Evidence supporting vertical transmission of Salmonella in dairy cattle.

We set out to investigate whether Salmonella enterica could be recovered from various tissues of viable neonatal calves immediately following parturition. Eleven samples were aseptically collected from each of 20 calves and consisted of both left and right subiliac and prescapular lymph nodes (LN), mesenteric LN, spleen and liver, as well as intestinal tissue (including luminal contents) from the small intestine, caecum, spiral colon and rectum. In addition, a faecal sample was collected from 19 of the dams. Salmonella was recovered from at least one sample from 10 of the 20 neonates. Across all calves, Salmonella was recovered from 12·7% of all samples and from LN in particular, Salmonella was recovered from 10·0%, 5·0%, and 5·0% of subiliac, prescapular, and mesenteric LN, respectively. Within calves, Salmonella was recovered from 0% to 73% of samples and across tissues, estimates of Salmonella prevalence were greatest in the caecum (30%) but was never recovered from the right pre-scapular LN. These data provide evidence of vertical transmission from a dam to her fetus such that viable calves are born already infected and thereby not requiring faecal-oral exposure for transmission. This new knowledge ought to challenge - or at least add to - existing paradigms of Salmonella transmission dynamics within cattle herds.

Risk factors for early death or euthanasia within 100 days of diagnosis in dogs with meningoencephalitis of unknown origin.

Meningoencephalitis of unknown origin (MUO) in the dog is an inflammatory condition of the central nervous system with variable short- and long-term prognosis. Previous studies have attempted to identify risk factors for early death; however, the findings were inconsistent and prognostication and treatment selection remain difficult for cases of MUO. The aim of this study was to compare the influence of putative prognostic factors on early survival in dogs with MUO. Logistic regression was used to analyse the effect of clinical and magnetic resonance imaging (MRI) features at diagnosis and type of immune-suppressive treatment received on survival at three-time points; 7 days, 30 days, and 100 days post-diagnosis. Ninety eight dogs were included. Dogs that were obtunded at presentation had a 6.6 times increased odds of death in the first 7 days after diagnosis, a 2.1 times increased risk of death 8-30 days after diagnosis, and a 1.9 times increased risk of death 31-100 days after diagnosis. No other clinical, MRI feature, or treatment was found to have a significant influence on survival. Obtundation at presentation was found to increase risk of early euthanasia in dogs with MUO, while the addition of an IV infusion of cytarabine to immune-suppressive corticosteroid therapy (prednisolone and/or dexamethasone) at initial treatment did not improve the odds of survival at 7, 30, or 100 days after diagnosis.

Evaluation of a Preharvest Bacteriophage Therapy for Control of Salmonella within Bovine Peripheral Lymph Nodes.

ABSTRACT: A series of proof-of-concept studies were developed to determine whether a commercial bacteriophage cocktail could be utilized for the mitigation of Salmonella in bovine peripheral lymph nodes (LNs). The first objective sought to determine whether exogenous phage could be isolated from the LNs following administration. If isolation were successful, the second objective was to determine whether the phage in the LNs could effectively reduce Salmonella. Salmonella Montevideo was inoculated intradermally at multiple sites and multiple times, followed by delivery of the phage cocktail subcutaneously in two injections around each of the right and left prescapular and subiliac LNs. At the conclusion of each study, animals were euthanized, and the popliteal, prescapular, and subiliac LNs were examined. The inoculated phage was successfully isolated from the LNs; transmission electron microscopy revealed phages in the LNs of the treated cattle, and these phages were identical to those in the cocktail. Levels of phage were higher (P < 0.01) in the prescapular and subiliac LNs in the phage-treated than in the control cattle. In subsequent studies, the protocols were modified to increase Salmonella and phage levels within the LNs. Compared with the first study, overall Salmonella levels were increased in the LNs, and phage treatment decreased (P < 0.01) Salmonella in the some of the LNs. Phage levels were numerically but not significantly increased (P = 0.12) in the treated cattle. The final study was modified, hypothesizing that a 48-h postmortem period before LN removal would facilitate phage-Salmonella interaction; however, no differences (P > 0.10) in Salmonella levels were found among treatments. Salmonella-specific phages administered to live cattle can translocate to the LNs; however, these phages had limited to no effect on Salmonella in these LNs under these experimental conditions.

Quantitative Diffusion and Spectroscopic Neuroimaging Combined with a Novel Early-Developmental Assessment Improves Models for 1-Year Developmental Outcomes.

BACKGROUND AND PURPOSE: Preterm infants are at risk for overt and silent CNS injury, with developmental consequences that are difficult to predict. The novel Specific Test of Early Infant Motor Performance, administered in preterm infants at term age, is indicative of later developmental gross motor and cognitive scores at 12 months. Here, we assessed whether functional performance on this early assessment correlates with CNS integrity via MR spectroscopy or diffusional kurtosis imaging and whether these quantitative neuroimaging methods improve predictions for future 12-month developmental scores. MATERIALS AND METHODS: MR spectroscopy and quantitative diffusion MR imaging data were acquired in preterm infants (n = 16) at term. Testing was performed at term and 3 months using the Specific Test of Early Infant Motor Performance and the Bayley Scales of Infant and Toddler Development, Third Edition, at 12 months. We modeled the relationship of MR spectroscopy and diffusion MR imaging data with both test scores via multiple linear regression. RESULTS: MR spectroscopy NAA ratios at a TE of 270 ms in the frontal WM and basal ganglia and kurtosis metrics in major WM tracts correlated strongly with total Specific Test of Early Infant Motor Performance scores. The addition of MR spectroscopy and diffusion separately improved the functional predictions of 12-month outcomes. CONCLUSIONS: Microstructural integrity of the major WM tracts and metabolism in the basal ganglia and frontal WM strongly correlate with early developmental performance, suggesting that the Specific Test of Early Infant Motor Performance reflects CNS integrity after preterm birth. This study demonstrates that combining quantitative neuroimaging and early functional movement improves the prediction of 12-month outcomes in premature infants.

Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial.

BACKGROUND: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimer's disease. OBJECTIVE: Determine whether memantine improves cognitive performance (CP) among subjects with multiple sclerosis (MS) and cognitive impairment (CI). METHODS: This double-blind, randomized, placebo-controlled trial (Clinicaltrials.gov NCT00300716) compared memantine 10 mg twice a day (4 week titration followed by 12 weeks on the highest tolerated dose) with placebo. The primary outcome was the change from baseline to exit on the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test-II (CVLT-II) Long Delay Free Recall (LDFR). Secondary outcomes included additional neuropsychological tests; self-report measures of quality of life, fatigue, and depression; and family/caregiver reports of subjects' CI and neuropsychiatric symptoms. RESULTS: The differences between the groups on the change on the PASAT (placebo-memantine = 0.0 correct responses, 95% CI 3.4, 3.4; p = 0.9) and on CVLT-II LDFR (placebo-memantine =-0.6 words, 95% CI -2.1, 0.8; p = 0.4) as well as on the other cognitive tests were not significant. Subjects on memantine had no serious adverse events (AEs) but had more fatigue and neurological AEs as well as, per family members' reports, less cognitive improvement and greater neuropsychiatric symptoms than subjects on placebo. CONCLUSION: Memantine 10 mg twice a day does not improve CP in subjects with MS, ages 18-65, without major depression, who have subjective cognitive complaints and perform worse than one SD below the mean on the PASAT or on the California Verbal Learning Test-II (total recall or delayed free recall).

Evaluation of the Efficacy of Three Direct Fed Microbial Cocktails To Reduce Fecal Shedding of Escherichia coli O157:H7 in Naturally Colonized Cattle and Fecal Shedding and Peripheral Lymph Node Carriage of Salmonella in Experimentally Infected Cattle.

Two experiments were conducted to evaluate the feeding of direct fed microbials (DFMs) on fecal shedding of Escherichia coli O157:H7 in naturally infected cattle (experiment I) and on Salmonella in the feces and peripheral lymph nodes (PLNs) of experimentally infected cattle (experiment II). Thirty cattle, 10 per treatment, were used in each experiment. Treatments in experiment I consisted of a control (lactose carrier only); DFM1, a 1:1 ratio of Enterococcus faecium and Lactobacillus animalis; and DFM2, a 1:1 ratio of Lactobacillus acidophilus and Pediococcus acidilactici. In Experiment II, DFM1 was replaced with DFM3, a 1:2 ratio of Lactobacillus reuteri and other Lactobacillus strains. Additives were mixed in water and applied as a top-dressing to each pen's daily ration for 50 days. Approximately half-way through each experiment, the DFM concentration was doubled for the remainder of the study. Fecal samples were collected throughout experiment I and cultured for E. coli O157:H7. Cattle in experiment II were inoculated intradermally with Salmonella Montevideo on days 32, 37, and 42 and then necropsied on days 49 and 50 (five cattle per treatment on each day). Innate immune function was assessed on days 29, 49, and 50. In experiment I, fecal concentration and prevalence of E. coli O157:H7 were not different (P > 0.10) nor was there an effect (P = 0.95) on the percentage of super shedders (cattle shedding ≥3.0 log CFU/g of feces). In experiment II, no treatment differences (P > 0.05) were observed for Salmonella in the PLNs except for the inguinal nodes, which had a significantly lower Salmonella prevalence in DFM-supplemented cattle than in the controls. Immune function, as measured by monocyte nitric oxide production and neutrophil oxidative burst, was decreased (P < 0.05) in the DFM treatment groups. Although results of this research indicate little to no effect of these DFMs on E. coli O157:H7 or Salmonella in cattle, an increase in the duration of administration to that similar to what is used for commercial cattle might elicit treatment differences.

Identification of fructose 3-phosphate in the lens of diabetic rats.

Fructose 3-phosphate, a novel monosaccharide phosphate, has been identified in the lens of diabetic rats. This compound, which is not present in normal lenses, is a protein glycosylating agent and enzyme inactivator. In addition, because of its structural features, this metabolite is relatively labile and undergoes hydrolysis to yield inorganic phosphate and the potent glycosylating agent, 3-deoxyglucosone. The increase in the concentration of fructose 3-phosphate in the lens of diabetic rats suggests that it and its hydrolysis product, 3-deoxyglucosone, may be responsible in part for the development of some diabetic complications in the lens.

Induction of autoimmune thyroiditis in chickens by dietary iodine.

Clinical studies have suggested that excess dietary iodine promotes autoimmune thyroiditis; however, the lack of a suitable animal model has hampered investigation of the phenomenon. In this study, different amounts of potassium iodide were added to the diets of chicken strains known to be genetically susceptible to autoimmune thyroiditis. Administration of iodine during the first 10 weeks of life increased the incidence of the disease, as determined by histology and the measurement of autoantibodies to triiodothyronine, thyroxine, and thyroglobulin. Further support for the relation between iodine and autoimmune thyroiditis was provided by an experiment in which iodine-deficient regimens decreased the incidence of thyroid autoantibodies in a highly susceptible strain. These results suggest that excessive consumption of iodine in the United States may be responsible for the increased incidence of autoimmune thyroiditis.

Cellular applications of 31P and 13C nuclear magnetic resonance.

High-resolution nuclear magnetic resonance (NMR) studies of cells and purified mitochondria are discussed to show the kind of information that can be obtained in vivo. In suspensions of Escherichia coli both phosphorus-31 and carbon-13 NMR studies of glycolysis and bioenergetics are presented. In rat liver cells the pathways of gluconeogenesis from carbon-13-labeled glycerol are followed by carbon-13 NMR. In the intact liver cells cytosolic and mitochondrial pH's were separately measured by phosphorus-31 NMR. In purified mitochondria the internal and external concentrations of inorganic phosphate, adenosine diphosphate, and adenosine triphosphate were determined by phosphorus-31 NMR while the pH difference across the membrane was measured simultaneously.

Clinical diagnosis and treatment of suspected neuropathic pain in three dogs.

Three dogs were referred to The Queen's Veterinary School Hospital at University of Cambridge for chronic behavioural or locomotor disorders associated with pain. All three had been unsuccessfully treated with conventional analgesics, including non-steroidal anti-inflammatory drugs, glucocorticoids and opiate agonists, prior to referral, with minimal or no response. They were investigated by neurological examination plus conventional ancillary diagnostic tests and therapeutic drug trials. Ruling out other causes of pain and applying previously well-described criteria, each case was diagnosed as consistent with neuropathic pain, a poorly recognised condition in domestic dogs. Treatment with the tricyclic antidepressant drug, amitriptyline, or the antiepileptic drug, gabapentin, resulted in either a dramatic improvement or full resolution of clinical signs in all cases.

Use of a lateral surgical approach to the femoral nerve in the management of two primary femoral nerve sheath tumours.

This case report describes the diagnosis and management of primary femoral nerve sheath tumours in two dogs. Both of the tumours were localised by electromyography (EMG) and magnetic resonance imaging (MRI), and were then surgically resected using a novel approach to the iliopsoas muscle via osteotomy of the ventral ilial wing. This approach should be considered when attempting surgical treatment of conditions affecting the iliopsoas muscle or the femoral nerve because it provides excellent exposure of these structures.

Prolonged Microgravity Affects Human Brain Structure and Function.

BACKGROUND AND PURPOSE: Widespread brain structural changes are seen following extended spaceflight missions. The purpose of this study was to investigate whether these structural changes are associated with alterations in motor or cognitive function. MATERIALS AND METHODS: Brain MR imaging scans of National Aeronautics and Space Administration astronauts were retrospectively analyzed to quantify pre- to postflight changes in brain structure. Local structural changes were assessed using the Jacobian determinant. Structural changes were compared with clinical findings and cognitive and motor function. RESULTS: Long-duration spaceflights aboard the International Space Station, but not short-duration Space Shuttle flights, resulted in a significant increase in total ventricular volume (10.7% versus 0%, P < .001, n = 12 versus n = 7). Total ventricular volume change was significantly associated with mission duration (r = 0.72, P = .001, n = 19) but negatively associated with age (r = -0.48, P = .048, n = 19). Long-duration spaceflights resulted in significant crowding of brain parenchyma at the vertex. Pre- to postflight structural changes of the left caudate correlated significantly with poor postural control; and the right primary motor area/midcingulate correlated significantly with a complex motor task completion time. Change in volume of 3 white matter regions significantly correlated with altered reaction times on a cognitive performance task (bilateral optic radiations, splenium of the corpus callosum). In a post hoc finding, astronauts who developed spaceflight-associated neuro-ocular syndrome demonstrated smaller changes in total ventricular volume than those who did not (12.8% versus 6.5%, n = 8 versus n = 4). CONCLUSIONS: While cautious interpretation is appropriate given the small sample size and number of comparisons, these findings suggest that brain structural changes are associated with changes in cognitive and motor test scores and with the development of spaceflight-associated neuro-optic syndrome.

25-Hydroxy vitamin D3 serum concentration in dogs with acute polyradiculoneuritis compared to matched controls.

OBJECTIVES: To determine if dogs with acute polyradiculoneuritis have lower serum 25-hydroxy vitamin D3 concentration compared to a control group of dogs with idiopathic epilepsy. MATERIALS AND METHODS: Retrospective case-control study of 21 dogs with acute canine polyradiculoneuritis and 21 control dogs with idiopathic epilepsy matched for year and season of presentation from a referral hospital population in the UK. Serum concentration of 25-hydroxy vitamin D3 was compared between groups using Student's t-test. RESULTS: Dogs with acute canine polyradiculoneuritis had significantly lower (P=0·033) serum 25-hydroxy vitamin D3 concentration (87·1 nmol/L ±55·4 nmol/L) compared to a control group with idiopathic epilepsy (113 nmol/L ±66·3 nmol/L). CLINICAL SIGNIFICANCE: The cause and clinical significance of the altered vitamin D status in dogs with acute polyradiculoneuritis are not clear and require further investigation. Our findings pave the way for improved understanding of acute canine polyradiculoneuritis and, potentially, improved clinical management, if a causal role for 25-hydroxy vitamin D3 is defined.

Uptake and metabolism of iodine is crucial for the development of thyroiditis in obese strain chickens.

To assess the importance of the role of thyroidal iodine in the pathogenesis of thyroiditis in the obese strain (OS) chicken, a model of spontaneous and severe disease, we studied the effect of antithyroid drugs that reduce thyroidal iodine or prevent its metabolism. Reduction of thyroidal iodine was achieved with KClO4, an inhibitor of iodine transport and mononitrotyrosine (MNT), a drug that promotes loss of thyroidal iodine as iodotyrosines. A regimen consisting of KClO4 and MNT administration beginning in ovo and continuing after hatching reduced thyroidal infiltration to 2% of control values and decreased thyroglobulin antibody (TgAb) production for as long as 9 wk. Untreated birds had severe disease by 5 wk of age. The suppression of disease was independent of TSH, not mediated by generalized immunosuppression and reversed by excess dietary iodine. Two drugs that inhibit the metabolism of iodine, propylthiouracil (PTU) and aminotriazole, reduced thyroidal infiltration and TgAb levels, although to a lesser extent. When splenocytes from OS chickens with thyroiditis were transferred to Cornell strain (CS) chickens, a related strain that develops late onset mild disease, only the recipients that were iodine supplemented developed thyroiditis. In conclusion, autoimmune thyroiditis in an animal model can be prevented by reducing thyroidal iodine or its metabolism and optimal effects require intervention at the embryonic stage.

Familial gynecomastia with increased extraglandular aromatization of plasma carbon19-steroids.

We evaluated a family in which gynecomastia occurred in five males in two generations. In each affected subject, gynecomastia and male sexual maturation began at an early age. The ratio of the concentration of plasma estradiol-17 beta to that of plasma testosterone was elevated in each affected subject. In the three siblings with gynecomastia, the transfer constant of conversion of androstenedione to estrone (i.e., the fraction of plasma androstenedione that was converted to estrone as measured in the urine) was 10 times that of normal persons. The transfer constant of conversion of testosterone to estradiol-17 beta in the one subject studied also was 8-10 times that of normal men, whereas the transfer constants of conversion of estrone to estradiol-17 beta and of estradiol-17 beta to estrone were normal. Despite the elevation in extraglandular aromatase activity, there was a normal response of the hypothalamic-pituitary axis to provocative stimuli. This is the second documentation of gynecomastia that is associated with increased extraglandular aromatase activity, and the first time that the defect was found to be familial with a probable X-linked (or autosomal dominant, sex limited) mode of inheritance.

Retinoblastoma protein disrupts interactions required for RNA polymerase III transcription.

The retinoblastoma protein (RB) has been shown to suppress RNA polymerase (Pol) III transcription in vivo (R. J. White, D. Trouche, K. Martin, S. P. Jackson, and T. Kouzarides, Nature 382:88-90, 1996). This regulation involves interaction with TFIIIB, a multisubunit factor that is required for the expression of all Pol III templates (C. G. C. Larminie, C. A. Cairns, R. Mital, K. Martin, T. Kouzarides, S. P. Jackson, and R. J. White, EMBO J. 16:2061-2071, 1997; W.-M. Chu, Z. Wang, R. G. Roeder, and C. W. Schmid, J. Biol. Chem. 272:14755-14761, 1997). However, it has not been established why RB binding to TFIIIB results in transcriptional repression. For several Pol II-transcribed genes, RB has been shown to inhibit expression by recruiting histone deacetylases, which are thought to decrease promoter accessibility. We present evidence that histone deacetylases exert a negative effect on Pol III activity in vivo. However, RB remains able to regulate Pol III transcription in the presence of the histone deacetylase inhibitor trichostatin A. Instead, RB represses by disrupting interactions between TFIIIB and other components of the basal Pol III transcription apparatus. Recruitment of TFIIIB to most class III genes requires its binding to TFIIIC2, but this can be blocked by RB. In addition, RB disrupts the interaction between TFIIIB and Pol III that is essential for transcription. The ability of RB to inhibit these key interactions can explain its action as a potent repressor of class III gene expression.

Spatio-temporal analysis of molecular delivery through the blood-brain barrier using focused ultrasound.

The deposition of gadolinium through ultrasound-induced blood-brain barrier (BBB) openings in the murine hippocampus was investigated. First, wave propagation simulations through the intact mouse skull revealed minimal beam distortion while thermal deposition simulations, at the same sonication parameters used to induce BBB opening in vivo, revealed temperature increases lower than 0.5 degrees C. The simulation results were validated experimentally in ex vivo skulls (m = 6) and in vitro tissue specimens. Then, in vivo mice (n = 9) were injected with microbubbles (Optison; 25-50 microl) and sonicated (frequency: 1.525 MHz, pressure amplitudes: 0.5-1.1 MPa, burst duration: 20 ms, duty cycle: 20%, durations: 2-4 shots, 30 s per shot, 30 s interval) at the left hippocampus, through intact skin and skull. Sequential, high-resolution, T1-weighted MRI (9.4 Tesla, in-plane resolution: 75 microm, scan time: 45-180 min) with gadolinium (Omniscan; 0.5 ml) injected intraperitoneally revealed a threshold of the BBB opening at 0.67 MPa and BBB closing within 28 h from opening. The contrast-enhancement area and gadolinium deposition path were monitored over time and the influence of vessel density, size and location was determined. Sonicated arteries, or their immediate surroundings, depicted greater contrast enhancement than sonicated homogeneous brain tissue regions. In conclusion, gadolinium was delivered through a transiently opened BBB and contained to a specific brain region (i.e., the hippocampus) using a single-element focused ultrasound transducer. It was also found that the amount of gadolinium deposited in the hippocampal region increased with the acoustic pressure and that the spatial distribution of the BBB opening was determined not only by the ultrasound beam, but also by the vasculature of the targeted brain region.

An exploratory study into factors influencing development of acute canine polyradiculoneuritis in the UK.

OBJECTIVES: To investigate whether the development of acute canine polyradiculoneuritis is associated with various putative risk factors. MATERIALS AND METHODS: Retrospective case-control study with conditional logistic regression analysis from a referral hospital population in the UK where controls were matched for year of presentation. RESULTS: Forty-three cases were identified with acute canine polyradiculoneuritis and 86 controls were selected. Jack Russell terriers and West Highland white terriers were found to have a significantly greater odds of developing acute canine polyradiculoneuritis compared to a mixed baseline group of dogs. The odds of developing acute canine polyradiculoneuritis were greater in the autumn and winter compared to spring. Vaccination, rural/urban habitation, sex, neuter status and age were not associated with development of acute canine polyradiculoneuritis in our population of dogs. CLINICAL SIGNIFICANCE: Breed and season were associated with development of acute canine polyradiculoneuritis. However, this is a small sample and so this observation needs confirmation in further studies and other factors may also be involved. Nevertheless, these findings may be important in further understanding the aetiopathogenesis of this condition.

Unique prefrontal GABA and glutamate disturbances in co-occurring bipolar disorder and alcohol dependence.

Bipolar disorder (BD) and alcohol dependence (AD) frequently co-occur, and co-occurring BD and AD are associated with devastating public health costs. Minimal neurobiological research exists to guide the development of effective treatments for this treatment-resistant population. We believe the present study represents the first investigation of prefrontal gamma-aminobutyric acid (GABA) and glutamate levels in co-occurring BD and current AD. The participants were 78 individuals who met DSM-IV criteria for BD I/II and current AD (n=20), BD I/II alone (n=19), current AD alone (n=20) or no diagnosis (n=19). The participants completed a baseline diagnostic visit, then returned approximately 4 days later for a two-dimensional J-resolved proton magnetic resonance spectroscopy (1H-MRS) acquisition in dorsal anterior cingulate cortex (dACC). All participants were required to demonstrate ⩾1 week of abstinence from alcohol/drugs via serial biomarker testing before 1H-MRS. A 2 × 2 factorial analysis of variance of cerebrospinal fluid (CSF)-corrected GABA/water concentrations demonstrated a significant BD × AD interaction (F=2.91, P<0.05), signifying uniquely low levels of GABA in BD+AD; this effect doubled when the sample was restricted to individuals who consumed alcohol within 2 weeks of 1H-MRS. There were no overall effects of BD/AD on CSF-corrected glutamate/water levels. However, the BD × AD interaction, signifying uniquely low levels of glutamate in BD+AD, approached statistical significance (F=3.83, P=0.06) in individuals who consumed alcohol within 2 weeks of 1H-MRS. The dACC GABA levels were significantly, negatively associated with Barratt Impulsiveness Scale (r=-0.28, P=0.02) and Obsessive Compulsive Drinking Scale (r=-0.35, P<0.01) scores. If replicated, these results may suggest that future treatment studies should preferentially evaluate therapeutics in BD+AD known to increase prefrontal GABA and glutamate levels.

Prognostic Factors Associated with Recovery of Ambulation and Urinary Continence in Dogs with Acute Lumbosacral Spinal Cord Injury.

BACKGROUND: Limited information is available about prognostic factors for recovery after spinal cord injury (SCI) to the L4-S3 segments. Previous research suggests that L4-S3 SCI does not have a worse prognosis than T3-L3 SCI. HYPOTHESIS/OBJECTIVES: To elucidate prognostic factors for regaining urinary continence and ambulation in dogs with L4-S3 SCI and compare prognosis to T3-L3 SCI. ANIMALS/METHODS: A retrospective study on 61 nonambulatory dogs with L4-S3 SCI, matched to dogs with T3-L3 SCI, compared 3 weeks after onset. Prognostic factors explored using logistic regression and used for matching: nonchondrodystrophic dogs >15 kg versus dogs that were chondrodystrophic or <15 kg; compressive versus noncompressive lesions; presence versus absence of conscious pain perception (CPP); and lower vs upper motor neuron (LMN/UMN) incontinence. RESULTS: Fewer L4-S3 dogs regained continence compared to T3-L3 dogs (64 vs 85%, P = .0033), but no difference existed for regaining ambulation (66 vs 75%, P = .1306). In L4-S3 SCI dogs, fewer dogs regained continence with loss of CPP (P < .001), LMN incontinence (P = .004), and noncompressive lesions (P = .006). Negative prognostic factors for regaining ambulation included absent CPP (P < .001) and large nonchondrodystrophic breed (P = .022). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with L4-S3 SCI have a poorer short-term prognosis than do dogs with T3-L3 SCI. Dogs with L4-S3 SCI had a poor prognosis with loss of CPP, or noncompressive lesions combined with LMN incontinence. Small-breed or chondrodystrophic dogs with retained CPP, compressive lesions, and UMN incontinence had an excellent prognosis. These findings may help guide decision-making in L4-S3 SCI.