Author(s): Elaine Tsao, MD, Jared Levin, MD
Originally published: April 20, 2023 Last updated: April 20, 2023
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Disease/ Disorder

Definition

Posterior fossa syndrome (PFS), or post-operative pediatric cerebellar mutism syndrome, is characterized by mutism or reduced speech and mood/affect change after cerebellar or fourth ventricular tumor resection with potential long-term effects.  Other features may include motor dysfunction (i.e., hypotonia, ataxia, and apraxia), brainstem dysfunction (i.e., long tract signs and cranial neuropathies), dysphagia, and neurocognitive changes.1,2

Etiology

PFS is related to central nervous system disruption, usually as a result of tumor removal in the posterior fossa.  However, PFS has also been described in cases of cerebellar stroke, acute disseminated encephalomyelitis, and acute cerebellitis.

Epidemiology including risk factors and primary prevention

Brain and other nervous system cancers rank as the second most common type of childhood cancer, with posterior fossa tumors representing approximately half of all pediatric brain tumors.  Reported incidence rate of PFS ranges widely from 7 to 50% in various study populations.  Potential risk factors for PFS including medulloblastoma histology, midline tumor involvement, and brainstem invasion.  Other risk factors have been proposed but shown inconsistent across various studies, including age at diagnosis, degree of tumor resection or residual tumor, post-operative infection, and edema in the middle and superior cerebellar peduncles. Though suggested associations exist, there is insufficient data on surgical techniques influencing the risk of PFS development.3

Patho-anatomy/physiology

The pathoanatomy in PFS is thought to involve a disruption of an outflow tract called the dentato-thalamo-cortical (DTC) pathway, resulting in cerebello-cerebral diaschisis.  The dentate nucleus, superior cerebellar peduncle, and mesencephalic tegmentum comprise the proximal portion of the DTC pathway, which extends through the contralateral red nucleus and thalamus to the contralateral cerebral cortex.  The exact pathophysiology of PFS is unclear, though direct surgical injury, parenchymal edema, direct axonal injury during surgical manipulation, and thermal injury by surgical instruments have been implicated in the causes for PFS.  Neuronal dysfunctions, such as alterations in neurotransmitter levels and trans-synaptic degeneration, have also been considered as potential causes.4

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Onset of PFS may be immediate or delayed after posterior fossa tumor resection, usually occurring in the first post-operative week.  Duration of PFS varies.  In a study of 450 children with medulloblastoma, 8% of the 107 patients who developed PFS reported overall symptoms lasting <1 week, whereas 49% reported symptom duration of 1-4 weeks, and 43% experienced >4 weeks of symptoms.5

Mutism usually resolves in PFS, but there is a substantial risk of long-term sequelae.  Twelve months after initial diagnosis, children may still demonstrate ataxia, speech and language difficulties, neurocognitive changes, ocular movement disorders, or dysphagia.5,6 Complete mutism in initial presentation of PSF may be a predictor of symptom severity and long-term sequelae.6

Specific or associated conditions and complications

N/A

Essentials of Assessment

History

Symptoms of PFS generally present within the first few days after tumor resection. Though mutism is the hallmark of PFS, reduced/altered speech production may instead be reported. In most patients, PFS symptoms are usually most severe on initial presentation but improve over time.1

Physical examination

Physical examinations can be highly useful in confirming the diagnosis of PFS and monitoring recovery. Initially, a physical examination may be limited to observation and basic interaction, depending on a child’s affect and willingness to participate. If possible, a full neurologic examination, including evaluation of cranial nerves, strength, sensation, reflexes, cerebellar function, speech and language, and cognition, should be obtained.  Balance, vestibular and ambulation testing are often useful for tracking progress and can be tailored to each patient.  Suggested tools include Rhomberg, timed single leg support, Modified Balance Error Scoring System (M-BESS), and tandem gait.  Examinations can also be tailored to functional tasks with which the patient or family reports difficulty.1,2,7

Functional assessment

Choice of functional assessment is often guided by a patient’s symptom presentation.  Swallow evaluations should be considered given the risk of dysphagia in PFS.1 An ophthalmologic examination may be recommended if visual deficits or abnormal eye movements are present. Neuropsychological testing is recommended when appropriate and available.1,7 

Laboratory studies

In general, laboratory studies are not necessary for guiding the diagnosis or management of PFS. Genetic, epigenetic, and transcriptomic analyses have led to identification of distinct subgroups of medulloblastoma based on molecular characteristics and clinical presentations.  Of the medulloblastoma molecular subgroups, Wingless (WNT), Group 3 and Group 4 (also called non-WNT/non-SHH) tumors have been shown to have a higher incidence of PFS compared to Sonic Hedgehog (SHH) in one study.8 Otherwise, metabolic testing and blood count are often monitored during tumor treatment.

Imaging

Imaging studies are rarely warranted for the diagnosis or management of PFS.  Initial onset of PFS symptoms may trigger an evaluation with a head CT or HASTE MRI to rule out hydrocephalus or bleeding at the surgical site.  T2-weighted signal abnormality involving the superior cerebellar peduncle on immediate and delayed post-operative MRI scans has been shown in children with PFS.9 A reduction in fractional anisotropy, a marker of axonal integrity, in bilateral cerebellar peduncles has also been seen on diffusion tensor imaging in patients with longer lasting symptoms of PFS.  Dynamic susceptibility contrast perfusion imaging has shown reduction in cerebral blood flow within the bilateral frontal regions in children with PFS, implicating cerebello-cerebral diaschisis secondary to a cerebellar insult.10 However, these studies rarely have clinical application.

Supplemental assessment tools

There have been several recent publications by the Posterior Fossa Society, composed of medical specialists with particular interest in PFS internationally, to help codify the assessment of PFS.1  In 2020, a diagnostic criteria for assessing patients with PFS was published based on survey findings of experts in PFS.2  However, there is yet to be additional literature assessing the efficacy of this tool.  As PFS appears to have a wide spectrum of both symptoms and severity with high variability in recovery, a severity scale was put forth in 2021.11 Further research will be needed to assess how severity attributed by this scale correlates with outcomes and functional recovery.

Early predictions of outcomes

Though there is limited supportive literature, it has been observed that severity of presentation onset may correlate with length and degree of recovery.5 Also, there is some limited evidence that higher preoperative language function may be protective of mutism.12

Environmental

Environmental factors associated with PFS are unknown at this time.

Social role and social support system

It cannot be understated that the presentation of PFS after tumor resection can be an upsetting and challenging experience for patients and their families.  Education and provision of support during these times should be considered a major aspect of management.  Socioeconomic factors may affect access to care for patients affected by PFS and should be addressed early to ensure access to treatment and long-term care. 

Professional issues

N/A

Rehabilitation Management and Treatments

Available or current treatment guidelines

Currently, there are no established rehabilitation guidelines for PFS.  However, a multidisciplinary approach to treatment of children affected by PFS is widely recommended.  A rehabilitation team may include physiatry, speech therapy, occupational therapy, physical therapy, neuropsychology, psychology, education specialist, social work, and therapeutic recreation specialist.  The rehabilitation team can address functional impairments of the affected child, as well as provide family-centered education and training for acute and potentially prolonged effects of PFS.  Pharmacologic interventions, such as bromocriptine, benzodiazepines, or modafinil for acute symptoms of PFS have been described in case reports; however, more research is needed to assess the efficacy and side effects of these medications.13,14  

At different disease stages

If possible, patients should be assessed pre-operatively and within the first 48 hours postoperatively on speech and language, functional mobility, and self-care abilities.  A brief neuropsychological assessment should also be considered, focusing on processing speed, attention, executive function and memory, mood and behavior, and adaptive skills.  An inpatient rehabilitation program may be indicated to address a child’s acute PFS symptoms.  Rehabilitative interventions and surveillance evaluations for speech and language deficits, neurocognitive and emotional challenges, and motor disturbances should be part of all stages of management of the syndrome, including long term.  A full neuropsychological assessment at 12 months post treatment and annually for the 5 years has been suggested.1 However, indication and frequency of assessments should be individualized based on a patient’s specific needs.

Coordination of care

The care of a patient affected by PFS requires a multidisciplinary team approach, both in the acute and long-term settings. In addition to the Rehabilitation team as described above, collaboration with other specialists in Neuro-oncology, Radiation Oncology, Neurology, and/or Neurosurgery is paramount in ensuring comprehensive care for patients affected by PFS.

Patient & family education

Education and training of patients and families affected by PFS should be initiated soon after diagnosis.  Anticipatory guidance of the potential prolonged effects of PFS may help families with formulation of behavioral plans and adaptive skills support and hopefully ease anxiety of parents and caregivers associated with the diagnosis.

Measurement of treatment outcomes

The Post-operative Pediatric Cerebellar Mutism Syndrome Scale is a proposed tool that may aid in early diagnosis and evaluation of symptom severity.  The scale offers a method to stratify duration and severity of four major symptoms of PFS, specifically mutism, emotional lability, hypotonia, and dysphagia.  Symptom duration and severity are each measured on a 3-point scale and contribute to an “Overall Severity Scale” of mild, moderate, or severe.  However, the authors acknowledge the need for standardization of rating scales and of symptom severity definitions.11

The Pediatric Scale for the Assessment and Rating of Ataxia (SARA) or Brief Ataxia Rating Scale (BARS) enables quantification of ataxia severity.15,16 Development of fine and gross motor control and coordination may be measured by the Bruininks-Oseretsky test of Motor Proficiency Second Edition (BOT-2).17 The Pediatric Evaluation of Disability Inventory (PEDI) is a measure of functional skills and participation for children.18

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Consensus of terminology describing this syndrome has yet been consistent, though posterior fossa syndrome and post-operative pediatric cerebellar mutism syndrome are the two more commonly used terminologies in the literature in recent years.  Recognition of risk factors in patients with posterior fossa tumor and utilization of available diagnostic criteria may aid in early diagnosis of PFS.  Education and training of affected patients and families should include management of acute symptoms as well as potential long-term motor, behavioral, and cognitive challenges.  Rehabilitative interventions and functional and participation measures may support and monitor children’s recovery through various stages of PFS.  Additional research is indicated for pharmacological interventions in PFS treatment.

Cutting Edge/ Emerging and Unique Concepts and Practice

In recent years, several studies have shown that surgical technique may alter outcomes. Studies have shown that preferring a telovelar over transvermian approach to tumor resection and minimization of heavy retraction during surgery may offer a reduction in PFS occurrence, though additional studies on the influence of surgical techniques on PFS risk are warranted.19,20

As detailed above, much interest has been placed on the use of pharmaceutical agents for improving recovery.13,14 These medications are proposed to work by modifying cerebral neurotransmitters, interestingly mostly within dopaminergic pathways. These studies are all limited in study design, scope, and cohort size but may suggest promising areas of future research.

Gaps in the Evidence-Based Knowledge

There are many greatly needed avenues of further study of PFS.  Evaluation and consensus of recently established diagnostic criteria and severity grading, short and long-term assessment of outcomes, and the prospective study of current interventions, including novel treatment modalities and therapy/rehabilitation, would help guide standardization of treatment.

References

  1. Gudrunardottir T, Morgan AT, Lux AL, Walker DA, Walsh KS, Wells EM, Wisoff JH, Juhler M, Schmahmann JD, Keating RF, Catsman-Berrevoets C; Iceland Delphi Group. Consensus paper on post-operative pediatric cerebellar mutism syndrome: the Iceland Delphi results. Childs Nerv Syst. 2016 Jul;32(7):1195-203. doi: 10.1007/s00381-016-3093-3. Epub 2016 May 3. PMID: 27142103.
  2. Wickenhauser ME, Khan RB, Raches D, Ashford JM, Robinson GW, Russell KM, Conklin HM. Characterizing Posterior Fossa Syndrome: A Survey of Experts. Pediatr Neurol. 2020 Mar;104:19-22. doi: 10.1016/j.pediatrneurol.2019.11.007. Epub 2019 Nov 29. PMID: 31911026; PMCID: PMC7010537.
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  4. Avula S, Mallucci C, Kumar R, Pizer B. Posterior fossa syndrome following brain tumour resection: review of pathophysiology and a new hypothesis on its pathogenesis. Childs Nerv Syst. 2015 Oct;31(10):1859-67. doi: 10.1007/s00381-015-2797-0. Epub 2015 Sep 9. PMID: 26351235.
  5. Robertson PL, Muraszko KM, Holmes EJ, Sposto R, Packer RJ, Gajjar A, Dias MS, Allen JC; Children’s Oncology Group. Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children’s Oncology Group. J Neurosurg. 2006 Dec;105(6 Suppl):444-51. doi: 10.3171/ped.2006.105.6.444. PMID: 17184075.
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  7. Paquier, Philippe F., et al. “Post-Operative Cerebellar Mutism Syndrome: Rehabilitation Issues.” Child’s Nervous System, vol. 36, no. 6, June 2020, pp. 1215–1222.
  8. Jabarkheel, Rashad, et al. “Molecular Correlates of Cerebellar Mutism Syndrome in Medulloblastoma.” Neuro-Oncology, vol. 22, no. 2, Feb. 2020, pp. 290–297.
  9. Toescu SM, Hettige S, Phipps K, Smith RJP, Haffenden V, Clark C, Hayward R, Mankad K, Aquilina K. Post-operative paediatric cerebellar mutism syndrome: time to move beyond structural MRI. Childs Nerv Syst. 2018 Nov;34(11):2249-2257. doi: 10.1007/s00381-018-3867-x. Epub 2018 Jun 20. PMID: 29926177; PMCID: PMC6208673.
  10. Miller NG, Reddick WE, Kocak M, Glass JO, Lobel U, Morris B, Gajjar A, Patay Z (2010) Cerebellocerebral diaschisis is the likely mechanism of postsurgical posterior fossa syndrome in pediatric patients with midline cerebellar tumors. AJNR Am J Neuroradiol 31:288–294. https://doi.org/10.3174/ajnr.A1821
  11. Ricci FS, D’Alessandro R, Somà A, Salvalaggio A, Rossi F, Rampone S, Gamberini G, Davico C, Peretta P, Cacciacarne M, Gaglini P, Pacca P, Pilloni G, Ragazzi P, Bertin D, Vallero SG, Fagioli F, Vitiello B. Development and application of a diagnostic and severity scale to grade post-operative pediatric cerebellar mutism syndrome. Eur J Pediatr. 2022 Mar;181(3):941-950. doi: 10.1007/s00431-021-04290-x. Epub 2021 Oct 14. PMID: 34651204; PMCID: PMC8897365.
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  15. Lawerman TF, Brandsma R, Burger H, Burgerhof JGM, Sival DA; the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society. Age-related reference values for the pediatric Scale for Assessment and Rating of Ataxia: a multicentre study. Dev Med Child Neurol. 2017 Oct;59(10):1077-1082. doi: 10.1111/dmcn.13507. Epub 2017 Aug 17. PMID: 28815574.
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  20. Renne B, Radic J, Agrawal D, Albrecht B, Bonfield CM, Cohrs G, Davis T, Gupta A, Hebb ALO, Lamberti-Pasculli M, Knerlich-Lukoschus F, Lindsay S, McNeely PD, Pillai S, Rai HIS, Sborov KD, Vitali A, Walling S, Woerdeman P, Suryaningtyas W, Cochrane D, Singhal A, Steinbok P. Cerebellar mutism after posterior fossa tumor resection in children: a multicenter international retrospective study to determine possible modifiable factors. Childs Nerv Syst. 2020 Jun;36(6):1159-1169. doi: 10.1007/s00381-019-04058-7. Epub 2019 Jan 18. PMID: 30659354.

Author Disclosure

Elaine Tsao, MD
Nothing to Disclose

Jared Levin, MD
Nothing to Disclose