Transient Neurologic Disturbances, Brain Tumors, and
Normal Computed Tomography Scans
RUSSELL WALKER, MD,' ABRAHAM N. LIEBERMAN, MD,' RICHARD PINTO, MD,t AJAX GEORGE, MD,t
JOSEPH RANSOHOFF, MD,* MAX TRUBEK, MD,§ AND ARLENE WISE, MAS

During a 4-year period, four patients presented with transient disturbances in neurologic function that
were diagnosed as seizures in two and transient ischemic attacks in the other two. Computed tomography
(CT scan), both with and without contrast, was normal in all four patients. Isotopic brain scans (3
patients), cerebral angiograms (4 patients), and lumbar punctures (4 patients) were normal. Electroencephalograms (EEG) were normal in two patients and abnormal in two patients (consisting of focal
slowing). Within 4.5 months, all patients developed symptoms and signs of a brain tumor, and in all
four, CT scan now revealed a large mass lesion which at surgery was shown to be a malignant astrocytoma. These four patients constituted 4% of the total number of patients with malignant astrocytomas
that were seen at the NYU Medical Center during this same time period. It is stressed that the CT
scan may be normal early in the course of patients with brain tumors, particularly if they present with
a transient disturbance in neurologic function. The first evidence of the tumor in such patients may be
a slow-wave abnormality on the EEC. Patients who are suspected of having a brain tumor should, if
the initial CT scan is normal, have the scan repeated later.
Cancer 52:1502-1506, 1983.

C

ONTRAST-ENHANCED computed tomography (CT

scan) is the best method of diagnosing brain tumors. It is not generally appreciated, however, that the
CT scan may be normal early in the course of a patient
with a brain tumor, especially when the initial presentation of the tumor is that of transient neurologic disturbance (a seizure and/or a transient ischemic attack).
This article reports our experience with four such patients.
Methods
Four patients, during a 4-year period of time (1977
to 1980), were referred to the New York University
Medical Center (NYUMC) for evaluation of a transient
neurologic disturbance. The initial CT scans in all four
of these patients were normal, while repeat CT scans a
few months later revealed large mass lesions that histologically were shown to be malignant astrocytomas.
From the Department of Neurology,* the Department of Radiology,t the Department of Neurosurgery,$ and the Department of Med-

icine,§ New York University School of Medicine, New York, New
York.
Address for reprints: Abraham N. Lieberman, MD, Professor of
Neurology, NYU Medical Center, 530 First Avenue, Suite 5A, New
York, NY 10016.
The authors thank the following individuals for their cooperation:
Sun Hoo Foo, MD, Irvin Kricheff, MD, Joseph Lin, MD, Peter Pasternack, MD, Michael Ruoff, MD, and Edwin Weiss. MD, and Ms.
K.Faridazar for help in preparing the manuscript.
Accepted for publication July 9, 1982.

During the four years in which these patients were seen,
a total of 162 patients with malignant astrocytomas were
seen at the NYUMC. Thus, the four patients in this
report constituted 4% of the total number of patients
with malignant astrocytomas that were seen at the
NYUMC.
Assessment consisted of a detailed physical, neurologic, and laboratory examination including a hemogram, random and fasting blood sugars, calcium, phosphorous, blood urea nitrogen (BUN), and serum creatinine. CT scans with and without a single dose of
iodinated contrast were performed on an EM1 head
scanner Model #5005 (Cases 1, 3, and 4) or a General
Electric CT/T scanner Model # M O O (Case 2). These
scans were independently interpreted by two neuroradiologists (R.P.;A.G.). Electroencephalograms (EEGs)
were performed on all patients and records were obtained with the patient awake, drowsy and asleep, and
during hyperventilation and photic stimulation. Three
patients had isotope (technicium-99m) brain scans,
three patients had cerebral angiograms, and all four patients had lumbar punctures.
Case Reports

Case 1
A 38-year-old, right-handed man in previously good health
and o n n o medication, suffered six generalized seizures within

O008-543X/83/1015/1502$ I .05 0 American Cancer Society

1502

No. 8

BRAINTUMORS

- Walker et al.

1503

FIGS. 1A AND 1B. Upper cerebral convexity tomographic images utilizing a high-resolution GE CT/Tscanner, Model #8800, after a single
dose of iodinated contrast (Patient 2) reveals normal grey-white matter discrimination without distortion. effacement or obliteration of the cortical
sulci.

24 hours and was admitted to the NYUMC. Physical and
neurologic examination immediately after the last seizure revealed only postictal lethargy and confusion. CT scan with and
without contrast, cerebral angiography and lumbar puncture
were normal. An EEG, performed 24 hours later, revealed
paroxysmal bursts of 2 to 4 hertz (Hz)slow waves, on the right.
The patient was placed on phenytoin. Because of the occurrence of generalized seizures in a previously healthy adult and
the presence of focal slowing on the EEG, the patient was
regarded as a brain tumor suspect. Four months later, he returned complaining of headaches. Neurologic examination
revealed a left facial weakness, increased left-sided deep tendon
reflexes and papilledema. A CT scan now showed a large, nonuniformly enhancing mass lesion involving the right frontal
lobe with a shift of midline structures. The mass at craniotomy
(done by J.R.) was removed in toto and was shown to be an
astrocytoma with marked anaplasia. The patient was treated
with whole brain irradiation (6000 rads) and chemotherapy
(nitrosoureas). The tumor recurred after 3 months and the
patient again underwent a gross total removal of the tumor
(done by J.R.). The tumor recurred again in 3 months, and
the patient died shortly afterwards.

Case 2
A 6 1-year-old, right-handed man developed several episodes
of tingling that began in his left hand and then spread to his

left leg. The patient was admitted to a local hospital where
neurologic examination, CT scan with and without contrast,
EEG and isotope brain scan were normal. A diagnosis of a focal
seizure disorder was made and the patient was placed on anticonvulsant medication. The patient was re-admitted to the
hospital because of more episodes that included clonic movements of the left arm and leg. Repeat CT scan with and without
contrast and isotope brain scan were normal. Adjustments were
made in the patient’s anticonvulsant medications and he was
discharged. Despite adequate serum anticonvulsant levels, the
patient continued to have leR side of body focal motor seizures,
and one month later he was re-admitted to the hospital. CT
scan with and without contrast (Figs. 1A and IB), isotope brain
scan, lumbar puncture and cerebral angiography were normal.
An EEG revealed intermittent 2 to 6 Hz slow waves over the
right hemisphere. Further adjustments were made in the patient’s
anticonvulsant medications, but he continued to have left-sided
focal seizures. Four months later, over a 2-week period of time,

1504

CANCEROctober 15 1983

Vol. 52

FIGS. 2A AND 2B. Upper convexity tomographic images utilizing a high-resolution GE CT/T Scanner after a single dose of iodinated contrast
(Patient 2) reveals a large nonuniformly enhancing mass lesion with a necrotic center and surrounding edema.

he developed a left hemiparesis and was admitted to NYUMC.
Computed tomography now revealed a moderate sized mass
lesion with enhancing borders and a necrotic center involving
the right frontoparietal region (Figs. 2A and 2B). One day later,
the patient abruptly deteriorated and CT scan revealed hemorrhage into the tumor. At surgery (done by J.R.),the tumor
was found to be a malignant astrocytoma with marked anaplasia.
The patient was treated with whole brain irradiation and chemotherapy (nitrosoureas). The patient died 10 months later of
recurrent tumor.

Case 3
A 75-year-old, right-handed woman was admitted to the
NYUMC because of a loss of consciousness. On the day of
admission, the patient noted that, while talking on the telephone, her speech was slurred. She then felt the ground spinning beneath her and lost consciousness. She was found on
the floor 1 hour later by her husband who immediately brought
her to the hospital, where she was noted to be awake, alert,
rational, and coherent. There was a slight drift of the left arm,
and nystagmus on both right and left lateral gaze. The re-

mainder of the examination was normal and the neurological
deficit cleared within 24 hours. The patient was nondiabetic
and nonhypertensive. Computed tomography with and without contrast, isotope brain scan, EEG, lumbar puncture, 24hour Holter monitor and echocardiogram, were normal. A
diagnosis of vertebrobasilar insufficiency was made and the
patient was discharged. Four months later, while walking in
the street, she again lost consciousness. Computed tomography
at this time revealed a large nonuniformly enhancing mass
lesion involving the right frontal lobe that was removed in toto
at surgery, and was shown to be an astrocytoma with marked
anaplasia. The patient was treated with whole brain irradiation
(6000 rad) and nitrosoureas. The patient died of recurrent
tumor in 6 months.

Case 4
A 54-year-old, right-handed woman presented with a 2month history of episodic difficulty in speaking, each episode
lasting a few minutes. The patient also complained of episodic
difficulty in reading, each episode also lasting a few minutes.
Examination at the time of admission to NYUMC revealed

BRAINTUMORS

No. 8

Walker el al.

1505

Complete examination, including echocardiogram, 24-hour
Holter monitor, skull series, EEG, lumbar puncture and CT
scan both with and without contrast were normal. Cerebral
angiography was normal. A diagnosis of cerebrovascular disease was made and the patient was placed on anti-platelet
therapy. Six months later, the patient re-entered the hospital
because of increasing difficulty with speech. Computed tomography now revealed a large irregularly enhancing mass
lesion involving the left panetooccipital region that, at craniotomy (done by J.R.), was shown to be an astrocytoma with
marked anaplasia. The patient was treated with whole brain
irradiation (6000 rad) and nitrosoureas. The patient died of
recurrent tumor 6 months later.

Two of the patients (Cases 1 and 4) developed progressive neurologic dysfunction after their initial transient
disturbance in function: one patient (Case 3) had repeated transient disturbances in function, and one patient (Case 2) had repeated transient disturbances in
function and then developed a progressive neurologic
deficit. The location of the tumor was right frontal or
frontoparietal in three patients (Cases 1, 2, and 3), and
left parietooccipital in one patient (Case 4). The tumors
were all malignant astrocytomas with moderate to
marked anaplasia. Despite surgery, whole brain irradiation (6000 rad) and chemotherapy all four patients died
within 10 months of the time the tumor was diagnosed.

Neurologic Findings

Discussion

Mean age of the four patients was 57 years (range,
38-75 years). The transient disturbances in neurologic
function that were the presentation of the tumor in the
first two patients were seizures. In the first patient, the
seizures were generalized, but were associated with focal
(right hemispheric) slowing on the EEG. In the second
patient, the seizures were focal. Because of the occurrence of focal seizures (Case 2) or seizures associated
with a focally abnormal EEG (Case 1) in previously
healthy adults, both patients were regarded as brain tumor suspects. The disturbances in neurologic function
that were the presentation of the tumor in the last two
patients were initially diagnosed as transient ischemic
attacks, although both of them lacked any of the major
risk factors for stroke: diabetes, hypertension or heart
disease. Indeed cerebral angiography carried out in one
of them (Case 4) was free of extracranial or intracranial
vascular disease. An alternative explanation is that the
episodic disturbances in neurologic function in the last
two patients may have been partial complex seizures
rather than transient ischemic attacks.
All four patients had CT scans within 24 hours of
their initial episode, and in all, the scans, even in retrospect, were normal. One patient (Case 2) had three
separate normal-appearing scans. All four patients had
EEGs shortly after their CT scans and the EEGs were
abnormal in two patients (Cases 1 and 2) at what was
later shown to be the site of the tumor. Three of the
patients (Cases 1, 2, and 4) underwent cerebral angiography. The angiograms were normal in all three patients
without evidence of extracranial or intracranial vascular
disease. Isotope brain scans were performed in three
patients (Cases 1,2, and 4) and were normal. The mean
time from the initial CT scan to the one showing the
tumor was 4.5 months (range, 4-6 months). The CT
scans showing the tumors were typical for malignant
astrocytomas, consisting of moderate to large nonuniformly enhancing mass lesions with necrotic centers.’

This study demonstrates that the CT scan may be
normal early in the course of patients with brain tumors,
particularly when the patients present with a transient
disturbance in neurologic function, a seizure or an ischemic attack.’ One explanation for this may be that only
a few malignant cells are required to produce a seizure
or a transient ischemic attack either by altering the metabolism or the blood supply of the surrounding brain
tissue. Although the number of tumor cells may be too
small to be detected by the CT scan, the metabolic or
vascular alternation they produce may be detected by
the EEG. Another explanation as to why the tumor
might not be seen initially on the CT scan, is that in the
beginning the tumor cells may be isodense with the surrounding brain tissue.
Several articles have appeared on the accuracy of the
CT scanner in diagnosing intracranial tumors. Ambrose
er uL3 reported being able to detect 96% of malignant
gliomas without contrast administration, and 100%of
these tumors with contrast administration; while Kendall er aL4were able to detect 98% of malignant gliomas.
The accuracy of the CT scanner in diagnosing malignant
brain tumors is not in question, but the timing is of
importance.’*’ Thus, as documented in this report, the
tumor may initially present as a transient neurologic
disturbance, may be too small to be seen, and yet a few
months later may be highly visible. Such a scenario
seems reasonable given the known facts about the rapid
growth of malignant gliomas in man. Thus, the cell cycle
time of malignant gliomas has been calculated by Hoshino and Wilson6 as approximately 7 hours and the time
for the tumor to repopulate itself as 53 to 78 days. Furthermore, prior to the advent of high-voltage wholebrain irradiation and chemotherapy, it had been well
known that a malignant glioma (Kernohan grade 3 or
4) removed in toto at surgery was likely to regrow to its
original size within a 4- to 6-month period of
Thus, the presence of a large mass lesion on a CT scan

only that the patient had subtle difficulty in word finding.

CANCEROctober 15 1983

1506

4.5 months after the original normal scan is not surprising. Indeed in one of our patients (Case 1) after gross
total removal of the tumor, the tumor grew back to its
original size within 3 months despite irradiation and
chemotherapy.
The first question that arises is: when a transient disturbance in neurologic function occurs and the CT is
normal, when, if at all, should the CT scan be repeated:
In the first two patients, both of whom were suspected
of having a brain tumor, conventional plans based on
what were then judged to be reasonable considerations,
called for repeating the CT scan in 6 months to 1 year.
In retrospect, given our current experience, and based
on what is known about the growth rate of malignant
gliomas, we would recommend, even in the absence of
new symptoms, repeating the CT scan 4 months in patients who are suspected of having a brain tumor; and
if the results negative, repeating it periodically thereafter.
We emphasize that we do not make such a recommendation for all patients who have suffered a transient disturbance in neurologic function, but only for those who,
because they had seizures, are suspected of having a
brain tumor. Given the much lower incidence of malignant astrocytomas as compared to cerebrovascular
disease, transient ischemic attacks are much more likely
to be related to cerebrovascular disease than to malignant a s t r o c y t ~ m a s .Thus,
~ ~ ' ~ it would be unreasonable
to recommend periodically rescanning every patient
who has had a transient ischemic attack on the assumption that a small percentage of these patients might
harbor tumors. Nonetheless, among patients who are
having repeated ischemic episodes (Case 4) and who are
without risk factors for vascular disease, the suspicion
should be entertained that the patient could have a
tumor. '
It should be emphasized that, at the time of this investigation, all of our patients were scanned after a single
dose of iodinated contrast; three were scanned on the
EM1 head scanner, while one was scanned on the new
high-resolution General Electric CT/T scanner. It is thus
conceivable, although we think not likely, that a small
lesion that was not detected on the EM1 scanner, might
have been detected on the high resolution scanner, especially after a double dose of iodinated contrast. Parenthetically. we should add that only in patients who are
strongly suspected of having a brain tumor do we recommend a double dose of iodinated contrast.

'

Vol. 52

It may be pertinent to ask what value there is in making an early diagnosis of malignant glioma given the
limitations of the treatment that is currently available.'*
We would answer this question by pointing out the rapid
strides that are being made in the treatment of many
systemic malignancies where early diagnosis is important in influencing outcome. We would fully expect that
the same principles will apply to malignant gliomas.
The final question that arises is: At what point does
a patient who suffers a transient neurologic disturbance,
has a normal CT scan and is suspected of having a brain
tumor cease being a tumor suspect? This question cannot be answered from the current study. However, given
our current knowledge on the growth of malignant brain
tumors, it would appear reasonable, in the absence of
new symptoms, to obtain CT scans periodically on such
patients for up to 2 years.
ADDENDUM
Since this article was accepted an article making similar points has
appeared. Wulff JD, Proffitt PQ, Panszl JG, Ziegler DK. False-negative
CT in astrocytoma: The value of repeat scanning. Neurology (NY) 1982;
321766-769.
REFERENCES
I . Butler AR, Horli SC, Kricheff II. Computed tomography in astrocytoma. Radiology 1978; 129:433-439.
2. Tentler RL, Palacios E. False-negative computerized tomography in brain tumor. JAMA 1977; 238:339-340.
3. Ambrose J, Gooding MR, Richardson AE. An assessment of the
accuracy of computerized transverse axial scanning (EM1 scanning)
in the diagnosis of intracranial tumor. Bruin 1975; 98569-582.
4. Kendall BE. Jakubowski J, Pullicino P. Difficulties in diagnosis
of supratentorial gliomas by CAT scan. J Neurol Niwosurg P.vychiutr
1979; 41~485-492.
5. Steinhoff H, Grumme TH. Kazner E. Axial transverse cornputerized tomography in 73 glioblastomas. Ana Neurochir (Wien) 1978;
42x45-56.
6. Hoshino T, Wilson CB. Cell kinetic analysis of human malignant
brain tumors (gliomas). Cancer 1979; 44:956-962.
7. Frankel SA, German WJ. Glioblastoma multiforme. J Neurosurg
1958; 15:489-503.
8. Matuskado Y , MacCarty CS, Kernohan JW. The growth of glioblastoma multiforme (astrocytomas, grades 3 & 4) in neurosurgical
practice. J Neurosurg I96 I ; 18:636-644.
9. Dyken ML, Conneally PM, Haerer AF. Cooperative study of
hospital frequency and character of transient ischemic attacks. JAMA
1977; 2371882-886.
10. Weisberg LA, Nice CN. Intracranial tumors simulating the presentation of cerebrovascular syndromes. Am J Med 1977; 63:5 17-524.
1 1 . Lin JP, Siew FP. Glioblastoma multiforme presenting angiographically as intracranial atherosclerotic vascular disease. Radiology
1971; 101:353-354.
12. Lieberman A, Ransohoff J. Treatment of primary brain tumors.
Med Clin North Am 1979; 63:835-848.