Amyloid Angiopathy related inflammation and paroxysmal events refractory to anti-seizure therapy: amyloid spells or seizures?

Introduction: The accumulation of amyloid within the walls of intracerebral vessels can cause recurring and stereotyped transient focal neurological episodes (TFNE) with positive or negative symptoms, once defined as "amyloid spells". Although the etiopathogenesis is not yet clearly defined, TNFE are a differential diagnosis of epileptic seizures. We report the case of a 72 year-old patient who presented late-onset paroxysmal neurological episodes refractory to anti-seizure medications (ASMs), resulting in complex management and difficult interpretation. Case Presentation: A 72-year-old woman was admitted for an episode of transient mental confusion and aphasia. In anamnesis, some similar transient episodes were present in the previous 2 years, associated with hemiparesis and left hemianopsia or visual hallucinations. For the suspected cerebrovascular origin, ASA was introduced, then associated with Clopidogrel. After following recurrences, an epileptic nature was hypothesized and Levetiracetam was started. In the subacute phase, EEGs demonstrated slow wave abnormalities, which were attributed to post-ictal dysfunction. Hematochemical and cerebro-spinal fluid examinations were negative for inflammatory (including markers of autoimmunity) and infective signs and contrast-enhanced brain MRI shows cortical-subcortical signal alterations in the FLAIR sequences, located in the parieto-occipital region, prevalent on the right where was associated with edema, and right temporo-basal area, in the presence of leukoaraiosis and rare cortical microbleeds. The EEG and neuroradiological findings improved only after high-dose ev corticosteroid therapy and worsened during the recurring episodes. Cognitive functions also temporarily improved, but showed a progressive decline over the two years observation (MoCa test from 25/30 to 21/30). Given the neuroradiological findings and the response to steroids, a "Cerebral amyloid angiopathy-related inflammation" (CAARI) was hypothesized. The cerebral amy-Pet confirms the presence of a widespread accumulation of beta-amyloid. A low-dose corticosteroid therapy was begun and the patient is currently free from paroxysmal episodes for about a year. Conclusions: The differential diagnosis of transient neurological events like that one reported is challenging, including TIA, amyloid spells, or epileptic seizures in the course of CAARI. This case underlines the importance of considering the presence of amyloid angiopathy when suspecting late-onset epileptic seizures, resistant to ASMs, especially if in conjunction with cognitive deterioration, in order to establish the most appropriate therapy.