What is the diagnostic approach for lupus cerebritis?

Diagnostic Approach for Lupus Cerebritis

The diagnostic workup for lupus cerebritis should mirror the evaluation of any non-SLE patient presenting with the same neuropsychiatric symptoms, with the primary goal being exclusion of alternative causes (particularly infection) before attributing symptoms to SLE. 1

Initial Clinical Assessment

Recognize the temporal pattern: Neuropsychiatric manifestations occur within the first year of SLE diagnosis in 50-60% of cases, commonly (40-50%) coinciding with generalized disease activity. 1 However, lupus cerebritis can present as acute confusional state, psychosis, seizures, or focal neurological deficits. 1

Key clinical presentations of cerebritis include:

• Acute confusional state with fluctuating consciousness and decreased attention 1
• Psychosis characterized by delusions or hallucinations (distinct from steroid-induced psychosis which manifests primarily as mood disorder in 93% of cases) 1
• Seizures (though single isolated events are more common than recurrent epilepsy) 1

Essential Diagnostic Investigations

Cerebrospinal Fluid Analysis

Perform lumbar puncture primarily to exclude CNS infection, not to confirm NPSLE. 1, 2

• Include PCR for herpes simplex virus (HSV) and JC virus when clinically indicated 1
• Mild CSF abnormalities (elevated protein, pleocytosis) occur in 40-50% of NPSLE cases but are non-specific and do not confirm the diagnosis 1, 2
• Intrathecal IgG and IgM production is observed in 25-66% of CNS lupus patients 3

Neuroimaging Protocol

The recommended MRI protocol includes conventional sequences (T1/T2, FLAIR), diffusion-weighted imaging (DWI), and gadolinium-enhanced T1 sequences. 1

MRI findings and their limitations:

• Average sensitivity of MRI in active NPSLE is 57% (64% in major vs 30% in minor NPSLE, 76% in focal vs 51% in diffuse NPSLE) 1
• Most frequent pattern: small punctate hyperintense T2-weighted focal lesions in subcortical and periventricular white matter, typically in frontal-parietal regions 1
• Critical caveat: These MRI lesions are also present in many SLE patients without neuropsychiatric manifestations (specificity only 60-82%) 1
• For lupus psychosis specifically, brain MRI has modest sensitivity (50-70%) and specificity (40-67%) 1

Electroencephalography

Order EEG to diagnose underlying seizure disorder or when acute confusional state is present. 1

• EEG abnormalities are common (60-70%) in SLE patients with seizure disorder 1
• Typical epileptiform EEG patterns are only present in 24-50% but are predictive of seizure recurrence (positive predictive value 73%, negative predictive value 79%) 1

Brain SPECT Imaging

Consider brain SPECT for acute confusional state and psychosis, as it has higher sensitivity than MRI for these manifestations. 1

• Brain SPECT is 93% sensitive for acute confusional state and may help monitor treatment response 1
• For severe psychosis, brain SPECT identifies perfusion deficits in 80-100% of cases 1
• Residual hypoperfusion during clinical remission correlates with future relapse 1

Laboratory Evaluation for Risk Stratification

Test for antiphospholipid antibodies (anticardiolipin, anti-β2-glycoprotein IgG/IgM, lupus anticoagulant), as they represent a strong risk factor (fivefold increase) for NPSLE. 1

• Antiphospholipid antibodies are particularly associated with cerebrovascular disease, seizures, chorea, and myelopathy 1
• Anti-ribosomal-P antibodies have limited diagnostic accuracy (sensitivity 25-27%, specificity 75-80%) for psychiatric SLE 1

Critical Differential Diagnosis

Always exclude these alternative causes before attributing symptoms to lupus cerebritis:

1. CNS infections - mandatory CSF analysis with microbiological studies 1
2. Metabolic disturbances - especially in acute confusional state 1
3. Steroid-induced psychosis - occurs in 10% of patients on prednisone ≥1 mg/kg, manifests primarily as mood disorder (93%) rather than psychosis 1
4. Thrombotic/embolic events - particularly in antiphospholipid antibody-positive patients 1

Distinguishing steroid-induced psychosis from lupus cerebritis:

• Clear timeline of symptom onset relative to steroid dosing is crucial 4
• MRI patterns can help clarify: lupus cerebritis typically shows inflammatory changes while steroid-induced psychosis has normal or non-specific findings 4

Diagnostic Algorithm Summary

When evaluating suspected lupus cerebritis, follow this sequence:

1. Perform comprehensive neurological examination looking for focal deficits, altered consciousness, or psychiatric symptoms 1
2. Order brain MRI with recommended protocol (T1/T2, FLAIR, DWI, gadolinium-enhanced T1) 1
3. Conduct lumbar puncture with CSF analysis including cell count, protein, glucose, and PCR for HSV/JC virus to exclude infection 1
4. Obtain EEG if seizures or acute confusional state are present 1
5. Consider brain SPECT for acute confusional state or psychosis when MRI is non-diagnostic 1
6. Test for antiphospholipid antibodies to assess thrombotic risk 1
7. Assess for concurrent generalized SLE activity 1

The diagnosis of lupus cerebritis is ultimately clinical, made after excluding other causes, in the context of active SLE, with supportive (but not confirmatory) imaging and laboratory findings. 1