Clinical History
A 41-year-old Spanish male presented to the Emergency Department complaining of instability. Laboratory tests were normal. No other signs or symptoms were reported.
Imaging Findings
Unenhanced brain CT showed multiple rounded well-delimitated hyperdense lesions with punctuate calcifications inside, with diameters ranging from 0.5 to 1 cm (figure 1). They were located in the left frontal lobe, right temporal lobe, left cerebral peduncle, pons and midbrain.
Magnetic resonance imaging performed on the patient proved the lesions to be hyperintense on T1-weighted sequences (figure 2), and of mixed signal intensity on the T2-weighted sequences (figure 3). T2*-weighted images showed a dark peripheral rim inside the lesions, and revealed additional hypointense lesions that were not depicted in the other sequences (figure 4).
Revision of the patient´s medical history revealed episodes of brain haemorrhages in his mother and 10-year-old son, which in addition to the described imaging findings allowed for the confident diagnosis of familial cavernous cerebral malformation.
Discussion
Cerebral cavernous malformations (CCM) have a prevalence of 0.5% in the general population. They consist of clusters of deformed vessels surrounded by endothelium without muscular tissue or brain parenchyma, and are filled with blood at various stages of evolution [2]. They are usually supratentorial (in up to 80% of the cases), even though they can be found anywhere, including the brainstem [3]. 60% of patients with this malformation become symptomatic between the third and the fifth decade, the most frequent clinical manifestations being seizures, neurologic deficits and chronic headaches [1, 2].
There are two forms of cavernous cerebral malformation: the sporadic and the multiple (familial) form. The second one has an autosomal dominant pattern of inheritance with variable penetrance, and is more prevalent in Hispanic descendents [2], on which the presence of multiple lesions is characteristic.
Non-enhanced brain CT may be negative in up to 50% of the cases, but when brain cavernous malformations are visible, they appear as well delineated hyperdense round or ovoid lesions, with calcium in 50% of the cases, and with no mass effect unless there is recent haemorrhage [2]. MRI is the best imaging technique for the evaluation of these lesions, as it has higher sensitivity than computed tomography. On T1-weighted sequences, their appearance is variable, ranging from hypo to hyperintense depending on their stage of haemorrhage. On T2-weighted sequences, their most common appearance is “popcorn-like” (a mixed signal core with complete hypointense hemosiderin rim), although they may also less commonly be hypointense [1]. Gradient Echo T2*-weighted sequence shows prominent susceptibility effect (hypointense “blooming”), and is key for the diagnosis of this disease, above all in the familial forms, as it shows numerous hypointense lesions that are usually not depicted on CT or even on spin-echo sequences. T1 post contrast sequences are useful for the depiction of associated anomalies, e.g., developmental venous anomalies [1].
The diagnosis of familial cerebral cavernous malformation is established by the demonstration of multiple CCMs, one CCM and at least one other relative with one or more CCMs, or a heterozygous pathogenic variant in the genes KRIT1, CCM2 or PDCD10 [3]. The treatment of choice is to alleviate the symptoms, although surgical removal of the lesions producing seizures or focal deficits from recurrent haemorrhages or mass effect that are intractable may also be considered [1].
Differential Diagnosis List
Cavernous familial cerebral malformation
Hemorrhagic primary neoplasm (glioblastoma multiforme)
Hemorrhagic secondary neoplasm (metastatic melanoma
thyroid
renal cell
choriocarcinoma
Cavernous cerebral malformation
Final Diagnosis
Cavernous familial cerebral malformation
