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The cerebral biomarkers, neurofilament light chain (NfL), amyloid-β, 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-β 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.

Background Current diagnosis of brain disease in dogs is dependent on imaging and cerebrospinal fluid (CSF) analysis, including total nucleated cell counts and albumin concentrations. Hypothesis/Objectives To determine whether multiplex cytokine/chemokine (Ct/Cm) analysis can differentiate among dogs with meningoencephalitis of unknown origin (MUE), idiopathic epilepsy (IE), and brain neoplasia. Animals Client owned dogs diagnosed with brain disease with MRI and CSF diagnostics. Groups included 18 dogs with a diagnosis of MUE, 21 dogs with IE, and 7 dogs with brain tumors. Methods A retrospective observational study; a multiplex immunoassay was utilized to measure CSF concentrations for the following: Interleukin (IL)‐2, IL‐6, IL‐7, IL‐8, IL‐10, IL‐15, and IL‐18, granulocyte macrophage colony‐stimulating factor (GM‐CSF), interferon gamma (IFN‐γ), keratinocyte chemoattractant (KC)‐like protein, IFN‐γ‐inducible protein‐10 (IP‐10), monocyte chemotactic protein 1 (MCP‐1), and tumor necrosis factor alpha (TNF‐α). Results Several Ct/Cm were detected only in MUE cases: GM‐CSF (9/18), IFN‐γ (13/18), IL‐2 (8/18), IL‐15 (4/18), and TNF‐α (11/18). Other Ct/Cm concentrations were significantly higher in MUE cases (IL‐8: median 101 pg/mL, range 144, p = 0.019; IL‐18: median 3 pg/mL, range 0.52, p < 0.001; MCP‐1: median 814 pg/mL, range 1319, p = 0.004; and IL‐6: median 5 pg/mL, range 16, p < 0.001) compared to epilepsy and neoplasia. Conclusions and Clinical Importance IFN‐γ, TNF‐α, GM‐CSF, IL‐2, and IL‐15 might be specific markers of MUE in canine CSF and could be potentially useful biomarkers in the diagnosis of MUE.

Background In small breed dogs, enlarged ventricles of the brain are a common finding on magnetic resonance imaging (MRI). In humans, enlarged lateral ventricles are usually the consequence of mesencephalic aqueduct stenosis. Cerebrospinal fluid (CSF) velocity measurements indicating obstruction are lacking in dogs. Objectives Measure CSF velocity in small breed dogs with ventricular enlargement. Animals Velocity of CSF in 17 small breed dogs with enlarged ventricles and 8 small breed dogs with normal‐sized ventricles was measured by phase‐contrast MRI at the mesencephalic aqueduct, foramen magnum (FM) and second cervical vertebra (C2). Methods Peak systolic (PSV) and diastolic (PDV) velocity, peak velocity (PV), difference between peak systolic and diastolic velocity (DPV), average velocity (AV) and maximum average velocity (MAV) were measured. Results Dogs with enlarged ventricles had lower PDV, PV, AV, and MAV at the dorsal subarachnoid space of the FM compared with dogs without enlargement (p < 0.05). At the ventral subarachnoid space of FM, moderate decreases in PDV, PV, DPV, AV, and MAV were found with increasing severity of ventricular enlargement. Conclusion Ventricular enlargement may be associated with or result in altered CSF flow dynamics, particularly decreased velocity at the craniocervical junction. This relationship may, in turn, reflect underlying structural changes, such as skull shape or craniocervical abnormalities. Therefore, enlarged ventricles in small breed dogs should be considered pathological findings.

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 Aβ42 and Aβ40 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 Aβ 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 TPAβ42/40 facilitated discrimination between CI‐MCI and CU aged dogs with area under curve ≥ 0.79. CSFAβ42 levels were higher (P = .09) in CU (1.25 ± 0.28 ng/mL) than in MCI (1.04 ± 0.32 ng/mL) dogs. CSF Aβ42 levels were correlated with the CP fragment (CPAβ40: P = .02, CPAβ42: P = .02). CPAβ42 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 Aβ should be determined in all of the 3 plasma fractions (TP, FP, CP). In the clinical approach, TPAβ42/40 could be used as an efficient preselection tool for the aged canine population targeting dogs with mild cognitive impairment.

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.

Background In dogs with idiopathic epilepsy (IE), 33% develop resistance to conventional anti‐seizure medication (ASM) despite adequate treatment. In human medicine, an immune‐mediated etiology is suspected in a subset of ASM‐resistant patients with epilepsy and cerebrospinal fluid (CSF)‐specific immunoglobulin G (IgG)‐type oligoclonal bands (OCBs) have been detected. In dogs, cases of autoimmune encephalitis recently were reported. Neuroinflammation may provide an additional explanation for the lack of response of certain dogs with IE to ASM. Hypothesis Cerebrospinal fluid‐specific OCBs are found in a subgroup of dogs with ASM‐resistant IE. Animals Eighty‐four dogs with IE were recruited from 3 referral centers and classified based on their response to ASM treatment (responsive, n = 56; resistant, n = 28). Methods Detection of OCBs was performed using isoelectric focusing (IEF) followed by immunoblotting. Associations of CSF‐specific OCBs with seizure type, severity, and response to ASM were calculated using logistic regression models. Results The overall frequency of CSF‐specific OCBs in dogs with IE was 15.5% (95% confidence interval [CI], 8.5%‐25%). In dogs with ASM‐resistant IE, 21.4% (6/28) had CSF‐specific OCBs compared with only 12.5% (7/56) in those responsive to ASM, but no evidence of an association was detected (odds ratio, 1.9; 95% CI, 0.57‐6.35; P = .29). Conclusions and Clinical Importance Cerebrospinal fluid‐specific OCBs were detected in a subgroup of dogs with IE. This finding could indicate that intrathecal IgG synthesis as a sign of neuroinflammation may play a role in disease pathogenesis.

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 (R 2 (Y) = 0.997, Q 2 (Y) = 0.828), from which norepinephrine was putatively identified as an important discriminative metabolite.

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-1β) was reported in epileptogenic foci. We hypothesized that there is an elevation of IL-1β 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-1β 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-1β 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-1β 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-1β levels. Statistically noticeable ( p  = 0.0630) was that approximately 10% of dog with epilepsy (R 2  = 0.105) had increased seizure frequency and IL-1β elevation. Conclusion Increased IL-1β 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-1β in brain tissue is desired.

Cerebrospinal fluid (CSF) plays a crucial role in maintaining brain homeostasis by facilitating the clearance of metabolic waste and regulating intracranial pressure. Dysregulation of CSF flow can lead to conditions like syringomyelia, and hydrocephalus. This review details the anatomy of CSF flow, examining its contribution to waste clearance within the brain and spinal cord. The review integrates data from human, canine, and other mammalian studies, with a particular focus on brachycephalic dogs. Certain dog breeds exhibit a high prevalence of CSF-related conditions due to artificial selection for neotenous traits, making them valuable models for studying analogous human conditions, such as Chiari-like malformation and syringomyelia associated with craniosynostosis. This review discusses the anatomical features specific to some brachycephalic breeds and the impact of skull and cranial cervical conformation on CSF flow patterns, providing insights into the pathophysiology and potential modelling approaches for these conditions.

Background The biomarker Calcitonin Gene‐Related Peptide (CGRP) is elevated in human conditions associated with neuropathic pain, but has not yet been studied in Cavalier King Charles Spaniels (CKCS) with Chiari‐like malformation (CM). Hypothesis/Objectives Cavalier King Charles Spaniels with clinical signs of CMSM would have higher CSF concentrations of CGRP than asymptomatic CKCS. Our aim was to measure CSF CGRP concentrations in CKCS with and without clinical signs of CMSM. Animals Twenty‐nine CKCS drawn from research and clinical cases underwent quantification of pain and scratching, a brain and spinal cord MRI, and lumbar CSF collection. Methods This was a prospective study with both normal and clinically affected CKCS recruited. The CSF concentration of CGRP (C‐CGRP) was measured using an ELISA assay. Dogs were grouped by the presence of SM, pain, and scratching, and concentrations of C‐CGRP were compared between groups using Wilcoxon Rank Sum. The concentration of C‐CGRP, pain score, and SM diameter were evaluated using linear regression. Results Concentration of C‐CGRP was significantly higher in painful dogs (median 116.1, range: 11.6–238.3 pg/mL) as compared to non‐painful dogs (median 77.7 pg/mL, range 0–266.2 pg/mL; p = 0.0124). No significant difference in C‐CGRP concentration was noted between dogs with (median 99.3, range 0–226.6 pg/mL) and without (median 102.2, range 6.0–266.2 pg/mL) SM (p = 0.305). Conclusions and Clinical Importance Cerebrospinal fluid CGRP concentration is elevated in CKCS exhibiting pain regardless of the presence of SM. CGRP might contribute to neuropathic pain in CMSM and could be a target for therapeutic intervention.