Pediatr Radiol (2006) 36: 61–64
DOI 10.1007/s00247-005-0008-y
CASE REPORT
Veena A. Nagar . Meher A. Ursekar .
Pradeep Krishnan . Bhavin G. Jankharia
Krabbe disease: unusual MRI findings
Received: 23 April 2005 / Revised: 27 July 2005 / Accepted: 31 July 2005 / Published online: 25 October 2005
# Springer-Verlag 2005
Abstract We present the MRI findings in a case of
infantile-onset Krabbe disease. Enlargement of the intra-
cranial optic nerves and cervical cord were detected in ad-
dition to more typical changes in the cerebral white matter
and thalami. We also review the proton MR spectroscopic
findings in Krabbe disease.
Keywords Krabbe disease . Brain . Optic nerves . MRI .
MR spectroscopy . Child
Introduction
Krabbe disease is an autosomal recessive leukodystrophy
with an estimated incidence of 1 in 100,000–200,000 live
births [1]. Intracranial findings on MRI and CT have been
well documented. Typical findings include signal abnor-
malities in the cerebral and cerebellar white matter and
thalami. We report a case of infantile-onset Krabbe disease
that also confirms the previously reported finding of bi-
lateral enlargement of the optic nerves. An unusual finding
not previously reported is enlargement of the cervical cord.
Case report
A 7-month-old girl presented with excessive crying, refusal
to feed and delayed milestones. There was spasticity of all
limbs, more prominent in the lower limbs. The birth history
was uneventful.
MRI of the brain was performed on a 1.5-T system
(Sonata Siemens, Erlangen, Germany). The MRI protocol
included axial T2-weighted (T2-W), sagittal T1-weighted
(T1-W) and axial FLAIR images. Generalized cerebral
V. A. Nagar (*) . M. A. Ursekar . P. Krishnan . B. G. Jankharia
Jankharia Imaging Centre,
Bhaveshwar Vihar, 383 Sardar V P Road,
Mumbai, 400004, India
e-mail: drv9@hotmail.com
Tel.: +91-22-23884015
Fax: +91-22-23829595
cortical atrophy with ventricular enlargement was noted.
Abnormal T2 prolongation was documented in the deep
cerebral white matter bilaterally, and in the corpus cal-
losum, internal capsule and pyramidal tracts (Fig. 1). The
periventricular and deeper white matter were more severely
involved than the subcortical white matter, which seemed
to be relatively spared. The cerebellar white matter was
also involved (Fig. 2). The thalami showed an abnormal
decrease in signal intensity on T2-W images. There was
marked, symmetrical hypertrophy of the intracranial seg-
ments of both optic nerves (Fig. 3). Expansion of the spinal
cord was noted in the cervical region (Fig. 4).
CT showed bilateral thalamic hyperdensity and punctate
densities in the paraventricular white matter, which prob-
ably represented foci of calcification. Magnetic resonance
spectroscopy (MRS) was performed using a multivoxel 3D
CSI technique with TR/TE of 1000/135. There was marked
elevation of the choline/creatine ratio within the abnormal
white matter and reduction in the N-acetylaspartate/cre-
atine ratio (Fig. 5) as compared with normal control values.
Blood investigation for lysosomal enzymes showed low
levels of β-galactocerebrosidase.
Discussion
Krabbe disease is a disorder of lysosomal function. The
basic defect is deficiency of galactocerebroside β-galacto-
sidase. The genetic basis for the enzymatic defect has been
traced to a faulty gene on chromosome 14q31 [2]. Absence
of the enzyme results in accumulation of galactocerebro-
side and psychosine in macrophages. Psychosine is toxic to
the brain, oligodendroglia in particular, but the mechanism
of demyelination and dysmyelination is unclear [3]. The
two major histological characteristics are severe loss of
oligodendrocytes and presence of globoid cells [4]. Intra-
cellular accumulation of galactocerebroside leads to the
formation of the globoid cells.
Krabbe disease most commonly presents in the first 6
months of life, manifested by hyperirritability, increased
muscular tone, fever and developmental arrest. With
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Fig. 1 Axial T2-W MRI shows abnormal T2 prolongation in the

deep periventricular white matter, internal capsule and corpus
callosum. Note the decrease in signal intensity within the thalami
progression, there is further cognitive decline, myoclonus,
opisthotonus, nystagmus and optic atrophy. Eventually,
there is spasticity with loss of responses. Early in the course
of the disease, non-enhanced CT may show areas of
symmetrically increased attenuation within the basal gan-
glia, thalami and centrum semiovale [4–6]. Signal abnor-
malities in a similar distribution have been reported on
MRI by Baram et al. [7]. Thalami and basal ganglia show
Fig. 2 Axial T2-W MRI demonstrates involvement of the cerebellar
white matter
low signal intensity on T2-W images and are hyperintense
on T1-W images. The pathogenesis of the signal changes
remains uncertain, with hypotheses attributing the signal
change to calcification [8] or grouping of globoid cells [5].
In intermediate stages, patchy hyperintensities may be
seen in these areas on T2-W MRI with decreased atten-
uation on CT [7]. The late stage is characterized by marked

Fig. 3 Bulbous enlargement of the intracranial segment of optic nerves seen on (A) axial FLAIR and (B) coronal T2-W MRI

Fig. 4 Thickening of the cervical cord seen on sagittal T1-W MRI
cerebral and cerebellar atrophy. In the cerebellum, the
dentate nuclei and white matter are typically involved [9].
Involvement of the optic nerves, as seen in our patient,
has been reported previously. Krabbe originally described
“solid, hard and thickened” optic nerves in one of five
children evaluated [10]. Ieshima et al. [11] also reported a
case of enlarged optic nerves at autopsy. Jones et al. [6]
reported two cases of Krabbe disease with marked en-
largement of intracranial optic nerves. They found that this
enlargement is due to the accumulation of numerous glo-
boid cells and diffuse optic nerve atrophy, which is a fea-
ture in some patients with Krabbe disease, and could be a
result of oligodendrocyte loss from psychosine toxicity.
Optic nerve enlargement has also been described by
Hittmair et al. [12]. They found marked enlargement of
the optic nerves and other cranial nerves that was confirmed
on biopsy. Microscopically, the enlarged optic nerves
showed numerous globoid cells with extensive gliosis.
They suggested that neuronal tissue outside the brain may
react differently, with enlargement rather than atrophy in
response to the presence of cerebroside in Krabbe disease.
This enlargement is more significant in the later stages, and
hence does not serve as a criterion for early diagnosis.
Spinal involvement in Krabbe disease was first reported
by Vasconcellos and Smith [13]. They presented a case of
63
Fig. 5 Proton MRS with the voxel placed in the abnormal white
matter reveals a prominent choline peak and a reduced NAA peak
abnormal enhancement of the lumbosacral nerve roots in
the infantile form of the disease without intracranial man-
ifestations. Given et al. [14] reported a further case,
showing abnormal contrast enhancement of lumbosacral
nerve roots, in addition to the typical intracranial findings.
However, to the best of our knowledge, there has been no
previous report of the imaging finding of enlargement of
the spinal cord in this disease. The pathogenetic basis of
this finding is unknown and requires further studies.
Proton MRS in Krabbe disease has been described by
Zarifi et al. [15]. In their study, N-acetylaspartate was
found to be markedly reduced with a prominent choline
peak and abnormally high choline/N-acetylaspartate ratio.
Prominent choline peaks have been associated with glial
cells and accumulation of myelin breakdown products.
Low N-acetylaspartate indicates axonal loss within the
white matter, suggesting that the phase of disease char-
acterized by axonal loss and gliosis has already begun [16].
MRS patterns in different forms of the disease have been
described by Brockmann et al. [17]. In juvenile Krabbe
disease, there is predominant astrocytosis without neu-
roaxonal damage, as reflected by an increased inositol/
N-acetylaspartate ratio and a normal choline/N-acetylas-
partate ratio, while metabolite concentrations in adult
Krabbe disease are close to normal. Mild-to-moderate
increases in choline and inositol with a decrease in N-
acetylaspartate in the infantile form of the disease reflect
astrocytosis and neuronal degeneration. Our proton MRS
findings corroborate the pathological features of the late
stages of globoid cell leukodystrophy, which are reactive
astrocytic gliosis, widespread demyelination and second-
ary axonal degeneration [15].
In conclusion, Krabbe disease should be considered in
the differential diagnosis of children with optic nerve en-
largement, especially if associated with typical intracranial
findings. In addition, spinal cord enlargement may also be
present. Proton MRS is a useful tool to assess the extent of
brain damage in Krabbe disease.
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