Neuropsychiatric Systemic Lupus Erythematosus
Imaging can play an important role in ruling out other causes of neuropsychiatric systemic lupus erythematosus (NPSLE), which could be caused by SLE-mediated organ dysfunction, infection, medication side effects, metabolic abnormalities, or an unrelated condition, according to Dr. Patricia C. Cagnoli, a rheumatologist at the University of Michigan in Ann Arbor.
“You have to figure out if the [NPSLE] symptoms are related to the lupus,” Dr. Cagnoli said. But “we don't have any specific imaging technique that can tell you that.”
The diagnostic approach also depends in part on the presentation. Are the symptoms focal or acute or more diffuse? For example, in the case of acute symptoms, CT can help rule out ischemic strokes, large tumors, and massive bleeds—the most acute and urgent conditions that would require immediate treatment/surgery. If a patient has more diffuse symptoms, infection should be ruled out first with a lumbar puncture in addition to imaging.
“MRI is probably the cornerstone imaging technique to use in the diagnosis of neuropsychiatric lupus,” Dr. Cagnoli said. Multiple imaging sequences and intravenous administration of contrast are employed to accurately delineate abnormal areas in the brain. “More often than not, MRI will reveal several lesions that were not detected by CT scanning.” These areas of new injury are likely capable of responding to treatment and healing in ways that cannot be seen by CT.
MRI also frequently identifies small bright spots in the subcortical white matter that are of uncertain significance and are sometimes referred to as “unidentified bright objects,” or UBOs.
“Most of the patients with neuropsychiatric lupus will have these hyperintense white matter lesions, but so do apparently normal individuals,” she said.
These lesions are not specific to NPSLE. It's not uncommon for patients to have small white-matter lesions on MRI that are considered to be areas of possible demyelinization, similar to multiple sclerosis. In fact, patients are often referred to Dr. Cagnoli's group to help determine if patients have MS or lupus with CNS involvement. MS lesions tend to be bigger, to coalesce, and to progress quickly.
However, imaging is only part of the picture. “It's the rest of your physical assessment, your clinical impression, your laboratory evaluation that will tell you, in the end, what it is,” she said.
Functional MRI techniques such as MR spectroscopy, diffusion-weighted imaging, and diffusion tensor imaging (DTI) are beginning to reveal which patients have functional abnormalities.
When comparing structural and functional MRI, “you have a normal conventional MRI and you see already evidence of neuronal loss or brain injury in the functional MRI,” Dr. Cagnoli said.
The researchers hope to use these techniques to identify patients with preclinical NPSLE-type lesions, in order to begin treatment as early as possible. “Eventually, our hope is that we might be able to treat these patients sooner rather than later,” she said. “One of the problems we have with [NPSLE] is trying to identify those patients” who require earlier and more aggressive treatment, “as opposed to those patients who can benefit from a more conservative approach.”
NPSLE requires treatment not just for the neuropsychiatric symptoms, with antipsychotics for psychosis as an example, but also for the underlying SLE, with immunosuppressants and high doses of corticosteroids. “So you treat the symptom—psychosis is the symptom in this case—but also the underlying mechanism, which is the lupus,” said Dr. Cagnoli, who is also the associate director of the Michigan Lupus Program.
She and several colleagues are currently enrolling patients in a pilot study to evaluate whether MR spectroscopy, MR perfusion imaging, and MR DTI can detect alterations in brain function distinctive for NPSLE and compare the findings with those found in an existing cohort of 20 normal, healthy controls.
MRI shows NPSLE lesions with fluid attenuated inversion recovery (FLAIR), T2-weighted, and T1-weighted, gadolinium contrast sequences. Courtesy Dr. Pia Maly-Sundgren