Adult-onset medulloblastoma presenting in the setting of untreated spina bifida: illustrative case

Abstract

BACKGROUND

Adult-onset medulloblastoma in the setting of untreated spina bifida and Chiari type II malformation is exceptionally rare and has not been previously reported. The relationship between medulloblastoma and spina bifida remains poorly understood.

OBSERVATIONS

An adult male with untreated spina bifida presented to the emergency department with headaches and was found to have a left cerebellar medulloblastoma and obstructive hydrocephalus. He underwent preoperative catheter-based angiography, which revealed inferior displacement of the venous sinuses. A suboccipital craniotomy for resection was performed, followed by radiation therapy and chemotherapy. Follow-up imaging at 3 months postoperatively demonstrated no evidence of residual tumor.

LESSONS

Given the abnormal posterior fossa development in patients with spina bifida and Chiari type II malformation, posterior fossa surgery requires a thorough understanding of the patient’s venous sinus anatomy to achieve a maximal safe resection and prevent venous sinus injury or thrombosis. While the role of CSF diversion in adults with untreated spina bifida is unknown, the authors opted to proceed with postresection ventriculoperitoneal shunt placement given the persistent mass effect on the fourth ventricle from peritumoral swelling. Additional studies are needed to establish a molecular and/or genetic relationship between medulloblastoma and spinal dysraphism.

https://thejns.org/doi/10.3171/CASE24897

Spina bifida is one of the most prevalent congenital disorders affecting the central nervous system, often leading to lifelong disabilities.¹ Myelomeningoceles are the most severe form, characterized by the spinal cord and nerve roots protruding into a sac filled with CSF.¹ Spina bifida affects approximately 3.65 in 10,000 live births in the United States.² Advances in managing complications such as hydrocephalus and neurogenic bladder have greatly improved survival rates. Currently, about 85% of children diagnosed with spina bifida survive into adulthood, and adults now make up 67% of the spina bifida population in the United States.^3–6 This growing adult population has led to a shift in clinical care, as adults present with unique challenges compared to pediatric patients.

Population studies have demonstrated up to a threefold increase in cancer incidence in patients born with spina bifida.⁷ This increased risk includes disease-specific malignancies such as lower urinary tract cancers, radiation-induced malignancies from repetitive radiation exposure for imaging acquisition, and age-appropriate malignancies such as colon and breast cancer given that many spina bifida patients are surviving into adulthood.^7–16

Medulloblastoma is a malignant brain tumor that primarily affects the cerebellum and accounts for up to 20% of pediatric CNS tumors.^17–20 In North America and Europe, the incidence of medulloblastoma ranges from 3.8 to 6.9 cases per million children.¹⁸,^20–22 In adults, medulloblastoma is significantly less common with unique clinical and genetic variations in comparison with pediatric cases.²³ While one study suggested that up to 13% of patients with medulloblastoma exhibit radiological evidence of spina bifida occulta, no established relationship exists between myelomeningoceles and medulloblastoma.²⁴ In this unique case, we report on an adult patient with untreated spina bifida who developed medulloblastoma.

Illustrative Case

Case Presentation

A male in his early 30s who emigrated from an underdeveloped Middle Eastern country with a history of untreated spina bifida presented to the emergency department with 3 months of progressive headaches that acutely exacerbated over a few days. The patient had baseline paraplegia, lumbar myelomeningocele, neurogenic bowel and bladder incontinence with a chronic indwelling Foley catheter, and Chiari type II malformation. Importantly, he had no history of myelomeningocele repair or CSF diversion.

With the assistance of an interpreter, the patient was awake, alert, and oriented without focal cranial neuropathies. He had full strength in his bilateral upper extremities with mild left upper extremity dysmetria and baseline paraplegia in his lower extremities with a traumatic left lower extremity amputation. He had chronic loss of sensation below the umbilicus, and a chronic indwelling Foley catheter was in place. An untreated lumbar myelomeningocele was visualized and heavily scarred (Fig. 1A).

FIG. 1.

A: Untreated lumbar myelomeningocele. B: Noncontrast CT scan of the head, demonstrating obstructive hydrocephalus. C: CT scan of the head, showing a 3.9-cm hyperdense left cerebellar mass with compression of the fourth ventricle.

Imaging

Noncontrast CT of the head demonstrated a 3.9-cm hyperdense left cerebellar mass with obstructive hydrocephalus (Fig. 1B and C). While the initial differential diagnosis was broad, the hyperdensity on CT was suggestive of a tumor with a high nuclear to cytoplasmic ratio, as is commonly seen in medulloblastoma. In the context of untreated spina bifida with a lumbar myelomeningocele, contrast MRI of the neuroaxis was performed. Given the patient’s presentation with symptomatic obstructive hydrocephalus, a left-sided external ventricular drain was placed for CSF diversion (opening pressure > 20 cm H₂O) and intracranial pressure management prior to obtaining the MRI studies. The left side was chosen in anticipation that the patient might need a shunt contralateral to the lesion for permanent CSF diversion. MRI of the brain demonstrated a 3.9-cm heterogeneously enhancing left cerebellar mass with diffusion restriction and effacement of the fourth ventricle as well as a Chiari type II malformation (Fig. 2A and B). Spinal MR images demonstrated cervical and thoracic spinal cord atrophy with a 10.1-cm myelomeningocele and tethered cord with a low-lying conus (Fig. 2C).

FIG. 2.

A: Axial T1-weighted MR image of the brain without contrast, demonstrating a 3.9-cm hypointense left cerebellar mass. B: Axial MR image of the brain with contrast, demonstrating heterogeneous enhancement of the left cerebellar mass. C: Sagittal T2-weighted MR image of the lumbar spine, demonstrating a lumbar myelomeningocele.

A preoperative catheter-based angiogram was obtained to assess venous sinus anatomy in relation to the tumor for operative planning. An inferiorly displaced, dominant left transverse sinus was identified in the setting of an already reduced posterior fossa volume, given the patient’s history of spina bifida and Chiari type II malformation (Fig. 3).

FIG. 3.

Early venous phase (left) and late venous phase (right) lateral projections of catheter-based angiograms demonstrating a dominant and inferiorly displaced left transverse sinus.

Operative and Hospital Course

Given that the patient had symptomatic, obstructive hydrocephalus with a space-occupying lesion in the left cerebellum, resection was recommended, to which the patient agreed. The patient was positioned prone in Mayfield fixation for a left paramedian suboccipital craniotomy with image-guided navigation. Importantly, the left transverse sinus and torcula were found to be approximately 1.5 cm below the inion (Fig. 4). A left-sided craniotomy was performed with exposure of the inferior third of the transverse sinus (Fig. 4). CSF was drained from the cisterna magna and from the external ventricular drain to relax the cerebellum. Image-guided navigation and intraoperative ultrasound were used to perform a corticectomy and identify the tumor boundaries. The tumor was removed in a piecemeal fashion using a combination of bipolar cautery and gentle suction. The superior portion of the tumor had to be collapsed down into the field of view as this portion was not readily visible given the low-lying left transverse sinus. Resection was continued until the tentorium was reached superiorly. Intraoperative frozen pathology revealed the presence of small round blue cells. The dura was closed in a watertight manner using both a suturable graft and a dural sealant. A titanium mesh implant was used to cover the craniectomy defect (Video 1).

FIG. 4.

Intraoperative photographs. Left: The superior boundary of the tumor and our incision (white arrow). The course of the left transverse sinus (black arrow). Right: The course of the left transverse sinus based on intraoperative image-guided navigation (white arrow).

Video 1. Operative video of suboccipital craniotomy for resection of left cerebellar medulloblastoma. Click here to view.

The patient did well postoperatively and remained at his neurological baseline with only minor, intermittent headaches. Postoperative MRI showed no evidence of residual tumor (Fig. 5). Despite attempts to wean the external ventricular drain, he continued to have persistent ventriculomegaly and fourth ventricular effacement, so a right parietal ventriculoperitoneal shunt with a programmable valve was placed. The patient was ultimately discharged home at his neurological baseline.

FIG. 5.

A and B: Immediate postoperative axial T1-weighted MR images of the brain without (A) and with (B) contrast, demonstrating expected postoperative changes and no enhancing residual mass. C and D: Three-month follow-up coronal MR images of the brain without (C) and with (D) contrast, demonstrating no residual mass.

Pathology and Follow-Up

Final pathology demonstrated a highly cellular neoplasm with poorly differentiated, hyperchromatic, moderately pleomorphic nuclei. The specimen showed high mitotic activity, and the Ki-67 proliferation index was approximately 80%. The final diagnosis was WHO grade 4 medulloblastoma with desmoplastic morphology and sonic hedgehog (SHH) variant, as determined by DNA methylation profiling. Postoperatively, the patient completed craniospinal irradiation of 23.4 Gy over 13 fractions with a 30.6-Gy boost to the posterior fossa over 17 fractions. He is next planned for chemotherapy with cisplatin and vincristine. Three-month postoperative MRI demonstrated no residual tumor within the posterior fossa or metastatic lesions within the neuroaxis (Fig. 5).

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

The incidence of myelomeningocele repairs has declined in the United States largely due to widespread public health initiatives, but it remains a challenging disease to treat in underdeveloped nations.²⁵ Myelomeningoceles are associated with significant neurological morbidity and mortality, particularly if left untreated. In fact, repair as early as during the prenatal period is often indicated.²⁶ Shunt complications and infections are among the leading causes of hospitalizations in patients with myelomeningoceles, and shunt-related complications are the leading cause of in-hospital deaths.²⁷ In population survival analysis studies, patients with shunted hydrocephalus had a survival rate of 90% at the age of 16 years, while patients with untreated hydrocephalus had a survival rate as low as 58%.²⁸ Given the high rate of infectious and hydrocephalus-related complications, untreated myelomeningoceles in adults are exceedingly rare, and there are limited reports in the current literature.

Furthermore, a paucity of evidence and data limits understanding of CSF dynamics in the untreated, adult patient with spina bifida and Chiari type II malformation. This patient presented in adulthood with no prior shunt history. The role of CSF diversion in patients with prolonged, untreated spina bifida is unknown. Among patients with spina bifida who survive into adulthood, upward of 80%–90% are shunt dependent.²⁹ For those who do not undergo shunt treatment early in childhood, the need for CSF diversion later in life is unclear.

Last, while genetic studies have identified an association between neural tube defects and neuroectodermal tumors, there is no well-established relationship between spina bifida and medulloblastoma.²⁴,³⁰

Lessons

Here, we present the unique case of an adult male with an untreated myelomeningocele who was found to have a left cerebellar medulloblastoma with effacement of the fourth ventricle and resulting hydrocephalus. There are several key lessons.

First, it is important to recognize that the imminent, life-threatening condition that must be addressed first is the patient’s hydrocephalus. Early CSF diversion and intracranial pressure monitoring are critical, particularly in our case in which the patient was supine for an extended period for multiple additional diagnostic studies, including MRI of the neuroaxis and angiography. To avoid intracranial pressure with the patient flat for an extended period of time, we elected to place an external ventricular drain, which demonstrated elevated opening pressure.

Next, a thorough understanding of the anatomy of the posterior fossa vasculature is critical during preoperative planning in patients with spina bifida and Chiari type II malformations due to the abnormal development of the posterior fossa.^31–33 Specifically, our case highlights the importance of evaluating venous sinus structures, which are often displaced compared with traditional anatomical landmarks.³¹ In our case, we used catheter-based angiography to better delineate the posterior fossa venous sinus anatomy. Ultimately, a thorough understanding of dural venous anatomy allowed the identification of a safe corridor for resection, despite the low-lying, dominant transverse sinus on the side of the lesion. Alternative approaches included a transtentorial approach from above the transverse sinus versus a retrosigmoid craniotomy. However, a transtentorial approach risked significant injury to large draining veins, such as the vein of Labbé. Based on catheter-based angiography findings, a retrosigmoid craniotomy was deemed infeasible due to the severe inferior slope of the transverse sinus as it coursed medial to lateral.

During the patient’s postoperative course, serial imaging demonstrated persistent ventriculomegaly. While the patient remained at his neurological baseline postoperatively, the role of permanent CSF diversion remained unclear. Given persistent ventriculomegaly and fourth ventricular effacement due to peritumoral swelling, the risks and benefits of permanent CSF diversion were discussed with the patient, and a shared decision was made for the placement of a ventriculoperitoneal shunt. The decision for shunting was simplified due to the continued compression of the fourth ventricle; however, in the absence of compression, the need for shunting in a patient with prolonged, untreated spina bifida, as in our case, remains unclear.

As previously mentioned, patients with spina bifida have an increased risk of developing malignancies, including bladder cancer, radiation-induced malignancies, and age-appropriate cancers given their improved life expectancy.¹⁶ Population-based studies have also identified an increased risk of acute lymphoblastic leukemia, hepatoblastoma, sarcomas, and CNS tumors.³⁴ Bladder cancer malignancies are thought to be related to urological complications of spina bifida, including urothelial changes resulting from reconstructive surgeries and chronic infections. In addition, childhood exposure to radiation has been associated with the development of leukemia.³⁵ Indeed, patients with spina bifida are exposed to significant amounts of radiation during their childhood. Although the relationship between spina bifida and CNS tumors remains to be fully established, it is believed that the underlying mechanisms may be related to genetic and molecular pathways.

Among CNS tumors, no established relationship exists between myelomeningoceles and medulloblastoma. Medulloblastomas are divided into four subgroups, including Wingless/INT1 (WNT), SHH, group 3, and group 4. The WNT subtype is associated with a better prognosis, while SHH is the most common subtype.³⁶ Although limited data exist, there is evidence suggesting a role of the SHH pathway in neural tube defects.^37–39 Specifically, SHH promotes the activation of Gli2, and spina bifida has been associated with reduced expression of Gli2, which typically functions to repair damaged DNA.

While both spina bifida and medulloblastoma are rare pathologies, their co-incidence in our case raises the question of whether overlapping genetic pathways play a role in pathogenesis. Additional molecular and genetic studies are needed to better establish this relationship and to determine whether it pertains to particular molecular subtypes of medulloblastoma.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Algattas, Patel, Lim, Carver. Acquisition of data: Algattas, Patel, Lim, Gugino, Carver. Analysis and interpretation of data: Algattas, Patel, Lim, Carver. Drafting the article: Algattas, Patel, Riea, Lim, Gugino. Critically revising the article: Algattas, Patel, Lim, Gugino. Reviewed submitted version of manuscript: Patel, Lim, Khan, Carver, Snyder. Approved the final version of the manuscript on behalf of all authors: Algattas. Statistical analysis: Patel. Administrative/technical/material support: Patel, Lim, Gugino, Carver. Study supervision: Patel, Carver.

Supplemental Information

Videos

  Video 1. https://vimeo.com/1057537073.

Correspondence

Hanna N. Algattas: University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY. halgattas@ubns.com.