MRI Can Avoid Misdiagnosis in Seronegative Antiphospholipid Syndrome ( SN-APS ) of

1. EP-24 MRI Can AvoidMisdiagnosis in SeronegativeAntiphospholipidSyndrome (SN-APS) of Central NervousSystem (CNS) with Small VesselBrainLesions. MJ Picado, N Calvo, L Pallarés, A Mas-Bonet, A Moll, B Rodríguez Hospital Universitari Son Espases. Palma de Mallorca.

2. Disclosure: Nothing to disclose

3. PURPOSE Antiphospholipid syndrome (APS) is characterized by recurrent arterial and/or venous thrombosis, pregnancy complications and presence of circulating antiphospholipid antibodies (aPA):anticardiolipin antibody (aCL) IgG and IgM, lupus anticoagulant (LA), and anti-B2-glycoprotein-1 (anti-B2-GP1) IgG and IgM. The diagnostic criteria for APS includes the fulfillment of both clinical and laboratory criteria. However, some routine laboratory tests to detect LA, aCL and anti-B2-GP1 come back negative in patients who present clinical signs suggestive of APS. The term Seronegative Antiphospholipid Syndrome (SN-APS) was proposed to include these patients with clinical manifestations suggestive of APS and persistent negative results for aPA.

4. PURPOSE Nowadays, the criteria for APS diagnosis includes three standardized laboratory tests: the determination of LA, aCL and anti-B2-GP1. Recently, different antibodiesdirected against other molecules such as phosphatidylethanolamine, phosphatidylserine/prothrombin complex, annexin V and vimetin/cardiolipin complex have been found in APS patients. In patients with SN-APS these antibodies could play an important role in its diagnosis.

5. PURPOSE Central nervous system (CNS) involvement in APS is highly prevalent, and the most frequent radiological pattern described is the presence of white matter lesions (WML) in brain magnetic resonance imaging (MRI). Small vessel brain lesions includes different clinical manifestations such as memory loss, progressive cognitive impairment and a history of migraine headache The main purpose is to define the usefulness of the MRI in the diagnosis of SN-APS of CNS with small vessel brain lesions, defined as the presence of clinical and MRI findings suggestive of APS and persistent negative habitual aPA.  

6. METHODS AND MATERIALS • We included a series of 42 patients recruited between 2011 and 2014 in our institution. • - Control group: 13 patients (76.92% females and 23.08% males, with mean age of 47.23 years and mean following time of 6 years) with confirmed APS of CNS, small vessel brain lesions at MRI and presence of habitual aPA. • - Study group: 29 patients (75.86% females and 24.14% males, with mean age of 48.07 years and mean following time of 6 years) with small vessel lesions at MRI and related CNS symptoms, with suspected APS and habitual aPAstudy persistent negative. These patients had no cardiovascular risk factors, and the thrombophilia study was negative. Degenerative and inflammatory diseases that could mimic the MRI pattern were also discarded. All patients had similar lesions in the MRI to the ones seen in the Control group, which were first classified as ischemic. Moreover they had several negative measurements for the habitual aPA.

7. METHODS AND MATERIALS We performed the following non-habitual antiphospholipid antibodies (NH-aPA) determinations in the study group: B2-GP1 Domain I, IgA Isotype (aCL and B2-GP1), and phosphatidylserine/prothrombin (FS/PT) complex. 28 MRI studies were performed with a 1.5T MR General Electric Optima MR360, and 14 with a 3T MR General Electric SignaHDxt Optima Edition.   The MR imaging protocol included T2 and T1 weighted Fast Spin Echo (FSE), Fluid attenuated inversion recovery (FLAIR), diffusion-weighted (DWI) and Gradient-echo (GRE) images.

8. METHODS AND MATERIALS All the images were reviewed by two neuroradiologists with more than ten years of experience. Neither radiologists knew to which group each patient belonged. The radiologists achieved consensus by discussing the cases. The reported findings were: atrophy, WML, corpus callosum lesions, cerebral infarction and acute/subacute ischemia. The WML were classified according to the distribution, anatomical location, number and size. We applied the Fazekas scale to determine the degree of white matter involvement.  

9. METHODS AND MATERIALS Fazekas scale gives information related to the white matter involvement across the brain.  According to the scale, non-confluent white matter punctiform lesions are classified as Fazekas 1.  Incipient bridging lesions are Fazekas 2, and when large, confluent and diffuse lesions appear they are graded as Fazekas 3. We used FLAIR images to grade the studies. Fazekas 1 Fazekas 2 Fazekas 3

10. METHODS AND MATERIALS Statistical Analysis: For comparison between two categorical variables we have used the Chi-square test. For comparison of a continuous variable with two categories, we have used the T-Student test. Statistical significance level: 5% (0.05).

11. RESULTS We found 18 (62.06%) patients from the study group with presence of 1 or more NH-aPA that allowed the SN-APSdiagnosis. The most frequent NH-aPA found was the FS/PT complex IgGisotype in 13 (44.82%) patients, followed by the FS/PT complex IgMisotype in 7 (24.14% patients) and the B2-GP1 IgA isotype in 2 (6.9%) patients.

12. RESULTS When we compared the MRI patterns between Study group and Control group, no differences were found with the exception of the atrophy (p=0.03). Atrophy has already been described in systemic lupus erythematosus and APS patients, and differences between two groups might be related to a higher association of LA and aCL with atrophy than FS/PT, instead of  a different etiopathogeny. The MRI pattern with more than 6 supratentorial lesions and Fazekas scale ≥2 has been the most consistent finding, and also highly associated with NH-aPA.

13. RESULTS 49 year old woman with systemic lupus erythematosus (SLE). She was diagnosed of APS due to dizziness, instability episodes, and positive aPA in two occasions (LA and aCL). MRI showed non-confluent punctiform WML (Fazekas 1). 54 year old woman diagnosed of SN-APS by the combination of migraine and one positive determination of aCL. In the image, multiple non-confluent punctiform WML (Fazekas 1) can be observed. MRI patterns between Study group and Control group

14. RESULTS 46-year-old woman with systemic lupus erythematosus (SLE). She was diagnosed of APS due to migraine, sensory motor syndrome and positive aPA in two occasions (LA, aCL and anti-B2-GP1). MRI showed incipient bridging WML (Fazekas 2). 59-year-old man with a clinical diagnosis of SN-APS due to Parkinson clinical signs, cognitive impairment and a history of deep vein thrombosis and pulmonary thromboembolism, with persistently negative habitual aPA. MRI showed incipient bridging WML (Fazekas 2). MRI patterns between Study group and Control group

15. RESULTS 46-year-old man with APS diagnosed by the combination of an atypical akinetic-tremoric syndrome with small vessel lesions seen in the MRI, and two positive aPA (LA and anti-B2-GP1) determinations. MRI showed large and confluent WML (Fazekas 3).  41 year old woman with a clinical diagnosis of SN-APS due to vertiginous syndrome and occasionally headache, with persistently negative habitual aPA. Large and confluent WML were seen on the MRI (Fazekas 3). MRI patterns between Study group and Control group

16. RESULTS We analyzed the Study group comparing the MRI pattern between patients with presence of some NH-aPA and patients with absence of the determined NH-aPA. No significant differences were found in the main findings: more than 6 supratentorial WML and Fazekas scale ≥2.

17. RESULTS 49 year old woman with acute deafness and numbness of the 2nd finger of the right hand.  The MRI showed multiple non-confluent punctiform WML (Fazekas 1). Habitual APS study was negative but she had positive PS/PT IgG determinations.  She was diagnosed with SN-APS and started treatment with acetylsalicylic acid and pravastatin. 48 year old woman with anosmia and memory loss. Multiple non-confluent punctiform WML (Fazekas 1) can be observed on the MRI. The habitual APS and NH-APS study were negative. MRI pattern between patients with positive or negative NH-aPA

18. RESULTS 47 year old woman with history of high blood pressure (HBP) that suffered dizziness. MRI showed bridging WML (Fazekas 2). Thrombophilia study was negative (habitual APS included), but she had positive PS/PT IgG determinations.  She was diagnosed with SN-APS and started treatment with acetylsalicylic acid and olmesartan/amlodipine. 47 year old man with numbness and loss of consciousness episodes. Incipient bridging WML were seen on the MRI (Fazekas 2). The habitual APS and NH-APS study were negative. MRI pattern between patients with positive or negative NH-aPA

19. RESULTS 66 year old woman with history of migraine and rapidly progressive cognitive impairment.  Atrophy and large and confluent WML were seen on the MRI. The thrombophilia study was negative (habitual APS), but she had positive PS/PT IgG determinations, so she was diagnosed with SN-APS. 41 year old woman with vertiginous syndrome and occasionally headache. Large and confluent WML were seen on the MRI. The habitual APS and NH-APS study were negative. MRI pattern between patients with positive or negative NH-aPA

20. CONCLUSION We have identified a MRI pattern defined by more than 6 supratentorial lesions and Fazekas scale ≥2 in patients with small vessel brain lesions strongly associated with APS. In the absence of habitual aPA, this pattern is highly associated with NH-aPA, and a diagnosis of SN-APS should be suggested. The most characteristic symptoms of CNS involvement in APS patients are memory loss, progressive cognitive impairment and migraine. In the absence of habitual aPA, the above mentioned MRI pattern could be really helpful in order to start a treatment.

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