Jsap_172 588.595

Combined cytosine arabinosideand prednisone therapy formeningoencephalitis of unknownaetiology in 10 dogs OBJECTIVES: The differential diagnosis for young to middle-aged dogs with progressive neurological signs, focal or multifocal computed tomography/magnetic resonance imaging lesions, mononuclear phalomyelitis is non-specific and insensi- cerebrospinal fluid pleocytosis and negative infectious titres tive; the inciting cause is unknown inup to 66 per cent of cases (Tipold includes granulomatous meningoencephalomyelitis, breed-specific meningoencephalitis, infectious meningoencephalitis of unknown diagnosis for young to middle-aged dogswith focal or multifocal central nervous origin and central nervous system neoplasia. The terminology meningoencephalitis of unknown aetiology may be preferable for (CSF) mononuclear pleocytosis, focal ormultifocal variably contrast-enhancing cases that lack histopathological diagnoses. The safety and efficacy of a combination of cytosine arabinoside and prednisone (CT)/magnetic resonance imaging lesionsand negative infectious disease titres typ- protocol is evaluated, in this study, for the treatment of meningoencephalitis of unknown aetiology in 10 dogs.
cephalomyelitis (GME), the breed-specificmeningoencephalitides (necrotising men- METHODS: Cases were selected based on neuroanatomical localisation, negative regional infectious disease titres, and Maltese terriers and necrotising leu-coencephalitis [NLE] of Yorkshire terriers cerebrospinal fluid pleocytosis and brain imaging. Clinical response and other small breeds), neoplasia or in- was gauged through follow-up examinations, owner and referring fectious meningoencephalitis of unknownorigin. Without a histopathological diag- veterinarian surveys and review of medical records.
with this clinical presentation is typically ESULTS: Partial or complete remission was achieved in all dogs; the median survival time for the 10 dogs was 531 days cephalitis of unknown aetiology is proposed (range 46 to 1025 days), with five of the 10 dogs alive to describe dogs with CNS inflammatorydisease that lacks a histopathological diagnosis. Empirical and symptomatictherapy CLINICAL SIGNIFICANCE: Prednisone/cytosine arabinoside is a safe prednisone) has been evaluated in 10 cases empirical therapy for dogs with meningoencephalitis of unknown of so-called meningoencephalitis of un-known aetiology.
aetiology; this drug combination may prolong survival time.
in proven cases of GME, NME and NLEis considered to be poor (Cordy 1979, University of Wisconsin-Madison, 2015 Linden Tipold and others 1993, Stalis and others *College of Veterinary Medicine, University of yCornell University, College of Veterinary to six months of initial presentation.
8045 West Hampden Avenue, Lakewood,CO 80227, USA 42 dogs with histopathologically confirmed Journal of Small Animal Practice Á Vol 47 Á October 2006 Á Ó 2006 British Small Animal Veterinary Association Cytosine arabinoside therapy for meningoencephalitis consisted of the following: complete blood ferentiation in culture (Griffin and others and blood serology for infectious enceph- alitis: Anaplasma phagocytophilum, Ehrli- caninum and Cryptococcus (nine dogs).
prognosis in these studies may be biased.
the liver, plasma, granulocytes and gastro- intestinal tract. Side effects in dogs are suppression and gastrointestinal upset.
CSF analysis were performed (Table 1).
CA is an effective chemotherapeutic agent for several neoplastic conditions in both protein (normal ,25 mg/dl) in dog 7.
steroid monotherapy is variable and it is was prioritised based on agents most com- mon in upstate New York. All serum titres were interpreted to be either negative or the safety and efficacy of CA for long-term consistent with exposure only. Intrathecal any case: all CSF titres were negative or lenges to follow-up, ethical considerations serum titres. One dog (dog 4) had a posi- tive CSF culture (aerobic) for Staphylococ- cus intermedius, but it was thought to be devoid of neutrophils and therefore incon- sistent with septic meningoencephalitis).
All CT scans of the brain included precon- CA. Six criteria were evaluated for these munosuppressive doses of corticosteroids.
aetiology: (1) focal or multifocal neuro- At the time of CT/CSF tap, some dogs (cases anatomical localisation, (2) negative blood 4, 5, 6, 7, 9 and 10) received a single im- and/or CSF infectious disease titres, (3) munosuppressive dose of 0Á1 to 1Á0 mg/kg parenteral dexamethasone sodium phosphate brain consistent with focal or multifocal and Upjohn Co.). At the time of diagnosis, all dogs received 1 to 2 mg/kg prednisone (Roxane Laboratories Inc.) twice a day.
cin hydrochloride; Greenstone Ltd.) twice polymerase in mitotically active cells.
ical confirmation of meningoencephalitis.
fulfilled criteria 1 and 2 and at least one twice a day were given initially, but these others 2001, Gmeiner and others 2003).
ation of negative infectious disease titres (typically five to seven days after diagnosis).
Journal of Small Animal Practice Á Vol 47 Á October 2006 Á Ó 2006 British Small Animal Veterinary Association Journal of Small Animal Practice Á Vol 47 Á October 2006 Á Ó 2006 British Small Animal Veterinary Association Cytosine arabinoside therapy for meningoencephalitis veterinarians, dogs 6, 7, 8, 9 and 10 are discernible side effects; dog 10 had focal (from zero to 60 days later) as an adjunct alive with subjectively fair (dog 6), good and ventrum that resolved spontaneously.
dlimb weakness that resolved with a single sar; Faulding Pharmaceuticals) at a dose of at the time of writing (see Table 2).
dose of parenteral corticosteroid adminis- tered by the dog’s local veterinarian. The and others 2002). The subcutaneous treat- post-mortem histopathology (disclosing NLE) twice a day every three weeks in refractory irritation of the surrounding tissues. Three weeks after the first course, each dog was tapered over several weeks after initiation of CA therapy. In several cases (dogs 1, 2, SQ twice a day for two consecutive days.
3, 4, 5, 6, 7 and 9), prednisone treatment recurrence of clinical signs, in an attempt logical imaging can be misleading and are therapy. Side effects in prednisone-treated dogs included polyphagia, polyuria, poly- rely upon clinical signs, CSF, neuroimag- with recurrence of clinical signs, predni- ing and negative infectious disease titres.
in dog 5). Patients 1 and 6 required pheno- interval was shortened permanently to the barbital and/or potassium bromide for per- last effective interval. Some dogs required sistent, episodic seizure activity. Patient 8 received azathioprine for a history of im- dominantly affects the CNS white matter.
owners of three dogs in the study reported transient post-treatment lethargy, dyspha- alopecia, mild localised dermatitis in four disseminated, focal and ocular. Eight dogs nisone. In two cases (dogs 8 and 10), the from disseminated disease consistent with Journal of Small Animal Practice Á Vol 47 Á October 2006 Á Ó 2006 British Small Animal Veterinary Association Journal of Small Animal Practice Á Vol 47 Á October 2006 Á Ó 2006 British Small Animal Veterinary Association Cytosine arabinoside therapy for meningoencephalitis current diseases (see Table 2). Post-mortem multifocal neurological signs; therapy pro- vided only partial remission. Post-mortem examination of the brain disclosed a nota- (dog 2) and the other is alive at 671 days after diagnosis (dog 7). It is worthy of note lack of recovery in this case may reflect tation or relative ineffectiveness of CA for use in breed-specific meningoencephalitides.
cycle (S phase) and rate of DNA synthesis report is the restricted number of infec- tious disease titres performed. Infectious quantitatively measured. However, pharma- upstate New York; for practical and finan- cial reasons, most cases were tested only for A phagocytophilum, E canis, T gondii, N caninum and Cryptococcus (Table 1).
address acute disease, but in several dogs, maintaining fair (or better) quality of lives.
In the two cases in which prednisone ther- apy was completely discontinued, it might sion and gastrointestinal epithelial injury sion), the dog’s local veterinarian attemp- ted to increase the CA treatment interval one study in which dogs received an intra- the dog had a relapse in neurological signs, vidual variation in immunological status.
remission rather than a cure. When clini- cal signs recurred, they were more refrac- sion nor gastrointestinal disturbance was initial observed response. Relapses there- munomodulatory therapy whenever allowed.
observed in the cases reported here. How- fore should be addressed aggressively. In ever, alopaecia, dermatitis or other mild suspected to be due to CA treatment.
mide in dog 5) based upon refractory dis- clinical signs that may be associated with relapses, lengthening the CA inter-treat- disease progression. Both dogs were receiv- ressive pelvic limb paresis (dogs 6, 9 and rently, so corticosteroid-induced weakness definitive conclusions for survival times associated with treating specific meningo- limb weakness is unclear (particularly in encephalitides. The only definitive diag- pression may suggest a better prognosis.
Time from onset of clinical signs to addi- study were euthanased as a result of con- Journal of Small Animal Practice Á Vol 47 Á October 2006 Á Ó 2006 British Small Animal Veterinary Association steroid monotherapy with CA/prednisonecombination therapy in treating cases ofcanine meningoencephalitis.
AcknowledgementsThe authors acknowledge the owners andreferring veterinarians of the dogs in thisstudy for their commitment to managingand providing thorough feedback on thisdifficult condition.
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