Primary Angiitis of the Central Nervous System: New Potential Imaging Techniques and Biomarkers in Blood and Cerebrospinal Fluid

Abstract

Primary angiitis of the central nervous system (PACNS) is an inflammatory brain disease affecting the medium and small vessels of the CNS. Although recent data of patients with PACNS have advanced the understanding of the disease, the diagnosis remains challenging. Clinical presentation of PACNS is broad and unspecific and the majority of the diagnostic approaches are hallmarked by a low specificity. Thus, PACNS is commonly misdiagnosed. In addition, due to its potential aggressive course which may be altered by an adequate immunosuppressive treatment, delineation from other vasculopathies and PACNS mimics is crucial. New diagnostic tools and biomarkers which increase specificity and facilitate the diagnosis for patients with suspected PACNS are highly desirable. This short review summarizes the current procedures within the diagnostic process and aims to illustrate its difficulties and challenges. Furthermore, it highlights emerging biomarkers in the cerebrospinal fluid and peripheral venous blood as well as novel potential imaging tools that may corroborate the diagnosis. With new imaging techniques and a panel of biomarkers the certainty of the diagnosis may be increased and diagnostic processes more accelerated in the future.

Circulating Endothelial Cells as Promising Biomarkers in the Differential Diagnosis of Primary Angiitis of the Central Nervous System

“…CEC levels are increased in active vasculitis patients compared to healthy controls and patients under successful immunosuppressive treatment. Of note, we observed similar results in patients with PACNS (10,11). We found highly elevated CEC numbers in patients with an active PACNS, whereas CECs were significantly lower in healthy subjects, patients in remission, but also in patients with cerebrovascular risk factors.…”

“…Studies of small vessel vasculitis associated with antineutrophil cytoplasmatic antibodies (ANCA) showed increased CECs in patients with an active disease whereas CEC levels decreased under successful immunosuppressive treatment (16) indicating CECs being a diagnostic marker but also a marker of activity. In line with this, we demonstrated highly elevated CEC numbers also in patients with an active PACNS compared to patients in remission and healthy controls (10,11). The present study aimed to verify these results and address the question if CECs may also serve as biomarkers to distinguish an active PACNS from its important differential diagnosis.…”

“…In particular, it is important to exclude other diseases which bear the closest resemblance to PACNS such as reversible cerebral vasoconstriction syndrome (RCVS) or moyamoya disease (MMD), both representing noninflammatory vasculopathies (7)(8)(9). We have previously shown that circulating endothelial cells (CEC) could be a potential biomarker in PACNS (10,11). CECs are well-known as a marker of endothelial damage (12,13).…”

Primary Angiitis of the Central Nervous System (PACNS): A Commentary on a Proposed Screening Algorithm and an Update on Diagnosis and Treatment

“…This MRI sequence is more sensitive to pathological changes like wall thickening and wall enhancement, and can aid in differentiating between inflammation, intracranial atherosclerosis and other wall abnormalities based on typical enhancement patterns reported [5,6]. In contrast-enhanced MRI, signal of the blood is suppressed (thus the name 'black blood' or 'dark blood' imaging) and discrimination of the vessel wall from the lumen is increased: in PACNS there is usually a smooth, concentric, and long-segment wall thickening with strong enhancement and perivascular edema, whereas intracranial arteriosclerosis exhibits a more eccentric, irregular, and short-segment wall thickening without perivascular edema and only mild enhancement, depending on composition and activity of the plaque [7]. Vessel wall imaging (VWI) appears to be safe and very promising in clinical practice, but some limitations need to be addressed: first of all, most VWI techniques require a 3T MRI, limiting their availability on a large scale.…”

Single-Cell Microwell Platform Reveals Circulating Neural Cells as a Clinical Indicator for Patients with Blood-Brain Barrier Breakdown

“…Elevated levels of CECs are diagnostic indicators of MI-associated arterial plaque rupture [ 22 ]. There have been reports of studies within the past few years identifying CECs as possible biomarkers for primary angiitis [ 23 , 24 ]. Circulating fetal cells are another clinically important type of circulating cells, as they host the entire fetal genome and provide noninvasive prenatal testing for genetic disorders [ 25 ].…”