood disorders.
CAT and MRI: Normal. CSF:Normal
Steroidal psicoisis
Ketiapine 200mg, Prednisone 35mg, Sertraline 50mg MMF
2 gr /d.
SLEDAI 0 (low complement levels) slow prednisone tappering and
MMF.
Regional hospital : MMF 500mg d.
15. Case 1 (Readmission)
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.
35. eular
EULAR Recommendations for the Management of Neuropsychiatric
SLE
Neuropsychiatric SLE – General statements
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 antiphospholipid 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).
36. •
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.
39. Median monthly values of visual analogue scale ratings for changes in
muscular strenght in NP and TM patients
P=0.04
0= No changes from basal conditions; 10= the best possible
improvement
44. 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.
45. Oct 3 2010: Hyperstetic sensitive level C5 and
T7, medular discharges, hyporeflexia.
MRI: Hyper intensity with T1
enhancement, suggestive of
longitudinal myelopathy
From C2 to T12 with high activity in
neuro-imaging
50. 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.
51. 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.
Notas del editor
2007 recibiendo tratamiento con diclofenaco, prednisona 5mg día, cloroquina 150mg, azatioprina 100mg día. Buena respuesta y lo dejo de tomar.2009 metotrexato 10mg y prednisona 5mg. 72 hrs. posterior a medicación.
Infarto embolico, por ser cortical y 2 territorios diferentes., con restricción de la difusión y ADC bajo.Infección por microorganismo oportunista Toxoplasmosis por inmunosupresión o abceso cerebral por cefalea, fiebre y crisis convulsivas.Neurocirugía: Imagen isointensa en T1 e hiperintensa en T2 a nivel frontal derecho, parietal izquierdo y occipital derecho cortico subcortical con edema perilesional leve, que no refuerzan con medio de contraste.
