Surgical treatment for symptomatic ventriculus terminalis: case series and a literature review

Background Ventriculus terminalis is a cystic embryological remnant within the conus medullaris that normally regresses after birth. In rare cases, it may persist into adulthood and give rise to neurological symptoms, for which the optimal treatment remains uncertain. The aim of this study was to present our experience from a population-based cohort of patients with ventriculus terminalis and discuss our management strategy as compared to the existing literature. Methods A retrospective review was conducted of all adult (≥ 15 years) patients with ventriculus terminalis who were referred to the Karolinska University Hospital between 2010 and 2018. Results Fourteen patients were included. All patients were symptomatic at the time of referral, and the most common symptom was lower limb weakness (n = 9). Microsurgical cyst fenestration was offered to all patients and performed in thirteen. Postoperative imaging confirmed cyst size reduction in all surgically treated patients. No surgical complications were reported. Eleven of the surgically treated patients showed clinical improvement at long-term follow-up. One patient declined surgery, with progression of the cyst size and clinical deterioration observed at follow-up. Conclusions Surgery for ventriculus terminalis seems to be a safe and effective option for relief of symptoms. We propose that surgery should be offered to all patients with symptomatic ventriculus terminalis.


Introduction
Ventriculus terminalis, also known as the fifth ventricle, is an ependymal lined cerebrospinal fluid (CSF)-filled cavity within the conus medullaris. It is formed between the 43rd and the 48th day of embryogenesis, via canalization and retrogressive differentiation of the caudal end of the developing spinal cord and typically regresses completely after birth [1]. However, in rare cases, a residual ventricular cyst may persist into adulthood [2] (Figs. 1 and 2) and give rise to neurological symptoms, including sensorimotor disturbances and urorectal dysfunction [3]. Contrary to intramedullary tumors and/or syringomyelia, ventriculus terminalis is rounded, not contrast enhancing and exclusively found in the conus region of the spine [4].
The treatment for symptomatic ventriculus terminalis, whether conservative or surgical, remains uncertain. To date, there are only 54 described cases of surgical treatment reported in the literature   (Table 1). An important challenge is to identify patients where the potential benefits of surgery outweigh the risks. In an effort to facilitate this, de Moura Batista and colleagues established a clinical classification system based on the available literature ("cystic lesion of the ventriculus terminalis classification" (CLVT) [10], later revised by Ganau et al. based on their cohort of 13 patients [2], in which patients are categorized into CLVT type Ia (stable nonspecific symptoms without clear relation to ventriculus terminalis), type Ib (nonspecific but progressing symptoms), type II (focal neurological deficits), and type III (sphincter disturbances). The system proposes that type Ia lesions are best managed conservatively, while surgery is recommended for the remaining types.   (A2) T2-weighted magnetic resonance images showing  an intramedullary ventriculus  terminalis. Postoperative sagittal  (B1) and axial (B2) T2-weighted  magnetic resonance images  showing the same lesion 3 months  after cyst fenestration The aim of this study was to present our institutional experience of patients with ventriculus terminalis. In view of the limited data available in the literature, the presented material can provide additional insight to assist in decision-making for this patient category.

Methods
All adult patients (≥ 15 years) with ventriculus terminalis who were referred to the Department of Neurosurgery, Karolinska University Hospital (Stockholm, Sweden), between 2010 and 2018, were included in the study. No patients were excluded. The Karolinska University Hospital is a publicly funded and owned tertiary care center serving a region of approximately 2 million inhabitants and the only hospital in the region that accepts referrals for ventriculus terminalis. Thus, there was no selection bias. Medical records and imaging data from digital hospital charts were retrospectively reviewed using the health record software TakeCare (CompuGroup Medical Sweden AB, Farsta, Sweden). Outcome was assessed by change in cyst size and clinical status. The study was approved by the Regional Ethical Review Board in Stockholm, Sweden (Dnr: 2016/1708-31/4) who waived the need for informed consent.

Patient management
Following referral, a detailed neurological examination was performed in all patients. Special attention was given to any differential diagnoses that might explain the patients' symptoms. Patients were offered surgery if they had an MRIverified ventriculus terminalis and symptoms consistent with compression at the level of the conus medullaris.
The surgical treatment of choice was cyst fenestration through a laminotomy and subsequent myelotomy. Prior to surgery, the spinous process of the vertebra above the cyst was identified using CT guidance and marked with injection of a sterile carbon suspension. With the patient in the prone position, a laminotomy was performed via a midline approach, using an ultrasonic bone scalpel (Misonix Inc., Farmingdale, NY, USA). Under the microscope, the dura was incised in the midline and held open by sutures, after which the arachnoid was opened and the cyst exposed. Following this, a 4-5-mm longitudinal fenestration was made, using a sharp cannula or a diamond knife, at the thinnest part of the cyst wall. If there was no apparent thin area, a midline fenestration was performed instead. In two patients with no evident cyst wall, a midline fenestration was performed and a cyst-subarachnoid shunt was placed and fixed with nonabsorbable sutures. The dura was then closed using resorbable sutures, and the lamina affixed with titanium microplates. No duraplasty or expansion was performed. Following surgery,  [24] 6 Fenestration and a cyst-subarachnoid shunt Improved (5), unchanged (1) Present study 13 Fenestration (11) and a cyst-subarachnoid shunt (2) Improved (11), unchanged (2) Summary 67 Fenestration (55) and a cyst-subarachnoid shunt (9) Magnetic resonance imaging-guided aspiration (3) Improved (60), unchanged (5), unknown (2) patients were kept on bed rest for 24 h and subsequently mobilized. All patients were discharged to a rehabilitation facility before returning home.
In adherence with routine protocols, all surgically treated patients underwent a follow-up MRI and clinical examination by the treating physician/surgeon after 3 months. Additional MRI at other time-points was performed in selected cases, when clinically indicated. To assess long-term clinical outcome, all patients were evaluated with a telephone interview at an average (median) of 61 months (range 7-124) after surgery.

Baseline characteristics
During the study period, 14 patients were referred for MRIverified ventriculus terminalis. All patients were symptomatic at the time of referral, and the most common symptom was lower limb weakness (n = 9). Thirteen (93%) of the patients were female, and the median age was 45 years (range 35-71). The median cyst volume, as measured by a neuroradiologist using the formula (length × width × height)/2, was 2 ml (range 0.4-23). The lesions were located at levels T11-T12 (n = 4), T12-L1 (n = 9), and L2-S2 (n = 1). None of the patients had previously undergone spinal surgery. Eight patients had a concurrent spinal pathology (lumbo-sacral disk herniation (n = 4), lumbo-sacral disk degeneration (n = 2), combined cervical disk herniation and spinal stenosis (n = 1), and combined cervical spinal stenosis and a sacral perineural cyst (n = 1)). However, none of these concurrent pathologies were believed to adequately explain all the patients' symptoms. All patients were retrospectively categorized based on the CLVT classification (two type Ia, one type Ib, four type II, and seven type III) ( Table 2). The CLVT classification system was not used in the selection of surgical candidates in our cohort.

Treatment
All 14 patients were offered surgery. One patient opted for conservative treatment instead (patient no. 14), while the remaining thirteen patients underwent microsurgical cyst fenestration. The median time between the onset of symptoms and surgery was 24 months (range 9-120). The postoperative MRI confirmed cyst size reduction in all patients ( Figs. 1 and 2). No postoperative complications, including pseudomeningocele, were observed.

Outcome
For the surgically treated cohort, the median long-term followup time was 60 months (range 7-103). This included data acquired from patients' primary health care providers as well as the structured telephone interview. In total, 11 (85%) of the surgically treated patients showed clinical improvement at long-term follow-up, while the other two remained unchanged. Of the 11 patients with clinical improvement, one patient experienced complete symptom relief following surgery (patient no. 3). For the remaining patients with partial symptom relief, there was no clear indication as to which specific neurological symptom was most likely to be resolved following surgery (Table 3).
Seven patients underwent additional imaging (median 44 months after surgery, range 17-89), among which partial cyst recurrence was evident in three. One of the patients with partial cyst recurrence also had concurrent symptom reccurence and thus underwent successful renewed surgical fenestration 7 years after the initial operation (patient no. 1; Table 2).
The conservatively treated patient (patient no. 14) was followed clinically and radiologically for 124 months. During follow-up, the cyst volume increased from 1.5 to 3.2 ml. Clinically, the patient's sciatica progressed. Despite the new findings and symptoms, representing a transition from CLVT types Ia to Ib, the patient continued to decline surgical treatment.

Discussion
Ventriculus terminalis is a rare condition typically identified in patients investigated for low back pain or neurological symptoms in the lower extremities, including urorectal symptoms [3]. The majority of the patients are female [23], although the explanation for this is unknown. Data to support evidencebased treatment guidelines is scarce. The CLVT classification system [2,10] was designed to avoid unwarranted surgery. According to the CLVT classification, patients with type Ia lesions should be treated conservatively. This is mainly supported by case studies that have shown a stable clinical status in conservatively treated type Ia patients [2,4]. To the best of our knowledge, there are only three previously reported cases of attempted surgical treatment for patients with type Ia lesions, all of whom were treated without surgical complications or neurological deterioration [12,24]. However, Brisman et al. reported a case of a conservatively treated type Ia patient who developed acute cauda equina syndrome and required emergency surgery, highlighting the fact that these patients may deteriorate due to cyst growth [8]. Similarly, the type Ia patient in our cohort, who opted to be treated conservatively (patient no. 14), showed progressing cyst size and clinical deterioration at long-term follow-up. Considering the risk of cyst growth, as well as the fact that cyst fenestration for ventriculus terminalis appears to be safe and effective, we argue that surgery should be offered for type Ia lesions as well. Despite MRI-verified cyst size reduction, two of our patients experienced no symptom relief following surgery (patient no. 7 and 11). One reason behind the dissociation between radiological and clinical outcome may be the prevalence of concurrent spinal pathology, making it difficult to distinguish symptoms related to the ventriculus terminalis from those related to the degenerative disease. This is further illustrated by the global incidence of asymptomatic degenerative spinal disorders estimated to be as high as 19-84% [25]. Considering this, exhaustive diagnostic workup is warranted, but not necessarily enough to resolve this issue. In our surgically treated cohort, eight patients (62%) had concurrent spinal pathology, and all but one showed postoperative clinical improvement at long-term follow-up. Thus, we believe that excluding patients from being surgically treated, solely on the basis of concurrent spinal pathology, could result in inadequate treatment.

Surgical method
All operated patients in our cohort were treated with laminotomy and cyst fenestration, which is the most commonly described technique . We found that 85% of surgically treated patients sustained symptomatic improvement at long-term follow-up, which is comparable to the 87% success rate reported in the literature (Table 1). Furthermore, none of the patients developed complications that could be attributed to the surgical procedure. Thus, on a group level, surgical treatment for ventriculus terminalis appears to be both safe and effective.
Two of our surgically treated patients were treated with combined cyst fenestration and placement of a cystsubarachnoid shunt, both without complications (patient no. 2 and 11). In theory, the shunt eliminates concerns for closure of the cyst wall and reduces the risk of postoperative cyst recurrence. This method has been reported in seven previous cases (Table 1), and there have been no reports of shunt obstruction or postoperative cyst recurrence in these patients [13,24]. Of note, three other patients in our cohort, who did not receive cyst-subarachnoid shunts, later presented with partial cyst recurrence patients no. 1, 6 and 7. One of these patients underwent renewed surgical fenestration due to symptom reccurence (patient no 1). It is possible that this could have been avoided if a cyst-subarachnoid shunt had been placed. Thus, placement of a cyst-subarachnoid shunt appears to be safe and may decrease the risk of postoperative cyst recurrence. However, more long-term outcome data is needed to establish evidence-based treatment guidelines. While laminotomy and cyst fenestration is the most commonly described technique for treating ventriculus terminalis, an alternative method of percutaneous aspiration using realtime MRI has been described in three patients with good results [21]. This minimally invasive method might have the advantage of shorter hospital stay and no postoperative surgical site symptoms, but has yet to be validated by others.

Recommendation
To the best of our knowledge, this is the largest cohort study of patients with surgically treated ventriculus terminalis. Based on our experience, and in accordance with the CLVT classification, we agree that surgical treatment should be offered for type Ib, II, and III lesions to partially or completely relieve symptoms. In addition, we argue that patients with type Ia lesions should be offered surgery to decrease the risk of cyst growth and associated neurological deterioration. Furthermore, patients that decline surgery should be closely monitored as cyst growth and symptom progression may occur rapidly.

Conclusions
Microsurgical cyst fenestration is a safe and effective treatment option for ventriculus terminalis and should be offered to all symptomatic patients.

Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of interest.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent The study was approved by the Regional Ethical Review Board in Stockholm, Sweden, who, in accordance with Swedish Law, waived the need for informed consent.