Inflammatory Cerebral Amyloid Angiopathy A review of 3 cases with multiple areas of diffusion restriction in 1 case ASNR 2015, CHICAGO EP-25 Dr Debarata Bhattacharya Dr Eugene McKenna Dr Brian Herron Neuroradiology Neuroradiology Neuropathology Royal Victoria Hospital Ulster Hospital Dundonald Royal Victoria Hospital BELFAST, NORTHERN IRELAND, UK

Introduction Acute Inflammatory Cerebral Amyloid Angiopathy is a relatively underdiagnosed but severe acute inflammatory disorder of the brain in adults. Characteristic imaging features include diffuse white matter abnormalities with microhaemorrhages. We describe our experience in 3 patients diagnosed with AA, with varied and slightly atypical imaging findings in 1 case.

Materials and Methods We describe the spectrum of imaging findings of acute cerebral inflammatory amyloid angiopathy (AA) in a series of three adult patients with a short description of their clinical course and eventual outcomes. We also describe the histopathological findings of the 2 patients who had brain biopsies performed. We propose a possible hypotheses correlating the presence of diffusion restriction (an unusual finding) seen in a single patient, to the pathology findings.

Patient 1 Previously well 67 year old male presented with persistent headaches.Initial MR (Fig1) showed white matter T2/FLAIR hyperintense signal change in the frontal/parietal lobes ; patient clinically deteriorated over next few weeks. Fig 1

Patient 1 Repeat imaging showed progression of white matter changes with microhaemorrhages on Susceptibility Weighted/Gradient Echo Imaging (Fig 2,3,4) A presumed diagnosis of Acute Cerebral Inflammatory AA was made; the patient was commenced on high does immunosuppressive therapy and made a full clinical recovery. Fig 2,3,4

Patient 2 Previously well 77 year old female presented with 1 month history of headaches. Initial MR was unremarkable; patient gradually deteriorated with increasing confusion. Repeat MR demonstrated widespread abnormal T2/ FLAIR hyperintensity within the sulci overlying both cerebral hemispheres as well as abnormal signal change within the cortex and subcortical white matter of the left temporal lobe (Fig 5,6) Fig 5,6

Patient 2 Multiple punctate foci of diffusion restriction were seen as well, with several microhaemorrhages in the supra and infratentorial brain (Fig 7,8) Fig 7,8

Patient 2 Patient 2 showing multiple microhaemorrhages (Fig 9) Fig 9

Patient 2 The differential for the changes included amyloid angiitis and diffuse meningiitic process with mutiple microinfarcts. Given the unusual imaging findings and diagnostic uncertainty Patient 2 underwent a right frontal brain biopsy which confirmed amyloid angiopathy.

Patient 2 Histopathology confirmed a severe rare type of congophilic AA inducing an inflammatory/vasculitic/granulamatous response. Fig 10 shows capillary filled with inflammatory exudate with granulomatous infiltration Fig 10

Patient 2 (Fig 12,13,14) GC H G Haemosiderin (H) indicating previous haemorrhage Giant cell (GC) and granulomatous (G) reaction G

Patient 2 (Fig 15,16) Meningeal blood vessel (V) with lumen (Lu) occluded by Inflammatory reaction. Amyloid (A) in the wall and fibrin (F)and lymphocytes (L) surrounding F A Lu Cortical blood vessel showing similar F

A L Patient 2 (Fig 17) Severe perivascular inflammatory reaction showing amyloid in the vessel wall A Lu

Patient 2 Patient 2 was treated with high dose immunosuppressant therapy and made a good clinical recovery. Follow up imaging showed resolution of changes including diffusion abnormalities (Fig 11) Fig 18

Patient 3 A previously well 62 year old male presented with ongoing headaches and a short history of confusion. Initial MR showed abnormal T2/FLAIR hyperintense signal change in the left temporal lobe white matter (Fig 12/13) Fig 19, 20

Patient 3 A presumptive diagnosis of an encephalitic process was made; the patient did not respond to therapy and clinically deteriorated. Repeat scan showed progression of changes with ill defined contrast enhancement in the left temporal lobe and no diffusion restriction ( Fig 14,15) Fig 21,22

Patient 3 Single voxel MR spectroscopy of the abnormal left temporal region was inconclusive (Fig 23)

Patient 3 The patient underwent a left frontal brain biopsy; histopathology confirmed AA. He was treated aggressively with immunosuppressants and made a full recovery.

V V V Patient 3. Fig 24 Beta A4 amyloid in vessels (V) And diffuse plaques (P) P

Patient 3. Fig 25 Beta A4 amyloid in vessels. Note vessel Below almost completely occluded Apart from tiny lumen (Lu) Lu

Discussion Acute inflammatory cerebral amyloid angiopathy is thought to be relatively underdiagnosed but it is however a potentially reversible disease. It is characterized by the presence of amyloid in brain tissue with varying degrees of inflammatory response, including vasculitis.1,3 In our series of three patients each demonstrated distinct imaging findings. In addition to the more commonly associated findings of white matter abnormalities and microhemorrhages, we noted the presence of multiple areas of diffusion restriction in one patient a previously unreported imaging trait of inflammatory amyloid angiopathy.

Discussion We hypothesize that the severe inflammatory/vasculitic and granulomatous response seen on the histopathology analysis of Patient 2 would correlate with the ischemic rather than the hemorrhagic complications normally seen with this disease. Subacute cognitive decline is often the predominant clinical symptom in the patients suffering from the inflammatory variant of amyloid2 and this was the case in all of our patients. Whilst brain biopsy is often required for definitive diagnosis increasing knowledge of the varied imaging findings, including unusual ones such as DWI findings, may enable clinicians in future to increasingly treat on the basis of radiological findings alone.

Conclusion Acute Inflammatory Cerebral Amyloid Angiopathy has a varied spectrum of imaging findings, including diffusion restriction , as we have demonstrated. Increasing knowledge of the variety of imaging findings will make radiological diagnosis more common, potentially negating the need for invasive modes of diagnosis.

References 1 Sakaguchi H et al. Cerebral amyloid angiopathy-related inflammation presenting with steroid-responsive higher brain dysfunction: case report and review of the literature. Journal of Neuroinflammation 2011:8:116 2 Jessica A et al. Clinical manifestations of cerebral amyloid angiopathy–related inflammation.Annals of Neurology 2004:55:2:250–256 3 S.I. Bekkelunda, C.E. Midtbua et al. Good Outcome in a Patient Treated for Cerebral Amyloid Angiopathy Presenting as an Expansive Process with Inflammation and Contrast Enhancement. AJNR Am J Neuroradiol 2011: 32(4) :E75