R.C. da Costa

Current insights and controversies in the pathogenesis and diagnosis of disc-associated cervical spondylomyelopathy in dogs

Disc-associated cervical spondylomyelopathy (DA-CSM) is the most common cause of cervical spondylomyelopathy in dogs. In this condition, progressive caudal cervical spinal cord compression is typically caused by protrusion of one or more intervertebral discs. This disc-associated compression is sometimes seen in combination with mild vertebral abnormalities and dorsal compression resulting from ligamentum flavum hypertrophy. The intervertebral disc space between the sixth (C6) and seventh (C7) cervical vertebrae is most commonly affected. Although several large breed dogs can be affected, the adult to older dobermann is overrepresented. Clinical signs vary from cervical hyperaesthesia to tetraplegia. Dogs can present with a chronic progressive or an acute onset of clinical signs. Many aspects of this multifactorial neurological syndrome are not completely understood and are the subject of controversy and debate. Although several factors have been proposed, the underlying pathology and aetiology remain unknown. Recently, new insights have been gained in the pathogenesis, diagnosis and treatment of this challenging neurological syndrome. This review outlines current controversies and new developments concerning the pathogenesis and diagnosis of DA-CSM.

Micromorphometry and Cellular Characteristics of the Canine Cervical Intervertebral Discs

BACKGROUND Dogs have a high prevalence of disc-associated cervical spinal cord disorders. Despite this, there are no descriptions of the micromorphometry or cellular characteristics of canine cervical intervertebral discs. HYPOTHESIS/OBJECTIVES To compare micromorphometric and cellular characteristics at 4 disc regions (outer annulus [OA], inner annulus [IA], transitional zone [TZ], nucleus pulposus [NP]). We hypothesized that measurements would differ between chondrodystrophic (CH) and nonchondrodystrophic (NCH) dogs. ANIMALS Six CH dogs and 6 NCH dogs, under 3 years old. METHODS Histologic sections of all cervical discs from each dog were examined. Micromorphometric variables included relative ratio of ventral to dorsal annulus fibrosus (AF), number and mean width of AF fibers, and relative percentage of NP. Cellular variables included cell density, morphology, and grouping. RESULTS The NP from CH dogs was smaller, more rounded, and more dorsally located compared with that from NCH dogs. The NP occupied a greater proportion of the disc in NCH dogs compared with CH dogs (27.7 versus 15.8%; P<.001). The ratio of ventral to dorsal AF was approximately 3:1 in the CH group and 2:1 in the NCH group. Cellular variables were region dependent. Cell density was 2.4-fold higher in the OA compared with the NP. Approximately 50 of NP cells and 4.5% of OA cells occurred in groups. CONCLUSIONS AND CLINICAL IMPORTANCE Micromorphometric variables differed by CH status. Cellular variables differed by disc region. Our findings potentially can explain the high incidence of intervertebral disc extrusions in CH dogs compared with NCH dogs.

Force Plate Gait Analysis in Doberman Pinschers with and without Cervical Spondylomyelopathy

BACKGROUND The most accepted means of evaluating the response of a patient with cervical spondylomyelopathy (CSM) to treatment is subjective and based on the owner and clinicians perception of the gait. OBJECTIVE To establish and compare kinetic parameters based on force plate gait analysis between normal and CSM-affected Dobermans. ANIMALS Nineteen Doberman Pinschers: 10 clinically normal and 9 with CSM. METHODS Force plate analysis was prospectively performed in all dogs. At least 4 runs of ipsilateral limbs were collected from each dog. Eight force platform parameters were evaluated, including peak vertical force (PVF) and peak vertical impulse (PVI), peak mediolateral force (PMLF) and peak mediolateral impulse, peak braking force and peak braking impulse, and peak propulsive force (PPF) and peak propulsive impulse. In addition, the coefficient of variation (CV) for each limb was calculated for each parameter. Data analysis was performed by a repeated measures approach. RESULTS PMLF (P = .0062), PVI (P = .0225), and PPF (P = .0408) were found to be lower in CSM-affected dogs compared with normal dogs. Analysis by CV as the outcome indicated more variability in PVF in CSM-affected dogs (P = 0.0045). The largest difference in the CV of PVF was seen in the thoracic limbs of affected dogs when compared with the thoracic limbs of normal dogs (P = 0.0019). CONCLUSIONS AND CLINICAL IMPORTANCE The CV of PVF in all 4 limbs, especially the thoracic limbs, distinguished clinically normal Dobermans from those with CSM. Other kinetic parameters less reliably distinguished CSM-affected from clinically normal Dobermans.

Three-dimensional kinematic gait analysis of Doberman Pinschers with and without cervical spondylomyelopathy.

BACKGROUND The optimal treatment of cervical spondylomyelopathy (CSM) is controversial, with the owners and clinicians perception of gait improvement often being used as outcome measures. These methods are subjective and suffer from observer bias. OBJECTIVES To establish kinematic gait parameters utilizing digital motion capture in normal Doberman Pinschers and compare them with CSM-affected Dobermans. ANIMALS Nineteen Doberman Pinschers; 10 clinically normal and 9 with CSM. METHODS All dogs were enrolled prospectively and fitted with a Lycra(®) body suit, and motion capture was performed and used to reconstruct a 3-D stick diagram representation of each dog based on 32 reflective markers, from which several parameters were measured. These included stride duration, length, and height; maximal and minimal spinal angles; elbow and stifle flexion and extension; and maximum and minimum distances between the thoracic and pelvic limbs. A random-effects linear regression model was used to compare parameters between groups. RESULTS Significant differences between groups included smaller minimum (mean = 116 mm; P = .024) and maximum (mean = 184 mm; P = .001) distance between the thoracic limbs in CSM-affected dogs. Additionally, thoracic limb stride duration was also smaller (P = .009) in CSM-affected dogs (mean = 0.7 seconds) when compared with normal dogs (mean = 0.8 seconds). In the pelvic limbs, the average stifle flexion (mean = 100°; P = .048) and extension (mean = 136°; P = .009), as well as number of strides (mean = 2.7 strides; P = .033) were different between groups. CONCLUSIONS AND CLINICAL IMPORTANCE Our findings suggest that computerized gait analysis reveals more consistent kinematic differences in the thoracic limbs, which can be used as future objective outcome measures.

von Frey anesthesiometry to assess sensory impairment after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs.

Sensory threshold (ST) was measured using an electric von Frey anesthesiometer (VFA) in all limbs of 20 normal dogs and 29 dogs with acute thoracolumbar spinal cord injury (SCI) caused by spontaneous intervertebral disc extrusion. ST values were measured at three separate time points in normal dogs and on days 3, 10 and 30 following decompressive surgery in dogs with SCI. ST values were compared between groups and correlated with locomotor recovery in SCI-affected dogs. ST values were significantly higher (consistent with hypoalgesia) in the pelvic limbs of SCI-affected dogs at day 3, day 10 and day 30 when compared to normal dogs (P <0.05), while no significant difference in thoracic limb ST values was observed between groups. A progressive decrease in pelvic limb ST values occurred in SCI-affected dogs over time, consistent with improvement toward normal sensation or development of allodynia. This finding correlated inversely with locomotor score at 3 and 10 days after surgery. A significant decline in ST values across testing sessions was observed for all limbs of normal and SCI-affected dogs and may be related to patient acclimation, operator training effect, or effect of analgesic medications. This study supports the feasibility of VFA to assess differences in ST between normal and SCI-affected dogs. However, future studies must focus on techniques to minimize or compensate for clinical, environmental and behavioral factors which may impact ST values in the clinical setting.

Cervical spondylomyelopathy in Great Danes: A magnetic resonance imaging morphometric study

Morphometric investigations comparing normal and affected animals increase our understanding of spinal diseases in dogs. The aim of this study was to generate morphometric data for osseous-associated cervical spondylomyelopathy (CSM) in Great Danes (GDs). Magnetic resonance imaging (MRI) morphometric features of the cervical vertebral column of GDs with and without clinical signs of CSM were characterized and compared. Thirty client-owned GDs were prospectively enrolled, including 15 clinically normal and 15 CSM-affected GDs. All dogs underwent MRI of the cervical to thoracic vertebral column (C2-C3 through T1-T2). Areas of the cranial and caudal articular processes, and the height, width and areas of the vertebral canal and spinal cord were determined. Middle foraminal heights were measured. Intervertebral disc width was measured before and after traction. Intraobserver and interobserver agreement were calculated. CSM-affected GDs had larger areas of the caudal articular processes from C2-C3 through T1-T2. In CSM-affected GDs, the vertebral canal and spinal cord areas were significantly smaller at C5-C6 and C6-C7, the vertebral canal width was significantly narrower at C6-C7 and C7-T1, and the spinal cord width was significantly narrower at C5-C6 and C6-C7. Middle foraminal height was smaller in CSM-affected GDs from C3-C4 through C7-T1. Neutral intervertebral disc widths were smaller in CSM-affected GDs. It was concluded that the cervical vertebral canal dimensions are significantly different between normal and CSM-affected GDs. Absolute vertebral canal stenosis and severe foraminal stenosis involving the cervical vertebrae distinguish CSM-affected from clinically normal GDs. These findings are relevant to the pathogenesis of osseous-associated CSM and should be taken into consideration when performing imaging studies and planning surgery.

Multisystem Axonopathy and Neuronopathy in Golden Retriever Dogs

Central axonopathies are uncommon in dogs. Several terms have been used to describe these diseases, such as axonopathy, leukomyelopathy, axonal degeneration, and neuroaxonal degeneration. The majority of reported cases were breed-specific with peculiar clinical and pathological features seen in each breed. The association of central axonopathy and motor neuronal degeneration has not been reported. We report a progressive multisystem central axonopathy and motor neuronopathy in 3 Golden Retriever littermates with unique clinical and pathological features. Dog 1 was a 3-month-old female intact Golden Retriever dog referred to the Small Animal Clinic of the Ontario Veterinary College (OVC) with a 6-week history of pelvic limb weakness. The owners noticed that the dog appeared smaller than the other littermates and that her pelvic limb musculature was underdeveloped. She had difficulty in getting up, and when resting in lateral recumbency had fine muscle tremors in the limb muscles. The clinical signs progressed to involve the thoracic limbs with generalized weakness observed 2 weeks before presentation. On physical examination, no other abnormalities were detected except for generalized muscle atrophy. On neurological examination, short-strided tetraparesis, with no evidence of proprioceptive ataxia, was observed. The postural reactions (proprioceptive positioning and hopping) were adequate, as were the cranial nerve reflexes and responses. The flexor and patellar reflexes were mildly decreased. Resting, high-frequency, low-amplitude muscle tremors were seen in all limbs. These tremors could be elicited by palpation of the limb muscles. Based on the findings of lower motor neuron (LMN) tetraparesis, absence of proprioceptive ataxia, normal postural reactions, and mildly decreased reflexes, a neuromuscular disease was suspected. CBC, biochemistry profile, and urinalysis were performed. Abnormalities on the biochemistry profile were a creatine kinase (CK) activity of 517U/L (reference range, 40–255U/L) and a globulin concentration of 17 g/L (reference range, 21–42 g/L). No cause for the mild hypoglobulinemia was identified and it was assumed to be associated with the young age of the dog. No abnormalities were identified on the CBC or urinalysis. Electromyography, nerve conduction studies, and nerve and muscle biopsies were proposed, but declined by the owners. The dog continued to deteriorate and was re-evaluated at 6 months of age. At that time, the dog was markedly tetraparetic and the patellar reflexes were no longer present. Some extensor muscle tone was still present. Euthanasia and necropsy were performed. Two other littermates had a similar history and presentation. Dog 2, a male intact Golden Retriever, began to show signs of weakness and tremors at 15 weeks of age. By 5 months of age, severe generalized muscle atrophy and fatigue were obvious. CBC and biochemistry profile at that time were normal. The dog was referred and examined at 8 months of age. The neurological examination identified a kyphotic posture (Fig 1), generalized muscle atrophy, neuromuscular type (short-stride) tetraparesis, absence of ataxia, mildly decreased spinal reflexes, and head and body tremors. The nature of the tremors was suggestive of muscle weakness and not intentional tremors as seen with cerebellar disorders. Cranial nerve examination and postural reactions were adequate. CBC and biochemistry profile did not identify any clinically relevant abnormalities. Serum and whole blood were submitted for metabolic screening for amino acids, organic acids, and carbohydrates to investigate a possible metabolic or storage disease. Results of these tests were within reference limits. Euthanasia and necropsy were performed. Dog 3, a male intact Golden Retriever littermate, was presented to the OVC at 8 months of age. Weakness and body tremors were first observed when the dog was 3 months old. At presentation, the dog was markedly tetraAbbreviations:

Transcranial magnetic motor evoked potentials in Great Danes with and without clinical signs of cervical spondylomyelopathy: Association with neurological findings and magnetic resonance imaging

Transcranial magnetic motor evoked potentials (TMMEPs) assess the functional integrity of the descending motor pathways, which are typically compromised in canine cervical spondylomyelopathy (CSM). The objective of this prospective study was to establish the reference ranges of TMMEP latency and amplitude in clinically normal (control) Great Danes (GDs), compare TMMEPs obtained in GDs with and without CSM, and determine whether there is any association between TMMEP data and severity of neurological signs or magnetic resonance imaging (MRI) findings. Twenty-nine client-owned GDs were enrolled (15 controls, 14 CSM-affected). All dogs underwent TMMEPs under sedation, and latencies and amplitudes were recorded from the extensor carpi radialis (ECR) and cranial tibial (CT) muscles. MRI of the cervical vertebral column was performed to evaluate the presence and severity of spinal cord (SC) compression, and the presence of SC signal changes. ECR and CT latencies were significantly longer in CSM-affected than control GDs. No significant differences between groups were found for amplitudes or neuronal path lengths. For the CT TMMEPs, CSM-affected GDs with moderate and severe clinical signs had significantly longer latencies than those with mild clinical signs. Significantly longer CT latencies were found in dogs with moderate and severe SC compression compared with dogs with mild compression. CT TMMEPs could not be recorded in 7/9 CSM-affected GDs with SC signal changes. These results provide a reference range for TMMEPs of clinically normal GDs. The use of TMMEPs is a valid ancillary test to assess the integrity of motor pathways in GDs with CSM.

A novel spongiform leukoencephalomyelopathy in Border Terrier puppies.

Dog 1 was a 3-week-old male Border Terrier puppy referred to the Neurology and Neurosurgery Service of the Veterinary Medical Center, The Ohio State University, for ataxia and tremors. The signs were first noticed 5 days before presentation when the puppy first attempted to walk on its own. The owners reported that the tremors affected mainly the hindquarters. No improvement or worsening of the tremors had been noted over this period. An injectable corticosteroid (unknown type and dose) had been administered 4 days before referral, with no changes in the clinical signs. The tremors were reported to disappear when the puppy was sleeping. There were 3 other puppies from the same litter, which were reported to be normal, as were the parents. On presentation, the puppy showed severe generalized coarse body tremors (with low frequency and high amplitude), most severe in the hindquarters, which showed a characteristic swinging side-to-side or “rocking horse” movement (as illustrated in the supplementary Video S1). The tremors also involved the head and thoracic limbs, but to a lesser degree, and disappeared when the dog was asleep or at rest. Cerebellar ataxia was noted when the dog was trying to walk. The neurological examination was difficult because of the severity of the tremors, but it showed an absent menace bilaterally (considered normal for a 3-week-old puppy), delayed proprioceptive positioning, and hopping that was slightly hypermetric on all limbs. The remaining cranial nerves, spinal reflexes, cutaneous trunci reflex, and vertebral column palpation were unremarkable. Physical examination was within normal limits. Because the characteristics of the tremors, which were coarse and affected mainly the hindquarters, a diffuse or multifocal CNS disorder such as a congenital disorder of myelination was considered the main differential diagnosis. A cerebellar lesion (infectious or inflammatory cerebellar disease, cerebellar hypoplasia, neonatal cerebellar ataxia) also was considered possible, although less likely, based on the type of tremors noted. A complete blood count (CBC) and biochemical profile showed changes considered normal for a puppy. The owners, who also were the breeders, chose humane euthanasia. A complete necropsy was performed. A cerebrospinal fluid (CSF) sample was collected from the cerebellomedullary cistern immediately after euthanasia. The fluid was colorless and clear, with a total protein of 55 mg/ dL (reference range, <25 mg/dL), a white blood cell (WBC) count of 34 cells/lL (reference range, <5 cells/ lL) and a red blood cell (RBC) count of 452 cell/lL (reference range, <5 cells/ll). On cytology, there were 91% large mononuclear cells, 8% lymphocytes and 1% nondegenerate neutrophils. Occasional ependymal cells were noted and considered an incidental finding. The findings were consistent with a mild-to-moderate nonsuppurative pleocytosis and mild blood contamination. In addition, a urine sample was collected by cystocentesis immediately after euthanasia and sent to University of Pennsylvania for a metabolic screening panel. Results of the metabolic panel indicated increased aminoaciduria, increased lactate, increased hydroxy-lysine-glycoside, and a strongly positive response to mucopolysaccharides (MPS) spot test. The aminoaciduria was interpreted as an age-related finding. The increased lactate and strong positive MPS spot test were interpreted as suggestive of a defect in intermediary metabolism, possibly consistent with a metabolic disorder. Three other Border Terrier puppies, dogs 2–4, had a similar history and presentation. They were presented to one of the authors (KHJ) at the Swedish University of Agricultural Sciences, Uppsala, Sweden (dogs 2 and 3) and the Norwegian School of Veterinary Science in Oslo, Norway (dog 4). These puppies were two 6-week-old female littermates and one 5-week-old From the Department of Veterinary Clinical Sciences (MartinVaquero, da Costa) and the Department of Biosciences, College of Veterinary Medicine (Simmons, Beamer, Oglesbee), The Ohio State University, Columbus, OH; and the Department of Companion Animal Clinical Sciences, Norwegian School of Veterinary Science, Oslo, Norway (Jaderlund). This work was performed at the College of Veterinary Medicine, The Ohio State University, Columbus, OH. This article was presented in part as a Research Report at the 2011 American College of Veterinary Internal Medicine (ACVIM) Forum, Denver, Colorado. Corresponding author: P. Martin-Vaquero, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp Street, Columbus, OH 43210; e-mail: martin-vaquero.1@osu.edu Submitted September 7, 2011; Revised November 24, 2011; Accepted December 14, 2011. Copyright

Cervical Vertebral Trabecular Bone Mineral Density in Great Danes With and Without Osseous‐Associated Cervical Spondylomyelopathy

Background Great Danes (GDs) with osseous‐associated cervical spondylomyelopathy (CSM) have osteoarthritis (OA) of the cervical vertebrae. OA is often associated with increases in bone mineral density (BMD) in people and dogs. Hypothesis/Objectives To compare the trabecular BMD of the cervical vertebrae between clinically normal (control) GDs and GDs with osseous‐associated CSM by using computed tomography (CT). We hypothesized that the vertebral trabecular BMD of CSM‐affected GDs would be higher than that of control GDs. Animals Client‐owned GDs: 12 controls, 10 CSM affected. Methods Prospective study. CT of the cervical vertebral column was obtained alongside a calibration phantom. By placing a circular region of interest at the articular process joints, vertebral body, pedicles, and within each rod of the calibration phantom, trabecular BMD was measured in Hounsfield units, which were converted to diphosphate equivalent densities. Trabecular BMD measurements were compared between CSM‐affected and control dogs, and between males and females within the control group. Results Differences between CSM‐affected and control dogs were not significant for the articular processes (mean = −39; P = .37; 95% CI: −102 to 24), vertebral bodies (mean = −62; P = .08; 95% CI: −129 to 6), or pedicles (mean = −36; P = .51; 95% CI: −105 to 33). Differences between female and male were not significant. Conclusions and Clinical Importance This study revealed no difference in BMD between control and CSM‐affected GDs. Based on our findings no association was detected between cervical OA and BMD in GDs with CSM.