Historically, research and management of CMS in children were limited by ambiguity introduced by inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty surrounding risk factors and etiology. Consequently, the significant variance in range of incidence in the literature is likely secondary to the lack of consensus in definition of CMS. The largest prospective study to date incorporating patients from 2 large cooperative group medulloblastoma treatment trials (CCG9931 and POG A9961) surveyed 450 children undergoing posterior fossa resection of medulloblastoma. These authors defined PFS as mutism, ataxia, hypotonia, irritability or emotional lability and observed CM to occur in 24% (107 children developing CM) of their cohort. Since, an Icelandic group published their Delphi consensus results for the definition of CMS (synonym: PFS) to be “characterized by delayed onset mutism/reduced speech and emotional lability after cerebellar or 4th ventricular tumor surgery in children. Additional common features include hypotonia and oropharyngeal dysfunction/dysphagia. It may be frequently accompanied by cerebellar motor syndrome, cerebellar cognitive affective syndrome and brainstem dysfunction including long tract signs and cranial neuropathies. The mutism is always transient and language my not return to normal, and other cognitive, affective and motor function often persist”.
Many studies, though in small cohorts, have identified risk factors for CM. And from these, many theories to explain the postoperative paucity of speech have been postulated including: bilateral destruction or edema of the cerebellar nuclei, vasospasm, post-operative meningitis, unrecognized hydrocephalus, and psychiatric origin. Risk factors most commonly associated with development of CMS include midline tumor location, surgical approach[3, 25, 41–46], brain stem invasion or compression[8, 14, 47–49], tumor size[3, 26, 38], diagnosis of medulloblastoma[3, 21, 50, 50–53] and specific tumor subtype[20, 50], younger age at diagnosis[22, 23] and preoperative language impairment, lower volume centers, male gender[23, 54], left handedness[38, 55]. Other authors failed to find an association between age, ventricular size[19, 22], extent of resection[8, 19, 22], tumor size, handedness35, surgical approach, location in the cerebellar hemisphere, ultrasonic aspirator use, low volume center nor second surgery. Furthermore, advances in imaging techniques have shed some light onto the anatomical substrate(s) of CMS with a proposed etiology of CMS which includes disruption of the cerebellar outflow tracts (i.e., dentothalamocortical tract)[6, 35, 37, 57], with changes radiologically identified in the supplementary motor area[24, 36, 58–61], the cerebellar nuclei (i.e., fastigial nucleus)[36, 57], periaqueductal gray matter, and their efferent projections through the superior cerebellar peduncle[4, 37, 48].
Despite many of these observations, there is little consensus on the preventative steps that can be taken to minimize the risk of CM occurrence. Armed with the knowledge that brainstem infiltration, and disruption of adjacent structures such as the superior cerebellar peduncle andperiaqueductal gray matter, we hypothesized that there are intraoperative physiological prompts to notify a neurosurgeon of operative maneuvers that may place the child at an increased risk of developing CM. Nearby structures such as locus caeruleus, a neuromodulator of norepinephrine in the brain, if disrupted may provide feedback to neuroanaesthetists and neurosurgeons with respect to limits of brainstem manipulation in efforts to dissect or resect the tumor lesion. In this multicenter cohort, we identified an association with abrupt changes, defined as ≥ 20% from baseline, in heart rate but not blood pressure to be significantly associated with the development of post-operative CM. These cues should be carefully considered and integrated into an active revision to the intraoperative microsurgical plan.
Contemporary treatment for CMS remains supportive as attempts to provide adjuncts such as fluoxetine, zolpidem, bromocriptine[65, 66], and midazolam have in a small case reports and series shown efficacy but remain off-licence in their use. Recently, it has been observed that despite multidisciplinary interventions, the functional outcome in these children is less favorable than previously described. Resolution of symptoms occurred at a median of 16 days after which a plateau in improvement has been described. The resolution of symptoms is also heterogeneous with description of children experiencing complete CM (also known as posterior fossa syndrome 1) in whom 25% of children never regain independent ambulation. Objectively, Cámara and colleagues found gender matched children who developed CMS after a posterior fossa tumor resection performed less well in neuropsychological assessment[47, 69] exacerbated by the provision of adjuvant therapy
The current study has certain methodological strengths compared to the published literature The study population is vulnerable, and CM is a rare event. The multicentre nature of the study provided larger sample increasing study power. To the best of our knowledge, it is largest study to date. There is also increased generalisability of the findings to the wider populations. There are however inherent limitations to the study design. Firstly, it is a retrospective design prone to data inaccuracy and missing data. We used complete set analysis to avoid inaccurate imputation of missing data such as undetermined or not mentioned in intraoperative decisions. Secondly, the sample size is likely small and the stuyd is underpowered to draw definite conclusion from the findings. The findings should be interpreted with caution.
Due to the treatment-refractory nature of CM and the devastating sequelae for children and families experiencing the surgical complication, understanding the factors associated with its post-operative development is paramount. High grade lesions with infiltration into deep structures, finding adherence to the floor of the fourth ventricle and abrupt changes in vital signs intraoperatively should alert the surgeon to pause and re-review the operative strategy to prevent the devastating sequalae of CMS.