Normal Doberman Research Articles

Three‐Dimensional Kinematic Gait Analysis of Doberman Pinschers with and without Cervical Spondylomyelopathy

The optimal treatment of cervical spondylomyelopathy (CSM) is controversial, with the owner's and clinician's perception of gait improvement often being used as outcome measures. These methods are subjective and suffer from observer bias. To establish kinematic gait parameters utilizing digital motion capture in normal Doberman Pinschers and compare them with CSM-affected Dobermans. Nineteen Doberman Pinschers; 10 clinically normal and 9 with CSM. 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. 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. 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.

INTERVERTEBRAL AND INTRAVERTEBRAL RATIOS IN DOBERMAN PINSCHER DOGS WITH CERVICAL SPONDYLOMYELOPATHY

No screening method is currently available to differentiate dogs with and without cervical spondylomyelopathy. Intravertebral and intervertebral ratios are used in horses and can predict cervical vertebral malformation. Intervertebral ratios could be a useful screening method for canine cervical spondylomyelopathy. Our purpose was to compare cervical intervertebral and intravertebral ratios in normal vs. affected Doberman pinschers. Forty dogs were studied, 27 affected and 13 normal. Cervical radiographs were obtained in all dogs. The minimum intra- and intervertebral sagittal diameter ratios were established for each cervical vertebrae and disc space from C(2) to C(7) . Comparisons were made between groups and specific vertebral body and disc levels. The effect of gender, age, and method of measurement (analog or digital radiographs) was also studied. There was no difference in either the intervertebral or intravertebral ratio between normal vs. affected dogs. The ratios decreased progressively along the cervical spine, being smallest at C(6) -C(7) and C(7) , respectively. Age, gender, and method of measurement had a significant influence on both inter- and intravertebral ratios, with smaller ratios seen as dogs aged and in male dogs. Based on our results, inter- or intravertebral ratios have no value to distinguish between clinically normal Doberman pinschers and Doberman pinschers with cervical spondylomyelopathy.

Intervertebral disk width in dogs with and without clinical signs of disk associated cervical spondylomyelopathy

BackgroundDisk-associated cervical spondylomyelopathy (DA-CSM) is a multifactorial neurological disorder in which progressive caudal cervical spinal cord compression is mainly caused by one or more intervertebral disk protrusions. The Doberman pinscher breed seems predisposed for this condition. The underlying cause and pathophysiology of DA-CSM are currently unknown. Recently, wider intervertebral disks have been put forward as a risk factor for development of clinically relevant DA-CSM. However, little is known about other factors affecting intervertebral disk width. Therefore the aim of this study was to assess the association between intervertebral disk width, measured on magnetic resonance imaging (MRI), and clinical status, age, gender and intervertebral disk location in dogs with and without clinical signs of DA-CSM.MethodsDoberman pinschers with clinical signs of DA-CSM (N=17),clinically normal Doberman pinschers (N=20), and clinically normal English Foxhounds (N=17), underwent MRI of the cervical vertebral column. On sagittal T2-weighted images, intervertebral disk width was measured from C2-C3 to C6-C7. Intra –and interobserver agreement were assessed on a subset of 20 of the 54 imaging studies.ResultsIntervertebral disk width was not significantly different between Doberman pinschers with clinical signs of DA-CSM, clinically normal Doberman pinschers or clinically normal English Foxhounds (p=0.43). Intervertebral disk width was positively associated with increasing age (p=0.029). Each monthly increase in age resulted in an increase of disk width by 0.0057mm. Intervertebral disk width was not significantly affected by gender (p=0.056), but was significantly influenced by intervertebral disk location (p <0.0001). The assessed measurements were associated with a good intra –and interobserver agreement.ConclusionsThe present study does not provide evidence that wider intervertebral disks are associated with clinical status in dogs with and without DA-CSM. Instead, it seems that cervical intervertebral disk width in dogs is positively associated with increase in age.

Morphometric dimensions of the caudal cervical vertebral column in clinically normal Doberman Pinschers, English Foxhounds and Doberman Pinschers with clinical signs of disk-associated cervical spondylomyelopathy

Client-owned, clinically normal Doberman Pinschers (n=20), English Foxhounds (n=17), and Doberman Pinschers with clinical signs of disk-associated cervical spondylomyelopathy (DA-CSM) (n=17) were prospectively studied. All dogs underwent magnetic resonance imaging (MRI) of the cervical vertebral column. To evaluate vertebral canal stenosis, the canal occupying ratios of the spinal cord and cerebrospinal fluid (CSF)-column were calculated from C5 to C7. To evaluate the degree of spinal cord compression and the amount of canal compromise, the compression ratio, remaining spinal cord and CSF-column area, and vertebral canal and dorsoventral vertebral canal compromise ratios were calculated at the site of most severe compression. For each canal occupying ratio, there was a significant higher value (implicating less space available for the spinal cord in the vertebral canal) at the level of C7 for clinically affected Doberman Pinschers compared with clinically normal English Foxhounds. The remaining spinal cord area was significantly smaller in dogs with clinically relevant spinal cord compression compared to dogs with clinically irrelevant spinal cord compression. Relative stenosis of the caudal cervical vertebral canal occurred more often in Doberman Pinschers with DA-CSM compared to English Foxhounds and a critical degree of spinal cord compression should be reached to result in clinical signs.

Transcranial magnetic stimulation in Doberman Pinschers with clinically relevant and clinically irrelevant spinal cord compression on magnetic resonance imaging

To evaluate the use of transcranial magnetic stimulation for differentiating between clinically relevant and clinically irrelevant cervical spinal cord compression on magnetic resonance imaging (MRI). Validation study. Clinically normal Doberman Pinschers without (n = 11) and with (6) spinal cord compression on MRI and 16 Doberman Pinschers with disk-associated wobbler syndrome (DAWS). After dogs were sedated, transcranial magnetic motor evoked potentials were recorded from the extensor carpi radialis muscle (ECRM) and cranial tibial muscle (CTM). Onset latencies and peak-to-peak amplitudes were measured. Magnetic resonance imaging was performed to identify spinal cord compression. There were significant differences in ECRM and CTM onset latencies between Doberman Pinschers with DAWS and each of the 2 groups of clinically normal dogs, but there were no significant differences in ECRM and CTM onset latencies between the 2 groups of clinically normal dogs. There were significant differences in CTM peak-to-peak amplitudes between Doberman Pinschers with DAWS and each of the 2 groups of clinically normal dogs, but there were no significant differences in ECRM peak-to-peak amplitudes among groups or in CTM peak-to-peak amplitudes between the 2 groups of clinically normal dogs. There was a significant correlation between severity of spinal cord compression and ECRM onset latency, CTM onset latency, and CTM peak-to-peak amplitude. Results suggested that transcranial magnetic stimulation may be a useful diagnostic tool to differentiate between clinically relevant and clinically irrelevant spinal cord compression identified on MRI alone.

Low-field magnetic resonance imaging findings of the caudal portion of the cervical region in clinically normal Doberman Pinschers and Foxhounds

Low-field magnetic resonance imaging findings of the caudal portion of the cervical region in clinically normal Doberman Pinschers and Foxhounds

Low-field magnetic resonance imaging findings of the caudal portion of the cervical region in clinically normal Doberman Pinschers and Foxhounds

To determine the spectrum and frequency of abnormalities for low-field magnetic resonance imaging (MRI) examinations of clinically normal Doberman Pinschers and Foxhounds. 37 clinically normal dogs (20 Doberman Pinschers and 17 Foxhounds). For each dog, MRI of the cervical vertebrae (sagittal, dorsal, and transverse T1- and T2-weighted images) was performed. Variables assessed were intervertebral disk degeneration, disk-associated compression, compression of the dorsal portion of the spinal cord, vertebral body abnormalities, and changes in intraparenchymal signal intensity. Associations between these variables and age, breed, sex, and location of the assessed intervertebral disk spaces were evaluated. Severe MRI abnormalities were detected in 17 dogs, including complete disk degeneration (n = 4 dogs), spinal cord compression (3), or both (10). Vertebral body abnormalities were detected in 8 dogs, and hyperintense signal intensity was detected in 2 dogs. Severity of disk degeneration and disk-associated compression was significantly associated with increased age. There was a significant association between disk degeneration, disk-associated compression, and compression of the dorsal aspect of the spinal cord and location of the assessed intervertebral disk space, with the intervertebral disk spaces in the caudal portion of the cervical region being more severely affected. Abnormalities were commonly seen on MRI examinations of the caudal portion of the cervical vertebral column and spinal cord of clinically normal Doberman Pinchers and Foxhounds. Such lesions were probably part of the typical spinal cord degeneration associated with the aging process of dogs.

Localization of Non-Factor VIII Sequence Involved in the Factor VIII Gene Inversion in Hemophilia A Dogs.

There is a common gene inversion at the telomere of the canine X chromosome in which factor VIII intron 22 DNA recombines with homologous sequence outside the gene. This mutation disrupts factor VIII synthesis and causes severe hemophilia A in dogs, analogous to a common inversion seen in humans (Lozier et al, PNAS 2002 99:12991–6). This mutation appears to be the only spontaneous gene inversion in an animal that replicates a corresponding disease of humans. The coding region for canine factor VIII spans approximately 146 kb and is found at the telomere of the X chromosome between bases 126,063,525 and 125,917,394 in the canine genome project, version 46.2d. Much of the canine factor VIII intron 22 remains unsequenced and the presence of F8A (the putative site of recombination in the factor VIII gene) in this region is inferred from PCR and Southern blot analysis of BAC clones that encompass this region. We have therefore focused on localizing the non-factor VIII site of the recombination and have found its essential elements in sequence located telomeric (upstream) to the canine factor VIII coding start site. We have used the boxer canine genome sequence (version 46.2d) as a template and reference for sequence analysis of BAC clone 291M9 (from normal Doberman pinscher genomic DNA library RPCI-81). Comparison of >100,000 bp of sequence common to the boxer and Doberman in this region showed >99% identity between the two breeds as expected. The BAC clone 291M9 was previously shown by DNA fiber FISH to be the region outside the factor VIII gene that participates in the gene inversion. This clone contains both F8A sequence (the putative site of recombination) as well as the sequence (ch8) that replaces the last four exons of the factor VIII transcript in hemophilia A dogs after the inversion. F8A sequence found in the Doberman BAC clone 291M9 matches sequence starting at nucleotide 126,317,916, in the boxer canine genome project (from RPCI-82 boxer BAC clone XX-145E20). This is outside the factor VIII gene, and approximately 400,000,000 base pairs upstream/telomeric to F8A found within the factor VIII gene. Approximately 20 kb from F8A is ch8, the sequence spliced into the abnormal hemophilia A factor VIII mRNA. The 7.5 kb region where the F8A sequence is found is extremely rich in guanosine and cytosine nucleotides (73% GC content) and has at least six putative CpG islands (as identified by the EMBOSS CpG analysis software (http://www.ebi.ac.uk/emboss/cpgplot/). This is consistent with the finding that F8A gene sequences outside the human factor VIII gene are found in CpG islands. There may be additional copies of the canine F8A sequence in or near this region (as is the case for the human genome), since gaps remain in this region of the known genomic sequence. The high GC content and highly repetitive nature makes sequence analysis and assembly problematic. These properties are consistent with DNA that is susceptible to homologous recombination and gene inversion as is seen with hemophilia in dogs and man. [Display omitted]

Assessment of Diastolic Function by Doppler Echocardiography in Normal Doberman Pinschers and Doberman Pinschers with Dilated Cardiomyopathy

Background: Assessment of diastolic function in patients with dilated cardiomyopathy (DCM) has the potential to add valuable information regarding hemodynamics, disease severity, and prognosis. The purpose of this study was to determine transmitral flow (TMF), isovolumic relaxation time (IVRT), pulmonary venous flow (PVF), flow propagation velocity (Vp), and mitral annular velocities by tissue Doppler in Doberman Pinschers with and without DCM. Hypothesis: It was anticipated that normal and DCM Dobermans would differ with respect to these parameters, and that associations with time to congestive heart failure (CHF) or death would be found. Animals: Thirty client‐owned Doberman Pinschers (10 each of normal, occult DCM, and overt DCM) were studied. Methods: Each dog underwent echocardiography with or without thoracic radiography (to confirm CHF) for classification as normal or DCM‐affected, followed by collection of echocardiographic diastolic parameters. Results: The group with occult DCM exhibited features of pseudonormal TMF, reduced systolic to diastolic PVF ratio, and reduced Vp. Shorter early TMF deceleration time (DTE) was associated with shorter time to CHF or sudden death. The group with overt DCM exhibited restrictive TMF, blunted systolic PVF, and reduced early and late diastolic mitral annular velocities. Conclusions and Clinical Importance: Doberman Pinschers showed evidence of moderate and severe diastolic dysfunction in occult and overt DCM, respectively. Short DTE may be a useful predictor of onset of CHF or sudden death.

Assessment of Diastolic Function by Doppler Echocardiography in Normal Doberman Pinschers and Doberman Pinschers with Dilated Cardiomyopathy

Assessment of diastolic function in patients with dilated cardiomyopathy (DCM) has the potential to add valuable information regarding hemodynamics, disease severity, and prognosis. The purpose of this study was to determine transmitral flow (TMF), isovolumic relaxation time (IVRT), pulmonary venous flow (PVF), flow propagation velocity (Vp), and mitral annular velocities by tissue Doppler in Doberman Pinschers with and without DCM. It was anticipated that normal and DCM Dobermans would differ with respect to these parameters, and that associations with time to congestive heart failure (CHF) or death would be found. Thirty client-owned Doberman Pinschers (10 each of normal, occult DCM, and overt DCM) were studied. Each dog underwent echocardiography with or without thoracic radiography (to confirm CHF) for classification as normal or DCM-affected, followed by collection of echocardiographic diastolic parameters. The group with occult DCM exhibited features of pseudonormal TMF, reduced systolic to diastolic PVF ratio, and reduced Vp. Shorter early TMF deceleration time (DTE) was associated with shorter time to CHF or sudden death. The group with overt DCM exhibited restrictive TMF, blunted systolic PVF, and reduced early and late diastolic mitral annular velocities. Doberman Pinschers showed evidence of moderate and severe diastolic dysfunction in occult and overt DCM, respectively. Short DTE may be a useful predictor of onset of CHF or sudden death.

Morphologic and morphometric magnetic resonance imaging features of Doberman Pinschers with and without clinical signs of cervical spondylomyelopathy

To compare morphologic and morphometric features of the cervical vertebral column and spinal cord of Doberman Pinschers with and without clinical signs of cervical spondylomyelopathy (CSM; wobbler syndrome) detected via magnetic resonance imaging (MRI). 16 clinically normal and 16 CSM-affected Doberman Pinschers. For each dog, MRI of the cervical vertebral column (in neutral and traction positions) was performed. Morphologically, MRI abnormalities were classified according to a spinal cord compression scale. Foraminal stenosis and intervertebral disk degeneration and protrusion were also recorded. Morphometric measurements of the vertebral canal and spinal cord were obtained in sagittal and transverse MRI planes. 4 of 16 clinically normal and 15 of 16 CSM-affected dogs had spinal cord compression. Twelve clinically normal and all CSM-affected dogs had disk degeneration. Foraminal stenosis was detected in 11 clinically normal and 14 CSM-affected dogs. Vertebral canal and spinal cord areas were consistently smaller in CSM-affected dogs, compared with clinically normal dogs. In neutral and traction positions, the intervertebral disks of CSM-affected dogs were wider than those of clinically normal dogs but the amount of disk distraction was similar between groups. The incidence of intervertebral disk degeneration and foraminal stenosis in clinically normal Doberman Pinschers was high; cervical spinal cord compression may be present without concurrent clinical signs. A combination of static factors (ie, a relatively stenotic vertebral canal and wider intervertebral disks) distinguished CSM-affected dogs from clinically normal dogs and appears to be a key feature in the pathogenesis of CSM.

Correlation of motor evoked potentials with magnetic resonance imaging and neurologic findings in Doberman Pinschers with and without signs of cervical spondylomyelopathy

To establish the reference ranges for motor evoked potential (MEP) latency and amplitude in clinically normal Doberman Pinschers, compare the MEPs of Doberman Pinschers with and without clinical signs of cervical spondylomyelopathy (CSM; wobbler syndrome), and determine whether MEP data correlate with neurologic or magnetic resonance imaging (MRI) findings. 16 clinically normal and 16 CSM-affected Doberman Pinschers. Dogs were classified according to their neurologic deficits. After sedation with acepromazine and hydromorphone, transcranial magnetic MEPs were assessed in each dog; latencies and amplitudes were recorded from the extensor carpi radialis and cranial tibial muscles. Magnetic resonance imaging was performed to evaluate the presence and severity of spinal cord compression. Significant differences in cranial tibial muscle MEP latencies and amplitudes were detected between clinically normal and CSM-affected dogs. No differences in the extensor carpi radialis MEP were detected between groups. There was a significant correlation (r = 0.776) between the cranial tibial muscle MEP latencies and neurologic findings. Significant correlations were also found between MRI findings and the cranial tibial muscle MEP latencies (r = 0.757) and amplitudes (r = -0.453). Results provided a reference range for MEPs in clinically normal Doberman Pinschers and indicated that cranial tibial muscle MEP latencies correlated well with both MRI and neurologic findings. Because of the high correlation between cranial tibial muscle MEP data and neurologic and MRI findings, MEP assessment could be considered as a screening tool in the management of dogs with spinal cord disease.

Alterations in the organisation, ultrastructure and biochemistry of the myocardial collagen matrix in Doberman pinschers with dilated cardiomyopathy

Remodelling of the collagen matrix of the myocardium has been implicated in the pathogenesis of dilated cardiomyopathy, a major cause of heart failure in Doberman pinschers. The aim of this study was to characterise the myocardial collagen matrix of Dobermans. In clinically normal Dobermans there was evidence of focal fibrosis. Collagen cross-links were altered in both diseased and clinically normal Doberman myocardium as compared with myocardium from control dogs. Extensive remodelling, in the form of a loss of collagen tethers, increased collagen synthesis and alterations in the collagen cross-links, occurs in diseased Doberman myocardium. Changes in the collagenous matrix are also present in apparently normal Dobermans. These changes are likely to be involved in the progression of the disease and may explain the predisposition of this breed to dilated cardiomyopathy.

Heart rate variability in Doberman Pinschers with and without echocardiographic evidence of dilated cardiomyopathy.

To characterize the salient variables of the time-domain analysis of heart rate variability (HRV) in clinically normal Doberman Pinschers and to compare those variables with those of Doberman Pinschers with cardiomyopathy and mild to moderate myocardial failure. 46 Doberman Pinschers. HRV was analyzed in the time-domain from 24-hour Holter recordings obtained from 28 Doberman Pinschers with normal echocardiograms and 18 Doberman Pinschers with echocardiograms consistent with mild to moderate myocardial failure. Significant differences in HRV variables between the 2 groups of dogs were not detected. The HRV was greater during the nighttime (12 AM to 6 AM), compared with the 24-hour day and an 18-hour (6 AM to 12 AM) period. HRV of dogs with mild to moderate myocardial failure was not different from that of clinically normal dogs, because there were no disturbances of autonomic balance, baroreceptor function, and other factors that influence HRV in the dogs with cardiomyopathy, or the sensitivity of time-domain analysis was overwhelmed by normal sinus arrhythmia. The techniques now used to study HRV have important limitations, especially in dogs, and better noninvasive tests of autonomic function are needed.

Signal-averaged electrocardiograms in normal Doberman pinschers.

Signal-averaged electrocardiograms (SAECGs) were performed on nonsedated normal dogs in left-lateral recumbency. Following signal averaging, both time-domain and 3-dimensional frequency-domain analyses were performed. For time-domain analysis, the high-frequency QRS (HFQRS) duration, duration of the terminal QRS complex less than 40 microV (LAS40), and root mean square (RMS) voltages (microV) of the terminal 40 milliseconds (RMS40) and 30 milliseconds of the QRS complex were calculated. For frequency-domain analysis, correlation ratios were calculated for 30-, 40-, 50-, and 60-millisecond segment lengths begun 10, 15, or 20 milliseconds before the end of the QRS complex. Spectro-temporal mapping was also performed. All of the parameters of the SAECGs analyzed in the time domain were associated with each other. LAS40 and RMS voltages regressed significantly (P < .0000) on the HFQRS duration. Ninety-five percent of the HFQRSs were 55-75 milliseconds, 95% of the LAS40s were 9-26 milliseconds, and 95% of the RMS40 voltages were 177-444 microV. None of the SAECGs contained evidence of ventricular late potentials. Spectro-temporal maps were similar in each dog when the same segment lengths and starting points were compared. No evidence of ventricular late potentials was observed. Correlation ratios were lower when windowed segments included 15 or 20 milliseconds (versus 10 milliseconds) of the terminal QRS complex. When only 10 milliseconds of the terminal QRS complex were included in windowed segments, the mean correlation ratios for 30- and 40-millisecond segment lengths were > 0.8 and > 0.61 in 67% of all analyses, respectively.

Animal model: Chromosomal fragile site expression in dogs: I. Breed specific differences

Peripheral blood lymphocytes from clinically normal Doberman pinscher and boxer dogs were cultured for folate-sensitive and, in preliminary studies, aphidicolin-inducible fragile site expression. Both autosomal and X chromosomal fragile sites were observed in canine cells cultured under folate/thymidine depletion and in cells cultured in medium containing aphidicolin. Results from the three dogs evaluated for both folate-sensitive and aphidicolin-inducible fragile site expression showed that the frequency of fragile site expression was significantly (P less than 0.05) greater in cells cultured in medium containing aphidicolin than in cells cultured in folate/thymidine-depleted medium. Cells from the boxer dog expressed a high percentage (66.67%) of aphidicolin-inducible fragile sites in contrast to the Doberman pinscher dog in which only 21.10% of the lymphocytes expressed aphidicolin-inducible fragile sites. The frequencies of spontaneous and folate-sensitive fragile site expression did not vary significantly by breed of dog. Age of dog was significantly and positively correlated with frequency of folate-sensitive fragile site expression in dogs of the boxer breed, but not in dogs of the Doberman pinscher breed. The dog X chromosome expressed three folate-sensitive and aphidicolin-inducible fragile sites. The G-band location of these three fragile sites showed homology with three recognized constitutive common fragile sites on the human X chromosome: Xp22, Xq21, and Xq27.2. Two specific autosomal fragile sites were identified, one on the distal end of the long arm of chromosome 1 and one on the distal end of the long arm of chromosome 8. Other autosomal fragile sites were also apparent but could not be assigned reliably to specific chromosomes.