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Magnetic resonance imaging findings in acute canine distemper virus

infection

Article  in  Journal of Small Animal Practice · June 2008

DOI: 10.1111/j.1748-5827.2008.00552.x · Source: PubMed

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CASE REPORT

Magnetic resonance imaging findings

in acute canine distemper virus
infection
Demyelination is the prominent histopathological hallmark in the demyelination (Atkins and others 2000,
Scarisbrick and Rodriguez 2003).
acute stage of canine distemper virus infection. Magnetic resonance Studies performed in human beings
imaging is an important diagnostic tool in human beings to and in canine models have shown that
damage to myelin can be visualised
determine demyelination in the brain, for example in multiple by magnetic resonance imaging (MRI;
sclerosis. Five young dogs with clinically suspected canine Kuharik and others 1988, Percy and
others 1994, Barkovich 2000, 2005,
distemper virus infection were subjected to magnetic resonance McGowan and others 2000). The appear-
imaging of the brain and histopathological and ance of myelin in MRI is based upon
the water content in the myelin sheath,
immunohistochemical examinations. Hyperintense lesions and loss resulting in differences in T1- and T2-
of contrast between grey and white matter were detected in relaxation times. In entire myelin, water
is located within the myelin sheaths with
T2-weighted images in the cerebellum and/or in the brainstem relatively short T1- and T2-relaxation
of three dogs, which correlated with demyelination demonstrated times. In consequence, myelin has a
T1-hyperintense and T2-hypointense
in histopathological examination. Furthermore, increased signal appearance (Barkovich 2000). With de-
intensities in T2-weighted images were seen in the temporal lobe of generation of the myelin sheath, relatively
more ‘‘free’’ water exists, which is located
four dogs with no evidence of demyelination. Magnetic resonance intra-axonally or interstitially. This water
imaging seems to be a sensitive tool for the visualisation of in vivo is not bound to macromolecules and has
therefore longer T1- and T2-relaxation
myelination defects in dogs with acute canine distemper virus times resulting in a T1-hypointense and
infection. Postictal oedema and accumulation of antigen positive T2-hyperintense appearance of demyeli-
nated tissue (Barkovich 2000). This under-
cells have to be considered an important differential diagnosis. lying principle allows visualisation of
demyelination in anatomical MRI.
In the present retrospectively evaluated
A. BATHEN-NOETHEN*y, V. M. STEIN*, INTRODUCTION case series, we tried to ascertain whether
C. PUFFz, W. BAUMGAERTNERz AND demyelinating lesions because of CDV
A. TIPOLD* Infection with the canine distemper virus infection can be correlated with findings
(CDV) results in a systemic disease in in anatomical routine MRI.
Journal of Small Animal Practice (2008)
49, 460–467 the dog. Ten to 14 days after an infection,
DOI: 10.1111/j.1748-5827.2008.00552.x the virus can spread into the central ner-
vous system (CNS; Appel 1969, Tipold
and others 1992, Vandevelde 2004, CASE HISTORIES
Baumgärtner and Alldinger 2005). In
the acute phase of CDV infection, demy- Signalment, clinical signs,
elination predominates and histopatho- general and neurological
logical features are damage to myelin, examination findings
such as ballooning of myelin sheaths, vac- Dog 1. A four-month-old female
uolation of the white matter, myelin mixed breed dog, weighing 5 kg, was pre-
*Department of Small Animal Medicine and
phagocytosis and astrocytic swelling in sented with a history of generalised sei-
Surgery, University of Veterinary Medicine, the absence of inflammation (Vandevelde zure since two days. The dog was born
Bischofsholer Damm 15, D-30173 Hannover, 2004). CDV is a recognised animal model in Germany and was vaccinated against
Germany
for multiple sclerosis (MS) in human CDV for the first time 48 hours before
yVeterinary Practice, Bahnhofstrasse 9, D-51789 beings (Appel and Gillespie 1972, Dal the onset of seizures. During the physical
Lindlar, Germany
Canto and Rabinowitz 1982). The cause examination, the dog showed a slightly
zDepartment of Pathology, University of
Veterinary Medicine, Buenteweg 17, D-30559 of MS is unknown; an infectious agent is elevated body temperature (39
3°C, ref-
Hannover, Germany suspected which induces immune-mediated erence ,39
0°C) and signs of lower

460 Journal of Small Animal Practice
Vol 49
September 2008
Ó 2008 British Small Animal Veterinary Association

respiratory tract disease. Interictal neuro-
logical examination revealed generalised
ataxia and proprioceptive deficits in all
four limbs. Because of seizure activity,
an intracranial lesion, mainly with fore-
brain involvement, was suspected. Hae-
matology showed an anaemia (31 per
cent, age-related reference ;43 per cent;
Anderson and Gee 1958) and a mono-
cytosis with a normal total leucocyte
count (1397/ll, reference 0 to 600/ll;
10,740/ll, reference 6000 to 12,000/ll),
blood chemistry was within normal
ranges. CDV antibodies were positive in
the blood, but CDV nucleoprotein could
not be detected through PCR (Institute
of Virology, University of Veterinary
Medicine). MRI and cerebrospinal fluid
(CSF) examination were performed, and
a diagnosis of CDV infection was pre-
sumed. Despite antiepileptic treatment
with phenobarbitone and diazepam intra-
venously, the dog continued seizuring.
The owner elected euthanasia because of
poor prognosis.
Dog 2. An eight-month-old female
Siberian husky, weighing 15 kg, was pre-
sented because of generalised seizures
some hours ago. The dog had a history
of diarrhoea for the last three days. No
vaccination had been performed so far.
The physical examination revealed muco-
purulent ocular discharge and hyperkera-
tosis of the nose and footpads. The dog
showed generalised ataxia and propriocep-
tive deficits in all four limbs and a reduced
menace response. The neuroanatomical
localisation was considered intracranially,
mainly with forebrain involvement.
Because of the history and the clinical
findings, a CDV infection was suspected.
The haematogram revealed a reduced hae-
matocrit (29 per cent, reference 40 to
55 per cent), monocytosis (1071/ll, refer-
ence 0 to 600/ll, with normal total leuco-
cyte count 6300/ll, reference 6000 to
12,000/ll). During hospitalisation, the
dog developed myoclonus, leucopenia
(1930/ll), thrombocytopenia (33,000/ll,
reference 150,000 to 500,000/ll) and
the haematocrit further decreases (24 per
cent, reticulocytes 18,500/ll). Detection
of CDV nucleoprotein through PCR of
the blood was positive (Institute of Virol-
ogy, University of Veterinary Medicine).
MR images of the brain were acquired.
Journal of Small Animal Practice
Vol 49
MRI findings in acute CDV infection
Because of the very poor prognosis, the
dog was euthanased on request of the
owner immediately after MRI and histo-
pathological examination was performed.
Dog 3. A three-month-old male
mastiff-crossbreed puppy, weighing 2 kg,
was presented with a one week history
of sneezing and coughing and focal seiz-
ures for the last nine hours. Three weeks
ago, the dog showed a period of diarrhoea.
The dog was from Poland with an un-
known vaccination status. The physical
examination revealed a non-febrile dog
with abnormal breathing sounds of the
lung. During the examination, the dog
showed focal motor seizures of the masti-
catory muscles (‘‘chewing gum fits’’) and
miotic but responsive pupils. Propriocep-
tion was normal. A multifocal intracranial
localisation with forebrain and midbrain
involvement caused by CDV infection
was suspected. Haematology showed
a reduced haematocrit (25 per cent, age-
related reference ;41 per cent; Anderson
and Gee 1958), lymphopenia and mono-
cytosis with a normal total leucocyte count
(803/ll, reference 900 to 3600/ll; 1397/
ll, reference 0 to 600/ll, respectively;
10,040/ll, reference 6000 to 12,000/ll),
blood chemistry was within normal
ranges. An abnormal bronchial pattern
was found on a survey thoracic radio-
graph. During hospitalisation, the disease
progressed within the next 24 hours and
generalised seizures despite anticonvulsant
therapy with diazepam were observed.
MRI of the brain was performed. The
owner elected euthanasia immediately
after MRI because of poor prognosis.
The dog was sent to histopathological
examination.
Dog 4. A six-month-old mixed breed
male dog, weighing 16 kg, was presented
with a history of diarrhoea and fever.
Within the last few hours, the dog also
presented focal seizures. The dog was
born in Germany and not vaccinated.
Physical examination revealed an elevated
body temperature (39
9°C, reference
,39
0°C), abnormal breathing sounds
of the lungs and hyperkeratosis of the
footpads (Fig 1). The dog was apathic
but did not show proprioceptive or cranial
nerve deficits. During examination, the dog
started with focal motor seizuring of the
right front limb and masticatory muscles

September 2008
Ó 2008 British Small Animal Veterinary Association
(‘‘chewing gum fits’’), urination and saliva-
tion. The neuroanatomical localisation was
considered to be the forebrain. Haematol-
ogy showed a reduced haematocrit (32 per
cent, reference 40 to 55 per cent), mild
monocytosis with a normal leucocyte count
(823/ll, reference 0 to 600/ll; 10,560/ll,
reference 6000 to 12,000/ll). A bronchial
pattern was found on a survey thoracic
radiograph. The dog was hospitalised for
further examination and CSF was col-
lected. Within the next 24 hours, the
dog developed generalised seizures despite
administration of diazepam and the owner
elected euthanasia because of poor prog-
nosis. Post-mortem MRI and histopatho-
logical examination were performed.
Dog 5. A three-month-old male Shi-
Tzu-puppy, weighing 1
5 kg, was pre-
sented with a nine days history of ataxia
and focal seizures. The dog was born in
Moldavia and had been vaccinated for
the first time two weeks before the onset
of clinical signs. The patient was apathic,
non-ambulatory with persistent myoclo-
nus of the thoracic muscles and had an
alternating head tilt at the time of presen-
tation. Except a slightly elevated body
temperature (39
1°C, reference ,39
0°C),
the physical examination was normal.
During the neurological examination, a
ventrolateral strabismus, an absent men-
ace response in both eyes and a reduced
proprioception in all four limbs were
found. Spinal reflexes were unremark-
able. The localisation of the lesion in
this dog was considered to be multifocal
intracranial with brainstem and fore-
brain involvement (spinal cord localisa-
tion for the myoclonus cannot totally
be excluded). A CDV infection was
suspected. A blood cell count showed
a decreased haematocrit (30 per cent,
age-related reference ;41 per cent;
Anderson and Gee 1958) and a moderate
leucocytosis with lymphopenia (18,400/
ll, reference 6000 to 12,000/ll; 368/ll,
reference 900 to 3600/ll). The dog
was hospitalised for further examina-
tion and CSF was collected. The disease
progressed to generalised seizures within
48 hours, and the dog died sponta-
neously despite supportive care and
antiepileptic drugs. Post-mortem MRI
and histopathological examination were
performed.
461

MRI and CSF analysis
Anatomical MRI was performed (Magne-
tom Impact Plus, 1.0 Tesla; Siemens)
under general anaesthesia. Anaesthesia
was initiated with diazepam (DiazepamÒ;
Ratiopharm) and propofol (NarcofolÒ;
cp-Pharma) and maintained using iso-
flurane and oxygen (IsofluranÒ; Baxter).
Transverse, sagittal and dorsal plane images
were acquired in T1 (time to repeat
(TR)=330 ms and time to echo (TE)=12
ms) and T2 (TR=3458 ms and TE=96
ms) sequences in an extremity coil. Addi-
tionally, transverse T1-weighted images
were acquired after intravenous admin-
istration of gadolinium dimeglumine
(MagnevistÒ; Schering) in the three dogs
with antemortem MRI. Fluid-attenuated
inversion recovery (FLAIR) images were
only obtained from dog 4 (TR=9000
ms and TE=105 ms).
MRI of the five dogs was performed
one to seven days after the last seizure.
MR images were abnormal in all dogs.
Large round or ovoid-shaped lesions were
found in different parts of the forebrain in
four dogs (numbers 1 to 4). The lesions
were distributed asymmetrically in the
grey matter of the forebrain. These lesions
were seen in transverse as well as in dorsal
and sagittal planes. The primarily affected
location in the forebrain of four dogs was
the grey matter of the temporal lobe
(Figs 2 and 3A-C). In dog 5, a small
round-shaped hyperintense lesion was
detected in the left brainstem in T2-
weighted transverse planes (Fig 4), and
a patchy hyperintense lesion was found
in the caudal part of the cerebellar subcor-
tical white matter in T2-weighted sagittal
planes (Fig 5). All lesions were hypoin-
tense or isointense in T1-weighted images
and hyperintense in T2-weighted images
relative to unaffected grey matter (Figs 2,
3A,B, 4 and 5).
The contrast of the arbour vitae and
the cerebellar cortex, representing the dif-
ference between white and grey matter,
was diminished in two dogs in T2-
weighted images (dogs 3 and 4; Fig 6A).
FLAIR images were only obtained in
dog 4 and showed a hyperintense lesion
in the temporal lobe which corresponded
to the one seen in the T2-weighted images
(Fig 3C). Contrast medium was adminis-
tered in three dogs, and mild enhance-
462
A. Bathen-Noethen and others
ment was found in one forebrain lesion
of dog 1 (Fig 7).
CSF was obtained only from three dogs
(numbers 1, 4 and 5) because of owner
restrictions. CSF was collected by punc-
ture of the cerebellomedullary cistern in
lateral recumbency. The examination of
the CSF included total nucleated cell
count and determination of total protein
content.
In dog 1, a slightly elevated CSF
protein content (32 mg/dl; reference
,25 mg/dl) without an elevation of total
nucleated cells occurred. Mononuclear
pleocytosis was detectable in dogs 4 and
5 (18 to 205 leucocytes/ll, reference ,3
leucocytes/ll, with a total protein of 30
to 44 mg/dl).
Necropsy and histopathological
examination
Necropsy, histopathology and immuno-
histochemistry for detection of CDV anti-
gen were performed in all five dogs with
special emphasis on organs which are char-
acteristically concerned with CDV infec-
tion. All dogs suffered from moderate to
severe interstitial pneumonia. In one case
(dog 1), intranuclear and cytoplasmatic
inclusion bodies were seen in the bron-
chial epithelium. These inclusion bodies
were also found in the renal pelvis, stom-
ach and lymph nodes. Three of the dogs
(numbers 2, 3 and 4) showed typical
hyperkeratosis of footpads (Fig 1) and
nose. Follicular hyperplasia of the spleen
with central fibrinoid necrosis was diag-
nosed in dog 2 and marked depletion of
lymph nodes in dog 4. Representative sec-
tions of the areas of forebrain, cerebellum
and brainstem were prepared. The brains
FIG 1. Dog 4 showed a hyperkeratosis of the
footpads (hard pad disease)
Journal of Small Animal Practice
Vol 49
of all dogs showed signs of demyelination
mainly in the cerebellum (Fig 6C,D) but
also in the brainstem of dog 5 (Table 1).
A monoclonal antibody (mouse anti-
canine distemper virus; Serotec Ltd) was
used for detection of CDV nucleoprotein
which could be detected in the brains of all
dogs (Fig 3D,E). In the brainstem of dog
5, a high CDV load was found in the area
of demyelination. In dog 4, multiple sec-
tions of the temporal and frontal lobes
were evaluated. The temporal lobe of this
dog contained a high number of CDV
antigen positive cells in the white matter
(Fig 3D), whereas in the frontal lobe,
white matter CDV antigen positive cells
were rarely observed (Fig 3E). Referring
to the immunohistochemistry, the post-
mortem examination confirmed the pre-
sumed antemortem diagnosis of CDV
infection.
Comparing the results of histopatho-
logical examination and MRI, histopatho-
logical results were supportive of MRI
findings: increased signal intensity in
T2-weighted images and loss of contrast
between white and grey matter in the cer-
ebellum could be explained by severe
demyelination in three cases or a high
virus load in one case. In the remaining
two dogs, other causes for the abnormal-
ities in MRI have to be considered.
DISCUSSION
In white matter diseases in human beings,
such as leucodystrophies or MS, anatomic
MRI is used as a diagnostic tool (Percy and
others 1994, McDonald and others 2001,
Arnold and Matthews 2002). MRI led to
dramatic improvement confirming an
antemortem diagnosis of MS (Sheldon
and others 1985, Grossman and others
1986). Standard protocols using T1- and
T2-weighted images, precontrast and post-
contrast and FLAIR sequences are rou-
tinely applied (Cifelli and others 2004).
MS lesions in human beings present
increased signal intensities in T2-weighted
images (Scotti and others 1986, Paty
1987, Cifelli and others 2004) as found
in the current study in CDV infection.
In demyelinating diseases because of the
disappearance of the myelin sheath, an

September 2008
Ó 2008 British Small Animal Veterinary Association
 Table 1. Clinical neuroanatomical localisation, results of CSF examination, MRI findings and results of post-mortem examination in five dogs with natural canine
distemper virus infection
Dog number Clinical CSF MRI findings CE Histopathology Immunohistology
(age) localisation

1 (4 months) Forebrain 0 cells; TP: 32 mg/dl T2: hyperintensity in the right 1 Necrosis of neurons in the 2 Parietal lobe
temporal (Fig 2) and frontal lobe hippocampus 2 Hippocampus
passing to olfactory bulb 2 Brainstem
T1: hypointensity of the temporal

Journal of Small Animal Practice

lobe right . left, reaching to the

hippocampus
T2: second hyperintense lesion
periventricularly in the ventral

Vol 49
thalamus
T1: lesion isointense Subacute multifocal demyelination in 1 Cerebellum
the cerebellum
2 (8 months) Forebrain n.d. T2: inhomogenic hyperintensity in 2 1 Forebrain; multifocally
the temporal lobe dorsal bilaterally
symmetrical reaching to the
olfactory bulb
T2: second hyperintense lesion in
the right parietal lobe
T1: lesions isointense Moderate spongy state multifocally 1 Cerebellum
in the cerebellar white matter,
proliferation of glia cells and
gemistocytes (multifocal
leucoencephalomalacia)
3 (3 months) Forebrain and midbrain n.d. T2: hyperintensity in left temporal 2 1 Forebrain
lobe next to the brainstem 1 Brainstem
T1: lesion isointense
T2: loss of contrast between white Cerebellum: multifocal swelling of 1 Cerebellum
and grey matter in the cerebellum the myelin sheath
4 (6 months) Forebrain 205 leucocytes/ll; TP: 44 mg/dl T2: hyperintensity in the left n.a. 11 Temporal lobe
temporal lobe (Fig 3A) 1 Frontal lobe
T1: hypointensity in the left temporal
lobe (Fig 3B)
FLAIR: increased signal in the left
temporal lobe (Fig 3C)
T2: loss of contrast between white Cerebellum: demyelination 1 Cerebellum
MRI findings in acute CDV infection

September 2008
Ó 2008 British Small Animal Veterinary Association

and grey matter in the cerebellum (Fig 6C,D), gemistocytes and
(Fig 6A) gitter cells with eosinophilic
intracytoplasmatic inclusion
bodies in astrocytes
5 (3 months) Forebrain and brainstem 18 leucocytes/ll; TP: 30 mg/dl T2: hyperintense focal lesion in the n.a. Brainstem: severe subacute focal 1 Forebrain
left brainstem (Fig 4) demyelinating encephalitis with 11 Brainstem
gemistocytes, gitter cells,
spheroids, mild glia cell
proliferation and eosinophilic
intranuclear inclusion bodies
T1: not performed
T2: hyperintense lesion in the caudal Cerebellum: subacute multifocal 11 Cerebellum
subcortical white matter of the moderate demyelinating
cerebellum (Fig 5) encephalitis with neuronal
necrosis, satellitosis, glia
proliferation, spheroids and
eosinophilic intranuclear inclusion
bodies
T1: not performed

CSF Cerebrospinal fluid, MRI Magnetic resonance imaging, CE Contrast enhancement, TP Total protein, n.d. Not determined, T1 T1-weighted images, T2 T2-weighted images, FLAIR Fluid-attenuated inversion recovery, n.a. Not applied In CE,
1 indicates contrast enhancement, 2 indicates no contrast enhancement. In immunohistology, 2 Negative, 1 Moderate number of antigen positive cells, 11 High number of antigen positive cells. In MRI, Intensities were evaluated
relative to normal grey matter. T1: TR=330 ms, TE=12 ms; T2: TR=3458 ms, TE=96 ms; FLAIR: TR=9000 ms, TE=105 ms

463
 A. Bathen-Noethen and others

FIG 2. Dog 1, transverse plane T2-weighted
image with a high-intensity lesion in the right
temporal lobe (arrow)
empty space in the parenchyma develops
filled with extracellular water. An increase
in the water content of tissue causes hyper-
intensity in T2-weighted images in MRI
(Barkovich 2000, Cifelli and others 2004).
Other demyelinating diseases known
to occur in dogs are globoid cell leucodys-
trophy (Cozzi and others 1998, Wenger
and others 1999), spongy degeneration
(Mariani and others 2001) and artificial
experimental allergic encephalomyelitis
(EAE; Kuharik and others 1988). Consis-
tent with findings of CDV, MRI in these
diseases is also characterised by hyperin-
tense lesions in T2-weighted images
(Kuharik and others 1988, Cozzi and
others 1998, Wenger and others 1999,
Mariani and others 2001).
In the presented cases, clinical sus-
pected CDV infection could be confirmed
by histopathology. As frequently observed
in inflammatory CNS diseases (Tipold
1995), histopathology does not always
correlate with clinical signs, and this phe-
nomenon was also found in the dogs
described above. Histopathology corre-
lated better but not consistently with
MRI findings: hyperintense lesions in
the cerebrum, cerebellum or brainstem
were found in the brains of all dogs in
T2-weighted images. However, histopath-
ological examination only revealed demy-
elination in the cerebellum and the
brainstem but not in the forebrains,
respectively, in the temporal lobe of the
affected dogs. For these lesions, other
correlates have to be identified, such as
inflammation, oedema, haemorrhage, re-
myelination, axonal loss or gliosis (Bradley
1993, Percy and others 1994, Thomas
and others 1997, Mellema and others
1999, Cifelli and others 2004, Cherubini
and others 2006, Wessmann and others
2006). In the presented cases, the fore-
brain lesions seen in four dogs were

FIG 3. (A) Dog 4, transverse plane T2-weighted image with a high-intensity lesion in the left temporal lobe (arrow). (B) Dog 4, transverse plane
T1-weighted image with a hypointense lesion in the left temporal lobe (arrow). (C) Dog 4, transverse plane fluid-attenuated inversion recovery
image with a high-intensity lesion in the left temporal lobe (arrow) (same lesion as shown in Fig 3A, B). (D) Dog 4, high number of CDV antigen positive
cells in the white matter of the left temporal lobe, immunohistochemistry, ABC method, 2
53. (E) Dog 4, moderate number of CDV antigen positive
cells in the white matter of the left frontal lobe, immunohistochemistry, ABC method, 2
53

464 Journal of Small Animal Practice
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FIG 4. Dog 5, transverse plane T2-weighted
image with high-intensity lesion in the left
brainstem (arrow)
isointense or hypointense in T1-weighted
images. These characteristics correspond
to lesions seen in demyelinating diseases
including spongy degeneration (Mariani
and others 2001), EAE (Kuharik and
others 1988), MS (Barkhof and van
Walderveen 1999, Cifelli and others
2004) or in oedema (Mellema and others
1999, Hicdonmez and others 2003).
FLAIR images are used to detect peri-
ventricular lesions, which might be
masked in T2-weighted images (Bakshi
and others 2001). In the dogs of the pres-
ent study, FLAIR images could detect
hyperintense lesions in the localisations
corresponding to those seen in T2-
weighted images and no further lesions
were found.
Contrast medium was administered in
the three dogs with antemortem MRI, but
contrast enhancement was only found in
FIG 5. Dog 5, sagittal plane T2-weighted
image, hyperintense patchy lesion in the caudal
subcortical cerebellar white matter (arrow)
Journal of Small Animal Practice
Vol 49
MRI findings in acute CDV infection
one dog. In MS, contrast enhancement
is associated with active lesions and is
an indicator of acute to subacute inflam-
matory activity (Grossman and others
1986, Gonzalez-Scarano and others
1987, Cifelli and others 2004). The cases
presented here suffered from the acute
stage of CDV infection where inflamma-
tion is not primarily expected. However,
contrast enhancement was found in one
dog, which might have already a slight
inflammation as shown by a slight pleo-
cytosis in the CSF.
Newcombe and others (1991) showed
that MRI findings did not always correlate
with lesion localisations in histopathology
in MS. In MRI, extensive highlighted
lesions in T2-weighted images were dem-
onstrated, but only small histopathologi-
cal plaques existed in corresponding
localisations. The authors assumed that
this difference might result from vascular
permeability changes in the areas sur-
rounding plaques causing hyperintensity
in T2-weighted images by increasing
extracellular water content which repre-
sents oedema. A similar pathogenesis
may be applicable for the hyperintensity
in the temporal lobes in the present cases.
Acute oedema, and especially cytotoxic
rather than vasogenic oedema, is difficult
to identify during post-mortem histopath-
ological examination and might require
transmission electron microscopy in addi-
tion (Summers and others 1995).
Oedema, as a consequence of seizures,
has been demonstrated in dogs and human
beings (Mellema and others 1999,
Hicdonmez and others 2003). Postictal
oedema in the dog was suspected in four
dogs showing hyperintensity in T2- FIG 6. (A) Dog 4, sagittal plane T2-weighted
weighted images but could only be con- image, loss of contrast between the white and
grey matter in the caudodorsal cerebellum
firmed by histopathology in one case with (arrow). (B) Cerebellum of a normal eight-
additional meningioma, where brain week-old dog with good contrast between the
biopsy was performed (Mellema and white and grey matter. (C) Dog 4, cerebellum:
acute demyelinating lesion in distemper
others 1999). As in the presented cases encephalitis. Luxol fast blue staining (LFB), N
here, lesions were found primarily in the normal degree of myelination, D focal area of
temporal lobes. Postictal oedema is con- demyelination, 2
53. (D) Dog 4, cerebellum:
acute demyelinating lesion in distemper
sidered to be partially resolve in 10 to encephalitis. Luxol fast blue staining, N
16 weeks after cessation of seizures normal degree of myelination, D focal area of
(Mellema and others 1999) and can be demyelination, 103
distinguished from other lesions such as
demyelination or gliosis using follow-up appearance of the brain lesions in these
examinations. As the dogs in the present dogs could be because of acute, possibly
study all had generalised seizures in the last cytotoxic, postictal oedema. Follow-up
four days before MRI, the hyperintense MRI could be useful for differentiating

September 2008
Ó 2008 British Small Animal Veterinary Association 465

FIG 7. Dog 1, transverse plane postcontrast
T1-weighted image with a mild contrast
enhancement in the right temporal lobe (arrow)
between postictal oedema, and more per-
sistent pathological changes such as demy-
elination and gliosis.
Another possible explanation for an
increased signal in T2-weighted images
is the presence of other diamagnetic mate-
rials than water, such as oxyhaemoglobin,
copper, gold or proteinaceous cysts (Kjos
and others 1985, Harms 1989, Bradley
1993, Bagley and others 2000). Therefore,
diamagnetism may also be a result of high
protein in CDV containing cells as the
hyperintense area in the temporal lobe
of dog 4 was identical to the area with high
antigen load in immunohistochemistry. In
the frontal lobe with normal intensity in
MR images, the number of antigens
seemed to be lower (dog 4). High antigen
load with demyelination was also found in
the T2-hyperintense lesion of the brain-
stem of dog 5.
Abnormal MRI findings were also
detected in the cerebellum in terms of
a loss of contrast of white to grey matter
in T2-weighted images as described in
other cases with demyelinating diseases
(Percy and others 1994, van der Knaap
and others 2002). Corresponding to these
findings, demyelination in the cerebellum
was demonstrated by histopathology in
the dogs of the presented cases.
To assess whether the MRI findings are
because of demyelination or oedema, it
might be valuable to use special MR tech-
niques. An advanced MR method, which
would provide more information about
the source of the MRI changes, is magnet-
isation transfer imaging (MTI) and the
466
A. Bathen-Noethen and others
magnetisation transfer ratio (MTR).
MTR is strongly decreased in demyelin-
ation, which appears as a highlighted
lesion in MTI, and is only mildly
decreased in oedema (Dousset and others
1992, Grossman 1994, Grossman and
others 1994, Hiehle and others 1995, Bro-
chet and Dousset 1999, McGowan and
others 2000). Unfortunately, this
advanced technique could not be per-
formed in the dogs of the present study
because of technical restrictions.
Conclusions
In the present case series, all dogs with his-
topathologically confirmed acute CDV
lesions showed abnormal findings in
MRI in terms of hyperintense lesions
and loss of contrast of cerebellar white
and grey matter in T2-weighted images.
Correlation of MRI and histopathological
findings of demyelination in the affected
areas was good for the lesions in brainstem
and cerebellum. In the forebrain, histopa-
thology could not explain the aberrations
seen in MRI sufficiently. Furthermore,
postictal changes and a high viral load
were suspected to have caused the lesions.
MRI seems to be a sensitive tool for ante-
mortem diagnosis of the extent of demy-
elinating lesions because of CDV infection
or viral antigen load, although specificity
is limited.
Acknowledgements
The authors thank Dr Henning Schenk,
Axel Gerdwilker and Andreas Nöthen
for technical support.
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