Infantile brainstem tumors presenting with recurrent pneumonia and dysphagia: a report of two cases and literature review

Abstract

Background

Brainstem gliomas rarely occur during infancy and typically present without the classic neurological signs seen in older children. Instead, affected infants develop nonspecific symptoms, recurrent pneumonia, dysphagia, and feeding difficulties that closely mimic common pediatric conditions, leading to diagnostic delay. We report two infants with brainstem tumors whose initial presentations were attributed entirely to respiratory or gastrointestinal disease.

Case presentations

Case 1 was a 7-month-old girl with progressive dysphagia, recurrent respiratory infections, a weak cough, and motor regression. Cranial MRI identified a right medullary mass; diffusion-weighted imaging (DWI) demonstrated restricted diffusion consistent with high cellularity, supporting a high-grade glial pathology without tissue biopsy. Case 2 was an 8-month-old boy treated for months under presumptive diagnoses of gastroesophageal reflux and recurrent pneumonia. Cranial MRI revealed a large cystic-solid mass in the brainstem-cerebellar region with obstructive hydrocephalus. As no biopsy was obtained, the diagnosis rested on imaging: the mass was heterogeneous with extension into the cerebellar vermis and signal characteristics on T1, T2, and DWI consistent with a glial neoplasm. Loss of previously attained head control identified on parental history constituted developmental regression, the critical diagnostic red flag.

Conclusions

Brainstem tumors should be considered a rare differential diagnosis in infants with unexplained, refractory feeding difficulties and recurrent pneumonia, particularly when neurological abnormalities or motor regression are present, after more common etiologies have been excluded. Early MRI is essential. When tissue biopsy is not feasible, the radiological basis of the diagnosis must be explicitly acknowledged and serial imaging follow-up is mandatory.

Introduction

Brainstem gliomas account for approximately 10–20% of pediatric central nervous system (CNS) tumors, but they are exceedingly rare during infancy (age < 1 year) [1, 2]. Their rarity keeps clinical suspicion low, and the atypical presentations in this age group further confound recognition [3, 4]. Whereas older children typically manifest the classic triad of cranial nerve palsies, long-tract signs, and ataxia, infants present with vague systemic features such as irritability, feeding difficulty, and vomiting, symptoms that closely mimic common respiratory infections or gastrointestinal disorders [2, 4, 5].

Tumor infiltration of the medulla oblongata or pons disrupts the neural circuits governing swallowing and airway protection, causing neurogenic dysphagia and recurrent aspiration pneumonia [5–7]. Respiratory and feeding symptoms therefore dominate the clinical picture while the neurological origin goes unrecognized [7].

This report describes two infants in whom brainstem tumors masqueraded as refractory respiratory and gastrointestinal illness. We review the clinical and radiological features of infantile brainstem tumors, emphasizing the role of early neuroimaging, and discuss relevant molecular considerations in the context of radiologically diagnosed cases.

Case presentations

The clinical characteristics of both cases are summarized in Table 1.

Table 1.

Comparative clinical and imaging features of the two cases

Feature	Case 1 (Female)	Case 2 (Male)
Age of Symptom Onset	~ 6 months (severe symptoms)	4 months
Primary Presenting Symptoms	Recurrent pneumonia, severe cough, dysphagia (choking), rattling in throat	Dysphagia (choking), rattling in throat, recurrent pneumonia
Key Neurological Signs	Head tilt, asymmetric nasolabial folds, hypotonia, weak cry, motor regression	Poor head control, hypotonia, motor regression
Initial Misdiagnosis	Bronchitis, pneumonia	Gastroesophageal reflux, recurrent pneumonia
Key Ancillary Investigations	Chest CT: Pneumonia/atelectasis	VFSS: Severe dysphagia (PAS score 8); Gesell assessment: Global developmental delay
Cranial MRI Findings	Space-occupying lesion in the right medulla oblongata	Large cystic and solid brainstem-cerebellar mass with obstructive hydrocephalus
Final Outcome	Death after withdrawal of care	Transferred to another facility for high-risk surgery

Case 1

A 7-month-old girl was admitted with progressive respiratory distress, feeding difficulty, and motor regression. At one month of age she had been treated for neonatal infection; cranial ultrasound then showed mild widening of the left lateral ventricle. After discharge she experienced intermittent nasal congestion and occasional choking during feeds. A developmental assessment at six months was reported as normal.

Three weeks before admission she developed throat congestion and rattling sounds, followed by worsening cough, choking on milk, and vomiting. Examination revealed asymmetric nasolabial folds, rightward head tilt, neck hypotonia, inability to sit independently, and a weak cry, all indicating bulbar dysfunction.

A complete blood count showed leukocytosis, and a chest CT demonstrated pneumonia with atelectasis. Despite antibiotics, the infant deteriorated rapidly with high fever, labored breathing, rising inflammatory markers, requiring PICU admission for respiratory failure. Given the unexplained neurological signs, cranial MRI was performed, revealing a space-occupying lesion in the right medulla oblongata consistent with a glioma (Fig. 1A-C).

Fig. 1.

Neuroimaging findings for Case 1 and Case 2. Case 1 (A-C): Cranial MRI of a 7-month-old girl. A Axial T2-weighted and (B) axial T1-weighted images show a poorly defined space-occupying lesion in the right medulla oblongata with effacement of adjacent structures. C DWI demonstrates mildly hyperintense signal consistent with increased cellularity and a gliomatous process. Case 2 (D-F): Cranial MRI of an 8-month-old boy. D Axial T1-weighted and (E) axial T2-weighted images show a large complex cystic-solid mass in the brainstem with extension into the cerebellar vermis and left cerebellar hemisphere, markedly compressing the fourth ventricle and causing obstructive hydrocephalus. F DWI delineates the heterogeneous nature of the mass

The medullary tumor accounted for all her symptoms: neurogenic dysphagia causing chronic aspiration, recurrent pneumonia, and respiratory failure. As no tissue biopsy was obtained, the diagnosis of a brainstem glioma was established on a radiological basis. The MRI features supporting this conclusion included a poorly defined, infiltrative mass within the right medullary parenchyma on T1- and T2-weighted sequences; DWI demonstrated mildly hyperintense signal reflecting restricted diffusion consistent with increased cellularity, supporting a high-grade glial process. DWI evidence of restricted diffusion indicated high cellularity consistent with a malignant phenotype, and the prognosis was deemed extremely poor. After counseling, the family withdrew life-sustaining measures; the infant died shortly thereafter. No post-mortem examination was performed at the family’s request; histopathological confirmation was therefore not obtained.

Case 2

An 8-month-old boy was admitted with a four-month history of feeding difficulty, recurrent pneumonia, and motor regression. Symptoms began at four months of age with regurgitation, choking on feeds, and rattling throat sounds. He had been hospitalized for wheezing bronchopneumonia on multiple occasions and had three documented pneumonia episodes. An upper gastrointestinal series performed elsewhere suggested gastroesophageal reflux, a common misdiagnosis in such cases [4].

A critical feature of the history was developmental regression. Home videos confirmed robust head control at four months; by eight months he had lost this ability, exhibiting a profound lack of head control and inability to sit independently. This loss of a previously attained milestone constituted developmental regression, categorically different from, and more alarming than, simple developmental delay, and served as the key diagnostic red flag.

Aspiration pneumonia was diagnosed clinically based on predisposing factors (e.g., regurgitation, choking, dysphagia, developmental delay, and gastroesophageal reflux), poor response to antibiotics, characteristic CT lesions in the dorsal lower lobes, and bronchoscopic evidence of bilateral scattered secretions. Videofluoroscopic swallow study (VFSS) demonstrated a Penetration-Aspiration Scale score of 8, indicating silent aspiration without a cough reflex [8]. Gesell Developmental Schedules confirmed global delay, most pronounced in gross motor domains.

Cranial MRI revealed a large cystic-solid tumor in the brainstem-cerebellar region with severe obstructive hydrocephalus (Fig. 1D-F). As no tissue biopsy was obtained, the diagnosis of a brainstem glioma was established on a radiological basis. The supporting MRI features included a large heterogeneous cystic-solid mass centred in the brainstem extending into the cerebellar vermis, exerting marked compression on the fourth ventricle, with T1, T2, and DWI signal characteristics consistent with a glial neoplasm. Neurosurgical evaluation concluded the tumor was inoperable with an extremely poor prognosis. After full disclosure, the family transferred the boy to another centre for high-risk surgical intervention. Whether a definitive histopathological diagnosis was subsequently established at the receiving institution is unknown to the authors.

Discussion

Neurological disease masquerading as common illness

Both cases illustrate a well-recognized but underappreciated pitfall: infantile brainstem tumor presenting exclusively as respiratory or gastrointestinal illness. Case 1 was repeatedly treated for respiratory infection; Case 2 was managed for presumed gastroesophageal reflux and pneumonia. In each instance, attention focused on common peripheral causes while the central neurological etiology was missed.

This pattern is documented in the literature. Mahony et al. reported brainstem glioma presenting solely as gastroesophageal reflux [9]. Posterior fossa tumors have similarly manifested as failure to thrive, directing workup toward metabolic or gastrointestinal causes rather than neuroimaging [10]. Diencephalic tumors are another group of congenital CNS neoplasms prone to misdiagnosis, often presenting with failure to thrive and endocrine disturbances in the absence of overt neurological signs [11]. A summary of published cases with similar atypical presentations is provided in Table 2.

Table 2.

Summary of key findings from relevant literature

Author(s)	Year	Number/Type of Cases	Key Clinical Presentation	Main Conclusion/Implication
Mahony et al. [9]	1987	3 children	Atypical, late-onset gastroesophageal reflux	Brainstem gliomas can present solely with GI symptoms, potentially delaying diagnosis.
Conway et al. [12]	2016	1 case (21-month-old)	Failure to thrive (FTT), motor delay, stridor	Posterior fossa tumors should be in the differential for unexplained, severe FTT.
Gabel et al.[13]	2014	1 case (4-day-old neonate)	Hypotonia, feeding difficulty, respiratory abnormalities, silent aspiration	Brainstem tumors can be congenital and should be considered in neonates with unexplained neurological and feeding dysfunction.
Trezza et al.[14]	2022	Systematic review (127 cases)	Varied presentations of cervicomedullary gliomas (CMG)	Emphasizes the importance of early diagnosis and maximal safe resection for CMGs, which are often low-grade.

The most actionable diagnostic signal in both cases was therapeutic refractoriness. Failure to respond to appropriate treatment, antibiotics for pneumonia, anti-reflux therapy for presumed GER, indicates that the underlying diagnosis has been missed. Persistent or worsening symptoms despite standard management should prompt reassessment and active consideration of a central neurological etiology.

How brainstem tumors produce systemic symptoms

The systemic presentations in both cases reflect direct tumor disruption of neural networks in the brainstem. The medulla oblongata contains the nuclei of cranial nerves IX, X, and XII and the central pattern generators for swallowing and airway protection [15, 16]. Lesions in this region impair deglutition, abolish or diminish the protective cough reflex, and initiate a cascade of aspiration, pneumonia, malnutrition, immunocompromise, and respiratory failure, as observed in Case 1 [17].

In early infancy, this process is especially difficult to detect. The laryngeal chemoreflex, a primitive response involving apnea or swallowing rather than coughing, predominates over the laryngeal cough reflex, which has not yet fully matured [16]. Aspiration therefore occurs silently, manifesting only as recurrent fever, wheezing, or respiratory distress. This normal developmental physiology masks the neurological origin of symptoms, making early recognition dependent on a high index of suspicion.

Developmental regression as a diagnostic alarm

These cases highlight the critical importance of distinguishing developmental regression from developmental delay. Although sometimes used interchangeably, these terms denote fundamentally different clinical processes with distinct differential diagnoses.

In Case 2, the Gesell Developmental Schedules documented global developmental delay, a snapshot of current function relative to age norms. This label alone was misleading. The parental history revealed an active loss of a previously attained skill: head control. Such regression is a specific red flag for metabolic disorders, severe epileptic encephalopathies, or expanding CNS neoplasms. Clinicians must actively inquire about skill loss, however subtle, beyond simply reviewing standardized test scores. Any confirmed regression warrants urgent neuroimaging to exclude a space-occupying lesion.

Neuroimaging: role and limitations

In both cases, cranial MRI provided the definitive diagnosis after weeks to months of diagnostic delay attributable to pursuit of non-neurological investigations. MRI is the investigation of choice for brainstem lesions, offering superior soft-tissue contrast and multiplanar capability. These cases support a lower threshold for MRI in infants with unexplained, refractory feeding or respiratory symptoms, particularly when failure to thrive, hypotonia, or neurological regression is present.

Advanced sequences, DWI for cellularity, perfusion-weighted imaging, and MR spectroscopy, provide useful adjunctive information for lesion characterization. In Case 1, DWI restricted diffusion supported a high-grade glial pathology without tissue sampling. However, advanced neuroimaging does not substitute for histopathological diagnosis, which remains the gold standard. When biopsy is feasible and radiologically guided, tissue confirmation should be pursued. When surgery is not possible and the diagnosis is based solely on imaging, this must be clearly documented and serial imaging follow-up is mandatory.

Literature review: differential diagnosis and tumor classification

The differential diagnosis of a brainstem mass in an infant is broad and should not default to glioma. Important entities include atypical teratoid/rhabdoid tumor (ATRT), ependymoma, medulloblastoma with brainstem invasion, pilocytic astrocytoma, hemangioblastoma, and non-neoplastic conditions such as encephalitis, demyelinating disease, and vascular malformations. Age, clinical context, lesion morphology, and MRI signal characteristics are all essential in narrowing this differential.

Among brainstem gliomas, outcome varies markedly with grade and morphology. Focal, well-circumscribed tumors, most commonly pilocytic astrocytoma (WHO Grade I), may be amenable to surgical resection and potentially cured with complete excision [18]. Diffuse midline gliomas (DMGs), encompassing the historically termed diffuse intrinsic pontine glioma (DIPG), are infiltrative and unresectable, with a median survival of less than 18 months; radiotherapy offers palliation but not cure. Critically, DMG is uncommon in infants under one year of age; focal and low-grade subtypes predominate at this age. Clinicians should not presume a diffuse high-grade pathology based on age alone.

Molecular profiling has reshaped the classification of pediatric brainstem tumors [19]. The H3K27M alteration, identified in the majority of DMGs, is now a defining diagnostic criterion associated with epigenetic dysregulation and poor prognosis. Co-occurring alterations in ATRX and PDGFRA have been described, and these markers define targets under active investigation in clinical trials, including PDGFRA inhibitors and immunotherapeutic strategies. As neither case in this report underwent biopsy, molecular data were unavailable, underscoring the ongoing need for tissue acquisition wherever it can be safely performed.

Limitations

This report has two main limitations. First, as a two-case series, findings cannot be generalized to the broader population of infants with brainstem tumors. Second, histopathological confirmation was not obtained in either case, as biopsies were not performed owing to tumor location, procedural risk, and the families’ decisions. The diagnosis of glioma therefore rested on clinical features and neuroimaging. While radiological diagnosis is an accepted practice for inoperable diffuse brainstem lesions in which procedural risk outweighs diagnostic benefit, the absence of tissue confirmation remains an important limitation.

Conclusions and clinical implications

Infantile brainstem tumors may present insidiously, mimicking common respiratory or feeding disorders and causing substantial diagnostic delay. The key lesson from these cases is that motor developmental regression, the loss of a previously attained skill, is an urgent alarm requiring immediate neuroimaging to exclude a CNS space-occupying lesion.

The combination of refractory respiratory or feeding difficulties, failure to thrive, and neurological signs such as hypotonia or a weak cry constitutes a clinical triad that should prompt urgent neurological consultation and early MRI rather than continued peripheral investigation.

Early and accurate diagnosis, whether histopathological or, when unavoidable, radiological, is the essential first step toward appropriate management, timely family counseling, and, in the evolving era of molecularly guided therapy, access to targeted treatment.

Authors' contributions

Wei Wang was responsible for the primary draft and figure preparation, while Wei Wang and Yabin Wu collaboratively refined the text to its final form. All authors reviewed and approved the final manuscript.

Funding

No funding.

Data availability

The clinical imaging data analyzed during the current study are not publicly available due to patient privacy and ethical restriction.

Declarations

Ethics approval and consent to participate

The study was approved by the Ethics Committee of Maternal and Child Health Hospital of Hubei Province. Written informed consent was obtained from the participants’ parents.

Consent for publication

Written informed consent for publication was obtained from the parents of both patients.

Competing interests

The authors declare no competing interests.