Allen
D. Elster,
MD
Elias
G. Theros,
#{149}
Cranial Imaging Osteopetrosis Part
and
The authors reviewed cranial imaging studies (radiographs, computed tomographic scans, and magnetic resonance [MR] images) in 13 infants and children with the autosomal recessive form of osteopetrosis to characterize
of skull
patterns
base,
and cranial nerve involvement sentation and with progression disease. Marked sclerosis and tion
of osteopetrotic
bone
brain, at preof deposi-
was noted
along the anterior (but not posterior) occipitomastoid suture (n = 8), at the basioccipital-exoccipital synchondrosis (n 9), and along the sphenooccipital synchondrosis (n = 8). Endobones, presumably representing unresorbed primitive ossification centers, were seen in the sphenoidal body and basioccipital bone in 11 of the 13 patients. Marked cupping at the basioccipital-exoccipital synchondrosis was observed in three. Neurologic deficits included blindness (n = 11), conductive hearing loss (n = 11), and facial nerve palsies (n = 4). Delayed myelination was seen with MR imaging in two of five retarded infants, including one with a docu-
mented
coexisting
neuronal
storage
defect. Prominent extracerebral cerebrospinal fluid spaces were present
over the frontal eight
lobes
in five of the
developmentally
normal patients, representing either subclinical parenchymal disease or a phenome-
non related rates
to discordant
between
skull
Key, MD2
#{149}
in Autosomal
Base
II#{149} Skull
L. Lyndon
MD
O
STEOPETROSIS
a family
represents
of bone abnormalities characterized by a generalized increase in the density of the skeleton. In part I of this series (1), we described in some detail the radiologic abnormalities in portions of the skull derived pnncipally from membranous bone, including the mandible, middle of the face, and calvarium. In this part, we describe the computed tomographic (CT) and magnetic resonance (MR) imaging findings in those portions of the skull derived principally from cartilage, including the central skull base, temporal bone, and occipital bone. We also discuss imaging findings related to involvement of the central nervous system that may accompany the bone abnormalities.
SUBJECTS
AND
METHODS
The patients consisted of 13 infants and children with biopsy-proved osteopetrosis referred
for cranial imaging over a 6-year All of the patients had at least one set of conventional skull radiographs, a period.
routine cranial CT scan, and high-resolution (1.5-mm) CT scans of the orbits, skull base, and temporal bones. Six patients underwent cranial MR imaging, and follow-up CT scans and/or MR images were available in nine patients. Details of patient history and technical factors pertain-
vous
system
MR studies
was
were
evaluated
ophthalmologist,
can be
at
least
All
once
a pediatric
and nerpatients
by a pediatric
neurologist,
Departments of Radiology (A.D.E., and Pediatrics (L.L.K.), Bowman Gray School of Medicine, Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157-1022. Received August 30, 1991; revision requested October 14; revision received October 23; accepted November 13. Address reprint requests to A.D.E. 2 Current address: Department of Pediatrics, I
From
extensive.
the
E.G.T., M.Y.M.C.)
Index
Bones,
terms:
Bones,
abnormalities,
osteochondrodysplasias,
growth
and
development,
iO.i2i4 10.1211
#{149} Nerves,
cranial,
#{149} Skull,MR,10.12i4
12.1552
12.1552
#{149} Brain,
iO.i552
#{149} Brain,
iO.1552
#{149} Skull,
MR. CT,
Medical ton,
Radiology
1992;
183:137-144
MD
Recessive
found in part I of this series (1). Clinical evaluation of the head
growth
Y. M. Chen,
Brain’
ing to the CT and
and brain.
Michael
#{149}
©
SC. RSNA,
University 1992
of South
Carolina,
Charles-
and an otolaryngologist. and/or
brain
Audiograms
stem-evoked
potentials
obtained in every case. Specialized logic tests (such as visually evoked sponses
and
were
neurore-
electroencephalography)
were performed in selected cases to supplement the clinical and radiologic examinations. A summary of the clinical findings in
these
patients
is presented
Criteria for optic based on standards children established (2).
We
used
a 3-mm
limit for normal patients
younger
in Table
diameter
as the lower
size of the optic canal in than 2 years of age and 4
mm for those aged 2-12 years. the optic nerve was diagnosed
diameter
1.
canal stenosis were for healthy infants and by Harwood-Nash
on coronal
images
Atrophy of when its
was less than
3mm(3).
RESULTS A relatively large number of new and consistent findings concerning involvement of the skull base by osteopetrosis were observed. We now describe, illustrate, and tabulate these findings on a region-by-region basis. A summary of these findings is presented in Table 2.
Occipital The sents
Bone mature a fusion
occipital of several
bone
repre-
components
with different embryologic origins (squamous, exoccipital, and basioccipital). Its involvement with osteopetrosis will therefore depend on the particular subregion specified. The appearance of the occipital bone is also a function of patient age, and hence, duration of disease. The squamous part of the occipital bone, ossifying in membrane, has an appearance similar to that of the membrane-derived calvarium described in part I of this series (1). In the three youngest patients, we observed a three-layer pattern of the squamous occipital bone with a highattenuation inner table, low-attenuation diploic space, and slightly 137
higher-attenuation outer portion on CT scans (Fig la). In these patients, a low-attenuation band was also noted immediately adjacent to the basioccipital-exoccipital synchondrosis. With advancing age (Fig ib), the occipital bone had a more uniformly dense texture. Marked sclerosis was noted along the anterior occipitomastoid suture in all eight
patients
(Fig
ib).
Such
was
never
older
focal
6 months
however,
separately
posterior
portion
possible
than
sclerosis,
that
seen
along
of this
this
Table 1 Ophthalmologic,
It is
phenomenon
was
patients. marked
observed
In three “cupping”
drosis
was
also
in nine
of the
observed
(Fig
can
also
of the
be seen
in the
base. A prominent
in the basal
cipital
bone
cipital bones
synchondrosis. have long
common
portion
radiologic
4/M
3 mo
Blind
CHL, effusions
5/M
5 mo
Normal
CHL,
6/F 7/F
7 mo 9 mo
Blind Blind
CHL, tubes CHL, effusions
1y I y
reasonable
assume
that
might
Normal
Normal SNHL,
Seizures, neuronal
peripheral
hypotonia, storage
disorder Normal
tubes
Normal Normal
Hypotonia,
develop-
vision
CHL, tubes CHL, tubes
delayed
Normal Bilateral
CN VII develop-
mentally iO/F
1y
Extremely
il/F
2 y
vision Blind
12/M
4y
Blind
decreased
delayed,
weakness Right CN VII palsy
CHL, tubes SNHL, possible effusions
CHL,
Hypotonia, mentally
CHL
developdelayed
Left CN VII palsy, developmentally
i3/M
9y
Decreased sion,
conductive
=
color viacuity
hearing
delayed Right CN VII palsy,
CHL, tubes
normal
loss, CN
seizures cranial
=
nerve,
SNHL
=
sensorineural
hearing
loss.
Table
2 of Abnormalities
Summary
Seen
in the Skull
Base and Brain in Osteopetrosis Abnormalities
Region
Occipital
bone
Sclerosis
along
anterior
occipitomastoid
suture,
sclerosis
along basioccipital-exoccipital synchondrosis, cupping of basioccipital-exoccipital synchondrosis, endobone in basioccipital Sphenoid
bone
Sclerosis
bone
along
in midline,
oc-
sella turcica, Temporal
synchondrosis,
dorsum
thickened
sellae,
clinoid
endobones
reduced
processes,
volume
of
no pneumatiza-
tion of sphenoid sinus, optic canal narrowing No formation of mastoid air cells, enlarged subarcuate fossae, channels for subarcuate vessels, ossicular involvement, narrowing of middle ear cavity, stenosis of facial nerve canal, stenosis of internal auditory canal, middle ear effusion, deformity of stapes Delayed myelination, white matter disease (storage disor-
bones
Brain
as a
spheno-occipital spiculated
der), basal ganglia tubular frontal
skeleton
to
acidosis), extracerebral
and deep
cerebral
calcification
atrophy, hydrocephalus, cerebrospinal fluid
(renal
prominent space, optic
nerve
atrophy
be found
base. from trotic
Bone
Prominent
the low-signal-intensity bones of the skull
Small,
sclerosis
along
both
rectangular
bones
were
led appearance
noidal
and
was frequently cially on the
spheno-occipital
of the sclerotic encountered, sphenoidal
side.
synchondrosis
margin espeThe
was
easily visualized on Ti-weighted sagittal MR images. The higher-signalintensity fibrocartilage within the synchondrosis was easily differentiated
Radiology
base
osteope(Fig 2b).
endobones
were
encountered in the midline of the sphenoidal body in 11 of the 13 patients (Fig 2d). Generally, two endo-
sides of the spheno-occipital synchondrosis was noted in eight of the 13 patients (Fig 2c). An irregular, speck-
#{149}
Normal
Normal CHL, possible effusions
Decreased Blind
of osteo-
It is therefore
138
at-
palsy,
of this endoand usually spheno-oc-
(Fig if).
Sphenoid
3 mo
13 patients
feature
also
3/M
rophy Blind
Note.-CHL
of the
in the
they
Early optic nerve
skull
petrosis
in the skull
Normal
2 mo
a
Such endorecognized
been
3 wk
was
location midline, to the
Neurologic Findings
i/F
disease
central
in 12 of the
(Fig le, 2a). The bone was strictly in close proximity
Otologic Findings
ib),
“endobone”
noted
Ophthalmologic Findings
2/F
8/M 9/F
13
of these patients at the synchon-
manifestations
Findings
mentally
which was judged to be out of proportion to the curvilinear irregularity normally seen at this developing suture. Both metaphyseal lucencies and cupping are common features of osteopetrosis in the peripheral skeleton (Fig ic). Presumably, some of these same
and Neurologic
is a
manifestation of differing rates of growth of the skull base along different portions of this suture. The appearance of the basioccipitalexoccipital synchondrosis was also variable. In three younger patients, a band of low attenuation was present on both sides of the synchondrosis at CT (Fig la). A frank sclerosis along the basioccipital-exoccipital synchondrosis
Age at First Imaging Evaluation
Patient No/Sex
the
suture.
Otologic,
portions
lated dorsum
seen,
one
one
in the
of the
bone.
or “comblike” sellae
was
in the
presphe-
postsphenoidal A peculiar
appearance encountered
ance on lateral radiographs. Actual sellar volumes were not calculated, however, since none of our patients had pituitary dysfunction, and hypopituitarism is not a recognized feature of osteopetrosis. The optic canals were determined to be narrowed
at CT
spicu-
patients
of the
optic
nerves
in
with
MR imaging
four patients (Fig 2e). Prominent thickening of the posterior and antenor clinoid processes was commonly noted, giving the sella a small appear-
(Fig
atrophy
was
demonstrated
easily
scopic
These were
of clinical findings
13
of the
or CT in eight
tients (Fig 3b, 3c). findings, however,
predictors
in 12 of the
3a). Frank
(Table
pa-
radiologic only crude
and
ophthalmo-
1).
April
1992
Figure 1. Involvement of the occipital bone in osteopetrosis. (a) CT scan shows threelayer pattern in the bone similar to that de-
scribed the
for the calvarium.
three
bands sides
This was seen in
patients.
Characteristic
of low attenuation of the
drosis the
youngest
(arrowheads).
advancing
developed
a more
appearance.
sclerosis
along
both
synchon-
(b) With
bone
dense
marked
along
basioccipital-exoccipital
occipital
formly
are seen
the
age, uni-
CT scan
shows
anterior
(black
arrow) but not posterior (arrowhead) occipitomastoid suture, which was seen in eight of the 13 patients. Sclerosis and cupping at the
basioccipital-exoccipital
(white
arrow)
was
(c) Radiograph sclerosis, hires
ton-in
b.
a.
scan rosis in the shows row) in i2
V
*
and
shows
of osteopetrosis
the knees
_:
I
..
(AJ d.
C.
6
cupping,
errors-typical in the
fea-
peripheral
of the same
skele-
patient.
(d) CT
shows a featureless thickening and scleof the occipital bone; this was observed three oldest patients. (e) CT scan a prominent midline endobone (arin the basioccipital bone; this was seen of the i3 patients (see also Fig 2a).
shows
in-bone, which are ings in the peripheral
.
metaphyseal
remodeling
(0 Radiograph
fr
synchondrosis
also characteristic.
also
endobones
or bone-
characteristic skeleton.
find-
The subarcuate fossae were enlarged in all patients, although this feature was less noticeable with advancing age. A prominent vascular channel believed to represent persistence of subarcuate vessels was observed in five of the 13 patients (Fig 4a). This appearance was similar to the vascular channels made by the anterior and posterior ethmoidal arteries in the dense ethmoid bone, as demonstrated in part I of this series (1).
The middle in size or only osteopetrotic
ear cavity was normal slightly narrowed by encroachment.
The
ossi-
des were prominently involved in nine of the 13 patients (Fig 4b, 4c). Sclerosis of the optic capsule was noted in all cases, but the oval window was not preferentially involved. A consistent finding in all but the two youngest patients in our series was the presence of a middle ear effusion. Tympanotomy tubes were placed in 10 of the i3 patients at some time during the clinical course while undergoing follow-up at our institution. An important clinical correlate of middle ear disease is that some degree of hearing loss was experienced e.
f.
Temporal
Bones
Like the other base, the temporal formly and osteopetrotic
bones of the skull bones were uniseverely involved by the process.
mastoid
air cells
Volume
183
were
Number
#{149}
Pneumatized
not 1
encoun-
tered in any of the i3 patients. However, the aditus ad antrum and epitympanic space were well formed in every case. Substantial stenosis of the external auditory canal was not noted in any case.
by all of the
patients
older
than
3
months of age. Furthermore, this hearing loss was primarily conductive and improved in those patients subsequently receiving tympanotomy tubes (Table i). In only one patient was there definite evidence for primary sensorineural hearing loss. Peripheral facial nerve palsies were observed in four older patients and Radiology
139
#{149}
were unilateral in three and bilateral in one. Unfortunately, neurologic testing most of precise patient, associated and the
near
was
not
these
sufficiently
cases
detailed
to document
in
the
site of the compression. In one decreased lacrimation was with the facial nerve palsy, lesion was believed to be at or
the
geniculate
ganglion.
this patient revealed rowing of the facial
the
geniculate
less
involvement
limb
(Fig 5).
CT in
substantial nerve canal
ganglion
with
of the
narnear
rather
descending
impairment ranging from mild developmental delay to severe mental retardation. One patient (patient 3) had generalized seizures and marked hypotonia; results of fibroblast culture revealed a lysosomal storage disorder. MR imaging in this patient showed cerebral atrophy and delayed myelination (Fig 6). A second patient (patient 7) was also suspected of having a neuronal storage disorder, but died before full evaluation could be undertaken. Her MR image revealed moderate cerebral atrophy and delayed myelination but no focal abnormalities.
Brain The
neurologic
patients Excluding
are summarized peripheral
cranial
nerves
tients
findings
had
II, VII,
normal
in our
i3
in Table compressions
i.
or VIII,
of
six pa-
neurologic
exami-
nations. One additional patient (patient 13) had a history of complex partial seizures with a temporal lobe focus but was otherwise neurologically normal.
The
remaining
varying
degrees
six patients of general
had neurologic
Figure bone
2. Involvement in osteopetrosis.
prominent
sclerosis
moderate delay
mild was
use9, who
was
with
referred
to our
institution
upper extremity weakness, severe developmental delay, blindness, and bilateral facial nerve paralysis. CT performed at admission revealed hydrocephalus. MR imaging (Fig strated brain stem compression obstruction of cerebrospinal
7) demonand
fluid flow by impingement at the foramen magnum. A clear cause for gross neurologic dysfunction was apparent in most however, in two.
the cause was not Each of these children
cerebral also
sessed
or marked and
had
atrophy
noted
that
developmentally
of
at cranial five
CT. It
of the
normal
variable
devel-
evidence eight
patients
degrees
pos-
of cerebral
atrophy and prominent extracerebral cerebrospinal fluid spaces over their frontal convexities. A representative example is shown in Figure 8 (patient 6), which
shows
sion of ventricular 4-month interval. sessment
showed
advanced skills
MR imaging proved extremely ful in the evaluation of patient
cases; obvious
exhibited opmental
for
in both her
age
the
interval
progres-
enlargement Developmental this
patient
intellect of ii
over a asto be
and
motor
months.
DISCUSSION Involvement of the skull base has long been recognized as a prominent and invariable feature of osteopetrosis. On conventional radiographs, these cranial findings include basilar sclerosis, thickening of the posterior clinoid processes and, to a lesser degree, the anterior clinoid processes, decreased volume of the sella, obliteration of the sphenoid and mastoid sinuses,
and
narrowing
of the
basilar
foramina (4-6). To our knowledge, cranial CT findings in osteopetrosis
of the sphenoid (a) CT scan shows
along
both
sides
of the
spheno-occipital synchondrosis with an irregular, speckled appearance (curved arrow). Note also the basioccipital endobone (straight arrow). (b) Ti-weighted MR image (repetition time, 500 msec; echo time, 20 msec [500/20j) shows that the fibrocartilage within
the spheno-occipital has an intermediate easily differentiated tensity osteopetrotic
(c) Sagittal
oblique
synchondrosis
(arrow)
signal intensity and is from the low-signal-inbones at the skull base.
CT reformation
of the
spheno-occipital synchondrosis (arrow) provides an appearance similar to that of b. S = sella turcica. (d) CT scan shows midline rectangular endobones (arrows) in the sphenoidal body; this was seen in 11 of the 13 patients. Two endobones could usually be identified, one in the presphenoidal portion
and (1’
o’e ‘
r
in the postsphenoidal scan
shows
portion. comblike
d.
C.
140
a peculiar,
Radiology
#{149}
e.
April
1992
have once
been previously (7). Now, with
scanning techniques tient population,
firm,
correct,
these
observations
reported improved and
only CT
a larger
we were able extend many
and
from
the
pa-
to conof
earlier
radiology literature. An interesting and, to our knowledge, previously unreported feature of osteopetrotic involvement of the skull base was the frequent visualization of endobones within the sphenoid and occipital bones. Such endobones
are
skeleton
frequently
seen
of patients
in the
with
Caffey
(9) referred
bones
as “inserts,”
Beiler
(iO) apparently
phrase
“bone
Figure tients.
3. Optic (b, c) MR
live as a simple
while
in the
nerve images
and
which
involvement. (500/20) show
was
of the
Patholo-
first recognized retain representaof the development
Engfeldt
et al (i2)
with
small
amounts
in evaluating
these
seen
directly
the
anterior
to specuvestiges of
presphenoid Similarly,
in the
and the
middle
of the
of the occipital bone a remnant of the fetal ossification center. How-
development
of the
is exceedingly complex drawing a one-to-one
dence
of
between
these
skull
(i3,14), correspon-
endobones
and
a select few of the many intermediate ossification centers that appear during development may represent a gross oversimplification of the process. Narrowing of the optic canals with
of
which we have previ(1), the embryologic sphenoidal and occipi-
narrowing nerve
endobone
base and
tal endobones are more obscure. When seen, there were usually two midline endobones within the body
optic
separate bones.
ever,
that
spongy bone. the triangular endobone
one
the fetally postsphenoid basal portion may represent basioccipital
con-
in their elegant demonstrating
sphenoid,
to the other. It is tempting late that these represent
is built up of remnants bone, that is, mainly cal-
cartilage
unresorbed Unlike
(a) CT scan demonstrates direct atrophy of the
examination
removed.
concept studies,
the mandible, ously described origins of the
the
bone,”
ophthalmologic
cified
miniature
coined
(ii). this
the endobone of medullary
axial
Hinkel
are normally
gist Carla Zawisch that marble bones tions of all stages firmed histologic
textbook,
to these
that
latinized to “os-in-os.” thus represent fetal yescontain embryonic strata
of bones
osteopetroas early
sis, having been recognized as 1934 (8). In his original
subsequently Endobones tiges and
subsequent
nized
of the optic canals (arrows); chiasm, or tracts (arrowheads);
visual
loss
complication
this was however,
is a well-recog-
of osteopetrosis.
documented MR imaging
in 12 of the 13 pawas not as sensi-
patients.
1
#{149}1 b.
a. Figure 4. consistent
Temporal finding.
tamed
through
tremely
high
Volume
183
bone Persistent
involvement channels
the temporal attenuation.
Number
#{149}
bone. A middle
1
c.
in osteopetrosis. (arrowheads)
The internal ear
effusion
for
(a) Axial CT scan shows the subarcuate arteries
auditory
canal
is noted
with
(arrow retraction
enlargement were seen
in b) is short of the
and
of the subarcuate fossae (arrow), in five of the 13 patients. (b, c) Coronal
somewhat
trumpet-shaped,
and
which was CT scans
the ossicles
have
a ob-
ex-
drum.
Radiology
141
#{149}
Clinical present similar
nerve
evidence of visual loss was in ii of our i3 patients, and high percentages of optic
involvement
other series encroachment canal
by
are reported
in
(7,iO,15-22). Although of the optic nerve
osteopetrotic
bone
in its
is the
commonly accepted mechanism for visual loss in most of these patients, primary retinal degeneration may be implicated in others (17,2i). Surgical unroofing of the optic canals failed to arrest or reverse the visual decline in two of our patients. In conjunction with similar failed procedures reported by others (i7), we thus strongly caution against the use of CT mea-
a.
surements showing progressive optic canal narrowing to justify aggressive surgery in these patients.
Figure 5. Facial nerve canal stenosis. CT scans in a patient with left facial nerve palsy and decreased lacrimation in the left eye. Marked narrowing is seen in the region of the geniculate ganglion (arrow in a). Descending facial canal was not as severely affected (arrow in b).
b.
Our findings concerning osteopetrotic involvement of the temporal bone are in general agreement with those reported in the CT (7) and pathology literature (23-26). We found no evidence of mastoid sinus formation, although the middle ear cavities were well preserved. Frank thickening and enlargement of the ossicles were encountered in several cases. We did not find trumpet-shaped internal auditory canals except in our youngest
patients;
we
thus
can
only limited support to the “persistent fetal state” description of the teopetrotic temporal bone endorsed by Bartynski
.:
I
give
Os-
et al (7).
We do agree,
however, that prominent subarcuate fossae are frequently encountered in these patients, giving the bone a somewhat fetal appearance. The subarcuate fossa is a de-
a.
pression
Figure
on
the
posterior
the petrous temporal the internal auditory the projection of the posterior semicircular fossa
is uniformly
surface
of
bone just above canal and within superior and canals. This
seen
in the
healthy
newborn but is gradually obliterated over the first 2 years of life. In most of our patients with osteopetrosis, how-
ever, the subarcuate
fossae
remained
prominent for several years. Additionally, persisting large channels for penetrating subarcuate vessels were noted in five of the i3 patients. Because
the
mastoid
does
not
pneuma-
tize properly, but remains filled with osteopetrotic bone and nests of marrow, the subarcuate vascular supply remains robust. Failure of these yessels
to regress,
coupled
with
generally
slow remodeling of the entire temporal bone due to osteoclast deficiency, contributes to a prolonged fetal or neonatal appearance, which may persist
throughout
We agree 142
Radiology
#{149}
the
with
ist
other
year
of life.
investigators
b. 6.
Coexisting
osteopetrosis
tient 3). (a) Ti-weighted eralized cerebral atrophy
that
hearing
symptom sis. Unlike
loss
and
(500/20) and and delayed
neuronal
with
osteopetro-
several
early reports, howthat conductive loss (rather than sensorineural loss) dominates the clinical picture. Audiometry and brain stem-evoked responses documented that, in nine of the iO
ever,
we believe
patients
with
hearing
loss,
it was
disorder
in a 6-month-old
(3,000/100)
axial
boy
MR images
(pa-
reveal
gen-
caused by middle ear inflammatory disease; this, in turn, may be secondary to stenosis of the eustachian canal and poor mechanical drainage of the middle ear cavity. Other contributory factors to the conductive loss may include immobilis primarily
is a prominent
in children
storage
(b) T2-weighted myelination.
pri-
manly due to a conductive defect; sensorineural loss was dominant in only one case. Additionally, all iO of these patients had recurrent bouts of otitis media, which were believed by the otolaryngologist to be contributory to their hearing loss. Furthermore, iO of these patients underwent the placement of tympanotomy tubes with subsequent improvement in hearing. It thus seems likely that hearing loss in children with osteopetrosis
ity of the tympanic
of the fication ligaments, ossicles
malleus and encroachment,
oval
and
incus
round
from obliteration
epi-
windows,
ossi-
of the mallear and incudal and replacement of the by osteopetrotic bone (i6).
do not doubt that eventually develop symptoms.
We
may
personally
docu-
have
mented this in one adult nign form of the disease. children with osteopetrosis, it is our
experience
hearing
loss
We
older patients sensorineural
dominates
that
with the beIn young however, conductive
the
early
clini-
April
1992
Figure 7. Utility of MR imaging in a patient with weakness and spasticity (patient 9). CT
scan (not shown) revealed hydrocephalus, which is also seen on the T2-weighted axial MR image (2,600/80) (a). Sagittal Ti-weighted MR
image
(b) shows
(500/20)
compression
and
magnum.
Note
brain stem
narrowing tonsillar
at the foramen herniation
(arrow).
associated with a neuronal storage disorder. Fitch et al (29) first called attention to this association in a 40week-old stillborn with osteopetrosis, hydrocephalus, cerebral malformations,
and
axonal
dystrophy.
et al (i9) described of laminar cortical acid-Schiff-positive axonal spheroids
a.
trosis. ,.
:‘
Ambler
et al (30)
pathologic storage
evidence disorder
Lehman
autopsy findings necrosis, periodic neurons, and in a case of osteopeprovided
of a neuronal probably
caused
by
a lysosomal enzyme deficiency in a third patient with osteopetrosis. In addition to providing insights toward understanding the ultimate biochemical defect in osteopetrosis, identifying the presence of a coexisting neuronal storage disorder has several immediate practical consequences provides
in patient prognostic
treatment. information
First,
it to
the families of such patients, portending an ultimately dismal neurologic outcome. Second, the presence of an associated
a.
b.
Figure
8.
Prominence of subarachnoid spaces in this developmentally (a) Baseline CT scan obtained at 7 months. (b) Follow-up CT scan shows progressive atrophy despite normal intellect.
normal
obtained
cases logic
(16,24,27,28).
Two
mechanisms posed: (a) ischemia stenosis
at any
pathophysio-
have been profrom facial canal
point
from
the
genicu-
late ganglion to the stvlomastoid foramen and (b) dehiscence of the facial nerve canal above the oval window with compression by bony overgrowth from the epitympanum and into the immobile stapes (26,27). Although we could identify the facial nerve canal along its entire course in every
patient,
able
to predict
Volume
183
we
the
were
Number
#{149}
generally
site,
cause, I
un-
or even
degeneration
(3i).
patient.
at age 11 months
CT is insensitive for demonstrating the presence of a coexisting neuronal storage grees
cal picture. Tympanotomy tube ventilation of the middle ear is a simple and effective method to improve hearing in most of these patients. Facial nerve paralysis is a common affliction in malignant osteopetrosis, occurring in 10%-50% of reported
neuronal
represents a relative contraindication to bone marrow transplantation, the only known curative procedure for the bone component of the disease
presence with CT. Gross
of facial
nerve
neurologic
dysfunction
impairment
or
developmental delay was documented in five of our 13 patients. Similar findings have been reported in other clinical studies of osteopetrosis (i8,19). In some cases, such as our patient with extraventricular obstructive hydrocephalus and brain stem compression, an obvious and easily treatable cause can be established. In other cases,
the
cause
icit remains sessment
of the
obscure. of such
The children
more
difficult
when
sider
the
of severe
role
neurologic
one
def-
clinical
as-
is made
must sensory
condepri-
vation (visual and auditory) in the origin of their developmental delay. In certain cases, such as patient 3 in our series, osteopetrosis may be
disorder, of atrophy
since variable or ventricular
deen-
largement can be seen in many developmentally normal patients with osteopetrosis. The ability of MR imaging to depict delayed myelination in addition to atrophy provides a noninvasive
method
group
of patients
possess
to identify
who
a neuronal
that
sub-
potentially
storage
disease
or
other metabolic derangement. In another rare association (not encountered in this series), osteopetrosis may
coexist
with
II deficiency
and
renal
sis (32).
may
result
This
carbonic
anhydrase
tubular
acido-
in extensive
intracranial parenchymal calcifications, which may be seen with CT (33) or MR imaging (34). Such patients, however, are usually neurologically normal. In conclusion, we documented in this
and
the
preceding
part
(1) many
Radiology
143
#{149}
new clinical and radiologic findings in cranial osteopetrosis. We have attempted to illustrate those features of the disease we believe are both common and characteristic, as well as to demonstrate the rich diversity of imaging findings possible within the disease spectrum. We have been able to relate some of our radiologic observations in the skull to similar manifestations of osteopetrosis in the peripheral skeleton. Ideally, this comprehensive study of cranial osteopetrosis will lead to better understanding and management of the cosmetic, otolaryngologic, ophthalmologic, and neurologic complications of this rare disease. #{149}
5.
6.
7.
8.
9. 10. 11. 12.
The authors express sinto Beth Hales for her assistance of this manuscript.
in
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April
1992