The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology.

The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m2 as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5-2 mg kg-1 day-1 ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 µg/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 µg/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m2 SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.

Plasma and serum concentrations of cytarabine administered via continuous intravenous infusion to dogs with meningoencephalomyelitis of unknown etiology.

The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client-owned dogs received a CRI of CA at a dose of 25 mg/m2 /h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high-pressure liquid chromatography. The mean peak concentration (CMAX ) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 µg/mL and 11.39 ± 3.37 h·µg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 µg/mL and 16.91 + 3.60 h·µg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 µg/mL at both the 1- and 8-h time points. The steady-state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma.

The pharmacokinetics of midazolam after intravenous, intramuscular, and rectal administration in healthy dogs.

Intravenous benzodiazepines are utilized as first-line drugs to treat prolonged epileptic seizures in dogs and alternative routes of administration are required when venous access is limited. This study compared the pharmacokinetics of midazolam after intravenous (IV), intramuscular (IM), and rectal (PR) administration. Six healthy dogs were administered 0.2 mg/kg midazolam IV, IM, or PR in a randomized, 3-way crossover design with a 3-day washout between study periods. Blood samples were collected at baseline and at predetermined intervals until 480 min after administration. Plasma midazolam concentrations were measured by high-pressure liquid chromatography with UV detection. Rectal administration resulted in erratic systemic availability with undetectable to low plasma concentrations. Arithmetic mean values ± SD for midazolam peak plasma concentrations were 0.86 ± 0.36 µg/mL (C0) and 0.20 ± 0.06 µg/mL (Cmax), following IV and IM administration, respectively. Time to peak concentration (Tmax ) after IM administration was 7.8 ± 2.4 min with a bioavailability of 50 ± 16%. Findings suggest that IM midazolam might be useful in treating seizures in dogs when venous access is unavailable, but higher doses may be needed to account for intermediate bioavailability. Rectal administration is likely of limited efficacy for treating seizures in dogs.

The pharmacokinetics of cytarabine in dogs when administered via subcutaneous and continuous intravenous infusion routes.

This crossover study compared the pharmacokinetics of cytarabine in six healthy dogs following intravenous constant rate infusion (CRI) and subcutaneous (SC) administrations, as these are two routes of administration commonly employed in the treatment of meningoencephalitis of unknown etiology. Each dog received a SC cytarabine injection of 50 mg/m(2) or an 8 h CRI of 25 mg/m(2) per hour, with a 7-day washout before receiving the alternative treatment. Blood samples were collected for 16 h after CRI initiation and for 8 h after SC injection. Plasma concentrations were measured by high-pressure liquid chromatography (HPLC). Pharmacokinetic parameters were estimated using the best-fit compartmental analysis for both CRI and SC routes. Terminal half-life (T(1/2) ) of cytarabine was 1.35 ± 0.3 and 1.15 ± 0.13 h after SC administration and CRI, respectively. Mean peak concentration (Cmax ) was 2.88 and 2.80 µg/mL for SC and CRI administration, respectively. Volume of distribution was 0.66 ± 0.07 l/kg. The 8-h CRI produced steady-state plasma concentrations as determined by consecutive measurement that did not decline until the end of the infusion. The SC administration did not achieve steady-state concentrations because cytarabine administered by this route was rapidly absorbed and eliminated quickly. The steady state achieved with the cytarabine CRI may produce a more prolonged exposure of cytarabine at cytotoxic levels in plasma compared to the concentrations after SC administration.

Effects of alfaxalone, propofol and isoflurane on cerebral blood flow and cerebrovascular reactivity to carbon dioxide in dogs: A pilot study.

Propofol total intravenous anesthesia is a common choice to anesthetize patients with increased intracranial pressure, reducing cerebral blood flow while maintaining cerebrovascular reactivity to CO2. Propofol and alfaxalone are commonly used for total intravenous anesthesia in dogs, but the effects of alfaxalone on cerebral blood flow and cerebrovascular reactivity to CO2 are unknown. Our hypothesis was that alfaxalone would not be significantly different to propofol, while isoflurane would increase cerebral blood flow and decrease cerebrovascular reactivity to CO2. Six healthy hound dogs were evaluated in this randomized crossover trial. Dogs were anesthetized with 7.5 mg/kg propofol, 3 mg/kg alfaxalone or 8 % sevoflurane, mechanically ventilated and maintained with propofol (400 µg/kg/min), alfaxalone (150 µg/kg/min) or 1.7 % end-tidal isoflurane, respectively, with one week washout between treatments. Cerebral blood flow and cerebrovascular reactivity to CO2 during hypercapnic and hypocapnic challenges were measured using arterial spin labelling and blood oxygen level-dependent magnetic resonance imaging sequences, respectively. Median (interquartile range, IQR) normocapnic cerebral blood flow was significantly lower (P = 0.016) with alfaxalone compared to isoflurane, in the whole brain 15.39 mL/min/100 g (14.90-19.90 mL/min/100 g) vs. 34.10 mL/min/100 g (33.35-43.17 mL/min/100 g), the grey matter 14.57 mL/min/100 g (13.66-18.72 mL/min/100 g) vs. 32.37 mL/min/100 g (31.03-42.99 mL/min/100 g), the caudal brain 15.47 mL/min/100 g (13.37-21.45 mL/min/100 g) vs. 36.85 mL/min/100 g (32.50-47.18 mL/min/100 g) and the temporal lobe grey matter 18.80 mL/min/100 g (15.89-20.84 mL/min/100 g) vs. 43.32 (36.07-43.58 mL/min/100 g). Median (IQR) hypocapnic cerebrovascular reactivity to CO2 was significantly higher (P = 0.016) for alfaxalone compared to isoflurane 8.85 %S/mm Hg (6.92-10.44 %S/mm Hg) vs. 3.90 %S/mm Hg (3.80-4.33 %S/mm Hg). Alfaxalone maintained lower cerebral blood flow and higher hypocapnic cerebrovascular reactivity to CO2 than isoflurane.

The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital.

Levetiracetam (LEV) is a commonly used add-on medication in dogs with refractory epilepsy. The objective of this study was to determine if the pharmacokinetics of LEV are altered by concurrent administration of phenobarbital (PB). Six healthy dogs received a single oral dose of LEV (16.7-27.8 mg/kg). Blood samples were collected at baseline and intermittently for 24 h. The study was repeated after the dogs received oral PB (2.0-3.3 mg/kg) twice daily for 21 days. Plasma LEV levels were evaluated by high pressure liquid chromatography, and data analyzed using a compartmental model. Compared with values determined when LEV was administered alone, concurrent administration of PB resulted in a decrease in LEV peak concentration (C(max) ) from 32.39 ± 6.76 to 18.22 ± 8.97 (P = 0.0071), a decrease in elimination half-life (T(1/2) ) from 3.43 ± 0.47 to 1.73 ± 0.22 (P = 0.0005), and an increase in oral clearance from 124.93 ± 26.93 to 252.99 ± 135.43 ml/h/kg (P < 0.0001). Concurrent PB administration significantly alters the pharmacokinetics of LEV in the dog, indicating that dosage adjustments might be necessary when the drug is administered with PB.

Placebo effect in canine epilepsy trials.

BACKGROUND: The placebo effect is a well-recognized phenomenon in human medicine; in contrast, little information exists on the effect of placebo administration in veterinary patients. HYPOTHESIS: Nonpharmacologic therapeutic effects play a role in response rates identified in canine epilepsy trials. ANIMALS: Thirty-four dogs with epilepsy. METHODS: Meta-analysis of the 3 known prospective, placebo-controlled canine epilepsy trials. The number of seizures per week was compiled for each dog throughout their participation in the trial. Log-linear models were developed to evaluate seizure frequency during treatment and placebo relative to baseline. RESULTS: Twenty-two of 28 (79%) dogs in the study that received placebo demonstrated a decrease in seizure frequency compared with baseline, and 8 (29%) could be considered responders, with a 50% or greater reduction in seizures. For the 3 trials evaluated, the average reduction in seizures during placebo administration relative to baseline was 26% (P = .0018), 29% (P = .17), and 46% (P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: A positive response to placebo administration, manifesting as a decrease in seizure frequency, can be observed in epileptic dogs. This is of importance when evaluating open label studies in dogs that aim to assess efficacy of antiepileptic drugs, as the reported results might be overstated. Findings from this study highlight the need for more placebo-controlled trials in veterinary medicine.

Prevalence of urinary tract infection in dogs after surgery for thoracolumbar intervertebral disc extrusion.

BACKGROUND: Urinary tract infection (UTI) is a common complication in people with spinal cord injury (SCI). Dogs with acute intervertebral disc extrusion (IVDE) have similar risk factors for UTI when compared with human SCI patients and have a high perioperative prevalence of UTI. OBJECTIVES: Determine the prevalence of UTI in dogs for 3 months after surgery for thoracolumbar IVDE and identify risk factors for development of UTI. ANIMALS: Twenty-five dogs treated surgically for 26 acute disc extrusions. METHODS: Prospective study. Urinalysis and urine culture were performed perioperatively. At home, owners monitored urine with dipsticks every 48 hours for 1 month then once a week until 3 months. Dogs returned for assessment of motor function, urinalysis, and urine culture at 1 and 3 months after surgery. Presence of UTI over the 3-month period was correlated to potential risk factors. RESULTS: Ten dogs (38%) developed 12 UTIs over the 3-month period, with the majority occurring between weeks 1 and 6; 60% of the UTIs were occult. Hematuria in the absence of pyuria or UTI was a common finding in the perioperative period. Sex, breed, and ambulatory status influenced the risk of developing a UTI. CONCLUSIONS AND CLINICAL IMPORTANCE: There is a high prevalence of UTIs, many of which are occult, in the 3 months after surgery for thoracolumbar IVDE. These dogs should be routinely monitored for UTI with urine culture regardless of urinalysis results.

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.

Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy.

BACKGROUND: Levetiracetam (LEV) is a common add-on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs. HYPOTHESIS/OBJECTIVES: To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs. ANIMALS: Eighteen client-owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB-BR group, n = 6). METHODS: Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area-under-the-curve (AUC) calculated to the last measured time point. RESULTS: Compared to the PB and PB-BR groups, the BR group had significantly higher peak concentration (Cmax ) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 µg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*µg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add-on treatment with phenobarbital in dogs.

Chronic and acute compressive spinal cord lesions in dogs due to intervertebral disc herniation are associated with elevation in lumbar cerebrospinal fluid glutamate concentration.

Acute injury to the central nervous system initiates a series of biochemical events that cause secondary tissue damage. The accumulation of excessive concentrations of glutamate in the extracellular space causes excitotoxic damage, and is incriminated as a mediator of this secondary tissue damage. The aim of this study was to measure the concentration of glutamate in cerebrospinal fluid (CSF) obtained from the cerebellomedullary cistern and lumbar subarachnoid space in dogs with acute and chronic compressive injuries of the cervical and thoracolumbar spinal cord, and to correlate the glutamate concentration with injury severity. The results demonstrate that focal injuries of the spinal cord do not affect the glutamate concentration in CSF taken from the cerebellomedullary cistern. However, dogs with severe, acute thoracolumbar disc herniations have two- to 10-fold increases in glutamate concentration in their lumbar CSF at intervals of >12 h after injury. Moreover, the severity of their clinical signs is directly related to the glutamate concentration. Dogs with chronic compressive thoracolumbar lesions have a two-fold elevation of CSF glutamate concentration, suggesting that excitotoxicity may also be a component of chronic spinal cord compression.

Feline ocular and cerebrospinal fluid Toxoplasma gondii-specific humoral immune responses following specific and nonspecific immune stimulation.

Toxoplasma gondii-naive cats and cats previously infected orally with T. gondii tissue cysts were inoculated with soluble tachyzoite antigens plus adjuvant or adjuvant alone. Toxoplasma gondii-specific IgM and IgG were measured in serum, aqueous humor, and cerebrospinal fluid (CSF). The Goldman-Witmer coefficient (C value) for ocular or central nervous system (CNS) antibody production was calculated for aqueous humor or CSF samples positive for T. gondii-specific antibodies. Following inoculation with adjuvant plus soluble tachyzoite antigens, ocular and CNS T. gondii-specific IgG C values increased in the three previously infected cats. Following inoculation with adjuvant, the two previously infected cats had increases in ocular and CNS T. gondii-specific IgG C values. Ocular (2/3 cats) or CNS (1/3 cats) T. gondii-specific IgG C values of over 1 were detected in some T. gondii-naive cats following inoculation with adjuvant plus soluble tachyzoite antigens. The results of this study suggest that T. gondii-specific IgG C values of over 1 in aqueous humor or CSF do not prove active ocular or CNS infection in all cats.

Neurological manifestations of Niemann-Pick disease type C in cats.

Seven Domestic shorthair cats with a lysosomal storage disorder analogous to human Niemann-Pick disease type C, from a breeding colony were studied to characterize the neurological manifestations of this disorder. Affected cats were identified by means of liver biopsies at 4 to 6 weeks of age. Neurological examinations were performed at 2 week intervals from the onset of clinical signs. All cats displayed signs referrable to the cerebellum, with a subtle intention tremor noticed initially at 8 to 12 weeks of age; the disease was rapidly progressive. The tremor became more pronounced, menace response was lost, and severe dysmetria and ataxia developed. Three cats also had signs referrable to other areas of the central nervous system. Cats died or were euthanized between 12 and 43 weeks of age. Pathological findings included accumulation of substrate within neurons throughout the central nervous system, and axonal spheroid formation. The clinical and pathological findings in these cats are comparable to those in the human form of the disease.

Development of a functional scoring system in dogs with acute spinal cord injuries.

OBJECTIVES: To develop and compare the reliability of 2 methods of scoring pelvic limb gait in dogs recovering from thoracolumbar spinal cord injuries and to use this scoring system to determine the rate and level of functional recovery of dogs with acute thoracolumbar intervertebral disk herniations. ANIMALS: 46 dogs with spinal cord injuries resulting from intervertebral disk herniations. PROCEDURE: Dogs' gaits were videotaped at different time intervals after injury. In phase 1 of the study, the stages of recovery of pelvic limb function were identified, and a numeric scoring system was devised to reflect that recovery. In phase 2, pelvic limb gait was scored by different observers, using a numeric and a visual analog scale. Intra- and interobserver coefficients of variability of both methods were compared. In phase 3, pelvic limb function was scored, using the numeric scale at various intervals after acute thoracolumbar disk herniations. RESULTS: The numeric scale was significantly more reliable than the visual analog scale when both intra- and interobserver coefficients of variability were evaluated. Dogs that were paraplegic with no deep pain sensation recovered at different rates during the first 3 months, whereas dogs that were paraplegic with deep pain sensation typically recovered within 1 month of injury. CONCLUSIONS: Pelvic limb gait of dogs recovering from thoracolumbar spinal cord injuries can be reliably quantified, using a numeric scale. This scale will facilitate the performance of clinical trials aimed at improving the outcome of acute spinal cord injuries.

Toxoplasma gondii-specific antibodies in the aqueous humor of cats with toxoplasmosis.

We decided to determine whether Toxoplasma gondii-specific IgM or IgG is produced locally or is deposited in the aqueous humor of T gondii-naive cats after primary or secondary inoculation with T gondii. Cats were orally inoculated with T gondii tissue cysts during weeks 0 and 36. Aqueous humor and serum T gondii-specific IgM and IgG were measured, using ELISA, during weeks 0, 2, 4, 6, 8, 12, 16, 20, 26, 34, 38, 40, 42, 44, 48, 56, 62, 66, and 72 after primary oral inoculation. Total immunoglobulin-based Goldmann-Witmer coefficients were calculated to verify intraocular antibody production. Toxoplasma gondii-specific IgM was not detected in the aqueous humor of any cat. Data indicate that cats have transient local production of T gondii-specific IgG in the aqueous humor after primary and secondary oral inoculations with T gondii tissue cysts. The intraocular immune response to systemic T gondii infection may signal ocular recruitment of antigen-specific lymphocytes that function independently from the general humoral response to T gondii infection. Cautious interpretation of results that suggest intraocular production of T gondii-specific IgG in cats with uveitis is warranted.