Extensive Cerebral Amyloid Angiopathy-Related Inflammation Caused by Rheumatoid Arthritis with Histopathological Findings

Sir, We present a 74-year-old female patient presented with cognitive impairment and behavioral change in the last four months. She had rheumatoid arthritis (RA) for 15 years, a history of oral corticosteroid and methotrexate for 10 years, oral leflunamide for 9 months, and weight loss of approximately 30 kg due to RA. In her neurological examination, the patient was apathetic and was non-orientated to place, time, and person. MMDS was 20/30. Cranial MRI indicated right dominant symmetric, patchy, and widespread T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensities, extending from the subcortical white matter to the cortex with the existence of numerous microhemorrhages on Susceptibility-weighted imaging (SWI) sequences in temporo-parieto-occipital regions, and there was no contrast-enhancement [Figures 1 and 2]. Brain CT angiography was normal.Figure 1: (a) Cranial axial T2-weighted and FLAIR images show confluent, multifocal hyperintensities in both temporal, parietal, and occipital lobes involving the cortex and subcortical white matter and (b) The lesions were hypointense on T1-weighted imagesFigure 2: (a) Cranial MRI showed bilateral temporo-parieto-occipital white matter hyperintensity on axial T2-weighted and coronal FLAIR sequences, (b) hypointensity on T1-weighted sequences, with dominancy in the right hemisphere, consistent with vasogenic edema. There was non-contrast enhancement with gadolinium contrast (c) SWI sequence shows numerous punctate bilateral microbleeds in the cortex and subcortical white matterCSF protein was high (132.86 mg/dL) and glucose was normal (56.87 mg/dL). Serum and CSF JCV PCR, limbic encephalitis, and paraneoplastic panel were negative. The patient had a secondary generalized seizure then controlled with levetiracetam 2000 mg/day. Brain CT revealed an increased area of edema shifting to the left lateral ventricle. A right temporal lobectomy was performed. A brain biopsy revealed the perivascular inflammatory infiltration associated with beta-amyloid deposition and hemorrhage foci in vessel walls, applying Congo red or crystal violet. In immunohistochemically, the inflammatory cells upon the vessels were mostly macrophages demonstrated by CD68+. There was no finding in favor of neoplastic lesions [Figure 3a–d]. The histopathological findings were consistent with CAA-RI.Figure 3: (a–c) Brain biopsy stained with hematoxylin and eosin discloses perivascular lymphocytes, giant cells, and plasma cells, but there are no neutrophils. Immunohistochemically the inflammatory cells upon the vessels are mostly macrophages demonstrated by CD68+ and (d) Congo Red stain highlights amyloid deposits with immunoreactive antibodies to AβThe patient was administered 1 g/day IVMP for 10 days. After IVMP treatment, the patient was conscious and oriented to place, time, and person. Cranial MRI revealed diffuse confluent hyperintense areas in both hemispheres were regressed [Figure 4]. Although the patient clinically benefited from IVMP treatment, she was immobile, feeding with a tube, and died of aspiration pneumonia.Figure 4: (a) After IVMP treatment, cranial MRI revealed that diffuse confluent hyperintensities on T2-weighted, FLAIR and T1-weighted sequences were regressed (b) SWI sequence showed punctate bilateral microbleeds in bilateral hemisphereCognitive and behavioral changes are the most common symptoms of CAA-RI, followed by focal neurological signs, headache, and seizures.[1] There is a rare relationship between inflammatory CAA and connective tissue disease, especially RA.[2] RA may cause CAA-RI, regardless of anti-rheumatic drugs or immunosuppressant drugs the treatment received for RA. Due to the chronic systemic inflammation, which can lead to the accumulation of amyloid-β protein in the blood vessels of the brain.[3] Cerebral vasculitis is another clinical entity that should be considered in the differential diagnosis.[4] Rheumatoid vasculitis was excluded because of no evidence supporting vasculitis on cranial MRI and CT angiography. To our knowledge, this is the first extensive case of CAA-RI with RA undergoing decompression surgery in the literature. Extensive CAA-RI should be considered among the differential diagnoses in RA patients with subacute cognitive decline and behavioral change symptoms associated with petechial hemorrhages on SWI sequences on MRI in elderly individuals. Despite its rarity, early diagnosis is important. Although immunosuppressive treatment can improve outcomes, it should be considered that RA may present with extensive radiological findings indicating poor outcomes. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.