ReviewPosterior fossa tumors and their impact on sleep and ventilatory control: A clinical perspective☆
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)
- et al.
DTI fiber tracking to differentiate demyelinating diseases from diffuse brain stem glioma
NeuroImage
(2010) - et al.
Arnold-Chiari malformation type I and sleep-disordered breathing: an uncommon manifestation of an important pediatric problem
Journal of Pediatric Health Care: Official Publication of National Association of Pediatric Nurse Associates & Practitioners
(2003) - et al.
Effects of lesions of the caudal cerebellar vermis on cardiovascular regulation in awake cats
Brain Research
(2002) - et al.
Pediatric brain stem gliomas with the predominant symptom of sleep apnea
International Journal of Pediatric Otorhinolaryngology
(1996) - et al.
Drive and timing components of ventilation
Chest
(1976) - et al.
Role of cerebellum in fine speech control in childhood: persistent dysarthria after surgical treatment for posterior fossa tumour
Brain and Language
(2011) - et al.
Laryngeal abductor activity during sleep
Chest
(1978) - et al.
The human tongue during sleep: electromyographic activity of the genioglossus muscle
Experimental Neurology
(1976) - et al.
Respiratory muscle function and the use of respiratory muscle electromyography in the evaluation of respiratory regulation
Chest
(1976) - et al.
Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data
NeuroImage
(2006)
Advances in functional and structural MR image analysis and implementation as FSL
NeuroImage
Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study
NeuroImage
Abnormal control of ventilation in adolescents with myelodysplasia
Journal of Pediatrics
Brain stimulation studies of non-motor cerebellar function: A systematic review
Neuroscience and Biobehavioral Reviews
An uncommon case of brainstem tumor with selective involvement of the respiratory centers
Chest
Occlusion pressure as a measure of respiratory center output in conscious man
Respiration Physiology
Stimulating fastigial nucleus alters central mechanisms regulating phrenic activity
Respiration Physiology
Update on pediatric sleep-disordered breathing
Pediatric clinics of North America
Obstructive sleep apnea in association with posterior fossa neurologic disease
Archives Of Neurology
Arnold-Chiari malformation associated with sleep apnea and central dysregulation of arterial pressure
Acta Neurologica Scandinavica
Neurobehavioral morbidity associated with disordered breathing during sleep in children: a comprehensive review
Sleep
Physiology of the mouth and pharynx, Waldeyer's ring, taste and smell
B-Ent
A prospective controlled study of sleep respiratory events in patients with craniovertebral junction malformation
Journal of Neurosurgery
The effects of posterior fossa decompressive surgery in adult patients with Chiari malformation and sleep apnea
Journal of Neurosurgery
Disordered respiratory control in children with partial cerebellar resections
Pediatric Pulmonology
Autonomic dysfunction and sleep apnea in olivopontocerebellar degeneration
Archives of Neurology
The surgical and natural morbidity of aggressive resection for posterior fossa tumors in childhood
Pediatric Neurosurgery
Respiration during sleep in normal man
Thorax
Looking for inspiration: new perspectives on respiratory rhythm
Nature Reviews. Neuroscience
Sleep-disordered breathing in patients with Chiari malformation: improvement after surgery
Neurology
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
Peripheral chemoreceptor function in children with the congenital central hypoventilation syndrome
Journal of Applied Physiology
Obstructive sleep apnea syndrome in a patient with medulloblastoma
Neuro-oncology
The cerebellum and respiratory control
Cerebellum
Functional magnetic resonance imaging during hypoxia challenges in Congenital Central Hypoventilation Syndrome (CCHS) reveals lateralized neural responses
Society for Neuroscience Abstract
Ventilatory and heart rate responses to hypoxia and hypercapnia during sleep in adults
Journal of Applied Physiology
The AASM manual for the scoring of sleep and associate events. Rules, terminology and technical specifications
Hypercarbic periodic breathing during sleep in a child with a central nervous system tumor
American Review of Respiratory Disease
Neural circuits controlling diaphragm function in the cat revealed by transneuronal tracing
Journal of Applied Physiology
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2018, Clinical Neurology and NeurosurgeryCitation 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.
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2014, Clinics in Chest MedicineCitation 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.
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2019, Heart and LungCitation 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.
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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.