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White matter hyperintensity features in Neuropsychiatric Systemic Lupus Erythematosus: a retrospective case-control study.

Francesca Inglese¹, Myriam G. Jaarsma-Coes¹, Gerda M. Steup-Beekman², Tom Huizinga², Mark A. van Buchem¹, Itamar Ronen¹, and Jeroen de Bresser¹
¹Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands

Synopsis

Systemic Lupus Erythematosus (SLE) often presents with neuropsychiatric (NP) symptoms. These symptoms can be directly associated with SLE (NP-SLE) or not (non-NP-SLE). We investigated whether white matter hyperintensity (WMH) features (such as type, volume and shape) may contribute to the diagnosis of NP-SLE. Patients with NP-SLE more often had deep WMH (DWMH) compared to patients with non-NP-SLE. There were no significant differences in WMH volume and shape features between NP-SLE patients compared to non-NP-SLE patients. In conclusion, NP-SLE patients more often had DWMH compared to non-NP-SLE patients and this may help in the diagnostic process of NP-SLE.

INTRODUCTION

Systemic Lupus Erythematous (SLE) is an autoimmune disease that may present with a broad spectrum of neuropsychiatric (NP) symptoms^1,2. Attribution of NP symptoms directly to the disease (NP-SLE), or to an alternative etiology such as side effects of medication or the involvement of other organs (non-NP-SLE)³ is highly uncertain, as no gold standard exists. Currently, MRI features can only contribute in a limited way in the diagnostic process. Discovering MRI biomarkers may help in the diagnostic process.
White matter hyperintensities (WMH) in the brain are related to both NP-SLE and non-NP-SLE^4,5. WMH lesions are currently mainly expressed in terms of volume, but this does not contribute to distinguishing between different etiologies⁶. On the other hand, type and shape of WMH lesions may provide additional etiological information⁷.
In this retrospective study, we investigated whether conventional (volume) and advanced WMH (type and shape) features are different in NP-SLE patients versus non-NP-SLE patients.

MATERIAL AND METHODS

130 patients were included in this study: 29 with NP-SLE and 101 with non-NP-SLE. Patients were diagnosed following a one-day standardized evaluation comprising a combination of multidisciplinary medical assessments, including a brain MRI scan on a Philips Achieva 3T MRI scanner. The MRI acquisition protocol included 3D T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences.
The FLAIR images were registered to the 3D T1-weighted images⁸. WMH segmentations were performed on the registered FLAIR and thresholded on a probability of 0.2⁹. Lateral ventricular segmentation was performed on the 3D T1 image or on the registered FLAIR to the T1¹⁰. Figure 1 shows the image-processing pipeline. The Periventricular WMH (PVWMH) type was assigned to WMH within 10 mm from the lateral ventricles. The Confluent WMH (CWMH) type was assigned to PVWMH that extended to more than 10 mm from the lateral ventricles. The Deep WMH (DWMH) type was assigned to WMH that were located >10mm from the lateral ventricles. Figure 2 shows WMH types. WMH shape features were calculated from the WMH segmentation. Solidity, convexity, concavity index and fractal dimension were used for PVWMH and CWMH. Eccentricity and fractal dimension were used for DWMH¹⁰. Mean or median values per feature were calculated per patient.
Group differences in WMH volumes, WMH type and WMH shape features between groups were studied by linear or logistic regression analyses corrected for age and gender and for WMH volume additionally for total intracranial volume (TIV). All analyses were performed in IBM SPSS version 23.

RESULTS

Table 1 shows the characteristics of the patient population. No significant differences between the two patient groups (NP-SLE and non-NP-SLE) were found, except for the SLE disease activity index (SLEDAI), which was higher in NP-SLE.
The DWMH type was more often present in NP-SLE patients compared to non-NP-SLE patients (Table 2). Although NP-SLE patients showed a higher number of deep lesions per patients, a higher volume of total WMH and PV/CWMH compared to non-NP-SLE patients, these differences were not statistically significant (Table 2). No significant between group differences were found in WMH shape features for both PV/CWMH and DWMH (Table 2).

DISCUSSION AND CONCLUSION

We found that NP-SLE patients more often had deep white matter hyperintensities compared to non-NP-SLE patients.
Studying WMH features besides volumes is relatively new¹⁰ and this is the first study on SLE patient populations to our knowledge. This approach may lead to improve our understanding on the etiology and underlying prognostic information of diseases, as well as to differentiate between WMH of presumed vascular origin from other causes¹¹. In particular, previous brain histopathological studies showed that different type and features of WMHs are associated with different brain parenchymal changes¹².
It has been shown that DWMH lesions have different functional, microstructural and clinical characteristics compared to PVWMH lesions. In particular, DWMH lesions are related to disruption of short connections in the white matter, are more heterogeneous compared to PVWMHs, and are characterized by more axonal loss, vacuolization and arteriolosclerosis. DWMH lesions are also related to more hypoxic/ischemic changes compared to PVWMH¹³.
In conclusion, we showed that NP-SLE patients more often had deep white matter hyperintensities compared to non-NP-SLE patients. This finding may contribute to the diagnosis of NP-SLE and this may suggest that NP symptoms are related more to DWMH load than load of other WMH types. Furthermore, there may be a different underlying etiology of WMH lesions between NP-SLE and non-NP-SLE patients. Further studies are needed to fully understand the relation between DWMH and NP symptoms.

Acknowledgements

No acknowledgement found.

References

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Figures

Figure 1. Pipeline analysis. FLAIR images were registered to the 3D T1-weighted images by using the FMRIB's Linear Image Registration Tool (FLIRT) from FMRIB Software Library v5.0(FSL). WMH segmentations were performed on the rFLAIR using the lesion prediction algorithm (LPA) within the Lesion Segmentation Toolbox (LST) for statistical parametric mapping (SPM12). Lateral ventricular segmentation was performed on the T1 image or on the registered FLAIR to the T1 using the toolbox ALVIN in SPM8.

Figure 2. White matter hyperintensity types. In blue 3 mm space distance from the lateral ventricles. In purple 10 mm space distance from the lateral ventricles. In red white matter hyperintensities (WMH).

TABLE 1. Characteristics of the patient population. Sex, age, cardio-vascular risk factors and damage indexes are shown. SLEDAI-2K = Systemic lupus erythematosus disease activity index 2000. SDI = Systemic lupus international collaborating clinics Damage Index.

TABLE 2. Comparison between NP-SLE and non-NP-SLE patients. Variables are shown in terms of: mean±SD in case of normally distributed variables; or median (10-90 CI) in case of not normally distributed variables. Non normally distributed variables were multiplied by 1000 and then natural log transformed before the logistic or linear regression analysis. DWMH are more often present in NP-SLE patients compared to non-NP-SLE patients. NA = not applicable.

Proc. Intl. Soc. Mag. Reson. Med. 28 (2020)

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