NOTE Internal Medicine

Clinical and MRI Findings of Lissencephaly in a Mixed Breed Dog

Kyo-Im LEE1), Chae-Young LIM1), Byeong-Teck KANG1) and Hee-Myung PARK1)*

1)
BK21 Basic & Diagnostic Veterinary Specialist Program for Animal Diseases and Department of Veterinary Internal Medicine, College
of Veterinary Medicine, Konkuk University, Seoul 143–701, Korea

(Received 14 March 2011/Accepted 5 June 2011/Published online in J-STAGE 17 June 2011)

ABSTRACT. A 7-year-old castrated male mixed-breed dog was presented with a complaint of acute pain. The dog had suffered from iso-
lated seizures for two years. Magnetic resonance imaging (MRI) of the brain revealed a smooth brain surface due to lack of gyri and
sulci formation of the cerebrum and thick cortical grey matter. Additionally, ventriculomegaly and an arachnoid cyst were noted. Mul-
tiple spinal cord compressions induced by intervertebral disc protrusion were observed on a cervical MRI. Based on these findings, the
dog was diagnosed as having lissencephaly concurrent with intervertebral cervical disease. After therapy for seizure and cervical pain,
the clinical signs were completely resolved. To the author’s knowledge, this is the case report to diagnose lissencephaly in a mixed-
breed dog.
KEY WORDS: canine, lissencephaly, MRI.
J. Vet. Med. Sci. 73(10): 1385–1388, 2011

Lissencephaly is a brain malformation that is character-
ized by a paucity of gyral formation and a thickening of the
cerebral cortex [19]. The smooth brain surface is caused by
disturbed migration of neurons during fetal development
[8]. In humans, lissencephaly has been found to be associ-
ated with mutation of the DCX gene on the X chromosome
and the LIS1 gene on chromosome 17 [4, 7, 9, 20].
In veterinary medicine, lissencephaly has been reported
in only 5 dogs, all of which were Lhasa Apsos [5, 14, 18].
The etiologic mechanism for dog lissencephaly is uncertain;
however, it is assumed to be associated with genetic disease
rather than teratogenic disease because most of the cases
that have been reported to date occurred in Lhasa Apso dogs
[5].
In dogs, lissencephaly predominantly results in signs of
forebrain disease such as seizures, visual deficits and behav-
ioral abnormalities including difficulty in training [5, 14,
18]. Histopathologic findings of the lissencephalic brain
revealed a lack of gyral development accompanied by a lack
of corona radiata in those affected areas, as well as a thick-
ening of the neocortex [5, 14, 18]. In one report, magnetic
resonance imaging (MRI) showed a smooth cerebral surface
and a thick neocortex with an absence of the corona radiata
[14]. Thus, MRI is considered as the method of choice for
antemortem diagnosis of lissencephaly.
This case report describes the clinical and MRI findings
of lissencephaly in a mixed- breed dog.
A 7-year-old castrated male mixed-breed dog weighing 5
kg was admitted due to a history of acute pain. The appear-
ance of this dog was similar to a Pekingese. The dog also
had a history of isolated seizures over two years. The sei-
zures were described as a generalized tonic-clonic type with
* CORRESPONDENCE TO: PARK, H.-M., Department of Veterinary
Internal Medicine, College of Veterinary Medicine, Konkuk Uni-
versity, # 1 Hwayang-dong, Kwangjin-gu, Seoul 143–701, South
Korea.
e-mail: parkhee@konkuk.ac.kr
autonomic signs (urination and defecation) and hypersaliva-
tion. Although treatment for the seizures with phenobarbital
(Solondo®, Yuhan, Korea; 1.5 mg/kg, PO, twice a day) was
initiated 6 months previously at a local animal hospital, the
seizures were not controlled. Upon inquiry, it was found
that the owner was having difficulty in managing house
training. In addition, the dog was aggressive and had to be
coaxed by the owner to allow anyone to touch him. The dog
had had behavioral abnormalities throughout his life, but no
visual deficits were noticed by the owner.
On neurological examination, the dog’s gait and postural
reaction were normal. In addition, cranial nerve function
examination revealed an asymmetrical face. The dog’s
pupils were dilated and pupillary light reflexes decreased
bilaterally. The menace response and visual placing
response were normal. Pain was elicited on palpation of the
cervical vertebrae. Neurologic localizations included cervi-
cal and forebrain lesion.
Complete blood counts revealed mild leukocytosis, 18.26
 10³/μl [reference range: 6–17  10³/ μl], increased hepatic
enzymes (alkaline phosphatase, 142 IU/l [reference range:
15–127 IU/l]; alanine aminotransaminase, 78 IU/l [refer-
ence range: 19–70 IU/l]) and mild hyperglycemia, 137 mg/
dl [reference range: 70–118 mg/dl]. The findings of tho-
racic and abdominal radiography were not remarkable.
For the evaluation of the brain and cervical lesions, MRI
was performed on this dog. Anesthesia was induced using
intravenous propofol (AnepolInj®, Hana, Korea) and was
then maintained with an isoflurane (Ifran®, Hana, Korea)
and 100% oxygen mixture. MRI of the brain was performed
using a 0.2 Tesla MRI (Vet-MR, Esaote, Genoa, Italy). T1-
weighted (TR=500, TE=26) and T2-weighted (TR=3500,
TE=90) spin echo sequences were obtained.
When compared with MR images of a normal dog, the
brain surface of this dog was found to be smooth due to an
almost complete lack of gyri and sulci. In addition, the cor-
tical gray matter was thicker than in the normal dog (Fig. 1).
1386 K.-I. LEE ET AL.
Fig. 1. Transverse MR image of the lissencephalic mixed-breed
dog. (A) Transverse T1-weighted MR image and (B) T2-
weighted MR image at the level of the frontal lobe in the lissen-
cephalic mixed-breed dog. The surface of the cerebrum is
smooth (almost agyria) with thick cortical gray matter. There are
no sulci, including the marginal, sylvian, ectosylvian and supra-
sylvian sulci. There is asymmetric ventriculomegaly of both lat-
eral ventricles. (C) Transverse T1-weighted MR image and (D)
T2-weighted MR image at the level of the rostral part of the cer-
ebellum in this lissencephalic mixed-breed dog. There is a well-
defined isointensity associated with cerebrospinal fluid in the
quadrigeminal cistern.
Upon examination of dorsal MR images at the level of the
corpus callosum, gyri and sulci were absent in this lissen-
cephalic case. Moreover, there were bilateral asymmetric
ventriculomegaly and a cystic lesion in the quadrigeminal
cistern (Figs. 2 and 3). Evaluation of the pulse sequences
revealed that this cystic lesion was isointense to cerebrospi-
nal fluid. There was no evidence of contrast enhancement
or mass effect. Other parts of the brain appeared to be nor-
mal. A cerebrospinal fluid (CSF) analysis showed no abnor-
malities. Viral infections (canine distemper virus, canine
herpesvirus) were excluded by polymerase chain reaction in
the acquired CSF. Cervical MRI revealed a multiple spinal
cord compression induced by intervertebral disc protrusion.
Specifically, multiple lesions were located in C2–3, C5–6
and C6–7. No other abnormalites were not observed in cer-
vical MR images. Based on these findings, this dog was
diagnosed as having lissencephaly and an intracranial arach-
noid cyst (IAC) concurrent with cervical intervertebral disc
disease.
To control cervical pain and seizure, administration of
prednisolone (Solon®, Yuhan, Korea; 1 mg/kg, PO, twice a
day) and phenobarbital (phenobarbital®, Hana, Korea; 3 mg/
kg, PO, twice a day) was started. The pain and seizure activ-
ity gradually improved over two weeks. The owner said that
Fig. 2. Dorsal MR image in the mixed-breed dog with lissenceph-
aly. (A) Dorsal T1-weighted MR image and (B) T2-weighted
MR image at the level of the corpus callosum in the mixed-breed
dog with lissencephaly. The surface of the cerebrum is smooth.
There is a well-defined isointensity associated with the cere-
brospinal fluid in the quadrigeminal cistern. (C) Dorsal T1-
weighted MR image and (D) T2-weighted MR image at the level
of hippocampus in this lissencephalic mixed-breed dog. Note the
absent gyri and thick cortex on the bilateral hemispheres.
Fig. 3. Mid-sagittal MR image in this lissencephalic mixed-breed
dog. (A) Mid-sagittal T1-weighted MR image and (B) T2-
weighted MR image in this lissencephalic mixed-breed dog. The
surface of the cerebrum is smooth due to an almost complete
lack of gyri and sulci. There is a well-defined isointensity associ-
ated with the cerebrospinal fluid in the quadrigeminal cistern.
the last seizure was observed at six months before this report
was written (from first referral day) and that none had
occurred since that time.
In humans, lissencephaly has been found to be associated
with mutation of the DCX gene and the LIS1 gene [4, 7, 9,
20]. Lissencephaly in dogs is assumed to be associated with
genetic disease because most of the cases that have been
reported to date have occurred in Lhasa Apso dogs [4]. The
Lhasa Apso dog has a kind of brachycephaly. Generally,
 LISSENCEPHALY IN A DOG
Asian brachycephalic breeds, such as the Pekinese, Shih-
tzu, and Lhasa Apso, resemble each other in outer appear-
ance, and a close relationship among these three breeds were
well observed by microsatellite genotyping [12]. Even
though, the dog in the present case was a mixed breed and
had characteristics of Asian brachycephaly, it was difficult
to prove the genetic closeness between the Lhasa Apso and
the present dog due to the difficulty of obtaining pedigree
information.
Lissencephaly in humans results in mental retardation,
spastic quadriparesis, spastic paraparesis, focal deficits,
hypotonia, cerebellar symptoms, muscular hypotonia and
seizure [10]. In dogs, lissencephaly primarily results in
signs of forebrain disease such as seizures, visual deficits,
and behavioral abnormalities [5, 14]. In a previous report,
the gait and postural defects were mild in dogs when com-
pared with those in humans with lissencephaly [5]. In this
case, the dog had normal postural reactions. When com-
pared with humans, the differences in clinical signs are
likely because there is less dependence on the cortex in dogs
than in humans [14].
Nonprogressive isolated seizure is a relatively common
finding in dogs with lissencephaly [5, 14, 18], and it is
thought that this is due to the most severe cerebral cortex
malformation. The association of seizures and cortical dis-
ease is well recognized in dogs [13]. All of the previously
reported Lhasa Apso dogs with lissencephaly were found to
have an early onset of seizures, with three of the dogs being
less than one year old at the time of onset and the others
being middle aged [5, 14, 18]. The onset of seizures in this
case occurred later than in previous cases. Difficulty in
house training and behavioral abnormalities are clinical
signs of lissencephaly of humans and dogs. In this case, the
owner also felt that the dog might be less responsive to its
surroundings and aggressive. In previous reports, all the
dogs had seizure and behavioral problems, similar to the dog
reported here, yet their postural reaction did not seem as
severe as those in humans [5, 14, 18].
In this case, MRI showed typical findings of lissenceph-
aly. The MR findings showed a thickened neocortex and a
smooth cerebral surface due to an almost complete lack of
gyri and sulci. This was similar to a previous report in dogs
and classical lissencephaly in humans [6, 14]. Additionally,
ventriculomegaly and an arachnoid cyst were also found in
this case. Intracranial arachnoid cyst (IAC) in the quad-
rigeminal cistern and ventriculomegaly have been reported
previously in a Lhasa Apso dog with lissencephaly [14].
Ventriculomegaly is a relatively common finding in human
lissencephaly, and the possible cause was thought to be a
diminished cerebral volume [3]. Previously, IAC was sus-
pected to be of developmental origin in dogs [17]. Because
the perimedullary mesh is a loose layer of mesenchymal tis-
sue, the CSF flows into the embryonic perimedullary mesh,
resulting in a diverticulum or cyst [2, 11]. Lissencephaly is
considered to be the most severe type of neuronal migration
disorder and is assumed to result from the arrest of neuronal
migration in humans [15, 19, 20]. However, the pathophys-
1387
iology of IAC differs from lissencephaly. Although lissen-
cephaly and IAC were diagnosed concurrently in this case,
IAC is a relatively common finding in brachycephalic
breeds [17].
Generally, lissencephaly can be diagnosed on the basis of
histopathologic findings. However, this case was based on
MR findings only because MRI showed abnormal structures
of lissencephaly and necropsy was not performed. In recent
years, the correlation between histopathological and imag-
ing features has been well established; therefore, the diagno-
sis of lissencephaly by imaging alone is now well accepted
in humans and dogs [1, 14, 16]. In this case, MRI was an
efficient imaging modality for antemortem diagnosis of lis-
sencephaly in a dog. Therefore, this is the first case report
of describing lissencephaly in a mixed-breed dog diagnosed
by MRI.
ACKNOWLEDGMENT. This work was supported by
Brain Korea 21.
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