Arcuate fasciculus and pre-reading language development in children with prenatal alcohol exposure

IntroductionPrenatal alcohol exposure (PAE) contributes to widespread neurodevelopmental challenges, including reading, and has been associated with altered white matter. Here, we aimed to investigate whether arcuate fasciculus (AF) development is associated with pre-reading language skills in young children with PAE.MethodsA total of 51 children with confirmed PAE (25 males; 5.6 ± 1.1 years) and 116 unexposed controls (57 males; 4.6 ± 1.2 years) underwent longitudinal diffusion tensor imaging (DTI), for a total of 111 scans from participants with PAE and 381 scans in the unexposed control group. We delineated the left and right AF and extracted mean fractional anisotropy (FA) and mean diffusivity (MD). Pre-reading language ability was assessed using age-standardized phonological processing (PP) and speeded naming (SN) scores of the NEPSY-II. Linear mixed effects models were run to determine the relationship between diffusion metrics and age, group, sex, and age-by-group interactions, with subject modeled as a random factor. A secondary mixed effect model analysis assessed the influence of white matter microstructure and PAE on pre-reading language ability using diffusion metric-by-age-by-group interactions, with 51 age- and sex-matched unexposed controls.ResultsPhonological processing (PP) and SN scores were significantly lower in the PAE group (p < 0.001). In the right AF, there were significant age-by-group interactions for FA (p < 0.001) and MD (p = 0.0173). In the left AF, there was a nominally significant age-by-group interaction for MD that failed to survive correction (p = 0.0418). For the pre-reading analysis, a significant diffusion-by-age-by-group interaction was found for left FA (p = 0.0029) in predicting SN scores, and for the right FA (p = 0.00691) in predicting PP scores.DiscussionChildren with PAE showed altered developmental trajectories for the AF, compared with unexposed controls. Children with PAE, regardless of age, showed altered brain-language relationships that resembled those seen in younger typically developing children. Our findings support the contention that altered developmental trajectories in the AF may be associated with functional outcomes in young children with PAE

Pharmacokinetics of Single-Dose Oral Pregabalin Administration in Normal Cats

Objective: To describe the pharmacokinetic parameters of oral pregabalin in normal cats after single oral dosing.Animals: Six healthy adult research cats.Procedures: Following sedation and indwelling catheter placement, one oral (4 mg/kg) dose of pregabalin was administered. Blood samples were collected at 0, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 h after administration. Plasma pregabalin concentrations were measured by high-performance liquid chromatography and subjected to pharmacokinetic analysis using commercial software.Results: Four of six cats developed moderate sedation after pregabalin administration. The peak pregabalin concentration was 8.3 ± 1.6 μg/ml which occurred at 2.9 ± 1.2 h. Elimination half-life was 10.4 ± 2.6 h and area under the curve was 133.9 ± 71.5 μg-h/ml. Time above the minimum therapeutic concentration for seizure control in dogs and people (2.8 μg/ml) was 17.6 ± 6.2 h. Using these data, predicted minimum, maximum and average steady state concentrations were calculated for 12 and 24 h dosing intervals.Conclusions and Clinical Relevance: Pregabalin (4 mg/kg) administered orally to cats results in plasma concentrations within the range considered to be efficacious for seizure control in dogs and humans between 1.5 and at least 12 h. Because of moderate sedative side effects in the majority of cats at this dose and high calculated maximum steady state concentrations, a lower dose, given more frequently (1–2 mg/kg q 12 h), should be evaluated in prospective clinical studies

Little brainiacs and big dummies: Are we selecting for stupid, stout or small dogs?

Background: Brain size has been associated with intelligence of various orders and families of animals, leading to the concept of encephalization. Brain size scales with body weight between species within mammals to approximately the 0.67 power. However, within species, this scaling exponent appears to be much smaller (approximately 0.27 power). Aim: We examined whether this relationship has persisted in dogs over the 120 years since this was originally observed. Methods: Comparative cross-sectional study of magnetic resonance imaging (MRI) data obtained from 127 dogs, compared to historical data from 157 dogs and 24 non-dog canid species. Results: Brain size in dogs measured by MRI had a scaling exponent virtually identical to that observed previously (0.24 vs 0.26). However, the proportionality constant was smaller, suggesting that dogs in the study cohort had relatively smaller brains than the historical cohort. Absolute brain size appeared to have both a lower and upper limit in dogs. When compared to non-dogs canids, the most appropriate “representative” size for a “typical dog” when examining allometric scaling across Canidae appeared to be approximately 10-15 kg. Conclusions: We interpreted the slight reduction in relative brain size to be a function of increased obesity in the study cohort compared to dogs examined 120 years ago. Further, we suggest that dog brains have a finite lower size limit. Finally, concepts of encephalization should not be applied to dogs

A Subset of Dogs with Presumptive Idiopathic Epilepsy Show Hippocampal Asymmetry: A Volumetric Comparison with Non-Epileptic Dogs Using MRI

MRI-acquired volumetric measurements from 100 dogs with presumptive idiopathic epilepsy (IE) and 41 non-epileptic (non-IE) dogs were used to determine if hippocampal asymmetry exists in the IE as compared to the non-IE dogs. MRI databases from three institutions were searched for dogs that underwent MRI of the brain and were determined to have IE and those that were considered non-IE dogs. Volumes of the right and left hippocampi were measured using Mimics® software. Median hippocampal volumes of IE and non-IE dogs were 0.47 and 0.53 cm3, respectively. There was no significant difference in overall hippocampal volume between IE and non-IE dogs; however, IE dogs had greater hippocampal asymmetry than non-IE dogs (P < 0.012). A threshold value of 1.16 from the hippocampal ratio had an 85% specificity for identifying IE-associated asymmetry. Thirty five percent of IE dogs had a hippocampal ratio >1.16. Asymmetry was not associated with any particular hemisphere (P = 0.67). Our study indicates that hippocampal asymmetry occurs in a subset of dogs with presumptive idiopathic/genetic epilepsy, suggesting a structural etiology to some cases of IE

Histopathologic characteristics of biopsies from dogs undergoing surgery with concurrent gross splenic and hepatic masses: 125 cases (2012–2016)

Abstract Objective To investigate the histopathologic characteristics of concurrent splenic and liver masses in dogs undergoing splenectomy and liver mass biopsy/resection. Medical records of 125 client-owned dogs found to have splenic mass or masses and a liver mass or masses during surgery were examined. Signalment (age, sex, breed), body weight, and results of histopathology were recorded for all dogs. Results Twenty-seven percent (34/125) of the dogs in this study had no evidence of malignancy in either the liver or the spleen. Sixty of 125 dogs (48.0%) had malignancy in the spleen and liver, and 56 (56/60, 93.3%) of those dogs had the same malignancy in both organs. Signalment was similar to that in other reports of splenic pathology. In this clinical population of dogs, 27% of dogs with concurrent gross splenic and liver masses discovered intraoperatively had benign lesions in both locations and therefore had a favorable prognosis

Interthalamic adhesion size in aging dogs with presumptive spontaneous brain microhemorrhages: a comparative retrospective MRI study of dogs with and without evidence of canine cognitive dysfunction

Objective Spontaneous brain microhemorrhages in elderly people are present to some degree in Alzheimer’s disease patients but have been linked to brain atrophy in the absence of obvious cognitive decline. Brain microhemorrhages have recently been described in older dogs, but it is unclear whether these are associated with brain atrophy. Diminution of interthalamic adhesion size-as measured on MRI or CT-has been shown to be a reliable indicator of brain atrophy in dogs with canine cognitive dysfunction (CCD) in comparison with successfully aging dogs. We hypothesized that aging dogs with brain microhemorrhages presenting for neurologic dysfunction but without obvious features of cognitive decline would have small interthalamic adhesion measurements, like dogs with CCD, compared with control dogs. The objective of this study was to compare interthalamic adhesion size between three groups of aging (>9 years) dogs: (1) neurologically impaired dogs with presumptive spontaneous brain microhemorrhages and no clinical evidence of cognitive dysfunction (2) dogs with CCD (3) dogs without clinical evidence of encephalopathy on neurologic examination (control dogs). MR images from 52 aging dogs were reviewed and measurements were obtained of interthalamic adhesion height (thickness) and mid-sagittal interthalamic adhesion area for all dogs, in addition to total brain volume. Interthalamic adhesion measurements, either absolute or normalized to total brain volume were compared between groups. Signalment (age, breed, sex), body weight, presence and number of SBMs, as well as other abnormal MRI findings were recorded for all dogs. Results All interthalamic adhesion measurement parameters were significantly (P < 0.05) different between control dogs and affected dogs. Both dogs with cognitive dysfunction (12/15; 80%) and dogs with isolated brain microhemorrhages had more microhemorrhages than control dogs (3/25; 12%). Affected dogs without cognitive dysfunction had significantly more microhemorrhages than dogs with cognitive dysfunction. In addition to signs of cognitive impairment for the CCD group, main clinical complaints for SBM and CCD dogs were referable to central vestibular dysfunction, recent-onset seizure activity, or both. Geriatric dogs with spontaneous brain microhemorrhages without cognitive dysfunction have similar MRI abnormalities as dogs with cognitive dysfunction but may represent a distinct disease category

Transnasal, endoscopically guided skull-based surgery by pharyngotomy for mass removal from the sphenopalatine sinus in a horse

OBJECTIVE: To report a transnasal, endoscopically guided ventral surgical approach for accessing the cranial and caudal segments of the sphenopalatine sinus for mass removal in a horse. STUDY DESIGN: Case report. ANIMAL: Adult horse with acute onset blindness referable to a soft tissue mass within the sphenopalatine sinus. CLINICAL REPORT: A 7-year-old Warmblood gelding presented with a history of running into a fence and falling. No neurologic signs were identified at initial examination but acute blindness was noted 3 weeks later. On computed tomography (CT) the sphenopalatine sinus was filled with a large homogeneous mass with poor contrast enhancement that extended dorsally with thinning to the dorsal cortex of the sphenoid bone, just rostral to the entrance of the optic canals into the cranial cavity. Surgical access to the sphenopalatine sinus was achieved using a transnasal, endoscopically guided ventral pharyngotomy approach and the mass lesion was removed. A presumptive diagnosis of chondroma was made based on histopathology. The horse recovered well from surgery, and although it has not regained vision as of 6.5 years postoperatively, the disease has not progressed. CONCLUSION: Transnasal, endoscopically-guided ventral surgical access to the sphenopalatine sinus is possible in horses and may improve access in horses with disease extending caudally beyond the palatine portion of the sinus. Use of smaller diameter or specialized instruments, such as various endoscopic bone cutting instruments, and CT image guidance may improve sinus access by this route