On the utility of cerebrospinal fluid biomarkers in canine neurological disorders.

The cerebral biomarkers, neurofilament light chain (NfL), amyloid-ß, tau, and neuron specific enolase (NSE) reflect a wide spectrum of neurological damage in the brain and spinal cord. With this study, we aimed to assess whether these biomarkers hold any potential diagnostic value for the three most common canine neurological diseases. Canines suffering from meningoencephalitis of unknown origin (MUO), brain tumors, and selected non-infectious myelopathies were included. For each diagnosis, we analyzed these biomarkers in the cerebrospinal fluid collected via cranial puncture from the cisterna magna. Elevated levels of CSF tau, NfL, and NSE were observed in MUO, with all three biomarkers being intercorrelated. Tau and NSE were increased while amyloid-ß was decreased in dogs suffering from tumors. In contrast, no biomarker changes were observed in dogs with myelopathies. Covariates such as age, sex, or castration had minimal impact. CSF biomarkers may reflect molecular changes related to MUO and tumors, but not to non-infectious myelopathies. The combination of NfL, tau, and NSE may represent useful biomarkers for MUO as they reflect the same pathology and are not influenced by age.

Towards a better understanding of idiopathic epilepsy through metabolic fingerprinting of cerebrospinal fluid in dogs.

Cerebrospinal fluid metabolomics is a promising research technology in the elucidation of nervous system disorders. Therefore, in this work, a cerebrospinal fluid (CSF) metabolomics method using liquid chromatography coupled to mass spectrometry was optimized and validated to cover a wide range of metabolites. An acceptable coefficient of variance regarding instrumental, within-lab and intra-assay precision was found for 95, 70 and 96 of 102 targeted metabolites, together with 1256, 676 and 976 untargeted compounds, respectively. Moreover, approximately 75% of targeted metabolites and 50% of untargeted compounds displayed good linearity across different dilution ranges. Consequently, metabolic alterations in CSF of dogs with idiopathic epilepsy (IE) were studied by comparing CSF of dogs diagnosed with IE (Tier II) to dogs with non-brain related disease. Targeted metabolome analysis revealed higher levels of cortisol, creatinine, glucose, hippuric acid, mannose, pantothenol, and 2-phenylethylamine (P values < 0.05) in CSF of dogs with IE, whereas CSF of dogs with IE showed lower levels of spermidine (P value = 0.02). Untargeted CSF metabolic fingerprints discriminated dogs with IE from dogs with non-brain related disease using Orthogonal Partial Least Squares Discriminant Analysis (R2(Y) = 0.997, Q2(Y) = 0.828), from which norepinephrine was putatively identified as an important discriminative metabolite.

Mycobacterium haemophilum infection in canine cerebrospinal fluid.

A 4-year-old female spayed Australian cattle dog was presented to the Emergency Service at the University of Missouri Veterinary Health Center Small Animal Hospital for generalized pain and lethargy. At presentation, the dog showed severe cervical spinal pain and thoracic limb deficits consistent with a multifocal neuroanatomic localization. Magnetic resonance imaging of the cervical spine revealed T2 and T1 postcontrast intense signal extending from the level of the medulla through C5 most marked in the caudal brainstem and cranial cervical spinal cord. The suspected diagnosis was severe meningoencephalomyelitis and secondary edema. Analysis of cerebrospinal fluid (CSF) collected from the cerebellomedullary cistern revealed a marked mixed pleocytosis with intralesional structures morphologically consistent with Mycobacterium sp. Standard DNA PCR assay performed on the CSF yielded the presence of Mycobacterium haemophilum. To the authors' knowledge, this is the first reported case of CNS mycobacteriosis diagnosed on CSF analysis in a dog.

A potential early clinical phenotype of necrotizing meningoencephalitis in genetically at-risk pug dogs.

BACKGROUND: Necrotizing meningoencephalitis (NME) in the pug dogs is a fatal neuroinflammatory disease associated with rapid progression and poor response to conventional immunosuppressive therapy. Diagnosis is typically made after severe neurological abnormalities have manifested. HYPOTHESIS/OBJECTIVE: Pug dogs at genetic risk for NME might manifest neurological abnormalities before developing pathognomonic clinical signs of NME. ANIMALS: Thirty-six pug dogs less than 4 years of age asymptomatic for NME. METHODS: Prospective observational cohort study with germline genome-wide genotyping. Neurological examinations were performed 4 weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination. RESULTS: The overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8/24 (33%) genetically at-risk dogs and 0/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8/8, reduced menace response in 5/8, and lateralizing postural reaction deficits in 5/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype (P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Our findings suggest the presence of a novel early clinical phenotype of NME in apparently asymptomatic genetically at-risk pugs which might be used to plan early diagnostic and therapeutic clinical trials.

Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation.

Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling, including high-resolution liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics was performed. Cerebrospinal fluid of nine dogs with IVDH and six healthy controls were used for the analyses, and an additional five IVDH samples were used for proteomic data validation. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omics layers, leading to an improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins follistatin Like 1 (FSTL1), secretogranin V (SCG5), nucleobindin 1 (NUCB1), calcitonin re-ceptor-stimulating peptide 2 precursor (CRSP2) and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, and neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of a novel integrative interdisciplinary approach may provide new opportunities to apply innovative diagnostic and monitoring methods as well as improve treatment strategies and personalized care for patients with degenerative spinal disorders.

Cerebrospinal fluid analysis in dogs: Main patterns and prevalence of albuminocytological dissociation.

BACKGROUND: Albuminocytological dissociation (ACD) of the cerebrospinal fluid (CSF) is defined as an increased total protein concentration with normal total nucleated cell count. It is suspected to occur in diseases that alter the blood-brain barrier, increase the production of protein or obstruct the flow of CSF. The purposes of this study were to review the CSF analysis results of a large cohort of dogs with neurological conditions, to analyse the total prevalence of ACD and to describe which diseases have a higher prevalence of ACD. STUDY DESIGN AND METHODS: Medical records were retrospectively searched for dogs whom CSF was sampled from 2012-2019. Data collected included signalment, body weight, site of collection of the CSF, CSF analysis results, and final diagnosis. RESULTS: A total of 497 dogs met the inclusion criteria. ACD was identified in 16.5% (82/497) of dogs. The diseases with higher proportion of ACD were cranial nerve neuropathy (6/10; 60.0%), brain tumour (10/24; 41.7%), idiopathic vestibular disease (7/17; 41.2%) and brain vascular disease (4/13; 30.8%). CLINICAL SIGNIFICANCE: This study describes the CSF patterns of the most common neurological conditions in dogs, also characterizing, for the first time in dogs, the prevalence and causes of ACD, which was identified in 16.5% of the samples. The diseases with highest proportions of ACD were cranial nerve neuropathy, brain tumour, idiopathic vestibular disease and brain vascular disease.

Cytologic detection of Toxoplasma gondii in the cerebrospinal fluid of a dog and in vitro isolation of a unique mouse-virulent recombinant strain.

Parasites resembling Neospora caninum or Toxoplasma gondii were detected by cytologic examination of cerebrospinal fluid (CSF) from a dog with neurologic disease. The dog became severely ill and was euthanized. Canine tissue homogenates were used for direct parasite isolation in cell culture, bioassay in 2 mouse lineages, and PCR. T. gondii was isolated in monkey kidney cells, and species identity was confirmed by PCR. Inoculated parasites were highly virulent for mice, which developed clinical signs and were euthanized immediately. PCR-RFLP for T. gondii using the cultured isolate (TgDgBA22) was conducted with 12 genetic markers, and a unique recombinant strain was identified. Detection of T. gondii by CSF cytology, although described in humans, had not been reported previously in dogs, to our knowledge, and was crucial for the diagnosis of toxoplasmosis in the examined dog.

Amyloid-beta plasma and cerebrospinal fluid biomarkers in aged dogs with cognitive dysfunction syndrome.

BACKGROUND: Cognitive dysfunction syndrome (CDS) is a common progressive neurodegenerative disease that is poorly defined. Specific multitargeted protocols do not exist for setting the diagnosis and the prognosis of the syndrome. HYPOTHESIS/OBJECTIVES: To quantify Aß42 and Aß40 peptides in blood and cerebrospinal fluid (CSF) and to investigate their contribution to CCDS. ANIMALS: A total of 61 dogs from a hospital population. METHODS: Case-control study. Six young (YG: 0-4 years old), 8 middle-aged (4-8 years old), 17 cognitively unimpaired and aged (CU: 8-20 years old), and 30 cognitively impaired and aged (CI: 8-17 years). From the CI group, 10 dogs exhibited mild impairment (CI-MCI) and 20 exhibited severe impairment (CI-SCI). Cognitive status was assessed using a validated owner-based questionnaire. Direct and indirect Aß markers were determined in plasma fractions (total-TP, free-FP, bound to plasma components-CP) and CSF using commercial ELISA assays (AΒtest, Araclon Biotech). RESULTS: TPAß42/40 facilitated discrimination between CI-MCI and CU aged dogs with area under curve ≥ 0.79. CSFAß42 levels were higher (P = .09) in CU (1.25 ± 0.28 ng/mL) than in MCI (1.04 ± 0.32 ng/mL) dogs. CSF Aß42 levels were correlated with the CP fragment (CPAß40: P = .02, CPAß42: P = .02). CPAß42 was higher in the CI-MCI (23.03 ± 11.79 pg/µL) group compared to the other aged dogs (CU: 10.42 ± 7.18 pg/µL, P = .02, SCI: 11.40 ± 12.98 pg/µL, P = .26). CONCLUSION AND CLINICAL IMPORTANCE: The Aß should be determined in all of the 3 plasma fractions (TP, FP, CP). In the clinical approach, TPAß42/40 could be used as an efficient preselection tool for the aged canine population targeting dogs with mild cognitive impairment.

Thoracolumbar meningeal fibrosis in pugs.

BACKGROUND: Thoracolumbar myelopathies associated with spinal cord and vertebral column lesions, with a similar clinical phenotype, but different underlying etiologies, occur in pugs. OBJECTIVES: To further characterize the clinical and neuropathological characteristics of pugs with longstanding thoracolumbar myelopathy. ANIMALS: Thirty client-owned pure-bred pugs with a history of more than a month of ataxia and paresis of the pelvic limbs, suggesting a myelopathy localized to the thoracolumbar spinal cord, were included in the study. METHODS: Prospective clinicopathological study. Included pugs underwent a complete neurological examination and gross and histopathologic postmortem studies with focus on the spinal cord. Computed tomography (n = 18), magnetic resonance imaging (n = 17), and cerebrospinal fluid analysis (n = 27) were performed before or immediately after death. RESULTS: Twenty male and 10 female pugs had a median age at clinical onset of 84 months (interquartile range, 66-96). Affected pugs presented with a progressive clinical course and 80% were incontinent. There was circumferential meningeal fibrosis with concomitant focal, malacic, destruction of the neuroparenchyma in the thoracolumbar spinal cord in 24/30 pugs. Vertebral lesions accompanied the focal spinal cord lesion, and there was lympho-histiocytic inflammation associated or not to the parenchymal lesion in 43% of the pugs. CONCLUSIONS AND CLINICAL IMPORTANCE: Meningeal fibrosis with associated focal spinal cord destruction and neighboring vertebral column lesions were common findings in pugs with long-standing thoracolumbar myelopathy.

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. ANIMALS: One hundred two dogs with HS, 62 dogs with meningioma. METHODS: Retrospective case series. Records were reviewed for results of cerebrospinal fluid (CSF) analysis, CBC, treatment, and outcome data. RESULTS: Predisposition for CNS HS was seen in Bernese Mountain Dogs, Golden Retrievers, Rottweilers, Corgis, and Shetland Sheepdogs (P ≤ .001). Corgis and Shetland Sheepdogs had predominantly primary tumors; Rottweilers had exclusively disseminated tumors. Marked CSF inflammation was characteristic of primary rather than disseminated HS, and neoplastic cells were detected in CSF of 52% of affected dogs. Increased neutrophil to lymphocyte ratios were seen in all groups relative to controls (P <.008) but not among tumor subtypes. Definitive versus palliative treatment resulted in improved survival times (P < .001), but overall prognosis was poor. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinicopathological differences between primary and disseminated HS suggest that tumor biological behavior and origin may be different. Corgis and Shetland Sheepdogs are predisposed to primary CNS HS, characterized by inflammatory CSF. High total nucleated cell count and the presence of neoplastic cells support the use of CSF analysis as a valuable diagnostic test. Prognosis for CNS HS is poor, but further evaluation of inflammatory mechanisms may provide novel therapeutic opportunities.

Comparison of cerebellomedullary and lumbar cerebrospinal fluid analysis in dogs with neurological disease.

BACKGROUND: Cerebrospinal fluid (CSF) analysis aids in categorizing underlying disease processes in patients with neurologic disease. Convention suggests that CSF should be collected caudal to the lesion. However, little evidence exists to justify this assertion. HYPOTHESIS/OBJECTIVES: Evaluate the clinicopathologic differences between CSF collected from the cerebellomedullary (CM) and lumbar cisterns in dogs presented for evaluation of neurologic disease. ANIMALS: Fifty-one client-owned dogs undergoing magnetic resonance imaging (MRI) and CSF collection for investigation of neurologic disease. METHODS: Cerebrospinal fluid was prospectively collected from the CM and lumbar cisterns in all patients. The total protein (TP) concentration, red blood cell (RBC) count, and total nucleated cell count (TNCC) were analyzed within 30 minutes of collection. Results and cytology findings were interpreted by a single pathologist. RESULTS: Fifty-one paired samples were collected. The TNCC (P < .001), RBC (P < .001), and TP (P < .001) were different between collection sites. When grouped by neurolocalization, TP (intracranial, P < .001; cervical, P < .001; thoracolumbar, P < .001) and RBC (intracranial, P < .001; cervical, P ≤ .002; thoracolumbar, P = .006) counts were significantly different. The TNCC was significantly different in the cervical (P = .04) and thoracolumbar localizations (P = .004) but not for intracranial (P = .30) localizations. The pathologist's interpretation differed between sites in 66.7% of the cases (34/51). CONCLUSIONS: In dogs with lesions that neurolocalized to the brain or cervical spinal cord, there may be clinical benefit in collecting fluid from both the CM and lumbar cisterns. In dogs with thoracolumbar myelopathy, CSF collected from the CM cistern may not be representative of the underlying disease process.

Cerebrospinal fluid and serum glycosphingolipid biomarkers in canine globoid cell leukodystrophy (Krabbe Disease).

Globoid cell leukodystrophy (GLD, Krabbe disease, Krabbe's disease) is caused by genetic mutations in the gene encoding, galactosylceramidase (GALC). Deficiency of this enzyme results in central and peripheral nervous system pathology, and is characterized by loss of myelin and an infiltration of globoid cells. The canine model of GLD provides a translational model which faithfully recapitulates much of the human disease pathology. Targeted lipidomic analysis was conducted in serum and cerebrospinal fluid (CSF) over the lifetime of GLD affected and normal canines, and in brain tissue at humane endpoint to better understand disease progression and identify potential biomarkers of disease. Psychosine, a substrate of GALC and primary contributor to the pathology in GLD, was observed to be significantly elevated in the serum and CSF by 2 or 4 weeks of age, respectively, and steadily increased over the lifetime of affected animals. Importantly, psychosine concentration strongly correlated with disease severity. Galactosylceramide, glucosylceramide, and lactosylceramide were also found to be elevated in the CSF of affected animals and increased with age. Psychosine and galactosylceramide were found to be significantly increased in brain tissue at humane endpoint. This study identified several biomarkers which may be useful in the development of therapeutics for GLD.

Investigation of astrovirus and bornavirus in the cerebrospinal fluid of dogs clinically diagnosed with meningoencephalitis of unknown etiology.

BACKGROUND: Non-suppurative encephalitides in a variety of species, including humans and dogs, have been linked to infection by astroviruses and bornaviruses. HYPOTHESIS/OBJECTIVES: To determine whether or not ribonucleic acid of astroviruses or bornaviruses was present in the cerebrospinal fluid (CSF) of dogs with clinically diagnosed meningoencephalomyelitis of unknown etiology (MUE). ANIMALS: Twenty-five client-owned dogs evaluated by CSF analysis at a single university referral hospital. METHODS: Prospective case-control study. Cerebrospinal fluid was collected from clinically diagnosed MUE and control cases and evaluated by reverse-transcriptase polymerase chain reaction for the presence of astrovirus and bornavirus. RESULTS: Neither astrovirus nor bornavirus nucleic acids were identified in CSF collected from 20 clinically diagnosed MUE and 5 control cases. CONCLUSIONS AND CLINICAL IMPORTANCE: The negative results of this investigation suggest that astrovirus and bornavirus are not commonly detectable in CSF of dogs with MUE.

Cerebrospinal fluid and blood lactate concentrations as prognostic biomarkers in dogs with meningoencephalitis of unknown origin.

Meningoencephalitis of unknown origin (MUO) is a common inflammatory disease of the central nervous system. Several studies investigated finding prognostic factors, but results are contradictory. The aim of this study was to determine the concentrations of blood lactate (Blood-L) and cerebrospinal fluid lactate (CSF-L) in dogs with MUO for prognostic purposes. A total of 45 dogs with MUO (MUO group) and 11 with idiopathic epilepsy (IE group) were included. In the MUO group, 22 dogs were treated with prednisolone + cytosine arabinoside, 17 with prednisolone ± cyclosporine, and six received no treatment. In the MUO group, there was a strong-moderate positive correlation between Blood-L and CSF-L (ρ = 0.63557; P < 0.0001), a strong-moderate negative correlation between survival and CSF-L (ρ= -0.50210; P < 0.0004), and a weak negative correlation between survival and Blood-L (ρ= -0.35685; P < 0.0220). Dogs with a favourable response to treatment at 1 month had lower initial concentrations of Blood-L and CSF-L (P < 0.0010; P < 0.0037), and those with a worse response had higher values (P < 0.0497; P < 0.0004). Dogs that remained stable with treatment showed lower CSF-L concentrations (P < 0.0013). Dogs with Blood-L>4 mmol/L (P < 0.03) and/or CSF-L> 4 mmol/L (P < 0.009) had lower survival rates with the latter also showing more severe signs, probably indicating severe neuronal damage. These findings suggest that concentrations of CSF-L and Blood-L in dogs with MUO could be used as prognostic indicators.

MicroRNA expression in the cerebrospinal fluid of dogs with and without cervical spondylomyelopathy.

BACKGROUND: Osseous-associated cervical spondylomyelopathy (OA-CSM) is a common condition of the cervical vertebral column that affects giant dog breeds. MicroRNAs (miRNAs) are small RNAs that regulate gene expression, and recent data suggest that circulating miRNAs present in biological fluids may serve as potential biomarkers for disease. The miRNA profiles of cerebrospinal fluid (CSF) from healthy dogs and dogs clinically affected by OA-CSM have not been described. OBJECTIVE: To characterize the expression levels of miRNAs present in the CSF of normal Great Danes and identify differentially expressed miRNAs in the CSF of Great Danes clinically affected with OA-CSM. ANIMALS: Client-owned dogs: 12 control, 12 OA-CSM affected. METHODS: Cerebrospinal fluid samples were collected prospectively. MicroRNA expression was evaluated using the NanoString nCounter platform and quantitative real-time PCR. RESULTS: We identified 8 miRNAs with significant differential expression. MiR-299-5p and miR-765 had increased expression levels in the CSF of OA-CSM-affected dogs, whereas miR-494, miR-612, miR-302-d, miR-4531, miR-4455, and miR-6721-5p had decreased expression levels in OA-CSM affected dogs compared to clinically normal dogs. Quantitative real-time PCR was performed to validate the expression levels of 2 miRNAs (miR-494 and miR-612), and we found a 1.5-fold increase in miR-494 expression and a 1.2-fold decrease in miR-612 in the CSF of the OA-CSM affected group (P = .41 and .89, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Data generated from our study represent an initial characterization of the miRNA profile of normal canine CSF and suggest that a distinct CSF miRNA expression profile is associated with OA-CSM.

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.

Cerebrospinal fluid lactate in dogs with inflammatory central nervous system disorders.

BACKGROUND: Cerebrospinal fluid (CSF) lactate is frequently used as a biomarker in humans with inflammatory central nervous system (CNS) disorders including bacterial meningitis and autoimmune disorders such as multiple sclerosis. HYPOTHESIS: Cerebrospinal fluid lactate concentrations are increased in a subset of dogs with inflammatory CNS disorders. ANIMALS: One hundred two client-owned dogs diagnosed with inflammatory CNS disease. METHODS: Case series. Cases were identified both prospectively at the time of diagnosis and retrospectively by review of a CSF biorepository. Cerebrospinal fluid lactate was analyzed with a commercially available, handheld lactate monitor. Subcategories of inflammatory disease were created for comparison (eg, steroid-responsive meningitis arteritis, meningoencephalitis of unknown etiology). RESULTS: Cerebrospinal fluid lactate concentrations were above reference range in 47% of dogs (median, 2.5 mmol/L; range, 1.0-11.7 mmol/L). There was no significant difference in lactate concentrations between disease subcategories (P = .48). Significant but weak correlations were noted between CSF lactate concentration and nucleated cell count (r = .33, P < .001), absolute large mononuclear cell count (r = .44, P < .001), absolute small mononuclear cell count (r = .39, P < .001), absolute neutrophil cell count (r = .24, P = .01), and protein (r = .44, P < .001). No correlation was found between CSF lactate concentration and CSF red blood cell count (P = .58). There was no significant association of CSF lactate concentration with survival (P = .27). CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid lactate concentrations could serve as a rapid biomarker of inflammatory CNS disease in dogs.

Detection of Intraspinal Spirocerca lupi in Canine Cerebrospinal Fluid by Polymerase Chain Reaction.

Aberrant migration of Spirocerca lupi into the spinal cord is an important cause of severe progressive neurological dysfunction in dogs. Although early diagnosis is essential to prevent deterioration, ante-mortem diagnosis of this condition remains challenging. The aim of this study was to evaluate the detection of the 18S ribosomal DNA (rDNA) S. lupi gene in the cerebrospinal fluid (CSF) of presumptively-affected dogs using polymerase chain reaction (PCR). Dogs with a non-compressive spinal cord lesion, pleocytosis with presence of eosinophils in the CSF and a characteristic clinical presentation were included. CSF samples from eight dogs were available for the study, of which seven were definitively diagnosed with intraspinal spirocercosis by PCR of either the CSF samples (6/7) or tissue samples obtained at necropsy examination (3/7), or both (2/7). Of these seven positive cases, only one dog had a negative CSF PCR, indicating a sensitivity of 86% for detecting nematode DNA in the CSF of infected dogs using this PCR protocol. The nematode DNA sequences obtained from the CSF of six dogs and the spinal cord tissue of three dogs were 98-100% identical to the publicly available sequences of S. lupi, confirming the diagnosis. These findings indicate that PCR targeting the 18S rDNA of S. lupi in CSF is useful for the ante-mortem diagnosis of canine intraspinal spirocercosis.

Clinical characteristics, breed differences, and quality of life in North American dogs with acute steroid-responsive meningitis-arteritis.

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is a common inflammatory neurologic disorder of dogs for which certain breeds are predisposed. OBJECTIVES: To determine whether breed differences exist in clinical features, treatment response, and relapse in a population of North American dogs with SRMA, and to evaluate the effect of disease on dogs' quality of life (QoL). ANIMALS: Sixty-one client-owned dogs with SRMA: 29 dogs identified through an American Kennel Club-Canine Health Foundation survey and 32 dogs from North Carolina (NC) State Veterinary Hospital. METHODS: Retrospective case series. Caregivers completed an online survey to assess QoL. RESULTS: Breeds represented most often included the Golden Retriever (n = 12), Bernese Mountain Dog (10), Wirehaired Pointing Griffon (9), Boxer (9), and Beagle (6). No breed differences were identified with respect to clinical severity, diagnostic findings, or outcome. Twenty-nine dogs (48%) had ≥1 disease relapse. There was a significant effect of cerebrospinal fluid nucleated cell count on the frequency of disease relapse (P = .003), but no relationship was identified between treatment protocol and relapse. Dogs' QoL was associated with the severity of corticosteroid-related adverse effects (P = .03), which were dose-related (r = .24, P = .02) and more prevalent in Wirehaired Pointing Griffons than in other breeds (P = .04). CONCLUSION AND CLINICAL IMPORTANCE: Golden Retrievers and Wirehaired Pointing Griffons should be considered among the breeds recognized to develop SRMA. Treatment with higher corticosteroid dosages is correlated with more severe adverse effects and worse QoL, but it may not improve clinical outcome.

Evaluation of IL-1ß levels in epilepsy and traumatic brain injury in dogs.

BACKGROUND: Epilepsy is a common neurological disease in dogs affecting approximately 0.6-0.75% of the canine population. There is much evidence of neuroinflammation presence in epilepsy, creating new possibilities for the treatment of the disease. An increased expression of interleukin-1 beta (IL-1ß) was reported in epileptogenic foci. We hypothesized that there is an elevation of IL-1ß in serum and CSF of dogs with epilepsy, as well as in serum of dogs with TBI, reflecting involvement of this cytokine in pathophysiology of naturally occurring canine epilepsy in a clinical setting. RESULTS: IL-1ß levels were evaluated in CSF and serum of six healthy and 51 dogs with epilepsy (structural and idiopathic). In 16 dogs with TBI, only serum was tested. IL-1ß concentrations in CSF were not detectable. Serum values were not elevated in dogs with TBI in comparison to healthy controls (p > 0.05). However, dogs with epilepsy had increased levels of IL-1ß in serum (p = 0.003) regardless of the underlying cause of the disease (p = 0.0045). There was no significant relationship between the variables and IL-1ß levels. Statistically noticeable (p = 0.0630) was that approximately 10% of dog with epilepsy (R2 = 0.105) had increased seizure frequency and IL-1ß elevation. CONCLUSION: Increased IL-1ß levels were detected in the peripheral blood in dogs with idiopathic and structural epilepsy leading to the assumption that there is an involvement of inflammation in pathophysiology of epilepsy which should be considered in the search for new therapeutic strategies for this disease. However, to better understand the pathogenic role of this cytokine in epilepsy, further evaluation of IL-1ß in brain tissue is desired.