Articles
Postoperative speech impairment and surgical approach to posterior fossa tumours in children: a prospective European multicentre cohort study

https://doi.org/10.1016/S2352-4642(21)00274-1Get rights and content

Summary

Background

Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors.

Methods

In this observational prospective multicentre cohort study, we included children (aged <18 years) undergoing primary surgery for a posterior fossa tumour at 26 centres in nine European countries. Within 72 h of surgery, the operating neurosurgeon reported details on the tumour location, surgical approach used, duration of surgery, use of traction, and other predetermined factors, using a standardised surgical report form. At 2 weeks, 2 months, and 1 year after surgery, a follow-up questionnaire was filled out by a paediatrician or neurosurgeon, including neurological examination and assessment of speech. Speech was classified as mutism, reduced speech, or habitual speech. POSI was defined as either mutism or severely reduced speech. Ordinal logistic regression was used to analyse the risk of POSI.

Findings

Between Aug 11, 2014, and Aug 24, 2020, we recruited 500 children. 426 (85%) patients underwent primary tumour surgery and had data available for further analysis. 192 (45%) patients were female, 234 (55%) patients were male, 81 (19%) patients were aged 0–2 years, 129 (30%) were aged 3–6 years, and 216 (51%) were aged 7–17 years. 0f 376 with known postoperative speech status, 112 (30%) developed POSI, 53 (14%) developed mutism (median 1 day [IQR 0–2]; range 0–10 days), and 59 (16%) developed reduced speech after surgery (0 days [0–1]; 0–4 days). Mutually adjusted analyses indicated that the independent risk factors for development of POSI were younger age (linear spline, p=0·0087), tumour location (four levels, p=0·0010), and tumour histology (five levels, p=0·0030); surgical approach (six levels) was not a significant risk factor (p=0·091). Tumour location outside the fourth ventricle and brainstem had a lower risk of POSI (with fourth ventricle as reference, odds ratio (OR) for cerebellar vermis 0·34 [95% CI 0·14–0·77] and OR for cerebellar hemispheres 0·23 [0·07–0·70]). Compared with pilocytic or pilomyxoid astrocytoma, a higher risk of POSI was seen for medulloblastoma (OR 2·85 [1·47–5·60]) and atypical teratoid rhabdoid tumour (10·30 [2·10–54·45]). We did not find an increased risk of POSI for transvermian surgical approach compared with telovelar (0·89 [0·46–1·73]). Probability of speech improvement from mutism reached 50% around 16 days after mutism onset.

Interpretation

Our data suggest that a midline tumour location, younger age, and high-grade tumour histology all increase the risk of speech impairment after posterior fossa tumour surgery. We found no evidence to recommend a preference for telovelar over transvermian surgical approach in the management of posterior fossa tumours in children in relation to the risk of developing POSI.

Funding

The Danish Childhood Cancer Foundation, the Swedish Childhood Cancer Foundation, the UK Brain Tumour Charity, the Danish Cancer Society, Det Kgl Kjøbenhavnske Skydeselskab og Danske Broderskab, the Danish Capitol Regions Research Fund, Dagmar Marshall Foundation, Rigshospitalet's Research Fund, and Brainstrust.

Introduction

Brain tumours are the most common tumours in European children, with 3·7 new cases diagnosed annually per 100 000 population.1 Half of these tumours occur in the posterior fossa2—the cerebellum, brainstem, cerebello-pontine angle, and the fourth ventricle.

Research in context

Evidence before this study

We searched PubMed for all reports in English with available abstracts published until Jan 1, 2021, using the search terms “cerebellar mutism”, “posterior fossa syndrome”, “telovelar”, “transvermian”, and revealed 297 references of interest. All abstracts were read for content of surgical approach and cerebellar mutism, cerebellar mutism syndrome, or posterior fossa syndrome. No further inclusion or exclusion criteria were used. Postoperative speech impairment (POSI) is described as a complication of surgical removal of mainly midline tumours in the posterior fossa in children (aged <18 years). POSI occurs within days of surgery and improves within months, but the terminology for speech impairment differs between studies. Route of surgical access to the tumour is thought to influence this functional outcome; however, previous studies had few patients or a retrospective design, and their conclusions are divergent.

Added value of this study

This study presents new prospectively collected data about speech impairment after posterior fossa tumour resection in children, using different surgical approaches. Our study suggests a new framework for categorising POSI and provides prognostic models to estimate the time to improvement. The data did not suggest a difference in risk of POSI between telovelar or transvermian surgical approaches. Mutually adjusted analyses indicated that the risk of developing POSI was higher in younger children, in children with tumours in the fourth ventricle and brainstem, and in children with medulloblastoma and atypical teratoid rhabdoid tumour.

Implications of all the available evidence

Our study does not implicate a preference for surgical approach in posterior fossa tumour management in children. Our findings suggest that the biology and location of the tumour influence the risk of POSI. Risk stratification for POSI by age and tumour location should be applied when informing patients and parents before surgery, and the prognostic models on recovery of speech will provide new information for patients with POSI and their families.

Surgical resection is a cornerstone of posterior fossa tumour management but it is complicated by postoperative cerebellar mutism syndrome (CMS), of which postoperative speech impairment (POSI) is a cardinal symptom, in around a quarter of patients.3, 4, 5, 6, 7, 8 CMS might last for weeks or months6, 7 and frequently leaves some long-term speech impairment.9, 10, 11, 12 CMS is characterised by the onset of mutism or severely reduced speech and emotional lability within days of surgery, and is often accompanied by ataxia, hypotonia, dysphagia, and brainstem dysfunction.13

Although injury to the dentate nuclei and their efferents has been associated with developing CMS,14 no consensus exists regarding optimal surgical strategy to avoid CMS. A transvermian surgical approach, with dissection of the inferior vermis, has been suggested as a risk factor for developing CMS,4, 5, 15 although the results from surgical series in which the vermis was spared were not consistent.16, 17, 18 A telovelar approach has become more widely used over the past decade. This approach has been suggested to decrease the risk of CMS,19 but not in other studies.20, 21, 22

We present a prospective, international, multicentre cohort study of children undergoing surgery for posterior fossa brain tumours. We aimed to investigate risk of POSI and its association with surgical approach and other clinical factors.

Section snippets

Study design and cohort

The study was designed as an observational prospective multicentre cohort study; details have been published previously.23 We included patients younger than 18 years who were diagnosed with a tumour in the posterior fossa and underwent primary surgical resection or open biopsy at one of 26 participating centres in nine European countries (full list of countries and centres given in the appendix p 6). Postoperative inclusion was accepted when logistical reasons or acute surgery rendered

Results

Between Aug 11, 2014, and Aug 24, 2020, we recruited 500 patients. 43 (9%) patients were not undergoing primary tumour surgery and 31 (6%) had key data missing (figure 2). Thus, 426 (85%) patients underwent primary tumour surgery and had data available for further analysis. 192 (45%) patients were female, 234 (55%) patients were male, 81 (19%) patients were aged 0–2 years, 129 (30%) were aged 3–6 years, and 216 (51%) were aged 7–17 years (table 1). Tumour histology was pilocytic or pilomyxoid

Discussion

This prospective multicentre cohort study of children undergoing surgery for posterior fossa brain tumours is the largest of its kind to date and showed a range of surgical, tumour-related, and demographic risk factors for developing POSI.

The main finding of this study was that surgical approach was not associated with POSI when adjusted for tumour location and tumour histology. We found no statistical evidence to support the hypothesis that a telovelar approach carries a lower risk of POSI

Data sharing

Data in this study are being collected in an ongoing clinical trial, with the original aim of 500 patients amended to 1000 patients. After completed follow-up of the last patient, Ddata will be available for sharing upon request from the corresponding author.

Declaration of interests

We declare no competing interests.

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    • A presurgical voxel-wise predictive model for cerebellar mutism syndrome in children with posterior fossa tumors

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      However, the description of the tumor location was brief in previous studies. In most cases, tumor location was classified into midline location and lateral location (Gora et al., 2017; Küpeli et al., 2011), and in some cases, it was divided into the vermis, fourth ventricle, and cerebellar hemisphere (Grønbæk et al., 2021; Robertson et al., 2006). Generally, the midline location was associated with an increased risk of CMS, whereas the hemisphere location with lower risk of CMS (Pettersson et al., 2022).

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      Surgical approaches to the posterior fossa, specifically to the fourth ventricle, the telovelar versus transvermian approach, have also been controversial as a potential modifiable risk factor. The largest prospective multicenter study with 500 children assessing the surgical approach and postoperative speech impairment found no difference in the incidence of mutism between these two surgical approaches.26 It has also been proposed to use cerebellocortical stimulation to monitor the integrity of the cerebellothalamocortical outflow pathways intraoperatively.27

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    List of contributors given in the appendix (p 10)

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