Selected research communications of the 29th Symposium of the ESVN‐ECVN Edinburgh,
United Kingdom 16th to 17th September 2016 TIMETABLE OF THE SYMPOSIUM
Friday 16th September
8.00
Registration
APPLIED TRANSLATIONAL NEUROSCIENCE
8.15
Introduction/Welcome
8.30
INVITED SPEAKER SESSION
Dominic Wells
Stem cells research and Motor Neuron Disease and Amyotrophic Lateral Sclerosis (How
basic science has informed change in clinical practice)
9.15
Joan Coates
Canine Degenerative Myelopathy and Amyotrophic Lateral Sclerosis (from lab to practice
– How basic science changed my understanding and clinical practice)
10.45
Coffee break, poster exhibition and sponsors
11.15
RESEARCH ABSTRACTS
(1) Assessing the role of canine and feline ABCG2 as a mediator of pharmacoresistant
epilepsy
T. Jukier; S. Dassanayake; T. Coffey; A. Chen; K. Mealey
(2) Clinical presentation, magnetic resonance imaging findings and outcome of dogs
diagnosed with intracranial empyema
A. K. Forward, I. N. Plessas, S. De Decker
(3) The novel homozygous KCNJ10 c.986T>C (p.Leu329Pro) variant is pathogenic for the
sesame/east homologue in malinois dogs
K. Stee, M. Van Poucke, S. Bhatti, A. Vanhaesebrouck, L. Bosseler, L. Peelman, L.
Van Ham
(4) Juvenile polyneuropathy in American Staffordshire Terriers
H. Vandenberghe, V. Mayousse, C. Escriou, S. Blot
(5) Magnetic resonance elastography – towards a stiffness atlas of the canine brain
for translational neurology
N.M. Rzechorzek, L. Hiscox, E. Barnhill, S. Hirsch, P. Kennedy, J. Huston, T. Schwarz,
I. Sack, S. Semple, K. Marioni‐Henry, N. Roberts
(6) Therapeutic potential of ATP precursors in experimental stroke
K. Faller, W. Holmes, C. McCabe, I. Macrae, B. Frenguelli
(7) Analysis of blood degradation products and ferritin in the cerebrospinal fluid
of dogs with acute thoracolumbar intervertebral disc extrusion
S. Bittermann, E. Marti, J. Mirkovitch, C. Schild, D. Henke
13.00
Lunch, exhibition and poster session (Posters attended by authors)
14.15
INVITED SPEAKER SESSION
Nina Rzechorzek
Cold shock ‐ repurposing a single neuroprotective strategy into multiple therapeutic
targets
14.45
Natasha Olby
How to unravel the riddle of acute spinal cord diseases and novel treatment options
(from lab to practice – How basic science changed my understanding and clinical practice)
16.15
Coffee break, poster exhibition and sponsors
16.45
FLASH PRESENTATIONS
(F1) A canine brain template for image processing of clinical magnetic resonance imaging
data
S. Schulze, M.J. Schmidt, T. Flegel, E. Ludewig, M. Gounis, N. Ondreka, J. Boltze
and B. Nitzsche
(F2) Remote ischemic postconditioning in dogs undergoing elective spinal cord decompressive
surgery
V. Mortera, N. Granger
(F3) Surgical treatment of chronic spinal cord compression in two coatis
N. Meyerhoff, M. Fehr, J. Neßler, A. Maiolini, J. Tünsmeyer, P. Dziallas, V. Molnár,
C. Ludwig, V. Stein, A. Tipold
(F4) Facial nerve paralysis in dogs: a retrospective study of 69 cases
C. Ricco, L. Giraud, L. Cauzinille
(F5) Magnetic resonance imaging characteristics of cauda equina nerve roots in 50
dogs with degenerative lumbosacral stenosis
D. Alder, S. Ohlert, F. Steffen
(F6) Syringomyelia classification according to associated magnetic resonance imaging
findings in French Bulldogs: 64 cases (2008–2016)
A. Suñol Iniesta, M. López‐Font, C. Morales, J. Mascort, M. Manera, P. Montoliu
(F7) Pathological circling patterns in dogs with brain lesions diagnosed
D. Faissler, L. Grobicki
(F8) Application of a functional brain atlas to interpret human epileptic seizure‐related
FMRI maps and considerations for application in animals
M. Charalambous, L. A. van Graan, A. Liston, L. Lemieux
(F9) Species‐specific differences in cellular aggregation and localisation of virally‐transduced
mutant and normal canine and equine superoxide dismutase 1 (SOD1) proteins
A. Draper, Z. Windley, C. Maile and R.J. Piercy
(F10) Intraoperative ultrasound elastography of the canine spinal cord
J. Prager, A. Delaney, J. Rose, T. Harcourt‐Brown, D. Chari, N. Granger
(F11) Inflamed intracranial meningioma mimicking brain abscess in a dog
C. Tästensen, S. Hanemann, M.‐K. Müller, M. Rosati, K. Matiasek, T. Flegel
(F12) Overshunting and subdural haemorrhage after implantation of a low‐pressure valve
ventriculoperitoneal shunt in a dog with hydrocephalus internus, quadrigeminal cyst
and high intracranial pressure
S. Hanemann, I. Merseburger, V. Fromme, S. Piesnack, T. Flegel
(F13) Cannabinoid receptor type 2 (CB2) expression in canine steroid‐responsive meningitis‐arteritis
(SRMA) and intraspinal spirocercosis
J. Freundt‐Revilla, F. Heinrich, M.H. Shamir, A. Oevermann, W. Baumgärtner, A. Tipold
17.36
AGM
20.00
Gala Dinner
Saturday 17th September
8.00
Registration
8.30
INVITED SPEAKER SESSION
Richard Piercy
New insights into pathophysiology and treatment of laryngeal paralysis (from lab to
practice – How basic science changed my understanding and clinical practice)
9.15
RESEARCH ABSTRACTS
(8) The odds of demographic, social and environmental factors influencing the development
of acute canine polyradiculoneuritis in the UK
E. J. Laws, T. R. Harcourt‐Brown, N. Granger, J. H. Rose
(9) Accuracy of a patient‐specific 3D‐printed drill guide for vertebral pedicle screw
placement
S. Bennett, S. Behr, B. Oxley
(10) Clinical features and magnetic resonance imaging findings in 20 cats with confirmed
neurological feline infectious peritonitis
A. Crawford, A. Stoll, A. Shea, J. Michaels, A. Fraser, E. Beltran
10.00
Coffee break, poster exhibition and sponsors
10.30
RESEARCH ABSTRACTS
(11) Safety and efficiency of an increased standardised protocol for the treatment
of meningoencephalitis of unknown origin in dogs
C. Ricco, L. Cauzinille
(12) Genetically modifying canine olfactory ensheathing cells for spinal cord injury
repair
D. Carwardine, E. Muir, LF. Wong, N. Granger
(13) Utility of the electronic von Frey aesthesiometer to quantify cervical skin sensitivity
in dogs with syringomyelia
H. Williams, S. Sanchis, H.A.Volk, L. Pelligand, J. Murrell, N. Granger
(14) Kinematic measures for assessing gait in dogs with Degenerative Myelopathy
J. Neeves, L.F. Wong, N. Granger
(15) Canine Degenerative Myelopathy associated SOD1 gene mutation (E40K) alters the
cellular behaviour and the steady state level of SOD1 protein
Y. Qi, P. Montague, I.N.F. Shafie, P.E. Johnston, T.J. Anderson, M. McLaughlin
(16) High prevalence of equine polysaccharide storage myopathy in horses with signs
suggestive of equine motor neuron disease
C. Massey, R.J. Piercy
(17) Bovine dorsal root ganglia culture as an in vitro model for listeria monocytogenes
brain invasion
A. Fadda, M. Bärtschi, H.R. Widmer, A. Zurbriggen, A. Oevermann
(18) The dog model of human brain aging and early Alzheimer's disease: a translational
study of neuropathological markers
T. Schütt, L. Helboe, L.Ø. Pedersen, G. Waldemar, M. Berendt, J.T. Pedersen
12.30
Lunch, exhibition and poster session (Posters attended by authors)
13.45
INVITED SPEAKER
Richard Piercy
Treatment for neuromuscular disease (How basic science has informed change in clinical
practice)
14.25
RESEARCH ABSTRACTS
(19) Bidirectional benefits of a naturally occurring canine model for testing and
development of drugs for status epilepticus
E. Patterson, I. Leppik, L. Coles, J. Cloyd
(20) Environment in canine ambulatory electroencephalography
F. James, K. Vurik, L. Gaitero, S. Nykamp, J. LaMarre, T. Jokinen, H. Lohi
(21) Magnetic resonance (MR) imaging characteristics of histopathologically confirmed
non‐functional sellar masses in dogs
A. Chen, T. Owen, L Martin, A. Turner, S. Carrera‐Justiz, K. Karnik, D. Bruyette
15.10
Coffee break, poster exhibition and sponsors
15.40
RESEARCH ABSTRACTS
(22) Why, when, how and post‐operative care of dogs undergoing transphenoidal hypophysectomy
for large sellar masses
T. Owen, A. Chen, L. Martin
(23) Treatment of canine frontal and olfactory lobe meningioma with either surgical
debulking alone, surgery and metronomic chemotherapy or surgery and definitive radiation
therapy
D. Faissler, T. Bentley, A. Bilderback, A. Sato
(24) Paclitaxel releasing mesenchymal stromal cells treatment in canine gliomas
O. Zeira, E. Ghezzi, M. Aralla, N. Asiag, M. Konar, A. Pessina, G. Alessandri
(25) Evaluation of a modified transfrontal craniotomy technique in 8 dogs
R.T. Bentley, S.A. Thomovsky
(26) IL‐6 is increased in CSF and plasma of dogs with acute ischaemic stroke
H. Gredal, B. Thomsen, A. Boza‐Serrano, L. Garosi, C. Rusbridge, D. Anthony, A. Møller,
B. Finsen, T. Deierborg, K. L. Lambertsen, M. Berendt
16.55
Closing comments and competition winner
ORAL PRESENTATIONS
Assessing the Role of Canine and Feline ABCG2 as a Mediator of Pharmacoresistant Epilepsy
T. Jukier
1, S. Dassanayake2, T. Coffey3, A. Chen1, K. Mealey2
1Department of Veterinary Clinical Sciences, Washington State University, Collage
of Veterinary Medicine Pullman, Pullman, WA, USA2Program in Individualized Medicine,
Washington State University, Collage of Veterinary Medicine Pullman, Pullman, WA,
USA3Department of Statistics, Washington State University, Collage of Veterinary Medicine
Pullman, Pullman, WA, USA
Epilepsy is a chronic condition of recurring unprovoked epileptic seizures. Of the
population of idiopathic epileptics, a subset of them fail to respond to medical management.
This study investigated whether or not anti‐epileptic drugs (AED) are substrates for
canine or feline orthologs of the drug efflux transporter ABCG2.
Human embryonic kidney cells (HEK‐293) that had been stably transfected with plasmids
containing either canine or feline ABCG2 cDNA were utilized for these experiments.
Levetiracetam, phenobarbital, gabapentin, zonisamide, and lamotrigine were the AED
evaluated with a flow cytometry‐based competitive transport assay. Mitoxantrone, a
classic ABCG2 substrate, is an intrinsically fluorescent molecule. Transfected HEK‐293
cells expressing ABCG2 are expected to extrude mitoxantrone from the cell resulting
in low intracellular fluorescence. Addition of another ABCG2 substrate results in
competition for ABCG2 transport, decreasing mitoxantrone extrusion and increasing
intracellular fluorescence. Analysis was performed separately for each AED with either
canine or feline ABCG2‐transfected cells. One‐way ANOVA was used to assess a statistical
difference between groups followed by Dunnett's test for comparisons against control.
Statistical significance was achieved for one concentration in the canine zonisamide
group. Because fluorescence actually decreased, indicating influx rather than efflux,
the clinical significance is unknown.
Results of this study suggest that ABCG2 does not contribute to pharmacoresistant
epilepsy for the evaluated AED.
Clinical Presentation, Magnetic Resonance Imaging Findings and Outcome of Dogs Diagnosed
with Intracranial Empyema
A. K. Forward
1, I. N. Plessas2, S. De Decker1
1Royal Veterinary College, University of London, Hatfield, UK2Davies Veterinary Specialists,
Hertfordshire, UK
Intracranial empyema is a rare neurological emergency that requires rapid and aggressive
intervention. This case series aims to describe the clinical presentation, advanced
imaging findings, and short and long term outcomes in dogs with intracranial empyema.
Medical records from two referral hospitals were searched and identified dogs diagnosed
with intracranial empyema. Inclusion criteria comprised of an MRI consistent with
contiguous infection from adjacent structures, a CSF analysis suggestive of empyema
or direct visualization of purulent material during intracranial surgery.
Ten dogs were included, with a median age of 2 years (range 4 months–12.5 years).
All presented as emergencies with 8/10 showing neurological abnormalities and 2/10
with retro‐bulbar swelling and exophthalmos. 6/10 had surgical intervention, 2/10
were medically managed and the remaining 2/10 were euthanised. Typical MRI findings
included extra‐axial, T1‐weighted hypo‐ isointense, T2‐weighted hyperintense material
with varying degrees of contrast enhancement, with 6/9 showing evidence of contiguous
infection from adjacent structures on MRI. 6/10 had culture and sensitivity performed
with 2/6 returning Enterococcus and Streptococcus species respectively. The median
antimicrobial course length was 6 weeks (range 2–28 weeks). 8/10 survived to discharge,
with a median hospitalisation time of 6.5 days (range 4–10 days). 5/8 are still alive
at the time of writing (1 lost to follow up; 2 euthanised for other reasons) with
all five considered neurologically normal with a successful long term outcome.
Whilst intracranial empyema in dogs is a rare condition, excellent outcomes are possible
in those cases treated appropriately.
The Novel Homozygous KCNJ10 C.986T>C (P.LEU329PRO) Variant is Pathogenic for the Sesame/East
HomOLOGUE in Malinois Dogs
K. Stee
1, M. Van Poucke2, S. Bhatti1, A. Vanhaesebrouck3, L. Bosseler4, L. Peelman2, L. Van
Ham1
1Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine,
Ghent University, Belgium2Department of Nutrition, Genetics and Ethology, Faculty
of Veterinary Medicine, Ghent University, Belgium3Department of Clinical Neurosciences,
John Radcliffe Hospital, University of Oxford, UK4Department of Pathology, Bacteriology
and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Belgium
SeSAME (Seizures, Sensorineural deafness, Ataxia, Mental retardation, and Electrolyte
imbalance) or EAST (Epilepsy, Ataxia, Sensorineural deafness, Tubulopathy) syndrome
is a multisystemic disorder in man. The condition is exclusively caused by homozygous
or compound heterozygous variations in the KCNJ10 gene. Here we describe a similar
syndrome in the Malinois dog breed. This mutation differs from the already identified
KCNJ10 mutation in the Russell group of terriers responsible for spinocerebellar ataxia
with myokymia, seizures, or both.
Four 4‐month‐old Malinois of 2 unrelated families were presented for an uncoordinated
gait since the age of 12 weeks. Neurological examination revealed severe generalized
hypermetric ataxia in all dogs, involuntary vermicular muscle twitching (myokymia)
triggered by excitement in 2 dogs and epilepsy in 2 dogs. Absent patellar reflexes
were noted in all dogs. Complete blood count, serum biochemistry, urinalysis, magnetic
resonance imaging of the brain and CSF analysis did not reveal any abnormalities.
Electromyography showed neuromyotonic discharges in the clinically affected muscles.
Results of motor nerve conduction and repetitive nerve stimulation did not differ
from two age‐matched Malinois control dogs, however, brainstem auditory evoked potentials
showed disappearance of wave components and mildly prolonged latencies in the affected
dogs. Histopathology revealed bilateral myelopathy with predominant axonopathy and
myelin vacuolization in the central nervous system. Genetic analysis detected a novel
pathogenic KCNJ10 c.986T>C (p.Leu329Pro) variant, which is inherited in an autosomal
recessive way.
Conclusively, these mutant Malinois dogs may serve as a promising animal model to
elucidate the pathogenesis and treatment of this disorder in man.
Juvenile Polyneuropathy in American Staffordshire Terriers
H. Vandenberghe
1, V. Mayousse1, C. Escriou2, S. Blot1
1Unité de neurologie, ChuvA, Université Paris‐Est, Ecole nationale vétérinaire d'Alfort,
Maisons‐Alfort, France2Unité de neurologie, VetAgro‐Sup, Université de Lyon, Campus
vétérinaire de Lyon, Marcy L'Etoile, France
Inherited juvenile‐onset polyneuropathy with laryngeal paralysis has been reported
in several breeds of dogs such as Dalmatian, Alaskan Malamute, Leonberger, Russian
Black terrier, Rottweiler and Pyrenean mountain dogs, with a suspected autosomal recessive
inheritance pattern.
Eight young American Staffordshire Terriers were presented for inspiratory stridor
and dyspnoea (7/8), locomotor weakness (8/8) with palmigrade and plantigrade stance
(5/8), with an age of onset ranged from two to six months. Neurological evaluation
revealed four limbs ataxia with high stepping pelvic limb gait (8/8), limb muscles
atrophy (6/8), cutaneous hypoesthesia (5/8) and decreased spinal reflexes (5/8).
Laryngeal paralysis was diagnosed during laryngoscopy in seven dogs. Electrophysiological
investigations showed abnormal spontaneous electrical activities in the laryngeal
muscles (7/8) and appendicular muscles (8/8), marked attenuation of compound muscle
action potentials amplitude (8/8), reduced motor nerve conduction velocities (7/8),
decreased or absent sensory nerve action potentials (8/8).
Muscle biopsies were performed in six cases and histologic analysis was consistent
with neurogenic atrophy and intramuscular nerve branches myelinated fiber loss. Fibular
nerve biopsy analysis, when performed (four cases), was consistent with chronic and
severe extensive nerve fiber loss resulting from axonal degeneration.
To the authors’ knowledge, this is the first report of a juvenile‐onset polyneuropathy
with laryngeal paralysis in American Staffordshire Terrier. One of the dogs is a backcross
and an autosomal recessive mode of inheritance is suspected. If pedigree analysis
and genotyping are consistent with this hypothesis, the American Staffordshire Terrier
polyneuropathy could be considered as a new spontaneous animal model of inherited
axonal neuropathy (Charcot‐Marie‐Tooth disease). Genotyping could lead to the discovery
of new genes involved in axonal degeneration.
Magnetic Resonance Elastography – Towards a Stiffness Atlas of the Canine Brain for
Translational Neurology
N. M. Rzechorzek1,2, L. Hiscox3,4, E. Barnhill5, S. Hirsch5, P. Kennedy3, J. Huston6,
T. Schwarz7, I. Sack5, S. Semple3, K. Marioni‐Henry1, N. Roberts3
1Neurology/Neurosurgery Service, Hospital for Small Animals, Royal Dick School of
Veterinary Studies and Roslin Institute, University of Edinburgh, UK2Centre for Clinical
Brain Sciences, University of Edinburgh, UK3Clinical Research Imaging Centre CRIC,
Queen's Medical Research Institute, University of Edinburgh, UK4Alzheimer Scotland
Dementia Research Centre, University of Edinburgh, UK5Institute of Medical Informatics,
Charité, Universtätsmedizin, Berlin6Department of Radiology, Mayo Clinic, Rochester,
MN7Diagnostic Imaging Service, Royal Dick School of Veterinary Studies and Roslin
Institute, University of Edinburgh, UK
Tissue mechanical properties vary over several orders of magnitude in the disease
state and elude current veterinary neuroimaging modalities. Magnetic Resonance Elastography
(MRE) combines conventional MRI with acoustic wave propagation to generate high‐resolution
viscoelasticity or ‘stiffness’ data and is emerging as a valuable, non‐invasive diagnostic
tool in human neurology. The purpose of this study was to establish whether MRE could
be applied to the canine brain.
Post‐mortem brain scans were performed on canines euthanized on welfare grounds with
approval of the R(D)SVS Veterinary Ethical Review Committee. A standard cartesian
Echo Planar Imaging sequence with additional motion encoding gradients was used for
multiple frequency (30–100 Hz) acquisition on a 3T Verio MRI system (Siemens Medical
Systems), with vibrations generated by the Resoundant actuator and head pillow (http://resoundant.com/).
Raw phase images were analysed with the Elastography Software Pipeline to produce
maps of viscoelastic parameters.
Our protocol readily propagated waves into the specimens enabling construction of
high‐resolution elastograms of the canine brain. Variation in tissue stiffness across
different brain regions was observed, as noted in the human brain in vivo. Mean whole
brain tissue viscoelasticity ± standard error was 2.99 ± 0.30 kPa (n = 3).
This is the first demonstration that acoustic waves can be propagated into the canine
brain in situ. Our follow‐on objective is to construct a reference atlas of canine
brain stiffness against which to test the sensitivity of MRE for detecting and differentiating
age‐related and pathological changes. ‘Virtual palpation’ of the brain with MRE has
the potential to revolutionize veterinary neuroimaging.
Therapeutic Potential of ATP Precursors in Experimental Stroke
K. Faller
1,2, W. Holmes2, C. McCabe2, I. Macrae2, B. Frenguelli3
1School of Veterinary Medicine, College of Medical, Veterinary, and Life Sciences,
University of Glasgow, Glasgow, UK2Institute of Neuroscience & Psychology, College
of Medicine, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK3School
of Life Sciences, University of Warwick, Coventry, UK
Brain damage causes profound and prolonged ATP loss. Prior in vitro studies showed
that supplementation of ischaemic brain slices with precursors of ATP synthesis, D‐ribose&Adenine
(RibAde), restores ATP levels. We aimed to assess the therapeutic potential of RibAde ± Allopurinol
in a rat model of transient focal cerebral ischaemia. Allopurinol should potentiate
the effect of RibAde by preserving hypoxanthine, also used in the purine salvage pathway.
This study conforms to the UK Animals (Scientific Procedures) Act. Male Wistar rats
were randomised to three groups and the investigator was blinded to treatment. After
1‐h transient focal ischaemia, RibAde group received at reperfusion an intravenous
infusion of ribose (200 mg/kg/h) and adenine (10 mg/kg/h) over 6 h. RibAde&Allopurinol
group also received allopurinol (10 mg/kg, IP). Saline group received intravenous
and intraperitoneal injections of saline. Acute ischaemic injury and subsequent infarction
were assessed by MRI immediately prior to reperfusion (diffusion weighted imaging)
and 7 days after reperfusion (T2‐weighted imaging). Functional outcome was assessed
at days 1, 3 and 7 post‐stroke.
RibAde ± Allopurinol had no significant side‐effect. A greatest reduction in lesion
volume between day 0 and day 7 was observed in the RibAde ± Allopurinol (50 % reduction,
n = 8) and RibAde groups (38 %, n = 8) compared to Saline group (18 %, n = 6). This
did not achieve statistical significance but was accompanied by a trend for faster
functional recovery.
This pilot study suggests RibAde&Allopurinol as a potential therapy for stroke. Larger
studies are required for confirmation of these preliminary results, before translation
as a therapeutic option in clinical settings.
Analysis of Blood Degradation Products and Ferritin in the Cerebrospinal Fluid of
Dogs with Acute Thoracolumbar Intervertebral Disc Extrusion
S. Bittermann
1,2, E. Marti3, J. Mirkovitch3, C. Schild4, D. Henke1,2
1Division of Neurological Sciences, Department of Clinical Veterinary Medicine, Vetsuisse
Faculty, University of Bern, Switzerland2Division of Clinical Veterinary Neurology,
Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern,
Switzerland3Department of Clinical Research and Veterinary Public Health, Vetsuisse
Faculty, University of Berne, Vetsuisse Faculty, University of Bern, Switzerland4Institute
of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern,
Switzerland
Intervertebral disc extrusion (IVDE) is a common cause of severe spinal cord injury,
and an accurate prognosis remains challenging. Hemorrhage in the spinal cord or in
the subarachnoidal space may have an important impact on damage of the spinal cord
parenchyma and outcome, and thus, may be relevant for the prognosis of dogs with IVDE.
Therefore, the aim of the study was to evaluate if blood degradation products and
ferritin are measurable in the CSF of dogs with thoracolumbar IVDE, and if there is
an association to clinical parameters.
Measurements of net oxyhemoglobin absorption (NOA), net bilirubin absorption (NBA)
and ferritin concentration were prospectively performed in the CSF of 34 dogs with
thoracolumbar IVDE, 21 dogs with idiopathic epilepsy either native (IE) or artificially
contaminated with blood (IEc), and 9 dogs with steroid responsive meningitis arteritis
(SRMA).
The NOA was significantly higher in the IVDE group compared to the IE (P < 0.001)
and SRMA (P < 0.001), but not to the IEc group (P = 0.89). The NBA was significantly
higher in the IVDE group compared to all control groups (P < 0.001, respectively).
Ferritin concentration was significantly higher in the IVDE compared to the IE group
(P = 0.03). In dogs with IVDE, there was no association between NOA, NBA and ferritin
concentration and severity and duration of clinical signs, and outcome.
It is possible to quantify blood degradation products and ferritin in the CSF. However,
larger case numbers are needed to evaluate their relevance as prognostic indicator
in dogs with thoracolumbar IVDE.
The Odds of Demographic, Social and Environmental Factors Influencing the Development
of Acute Canine Polyradiculoneuritis in the UK
E. J. Laws, T. R. Harcourt‐Brown, N. Granger, J. H. Rose
University of Bristol, Bristol, UK
Immune‐mediated diseases, in animals and man, have been linked to factors and triggers
that contribute to the pathogenesis of disease. The aim of this study was to identify
if the development of acute canine polyradiculoneuritis (ACPRN) is associated with
recent vaccination, breed, season, rural/urban habitation, sex, neuter status or age.
A retrospective case‐control study with conditional logistic regression analysis was
performed. Dogs were selected from a referral hospital population in the UK and controls
were matched for year of presentation.
Forty‐three cases were identified with ACPRN and 86 controls were selected. Jack Russell
Terriers (P = 0.003) and West‐Highland White Terriers (P = 0.021) were found to have
a significantly greater odds of developing ACPRN compared to ‘other breeds’ in our
population of dogs. The odds of developing ACPRN were greater in the autumn (P = 0.043)
and winter (P = 0.032) compared to spring. Vaccination, rural/urban habitation, sex,
neuter status and age were not found to increase the odds of developing ACPRN.
In conclusion breed and season were found to increase the odds of developing ACPRN.
This may be important in further understanding the pathogenesis of disease. This may
allow identification of triggers or genetics that play a role in ACPRN and allow us
to develop breeding programs, avoid triggers or even produce preventative treatments
to reduce the prevalence of the disease.
Accuracy of a Patient‐Specific 3D‐Printed Drill Guide for Vertebral Pedicle Screw
Placement
S. Bennett, S. Behr, B. Oxley
Department of Neurology and Neurosurgery, Willows Referral Service, Solihull, England
The aim of this study was to develop a patient‐specific 3D‐printed drill guide for
placement of caudal cervical bicortical pedicle screws as part of the treatment of
disc‐associated wobbler syndrome and to validate its accuracy.
CT scans of the cervical vertebrae from two patients were acquired. These data were
exported to medical image processing software and virtual 3D models of the vertebrae
created for processing in computer aided design (CAD) software. This was used to determine
the optimal trajectory and size of the pedicle screws. For each patient virtual drill
guides were created, 3D‐printed, and used intraoperatively. Locking titanium screws
were used to reduce metal artifact on post‐operative CT; screw heads were bonded with
polymethylmethacrylate cement to stabilise affected vertebral segments. Post‐operative
CT was performed for each patient; the degree of vertebral canal violation was subsequently
graded as 0 (no violation), 1 (<2 mm), 2 (2–4 mm) and 3 (>4 mm). For each screw CAD
files were analysed to yield a screw‐diameter‐to‐pedicle‐width‐ratio (SDPWR) at the
narrowest point of the pedicle; this was expressed as a percentage.
A total of 22 screws were placed; 11 screws were 3.5 mm, nine were 2.7 mm and two
were 2.4 mm. 20 screws (90.9%) were grade 0, 2 (9.1%) were grade 1 and no screws were
grade 2 or 3. This was achieved despite a mean SDPWR of 73.6 % (range 57.9–93.3%).
The use of a 3D‐printed patient‐specific drill guide permitted accurate placement
of bicortical pedicle screws in the caudal cervical vertebrae. This technique has
the potential to improve clinical outcome through increased osteosynthesis strength,
reduced surgical time and reduced morbidity.
Clinical Features and Magnetic Resonance Imaging Findings in 20 Cats with Confirmed
Neurological Feline Infectious Peritonitis
A. Crawford1, A. Stoll1, A. Shea2, J. Michaels3, A. Fraser4, E. Beltran1
1Department of Clinical Science and Services, Royal Veterinary College, London, UK2Animal
Health Trust, Newmarket, UK3Department of Veterinary Medicine, University of Tennessee,
USA4UVet, The University of Melbourne, Victoria, Australia
Feline infectious peritonitis (FIP) is the most common infectious central nervous
system disease in the cat, and is invariably fatal. Improved means of ante mortem
diagnosis are required to facilitate clinical decision‐making. Information regarding
the magnetic resonance imaging (MRI) findings in cases of FIP is currently limited,
resulting in the need for better descriptions to optimize the use of this imaging
modality as a diagnostic tool in suspected cases.
The aim of this study was to describe the MRI findings in cases of confirmed neurological
FIP. Archived records from 4 institutions were retrospectively reviewed to identify
cases with confirmed neurological FIP that had undergone MRI of the brain and/or spinal
cord. Signalment, clinical, clinicopathological, histopathological findings and outcome
were evaluated.
MRI abnormalities were detected in all 20 cases, including periventricular contrast
enhancement (17), leptomeningeal contrast enhancement (18), ventriculomegaly (17),
syringomyelia (14) and foramen magnum herniation (12). CSF was analysed in 10 cases,
all of which demonstrated a marked increase in both total protein and total nucleated
cell count.
All 20 cases were euthanized due to the grave prognosis. The median survival time
from onset of clinical signs to euthanasia was 14 days (range 2–105).
Histopathological analysis revealed perivascular pyogranulomatous and/or lymphoplasmacytic
infiltrates affecting the leptomeninges in 13 cases, the choroid plexus in 13 cases,
periventricular infiltrates in 11, the spinal cord parenchyma in 7 and the brain parenchyma
in 3.
MRI provides a sensitive means of detecting neurological FIP, particularly in combination
with consistent signalment, clinical presentation and CSF analysis.
Safety and Efficiency of an Increased Standardised Protocol for the Treatment of Meningoencephalitis
of Unknown Origin in Dogs
C. Ricco, L. Cauzinille
Centre Hospitalier Vétérinaire Frégis, Arcueil France
Despite being a common diagnosed disease in veterinary neurology, treatment options
in literature for méningo‐encephalo‐myelitis of unknown origin are quite variable
and poorly standardised. The use of Cytarabine Arabinoside (CA) (50 mg/m2 at repeated
injections) in combination with prednisolone has been previously reported with variable
success rates. The aim of the paper was to determine the efficiency and safety of
high dosage CA (100 mg/m2) protocol in conjunction with prednisolone and the outcome
for dogs according to previously reported variables. These were assessed through a
repeated cerebrospinal fluid collection obtained around the 6th CA administration
(average – 3, 4 months) after the initiation of protocol, records of survival, relapse
rates and side effects.
The Chihuahua appeared statistically over‐represented in this study in regard to our
regular hospital population. Eighty seven percent of dogs (77/89) were alive by the
completion of the protocol, 81% were considered to have a positive outcome and 46%
of dogs did not require any further CA administration. Thirty percent of dogs (27/89)
relapsed during the protocol period and 15% after its completion. Cerebrospinal fluid
analysis did not allow to predict relapse in this study. Dogs with a forebrain lesions
and a higher initial dose of glucocorticoids had increased odds of a positive outcome.
Brainstem lesions appear to carry a worse outcome. The degree of pleocytosis and protein
contents at the first CSF collection was not a prognostic factor of outcome.
This (100 mg/m2 SQ for 48 h every 3 weeks, 6 times) protocol of CA appears safe and
enabled to reduce faster the initial immumusuppressive dosage of prednisolone with
lower risks of heavy side effects and a better short term outcome.
Genetically Modifying Canine Olfactory Ensheathing Cells for Spinal Cord Injury Repair
D. Carwardine
1, E. Muir3, L. F. Wong2, N. Granger1
1School of Veterinary Sciences, University of Bristol2School of Clinical Sciences,
University of Bristol3Department of Physiology, Development and Neuroscience, University
of Cambridge
A multitude of factors must be overcome following spinal cord injury. Chondroitin
sulphate proteoglycans (CSPGs) of the glial scar present a significant block to axonal
regeneration. Digestion of CSPGs by the bacterial enzyme chondroitinase ABC (ChABC)
leads to axonal regeneration, neuronal plasticity and functional improvement in rodent
spinal cord injury models. However, the enzyme degrades within 24–72 h at body temperature,
limiting its application. Another therapy for spinal cord repair, the olfactory ensheathing
cell (OEC) transplant, has been shown to be beneficial in numerous rodent spinal cord
injury paradigms and in naturally occurring spinal cord injury in canine patients.
OECs support and guide axonal regeneration across the lesion gap. We have genetically
modified canine OECs to produce a mammalian ChABC using a lentiviral vector thereby
combining these two promising therapies.
We have demonstrated digestion of CSPGs with OECs expressing ChABC in vitro using
an enzyme assay and western blotting. In nude rats with dorsal column crush injury,
we also observed digestion of CSPGs following transplantation of OECs expressing ChABC.
To improve the safety and clinical applicability of the system, we have developed
a tetracycline regulated lentiviral vector (Tet‐On) capable of switching ChABC production
‘on’ when oral doxycycline is given to the animal. We have achieved efficient lentiviral
transduction of neurons and regulatable digestion of CSPGs in vitro and in vivo with
the addition or removal of doxycycline.
In conclusion, we have generated a novel cell therapy that we plan to develop further
using dogs with naturally occurring spinal cord injury.
Utility of the Electronic Von Frey Aesthesiometer to Quantify Cervical Skin Sensitivity
in Dogs with Syringomyelia
H. Williams
1, S. Sanchis2, H. A. Volk2, L. Pelligand2, J. Murrell1, N. Granger1
1The School of Veterinary Sciences, University of Bristol, Bristol, UK2Queen Mother
Veterinary Hospital, The Royal Veterinary College, Hatfield, UK
Only 35% of Cavalier King Charles Spaniels (CKCS) with syringomyelia display pain‐associated
behaviours, but we suspect that a greater proportion experience pain. An objective
means of detecting pain in these dogs is lacking. Electronic von Frey aesthesiometer
(eVF) testing consists of applying pressure onto the skin via a plastic tip. The pressure
value is displayed electronically. Exceeding a certain pressure, defined as the skin
sensitivity threshold, triggers a behavioural response from the dog.
We conducted an ethically‐approved, two‐centre prospective observational study to
assess whether the eVF could differentiate, based on cervical skin sensitivity threshold,
CKCS with: (i) syringomyelia and clinical signs (syringomyelia‐symptomatic – SM‐S);
(ii) syringomyelia without clinical signs (syringomyelia‐asymptomatic – SM‐A); and
(iii) no syringomyelia (syringomyelia‐free ‐ SM‐F). All dogs had cervical and caudal
fossa magnetic resonance imaging.
Following acclimatisation, the eVF was applied by an investigator blinded to the eVF
display and skin sensitivity threshold recorded at C2 and C4 vertebrae bilaterally
(three measures per site) and at the right dorsal metatarsal (RH). Data were analysed
with multiple analysis of variance including fixed factors (centre, medication, group)
and covariates (RH, age, clinical signs duration).
Seventy CKCS were recruited into: SM‐S (37), SM‐A (15), SM‐F (18). No difference in
sensitivity was found between groups, except for the RH when analysed as a covariate
(P = 0.031) but not post‐hoc as a dependent variable (P = 0.885). Split plot analysis
of variance demonstrated differences between cervical sites, independently of syringomyelia
group (P < 0.001).
In conclusion, eVF assessment of skin sensitivity does not differ significantly by
syringomyelia status.
Kinematic Measures for Assessing Gait in Dogs with Degenerative Myelopathy
J. Neeves
1, L. F. Wong2, N. Granger1
1School of Veterinary Sciences, University of Bristol2School of Clinical Sciences,
University of Bristol
Canine degenerative myelopathy (DM) is a progressive, adult‐onset, neurodegenerative disease
of the spinal cord with features similar to amyotrophic lateral sclerosis (ALS) in
humans. Some forms of human ALS / canine DM are associated with mutations of the superoxide
dismutase‐1 (SOD1) gene. As such, dogs with DM might serve as a model population to
test new therapies for SOD1‐ALS. However, we are lacking objective measures in DM
dogs to quantify their locomotor deficits.
To fill this gap, we recorded the gait of 10 DM dogs with 3D motion capture technology
during treadmill locomotion and quantified pelvic/thoracic limb coordination in each
inter‐girdle pair of limbs (described as right and left diagonal coupling intervals)
and pelvic limb lateral stability. We compared these to 15 neurologically healthy
controls and 10 dogs diagnosed with intervertebral disc herniation. Dogs were diagnosed
with MRI and tested for SOD1 mutation. We also sequenced C9orf72, TARDBP, FUS, and
VCP genes linked to human ALS. One DM dog was negative for the SOD1 mutation but bore
a FUS mutation.
Marked kinematic differences were revealed between DM and control dogs for pelvic/thoracic
limb coordination (P < 0.001) and pelvic limb lateral stability (P = 0.015). Dogs
with DM had significantly greater difference between right and left diagonal coupling
intervals (P = 0.046) compared to disc cases. This supported the known clinical finding
that DM dogs are usually asymmetrically affected during the course of their disease.
These preliminary data altogether provide baseline kinematic measures for DM dogs
that might serve as a benchmark for future studies.
Canine Degenerative Myelopathy Associated SOD1 Gene Mutation (E40K) Alters the Cellular
Behaviour and the Steady State Level of SOD1 Protein
Y. Qi1, P. Montague2, I. N. F. Shafie3, P. E. Johnston1, T. J. Anderson1, M. McLaughlin
1
1School of Veterinary Medicine, College of MVLS, University of Glasgow2Institute of
Infection, Inflammation & Immunity, College of MVLS, University of Glasgow, Glasgow,
Scotland3Faculty of Veterinary Medicine, University Putra Malaysia, Serdang, Malaysia
Canine degenerative myelopathy (DM) is a progressive neurological disorder associated
with a 118G>A mutation of the SOD1 gene and is inherited in an autosomal recessive
manner. The impact of this mutation on the dynamics of the wild type and mutant forms
of the SOD1 proteins is largely unknown. Here we investigated the steady state levels
of the SOD1 in the thoracic spinal cord of homozygotes. The cellular behaviour of
SOD1 proteins was explored using an in vitro transfection system to track the distribution
of wild type and mutant SOD1 fusion proteins containing either a Cherry or EGFP fluorescent
tag.
We report that the spinal cord level of SOD1 is significantly reduced in DM and SOD1
solubility properties are altered. The in vitro studies confirmed the fusion proteins
had enzymatic activity using a native gel system. SOD1 aggregates accumulate in cells
expressing mutant but not wild type Sod1 cDNA recombinants. Wild type and mutant fusion
proteins with different fluorescent tags co‐localise in co‐transfectants suggesting
a direct interaction and also form aggregates.
This study suggests that the Sod1 mutation affects the turnover dynamics of SOD1 and
aggregate formation in vitro. Evidence for a direct association between wild type
and the DM mutant forms of SOD1 together with aggregate formation suggests a potential
for a toxic mechanisms in the heterozygous scenario. This experimental paradigm will
assist in identifying the mechanisms affecting SOD1 dynamics and explain why heterozygotes,
in general, do not develop DM.
Ethical approval was granted for the collection of tissue.
High Prevalence of Equine Polysaccharide Storage Myopathy in Horses with Signs Suggestive
of Equine Motor Neuron Disease
C. Massey, R. J. Piercy
Department Clinical Science and Services, Royal Veterinary College, London, UK
Equine motor neuron disease (EMND), a degenerative polyneuropathy, is characterised
by an insidious onset of generalised muscle atrophy, and mild elevations in plasma
muscle enzyme activities. Affected horses are paretic and present with an ‘elephant
on a drum’ stance and intermittent muscle fasciculation. Ante‐mortem, gold standard
diagnosis is achieved by biopsy of the sacrocaudalis dorsalis muscle.
In this study, we hypothesised that these classic clinical signs are a manifestation
of various neuromuscular problems, rather than being specific for EMND. We retrospectively
examined muscle biopsy submissions from horses with suspected EMND and compared them
with the final diagnosis.
Of a total of 85 biopsy samples from horses with possible EMND, 24 had neuropathic
histological features, of which EMND was diagnosed in 18 (21%). 28 (33%) had various
myopathic features, of which 9 (11%) had polysaccharide storage myopathy (PSSM). 24
(28%) biopsy submissions were considered normal and 9 (11%) had an open diagnosis.
Of the 9 PSSM cases, 3 were homozygous for the R309H GYS1 mutation responsible for
PSSM1, 2 were heterozygotes, 1 was wild type and therefore diagnosed with PSSM2. Genotyping
was unavailable for the remaining 3.
This study reveals the high prevalence of primary myopathies in horses suspected to
have EMND, in particular of PSSM. It emphasizes the need for additional testing, because
the final result would likely influence prognosis and disease management.
Bovine Dorsal Root Ganglia Culture as an In Vitro Model for Listeria Monocytogenes
Brain Invasion
A. Fadda1,2, M. Bärtschi1, H. R. Widmer3, A. Zurbriggen1, A. Oevermann1
1Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Switzerland2Graduate
School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland3Neurocenter
and Regenerative Neuroscience Cluster, University Hospital and University of Bern,
Bern, Switzerland
Listeria monocytogenes (LM) causes rhombencephalitis in humans and ruminants associated
with high mortality rates. Previous studies indicated that Schwann cells are a port
of entry for brain invasion of LM. The aim of this study was to characterize primary
dorsal root ganglia (DRG) cultures from calves slaughtered for food consumption and
to assess their suitability as a host specific model for LM infection of peripheral
nerves and brain invasion.
Dissociated DRG cultures consisted of neurons, Schwann cells and satellite cells.
Neurons survived for more than 4 weeks. Growth factor (GF) supplementation was not
required for neuronal survival but promoted neurite outgrowth and branching. Cultures
were susceptible to infection with a LM bovine rhombencephalitis isolate (JF5203)
from sequence type 1 (lineage I). Bacterial invasion of DRG cells was similarly efficient
as that of cell lines, but replication was lower and reached an early plateau phase.
Bacteria showed tropism for Schwann and satellite cells and were rarely observed in
neurons and axons. Inactivated bacteria were not internalized indicating that infection
of satellite cells involves an active receptor‐mediated invasion mechanism rather
than phagocytosis. The isogenic InlA‐deletion mutant of JF5203 was less efficient
in invasion than the parental strain JF5203 suggesting that the bacterial virulence
factor Inl‐A is involved in satellite cell invasion.
DRG cultures from slaughtered calves represent a useful host specific model for the
mechanistic study of peripheral nervous system invasion by LM. Results indicate that
neurons are not the primary target and are invaded by non‐receptor dependent spread
from Schwann/satellite cells.
The Dog Model of Human Brain Aging and Early Alzheimer's Diesase: A Translational
Study of Neuropathological Markers
T. Schütt
1, L. Helboe2, L. Ø. Pedersen2, G. Waldemar3, M. Berendt1, J. T. Pedersen2
1Department of Veterinary Clinical and Animal Sciences, University of Copenhagen,
Denmark2Department of Neurodegeneration, H. Lundbeck A/S, Valby, Denmark3Danish Dementia
Research Centre, Rigshospitalet, University of Copenhagen, Denmark
Canine cognitive dysfunction (CCD) or “canine dementia” is a neurobehavioural syndrome
in aged dogs characterized by varying degree of progressive cognitive decline and
with certain similarities to the clinical and neuropathological changes associated
with Alzheimer's disease (AD) in humans.
The present study investigated specific markers of brain pathology related to aging
and cognitive dysfunction in dogs and compared these findings to human AD neuropathology.
The neuropathological investigations included evaluation of amyloid‐β (Aβ) plaque
deposition (including N‐terminally truncated and pyroglutamyl‐modified Aβ) and tau
pathology in the prefrontal cortex from fifteen aged dogs with normal cognitive function,
mild cognitive impairment or CCD and compared with findings in the prefrontal cortex
from two young control dogs and sections from human AD subjects.
Cortical Aβ deposition was found to be only of the diffuse subtype as no dense‐core
or neuritic plaques were found. The Aβ deposition followed a progressive pattern in
four maturation stages. Accumulation of the Aβ peptide was also extensively observed
in the vessel walls. Both immunohistochemically and biochemically measured levels
of Aβ pathology in the prefrontal cortex showed a consistent positive correlation
to age but not to cognitive decline. No evidence of neurofibrillary tau pathology
was found.
In conclusion, the findings support the senescent dog with spontaneous cognitive dysfunction
as a valuable non‐transgenic model for further investigations of the molecular events
involved in the neurodegenerative processes associated with aging and early stage
AD, especially the Aβ‐related pathology.
Bidirectional Benefits of a Naturally Occurring Canine Model for Testing and Development
of Drugs for Status Epilepticus
E. Patterson
1, I. Leppik2,3, L. Coles2, J. Cloyd2
1University of Minnesota – College of Veterinary Medicine2College of Pharmacy, St.
Paul and Minneapolis Minnesota3Department of Neurology – Medical School, St. Paul
and Minneapolis Minnesota
Compounds for status epilepticus (SE) have exclusively been developed from drugs for
chronic therapy. With 20–40% mortality for SE in both people and dogs, there is a
need to develop novel drugs with unique properties. The purpose of these studies have
been to validate the canine model of SE via RCTs, and to utilize 4–6 research dog
with naturally occurring epilepsy to initially test compounds.
Pharmacokinetic analysis of IV levetiracetam, and IV fosphenytoin was performed in
4–6 research dogs with modeling simulations that led to RCTs for SE of 30–60 mg/kg
of IV levetiracetam and 15 mg/kg phenytoin equivalent of fosphenytoin in 19 and 31
client owned dogs respectively. 10–20 mg/kg of a novel formulation of IV topiramate
was studied for pharmacokinetic and EEG pharmacodynamic parameters.
The RCT for levetiracetam resulted in a response rate of 56% vs 10% for placebo, and
for fosphenytoin of 63% vs 23%. Pharmacokinetic modeling of topiramate indicated that
20 mg/kg IV for dogs not on phenobarbital, and 25–30 mg/kg for dogs on chronic phenobarbital
might potentially be effective for SE. EEG analysis during topiramate administration
indicated it had similar spectral changes to 0.5 mg/kg IV diazepam. We will be performing
similar studies of up to 4 mg/kg IV of allopregnanolone, a novel neurosteroid, over
the summer of 2016.
In conclusion, pharmacokinetic and EEG pharmacodynamic testing of established drugs
validated the utility of the canine model. In addition, in testing novel IV formulations
in the canine model, there is hope for new future therapies of SE for both species.
Environment in Canine Ambulatory Electroencephalography
F. James
1, K. Vurik2, L. Gaitero1, S. Nykamp1, J. LaMarre1, T. Jokinen3, H. Lohi4
1Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada2Veterinary
Neurology Center, Tustin, California, USA3Department of Clinical Veterinary Sciences,
University of Helsinki, Helsinki, Finland4Department of Medical Genetics, Biomedicum
Helsinki, University of Helsinki, Helsinki, Finland
Ambulatory electroencephalography (EEG) is a technique used to diagnose epilepsy in
humans. Canine ambulatory EEG involves the application of new wireless, portable video
equipment while recording EEG in unsedated dogs. This technology has yet to be evaluated
outside the clinical environment. It was hypothesized that recording ambulatory video
EEG (vEEG) would be equally achievable in three distinct environments: the intensive
care unit (ICU), the neurology examination room, and the home, as measured by physiologic
and non‐physiologic artifacts. Six healthy dogs were randomized by modified latin
square to undergo 2 h vEEG recording in each of the three environments. Twenty minute
vEEG epochs (early, middle, and late) were scored in blinded fashion for artifact.
Artifact scores were compared for each environment. Instrumental artifact was significantly
different between the home kennel and the neurology examination room (P = 0.044) as
well as the ICU (P = 0.008). There was no significant difference found between environments
for all other artifacts. Based on these findings, three client‐owned dogs were instrumented
and sent home for ambulatory vEEG recording. The first was accompanied home by the
researchers where recording was discontinued after the events of interest occurred.
The second and third dogs were sent home in the care of their owners and returned
after 24 h of recording. One case was found to have had premature termination of recording
before 14 h had elapsed due to drained batteries. This proof of concept study highlights
the feasibility of in‐home ambulatory vEEG for dogs.
Magnetic Resonance (MR) Imaging Characteristics of Histopathologically Confirmed Non‐Functional
Sellar Masses in Dogs
A. Chen
1, T. Owen1, L. Martin1, A. Turner1, S. Carrera‐Justiz2, K. Karnik2, D. Bruyette2
1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington
State University, Pullman, Washington2West Los Angeles Animal Hospital, Los Angeles,
California
Limited information is available regarding the MR imaging characteristics of non‐functional
sellar masses. The purpose of this study was to determine whether pituitary adenomas
can be distinguished from other sellar masses based on MR imaging characteristics
since these tumors carry variable prognosis with treatment.
MR images were retrospectively reviewed for ten histologically confirmed non‐functional
sellar masses. Histopathology revealed chromophobe pituitary adenomas (n = 4), meningiomas
(n = 2), and one each of the following tumor types: pars intermedia adenoma, chromophobe
pituitary adenocarcinoma, ependymoma, and craniopharyngioma. All masses were ≥ 2 cm
at the largest margin except for 1. All masses were predominately T2 and FLAIR hyperintense
with 8/10 masses having some variable intensities within. Both pituitary adenomas
and other sellar masses had hemorrhage based on GRE images (7/10). Mild peri‐lesional
edema was seen with one pituitary adenoma and the pituitary adenocarcinoma. On T1‐weighted
post‐contrast images, all masses were round and discrete and showed moderate to strong
contrast enhancement. Bilateral lateral ventricular dilation was seen secondary to
one pituitary adenoma and the ependymoma.
Fifty percent of non‐functional sellar masses were pituitary adenomas. Pituitary adenomas
have similar MR imaging characteristics as other sellar masses. Regardless of histopathology,
all sellar masses had a tendency to be large and contained hemorrhage. Sellar masses
rarely had concurrent perilesional edema, hydrocephalus, or herniation.
Why, When, How and Post‐Operative Care of Dogs Undergoing Transphenoidal Hypophysectomy
for Large Sellar Masses
T. Owen, A. Chen, L. Martin
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington
State University, Pullman, Washington
Sellar‐based masses including pituitary tumors are common in veterinary medicine.
Large pituitary masses with a high pituitary/brain (P/B) ratio have historically been
difficult to remove and have poorer outcome as compared to tumors with lower P/B ratios.
This retrospective and ongoing clinical series is evaluating the intra‐operative complications,
post‐operative care and long‐term follow‐up of dogs with large sellar masses. The
goal is to assimilate this information into an algorithm to aid in surgical decision‐making.
The surgical protocol is based on Meij's original work with the addition of a novel
telescope and high‐definition camera for excellent magnification and illumination
of the surgical field. Our pituitary team consists of a surgeon, neurosurgeon and
critical care specialist which all play an integral part in each aspect of the patient's
care.
Twenty‐two of 34 dogs (65%) evaluated have a P/B ratio of > 0.70 (normal canine P/B
ratio < 0.32) with a mean P/B ratio of 0.95. Preliminary results have been very encouraging
with some dogs living greater than 2 and 3 years after surgery, either with complete
or incomplete resection of their tumor. Those dogs surviving surgery have improvement
in their neurologic status and those with hormonally functional tumors show improvement
in their hormonal status. Surgical debulking has been followed with radiation therapy
in some dogs with promising results. Median long‐term survival is currently being
investigated.
Our ongoing evaluation has been encouraging for those dogs with large sellar masses
and we have had success removing tumors with a P/B ratio of >0.70.
Treatmnent of Canine Frontal and Olfactory Lobe Meningioma with Either Surgical Debulking
Alone, Surgery and Metronomic Chemotherapy or Surgery and Definitive Radiation Therapy
D. Faissler
1, T. Bentley2, A. Bilderback3, A. Sato1
1Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA2Perdue
University, College of Veterinary Medicine, West Lafayette, IL, USA3Long Island Veterinary
Specialists, Plainview, NY, USA
The goal of this retrospective study was to examine outcome in dogs with frontal lobe
meningiomas undergoing transfrontal craniectomy alone (group 1), surgery and metronomic
chemotherapy (group 2) or surgery followed by definitive radiation therapy (group
3). In order to examine the influence of tumor location a control group with temporal,
parietal, occipital and cerebellar meningiomas treated with surgery alone was enrolled.
Criteria of inclusion were access to complete medical history and information of final
outcome. Only dogs discharged from the hospital and free of concurrent disease at
the time of diagnosis were included.
Forty dogs with a median age of 9.9 years were enrolled. Seizures (n = 36) were the
most frequent clinical sign. Eight dogs were assigned to group 1, 8 to group 2, and
18 to group 3. The control group included 6 dogs. In group 2 CCNU (n = 3) and hydroxyurea
(n = 5) was used. The median total radiation dose was 48 gray. Life‐threatening perisurgical
complications (n = 3) included pneumoencephalus, brain herniation and aspiration pneumonia.
Two dogs developed histologically proven radiation necrosis. Four dogs are alive,
15 were euthanized for disease progression and 21 for other reasons. Median survival
times were the following; Group 1: 9.5 months, group 2: 14.9 months, group 3: 27.6 months
and control group: 30.5 months.
In frontal lobe meningiomas surgery and radiation therapy have the best survival (P = 0.049)
similar to non‐frontal cases treated with surgery alone, most likely due to the more
complete tumor removal in this group. Metronomic chemotherapy does not significantly
extend survival time.
Paclitaxel Releasing Mesenchymal Stromal Cells Treatment in Canine Gliomas
O. Zeira
1, E. Ghezzi1, M. Aralla1, N. Asiag1, M. Konar1, A. Pessina2, G. Alessandri3
1San Michele Veterinary Hospital, Tavazzano, Italy2Dept. of Medical Science, University
of Milan, Italy3Stroke Unit, Ist. Neurologico Besta, Milan, Italy
Mesenchymal stromal cells (MSCs) are able to upload and release drugs. MSCs preloaded
by paclitaxel (MSCsPTX) have a strong anti‐tumor activity, both in vitro and in vivo,
due to their homing capacity towards the tumor and its microenvironment.
Our study evaluates safety, feasibility and efficacy of MSCsPTX as growth inhibitor
of canine gliomas.
After harvesting bone marrow (BM) from dogs and generating BM‐MSCsPTX, we evaluated,
in vitro, their activity on canine gliomas by means of binding the tumoral cells and
their anti‐angiogenesis activity.
Three dogs with brain gliomas, diagnosed by clinical signs, MRI characteristics and
histologic exam, underwent treatment schedule consisting of: day 0‐ MSCsPTX administrated
intrathecally; day 5‐temozolomide (100 mg/m² for 5 days every 28 days); day 15‐ MSCsPTX
administrated intravenously. Schedule has been repeated for 5 months. Other three
dogs were treated with temozolomide only. All patients had no other treatments. Follow‐up
included neurologic exam and MRI 3 months after the beginning of treatment.
In vitro results showed a considerable killing activity of BM‐MSCsPTX; no adverse
effects followed BM‐MSCsPTX administration. Neurologic exams were normal. MRI showed
no further tumor development in the first group.
The results suggest that BM‐MSCsPTX may be a safe and feasible optional treatment
for canine gliomas.
Evaluation of a Modified Transfrontal Craniotomy Technique in 8 Dogs
R. T. Bentley, S. A. Thomovsky
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary
Medicine, West Lafayette, IN, USA
The study purpose was to evaluate a modified transfrontal surgical approach providing
greater rostral cerebral and falcine access. Medical records were searched for dogs
undergoing transfrontal craniotomy, and data retrieved regarding signalment, surgical
procedure, complications, histopathologic diagnosis and outcome. Patients were predominantly
large mixed‐breed dogs, median age 9.5 years (range 3.6–14.3), including 7 spayed
females and 1 castrated male.
A sagittal saw used to create a diamond‐shaped opening in the frontal sinus. The rostral
portion of the diamond was conventional in shape and design. Caudally, the bony opening
was enlarged laterally compared to the conventional approach, via exposure enhanced
by temporalis elevation. This afforded 68% (95% CI, 42–93%) wider access to the mid‐frontal
lobes when pre‐operative imaging was assessed.
The procedure was easily combined with rostrotentorial craniectomy (n = 2). Median
surgical time was 280 minutes (first 4 cases) or 170 minutes (subsequent 4 cases).
Five dogs suffered complications but recovered fully: CSF rhinorrhea, cutaneous infection,
subcutaneous emphysema, aspiration pneumonia, prolonged neurological recovery. There
was 1 peri‐operative death. Median hospitalization was 6 days. Magnetic resonance
imaging confirmed complete resection (n = 5). Diagnoses were meningioma (n = 4), oligodendroglioma
(n = 3) and granuloma (n = 1). Euthanasia occurred due to recurrence (n = 2; 9 and
12 months) and unrelated disease (n = 1; 8 months). Four patients remain alive (1–10 months).
Median survival (Kaplan‐Meier analysis) was 22 months.
A diamond‐shaped opening of the frontal sinus, made wider caudally via elevating temporalis
musculature, provides excellent access to the mid‐caudal frontal lobes. Despite short‐term
complications, long‐term outcome can be excellent.
IL‐6 is Increased in CSF and Plasma of Dogs with Acute Ischaemic Stroke
H. Gredal
1, B. Thomsen1, A. Boza‐Serrano2, L. Garosi3, C. Rusbridge4, D. Anthony5, A. Møller6,
B. Finsen7, T. Deierborg2, K. L. Lambertsen7,8, M. Berendt1
1Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical
Sciences, University of Copenhagen, Frederiksberg, Denmark2Experimental Neuroinflammation
Laboratory, Department of Experimental Medical Science, BMC, Lund University, Lund,
Sweden3Davies Veterinary Specialists, Manor Farm Business Park, Higham Gobion, Hitchin,
UK4Fitzpatrick Referrals, Halfway Lane, Eashing, Godalming, Surrey, UK5Department
of Pharmacology, University of Oxford, Mansfield Road, UK6Centre of Functionally Integrative
Neuroscience, Aarhus University, Aarhus C, Denmark7Department of Neurobiology Research,
Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsloewsvej,
Odense, Denmark8Department of Neurology, Odense University Hospital, Odense C, Denmark
Inflammatory cytokines are potential modulators of infarct progression in acute ischaemic
stroke. They are therefore possible targets for new treatment strategies in humans.
From a translational research perspective, dogs with spontaneous ischaemic stroke
offer an opportunity of studying the cytokine response in a non‐invasive setup, and
thus may complement current experimental stroke models.
The aim of our study was to investigate cytokine concentrations in plasma and cerebrospinal
fluid (CSF) in dogs with acute ischaemic stroke, and to search for correlations between
infarct volume and cytokine concentrations.
Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic
stroke. Infarct volumes were estimated on magnetic resonance images. IL‐2, IL‐6, IL‐8,
IL‐10 and TNF in plasma, CSF and brain homogenates from the infarct core were measured
employing a canine‐specific multiplex immunoassay and compared to healthy control
dogs.
IL‐6 was significantly increased in plasma (P = 0.04) and CSF (P = 0.04) in stroke
dogs compared to healthy controls. The concentrations of other cytokines, such as
TNF and IL‐2, were unchanged. Plasma IL‐8 levels correlated significantly with infarct
volume (Spearman r = 0.8, P = 0.013).
The findings of increased concentrations of IL‐6 in CSF and plasma in dogs compare
to previous findings in humans. This suggests that the inflammatory response in dogs
with spontaneous stroke resembles that in humans, and that dogs could provide alternative
opportunities for studies of the inflammatory processes that accompany stroke.
POSTER PRESENTATIONS
Canine Peripheral Nerve Sheath Tumors: Clinical Aspects, MRI Findings and Comparision
of Palliation Surgery and Stereotactic Radiotherapy
M. Dolera
1, L. Malfassi1, S. Marcarini1, S. Pavesi1, G. Mazza1, M. Sala1, N. Carrara1, S. Finesso1,
G. Urso1,2
1La Cittadina Fondazione Studi e Ricerche Veterinarie, Romanengo, Italy2Azienda Socio
Sanitaria Territoriale di Lodi, Lodi, Italy
No updates for canine peripheral nerve sheaths tumor (PNST) appeared in recent literature.
The aim of this study was to evaluate the correlation between clinical aspects and
MRI findings of tumors involving a major peripheral nerve, plexus or root and to determine
the survival time in dogs treated with palliation, surgery or stereotactic radiotherapy
(SRT).
Records of dogs with PNST evaluated from 2000 to 2014 were reviewed to determine signalment,
duration of clinical signs, neurological examination, MRI features, treatment option
(palliation, surgery, stereotactic hypo fractionated radiotherapy). Time to first
event, survival times and statistical differences across categories were calculated
by the Kaplan‐Meier product limit method and log‐rank test.
Forty‐seven dogs (median age 9 years, male:female ratio 1.76) were included, with
Labrador retrieveroverrepresented (17%). Roots lesions were the most frequent (46.8%),
with C5‐T1, V nerve and left side more involved (25.5%, 19.1% and 61.7%). Presenting
sings were lameness, paresis and pain. Mean duration of clinical signs was 90 days.
MRI findings comprises increased diameter, hyper intense and contrast enhancing nerve
roots (57.1%), plexus or peripheral nerve (42.9%), focal hypomiotropy and muscle hyper
intensity (73%). The time to first event was 30 days after surgery and 240 days after
SRT. Overall mean survival was 97, 144 and 371 days with palliation, surgery and SRT.
A predilection for Labrador retriever is observed.
Comparing our results with published data, SRT seem to promise better results than
palliation or surgery and warrant further evaluation.
Brain‐Sparing Irradiation of Stage IV Canine Nasal Tumors: A Feasibility Study and
First Clinical Experiences
M. Dolera, L. Malfassi, S. Pavesi, M. Sala, G. Mazza, S. Marcarini, N. Carrara, S.
Finesso
La Cittadina Fondazione Studi e Ricerche Veterinarie, Romanengo, Italy
The prognosis for canine nasal tumors with intracranial extension is poor with an
expected survival of 1 month with palliation and 6.7 months with irradiation. However,
studies regarding stage IV nasal tumors treated with brain‐sparing irradiation techniques
are lacking.
The aim of this prospective study was to evaluate feasibility and efficacy of definitive
intent stereotactic radiotherapy in dogs with nasal tumors with massive intracranial
extension.
Seven dogs with stage IV nasal tumors were treated with high‐dose hypo‐fractionated
stereotactic radiotherapy with VMAT technique. Dose prescriptions were 32–36 Gy in
four consecutive‐day fractions to the gross tumor and 30 Gy to limphatics. Adjuvant
treatment included carboplatin. Serial clinical and CT/ MRI examination were performed.
Disease control and toxicity effects were evaluated according to RECIST and VRTOG
criteria. Median survival time (MST) was evaluated using Kaplan‐Meier curves. Six
carcinoma and 1 sarcoma were treated. Prescription goals were obtained in four cases
with V95%>95% and V107%>2% whereas in 3 dogs V95% = 86–90% was accepted to limit maximum
brain punctual dose <27 Gy. Two partial response and 5 complete responses were obtained.
MST was 9 months. One grade II late brain radiotoxicity and two brain ascending infections
were observed. Relapse pathways involves diffuse meningeal and sphenoid invasion.
The initial experiences with the RT regimen adopted indicate a feasibility and effectiveness
in modified stage IV nasal tumors. The relapse pathways observed suggest to evaluate
alternative adjuvant treatment in dogs treated with stereotactic radiotherapy.
Contrast‐Enhancing Extra‐Axial Central Nervous System Masses in Dogs: Magnetic Resonance
Imaging Differential Diagnoses for Meningioma
R. T. Bentley
1, S. Carrera‐Justiz2, S. A. Thomovsky1
1Department of Veterinary Clinical Sciences, Purdue University College of Veterinary
Medicine, West Lafayette, IN, USA2Department of Small Animal Clinical Sciences, University
of Florida College of Veterinary Medicine, Gainesville, FL, USA
Limited information is available to inform differential diagnoses for meningiomas
on canine magnetic resonance imaging (MRI). A retrospective study and a literature
review of lesions with similar imaging appearance to meningioma was performed. Inclusion
criteria were contrast‐enhancing intra‐dural extra‐parenchymal MRI mass lesions and
histologic confirmation. Brain and spinal lesions were eligible. Meningiomas and ventricular
lesions were excluded. We investigated radiologic criteria that could aid in differentiating
other etiologies from meningiomas.
Nineteen cases were retrospectively identified. Brain histological diagnoses included:
histiocytic sarcoma (n = 2), granuloma (n = 2), glioma (n = 2), and craniopharyngioma
(n = 2). There were single cases of granular cell tumor, hemangioblastoma, hematoma,
esthesioneuroblastoma, gliomatosis cerebri and germ cell tumor. Spinal lesions included
two intradural‐extramedullary nerve sheath tumors, two nephroblastomas and an undifferentiated
sarcoma. Irregular or indistinct margins were useful in discriminating from meningioma.
Craniopharyngiomas and germ cell tumors were seen in the sella turcica region only.
Otherwise, these lesions could not be readily distinguished from meningioma.
Literature review identified 93 cases, highlighting the frequency with which the following
lesions are described as contrast‐enhancing extra‐axial masses or preliminarily diagnosed
as meningiomas: pituitary adenoma, nerve sheath tumors (trigeminal and spinal), granular
cell tumor, lymphoma, glioma, fungal granuloma and histiocytic sarcoma. Sarcoma, metastasis
and various sporadic pathologies were rare.
Many neoplasms and granulomas can have similar or identical MRI appearance to meningioma.
A poorly defined or irregular margin on MRI might decrease the suspicion of meningioma.
Differential diagnoses for sella turcica masses should include craniopharyngioma and
germ cell tumor.
Morphological and Immunohistochemical Study of the Vascular Components in Spontaneous
Canine Gliomas
F. Fernández‐Flores1, J. Soto1, E. Blasco1,2, M. Pumarola1,2
1Department of Animal Medicine and Surgery, Universitat Autònoma de Barcelona, Barcelona,
Spain2Mouse and Comparative pathology Unit UPMiC, Universitat Autònoma de Barcelona,
Barcelona, Spain
Gliomas are among the most vascularized human solid tumours and are related with their
poor prognosis. While neovascularization occurs by vasculogenesis in embryonic stages,
angiogenesis is mostly related with adult tissue development. However, there are five
different mechanisms by which gliomas achieve neovascularisation: vascular co‐option
(CO), angiogenesis, vasculogenesis, vascular mimicry (VM) and glioblastoma endothelial
cell transdifferentiation. The objective of this study is to evaluate the neovascularization
features of spontaneous canine gliomas.
Eighteen spontaneous canine gliomas were retrospectively selected from the databases
of the Mouse and Comparative Pathology Unit of the Universitat Autònoma de Barcelona,
including 12 anaplastic oligodendrogliomas, 3 oligodendrogliomas and 3 glioblastomas.
Vascular features were evaluated by slides stained with Hematoxylin‐Eosin. The immunohistochemical
study was performed by a semiquantitative evaluation of representative fields using
CD31 as a mature endothelial cell adhesion protein marker and VEGFR‐2 as an angioblast
plasmatic membrane receptor cell marker.
The morphological study showed that low‐grade gliomas (LGG) mostly display a generalized
capillary proliferation and high‐grade gliomas (HGG) mostly contains capillary glomeruloid
formations (GC) in peripheral areas. Self‐organization of neoplastic cells with presence
of CO mechanisms were present in LGGs while MI was only present in HGGs. No expression
of vascular markers was observed in CO or VM areas, confirming that they occur independently
of endothelial proliferation. GC showed a variable CD31+/VEGFR‐2+ cells, indicating
their high angiogenic potential in HGG. These results are similar than those described
in human gliomas indicating that vascular markers are useful for to localize neurogenic
areas as therapeutical targets.
Clinical Characteristics and Outcome in Dogs Treated with Transsphenoidal Hypophysectomy
for Non‐Functional Sellar Masses
L. Martin
1, T. Owen1, A. Chen‐Allen1, A. Turner1, S. Carrera‐Justiz2, D. Bruyette2
1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington
State University, Pullman, Washington, USA2VCA West Los Angeles Animal Hospital, Los
Angeles, California, USA
Transsphenoidal hypophysectomy (TSH) is an effective therapy for functional pituitary
corticotroph adenomas; however, little is known about the clinical presentation and
outcome of non‐functional sellar masses following TSH. The purpose of this study was
to characterize the clinical features and outcome post‐TSH in dogs with non‐functional
sellar masses.
Medical records were retrospectively reviewed for historical and neurological findings,
histopathological diagnosis, and outcome. Ten dogs had TSH performed as therapy for
their non‐functional sellar masses. The Bulldog was the most common breed represented
(4 dogs) and all but one breed represented were brachycephalic. Median body weight
was 22.5 kg and median age at time of diagnosis was 8.8 years. Six dogs had a history
of progressive dullness, 3 dogs had behavior or personality changes, 2 dogs had head
or generalized tremors, and 2 dogs had vision loss. Neurologic findings included:
dull mentation (7 dogs) with the other 3 dogs reported to be obtunded, delayed or
absent conscience proprioception (5 dogs), and ataxia (3 dogs). Histopathology revealed
that 4 dogs had chromophobe pituitary adenomas, 2 dogs had meningiomas, and one each
of the following tumor types was seen: pars intermedia adenoma, ependymona, craniopharyngioma,
and chromophobe pituitary adenocarcinoma. Overall median survival post‐TSH was 232 days
(range 0–1190 days). Median survival for dogs with adenomas was 487 days (range 182–1190 days).
Non‐functional sellar masses were commonly identified in brachycephalic breeds and
dull or obtunded mentation was commonly identified on neurologic examination. TSH
may be an effective therapy for dogs with non‐functional pituitary adenomas.
Volumetric Modulated ARC Radiotherapy for Canine Trigeminal Nerve Tumors
M. Dolera
1, L. Malfassi1, M. Sala1, S. Marcarini1, G. Mazza1, S. Pavesi1, N. Carrara1, C. Bianchi1,
L. Corbetta1, S. Finesso1, G. Urso1,2
1La Cittadina Fondazione Studi e Ricerche Veterinarie, Romanengo, Italy2Azienda Socio
Sanitaria Territoriale di Lodi, Lodi, Italy
Peripheral nerve sheath tumors (PNST) affecting the trigeminal nerve are relatively
uncommon in dogs and few literature data regarding the best treatment are available.
The aim of this work was to evaluate the feasibility and effectiveness of curative
high dose hypo fractionated frameless Volumetric Modulated Arc Radiotherapy (VMAT).
The primary endpoints were the recurrence or the progression of the tumor, the death
from any cause and the death from the considered disease.
A prospectic clinical trial was conducted from February 2010 to December 2013 on client‐owned
dogs with presumptive imaging‐based diagnosis of trigeminal PNST. The treatment was
performed using a 6 MV linear accelerator equipped with an external beam micro‐multileaf
collimator. The plans were computed with Montecarlo algorithm. Overall survival was
estimated using the Kaplan–Meier product method.
Seven dogs were enrolled and treated with 37 Gy in 5 fx. MRI follow‐up examinations
revealed complete response in 1 dog, partial response in 4 dogs, stable disease in
2 dogs as the best treatment results. No major complications occurred. One dog develop
disease progression at 483 days and deceased for proven relapse at 523 days. Considering
all deaths, mean and median overall survival were, respectively, 609 days (range,
313–952) and 952 days.
Comparing the obtained survival with previously published studies, VMAT appears to
be safe, effective and offer the best median survival time in dogs suffering from
trigeminal PNST. Due to the rarity of intracranial canine PNST, further multi center
cooperative trials are advisable.
Multislice Computed Tomography for the Detection of Compressive Hydrated Nucleus Pulposus
Extrusion in Dogs
E. Royaux1, I. Gielen2, K. Kromhout2, E. Van der Vekens2, B. J. G. Broeckx3, L. Van
Ham1, V. Martlé
1
1Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine,
Ghent University, Belgium2Department of Veterinary Medical Imaging and Small Animal
Orthopedics, Faculty of Veterinary Medicine, Ghent University, Belgium3Laboratory
of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University,
Belgium
Compressive hydrated nucleus pulposus extrusion (HNPE) is defined as an acute extradural
compressive lesion consisting of hydrated nucleus pulposus material, occurring at
the level of the associated intervertebral disc in dogs. Magnetic resonance imaging
(MRI) is the imaging modality of choice to diagnose HNPE. This study examines the
possibility to detect compressive HNPE with computed tomography (CT). A first objective
of the study was to determine the capability of CT to detect HNPE and to describe
the CT characteristics. The second objective of the study was to determine the sensitivity
and specificity of CT to detect HNPE.
A retrospective analysis of the clinical and imaging data of dogs diagnosed with compressive
HNPE on MRI was performed. Both CT and MR images had to be available to be included.
The CT images of MRI confirmed cases were assessed by a non‐blinded image reader to
define the CT characteristics. The sensitivity and specificity of CT to detect a cervical
HNPE was determined by 2 blinded observers using a control group of dogs with acute
type 1 disc disease.
HNPE was characterized on CT as a hypodense extradural compressive lesion dorsal to
the intervertebral disc space with rim enhancement on postcontrast images. The sensitivity
and specificity to detect HNPE with CT was respectively very good (91%) and excellent
(100%). CT is a useful technique to detect compressive HNPE in dogs. However, if no
clear lesion is identified with CT or if information about intramedullary changes
is needed, MRI still needs to be performed.
Engineering Canine Olfactory Cell Grafts using Magnetic Particle Mediated Delivery
of Therapeutic Genes: Implications for Canine Spinal Injury
C. Adams1, A. Delaney1, D. Carwardine2, A. Fernandes1, A. Al‐Shakli1, N. Granger
2, D. Chari1
1Cellular and Neural Engineering Group, Institute of Science and Technology in Medicine,
Keele University, Keele, UK2School of Veterinary Sciences, University of Bristol,
Bristol, UK
A clinical trial in spinal cord injured dogs demonstrated that implantation of autologous
canine olfactory mucosa cells (cOMCs) lead to recovery of some motor function. However,
not all dogs responded to cOMCs and there was no improvement in long‐tract functionality.
One strategy to enhance transplant‐mediated regeneration is genetically engineering
cOMCs to release therapeutic biomolecules. To achieve this clinically, magnetic particle
(MP) based vectors are emerging as key non‐viral alternatives for genetically engineering
therapeutic cell populations. In particular, magnetofection with various magnetic
fields has been shown to safely and efficiently transfect a range of neural cells.
Here, we optimised MP mediated gene delivery to cOMCs and demonstrated delivery of
Brain Derived Neurotrophic Factor (BDNF; shown to promote repair in spinal injury)
encoded by the advanced minicircle vector platform. Along with MPs, minicircles have
significant advantages for translation compared to conventional plasmids, resulting
from bacterial backbone removal. Therefore, they can incorporate larger genes, do
not undergo transcription silencing and do not elicit immune responses, leading to
higher safety.
Under the no‐field condition, 86 ± 0.8% of cells displayed MP uptake and 34.9 ± 2.9%
expressed the reporter gene. These values were significantly enhanced by application
of all tested magnetic fields to ca. 95% (MP uptake) and 55% (transfection efficiency)
whilst maintaining high cOMC viability. Minicircle encoded BDNF was successfully delivered
to cOMCs (transfection efficiency of 8.1 ± 0.3%) resulting in a fourfold concentration
increase of BDNF in conditioned media (transfected cells versus controls).
This is a major refinement of the cOMC therapy now requiring testing in the clinic.
Urodynamic Characteristics of Neurogenic Bladder Dysfunction in the Canine Clinical
Model of Spinal Cord Injury
N. Granger
1, H. Z. Hu2, V. Kichler2, C. Marko2, N. D. Jeffery2
1School of Veterinary Sciences, University of Bristol, Bristol, UK2Department of Veterinary
Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, USA
Supra‐sacral spinal cord injury, common following intervertebral disc herniation in
dogs, causes dysfunction of urine storage and voiding leading to urinary incontinence
and retention. Severe dysfunction of this nature is currently incurable and may lead
to serious, even fatal, secondary complications.
Our objectives in this study were to characterise lower urinary tract dysfunction
in chronic supra‐sacral spinal cord injury in dogs and analyse the relationship of
bodyweight, chronicity and severity of injury with bladder compliance, to serve as
baseline data for future clinical trials using this natural animal model.
After receiving ethical permission, we prospectively recruited dogs as part of randomized
clinical trials on treatment for severe chronic (>6 weeks) thoracolumbar spinal cord
injury for cystometric evaluation. Relationships of bodyweight, chronicity and severity
of injury with compliance were analysed using logistic regression. In 84 dogs, mean
bladder capacity was 73% of that expected for bodyweight. 58 dogs (69%) had premature
urine leakage. Of 38 dogs in which it was measured, 21 (55%) had unprovoked involuntary
detrusor contractions (median = 3 contractions/cystometry – range = 1–11) during bladder
filling with bladder pressure reaching a mean of 32.2 cmH2O (range = 10–54 cmH2O).
58/84 dogs had reduced bladder compliance (defined as <12.5 mL/cmH2O) with a median
of 5.8 mL/cmH2O (range = 2.8–16.5 mL/cmH2O). Compliance was not associated with bodyweight,
chronicity or severity of injury.
This population of spinal cord‐injured dogs exhibited many features of lower urinary
tract dysfunction also found in injured humans. It constitutes an available model
to test putative therapies for abrogating the loss of bladder control caused by severe
spinal cord injury.
Electrophysiological Evidence of Spinal Cord Plasticity in Dogs with Chronic Severe
Spinal Cord Injury
N. Granger
1, H. Z. Hu2, N. D. Jeffery2
1School of Veterinary Sciences, University of Bristol, Bristol, UK2Department of Veterinary
Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, USA
Estimation of the severity of thoracolumbar spinal cord injury (SCI) following canine
intervertebral disc herniation relies on neurological examination. Cases lacking conscious
pain perception (CPP) are problematic because: (i) many will recover but predicting
an individual's prognosis is not possible; and (ii) assessing CPP is not standardised
or truly objective. Having a means of objectively teasing out different severities
of SCI within the ‘deep pain negative’ group would be useful.
Our objective in this study was to describe the presence/absence of ascending somatosensory
evoked potentials (SSEPs) and descending transcranial magnetic motor evoked potentials
(TMMEPs) in the chronic phase of SCI in dogs.
After receiving ethical permission, we prospectively recruited 82 dogs as part of
randomized clinical trials on treatment for severe (lacking CPP) chronic (>6 weeks)
thoracolumbar SCI for electrophysiological evaluation under sedation. In 31 dogs in
which brain recording was done, SSEPs could be detected over the left cortex in 9
(29%) (latency = 25.5 ± 2.9 ms, amplitude = 0.318 ± 0.196 μV) and over the right cortex
in 5 (16%) (latency = 27.9 ± 3.0 ms, amplitude = 0.523 ± 0.323 μV) with 5 dogs having
detectable waves bilaterally. In 51 dogs, we attempted to record sensory evoked spinal
potentials but no wave could be recorded above the lesion. Of 82 dogs, TMMEPs could
be detected in the left pelvic limb in 16 (19%) (latency = 57.4 ± 23.0 ms), in the
right pelvic limb in 13 (16%) (latency = 54.0 ± 16.7 ms), and bilaterally in 9 dogs.
Dogs lacking CPP can be divided into 2 groups based on the presence/absence of SSEPs/TMMEPs.
This distinction might help case selection to test putative therapies for SCI repair.
Ultrasonographic Imaging of Atlantoaxial Subluxation in a Pediatric Canine Patient
D. W. Hague, A. C. Billhymer, M. E. Howes, L. Underwood, S. Joslyn
Veterinary Clinical Medicine Dept., University of Illinois, Urbana, Illinois
An 8‐week‐old intact female Chihuahua was evaluated for acute tetraparesis progressing
to non‐ambulatory paraparesis. On neurologic examination, the patient was non‐ambulatory
tetraparetic with subtle motor and ataxia in the thoracic limbs and mild motor in
the pelvic limbs. There was increased extensor tone with normal reflexes in all four
limbs. Placing responses were absent in all four limbs and hopping was decreased to
absent in all four limbs. The dog demonstrated discomfort over the calvarium and cervical
spine. The neuroanatomic localization was to the cervical spine, with or without the
involvement of the brain, based on the hyperesthesia.
Ultrasound assessment of the cranium ruled out hydrocephalus and was used further
to assess the craniocervical junction. A small curvilinear ultrasound probe was applied
to the cranial neck and the C1 and C2 vertebrae were visualized in extension and with
mild flexion. There was repeatable distraction of these bony landmarks and visualization
of the spinal cord revealed kinking at the level of the atlanto‐axial articulation.
Radiographs and CT were performed to corroborate the suspected ultrasound diagnosis
of atlantoaxial subluxation.
The relative safety of this procedure makes it more favorable than traditional radiography
that usually requires flexion of the neck and can require general anesthesia. This
imaging modality may be limited in its success to very young animals which are skeletally
immature. Ultrasound can also potentially provide a more cost‐effective preliminary
diagnostic tool prior to pursuing more expensive diagnostics such as CT and MRI.
Phenobarbital or Potassium Bromide as an Add‐On Anti‐Epileptic Drug for the Management
of Canine Idiopathic Epilepsy Refractory to Imepitoin
E. Royaux1, L. Van Ham1, B. Broeckx2, I. Van Soens3, I. Gielen4, D. Deforce2, S. Bhatti1
1Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine,
Ghent University, Merelbeke, Belgium2Laboratory of Pharmaceutical Biotechnology, Faculty
of Pharmaceutical Sciences, Ghent University, Ghent, Belgium3Companion Animal Internal
Medicine Section, Faculty of Veterinary Medicine, Liège University, Liège, Belgium
and Orion Veterinary Clinic, Noorderwijk, Belgium4Department of Medical Imaging of
Domestic Animals and Orthopaedics of Small Animals, Faculty of Veterinary Medicine,
Ghent University, Merelbeke, Belgium
Imepitoin has recently been registered for the management of dogs with idiopathic
epilepsy (IE). Currently, there is no evidence‐based information available on which
antiepileptic drug (AED) to add to the treatment of dogs with IE that are not well
controlled with imepitoin.
The goal of this study was to evaluate the efficacy of phenobarbital (PB) or potassium
bromide (KBr) as an add‐on AED for controlling dogs refractory to a maximum dose of
imepitoin. The study was performed as a prospective, randomized, controlled clinical
trial. The efficacy of PB or KBr was evaluated by comparing monthly seizure frequency
(MSF), monthly seizure day frequency (MSDF) and the presence of cluster seizures during
a retrospective 2‐month period with a prospective follow‐up period of 6 months. Also
the 50% responder rate (RR) was investigated. Twenty‐seven dogs were included in the
study, 14 dogs in the PB group and 13 dogs in the KBr group. A significant decrease
in median MSF and MSDF was found in the PB group (P = 0.001 and P = 0.001, respectively)
and in the KBr group (P = 0.004 and P = 0.003, respectively). Overall, the number
of dogs with cluster seizures decreased significantly (P = 0.0005). The RR was 79%
vs. 69% in the PB and KBr group, respectively.
We conclude that PB or KBr add‐on treatment efficiently decreases median MSF and MSDF
in dogs refractory to a maximum dose of imepitoin. Combination therapy was generally
well tolerated and resulted in an improvement in seizure management in the majority
of the dogs.
The MR Volumetric Brain Assessment in Canine Epileptic Patients – A Pilot Study
M. Wrzosek, P. Podgórski, P. Drobot, W. Bodys, J. Nicpoń
Department of Internal Medicine and Clinic for Horses, Dogs and Cats, Center of Experimental
Diagnostics and Innovative Biomedical Technology, The Faculty of Veterinary Medicine,
Wrocław University of Environmental and Life Sciences, Poland
Canine epilepsy MR imaging is still a diagnostic challenge for veterinary professionals.
MR volumetry is technique of non‐invasive volume measurement of the selected anatomical
structures, that could allow to determine a possible structural changes in a CNS.
Quantitative MR imaging in humans exceeds the findings of visual inspection of clinical
MR imaging studies.
The aim of the work is to study the canine brains in terms of its volumetric construction
designed to demonstrate the possible brain volume changes in canine epileptic patients
as a possible model for human patients.
The study was carried out on 22 MRI scans (1.5T Ingenia Philips), 13 dogs with diagnosed
idiopathic epilepsy (according to IVETF guidelines), 9 normal control. All dogs were
patients of the Department of Internal Medicine and Clinic for Horses, Dogs and Cats,
Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences,
Poland. Analyzed MRI research dimensional sequence were T1‐weighted (sT1W_3D, TE 5.2,
TR: 25.0, FOV: 220, layer thickness: 0.8 mm, GAP: −0.4 mm, voxel size: 0.75 × 0.75 × 0.375).
The analysis was conducted by using Slicer software (version 4.5.0). A ratio of ventricular
system to brain tissue (V‐B) was counted with special reference for white to gray
matter (W‐G) comparison. There was a significant difference in a V‐B ratio in between
the IE and control groups (respectively 0.0056–0.0153) found, and no difference in
the W‐G ratio (0.261–0.232).
These preliminary results suggest a possible reduce of the brain volume in epileptic
patients with a preservation of the white‐to gray matter ratio.
Epilepsy and Compulsive Disorders in Dogs
C. Escriou, M. Garrone
Unité de neurologie, VetAgro‐Sup, Université de Lyon, Campus vétérinaire de Lyon,
Marcy L'Etoile, France
There is a long‐recognized association between obsessive–compulsive disorder (OCD)
and chronic epilepsy in humans, most notably refractory temporal lobe epilepsy (TLE).
In dogs, neurobehavioral comorbidities associated with development of epilepsy have
been recently demonstrated. Compulsive disorder (CD) are well described in dogs with
breed specific CD like breed specific idiopathic epilepsy. Our aim was to assess the
association between CD and idiopathic epilepsy in a comparative design.
Fifty dogs diagnosed with idiopathic epilepsy in the neurology unit of a universitary
referral center between the 01/01/2010 and the 31/12/2014 were enrolled. All dogs
completed tier 1 and tier 2 diagnostic approach proposed by the “international veterinary
epilepsy task force”. 100 healthy non‐epileptic dogs (2 healthy dogs (same breed,
same age) for one epileptic dog) chosen in the referral center clinical database were
enrolled as control. Owners were asked to complete a questionnaire designed to assess
the presence or absence of all CD described in dogs during a telephone conversation
conducted by always the same investigator.
Significant association were found between the CD pacing, head bobbing, self‐biting,
face‐ rubbing, self‐licking, inanimate objects aggression, whining, chewing or eating
objects, and polyphagia – polydipsia. Head bobbing and inanimate objects aggression
was neither reported in control dogs.
Although antiepileptic drugs can induce some CD like polyphagia‐polydipsia, our study
is the first to assess comorbidities between CD and idiopathic epilepsy in dogs. As
some CD remains infrequent behavior, our results probably underestimate their link
with idiopathic epilepsy and increasing statistical strength of the study with larger
population is mandatory.
An Assessment of Neuronal Cell Body and Synaptic Terminal Density in the Spinal Cord
and Red Nucleus of Canine Degenerative Myelopathy
L. Henderson, P. E. Johnston, L. Stevenson, J. Leach, T. J. Anderson, M. McLaughlin
School of Veterinary Medicine, College of MVLS, University of Glasgow
Canine degenerative myelopathy (DM) is a late onset disorder characterised by progressive
general proprioceptive ataxia and paresis of the pelvic limbs which progresses to
affect the thoracic limbs. A missense mutation (118G>A) in the superoxide dismutase
1 gene (Sod 1) is associated with DM but it is unclear how this mutation leads to
the disease.
The purpose of this study was to determine if pathology in specific anatomical regions
could account for clinical features of the disease. Specifically, we investigated
whether the accumulation of SOD‐1 in neurons impacted on the density of neuronal cell
body and synaptic terminals in the thoracic and cervical regions of the spinal cord
and the red nucleus.
Immunohistochemistry was performed on paraffin embedded sections from both control
and DM cases and staining intensity was quantified using Image J software. SOD1 staining
was higher in spinal cord regions of DM dogs compared with controls but the density
of neuron cell bodies was comparable. The synaptic density was unchanged in both the
thoracic or cervical spinal cord. However, in the red nucleus, SOD1 staining was comparable
between control and DM but synaptic density was significantly decreased in DM.
In conclusion, the results of this study suggest the accumulation of SOD1 does not
alter neuronal density, however it has an impact on synaptic density in the red nucleus,
one of the brainstem nuclei involved with motor co‐ordination and may relate to clinical
features associated with DM. Ethical approval was granted for use of all tissues in
this study.
Visualization of Intracranial Vessels in Toy‐Breed Dogs using Three Dimensional Time‐of‐Flight
Magnetic Resonance Angiography
C. Ishikawa, D. Ito, N. Tanaka, S. Ohta, M. Kitagawa
School of Veterinary Medicine, Nihon University, Kanagawa, Japan
Accurate visualization of canine intracranial vessels using three dimensional time‐of‐flight
magnetic resonance angiography (3D TOF MRA) have been reported, which were evaluated
dogs with more than 9 kg. We hypothesize that image quality of intracranial vessels
between small‐sized (toy‐breed) dogs and large‐sized dog might be different, as vessels
in small‐sized dog would be thinner than those in large‐sized dog. Therefore, the
aim of this study was to evaluate image quality of intracranial vessels in small‐sized
dogs using 3D TOF MRA.
This study was approved by Nihon University Animal Medical Center ethical committee.
Five small‐sized dogs (mean body weight 2.8 kg) were enrolled, which were diagnosed
as idiopathic epilepsy using 1.5T MRI. A total of 13 intracranial arteries were evaluated
on MIP images. For each vessel, image quality was reviewed by three veterinarians,
and divided into four categories: excellent, good, fair and poor. Excellent and good
were assessed as worth of diagnostic image.
Segment of the internal carotid artery in three of five (3/5) dogs and the rostral
cerebellar artery in 2/5 dogs were evaluated as fair or poor. Most of remaining vessels
was evaluated as excellent or good.
In conclusion, segment of intracranial carotid artery and rostral cerebellar artery
in small‐sized dogs might not be clearly identified using 1.5T 3D TOF MRA. As they
were identified in previous studies using 3T, visualization of them might be affected
by not only body size but field strength of MRI. Intracranial vessels in toy‐breed
dogs could be evaluated using this method, although further studies are necessary
to evaluate about image quality of vessel on 3D TOF MRA.
Cerebrospinal Fluid Movement using Magnetic Resonace Spin Labeling in 3 Dogs with
Congenital Hedrocephalus
N. Tanaka
1,2, D. Ito1, C. Ishikawa1, S. Ohta1, M. Kitagawa1
1School of Veterinary Medicine, Nihon University, Kameino, Fujisawa, Kanagawa, Japan2Grace
animal hospital, Ogikubo, Suginamiku, Tokyo, Japan
Diagnosis of hydrocephalus is to obtain image observation of the ventriculomegaly.
In human, time spatial labeling inversion pulse (time‐SLIP) is used to research about
cerebrospinal fluid (CSF) dynamics. In dogs, it is thought that common causes of congenital
hydrocephalus are flow obstacles of CSF, but actual CSF dynamics in dogs was not understand.
Therefore, we investigate CSF dynamics in dogs with hydrocephalus using time‐SLIP.
This study was approved by Nihon University Animal Medical Center ethical committee.
Two dogs that diagnosed stenosis/obstruction at outlet of the forth ventricle on conventional
MRI and one dog with aqueduct stenosis/obstruction was underwent further images, time‐SLIP.
We observed CSF dynamics at the aqueduct and pre‐pontine cisterns on mid‐sagittal
brain.
In all dogs, CSF flow (one direction movement) was observed in the aqueduct and the
pre‐pontine cisterns.
It is conceivable that CSF flow in the aqueduct and CSF circulation of outside of
the ventricular system would stop when CSF flow in the aqueduct is obstructed completely.
However CSF flow was observed in the aqueduct and the pre‐pontine cisterns. Therefore
the cause of hydrocephalus might be stenosis of the aqueduct, not obstruction.
CSF flow at the pre‐pontine cisterns might be affected in dogs with stenosis/obstruction
at outlet of the forth ventricle. Because dilation of the fourth ventricle compress
the brain stem and space of the cistern would be getting thinner. But again, CSF flow
was observed at both pre‐pontine cistern and aqueduct, this mean the isle of CSF at
exit of the fourth ventricle was not closed.
CSF flow was visualized by time‐SLIP in all dogs with congenital hydrocephalus. This
method might be help for explication of CSF dynamics in hydrocephalus.
CSF Aquaporin‐4,‐1 and Interleukin‐6 in Dogs with Naturally Occurring Communicating
Internal Hydrocephalus before and after Ventriculoperitoneal Shuntig
M. J. Schmidt
1, C. Rummel1, J. Hauer1, M. Kolecka1, N. Ondreka1, V. McClure2, J. Roth3
1Small Animal Clinic Department Of Small Animal Surgery, JL University, Giessen, Germany2Institute
for Veterinary Physiology and Biochemistry, Justus‐Liebig‐University, Giessen, Germany3Department
of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of
Pretoria, Onderstepoort, Republic of South Africa
Studies in animal models, in which internal hydrocephalus has been induced by obstructing
the cerebrospinal fluid pathways, have documented an up‐regulation of the concentrations
of aquaporin‐4 (AQP4) in the brain. In this study, the concentrations of aquaporin‐1
(AQP1), AQP1, AQP4 and Interleukin‐6 (IL‐6) were determined in the CSF of dogs with
idiopathic communicating hydrocephalus before and after the reduction of intraventricular
volume following ventriculo‐peritoneal shunt (VP‐shunt) treatment.
The concentrations of AQP4 and IL‐6 were increased in the cerebrospinal fluid of dogs
with hydrocephalus compared to controls. Both parameters significantly decreased after
surgical treatment, accompanied by decrease of ventricular size and the clinical recovery
of the dogs. AQP1 was not detectable in CSF.
Brain AQP4 up‐regulation might be a compensatory response in dogs with hydrocephalus.
Future determination of AQP4 at the mRNA and protein level in brain tissue is warranted
to substantiate this hypothesis.
Sound Localisation in Dogs with Vestibular Disease: A Preliminary Study
P. Gardiner, P. Freeman
Department of Veterinary Medicine, University of Cambridge, UK
Vestibular disease is a common neurological presentation in small animal practice
and has many possible aetiologies. An important step in the investigation of vestibular
disease is to determine whether the signs are caused by a peripheral or central lesion,
as this informs both the prognosis and the most appropriate diagnostic investigations.
In human medicine determining whether there is any hearing loss associated with the
vestibular signs is part of the initial assessment. This information aids in localisation
of the lesion as unilateral deafness is common in peripheral vestibular disease but
rare in central disease. Demonstrating unilateral deafness in dogs relies on specialist
equipment to investigate brainstem auditory evoked potentials (BAEP), and the equipment
required for this is not widely available in first opinion practice.
This study used a simple test involving a squeaky toy suitable for use in first opinion
practice to demonstrate localisation of sound in dogs.
The preliminary component of the study establishes a baseline of responsiveness in
39 healthy dogs with which to compare animals with vestibular disease. It also establishes
and validates the test protocol as a practical way of measuring this response to sound.
Noise Inducted Hearing Loss in a Police Dog
D. W. Hague
Veterinary Clinical Medicine Dept., University of Illinois, Urbana, Illinois
A 4 year old intact male Belgium Malinois was evaluated for acute hearing loss. The
dog was a working police dog involved in a training exercise where a gun was fired
five times on his right side. The estimated noise level was approximately 140 decibels.
Later that day, the dog was involved in bite work and the handler noted the dog was
not responding to verbal commands. He presented three days later for evaluation of
hearing. There was no evidence of any abnormalities on neurologic or physical examination.
Brainstem auditory evoked response (BAER) testing was performed in both ears with
a 70 and 90 decibel click stimulus using a mastoid reference and masking tone in the
opposite ear. There was evidence of an absence of waveforms. Based on the history,
the patient was diagnosed with a noise‐induced hearing loss. Two weeks later, a repeat
BAER test showed evidence of intact waveforms (I‐V) in both ears. The handler reported
the dog was responsive to oral commands. This case represents the risk of noise‐induced
hearing loss in working dogs. Therefore, hearing protective devices should be considered
in working dogs exposed to episodic or chronic loud noises.
Autophagy Versus Apoptosis – Myofibre Death in Canine Immune Mediated Myositis (CIMM)
M. Rosati, M. Leipig, K. Matiasek
Section of Clinical & Comparative Neuropathology, Ludwig‐Maximilians University, Munich,
Germany
Muscle fibre death in immune‐mediated inflammatory myopathies is poorly understood.
MHC‐II myocytic expression in CIMM represents a shift towards an antigen presenting
cell phenotype and breaking of immuno‐tolerance. Autophagy can impact the immune response
through its role on antigen delivery to the MHC. In order to unravel myofibre death
mechanisms we investigated autophagy and apoptosis in CIMM.
Thirty four CIMM dogs (11 MMM and 23 PM), 10 dogs with non‐inflammatory myopathy,
10 dogs with neurogenic muscle atrophy and 4 dogs without neuromuscular disorders
were evaluated immunohistologically for the expression of MHC‐II, LC3 and Cleaved
Caspase‐3 in muscle biopsies. Their expression was semiquantitatively scored and sorted
for subcellular distribution (MHC‐II) after which group specific data were obtained
according to standard algorithms.
CIMM presented with significantly higher (P < 0.05) scores for MHC‐II and LC3 if compared
to the other diseases and controls, while Cleaved Caspase‐3 was not expressed by myocytes
throughout the groups. There was no difference in MHC‐II and LC3 expression in MMM
and PM. No correlation could be found between MHC‐II and LC3 in CIMM.
MHC‐II regulation seems to be driven by inflammation rather than be triggered by autophagy
with subsequent exposure of self‐antigens to T helper cells. However increased expression
of LC3 with activation of macroautophagy might be responsible for sarcopenia in course
of CIMM together with direct destruction of myofibres by inflammatory infiltrates.
Lack of Cleaved Caspase‐3 expression on the other hand suggests that myocytes do not
undergo apoptosis and T‐cells exert their lethal hit by a different mechanism.
1H NMR Cerebrospinal Fluid Profile in Dogs with Polyradiculoneuritis – Case Series
M. Musteata
1, A. Nicolescu2, G. Solcan1, C. Deleanu2
1Department of Clinical Sciences – Internal Medicine, Faculty of Veterinary Medicine
Iasi, Romania2“Petru Poni” Institute of Macromolecular Chemistry, Romanian Academy,
Iasi, Romania
The aim of this study was to describe the cerebrospinal fluid (CSF) metabolites identified
and quantified by 1H NMR spectroscopy in four dogs with polyradiculoneuritis (PRN).
The diagnosis was fixed based on clinical appearance (acute flaccid tetraparesis,
dysphonia) and electrodiagnostic tests (positive sharp waves and complex repetitive
discharges on EMG, and slow NCS). The CSF samples were harvested from altantoccipital
space under general anaesthesia and they were analyzed for proteins and cells. The
1H NMR spectra were recorded from four dogs with PRN and were compared with those
obtained from 10 healthy dogs, 13 metabolites being identified and quantified. The
data were analyzed with PASW Statistics 18.
On routine examination, the CSF samples were characterized by a normal number of cells
(<5 cells/μL) with normal or a moderate increase of protein amount (<40 mg/L). Using
1H NMR examination, a decreased concentration of pyruvate (0.058 ± 0.361 nmol/L vs
0.234 ± 0.011 nmol/L, P < 0.001) and myo‐inositol (0.408 ± 0.023 nmol/L vs. 0.499 ± 0.017 nmol/L,
P = 0.012) and an increase concentration for glucose (0.467 ± 0.028 nmol/L vs 0.398 ± 0.013 nmol/L,
P = 0.03) were observed when compared with normal group. Citrate was found in ¼ dogs
and ascorbic acid was absent in all PRN cases.
Our results may suggest that in PRN CSF reflects a major alteration in the energetic
metabolism of the neurons, similar with those reported in humans’ central nervous
system chronic demyelinating diseases.
Alpha‐Chloralose Poisoning in a Cat
L. Grau‐Roma1, A. Stephens1, A. Wessmann
2, N. Carmichael3, S. de Brot1
1School of Veterinary Medicine and Sciences, University of Nottingham2Pride Veterinary
Centre, Neurology3Carmichael Torrance Veterinary Diagnostic Laboratory
A 5‐year‐old domestic cat presented with acute onset of ataxia, depressed mentation,
hyperaesthesia, hypothermia, and continuous twitching/seizure activity in the morning
after having been outside overnight. Despite immediate treatment, the cat progressed
within 24 h to a comatose state, opisthotonus and severe miosis unresponsive to light.
Given a poor prognosis, euthanasia was elected. Gross findings were disappointing
and consisted of a non‐specific lung oedema and congested lungs and spleen. Surprisingly,
within the stomach and intestines, fragments of cockshafers were found. Histologic
examination confirmed the gross findings and additionally showed evidence of mild
brain oedema, but failed to identify a cause for the severe clinical symptoms. In
a final attempt to solve the case, a urine sample was tested for toxic substances
and it was found to contain a significant amount of alpha‐chloralose.
Alpha‐chloralose (AC), a chlorinated acetal derivative of glucose, is used as a rodenticide,
avicide and repellent, often in form of hypnotic baits to immobilize and live‐capture
pest animals. It is moderately toxic to mammals and fish, and highly toxic to birds.
In animals, accidental AC poisoning is only poorly reported. The most common clinical
signs are seizures, muscle tremor, hyperaesthesia, hypothermia, salivation, miosis,
stupor, coma and ataxia. Coma and hypothermia was more common in cats, whereas salivation,
ataxia and hyperthermia was more frequently seen in dogs.
AC poisoning in pet animals within Europe or the United States is poorly reported
and no case has been described within the UK, as far as the authors are aware.
Genome Sequencing Reveals a Splice Donor Site Mutation in the SNX14 Gene Associated
with a Novel Cerebellar Cortical Degeneration in the Hungarian Vizsla Dog Breed
J. Fenn
1, M. Boursnell2, R. J. Hitti2, C. A. Jenkins2, R. L. Terry3, S. L. Priestnall3, P.
J. Kenny1, C. S. Mellersh2, O. P. Forman2
1Department of Clinical Science and Services, Animal Health Trust, Kentford, Newmarket,
Suffolk, UK2Kennel Club Genetics Centre, Animal Health Trust, Kentford, Newmarket,
Suffolk, UK3Department of Pathology and Pathogen Biology, Royal Veterinary College,
Hawkshead Lane, North Mymms, Hertfordshire, UK
Cerebellar cortical degeneration (CCD) is a neurodegenerative disease affecting many
dog breeds. Typical presentation consists of progressive cerebellar ataxia, with variable
onset ages and rates of progression. Causative genes have been identified associated
with CCD in several breeds, allowing screening for selective breeding to reduce disease
prevalence. There have been no previous reports of CCD in Hungarian Vizslas.
Two full‐sibling Hungarian Vizsla puppies from a litter of nine presented with progressive
ataxia, starting around three months old. Clinical signs included cerebellar ataxia,
truncal sway, intention tremors, absent menace responses and nystagmus in one dog.
Routine diagnostic investigations were unremarkable, and magnetic resonance imaging
in one dog demonstrated cerebellar atrophy. Euthanasia was elected shortly after the
onset of signs. Histopathological examination revealed primary Purkinje neuron loss
consistent with CCD. Whole genome sequencing identified a disease‐associated splice
donor site variant in the sorting nexin 14 gene (SNX14) as a strong causative candidate.
An altered SNX14 splicing pattern was demonstrated by RNA analysis, and no SNX14 protein
could be detected in CCD case cerebellum by western blotting. Genetic screening of
133 unaffected Hungarian Vizslas revealed three heterozygotes, supporting the presence
of carriers in the wider population.
SNX14 is involved in maintaining normal neuronal excitability and synaptic transmission,
and a mutation causes autosomal recessive cerebellar ataxia and intellectual disability
syndrome in humans. This is the first report of CCD in Hungarian Vizsla dogs and identifies
a splice donor site mutation in SNX14 as the likely cause, with an autosomal recessive
mode of inheritance suspected.
Aspartoacylase Deficiency in a Domestic Cat with Leukodystrophy
M. Kohyama
1,2, T. Fujimura3, N. Matsuki4, K. Uchida5, A. Yabuki1, M. Shima‐Sawa1,2, O. Yamato1
1Laboratory of Clinical Pathology, Joint Faculty of Veterinary Medicine, Kagoshima
University, Kagoshima, Japan2Research Fellow of Japan Society for the Promotion of
Science, Tokyo, Japan3Minnie Animal Hospital, Chiba, Japan4Laboratory of Veterinary
Clinical Pathology, the University of Tokyo, Tokyo, Japan5Laboratory of Veterinary
Pathology, the University of Tokyo, Tokyo, Japan
Aspartoacylase (ASPA) deficiency, also called Canavan disease in humans, is a rare
autosomal recessive neurodegenerative disease and is a type of leukodystrophy. The
deficiency is caused by mutations in the ASPA gene. Absence of ASPA activity results
in accumulation of N‐acetylaspartate (NAA) in the brain, visceral organs, and urine.
In animals, naturally occurring ASPA deficiency has not been reported yet. Recently,
ASPA deficiency was diagnosed in a domestic cat with leukodystrophy, and a candidate
causative mutation was identified in the feline ASPA gene.
A 4‐month‐old female domestic cat weighting 1 kg was presented with frequent vomiting,
head tremors, and frequent falling due to body imbalance. Magnetic resonance imaging
showed T2‐weighted hyperintensity and T1‐weighted hypointensity in the brain stem
and cerebellum. Gas chromatography‐mass spectrometry analysis of the urine revealed
unusual excretion of NAA, which is indicative of ASPA deficiency. The cat finally
died at 7 months of age, and histopathological spongy degeneration was observed in
the cerebrum and cerebellar region. Direct sequence analysis identified a homozygous
missense mutation in the coding region of the feline ASPA gene. A genotyping survey
using real‐time PCR did not detect this mutation in approximately 1,000 domestic cats,
thereby suggesting that this mutation is most possibly a causative mutation in this
disease. Ethical approval for this study was obtained from the Animal Research Committee
at Kagoshima University (approval number VM15041).
In conclusion, this is the first report of naturally occurring ASPA deficiency in
animals, and the cat represents a model of human Canavan disease.
Hypophysitis in a Scottish Terrier with Associated Panhypopituitarism and Hypothalamitis
Mimicking a Pituitary Gland Neoplasia
M. Oliveira
1, L. Polledo2, J. Adamany2, A. Wessmann1, P. Graham3, M. Dhumeaux2, K. Baiker3
1Department of Neurology and Neurosurgery, Pride Veterinary Centre, Derby, UK2Department
of Internal Medicine, Pride Veterinary Centre, Derby, UK3School of Veterinary Medicine
and Science, University of Nottingham, UK
A 6‐year‐old, neutered male Scottish Terrier was referred for progressive lethargy
and anorexia of a week duration. Neurological examination revealed a low head carriage,
hind limb ataxia, and decreased bilateral nasal sensation localising the lesion to
the forebrain. MRI of the brain revealed a rounded, well‐defined, central mass measuring
12 mm in diameter located dorsally and slightly rostrally to the pituitary fossa.
The mass was slightly hyperintense to cortical grey matter on T2W, hypointense on
T1W and without T2* signal void. There was a central fusiform enhancement of the mass
after contrast administration suggestive of neoplasia. T4 and TSH levels raised the
suspicion of secondary hypothyroidism. The cortisol ACTH ratio was < 0.0132 suggestive
of primary hypoadrenocorticism. During hospitalisation, the dog developed an acute
severe hypernatremia and died. Post mortem examination showed a severe lymphocytic
panhypophysitis with extension to the hypothalamus; most lymphocytes were CD3 positive
T‐cells. Immunohistochemistry for Neospora caninum antigen was negative.
To the authors’ knowledge, a lymphocytic panhypophysitis with extension to the hypothalamus
has never been reported. Hypothalamic involvement in autoimmune hypophysitis has rarely
been described in people and usually manifests with central Diabetes Insipidus as
suspected in our case due to the sudden onset of severe hypernatremia. This is the
first MRI description of autoimmune hypophysitis in a dog. Like in humans, the clinical
and MRI findings can be difficult to differentiate from other more common pituitary
masses. Therefore, transphenoidal biopsies may be required for conclusive histopathological
diagnosis and prompt institution of adequate treatment.
Computer Tomography (CT) Guided Drainage of a Brainstem Abscess in a Cat as a Life
Saving Procedure
E. Bersan, T. W. Maddox, G. Walmsley, R. Burrow
School of Veterinary Sciences, University of Liverpool, Small Animal Teaching Hospital,
Neston, UK
A 3‐year‐old male neutered domestic short haired cat was presented with progressive
lethargy and abnormal behaviour.
Clinical exam found cardiovascular signs suggestive of raised intracranial pressure.
Neurological examination found obtunded mentation, non‐ambulatory tetraparesis with
left sided pleurothotonus and intermittent decerebellate rigidity. The postural responses
were reduced in all four limbs, worse on the right. Cranial nerve evaluation found
absent menace response and reduced facial sensation on the right, vertical positional
nystagmus, anisocoria (right sided mydriasis) and an absent pupillary constriction
on the right in response to direct and indirect PLR. Neurolocalisation was to multifocal
lesions involving the right brainstem and forebrain.
Magnetic resonance imaging of the brain revealed a large, well‐defined, predominantly
fluid‐filled extra‐axial mass causing severe dorsal displacement of the pons and the
medulla oblongata and cerebellar vermis herniation through the foramen magnum. These
findings were most consistent with an intracranial abscess.
Emergency CT‐guided needle drainage of the space‐occupying lesion was performed through
the soft palate and basioccipital bone. Bacteriology revealed heavy growth of Arcanobacterium
haemolithicum and mixed growth of pleomorphic, mainly Gram‐negative rods (Cl.hastiforme,
Cl.Septicum, Cl.perfringens and Treponema/Serpulina spp). At discharge the cat had
normal mentation and mild ambulatory tetraparesis. Broad‐spectrum antibiotics based
on culture and sensitivity were continued for 8 months and repeat imaging prior to
withdrawal found complete resolution. Follow‐up examination 16 months later found
only mild right sided postural reaction deficits that did not affect quality of life.
CT guided drainage of a brainstem abscess is not without risk however in this case
it reduced intracranial pressure and provided a diagnostic sample.
Evaluation of the Proprioceptive Positioning Response and Patellar Tendon Reflex in
Dogs with no Neurological Clinical Signs
E. Daniell
1, S. Gomes1, A. Jeandel2, P. Freeman1
1The Queen's Veterinary School Hospital, Department of Veterinary Medicine, University
of Cambridge, UK2Davies Veterinary Specialists, Hitchin, UK
The proprioceptive positioning response (PPR) and patellar tendon reflex (PTR) are
clinical tests commonly used to assess and localise neurological conditions in dogs.
The primary aim of this study was to investigate the specificity of these tests by
evaluating test outcomes in the hindlimbs of a population of dogs showing no overt
signs of neurological disease. The secondary aim was to investigate the influence
of age on these tests.
Twenty‐nine dogs without evidence of neurological or hindlimb orthopaedic disease
were selected and divided into two groups: A (<10 years‐old, n = 20) and B (≥10 years‐old,
n = 9). A European Specialist in Veterinary Neurology, blinded to the age of the dogs,
performed the tests.
The PTR was considered normal in all of the study population, while the PPR was abnormal
in 17% of the dogs. The proportion of dogs with an abnormal PPR in one or more hindlimb
was 10% in group A and 33% in group B; this difference was not statistically significant
(P = 0.29). Only dogs in group B had bilateral PPR deficits (22%), but this difference
between groups was not statistically significant (P = 0.089).
The finding that some dogs had PPR deficits despite having no overt neurological disease
has implications for neurological examination interpretation: deficits should be interpreted
with caution. There was no statistically significant difference in the proportion
of PPR deficits between the two age groups. The PTR was normal in all cases, suggesting
a lower prevalence of absent patellar reflexes in the general population than recorded
in previously published literature.
Species‐Specific Differences in Cellular Aggregation and Localisation of Virally‐Transduced
Mutant and Normal Canine and Equine Superoxide Dismutase 1 (SOD1) Proteins
A. Draper, Z. Windley, C. Maile, R. J. Piercy
Department of Clinical Science and Services, Royal Veterinary College, London, UK
Canine Degenerative Myelopathy (DM) is associated with a substitution mutation of
a glutamic acid (E) to lysine (K) residue in SOD1 (E40K) which increases its tendency
to aggregate in cells. E40 is highly conserved across mammalian species with the exception
of horses, which naturally express a K residue. We hypothesised that normal horse
SOD‐1 has the same tendency to aggregate as mutant DM‐affected dog SOD1 in contrast
to its E40 counterpart.
cDNAs from wild‐type (E40) and mutant (K40) canine SOD1 and wild‐type (K40) equine
SOD1 were amplified by PCR and cloned with N‐terminal GFP‐tags. PCR‐mutagenesis was
used to create an equivalent equine E40 SOD1 variant. Inserts were sub‐cloned and
transduced, alongside a GFP‐only vector as lentiviral particles into human neuroblastoma
cells (SHSY‐5Y). Aggregates (nuclear or cytosolic) were quantified following fluorescence
microscopy, in a blinded fashion (n = 3 coverslips per variant, on 3 separate occasions;
minimum of 1500 cells counted per condition).
There were significantly more cytoplasmic SOD1 aggregates in the GFP‐mutant dog SOD1
expressing cells (mean %±SEM; 23%±5), compared to the wild‐type dog (6.7%±1.3) or
GFP‐only vector (1.7%±0.5) (P < 0.05); there were significantly more nuclear aggregates
in both GFP‐horse SOD‐1 variants (K40: 50.4%±5.2, E40: 68.1%±4.9) compared to the
GFP‐only vector (8.2%±1.2) (P < 0.05).
These results suggest that there are species‐differences in vitro in the tendency
of mutant and normal SOD1 proteins to aggregate and localise.
Cognitive Deficits and Pathological Features of Cerebral Amyloid Angiopathy in 27
Elderly Dogs
R. A. Marcasso1, J. R. Moreira2, M. V. Bahr Arias
3, A. P. F. R. L. Bracarense2
1Laboratory of Animal Pathology, UNOPAR, Arapongas, Paraná, Brazil2Laboratory of Animal
Pathology, Universidade Estadual de Londrina, Paraná, Brazil3Department of Veterinary
Clinics, Universidade Estadual de Londrina, Paraná, Brazil
Cerebral amyloid angiopathy (CAA) is defined as the deposition of beta amyloid proteins
within leptomeningeal and cortical vessels, being associated to Alzheimer disease
and canine cognitive disease.
This study aimed to evaluate in elderly dogs the association between cerebral amyloid
deposition and pathologic lesions in the development and clinical manifestation of
cerebral dysfunction. Local ethical permission was obtained for this study.
Gross evaluation of 44 brains of elderly dogs revealed cortical atrophy and ventricular
widening in 22.7% (10/44) specimens. Congo red stain was utilized to classify the
61.4% (27/44) positive dogs (9–19 years old, mean 13.9 years old) to CAA. CAA were
graded in mild (13/27 dogs), moderate (3/27 dogs) and severe (11/27 dogs). In all
groups the most common clinical sign was disorientation. By the immunohistochemistry
using polyclonal anti‐beta amyloid 1–42 antibody, the average of positive vessels
to beta‐amyloid increased with age. Association of cortical atrophy, neuron loss and
micro hemorrhages contribute to the developing of cognitive deficits.
The consistent presence of this change in a variety of dogs above the age of 13 years,
the correlation with intracerebral hemorrhage, and the similarity of the affected
regions between dogs and humans, all uphold the utility of aged dogs as a natural
model for studies about cerebral amyloid angiopathy.
Three Years after Clinical Onset of Cerebellar Cortical Degeneration in a Juvenile
Coton De Tulear – What Comes after Inflammation?
C. Ricco
1, A. Fouhetti1, M. Rosati2, K. Matiasek2, L. Cauzinille1
1Centre Hospitalier Vétérinaire Frégis, Arcueil, France2Ludwig‐Maximilians‐University,
Munich, Germany
Cerebellar disorders in dogs can be subclassified into congenital, developmental and
abiotrophic/degenerative types. Among the abiotrophies, the term cerebellar cortical
degeneration (CCD) has been introduced lately, which includes an uncommon form mainly
affecting granular cells. This variant has been described in several breeds including
the Coton de Tulear. In this specific breed an immune‐mediated disease process has
been suggested. In this case report we describe a late stage presentation of a cerebellar
granuloprival degeneration.
A 7‐month‐old, Coton de Tuléar was presented with a history of progressive ataxia.
The puppy was clear of the breed specific neonatal cerebellar ataxia.
Neurological examination revealed generalised ataxia, hypermetric gait, head tremors,
decreased proprioception in the hind limbs and an inconstant bilateral menace response.
MRI revealed a cerebellum mildly decreased in size and a normal cerebrospinal fluid
analysis. Clinical signs progressed over time and the dog was euthanized at the age
of 3 years.
Histopathology confirmed diffuse, chronic and severe granuloprival cerebellar cortical
degeneration accompanied by severe gliosis of the cerebellum. Signs of inflammatory
infiltrates were not detected on conventional stains and immmunohistochemistry.
This Coton de Tulear appears as the first report of a chronic form of granuloprival
CCD in this breed. Although the lack of inflammatory cells could suggest the absence
of an immune mediated disease, these findings are most likely stage related and might
reflect successful removal of the immunogenic target.
Further studies should focus on the research of a genetic mutation associated with
these histologic findings.
Evaluation of GFAP Levels in Serum and Cerebrospinal Fluid in Dogs
D. Kostic, R. Carlson, S. Wicha, A. Tipold
Department Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover,
Germany
Glial fibrillary acidic protein (GFAP) is the main intermediate filament protein in
astrocytes and a potential biomarker for intracranial disorders. The hypothesis should
be proven that severe brain tissue destruction leads to measurable GFAP serum levels
independent of the cause of the disease. Furthermore, it should be proven that GFAP
levels in cerebrospinal fluid (CSF) are reflecting disease categories.
Six healthy Beagles and patients (n = 198) with the clinical diagnoses idiopathic
epilepsy, brain tumor, inflammation, spinal cord injury (SCI) and traumatic brain
injury (TBI) were included. GFAP concentrations were determined by ELISA. In serum,
GFAP was only measurable in single cases. However, all CSF samples were positive for
GFAP. Using Wilcoxon test, significant differences were found between GFAP CSF levels
of dogs with tumor and epilepsy (P < 0.0004) and between inflammatory diseases and
epilepsy (P < 0.0408). There was no correlation between GFAP values and severity,
type and seizure frequency and severity of neuroparenchymal damage. In TBI patients
high serum GFAP levels had a strong correlation with the Glasgow Coma Scale score.
In dogs with SCI no significant difference between chronic and acute cases and severity
of clinical signs could be detected.
In conclusion, GFAP cannot be recommended as a marker for a specific disease. However,
serum levels in TBI patients may have predictive value for the outcome.
Eight Cases of Eosinophilic Meningoencephalitis (EME) in Dogs from 2009 to 2015
S. Guo, D. Lu
Peace Avenue Veterinary Clinic, Hong Kong
Idiopathic eosinophilic meningoencephalitis (EME) is a rare condition of unknonw etiology
and has been described in different breeds such as Golden Retriever, Rottweiler, Yorkshire
Terrier, etc1. When the eosinophils in the cerebrospinal fluid (CSF) is <5%, this
finding is considered nonspecifit; it is recommended that an eosinophilia of 10% of
the total white cells in the CSF should be used as a minimum criteria for the diagnosis
of EME in people2.
This retrospective study described 8 cases of EME seen in a private referral practice
in Hong Kong from 2009 to 2015, affecting several breeds of dogs.
EME is a rare condition and makes up to 4.6% of all the MUE cases seen in a Hong Kong
referral clinic from 2009 to 2015. The clinical presentation and MR images were variable
and diagnosis was mainly made by the presence of eosinophilic pleocytosis of CSF.
In general they carry good prognosis following immunosuppresive treatment, with 5
out of 8 cases (62.5%) in remission (off treatment) and 1 (12.5%) only needed AED
due to persistent seizure.
Cannabinoid Receptor Type 2 (CB2) Expression in Canine Steroid‐Responsive Meningitis‐Arteritis
(SRMA) and Intraspinal Spirocercosis
J. Freundt‐Revilla
1, F. Heinrich2, M. H. Shamir3, A. Oevermann4, W. Baumgärtner2, A. Tipold1
1Department Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover,
Germany2Department of Pathology, University of Veterinary Medicine Hannover, Germany3Korea
School of Veterinary Medicine, The Hebrew University of Jerusalem, Israel4Department
Clinical Research and Veterinary Public Health, Vetsuisse, University of Bern, Switzerland
Increased levels of endocannabinoids were recently found in CSF of dogs suffering
from Steroid‐Responsive Meningitis‐Arteritis (SRMA) and Intraspinal Spirocercosis
(IS) (Abstract ECVN 2013). These endogenous ligands interact with two main types of
cannabinoid receptors (CB1 and CB2). The CB2 receptor is highly expressed in inflammatory
cells and is up‐regulated in early phases of inflammation in cells of the CNS.
In the present study, CB2 receptor expression was evaluated in spinal cord lesions
of dogs with SRMA (n = 8) and IS (n = 2) and compared to healthy control dogs (n = 6).
Therefore, a rabbit polyclonal anti‐human CB2 antibody (LSBio®) was established on
canine paraffin‐embedded tissue samples using routine immunohistochemistry.
In cervical, thoracic, and lumbar spinal cord sections of dogs with SRMA and IS, CB2
was strongly expressed on the cellular surface of infiltrating leukocytes (i.e. neutrophils,
eosinophils, lymphocytes, plasma cells, and macrophages). In SRMA, CB2‐positive inflammatory
cells were located within the adventitia of vessels, perivascular, subdural, subarachnoidal,
and within white and grey matter. Moreover, moderate to strong CB2‐positive endothelial
cells and arachnoid mesothelial‐like cells were present. In IS, CB2‐expressing leukocytes
were found adjacent to the parasite accompanied by severe necrosis and haemorrhage.
Both diseases showed CB2‐positive glial cells exhibiting a moderate to strong membranous
signal. Likewise, scattered myelinophages and spheroids stained intensely positive
with CB2. Dorsal and ventral neurons showed inhomogeneous slight to strong cytoplasmic
immunoreactivity.
The present study demonstrates CB2 expression in inflammatory lesions of SRMA and
IS and highlights the endocannabinoid system as a potential target for treatment of
inflammatory CNS diseases.
Inflamed Intracranial Meningioma Mimicking Brain Abscess in a Dog
C. Tästensen
1, S. Hanemann1, M.‐K. Müller1, M. Rosati2, K. Matiasek2, T. Flegel1
1Department of Small Animal Medicine, University of Leipzig, Germany2Clinical and
Comparative Neuropathology, Centre for Clinical Veterinary Medicine, LMU Munich, Germany
An 11‐year‐old mixed breed dog was presented with an acute onset of cluster seizures.
At presentation, the dog showed a status epilepticus, which could be interrupted with
anticonvulsive medication. Due to the stuporous state of the patient the following
day, a thorough neurological examination could not be performed.
MRI of the head revealed an inhomogeneously contrast enhancing mass within the right
frontal lobe adjacent to the cribriform plate and extending caudally to the rostral
thalamus. CSF analysis showed a severe pleocytosis of 11540 cells/µL with 70% neutrophils
and 30% monocytes and a protein of 2.63 g/L. Based on MRI findings and CSF analysis
main differentials were intracranial abscess versus neoplasia. Surgery was performed
and a major part of the intracranial mass was removed through a bilateral transfrontal
approach. Histological examination revealed a WHO grade I conforming meningothelial
meningioma with multiple intratumoural microabscesses. Neither the CSF nor the mass
itself showed bacterial growth. The dog recovered well over the following 7 days and
was discharged for radiotherapy at which time the dog was neurological unremarkable.
This case report illustrates that even a severe neutrophilic pleocytosis in the CSF
cannot rule out an intracranial neoplasia. To our knowledge this is the first report
of a meningioma with sterile microabscesses in a dog.
Clinical and Epidural Histopathological Differences Observed in Cervical and Thoracolumbar
Intervertebral Disc Extrusion in Dogs
L. Züger
1,2, A. Fadda1,2, A. Oevermann1,3, F. Forterre4,2, D. Henke1,2
1Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Switzerland2Department
of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Switzerland3Department
of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of
Bern, Switzerland4Division of Veterinary Surgery, Vetsuisse Faculty, University of
Bern, Switzerland
Marked differences in clinical presentation and outcome between cervical and thoracolumbar
disc extrusions have only been partially explained. We have recently shown that the
inflammatory response in the epidural space has an impact on the outcome in thoracolumbar
IVD extrusions.
The aims of the present study were to evaluate clinical data and histopathological
parameters of epidural material from 55 dogs with cervical IVD extrusion, and to compare
these data to those from 80 dogs with thoracolumbar IVD extrusion from a previous
study.
Cervical epidural material was histologically examined, and associations between severity
of inflammation and selected clinical and pathological parameters, impact of chondrodystrophic
phenotype, and anatomic localization were evaluated statistically.
Dogs with a cervical IVD extrusion were significantly older (P < 0.001), had less
severe and a longer duration of neurological signs (both P < 0.001), were more painful
(P = 0.038), had a better outcome (P = 0.005), and revealed less severe calcification
(P = 0.002) and inflammation (P < 0.001) in histopathology than dogs with a thoracolumbar
IVD extrusion. No significant differences regarding chondrodystrophic phenotype were
found.
In conclusion, the present study revealed obvious differences in clinical presentation
and epidural space pathology between cervical and thoracolumbar IVD extrusions. Notably,
there was a significantly less intensive epidural inflammatory response in the former.
This correlated positively with a significantly lower degree of nucleus pulposus calcification
in cervical extrusions indicating biochemical/ metabolic and biomechanical differences
between the two locations which remain to be characterized in future studies.
Somatosensory and Motor Evoked Potentials Under General Anesthesia in Dogs with Thoracolumbar
Intervertebral Disc Extrusion
M. C. C. M. Inglez de Souza
1, R. J. R. Ferreira2, G. C. F. Patricio1, J. M. Matera1
1School of Veterinary Medicine ‐ University of São Paulo, São Paulo, Brazil2Institute
of Orthopaedics and Traumatology, University of São Paulo, São Paulo, Brazil
Somatosensory evoked potentials (SEPs) and transcranial motor evoked potentials (TMEPs)
provide information regarding sensory and motor pathways, and dogs are considered
translational models for naturally‐occurring spinal cord injury. Our aim was to describe
SEPs and TMEPs technique in uninjured and in affected chondrodystrophic dogs (CD).
Paraplegic CD (5 with pain perception, 5 with loss of pain perception) due to thoracolumbar
disc extrusions confirmed by computed tomography; and 5 neurologic normal CD were
anesthetized with Fentanyl and Propofol in a continuous infusion rate.
SEPs were recorded with electrodes positioned subcutaneously on scalp following median
and tibial nerves stimulation. TMEPs were obtained by electrical stimulation applied
transcranially and captured via electrodes inserted into extensor carpi radialis and
cranial tibial muscles.
SEPs waves were identified in all dogs after median nerve stimulation, and 5 dogs
had no SEPs recordings on pelvic limbs, and they were clinically without pain perception.
TMEPs were recorded on thoracic limbs in all dogs, but were severe attenuated in 7
dogs and absent in 3 dogs. Even if no voluntary movement could be detected clinically,
electrophysiological responses were present caudal to spinal cord lesion, i.e., these
patients may be paraplegic from clinical assessment, but not concerning electrophysiological
function. All neurologically normal CDs presented SEPs and TMEPs on pelvic limbs.
Combined SEPs and TMEPs techniques appear to be reliable for spinal cord lesion evaluation
under general anesthesia. TMEPs could be detected caudal to the lesion even in severely
affected patients, possibly being a useful tool for spinal cord therapies evaluation.
Comparison of Pre‐Operative Quantitative MRI and Clinical Assessment of Deep Pain
Perception as Prognostic Tools for Recovery of Motor Function in Paraplegic Dogs
A. Wang‐Leandro, M. K. Hobert, P. Dziallas, V. M. Stein, A. Tipold
Department of Small Animal Medicine and Surgery, University of Veterinary Medicine
Hannover, Germany
Development of objective prognostic tools for paraplegic dogs suffering from spinal
cord injury (SCI) is mandatory for novel treatment selection and implementation. The
aim of the study was to compare fractional anisotropy (FA) values with intramedullary
hyperintensity length (IMHL) in T2‐weighted (T2W) MRI sequences and presence or absence
of deep pain perception (DPP) as prognostic factors for motor function recovery (MFR).
Thirty‐three paraplegic dogs with acute or subacute thoracolumbar SCI were prospectively
recruited and tested for presence or absence of DPP. MRI including T2W and diffusion
tensor sequences of the thoracolumbar spinal cord was performed using a 3T MRI scanner.
IMHL was measured and compared to the length of L2 vertebral body; FA values were
obtained from SCI epicentre and one vertebral body cranially and caudally of the lesion
epicentre. After surgical decompression 19 dogs showed MFR, 14 dogs did not recover.
Variance analysis and logistic regressions were calculated between dogs with and without
MFR for IMHL and FA values. Sensitivity and specificity were calculated for DPP as
dichotomous model.
Neither group differences nor prognostic value could be determined for IMHL. FA values
measured caudally of the lesion were significantly different between dogs with and
without MFR (P = 0.0271). Negative outcome could be predicted using FA with a 62.5%
sensitivity, 63.16% specificity, applying cut‐off value set at FA > 0.714, whereas
DPP revealed 62.5% sensitivity and 73,68% specificity.
In conclusion, pre‐operative quantitative MRI displayed no advantage over DPP testing
concerning MFR in paraplegic dogs.
EX‐VIVO Evaluation of the Three‐Column Concept in Thoracolumbar fractures in Dogs
G. A. C. Diamante1, P. V. T. Marinho2, C. C. Zani1, M. V. Bahr Arias
1
1Department of Veterinary Clinics, Universidade Estadual de Londrina, Paraná, Brazil2Faculdade
de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, Brazil
The three‐column theory was developed in human medicine to assess the presence of
vertebral instability by imaging and assist in the selection of treatment, with biomechanical
studies that demonstrate its applicability in humans. Despite the anatomical and postural
differences between humans and dogs, this theory has been applied in veterinary medicine
for 26 years, without biomechanical studies in dogs.
The objective of this study was to evaluate the applicability of three‐column theory
in thoracolumbar fractures in dogs. Local ethical permission was obtained for this
study. Eighteen intact thoracolumbar segments (T12‐L2) were collected from dogs that
had died for reasons unrelated to this study, and then T12 and L2 vertebrae were fixed
in a resin base. After that, they were subjected to computed tomography (CT) scanning
to detect any fractures or injuries that had not been diagnosed previously. The range
of motion (ROM) parameters of flexion‐extension and lateral bending was measured with
a goniometer before trauma. Fractures were induced using a powered machine applying
compressive loads; after the fracture induction, CT scanning was used to classify
the test units according to fractures affecting one, two, or three columns. ROM parameters
of all specimens were measured again, and statistically compared.
Results showed that specimens that had a fracture in only one column had no statistical
difference in ROM in any of the axis, while the specimens that had fractures in two
or three columns showed instability in both axis, concluding this way that the three‐column
concept can be applied to thoracolumbar segment fracture in dogs.
Remote Ischemic Postconditioning in Dogs Undergoing Elective Spinal Cord Decompressive
Surgery
V. Mortera, N. Granger
University of Bristol, The School of Veterinary Science, Bristol, UK
Ischemia‐reperfusion injury is a common pathological mechanism in chronic compressive
myelopathies. It contributes to neurological deterioration after spinal cord surgical
decompression, which can be severe, resulting in prolonged hospitalisation, cost and
complications.
Remote‐ischemic postconditioning (RIPC) consists of eliciting temporal ischemia‐reperfusion
in a chosen body part to protect distant organs against the consequences of an anticipated
episode of ischemia‐reperfusion injury. It is effective for spinal cord protection
in laboratory animals. A primary concern for companion animals is to ensure safety
of the technique.
We applied RIPC to one forelimb (three cycles of 5‐minutes ischemia‐reperfusion) in
ten dogs with chronic cord compression (7 sub‐arachnoid cysts, 3 intervertebral disc
protrusion) during anaesthesia and before the start of elective decompressive surgery.
Seven dogs deteriorated neurologically postoperatively. No adverse effects were observed
during RIPC and for 48 h after surgery. During RIPC, the heart rate increased up to
a maximum of 15 heart beats per minutes and the mean arterial blood pressure increased
up to a maximum of 20 mmHg from pre‐RICP baseline values. Serum potassium, lactate
and blood gases remained within normal limits and we collected pre, intra and postoperative
serum to measure S100β and neuron specific enolase as biomarkers of neuronal damage.
Thromboelastography showed a reduction in maximal amplitude and G‐value (clot strength)
after RIPC, however no dog showed post‐operative vascular complication.
RIPC was safe and easy to perform in the studied dogs. These preliminary results allow
us to progress to a randomised trial looking at RIPC benefits for dogs with chronic
cervical myelopathy.
Surgical Treatment of Chronic Spinal Cord Compression in Two Coatis
N. Meyerhoff
1, M. Fehr1,2, J. Neßler1, A. Maiolini1, J. Tünsmeyer1, P. Dziallas1, V. Molnár3,
C. Ludwig4, V. Stein1, A. Tipold1
1Small Animal Clinic, University of Veterinary Medicine Hannover, Germany2Clinic for
small mammals, reptiles and birds, University of Veterinary Medicine Hannover, Germany3Hannover
Adventure Zoo, Germany, 4Allwetterzoo Münster, Germany
Whereas intervertebral disc herniation (IVDH) is considered a frequently occurring
diagnosis in dogs, clinical signs and outcome of chronic IVDH with spinal cord compression
in coatis (Nasua nasua) are unknown.
The purpose of this case report is the description of successful surgical treatment
of chronic IVDH despite challenging circumstances of postoperative care in zoo animals.
Two male, middle‐aged coatis were presented with mild chronic progressive paraparesis.
MRI revealed moderate to severe ventral spinal cord compression due to herniated disc
material between the first and second lumbar vertebrae, resp. the twelfth and thirteenth
thoracic vertebrae. Treatment included mini‐hemilaminectomy and partial corpectomy
in one animal, in the other one dorsal laminectomy. The spinal cord was bluish, compressed
and deviated. After surgery, both coatis were isolated from the group, objects for
climbing were removed from the cage to grant restricted mobility. Follow‐up was achieved
via personal visits and video‐observation. Both coatis were ambulatory the day after
surgery and showed continuous slow improvement of neurological status. Both coatis
are again presented to the public, one has a completely normal gait 6 months after
surgery while the second shows low carriage of the tail. In conclusion, surgical treatment
followed by restricted mobility seems to be a useful treatment in chronic IVDH in
coatis.
Cervical Intervertebral Disc Extrusions in French Bulldogs: 50 Cases (2004–2016)
A. Recio, C. de la Fuente, S. Añor
Neurology‐Neurosurgery Service of the Veterinary Teaching Hospital at the Universitat
Autònoma de Barcelona
Intervertebral disc disease is one of the most common neurologic disorders in chondrodystrophic
breeds. Cervical Intervertebral Disc Herniation (IVDH) represents about 15% of all
IVDH.
The objective of this retrospective study was to identify specific features of cervical
IVDH in French Bulldogs.
Fifty French Bulldogs with surgically confirmed cervical IVDH, managed at our hospital
from 2004 to 2016, were selected. Cervical IVDH were 26% of all IVDH (192) in this
breed. Thirty‐one dogs were males (62%). Mean age at presentation was 4.9 years, and
mean weight was 13.1 kg. Patients were grouped according to the severity of neurological
deficits: 28 dogs (56%) with neck pain as only clinical sign, 10 dogs (20%) with ambulatory
tetraparesis, and 12 dogs (24%) with non‐ambulatory tetraparesis. Mean duration of
clinical signs before presentation was 9.9 days. Time from surgery to greatest neurological
improvement after surgery (recovery time) was 18, 19.2 and 46.5 days for each group,
respectively. The most commonly affected disc space was C3‐C4 (31 dogs, 62%), followed
by C2‐C3 and C4‐C5 (7 dogs each, 12%). Neck pain as sole clinical sign was the most
frequent sign.
The results suggest that C3‐C4 is the most commonly herniated cervical disc in French
Bulldogs, and this differs from affected discs in others chondrodystropic breeds such
as Beagles or Dachshunds (C2‐C3). French Bulldogs appear to develop IVDH at younger
age (4.9 years old) than these other breeds, to have a higher male predisposition
and longer recovery time, and cervical IVDH seems to have a higher prevalence in our
study population than in others previously described.
The Effect of Kyphoscoliosis on Intervertebral Disc Extrusion in French Bulldogs
M. C. C. M. Inglez de Souza
1,2, R. Ryan2, R. M. A. Packer2, G. Ter Haar2, S. De Decker2
1Depatment of Surgery, School of Veterinary Medicine ‐ University of São Paulo, São
Paulo, Brazil2Royal Veterinary College, University of London, Hatfield, UK
Although thoracic hemivertebra with kyphoscoliosis is often considered an incidental
finding in brachycephalic breeds, it has been suggested to interfere with spinal biomechanics
and intervertebral disc degeneration. Our aim was to evaluate if the occurrence of
kyphoscoliosis was associated with a higher prevalence of cervical or thoracolumbar
intervertebral disc extrusion (IVDE) in French Bulldogs (FB). FB that underwent computed
tomography for reasons unrelated to spinal disease (n = 70), FB with cervical IVDE
(n = 24), and FB with thoracolumbar IVDE (n = 35) were included. Signalment, occurrence,
number and anatomical location of hemivertebra, spinal kyphosis, scoliosis, and, if
relevant, location of IVDE were recorded. Imaging studies were evaluated by two authors,
after which a consensus opinion was reached.
There was no significant association between the presence of kyphosis, scoliosis,
or hemivertebrae and the occurrence of thoracolumbar or cervical IVDE. There was no
significant association between the occurrence of kyphosis, scoliosis, or hemivertebrae
and the age of dogs with cervical or thoracolumbar IVDE. There was a significant association
between the presence of kyphosis and the anatomical location of thoracolumbar IVDE
(P = 0.036). Dogs with kyphosis were more likely to have caudal lumbar IVDEs (L2‐L6)
compared to FB without kyphosis. There was no association between the presence of
scoliosis and the location of the affected disc.
The results of this study do not support the hypothesis that vertebral malformations
in French Bulldogs increase the risk of cervical or thoracolumbar IVDE. In agreement
with previous findings, dogs with kyphosis are more likely to have a caudal lumbar
IVDE.
Comparison of the Accuracy of Radiography and Conventional Computed Tomography for
Detection of Congenital Thoracic Vertebral Malformations in Brachycephalic “Screw‐Tailed”
Dog Breeds
J. Brocal
1, S. De Decker2, R. Jose‐Lopez1, J. Guevar1, M. Ortega3, G. Ter Haar2, R. Gutierrez‐Quintana1
1College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow,
UK2Clinical Science and Services, The Royal Veterinary College, Hatfield, Hertfordshire,
UK3Centro Clinico Veterinario Indautxu, Bilbao, Spain
Congenital vertebral malformations (CVM) are relatively common in the thoracic vertebrae
of brachycephalic dogs. They can lead to kyphosis of the vertebral column and secondary
neurological deficits. The purpose of this retrospective study was to compare the
accuracy of radiography and computed tomography (CT) for detection of CVM's.
Brachycephalic dogs, which had both radiographs and CT of the thoracic vertebral column
performed for a variety of reasons, were retrospectively reviewed by three observers,
which classified each thoracic vertebra into normal or abnormal. This process was
performed with lateral radiographs alone, with both lateral and ventro‐dorsal views,
and CT independently. One observer reviewed the images again two weeks later. The
intra and inter‐observer agreement was calculated.
A total of 630 vertebrae in 49 dogs were reviewed. All observers identified more affected
vertebrae when evaluating lateral and ventro‐dorsal radiographic views compared to
lateral views alone (P < 0.05); and more with CT when compared to lateral and ventro‐dorsal
radiographic (statistically significant in two observers). Intra‐observer agreement
in diagnosing absence/presence of malformations for all three techniques was very
good (κ: 0.91). Inter‐observer agreement varied from moderate (κ: 0.588) to good (κ:
0.755).
Approximately 60% of dogs had more than one affected vertebra and the number of dogs
identified with no CVM's was not significantly different between the two comparisons
described above.
A hereditary component for the development of CVM's has been suggested and CT seems
to be an accurate imaging screening modality for selective breeding.
Results of Non‐Surgical Treatment for Congenital Vertebral Body Malformations in Eleven
Dogs
S. Wyatt
1, R. Gonçalves2, R. Gutierrez‐Quintana3, S. De Decker1
1Royal Veterinary College, Hatfield, UK2University of Liverpool, Neston, UK3University
of Glasgow, Glasgow, UK
Although several surgical techniques have been reported, little is known regarding
results of medical management for dogs with clinically relevant hemivertebra. The
aim of this study was to evaluate the outcome of medical management for dogs with
thoracolumbar hemivertebra.
An electronic medical database was searched for dogs with neurological signs caused
by hemivertebra with or without spinal kyphosis. Diagnosis was confirmed by MRI in
all cases. Dogs were excluded if records or imaging studies were incomplete or unavailable
for review, or if dogs had concurrent disorders that could contribute to clinical
signs. Medical management typically consisted of exercise modification in combination
with anti‐inflammatory or analgesic drugs. Follow‐up data was obtained by information
from re‐examination visits and a standardized telephone questionnaire.
Eleven dogs of screw‐tailed brachycephalic breeds with a median age of 6 months were
included. All dogs presented with ambulatory paraparesis and ataxia and in one dog
spinal hyperesthesia could be elicited. Medical/ conservative management consisted
of restricted exercise with (n = 3 dogs) or without (n = 3) physiotherapy in six dogs,
physiotherapy without restricted exercise in three dogs, and no exercise modification
in two dogs. Seven dogs received additional medication, which consisted of prednisolone
in five dogs and gabapentin in two dogs. Of the eleven dogs included, four were ultimately
euthanized due to progressive neurological deterioration, 2 underwent surgery due
to progressive neurological deterioration, and the remaining five dogs were alive
despite progressive neurological deterioration.
Medical management was not associated with a favourable outcome as all dogs demonstrated
progression of clinical signs.
Case Series: MRI Findings and Follow‐Up after Surgical Treatment in Three French Bulldogs
with Meningomyelocele
L. Martin1, V. Cervera2, J. Cabré3, S. Ródenas1
1Service of Neurology and Neurosurgery of Valencia Sur Hospital, Silla Valencia, Spain2Service
of Imaging Diagnosis of Valencia Sur Hospital, Silla Valencia, Spain3Vetamic Veterinaris
Hospital, Cambrils Tarragona, Spain
Spina bifida (SB) is a developmental defect characterized by incomplete fusion of
the vertebral arches. Spina bifida can be accompanied by meningocele/meningomyelocele
(protrusion of meninges/nervous tissue). Only one case of SB with meningomyelocele
describing MRI findings and surgical treatment has been reported in dogs. The aim
of this case series study is to report MRI findings, surgical treatment and follow
up in three French bulldogs with SB and meningomyelocele.
Three French bulldogs were enrolled in this study: one 5 month old male and two 4 month
old female littermates. Common clinical signs were fecal, urinary incontinence and
dimpling of the skin. All cases showed hipoalgesia of the perineal area and absence
of perineal reflex and tone. Only one dog presented mild paraparesis.
Lumbar MRI revealed an incomplete dorsal lamina of the L7 and sacrum in two dogs,
and the same defect in L6‐L7 in the other dog, with protrusion of the meningeal sac
and nervous tissue in all cases.
Surgical treatment consisted in dissection of the abnormal skin attached to the meningeal
structures.
Two cases remained incontinent and the other case was urinary continent after surgical
treatment.
In this study one dog was successfully urinary continent after surgery. MRI was very
useful in order to characterize the protrusion of the nervous tissue and meninges
through the defect. Early surgical treatment as in humans is indicated in dogs with
SB and meningomyelocele. Surgery of SB/meningomyelocele may be successful in some
dogs in order to regain urinary continence.
Syringomyelia Classification According to Associated Mangetic Resonance Imaging Findings
in French Bulldogs: 64 Cases (2008–2016)
A. Suñol Iniesta
1, M. López‐Font2, C. Morales1,3, J. Mascort1, M. Manera4, P. Montoliu1,3
1Hospital Ars Veterinaria, Barcelona2Diagnosi Veterinaria, Barcelona3Neurocat Veterinaris,
Barcelona4Imagovet, Barcelona
Syringomyelia is reported mainly associated to Chiari‐Like Malformation syndrome (CLM).
In dogs, it has infrequently been related to other causes, including other craniocervical
malformations and spinal or brain neoplasia. In human medicine, syringomyelia is classified
according to suspected aetiology.
The objective of this retrospective study was to evaluate syringomyelia in French
bulldogs according to suspected aetiology based on magnetic resonance imaging (MRI)
findings.
Medical records and MRI series of French bulldogs with diagnosis of syringomyelia
were retrieved from two MRI centres (2008–2016). Signalment, indication for MRI, location
of syringomyelia, primary diagnosis, other imaging findings, presence of CLM, and
presence of ventricular enlargement were evaluated for each dog.
Sixty‐four dogs met the inclusion criteria, 21(33%) females and 43(67%) males. Median
age was 6 years. Clinical signs could be related to syringomyelia in 48(75%) dogs,
whereas in 16(25%) dogs syringomyelia was considered an incidental finding. Only 6
dogs were referred for cervical hyperaesthesia or phantom scratching. In addition
to syringomyelia, a total of 115 lesions were identified; 46(72%) dogs had at least
2 abnormalities. Alterations apparently associated to the syringomyelia were classified
into 5 categories: craniocervical malformations (CLM, atlantooccipital overlapping,
dural band) in 19(30%) cases, intracranial space‐occupying lesions (including hydrocephalus)
in 22(34%), spinal compressive diseases (mainly disc herniation) in 13(20%), and non‐compressive
hemivertebra in 4(5%). In 6(11%) dogs no associated lesion was identified.
Results suggest that syringomyelia in French bulldogs is frequently unrelated to CLM.
Males were overrepresented, and signs of neuropathic pain are uncommon or poorly recognized
in this breed.
Intraoperative Ultrasound Elastography of the Canine Spinal Cord
J. Prager
1, A. Delaney2, J. Rose1, T. Harcourt‐Brown1, D. Chari2, N. Granger1
1University of Bristol, The School of Veterinary Science, Bristol, UK2University of
Keele, Institute for Science and Technology in Medicine, Keele, UK
This pilot study investigated the feasibility of using intraoperative ultrasound elastography
to determine elasticity of the canine spinal cord. Establishing the mechanical characteristics
of injured spinal cord may: (i) help predict recovery; and (ii) allow design of novel
therapies such as implantable hydrogels with tissue‐matched elasticity.
Dogs undergoing routine decompressive surgery following acute thoraco‐lumbar intervertebral
disc herniation were recruited. Measurement of shear wave velocity (m/s) of the spinal
cord was obtained using Acoustic Radiation Force Impulse Elastography (Siemens Acuson
S2000 ultrasound machine), with sterile saline used as contact medium. Shear wave
velocity was recorded cranially, caudally and at the lesion site. Ultrasound elastography
was also performed at the thoraco‐lumbar junction on unfixed fresh normal canine spinal
cord specimens within 8 h of euthanasia. A CIRS Ultrasound Elastography QA Phantom
(Model 049A) was used to provide known values of elasticity (kPa).
Measurements were obtained from 6 dogs intraoperatively taking <15 minutes each. The
median cord elasticity was 13.3 kPa (interquartile range: 10.3–63.9 kPa) at the lesion
epicentre, and 30.5 kPa (interquartile range: 15.4–35.6 kPa) and 26.7 kPa (interquartile
range: 16.7–56.3 kPa) cranial and caudal to the lesion respectively, although this
was not different from the epicentre values. Median cadaver spinal cord elasticity
was 7.58 kPa (interquartile range: 3.41–18.4 kPa) and significantly different from
intraoperative values (P = 0.0081, Mann‐Whitney U). Elasticity values calculated from
ultrasound measurement of the phantom were within 30% of certified values.
We demonstrate that intraoperative ultrasound elastography of the canine spinal cord
is feasible, and that post‐mortem spinal cord elasticity is not representative of
in vivo elasticity.
Magnetic Resonance Imaging Characteristics of Cauda Equina Nerve Roots in 50 Dogs
with Degenerative Lumbosacral Stenosis
D. Alder
1, S. Ohlert2, F. Steffen1
1Clinic for Small Animal Surgery, Vetsuisse Faculty, University of Zurich, Switzerland2Section of
Diagnostic Imaging, Vetsuisse Faculty, University of Zurich, Switzerland
Nerve root position and morphology observed on MRI yield important diagnostic information
in people with lumbar pain because they can be used to differentiate between non‐specific
back pain and compressive lesions. In dogs, demonstration of nerve root compression
is the main imaging criteria for the diagnosis of DLSS. While histopathologic alterations
in chronically compressed nerve roots have been described, MRI‐abnormalities in nerve
root morphology and signal behaviour have not been reported in dogs with DLSS.
MR images of 50 dogs with and 17 dogs without clinical signs of DLSS were retrospectively
evaluated for presence of abnormalities in size and signal behaviour of cauda equina
nerve roots. Three evaluators used sagittal and transverse T2‐weighted images to independently
score the subjective increase in size and signal changes of L7‐ and S1‐ roots. The
findings were correlated with the presence of foraminal and/or central stenosis. Interobserver
agreement for nerve root changes was assessed with Cohen's kappa (paired comparison).
A total of 268 nerve roots were examined: 20% were enlarged (L7: 69%; S1: 31%) and
16% were hyperintense (L7: 72%, S1: 28%). No enlarged nerve roots were found in control
cases. Foraminal stenosis was present in 64/134 foramina, and central stenosis was
found in 33/67 cases. Association between enlarged nerve roots and foraminal/central
stenosis was significant. Interobserver agreement was fair (0.41 to 0.6) to good (0.61
to 0.8) for both criteria, increase in size and hyperintensity.
In conclusion, L7 and S1 nerve root changes occur frequently in dogs with DLSS and
support the clinical diagnosis.
Clinical Presentation and Management of German Shepherd Dogs with Lumbosacral Pain
Presented in First Opinion Practice
G. Harris
1, D. O'Neill2, D. Brodbelt2, D. Church2, S. De Decker2
1The Queens Veterinary School Hospital, Cambridge University, Madingley Road, Cambridge
UK2The Royal Veterinary College, University of London, Hatfield, UK
German Shepherd Dogs (GSDs) are predisposed for lumbosacral disease. Previous research,
evaluating dogs presented at a referral institution, suggested medical management
of LS disease was associated with a fair prognosis. This study evaluates clinical
management of LS pain in GSDs in first‐opinion practice.
Data on GSDs with confirmed lumbosacral pain was extracted from the VetCompass database
of primary‐care veterinary clinical records in the UK. Of 85 GSD identified, 60.0%
were female, and 68.5% were neutered. The median age at diagnosis was 8.3 years. Concurrent
hip pain was shown in 57.7% of cases. Of the 44.7% of dogs that underwent neurological
examination, 31.8% had proprioceptive deficits. Incontinence was recorded in 10.6%
of dogs. 4.7% dogs were referred to a referral hospital. Radiographs were performed
in 25.9% of cases. Analgesia was given to 95.3% of dogs. Non‐steroidal‐anti‐inflammatory‐drugs
were given to 84.7% of dogs. The most used analgesic protocols were NSAIDS alone (50.6%),
opioids and NSAIDS (17.7%) and glucocorticoids and NSAIDS (11.8%). Rest was advised
in 23.5% of cases. The vet or owner noted improvement in 64.7% of cases.
During the study period, 44.7% of the dogs died with 34.2% of these deaths being ascribed
to lumbosacral pain.
Although this study had limitations in diagnostic accuracy, it overcame selection
biases from those dogs that are referred for their condition. This study shows very
low numbers of dogs are referred, therefore allowing a different population of dogs
with lumbosacral pain to be evaluated.
Magnetic Resonance Imaging Findings of Spinal Dysraphism in a Weimaraner Dog
F. Tirrito
1, F. Cozzi1, M. Bonaldi1, R. Lombardo1,2
1Clinica Neurologica Veterinaria, Milan, Italy2Department VESPA, Faculty of Veterinary
Medicine, University of Milan, Milan, Italy
Spinal dysraphism (SD) is an abnormal condition characterized by a variety of structural
and functional anomalies of the spinal cord, due to a defect in closure of neural
tube and malformative lesions of spinal cord structures, mostly in lower thoracic
and lumbosacral regions.
SD has been mostly described in Weimaraners and a hereditary basis has been identified.
Characteristic clinical signs are observed by 4–6 weeks of age and include postural
abnormalities, simultaneous hind limb gait (bunny hopping), ataxia and paresis, bilateral
synchronous withdrawal reflex in the hind limbs.
A 1.5 year old male Weimaraner was presented with a history of non progressive gait
abnormalities. Neurological exam revealed hind limbs ataxia and mild paresis, bunny
hopping and simultaneous bilateral flexor reflex of both hind limbs.
Spinal magnetic resonance (MR) showed a well defined T2‐WI and STIR linear hyperintensity,
iso‐hypointense in T1‐WI, extending on the dorsal spinal cord midline from T9 to L1.
On transverse images, this midline T2‐WI hyperintense area expanded from dorsal to
central parts of the spinal cord, with supposed direct connection with the dorsal
subarachnoid space. As a consequence of these alterations, the spinal cord appeared
almost heart shaped. No abnormal gadolinium enhancement was observed.
These MR findings were considered suggestive of a neural tube defect such as partial
duplication of the spinal cord (hemidydemia), diastematomyelia, spinal cord midline
cavitations (siringomyelia) or other aberrations possibly associated with abnormal
cerebrospinal fluid distribution.
To author's knowledge MR findings of spinal dysraphism have not been previously described
in dogs.
Lipomeningomyelocele Associated with Diplomyelia in a Dog
S. Schulze, N. Ondreka, M. Kolecka, M. J. Schmidt
Small Animal Clinic Department of Veterinary Clinical Sciences University of Giessen,
Germany
A 2 year‐old male neutered mixed breed dog presented with a soft tanged subcutaneous
mass dorsal to the spinous processes of T11/12, which was tender on palpation. Furthermore
proprioceptive ataxia of the hind limbs was noted upon clinical workup. On magnetic
resonance imaging (MRI) the spinous process of T11 presented a sagittal split intersected
by epidural and epaxial soft tissue. A thin T2‐hypointense band could be traced from
the skin surface to the dura through the split spinous process of T11. The dural tube
was focally lifted towards this T2‐hypointense band. Level with the disc space T11/T12
severe dilation of the subarachnoid space was noted. At T12 the spinal cord was U‐shaped
with a dorsal split and then completely bipartite into two cords at T11. From T6 to
T8 the central canal presented marked widening. The MRI findings were consistent with
a spina bifida with a lipomeningomyelocele and diplomyelia. Surgery was performed
to remove the lipomeningomyelocele via hemilaminectomy. On necropsy and patho‐histology
connective and fatty tissue with vessel sections were found.
The MRI findings as well as the patho‐histological results in this report are compatible
with a spina bifida with a lipomeningomyelocele and diplomyelia in the caudal thoracic
spine. To the author's knowledge this is the first case‐report of a lipomeningomyelocele
associated with diplomyelia in a dog.
A Canine Brain Template for Image Processing of Clinical Magnetic Resonance Imaging
Data
S. Schulze
1, M. J. Schmidt1, T. Flegel2, E. Ludewig2, M. Gounis3, N. Ondreka1, J. Boltze4, B.
Nitzsche5
1Small Animal Clinic Department of Veterinary Clinical Sciences University of Giessen,
Germany2Department of Small Animal Medicine, University of Leipzig, Germany3New England
Center for Stroke Research, Worchester, USA4Fraunhofer Research Institution for Marine
Biotechnology and Institute for Medical and Marine Biotechnology, University of Lübeck,
Germany5Clinic for Nuclear Medicine, University of Leipzig, Germany
In humans, surgical treatment of drug resistant epilepsy (‘epilepsy surgery’) reduces
the seizure frequency with a good prognostic outcome. Knowledge of epileptogenic zones,
especially in focal cortical malformations are essential for the successful resection
of an epileptogenic focus. Structural and functional magnetic resonance imaging (MRI)
support the focus determination but, unfortunately, diagnostic capability is limited
by missing brain references. Computational neuroscience may overcome the limitation
with the help of population‐averaged reference space (template). The techniques allow
for comparison across individuals including quantification of anatomical features.
Here we present an atlas of the canine brain that may be suited for this purpose.
T2‐weighted MRI data (3 T Siemens and 1 T Gyroscan Intera Phillips) of 37 dogs without
structural or cerebral‐functional lesions were used. Statistical Parametric Mapping
(SPM8, UK) and Matlab (Mathworks, UK) were used for the co‐registration of canine
neuroimages. This includes manual (by using F is ImageJ, FIJI, Germany) and automatic
‘unified’ segmentation procedure of SPM to retrieve grey (GM) and white (WM) matter
as well as cerebrospinal fluid (CSF).
The established template showed detailed and precise defined GM, WM just as CSF. Cerebral
gyri and sulci are highly contrasted and exactly described. Consequently, our framework
provides an automatically neuroimage processing of clinical canine MRI data for brain
tissue analysis. Further work will include more decided templates and a priori tissue
information in respect to the morphologically variance of different breeds. This includes
a spatial canine brain model with labelled areas to allow further analyses of cortical
structures.
Application of a Funtional Brain Atlas to Interpret Human Epileptic Seizure‐Related
fMRI Maps and Considerations for Application in Animals
M. Charalambous
1, L. A. van Graan1, A. Liston2, L. Lemieux1
1Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Faculty
of Brain Sciences, University College London, UK2Department of Medical Physics, University
College London, UK
Contrary to veterinary patients, humans with drug‐resistant epilepsy might be considered
for epilepsy surgery. Advanced neuroimaging techniques such as magnetic resonance
imaging (MRI) are routinely used to help localize the surgically resectable epileptogenic
area successfully in some patients. However, this approach often fails and new methods
need to be developed. Recently, functional MRI (fMRI) has been used alone or in combination
with electroencephalography (EEG) to obtain maps of cerebral activity during ictal
and interictal phases, thereby providing a possible avenue for improved localization
of the brain areas directly responsible for epileptic seizures.
In our project, seven patients with drug‐resistant epilepsy were studied. Simultaneous
EEG‐fMRI was performed to map the specific brain networks involved during seizures,
which were divided into a series of phases: ictal onset, ictal established and late
ictal. Statistical parametric mapping (SPM) was then used to generate haemodynamic
maps which were analyzed using a new atlas to measure the levels of involvement of
ten normal functional brain networks. Similarities in brain activation during seizures
across patients were found, and the level of involvement of the networks varied across
ictal phases.
In conclusion, we have measured the relationship between ictal activity and brain
networks involved in normal brain activity, opening the way to a more quantitative
approach to the study of ictal semiology. To consider this in veterinary medicine,
similar neuroimaging methods should be recruited and developed. The increasing use
of EEG in veterinary patients might be a stepping‐stone for the introduction of further
neuroimaging techniques, which could actually form the base of epilepsy surgery in
animals.
The Edinburgh Companion Animal Brain Bank – A New Resource for Cross‐Translational
Neurology
N. M. Rzechorzek1,2, M. Flook3, C. Pennycook3, E. Jeffery1, S. Smith3,4, C. Smith2,
K. Marioni‐Henry1
1Neurology/Neurosurgery Service, Hospital for Small Animals, Royal Dick School of
Veterinary Studies and Roslin Institute, University of Edinburgh, UK2Centre for Clinical
Brain Sciences, University of Edinburgh, UK3Easter Bush Pathology, Royal Dick School
of Veterinary Studies, University of Edinburgh, UK4Centre for Comparative Pathology,
University of Edinburgh, UK
Access to high quality brain tissue is critical for understanding disease pathogenesis
and to validate novel pre‐mortem biomarkers for neurological disorders. An optimal
resource would promote cross‐translation between human and veterinary neurologists,
through comparative clinical and molecular phenotyping. Successful human brain banks
continue to expand, yet there is no equivalent archive for veterinary patients. We
sought to establish the UK's first Companion Animal Brain Bank.
Adapting protocols from the MRC Edinburgh Brain Bank, we have developed standardized
methods for archiving brain tissue from animals euthanased on welfare grounds. Samples
are collected with informed consent and approval of the R(D)SVS Veterinary Ethical
Review Committee. Whole brains are evaluated grossly then bisected to provide fresh‐frozen
and formalin fixed tissue for matched molecular and histopathological readouts respectively.
Fixed hemibrains are processed in transverse section and 31 specified brain regions
are embedded.
To date, 30 brains have been banked. 11 of these are derived from animals with non‐neurological
conditions (designated control tissue). Mean canine fresh brain parameters ± standard
error include brain length (rostral tip of the frontal cortex to the caudal tip of
cerebellar vermis; 79.0 ± 1.5 mm), brain weight (91.8 ± 3.72 g) and post‐mortem interval
(28.2 ± 4.7 h). Brain length and weight correlate with r2 = 0.843.
Our protocols optimise sample quality within the logistics of a referral setting and
can be reproduced for multi‐centre collaborations or for donation to a central bank.
Our objective is to create an online searchable database to facilitate tissue requests
for ethically‐approved research.
Brainstem Auditory Evoked Potentials in Dogs with Idiopathic Peripheral Vestibular
Syndrome
T. A. Shaw, F. Liebel, N. Granger, T. R. Harcourt‐Brown
The School of Veterinary Sciences, University of Bristol, UK
Dogs with idiopathic vestibular syndrome can also have involvement of nearby cranial
nerves (for instance the facial nerve in idiopathic facial neuropathy). The proximity
of the sensory axons transmitting vestibular and auditory information within cranial
nerve VIII means that concomitant vestibular and auditory dysfunction is plausible
in these dogs, but remains to be investigated. The aim of this study was to evaluate
dogs with idiopathic vestibular syndrome for hearing loss and cochlear nerve dysfunction.
In this retrospective study (over 6 years including 12 dogs), we reviewed BAEP traces
of dogs diagnosed with idiopathic vestibular syndrome. Wave I‐II and I‐V interpeak
latency (IPL) was compared between the affected side (ipsilateral to the vestibular
localisation) and the unaffected contralateral side via a repeated measures t‐test.
Nine dogs were diagnosed with idiopathic facial neuropathy and ipsilateral idiopathic
vestibular syndrome and three dogs were diagnosed with idiopathic vestibular syndrome
only. All dogs were considered to have morphologically normal I, II and V waveforms.
Affected/unaffected I‐II and I‐V IPLs were 0.91 ± 0.049/0.90 ± 0.067 ms and 2.72 ± 0.23/0.277 ± 0.26 ms,
respectively. The difference between the affected and unaffected side was not statistically
significant (I‐II IPL: mean difference 0.01583 ms; 95% confidence interval −0.00892,
0.0405; P = 0.187; I‐V IPL: mean difference −0.482 ms; 95% confidence interval −0.102,
0.00546; P = 0.927).
The data do not support the hypothesis that dogs with idiopathic vestibular syndrome
have cochlear nerve dysfunction, and suggest that all dogs were able to hear. This
information could help further characterise canine idiopathic vestibular syndrome
and idiopathic cranial polyneuropathies.
Facial Nerve Paralysis in Dogs: A Retrospective Study of 69 Cases
C. Ricco, L. Giraud, L. Cauzinille
Centre Hospitalier Vétérinaire Frégis, Arcueil, France
Facial paralysis is readily recognised in small‐animal veterinary practice because
of its manifestation of facial asymmetry; the idiopathic form has been previously
reported to be present in 75% of dogs. The purpose of this study in dogs was to classify
and determine the origin of facial nerve dysfunction using enhanced diagnostic procedures,
including magnetic resonance imaging (MRI).
The medical records of 69 dogs admitted for facial paralysis were reviewed. Neurological
examination confirmed facial nerve abnormalities, which were all investigated with
MRI.
Idiopathic facial paralysis was diagnosed in 48% of dogs. Vestibular signs were the
most common additional clinical signs and were observed in 36% of dogs with idiopathic
facial paralysis.
Peripheral nervous system disease was diagnosed in 19% of dogs, and central nervous
system disease occurred in 30% of dogs. Two new predisposed breeds are added, the
French bulldog and the Cavalier King Charles spaniel.
Improved diagnostic methods enabled the diagnosis of a higher percentage of inflammatory/infectious
diseases, which were absent in the central nervous system aetiologies of a previous
similar study, and revealed metabolic (hypothyroidism), inflammatory and neoplastic
aetiologies for peripheral nervous system disease.
Comparison of the Interobserver Agreement in the Evaluation of the Patellar Tendon‐
and Bicipital Reflex in Dogs
F. Giebels, B. Kohn, L. Pieper, S. Loderstedt
Small Animal Clinic, Faculty of Veterinary Medicine, Freie Universität Berlin, Berlin,
Germany
The reliability of reflex‐assessment differs between the authorship. Since the patellar
tendon reflex (PTR) is accepted to be highly reliable, the biceps tendon reflex (BTR)
is regarded to be of low reliability. Nevertheless, these statements base on subjective
observations than on an empirical study. It has been postulated, that the expertise
of the observer influences the interobserver agreement (IA). The goals of this study
were: (1) quantification of the interobserver agreement of PTR and BTR and (2) evaluation
of the influence of the observer´s level of expertise on the IA.
For BTR‐assessment 56 forelimbs and for PTR‐assessment 64 hindlimbs of neurological
unremarkable dogs were examined in lateral recumbency by the same examiner and videotaped.
Examination sequences were anonymised and evaluated blinded by 12 observers divided
in 3 groups of 4 observers: veterinary‐neurologists (group1), veterinary‐surgeons
(group2), last year veterinary‐students (group3). Observers evaluated two categories:
reflex‐presence (0;1), reflex‐briskness (0 (absent)‐4 (clonic)). IA was evaluated
with reliability analysis for BTR and PTR separately and compared to each other.
Reflex‐presence IA was significantly highest for group1 in both reflexes. Reflex‐briskness
IA of BTR was significantly highest for group1, for PTR significantly lowest for group3.
Reflex‐briskness IA was higher for BTR compared to PTR in group1. In group2 and 3
reflex‐briskness of PTR showed higher IA. Level of expertise showed a higher influence
on reflex‐briskness IA of BTR.
BTR can be assessed by neurologists more reliable than PTR and reflex assessment is
highly dependent on observer´s level of expertise.
Canine Idiopathic Epilepsy: Real World Effectiveness of Treatment and its Effect on
Dog and Owner Quality of Life
L. A. I. Smith, P. Freeman, L. Alves
Department of Veterinary Medicine, The University of Cambridge
A retrospective, questionnaire based study was carried out to: assess the effectiveness
of treatment of idiopathic epilepsy (IE) in terms of the owners’ perceptions, to discover
how caring for an epileptic dog affects owner's quality of life (QOL), and to assess
how IE and its treatment affects the QOL of dogs.
Cases of canine IE were found by searching the database of the Queen's Veterinary
School Hospital, Cambridge. An online questionnaire was designed based on previous
studies and the QOL assessment questionnaire designed by Wessman et al. (2014), and
sent to owners.
19 completed questionnaires were returned. 30% of owners described the seizure frequency
of their dogs on treatment as not acceptable. There was no correlation between owners’
perception of acceptability of seizure frequency and seizure frequency. 89% of dogs
showed adverse effects of anti‐epileptic drugs (AEDs). Abnormal behaviours were present
in 63% of dogs. AEDs improved some behaviours and made others worse. 68% of owners
described their dog's QOL as good, but QOL improved on treatment in only 42% of dogs.
95% of owners reported that caring for their dog was either not at all or only slightly
bothersome.
Owners’ ideas of effective seizure control are variable. IE in dogs is linked with
behavioural changes and treatment worsens some behaviours while improving others.
Owners perceive that their dogs have a good QOL although this may not be improved
by treatment, and while caring for them does impact on the owners’ lifestyle they
do not see this as overly bothersome.
Overshunting and Subdural Haemorrhage after Implantation of a Low‐Pressure Valve Ventriculoperitoneal
Shunt in a Dog with Hydrocephalus Internus, Quadrigeminal Cyst and High Intracranial
Pressure
S. Hanemann, I. Merseburger, V. Fromme, S. Piesnack, T. Flegel
Department of Small Animal Medicine, University of Leipzig, Germany
A 3‐month‐old mixed breed dog was presented with generalized ataxia, hypermetria,
head tilt, intention tremor and absent menace response. MRI revealed hydrocephalus
internus, quadrigeminal cyst and foramen magnum herniation. A ventriculoperitoneal
shunt (VPS) with opening pressure of 5 cmH2O was placed in the right ventricle. Intraoperatively
intracranial pressure (ICP) was 21 cmH2O.
One month later the dog was presented with acute onset of nausea, salivation and right‐sided
central blindness. MRI revealed a bilateral high grade subdural haemorrhage with collapse
of underlying brain parenchyma and deterioration of the foramen magnum herniation.
Trepanation with hematoma evacuation was performed and the VPS was ligated. After
initial improvement, the dog showed acute vestibular signs again. A third MRI pictured
a mild subdural hematoma and a high degree of foramen magnum herniation. Foramen magnum
decompression and fenestration of quadrigeminal cyst was performed. Two months later,
the dog presented without neurological deficits except of a mild hypermetria. Control
MRI showed no recurrence of the quadrigeminal cyst, an organisation of the remnants
of the subdural hematoma. There were no signs of increased ICP.
It can be speculated that the quadrigeminal cyst was communicating with the hydrocephalus
internus. So foramen magnum decompression and fenestration of the cyst could have
been enough to drain the hydrocephalus. Overshunting is one complication after VPS
implantation. That's why ICP measurement should be performed before VPS surgery and
the opening pressure should be selected accordingly. However, if overshunting develops,
it can be treated successfully by reducing CSF drainage and removal of subdural hematoma.
Frameless Stereotactic Volumetric Modulated Arc Radiotherapy of Brachial Plexus Tumors
in Dogs: 10 Cases
M. Dolera
1, L. Malfassi1, C. Bianchi1, N. Carrara1, L. Corbetta1, S. Finesso1, S. Marcarini1,
G. Mazza1, S. Pavesi1, M. Sala1, G. Urso1,2
1La Cittadina Fondazione Studi e Ricerche Veterinarie, Romanengo, Italy2Azienda Socio
Sanitaria Territoriale di Lodi, Lodi, Italy
Canine peripheral nerve sheath tumors (PNSTs) can involve the brachial plexus, its
peripheral branches, proximal nerves, and roots. Prognosis after surgical resection
is poor. The aim of this study was to evaluate the feasibility and the efficacy of
stereotactic radiotherapy.
Dogs with clinical signs and MRI findings consistent with PNSTs of brachial plexus,
branches and nerve roots were treated with LINAC based Volumetric Modulated Arc Radiotherapy
(VMAT). Mean delivered dose was 35 Gy in 5 fractions. Clinical and MRI follow‐up examinations
were planned every two months. Neurological disfunction, volumetric response and radiotoxicity
were graded and recorded. Overall and progression‐free survival time were estimated.
Ten dogs were enrolled. Progressive forelimb paresis, axillary pain and various degrees
of tetraparesis were the most frequent presenting complaints. Tumors involved the
plexus and proximal nerves in 3 dogs, the plexus, proximal nerves and nerve roots
in 5 dogs, the nerve roots and proximal nerves in 2 dogs. Partial or complete reduction
of neurological deficits were observed in all treated dogs. Partial responses were
observed in 10/10 patients. Local recurrence was observed in 9/10 of treated dogs.
Mean overall survival of 371 days and mean progression‐free survival of 240 days are
comparable to surgical literature data regarding the plexus and proximal nerves localization
but are superior in comparison to nerve roots localization. No radiotoxic effects
occurred.
VMAT RT can be a safe and viable alternative to surgery in case of canine brachial
plexus PNSTs involving the proximal nerves and roots.
Frameless Stereotactic Radiotherapy Alone and Combined with Temozolomide for Canine
Gliomas
M. Dolera
1, L. Malfassi1, C. Bianchi1, N. Carrara1, L. Corbetta1, S. Finesso1, S. Marcarini1,
G. Mazza1, S. Pavesi1, M. Sala1, G. Urso1,2
1La Cittadina Fondazione Studi e Ricerche Veterinarie, Romanengo, Italy2Azienda Socio
Sanitaria Territoriale di Lodi, Lodi, Italy
The aims of this work were to evaluate curative intent volume modulated arc hypo fractionated
radiotherapy (VMAT RT) for canine gliomas alone andin combination with temozolomide.
A prospective trial was performed in dogs with brain gliomas. The cohort was divided
into three arms: palliation, radiotherapy alone (RT), RT+temozolomide (RT+TMZ). The
RT schedule was ranged between 33 Gy/5 fx and 42 Gy/10 fx. Temozolomide was administered
during and after the treatment. Serial clinical and MRI examinations were planned
2, 4, 6, 12, 18, 24 months after irradiation. Overall and disease specific survival
time was estimated.
Thirty dogs were palliated, 22 dogs were treated with RT and 20 with RT+TMZ. Complete
and partial responses were observed on the whole in 63.2% and 90.9% of alive patients
in RT and RT+TMZ arm at 1 year. Median survival in palliation arm was 94 days. Median
survival of RT arm (383 days) and RT+TMZ arm (420 days) were not significantly different
(P = 0.61). The progression free survival in RT arm (255 days) and RT+TMZ arm (345 days)
were significantly different (P = 0.027). The grade of the tumor was not correlated
with the survival. The ratio between tumor and brain volume <5% and the clinical presentation
with normal mental status were positively correlated with the survival.
VMAT hypo fractionated RT is feasible and effective for canine brain gliomas. The
combination with TMZ ameliorate the progression‐free survival. A further escalation
of TMZ dose trial could be advisable.
Somastatin Receptor (SSTR2) in Canine Meningioma: Preliminary Results of Immunohistochemical
and qRT‐PCR Investigations
G. Foiani, G. Guelfi, C. Trivelli, C. Boccanera, M. T. Mandara
Department of Veterinary Medicine, University of Perugia, Italy
The neuropeptide somatostatin (SST) plays an important regulatory role in the proliferation
of both normal and neoplastic cells. Five subtypes of somatostatin receptors (SSTRs)
have been identified in several human tumours, including meningioma. The receptor
most commonly identified is the SSTR2a subtype. Long half‐life somatostatin analogues
(i.e. octreotide) are today included in chemotherapy schedules for unresectable or
radiation‐refractory recurrent human meningiomas.
The aim of this study is to test the expression of SSTR2a in canine meningioma by
immunohistochemistry and qRT‐PCR analyses. Twenty‐one FFPE meningiomas were used for
IHC investigations performed with rabbit anti‐human SSTR2 antibody (1:500, Alomone
Labs, Jerusalem, Israel) and avidin‐biotin‐peroxidase complex method. For each tumour,
area of labeling was assessed in five grades, ranging from (‐) = absent to (++++)
= > 75% of tumour.
Twenty‐five meningiomas were also submitted to qRT‐PCR investigations performed with
Taqman probe (Life Technologies). Total RNA was extracted from 5 µm sections of FFPE
tissue with FFPE‐RNA Purification Kit (Norgen), and mRNA was reverse‐transcribed with
iScript cDNA synthesis (Bio‐rad). At IHC, SSTR2a was expressed in 17/21 cases (81%)
showing a diffuse cytoplasmic immunoreaction. The most common histotypes, including
meningothelial, fibroblastic, and transitional meningiomas as well as the papillary
meningiomas were positive, ranging from (+) to (++++). Grade I, grade II and grade
III expressed SSTR2 in 86%, 91%, and 33%, respectively. The PCR‐amplification tests
gave positive results in the majority of the canine meningiomas. These preliminary
results encourage continuing this study aimed to find new chemotherapeutic protocols
for dogs.
Inflammatory Myofibroblastic Tumour Affecting the Spinal Cord in Three Dogs
M. T. Mandara1, G. Foiani1, S. Felici1, A. Sidoni2, F. Gernone3, N. Gasparinetti4,
M. Baroni5
1Department Veterinary Medicine, University of Perugia, Italy2Department Experimental
Medicine, University of Perugia, Italy3“Pingry” Veterinary Hospital, Bari Italy4“Diagnostica
Piccoli Animali”, Vicenza, Italy5“Valdinievole” Veterinary Clinic, Monsummano Terme,
Italy
Inflammatory Myofibroblastic Tumour (IMT) has long been described as an Inflammatory
Pseudotumour (IP) lesion. Today, it is recognized as a neoplastic lesion in human
medicine, more clearly distinguished from IP. Albeit IMT generally shows a benign
behaviour, an aggressive behaviour has been recognized in humans.
In this study three cases of canine neurological IMT affecting the spinal cord are
described. They occurred as extradural masses, at T6‐T7, T9‐T10 and T4, respectively.
In all cases, the mass was removed with hemilaminectomy. It extended to a maximum
of 2.5 cm. For the diagnosis, histological examination of the removed masses showed
in all three cases a spindle cell proliferation associated with a mixed inflammatory
infiltration mainly of lymphocytes and plasma cells. Based on the prevalence of spindle
cells on the inflammatory cells, a fibrohistiocytic histotype was recognized. At immunohistochemistry
study, spindle cells were positive for vimentin and smooth muscle actin (SMA) in all
three cases, and positive for desmin in two cases. Spindle cells were positive for
anaplastic lymphoma kinase‐1 (ALK‐1) in all cases. A mild mitotic index was observed
at Ki67‐immunoreaction. At the time of writing (32, 15 and 9 months, respectively)
the dogs do not show recurrent neurological signs. Compared to ALK‐1 negative IMT,
for ALK‐1 positive IMT a complete resection is strongly recommended.
Gene Expression of MMP‐2 and MMP‐9 and Correlated Ratio with Specific Inhibitors (TIMP‐1
AND TIMP‐2) in Canine Meningioma
M. T. Mandara, A. Reginato, G. Guelfi, G. Foiani
Department of Veterinary Medicine, University of Perugia, Italy
In the recent years, metalloproteinase activity of neoplastic cells has been studying
as a possible independent prognostic marker and target for therapeutic options. Degradation
of extracellular matrix is associated with tumour invasion and metastasis, and matrix
metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are
the key mediators of this process. In this study the expression of MMP‐9 and MMP‐2,
known as type IV collagenases, and their inhibitors TIMP‐1 and TIMP‐2 was investigated
in canine meningioma. Forty‐three cases of both intracranial and spinal tumours were
selected for the study. RNA was obtained from FFPE tissue, converted to cDNA and submitted
to quantitative PCR. Statistical analysis was performed to assess the variation of
the expression of these molecules and their relative ratio among the three histological
grades of meningioma.
MMP‐9 expression was undetectable in all the investigated meningiomas, while TIMP‐1
expression increased significantly from grade I to grade II (P < 0.001) and in papillary
meningiomas (P < 0.5), and it decreased in grade III tumours with no significant difference
between benign and anaplastic meningiomas. All the tumours expressed MMP‐2 though
without any significant differences in the three histological grades. MMP‐2/TIMP‐2
ratio didn't differ in benign, atypical and anaplastic meningiomas. Significantly
higher (P < 0.001) was the expression of MMP‐2 in the papillary meningiomas that showed
MMP‐2/TIMP‐2 ratio strongly skewed in favour of metalloproteinase. This finding suggests
MMP‐2/TIMP‐2 imbalance as one of the molecular bases of the aggressive biological
behaviour that seems to characterize this histologic subtype also in dogs.