Steroid-responsive meningitis-arteritis

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Steroid responsive meningitis arteritis (SRMA). Adjacent to the cervical spinal cord white matter (WM) the blood vessels of the leptomeninx (LM) show a moderate vasculitis and infiltration of mononuclear inflammatory cells (arrow heads) as well as neutrophilic granulocytes (arrows). Mononuclear cells consist mainly of B cells, plasma cells, and few macrophages. Leptomeninx with adjacent spinal cord white matter[1]

Steroid-responsive meningitis-arteritis (SRMA) is a systemic inflammatory disease of young dogs, with a predisposition in the Boxer breed[2].

SRMA manifests predominantly within the cervical meninges, and is associated with an aseptic suppurative meningoencephalitis[3] characterized by increased immunoglobulin A (IgA) levels in serum and cerebrospinal fluid (CSF), and a shift of the B:T cell ratio towards a higher percentage of B cells[4].

Although there is thought to be an infectious agent involved, the cause is unclear[5], since gene mapping suggests loci associated with this disease are closely related to those observed in dogs with immune-mediated systemic lupus erythematosus[6].

Clinical signs are characterised by cervical rigidity, spinal pain, discospondylitis, seizures, cardiac arrhythmias and pyrexia[7][8].

In a less common, chronic form of SRMA, additional neurological deficits consistent with a spinal cord or a multi-focal neurological disorder may be present, often accompanied by a mononuclear CSF pleocytosis[9].

The diagnosis is based on histopathological findings. Advanced imaging techniques and the examination of the cerebrospinal fluid are helpful to receive a definitive or presumptive diagnosis[10]. C-reactive protein, haptoglobin and serum amyloid A have been identified as significant diagnostic 'markers' for this disease[11], however, the presence of D-dimers in CSF samples and elevated levels of cardiac troponin I[12] are characteristic of this disease.

Testing of paired CSF and serum samples for IgA showing rising titres is recommended[13].

A differential diagnosis would include other causes of meningitis.

The prognosis for young dogs in the acute stage of SRMA is relatively good with early and aggressive anti-inflammatory or immunosuppressive therapy. Prednisolone appears to be more successful drug of choice[14].

In more protracted, relapsing cases of SRMA the prognosis is guarded, and therapy requires more aggressive, long term immunosuppression[15].

References

  1. Spitzbarth I et al (2012) The role of pro- and anti-inflammatory cytokines in the pathogenesis of spontaneous canine CNS diseases. Vet Immunol Immunopathol 147(1-2):6-24
  2. Wrzosek M et al (2009) Cerebral extension of steroid-responsive meningitis arteritis in a boxer. J Small Anim Pract 50(1):35-37
  3. Schwartz M et al(2010) Marked MMP-2 transcriptional up-regulation in mononuclear leukocytes invading the subarachnoidal space in aseptic suppurative steroid-responsive meningitis-arteritis in dogs. Vet Immunol Immunopathol 133(2-4):198-206
  4. Schwartz M et al (2008) Selective CD11a upregulation on neutrophils in the acute phase of steroid-responsive meningitis-arteritis in dogs. Vet Immunol Immunopathol 126(3-4):248-255
  5. Schwartz M et al(2011) Pathogenetic factors for excessive IgA production: Th2-dominated immune response in canine steroid-responsive meningitis-arteritis. Vet J 187(2):260-266
  6. Wilbe M et al(2010) Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nat Genet 42(3):250-254
  7. Snyder Ket al (2010) Arrhythmias and elevated troponin I in a dog with steroid-responsive meningitis-arteritis. J Am Anim Hosp Assoc 46(1):61-65
  8. Tipold A & Schatzberg SJ (2010) An update on steroid responsive meningitis-arteritis. J Small Anim Pract 51(3):150-154
  9. Nghiem PP & Schatzberg SJ (2010) Conventional and molecular diagnostic testing for the acute neurologic patient. J Vet Emerg Crit Care (San Antonio) 20(1):46-61
  10. Tipold A & Stein VM (2010) Inflammatory diseases of the spine in small animals. Vet Clin North Am Small Anim Pract 40(5):871-879
  11. Eckersall PD & Bell R (2010) Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine. Vet J 185(1):23-27
  12. Navarro-Cubas J et al (2011) Steroid-responsive meningitis-arteritis with spontaneous echocardiographic contrast and elevated cardiac troponin I in a dog. Vet Rec 169(20):527
  13. Maiolini A et al (2012) Determination of immunoglobulin A concentrations in the serum and cerebrospinal fluid of dogs: an estimation of its diagnostic value in canine steroid-responsive meningitis-arteritis. Vet J 191(2):219-224
  14. Lowrie M et al (2009) Steroid responsive meningitis-arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006-2008). J Vet Intern Med 23(4):862-870
  15. Moore SA et al (2012) Extracellular hsp70 release in canine Steroid Responsive Meningitis-Arteritis. Vet Immunol Immunopathol 145(1-2):129-133