Inflammatory CNS Disease - A Practical Approach
World Small Animal Veterinary Association Congress Proceedings, 2017
Hanne Gredal, DVM, PhD
Associate Professor, Department of Veterinary Clinical Sciences, University of Copenhagen, Dyrlregevej, Frederiksberg C, Copenhagen, Denmark

Inflammatory conditions of the central nervous system may be categorised according to their anatomical localisation as 1) meningitis; i.e., inflammation of the meninges; 2) encephalitis; i.e., inflammation of the brain; and, 3) myelitis; i.e., inflammation of the spinal cord. However, very often the inflammatory condition affect more than just one structure, resulting in a meningoencephalitis, a meningomyelitis, or even a meningoencephalomyelitis.

The focus of this presentation will be on inflammatory diseases of the central nervous system (CNS) in dogs.


Inflammatory disease of the central nervous system may be caused by infectious agents, including bacterial, viral, protozoal and fungal infections, but in fact most inflammatory CNS conditions in dogs have a noninfectious aetiology, and are presumably immune­mediated.1

Non-infectious inflammatory CNS diseases in dogs may be further categorised into steroid responsive meningitis­arteritis (SRMA), granulomatous meningoencephalitis (GME), necrotising encephalitis (NE), and necrotising leukoencephalitis (NLE.) Whereas SRMA has a fairly distinct clinical pattern and primarily affects the meninges, distinguishing between the different non-inflammatory conditions affecting the brain parenchyma (GME, NE, and NLE) requires post-mortem histopathology, and the overall term ‘meningoencephalitis of unknown origin’ (MUO) thus seems more relevant from a clinical perspective. In the following, SRMA and MUO will be presented separately.

Steroid-Responsive Meningitis-Arteritis (SRMA)

Steroid-responsive meningitis-arteritis (also known as aseptic meningitis, necrotizing vasculitis, poly- or panarteritis, or beagle pain syndrome is characterised by inflammatory changes of the leptomeninges and the associated arteries.2,3

The disease is typically seen in young dogs (6–18 months), although it may occur at any age. Any breed can get SRMA, but the disease appears to be more common in, e.g., Boxers, Beagles, Bernese Mountain dogs, Nova Scotia duck tolling retrievers and Weimaraners.

Dogs with acute SRMA typically present with a stiff and painful gait, cervical rigidity and a lowered head carriage, hyperaesthesia along the spinal cord, and pyrexia.4 Most appear mentally depressed, hiding away and unwilling to play, and some in such pain that even the slightest manipulation will elicit a clearly painful response.

The diagnostic work-up of a suspected SRMA case includes routine haematology and biochemistry, serum C-reactive protein (CRP) measurements, magnetic resonance imaging (MRI) of the brain, and cerebrospinal fluid (CSF) analysis. Blood results may reveal signs of a systemic inflammatory response with an increase in white blood cell (WBC) count and serum CRP, although it should be emphasised that the absence of these changes does not rule out SRMA.5,6 MRI may reveal subtle contrast enhancement of the meninges, but is usually otherwise unremarkable.

The most important diagnostic tool in the work-up of SRMA patients is the CSF analysis, which is characterised by pleocytosis, usually>50 WBC/ml (normal reference <5 WBC/ml), often dominated by neutrophils, and increased amounts of protein (>30 mg/dl if collected from the atlanto-occipital site).2 However, mononuclear cells are also a common finding.5

As indicated by the name, SRMA responds positively to treatment with steroids (prednisolone). A standard treatment protocol cannot be established, as this must be carefully tailored for the individual patient to optimise control of the disease while at the same time aiming at reducing side effects to a minimum. However, overall guidelines include:2,5


  • 2 mg/kg BID for 2 days, followed by
  • 1 mg/kg BID for 1–2 weeks
  • 0.5–0.75 mg/kg BID for 2 weeks
  • 0.5 mg/ kg BID for 2–4 weeks
  • Then the dosage is gradually reduced over months to 0.5 mg/kg every 48 to 72 hours
  • Treatment can usually be stopped after 5–7 months, but depends on the individual course of disease

During treatment, dogs should receive regular check­ ups every 4–6 weeks, and haematology and serum biochemistry performed in order to monitor possible signs of systemic inflammation and adverse reactions in relation to prednisolone. If an increase in serum CRP was present as part of the initial clinical picture, this may also be a useful parameter to monitor inflammation and possible relapse.5

In most cases, the prognosis of SRMA is good, although relapses occasionally occur. It is important to stay in close contact with the owners during the entire treatment period and keep them informed of the side effects encountered with long-term prednisolone treatment. As the clinical disease wanes off, side effects take over, e.g., polyuria, polydipsia, polyphagia, generalised muscle atrophy and weakness, hepatomegaly, a reduced level of physical activity and a dull and unhappy appearance. Especially, this ‘depressed behaviour’ is an enormous challenge to most owners, who should be informed that these signs are reversible.

On rare occasions, a CSF tap may be normal, despite a classical clinical presentation of SRMA and a positive response to prednisolone. However, initiating treatment with prednisolone is not recommended, due to the many unwanted side effects seen with long-term prednisolone treatment, unless SRMA is highly suspected.

Meningoencephalitis of Unknown Origin (MUO)

As mentioned earlier, the term ‘meningoencephalitis of unknown origin’ covers a syndrome of non-infectious CNS inflammatory diseases, which cannot be distinguished on clinical grounds alone. Accordingly, in the following MUO will be reviewed as a general clinical syndrome, rather than as specific histopathological disease entities.

Although, MUO may affect any breed, toy and terrier breeds, pug dogs and Yorkshire terriers, seem to be overrepresented. Young dogs are predisposed, from 2–4 years of age, but dogs at all ages can get MUO.1

The clinical signs with MUO reflect the affected CNS region and hence vary from case to case. The disease usually has an acute onset, which progresses over the following days. Clinical signs are often multifocal, depending on how widespread the inflammatory changes are, and may include seizures, depression, circling, vestibule-cerebellar signs and visual deficits. MUO may also involve the spinal cord, or even present as myelopathy alone. Signs of systemic inflammatory disease, e.g. pyrexia and leucocytosis, are less common than with SRMA.7

The recommended diagnostic work-up of MUO is the same as for SRMA. However, MRI plays a significant role in MUO cases, which usually have multifocal or diffuse hyperintense lesions on T2-weighted images (WI) and fluid-attenuated inversion recovery (FLAIR), and possible contrast enhancement on T1-WI. The suspicion of inflammatory MUO is confirmed by CSF analysis, which reveals mild to moderate pleocytosis, typically dominated by mononuclear cells, but may also consist of mixed cells, and increased amounts of protein.

The treatment for MUO remains immunosuppression, usually involving corticosteroids, which are often administered at higher dosages than for SRMA.

The recommended protocol, given infectious causes have been ruled out, includes:7


  • 1.5 mg/kg BID for 3 weeks
  • 1.0 mg/kg BID for 6 weeks
  • 0.5 mg/kg BID for 3 weeks
  • 0.5 mg/kg SID for 3 weeks
  • 0.5 mg/kg every other day, possibly reduced

Adjunctive immunosuppression therapy with, e.g., cytosine arabinoside, cyclosporine, procarbazine or lomustine may be useful, if prednisolone is insufficient, or if the side effects are intolerable.

In general, the prognosis with MUO is considered less favourable than with SRMA, and many dogs die within the first couple of months.8 The prognosis may to some extent depend on the localisation of the lesion, as forebrain lesions presumably have a better prognosis than brain stem lesions.9 Furthermore, dogs with focal disease rather than multifocal disease have a better chance of survival.9


1.  Coates JR, Jeffery ND. Perspectives on meningoencephalomyelitis of unknown origin. Vet Clin Small Anim. 2014;44:1157–1185.

2.  Tipold A, Schaftzberg SJ. An update on steroid responsive meningitis­arteritis. J Small Anim Pract. 2010;51:150–1543. 3rd ed, WB Saunders Elsevier Science.

3.  Tipold A, Jaggy A. Steroid responsive meningitis-arteritis in dogs: long-term study of 32 cases. J Small Anim Pract. 1994;35:311–316.

4.  Lowrie M, Penderis J, McLaughlin M, Eckersall PD, Anderson TJ. Steroid responsive meningitis-arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006–2008). J Vet Int Med. 2009;23:862–870.

5.  Vestergaard TN, Kjelgaard-HansenM, Berendt M, Gredal H. Systemic inflammatory activity is frequently absent in dogs with acute inflammatory CNS disease. Poster at 13th EVECCS Meeting, Copenhagen, June 2013.

6.  Talarico LR, Schatzberg SJ. Idiopathic granulomatous and necrotising inflammatory disorders of the central nervous system: a review and future perspectives. J Small Anim Pract. 2010;51:138–149.

7.  Lowrie M, Smith PM, Garosi L. Meningoencephalitis of unknown or1gin: investigation of prognostic factors and outcome using a standard treatment protocol. Vet Rec. 2013;172:527.

8.  Munana KR, Luttgen PJ. Prognostic factors for dogs with granulomatous meningoencephalomyelitis: 42 cases (1982–1996). J Am Vet Med Assoc. 1998;212:1902–1906.


Speaker Information
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Hanne Gredal, DVM, PhD
Dept. of Veterinary Clinical Sciences
University of Copenhagen
Dyrlregevej, Frederiksberg C, Denmark

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