A 41-year-old active-duty Army officer presented with a new onset of grand mal seizure at an outpatient military clinic.
Douglas Mathis, MD
Joyce Moore Stovall, MD
Karen SantaCruz, MD
, from the Eisenhower VA Medical Center, Leavenworth, KS.
A 41-year-old active-duty Army officer presented with a new
onset of grand mal seizure at an outpatient military clinic. Prior
to this episode, he had experienced intermittent headaches for
approximately 5 to 7 days with no other significant neurological
symptoms. The patient's medical history is unremarkable for major
illnesses or surgical procedures. His neurological examination
disclosed pronator drift of his left arm and global 1+ reflexes.
Computed tomography (CT) (Figures 1 and 2) and magnetic resonance
imaging (MRI) (Figure 3) examinations were ordered.
Pre- and postcontrast CT scans of the brain (Figures 1 and 2) of
the brain at the time of the initial presentation revealed a
dominant ring-enhancing mass at the gray-white matter junction and
several small enhancing lesions in the right parieto-occipital
area. There was associated vasogenic edema, effacement of the right
lateral ventricle, and approximately 5 to 7 mm of midline shift to
the patient's left (Figure 1). CT slices through the
parieto-occipital area revealed multiple small enhancing lesions at
the grey-white matter junction with vasogenic edema (Figures
The postcontrast MRI scans were consistent with the CT scans.
MRI demonstrated a large ring-enhancing lesion with a hypointense
center of fluid consistency and multiple smaller enhancing lesions
in the right parieto-occipital lobe (Figure 3). There was
effacement of the right lateral ventricle.
The radiological differential diagnosis included brain
metastases, cerebral abscesses, lymphomas in AIDS patients, and
Based on the diagnostic imaging, the patient was started on
antibiotic therapy for the proposed diagnosis of multiple cerebral
abscesses. The patient was continued on Dilantin and Decadron for
Stereotactic-guided needle biopsy of the dominant cystic lesion
yielded tea-colored fluid under high pressure. The fluid was sent
for gram stain, cultures, sensitivity, and acid-fast bacilli. The
fluid contained debris and necrotic tissue but no pus. A frozen
section of the stereotactic needle biopsy revealed acute
inflammation with many polymorphonuclear lymphocytes, which were
thought to be consistent with cerebral abscess, although no frank
pus was found. The tests for cryptococcal and toxoplasmosis
antigens were negative. The blood cultures were negative for the
Microscopic examination (Figure 4) of hematoxylin and eosin
stained sections of tumor showed prominent pleomorphism, cellular
atypia, and glomeruloid vascular proliferation characteristic of
high-grade gliomas. Focal necrosis with pseudopalisading of tumor
cells further defined this neoplasm as a glioblastoma multiforme.
Glial fibrillary acidic protein (GFAP) immunostaining and an MIB-1
immunostain confirmed the glial nature and aggressive character of
the tumor cells. The final pathology returned as glioblastoma
multiforme for the multiple lesions. No distinct histological link
of multifoci within this tumor could be discerned.
The patient was discharged and received follow-up appointments
with the Radiation Oncology and Medical Oncology departments.
Radiation Oncology recommended tumor debulking to improve the
effectiveness of radiation therapy. The patient underwent a
subsequent right temporoparieto-occipital craniotomy with resection
of the middle fossa and parieto-occipital glioblastomas. The
patient tolerated the surgical procedure well without signs of
postoperative neurological deficits. Upon discharge, the patient
was ambulating without assistance.
Glioblastoma multiforme is the most common primary
supratentorial glial neoplasm. It primarily occurs in 40- to
55-year-old men. New onset of generalized seizures is a presenting
symptom in approximately 20% of patients.
Other symptoms include headache, nausea and vomiting, personality
changes, and psychomotor dysfunction. Glioblastoma multiforme is a
glial neoplasm with high cellularity, vascular endothelial
proliferation, and nuclear and cytoplasmic pleomorphism. It can
present a multiplicity of histological appearances. Glioblastoma
usually involves the white matter of the cerebrum: 35% of cases
involve the frontal lobe, 33% the parietal lobe, 22% the temporal
lobe, and 10% the occipital lobe.
Frequently, glioblastoma multiforme crosses the corpus callosum
extending bilaterally as a single entity in a butterfly pattern.
Multiple sclerosis and lymphomas also possess this capability.
Kernohan classification is the most commonly used method of
classifiying astrocytomas on a scale from 1 to 4. Glioblastoma
multiforme is a grade four, and is histologically the most
The World Health Organization and the Radiation Treatment Oncology
Group utilize three categories for classification: low-grade
astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme.
CT and MRI studies are valuable and are the most frequently used
diagnostic imaging modalities for detection of glioblastoma. The CT
and MRI appearance of glioblastoma are vasogenic edema, mass
effect, cystic and solid components, hemorrhage, and tumor
enhancement secondary to compromise of the blood-brain barrier. The
latter of these is extremely important in patient management. Its
ill-defined margins correlate with the aggressive infiltrative
properties of the lesion. The prognosis of glioblastoma multiforme
is grave. The mean survival time is usually 6 months from the time
In this case, the contrast-enhanced CT scan and MRI feature
multiple well-defined, ring-enhancing lesions with cystic and solid
components in the right parieto-occipital cortex that were thought
to be cerebral abscesses. Multiple ring-enhancing glioblastomas can
emulate brain metastases, cerebral abscesses, lymphomas in AIDS
patients, and toxoplasmosis. Accurate histopathologic assessment of
multiple brain masses mandates appropriate selections of areas to
perform stereotactic guided biopsies.
Multiple glioblastomas are uncommon and represent only 2.5% to
5% of all glioblastomas, usually involving one or more lobes of one
or both cerebral hemispheres. According to Lafitte et al,
multiple gliomas can appear early (synchronous), at the time of the
initial diagnosis, or they can appear at a later time
(metachronous) subsequent to the initial diagnosis. Multiple
glioblastomas are classified as multicentric, if they arise
independently in different sites; or multifocal, if they spread
from a primary focus to other sites in the brain.
It has been hypothesized that multifocal gliomas undergo genetic
cloning, and yield many satellite lesions from a single tumor.
This distinction necessitates histopathologic assessment of genetic
material for determination of clonality.
Multifocal gliomas can infiltrate the overlying meninges of the
cerebral cortex and subependymal route of the lateral ventricles,
which effects tumor seeding of the cerebrospinal fluid pathways in
the meningeal and subarachnoid spaces. The CT scan and MRI of
patients with multifocal glioblastomas will reveal enhancement of
the meninges or ventricles close to the lesion if there is
Postcontrast enhancement of the meninges or the ventricles on this
patient's CT scan and MRI was not observed. Ultimately, making the
distinction between multifocal and multicentric glioblastomas
offers little practical clinical value.
Perhaps the metabolic and functional attributes of proton MR
spectroscopy would have assisted in making the diagnosis of brain
tumors. Clinical proton MR spectroscopy can detect the four types
of metabolites in the brain that have a long echo time (135 to 270
msec): choline compounds, creatine/phosphocreatine,
N-acetylaspartate (NAA), and lactate. Clinical proton MR
spectroscopy distinguishes the metabolites in the brain that peak
at a short echo time (20 msec): lipids, myo-inositol, glycine,
glutamine/glutamate and macromolecules.
The phenotypes of the distinct metabolites will reflect different
MR peaks. The quantitative analysis of normal and pathological
brain tissue is reflected by amplitudes on an empirical algorithm.
MR spectra of brain tumors are interpreted on the basis of the
relative amplitudes for choline, creatine, NAA, lactate, and
lipids. In a normal brain MR spectroscopy, the highest amplitude is
the NAA peak; choline and creatine ratio are about equal and
markedly decreased when compared with NAA; and the lipid and
lactate concentrations are not elevated.
In low-grade gliomas, the choline metabolite in the proton spectrum
is slightly increased above the NAA metabolite, and lactate is
In high-grade gliomas (anaplastic astrocytoma and glioblastoma
multiforme) choline is markedly increased, NAA is markedly
decreased, and lactic acid and lipids are frequently high.
Areas of decreased NAA, choline, and creatine metabolites with
increased lactic acid and lipids are usually where the necrotic
portions of high-grade tumors are found.
Selection of stereotactic guided needle biopsy samples should be
avoided in such areas, because of the high probability of yielding
inflammatory or necrotic cells.
A new Single-Voxel Proton Brain Exam (PROBE/SV; GE Medical
Systems, Milwaukee, WI) is an automated and operationally
simplified MR spectroscopic technique that provides automatic
online data processing and display.
The selection of the voxel location area of interest to focus on
can be acquired to determine if there is a low-grade or high-grade
neoplasm, inflammatory process, and/or tumor necrosis. The voxel
selection location should be obtained from an area that is at least
in size and demonstrates elevated choline.
The PROBE/VS MR spectroscopic technique can help to improve the
physician's confidence on selections of areas to perform the
stereotactic-guided biopsy for histopathological assessment. The
exam can decrease 1) the number of biopsies, 2) the chance of voxel
contamination from unwanted tissue, 3) patient morbidity, and 4)
the number of diagnostic tests needed. It can be helpful in
differentiating between radiation necrosis and tumor recurrence
following radiation and chemotherapy.
Multiple glioblastomas on CT and conventional MRI can emulate
brain metastases, cerebral abscesses, lymphomas in AIDS patients,
and toxoplasmosis. PROBE/SV data, an automated MR spectroscopic
technique, in conjuction with CT and conventional MRI, can play a
beneficial role in aiding physicians in obtaining a more accurate
diagnosis. This automated MR spectroscopic technique can be helpful
in formulating the patient's therapeutic plan.
The authors thank Mrs. J. Gosselin, medical librarian of DDE
VAMC, for her help in retrieving articles; Mrs. S. Collins, medical
clerk, for retrieving patient information; Mr. K. Jahn, radiologic
technician for computer assistance; and Mr. A. Swieca for the