Neuropsychiatric systemic lupus erythematoaus (NPSLE) affects 14-75% of SLE patients depending on both the population studied and the methodology of assessment. Owing to the poor correlation between instrumental data and clinical manifestations, NPSLE remains a major diagnostic challenge. Although a wide range of neuroimaging tools have been used to evaluate CNS complaints, no single technique has proven to be definitive. Since neurometabolic impairment, neurochemistry and perfusional abnormalities may precede anatomic lesions, new functional techniques have been applied in order to identify early pathologic changes not detectable by conventional imaging. Conventional Magnetic Resonance Imaging (cMRI), given the excellent anatomic details yielded, is actually considered the referral morphological technique. Major limitations of cMRI are the inability to differentiate lesions indicating active acute NPSLE from chronic lesions that represents past NPSLE or changes unrelated to NPSLE. Therefore, cMRI is not very specific and even if small punctate lesions are common, their relationship with clinical picture should not always be interpreted as indicating active disease. Computed tomography (CT), due to its low sensitivity to the nonfocal presentations of NPSLE, is actually reserved in emergency clinical setting when dealing with acute neurological events. More recently, new MRI techniques have been applied for the evaluation of NPSLE. Among these, Magnetic Resonance Spectroscopy (MRS) uses the same technology as conventional MRI (cMRI),and allows to determine the biochemical composition of CNS tissue. MRS may be useful to explore cognitive dysfunction and to characterize lesions identified on cMRI contributing to define the type of injury being atrophic, ischemic or inflammatory. Magnetization Transfer Imaging (MTI) is able to show a diminished homogeneity of brain tissue. It has a high sensitivity in diagnosing and quantifying the structural brain damage and in monitoring the progression of the disease. Diffusion Weighted Imaging (DWI) allows the early detection of ischemic lesions. This method seems to be useful in the distinction between recent or past T2 hyperintense punctate lesions identified by cMRI. Perfusion Weighted Imaging (PWI) is a technique complementary to classical DWI which can be useful for studying cerebrovascular diseases. It is used to assess blood flow and residual tissue perfusion in ischemic areas. At present, reports on the use of PWI in NPSLE are still very few, and usually concern patients with acute focal symptoms only.Functional radionuclide brain scanning include Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT). PET is able to evaluate glucose uptake and utilization, brain oxygen consumption and cerebral blood flow (CBF). PET has a high sensitivity and a good correlation with disease outcome but, unfortunately, has a limited utility due to its high cost, elevated radiation dose and low specificity. PET remains an important research technique for metabolic and functional studies with limited indications in daily clinical practice. Brain SPECT performance is similar to PET concerning brain perfusion, but it is a much less expensive technique and a much more widely available technology. Its major drawback is that, together with PET, SPECT is characterized by low specificity. SPECT may be useful for patients' follow-up and to study perfusion abnormalities in patients with uncertain neurologic involvement or cMRI negative imaging. PET and SPECT must be used coupled with cMRI. In conclusion, due to the availability of new functional modalities useful to explore CNS involvement, neuroimaging has greatly advanced the understanding of NPSLE. Without a "gold standard" technique it is very difficult to identify an ideal and specific diagnostic approach. Dealing with NPSLE, it seems reasonable to combine different diagnostic tools (both anatomic and functional) considering that each modality may have special uses in the proper clinical and research situation. Further research and more follow up data may help to determine the best combination of methods to diagnose NPSLE and to understand underlying pathogenetic mechanisms. Finally it must be remembered that, to date, since the diagnose of NPSLE still lies on the clinical assessment, neuroimaging has a confirmatory role and is fundamental for the exclusion of other pathologies.
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