Residual volume of extruded disc material and residual spinal cord compression measured on postoperative MRI do not predict neurological outcomes in dogs following decompressive surgery for thoracolumbar intervertebral disc extrusion.

Published studies on the validity of using quantitative MRI measures of pre- and postoperative spinal cord (SC) compression as prognostic indicators for dogs undergoing surgery for intervertebral disc extrusion (IVDE) are currently limited. The aim of this retrospective analytical study was to describe the volume of postoperative residual extradural material (VREM) and the ratio of the cross-sectional area (CSA) of maximum SC compression to the CSA of SC in a compression-free intervertebral space as MRI measures of preoperative and postoperative compression (residual spinal cord compression, RSCC), and to compare these measures between the neurological outcome in a group of dogs. Inclusion criteria were dogs that underwent surgery for thoracolumbar IVDE, were imaged pre- and immediately postoperatively by MRI, and had a neurological follow-up examination 2 to 5 weeks postoperatively. Two blinded observers independently performed measurements in pre- and postoperative MRI studies. Dogs were classified into positive outcome (PO) and negative outcome (NO) groups based on follow-up neurologic examination scores. Seventeen dogs were included (12 PO, 5 NO). Interobserver agreement for MRI measurements was good to excellent (ICCs: 0.76-0.97). The prevalence of residual extradural material in postoperative MRI studies was 100%. No significant differences in mean preoperative SC compression, mean RSCC, mean SC decompression, or VREM were found between outcome groups (P = .25; P = .28; P = .91, P = .98). In conclusion, neither postoperative VREM nor RSCC could predict successful neurological outcomes.

Evaluation of different methods of environmental enrichment to control anxiety in dogs undergoing hemilaminectomy after acute intervertebral disc extrusion: a randomized double-blinded study.

Objective: The goal of this randomized, double-blinded, placebo-controlled study was to evaluate the effect of environmental enrichment (EE) on post-operative pain and anxiety in dogs following hemilaminectomy for acute intervertebral disc extrusion (IVDE). Methods: Twenty healthy client-owned dogs undergoing a hemilaminectomy for IVDE with the same immediate post-operative analgesia protocol were randomly assigned to either the EE or standard environment (SE) group post-operatively. Recovery was achieved in an intensive care room (SE) or a separate quiet room (EE) equipped with white noise and classical music. EE dogs were also exposed to dog-appeasing pheromones, essential oil scents, and positive human interactions and were provided meals through food toys. A blinded evaluator assessed all dogs using the modified Glasgow Composite Pain Scale (mGCPS) on presentation and at several time points post-operatively. A rescue injection of the opioid methadone was given to the dogs with an mGCPS score of ≥5/20. Dogs received the antidepressant trazodone when anxious behaviors (5 mg/kg) were observed. The mGCPS scores, the latencies to receive the first methadone and trazodone doses and to eat the first meal, the number of methadone and trazodone doses, and the number of meals ingested in the first 24 and 48 h post-surgery were compared using Wilcoxon tests, and Benjamini-Hochberg correction for false discovery rate was applied. Results: Although median mGCPS scores did not differ between the groups, compared to SE dogs (n = 10), EE dogs (n = 6) received trazodone earlier (p = 0.019), were administered fewer methadone injections at 24 h (p = 0.043), and ate more at 48 h post-surgery (p = 0.007). Therefore, EE and anti-anxiety medications could be beneficial in improving the wellbeing of dogs post-operatively.

Recording and manipulation of vagus nerve electrical activity in chronically instrumented unanesthetized near term fetal sheep.

BACKGROUND: The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli. This is due to the unique amenability of the unanesthetized fetal sheep to the surgical placement and maintenance of catheters and electrodes, allowing repetitive blood sampling, substance injection, recording of bioelectrical activity, application of electric stimulation, and in vivo organ imaging. Recently, there has been growing interest in the pleiotropic effects of vagus nerve stimulation (VNS) on various organ systems such as innate immunity and inflammation, and metabolism. There is no approach to study this in utero and corresponding physiological understanding is scarce. NEW METHOD: Based on our previous presentation of a stable chronically instrumented unanesthetized fetal sheep model, here we describe the surgical instrumentation procedure allowing successful implantation of a cervical uni- or bilateral VNS probe with or without vagotomy. RESULTS: In a cohort of 68 animals, we present the changes in blood gas, metabolic, and inflammatory markers during the postoperative period. We detail the design of a VNS probe which also allows recording from the fetal nerve. We also present an example of fetal vagus electroneurogram (VENG) recorded from the VNS probe and an analytical approach to the data. COMPARISON WITH EXISTING METHODS: This method represents the first implementation of fetal VENG/VNS in a large pregnant mammalian organism. CONCLUSIONS: This study describes a new surgical procedure allowing to record and manipulate chronically fetal vagus nerve activity in an animal model of human pregnancy.

Agreement of Magnetic Resonance Imaging With Computed Tomography in the Assessment for Acute Skull Fractures in a Canine and Feline Cadaver Model.

Computed tomography (CT) is the imaging modality of choice to evaluate patients with acute head trauma. However, magnetic resonance imaging (MRI) may be chosen in select cases. The objectives of this study were to evaluate the agreement of MRI with CT in the assessment for presence or absence of acute skull fractures in a canine and feline cadaver model, compare seven different MRI sequences (T1-W, T2-W, T2-FLAIR, PD-W, T2*-W, "SPACE" and "VIBE"), and determine agreement of four different MRI readers with CT data. Pre- and post-trauma CT and MRI studies were performed on 10 canine and 10 feline cadaver heads. Agreement of MRI with CT as to presence or absence of a fracture was determined for 26 individual osseous structures and four anatomic regions (cranium, face, skull base, temporomandibular joint). Overall, there was 93.5% agreement in assessing a fracture as present or absent between MRI and CT, with a significant difference between the pre and post trauma studies (99.4 vs. 87.6%; p < 0.0001; OR 0.042; 95% CI 0.034-0.052). There was no significant difference between dogs and cats. The agreement for the different MRI sequences with CT ranged from 92.6% (T2*-W) to 94.4% (PD-W). There was higher agreement of MRI with CT in the evaluation for fractures of the face than other anatomic regions. Agreement with CT for individual MRI readers ranged from 92.6 to 94.7%. A PD-W sequence should be added to the MR protocol when evaluating the small animal head trauma patient.

Monitoring Fetal Electroencephalogram Intrapartum: A Systematic Literature Review.

Background: Studies about the feasibility of monitoring fetal electroencephalogram (fEEG) during labor began in the early 1940s. By the 1970s, clear diagnostic and prognostic benefits from intrapartum fEEG monitoring were reported, but until today, this monitoring technology has remained a curiosity. Objectives: Our goal was to review the studies reporting the use of fEEG including the insights from interpreting fEEG patterns in response to uterine contractions during labor. We also used the most relevant information gathered from clinical studies to provide recommendations for enrollment in the unique environment of a labor and delivery unit. Data Sources: PubMed. Eligibility Criteria: The search strategy was: ("fetus"[MeSH Terms] OR "fetus"[All Fields] OR "fetal"[All Fields]) AND ("electroencephalography"[MeSH Terms] OR "electroencephalography"[All Fields] OR "eeg"[All Fields]) AND (Clinical Trial[ptyp] AND "humans"[MeSH Terms]). Because the landscape of fEEG research has been international, we included studies in English, French, German, and Russian. Results: From 256 screened studies, 40 studies were ultimately included in the qualitative analysis. We summarize and report features of fEEG which clearly show its potential to act as a direct biomarker of fetal brain health during delivery, ancillary to fetal heart rate monitoring. However, clinical prospective studies are needed to further establish the utility of fEEG monitoring intrapartum. We identified clinical study designs likely to succeed in bringing this intrapartum monitoring modality to the bedside. Limitations: Despite 80 years of studies in clinical cohorts and animal models, the field of research on intrapartum fEEG is still nascent and shows great promise to augment the currently practiced electronic fetal monitoring. Prospero Number: CRD42020147474.

Magnetic Resonance Imaging Findings in 13 Neurologic Pot-Bellied Pigs.

This study reports the magnetic resonance imaging (MRI) findings in 13 pot-bellied pigs presented to our institution with neurological deficits. Nine pigs had abnormal MRI findings (7 with spinal cord localization and 2 with brain localization), with three of them having histopathological confirmation of the diagnoses. MRI diagnoses included a myopathy suspected to be secondary to Erysipelothrix rhusiopathiae, a round cell neoplasia involving the vertebral canal, myelomalacia, a cervical cyst like extradural lesion, pelvic fracture with secondary cauda equina involvement, two cases of fibrocartilaginous embolism or acute non-compressive nucleus pulposus extrusion, multifocal brain infarcts, and a cystic fourth ventricle dilation resulting in obstructive hydrocephalus and syringomyelia. Four pigs had normal MRI studies, with one of them ultimately diagnosed with idiopathic vestibular disease. This retrospective study illustrates the wide variety of diagnoses achieved with MRI of the head or vertebral column in pigs, several of them having never been described in this species. Some of the conditions identified had a good outcome. This justifies using MRI as an ante-mortem diagnostic tool as it can provide relevant information about the prognosis which can significantly influence treatment recommendations. Our findings suggest that MRI should be considered as a valuable imaging modality, when feasible, in pigs with neurological deficits.

Risk factors associated with progressive myelomalacia in dogs with complete sensorimotor loss following intervertebral disc extrusion: a retrospective case-control study.

BACKGROUND: Progressive myelomalacia (PMM) is a usually fatal complication of acute intervertebral disc extrusion (IVDE) in dogs but its risk factors are poorly understood. The objective of this retrospective case-control study was to identify risk factors for PMM by comparing dogs with complete sensorimotor loss following IVDE that did and did not develop the disease after surgery. We also investigated whether any risk factors for PMM influenced return of ambulation. Medical records of client-owned dogs with paraplegia and loss of pain perception that underwent surgery for IVDE from 1998 to 2016, were reviewed. Dogs were categorized as PMM yes or no based on clinical progression or histopathology. Walking outcome at 6 months was established. Signalment, onset and duration of signs (categorized), steroids, non-steroidal anti-inflammatory drugs (yes or no), site of IVDE (lumbar intumescence or thoracolumbar) and longitudinal extent of IVDE were retrieved and their associations with PMM and walking outcome were examined using logistic regression. RESULTS: One hundred and ninety seven dogs were included, 45 with and 152 without PMM. A 6-month-outcome was available in 178 dogs (all 45 PMM dogs and 133 control dogs); 86 recovered walking (all in the control group). Disc extrusions at the lumbar intumescence were associated with PMM (p = 0.01, OR: 3.02, CI: 1.3-7.2). Surgery performed more than 12 h after loss of ambulation was associated with PMM (OR = 3.4; CI = 1.1-10.5, p = 0.03 for 12-24 h and OR = 4.6; CI = 1.3-16.6, p = 0.02 for the > 24 h categories when compared with the ≤12 h category). Treatment with corticosteroids was negatively associated with PMM (OR: 3.1; CI: 1.3-7.6, p = 0.01). The only variable to affect walking outcome was longitudinal extent of IVDE (OR = 2.6; CI = 1.3-5.3, p = 0.006). CONCLUSION: Dogs with lumbar intumescence IVDE are at increased risk of PMM. Timing of surgery and corticosteroid use warrant further investigations. PMM and recovery of walking are influenced by different factors.

Presence of cerebrospinal fluid antibodies associated with autoimmune encephalitis of humans in dogs with neurologic disease.

BACKGROUND: Presumed autoimmune diseases affecting the central nervous system (CNS) of dogs are common. In people, antibodies against neuronal cell surface antigens that are associated with a wide variety of neurological syndromes have been identified. The presence of cerebrospinal fluid (CSF) autoantibodies that target neuronal cell surface proteins has not been reported in dogs with neurologic disorders. OBJECTIVES: Autoantibodies to neuronal cell surface antigens can be found in the CSF of dogs with inflammatory CNS disease. Our aim was to determine whether 6 neuronal cell surface autoantibodies were present in the CSF of dogs diagnosed with inflammatory and noninflammatory CNS disease. ANIMALS: Client-owned dogs with CNS disease and complete diagnostic evaluation including magnetic resonance imaging and CSF analysis were included. One healthy dog was included as a negative control. METHODS: Cerebrospinal fluid was tested for 6 antigenic targets with a commercially available indirect immunofluorescence assay test kit. RESULTS: There were 32 dogs with neurological disease, 19 diagnosed with inflammatory disease (encephalitis and meningitis), 10 with noninflammatory disease (neoplasia, intervertebral disk disease, degenerative myelopathy, and epilepsy), 2 with no diagnosis, and 1 with neoplasia and meningoencephalitis. Anti-N-methyl-d-aspartate receptor 1 (NMDAR1) antibodies were detected in 3 dogs (3/32; 9.38%). All 3 dogs responded to treatment of meningoencephalomyelitis of unknown etiology (MUE). CONCLUSIONS AND CLINICAL IMPORTANCE: Further evaluation of the prevalence and clinical relevance of CSF and serum antibodies to neuronal cell surface antigens is warranted. Defining antigenic targets associated with encephalitis in dogs might allow diagnostic categorization of MUE antemortem.

Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad.

Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered "nontoxic" with acute oral median lethal doses (LD50) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6-19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.

Gabapentin reverses central pain sensitization following a collagenase-induced intrathalamic hemorrhage in rats.

PURPOSE: The treatment of central neuropathic pain remains amongst the biggest challenges for pain specialists. The main objective of this study was to assess gabapentin (GBP), amitriptyline (AMI), and carbamazepine (CARBA) for the treatment of a rodent central neuropathic pain model. METHODS: Male Sprague Dawley rats were trained on the rotarod, Hargreaves, Von Frey and acetone behavioral tests, and baseline values were obtained prior to surgery. A stereotaxic injection of either a collagenase solution or saline was made in the right ventral posterolateral thalamic nucleus. The rats were tested on days 2, 4, 8, and 11 postsurgery. They were retested at regular intervals from day 15 to day 25 postsurgery, after oral administration of either the vehicle (n=7 and n=8 rats with intracerebral injections of collagenase and saline, respectively) or the different drugs (GBP [60 mg/kg], AMI [10 mg/kg], CARBA [100 mg/kg]; n=8 rats/drug). RESULTS: A significant decrease in the mechanical thresholds and no change in heat threshold were observed in both hind limbs in the collagenase group, as we had previously shown elsewhere. Reversal of the mechanical hypersensitivity was achieved only with GBP (P<0.05). AMI and CARBA, at the dosages used, failed to show any effect on mechanical thresholds. Transient cold allodynia was observed in some collagenase-injected rats but failed to be statistically significant. CONCLUSION: Intrathalamic hemorrhaging in the ventrolateral thalamic nucleus induced a bilateral mechanical allodynia, which was reversed by GBP but not AMI or CARBA.

Pharmacokinetics of ketamine and xylazine in young and old Sprague-Dawley rats.

To compare the pharmacokinetics of coadministered intraperitoneal ketamine and xylazine in young (8 to 10 wk; n = 6) and old rats (2 to 2.4 y; n = 6), blood samples obtained at 15 and 30 min and 1, 2, and 4 h after drug administration were analyzed by HPLC-tandem mass spectrometry. In both groups, the withdrawal reflex was absent during anesthesia and was present at 1.1 (± 0.2) and 2.6 (± 0.7) h after drug administration in young and old rats, respectively, with the first voluntary movement at 1.5 ± 0.2 and 4.9 ± 1.0 h. Drug availability of ketamine and xylazine was 6.0 and 6.7 times greater, respectively, in old than young rats. The rate constant of elimination of both drugs was greatly decreased and the elimination half-life was significantly greater in old compared with young rats. In conclusion, age and associated factors affect the availability of ketamine and xylazine when coadministered to attain clinical anesthesia, changing the pharmacokinetics of these drugs and prolonging anesthesia duration and recovery times with aging. Compared with their young counterparts, aged rats required much higher doses to attain a similar level of anesthesia. Finally, the long half-life of both ketamine and xylazine, when coadministered to old rats, may be a factor in research protocols because residual plasma concentrations could still be present for as long as 3 and 5 d, respectively, after administration.

Bilateral central pain sensitization in rats following a unilateral thalamic lesion may be treated with high doses of ketamine.

BACKGROUND: Central post-stroke pain is a neuropathic pain condition caused by a vascular lesion, of either ischemic or hemorrhagic origin, in the central nervous system and more precisely involving the spinothalamocortical pathway responsible for the transmission of painful sensations. Few animal models have been developed to study this problem. The objectives of this study were to evaluate different modalities of pain in a central neuropathic pain rat model and to assess the effects of ketamine administered at different doses. Animals were evaluated on the rotarod, Hargreaves, Von Frey and acetone tests. A very small hemorrhage was created by injecting a collagenase solution in the right ventral posterolateral thalamic nucleus. Following the establishment of the neuropathy, ketamine was evaluated as a therapeutic drug for this condition. RESULTS: Histopathological observations showed a well localized lesion with neuronal necrosis and astrocytosis following the collagenase injection that was localized within the VPL. No significant change in motor coordination was observed following surgery in either the saline or collagensae groups. In the collagenase group, a significant decrease in mechanical allodynia threshold was observed. A sporadic and transient cold allodynia was also noted. No thermal hyperalgesia was seen following the collagenase injection. Ketamine was then tested as a potential therapeutic drug. A significant decrease in motor coordination was seen only following the administration of 25 mg/kg of ketamine in both groups. An alleviation of mechanical allodynia was achieved only with the high ketamine dose. The minimal effective ketamine serum concentration (150 ng/mL) was only achieved in animals that received 25 mg/kg. CONCLUSIONS: An intrathalamic hemorrhage induced a bilateral mechanical allodynia in rats. Cold hyperalgesia was observed in 60% of these animals. Mechanical allodynia was alleviated with high doses of ketamine which corresponded with therapeutic plasmatic concentrations.

Dissociable control of impulsivity in rats by dopamine d2/3 receptors in the core and shell subregions of the nucleus accumbens.

Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intra-NAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction.