Pediatric Gliomas

What are gliomas?

A category of brain tumors with a shared origin—but very different clinical behavior.

Gliomas are tumors that arise from glial (supportive) cells of the nervous system. In children, they account for the largest proportion of tumors of the brain and spinal cord.

They are generally divided into:

• Low-Grade Gliomas (LGG) — e.g., pilocytic astrocytoma, ganglioglioma, DNET, WHO grade II astrocytoma/oligodendroglioma. These tumors typically grow slowly, often occur in children and adolescents, and in many cases can be controlled for years—or even decades.
• High-Grade Gliomas (HGG) — such as anaplastic astrocytoma and glioblastoma. They demonstrate more aggressive biology, require multimodality therapy, and are associated with a more challenging prognosis.

A distinct subgroup—primarily defined by location—is brainstem glioma (e.g., DIPG, exophytic medullary glioma, tectal glioma), which has a characteristic clinical presentation and a specialized therapeutic approach.

How common are they, and at what ages do they occur?

Gliomas are the most common pediatric CNS tumor type.

In childhood, the annual incidence of brain and CNS tumors is approximately 5–6 cases per 100,000 children. Of these, more than half are gliomas.

Broadly:

• In children < 5 years, tumors may occur both supratentorially (cerebral hemispheres) and infratentorially (cerebellum, brainstem).
• Between 5–14 years, pilocytic astrocytoma is among the most frequent CNS tumors, with malignant gliomas occurring less commonly but remaining clinically significant.
• In adolescence, tumor patterns may resemble adult gliomas in some respects, but with important differences in molecular biology.

Children with congenital or genetic predisposition syndromes (e.g., neurofibromatosis type 1, tuberous sclerosis) have an increased risk of specific glioma subtypes (e.g., optic pathway gliomas, subependymal tumors).

What are the main types of gliomas in children?

Not all tumors are the same—accurate classification guides treatment.

Based on morphology and grade, common pediatric gliomas include:

• Pilocytic Astrocytoma (PA)
  The most common low-grade glioma in children. It often arises in the cerebellum, but may also involve the optic pathway or hypothalamus. It typically grows slowly and has an excellent prognosis when complete resection is achievable.
• Ganglioglioma (GG) & DNET
  Often located in the temporal lobe and may present with seizures. These are generally considered low-grade tumors.
• WHO grade II astrocytic / oligodendroglial tumors
  More diffuse low-grade tumors that may, in some cases, progress to a higher grade over time.
• High-Grade Gliomas (anaplastic astrocytoma, glioblastoma)
  More aggressive tumors with faster growth, typically requiring a combination of surgery, radiation therapy, and chemotherapy.

A special subgroup includes brainstem gliomas:

• Diffuse Intrinsic Pontine Glioma (DIPG) — a diffusely infiltrating tumor of the pons.
• Exophytic medullary gliomas — tumors of the medulla that “project” toward the fourth ventricle.
• Tectal glioma — small midbrain tumors often associated with hydrocephalus.

What causes them, and what are the genetic/molecular mechanisms?

In the vast majority of children with glioma, no specific environmental trigger is identified. In a small subset, inherited tumor-predisposition syndromes (e.g., neurofibromatosis, tuberous sclerosis) are present.

Today, we study in depth the molecular alterations that characterize pediatric gliomas. For example:

• In pilocytic astrocytomas, alterations involving BRAF (e.g., BRAF–KIAA1549 fusion) are common and affect signaling pathways that drive cell growth.
• In high-grade gliomas, pathways such as RAS/PI3K, p53, and retinoblastoma are frequently involved. Pediatric glioblastomas, in particular, have a molecular profile that differs from adult glioblastoma.

These data support more precise diagnosis and—progressively—enable targeted therapies in selected cases. For parents, the most important message is that nothing you did caused your child’s tumor.

How do they present—what symptoms should we watch for?

Symptoms depend on a child’s age, tumor location, and tumor biology.

In infants and very young children (< 3 years):

• Delay in, or loss of, developmental milestones.
• Unexplained irritability, excessive sleepiness, or behavioral changes.
• Increasing head circumference, a bulging fontanelle (when hydrocephalus is present).
• Feeding difficulties, poor weight gain or failure to thrive.

In older children:

• Recurrent headaches, often worse in the morning.
• Morning nausea and vomiting without an obvious gastrointestinal cause.
• Gait unsteadiness, frequent falls, difficulty running or using stairs.
• Double vision or visual changes, new strabismus, or changes in visual fields.
• Seizures, particularly with tumors of the cerebral hemispheres.
• Weakness or numbness of an arm/leg; reduced use of a limb.
• Changes in school performance, attention, or behavior.

In brainstem gliomas (e.g., DIPG):

• Facial weakness or asymmetry (e.g., an uneven smile).
• Difficulty moving the eyes or new strabismus.
• Swallowing difficulty or voice changes.
• Unsteadiness and difficulty walking.

Many of these symptoms are non-specific and may be caused by less serious conditions. However, when symptoms are persistent, progressive, or occur in combination, prompt neurologic evaluation and MRI imaging are warranted.

How is the diagnosis made, and what is the role of MRI?

MRI is the cornerstone of diagnosis; in most cases, tissue confirmation is required.

Evaluation typically includes:

• Clinical and neurologic examination by a pediatric neurologist and/or pediatric neurosurgeon, including assessment of reflexes, gait, visual fields, and cranial nerves.
• Brain MRI with and without contrast, usually across multiple sequences. MRI:
  • defines the tumor’s location and extent with high precision,
  • helps estimate whether a lesion is low- or high-grade (morphology, perfusion patterns),
  • detects associated hydrocephalus or mass effect.
• Advanced MRI techniques (e.g., perfusion imaging, MR spectroscopy) may further support differentiation between low- and high-grade tumors.
• Biopsy and/or surgical resection — in most cases, tissue is required for a definitive diagnosis (histology, immunohistochemistry, and molecular testing).

An exception involves certain diffuse brainstem gliomas (DIPG), where a classic MRI appearance may be sufficient for diagnosis and biopsy is not always necessary—or safe—depending on location and clinical context.

When is surgery needed, and what is the goal?

When safe and feasible, surgery is the central component of treatment.

The goal of the surgical team is to achieve gross total resection (GTR) whenever possible, while maximizing safety and minimizing neurologic risk for the child.

Extent of resection is a key prognostic factor:

• In low-grade gliomas, when complete resection is achieved, 10-year progression-free outcomes can exceed 80–85% in many series.
• In high-grade gliomas, a greater extent of safe resection is associated with improved outcomes and longer survival, but adjuvant oncologic therapy is typically required.

There are situations in which a tumor cannot be safely removed without unacceptable neurologic morbidity (e.g., diffuse brainstem glioma). In those cases, the plan may include:

• Biopsy for diagnosis (when appropriate),
• Partial decompressive debulking to relieve pressure or hydrocephalus in selected cases,
• Endoscopic third ventriculostomy (ETV) or a shunt for symptomatic hydrocephalus.

The decision for surgery is made after a detailed, transparent discussion with parents, involving both the pediatric neurosurgeon and pediatric oncologist.

What other treatments exist (chemotherapy, radiation therapy)?

Treatment is individualized based on tumor type and the child’s age.

Therapy is guided by histology, molecular features, the child’s age, and whether a safe resection is achievable. In addition to surgery, the following may be used:

• Chemotherapy
  In low-grade gliomas, chemotherapy is commonly used to:
  • control residual tumor after a subtotal resection,
  • delay or avoid radiation therapy, especially in very young children,
  • treat recurrence or progression.

  In high-grade gliomas, chemotherapy is typically administered in combination with radiation therapy. Regimens may include temozolomide or other agents, depending on institutional protocols and clinical context.

• Radiation therapy
  Radiation is a key component of treatment for high-grade gliomas in children older than 5 years, when clinically appropriate.

In selected centers, clinical trials may be available, including newer drugs or targeted therapies matched to specific molecular alterations. This is always evaluated on an individualized basis.

What is the prognosis, and what does it depend on?

There is no single “prognosis” for all gliomas—the spectrum is highly heterogeneous.

Outcomes depend on multiple factors, including:

• Tumor grade — low- versus high-grade.
• Extent of resection — gross total, near-total, subtotal, or biopsy only.
• Location — tumors in the cerebellum or on the cortical surface often have better outcomes than diffuse tumors of the brainstem.
• Child’s age and any associated neurodevelopmental or genetic conditions.

In general:

• Many low-grade gliomas, after complete or near-complete resection, have excellent long-term outcomes with a relatively low risk of recurrence.
• High-grade gliomas in children represent a serious diagnosis with more limited outcomes, despite combined surgery, radiation therapy, and chemotherapy.

Your pediatric neurosurgeon and pediatric oncologist will review your child’s individualized prognosis based on the tumor’s specific characteristics and the results of molecular testing.

What are the possible complications and long-term effects?

Our goal is not only disease control, but also preserving the best possible quality of life for your child.

Potential complications may relate to the tumor itself and/or its treatments:

From the tumor and its location:

• Persistent neurologic deficits (weakness, speech or vision disturbances).
• Ongoing seizures with cortical tumors.
• Hydrocephalus requiring long-term CSF diversion (shunt) or endoscopic third ventriculostomy.

From surgery:

• Bleeding, infection, brain swelling (rare).
• Anesthesia-related risks, ICU monitoring, temporary neurologic changes.

From radiation therapy and chemotherapy:

• Neurocognitive effects (memory, attention), especially in younger children.
• Endocrine effects (growth and hormonal regulation), depending on treatment and location.
• Secondary tumors or other late effects (rare, but recognized risks).
• Hematologic and infectious complications related to chemotherapy.

For these reasons, long-term follow-up is essential and may include a pediatrician, pediatric neurologist, endocrinologist, psychologist/neuropsychologist, and rehabilitation specialists, depending on your child’s needs.

How are the child and family supported over time?

Beyond surgical and oncologic care, we place strong emphasis on:

• Neuropsychological support — assessment of memory, attention, learning challenges, and emotional wellbeing.
• Physical and occupational therapy — to strengthen mobility, balance, and daily function.
• School reintegration — coordination with the school for accommodations and specialized educational support when needed.
• Psychological support for parents and siblings, because a brain tumor diagnosis affects the entire family.

The Neuroknife team can coordinate this multi-layered care in collaboration with pediatric oncologists, rehabilitation specialists, and psychologists.