Steroid-responsive Meningitis-arteritis Research Articles

Cerebral extension of steroid‐responsive meningitis arteritis in a boxer

A comatose 30-month-old, entire male boxer was presented because of an acute history of a cluster of three to four seizures. Neurological examination suggested a diffuse to multifocal intracranial lesion. Magnetic resonance tomography revealed symmetrical multifocal to diffuse changes of the cerebral grey matter and ependymal lining with sediment in the lateral ventricles. Haematological examination revealed leucocytosis with neutrophilia. Cerebrospinal fluid examination revealed high protein concentration and polymorphonuclear pleocytosis. Despite antiepileptic treatment, therapy against increased intracranial pressure and antibiosis, the dog's condition continued to deteriorate and he was euthanased. Pathological examination revealed fibrinosuppurative meningo-ependymitis and necrotising arteritis throughout the brain. In addition, chronic inflammation and arterial stenosis was found in the spinal meninges. No infectious agent was found. A diagnosis of steroid-responsive meningitis arteritis was made. The massive extension into the meninges and ventricular system of the forebrain has not been described previously in dogs with steroid-responsive meningitis arteritis and should be considered in the differential diagnosis when an intracranial suppurative infection is suspected.

Concentrations of Acute‐Phase Proteins in Dogs with Steroid Responsive Meningitis‐Arteritis

Measurement of concentrations of acute-phase proteins (APPs) is used as an aid in the diagnosis of a variety of diseases in animals. To determine the concentration of APPs in dogs with steroid responsive meningitis-arteritis (SRMA) and other neurologic diseases. One hundred and thirty-three dogs with neurologic diseases, 6 dogs with sepsis, and 8 healthy dogs were included in the study. Thirty-six dogs had SRMA (31 of which had monitoring), 14 dogs had other meningoencephalitides (ME), 32 had disk disease (IVDD/DLSS), 26 had tumors affecting the central nervous system (TCNS), and 25 had idiopathic epilepsy (IE). Prospective, observational study: C-reactive protein (CRP), alpha(2)-macroglobulin (AMG), and albumin concentrations were determined in the serum or plasma. CRP was also measured in the cerebrospinal fluid. Serum CRP was significantly higher in dogs with SRMA (x=142 microg/mL+/-75) and sepsis (x=114 microg/mL+/-67) in comparison with dogs with other neurologic diseases (x=2.3-21 microg/mL; P< .001). There was no significant difference detected in AMG between groups. Serum albumin concentration was significantly lower (P< .01) in dogs with SRMA (x=3.2 g/dL+/-0.41) than in other groups (x=3.6-3.9 g/dL). Serum CRP concentration of SRMA dogs correlated with alkaline phosphatase levels (r=0.515, P= .003). CRP concentrations in serum are useful in diagnosis of dogs with SRMA. Serum CRP could be used as a monitoring parameter in treatment management of these dogs.

Selective CD11a upregulation on neutrophils in the acute phase of steroid-responsive meningitis-arteritis in dogs

Steroid-responsive meningitis-arteritis (SRMA) is a systemic inflammatory disease of juvenile to young adult dogs with a relapsing course and most prominent manifestation in the cervical meninges. The most important laboratory finding is a marked neutrophilic pleocytosis. Integrin (CD11a, b, c) expression on polymorphonuclear cells (PMNs) was quantified by immunophenotyping and subsequent flow cytometric measurements. Values were determined for peripheral blood in the acute phase of SRMA ( n = 14) as well as during glucocorticosteroid treatment ( n = 16). Results were compared to those from dogs with other neurological diseases ( n = 49) and healthy individuals ( n = 7). Integrin expression was also investigated on PMNs deriving from cerebrospinal fluid (CSF) of dogs in the acute phase of SRMA ( n = 14). In a second part of the study PMNs of healthy dogs were incubated with sera of dogs in the acute phase of SRMA ( n = 12). The influence on integrin expression was studied and results were compared to those after incubation with pooled sera of dogs suffering from idiopathic epilepsy ( n = 3). PMNs in peripheral blood of dogs in the acute phase of SRMA showed higher values of CD11a expression when compared to dogs under treatment and to control groups, whereas CD11b and c expression was comparable among the different groups. In the acute phase of SRMA CD11b expression on PMNs in CSF was increased in comparison to that in peripheral blood. Incubation with SRMA sera caused a stronger upregulation of CD11a than did pooled epilepsy sera in 9/12 cases whereas an upregulation of CD11b and c was observed in single cases only. High CD11a expression on PMNs in peripheral blood appears to be an important factor in the pathogenesis of SRMA. This integrin is known to be essential for adhesion of PMNs within the neutrophil recruitment cascade and therefore might mediate the enhanced invasion of neutrophils into the subarachnoidal space eventually leading to meningitis and clinical signs. Since sera of dogs suffering from SRMA selectively induce an upregulation of CD11a it can be suspected that this fluid contains one or multiple factors being responsible for this.

The role of acute phase proteins in diagnosis and management of steroid-responsive meningitis arteritis in dogs

Acute phase proteins (APPs) have become an important tool in the diagnosis, management and prognosis of inflammatory diseases in humans and are developing a similar utility in domestic species. Steroid-responsive meningitis arteritis (SRMA) is a well-recognised inflammatory disease of the dog, the diagnosis of which remains unsatisfactory based on clinical criteria and non-specific laboratory investigations. In this prospective pilot study the authors examined the acute phase response throughout the course of SRMA in serum and cerebrospinal fluid (CSF) by evaluating three key stages in disease management: presentation, treatment response and putative relapse. Serum APPs were found to be of value in supporting the diagnosis of SRMA and monitoring its treatment. C-reactive protein (CRP), serum amyloid-A (SAA), alpha-1-acid glycoprotein (AGP) and haptoglobin (Hp) all exhibited an increase above our laboratory reference range in nine patients at initial presentation. During treatment APPs decreased significantly compared to presentation except Hp which increased (Wilcoxon–Signed–Rank-test: CRP, SAA and AGP P < 0.05). Serum CRP and SAA were also found to be of clinical value in the identification of putative relapse (seven cases), particularly in the light of unperturbed CSF parameters where APP concentrations were elevated. CSF APPs were found to be less reliable markers in the management of this disease. The results indicate that SRMA causes a significant APP response in dogs, which although not disease specific, is of value in supporting the diagnosis of SRMA.

Disproportionally strong increase of B cells in inflammatory cerebrospinal fluid of dogs with Steroid-responsive Meningitis-Arteritis

Steroid-responsive Meningitis-Arteritis (SRMA) is a systemic inflammatory disease of juvenile to young adult dogs with a relapsing course and most prominent manifestation in the cervical meninges. Immunophenotyping and flow cytometric measurement of lymphocytes in peripheral blood (PB) and CSF was performed in the acute phase of SRMA ( n = 12) and during glucocorticosteroid treatment ( n = 10). Values were compared to those from dogs with other neurologic diseases ( n = 63) and healthy individuals ( n = 7). Dogs with SRMA had high CD4:CD8α ratios in PB and low T:B cell ratios in PB and CSF suggesting that a T H2-mediated immune response occurs. The T:B cell ratio in CSF was markedly lower than that in PB indicating that either a selective recruitment of B cells or, alternatively, their strong intrathecal proliferation takes place. SRMA appears to be a valuable animal model for the investigation of compartmentalization of immune responses and for studies on differences in local central nervous system and systemic immune responses.

Steroid responsive meningitis-arteritis in dogs

Steroid responsive meningitis-arteritis (SRMA) in the dog is a disease well recognised in small animal practice. A typical presentation would be a juvenile dog (less than two years of age) of medium to large breed (often pure bred) with lethargy, pyrexia, inappetence and some degree of axial skeletal pain. Axial skeletal pain is most commonly evident as reluctance to move, low head carriage, cervical or thoracolumbar pain on examination (Fig. 1) and occasionally an arched back. Clinical signs can wax and wane over a period of months. Once a diagnosis has been made the prognosis for remission is usually excellent.

Meningoencephalomyelitis of unknown aetiology in dogs: What's new?

Companion AnimalVolume 12, Issue 7 p. 53-58 Meningoencephalomyelitis of unknown aetiology in dogs: What's new? Giunio Bruto Cherubini DVM DECVN MRCVS, Giunio Bruto Cherubini DVM DECVN MRCVS EUROPEAN SPECIALIST IN VETERINARY NEUROLOGY DICK WHITE REFERRALS, NEUROLOGY/NEUROSURGERY SERVICE, STATION FARM, SIX MILE BOTTOM, CAMBRIDGESHIRE. CB8 0UHSearch for more papers by this author Giunio Bruto Cherubini DVM DECVN MRCVS, Giunio Bruto Cherubini DVM DECVN MRCVS EUROPEAN SPECIALIST IN VETERINARY NEUROLOGY DICK WHITE REFERRALS, NEUROLOGY/NEUROSURGERY SERVICE, STATION FARM, SIX MILE BOTTOM, CAMBRIDGESHIRE. CB8 0UHSearch for more papers by this author First published: 30 September 2010 https://doi.org/10.1111/j.2044-3862.2007.tb00202.xAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume12, Issue7September 2007Pages 53-58 RelatedInformation

Steroid responsive meningitis arteritis in a nine month old Whippet

A nine month old male entire Whippet presented with a 7 day history of lethargy, depression and inappetence. The dog’s owners noted that his head carriage was low and he had a stiff gait, which seemed worse after rest (Fig. 1). Although the dog was keen to eat he was reluctant to lower his head to the food bowl, only eating if hand fed at head level (Fig. 2).There was no history of travel or trauma, and previous history was unremarkable.

Aseptic Suppurative Meningitis in Juvenile Boxer Dogs: Retrospective Study of 12 Cases

Immune-mediated central nervous system inflammation is described in a series of 12 juvenile boxer dogs. A diagnosis of steroid-responsive meningitis-arteritis was made based on the clinical presentation and on diagnostic findings. The boxer breed was at a higher risk for this inflammatory condition than other breeds. Long-term follow-up (>2 years) confirmed a better prognosis in this breed than in the beagle and the Bernese mountain dog. Complete resolution of clinical signs without significant deficits or recurrences was obtained in all cases. Early clinical recognition and immunosuppressive treatment resulted in a better response and complete resolution of the disorder.

Clinical and clinicopathologic findings in three dogs with steroid-responsive meningitis-arteritis (SRMA).

Clinical and clinicopathologic findings in three dogs with steroid-responsive meningitis-arteritis (SRMA).

Steroid‐Responsive Meningitis‐Arteritis in Dogs with Noninfectious, Nonerosive, Idiopathic, Immune‐Mediated Polyarthritis

Signs related to spinal pain are commonly reported in dogs with noninfectious, nonerosive, idiopathic immune‐mediated polyarthritis (IMPA). This study examined the prevalence and etiology of spinal pain in these dogs through a retrospective review of 62 case records of dogs with IMPA. All dogs with IMPA and signs suggestive of spinal pain were described with regard to age, gender, breed, physical stature, location of vertebral pain, rectal temperature, and clinical laboratory findings. The prevalence of spinal pain in these dogs was 29% (18 of 62). Fourteen of the 18 dogs with spinal pain and IMPA were male. Cerebrospinal fluid (CSF) from 11 dogs with signs of spinal pain was analyzed. Five of these (46%) had concurrent steroid‐responsive meningitis‐arteritis (SRMA). We concluded that SRMA does occur concurrently in some dogs having IMPA. Meningeal involvement may explain the origin of spinal pain observed in some of these dogs.

Steroid-responsive meningitis-arteritis in dogs with noninfectious, nonerosive, idiopathic, immune-mediated polyarthritis.

Signs related to spinal pain are commonly reported in dogs with noninfectious, nonerosive, idiopathic immune-mediated polyarthritis (IMPA). This study examined the prevalence and etiology of spinal pain in these dogs through a retrospective review of 62 case records of dogs with IMPA. All dogs with IMPA and signs suggestive of spinal pain were described with regard to age, gender, breed, physical stature, location of vertebral pain, rectal temperature, and clinical laboratory findings. The prevalence of spinal pain in these dogs was 29% (18 of 62). Fourteen of the 18 dogs with spinal pain and IMPA were male. Cerebrospinal fluid (CSF) from 11 dogs with signs of spinal pain was analyzed. Five of these (46%) had concurrent steroid-responsive meningitis-arteritis (SRMA). We concluded that SRMA does occur concurrently in some dogs having IMPA. Meningeal involvement may explain the origin of spinal pain observed in some of these dogs.

Long-term treatment of dogs with steroid-responsive meningitis-arteritis: clinical, laboratory and therapeutic results.

Steroid-responsive meningitis-arteritis is an immunopathological disease in dogs characterised by neck pain, pleocytosis of the cerebrospinal fluid (CSF) and increased serum and CSF immunoglobulin (Ig) A levels. A long-term treatment protocol (four to 20 months) with prednisolone was applied in 10 dogs with the condition. Clinical side effects, changes in blood and CSF values and long-term outcome were evaluated retrospectively. Eight of the 10 dogs were without clinical signs up to 29 months after the treatment was terminated. Long-term glucocorticosteroid treatment appears to result only in mild clinical side effects, such as polyuria/polydipsia, polyphagia and weight gain. All clinical and laboratory changes were reversible after the therapy was discontinued. Elevated serum and CSF IgA levels did not decrease to normal values during prednisolone treatment and were still slightly increased after the therapy was discontinued. A marked decrease in the cell count of the CSF was observed after therapy was initiated, although pleocytosis increased again during relapses of the disease. Monitoring of CSF cell count in dogs with this condition seems to be a sensitive indicator of success of treatment. In addition, older dogs with high IgA levels in the CSF and frequent relapses seem to require a longer duration of therapy and have a less favourable prognosis long term. The reason for high systemic and intrathecally produced IgA levels remains unknown, but seems not to be influenced by prednisolone treatment.

Diagnosis of inflammatory and infectious diseases of the central nervous system in dogs: a retrospective study.

The medical records of 220 dogs with inflammatory/infectious diseases of the central nervous system (CNS) were retrospectively examined. The aims of the study were to determine if clinical and clinicopathologic data (not including biopsy or necropsy examination) could distinguish inflammatory CNS diseases from diseases of other types, and to search for criteria allowing differentiation of specific inflammatory diseases. The signalment, historical findings, extraneural and neurological signs, and the lesion site contributed marginally to a specific diagnosis. Multifocal signs were only noticed in one third of the dogs with inflammatory/infectious diseases. Particular neurological abnormalities were more frequent in certain diseases than in others (eg, myoclonus was frequent in dogs with distemper, but it was also found in those with other meningoencephalomyelitides). Hematologic findings contributed to the diagnosis in certain conditions (eg, canine distemper encephalitis, protozoal encephalomyelitis, steroid-responsive meningitis-arteritis). Cerebrospinal fluid examinations, including immunoglobulin G index and cytology were useful to separate meningoencephalomyelitides from the other CNS diseases and to distinguish certain conditions from others. In most cases a specific diagnosis depended on a combination of clinical signs and ancillary diagnostic aids. Still, a specific diagnosis remained very difficult, if not impossible, in at least one third of the dogs.

Neuroimmunological studies in steroid-responsive meningitis-arteritis in dogs

The clinical and pathological expression of steroid-responsive meningitis-arteritis (SRMA) is predominantly neurological and the present study was therefore mostly concerned with the intrathecal humoral immune reponses of 13 dogs suffering from the disease. All the dogs synthesised IgG intrathecally, indicating that the immune response in SRMA is in part specifically directed towards the central nervous system (CNS). Half of the dogs also had high levels of IgM only in the cerebrospinal fluid (CSF) and nearly all of them had high levels of IgA in the CSF as well as in the serum. Six of the dogs had circulating immune complexes in the serum, but not in the CSF. Neither IgM nor IgA rheumatoid factors were found. A chemotaxis assay revealed enhanced migration of neutrophils into the CSF in three cases. All the dogs had marked meningeal inflammation and arterial lesions of the meaingeal blood vessels. Only one dog had arterial involvement outside the CNS. The acute vascular lesions consisted mostly of degenerative changes of the media and periarterial inflammation, and there was no evidence of immune complex deposition. Chronic lesions were mostly characterised by stenosis, adventitial thickening and periarteritis. Focal deposits of IgA were found in the vascular wall of one chronic case. It was concluded that the meningeal lesions in SRMA are a primary event, rather than the result of a generalised immune complex disease. These lesions are associated with an intrathecal Immoral immune response, in which IgA appears to play a central role. It is possible, that the uncontrolled IgA synthesis is induced by an infectious agent, but the localisation of the lesions in the CNS remains unexplained.

Intrathecal synthesis of major immunoglobulin classes in inflammatory diseases of the canine CNS

The IgG index, IgM and IgA contents in cerebrospinal fluid and serum were examined retrospectively using an enzyme-linked immunosorbent assay (ELISA) in 69 dogs with inflammatory central nervous system (CNS) diseases of various aetiologies. Fifteen normal dogs were used as controls. After measuring IgG and albumin contents in serum and cerebrospinal fluid (CSF), the IgG index was calculated according to the formula of Link and Tibbling to demonstrate intrathecal immunoglobulin synthesis. A surprisingly high number of animals with encephalitis, including dogs with protracted diseases such as chronic distemper encephalitis and granulomatous meningoencephalomyelitis, showed in addition to an elevated IgG production evidence of intrathecal IgM and IgA production. The highest values of intrathecal as well as systemic IgA levels were found in dogs suffering from steroid responsive meningitis-arteritis. It was concluded that the control of the humoral immune response in the brain differs from that in other tissues. Because of striking similarities between dogs and humans in respect to humoral neuroimmunological reactions, the dog can be considered to be a useful animal model for the study of the intrathecal humoral immune response.