Enlarged tumefactive perivascular, or Virchow-Robin, spaces and hydrocephalus: do we need to treat? Illustrative cases

Abstract

BACKGROUND

Perivascular spaces (PVSs) are spaces in brain parenchyma filled with interstitial fluid surrounding small cerebral vessels. Massive enlargements of PVSs are referred to as “giant tumefactive perivascular spaces” (GTPVSs), which can be classified into three types depending on their localization. These lesions are rare, predominantly asymptomatic, and often initially misinterpreted as cystic tumor formations. However, there are several reported cases in which GTPVSs have induced neurological symptoms because of their size, mass effect, and location, ultimately leading to obstructive hydrocephalus necessitating neurosurgical intervention. Presented here are three diverse clinical presentations of GTPVS.

OBSERVATIONS

Here, the authors observed an asymptomatic case of type 1 GTPVS and two symptomatic cases of type 3 GTPVS, one causing local mass effect and the other hydrocephalus.

LESSONS

GTPVSs are mostly asymptomatic lesions. Patients without symptoms should be closely monitored, and biopsy is discouraged. Hydrocephalus resulting from GTPVS necessitates surgical intervention. In these cases, third ventriculostomy, shunt implantation, or direct cyst fenestration are surgical options. For patients presenting with symptoms from localized mass effect, a thorough evaluation for potential neurosurgical intervention is imperative. Follow-up in type 3 GTPVS is recommended, particularly in untreated cases. Given the infrequency of GTPVS, definitive guidelines for neurosurgical treatment and subsequent follow-up remain elusive.

Perivascular spaces (PVSs) appear as small, linear, interstitial fluid–filled structures parallel to the known direction of perforating vessels, surrounding the small cerebral vessels as they pass the brain parenchyma.^1,2 Originally described by Durand-Fardel and Pestalozzi in 1842 and 1849, respectively, PVSs are today commonly referred to as “Virchow-Robin spaces” based on their descriptions by Rudolf Virchow and Charles Robin in 1851 and 1859, respectively.³

Although their exact functional involvement in the fluid drainage system of the brain is unclear, PVSs are assumed to be part of the lymphatic drainage pathways of the brain and therefore playing an important role in the immunology of the brain.¹ The increased visibility of PVSs is associated with risk factors such as age, hypertension, inflammation as well as various neurological conditions.^1,4,5

An extensive enlargement of a PVS is referred to as a “giant tumefactive perivascular space” (GTPVS). These lesions are mostly asymptomatic and are often initially mistaken for cystic tumor formations.⁶ GTPVSs can be classified into three types with type 1 relating to lenticulostriate arteries that lead into the basal ganglia, type 2 corresponding to the paths of the perforating medullary arteries, and type 3 corresponding to those in the mesencephalothalamic area.^7,8 For neurosurgeons, the differential diagnosis must be considered to prevent unnecessary surgical treatments. Nevertheless, several cases of GTPVS have been noted to cause neurological symptoms because of their size, mass effect, and location, resulting in obstructive hydrocephalus and therefore the need for neurosurgical treatment.⁵

The presented case series details three distinct clinical presentations of patients with diagnosed GTPVS: one case involving the development of subsequent hydrocephalus, one case presenting with localized mass effect, and a third case involving a patient with minimal extension of the lesions and exhibiting no discernible symptoms.

Illustrative Cases

Case 1

A 62-year-old male presented with a 4-month history of gait disturbance, followed by memory impairment, urinary incontinence, headache, and vertigo. His medical history showed no evidence of coexisting diseases or previous operations or trauma, nor had medication been prescribed.

The patient was alert, oriented in all qualities (person, time, place, and situation), but delayed in response. Speech was clear and fluent but delayed in answers. The patient recalled 3/3 objects at 5 minutes. His pupils were equal, round, and reactive to light and accommodation. No restrictions in eye movement were observed. Facial sensation was intact to pinprick in all three divisions bilaterally. Corneal responses were intact. His face was symmetric with normal eye closure and smile. His hearing was normal to rubbing fingers. His palate was elevated symmetrically. Phonation was normal. Moreover, head turning and shoulder shrug were intact. The tongue was midline with normal movements and no atrophy. Furthermore, the patient showed slight paresis (grade 4/5) of the left lower limb. His muscular tension was normal, and the muscle stretch reflexes were normal and symmetrical. No pyramidal tract signs were present. The patient had an unsteady gait pattern with small steps.

Magnetic resonance imaging (MRI) of the neurocranium revealed a multicystic lesion in the area of the right basal ganglia with extension into the crus cerebri, measuring 35 × 23 mm, which was classified as GTPVS based on its characteristic appearance on MRI (Fig. 1A). In addition, neuroimaging showed dilatated brain ventricles and significant periventricular, accentuated fluid-attenuated inversion recovery–hyperintense white matter alterations. Over a period of 24 hours, repeatedly performed ventriculography indicated the presence of occlusive hydrocephalus with extensive contrast of the external cerebrospinal fluid (CSF) spaces, minimal contrast accumulation in the fourth ventricle, and the absence of contrast in the third ventricle or lateral ventricles. Therefore, the location of the obstruction was detected at the transition from the third to the fourth ventricle, which was not affected by the local obstruction caused by the GTPVS. A spinal tap test showed an improvement in the gait disorder and the cognitive deficits. CSF examination revealed no pathological findings and no evidence of atypical, potentially malignant cells. Consequently, an indication for endoscopic ventriculostomy was made to address the obstruction between the third and fourth ventricle.

FIG. 1.

Axial T2-weighted MRI scans. A: Case 1. The scan depicts a substantial, 35 × 23 mm cystic lesion situated in the right basal ganglia region and extending into the crus cerebri. B: Case 2. A multicystic lesion localized in the right basal ganglia and notably extending into adjacent areas including the mesencephalon and pedunculus cerebelli. C: Case 3. A multicystic lesion, exceeding 1 cm in diameter, situated in the left basal ganglia.

The patient underwent uneventful endoscopic ventriculostomy of the third ventricle and incision of the cystic lesion. CSF was withdrawn during the operation to relieve pressure inside the inner CSF spaces. Interestingly, after the ventriculostomy was performed, there was less pulsation of the tissue as compared to findings in patients with occlusive hydrocephalus.

Microscopic examination of an intraoperatively obtained tissue sample from the cystic lesion showed cystic, altered, almost amorphous tissue without further categorization and without evidence of tumor cells.

During the further postoperative inpatient course, the patient reported considerable improvement of his gait disturbance, concentration disorders, and urge incontinence. In addition, there was significant improvement of the headache. No additional neurological deficits were observed postoperatively compared to his neurological status before the operation. Postoperative MRI of the neurocranium showed no significant changes in the ventricular dilatation or appearance of the cystic lesions.

The patient was initially discharged to a neurological rehabilitation center. A 3-month follow-up including cranial MRI was arranged. At the appointment, the patient and his wife reported a continuous improvement in memory deficits and slight improvement in gait disturbance. MRI showed a regression of ventricular dilatation with a constant size of the GTPVS and an unchanged appearance of the stoma in the CSF flow study sequences. No flow void was distinguishable from the perivascular spaces in the adjacent third ventricle. The patient then agreed to undergo implantation of a ventriculoperitoneal shunt in case of symptom recurrence. After a 4-month postoperative period, the patient presented with a progression of symptoms involving a concentration disorder and a deterioration of the gait disorder to his preoperative condition. Additionally, cranial imaging demonstrated an increase in ventricular width. Therefore, implantation of a ventriculoperitoneal shunt was indicated. After surgery, a significant improvement in the patient’s concentration on the first postoperative day was observed, and within a few days, the patient’s gait appeared more fluent and secure.

Case 2

A 63-year-old female presented with vertigo, headache, tinnitus, and postural instability. Diagnostic testing included MRI, which revealed a multicystic lesion in the area of the right basal ganglia and extending into the mesencephalon and pedunculus cerebelli (Fig. 1B). Importantly, there were no signs of hydrocephalus. Prior to presenting at our clinic, the patient had already undergone endoscopic third ventriculostomy and biopsy at a different hospital. Postoperatively, there was neither improvement nor a worsening of symptoms, and MRI findings remained stable. This case underscores the challenges associated with managing multicystic lesions in the basal ganglia and mesencephalon, as surgical intervention did not alter the patient’s clinical course.

Case 3

A 69-year-old female underwent diagnostic testing during an evaluation for migraines, with no other reported symptoms. MRI revealed an incidental finding of a multicystic lesion larger than 1 cm in the left basal ganglia (Fig. 1C). Notably, there were no signs of hydrocephalus. Given the absence of hydrocephalus or other significant pathological findings, aside from the small multicystic lesion, no treatment was indicated at the time. Over a follow-up period >10 years, no progression of the lesion was seen.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

In this case report, we presented three cases of GTPVS: one manifesting obstructive hydrocephalus, another exhibiting symptoms from local mass effect, and a third experiencing no symptoms. To our knowledge, roughly 170 GTPVS cases have been documented in the literature.^5–7,9–13

GTPVSs are characterized as dilated PVSs exceeding 15 mm in width. They predominantly arise in the mesencephalic region near the lenticulostriate arteries or penetrate the cerebral cortex, but they can also be found in areas such as the subinsular region, dentate nuclei, or cerebellum.^{6,8,9,11,14,15} GTPVSs can be categorized into three groups: type 1 is associated with the lenticulostriate arteries entering the basal ganglia, type 2 aligns with the trajectories of the perforating medullary arteries, and type 3 is located in the mesencephalothalamic region.^7,8 Given this classification, our first and second cases can be classified as type 3, whereas the third case can be categorized as type 1. Types 2 and 3 are more prevalent. Type 1 and 2 GTPVSs rarely cause neurological symptoms, which is in line with observations in our case series. Therefore, surgical treatment in these cases is rarely performed and has only been reported once in a case of type 1 and four times in cases of type 2 GTPVS.^16–19

Depending on its size and location, a type 3 GTPVS can become apparent through a wide range of neurological deficits such as hemiparesis, tremors, oculomotor nerve palsy, parkinsonism, or cerebellar ataxia.^6,7 In other cases, they cause symptoms due to obstructive hydrocephalus.^5–7,9 For patients with hydrocephalus resulting from type 3 GTPVS, the preferred treatment often involves redirecting CSF flow via ventriculoperitoneal shunt placement, third ventriculostomy, or direct GTPVS surgery.⁷ In the literature, the type and outcomes of surgical treatment have been reported in 59 of 80 published cases.⁷ Of 45 patients who underwent CSF diversion, 24 also received direct cyst treatments such as fenestration. The remaining 14 patients exclusively underwent direct cyst intervention without CSF diversion. Unfortunately, factors influencing the indication for surgery, for example, the size of the lesions, are not discussed in detail.

Generally, postoperative results are favorable; >60% of patients experience symptomatic relief after CSF diversion.^6,7 Of the 45 documented cases treated with CSF diversion, only three showed symptom exacerbation postprocedure. Interestingly, the data did not reveal any discernible risk factors linked to these adverse postoperative outcomes. To illustrate, a 42-year-old male experienced worsening of headaches and visual disturbances after ventriculoperitoneal shunt placement.²⁰ Similarly, a 10-year-old female presented with ataxia, nystagmus, and mild left-sided paresis a year after her surgery. An 11-month follow-up after her third surgery revealed the partial persistence of trochlear palsy.²¹ In another case, 4 years after onset and after ventriculoperitoneal shunt placement, a 30-year-old male displayed heightened parkinsonian motor issues, particularly in gait and stability, along with cognitive dysfunction.²²

Despite the absence of randomized controlled trials, defining the optimal treatment strategy remains complicated. For patients with symptoms from local mass effect, interventions such as cyst fenestration or intracystic catheter placement may be necessary, although they come with risks, including potential vessel damage within the GTPVS and consecutive intracerebral hemorrhage, particularly in sensitive areas like the mesencephalon.⁷

However, it is worth noting that enlarged PVSs are often incidental and do not usually result in neurological deficits. Given their generally benign nature and clear radiological diagnosis, biopsy is not recommended.¹⁰

Regarding follow-up guidance for GTPVS, existing comprehensive reviews lack directives for type 1 cases. In this series, we highlighted the case of an asymptomatic type 1 GTPVS that displayed no change in size for over 10 years. This implies that, as in type 2 GTPVS, type 1 might not require regular monitoring for asymptomatic patients. Conversely, for type 3 GTPVS, periodic checkups are recommended, especially for those untreated. The ideal protocol, however, remains undetermined.⁷

Lessons

GTPVSs predominantly present as asymptomatic lesions. Patients without symptoms should be closely monitored, and biopsy is discouraged when radiological findings are typical. Hydrocephalus resulting from GTPVS, though uncommon, necessitates surgical intervention. Available surgical options for cases with hydrocephalus include third ventriculostomy, shunt implantation, or direct cyst fenestration. For patients presenting with symptoms from localized mass effect, a thorough evaluation for potential neurosurgical intervention is imperative. Close follow-up of type 3 GTPVS is recommended, particularly in untreated cases. However, given the infrequency of GTPVS, definitive guidelines for neurosurgical treatments and subsequent follow-up remain elusive.

Author Contributions

Conception and design: Neyazi, Swiatek, Sandalcioglu. Acquisition of data: Neyazi, Swiatek, Hartmann, Zubel. Analysis and interpretation of data: Rashidi, Zubel, Amini. Drafting the article: Neyazi, Swiatek, Sandalcioglu. Critically revising the article: Neyazi, Swiatek, Stein, Hartmann, Rashidi, Amini, Sandalcioglu. Reviewed submitted version of manuscript: Swiatek, Amini, Sandalcioglu. Approved the final version of the manuscript on behalf of all authors: Neyazi. Administrative/technical/material support: Hartmann, Rashidi, Amini.

Supplemental Information

Previous Presentations

This case series has been previously presented as an ePoster at the 74th Annual Meeting of the German Society of Neurosurgery (DGNC), Tübingen, Germany, June 26, 2023. The abstract was consecutively published online for citation.