Endoscopic third ventriculostomy for the management of children with cerebrospinal fluid disorders, ventriculomegaly and associated Chiari I Malformation

doi:10.21203/rs.3.rs-1619633/v1

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Endoscopic third ventriculostomy for the management of children with cerebrospinal fluid disorders, ventriculomegaly and associated Chiari I Malformation

https://doi.org/10.21203/rs.3.rs-1619633/v1

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Purpose: Our objective was to review the outcomes of children with CIM and associated cerebrospinal fluid (CSF) disorders and ventriculomegaly undergoing endoscopic third ventriculostomy (ETV) as a primary intervention.

Materials and methods: A retrospective, single-centre, observational cohort study was conducted, of consecutive children with CIM with associated CSF disorders and ventriculomegaly treated first by ETV between January 2014 and December 2020.

Results: Raised intracranial pressure symptoms were the most frequent with ten patients followed by posterior fossa and syrinx symptoms in three cases.

One patient had a later closure of the stoma and required a shunt insertion. The success rate of the ETV in the cohort was 92% (11/12). There was no surgical mortality in our series. No other complications were reported.

The median herniation of the tonsils was not statistically different in the pre vs post-operative MRI (1.14 vs. 0.94, p=0.1). However, the median Evan’s index (0.4 vs 0.36, p<0.01) and the median diameter of the third ventricle (1.35 vs. 0.76, p<0.01) were statistically different between the two measurements.

The preoperative length of the syrinx did not change significantly when compared with the postoperative (5 vs. 1; p=0.052), nevertheless, the median transverse diameter of the syrinx did improve significantly after the surgery (0.75 vs. 0.32, p=0.03).

Conclusions: Our study supports the safety and effectiveness of ETV for the management of children with CSF disorders, ventriculomegaly and associated CIM.

Chiari

Neuroendoscopy

ETV

Hydrocephalus

Syrinx

Chiari I malformation (CIM) is a structural abnormality characterised by the herniation of the cerebellar tonsils through the foramen magnum.[1] However, CIM shouldn’t be considered as a single diagnostic entity, herniation of the hindbrain should be viewed as the consequence of different pathophysiological processes.[2] Among these, cerebrospinal fluid (CSF) disturbances are one of the most well described etiologist for tonsillar herniation.[3]

Overt hydrocephalus is diagnosed in 6.5–9.6% of patients with CIM, and most authors agree that the hydrocephalus should be treated first. However, more subtle disorders of CSF circulation may accompany CIM and might also benefit from intracranial pressure directed therapy.[2]

The treatment of patients with co-presenting CIM and CSF disorders is another point of contention. Whilst it could be argued that foramen magnum decompression (FMD) may relieve outflow obstruction at the foramen magnum to resolve hydrocephalus, there is a reasonable body of evidence that preoperative hydrocephalus is associated with CSF complications following FMD [1, 4]. This forms, in part, the basis for the recommendation for primary CSF diversion in such cases prior to consideration of FMD [2, 5]. Furthermore, there have been a number of studies to suggest that primary CSF diversion in CIM have prevented the future need of FMD [6], but further evidence is required.

There have been reports of cohort series analysing the long term outcome of ETV in CIM with overt hydrocephalus,[3, 6] however these were mostly done in adult patients or in mixed adult and paediatric populations. Yet, the pathophysiology behind CIM in adults and paediatric patients differs significantly.

Our objective was to review the outcomes of children with CIM and associated CSF disorders and ventriculomegaly undergoing ETV as a primary intervention.

Patient population

A retrospective, single-centre, observational cohort study was conducted, of consecutive children with CIM with associated ventriculomegaly treated first by ETV between January 2014 and December 2020. Patients were identified from the operative logs from Great Ormond Street Hospital by screening the clinical records of children who underwent ETV. Exclusion criteria included the presence of aqueduct stenosis or any other type of posterior fossa malformation other than CIM, prior foramen magnum decompression (FMD) or VPS, incomplete pre-or post-operative magnetic resonance imaging (MRI) and/or less than six months of follow up.

Although not an essential morphological feature of CIM [2], to remain consistent with existing literature the diagnosis of CIM was defined as a tonsillar herniation greater than 5mm below the foramen magnum on sagittal MRI images. Ventriculomegaly was confirmed if Evan’s index > 0.3 was measured on axial MRI.

Clinical outcomes

Clinical outcomes were determined on a review of the clinical documentation. The patients were clustered into two groups depending on the preoperative symptoms. Group 1: Raised intracranial pressure (ICP) symptoms - headache, vomiting, papilledema, hyporeactivity and macrocrania; Group 2: Posterior fossa or syrinx-related symptoms, occipital and tussive headache, neck pain, dysphagia, sleep apnoea and acute respiratory arrest, dysesthesia, paraesthesia, dissociated sensory loss and upper limbs weakness.

The clinical outcome during the follow up was also recorded. A good outcome was defined as complete resolution of all the symptoms.

The occurrence of surgery following ETV in the follow up was also recorded. The success of the ETV was defined as no need for a second surgery to treat the symptoms during the follow-up. This could include the need for VPS insertion, re-do of the ETV or FMD surgery.

Imaging

Patients routinely underwent T1- and T2-weighted MRI studies of the brain and spine pre- and post-ETV. The degree of tonsillar herniation was measured below the basion-opisthion line. The Evan’s index and the transverse diameter of the third ventricle were also recorded. Other findings recorded were the presence of a syrinx, along with the length of the syrinx (measured in the number of vertebral bodies), the maximum diameter of the syrinx and the morphology (uni- or multi-loculated).

Statistical analysis

Because of the limited sample size, continuous data were presented as the median and interquartile range (IQ), categorical data were presented as absolute frequency. To compare the pre-and postoperative continuous data we used the Wilcoxon Signed Rank test, after checking the assumptions. Significance was set at p < 0.05. The software STATA MP 14 (StataCorp, 4905 Lakeway Dr College Station, TX 77845, USA) was used to analyse the results.

Demographics

Fourteen children were detected with co-presenting CIM and ventriculomegaly who underwent ETV at our centre. After excluding two patients because of incomplete MRI studies, our cohort was composed of 12 children. The median age at ETV was seven years (3-10.5), and eight patients were males. Two children had previously been diagnosed with sagittal synostosis. The median follow- up was 25 months (11–36).

Clinical outcomes

The clinical findings are summarised in Table 1. Raised ICP (Group 1) symptoms were the most frequent, with ten patients (two cases with papilledema), followed by posterior fossa and syrinx symptoms (Group 2) in three cases.

Table 1
Patient	Age in years	Gender	Group 1 symptoms	Group 2 symptoms	Tonsillar herniation in cm	III ventricle diameter in cm	Syrinx	Final outcome	Follow-up in months
1	10	M	Headaches	-	1.06	0.86	No	A	26
2	3	M	Macrocrania	-	1.90	1.1	Yes	A	19
3	3	M	-	Hand weakness	1.49	1.27	No	A	36
4	6	F	Headaches	-	0.66	1.51	Yes	A	26
5	11	M	Papilledema	Cough occipital headaches	2.32	1.26	No	A	8
6	10	M	Headaches/ Vomits	-	1.50	1.51	No	A	8
7	13	F	-	Cough occipital headaches and Dissociated sensory loss	1.07	1.38	Yes	A	6
8	8	M	Headaches/ Vomits	-	1.43	1.13	Yes	S	14
9	< 1	F	Macrocrania	-	1.11	1.12	No	A	24
10	15	F	Headache	-	0.76	1.53	Yes	A	60
11	3	M	Headache/ Macrocrania	-	1.17	1.68	Yes	A	36
12	2	F	Headache/ Macrocrania/ Papilledema	-	0.62	1.80	Yes	S -VP shunt	72
M: Male
F: Female
A: Asymptomatic
S: Symptomatic
VP: Ventriculoperitoneal

The ten patients with raised ICP symptoms improved after the surgery. One patient had a later closure of the stoma and presented two months after surgery with recurrent symptoms of raised ICP, an MRI was done that showed closure of the stoma and a VPS was inserted. The three patients in the Group 2 resolved the symptoms after the ETV and remained asymptomatic on the last follow up. There was no surgical mortality in our series. No other complications were reported. The success rate of the ETV in the cohort was 92% (11/12) (Fig. 2).

Imaging outcomes

The measurements and statistical analyses are summarised in Table 2. All the patients had tonsillar ectopia before the surgery, the median herniation of the cerebellar tonsils was 1.14 cm (0.91–1.49) below the basion–opisthion line. The median preoperative Evan’s index was 0.4 (0.34–0.43) and the median transverse diameter of the third ventricle was 1.35 cm (1.12–1.52). Seven patients presented with syrinx in the preoperative spine MRI, with a median length of five body levels (1–18), and a median maximum transverse diameter of 0.75 cm (0.34–1.12). Of the seven cases of syrinx, two were uniloculated and five were multiloculated.

Table 2
Measurement	Pre-ETV	Post-ETV	P value
Presence of Chiari I (absolute frequency)	12/12	11/12
Degree of tonsillar herniation in cm (median and IQ range)	1.14 (0.91–1.49)	0.94 (0.73–1.53)	0.1
Evan’s index (median and IQ range)	0.4 (0.34–0.43)	0.36 (0.31–0.39)	0.005
Diameter III ventricle in cm (median and IQ range)	1.35 (1.12–1.52)	0.76 (0.63-.95)	0.003
Presence of syrinx (absolute frequency)	7/12	6/12
Length of the syrinx in body levels (median and IQ range)	5 (1–18)	1 (0–4)	0.052
Transverse diameter of the syrinx in cm (median and IQ range)	0.75 (0.34–1.12)	0.32 (0-0.46)	0.03
IQ: Interquartile
ETV: Endoscopic third ventriculostomy

In the postoperative analysis, 11/12 patients presented tonsillar ectopia. The median herniation of the cerebellar tonsils was 0.94 cm (0.73–1.53) below the basion–opisthion line. The median herniation of the tonsils was not statistically different in the pre vs post-operative MRI (1.14 vs. 0.94, p = 0.1) (Fig. 1). The median postoperative Evan’s index was 0.36 (0.31–0.39) and the median transverse diameter of the third ventricle was 0.76 cm (0.63-.95). Bothe the Evan’s index (0.4 vs 0.36, p < 0.01) and the diameter of the third ventricle (1.35 vs. 0.76, p < 0.01) were statistically different between pre and postoperative measurements (Fig. 2).

One patient completely resolved the syrinx (Fig. 3), while the other six cases showed some improvement. The median length of the syrinx after the ETV was one body level (0–4), and the median maximum transverse diameter was 0.32 cm (0-0.46). Of the six cases with syrinx, two were uniloculated and four were multiloculated. The preoperative length of the syrinx did not change significantly when compared with the postoperative (5 vs. 1, p = 0.052), nevertheless, the median transverse diameter of the syrinx did improve significantly after the surgery (0.75 vs. 0.32, p = 0.03) (Fig. 4).

The relationship between hydrocephalus and CIM was first described by Chiari in his original monograph [7] in 1987 where he makes the following statement “I have had the impression that the extension of the tonsils and medial sides of the inferior lobes probably always is the result of chronic and very early onset of cerebral hydrocephalus”. In the case of overt hydrocephalus, most authors believe it is the result of impaired CSF circulation in the outlets of the fourth ventricle. [8–10] Whilst overt hydrocephalus occurs in a relative minority of CIM patients, disordered CSF circulation may be more prevalent than previously believed.[2] Despite the uncertainty of the pathogenesis of hydrocephalus in CIM, most authors agree that the first line of treatment should be CSF diversion, either through VPS insertion or ETV.[11, 12] In recent years, ETV has gained widespread acceptance as a durable alternative for VPS placement in most cases of hydrocephalus with a success rate between 80–90% and a lower risk of brain infection and other complications.[13–16] The reduction in the size of the prepontine space in patients with CIM has been considered as a limiting factor for a successful ETV. However, in our review of the literature, at least 46 cases of CIM with overt hydrocephalus treated with ETV without any major complications were reported, demonstrating that it is a safe procedure to perform despite the small size in the prepontine space.

The success rate for ETV in patients with CIM and ventriculomegaly in the literature is 40/46 (86%) (Table 3). Most reports were done in adults, with the largest paediatric cohort presented by Massimisi et al.[17] in 2011 with 11 cases. However, in this cohort, the analysis was done in a population of both paediatric and adult patients. The problem with this analysis is that the physiology as well as the management of CSF disorders, especially in the presence of CIM, differs between adults and paediatric patients. Nevertheless, all the patients had a postoperative improvement in their symptoms. For those with a pre-operative syrinx, the syrinx resolved in 3/6, improved in 2/6 and remained stable in 1/6. Two cases required a redo ETV for obstruction of the stoma.

Table 3

Review of the literature and current series
Author	Year	Number of patients	Mean age	Success rate	Follow up in months
Decq et al.	2001	5	29.6 years	5/5	Mean 50.39
Hayhurst et al.	2008	16	31.9 years	15/16	Mean 42
Massimi et al.	2011	15	15.06 years	15/15	Mean 35
Yiping Wu et al.	2015	10	28.14 years	8/10	Mean 92
Current series	2022	12	7 years	11/12	Median 25

Hayhurst et al.[6] presented 16 patients (mean age 31.9 years) with CIM and hydrocephalus, 15 resolved the ICP symptoms, while 6 patients required FMD to deal with the posterior fossa symptoms. The syrinx improved in 4/6 patients, resolved in 1/6, and remained stable in 1/6. The third-largest series was presented by Wu et al.[18] with 10 cases (mean age 28.14 years) with a success rate of 80% (8/10) and two patients requiring a second surgery, one of them an FMD. Lastly, a series by Deq et al.[19] reported five cases (mean age 29.6 years), four of whom had a postoperative improvement in symptoms whilst one patient required a revision ETV.

Different from what Hayhurst[6] reported, in our series, all of the patients had a postoperative improvement in symptoms and there was no distinction between patients with raised ICP or posterior fossa symptoms. None of the patients required an FMD surgery after the ETV.

In terms of syrinx improvement, one patient had complete resolution of their syrinx, whilst the rest (6/7) significantly improved the length and transverse diameter of the syrinx. Previous reports[6, 17] showed a higher rate of complete resolution of the syrinx compared to ours, nevertheless, the definition that they used for resolution of the syrinx is unclear.

Tonsillar ectopia was resolved in one case after ETV, and even though an improvement in the descent of the tonsils (1.14 cm vs 0.94 cm) was seen, it was not statistically significant. On the other hand, the diameter of the third ventricle and the size of the lateral ventricles did improve after the surgery. Similar results were found by Wu et al.,[18] who reported a reduction of the mean transverse diameter of the third ventricle from 12.79 mm preoperatively to 6.34 mm postoperatively (p = 0.0035).

ETV has proven to be a safe procedure to treat CSF disorders in patients with ventriculomegaly and CIM. These observations allow us to hypothesise that there is no need to have an improvement in the tonsillar herniation to have a successful resolution of the symptoms. However, a reduction in the size of the ventricles after the surgery should be expected after a successful ETV. In terms of the syrinx and syrinx associated symptoms, resolution of the symptoms should be accomplished, even without complete disappearance of the syrinx. Still, all of the patients showed some improvement, mostly in the syrinx maximum diameter. The failure of the treatment was presented as instauration of symptoms.

Because of the small number of patients limiting the value of the statistical analysis, these data need to be validated using a larger number of patients.

Our study supports the safety and effectiveness of ETV for the management of children with CSF disorders, ventriculomegaly and associated CIM.

Ethics approval and consent to participate: Ethical approval was waived by the local Research Committee of at Great Ormond Street Hospital in view of the retrospective nature of the study and all the procedures being performed were part of the routine care. The study was conducted in accordance with the declaration of Helsinki.

Consent for publication: All the images and information presented in this article are anonymized and the submission does not include images that may identify the person.

Parental consent: Parents have consented to use their son\daughter information and images for research

Availability of data and materials: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests: The authors have no relevant financial or non-financial interests to disclose.

Funding: The authors did not receive support from any organisation for the submitted work.

Authors' contributions: All authors whose names appear on the submission made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work

Acknowledgements: Not applicable

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No competing interests reported.

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Endoscopic third ventriculostomy for the management of children with cerebrospinal fluid disorders, ventriculomegaly and associated Chiari I Malformation

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Abstract

Figures

Introduction

Materials And Methods

Patient population

Clinical outcomes

Imaging

Statistical analysis

Results

Demographics

Clinical outcomes

Imaging outcomes

Discussion

Conclusion

Declarations

References

Additional Declarations

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