Review
Posterior fossa tumors and their impact on sleep and ventilatory control: A clinical perspective

https://doi.org/10.1016/j.resp.2013.05.027Get rights and content

Highlights

Abstract

The cerebellum, classically viewed as a motor structure of the brain, may play a role in respiration. Brainstem dysfunction has been implicated in sleep disordered breathing (SDB), but apnea after surgery of brain tumors in the posterior fossa, not involving the brainstem has been reported. We report four cases with posterior fossa tumors without brainstem invasion who suffered SDB after surgery diagnosed by polysomnography (PSG). Advanced MRI techniques with DTI were used to find correlations with SDB. Abnormal signals in the superior, middle and inferior cerebellar peduncles were seen in these patients with the most severe changes in the inferior peduncle. SDB may be under diagnosed in the setting of posterior fossa tumors without brainstem involvement. Damage to the cerebellar peduncles, especially the inferior cerebellar peduncle, without brainstem involvement, can cause significant disruption of respiration.

Introduction

The cerebellum is classically viewed as one of the primary structures involved in motor coordination and pattern generation (Stoodley et al., 2012). Since breathing is a repetitive cyclic motor act, injury to the cerebellum may lead to alterations in ventilatory muscle control (Lu et al., 2013). Affected muscles include the diaphragm and those in the thoracic cage, but also those involved in keeping the upper airway patent, particularly during sleep (Chen et al., 2005). In addition to the motor act of breathing and maintenance of dynamic airway patency, emerging data suggest that the cerebellum has a role in central respiratory control, modulating those functions primarily housed in brainstem structures (Feldman and Del Negro, 2006, Lu et al., 2013, Smith et al., 2009).

Naturally occurring models that can be utilized to investigate the role of the cerebellum in respiratory control are congenital posterior fossa malformations and neoplasms, many of which affect pediatric populations. Brain tumors are the second most common tumor of childhood, and tumors of the posterior fossa (cerebellum and brainstem) are responsible for over 25% of cancer deaths in children (Smith et al., 2010). Clinically observed complications of surgical resection of these tumors include motor, cognitive, and ocular morbidities (Cochrane et al., 1994). Respiratory disturbances, including apnea and sleep disordered breathing (SDB), have been canonically associated with brainstem dysfunction (from primary tumor burden or post-operative complications) (Ito et al., 1996, Manning and Leiter, 2000, Osanai et al., 1994, Valente et al., 1993), but SDB is not as systematically described in those with abnormalities limited to the cerebellum. Illustrative reports of those with SDB subsequent to posterior fossa surgery and associated with primary cerebellar abnormalities lend strength to the cerebellum's role in respiratory control (Adelman et al., 1984, Chokroverty et al., 1984, Cochrane et al., 1994, Losurdo et al., 2013, Wolfe et al., 2010). Outside of the clinical realm, animal models implicating deep cerebellar nuclei, specifically the fastigial nucleus and outflow tracts in respiratory reflexes, also suggest a role of disordered coordinated central respiratory control in those with cerebellar injury (Xu and Frazier, 1997, Xu and Frazier, 2002). However, the gap connecting a cerebellar injury and subsequent clinically diagnosable SDB is apparent when current literature is reviewed.

Advanced magnetic resonance imaging (MRI) techniques may provide critical translational information linking neuroanatomic injury to clinical sequelae. These analytic techniques, which can be applied to routine MRI, help provide a translational bridge between “real-life” post-operative sequelae including SDB and neuroanatomic deficits. Thus, we present four pediatric cases with cerebellar tumors (without known brainstem involvement) who underwent surgical resection, and were later diagnosed with SDB after formal polysomnography (PSG). MRI correlates of clinical findings are reviewed. This clinical and translational approach to reviewing the impact of posterior fossa tumors on respiratory control will hopefully complement other approaches to the “Challenges of Ventilatory Control” discussed in this issue.

Section snippets

Subject population

This study was conducted at Seattle Children's Hospital after obtaining standard IRB approval for retrospective study review. We reviewed medical records of all cases between the ages of 2–21 with the primary diagnosis of posterior fossa neoplasms from January 1, 2000, to November 30, 2012. Those subjects who underwent both surgical resection and PSG were identified. Information collected included age, gender, clinical presentation, operative findings, and results of PSG. Those cases with

Results

Of 13 cases identified who had posterior fossa tumors and PSG, five cases were excluded for known brainstem involvement and one patient was excluded due to lack of operative resection (he was conservatively managed with surveillance imaging). Of the remaining seven cases, only four had adequate MRI images for analysis. One subject did not have follow-up imaging after his initial surgery due to cochlear implant placement, and two were excluded for poor quality DTI acquisition. Thus, we present 4

Summary

We present 4 pediatric cases with common posterior fossa tumors, without known brainstem involvement, who had evidence of severe SDB best characterized by a mixed disorder of central respiratory control and upper airway patency. As predicted, all cases had significant differences compared to age matched controls on MRI using FA measurements in several regions. At this preliminary stage, we did not find overt correlations between DTI values and severity of SDB, but are limited by small sample

Conclusion

The review of the literature and our series provide more evidence for the cerebellum's involvement in respiratory control. Involvement of the cerebellar peduncles, especially the inferior cerebellar peduncle, was associated with sleep disordered breathing, in the absence of brainstem invasion or injury.

References (80)

  • S.M. Smith et al.

    Advances in functional and structural MR image analysis and implementation as FSL

    NeuroImage

    (2004)
  • C.J. Stoodley et al.

    Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study

    NeuroImage

    (2012)
  • S. Swaminathan et al.

    Abnormal control of ventilation in adolescents with myelodysplasia

    Journal of Pediatrics

    (1989)
  • S.P. Tomlinson et al.

    Brain stimulation studies of non-motor cerebellar function: A systematic review

    Neuroscience and Biobehavioral Reviews

    (2013)
  • S. Valente et al.

    An uncommon case of brainstem tumor with selective involvement of the respiratory centers

    Chest

    (1993)
  • W.A. Whitelaw et al.

    Occlusion pressure as a measure of respiratory center output in conscious man

    Respiration Physiology

    (1975)
  • J.L. Williams et al.

    Stimulating fastigial nucleus alters central mechanisms regulating phrenic activity

    Respiration Physiology

    (1989)
  • M. Witmans et al.

    Update on pediatric sleep-disordered breathing

    Pediatric clinics of North America

    (2011)
  • S. Adelman et al.

    Obstructive sleep apnea in association with posterior fossa neurologic disease

    Archives Of Neurology

    (1984)
  • J.C.J. Arcaya et al.

    Arnold-Chiari malformation associated with sleep apnea and central dysregulation of arterial pressure

    Acta Neurologica Scandinavica

    (1993)
  • D.W. Beebe

    Neurobehavioral morbidity associated with disordered breathing during sleep in children: a comprehensive review

    Sleep

    (2006)
  • M. Bogaerts et al.

    Physiology of the mouth and pharynx, Waldeyer's ring, taste and smell

    B-Ent

    (2012)
  • R.V. Botelho et al.

    A prospective controlled study of sleep respiratory events in patients with craniovertebral junction malformation

    Journal of Neurosurgery

    (2003)
  • R.V. Botelho et al.

    The effects of posterior fossa decompressive surgery in adult patients with Chiari malformation and sleep apnea

    Journal of Neurosurgery

    (2010)
  • M.L. Chen et al.

    Disordered respiratory control in children with partial cerebellar resections

    Pediatric Pulmonology

    (2005)
  • S. Chokroverty et al.

    Autonomic dysfunction and sleep apnea in olivopontocerebellar degeneration

    Archives of Neurology

    (1984)
  • D.D. Cochrane et al.

    The surgical and natural morbidity of aggressive resection for posterior fossa tumors in childhood

    Pediatric Neurosurgery

    (1994)
  • N.J. Douglas et al.

    Respiration during sleep in normal man

    Thorax

    (1982)
  • J.L. Feldman et al.

    Looking for inspiration: new perspectives on respiratory rhythm

    Nature Reviews. Neuroscience

    (2006)
  • F. Gagnadoux et al.

    Sleep-disordered breathing in patients with Chiari malformation: improvement after surgery

    Neurology

    (2006)
  • A. Gajjar et al.

    Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma

    Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology

    (2004)
  • D. Gozal et al.

    Peripheral chemoreceptor function in children with the congenital central hypoventilation syndrome

    Journal of Applied Physiology

    (1993)
  • G. Greenough et al.

    Obstructive sleep apnea syndrome in a patient with medulloblastoma

    Neuro-oncology

    (1999)
  • R.M. Harper

    The cerebellum and respiratory control

    Cerebellum

    (2002)
  • R.M. Harper et al.

    Functional magnetic resonance imaging during hypoxia challenges in Congenital Central Hypoventilation Syndrome (CCHS) reveals lateralized neural responses

    Society for Neuroscience Abstract

    (1999)
  • L.L. Hedemark et al.

    Ventilatory and heart rate responses to hypoxia and hypercapnia during sleep in adults

    Journal of Applied Physiology

    (1982)
  • Ianelli, V., 2006. http://pediatrics.about.com/cs/sleep/a/sleep_apnea.htm, updated 9/22/2006 (accessed...
  • c. Iber et al.

    The AASM manual for the scoring of sleep and associate events. Rules, terminology and technical specifications

    (2007)
  • S.T. Kuna et al.

    Hypercarbic periodic breathing during sleep in a child with a central nervous system tumor

    American Review of Respiratory Disease

    (1990)
  • J.H. Lois et al.

    Neural circuits controlling diaphragm function in the cat revealed by transneuronal tracing

    Journal of Applied Physiology

    (2009)
  • Cited by (15)

    • Anesthetic Management of Patients Undergoing Open Suboccipital Surgery

      2021, Anesthesiology Clinics
      Citation Excerpt :

      Pulmonary status and airway should be examined closely preoperatively. Posterior fossa tumors are commonly associated with disordered respiratory patterns owing to the involvement of the respiratory centers in the medulla oblongata and possibly the cerebellum.14 Pathology of the glossopharyngeal and vagal nerves may lead to dysphagia, impaired gag reflex, and glottic insufficiency that can predispose patients to aspiration events.

    • Functional Convergence of Autonomic and Sensorimotor Processing in the Lateral Cerebellum

      2020, Cell Reports
      Citation Excerpt :

      Accordingly, rare, but dramatic, cases of sudden infant death syndrome (SIDS) have been attributed to acute respiratory arrest in relation to inferior olivary hypoplasia or delayed maturation of the cerebellar cortex (Cortez and Kinney, 1996; Cruz-Sánchez et al., 1997; Harper, 2000; Katsetos et al., 2014; Lavezzi et al., 2013), while cerebellar dysfunction has been observed in congenital central hypoventilation syndrome, which entails the inability to react to dyspnea (Harper et al., 2005, 2015; Kumar et al., 2008). Likewise, patients with a cerebellar tumor or hemorrhage frequently need mechanical ventilation after neurosurgery, often showing a relatively slow recovery of respiration (Arnone et al., 2017; Chen et al., 2005; Gewaltig and Diesmann, 2007; Lee et al., 2013; Tsitsopoulos et al., 2012). Moreover, most cerebellar ataxia patients have trouble modulating their breathing during exercise (De Joanna et al., 2008; Deger et al., 1999; Ebert et al., 1995).

    • Epidemiology and short-term surgical outcomes of children presenting with cerebellar tumors

      2018, Clinical Neurology and Neurosurgery
      Citation Excerpt :

      It is possible that higher income families have a better access to healthcare and represent higher numbers in an inpatient database. It is commonly known that posterior fossa tumors can involve the cerebellar peduncles, compress brainstem nuclei or induce hydrocephalus which can lead to respiratory arrest [20]. As demonstrated in our study, postoperative requirement for respiratory support is not uncommon after posterior fossa surgery.

    • Sleep-disordered breathing in neurologic conditions

      2014, Clinics in Chest Medicine
      Citation Excerpt :

      Posterior fossa tumors have also been associated with SDB.71 SDB can occur with involvement of the cerebellar peduncles, even in the absence of brainstem involvement.71 Acquired central alveolar hypoventilation (CAH) (previously known as Ondine curse) is a condition characterized by loss of automatic breathing during sleep.

    • ECG derived Cheyne–Stokes respiration and periodic breathing are associated with cardiorespiratory arrest in intensive care unit patients

      2019, Heart and Lung
      Citation Excerpt :

      There was also a trend showing that patients with a neurological/neurosurgical discharge diagnosis had more CSRPB per hour than patients with a medical-surgical discharge diagnosis; which may be the result of injury to the pons44 or cerebellum45,46 and impact the breathing center. Consequently, this study supports findings that abnormal breathing patterns, namely CSRPB, are found in ICU patients with a neurological discharge diagnosis.44–49 Lastly, overall adverse outcomes were evenly distributed among patients with cardiovascular, neurological/neurosurgical and medical-surgical diagnosis, suggesting that the higher rate of CSRPB is associated with adverse events, regardless of discharge diagnosis disposition.

    View all citing articles on Scopus

    This paper is part of a special issue entitled “Clinical Challenges to Ventilatory Control”, guest-edited by Dr. Gordon Mitchell, Dr. Jan-Marino Ramirez, Dr. Tracy Baker-Herman and Dr. Dr. David Paydarfar.

    View full text