Prevalence rate of around 130/100000 in USA

Can affect multiple organs, neurological damage is

common in adults as well as in children

NPSLE/ Neurolupus Associated with worse prognosis
and more cumulative damage in children and adults

Lupus Cerebritis: Term used in SLE patients with broad
central nervous system symptoms rather than more
specific diagnostic terms, not included by ACR in the
definitions for NPSLE
Muscal, E., & Brey, R. L. (2010). Neurological manifestations of systemic lupus erythematosus in children and
adults. Neurologic clinics, 28(1), 61.
Wide variation in different studies
because of substantial differences in the criteria used to designate
nervous system involvement
Regional differences: African american, Asians more prone
Ranging from 14% to 80% in adults
Ranging from 22% to 95% in children
A retrospective study on 185 Chinese children:
11% had NPSLE at the time of diagnosis of SLE
Another 17% developed NPSLE in a year
Mortality rate:
45% in children with NPSLE
17.4% in children without NPSLE
(1) Danchenko N, Satia JA, Anthony MS. Lupus 2006;15:308318. [PubMed: 16761508]
(2) Brey RL, Holliday SL, Saklad AR, et al. Neurology 2002;58:12141220. [PubMed: 11971089]
(3) Petri M, Naqibuddin M, Carson KA, et al. J Rheumatol 2008;35(9):177681. [PubMed: 18634154]
(4) Costallat L, Bertolo M, Appenzeller S. Lupus 2001;10:S32.
Likely to be multifactorial

May involve autoantibody production, microangiopathy, intrathecal
production of proinflammatory cytokines and premature
atherosclerosis

Postmortem histopathologic studies: Wide range of of brain
abnormalities caused by multifocal microinfarcts, cortical atrophy,
gross infarcts, hemorrhage, ischemic demyelination and patchy
multiple-sclerosis-like demyelination in people with SLE

Damage can be caused by antineuronal antibodies, cytokine
effects, and abnormal hypothalamic pituitary axis response

Muscal, E., & Brey, R. L. (2010). Neurological manifestations of systemic lupus erythematosus in children and
adults. Neurologic clinics, 28(1), 61.
Dementia in NPSLE: Documented to be related to antiphospholipid
syndrome
Cognitive dysfunction significantly associated with persistently
positive aPL (1) and aCL (2)

Antiglutamate receptors may also have a significant role (3)
40% of lupus patients possess serum titers of anti-NR2A/B
antibody. (4)
Anti NR2A/B presence is an indication of the potential for
neuropsychiatric manifestations during the course of the SLE

(1) McLaurin EY et al. Neurology 2005;64:297303.
(2) Menon S et al. Arthritis Rheum 1999
(3) Husebye ES, et al. Ann Rheum Dis 2005;64:12101213
(4) Robin, C., et al., 1995. Rev. Neurol. 1995; 151 (12), 699707.
Aseptic Meningitis
Cerebrovascular disease
Stroke
Transient Ischemic Attack
Cerebral Venous Sinus
Thrombosis
Cognitive Disorders
Delirium (Acute confusional
state)
Dementia
Mild Cognitive Impairment
Transverse Myelopathy

Demyelinating
syndromes
Headaches
Tension Headaches
Migraine Headaches
Movement disorders
(Chorea)
Psychiatric Disorders
Psychosis
Mood Disorders
Anxiety Disorder
Seizure Disorders

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus
syndromes. Arthritis Rheum 1999;42:599608.
Autonomic Neuropathy
Myasthenia Gravis
Peripheral neuropathy

Commoner: Psychiatric disorders, headache, seizures
(1425% (Joseph and Scolding, 2010)), ischemia
(associated with antiphospholipid syndrome), and
peripheral neuropathy (Mills, 1994).
Rare: Aseptic meningitis, myelopathy, myasthenic
syndrome, and myositis (Mills, 1994).

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus
syndromes. Arthritis Rheum 1999;42:599608.
No diagnostic test sensitive and specific for SLE-related
neuropsychiatric manifestations

Assessment based on
Clinical evaluation,
immunoserologic testing,
brain imaging, and
psychiatric and neuropsychological assessment.
Muscal, E., & Brey, R. L. (2010). Neurological manifestations of systemic lupus erythematosus in children and
adults. Neurologic clinics, 28(1), 61.
A reduction in cerebral and corpus callosum volumes
associated with disease duration and cognitive impairment

Structural MRI: The majority (40% to 80%) of abnormalities in
NPSLE are small focal lesions concentrating in periventricular
and subcortical white matter

Cortical atrophy, ventricular dilation, diffuse white matter and
gross infarctions are also common.

Multiple discrete white matter lesions in periventricular,
cortical/subcortical junction, and frontal lobe - seen more
commonly in patients with past NPSLE manifestations, than
in SLE patients without history of NPSLE
Muscal, E., & Brey, R. L. (2010). Neurological manifestations of systemic lupus erythematosus in children and
adults. Neurologic clinics, 28(1), 61.
Diagnostic Tool Description
Anti nuclear factors Nonspecific in older people
Anti Sm Comparatively higher specificity
Rheumatoid factor Higher prevalence in late-onset SLE
Anti-double stranded
DNA
Lower prevalence in neurolupus
CSF Abnormal in 30-90% of cases
Lymphocytic pleiocytosis and oligoclonal IgG bands
MRI Multifocal and nonspecific gray and white matter
lesions
Hypersignal in T2 (57.4%)
Frontal atrophy (52%)
SPECT Frontal lobe hypoperfusion, which resolves in the
same time than the resolution of the psychiatric
symptoms
Cohen-Sohal and Diamond, 2011; Joseph and Scolding, 2010; Mills, 1994; Rovensky and Tuchynova, 2008.
Corticosteroids, several immunosuppressants (intravenous
pulse of cyclophosphamide, azathioprine, and methotrexate),
or plasmapheresis

Evidence of treatment efficacy is limited to uncontrolled
clinical trials and anecdotal experience

Key to treatment: To establish the correct diagnosis by
carefully following the guidelines set in the ACR 1999 Case
Definitions

For many NPSLE syndromes, symptomatic treatment may
also be needed in addition to immuno-modulatory therapy
Muscal, E., & Brey, R. L. (2010). Neurological manifestations of systemic lupus erythematosus in children and
adults. Neurologic clinics, 28(1), 61.
Cyclophosphamide: (1)
i.v. (5001000 mg/m^2) for a six month induction followed by
quarterly maintenance doses for a period of two years
Cytotoxic immunosuppression with documented therapeutic
benefits in the severe NPSLE manifestations unresponsive to
other treatment modalities (nephritis and CNS manifestations)

RCT on long-term use of cyclophosphamide and
methylprednisolone (2): Better overall therapeutic control of SLE-
related neurological manifestations (refractory seizures, peripheral
and cranial neuropathy, and optic neuritis) with monthly intravenous
cyclophosphamide, with a similar incidence of new infections.

(1) Petri M, Brodsky R. High-dose cyclophosphamide and stem cell transplantation for refractory systemic lupus erythematosus.
JAMA 2006;295:559560
(2) Barile-Fabris L, Ariza-Andraca R, Olguin-Ortega L, et al. Controlled clinical trial of IV cyclophosphamide versus IV
methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann Rheumatic Dis
2005;64(4):6205.
Psychotropic medications (i.e anti-depressants and
atypical antipsychotics) may have an important
adjunctive role in SL patients with affective or psychotic
disorder manifestations.

Non-pharmacologic approaches:
Haupt et al. demonstrated the ability to improve coping using a
psychological group intervention
Patients receiving this intervention showed a significant and
sustained improvement on a number of symptoms, such as
depression, anxiety and overall mental burden.
Haupt M, Millen S, Janner M, et al. Improvement of coping abilities in patients with systemic lupus
erythematosus: A prospective study. Ann Rheum Dis 2005;64:16181623. [PubMed: 15829575]
Mortality: 7 to 19%

Cause of death is usually not the NPSLE itself but infections,
cardiovascular disorders and drug induced complications

It is also important to control risk factors like hypertension and
diabetes (often corticoinduced in these patients) and to add
acetylsalicyl acid.

Treatment in older people
Challenging because of drug interactions, the frailty of older
people and side effects of treatment (like sarcopenia,
malnutrition, bedsore and decreased healing processes,
impaired renal function, decreased immune function,
osteoporosis, etc.)
Compte, Nathalie, et al. "Cognitive decline in an old woman: Do not miss a rare etiology!." Experimental
gerontology 47.7 (2012): 534-535.