sessing disease severity . Analysis of CSF is important to exclude infection , integrity of the blood-brain barrier , presence of autoantibodies ( e . g ., α-phospholipid antibody , α-ribosomal-P , or α-NR2 ) or possibly Neuro-inflammatory mediators ( e . g ., lipocalin 2 or osteopontin ). Electroencephalography can assess for seizure disorder . Neuroimaging to evaluate brain structure ( e . g ., computed tomography or magnetic resonance imaging ) and / or brain function ( PET ) may reveal anatomic or functional abnormality . A variety of screening tools developed to assess neurodegenerative conditions may be used to evaluate cognitive dysfunction , depression , and anxiety in SLE patients . The Montreal Cognitive Assessment Questionnaire is sensitive ( 0.83-0.94 ) and moderately specific ( 0.27-0.46 ) for detecting cognitive disorder versus normal controls . The Center for Epidemiological Studies-Depression Scale and the Hospital Anxiety and Depression Scale are considered highly reliable for depression and anxiety screening . 8 , 9
Management
Treatment options for patients with NPSLE are not well-standardized since no robust , randomized controlled trials have been performed to validate therapies for specific NPSLE manifestations ; therefore , current treatment regimens are based on small , controlled trials , case studies , and expert opinion . 3 Therapy should be targeted at the type of neuropsychiatric event ( considering the 19 NPSLE syndromes ) and individualized based on symptom severity and time from onset , suspected mechanism ( detection of specific antibodies or thrombosis ), expected morbidity , acute-versus-chronic presentation , whether predominantly inflammatory or vascular involvement , whether disease flare is active and ongoing or resultant from secondary damage , and response to prior therapies . 3 , 10
Symptomatic therapy for mild manifestation of NPSLE such as headache or depression may be sufficient ; however , more severe NPSLE manifestations or inadequate response to symptomatic treatment may require aggressive therapy with immunosuppressive agents to control the underlying autoimmune process
3 , 10 , 11 and prevent organ damage .
For inflammatory NPSLE , systemic glucocorticoids are most often used and result in a beneficial response in 60-75 % of patients . 3 Differing dosing regimens from prednisolone 0.5 – 1 mg / kg / day to bolus IV methylprednisolone 500 mg to 1 g / day have been used but no strong data support a particular protocol . 10 In severe disease activity , additional immunosuppressive therapy with hydroxychloroquine , methotrexate , cyclophosphamide , and azathioprine have also been used . Rituximab and belimumab have also been used , with high response rates in severe NPSLE . For severe refractory NPSLE – particularly in cases where severe infection , pregnancy , or life-threatening symptoms are present – IV immunoglobulin and plasmapheresis have been used as bridge therapy pending establishment of a maintenance
10 , 11 regimen .
For ischemic NPSLE , the decision for secondary thromboprophylaxis is based on definitive presence of anti-phospholipid syndrome ( APS ). 11 The binding of anti-phospholipid ( aPL ) antibody to endothelial cells starts a cascade that favors platelet clot formation via increasing the expression of glycoprotein IIb / IIIa . Consequently , NPSLE who are APS + have a higher prevalence of accelerated atherosclerosis and vasculopathy . 12 In addition to statin therapy ( target LDL < 70mg / dL ), NPSLE patients seronegative for aPL ( or aPL positive but lacking criteria for APS ) may receive anti-aggregation platelet therapy with aspirin ( 50-325 mg / day ) monotherapy , the combination of aspirin plus extended-release dipyridamole , or clopidogrel ( 75 mg / day ) monotherapy . In SLE patients with stroke and fulfilling criteria for APS , the optimal treatment is controversial . Some authorities favor anti-aggregation antiplatelet therapy alone while others advocate for combined anti-platelet therapy and lower intensity anticoagulation with Warfarin ( INR 2.0- 3.0 ) or high-intensity oral anticoagulation ( INR > 3.0 ). 11 Low-molecular weight heparins ( e . g ., enoxaparin 30mg every 12 hours subcutaneously ) are efficacious therapy for SLE patients with vascular thrombosis . 4
Conclusion
The presence of NPSLE identifies those patients with a higher mortality than those without the manifestations of NPSLE . Therefore , for patients presenting with altered neurological features combined with a fitting clinical picture of SLE such as multi-system involvement , NPSLE should be included in the differential diagnosis to avoid delay in the diagnosis and management of SLE . 2
References
For a complete list of references , please email ams @ arkmed . org .
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Volume 118 • Number 6 DECEMBER 2021 • 133