Disk-associated cervical spondylomyelopathy is a multifactorial, complex, and poorly understood neurologic syndrome. It generally affects mature, large-breed dogs.1 Adult Doberman Pinschers appear to be particularly vulnerable to the development of this disorder.1–3 Dogs with DA-CSM have progressive compression of the caudal portion of the cervical spinal cord, which is typically caused by protrusion of 1 or more intervertebral disks, sometimes in combination with hypertrophy of the ligamentum flavum and abnormalities of the vertebral bodies.1 The clinical signs associated with DA-CSM range from signs of pain isolated to the neck region to tetraplegia.1–3 The most common clinical abnormality in dogs with DA-CSM is gait disturbance.1 Owners commonly report a gradual onset of clinical signs in affected dogs, although signs can sometimes develop acutely or exacerbate rapidly. Slowly progressing ataxia and paresis of the pelvic limbs are commonly reported.1,4 Clinical signs affecting all 4 limbs with a short, stilted gait of the thoracic limbs can also develop.1,2 Affected dogs often have a characteristic disconnected gait in which the thoracic and pelvic limbs seem to advance at different rates.4 The variation in onset and type of clinical signs associated with DA-CSM has resulted in the development of several grading systems for describing the severity of neurologic deficits.5–13
Controversy exists regarding the most appropriate treatment for DA-CSM.14 Generally, surgery is considered the most appropriate treatment, and a multitude of surgical techniques have been developed to treat DA-CSM.1–4 Although favorable results have been reported, surgical treatment of DA-CSM is associated with considerable difficulties and complications.1,15 Conversely, little is known about the outcomes for nonsurgical treatment of dogs with DA-CSM. Studies have described short-13 and long-term13,16,17 outcomes after conservative medical treatment for DA-CSM, and it was concluded that this type of treatment can be considered for selected dogs. However, there are minimal prospective data available about the evolution of clinical signs16 and the evaluation of prognostic indicators for dogs receiving conservative medical treatment for DA-CSM.13,17
The primary purpose of the study reported here was to characterize the evolution of clinical signs during conservative medical treatment for DA-CSM. Additionally, we assessed several prognostic indicators and evaluated the correlation among clinical signs recorded on initial examination, the severity of spinal cord compression and ISI changes assessed via low-field MRI, and results of electrophysiologic evaluation of the cervical portion of the spinal cord by use of TMS. It was hypothesized that dogs with more severe neurologic deficits would have more pronounced TMS abnormalities, spinal cord compression, and ISI changes. Additionally, it was hypothesized that older dogs that had clinical signs for a longer duration, more severe neurologic deficits, more pronounced TMS abnormalities, and a narrower vertebral canal with more pronounced spinal cord compression, vertebral canal compromise, and ISI changes would have a less favorable prognosis after conservative medical treatment for DA-CSM. To quantify vertebral column dimensions, ratios of absolute measurements were used for comparison among different dogs and breeds.
Materials and Methods
Animals—Twenty-one client-owned dogs were included in a prospective study. The experiment was conducted in accordance with the guidelines of the Animal Care Committee of Ghent University. Written consent was obtained from each dog's owner prior to study enrollment.
Physical examination and diagnostic testing—For each dog, a complete physical and neurologic examination, CBC, and serum biochemical analysis were performed. All Doberman Pinschers also underwent an additional echocardiographic examination and assessment of standardized mucosal bleeding times. Neurologic status at the time of study enrollment was graded from 0 to 6. Grade 0 was defined as no apparent neurologic deficits. Grade 1 was defined as hyperesthesia of the cervical area without neurologic deficits. Grade 2 was defined as ataxia of the pelvic limbs without noticeable paresis and no appreciable ataxia of the thoracic limbs. Grade 3 was defined as ataxia with noticeable paresis of the pelvic limbs and no appreciable ataxia in the thoracic limbs. Grade 4 was defined as ambulatory tetraparesis, generally characterized by broad-based ataxia with paresis of the pelvic limbs in combination with a short, stilted gait of the thoracic limbs. Grade 5 was defined as nonambulatory tetraparesis; affected dogs were able to stand and take a few steps before collapsing. Grade 6 was defined as tetraplegia; affected dogs were unable to stand or support their weight independently. For each dog, gait was videotaped for evaluation. All neurologic examinations were performed by the same investigator (SD).
TMS—Only Doberman Pinschers underwent TMS because this was the only breed for which there was information18,19 available for comparison. Transcranial magnetic stimulation is a noninvasive, painless, and sensitive technique for stimulating the cerebral cortex to evaluate the functional integrity of the fastest conducting descending motor pathways in the brain and spinal cord.20 Magnetic stimulation of the motor cortex evokes synchronized excitatory stimuli that descend down the spinal cord pathways21 and are recorded as TMMEPs.20
Transcranial magnetic stimulation was performed as described previously.19,22,23 The low- and high-frequency filters were set at 20 Hz and 10 kHz, respectively. Sensitivity was set at 10 mV/division. Analysis time was 100 milliseconds following the stimulus. Onset latency (in milliseconds) was measured as the shortest time between the application of the stimulus and the initiation of the initial phase; peak-to-peak amplitude (in millivolts) was measured between the 2 largest peaks of opposite polarity. Stimulations were applied until 2 reproducible TMMEPs were recorded. A TMS was considered to have negative results if 4 consecutive stimulations failed to elicit a reproducible TMMEP. For dogs in which TMS yielded negative results, onset latency was regarded as infinite and peak-to-peak amplitude was recorded as 0 mV. The neuronal path length was measured by the use of a tape measure by following the contours of each dog's body.
MRI—A permanent 0.2-T magneta was used to perform MRI. For each dog, anesthesia was induced with propofol and maintained by isoflurane in oxygen. Dogs were positioned in dorsal recumbency with the neck region positioned in a joint coil (circular transmit-receive coil) with an inner diameter of 19 cm. Then, T1-weighted spin echo and T2-weighted fast spin echo images were obtained in sagittal, dorsal, and transverse planes. The images of the transverse plane were aligned perpendicular to the spinal cord. The vertebral column was imaged from C2 through C7 in the sagittal and dorsal planes and from C4 through C7 in the transverse plane. The field of view was 29 cm in the sagittal plane, 24 cm in the dorsal plane, and 20 cm in the transverse plane. Slice thickness was 4 mm in the sagittal and dorsal sequences and 3 mm in the transverse sequences with no interslice gap for any sequences.
Relative stenosis of the vertebral canal was determined by calculating the canal occupying ratio of the spinal cord.24 The canal occupying ratio of the spinal cord was defined as the CSA of the spinal cord measured on T2-weighted images in the transverse plane divided by the CSA of the vertebral canal measured on T1-weighted images in the transverse plane.24,25 These measurements were performed at the midvertebral region from C5 through C7. This ratio represents the portion of the vertebral canal that is occupied by the spinal cord and provides an indication of the remaining free space available in the vertebral canal.24
Midsagittal vertebral canal height was determined by use of the CBHR and CBLR.26 Measurements were made on midsagittal T1-weighted images from C3 through C7. The CBHR was defined as the midvertebral canal height divided by midvertebral body height.26–28 The CBLR was defined as the midvertebral canal height divided by vertebral body length.26,28,29 The CBHR and CBLR were calculated only for Doberman Pinschers for comparison with existing information.26,30
To evaluate the degree of spinal cord compression, the spinal cord compression ratio and remaining spinal cord area were calculated at the site of the most pronounced compression. Measurements were made on T2-weighted images in the transverse plane. The spinal cord compression ratio was defined as the dorsoventral diameter of the spinal cord divided by the transverse diameter at the same level.31 A spinal cord compression ratio < 1 represented dorsoventral flattening of the spinal cord. The remaining spinal cord area was defined as the CSA of the compressed spinal cord segment divided by the CSA at the adjacent, noncompressed spinal cord segment. The adjacent, noncompressed CSA of the spinal cord was defined as the mean value of the CSA cranial and caudal to the compressed segment.25
To evaluate the degree of vertebral canal compromise, the vertebral canal compromise ratio was calculated at the site of the most pronounced compression.32,33 Measurements were made on T1-weighted images in the transverse plane. This ratio was defined as the protruded disk area divided by the total CSA of the vertebral canal at the corresponding level.32,33
Intraparenchymal signal intensity changes were graded from 0 to 3 on the basis of grading scales used in human neuroradiology.34–36 Grade 0 was defined as no ISI changes on T2- or T1-weighted images. Grade 1 was defined as a light (obscure) hyperintense ISI change on T2-weighted images (Figure 1). Grade 2 was defined as an intense (bright) hyperintense ISI change on T2-weighted images. Grade 3 was defined as a hyperintense ISI change on T2-weighted images, which corresponded to a hypointense ISI change on T1-weighted images.
Grade 1 (A) and grade 2 (B) ISI changes (arrows) on T2-weighted MR images of dogs with DA-CSM. Grade 1 was defined as a light (obscure) hyperintense ISI change, whereas grade 2 was defined as an intense (bright) hyperintense ISI change.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Grade 1 (A) and grade 2 (B) ISI changes (arrows) on T2-weighted MR images of dogs with DA-CSM. Grade 1 was defined as a light (obscure) hyperintense ISI change, whereas grade 2 was defined as an intense (bright) hyperintense ISI change.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Grade 1 (A) and grade 2 (B) ISI changes (arrows) on T2-weighted MR images of dogs with DA-CSM. Grade 1 was defined as a light (obscure) hyperintense ISI change, whereas grade 2 was defined as an intense (bright) hyperintense ISI change.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
All images obtained via MRI were evaluated by the same investigator (SD). Measurements were performed in a randomized sequence, and the investigator was unaware of the signalment and clinical status of the dogs from which the images were obtained. To minimize bias, 5 series of MR images from clinically normal Doberman Pinschers with spinal cord compression were included. However, the measurements for the clinically normal dogs were not included in the statistical analyses of the study reported here. Measurements were made directly at a workstation with commercially available imaging software.b
Treatment and follow-up—After a diagnosis of DA-CSM was made, all treatment options were explained to each dog's owner, and the owners were free to choose conservative medical treatment or surgical treatment. Conservative medical treatment consisted of restricted activity and prednisolone administration. Exercise was restricted for 4 weeks, which was followed by a period of gradually increasing activity. The use of a body harness instead of a neck collar was advised for walking the dog. Prednisolone treatment consisted of oral administration of a tapering dosage for 3 weeks (1 mg/kg [0.45 mg/lb], q 24 h for the first week; 0.5 mg/kg [0.23 mg/lb], q 24 h for the second week; and 0.25 mg/kg [0.11 mg/lb], q 24 h for the third week). At any time during the study, owners could choose surgical intervention.37 Dogs were reassessed via physical and neurologic examinations at 1, 3, 6, 12, and 24 months (and at additional times when requested by the owners or investigators) after DA-CSM diagnosis. During each evaluation, the dog was videotaped to allow for objective assessment of its gait at a later time. All owners were contacted by telephone at the end of the study period, and an interview about each dog's clinical status was conducted. Conservative medical treatment was considered unsuccessful if the neurologic status of a dog deteriorated, clinical signs of more severely (neurologic grades 3 through 6) affected dogs did not improve, clinical signs recrudesced when the prednisolone dose was lowered such that the tapering regimen could not be adhered to because of humane reasons, or the owner chose surgical intervention or euthanasia because the dog had become nonambulatory. The endpoint for conservative medical treatment was defined as the end of the study period or the time at which surgical intervention or euthanasia was performed. All evaluations were performed by the same investigator (SD).
Necropsy and histologic examination—Necropsy with histologic examination of the cervical portion of the spinal cord was performed on 2 dogs. The cervical portion of the spinal cord was removed from the body and fixed in neutral-buffered 10% formalin, processed, and embedded in paraffin. Tissue sections were cut in sections at a thickness of 5 μm, stained with H&E, and assessed by a neuropathologist (AO).
Data analysis—The effect of variables on the unsuccessful outcome of conservative medical treatment was analyzed by use of a logistic regression model. The effect of variables on time to surgery or euthanasia was analyzed by use of a Cox proportional hazards model. Results were summarized as hazard ratios, which were interpreted similar to ORs. For example, a hazard ratio of 1 meant the variable had no effect on the hazard, or risk, for surgery or euthanasia in dogs with DA-CSM, whereas a hazard ratio > 1 meant the variable increased the risk for surgery or euthanasia in dogs with DA-CSM (ie, the independent variable happened more frequently in dogs that had surgery or were euthanized than in dogs that did not have surgery or were not euthanized). All independent variables were continuous or binary in nature. Results for measurements of onset latency and peak-to-peak amplitude for pelvic limbs were dichotomized (ie, positive or negative). Pearson correlation coefficients were calculated for variables associated with age, duration of clinical signs, severity of clinical signs, MRI measurements (degree of spinal cord compression and ISI changes), and TMS results in thoracic limbs. Kendall τ correlation coefficients were calculated for results of TMS in the pelvic limbs, clinical abnormalities, and measurements obtained by use of MRI. Values of P < 0.05 were considered significant for all analyses.
Receiver operating characteristic curves were created for the vertebral canal compromise ratio and the remaining spinal cord area. An ROC curve was used to identify the value that maximized sensitivity and specificity for the variable under consideration and corresponded to the value on the most upper left point on the curve.
Results
Animals—Of the 21 dogs enrolled in the study, the majority (n = 17) were Doberman Pinschers; other breeds represented included Whippet (2), Dalmatian (1), and Weimaraner (1). There were 9 spayed females, 2 sexually intact females, 3 castrated males, and 7 sexually intact males. Age of affected dogs ranged from 4.2 to 10.8 years (mean, 7.7 years; median, 7.4 years). The duration of clinical signs reported by owners prior to initial examination ranged from 1 day to 2 years (mean, 4.6 months; median, 1 month).
Initial physical and neurologic examination—On initial examination, 2 dogs had neurologic grade 6, 1 dog had neurologic grade 5, 4 dogs had neurologic grade 4, 6 dogs had neurologic grade 3, 6 dogs had neurologic grade 2, and 2 dogs had neurologic grade 1. Two dogs that had neurologic grade 2 also had a nerve root signature of the right thoracic limb. Cervical hyperesthesia, defined as resistance to extension of the neck, was detected in 17 of 21 dogs.
Prednisolone treatment—Twenty of 21 dogs received prednisolone treatment. Subjectively, prednisolone had no effect on the clinical condition of 1 dog, had only a temporary beneficial effect on the clinical condition of 3 dogs, and alleviated the clinical signs in 6 dogs, but only at the high dose, such that the dose could not be tapered. Of the 6 dogs in which the prednisolone dose could not be tapered, 4 had surgery and 2 were euthanized after prolonged (7 to 10 months) administration of prednisolone. Clinical signs in the other 10 dogs began to resolve with the initiation of prednisolone administration and continued to improve such that the owners were able to adhere to the tapering dose schedule and discontinue administration over the prescribed 3-week period. Adverse effects associated with prednisolone administration were detected in 12 of the 20 dogs and included polyuria and polydipsia (n = 12), polyphagia (4), skin changes (2), weight gain (2), panting (1), restless behavior (1), muscle atrophy predominantly affecting the muscles of mastication (2), and hepatopathy (1). Two dogs had 4 adverse effects, 2 had 3 adverse effects, 3 had 2 adverse effects, and 5 had 1 adverse effect. The most severe adverse effects were detected in the 2 dogs that were euthanized after prolonged treatment with high doses of prednisolone.
Evolution of clinical signs—Examinations were performed on 20 of 21 dogs 1 month after DA-CSM had been diagnosed. One dog was not examined because it was euthanized after it remained nonambulatory at 24 days after DA-CSM diagnosis. Of the 20 dogs examined, 6 had a lower neurologic grade (ie, clinical status had improved), compared with the neurologic grade they had received on initial examination; 7 had a higher neurologic grade (ie, clinical status had deteriorated); and 7 had the same neurologic grade but had clinically improved (n = 2) or deteriorated (5) within that neurologic grade. All 12 dogs for which the clinical status had deteriorated within 1 month after initial DA-CSM diagnosis went on to have an unsuccessful outcome with conservative medical treatment; 6 were euthanized, 5 had surgery, and 1 continued to deteriorate but was still alive. Conversely, all dogs for which clinical status was improved at 1 month after initial DA-CSM diagnosis went on to have a successful outcome with conservative medical treatment.
Acute relapse of clinical signs was reported in 4 of 21 dogs, and the relapse happened between 4.5 and 12 months (mean, 8.6 months; median, 9.0 months) after diagnosis of DA-CSM. Three dogs were treated successfully with restricted exercise for 4 weeks and another 3-week course of the tapering dose of prednisolone, whereas 1 dog continued to have clinical relapses, and its condition deteriorated over the study period. Two dogs had short periods during which their clinical signs recurred, but their clinical status was generally improved and they were classified as having a successful outcome with conservative medical treatment.
Conservative medical treatment was successful for 8 (38%) dogs and unsuccessful for 13 (62%) dogs. The follow-up period for the successfully treated dogs ranged from 1 to 3.1 years (mean, 1.9 years; median, 2.0 years) after diagnosis of DA-CSM. Of the dogs that had an unsuccessful outcome with conservative medical treatment, 7 were euthanized (mean time from diagnosis of DA-CSM to euthanasia, 4.7 months; median, 5 months; range, 24 days to 10.2 months) because they had become nonambulatory, 5 had surgery (mean time from diagnosis of DA-CSM to surgery, 2 months; median, 2.4 months; range, 2 to 3.5 months) because of neurologic deterioration, and 1 was still alive 2.3 years after the diagnosis of DA-CSM was made despite continued neurologic deterioration.
Follow-up MRI results—A second MRI evaluation was performed on 3 dogs. The second MRI evaluation was performed on 1 dog because of an acute recurrence of clinical signs after 12 months of clinical improvement. Initial MRI results for that dog revealed spinal cord compression at the C6–7 intervertebral space. The second MRI evaluation revealed a comparable amount of disk protrusion and spinal cord compression at C6–7 with additional spinal cord compression at C5–6 (Figure 2). The second MRI evaluation was performed in the other 2 dogs immediately after they were euthanized because they had become nonambulatory. For both dogs, initial MRI revealed spinal cord compression at the C5–6 and C6–7 spaces. The second MRI evaluations revealed more pronounced spinal cord compression and increased ISI changes for both dogs (ISI grade 2 progressing to grade 3 at the C5–6 space for one dog and ISI grade 1 progressing to grade 2 at the C5–6 space and to grade 3 at the C6–7 space for the other dog; Figure 3). The second MRI evaluations of all 3 dogs revealed spinal cord atrophy, which was characterized by an increase in the signal intensity of CSF and the epidural fat area relative to the spinal cord area (Figure 4).
Sagittal (A and C) and transverse (B and D) T2-weighted MR images of a 10-year-old Whippet at the time of DA-CSM diagnosis (A and B) and 12 months later after acute deterioration of clinical status (C and D). The transverse images were obtained at the level of C5-C6. The initial MRI evaluation revealed compression of the spinal cord at the C6–7 intervertebral space. The second MRI evaluation revealed a stable to slightly improved compression at the C6–7 intervertebral space and an additional spinal cord compression at the C5–6 intervertebral space.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Sagittal (A and C) and transverse (B and D) T2-weighted MR images of a 10-year-old Whippet at the time of DA-CSM diagnosis (A and B) and 12 months later after acute deterioration of clinical status (C and D). The transverse images were obtained at the level of C5-C6. The initial MRI evaluation revealed compression of the spinal cord at the C6–7 intervertebral space. The second MRI evaluation revealed a stable to slightly improved compression at the C6–7 intervertebral space and an additional spinal cord compression at the C5–6 intervertebral space.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Sagittal (A and C) and transverse (B and D) T2-weighted MR images of a 10-year-old Whippet at the time of DA-CSM diagnosis (A and B) and 12 months later after acute deterioration of clinical status (C and D). The transverse images were obtained at the level of C5-C6. The initial MRI evaluation revealed compression of the spinal cord at the C6–7 intervertebral space. The second MRI evaluation revealed a stable to slightly improved compression at the C6–7 intervertebral space and an additional spinal cord compression at the C5–6 intervertebral space.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Transverse MR images at the C5–6 intervertebral space of a 5-year-old Doberman Pinscher at the time of DA-CSM diagnosis (A) and immediately after the dog was euthanized (B and C). The transverse T2-weighted image (A) at the time of diagnosis revealed no ISI changes. The postmortem MR images revealed hyperintense ISI changes (arrow) on the transverse T2-weighted image (B) and hypointense ISI changes (arrowhead) on the transverse T1-weighted image (C).
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Transverse MR images at the C5–6 intervertebral space of a 5-year-old Doberman Pinscher at the time of DA-CSM diagnosis (A) and immediately after the dog was euthanized (B and C). The transverse T2-weighted image (A) at the time of diagnosis revealed no ISI changes. The postmortem MR images revealed hyperintense ISI changes (arrow) on the transverse T2-weighted image (B) and hypointense ISI changes (arrowhead) on the transverse T1-weighted image (C).
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Transverse MR images at the C5–6 intervertebral space of a 5-year-old Doberman Pinscher at the time of DA-CSM diagnosis (A) and immediately after the dog was euthanized (B and C). The transverse T2-weighted image (A) at the time of diagnosis revealed no ISI changes. The postmortem MR images revealed hyperintense ISI changes (arrow) on the transverse T2-weighted image (B) and hypointense ISI changes (arrowhead) on the transverse T1-weighted image (C).
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Transverse T2-weighted MR images at the cranial aspect of the C6 vertebral body in a 10-year-old Whippet at the time of DA-CSM diagnosis (A) and 12 months after diagnosis (B). Notice an increase in signal intensity of the hyperintense CSF and epidural fat area relative to the spinal cord area in panel B; this finding suggests spinal cord atrophy.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Transverse T2-weighted MR images at the cranial aspect of the C6 vertebral body in a 10-year-old Whippet at the time of DA-CSM diagnosis (A) and 12 months after diagnosis (B). Notice an increase in signal intensity of the hyperintense CSF and epidural fat area relative to the spinal cord area in panel B; this finding suggests spinal cord atrophy.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Transverse T2-weighted MR images at the cranial aspect of the C6 vertebral body in a 10-year-old Whippet at the time of DA-CSM diagnosis (A) and 12 months after diagnosis (B). Notice an increase in signal intensity of the hyperintense CSF and epidural fat area relative to the spinal cord area in panel B; this finding suggests spinal cord atrophy.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Results of histologic examination—For the 2 dogs that were euthanized and underwent a second MRI evaluation, necropsy was performed immediately after completion of the second MRI evaluation. The cervical portion of the spinal cord was removed and submitted for histologic examination. The spinal cords of both dogs were flattened dorsoventrally at the site of compression, and the border between the gray matter and white matter was unidentifiable. White discoloration of the cuneate fascicles was detected in the portion of the spinal cord cranial to the compression in 1 dog (Figure 5). The spinal cord of each dog had a marked loss of tissue and collapse of gray matter and white matter, which was replaced by gliosis. This loss of tissue resulted in empty spaces that were separated by strands of glial tissue in multiple areas. The central canal was severely dilated and had ruptured, which resulted in the loss of ependymal lining and interstitial edema in the surrounding gray matter. Cranial and caudal to the compressive lesion, there was marked Wallerian degeneration and gliosis in the cuneate fascicle and ventral funiculi. Both dogs had chronic axonal degeneration and loss in multiple nerve roots. The histologic diagnosis was chronic segmental myelomalacia of the cervical portion of the spinal cord caused by compression (Figure 6).
Photomicrograph of a transverse section of the spinal cord at the C5–6 intervertebral disk space in the same Doberman Pinscher as in Figure 3. There is marked dorsoventral compression of the spinal cord. The central canal (C) is dilated and ruptured. The gray matter (G) has collapsed because of tissue necrosis and gliosis, and the boundary between the gray and white matter is blurred. H&E stain; bar = 1 mm.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Photomicrograph of a transverse section of the spinal cord at the C5–6 intervertebral disk space in the same Doberman Pinscher as in Figure 3. There is marked dorsoventral compression of the spinal cord. The central canal (C) is dilated and ruptured. The gray matter (G) has collapsed because of tissue necrosis and gliosis, and the boundary between the gray and white matter is blurred. H&E stain; bar = 1 mm.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Photomicrograph of a transverse section of the spinal cord at the C5–6 intervertebral disk space in the same Doberman Pinscher as in Figure 3. There is marked dorsoventral compression of the spinal cord. The central canal (C) is dilated and ruptured. The gray matter (G) has collapsed because of tissue necrosis and gliosis, and the boundary between the gray and white matter is blurred. H&E stain; bar = 1 mm.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Higher magnification of the same photomicrograph as in Figure 5. Loss of gray matter has resulted in empty spaces that are separated by strands of glial processes. Necrotic gray matter has been replaced by gliosis with hypertrophic astrocytes (arrows). One intact neuron remains (arrowhead). H&E stain; bar = 40 μm.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Higher magnification of the same photomicrograph as in Figure 5. Loss of gray matter has resulted in empty spaces that are separated by strands of glial processes. Necrotic gray matter has been replaced by gliosis with hypertrophic astrocytes (arrows). One intact neuron remains (arrowhead). H&E stain; bar = 40 μm.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Higher magnification of the same photomicrograph as in Figure 5. Loss of gray matter has resulted in empty spaces that are separated by strands of glial processes. Necrotic gray matter has been replaced by gliosis with hypertrophic astrocytes (arrows). One intact neuron remains (arrowhead). H&E stain; bar = 40 μm.
Citation: Journal of the American Veterinary Medical Association 240, 7; 10.2460/javma.240.7.848
Prognostic variables—All dogs in which the clinical condition had deteriorated at 1 month after DA-CSM diagnosis had an unsuccessful outcome for conservative medical treatment, whereas all dogs in which clinical condition had improved at 1 month after DA-CSM diagnosis had a successful outcome. Other variables associated with the unsuccessful outcome of conservative medical treatment for DA-CSM in dogs included vertebral canal compromise ratio (OR, 1.29; 95% CI, 1.05 to 1.57; P = 0.013), remaining spinal cord area (OR, 0.92; 95% CI, 0.85 to 0.99; P = 0.032), and CBHR at the level of C6 (OR, 1.15; 95% CI, 1.01 to 1.30; P = 0.036). Variables not associated with the outcome of conservative medical treatment for DA-CSM in dogs included age, duration of clinical signs prior to diagnosis, neurologic grade, onset latencies, peak-to-peak amplitudes for thoracic and pelvic limbs, and the remaining MRI variables assessed.
The ROC curve for the vertebral canal compromise ratio revealed that a value of 25.9 corresponded with a sensitivity of 0.90 (95% CI, 0.50 to 0.99) and a specificity of 0.85 (95% CI, 0.57 to 0.97). As the vertebral canal compromise ratio decreased, the sensitivity for predicting a successful outcome for conservative medical treatment of DA-CSM increased and specificity decreased, whereas as the vertebral canal compromise ratio increased, the sensitivity for predicting a successful outcome for conservative medical treatment of DA-CSM decreased and specificity increased. The ROC curve for the remaining spinal cord area revealed that a value of 62.6 corresponded with a sensitivity of 0.70 (95% CI, 0.35 to 0.95) and a specificity of 0.85 (95% CI, 0.57 to 0.97). As the remaining spinal cord area increased, the sensitivity for predicting a successful outcome for conservative medical treatment of DA-CSM increased and specificity decreased, whereas if the remaining spinal cord area decreased, the sensitivity for predicting a successful outcome for conservative medical treatment of DA-CSM decreased and specificity increased.
The time from DA-CSM diagnosis to surgery or euthanasia was associated with the vertebral canal compromise ratio (hazard ratio, 1.12; 95% CI, 1.02 to 1.21; P = 0.013) and CBR at the level of C6 (hazard ratio, 1.07; 95% CI, 1.01 to 1.13; P = 0.032). Time from DA-CSM diagnosis to surgery or euthanasia was not associated with any of the other clinical, MRI, or TMS variables.
Significant correlation was detected between the compression ratio and ISI changes (r = −0.65; P = 0.001) and between the onset latency and the peak-to-peak amplitude of the pelvic limbs (τ = −0.85; P < 0.001). There were no significant correlations between any of the other clinical, MRI, or TMS variables.
Discussion
In the study reported here, various clinical signs and prognostic variables for dogs treated conservatively for DA-CSM were assessed. Additionally, the correlation between successful outcome for conservative, medical treatment for DA-CSM and clinical, selected MRI, and TMS variables were evaluated. To our knowledge, this is the first prospective study that has provided a description of the results of serial neurologic evaluations to yield more information about the natural progression of DA-CSM and the outcome for conservative, medical treatment in dogs with the disease.
Few dogs with DA-CSM in the present study had a successful outcome after receiving conservative medical treatment. This is in agreement with results of a retrospective study13 conducted by our laboratory group. Failure of conservative medical treatment was generally characterized by a progressive deterioration of neurologic status after initial diagnosis of DA-CSM. Importantly, the neurologic status of dogs at 1 month after diagnosis of DA-CSM appeared to be critical for determining the outcome of conservative medical treatment. In the present study, neurologic condition had deteriorated at 1 month after diagnosis of DA-CSM for all dogs in which conservative medical treatment was unsuccessful. Conversely, neurologic condition had improved at 1 month after diagnosis of DA-CSM for all dogs in which conservative medical treatment was successful. Therefore, evaluation of neurologic condition at 1 month after diagnosis of DA-CSM can be used to identify dogs in which clinical condition is likely to deteriorate to a nonambulatory status. It is imperative to identify such dogs as soon as possible, before there is irreversible spinal cord damage that will reduce the likelihood for recovery if surgical intervention is attempted.
Similar to results of another study,13 most of the dogs with DA-CSM and for which conservative medical treatment was unsuccessful were euthanized within 6 months after DA-CSM diagnosis in the study reported here. This suggests that the neurologic condition of dogs with DA-CSM generally deteriorates rapidly instead of slowly. The rapid neurologic deterioration of dogs with DA-CSM is similar to that in humans38–41 with a comparable condition, and it emphasizes the importance of early recognition and treatment intervention. The success rate for conservative medical treatment of DA-CSM in another study13 as well as the present study was considerably lower, compared with the results for medical treatment of CSM in a study by da Costa et al.17 In that study,17 36 of 67 (54%) of dogs improved and 18 of 67 (27%) stabilized after medical treatment for CSM. The difference can probably be attributed, at least in part, to the fact that the investigators in that study17 focused on the long-term prognosis and therefore included only dogs that were available for follow-up monitoring for at least 6 months after CSM diagnosis.
Several dogs in the present study had an acute episode of neurologic deterioration after a long period of clinical improvement. Clinical relapse after initial recovery is a common complication after surgical intervention for DA-CSM.1–4,15 These episodes are generally caused by the development of a new compressive lesion on the spinal cord at a disk space adjacent to the surgically treated site.2 The exact etiopathogenesis of this complication is controversial.14 Although it is generally considered a complication associated with surgery,1–4 some investigators believe that the development of disease at adjacent segments of the spinal cord is part of the natural progression of DA-CSM.14 If that is true, DA-CSM should be considered a multifactorial and multifocal disease.14 The development of disease in adjacent segments of the spinal cord in dogs receiving conservative medical treatment for DA-CSM would support the theory that such development is part of the natural progression of DA-CSM. Unfortunately, a follow-up MRI evaluation at the moment of clinical relapse was performed in only 1 dog in the present study. For that dog, the first MRI evaluation revealed a spinal cord compression at the C6–7 space and the second MRI evaluation revealed an additional spinal cord compression at the C5–6 space.
As the severity of spinal cord compression increased, the prognosis for dogs with DA-CSM treated conservatively became worse. This was similar to findings in human studies33,41–43 and implies that severe spinal cord compression and vertebral canal compromise are indications for immediate surgery in dogs with DA-CSM. However, in another study25 conducted by our laboratory group, interobserver agreement was less than optimal for the assessment of these variables by use of low-field MRI. Therefore, we currently do not recommend the application of the calculated threshold values for spinal cord compression and vertebral canal compromise when making clinical decisions for individual dogs.
Hyperintense ISI changes are reliable morphological variables used to discriminate clinically relevant from clinically irrelevant compression of the spinal cord.9,44 In human medicine, there is considerable controversy regarding the prognostic value of ISI changes in patients with cervical spondylotic myelopathy. Investigators in some studies35,45–47 have reported a correlation between the outcome of surgical or conservative medical treatment and increased signal intensity on T2-weighted images, but investigators in other studies34,40–42,48 have not. Some consider ISI changes predictive for outcome only in patients with multilevel manifestation49,50 or in combination with hypointense changes on T1-weighted images.36,48,51–53 It has been suggested that high-intensity signal changes on T2-weighted images are nonspecific and may indicate edema, inflammation, ischemia, and gliosis of the spinal cord, which may or may not be reversible,47,54 whereas low signal changes on T1-weighted images may represent myelomalacia, which is considered irreversible.52,55 In 2 dogs of the present study, DA-SCM was diagnosed on the basis of the combination of a hyperintense ISI change on T2-weighted images corresponding to a hypointense ISI change on T1-weighted images. Although neither of these dogs recovered, the number was too small to draw reliable conclusions. For the 2 dogs that underwent postmortem MRI evaluation, only hyperintense ISI changes were detected on the images obtained at the time of DA-CSM diagnosis, but the postmortem images revealed hypointense ISI changes on T1-weighted images in addition to hyperintense ISI changes on T2-weighted images. Segmental chronic myelomalacia and gliosis (Figures 5 and 6) were detected during histologic examination of the spinal cords from these 2 dogs.
The outcome for dogs treated conservatively for DA-CSM was not associated with any of the variables assessed by use of TMS in the present study. Although results of other studies have indicated significant differences in TMS values between Doberman Pinschers with and without clinical signs of DA-CSM18 as well as between Doberman Pinschers with and without clinically relevant spinal cord compressions,19 the results of the present study indicate that TMS results are not useful for the determination of which dogs should receive conservative medical treatment for DA-CSM.
A challenge when interpreting reports on cervical spondylomyelopathy in dogs is the multitude of neurologic grading systems used to characterize dogs with DA-CSM.5–13 The use of multiple neurologic grading systems makes communication between clinicians difficult and comparisons between studies and for multicenter trials problematic.56 An ideal, objective neurologic grading system would be characterized by high agreement between raters, good correlation among imaging and electrophysiologic results and tissue disruption, and a high predictive value for functional outcome.56 In the present study, there was no significant correlation between the outcome of conservative medical treatment for DA-CSM and clinical signs, amount of spinal cord compression, and TMS results. Several factors could have contributed to this lack of a significant correlation. First, the neurologic grading system used was not ideal, as evidenced by the fact that several dogs had distinct clinical improvement detected on serial neurologic examinations but their neurologic grade remained the same. We believe serial neurologic grades for individual dogs did not change because the range of severity for abnormalities such as ataxia or paresis encompassed within an individual grade was too large. Second, neurologic grading systems have limitations. Neurologic grading scores do not identify the underlying cause of spinal cord damage and are imperfect at discerning between structural and functional lesions.57 For example, in the present study, 2 dogs that received a neurologic grade of 6 during initial examination because they developed acute tetraplegia became ambulatory 2 to 3 weeks after DA-CSM was diagnosed and subsequently had successful outcomes with conservative medical treatment. It was hypothesized that both of these dogs had acute concussion rather than chronic compression of the spinal cord because of the acute onset of clinical signs. The acute nature of the injury in these 2 dogs may have been the reason that they had a successful outcome with conservative medical treatment, whereas dogs with chronic but less severe neurologic signs did not have a successful outcome with conservative medical treatment.
Medical treatment in the present study consisted of the administration of prednisolone, a corticosteroid. The rationale for prednisolone treatment was to diminish vasogenic edema, which may result in a return to function without the removal of a protruded annulus.58 However, prolonged use of corticosteroids can be accompanied by several adverse effects.2,58,59 Many dogs in the present study developed some of the more common, less severe adverse effects (ie, polyuria and polydipsia) of corticosteroid administration, and 1 dog developed liver failure. It is impossible to prove a causal relationship between prednisolone administration and liver failure in that 1 dog, but hepatopathy has been associated with excess concentrations of glucocorticoids.60 Thus, alternative medications to treat chronic spinal cord compression in dogs need to be investigated, although preliminary results after treatment with 4-aminopyridine derivatives are promising.61
Limitations of the study reported here are the small number of dogs included and the fact that all diagnostic imaging evaluations were performed with a low-field MRI device. It is possible that the inclusion of more dogs and use of an MRI device with a higher field strength could have altered the results. Also, the definition of an unsuccessful outcome did not allow for the survival time of dogs treated conservatively for DA-CSM to be consistently calculated. The time period between diagnosis of DA-CSM and the decision to euthanize a dog was generally longer than the time period between diagnosis of DA-CSM and the decision for surgical intervention. Moreover, the endpoints differed among owners. Some owners chose surgical intervention after only slight deterioration in their dog's neurologic status, whereas other owners consistently declined surgery as long as their dog was ambulatory.
The present study indicates that the prognosis is guarded for dogs treated conservatively for DA-CSM. For dogs in which conservative medical treatment was unsuccessful, deterioration of clinical status was generally rapid and progressed to tetraplegia within 6 months after diagnosis of DA-CSM. Lack of improvement or continued deterioration of clinical status at 1 month after diagnosis of DA-CSM was associated with an unsuccessful outcome with conservative medical treatment and provides owners of affected dogs the opportunity to pursue surgical intervention before there is irreversible damage to the spinal cord. Although the extent of spinal cord compression and vertebral canal compromise are useful indicators for clinicians when making recommendations for surgical treatment or conservative medical treatment of dogs with DA-CSM, the reason that some dogs respond favorably to conservative medical treatment but other dogs have a rapid deterioration of clinical status is unknown. The only modest correlations between outcome with conservative medical treatment for dogs with DA-CSM and clinical, diagnostic imaging, and electrophysiologic results is disturbing and warrants further investigation.
ABBREVIATIONS
| CBHR | Canal height-to-body height ratio |
| CBLR | Canal height-to-body length ratio |
| CI | Confidence interval |
| CSA | Cross-sectional area |
| DA-CSM | Disk-associated cervical spondylomyelopathy |
| ISI | Intraparenchymal signal intensity |
| MR | Magnetic resonance |
| MRI | Magnetic resonance imaging |
| OR | Odds ratio |
| ROC | Receiver operating characteristic |
| TMMEP | Transcranial magnetic motor-evoked potential |
| TMS | Transcranial magnetic stimulation |
Airis Mate, Hitachi, Tokyo, Japan.
OsiriX Image processing software, Pixmeo, Geneva, Switzerland.
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