Keywords
virchow-robin space - enlarged perivascular space - atypical virchow-robin space -
cystic brain tumor
Palavras-chave
espaço de Virchow-Robin - espaço perivascular aumentado - espaço de Virchow-Robin
atípico - tumor cerebral cístico
Introduction
The Virchow-Robin spaces (VRSs), or perivascular spaces, are small cystic cavities
that usually surround the walls of arteries, arterioles, veins and venules at the
level of the basal ganglia, the anterior perforated substance and the thalamic-mesencephalic
junction, as they course from the subarachnoid space through the brain parenchyma.[1]
[2]
[3]
[4] These spaces, which are better visualized in magnetic resonance imaging (MRI) T2-weighted
images, are considered to be enlarged when the size exceeds 2 mm. Typically, its physicochemical
characteristics are similar to the cerebral spinal fluid (CSF), there is no contrast
enhancement and the tissues surrounding it are totally normal on brain computed tomography
(CT) and MRI images. Commonly, they are asymptomatic and are found in all age groups,
although the frequency with which they are observed increases with age. Although some
contemporary studies have suggested that it might be related to certain traumatic
brain injury and several other central nervous system (CNS) disorders, its real meaning
is unknown.[5]
[6]
[7]
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Occasionally, some enlarged VRSs can reach a very large volume, assume bizarre settings
and have reactional gliosis surrounding them. In these particular conditions they
are so-called atypical and tumefactive VRSs and may present themselves with symptoms
such as seizures, hydrocephalus and headache. Most often, atypical and tumefactive
VRSs are difficult to differentiate from a couple of pathologic conditions, especially
from some primary cystic brain tumors and vascular disorders. Sometimes, either follow-up
over time with serial imaging or a biopsy is needed to establish the correct diagnosis
and the most appropriate management.[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
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[25]
Case Reports
Case 1
A 25-year-old female patient, without any past medical history, was admitted to the
service complaining of early onset of short focal seizures with fast bilateral tonic
clonic progression. In that time, her clinical history and semiology features were
very suggestive of frontal lobe epilepsy and her neurological examination was unremarkable.
The brain MRI images showed multiple small cystic lesions, in the cortex and in the
white matter of the superior and middle frontal gyri, with intensities similar to
the CSF ([Fig. 1]). Faced with diagnostic hypotheses of symptomatic epilepsy, triggered by atypical
enlarged VRS or multinodulated vacuolar neuronal tumor or other cystic glioma tumor,
the patient underwent surgical treatment. We have performed an awake craniotomy -
with brain mapping - which was successful and got subtotal resection without any functional
impairment. The histopathological workup showed a wide VRS around capillary vessels
with normal surrounding tissue. On the immunohistochemical analysis, the tissue was
positively marked for Neu-N and CD34 delineating the vascular contour ([Fig. 2]).
Fig. 1 Case 1. Type 2 atypical enlarged VRS in the cerebral convexity mimicking a
cystic primary tumor. The MRI of the brain demonstrates a cystic lesion on the left frontal lobe. Visually,
the signal intensity of the cystic contents is identical to those of CSF with all
pulse sequences. The sign intensity of the brain parenchyma surrounding is slightly
higher than the normal tissue and there is no gadolinium enhancement. (A) Coronal T2-weighted image, (B) Axial T2-weighted brain slice, (C) Axial fluid-attenuated inversion-recovery (FLAIR) view.
Fig. 2 Histological characterization of the enlarged Virchow Robin Space. (A) photomicrograph showing cystic dilation of the Virchow-Robin space around a capillary
vessel (arrow). Surrounding the dilatation, normal brain tissue is observed. (B):
photomicrograph showing immunohistochemical marker (CD34) delineating the vascular
contour within a cystic dilation (arrow). (C): NeuN showing normal neuronal organization
in the brain parenchyma.
Case 2
A 38-year-old male patient was submitted to brain CT and MRI after mild accidental
traumatic brain injury. The MRI revealed small cystic lesions on T2-weighted in the
cingulate gyrus of the right frontal lobe without diffusion restriction ([Fig. 3]). There was no perilesional edema on fluid attenuation inversion recovery (FLAIR)
and no contrast enhancement. The patient has been followed-up for 6 years and remains
asymptomatic. His periodic brain images have not shown any progression of the lesions,
which strongly suggests the diagnosis of atypical VRS.
Fig. 3 Case 2. Type 2 atypical enlarged VRS, in the left anterior cingulate gyrus,
that could be misdiagnosed as a cystic primary tumor. The FLAIR images show that cystic contents, as well the neighboring cerebral cortex,
have identical signal intensity to those of CSF and the normal brain cortex, respectively.
The appearance of cystic lesions aligned with white matter tracts and with the perimedulary
veins strongly suggests an atypical enlarged VRS diagnosis and it was also reinforced
by the stability of the findings for 6 years (A) Coronal FLAIR view, (B) Sagital FLAIR image.
Case 3
A 49-year-old female patient was admitted to our service with reentrant epileptic
seizures. In her past medical history, it was reported that she had diabetes, hypertension,
and drug-resistant epilepsy for 10 years secondary to a right frontal lobe lesion.
She had been previously submitted to a stereotactic biopsy in an external service
with inconclusive findings. She underwent an MRI that revealed a small right frontal
lesion, with hyperintense signal on FLAIR and T2-weighted images, mild hyperintense
signal on T1 images, reasonable diffusion restriction, infiltrative behavior, minor
mass effect and no contrast enhancement. Adjacent to these, there were multiple clustered
cysts with signal very similar to CSF located in the frontal, temporal, insular and
parietal lobes; without restriction to the movement of water molecules in the diffusion
sequence, also without contrast enhancement ([Fig. 4]). The patient was submitted to surgical treatment for resection of those cystic
lesions that were compatible with VRS on histopathological analysis. In addition to
this procedure, we have performed a subtotal surgical resection of the infiltrative
lesion that, in the histopathological exam, was compatible with oligodendroglioma
(Grade II – World Health Organization [WHO]) with the 1p19q codeletion and Ki-67 of 2%. The immunohistochemistry stains were positive for glial fibrillary acidic
protein (GFAP) and negative for synaptophysin.
Fig. 4 Case 3. Tumefactive VRS located adjacent to an oligodendroglial tumor. The MRI demonstrates multiple tumefactive perivascular spaces of various sizes in
the right frontal, insular and temporal lobes adjacent to a suspected T2-hyperintense
frontal area which has T1 hyposignal and no enhancement after contrast. The anatomopathological
study of the whole lesion was consistent with enlarged VRS adjoining a 1p/19q codeleted
oligodendroglial tumor. (A) Coronal T2-weighted view, (B) Axial T2-weighted image, (C) Axial FLAIR image. ↓Typical enlarged VRS -.- > Atypical enlarged VRS * 1p/19q codeleted
oligodendroglioma tumor.
Case 4
An 8-year-old male patient, who has been affected by epilepsy for a year, has just
started his follow-up treatment in our service. The seizures were easily controlled
with levotiracetam and his brain MRI images revealed small cystic lesions on T2-weighted
in the right occipital lobe without diffusion restriction ([Fig. 5]). There was no perilesional edema on FLAIR and no contrast enhancement. The patient
remains with good seizure control and he has been followed-up for 4 years. His periodic
brain images have not shown any progression of the lesions, which is consistent with
the diagnosis of atypical VRS.
Fig. 5 Case 4. Type 2 atypical enlarged VRS, in the right occipital lobe. (A) Axial T2-weighted image shows linear to cystic hyperintense areas around the
right occipital horn. The signal intensity of the surrounding brain parenchyma is
normal; (B) Coronal Flair image shows that the spot has CSF-like content. In some
areas, around the cystic lesions, there is a thin layer with hyperintense signal,
and its appearance reflects gliosis, which is unusual.
Discussion
The VRSs are perivascular cystic cavities (2–3 mm) with a CSF-like component filling
inside within the brain parenchyma.[1]
[2]
[3] Those anatomic landmarks are observed in between 50 and 100% on MRI structural images
depending on the age of the patient and MRI resolution.[1]
[2]
[3] These spaces characterized by direct communication with subpial spaces are covered
by a double layer of piamater and have no communication with the subarachnoid compartment.[2]
[3]
[4]
[17] Studies with target radiotracers have shown that VRS has an important role for the
drainage of liquids and solute content from the gray matter, which reaching those
perivascular spaces, from the extracellular compartment through passive diffusivity,
works as a lymphatic pathway of the brain. Besides that, the VRS has a specific macrophagic
population that might be enrolled with some immunologic functions, even though it
has not been well documented.[1]
[2]
[3]
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The enlarged VRS is defined as perivascular spaces wider than 3 mm, which are rarely
located on the cortical surface and are often found in the inferior portion of the
basal ganglia, especially in the anterior perforated substance or even in the anterior
commissure, the substantia nigra, the dentate nucleus, the corpus callosum and the
cingulate gyrus.[2]
[3]
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[14] A study evaluation with high-resolution MRI from 125 healthy subjects reported an
occurrence of 100% and 1.6% of VRS and wide VRS, respectively.[2] It has been hypothesized a positive correlation between those enlarged VSRs with
a wide variety of neurological diseases such as psychiatric disorders, dementia, cognitive
disturbances, multiple sclerosis, brain trauma and microvascular anomalies of the
brain.[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
On MRI, the VRS shares similar characteristics to CSF, that is, hypointense signal
in T1- and hyperintense signal on T2-weighted images.[1]
[2]
[3]
[4]
[19]
[20]
[21]
[22]
[23] There is no restriction to diffusion, no gadolinium enhancement, and a suppressed
signal on FLAIR sequences. Occasionally, the white matter surrounding those perivascular
spaces might present a marked gliosis. On coronal and sagittal views, the VRS might
assume a radial linear or curvilinear appearance, since it follows the trajectory
of blood vessels, especially of medullary arteries. Grouped VRS on MRI are named “État
Criblé” or “Status Cribosum” since it has similar appearance to a sieve.[1]
[2]
[3]
[4]
[19]
[20]
[21]
[22]
[23] On brain CT, it might be identified as CSF-like cystic lesions, without calcifications
or contrast enhancement.[1]
[2]
[3]
[4]
[19]
[20]
[21]
[22]
[23]
These enlarged VRSs might be classified in three types: Type 1, the lenticulostriate
arteries are involved at the level of the basal ganglia and anterior perforated substance;
Type 2, if it is located around the medullary veins of the brain, in the superficial
cortical region or in the white matter surrounding it; Type 3, when the VRS is located
close to the brainstem, around the mesencephalic vessels, especially at the level
of the thalamomesencephalic junction.[1]
[20]
When very wide, the VRS are called tumefactive perivascular spaces.[7]
[13]
[23] A special variant of this, which sometimes can mimic cystic brain tumors, was recently
described and named anterior temporal lobe perivascular space. Most often, this entity
is associated with a looping of a branch of the middle cerebral artery as well as
with a focal region of cortical thinning or nonexistent.[13]
[23] Even though enlarged VRS or tumefactive perivascular spaces may have some degree
of gliosis or minor expansive effect, rarely any symptoms can be attributed to them.
The so-called atypical VRSs are enlarged perivascular spaces which really present
very large volumes or still take the form of voluminous multiple clustered cysts.
Although they may occur in the cerebral convexity cortex and be multifocal or bilateral,
atypical VRSs commonly are solitary and occur in the brainstem, notably in the thalamic-encephalic
junction. Unlike the other mentioned variants of perivascular spaces, atypical cases
are often accountable for symptoms such as headache, nausea, vomiting, seizures and
drowsiness. The main mechanisms involved in it are mass effect, perilesional edema,
gliosis and CSF flow disturbances caused by the distortion of the Sylvius aqueduct
and of the third ventricle, with consequent hydrocephalus.[3]
[6]
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[11]
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[20]
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Magnetic resonance imaging, with advanced imaging technique, is considered the gold
standard approach for VRS diagnosis and it permits the certainty of diagnosis in most
cases. Differential diagnosis includes arachnoid cysts, neuroepithelial cysts, lacunar
stroke, multicystic encephalomalacia, neurocysticercosis, neurocriptococcosis and
cystic brain tumors. Considering the above, usually arachnoid cysts are also asymptomatic
and there is no contrast enhancement; inflammatory diseases present marked contrast
enhancement and CSF laboratory changes; neurocysticercosis have a nodular component
inside the cysts and usually come with parenchymal calcifications; and vascular disorders
are associated with sudden symptoms in elderly people who have other risk factors
for stroke.[5]
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Despite advanced MRI techniques, sometimes it is still difficult to differentiate
VRS from some cystic brain tumors. Often, the density of the cystic contents of brain
tumors is slightly different from the one found in CSF, which frequently help for
a differential. In addition, brain tumors usually have indolent symptoms, mass effect
and perilesional edema. Although MRI usually clarifies the diagnosis, a biopsy or
even a surgical resection might be required for some atypical cases to have the diagnosis
of certain stablished or to have the symptoms under control. We have decided for surgical
approach on case 1 and 3 just to have the accurate diagnosis and to get seizure control.
In those cases, we also understood that obtaining a sample of tissue was important
to differentiate enlarged VRS from low-grade glioma and vacuolating multinodular neural
tumor. The last, which is described as an indolent neoplasm related to late-onset
epilepsy, was recently recognized as a new entity by the 2016 WHO classification,
and they behave more as a dysplastic/malformative lesion than as a true neoplasm with
origin from a progenitor type with origin from a progenitor neuroglial cell type showing
aberrant maturation.[25]
