RHEUMATOID PACHYMENINGITIS: Relevant MRI findings, Monitoring Treatment and Follow-up with Conventional MRI and Arterial Spin Labeling A Mas-Bonet*, D Quiñones Tapia**, J Fernandez Melon*, M Picado Valles*, A Marin Quiles*, N Calvo Rado*, A Moll Servera*, C Gassent Balaguer* * Son Espases University Hospital, Palma de Mallorca. SPAIN. ** Hospital del Rosario, Madrid

PURPOSE Rheumatoid pachymeningitis (RP) is a rare complication of rheumatoid arthritis (RA). Findings on magnetic resonance imaging (MRI) , associated with a long standing history of RA or histologic confirmation, led to diagnosis of RP. Complete or sustained remission was achieved with medical treatment. The patients experienced alternating phases of relapse and remission. Our purpose is to describe the most relevant MRI findings at the moment of diagnosis, including arterial spin labeling and also those findings associated with clinical remission and recurrence.

MATERIAL AND METHODS We reviewed the MRI imaging findings and ASL patterns in a series of four patients, studied during the last 4 years. There were three women and one man with ages ranging between 40 to 60 years. In two cases the diagnosis was made on the basis of imaging findings and clinical history of long standing RA, and in the other two patients biopsies were performed. MRI was obtained at the moment of diagnosis and repeated on the basis of clinical evolution.

CASES CASE AGE SEX DIAGNOSIS RA DIAGNOSIS MRI BIOPSY TREATMENT 1 76 M 2008 2012 NO CORTICOSTEROIDS DOLQUINE 2 58 F 2007 2014 + CORTICOSTEROIDS METROTEXATE 3 56 1992 2013 RITUXIMAB 4 2003 2015

Relevant MRI findings in RP Leptomeningeal enhacement Dural enhacement Effacement of gyral sulci Hyperintensity in the subarachnoid space Hyperperfusion pattern on ASL Juxtacortical vasogenic edema

CASE 1

CASE 1 2012 Sag T1. Effacement of right frontal sulci. Ax FLAIR. Hyperintensity in the subarachnoid space in the superior and middle frontal gyri. DW b-1000 value. Hyperintensities located in the frontal cortex.

CASE 1 2013 Ax FLAIR Cor T1 post-Gd DW 1 year control. We can observe parietal involvement (not present on the previous MRI). FLAIR hyperintensity, leptomeningeal enhacement and intraparietal hyperintensity on DW.

CASE 1 2013 Ax FLAIR Ax FLAIR post-Gd Ax T1 post-Gd 1 year control. Intense Leptomeningeal enhacement on post-Gd FLAIR along frontal and parietal gyri

CASE 1 2015 Ax FLAIR DW Ax T1 post-Gd 3 years control. The patient is asymptomatic. Minimal right gyral frontal and parietal effacement.

CASE 2

CASE 2 2014 DW. Slight hyperintensity in the subarachnoid space ASL. Ax T2. Effacement of medial frontal gyrus. Secundary Gyral hyperintensity . Maked hyperintensity in deep white matter secondary to vasogenic edema. DW. Slight hyperintensity in the subarachnoid space ASL. Globally increased flow in bilateral frontal cortex on the ASL CBF map.

CASE 2 BIOPSY AND HISTOPATHOLOGY 1. Surgical biopsy and anatomical pathological study (HE x10): Low-power micrograph of leptomeninges shows necrosis with occasional scattered multinucleated giant cells and dense lymphoplasmacytic infiltrate around small vessels within subarachnoid space. 2. Macroscopic view of the leptomeningial biopsy.

CASE 2 2014 Ax T1 post-Gd Cor T1 post-Gd T1 post-Gd demonstrates intense gyral leptomeningeal and dural enhancement. Also focal gyral thickening can be observed on the left medial frontal lobe in the coronal plane.

CASE 2 2015 Ax T2 DWI ASL 1 year control. Total resolution of the vasogenic edema in both frontal lobes. On DW we observe tiny residual hyperintensities in the left frontal lobe. ASL shows focal hyperperfusion in the frontal anterior interhemispheric fissure and in the lateral left frontal lobe.

CASE 2 2015 Ax T1 post- Gd Cor T1 post-Gd 1 year control. Clinical improvement after Metrotexate. Marked decrease of the leptomeningeal and dural thickening and enhacement.

CASE 3

CASE 3 2015 Ax FLAIR Ax T1 post-Gd ASL Previous study in another hospital. 1 year control after corticosteroids. Clinical relapse. Diffuse dural and leptomeningeal enhacement with predominant hyperperfusion pattern on ASL CBF map, except in left parietal lobe

CASE 3 2016 Ax FLAIR Cor T1 post-Gd DWI 1 year control after Rituximab. Clinical improvement without total recovery. Persistence of leptomeningeal enhacement in left frontal lobe.

CASE 4

CASE 4 January 2015 Ax FLAIR Cor FLAIR DWI Effacement of the left frontal sulci, slight hyperintensities on DW and juxtacortical frontal vasogenic edema in the superior frontal gyrus.

CASE 4 January 2015 Sag FLAIR Ax T1 post-Gd Cor T1 post-Gd Dural and leptomeningeal enhacement predominantly in the interhemispheric fissure and the left frontal convexity.

CASE 4 April 2015 Ax FLAIR Cor T1 post-Gd ASL 3 month control. Persistence of dural and leptomeningeal enhacement. Minimal clinical improvement.

CASE 4 November 2015 Ax T1 + Gd Ax T1 + Gd Ax T1 + Gd 10 month control. Worsening with clinical relapse. Effacement of frontal gyrus with hyperintensity on DWI.

CASE 4 November 2015 Ax T1 + Gd Cor T1 + Gd ASL 10 month control. Persistence of leptomeningeal and dural enhacement. Increased hyperperfusion in the cortex in ASL CBF map. After this MRI the patient was treated with Rituximab.

RESULTS All the patients presented a variety of different neurological symptoms. A similar MRI pattern was observed at the moment of diagnosis: T1 post-Gd showed a supratentorial focal or multifocal meningeal and cortical enhancement on the pial surface of the gyri, with pachymeningeal thickening (the most common lobes involved were the frontal and parietal). FLAIR and FLAIR post-Gd showed cortical hyperintensity with sulcal effacement. Hyperintensity of deep white matter, probably related to vasogenic edema. On diffusion (b-1000) we found subarachnoid hyperintensities. Focal hyperperfusion pattern was observed on ASL.

RESULTS With clinical response to treatment we observed a reduction of cortical enhacement, FLAIR hyperintensities and diffusion hyperintensities, as well as normalization of ASL. Two patients presented persistent clinical response: one with normal MRI and the other with mild gyral and dural enhacement with no vasogenic edema (pseudonormalization pattern). The other two had a clinical course with remissions and relapses. During the relapses the dural enhacement increased, as well as FLAIR and diffusion hyperintensities and the focal hyperperfusion pattern in ASL.

CONCLUSIONS RP is a rare complication of RA. The reported imaging findings associated with a history of long standing RA is suggestive of a diagnosis of RP. MRI with diffusion and ASL are useful tools in the monitoring and follow up of clinical response (with pseudonormalization pattern) in these patients with episodes of remission and relapses.

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