Inclusion Criteria

Medical records of dogs presented to the Neurology Department at Centre Hospitalier Vétérinaire Frégis (Arcueil, France) between January 2012 and December 2016 were reviewed. Cases were included if the following criteria were fulfilled: (1) dogs had supportive clinical signs of meningitis (neck pain and pyrexia [≥39.2°C]); (2) dogs were <36 mo of age at presentation; (3) CSF sample demonstrated neutrophilic pleocytosis (i.e., >50% neutrophilic cells) without organisms identified; (4) dogs were treated with a combination of prednisolone and Aza; (5) owners completed a questionnaire regarding treatment compliance, side effects, and relapsing; and (6) a minimum follow-up of 24 mo after diagnosis was available.

Cases were excluded if medical records were incomplete, if dogs had already received immunosuppressive treatment before presentation, or if dogs were lost to follow-up. An anti-inflammatory dosage of corticosteroids was defined from 0.5 to 1 mg/kg/day, and a dose above 1 mg/kg/day was considered immunosuppressive.

Data Collection

Data were collected from medical records and included signalment (breed, age, sex, and weight); duration between onset of clinical signs and presentation; clinical signs; neurological examination; results of complete blood cell count (CBC), biochemistry, and infectious disease testing; CSF analysis; treatment protocol; response to treatment; and drug-related adverse effects and outcomes including date of relapse, if it occurred.

CSF Analysis

All cerebrospinal fluid samples were collected by puncture from the cerebellomedullary cistern under general anesthesia with the dogs in lateral recumbency. CSF analysis included total protein concentration, total nucleated cell count (NCC), red blood cell (RBC) counts, cytological evaluation with differential nucleated cell count, and presence of fungi or bacteria.

CSF pleocytosis was defined as total NCC >5 cells per microliter. CSF protein content was considered increased if total protein concentration > 0.20 g/L. A neutrophilic pleocytosis was defined as ≥50% of the NCC being neutrophils. For cases with CSF RBC counts >500 cells per microliter, the NCC was adjusted by calculating and subtracting the number of leukocytes expected from peripheral blood contamination, using the ratio of 1 leukocyte to 500 RBCs following Bailey and Higgins’ recommendations.²⁵ In some dogs, CSF was also tested for infectious diseases (canine distemper virus, Neospora caninum, and Toxoplasma gondii) by polymerase chain reaction.

Treatment Protocol

All dogs received dexamethasone 0.2 mg/kg IV on the day of presentation followed by prednisolone at an immunosuppressive dosage (>1 mg/kg/day) and Aza 2 mg/kg once a day. Prednisolone was tapered after 3–5 days by half. The dose was then reduced by half every 2–4 wk. Aza was initiated at 2 mg/kg/day for 1 mo and then every other day for 2 mo. The corticosteroid treatment was individually adjusted according to the general status of the dog and well-being; variations are reported in Figure 1. To monitor Aza toxicity, a CBC and a liver profile were recommended every 2 wk after initiation of Aza for the first 2 mo, then monthly.

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Outcomes

To collect the follow-up data, one of the authors (L.G.) interviewed all dog owners face to face or by telephone using a predefined questionnaire (Supplementary Questionnaire 1). The questionnaire consisted of six parts including (1) signalments of the dog; (2) initial clinical signs and previous events; (3) medication prescribed and treatment compliance; (4) drug-related adverse events and assessment of quality of life; (5) additional tests performed following diagnosis; and (6) duration between dosage reduction or discontinuation and relapse, total number of relapses, and clinical signs associated with relapse. Owners with dogs still under treatment were called back every 2 mo. All data were recorded and analyzed. A clinical resolution was defined as the absence of clinical signs after completion of the prescribed treatment in dogs not receiving any treatment for SRMA at the time of follow-up (minimum 2 yr after diagnosis). A relapse was defined as recurrence of clinical signs after initial improvement, during treatment tapering, or after treatment discontinuation.

Animals

A total of 57 dogs were diagnosed with SRMA between January 2012 and December 2017. Among this population, 36 dogs were treated immediately with a combination of prednisolone and Aza. Five cases were excluded because the CSF cytology was no longer available, four because of loss of follow-up, and one for discontinued treatment after 1 mo. Four cases received only 2 mo instead of the 3 recommended for Aza but were kept in this retrospective study.

Twenty-six cases met the inclusion criteria. Breeds represented were boxer (7/26), Bernese mountain dog (6/26), beagle (3/26), Labrador retriever (2/26), and one each of the following breed: German shepherd dog, border collie, German shorthaired pointer, English bulldog, cocker spaniel, Beauceron, Dalmatian, and Argentine mastiff. There were 16 females (5 spayed and 11 sexually intact) and 10 males (all sexually intact). The median age at initial presentation was 9.5 mo. (range: 5–27 mo). The majority of dogs were <1 yr (18/26; 69%), 7/26 (27%) were between 1 and 2 yr, and 1/26 (4%) was >2yr of age. The median weight was 25.3 kg (range: 11–48 kg). The median duration of clinical signs prior to presentation was 4 days (range: 1 day to 6 wk). Major clinical complaints reported by owners at presentation were lethargy (26/26), decreased appetite (23/26), stiffness (15/26), reluctance to rise or walk (12/26), and weakness (4/26). The median follow-up time was 37 mo (range: 26–77 mo). Eighteen dogs had received either nonsteroidal anti-inflammatory drugs (n = 15) or corticosteroids at an anti-inflammatory dosage (n = 3) before presentation. The median rectal temperature was 39.8°C (range: 39.2–41°C). The remainder of the physical examination was unremarkable in all dogs. One dog (case 21), who suffered from a concomitant polyarthritis, was nonambulatory.

At diagnosis, CBC abnormalities included neutrophilic leukocytosis with a left shift in 21/26 dogs (81%). All biochemistry profiles were within the normal limits except for 1 dog (case 10) who demonstrated a mild increase in blood urea (urea: 0.87 g/L).

CSF analysis demonstrated a median NCC of 600 cells per microliter (range: 30–10,000 cells per microliter). The CSF NCC was >100 cells per microliter in 88% of dogs (23/26)—between 100 and 1000 cells per microliter in 15/26 dogs and >1000 cells per microliter in 8/26 dogs. CSF protein concentration was mildly elevated in 25/26 dogs (96%; median: 0.87 g/L; range: 0.2–18 g/L). CSF RBC counts were available for 22/26 dogs with a mean RBC count of 216 cells per microliter (range: 0–1200 RBCs per microliter). Polymerase chain reactions in CSF for Ncaninum, Tgondii, and canine distemper virus were run in 17 dogs (65%) and were negative for all dogs tested. Seven of these dogs were also tested^a and were negative for Ehrlichia canis, Eewingii, Borrelia burgdorferi, Anaplasma phagocytophilum,and Aplatys in blood.

Details on individual dog characteristics and laboratory results are reported in Table 1.

TABLE 1 Clinical Features and Cerebrospinal Fluid Laboratory Results at Presentation in the 26 Dogs with Steroid-Responsive Meningitis-Arteritis

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Treatment Outcomes

All dogs were treated with corticosteroids immediately after the CSF puncture and Aza was started as soon as the results of cytology and infectious diseases were known (<48 hr after the diagnostic tests were performed). Treatment was initiated with a single injection of dexamethasone in all patients and then switched to prednisolone. The initial prednisolone dosage ranged from 1 to 2.2 mg/kg/day (median: 1.6 mg/kg/day). The median duration of prednisolone treatment was 13 wk (range: 4–21 wk). All dogs except four received 12 wk of Aza treatment. Among these four dogs who received only 2 mo (instead of 3 as prescribed), one (case 12) relapsed during corticosteroids tapering.

Follow-Up and Relapses

The median follow-up time was 1141 days (range: 790–2342 days). Twenty-one owners (81%) stated that they followed the treatment plan carefully in strict compliance with dose adjustments. One owner (case 4) decreased corticosteroids faster than expected because his dog suffered from diarrhea. Two owners (cases 4 and 7) shortened the duration of Aza treatment because they judged that their dog no longer showed clinical signs, and two others (cases 12 and 20), advised by their referring veterinarian, gave only 2 mo of Aza. No relapse was observed in 21/26 dogs (81%). Of the five dogs experiencing a relapse of clinical signs, three relapsed once (cases 13, 15, and 19) before achieving complete clinical remission, case 12 relapsed twice, and case 22 relapsed three times. This last dog is still being treated. All the owners reported neck pain and loss of appetite as first signs of recurrence. Three of the dogs having relapsed were Bernese mountain dogs. The timing of relapse ranged from the tapering period (cases 12 and 22) up to 8 mo after treatment discontinuation. The owners of dog 22 complained that clinical signs recurred as soon as corticosteroids were <0.25 mg/kg/day. Case 19 relapsed 8 mo after discontinuation of any treatment, the next day after being attacked by another dog. Twenty-five dogs (96%) were still in remission at follow-up. One dog with associated polyarthritis (case 21), who was nonambulatory at the admission, still has mild intermittent right thoracic limb lameness but no sign of neck pain or any discomfort.

Treatment Side Effects

Clinical side effects were reported in 15 dogs (58%). Five dogs developed gastrointestinal disturbances (vomiting and diarrhea [n = 2] or diarrhea only [n = 3]) within the first days of treatment. All gastrointestinal signs easily resolved with a supportive treatment. Weight gain (n = 5), polyphagia (n = 5), polyuria/polydipsia (n = 7), hair loss (n = 2), and panting (n = 1) were reported by the owners and were presumed to be secondary to the administration of corticosteroids. All these adverse effects did not alter dogs’ quality of life according to the owners and did not require drug dose reduction except in one dog (case 15) who developed bronchopneumonia 2 wk after initiation of treatment. Clinical signs and pulmonary lesions rapidly improved with antibiotics (amoxicillin and clavulanic acid, 21 mg/kg q 12 hr) and resolved completely after 1 mo. Another dog (case 10) developed azotemia 9 mo after diagnosis (5 mo after discontinuation of treatment) compatible with bilateral renal dysplasia; however, renal biopsy was not performed. None of the dogs developed clinical signs compatible with acute hepatitis or pancreatitis.

Repeat CBC was performed in 12 dogs (46%) during treatment. The blood was collected on a mean time of 21 days (range: 10– 44 days) after the beginning of Aza treatment. None of the dogs demonstrated cytopenia. Two dogs had a mild to moderate leukocytosis respectively 2 wk and 4 wk after diagnosis (cases 11 and 17). The dog who developed bronchopneumonia (case 15) had a marked neutrophilic leukocytosis (31.0 × 10⁹/L, reference range: 6–13.0 × 10⁹) 2 wk after diagnosis. Biochemistries were available in 10 dogs (38%) and were performed on a mean time of 30 days (range: 10–65 days) after initiation of treatment. Four dogs demonstrated a mild increase in alkaline phosphatase (mean: 172.3 IU/L; range: 32–282 IU/L). Alanine aminotransferase was within the normal limits in all dogs tested.

Cerebrospinal fluid analysis was rechecked 3 mo after diagnosis in three dogs (cases 4, 24, and 25); all had a normal analysis.

None of the dogs of this study died or were euthanized.