Steroid-responsive Meningitis-arteritis Research Articles

Signalment, clinical characteristics and outcomes of an Australian population of dogs with steroid responsive meningitis-arteritis (SRMA) - 124 cases (2013-2023).

Variations in canine breeds presenting with steroid responsive meningitis-arteritis (SRMA) have been observed across different geographical regions internationally. However, there are no published studies describing affected dogs in an Australian population to date. This descriptive study aimed to characterise the signalment, as well as the clinical characteristics and outcomes in an Australian population of client-owned dogs with SRMA. Medical records from five veterinary referral hospitals in the state of New South Wales between 2013 and 2023 were retrospectively reviewed. One hundred and twenty four dogs were included in the study. The breeds which presented with SRMA most commonly included Golden Retriever (19/124, 15.3%), Italian Greyhound (11/124, 8.8%), Boxer (8/124, 6.5%), "Cavoodle" (Cavalier King Charles Spaniel x Poodle) (8/124, 6.5%), Corgi (7/124, 5.6%), Border Collie (6/124, 4.8%) and Australian Kelpie (5/124, 4.0%). The disease was observed more commonly in males, representing 79/124 (63.7%) of dogs. Presenting concerns, examination findings and laboratory abnormalities were otherwise consistent with international studies. The frequency of ≥1 relapse for dogs with a ≥6-month follow-up period was 32/85 (37.6%). A higher frequency of ≥1 relapse was seen in female dogs and in Corgi and Italian Greyhound breeds. All Corgis who relapsed demonstrated multiple relapses. In conclusion, this study observed a variation in breeds presenting with SRMA compared to international publications, which may reflect both differences in breed popularity, as well as varying interbreed susceptibility dependent on geographical location.

Steroid-Responsive Meningitis-Arteritis in a Small Breed Dog Case Report and Literature Review

Steroid-Responsive Meningitis-Arteritis in a Small Breed Dog Case Report and Literature Review

Magnetic resonance imaging findings in dogs with steroid-responsive meningitis-arteritis in the UK and their clinical significance: 53 cases (2013-2021).

To describe the MRI findings in a UK referral population of dogs with steroid-responsive meningitis-arteritis and to determine if they were associated with any specific clinical features or outcomes. We performed a multi-centre retrospective case series of dogs diagnosed with steroid-responsive meningitis-arteritis in the UK that underwent MRI. Blinded consensus review of the MRI studies was performed and the findings described. The presence or absence of specific MRI abnormalities were analysed for significant associations with presenting signs, results of investigations or case outcomes. Fifty-three dogs were included. The most common MRI findings were paravertebral muscle changes (30/53; 56.6%), meningeal contrast enhancement (13/41; 31.7%) and spinal cord parenchymal T2-W hyperintensity (15/53; 28.3%). Haemorrhage was observed in five of 53 (9.4%) cases - three intradural-extramedullary, one intramedullary and one extradural. Following binary logistic regressions, T2-W spinal cord parenchymal hyperintensity had a significant positive association with paresis/paralysis (odds ratio 14.86, 95% confidence interval 1.42 to 154.99) as did haemorrhage (odds ratio 16.12, confidence interval 2.05 to 126.73). Fifty-two (98.1%) dogs survived to discharge. Relapse occurred in nine of 29 (31.0%) dogs with sufficient follow-up, and no MRI finding had a significant relationship with its occurrence. Magnetic resonance imaging findings for steroid-responsive meningitis-arteritis can be severe and extensive, as can the clinical presentation. The presence of paresis/paralysis should raise concern for haemorrhage, though most dogs still have a good prognosis.

In sickness and health - a questionnaire based study regarding immune mediated diseases and neoplasia in Swedish Nova Scotia Duck Tolling Retrievers

BackgroundThe Nova Scotia Duck Tolling Retriever (NSDTR) has previously been highlighted as a breed at risk for developing immune mediated diseases and cancer. The immune response is of great importance for the development of neoplastic disease and a dysregulated immune response may predispose to cancer. Two of the commonly seen immune mediated diseases in NSDTRs are immune mediated rheumatic disease (IMRD), which bears similarities to systemic lupus erythematosus (SLE) affecting humans, and steroid-responsive meningitis-arteritis (SRMA), which is a non-infectious inflammation of the meninges and the leptomeningeal vessels. The aim of this survey study was to investigate the lifetime prevalence of immune mediated diseases and tumors among Swedish NSDTRs based on owners’ information. The study design was cross-sectional. A questionnaire was sent to 4102 persons who owned or had previously owned a NSDTR. The questions concerned information about the dog and its overall health status as well as specific diseases.ResultsThe response rate was 30%, including 935 live NSDTRs, corresponding to approximately 20% of the current population registered in Sweden (n = 4564), and 177 dead dogs. The surveyed dogs were spread over different ages and sex and corresponded to the typical demographic profile of the general dog population. Of the 935 individuals that were alive, 28 dogs (3%) were reported as previously diagnosed with IMRD and 33 dogs (3.5%) were reported as previously diagnosed with SRMA, one dog was reported to have been diagnosed with both SRMA and IMRD. There were 129 dogs (14%) reported to have or have had a neoplasia of some kind. For the dead dogs (n = 177), almost 40% of the owners reported neoplasia as the main reason for death/euthanasia.ConclusionThis study reports an estimated lifetime prevalence of IMRD and SRMA, in the studied population of Swedish NSDTRs, of 3.0 and 3.5% respectively. In this study, 14% of the living dogs (n = 935) were reported to have a neoplasia of some kind and almost 40% of the deceased dogs (n = 177) were euthanized due to neoplasia or suspicion of it.

Prevalence of neurological diseases associated with cervical pain and/or signs of cervical myelopathy in French bulldogs: a retrospective analysis of 105 cases.

French bulldogs can be affected by several neurological diseases, with myelopathies representing the most frequent cause of neurological signs. Studies focusing on the epidemiology of cervical diseases in this breed are lacking. This study aims to describe the prevalence of neurological pathologies responsible for cervical pain and/or signs of cervical myelopathy, assuming that intervertebral disc herniation represents the most common disease; a second aim was to evaluate how often different pathologies coexist in this spinal region in French bulldogs. A retrospective analysis of medical records from the database of a single referral center (AniCura I Portoni Rossi Veterinary Hospital-Zola Predosa, Bologna, Italy) was performed, including French bulldogs presented for neck pain and/or neurological deficits consistent with cervical myelopathy. Clinical and imaging data were reviewed and used as inclusion criteria. Based on the number of MRI-diagnosed diseases, the eligible dogs were divided into three groups. One hundred five French bulldogs met the inclusion criteria. The most commonly diagnosed condition was an intervertebral disc herniation (66.9%), followed by C2 idiopathic hypertrophic ganglioneuritis (15.1%), cervical syringomyelia (11.5%), congenital osseous malformations (1.4%), spinal arachnoid diverticula (1.4%), neoplasms (1.4%), steroid-responsive meningitis-arteritis (0.7%), traumatic vertebral fractures (0.7%), and other (0.7%). For the vast majority of dogs (75/105) a single pathology was diagnosed, with intervertebral disc herniations accounting for 86.7% of cases, involving C3-C4 IVD most commonly. In the remaining 30 dogs, two or three different and concurrent diseases were detected. Among these 30 dogs, intervertebral disc herniations still remained the most diagnosed condition, in combination with C2 idiopathic hypertrophic ganglioneuritis and syringomyelia in 19 and seven cases, respectively. The results of this study highlight that different pathologies can affect the cervical spinal cord in French bulldogs, with intervertebral disc herniations representing the most frequent condition, as previously described in the veterinary literature. In almost a third of cases, different pathologies can coexist at the cervical level. However, for cases in which different pathologies are present at the same time, it is not always possible to clearly establish their clinical significance.

Elevated levels of IL-12/IL-23p40 in Nova Scotia Duck Tolling Retrievers with autoimmune disease and lymphoma

The Nova Scotia Duck Tolling Retriever (NSDTR) is predisposed to immune mediated rheumatic disease (IMRD), steroid-responsive meningitis-arteritis (SRMA) and certain forms of cancer. Cytokines are the main regulators of the immune system. Interleukin 2 is a cytokine involved in activation of T regulatory cells, playing a role in central tolerance and tumor immunity. Interleukin 12 and interleukin 23 share the same subunit, p40, and are both pro-inflammatory cytokines. The aim of this study was to compare levels of IL-2 in healthy NSDTRs to those with cancer or autoimmune disease and to compare levels of IL-12/IL-23p40 in healthy NSDTRs and beagles versus NSDTRs with cancer or autoimmune disease. 62 dogs were included in the analysis of IL-12/IL-23p40; healthy NSDTRs (n = 16), healthy beagles (n = 16), NSDTRs autoimmune (n = 18) and NDSTRs lymphoma/mastocytoma (n = 12) and 68 dogs for IL-2; healthy (n = 20), autoimmune (n = 36) and lymphoma/mastocytoma/adenocarcinoma (n = 12). NSDTRs with autoimmune disease had higher levels of IL-12/IL-23p40 compared to healthy dogs (p = 0.008). NSDTRs with lymphoma also had higher levels of IL-12/IL-23p40 compared to healthy NSDTRs (p = 0.002). There was no difference in levels of IL-2 between healthy and diseased NSDTR. Statistical analysis was performed using Bonferroni corrections for multiple testing. These findings can contribute to the knowledge of autoimmune disease and cancer in dogs.

C-reactive protein concentration has limited value in the diagnosis of meningoencephalitis of unknown origin in dogs.

To evaluate blood and cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP) in dogs with meningoencephalitis of unknown origin (MUO); to evaluate whether blood CRP concentration is associated with epidemiological, clinicopathologic, and MRI findings; and to investigate blood CRP predictive power in survival. 30 client-owned dogs with MUO, 15 client-owned dogs with steroid-responsive meningitis arteritis (SRMA; positive control group), and 15 healthy dogs (negative control group). Blood CRP concentration was measured in each group, while it was performed in CSF only in the MUO and SRMA groups. The analysis of epidemiological data included breed, age, sex, duration of clinical signs, and history of seizures. Blinded analysis of MRI was performed based on a classification grid, and traditional CSF analysis parameters were assessed. The predictive power of blood CRP concentration regarding survival at 6 months was investigated. Of the 30 dogs with MUO, 9 (30%) had an increased CRP concentration in blood, and 3 (10%) showed a measurable CRP in CSF. Median blood CRP concentration in dogs with MUO was 0.1 mg/L (range, 0.1 to 102 mg/L), which was not statistically different from the healthy dog group but significantly lower than the SRMA control group. Only the duration of clinical signs was positively associated with an increased blood CRP level. Blood CRP concentration was not associated with survival at 6 months. Blood CRP concentration is of limited value for the diagnosis and prognosis of dogs with MUO. Chronicity of the disease may be associated with an increased concentration of blood CRP.

Neutrophil extracellular traps in CSF and serum of dogs with steroid-responsive meningitis-arteritis.

In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies.

Elevated Interleukin-31 Levels in Serum, but Not CSF of Dogs with Steroid-Responsive Meningitis-Arteritis Suggest an Involvement in Its Pathogenesis.

Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated disease, but the exact pathomechanism remains unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize that IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, and atopic dermatitis, and of healthy control dogs using a competitive canine IL-31 ELISA. The mean serum IL-31 level in dogs with SRMA (n = 18) was mildly higher compared to dogs with atopic dermatitis (n = 3, p = 0.8135) and MUO (n = 15, p = 0.7618) and markedly higher than in healthy controls (n = 10, p = 0.1327) and dogs with infectious meningoencephalitis (n = 3, no statistics). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value for dogs with SRMA (n = 23) was quite similar to that for healthy controls (n = 8, p = 0.4454) and did not differ markedly from dogs with MUO (n = 19, p = 0.8724) and infectious meningoencephalitis. Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 immune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.

MicroRNA profiling of cerebrospinal fluid from dogs with steroid responsive meningitis-arteritis and meningoencephalitis of unknown origin.

Non-infectious inflammatory diseases of the central nervous system in dogs, such as steroid responsive meningitis-arteritis (SRMA) and meningoencephalitis of unknown origin (MUO), represent a common clinical challenge that needs extensive and multimodal work-up to reach a presumptive diagnosis. Both diseases are presumably caused by dysregulations of the immune system, but further research is needed in order to understand the molecular mechanisms behind each disease and to optimize treatment. By next-generation sequencing and subsequent quantitative real-time PCR (qPCR) verification, we designed a prospective case-control pilot study to analyze the small RNA profiles of cerebrospinal fluid from dogs suffering from MUO (N = 5), dogs suffering from SRMA (N = 8), and healthy dogs (N = 5) presented for elective euthanasia used as the Control group. Our results showed an overall enrichment in Y-RNA fragments across all samples, followed by microRNAs (miRNAs) and ribosomal RNAs as the major findings. Additional traces of short RNA reads mapped to long non-coding RNAs and protein-coding genes were also found. From the detected canine miRNAs, miR-21, miR-486, miR-148a, miR-99a, miR-191 and miR-92a were among the most abundant. Dogs with SRMA showed higher differences in miRNA abundance than dogs with MUO when compared to healthy dogs, and miR-142-3p was consistently detected as differentially upregulated in both diseases, although at a low concentration. Moreover, miR-405-5p and miR-503-5p showed different profiles between SRMA and MUO dogs. Subsequent qPCR analyses confirmed miR-142-5p, miR-191-5p and miR-92a-3p as significantly upregulated miRNAs in dogs with SRMA and/or MUO. Cerebrospinal fluid is a challenging biological material to use for profiling miRNAs due to the low content of circulating RNAs. Despite this, we could confirm several miRNAs being differentially abundant when comparing healthy dogs and dogs with MUO and SRMA, respectively. The results of this study indicate a potential role of miRNAs in the underlying molecular mechanisms of these diseases and establish the basis for further studies.

Non‐traumatic hemorrhagic myelopathy in dogs

Non-traumatic spinal cord hemorrhage (NTSH) is an uncommon cause of myelopathy in dogs. Describe the clinical characteristics, concurrent medical conditions and underlying causes, magnetic resonance imaging (MRI) findings and outcome in dogs with NTSH. Dogs diagnosed with NTSH using gradient echo T2-weighted (GRE) sequences with or without histopathological confirmation of hemorrhage were included. Dogs with a traumatic cause were excluded, including those with compressive intervertebral disc extrusion. Retrospective descriptive study; the databases of 2 referral hospitals were searched between 2013 and 2021. Twenty-three dogs met inclusion criteria. The onset of signs was acute and progressive in 70% of cases; spinal hyperesthesia was variable (48%). Hemorrhage was identified in the thoracolumbar spinal segments in 65% of dogs. An underlying cause was identified in 65% of cases. Angiostrongylus vasorum represented 18% of the total cohort, followed by steroid-responsive meningitis arteritis (SRMA; 13%). Overall, 64% of dogs had a good or excellent outcome, regardless of cause; which was increased to 100% for SRMA, 75% for A. vasorum and 75% for idiopathic NTSH. Outcome was not associated with neurological severity. Recovery rate was 67% and 50% for nociception-intact and nociception-negative dogs, respectively. Larger prospective studies would be required to define prognostic factors for dogs with NTSH, but outcome appeared to be most influenced by the underlying cause, as opposed to neurological severity at presentation.

Immunoglobulin profiling with large high-density peptide microarrays as screening method to detect candidate proteins for future biomarker detection in dogs with steroid-responsive meningitis-arteritis.

Large high-density peptide microarrays are a suitable screening method to detect possible autoantigens which might be involved in the pathogenesis of SRMA. The IgA and IgG profile of pooled serum samples of 5 dogs with SRMA and 5 dogs with neck pain due to intervertebral disc herniation (IVDH) without ataxia or paresis were compared via commercially available high-density peptide microarrays (Discovery Microarray) containing 29,240 random linear peptides. Canine distemper virus nucleoprotein (CDVN) served as positive control as all dogs were vaccinated. Common motifs were compared to amino acid sequences of known proteins via databank search. One suitable protein was manually selected for further analysis with a smaller customized high-density peptide microarray. Pooled serum of dogs with SRMA and IVDH showed different IgA and IgG responses on Discovery Microarray. Only top IgG responses of dogs with SRMA showed a common motif not related to the control protein CDVN. This common motif is part of the interleukin 1 receptor antagonist protein (IL1Ra). On IL1Ra, dogs with SRMA displayed IgA binding to an additional epitope, which dogs with IVDH did not show. IL1Ra is an anti-inflammatory acute phase protein. Different immunoglobulin binding patterns on IL1Ra could be involved in the pathogenesis of SRMA and IL1Ra might be developed as future biomarker for SRMA.

Signalment and C-reactive protein values in dogs with immune-mediated polyarthritis and steroid responsive meningitis arteritis.

This retrospective multicentric study aims to evaluate the ability of CRP concentration to differentiate between dogs diagnosed with IMPA and SRMA. C-reactive protein (CRP) is a marker of inflammation widely used in two of the most commonly diagnosed immune-mediated diseases in dogs-Immune-mediated polyarthritis (IMPA) and steroid responsive meningitis arteritis (SRMA). Data collected from medical records of 167 client-owned dogs included age, breed, gender, neuter status, body weight, body temperature, CRP concentration, month and season of diagnosis. CRP was measured quantitatively in 142 dogs (84%) and semi-quantitatively in 27 dogs (16%). SRMA was diagnosed significantly more often in dogs < 12 months old and IMPA in dogs ≥12 months old (P < 0.001). Dogs diagnosed with SRMA had higher CRP concentration than dogs diagnosed with IMPA (P = 0.02). This difference was influenced by the dog's age-when a dog was <12 months old, a higher CRP concentration indicated IMPA (P = 0.02), whereas when a dog was ≥12 months old, a higher CRP concentration indicated SRMA (P = 0.02). CRP concentration as a sole diagnostic modality showed only fair discriminatory potential to differentiate between SRMA and IMPA (area under ROC curve close to 0.7). CRP concentration varied depending on patient age and definitive diagnosis. It may play some role in differentiating between SRMA and IMPA but should not be used as the sole diagnostic modality, given it has been demonstrated to only have fair discriminatory potential.

Assessment of oligoclonal bands in cerebrospinal fluid and serum of dogs with meningoencephalitis of unknown origin.

Meningoencephalitis of unknown origin (MUO) is an inflammatory disease of the canine central nervous system (CNS) that shares several features with multiple sclerosis (MS) in humans. In approximately 95% of MS patients, ≥ two immunoglobulin G (IgG) oligoclonal bands (OCBs) are detectable exclusively in the cerebrospinal fluid (CSF). To investigate OCBs in CSF and serum in dogs affected by MUO, intervertebral disc disease (IVDD), idiopathic epilepsy (IE), intracranial neoplasia (IN), steroid-responsive meningitis-arteritis (SRMA), and diseases outside the CNS. We hypothesize that the highest prevalence of CSF-specific OCBs (≥ two OCBs uniquely in the CSF) would be found in dogs affected by MUO. Client-owned dogs (n = 121) presented to the neurology service due to neurological deficits. Prospective study. Measurement of IgG concentration in CSF and serum via a canine IgG ELISA kit. OCB detection via isoelectric focusing (IEF) and immunoblot. Presence of CSF-specific OCBs was significantly higher in dogs with MUO (57%) compared to 22% in IN, 6% in IE, 15% in SRMA, 13% in IVDD, and 0% in the non-CNS group (p < .001). Dogs with MUO were 9.9 times more likely to show CSF-specific OCBs than all other diseases together (95% confidence interval, 3.7-26.4; p < .001). MUO showed the highest prevalence of CSF-specific OCBs, indicating an inflammatory B cell response. Future studies are needed to evaluate the prevalence in the specific MUO subtypes and a possible similarity with human MS.

Magnetic resonance imaging highlights the meningeal involvement in steroid responsive meningitis-arteritis and suggests the inflammation of the surrounding tissues (70 cases).

IntroductionSteroid-responsive meningitis-arteritis (SRMA) is an immune-mediated disorder of young dogs for which there is no definitive ante-mortem diagnostic test. Magnetic Resonance Imaging (MRI) can be used to explore other differentials and extensive reports about its usefulness in the diagnosis of SRMA are lacking. The aims of this study were to retrospectively investigate the characteristics of MRI studies of the cervical spine of dogs diagnosed with SRMA and to compare the diagnostic capability of MRI obtained with low-field and high-field units.Materials and methodsThis is a double center, retrospective case series. Databases were searched between 2008 and 2021 for dogs with a diagnosis of SRMA. Dogs were included if the following criteria were fulfilled: a diagnosis of cervical SRMA, results of CSF analysis, and MRI of the cervical spine available for re-evaluation.ResultsSeventy cases were selected. MRI abnormalities were found in 69 cases (98.6%). Enhancement of the meninges, nerve roots, synovium of the articular facets and paravertebral muscles was present in 61 (87.1%), 10 (14.3%), 34 (48.6%), and 34 (48.6%) cases, respectively, when considering all MRI. In the low-field MRI, enhancement of these structures was present in 45 (90%), 4 (8%), 21 (42%) and 23 (46%) cases, respectively. In the high-field MRI, enhancement of these structures was present in 16 (80%), 6 (30%), 13 (65%) and 11 (55%) cases, respectively. Fat suppressed T1W images showed meningeal enhancement better than T1W images. When all the MRIs were considered, a significant increase in cell count of the cerebrospinal fluid was found between the three groups based on the meningeal MRI score (p = 0.001). In cases with no meningeal enhancement but enhancement of synovium of the articular facets and/or muscles a significantly lower cerebrospinal fluid cell count was present (p = 0.043), when considering all MRIs.ConclusionsThe most frequent detection on cervical MRI of dogs affected by SRMA is meningeal enhancement, often accompanied by enhancement of the synovium of the articular facets and/or muscular enhancement. Both low-field and high-field MRI have good diagnostic capability but the latter enables a more thorough investigation thanks to specific sequences. MRI is useful as a complementary tool to cerebrospinal fluid analysis.

Detection of Extracellular Traps in Canine Steroid-Responsive Meningitis-Arteritis.

Extracellular traps (ETs) are DNA networks formed by immune cells to fight infectious diseases by catching and attacking pathogenic microorganisms. Uncontrolled ET formation or impaired ET clearance can cause tissue and organ damage. Steroid-responsive meningitis-arteritis (SRMA) represents an immune-mediated, presumably non-infectious, purulent leptomeningitis and fibrinoid-necrotizing arteritis and periarteritis of young-adult dogs. Chronic and recurrent cases of SRMA are characterized by lymphohistiocytic inflammatory cell infiltration in the meninges and perivascular tissue. This study aimed to identify extracellular traps in dogs with SRMA, a model for immune-mediated diseases in the central nervous system (CNS). Hematoxylin and eosin-stained samples of two young dogs with chronic, recurrent SRMA were examined by light microscopy for characteristic lesions and consecutive slices of affected tissues were stained for detection of ETs by immunofluorescence microscopy using antibodies against DNA–histone-1 complexes, myeloperoxidase, and citrullinated histone H3. Histology revealed purulent and lymphohistiocytic leptomeningitis (n = 2/2) with meningeal periarteritis (n = 2/2) and periadrenal located lymphohistiocytic periarteritis (n = 1). Extracellular DNA networks and inflammatory cell infiltrates of macrophages, neutrophil granulocytes, and lymphocytes were detected in the subarachnoid space of the leptomeninx (n = 2/2) and perivascularly in meningeal (n = 2/2) as well as periadrenal vessels (n = 1/1). In summary, extracellular DNA fibers and attached ET markers are detectable in affected perivascular and meningeal tissues of dogs suffering from SRMA. The proof of principle could be confirmed that ETs are present in canine, inflammatory, and non-infectious CNS diseases and possibly play a role in the pathogenesis of SRMA.

Screening for Viral Nucleic Acids in the Cerebrospinal Fluid of Dogs With Central Nervous System Inflammation.

Central nervous system (CNS) inflammation is a common cause of neurological dysfunction in dogs. Most dogs with CNS inflammation are diagnosed with presumptive autoimmune disease. A smaller number are diagnosed with an infectious etiology. Additionally, at necropsy, a subset of dogs with CNS inflammation do not fit previously described patterns of autoimmune disease and an infectious cause is not readily identifiable. Because viral infection is a common cause of meningoencephalitis in people, we hypothesize that a subset of dogs presented with CNS inflammation have an occult viral infection either as a direct cause of CNS inflammation or a trigger for autoimmunity. The goal of this research was to screen cerebrospinal fluid from a large number dogs with CNS inflammation for occult viral infection. One hundred seventy-two dogs with neurological dysfunction and cerebrospinal fluid (CSF) pleocytosis were identified. Of these, 42 had meningoencephalitis of unknown origin, six had steroid-responsive meningitis-arteritis, one had eosinophilic meningoencephalitis, five had documented infection, 21 had and undetermined diagnosis, and 97 had a diagnosis not consistent with primary inflammatory disease of the CNS (e.g., neoplasia). CSF samples were subsequently screened with broadly reactive PCR for eight viral groups: adenovirus, bunyavirus, coronavirus, enterovirus, flavivirus, herpesvirus, paramyxovirus, and parechovirus. No viral nucleic acids were detected from 168 cases screened for eight viral groups, which does not support occult viral infection as a cause of CNS inflammation in dogs. La Crosse virus (LACV) nucleic acids were detected from four cases in Georgia. Subclinical infection was supported in two of these cases but LACV could not be ruled-out as a cause of infection in the other two cases, suggesting further research is warranted to determine if LACV is an occult cause of CNS inflammation in dogs.

Inflammatory Disease Affecting the Central Nervous System in Dogs: A Retrospective Study in England (2010-2019).

The epidemiology of inflammatory diseases affecting the central nervous system (CNS) in dogs is largely unknown. We aimed to report the relative proportion of different causes of inflammatory disease affecting the CNS in dogs and identify predictors for infectious vs. immune-mediated conditions and predictors for the most common diseases affecting the brain and the spinal cord. This was a retrospective cohort study over a 10-year period in 2 referral institutions using multivariable and multinomial logistic regression for identification of risk factors. In total, 1,140 client-owned dogs diagnosed with inflammatory disease affecting the CNS were included. Fifteen different diagnoses were identified, with immune-mediated (83.6%) disease being more common than infectious conditions (16.4%). The most common immune-mediated conditions diagnosed were meningoencephalitis of unknown origin (47.5%) and steroid-responsive meningitis–arteritis (30.7%), and the most common infectious conditions were discospondylitis (9.3%) and otogenic intracranial infection (2.2%). Older age (p < 0.001, OR = 1.019, 95% CI: 1.014–1.024), higher body weight (p < 0.001, OR = 1.049, 95% CI: 1.025–1.074), male sex (p = 0.009, OR = 1.685, 95% CI: 1.141–2.488), longer duration of the clinical signs before presentation (p < 0.001, OR = 1.011, 95% CI: 1.006–1.017), progressive nature of the clinical signs (p < 0.001, OR = 2.295, 95% CI: 1.463–3.599), identification of a possibly associated preceding event (p = 0.0012, OR = 1.93, 95% CI: 1.159–3.213), and hyperesthesia on presentation (p < 0.001, OR = 2.303, 95% CI: 1.528–3.473) were associated with a diagnosis of infectious diseases. Our data shows that immune-mediated diseases are more common than infectious conditions as a cause for inflammatory CNS disease in dogs. The risk factors for the most common diagnoses were identified from signalment, history, and findings of the physical and neurological examinations to give valuable information that can guide clinicians with their investigations.

Clinical and paraclinical approach to patients with steroid-responsive meningitis-arteritis (SRMA)

Steroid-responsive meningitis-arteritis (SRM) is an inflammatory disease of the central nervous system, commonly seen in medium and large canine juveniles under two years of age. The examination of cerebrospinal fluid is the most reliable diagnostic method for diagnosing inflammatory diseases of the central nervous system (CNS). Six patients with a clinical presentation of hyperthermia and hyperalgesia on paraspinal palpation of the cervical segment were included in this study. Paraclinical examinations included serum C-reactive protein (CRP) determination, cytological examination of cerebrospinal fluid and determination of total CSF proteins. For 33.33% of the patients, the neurological examination revealed proprioception and/‌or locomotion deficits. The evolution of patients with MASR was acute, progressive, and after the initiation of medication, 100% complete remission was achieved.

Unilateral blindness associated with steroid‐responsive meningitis arteritis in a 9‐month‐old Beagle

AbstractA 9‐month‐old Beagle presented with a 24‐hour history of lethargy, pyrexia, and cervical and thoracolumbar pain. Cranial nerve examination revealed an absent menace response, an absent dazzle reflex, and absent direct and left‐to‐right consensual pupillary light reflexes in the left eye, indicating a non‐visual eye. Funduscopic examination and electroretinography were unremarkable. Complete blood profile showed moderate neutrophilia, monocytosis and elevated C‐reactive protein. Cerebrospinal fluid analysis revealed a neutrophilic pleocytosis. Magnetic resonance imaging of the head, thoracic and abdominal imaging, urinalysis, joint taps and infectious disease titres were unremarkable. A diagnosis of steroid‐responsive meningitis arteritis (SRMA) with left optic nerve involvement was concluded. Blindness has not been reported in cases with SRMA. An extension of the leptomeningeal inflammation into the optic nerve sheaths is hypothesized as the underlying pathophysiology. SRMA should be considered as a cause of blindness in the presence of other clinical signs compatible with this condition.