The Hemorrhagic Side of Primary Angiitis of the Central Nervous System (PACNS)

Abstract

Primary Angiitis of the Central Nervous System (PACNS) is a rare cerebrovascular disease involving the arteries of the leptomeninges, brain and spinal cord. Its diagnosis can be challenging, and the current diagnostic criteria show several limitations. Among the clinical and neuroimaging manifestations of PACNS, intracranial bleeding, particularly intracerebral hemorrhage (ICH), is poorly described in the available literature, and it is considered infrequent. This review aims to summarize the available data addressing this issue with a dedicated focus on the clinical, neuroradiological and neuropathological perspectives. Moreover, the limitations of the actual data and the unanswered questions about hemorrhagic PACNS are addressed from a double point of view (PACNS subtyping and ICH etiology). Fewer than 20% of patients diagnosed as PACNS had an ICH during the course of the disease, and in cases where ICH was reported, it usually did not occur at presentation. As trigger factors, both sympathomimetic drugs and illicit drugs have been proposed, under the hypothesis of an inflammatory response due to vasoconstriction in the distal cerebral arteries. Most neuroradiological descriptions documented a lobar location, and both the large-vessel PACNS (LV-PACNS) and small-vessel PACNS (SV-PACNS) subtypes might be the underlying associated phenotypes. Surprisingly, amyloid beta deposition was not associated with ICH when histopathology was available. Moreover, PACNS is not explicitly included in the etiological classification of spontaneous ICH. This issue has received little attention in the past, and it could be addressed in future prospective studies.

Keywords: ABRA; CAA; CAA-related inflammation; ICH; PACNS; SVD; intracranial hemorrhage; large vessels; medium vessels; small vessels; stroke.

Figure 1

Schematic diagram of the main findings in PACNS based on the main points of the diagnostic criteria (see Table 1), considering LV- and SV-PACNS.

Figure 2

Brain CT of a young patient with biopsy-proven PACNS and ICH at presentation. The patient had a history of headache lasting 6 months before imaging. Panels (a,b) show the non-contrast CT appearance of a large rounded parenchymal hematoma with the different densities of the blood degradation products, surrounded by a hypodense rim of edema. Panels (c,d) show the corresponding post-contrast slices highlighting the displacement of the right MCA by the hematoma and the peripheral contrast enhancement of the lesion.

Figure 3

Brain MRI of the same patient described in Figure 2. Panel (a): axial fluid-attenuated inversion recovery (FLAIR) sequence, showing the rounded hematoma as a hypointense lesion and the surrounding edema as a hyperintense signal. Panel (b): T1-weighted axial sequence at the same level. Panel (c): gradient echo (GRE) sequence showing the various hypointensities of the hematoma components. Panel (d): post-contrast T1-weighted axial sequence showing the strong contrast enhancement of the hematoma in its peripheral ring.