Clinical Characteristics of Dogs with Progressive Myelomalacia Following Acute Intervertebral Disc Extrusion.

BACKGROUND: Progressive myelomalacia (PMM) is a catastrophic disease associated with acute intervertebral disc extrusion (IVDE). Published data on the clinical characteristics of this disease are limited. OBJECTIVE: To describe the onset and progression of clinical signs of PMM in a large case cohort. ANIMALS: Fifty-one dogs, 18 with histopathologically confirmed PMM, 33 presumptively diagnosed based on clinical signs and diagnostic imaging. METHODS: Retrospective study. Dogs with confirmed IVDE and either a histopathologic diagnosis of PMM or a high clinical suspicion were identified by medical record search. Data on nature and progression of signs were extracted. RESULTS: Twenty-four of 51 dogs were Dachshunds. T12-T13 was the most common site of disc extrusion (12 of 56), and 18 of 55 of mid-to-caudal lumbar discs (between L3 and L6) were affected. Onset of PMM signs ranged from present at first evaluation (17/51) to 5 days after presentation, with 25 of 51 cases developing signs within 48 hours. Progression of signs from onset of PMM to euthanasia or death, excluding 7 cases euthanized at presentation, ranged from 1 to 13 days with 23 being euthanized within 3 days. Nonspecific systemic signs were documented in 30 of 51 dogs. CONCLUSION AND CLINICAL IMPORTANCE: The majority of dogs developed PMM within 2 days of presentation and was euthanized within another 3 days. However, onset can be delayed up to 5 days after presentation with progression to euthanasia taking as long as 2 weeks. Mid-to-caudal lumbar discs might be associated with an increased risk of PMM.

Associations Between Anesthetic Variables and Functional Outcome in Dogs With Thoracolumbar Intervertebral Disk Extrusion Undergoing Decompressive Hemilaminectomy.

BACKGROUND: Outcome of acute experimental spinal cord injury is strongly associated with tissue perfusion and oxygenation. Cardiopulmonary depression could affect outcome in dogs undergoing general anesthesia for surgical treatment of thoracolumbar intervertebral disk extrusion (IVDE). HYPOTHESIS/OBJECTIVES: To evaluate the effects of general anesthesia on functional outcome in dogs undergoing surgery to treat thoracolumbar IVDE. ANIMALS: Eighty-four client-owned dogs with acute thoracolumbar IVDE treated by decompressive hemilaminectomy. METHODS: Exploratory, retrospective observational study. Medical records were reviewed for clinical presentation and anesthetic monitoring variables, including duration of anesthesia and surgery, hypotension, bradycardia, temperature, and respiratory parameters. Multivariable regression tree analysis was performed to explore associations between anesthetic variables and functional outcome scores after 6 weeks, as well as return to ambulatory status. RESULTS: Episodes of bradycardia (69%) and hypotension (57%) were frequent. Across all outcome measures, regression tree analysis highlighted functional grade at presentation as the primary determining factor, and among pain perception negative dogs, there was a possible association between increased duration of surgery and poorer outcome. In dogs with intact pain perception, duration of bradycardia, mean body temperature, and mean end-tidal carbon dioxide were highlighted. CONCLUSIONS AND CLINICAL IMPORTANCE: Exploratory statistical methods can facilitate hypothesis-generating studies to inform prospective investigations in veterinary medicine. Although the mechanism is uncertain, increased duration of surgery might be associated with poorer outcome in pain perception negative dogs with thoracolumbar IVDE.

Effect of Cranberry Extract on the Frequency of Bacteriuria in Dogs with Acute Thoracolumbar Disk Herniation: A Randomized Controlled Clinical Trial.

BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. RESULTS: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.

Clinical and Diagnostic Imaging Features of Brain Herniation in Dogs and Cats.

BACKGROUND: Quantification of brain herniation on MRI and its immediate clinical implications are poorly described. OBJECTIVES: Define the normal position of caudal fossa structures on brain MRIs in dogs and cats utilizing morphometry, compare this to dogs and cats with caudal transtentorial herniation (CTH), foramen magnum herniation (FMH) or both identified on MRI, and investigate associations between herniation severity, clinical signs, and 24-hour outcome. ANIMALS: Ninety-two controls (66 dogs, 26 cats), 119 cases with herniation (88 dogs, 31 cats). METHODS: Retrospective case series. The MRI database was searched for controls with normal brain anatomy and cases with brain herniation. Morphometry in controls established TTX (transtentorial to rostroventral cerebellum) to quantify CTH and FMX (caudoventral cerebellum to foramen magnum) to quantify FMH. Measurements were compared between cases and controls. Correlations with specific clinical variables and outcome were investigated. RESULTS: Measurements in medium/large control dogs versus small dog and cat controls were significantly different (P < .001, TTX: -0.46, -0.305, -0.3, FMX: 0.695, 0.27, 0.25, respectively). 119/1564 (7.6%) cases that underwent brain imaging had brain herniation. TTX and FMX were significantly different between controls and cases with CTH or FMH (P < .001). 67/89 (75%) cases with supratentorial lesions had no signs directly attributable to herniation. 71/119 (60%) had a normal anesthetic recovery. TTX was significantly associated with 24-hour survival (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Brain herniation can be quantified on MRI. Clinical signs directly attributable to brain herniation commonly are absent, and more severe CTH based on TTX is associated with a worse short-term outcome.

Recovery of stepping and coordination in dogs following acute thoracolumbar intervertebral disc herniations.

Prospective data on the recovery of coordination in dogs suffering acute thoracolumbar intervertebral disc herniations (TL-IVDH) are limited. The purpose of this study was to use treadmill based and open field scores (OFS) to quantify recovery of stepping ability and forelimb, hindlimb coordination in the 6 weeks following surgical decompression of dogs with TL-IVDH. Sixty-three dogs were grouped at presentation as grades 3 (non-ambulatory paraparetic), 4 (paraplegic) or 5 (paraplegic without pain sensation) and were evaluated 2, 4, and 6 weeks post-operatively. Stepping scores and Regularity Index (RI), a measure of coordination, were calculated from treadmill walking, and an OFS incorporating supported and unsupported walking was assigned. Outcomes for the three measures were compared between groups and correlation between scoring methods was assessed. Grade 3 and 4 dogs recovered ambulation by 2 weeks, reaching median stepping scores of 96 and 90% by 6 weeks, respectively. Recovery of coordination differed between groups 3 and 4 with median RI scores of 93.9% and 63%, respectively, by 6 weeks. Eight grade 5 dogs failed to recover independent ambulation by 6 weeks. Nine dogs recovered with scores that were significantly worse than the grade 3 and 4 dogs at 6 weeks for stepping score (P < 0.001) and RI (P < 0.001). OFS correlated closely with stepping and RI scores and each group was significantly different using this ordinal scale. In conclusion, recovery of coordination was incomplete in dogs that showed good recovery of stepping. The data generated could be used for clinical trial design.

A Placebo-Controlled, Prospective, Randomized Clinical Trial of Polyethylene Glycol and Methylprednisolone Sodium Succinate in Dogs with Intervertebral Disk Herniation.

BACKGROUND: Acute intervertebral disk herniation (IVDH) is a common cause of spinal cord injury in dogs and currently there is no proven medical treatment to counter secondary injury effects. Use of methylprednisolone sodium succinate (MPSS) or polyethylene glycol (PEG) as neuroprotectants is advocated but controversial because neither treatment has been tested in placebo-controlled, randomized, blinded trials in dogs. HYPOTHESIS: Polyethylene glycol will improve the outcome of severe spinal cord injury caused by IVDH compared to MPSS or placebo. ANIMALS: Client-owned dogs with acute onset of thoracolumbar IVDH causing paralysis and loss of nociception for <24 hours. METHODS: Dogs were randomized to receive MPSS, PEG, or placebo; drugs appeared identical and group allocation was masked. Drug administration was initiated once the diagnosis of IVDH was confirmed and all dogs underwent hemilaminectomy. Neurologic function was assessed 2, 4, 8, and 12 weeks postoperatively using an open field gait score (OFS) as the primary outcome measure. Outcomes were compared by the Wilcoxon rank sum test. RESULTS: Sixty-three dogs were recruited and 47.6% recovered ambulation. 17.5% developed progressive myelomalacia but there was no association with group. There was no difference in OFS among groups. Although full study power was not reached, conditional power analyses indicated the futility of continued case recruitment. CONCLUSIONS: This clinical trial did not show a benefit of either MPSS or PEG in the treatment of acute, severe thoracolumbar IVDH when used as adjunctive medical treatment administered to dogs presenting within 24 hours of onset of paralysis.

Histiocytic sarcoma with central nervous system involvement in dogs: 19 cases (2006-2012).

BACKGROUND: Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1-3 animals. OBJECTIVE: The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement. ANIMALS: Nineteen dogs with HS examined at veterinary referral hospitals. METHODS: Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis. RESULTS: Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study.

Frameless stereotactic radiosurgery for the treatment of primary intracranial tumours in dogs.

Stereotactic radiosurgery (SRS) is a procedure that delivers a single large radiation dose to a well-defined target. Here, we describe a frameless SRS technique suitable for intracranial targets in canines. Medical records of dogs diagnosed with a primary intracranial tumour by imaging or histopathology that underwent SRS were retrospectively reviewed. Frameless SRS was used successfully to treat tumours in 51 dogs with a variety of head sizes and shapes. Tumours diagnosed included 38 meningiomas, 4 pituitary tumours, 4 trigeminal nerve tumours, 3 gliomas, 1 histiocytic sarcoma and 1 choroid plexus tumour. Median survival time was 399 days for all tumours and for dogs with meningiomas; cause-specific survival was 493 days for both cohorts. Acute grade III central nervous system toxicity (altered mentation) occurred in two dogs. Frameless SRS resulted in survival times comparable to conventional radiation therapy, but with fewer acute adverse effects and only a single anaesthetic episode required for therapy.

Characterization of immune cell infiltration into canine intracranial meningiomas.

Meningiomas are the most common intracranial tumors in dogs. A variety of inflammatory cells have been shown to invade these tumors in people, but little is known about interactions between the immune system and naturally occurring brain tumors in dogs. The purpose of this study was to investigate the presence of a variety of immune cell subsets within canine intracranial meningiomas. Twenty-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry with antibodies specific for CD3, CD79a, CD18, CD11d (αD), CD45RA, forkhead box P3, and Toll-like receptors 4 and 9. Immune cell infiltration was evident in all samples, with a predominance of CD3(+) T cells. Large numbers of CD18(+) microglia and macrophages were noted surrounding and infiltrating the tumors, and a subset of these cells within the tumor appeared to be CD11d(+). Scattered macrophages at the tumor-brain interface were TLR4(+) and TLR9(+). Rare CD79a(+) B cells were noted in only a small subset of tumors. Lesser numbers of lymphocytes that were CD11d(+), CD45RA(+), or FoxP3(+) were noted in a number of the meningiomas. Although the function of these cells is not yet clear, work in other species suggests that evaluation of this immune cell infiltrate may provide important prognostic information and may be useful in the design of novel therapies.

Diazepam pharmacokinetics after nasal drop and atomized nasal administration in dogs.

The standard of care for emergency therapy of seizures in veterinary patients is intravenous (i.v.) administration of benzodiazepines, although rectal administration of diazepam is often recommended for out-of-hospital situations, or when i.v. access has not been established. However, both of these routes have potential limitations. This study investigated the pharmacokinetics of diazepam following i.v., intranasal (i.n.) drop and atomized nasal administration in dogs. Six dogs were administered diazepam (0.5 mg/kg) via all three routes following a randomized block design. Plasma samples were collected and concentrations of diazepam and its active metabolites, oxazepam and desmethyldiazepam were quantified with high-performance liquid chromatography (HPLC). Mean diazepam concentrations >300 ng/mL were reached within 5 min in both i.n. groups. Diazepam was converted into its metabolites within 5 and 10 min, respectively, after i.v. and i.n. administration. The half lives of the metabolites were longer than that of the parent drug after both routes of administration. The bioavailability of diazepam after i.n. drop and atomized nasal administration was 42% and 41%, respectively. These values exceed previously published bioavailability data for rectal administration of diazepam in dogs. This study confirms that i.n. administration of diazepam yields rapid anticonvulsant concentrations of diazepam in the dog before a hepatic first-pass effect.

Magnetic resonance imaging of spongy degeneration of the central nervous system in a Labrador Retriever.

A 7-month-old, neutered female Labrador Retriever was evaluated for tetraparesis and subtle cerebellar dysfunction. Clinical signs progressed over a period of 6 weeks to severe ataxia, hypermetria, intention tremors, and finally non-ambulatory tetraparesis. On magnetic resonance imaging of the brain there were large, bilaterally symmetrical, ovoid lesions in the region of the deep cerebellar nuclei that were hyperintense on T2-weighted and proton density images and hypointense on T1-weighted images. There were similar but smaller bilaterally symmetrical lesions present within the thalamus. Euthanasia was performed and lesions consistent with the previously described spongy degeneration of Labrador Retrievers were identified. This disease and its relation to similar human heritable leukodystrophies are discussed.

Magnetic resonance imaging of cerebral cortical necrosis (polioencephalomalacia) in a dog.

A 3-year-old neutered female mixed breed dog was examined because of severe, generalized seizure activity, tetraparesis, and encephalopathic signs. Cerebrospinal fluid (CSF) evaluation was unremarkable except for a mild increase in protein. Serum and CSF titers for infectious diseases were negative. Magnetic resonance (MR) imaging examination of the brain was performed and lesions were found within the cerebral gray matter of the temporal and parietal lobes. The lesions had increased signal intensity on T1, T2, and proton density-weighted images. There was mild inhomogeneous enhancement following intravenous contrast medium administration. Neurologic status improved and the seizures were well controlled, but the dog never regained normal mentation and euthanasia was performed 10 weeks after initial evaluation. At necropsy, severe cerebral cortical necrosis was found in the regions corresponding to the lesions seen on MR imaging examination. Large numbers of fat-containing macrophages (gitter cells) were found within these areas, and are thought to be responsible for the characteristic hyperintensity seen on the MR images.

Paraneoplastic polyneuropathy and subsequent recovery following tumor removal in a dog.

A 10-year-old, intact female Brittany spaniel was presented for evaluation of progressive tetraparesis. Physical examination and diagnostic testing revealed masses within the right mammary chain and left caudal lung lobe. Neuromuscular electrodiagnostic and histopathological findings were compatible with a peripheral polyneuropathy. Upon removal of the tumors, the dog's paresis disappeared. To the authors' knowledge, this is the first reported case in the veterinary literature of improvement following therapy of a suspected paraneoplastic neuropathy.