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1.
J Vet Intern Med ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842297

ABSTRACT

BACKGROUND: Epilepsy in dogs and humans is associated with blood-brain barrier (BBB) dysfunction (BBBD), which may involve dysfunction of tight junction (TJ) proteins, matrix metalloproteases, and astrocytes. Imaging techniques to assess BBB integrity, to identify potential treatment strategies, have not yet been evaluated in veterinary medicine. HYPOTHESIS: Some dogs with idiopathic epilepsy (IE) will exhibit BBBD. Identifying BBBD may improve antiepileptic treatment in the future. ANIMALS: Twenty-seven dogs with IE and 10 healthy controls. METHODS: Retrospective, prospective cohort study. Blood-brain barrier permeability (BBBP) scores were calculated for the whole brain and piriform lobe of all dogs by using dynamic contrast enhancement (DCE) magnetic resonance imaging (MRI) and subtraction enhancement analysis (SEA). Matrix metalloproteinase-9 (MMP9) activity in serum and cerebrospinal fluid (CSF) was measured and its expression in the piriform lobe was examined using immunofluorescent staining. Gene expression of TJ proteins and astrocytic transporters was analyzed in the piriform lobe. RESULTS: The DCE-MRI analysis of the piriform lobe identified higher BBBP score in the IE group when compared with controls (34.5% vs 26.5%; P = .02). Activity and expression of MMP9 were increased in the serum, CSF, and piriform lobe of IE dogs as compared with controls. Gene expression of Kir4.1 and claudin-5 in the piriform lobe of IE dogs was significantly lower than in control dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Our findings demonstrate BBBD in dogs with IE and were supported by increased MMP9 activity and downregulation of astrocytic potassium channels and some TJ proteins. Blood brain barrier dysfunction may be a novel antiepileptic therapy target.

2.
J Zoo Wildl Med ; 55(1): 277-284, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38453512

ABSTRACT

Two female (FL 1, FL 2) and one male (ML) 11-wk-old, intact, captive African lion cubs (Panthera leo leo) were presented with a history of mild vestibular signs. Initial serum vitamin A concentrations were low (140 nmol/L) for ML. Calvarial hyperostosis was confirmed using computed tomography (CT) of the head and cervical vertebrae in each cub. CT measurements were adapted in relation to the skull width. ML showed the most pronounced thickening of the tentorium cerebelli and occipital bone, represented by a tentorium cerebelli to skull width ratio (TCR) of 0.08 (FL 1: 0.06, FL 2: 0.05) and a basisphenoid to skull width ratio (BBR) of 0.07 (FL 1: 0.06, FL 2: 0.04). Magnetic resonance imaging (MRI) revealed cerebellar herniation and cervical intramedullary T2-weighted hyperintensity from C1, extending caudally for at least two cervical vertebrae in all cubs. Treatment was initiated with subcutaneous vitamin A supplementation and feeding of whole carcasses. Improvement in ataxia was noticed 3 wk later. Follow-up CT and MRI examinations were performed in ML after 3 and 8 mon. The affected bones appeared slightly less thickened and TCR and BBR had decreased to 0.05 after 3 mon. The cerebellum remained mildly herniated, accompanied by amelioration of cervical T2w hyperintensities. After 8 mon, evaluation and diagnostic imaging revealed further improvement regarding the neurologic status and measurements (TCR 0.05, BBR 0.04) despite persistence of a subtle cerebellar herniation. In conclusion, bone remodeling and improvement in clinical signs may be achievable in young lion cubs presented with calvarial hyperostosis and may be attributable to high-dose vitamin A supplementation.


Subject(s)
Craniofacial Abnormalities , Hyperostosis , Lions , Vitamin A Deficiency , Male , Female , Animals , Vitamin A/therapeutic use , Vitamin A Deficiency/veterinary , Encephalocele/complications , Encephalocele/drug therapy , Encephalocele/veterinary , Dietary Supplements , Receptors, Antigen, T-Cell
3.
J Vet Intern Med ; 37(2): 606-617, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36847997

ABSTRACT

BACKGROUND: Blood-brain barrier (BBB) permeability can be assessed quantitatively using advanced imaging analysis. HYPOTHESIS/OBJECTIVES: Quantification and characterization of blood-brain barrier dysfunction (BBBD) patterns in dogs with brain tumors can provide useful information about tumor biology and assist in distinguishing between gliomas and meningiomas. ANIMALS: Seventy-eight hospitalized dogs with brain tumors and 12 control dogs without brain tumors. METHODS: In a 2-arm study, images from a prospective dynamic contrast-enhanced (DCE; n = 15) and a retrospective archived magnetic resonance imaging study (n = 63) were analyzed by DCE and subtraction enhancement analysis (SEA) to quantify BBB permeability in affected dogs relative to control dogs (n = 6 in each arm). For the SEA method, 2 ranges of postcontrast intensity differences, that is, high (HR) and low (LR), were evaluated as possible representations of 2 classes of BBB leakage. BBB score was calculated for each dog and was associated with clinical characteristics and tumor location and class. Permeability maps were generated, using the slope values (DCE) or intensity difference (SEA) of each voxel, and analyzed. RESULTS: Distinctive patterns and distributions of BBBD were identified for intra- and extra-axial tumors. At a cutoff of 0.1, LR/HR BBB score ratio yielded a sensitivity of 80% and specificity of 100% in differentiating gliomas from meningiomas. CONCLUSIONS AND CLINICAL IMPORTANCE: Blood-brain barrier dysfunction quantification using advanced imaging analyses has the potential to be used for assessment of brain tumor characteristics and behavior and, particularly, to help differentiating gliomas from meningiomas.


Subject(s)
Brain Neoplasms , Dog Diseases , Glioma , Meningeal Neoplasms , Meningioma , Dogs , Animals , Blood-Brain Barrier/diagnostic imaging , Blood-Brain Barrier/pathology , Meningioma/diagnostic imaging , Meningioma/veterinary , Retrospective Studies , Prospective Studies , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/veterinary , Brain Neoplasms/complications , Magnetic Resonance Imaging/veterinary , Glioma/diagnostic imaging , Glioma/veterinary , Glioma/complications , Meningeal Neoplasms/complications , Meningeal Neoplasms/pathology , Meningeal Neoplasms/veterinary , Contrast Media , Dog Diseases/diagnostic imaging
4.
J Am Vet Med Assoc ; 261(3): 384-390, 2022 12 07.
Article in English | MEDLINE | ID: mdl-36476412

ABSTRACT

OBJECTIVE: To evaluate the efficiency and safety of a doramectin-based treatment protocol in dogs affected by intraspinal spirocercosis (Spirocerca lupi). ANIMALS: Client-owned dogs that were admitted to a veterinary hospital during 2021 to 2022 with acute onset of neurological signs and diagnosed with intraspinal spirocercosis. All dogs underwent complete neurological evaluation, CSF analysis, PCR confirmation of CNS S lupi infection, and follow-up evaluation of at least 6 months. PROCEDURES: Upon diagnosis, dogs were treated with doramectin at a dose of 400 µg/kg, SC, q 24 h for 3 consecutive days, followed by the same dose once a week for 6 weeks. Prednisone was administered at a dose of 1 mg/kg, PO, q 24 h and tapered every 3 days. Antimicrobial clindamycin was administered at a dose of 12.5 mg/kg, PO, q 12 h for 7 days to reduce the risk of secondary spinal cord infection. Short- and long-term outcomes (1 week to 56 months) were recorded. RESULTS: 8 dogs fulfilled the inclusion criteria, 7 of which presented with neurological deficits and 1 with cervical pain. Initiation of treatment was associated with stopping the deterioration in 7 of 8 dogs. Seven dogs improved and 6 recovered ambulation. One dog was euthanized due to lack of improvement. Six of the recovered dogs were still ataxic on the last follow-up examination at 6 to 56 months. No adverse effects of the drug were noted. CLINICAL RELEVANCE: Frequent administration of doramectin was found to be safe and effective in preventing neurological deterioration in dogs with intraspinal spirocercosis.


Subject(s)
Dog Diseases , Thelazioidea , Dogs , Animals , Ivermectin/pharmacology , Ivermectin/therapeutic use , Polymerase Chain Reaction/veterinary , Clinical Protocols , Dog Diseases/diagnosis
5.
J Vet Diagn Invest ; 34(4): 684-688, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35459409

ABSTRACT

Protothecosis, an infectious disease caused by the green algae Prototheca zopfii and P. wickerhamii, occurs sporadically in domestic animals and humans. Diagnosis of CNS protothecosis is based on neurologic signs that indicate multifocal nervous system lesions and that follow a period of chronic diarrhea and weight loss, cytologic observation of algae in fecal culture or histopathology, and detection of the agent by PCR assay of infected tissues. Here, we report a case of a paraparetic dog with CNS protothecosis that was diagnosed definitively antemortem using CSF cytology, PCR, and DNA sequencing. A 4-y-old mixed-breed dog developed progressive paraparesis that followed weight loss and diarrhea. CSF analysis revealed marked eosinophilic pleocytosis. Prototheca organisms were detected by microscopic examination of the CSF, and speciated as P. zopfii by CSF PCR and DNA sequencing. Other possible causes of paraparesis were ruled out using computed tomography, serology, and CSF PCR. The dog's condition deteriorated despite treatment, developing forebrain and central vestibular system clinical signs, and it was euthanized at the owner's request. Postmortem examination was declined. Our findings indicate that when CNS protothecosis is suspected, antemortem diagnosis can be made using CSF analysis and a PCR assay.


Subject(s)
Dog Diseases , Infections , Prototheca , Animals , Diarrhea/veterinary , Dog Diseases/diagnosis , Dog Diseases/pathology , Dogs , Infections/diagnosis , Infections/pathology , Infections/veterinary , Paraparesis/veterinary , Plant Breeding , Prototheca/genetics , Skin Diseases, Infectious , Spinal Cord/pathology , Weight Loss
6.
J Vet Intern Med ; 36(2): 702-712, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35285550

ABSTRACT

BACKGROUND: The blood-brain barrier (BBB), which separates the intravascular and neuropil compartments, characterizes the vascular bed of the brain and is essential for its proper function. Recent advances in imaging techniques have driven the development of methods for quantitative assessment of BBB permeability. HYPOTHESIS/OBJECTIVES: Permeability of the BBB can be assessed quantitatively in dogs with meningoencephalitis of unknown origin (MUO) and its status is associated with the occurrence of seizures. ANIMALS: Forty dogs with MUO and 12 dogs without MUO. METHODS: Retrospective, prospective cohort study. Both dynamic contrast enhancement (DCE) and subtraction enhancement analysis (SEA) methods were used to evaluate of BBB permeability in affected (DCE, n = 8; SEA, n = 32) and control dogs (DCE, n = 6; SEA, n = 6). Association between BBB dysfunction (BBBD) score and clinical characteristics was examined. In brain regions where BBBD was identified by DCE or SEA magnetic resonance imaging (MRI) analysis, immunofluorescent staining for albumin, glial fibrillary acidic protein, ionized calcium binding adaptor molecule, and phosphorylated mothers against decapentaplegic homolog 2 were performed to detect albumin extravasation, reactive astrocytes, activated microglia, and transforming growth factor beta signaling, respectively. RESULTS: Dogs with BBBD had significantly higher seizure prevalence (72% vs 19%; P = .01) when compared to MUO dogs with no BBBD. The addition of SEA to routine MRI evaluation increased the identification rate of brain pathology in dogs with MUO from 50% to 72%. CONCLUSIONS AND CLINICAL IMPORTANCE: Imaging-based assessment of BBB integrity has the potential to predict risk of seizures in dogs with MUO.


Subject(s)
Dog Diseases , Meningoencephalitis , Animals , Blood-Brain Barrier/diagnostic imaging , Blood-Brain Barrier/metabolism , Dog Diseases/diagnosis , Dogs , Humans , Magnetic Resonance Imaging/veterinary , Meningoencephalitis/diagnostic imaging , Meningoencephalitis/veterinary , Prospective Studies , Retrospective Studies , Seizures/diagnostic imaging , Seizures/veterinary
7.
J Am Vet Med Assoc ; 260(7): 735-740, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35201995

ABSTRACT

OBJECTIVE: To evaluate the effect on seizure frequency of add-on telmisartan treatment in dogs with refractory idiopathic epilepsy. ANIMALS: 11 client-owned dogs with idiopathic epilepsy and ≥ 2 generalized seizures/mon that were currently being treated with ≥ 2 antiepileptic drugs. PROCEDURES: Telmisartan was administered at a dosage of 0.25 to 1 mg/kg, PO, every 12 hours for 4 to 16 months. Seizure frequencies before and during telmisartan treatment were recorded. RESULTS: 10 dogs completed the 4-month treatment protocol. One dog was excluded owing to a transient increase in serum creatinine concentration; no adverse effects of telmisartan were observed in the remaining 10 dogs. A reduction in seizure frequency greater than an estimated expected placebo effect of 30% was evident in 7 of the 10 dogs. Long-term (12 to 16 months) follow-up information was available for 6 dogs, of which 4 had a further reduction in seizure frequency. Differences in seizure frequency were not statistically significant. No significant difference was found in serum phenobarbital concentration throughout the treatment period in the 7 dogs that were tested. CLINICAL RELEVANCE: Telmisartan has the potential to reduce seizure frequency when administered as an add-on antiepileptic drug in dogs with refractory idiopathic epilepsy. A randomized, double-blind, placebo-controlled trial is needed to determine the true efficacy of telmisartan. On the basis of our results, a sample size of 54 dogs with refractory idiopathic epilepsy would be needed.


Subject(s)
Dog Diseases , Epilepsy , Telmisartan , Animals , Anticonvulsants/adverse effects , Dog Diseases/drug therapy , Dogs , Drug Therapy, Combination/veterinary , Epilepsy/drug therapy , Epilepsy/veterinary , Seizures/veterinary , Telmisartan/adverse effects , Treatment Outcome
8.
J Feline Med Surg ; 24(2): 91-97, 2022 02.
Article in English | MEDLINE | ID: mdl-33847537

ABSTRACT

OBJECTIVES: The aims of this study were to evaluate associations between abnormal head CT findings and outcome, and to examine the prognostic value of the Koret CT score (KCTS) in cats sustaining acute traumatic brain injury (TBI). METHODS: The medical records of cats hospitalised with TBI that underwent head CT scans within 72 h of admission were retrospectively reviewed. CT scans were evaluated independently by a radiologist and a neurologist who were blinded to the outcome. A KCTS and modified Glasgow Coma Scale (MGCS) were assigned to each cat and the association between abnormal CT findings, KCTS, MGCS and outcome were analysed. RESULTS: Fourteen cats were included in the study: nine (64.2%) survivors and five (35.7%) non-survivors. Of the nine cats that were discharged, one was a short-term survivor (10 days) and eight (57.1%) were long-term survivors (⩾6 months). Abnormal CT findings included lateral ventricle asymmetry/midline shift (42.8%), intracranial haemorrhage (35.7%), caudotentorial lesions (14.2%) and cranial vault fractures (14.2%), all of which were depressed. Intracranial haemorrhage was found to be significantly and negatively associated with short-term (P = 0.005) and long-term (P = 0.023) survival. KCTS was significantly associated with short-term survival (P = 0.002) and long-term survival (P = 0.004). A KCTS cut-off value of 2 yielded a 100% sensitivity and 100% specificity for short-term survival and 100% sensitivity and 80% specificity for long-term survival. A MGCS cut-off value of ⩾13 was associated with a 100% sensitivity and 100% specificity for short-term survival, and with a 100% sensitivity and 80% specificity for long-term survival. CONCLUSIONS AND RELEVANCE: KCTS, performed up to 72 h from injury, can be used as an additional diagnostic tool for the prediction of survival in cats with TBI.


Subject(s)
Brain Injuries, Traumatic , Cat Diseases , Animals , Brain Injuries, Traumatic/diagnostic imaging , Brain Injuries, Traumatic/veterinary , Cat Diseases/diagnostic imaging , Cats , Glasgow Coma Scale/veterinary , Prognosis , Retrospective Studies , Tomography, X-Ray Computed/veterinary
9.
Sci Transl Med ; 11(521)2019 12 04.
Article in English | MEDLINE | ID: mdl-31801888

ABSTRACT

A growing body of evidence shows that epileptic activity is frequent but often undiagnosed in patients with Alzheimer's disease (AD) and has major therapeutic implications. Here, we analyzed electroencephalogram (EEG) data from patients with AD and found an EEG signature of transient slowing of the cortical network that we termed paroxysmal slow wave events (PSWEs). The occurrence per minute of the PSWEs was correlated with level of cognitive impairment. Interictal (between seizures) PSWEs were also found in patients with epilepsy, localized to cortical regions displaying blood-brain barrier (BBB) dysfunction, and in three rodent models with BBB pathology: aged mice, young 5x familial AD model, and status epilepticus-induced epilepsy in young rats. To investigate the potential causative role of BBB dysfunction in network modifications underlying PSWEs, we infused the serum protein albumin directly into the cerebral ventricles of naïve young rats. Infusion of albumin, but not artificial cerebrospinal fluid control, resulted in high incidence of PSWEs. Our results identify PSWEs as an EEG manifestation of nonconvulsive seizures in patients with AD and suggest BBB pathology as an underlying mechanism and as a promising therapeutic target.


Subject(s)
Alzheimer Disease/physiopathology , Blood-Brain Barrier/physiopathology , Cerebral Cortex/physiopathology , Electroencephalography , Epilepsy/physiopathology , Aged , Aging/pathology , Animals , Dementia/physiopathology , Humans , Male , Mice , Nerve Net/physiopathology , Perfusion , Rats , Serum Albumin/metabolism
10.
Epilepsia ; 60(5): 1005-1016, 2019 05.
Article in English | MEDLINE | ID: mdl-31032909

ABSTRACT

OBJECTIVE: Dogs with spontaneous or acquired epilepsy exhibit resemblance in etiology and disease course to humans, potentially offering a translational model of the human disease. Blood-brain barrier dysfunction (BBBD) has been shown to partake in epileptogenesis in experimental models of epilepsy. To test the hypothesis that BBBD can be detected in dogs with naturally occurring seizures, we developed a linear dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) analysis algorithm that was validated in clinical cases of seizing dogs and experimental epileptic rats. METHODS: Forty-six dogs with naturally occurring seizures of different etiologies and 12 induced epilepsy rats were imaged using DCE-MRI. Six healthy dogs and 12 naive rats served as control. DCE-MRI was analyzed by linear-dynamic method. BBBD scores were calculated in whole brain and in specific brain regions. Immunofluorescence analysis for transforming growth factor beta (TGF-ß) pathway proteins was performed on the piriform cortex of epileptic dogs. RESULTS: We found BBBD in 37% of dogs with seizures. A significantly higher cerebrospinal fluid to serum albumin ratio was found in dogs with BBBD relative to dogs with intact blood-brain barrier (BBB). A significant difference was found between epileptic and control rats when BBBD scores were calculated for the piriform cortex at 48 hours and 1 month after status epilepticus. Mean BBBD score of the piriform lobe in idiopathic epilepsy (IE) dogs was significantly higher compared to control. Immunohistochemistry results suggested active TGF-ß signaling and neuroinflammation in the piriform cortex of dogs with IE, showing increased levels of serum albumin colocalized with glial acidic fibrillary protein and pSMAD2 in an area where BBBD had been detected by linear DCE-MRI. SIGNIFICANCE: Detection of BBBD in dogs with naturally occurring epilepsy provides the ground for future studies for evaluation of novel treatment targeting the disrupted BBB. The involvement of the piriform lobe seen using our linear DCE-MRI protocol and algorithm emphasizes the possibility of using dogs as a translational model for the human disease.


Subject(s)
Blood-Brain Barrier , Dog Diseases/physiopathology , Epilepsy/veterinary , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Albumins/cerebrospinal fluid , Algorithms , Animals , Brain Neoplasms/complications , Brain Neoplasms/physiopathology , Brain Neoplasms/veterinary , Contrast Media , Convulsants/toxicity , Dog Diseases/blood , Dog Diseases/cerebrospinal fluid , Dog Diseases/diagnostic imaging , Dogs , Epilepsy/diagnostic imaging , Epilepsy/metabolism , Epilepsy/physiopathology , Gliosis/etiology , Paraoxon/toxicity , Piriform Cortex/blood supply , Piriform Cortex/diagnostic imaging , Piriform Cortex/metabolism , Piriform Cortex/pathology , Prospective Studies , Rats , Serum Albumin/analysis , Signal Transduction , Status Epilepticus/chemically induced , Status Epilepticus/physiopathology , Transforming Growth Factor beta/physiology
11.
Vet Parasitol ; 253: 16-21, 2018 Apr 15.
Article in English | MEDLINE | ID: mdl-29604997

ABSTRACT

Spirocerca lupi is a nematode infecting dogs mostly in tropical and subtropical areas. Although its typical target is the esophageal wall, aberrant migration is not uncommon, including migration of unknown incidence into the spinal cord. While successful treatment of intraspinal S. lupi (ISSL) infection depends on early diagnosis, tools for definitive ante-mortem diagnosis are unavailable. We therefore aimed at characterizing clinical signs and clinical pathology findings of ISSL in dogs. For that, we analyzed medical records of dogs hospitalized in 2005-2016 presenting with neurological signs consistent with ISSL, which were diagnosed definitively post-mortem. Retrieved information included signalment, medical history, chief complaint, physical and neurological evaluation, neuroanatomical localization at presentation, clinical pathology, imaging findings, treatment, outcome and post-mortem findings. Ten midsize to large breed dogs were included, 7 of which had received prophylactic treatment. In all 10 dogs, onset was acute and neurological deterioration until presentation (2 h-6 d) was fast. Neurological examination localized the lesions within the spinal cord and paresis or paralysis was asymmetric in all dogs. Spinal pain was documented in 9/10 dogs. Cerebrospinal fluid (CSF) analysis was abnormal in all dogs and was characterized by pleocytosis in 8/10, whereas cytology revealed the presence of eosinophils in all dogs. Advanced imaging excluded spinal cord compression in all dogs tested. Post-mortem examination detected spinal cord migration tract in all cases. Nematodes were found in the spinal cord parenchyma (8/10) or adjacent to it (2/10) in all dogs. A larva was found in the subarachnoid space of one dog and an adult nematode in the thoracic intervertebral artery of another. Esophageal nodules were found in 5/10 dogs. These findings suggest that the combination of sudden onset of acute asymmetric paresis accompanied by pain, presence of eosinophils in the CSF and lack of compressive lesion may serve as sufficient evidence for tentative diagnosis of ISSL in endemic areas.


Subject(s)
Dog Diseases/pathology , Spirurida Infections/veterinary , Thelazioidea/isolation & purification , Animals , Dog Diseases/parasitology , Dogs , Female , Male , Risk Factors , Spinal Cord/parasitology , Spinal Cord/pathology , Spirurida Infections/parasitology , Spirurida Infections/pathology
12.
J Am Vet Med Assoc ; 252(7): 846-851, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29553897

ABSTRACT

OBJECTIVE To characterize and identify risk factors for intervertebral disk extrusion (IVDE) in Pekingese. DESIGN Retrospective case-control study. ANIMALS 426 Pekingese (81 with confirmed IVDE and 345 without IVDE) admitted to a veterinary teaching hospital from 2005 through 2015. PROCEDURES Medical records were reviewed and data were extracted regarding age, sex, body weight, body condition score, coat color, chief reason for initial evaluation, body system involved, and diagnosis. Survey radiographs of the vertebral column were examined. Data were compared between the confirmed IVDE and non-IVDE groups. RESULTS Confirmed IVDE was uncommon in dogs < 2 years of age (2/81 [2%]). The extrusion was primarily located in the thoracolumbar (n = 57 [70%]) and cervical (22 [27%]) regions; the most common sites were T12-13 and C6-7. The number of radiographically visible calcified disks was significantly greater in the confirmed IVDE versus non-IVDE group, and the presence of calcified disks in the T10-L4 region was associated with increased odds of IVDE (OR, 21.2). Black coat color was significantly more prevalent in the confirmed IVDE versus non-IVDE group and was associated with increased odds of developing IVDE (OR, 1.6). Mean body weight and the proportion of spayed female dogs were significantly greater in the confirmed IVDE versus non-IVDE group. CONCLUSIONS AND CLINICAL RELEVANCE Several risk factors for confirmed IVDE in Pekingese were identified that could be useful for counseling clients about the disease or, with additional research, designing selective breeding programs to reduce the prevalence of IVDE in the breed.


Subject(s)
Dog Diseases/epidemiology , Intervertebral Disc Degeneration/veterinary , Intervertebral Disc Displacement/veterinary , Animals , Case-Control Studies , Cervical Vertebrae , Dog Diseases/diagnostic imaging , Dog Diseases/genetics , Dogs , Female , Intervertebral Disc Degeneration/epidemiology , Intervertebral Disc Displacement/epidemiology , Israel/epidemiology , Lumbar Vertebrae , Male , Pedigree , Records/veterinary , Retrospective Studies , Risk Factors , Thoracic Vertebrae
13.
PLoS One ; 13(2): e0187197, 2018.
Article in English | MEDLINE | ID: mdl-29408878

ABSTRACT

Endocannabinoids (ECs) are involved in immunomodulation, neuroprotection and control of inflammation in the central nervous system (CNS). Activation of cannabinoid type 2 receptors (CB2) is known to diminish the release of pro-inflammatory factors and enhance the secretion of anti-inflammatory cytokines. Furthermore, the endocannabinoid 2-arachidonoyl glycerol (2-AG) has been proved to induce the migration of eosinophils in a CB2 receptor-dependent manner in peripheral blood and activate neutrophils independent of CB activation in humans. The aim of the current study was to investigate the influence of the endocannabinoid system in two different CNS inflammatory diseases of the dog, i.e. Steroid-Responsive Meningitis-Arteritis (SRMA) and Intraspinal Spirocercosis (IS). The two main endocannabinoids, anandamide (AEA) and 2-AG, were quantified by mass spectrometry in CSF and serum samples of dogs affected with Steroid- Responsive Meningitis-Arteritis in the acute phase (SRMA A), SRMA under treatment with prednisolone (SRMA Tr), intraspinal Spirocercosis and healthy dogs. Moreover, expression of the CB2 receptor was evaluated in inflammatory lesions of SRMA and IS and compared to healthy controls using immunohistochemistry (IHC). Dogs with SRMA A showed significantly higher concentrations of total AG and AEA in serum in comparison to healthy controls and in CSF compared to SRMA Tr (p<0.05). Furthermore, dogs with IS displayed the highest ECs concentrations in CSF, being significantly higher than in CSF samples of dogs with SRMA A (p<0.05). CSF samples that demonstrated an eosinophilic pleocytosis had the highest levels of ECs, exceeding those with neutrophilic pleocytosis, suggesting that ECs have a major effect on migration of eosinophils in the CSF. Furthermore, CB2 receptor expression was found in glial cells in the spinal cord of healthy dogs, whereas in dogs with SRMA and IS, CB2 was strongly expressed not only in glial cells but also on the cellular surface of infiltrating leukocytes (i.e. neutrophils, eosinophils, lymphocytes, plasma cells, and macrophages) at lesion sites. The present study revealed an upregulated endocannabinoid system in dogs with inflammatory CNS diseases, highlighting the endocannabinoid system as a potential target for treatment of inflammatory CNS diseases.


Subject(s)
Arteritis/veterinary , Dog Diseases/physiopathology , Endocannabinoids/physiology , Meningitis/veterinary , Spinal Diseases/veterinary , Spirurida Infections/veterinary , Animals , Arteritis/blood , Arteritis/cerebrospinal fluid , Arteritis/physiopathology , Chromatography, Liquid , Dog Diseases/blood , Dog Diseases/cerebrospinal fluid , Dogs , Endocannabinoids/blood , Endocannabinoids/cerebrospinal fluid , Mass Spectrometry , Meningitis/blood , Meningitis/cerebrospinal fluid , Meningitis/physiopathology , Spinal Diseases/blood , Spinal Diseases/cerebrospinal fluid , Spinal Diseases/physiopathology , Spirurida Infections/blood , Spirurida Infections/cerebrospinal fluid , Spirurida Infections/physiopathology , Tandem Mass Spectrometry
14.
Vet Clin Pathol ; 47(2): 289-293, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29406569

ABSTRACT

An 8-year-old mixed-breed dog was presented for acute, progressive weakness and ataxia, inappetence, and weight loss. The patient was mentally normal, but nonambulatory, with a right head tilt, right positional ventral strabismus, and slight head tremors. A neurologic lesion was localized to the cerebellum and right brainstem. Cerebrospinal fluid (CSF) analysis showed a markedly increased protein concentration and mixed pleocytosis, with eosinophil predominance (44%), intracytoplasmic inclusions within eosinophils, consistent with Ehrlichia canis (E canis) morulae, and Toxoplasma gondii (T gondii) or Neospora caninum (N caninum) tachyzoites within eosinophils and monocytes. A serum indirect immunofluorescent antibody test was positive for N caninum (titer 1:12 800) and negative for T gondii. Both blood and CSF PCR results were N caninum- and E canis-positive and T gondii- and Anaplasma phagocytophilum-negative, and blood PCR, but not CSF PCR, was Hepatozoon canis-positive. The dog was treated for 30 days with clindamycin, sulfamethoxazole-trimethoprim, doxycycline, prednisone, and cephalosporin, but did not improve neurologically, and was euthanized. Brain histopathology showed moderate multifocal, subacute meningoencephalitis with necrosis and gliosis. The neurologic disease was mostly attributed to central nervous system (CNS) neosporosis, with the possible contribution of ehrlichiosis, which was likely a manifestation of blood-brain barrier disruption. Hepatozoonosis was probably a result or cause of underlying immunosuppression. To our knowledge, this is the first report of CNSN caninum and E canis co-infection detected by both CSF PCR and cytology and E canis morulae identified within CSF eosinophils.


Subject(s)
Coccidiosis/veterinary , Dog Diseases/diagnosis , Ehrlichia canis , Ehrlichiosis/veterinary , Meningoencephalitis/veterinary , Neospora , Animals , Coccidiosis/complications , Coinfection , Dogs , Ehrlichiosis/complications , Female , Meningoencephalitis/complications , Meningoencephalitis/microbiology
15.
Vet Clin Pathol ; 47(1): 138-141, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29329490

ABSTRACT

Spinal spirocercosis due to aberrant Spirocerca lupi nematode migration is an emerging etiology for acute myelitis in dogs in Israel, causing severe, mostly nonsymmetrical hind limb paresis or paralysis, and sometimes tetraparesis or tetraparalysis. So far, incidental identification of parasites during spinal surgery or at necropsy provides the only definite diagnosis, while antemortem diagnosis of this condition has been uncertain. Specifically, antemortem diagnosis is based on the typical clinical presentation of acute, progressive, asymmetrical hind limb paresis or paralysis, with moderate to severe eosinophilic to mixed cerebrospinal fluid (CSF) pleocytosis and increased CSF protein concentration. Exclusion of other differential diagnoses also requires using spinal cord imaging. In this novel report, we document a case of an intradural spinal spirocercosis in a dog, diagnosed antemortem, by detecting S lupi eggs in the CSF, and subsequent treatment, resulting in the resolution of the clinical signs.


Subject(s)
Cytodiagnosis/veterinary , Dog Diseases/cerebrospinal fluid , Rhabditida Infections/veterinary , Rhabditida/isolation & purification , Spinal Cord/parasitology , Animals , Dog Diseases/diagnosis , Dog Diseases/parasitology , Dogs , Feces/parasitology , Female , Ovum , Parasite Egg Count/veterinary , Paresis/parasitology , Paresis/veterinary , Rhabditida Infections/cerebrospinal fluid , Rhabditida Infections/parasitology
16.
Am J Vet Res ; 78(9): 1085-1090, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28836840

ABSTRACT

OBJECTIVE To characterize CT findings and outcomes in dogs with head trauma and design a prognostic scale. ANIMALS 27 dogs admitted to the Koret School Veterinary Teaching Hospital within 72 hours after traumatic head injury that underwent CT imaging of the head. PROCEDURES Data were extracted from medical records regarding dog signalment, history, physical and neurologic examination findings, and modified Glasgow coma scale scores. All CT images were retrospectively evaluated by a radiologist unaware of dog status. Short-term (10 days after trauma) and long-term (≥ 6 months after trauma) outcomes were determined, and CT findings and other variables were analyzed for associations with outcome. A prognostic CT-based scale was developed on the basis of the results. RESULTS Cranial vault fractures, parenchymal abnormalities, or both were identified via CT in 24 of 27 (89%) dogs. Three (11%) dogs had only facial bone fractures. Intracranial hemorrhage was identified in 16 (59%) dogs, cranial vault fractures in 15 (56%), midline shift in 14 (52%), lateral ventricle asymmetry in 12 (44%), and hydrocephalus in 7 (26%). Hemorrhage and ventricular asymmetry were significantly and negatively associated with short- and long-term survival, respectively. The developed 7-point prognostic scale included points for hemorrhage, midline shift or lateral ventricle asymmetry, cranial vault fracture, and depressed fracture (1 point each) and infratentorial lesion (3 points). CONCLUSIONS AND CLINICAL RELEVANCE The findings reported here may assist in determining prognoses for other dogs with head trauma. The developed scale may be useful for outcome assessment of dogs with head trauma; however, it must be validated before clinical application.


Subject(s)
Craniocerebral Trauma/veterinary , Dogs/injuries , Tomography, X-Ray Computed/veterinary , Animals , Cohort Studies , Craniocerebral Trauma/diagnostic imaging , Female , Humans , Male , Prognosis , Retrospective Studies
17.
J Zoo Wildl Med ; 47(4): 1105-1108, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28080915

ABSTRACT

A 19-yr-old captive male Syrian bear ( Ursus arctos syriacus) presented with a right hind limb lameness that progressed to nonambulatory paraparesis over the course of 2 wk. When night enclosure confinement and a short course of glucocorticoids and antibiotics did not lead to improvement, radiographs were performed, followed by cerebrospinal fluid analysis and myelography, revealing a dynamic spinal cord compression at the level of T2-T3. Dorsal laminectomy of both T2 and T3 was performed to allow decompression. The bear recovered uneventfully with first sign of neurological improvement apparent at 10 days postoperatively. Following 6 mo of rehabilitation the bear was walking and using his hind limbs normally.


Subject(s)
Laminectomy/veterinary , Spinal Cord Compression/veterinary , Ursidae/surgery , Animals , Male , Spinal Cord Compression/surgery , Thoracic Vertebrae/pathology , Thoracic Vertebrae/surgery
18.
Article in English | MEDLINE | ID: mdl-26458162

ABSTRACT

OBJECTIVE: To evaluate the use of a combined protocol of prednisone and mycophenolate mofetil (MMF) for the treatment of meningoencephalomyelitis of unknown etiology (MUE) and to describe response, adverse effects, and outcome. DESIGN: Retrospective study (2005-2011). SETTING: University teaching hospital. ANIMALS: Twenty-five client-owned dogs with clinical signs, neuroimaging, and cerebrospinal abnormalities consistent with MUE. Five dogs whose MMF treatment was discontinued after 7-14 days due to gastrointestinal clinical signs were evaluated only for adverse effects. INTERVENTIONS: Dogs were initially treated with prednisone 2 mg/kg PO every 12 hours and with MMF 20 mg/kg PO or IV every 12 hours. Prednisone was tapered after 4 days to 1 mg/kg every 12 hours for 14 days, then to every 24 hours for 30 days, and again reduced by half every 2-4 months thereafter. When prednisone was tapered completely or to 0.5 mg/kg every 24-48 hours without clinical relapse, MMF was tapered in a similar manner. MEASUREMENTS AND MAIN RESULTS: Partial or complete clinical response was achieved in 95% (19/20) of the dogs. Median survival time by the end of the study was 250 days (range 6 to >1,679) with 40% (8/20) of the dogs still alive (336-1,679 days after diagnosis). All Pug dogs (4/20) included in the study died with a median survival time of 14 days. Adverse effects attributed to MMF, which included hemorrhagic diarrhea within the first 2 weeks of treatment, were recorded in 20% (5/25) of the dogs. CONCLUSIONS: MMF can be used as an adjunctive treatment for dogs with MUE. This protocol enables reduction of prednisone treatment or, in some cases, its complete withdrawal. The possibility of intravenous administration is advantageous in cases with severe neurological abnormalities and mentation changes, often seen in MUE. Attention is warranted for gastrointestinal adverse effects, especially in the first 2 weeks of treatment.


Subject(s)
Dog Diseases/drug therapy , Immunosuppressive Agents/therapeutic use , Meningoencephalitis/veterinary , Mycophenolic Acid/analogs & derivatives , Prednisone/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Dogs , Drug Therapy, Combination , Infusions, Intravenous , Meningoencephalitis/drug therapy , Mycophenolic Acid/therapeutic use , Retrospective Studies
19.
Can Vet J ; 56(1): 59-62, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25565716

ABSTRACT

A 14-month-old mixed-breed dog was presented with acute onset of exercise intolerance that quickly progressed to quadriparesis. Gross and microscopic autopsy findings indicated a type of degenerative polioencephalomyelopathy resembling subacute necrotizing encephalomyelopathy in dogs or Leigh's disease in humans. This syndrome has previously been reported only in purebred dogs.


Polioencéphalomyélopathie chez un chien de race croisée ressemblant au syndrome de Leigh. Un chien de race croisée âgé de 14 mois a été présenté avec l'apparition aiguë d'intolérance à l'exercice qui a rapidement progressé à la quadriparésie. Suite à la nécropsie, les constatations macroscopiques et microscopique ont indiqué un type de polioencéphalomyélopathie dégénérative ressemblant à l'encéphalomyélopathie nécrosante subaiguë chez les chiens ou au syndrome de Leigh chez les humains. Ce syndrome avait été signalé précédemment seulement chez les chiens de race pure.(Traduit par Isabelle Vallières).


Subject(s)
Brain Diseases, Metabolic, Inborn/veterinary , Dog Diseases/pathology , Animals , Brain Diseases, Metabolic, Inborn/diagnosis , Brain Diseases, Metabolic, Inborn/pathology , Dog Diseases/diagnosis , Dogs , Female
20.
Vet Surg ; 44(1): 41-5, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24724720

ABSTRACT

OBJECTIVE: To report 2 dogs that developed temporary pelvic limb paralysis with loss of deep pain sensation after topical intrathecal morphine administration during spinal surgery. STUDY DESIGN: Clinical report. ANIMALS: Dogs (n = 2). METHODS: A 5-year-old castrated male French Bulldog with a subarachnoid diverticulum at T9-T10 and a 9.5-year-old castrated male Belgian Shepherd dog with a herniated disc at T12-T13 and intradural component, had Gelfoam soaked with morphine placed over the dura mater defect. RESULTS: Pelvic limb paralysis and loss of deep pain sensation was noticed immediately after recovery from anesthesia. After intravenous naloxone administration, both dogs immediately regained ambulation and normal pain sensation; however the effect was temporary lasting only a few hours. Permanent resolution of clinical signs occurred 24 hours after surgery. CONCLUSIONS: Topical intrathecal morphine administration resulted in temporary pelvic limb paralysis and loss of deep pain sensation. This route of administration should be used cautiously until further determination of the efficacy and adverse effects associated with topical intrathecal morphine administration.


Subject(s)
Analgesics, Opioid/adverse effects , Diverticulum/veterinary , Dog Diseases/surgery , Intervertebral Disc Displacement/veterinary , Morphine/adverse effects , Paralysis/veterinary , Analgesics, Opioid/administration & dosage , Animals , Diverticulum/complications , Diverticulum/surgery , Dogs , Injections, Spinal/veterinary , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/surgery , Male , Morphine/administration & dosage , Pain Measurement/veterinary , Paralysis/chemically induced , Subarachnoid Space
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