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ORIGINAL ARTICLE
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Factors predicting “postoperative cerebellar mutism syndrome’’ after posterior fossa tumor excision in pediatric patients


1 Department of Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Neurosurgery, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India

Date of Submission18-Feb-2021
Date of Acceptance28-Mar-2021
Date of Web Publication07-Jan-2022

Correspondence Address:
Kamlesh Singh Bhaisora,
Department of Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh.
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_38_21

 

   Abstract 

Background: Central tumor location, brain stem involvement, and medulloblastoma have been implicated as risk factors for pediatric postoperative cerebellar mutism syndrome (pCMS) by most researchers. However, conflicting results have been reported for surgical factors, such as the extent of excision, surgical approach, and the need for cerebrospinal fluid diversion. The role of emergency or elective surgery is also not well established. Aim: To assess the role of surgical factors as a risk for pCMS. The secondary variables assessed include patient profile, histopathology, radiological features, and the effect of pCMS on patient survival. Materials and Methods: Overall, 162 consecutively operated patients with posterior fossa tumor (PFT) from July 2012 to March 2020, younger than 16 years of age, were included in the study. The study population was divided into two cohorts: the pCMS group and the non-pCMS group for statistical analysis. A P-value of less than 0.05 was considered statistically significant. Results: In the sample size of 162 patients, 129 patients were included for analysis. There were 11 patients in the pCMS group. Emergency surgery was found to be a significant risk for pCMS (P = 0.021). There was a trend toward statistical significance for the need for preoperative cerebrospinal fluid diversion. The extent of resection and surgical approach were not found to be statistically significant factors. Central tumor location and contrast enhancement were significant radiological risk factors (P < 0.05). Conclusion: Aggressive tumor resection causing iatrogenic injury to the cerebellar circuitry and the brain stem is the most important risk factor for pCMS. Patients with pCMS have adverse survival outcomes.


Keywords: Pediatric, posterior fossa tumors, postoperative cerebellar mutism syndrome



How to cite this URL:
Datta A, Kumar A, Singh S, Bhaisora KS, Srivastava AK, Sardhara J, Das KK, Mehrotra A, Jaiswal AK, Behari S. Factors predicting “postoperative cerebellar mutism syndrome’’ after posterior fossa tumor excision in pediatric patients. J Pediatr Neurosci [Epub ahead of print] [cited 2022 Jan 26]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=335205





   Introduction Top


The PFTs constitute 50–70% of overall brain tumors in the pediatric population.[1] The common pediatric PFTs are medulloblastoma, ependymoma, and astrocytoma.[2] All three of them possess a peculiar pathological and clinical course, and they have a distinct prognosis. Posterior fossa syndrome (PFS) is an unwanted, unknown, and rare clinical phenomenon that is seen after suboccipital craniotomy or craniectomy. The reported incidence varies from 8% to 24% in the literature.[3] The patient behaves in a psychologically absurd manner (either irritable, crying unnecessarily, pyrexia of unknown origin, unexplained headache, or pseudo-locked-in like state). The latest definition for postoperative pCMS or PFS is: “It is characterized by delayed onset mutism/reduced speech and emotional lability after cerebellar or 4th ventricle tumor surgery in children.”[4] Other rare clinical symptoms include hypotonia and oropharyngeal dysfunction/dysphagia, cerebellar motor syndrome, cerebellar cognitive affective syndrome, and brain stem dysfunction, including long tract signs and cranial neuropathies. Central tumor location, brain stem involvement, and medulloblastoma have been implicated as risk factors for pCMS by most researchers.[5],[6],[7],[8],[9] However, conflicting results have been reported for surgical factors, such as the extent of excision, surgical approach, and the need for cerebrospinal fluid (CSF) diversion.[10],[11],[12],[13] The role of emergency or elective surgery is also not well established. We aim at assessing the role of surgical factors as a risk for pCMS. The secondary variables assessed include patient profile, histopathology, and radiological features. We also evaluated the effect of pCMS on patient survival.


   Materials and Methods Top


Study design

This is a single-center, retrospective cohort study, analyzing our surgical database from July 2012 to March 2020. Only pediatric patients (younger than 16 years of age) were included in our study. The clinical data included age, gender, presenting symptoms, radiological details, surgery, complications, and follow-up. The histopathological details and adjuvant management (radiotherapy and chemotherapy) data were also retrieved from pathology and radiotherapy departments. The intraoperative data were noted from the prospectively maintained database on the hospital information system. Institutional ethical clearance was approved, and individual consent for the use of clinical or radiological data for publication was taken at the time of admission (as per our departmental policy).

Inclusion and exclusion criteria

Out of the 162 consecutively operated, pediatric patients (age younger than 16 years) with a PFT, we analyzed the patients who had cerebellar mutism or emotional lability within 30 days of surgery. Patients with altered sensorium, those who were on ventilator support, or those who were tracheostomized were excluded from the analysis (n = 33).

Study parameters

Cerebellar mutism was considered as the mutism that followed cerebellar lesion/insult rather than the involvement of the cerebrum or the lower cranial nerves, in an awake patient with intact comprehension. The muteness is usually transient, which is followed by varying degrees of linguistic sequelae. The terminology has overlapping definitions in the literature, and certain similar “terms” have been proposed for “nearly the same” clinical condition. We conducted a literature review, and [Table 1] describes these terminologies.
Table 1: Terminologies to describe similar clinical conditions as “posterior fossa syndrome”

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For the choice of approach, a departmental panel discusses the best possible approach and then a final corridor is chosen. The level of expertise is nearly similar among all senior operating surgeons. Maximal safe resection with minimal collateral damage was the surgical goal in all the cases. The lateral extension through the foramen of Luschka and the caudal extension below the foramen magnum were noted. The point of origin of the tumor was decided where there was tumor mass epicenter and loss of plane with the cerebellum, brain stem, or middle cerebellar peduncle. Complete and partial excision was noted from intraoperative surgical notes, and it depended on the discretion of the senior surgeon. It was confirmed on the immediate postoperative contrast CT head.

Immediate postoperative status was retrieved from patient case files. A subset of patients had extensive metastasis and hydrocephalus at initial presentation, had undergone only CSF diversion. Their parents did not consent to definitive surgery and were excluded from our statistical analysis.

Statistical analysis

The Statistical Package for the Social Sciences (SPSS, version 22.00, IBM, New York) was used for statistical analysis. Chi-square test was used to compare the mean distribution of study parameters among the groups. Univariate analysis for the factors predicting the occurrence of PFS was done. A P-value of less than 0.05 was considered statistically significant.


   Results Top


[Table 2] shows the clinicopathological details of all the 11 patients included in our study. All except one patient with pCMS had emotional lability. Eleven out of 129 patients included in the study had cerebellar mutism postoperatively. A subgroup analysis was done for patients with pCMS and was compared with the non-pCMS group [Table 3]. The mean age of the patients with pCMS was 7.82 ± 3.6 years (M:F = 1.2:1). The mean duration of symptoms was 3.2 ± 2.56 weeks. Seven patients had medulloblastoma and three patients had ependymoma as their histopathology. In preoperative magnetic resonance imaging (MRI), four patients had a lateral extension, three patients had a caudal extension, and eight patients had a variable degree of brain stem compression. Nine patients showed enhancement on contrast MRI (P < 0.05). All the 11 patients had a tumor in the midline/central location (P < 0.05). Ten patients underwent the trans-vermian approach (P > 0.05). Six patients underwent near-total excision, whereas four patients underwent total excision. Nine patients were operated on in emergency settings. Intraoperatively, six patients had their tumor originating from the floor of the fourth ventricle and five patients had their tumor originating from the vermis. Four patients underwent ventriculoperitoneal shunt in the preoperative period; overall, seven patients in the pCMS group underwent CSF diversion preoperatively. Postoperatively, two patients had a cerebrospinal fluid leak, wound bulge, and meningitis. Four patients died during the postoperative period.
Table 2: Clinical profile of all the included patients in our series (n = 162)

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Table 3: Comparison of variables between pCMS cohort and non-pCMS cohort

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   Discussion Top


In 1958, Daly and Love described the loss of speech in a child after the excision of a cerebellar tumor.[14] However, it was Rekate et al. who gained recognition with their landmark case series of six patients.[15] Subsequently, numerous case reports elaborated the assemblage of associated signs and symptoms, increasing the understanding of CMS. pCMS has primarily been described in the pediatric population, though a few adult cases are present in the literature.[16] The incidence in retrospective studies has been reported to be between 8% and 24%[17]; however, higher incidences have been reported in a few prospective studies.[18],[19] The possible reason for this could be the ambiguous spectrum of definitions of pCMS, with varied observations resulting in significant differences in the incidence and uncertainties regarding the outcome. The incidence of pCMS in our study was 8.52%. The true incidence is expected to be higher, as a significant number of patients were tracheostomized postoperatively for lower cranial nerve involvement or due to the need for prolonged ventilatory support.

Various names have been used to denote these “syndromes” that occur after PFS. These have subtle differences and include PFS, cerebellar mutism syndrome (CMS), cerebellar mutism/transient cerebellar mutism (CM/TCMS), mutism, and subsequent dysarthria, cerebellar motor syndrome (CMoS), and cerebellar cognitive affective syndrome (CCAS). However, there is no specific management protocol and these have to be dealt with by rehabilitation along with supportive measures. Differentiation among these syndromes may not be the prime requirement for the management.

Pathogenesis of posterior fossa syndrome and inciting factors

The pathophysiology of PFS remains unclear and elusive, with various proposed theories including the involvement of vermis or midline location, the involvement of brain stem, bilateral edema within the cerebellar peduncles postoperatively, aggressive surgery/retraction of the cerebellum intraoperatively, impairment of the dentato-thalamo-cortical pathways, focal vasospasm, and neurotransmitter dysfunction.

In 1994, Crutchfield et al. conducted the first study that recognized the value of the dentato-thalamo-cortical pathway in the pathogenesis of PFS.[18],[20] They postulated a phenomenon, namely the “Bilateral Crossed Cerebello-Cerebral Diaschisis (BCCCD),” as the principal cause. An imperative breakthrough took place with the unveiling of the dictum that bilateral surgical damage to any component of the proximal efferent cerebellar pathway (PECP) was crucial to causing pCMS. Based on sequential postoperative findings, Kusano et al. showed that damage to bilateral dentate nuclei (as evidenced by neuroimaging) was vital for the development of PFS.[21] Subsequent studies brought to light that bilateral damage to any constituent of the PECP, even if it is asymmetrical and incomplete, leads to PFS. Hence, avoiding damage to these components may reduce the possibility of developing PFS via the DTC pathway through BCCCD. Another functional circuit, the Guillain Mollaret Triangle/dentatorubroolivay triangle, may also be noteworthy with regards to PFS.[22] Lesions lead to changes in the inferior olivary nucleus, which is contralateral to the superior cerebellar peduncle and ipsilateral to the descending tegmental pathway. Various pathological and time-related stages have been described for the sequential degeneration of the same. Studies have proven hypertrophic olivary degeneration as a reliable marker of damage to the contralateral PECP, which can be appreciated on imaging, but this is a fairly delayed finding.[23] Therefore, surgical manipulation, coagulation of vessels, and embolic occlusions, among others, may all be the suspected intraoperative criminals. Delayed onset can be attributed to vasospasm, a disturbance may be attributed to transient ischemia, resolution may be attributed to regularization of blood flow, and recovery of mutism may be attributed to neuronal plasticity and reassignment of speech function within the cortical system.

Risk factors for pCMS

Patient and tumor-related factors

There are conflicting results, with younger age and male gender as risk factors for the occurrence of pCMS. We did not find either to be significant factors. Though most of the patients in the pCMS cohort had medulloblastoma, it was not found to be a statistically significant factor in predicting pCMS. This is against most studies, as medulloblastoma has been recognized as a consistent risk factor. However, Catsmann-Berrevoets et al. reported that medulloblastoma is a risk factor only when the tumor size is more than 5 cm.[24] Another study by Doxey et al. reported that the incidence of pCMS in patients with medulloblastoma specifically involving the brain stem was significantly higher; therefore, a conservative rather than an aggressive surgical approach should be applied in this population.[25] There was a trend for the need for CSF diversion preoperatively to be a significant determinant for pCMS occurrence. Also, patients in the pCMS cohort had more acute symptoms than the non-CMS group (a difference of two weeks on average). This suggests that patients with poor preoperative clinical status or those who are already decompensated are at a higher risk of developing pCMS.

Radiological predictors

The presentation of pCMS with characteristic delay postoperatively and a transient nature indicates mechanisms other than direct injury to the efferent cerebellar pathway (ECP) as contributing factors. The occurrence of brain stem/middle cerebellar peduncle edema or transient ischemia due to tumor handling, cerebellar retraction, focal vasospasm, and intraoperative hemodynamic fluctuations could be the possible reasons for transient functional derangement of cerebellar connections. The central location of the tumor was significantly more in the pCMS group. Most researchers have also reported it to be a significant risk factor for pCMS. These tumors remain closely associated with the brain stem and require significant manipulation for tumor exposure and dissection, as against tumors in the cerebellar hemisphere. Contrast enhancement on MRI was also found to be a significant risk factor. These tumors are of a high grade and vascular. Rapid moves during tumor decompression and desperate attempts for hemostasis in such tumors to restrict blood loss could injure surrounding structures. The association of a decrease in hematocrit and pCMS supports this finding.[26] The researchers found that brain stem compression on MRI had a similar distribution in both the cohorts. The extent of brain stem compression is seen as a better predictor of the risk of pCMS rather than mere compression. It is well recognized in the Rotterdam pCMS prediction model, in which the d-sagittal measurement of more than 0.58 cm is included for risk assessment.[27],[28] The researchers evaluated other radiological features such as the involvement of superior and middle cerebellar peduncle, tumor location, and brain stem invasion. We recommend the addition of contrast enhancement as an additional factor for risk prediction.

Operative factors and complication avoidance strategy

All the proposed theories of pCMS tend to incriminate injury to nearby eloquent structures and, thus, become the causative factors for the occurrence of PFS. Emergency surgery was found to be a significant risk factor for pCMS. As the principle of maximal safe resection was followed in all the surgeries, no significant difference was observed regarding the extent of resection between the two cohorts. There are conflicting results for the extent of tumor excision as a risk factor for pCMS.[8],[19],[25],[29] The authors indicated the occurrence of brain stem injury to achieve complete excision as the underlying cause. We adopted the following three surgical techniques to avoid brain stem injury: first, identification of the brain stem as the initial step before tumor decompression and the placement of a patty on the floor of the fourth ventricle as a marker; second, leaving a thin sliver of tumor attached to the brain stem if it originates from it; and third, not crossing the middle of the last part of the tumor attached to the brain stem. Part of the floor above and below was visualized, and the tumor was coagulated till it was within 1 to 2 mm of the line. We did not find any difference in the occurrence of pCMS in the transvermian and telo-velo-tonsillar approach. In most of our cases, only the lower part of the vermis was transacted for exposure. Most authors incriminated the transvermian approach as a risk of pCMS.[13] However, a few authors have reported a higher incidence of PFS in the telovelar approach also, suggesting it to be unrelated to vermian incision.[18] Undue retraction should be avoided. This can be aided by the use of an exoscope or by performing an endoscope-assisted tumor excision. With such evidence, aggressive resection rather than the approach seems to be the real risk factor. Postoperative wound complications or meningitis were not found to affect the occurrence of pCMS. Most authors reported similar findings.[9],[19]

No consensus exists on the specific management protocol of pCMS. Invariably, an early multidisciplinary approach with rehabilitative strategies and supportive care is indispensable while attempting to improve the cognitive, behavioral, social, academic, and motor outcomes of the affected child, thus facilitating a better quality of life. The occurrence of pCMS was found to adversely affect the survival of the patient.

Limitations

Our study has some limitations, the foremost being that it is a retrospective, single-center study. Subtle clinical signs would have been better analyzed had this study been a prospective one. Moreover, there were difficulties in assessing ataxia in bedridden patients (26 patients were bedridden) and mutism in tracheostomized patients (32 patients required tracheostomy). Nonetheless, the study provides a long-term follow-up of an unselected real-world population of patients managed at a single center.


   Conclusion Top


Aggressive tumor resection leading to iatrogenic injury to cerebellar circuitry is the most important risk factor for postoperative pCMS. Maximum safe resection with minimum collateral damage is the key to avoiding this complication. The central location of the tumor on radiology, contrast enhancement by the tumor, and emergency surgery are other major risk factors. Poor preoperative neurological status and histopathological diagnosis of medulloblastoma are also risk factors. Patients with pCMS have adverse survival outcomes.

Acknowledgment

No financial or material support was taken for this research. The content of this article has not been published/presented elsewhere. There is no potential conflict of interests.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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