Case Presentation: A 69 year old male presented with one week history of worsening delusional behavior and encephalopathy. His medical history included hepatitis C (in remission), hypertension, hyperlipidemia, and polysubstance abuse (cocaine, alcohol). Initial CT head revealed a hypodensity involving right temporal, parietal, and occipital lobes suggestive of acute infarction. Subsequent MRI brain revealed T2 hyperintensity in the right parietal and temporal lobes and numerous chronic microhemorrhages seen on diffusion weighted images. Differential diagnosis included subacute infarct, encephalitis, or inflammatory amyloid. CSF analysis revealed mildly elevated protein, however gram stain, culture, and viral panel were all negative. Despite unremarkable CSF findings, a course of acyclovir was administered for possible herpes encephalitis; the patient showed no clinical improvement. A diagnosis of cerebral amyloid angiopathy-related inflammation (CAA-ri) was suspected and the patient was started on high dose intravenous corticosteroids. A brain biopsy was performed to confirm the diagnosis. Pathology revealed beta amyloid deposits within vessel walls and intramural inflammation diagnostic of CAA-ri. Repeat MRI brain revealed decreased T2 hyperintensity and resolution of leptomeningeal enhancement, consistent with response to steroid treatment.
Discussion: CAA-ri is a rare subset of the more prevalent cerebral amyloid angiopathy (CAA). The pathophysiology involves an immune response to beta amyloid deposits within the cerebral vasculature. As opposed to CAA which typically presents with lobar hemorrhage, CAA-ri presents with acute to subacute cognitive decline, encephalopathy, headache and/or seizures. Definitive diagnosis is made with brain biopsy; however, a set of criteria has been developed to make a diagnosis in the absence of microscopy. Essential to this criteria are the hallmark MRI findings of asymmetric white matter hyperintensities and corticosubcortical hemorrhagic lesions. It is also imperative to rule out other etiologies of the patient’s presentation including infection and neoplasm; lumbar puncture is often done for this purpose. Management involves initiating immunosuppressive therapy; the typical regimen includes five day course of high dose corticosteroids followed by rapid taper. If there is no radiographic and/or clinical response, treatment with cyclophosphamide can be considered.
Conclusions: Approximately 70% of patients with CAA-ri will respond to immunosuppressive therapy, making this an important reversible etiology of encephalopathy.