Distributed brain co-processor for tracking spikes, seizures and behaviour during electrical brain stimulation.

Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources.

Thalamic deep brain stimulation modulates cycles of seizure risk in epilepsy.

Chronic brain recordings suggest that seizure risk is not uniform, but rather varies systematically relative to daily (circadian) and multiday (multidien) cycles. Here, one human and seven dogs with naturally occurring epilepsy had continuous intracranial EEG (median 298 days) using novel implantable sensing and stimulation devices. Two pet dogs and the human subject received concurrent thalamic deep brain stimulation (DBS) over multiple months.

Glioma-associated microglia/macrophages augment tumorigenicity in canine astrocytoma, a naturally occurring model of human glioma.

Background: Glioma-associated microglia/macrophages (GAMs) markedly influence glioma progression. Under the influence of transforming growth factor beta (TGFB), GAMs are polarized toward a tumor-supportive phenotype. However, neither therapeutic targeting of GAM recruitment nor TGFB signaling demonstrated efficacy in glioma patients despite efficacy in preclinical models, underscoring the need for a comprehensive understanding of the TGFB/GAM axis.

Ethylene vinyl alcohol copolymer to treat an intracranial arteriovenous malformation in a dog.

A 6-year-old neutered male German shepherd dog was evaluated for obtundation, blindness, and bilateral exophthalmos. A magnetic resonance imaging scan of the brain was performed and identified an arteriovenous malformation (AVM) with several feeding arterial branches, and venous drainage through the cavernous sinus. Venous vessels rostral to the AVM were severely distended and extended into the retrobulbar spaces.

Semi-supervised Training Data Selection Improves Seizure Forecasting in Canines with Epilepsy.

Objective: Conventional selection of pre-ictal EEG epochs for seizure prediction algorithm training data typically assumes a continuous pre-ictal brain state preceding a seizure. This is carried out by defining a fixed duration, pre-ictal time period before seizures from which pre-ictal training data epochs are uniformly sampled. However, stochastic physiological and pathological fluctuations in EEG data characteristics and underlying brain states suggest that pre-ictal state dynamics may be more complex, and selection of pre-ictal training data segments to reflect this could improve algorithm performance.

Diagnosis and clinical outcome following surgical resection of an intracranial grade III anaplastic gemistocytic astrocytoma in a cat.

Case Summary: A 10-year-old Maine Coon cat was presented for acute onset seizures and cerebrothalamic signs. An intracranial mass, suspected to be a meningioma, was diagnosed on MRI and surgically excised. Histopathology appeared consistent with an atypical meningioma.

Circadian and multiday seizure periodicities, and seizure clusters in canine epilepsy.

Advances in ambulatory intracranial EEG devices have enabled objective analyses of circadian and multiday seizure periodicities, and seizure clusters in humans. This study characterizes circadian and multiday seizure periodicities, and seizure clusters in dogs with naturally occurring focal epilepsy, and considers the implications of an animal model for the study of seizure risk patterns, seizure forecasting and personalized treatment protocols. In this retrospective cohort study, 16 dogs were continuously monitored with ambulatory intracranial EEG devices designed for humans.

Clinicopathological characteristics of histiocytic sarcoma affecting the central nervous system in dogs.

Background: Histiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic.

Objective: To characterize the clinicopathological inflammatory features, breed predisposition, and survival in dogs with CNS HS.

Congenital myasthenic syndrome in Golden Retrievers is associated with a novel COLQ mutation.

Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that may be presynaptic, synaptic, or postsynaptic. Causative mutations have been identified in 4 breeds including the Labrador Retriever, Jack Russell Terrier, Heideterrier, and Danish Pointing Dog.

Hypothesis/objective: Clinical and genetic characterization of a neuromuscular disorder in Golden Retriever (GR) puppies.

Phenotypic Effects of Retrogenes on Intervertebral Disc Disease in Dogs.

Two retrogenes on chromosomes 12 (12-RG) and 18 (18-RG) contribute to short-limbed phenotypes in dogs. 12-RG has also been associated with intervertebral disc disease (IVDD). Both of these retrogenes were found to be widespread among dog breeds with allele frequencies ranging from 0.

Surgical decompression, with or without adjunctive therapy, for palliative treatment of primary vertebral osteosarcoma in dogs.

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy.

Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial.

Nanoparticles' enhanced permeation and retention (EPR) variations due to tumor heterogeneity in naturally occurring brain tumors are commonly neglected in preclinical nanomedicine studies. Recent pathological studies have shown striking similarities between brain tumors in humans and dogs, indicating that canine brain tumors may be a valuable model to evaluate nanoparticles' EPR in this context. We recruited canine clinical cases with spontaneous brain tumors to investigate nanoparticles' EPR in different brain tumor pathologies using surface-enhanced Raman spectroscopy (SERS).

Intracranial pressure monitoring in normal dogs using subdural and intraparenchymal miniature strain-gauge transducers.

Background: Monitoring of intracranial pressure (ICP) is a critical component in the management of intracranial hypertension. Safety, efficacy, and optimal location of microsensor devices have not been defined in dogs.

Hypothesis/objective: Assessment of ICP using a microsensor transducer is feasible in anesthetized and conscious animals and is independent of transducer location.

Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds.

Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature.

Integrating Brain Implants With Local and Distributed Computing Devices: A Next Generation Epilepsy Management System.

Brain stimulation has emerged as an effective treatment for a wide range of neurological and psychiatric diseases. Parkinson's disease, epilepsy, and essential tremor have FDA indications for electrical brain stimulation using intracranially implanted electrodes. Interfacing implantable brain devices with local and cloud computing resources have the potential to improve electrical stimulation efficacy, disease tracking, and management.

retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.

Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed ( = 0.01) and intervertebral disc disease (IVDD) across breeds ( = 4.

Biomechanical Comparison of Locking Compression Plate versus Positive Profile Pins and Polymethylmethacrylate for Stabilization of the Canine Lumbar Vertebrae.

Objective: To compare the stiffness, angular deformation, and mode of failure of lumbar vertebral column constructs stabilized with bilateral pins and polymethylmethacrylate (Pin-PMMA) or with a unilateral (left) locking compression plate (LCP) with monocortical screws.

Study Design: Ex vivo biomechanical, non-randomized.

Samples: Cadaveric canine thoracolumbar specimens (n=16).

Kinetic and kinematic gait analysis in the pelvic limbs of normal and post-hemilaminectomy Dachshunds.

Objective: To compare pelvic limb kinetic and kinematic gait parameters between Dachshunds six months following hemilaminectomy for treatment of thoracolumbar disc extrusion (post-hemilaminectomy; PHL) and Dachshunds without history and clinical evidence of spinal cord disease (control; CON).

Methods: The CON (n = 8) and PHL (n = 6) Dachshunds were recruited for objective gait evaluation. Kinetic data collected included peak vertical force (PVF), stance phase duration and swing phase duration.

COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy.

Some Devon Rex and Sphynx cats have a variably progressive myopathy characterized by appendicular and axial muscle weakness, megaesophagus, pharyngeal weakness and fatigability with exercise. Muscle biopsies from affected cats demonstrated variable pathological changes ranging from dystrophic features to minimal abnormalities. Affected cats have exacerbation of weakness following anticholinesterase dosing, a clue that there is an underlying congenital myasthenic syndrome (CMS).

Feasibility Study of Canine Epidermal Neural Crest Stem Cell Transplantation in the Spinal Cords of Dogs.

Unlabelled: This pilot feasibility study aimed to determine the outcome of canine epidermal neural crest stem cell (cEPI-NCSC) grafts in the normal spinal cords of healthy bred-for-research dogs. This included developing novel protocols for (a) the ex vivo expansion of cEPI-NCSCs, (b) the delivery of cEPI-NCSCs into the spinal cord, and (c) the labeling of the cells and subsequent tracing of the graft in the live animal by magnetic resonance imaging. A total of four million cEPI-NCSCs were injected into the spinal cord divided in two locations.

Characteristics and Survival of 121 Cats Undergoing Excision of Intracranial Meningiomas (1994-2011).

Objective: To report clinical features and outcomes of cats undergoing excision of intracranial meningiomas.

Study Design: Retrospective, multicenter case series.

Sample Population: One hundred and twenty-one cats.

Stem cells in canine spinal cord injury--promise for regenerative therapy in a large animal model of human disease.

The use of cell transplantation for spinal cord injury is a rapidly evolving field in regenerative medicine. Numerous animal models are currently being used. However, translation to human patients is still a challenging step.

Squamous cell carcinoma of the anal sac in a spotted hyena (Crocuta crocuta).

A 25-yr-old spayed female spotted hyena (Crocuta crocuta) developed intermittent right pelvic limb lameness that persisted following conservative medical therapy. No obvious musculoskeletal lesions were noted on initial physical exam; however, spinal radiography was suspicious for possible intervertebral degenerative joint disease or discospondylitis. Despite prolonged medical therapy, the lameness progressed to minimal weight bearing and marked muscle atrophy of the right pelvic limb.

Canine epidermal neural crest stem cells: characterization and potential as therapy candidate for a large animal model of spinal cord injury.

The discovery of multipotent neural crest-derived stem cells, named epidermal neural crest stem cells (EPI-NCSC), that persist postnatally in an easy-to-access location-the bulge of hair follicles-opens a spectrum of novel opportunities for patient-specific therapies. We present a detailed characterization of canine EPI-NCSC (cEPI-NCSC) from multiple dog breeds and protocols for their isolation and ex vivo expansion. Furthermore, we provide novel tools for research in canines, which currently are still scarce.

Forecasting seizures in dogs with naturally occurring epilepsy.

Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG).