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Page 2 of 8 Rigamonti et al. Vessel Plus 2021;5:47 https://dx.doi.org/10.20517/2574-1209.2021.65

In the above publications, CCMs were reported as rare compared to other vascular anomalies with an
incidence of only 1% of all intracranial vascular lesions and 15% of all cerebral vascular malformations.
Their familial occurrence was thought to be exceptional.

[4]
A very large retrospective autopsy study suggested a prevalence of around 0.4% .

Because of the lack of adequate imaging, the older literature could only report surgically or autopsy-
confirmed cases. Large surgical series reported a clinical presentation of seizures in 35%-60% of the cases,
focal neurological deficits in about 30% of the cases, and headaches alone or associated with other signs of
increased intracranial pressure in about a fourth of the cases [5-11] .

A later prospective epidemiological study fundamentally corroborated the older data regarding the clinical
[12]
presentation .
Prior to the advent of computed tomography (CT), a thorough set of diagnostic tests for CCM would
include cerebral angiography, which was mostly negative or when positive demonstrating a nonspecific
finding. A higher degree of diagnostic sensitivity has been achieved more recently with the use of CT
angiography, even though its specificity is still questionable .
[13]

In reality, cavernous malformations were, for the most part, undetectable during routine angiography. This
fact led to the belief, as amply documented in the older literature, that they were AVMs not visible or
“angiographically occult” (also referred to as cryptic AVM) [3,14,15] . The unknown association of the CCM and
a developmental venous anomaly (DVA), which was clearly visible on angiography, explained management
decisions in which DVA was often erroneously considered the source of bleeding, leading to the often
disastrous extirpation of the DVA with consequent infarction of the brain drained by it [16,17] .

The advent of CT began to shed light into the clinical and epidemiological behavior of this condition. In a
[18]
seminal study, Hayman et al. described a family of 122 individuals studied over five generations; 15 of the
43 people studied with a CT had a finding suggestive of a CCM. Five patients had a confirmed pathological
diagnosis. Six individuals had multiple lesions.

POST-MRI PHASE
CT dramatically increased the ability to detect these lesions, even though it lacked sensitivity and specificity
when compared to the MRI. False-negative CT occurred in up to a third of the cases visualized on MRI .
[19]

By means of a rarely used iron-based staining technique, authors were able to effectively and convincingly
correlate the histological findings of hemosiderin-laden macrophages surrounding the CCMs and iron
depositions within glial cells in the adjacent white matter, with the MRI variations in signal intensity. The
very sensitive and fairly specific appearance of a CCM on MRI was described as falling into two distinct
categories: larger lesions appear as a reticulated core of mixed signal intensity (SI) with a characteristic rim
of decreased SI on T2-weighted images, while the small lesions present as areas of mostly decreased SI on
T2-weighted images unless accompanied by a small hemorrhage . Subsequent radiological and
[19]
pathological characterization in more extensive studies allowed classification into four groups or lesion
types.