Magnetic Resonance Imaging 24 (2006) 205 – 207

Magnetic resonance spectroscopy: a noninvasive diagnosis of

gliomatosis cerebri
Evangelia Kararizou a,*, Dimitrios Likomanosb, Konstantinos Gkiatasb, Ioannis Markoub,
Nikolaos Triantafylloua, Grhgorios Kararizosb
a
Department of Neurology, Eginition Hospital, Athens National University, Athens, Greece PC 11525
b
Neurological Clinic, Air Force Hospital, Athens, Greece PC 11525
Received 24 September 2005; revised 15 October 2005; accepted 15 October 2005

Abstract
Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of neoplastic glial cells with preservation of neuronal architecture. It can
be very difficult to diagnose during life because the clinical manifestations are protean and tests are often nondiagnostic. The diagnosis of GC
needs to be based on radiological, clinical and pathological criteria. We present a patient with GC, which initially presented as acute stroke
attack. We discuss the usefulness of noninvasive methods, such a MR spectroscopy, in the diagnosis, grading and management of GC.
D 2006 Elsevier Inc. All rights reserved.
Keywords: Gliomatosis cerebri; Magnetic resonance spectroscopy

1. Introduction noninvasive methods, such MR spectroscopy, in the

diagnosis, grading and management of GC.
Gliomatosis cerebri (GC) is a rare primary brain tumor of
unknown origin characterized by the proliferation of
neoplastic glial cells, and this process may involve multiple 2. Case report
brain regions [1– 4]. It can be very difficult to diagnose
A 59-year-old female patient presented with acute onset
during life because the clinical manifestations are protean
of dizziness, nausea, confusion and olfactory hallucinations.
and tests are often nondiagnostic [5,6]. The diagnosis of GC
She had a history of pulmonary embolism and had been
needs to be based on radiological, clinical and pathological
treated with anticoagulant drugs. There were no complaints
criteria [7,8]. Magnetic resonance imaging (MRI) has
of cognitive or behavioral impairments. The clinical exam-
become the radiological method of choice in the diagnosis
ination revealed decreased level of consciousness and con-
of GC [9]. Conventional MRI shows a diffuse signal
fusion. The motor strength was normal, and no sensory
intensity abnormality in T2-weighted and fluid-attenuated
deficits were detected. Babinski sign was negative. With
inversion recovery images with minimal or no mass effect
these findings and the acute onset of symptoms, the diag-
and a lack of contrast enhancement. Magnetic resonance
nosis of stroke attack was made in another institution.
spectroscopy (MRS), which may be added to conventional
Afterwards, the patient was admitted in Air Force
MRI exam, provides a noninvasive biochemical assay of
Hospital, and, immediately, a head CT scan was performed,
normal and pathological brain tissue and may help narrow
which revealed a heterogeneous lesion in the left frontal
the differential diagnosis in favor of a neoplastic lesion by
lobe, compressing the frontal horn of the left lateral
revealing increased Cho/Cr and Cho/NA and variably
ventricle and causing significant midline shift. Indefinite
decreased NA/Cr [10,11].
components of subarachnoid hemorrhage were also ob-
We present a patient with GC, which initially presented
served. Cranial MRI demonstrated extensive parenchyma-
as acute stroke attack. We discuss the usefulness of
tous lesions with the following features: (a) extensive signal
4 Corresponding author. Neurologic Clinic, Aeginition Hospital, 11528
changes in the left cerebral hemisphere, especially involv-
Athens, Greece. Tel.: +30 210 7289216; fax: +30 210 7250410. ing the white matter of the temporal lobe with a front-
E-mail address: ekarariz@med.uoa.gr (E. Kararizou ). oparietal spreading, including basal ganglia and internal
0730-725X/$ – see front matter D 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.mri.2005.10.032
206 E. Kararizou et al. / Magnetic Resonance Imaging 24 (2006) 205 – 207
Fig. 1. Concentrations of the spectroscopic metabolites.
capsule. (b) T2-signal abnormalities in the white matter of
the right hemicerebrum, especially occitotemporally via the
corpus callosum. (c) An ischemic lesion was observed in
the left occitotemporal district with peripheral hemorrhagic
elements. (d) Other ischemic lesions were recognised in the
left side of the midbrain and in the right side of pons. (e)
Cerebral edema was extended up to the cortex of the left
hemisphere, where cortical sulcuses were obscured. Mag-
netic resonance spectroscopy of the cerebral vasculature
revealed no stenosis or occlusion of either carotid or verte-
brobasilar circulation. From the imaging findings (head CT
scan, cranial MRI) the differential diagnosis included GC,
subacute encephalitis and any systemic disease with involve-
ment of the central nervous system. So further laboratory
examinations, including extended serologic tests for sys-
temic infectious and inflammatory diseases, connective tis-
sue and autoimmune diseases along with cancer, were
performed and the results were all normal. Interictal
EEG showed high-voltage activity with a left hemi-
spheric predominance.
As mentioned above, there was a history of pulmonary
embolism and treatment with anticoagulants and this was
the main reason that a brain biopsy was contraindicated.
Proton MRS was performed. Four NMR spectra of protons
with TE = 35 and 135 ms were taken from the lesion in the
left temporoparietal area and the respective area of the right
hemisphere (Fig. 1). The concentration of choline (Cho),
N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol
(MI), lactate, lipids as well as the metabolic ratios of
Cho/Cr, NAA/Cr and NAA/Cho was calculated (Table 1).
The concentration of Cho in the lesion is 45% higher than
that of the respective healthy region of cerebral hemisphere.
This finding is compatible with neoplasm (or malignancy).
Table 1
Area Cho (mM/kg) Cr (mM/kg) NAA (mM/kg)
Lesion 1 3.21 6.14 3.11
Lesion 2 3.41 6.61 3.12
Healthy region 2.36 7.40 8.88
The NAA concentration is quite low in the lesion area
(about 65%). The presence of Cr in the lesion area indicates
neoplasm of diffuse type (glioma), and the elevation of the
Cho/Cr is compatible with low-grade glioma. Finally, the
presence of lactic acid indicates the initiation of alteration in
parts of the lesion (anaplastic astrocytoma grade III). Taking
into account the neuroimaging findings (extension of the
lesion to the right hemisphere, heterogeneous contrast
enhancement), we found that this lesion fulfills the criteria
of WHO for being characterized as GC [12].
At that time the patient had been treated with cortico-
steroids that resulted in significant improvement of symp-
toms over a period of 3 months. Although the initial
symptoms of our patient included dizziness, nausea,
confusion and olfactory hallucinations, no neurological sign
or symptom was reported or revealed during hospitalization,
despite the extent of the cerebral lesion.
The last MRI, which was performed in May 2005, was
reported to be unchanged. The neurological examination did
not reveal any pathological findings.
3. Discussion
Gliomatosis cerebri is characterized by a diffuse infiltra-
tion of neoplastic glial cells with preservation of neuronal
architecture. It was first described in a case report by Nevin
[13] in 1938 as a glial neoplasm with diffuse infiltration
throughout the brain yet with relative preservation of
underlying neuronal architecture.
In the latest WHO classification GC is listed as a
subgroup of neuroepithelial tumors of uncertain origin with
involvement of at least two lobes without a cellular,
centrally necrotic center [12].
MI (mM/kg) NAA/Cr Cho/Cr MI/Cr
6.28 0.58 1.38 0.62
6.46 0.54 1.36 0.59
7.21 1.37 0.84 0.59
 E. Kararizou et al. / Magnetic Resonance Imaging 24 (2006) 205 – 207
The diagnosis of GC during life is problematic and needs
to be based on radiological, clinical and pathological criteria.
There are many reports of a delayed antemortem diagnosis
of GC [5,6].
In our case, brain biopsy was contraindicated because of
the treatment with anticoagulants. The diagnosis was based
especially on the neuroimaging studies. A recent report
suggests that noninvasive biochemical assay of normal and
pathological brain tissue with MR spectroscopy may be
helpful in diagnosing GC [10,11,14,15]. The typical MRI
appearance of GC is a lesion that grows without distinct
borders, diffusely infiltrating multiple brain regions. How-
ever, the changes in MR images are nonspecific and the
differential diagnosis includes ischemia, multiple sclerosis,
encephalitis, leukodystrophies and subacute sclerosing
panencephalitis [9]. Serologic and radiology tests excluded
all other conditions considered in the differential diagnosis.
Magnetic resonance spectroscopy is able to distinguish
between glial tumors and tumors of neuronal origin. A
number of previous studies have reported elevated Cho and
decreased NAA and Cr, and this spectroscopic pattern
of neoplastic brain lesions has been used to differentiate
and to establish prognostic parameters [10,11,14,15]. The
extent of Cho/Cr and Cho/NAA increases is of great
importance in the grading of gliomatosis. According to
the study of Fountas et al. [16], Cho/Pcr-Cr is a very
important marker determining the degree of malignancy.
Magnetic resonance spectroscopy can also be used for
follow-up examination.
The clinical manifestations of GC are usually progres-
sive and nonspecific, and the acute onset as stroke is rare
[1– 4].
With the use of radiation therapy and chemotherapy,
survival is about 5% and the natural course is quite variable,
with a duration between 25 days and 22 years [17,18].
Although the initial symptoms of our patient included
dizziness, nausea, confusion and olfactory hallucinations,
no neurological sign or symptom was reported or
revealed during hospitalization, despite the extent of the
cerebral lesion.
In conclusion, our report suggests that MRS is a useful
noninvasive method not only for diagnosis but also for
grading and prognosis of GC and especially when there are
contraindications for the biopsy study.
207
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