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Spontaneous Regression of Optic Gliomas
Thirteen Cases Documented by Serial Neuroimaging
Cameron F. Parsa, MD;
Creig S. Hoyt, MD;
Robert L. Lesser, MD;
Joel M. Weinstein, MD;
Charles M. Strother, MD;
Rafael Muci-Mendoza, MD;
Marcos Ramella, MD;
Riri S. Manor, MD;
William A. Fletcher, MD;
Michael X. Repka, MD;
James A. Garrity, MD;
Roberto N. Ebner, MD;
Mario L. R. Monteiro, MD;
Robert M. McFadzean, MD;
Irina V. Rubtsova, MD;
William F. Hoyt, MD
Arch Ophthalmol. 2001;119:516-529.
ABSTRACT
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Objective To demonstrate spontaneous regression of large, clinically symptomatic
optic pathway gliomas in patients with and without neurofibromatosis type
1 (NF-1).
Methods Patient cases were collected through surveys at 2 consecutive annual
meetings of the North American Neuro-Ophthalmology Society (NANOS) and through
requests on the NANOSNET Internet listserv. Serial documentation of tumor
signal and size, using magnetic resonance imaging in 11 patients and computed
tomography in 2 patients, was used to evaluate clinically symptomatic optic
pathway gliomas. All tumors met radiologic criteria for the diagnosis of glioma
and 4 patients had biopsy confirmation of their tumors. In 3 patients, some
attempt at therapy had been made many years before regression occurred. In
one of these, radiation treatment had been given 19 years before tumor regression,
while in another, chemotherapy had been administered 5 years before signal
changes in the tumor. In the third patient, minimal surgical debulking was
performed 1 year before the tumor began to shrink.
Results Spontaneous tumor shrinkage was noted in 12 patients. Eight patients
did not have NF-1. In an additional patient without NF-1, a signal change
within the tumor without associated shrinkage was detected. Tumor regression
was associated with improvement in visual function in 10 of 13 patients, stability
of function in 1, and deterioration in 2.
Conclusions Large, clinically symptomatic optic gliomas may undergo spontaneous
regression. Regression was seen in patients with and without NF-1. Regression
may manifest either as an overall shrinkage in tumor size, or as a signal
change on magnetic resonance imaging. A variable degree of improvement in
visual function may accompany regression. The possibility of spontaneous regression
of an optic glioma should be considered in the planning of treatment of patients
with these tumors.
INTRODUCTION
COMPUTED tomographic neuroimaging studies are now standard for the diagnosis
and management of optic gliomas. These studies are being applied widely in
prospective serial evaluations of changes in these tumors over the course
of months to years.1-6
Venes et al7 in 1984 reported the postoperative
regression of a partially resected chiasmal glioma. Hoffman et al8 in 1993 reported the same postsurgical phenomenon,
as did Takeuchi and colleagues9 in 1997. In
1992, Brzowski and associates10 presented the
first evidence of spontaneous tumor regression recorded by magnetic resonance
imaging (MRI), in a 2-year-old child with neurofibromatosis type 1 (NF-1).
In 1995, Parazzini et al4 noted similar involution
of small, asymptomatic optic gliomas in or around the chiasm in 4 children
with NF-1. Perilongo et al5 and Gottschalk
and colleagues6 reported similar findings in
4 other children in 1999. In 1998, Rubtsova et al reported, in Russian, the
spontaneous regression of a large and clinically symptomatic optic nerve glioma,
documented by serial MRI in a boy with probable NF-1.11-12
We report this case in English, along with 12 additional cases of spontaneously
regressing optic gliomas documented by neuroimaging studies.
REPORT OF CASES
CASE 1
A healthy 5-year-old boy was believed to have severe amblyopia with
hand motion vision in the right eye during a school examination. At age 7
years, right optic disc atrophy was recognized. His left eye was normal. He
had 7 café-au-lait spots, but no Lisch nodules on his irides. There
was no history of NF-1 or ocular problems in his family. Magnetic resonance
scans showed a large (3 x 3 x 3.2-cm) lobulated suprasellar tumor
connected to an expanded right optic nerve within the optic canal and the
orbital apex. In T1-weighted images, the mass seemed homogeneous (Figure 1A).
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Figure 1. A, T1-weighted coronal magnetic
resonance imaging (February 1988) shows a large (3 x 3 x 3.2-cm),
predominantly hypointense, lobulated tumor in the suprasellar cistern. B,
T1-weighted coronal magnetic resonance imaging after contrast (May 1992).
The tumor had decreased in size, measuring approximately 2.1 cm in its greatest
dimension (not shown). Central, nonenhancing foci are seen within the tumor
mass. C, T1-weighted coronal magnetic resonance imaging after contrast (August
1996). There is marked reduction in size of the mass that now measured only
15 x 7 mm. The tumor involved only the right intracranial optic nerve.
The chiasm was normal, and the enhancement is markedly reduced. Later images
(January 2000, not shown) revealed small areas of calcification within the
tumor.
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After neuro-ophthalmologic consultation at the University of California,
San Francisco, the decision was made to follow his case without treatment.
Four years later, at age 11 years, MRI scans showed clear diminution
in size of the suprasellar mass. There was prominent, but nonuniform paramagnetic
enhancement of the central portion of the tumor and a surrounding rim of low-signal
intensity (Figure 1B). Visual acuity
in the right eye had not changed.
At age 15 years, visual function had improved to 20/200 OD. He could
distinguish several pseudoisochromatic plates with the right eye. He had a
generally depressed field most pronounced inferiorly, and atrophy of the right
optic disc. He had been aware of a gradual visual improvement beginning 3
or 4 years earlier. Magnetic resonance imaging scans showed remarkable reduction
in the size of the tumor; it appeared to involve the right optic nerve only.
The area of paramagnetic enhancement within it was greatly reduced (Figure 1C). Four years later, his clinical
examination remained unchanged and MRI scans revealed small areas of calcification
within the tumor. During the 12-year period of follow-up, the patient grew
normally. Molecular genetic analysis, with a sensitivity of 70% for detecting
a mutation in the NF-1 gene, failed to verify or
disprove its presence.
CASE 2
A healthy 4-year-old girl complained of intermittent right eye pain
after having been struck in the right temple. She was brought to the Yale–New
Haven emergency department and was found to have a swollen disc and decreased
vision in the right eye. No family history or stigmata of NF-1 were present.
Computed tomographic (CT) scans disclosed tubular enlargement of the right
optic nerve in the orbit (Figure 2A).
Right frontocranial craniotomy showed the optic nerve was thickened back up
to the optic chiasm, and that the chiasm diameter thickened to approximately
twice its normal size. The right optic tract was also enlarged. A biopsy specimen,
measuring 2 mm in its greatest thickness, was taken anterior to the chiasm.
This was read as pilocytic astrocytoma, type 1.
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Figure 2. A, Axial computed tomographic
images after contrast (December 1983). Enlargement of the right optic nerve
is noted from globe to orbital apex. Coronal views (not shown) confirmed this
thickening. The left optic nerve was normal. The chiasm appeared normal. B,
Axial T1-weighted magnetic resonance imaging after contrast (December 1989).
The right optic nerve was essentially normal except at the orbital apex. Coronal
views within the orbit (not shown) revealed trace enlargement of the right
optic nerve.
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On her first neuro-ophthalmologic examination, visual acuity was 20/70
OD and 20/40 OS. A right afferent pupillary defect was present along with
a 10–prism diopter (PD) esotropia. Visual fields by confrontation revealed
a nasal depression in the right eye. The right optic disc was pale while the
left optic disc was pink. The patient was evaluated without treatment. Three
months later, at age 5 years, her visual acuity had improved to 20/40 OD and
20/25 OS. After a course of patching of the left eye, the patient's vision
was 20/25 OU. Her examination remained stable subsequently, while MRI scans
5 years later, at age 10 years, revealed the right optic nerve to be essentially
normal, with only trace enlargement when compared with the left (Figure 2B).
At age 12 years, visual acuity was 20/20 - 3 OD and 20/20 -
2 OS. The right disc was pale and cupped; the left, pink and flat. At age
17 years, visual acuity was unchanged, and no Lisch nodules were detected.
Computerized static perimetry showed a depressed inferior field in the right
eye. The left visual field was full. Magnetic resonance imaging was unchanged.
CASE 3
A 3-month-old girl presented with vomiting and signs of hydrocephalus.
A CT scan revealed a large, well-circumscribed, midline globular tumor in
the region of the chiasm. After several follow-up visits, a decision to defer
surgery was made based on the stability of her head size. At age 3 years,
the mother noticed that she was bumping into things. One year later, she was
referred to the Neuro-ophthalmology Unit at Hospital Vargas in Caracas, Venezuela,
for abnormal vision. By that time, the mother believed there had been consistent
improvement in her child's vision over the previous year. On examination,
visual acuity was roughly 20/400 OU with sensory nystagmus. Both discs were
chalk-white. There were no stigmata, nor any family history, of NF-1. Review
of the CT scans previously obtained at ages 7 months, 1 years, and
4 years revealed progressive shrinkage of her tumor (Figure 3A-C). Magnetic resonance imaging scans obtained at age 4
years showed small residual chiasmal tumor. The girl was visually handicapped,
but was otherwise healthy.
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Figure 3. A, Axial computed tomographic
imaging (May 1993) shows a large, midline, well-circumscribed mass at the
chiasm. There is severe brain atrophy. B, Axial computed tomographic imaging
(April 1994). There is marked reduction in the size of the mass. C, Axial
computed tomographic imaging (September 1996) shows further reduction in the
size of the mass.
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CASE 4
A 13-year-old boy was referred to the Neuro-ophthalmology Unit
at the Mayo Clinic, Rochester, Minn, for pain and disc edema. He had had an
upper respiratory infection 6 weeks before evaluation, with the onset of "bad
headaches" and pressure behind the left eye over the previous 4 weeks.
Corrected visual acuity was 20/20 OU. However, he had a mild relative
afferent pupillary defect on the left. Computerized perimetry revealed minimal
depression of the field with slight enlargement of the blind spot in the left
eye. No Lisch nodules were present. The left disc was chronically swollen
without hemorrhages. There were no stigmata of NF-1. Magnetic resonance imaging
scans revealed a fusiform enlargement and kinking of the left optic nerve,
extending from globe to the chiasm (Figure
4A-C).
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Figure 4. A, Axial T1-weighted magnetic
resonance imaging (December 1994) shows fusiform enlargement of the left optic
nerve, extending from the anterior aspect of the chiasm up to the globe. The
nerve had a prominent kink. B, After contrast, the nerve enhanced markedly,
most notably at the chiasm. C, Coronal T1-weighted magnetic resonance imaging
after contrast (December 1994) shows marked enlargement and enhancement of
the left optic nerve. D, Coronal T1-weighted magnetic resonance imaging with
paramagnetic contrast infusion 2 years later (December 1996) showed noteworthy
shrinkage of the tumor with no enhancement.
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Six months later headaches had resolved. Corrected visual acuity remained
20/20 OU, and there was only a trace afferent pupillary defect on the left.
The left disc was hyperemic, but not swollen. Magnetic resonance imaging at
age 14 years revealed that the tumor no longer enhanced and that it
had shrunk. At age 15 years, the relative afferent pupillary defect had disappeared
and the fundi were normal. Magnetic resonance imaging 6 months afterward revealed
that the tumor no longer enhanced and had also shrunk in size (Figure 4D). At 16 years of age, another scan revealed further
shrinkage of the tumor in its axial dimension.
CASE 5
A 13-year-old boy was evaluated at the University of Wisconsin, Madison,
for bilateral decreased vision of 1 year's duration. Visual acuity was 20/50
OD and 20/200 OS. He had bitemporal hemianopia and bilateral disc pallor.
Magnetic resonance imaging revealed a large homogeneous (in T1-weighted images)
chiasmal tumor consistent with glioma (Figure
5A). It enhanced with gadolinium and had a cystic area above the
right optic nerve. Abnormal signal was present in both optic tracts in T2-weighted
images. There was no family history of NF-1. The boy's growth was subnormal.
A craniotomy was performed. The optic nerve on the left side appeared grossly
abnormal, with a large mass extruding laterally, inferiorly, and medially.
Debulking of the tumor was performed by Cavitron ultrasonic aspiration. Debulking
of the right side of the chiasm was not attempted. Tumor fragments submitted
for pathological examination were in aggregate 3.0 x 2.0 x 1.0
mm and read as optic nerve glioma. Postoperatively, visual acuity was 20/80
OD and counting fingers at 1 ft OS with a total nasal field loss in the left
eye. The postoperative MRI scans showed no perceptible change in the size
of the tumor, no change in size of the cyst above the right optic nerve, persistent
high signal intensity along both tracts, and continued enhancement. Seven
months after surgery, visual acuity was 20/40 OD and 1/200 OS, with some improvement
of the temporal field bilaterally, but with persistence of a quadrantic inferonasal
field defect in the left eye.
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Figure 5. A, Sagittal T1-weighted magnetic
resonance imaging after paramagnetic contrast (October 1990) shows a large,
homogeneous chiasmal tumor. Separate T2-weighted images showed abnormal signal
along both optic tracts. B, Sagittal T1-weighted magnetic resonance imaging
after paramagnetic contrast (September 1992). Marked shrinkage of the tumor
occurred in all dimensions with minimal enhancement of the tumor. There was
no abnormal signal along the optic tracts on separate T2-weighted images.
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At age 14 years, visual acuity was 20/20 OD and 2/200 OS. Magnetic resonance
imaging scans now revealed shrinkage of both the solid and cystic components
of the tumor as well as decreased enhancement of the tumor and decrease in
the signal intensity along the optic tracts.
At age 15 years, visual acuity was 20/20 OD and 20/40 OS. While the
complete inferonasal defect persisted, the bitemporal field defects continued
to resolve. Magnetic resonance imaging scans now revealed marked shrinkage
in all dimensions of the tumor with minimal enhancement (Figure 5B). No abnormal signal was noted along the optic tracts
on separate T2-weighted images. At age 16 years, visual acuity improved to
20/25 OS. No further changes were noted in his MRI scans. At 20 years of age,
his tumor remained the same and he remained healthy.
CASE 6
A 14-year-old girl was referred to the Wilmer Ophthalmological Institute
after incidentally discovering decreased vision in her left eye. Visual acuity
was 20/15 OD and counting fingers at 4 ft OS. Automated threshold perimetry
revealed a full field in the right eye and a small superotemporal island of
vision in the left. The right disc was normal, while the left had mild temporal
pallor. The left eye was slightly proptotic (3 mm). No Lisch nodules or other
stigmata of NF-1 were present. Magnetic resonance imaging scans revealed an
enhancing cranio-orbital glioma with a prominent distal kink (Figure 6A and B). The tumor abutted the chiasm. Three months later
the patient reported improved vision. Her visual acuity was now 20/25 -
1 OS with pinhole. She had only a trace afferent pupillary defect. She could
now distinguish 6 of 12 pseudoisochromatic plates. Computerized perimetry
showed the left field had broadened out and lightened remarkably. Magnetic
resonance imaging scans showed the optic nerve to be smaller with less enhancement.
Two months later, visual acuity had improved to 20/25 OS and the patient could
distinguish 10 of 12 color plates. One month later, MRI scans revealed the
nerve to be smaller still and only very mildly enhancing (Figure 6D). Five months later visual acuity was 20/20 + 3 OS. Stereopsis
was normal. Perimetry revealed minimal reduction in sensitivity of the field
of the left eye. Magnetic resonance imaging scans 1 month later showed continued
shrinkage of the tumor along its entire course, with decrease in signal intensity
(Figure 6C). Eight months later,
visual acuity was 20/15 - 1 OS without an afferent pupil defect. Exophthalmometry
now showed recession of the left eye compared with the right.
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Figure 6. A, T2-weighted axial magnetic
resonance imaging (August 1997) shows a fusiform enlargement of the optic
nerve, hyperintense and homogeneous in signal intensity from the globe up
to the chiasm, measuring 1.5 x 2.5 cm in its intraconal course. The
left globe is proptotic. There is widening of the left neural foramen. B,
T1-weighted coronal magnetic resonance imaging after contrast (August 1997).
There is marked enlargement of the left intraorbital optic nerve, with prominent
and homogeneous signal enhancement. C, T2-weighted magnetic resonance imaging
(August 1998) shows shrinkage of the optic nerve tumor along its entire course,
with decrease in signal intensity, now measuring 0.8 x 1.8 cm in its
intraconal course. The left globe is no longer proptotic. D, T1-weighted coronal
magnetic resonance imaging (March 1998) shows clear reduction in optic nerve
diameter, with only trace signal enhancement centrally after paramagnetic
contrast infusion.
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CASE 7
An 11-year-old girl with a family history of NF-1, diagnosed as having
bilateral stable amblyopia since age 6 years, was referred to Foothills Hospital
in Calgary, Alberta. Visual acuity was 20/70 OD and 20/60 OS. Tangent screen
perimetry revealed a generalized depression, more so temporally, in the left
eye, with an absolute temporal hemianopia in the right eye. Numerous Lisch
nodules were present. Both optic discs were pale. Computed tomographic scans
showed a slightly dense enhancing suprasellar lesion between 2 and 3 cm in
diameter, with extension along both optic tracts. Three months later, the
patient reported further loss of vision. Visual acuity was 20/80 - 1
OD and 20/70 - 1 OS. Tangent screen perimetry detected shrinkage of
nasal field in the right eye. Three months later, visual acuity was somewhat
improved and fields were unchanged. Magnetic resonance imaging scans revealed
a globular enlargement of the chiasm that extended along the tracts bilaterally,
corresponding to the previous CT scan findings. Signal intensity was inhomogeneous
in T1-weighted images and lower on the right, possibly representing areas
of tumor necrosis (Figure 7A). There was a large T2-weighted high-signal lesion
in the region of the left internal capsule and lentiform nucleus without mass
effect, probably representing a hamartoma or a very low-grade glioma (Figure 7E).
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Figure 7. A, T1-weighted coronal magnetic
resonance imaging (MRI) (February 1990) shows globular enlargement of the
chiasm. Signal intensity is inhomogeneous to the right where it is lower.
B, T1-weighted coronal MRI (December 1996). The tumor has shrunk in size,
and in the midline, its signal intensity is less homogeneous. There are areas
of decreased signal intensity mainly on the right side of the chiasm and midline.
C, T1-weighted coronal MRI after contrast (April 1994). The tumor enhances
irregularly, with very high intensity mostly to the right and midline. Little
change was noted from previous MRI scans. D, T1-weighted coronal MRI after
contrast (December 1996). The tumor has shrunk in size as has its enhancing
portion. The enhancing portions correspond to the areas of low signal intensity
on the images taken without contrast, shown top right. E, T2-weighted axial
MRI image (February 1990). Reasonably large, high-signal lesion in the region
of the left internal capsule, lentiform nucleus, and midline with no mass
effect. These lesions probably represent hamartomas. F, T2-weighted axial
MRI (December 1996). The hyperintensities are markedly reduced and are now
barely perceptible.
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Eight months later, visual acuity dropped to 20/200 OD and 20/70 OS.
Tangent screen examination showed further contraction of the nasal field in
the right eye, but repeated MRI scans did not detect changes in the size of
the tumor. Eighteen months later, visual acuity dropped to 20/400 OD, but
remained 20/50 OS with further depression of the right nasal visual field.
Six months later, visual acuity continued to drop in the right eye, down to
counting fingers at 10 ft. Magnetic resonance imaging scans showed no change.
Nine months later visual acuity continued to decline in the right eye, to
counting fingers at 2 ft while remaining stable at 20/50 OS. Seven months
later clinical and neuroimaging findings remained unchanged (Figure 7C). Sixteen months later, MRI scans showed uniform shrinkage
of the tumor (Figure 7B and D).
Areas of decreased signal intensity were again noted on the right side of
the chiasm (Figure 7B). The T2-weighted
hyperintensities in the basal ganglia were less bright (Figure 7F). Magnetic resonance imaging scans 1 year later, at age
18 years, showed a continued uniform shrinkage of the tumor. The patient's
vision remained unchanged.
CASE 8
A 4-month-old boy was referred to the Pediatric Ophthalmology
Unit at the University of California, San Francisco, for progressive "shakiness"
of the eyes, with extreme photophobia. Fixation was central in the right eye,
and unmaintained in the left, with occasional head nodding. Both pupils reacted
sluggishly to light, but no relative afferent pupillary defect was present.
No family history of NF-1 was present. A CT scan detected an enhancing mass
thickening the left optic nerve with widening of the left optic foramen along
with mild thickening of the right optic nerve. Chiasmal involvement was not
evident. Magnetic resonance imaging scans confirmed the presence of the tumor
with extension into the chiasm and optic tracts (Figure 8A and B), with no other brain abnormalities. A 15-PD left
esotropia developed over the following months and patching therapy was instituted
while the nystagmus gradually dampened. By age 6 years, visual acuity was
20/20 OD and 20/400 OS with eccentric fixation, with full visual fields by
confrontation. There no longer was any nystagmus and strabismus surgery was
performed for a 30-PD left esotropia. Trace optic atrophy was present in the
right eye, with marked atrophy in the left. Although MRI scans had clearly
disclosed no tumor growth, it was later clear by age 5 years that substantial
reduction of the chiasmal portion of the tumor had already occurred and that
the left side of the chiasm was now smaller than the right (Figure 8C). By age 8 years, left eye visual acuity had declined
to counting fingers at 2 ft, but was unchanged in the right eye with a full
field on computerized perimetry. An MRI scan showed the entire chiasm to be
essentially normal in size and signal intensity (Figure 8D). The optic nerves remained unchanged, with prominent
tubular enlargement, kinking, and a "pseudo-CSF" sign.13-14
A genetics evaluation of the patient, his parents, his 2 siblings, and 2 grandmothers
failed to diagnose NF-1 in any member. Computerized perimetry continued to
show a full field in the right eye and he could identify all pseudoisochromatic
plates with the right eye. Lisch nodules remained absent. At age 12 years,
his MRI scan revealed that marked reduction of the diameters of both optic
nerves had occurred. The right optic nerve was normal in size and signal intensity,
while vision remained unchanged bilaterally. The boy grew normally and remained
otherwise healthy.
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Figure 8. A, T1-weighted coronal magnetic
resonance image (May 1986) shows enlargement of the chiasm, more prominent
on the left. B, T1-weighted coronal magnetic resonance image (May 1986) shows
bilateral, optic nerve enlargement, more pronounced on the left. A prominent
rim of low-signal intensity surrounds a central core of higher signal intensity,
more so on the left than the right, the so-called pseudo-CSF fluid sign.13-14 C, T1-weighted coronal magnetic resonance
image (February 1991) shows marked reduction in the size of the chiasmal portion
of the tumor. Furthermore, the left side is now smaller than the right. D,
T1-weighted axial magnetic resonance image after contrast (July 1994) now
shows the chiasm to be essentially normal in size and signal intensity. However,
both optic nerves continue to show prominent tubular enlargement with kinking.
Later images (October 1997, not shown) revealed marked reduction of the diameters
of both optic nerve tumors.
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CASE 9
A healthy 3-month-old boy with no family history of NF-1, but with multiple
café-au-lait spots, underwent neurological and pediatric neuro-ophthalmological
examinations at the University of California, San Francisco. All examinations
were normal. High-quality MRI scans of the brain and spine, with and without
paramagnetic contrast infusion, detected no abnormalities. Neither parent
had Lisch nodules or a history of NF-1. At 15 months of age, 2 small cutaneous
neurofibromas developed in the boy. Six months later, MRI scans demonstrated
an enhancing chiasmatic mass (2.0 x 1.2 x 1.2 cm) with some extension
posteriorly into the optic tracts. Both intracranial portions of the nerves
were enlarged and enhanced. No areas of high signal on T2-weighted images
were present elsewhere in the brain. However, areas of mild T2-weighted increased
signal intensity within the white matter tracts of the cerebellum and surrounding
the occipital horns were present, thought to represent early glial rests.
Observation was chosen. Magnetic resonance imaging scans were repeated 3 months
later and demonstrated a slight increase in the size of the tumor (2.3 x
1.7 x 1.7 cm) (Figure 9A).
His eye examination at that time revealed central, steady, and maintained
vision in the right eye, with central, steady, but unmaintained vision in
the left with a small angle esotropia. Four months later, visual acuity using
picture optotypes was a brisk 20/20 OU. Visual fields were full to confrontation
testing and there was no relative afferent pupillary defect. Trace left optic
disc atrophy was noted. Repeat MRI revealed slightly less enhancement of the
tumor, while a scan 3 months later detected no other changes in tumor characteristics.
Another scan 3 months later, however, showed a significant decrease in contrast
enhancement of the tumor with some possible shrinkage. Three months later,
a scan detected clear-cut shrinkage with further reduction in enhancement.
The mild T2-weighted abnormalities were not changed significantly in position
or intensity, particularly in the area of the atria and occipital horns of
the lateral ventricles. Four months later, continued decrease in tumor enhancement
was noted, while 4 months thereafter, visual acuity (picture optotypes) remained
a brisk 20/20 OU with full fields on confrontation testing. Magnetic resonance
imaging at this time revealed a marked decrease in signal enhancement and
a marked decrease in the size of the tumor; an MRI 6 months later revealed
a continued spontaneous decrease in the size of the tumor, with an essentially
normal chiasm (Figure 9B). The T2-weighted
signal abnormalities in the brachium pontis bilaterally, dentate nucleus of
the cerebellum, and optic tracts were similar to previous studies. At age
4 years, visual acuity remained 20/20 OU with no nystagmus or strabismus present.
Lisch nodules were absent, while the boy remained healthy, well-developed,
and quite bright.
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Figure 9. A, T1-weighted coronal magnetic
resonance imaging after contrast (August 1996). There is an enhancing chiasmal
tumor (2.3 x 1.7 x 1.7 cm). There was bilateral optic nerve involvement
extending beyond the orbital apex on separate images. Previous magnetic resonance
imaging (August 1994, not shown) revealed a normal chiasm and optic pathways.
B, T1-weighted coronal magnetic resonance imaging after contrast (July 1998).
The tumor has markedly decreased in size with essentially no enhancement.
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CASE 10
A 6-month-old boy diagnosed as having spasmus nutans and right hemianopia
was followed up at the Meir General Hospital in Kfar-Saba, Israel. No family
history of NF-1 was present. Computed tomographic scans at 1 year of age showed
an enhancing suprasellar mass and enlargement of the right optic nerve. Magnetic
resonance imaging scans at 14 months of age disclosed tumor involving the
optic chiasm, the left optic tract and some evidence of extension into the
basal ganglia.
At 2 years of age, the boy was nearly blind in the right eye.
Both discs were pale temporally. At 3 years of age, visual acuity
had declined to finger counting at 6 ft OS. Repeat MRI scans revealed involvement
of both optic tracts with the tumor extending to the left lateral geniculate
body and the mesial portions of the temporal lobe. In view of the continued
loss of vision, chemotherapy, consisting of vincristine and actinomycin D,
was given over an 18-month period, from ages 3 to 5 years. The patient's
vision continued to worsen, and on Goldmann perimetry, his remaining island
of vision continued to shrink. From ages 7 to 9 years, no vision could be
detected in his right eye. Magnetic resonance imaging scans at age 8 years
showed tumor in the optic tracts bilaterally, a left thalamic component, and
a left peduncular component (Figure 10A
and B). At age 9 years, he was seen at the University of California, San Francisco,
where only light perception in the right eye was confirmed. Visual acuity
was 20/200 OS with a constricted and depressed field. He remained otherwise
healthy. Three months later, the patient reported the ability to see out of
the right eye. Visual acuity was now counting fingers at 1.7 ft OD, and he
had a large central scotoma within a small field. Visual acuity was 20/100
OS with a field that had expanded slightly. Magnetic resonance imaging scans
did not show any changes in the tumor. Progressively over the next 6 years,
by age 15 years, visual acuity had improved to 20/300 OD and 20/70 OS. Computerized
perimetry revealed a temporal hemianopia in the right eye with a superior
field defect in the left eye. Magnetic resonance imaging scans at age 15 years
did not detect a change in the size of the chiasmal portion of the tumor,
but the optic tracts bilaterally, the left thalamic component, and the left
peduncular component were all decreased in signal intensity (Figure 10B and C). At age 16 years, 2 discrete areas of decreased
signal on T1-weighted MRI scans were noted on each side of the chiasm.
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Figure 10. A and B, Proton density–weighted
axial magnetic resonance imaging scans (April 1990). There is increased signal
intensity of the tumor in both optic tracts, a left thalamic component, and
a left peduncular component. Other images (not shown) revealed nonenhancing
involvement of the right optic nerve, a well-circumscribed bilobed chiasmal
mass with extension lateral to the right optic nerve, and involvement of the
left optic tract through to the occipital pole. C and D, Proton-density axial
magnetic resonance imaging scans (June 1996). There is decreased signal intensity
of both optic tracts, the left thalamic component, and the left peduncular
component of the tumor. The chiasmal portion of the tumor did not change in
size on scans between January 1984 and July 1997 (not shown).
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CASE 11
A 2-year-old boy underwent CT imaging with contrast for spasmus nutans,
which revealed the presence of a chiasmal mass. A biopsy confirmed the diagnosis
of pilocytic astrocytoma, type 1. No stigmata of NF-1 were present. He was
referred for follow-up to the Neuro-ophthalmology Unit at the British Hospital,
Buenos Aires, Argentina. Visual acuity was difficult to assess at the time
because of the lack of patient cooperation. At age 5 years, acuity was estimated
to be 20/200 OU. His mother and his schoolteachers believed, however, that
his vision had improved from previous years. Both optic discs appeared atrophic.
An MRI scan revealed a large, symmetric, globular, relatively homogeneous
suprasellar mass with preserved contours. Both optic tracts appeared involved
(Figure 11A and B). One year later,
at age 6 years, visual acuity was 20/100 OU. At age 8 years, visual acuity
was unchanged. Computerized perimetry at this point revealed a generalized
depression of the field with bilateral, temporal defects, greater on the left.
At age 10 years, magnetic resonance imaging revealed marked shrinkage of the
tumor, with a now normal right optic tract. Only the right side of the chiasm
enhanced with contrast (Figure 11C
and D). At 11 years of age, the boy reported having improved vision. Visual
acuity remained 20/100 OU, although brisker. Computerized static perimetry
also revealed an improvement, with less dense defects. Magnetic resonance
imaging scans showed complete regression of the tumor (Figure 11E and F). Trace, if any, contrast enhancement of the chiasm
remained. At 12 years of age, the boy was healthy with moderate visual handicap.
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Figure 11. A, T1-weighted axial magnetic
resonance imaging (MRI) (April 1992) shows a homogeneous, large, symmetric
suprasellar mass. Both optic tracts appear involved. B, T1-weighted sagittal
MRI (April 1992). A large, relatively homogeneous, globular tumor involving
the chiasm completely occupies the suprasellar cistern. C, T1-weighted coronal
MRI after contrast (December 1997) shows only mild enlargement of the chiasm.
Contrast signal enhancement is limited to the right lateral aspect of the
chiasm. D, T1-weighted sagittal MRI after contrast (December 1997) showed
marked reduction in chiasmal size with normal right optic tract and right
nerve. Contrast signal intensity was homogeneous in this off-midline sagittal
section. E, T1-weighted coronal MRI after contrast (February 1999). The chiasm
showed trace, if any, enhancement, and was normal in size. F, T1-weighted
sagittal MRI after contrast (February 1999). There was no enlargement or enhancement
of the chiasm. All structures appeared normal.
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CASE 12
A 3-year-old boy was referred for neuro-ophthalmologic consultation
at the São Paulo University Hospital, São Paulo, Brazil, after
reduced vision led to difficulties at school. Visual acuity was 20/80 OD and
counting fingers at 10 ft OS. Goldmann perimetry revealed bitemporal field
defects with additional paracentral defects in the left eye. The right optic
disc was slightly pale and the left disc moderately so. Lisch nodules and
café-au-lait spots were present in both the patient and his father.
Magnetic resonance imaging revealed a large, lobulated suprasellar tumor,
relatively homogeneous in T1-weighted images (Figure 12A). The boy had a slight delay in puberty, but no endocrine
abnormalities were found. After consultation with the family, the decision
was made to observe the boy. Nine months later, visual acuity had improved
to 20/30 OD and to 20/200 OS. Corresponding improvements were also noted in
the visual fields, obtained by the same experienced perimetrist. An MRI scan
5 months afterward, at age 15 years, revealed a substantial reduction in the
size of the tumor (Figure 12B).
Fifteen months later, at age 16 years, visual acuity continued to improve
to 20/20 OD and 20/40 OS, with corresponding improvements in the visual fields.
Magnetic resonance imaging revealed only minimal further reduction in the
size of the tumor. Fifteen months later, visual acuity and fields were unchanged
and the boy remained healthy.
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Figure 12. A, T1-weighted coronal magnetic
resonance imaging after contrast (May 1994) showed a large, lobulated tumor
in the suprasellar cistern, homogeneous in signal intensity. Note that the
tumor nearly filled much of the cistern both vertically and horizontally.
B, T1-weighted coronal magnetic resonance imaging after contrast (July 1995).
There was marked reduction in the size of the tumor. The pituitary stalk was
visible in the midline inferiorly.
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CASE 13
In Glasgow, a 3-year-old girl with hydrocephalus was found to have a
third ventricular tumor. The tumor was biopsied and found to be a juvenile
pilocytic astrocytoma, type 1. No stigmata or family history of NF-1 were
present. A ventriculoperitoneal shunt was placed and the patient underwent
radiotherapy. Clinical signs of precocious puberty developed and she received
hormonal treatment for gynecomastia. At that time, she was noted to have bilateral
optic atrophy with impaired vision.
At age 10 years, she presented with left hemiplegia, left facial weakness,
and moderate left-sided ataxia. A CT scan showed a large tumor deep in the
right temporoparietal region with compression of the posterior end of the
third ventricle. The lateral ventricles were enlarged. Her visual acuity was
20/80 OD and 20/40 OS, reportedly an improvement from her previous examination
4 years earlier. Visual acuity measurements from the previous examination,
however, are no longer available. Pupillary reactions were noted to be sluggish.
At age 11 years, best-corrected visual acuities were 20/200 OD and 20/60 OS.
Eight years later, at age 19 years, the patient's visual function was
unchanged. At age 20 years, she complained of intermittent dizziness with
staggering, blurring, and deterioration of her vision, and frequency of urination.
She was obese and had clinical panhypopituitarism. Visual acuity was counting
fingers OD and 20/80 OS, with a bitemporal hemianopia. A CT scan showed a
suprasellar tumor mass and dilatation of the ventricles (Figure 13A). Some calcification was noted on the right posterior
aspect of the tumor.
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Figure 13. A, Axial computed tomographic
scan (July 1988) reveals a suprasellar tumor. There was some calcification
on the right posterior aspect of the mass. B, Axial computed tomographic scan
(February 1992) showed marked regression of the tumor. Calcification within
the tumor was located closer to midline. C, Axial computed tomographic scan
(December 1996) showed continued regression of the tumor. Basal calcification
was more extensive, in proximity to the midline.
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Eight months later, the patient continued to gain weight and suffered
from polyuria and polydipsia. A CT scan showed an increase in the size of
the tumor, although vision remained unchanged. Ten months later, at age 21
years, the patient demonstrated continued stability of her visual function.
She had her first MRI scan, which showed that the tumor could not be differentiated
from the optic chiasm, and that there was associated edema extending into
the optic tracts. Eight months later, her appetite seemed to normalize along
with her urinary frequency, while her vision remained unchanged. A year later,
she showed signs of continued improvement with significant weight loss and
return of her menstrual periods. A CT scan 1 year later showed spontaneous
regression of the tumor by about 75% to 80% of its original size, with the
calcified portions of the tumor now apparently pulled closer to midline (Figure 13B). Three years later, at 27 years
of age, a CT scan showed more extensive bilateral basal calcification. Another
CT scan 16 months later revealed further reduction in the size of the tumor,
with calcified areas seen only in proximity to the midline (Figure 13C). Visual acuity was light perception OD and 20/200 OS.
Visual field assessment revealed a small nasal field in the left eye. Repeat
CT imaging 2 years later showed no change in the residual calcified suprasellar
lesion. There was no significant change in her visual function. At 31 years
of age, there were still no Lisch nodules or other stigmata of NF-1.
COMMENT
Spontaneous regression of juvenile pilocytic astrocytomas involving
the optic nerves and chiasm is a fact as exemplified by the 13 serially imaged
cases in this report. We do not know the frequency of this tumor behavior,
but we suspect that it is relatively high. The occurrence of spontaneous regression
of optic gliomas may be masked by several phenomena. Many gliomas occur and
are not detected, as NF-1 neuroimaging surveys have shown.1-3,15-17
These tumors can regress. Spontaneous regression can be overlooked in patients
known to harbor an optic glioma whose clinical condition has remained stable
for many months or years and for whom repeat scans are not performed, or for
whom the older scans are no longer available for comparison.
The cellular mechanisms in these low-grade gliomas that lead to their
regression remain a mystery. Lindenberg et al18
must have believed that an optic glioma could regress, for in 1973, he entitled
such an event in a necropsy illustration of an incidentally discovered chiasmal
thickening. Borit and Richardson19 in 1982
reported a case of biopsy-proven chiasmal glioma that spontaneously disappeared
as proven at necropsy 13 years later. These neuropathologists also presented
a second case of an incompletely resected orbital glioma that totally regressed.
The report of Liesti et al20 in 1996 exemplifies
another histologically proven instance, wherein a juvenile pilocytic astrocytoma
of the temporal-hypothalamic region regressed spontaneously. In 1999, Lazareff
and colleagues21 referred to 4 cases of histologically
proven hypothalamic chiasmatic gliomas that partially regressed. Schmandt
and coworkers22 and Colosimo and associates23 in 2000 each reported a case of biopsy-proven chiasmal
pilocytic astrocytoma that underwent spontaneous regression. Higher-grade
gliomas may also regress. Kernan and colleagues24
and Lenard and coworkers25 in 1998 provided
histological evidence for spontaneous regression of a fibrillary astrocytoma
of the hypothalamus and pons respectively.
Various theories have been proposed in the past to account for cases
in which spontaneous reduction in glial tumor size had been presumed or suspected.26-27 These include an endocrine-associated
decrease in vascular engorgement of the glioma, resorption of glioma-secreted
mucosubstance, or tumor cell necrosis secondary immunologic activity. We suggest
that other mechanisms, such as programmed cell death (apoptosis) outpacing
proliferation of cells may be involved. Given that the proliferation of juvenile
pilocytic astrocytoma cells slows down with age,28
it is plausible to think that given enough time, and the patient ability to
endure its presence, most such tumors would regress.
Several neuroimaging studies16, 29-30
have shown that at least 20% of NF-1 patients have gliomas. These studies
and others1, 17, 30, 32-35
have also indicated or shown T2-weighted signal abnormalities at some point
in as many as 80% of patients with NF-1. The fact that both T1- and T2-weighted
MRI signal abnormalities in NF-1 patients disappear later in life is indicative
that a process of spontaneous glial regression must be widespread.31-32,36 Neurofibromatosis
type 1 is not a requirement for regression of an optic glioma. Only 4 of our
13 cases involved patients with NF-1 (Table
1).
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Summary of Clinical and Neuroimaging Findings*
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It is crucially important that spontaneous regression of optic gliomas
be taken into consideration whenever the results of therapy (surgical debulking,
radiation, and chemotherapy) are being evaluated. We believe that examples
of optic glioma regression following partial resection could represent examples
of spontaneous tumor regression. In select cases, debulking could, however,
create sufficient space for continued tumor growth while sparing adjacent
structures. In some instances, this might permit the tumor to age sufficiently
enough to enter a phase of regression. The role of radiation and chemotherapy
in induction of tumor regression is more difficult to define. However, delayed
regression long after therapy should probably be regarded as spontaneous.
In this discussion, we wish to make several observations regarding visual
function in patients with regressing gliomas. Ten of our 13 cases demonstrated
improved vision with decrease in the size of the tumor or decrease in its
signal intensity (Table 1). Improvement
in vision was variable and did not correlate with the degree of tumor shrinkage.
Implications of these cases and others like them are obvious. The fact
that clinically significant intracranial or intraorbital optic gliomas may
spontaneously regress in patients with and without NF-1 must be entertained
in planning their treatment. To assess the frequency of such regressions,
a review of serial imaging collected to date, and additional time and observation,
from ongoing prospective MRI studies of NF-1 gliomas and non–NF-1 gliomas
is needed.
AUTHOR INFORMATION
Accepted for publication August 22, 2000.
Presented in part at the annual meetings of the Neuro-Ophthalmological
Society, Keystone, Colo, February 10, 1997, and Orlando, Fla, March 23, 1998.
We thank the North American Neuro-Ophthalmology Society, Albuquerque,
NM, for creating and maintaining the NANOSNET Internet listserv, making this
study possible; the Laboratory Corporation of America, Burlington, NC, for
undertaking molecular analysis for the NF-1 gene
in case 1; and Ben Kilburg, for his assistance in preparing the photographs.
Corresponding author/reprints: Cameron F. Parsa, MD, Maumenee 517, The
Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-9237 (e-mail: cparsa{at}jhmi.edu).
From the Wilmer Ophthalmological Institute, Johns Hopkins University
School of Medicine, Baltimore, Md (Drs Parsa and Repka); Department of Ophthalmology,
San Francisco School of Medicine, University of California, San Francisco
(Drs C. Hoyt and W. Hoyt); the Department of Ophthalmology and Visual Science,
Yale University School of Medicine, New Haven, Conn (Dr Lesser); the Departments
of Ophthalmology and Visual Sciences (Dr Weinstein) and Radiology (Dr Strother),
University of Wisconsin School of Medicine, Madison; Neuro-ophthalmology Unit,
Hospital Vargas, Caracas, Venezuela (Drs Muci-Mendoza and Ramella); Neuro-ophthalmology
Unit, Department of Ophthalmology, Sapir Medical Center, Meir Hospital, Kfar-Saba,
Israel (Dr Manor); the Departments of Clinical Neurosciences and Surgery (Ophthalmology),
University of Calgary, Calgary, Alberta (Dr Fletcher); Department of Ophthalmology,
Mayo Clinic, Rochester, Minn (Dr Garrity); Neuro-ophthalmology Unit, British
Hospital, Buenos Aires, Argentina (Dr Monteiro); Department of Ophthalmology,
Faculty of Medicine of the University of São Paulo, São Paulo,
Brazil (Dr Monteiro); Neuro-ophthalmology Unit, Institute of Neurological
Sciences, Southern General Hospital, Glasgow, Scotland (Dr McFadzean); and
the Department of Ophthalmology, Pavlov State Medical University, St Petersburg,
Russia (Dr Rubtsova).
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