Evaluation of Supratentorial High-Grade Gliomas in Children

Examination

A complete physical and neurological examination should be performed. Focal deficits may be found depending on location and size of the tumor.

• Infants and head circumference: In the case of infants, the anterior fontanelle and cranial sutures should be examined, and a head circumference measured and compared to previous measurements to determine potential head growth acceleration and rapidity of tumor growth.
• Ophthalmological assessment: Age-appropriate ophthalmological examination, including funduscopic and visual field evaluation, if possible, should be performed.  Papilledema may prompt higher doses of corticosteroids or ICU admission.

Laboratory Tests

• Standard preoperative laboratory tests:  In anticipation of surgery an assessment of renal function, hematocrit/hemoglobin, platelet count and aggregation if clinically indicated, coagulation studies, and blood typing for cross-matching of blood transfusions should be considered.
• Anticonvulsants: Serum anticonvulsant levels should be documented when appropriate.
• Markers for tumor: No serum marker exists to aid in the diagnosis of HGG.

Radiologic Tests

Access to sophisticated neuro-imaging has led to earlier diagnosis of some of these tumors.  Symptoms suggesting intracranial hypertension typically result in a CT or MRI of the brain being performed.  Typically, because sedation is rarely required, the CT is the first radiologic test acquired, followed by MRI.  Both are helpful in evaluating the child and the tumor, the CT to evaluate calcifications and the calvarium, and the MRI for high-resolution images of the intracranial contents.

CT Scan

• AAs – variable density, surrounding edema and enhancement: CT images typically may show variable attenuation, enhancement, and vasogenic edema. Even in very large lesions there may be little or no edema.

Axial CT scan of an AA: Scan shows isodense mass involving the diencephalon bilaterally.

• GBM – variable density and enhancement with surrounding edema: CT images of GBM show variable attenuation and enhancement, which may be ring-enhancing, and associated vasogenic edema contributing substantially to overall mass effect.

Axial CT scan of a GBM: Scan shows a hypodense lesion in the right frontal lobe with edema surrounding posterior margin.

MRI

• AAs – hypodense to isodense T1-weighted image: Post-contrast T1-weighted images reveal a diffuse lesion with variable enhancement (focal, homogeneous, nodular). Diffuse leptomeningeal spread is not common.

Enhanced axial T1-weighted MRI of an AA: Tumor is seen in right thalamus with mottled enhancement.

Enhanced coronal T1-weighted MRI of an AA: A large minimally enhancing tumor is seen in the right thalamus.

• AAs – hyperintense T2-weighted MRI with variable edema: T2-weighted MRI reveals high intensity with surrounding edema for large lesion, with little edema in smaller tumors. 

Axial T2-weighted MRI of an AA: Shown is a tumor in the right thalamus with variable signal intensity and feathery edema along its lateral margins.

Axial T2-weighted MRI of an AA: Shown is a smaller tumor in the right thalamus with minimal edema and mass effect.

• AAs bright on axial DWI: DWI shows diffusion restriction (bright area). 

Axial diffusion-weighted image of an AA: Shown is a large tumor of the right thalamus that restricts on DWI.

• GBM – hypointense T1-weighted MRI with ring enhancement: The T1-weighted images will typically show a hypointense, necrotic center, or a large, heterogeneously tumor with impressive infiltration of surrounding structures. Gadolinium enhancement may be ring shaped or heterogeneous.

Axial T1-weighted, gadolinium-enhanced MRI of a GBM: Shown is a tumor in the left insula with irregular ring enhancement and central hypointensity consistent with necrosis.

Coronal T1-weighted, gadolinium-enhanced MRI of a GBM: Shown is a central tumor involving the diencephalon bilaterally with irregular enhancement and multiple cysts.

• GBM – hyperintense T2-weighted and hypointense Flair imaging with surrounding, hyperintense edema. T2-weighted and Flair sequences will show edema better with Flair differentiating it from solid tumor.

Axial T2-weighted MRI of a GBM: Shown is insular tumor shown above in axial T1-weighted image with better resolution of surrounding edema.

Axial Flair MRI of a GBM: Shown is right frontal tumor in axial CT scan with better resolution of solid portion of tumor and surrounding edema and infiltrating tumor.

• GBM DWI – bright signal of restriction is typical. The tumor will restrict on DWI and show very bright.

Axial DWI of a GBM: This is the DWI of the tumor shown in the coronal T1-weighted image above.

Axial DWI of a GBM: This is the DWI of the insular tumor whose axial T1- and T2-weighted images are shown above. Note that the central area of necrosis does not restrict.

MR Spectroscopy

• Decreased NAA, lactate peak, and elevated choline/creatinine ratio: MR spectroscopy provides information about the metabolic and biochemical activity of the tumor (15). When compared to normal brain tissue in the same patient, high-grade tumors reveal a decreased NAA (N-acetylaspartate), a tall lactate peak or doublet, and an increase in the choline/creatinine ratio. 

Spectroscopy of child with an AA: Spectroscopy of child whose axial T1-weighted MRI is shown above. Early in his clinical course there was subtle weakness. This scan done at that time shows a high NAA and almost no lactate peak.

Spectroscopy of same child later in his course: At the time of this scan the child’s weakness had become significant. Note the significant rise in choline, drop in NAA, and large lactate peak.

Spectroscopy of child with GBM: This MR spectroscopy was done on child whose T1-weighted scan above showed a left-sided thalamic GBM. Note the high lactate peak seen in supratentorial HGGs like this GBM.

fMRI

fMRI of verbal function: The patient is a 12-year-old right-handed girl with left temporal-thalamic AA.

Diffusion Tensor Imaging (DTI)

DTI of motor fibers: The patient is a 12-year-old right-handed girl with left temporal-thalamic AA whose fMRI is seen immediately above.

Nuclear Medicine Tests

• PET used to evaluate hypermetabolism: PET may be helpful in the care of children with high-grade gliomas.  It is most often used to evaluate children after surgery when there is a question about whether MRI findings are compatible with tumor, postoperative changes, or radiation necrosis. It may be used preoperatively, however, to delineate areas of increased metabolism.

Electrodiagnostic Tests

• Not indicated: Electrodiagnostic tests are not indicated for supratentorial HGGs.

Neuropsychological Tests

• Neuropsychological tests establish baseline to follow: For children who are cooperative and not significantly impaired, particularly those with specific memory, cognitive, or intellectual symptoms, preoperative neuropsychological testing may be helpful if time permits. Such testing may serve as a baseline for future comparison during and after treatment (16).

Correlation of Tests

• Imaging and pace of symptom evolution: All of the above tests, along with the child’s medical and neurological condition, will help guide the timing and nature of treatment.