Retrospective evaluation of prognosis and survival with various immunosuppressants in 82 dogs diagnosed with meningoencephalitis of unknown etiology (2010-2021).

BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.

Pharmacokinetics of a cytosine arabinoside subcutaneous protocol in dogs with meningoencephalomyelitis of unknown aetiology.

Cytosine arabinoside (CA) is a commonly used treatment for dogs with meningoencephalomyelitis of unknown aetiology (MUE) with various proposed protocols, many requiring 24 hours (h) of hospitalization or two visits within 24 h. This is a unidirectional study evaluating the pharmacokinetics of a CA subcutaneous (SC) protocol and a standard constant rate infusion (CRI) protocol in 8 dogs with MUE. Dogs received the CRI (200 mg/m2 IV over 24 h), followed by a SC protocol (50 mg/m2 every 2 h for 4 treatments) four weeks later. Plasma CA concentrations were measured by high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS). Median peak CA concentration for the SC protocol (3.40 µg/ml, range 1.60-9.70 µg/ml) was significantly higher than the CRI (1.09 µg/ml, range 0.77-1.67 µg/ml; p = .02). Median concentration at 1h and 8h following initiation of treatment was significantly higher for the SC protocol (CA1 2.28 µg/ml, range 0.97-2.67; CA8 1.83 µg/ml, range 0.77-2.84) compared to the CRI (CA1 0.01 µg/ml, range 0-0.45; CA8 0.74 µg/ml, range 0.67-1.11; p = .01). While the PK properties of CA when administered as a CRI has been previously investigated, this study demonstrated that CA when administered via repeated 50 mg/m2 injections every 2 h over an 8-h period, provided sustained plasma levels above its therapeutic target and for a significantly longer duration of time than did a standard CRI protocol.

Evaluation of treatment with a combination of mycophenolate mofetil and prednisolone in dogs with meningoencephalomyelitis of unknown etiology: a retrospective study of 86 cases (2009-2017).

BACKGROUND: Combination therapy with glucocorticoids and adjunctive immunomodulating drugs has been generally accepted as a standard treatment regimen for meningoencephalomyelitis of unknown etiology (MUE). We hypothesized that treatment with MMF as an adjunctive agent along with glucocorticoids would be effective and well-tolerated protocol in dogs with MUE. Eighty-six dogs with MUE between May 2009 and June 2017 were included (59 females and 27 males; mean age of 5.93 years; mean body weight of 3.83 kg). The medical records of dogs with MUE treated with prednisolone and MMF were retrospectively evaluated to determine the therapeutic response, survival time, and treatment-related adverse effects. RESULTS: A partial or complete response (CR) was recorded for 75 dogs. The overall median survival time from the initiation of treatment was 558 days. Dogs that showed CR with no relapse over the treatment period (from diagnosis to death) had significantly longer median survival times. A significantly higher mortality hazard ratio of 4.546 was recorded in dogs that failed to achieve CR. The interval between the onset of clinical signs and the clinical presentation was not significantly associated with CR, relapse rate, and survival time. Adverse effects included gastrointestinal upsets in 26 dogs (30.23%), sporadic infections in 17 dogs (19.77%), and pancreatitis in seven dogs (8.14%). CONCLUSIONS: The results suggest that adjunctive MMF treatment for MUE is safe and comparable to other immunosuppressive protocols. The treatment should focus on the achievement of CR and preventing relapse for successful management.

The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology.

The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m2 as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5-2 mg kg-1 day-1 ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 µg/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 µg/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m2 SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.

Expression of sphingosine-1-phosphate receptor 1 in neuroinflammation of canine brains.

Sphingosine-1-phosphate (S1P) is a signaling lipid mediator that is involved in multiple biological processes. The S1P/S1P receptor (S1PR) signaling pathway has an important role in the central nervous system. It contributes to physiologic cellular homeostasis and is also associated with neuroinflammation. Therefore, this study was performed to evaluate the expression of S1PR in dogs with meningoencephalitis of unknown etiology (MUE) and experimental autoimmune encephalomyelitis (EAE). The analysis used 12 brain samples from three neurologically normal dogs, seven dogs with MUE, and two canine EAE models. Anti-S1PR1 antibody was used for immunohistochemistry. In normal brain tissues, S1PR1s were expressed on neurons, astrocytes, oligodendrocytes, and endothelial cells. In MUE and EAE lesions, there was positive staining of S1PR1 on leukocytes. Furthermore, the expression of S1PR1 on neurons, astrocytes, oligodendrocytes, and endothelial cells was upregulated compared to normal brains. This study shows that S1PR1s are expressed in normal brain tissues and leukocytes in inflammatory lesions, and demonstrates the upregulation of S1PR1 expression on nervous system cells in inflammatory lesions of MUE and EAE. These findings indicate that S1P/S1PR signaling pathway might involve physiologic homeostasis and neuroinflammation and represent potential targets for S1PR modulators to treat MUE.

Investigation of side effects to treatment and cause of death in 63 Scandinavian dogs suffering from meningoencephalitis of unknown origin: a retrospective study.

BACKGROUND: Meningoencephalitis of unknown origin is a common cause of severe neurological disease in dogs. The term covers a heterogeneous group of noninfectious inflammatory diseases, with immune dysregulation widely accepted as the underlying disease mechanism. Current treatment consists of immunosuppression, with corticosteroids being the mainstay of virtually all treatment regimens. However, side effects of corticosteroids can be severe, and might be the cause of death in some patients. This retrospective, multi-centric study aimed at describing a population of Scandinavian dogs with meningoencephalitis of unknown origin in regards to reported side effects and cause of death, and to highlight possible differences in survival, when comparing corticosteroid monotherapy with other treatment regimens. RESULTS: Within the 5-year study period, 63 dogs were included. Of these, 35 (49.3%) died or were euthanized during the study period. Median survival time from time of diagnosis based on Kaplan-Meier curves for the overall population was 714 days (equivalent to around 25 months, range 0-1678 days). There was no statistically significant difference (P = 0.31) in survival between dogs treated with corticosteroid monotherapy (n = 26, median survival time 716 days, equivalent to around 25 months, range 5-911 days), dogs receiving a combination of corticosteroids and ciclosporin (n = 15, median survival time 916 days, equivalent to around 31 months, range 35-1678 days), and dogs receiving corticosteroids combined with either cytosine arabinoside, leflunomide, or a combination of 2 or more add-on drugs (n = 13, median survival time 1186 days, equivalent to around 40 months, range 121-1640 days). Side effects were registered for 47/63 dogs. Polyphagia (n = 37/47), polyuria/polydipsia (n = 37/47), diarrhea (n = 29/47) and lethargy (n = 28/47) were most frequently reported. The most common cause for euthanasia was relapse (n = 15/35, 42.9%), followed by insufficient or lack of treatment response (n = 9, 25.7%). Side effects were the direct cause of euthanasia in 2/35 dogs (5.7%). CONCLUSIONS: A large proportion of dogs in the overall population were euthanized due to relapse, emphasizing a need for treatment regimens aimed at specifically preventing relapse for an improved long-term survival. Side effects in dogs receiving corticosteroid monotherapy were rarely a direct cause of death, but were reported for all dogs. No statistically significant difference in survival was found when corticosteroid monotherapy was compared to other treatment regimens.

A shortened whole brain radiation therapy protocol for meningoencephalitis of unknown origin in dogs.

Introduction: A variety of treatment options have been described for canine meningoencephalitis of unknown origin (MUO). Few studies focused on radiation therapy as a second line immunomodulating treatment, implicating its effective use. However, a standard radiation therapy protocol is lacking, and further research will help to evaluate the effect of different dose regimens. Methods: Ten dogs diagnosed with MUO based on MRI and CSF findings were prospectively enrolled. The dogs were treated with a shortened whole brain radiation therapy protocol (5 × 4 Gy) in combination with prednisolone. Neurologic changes were quantified using an established scoring scheme. Follow-up MRI and CSF examination was scheduled three months after radiation therapy. Overall survival and time to progression were calculated. Histopathology of the brain was performed in case of death. Results: Seven dogs were diagnosed de novo and three had a history of relapsing MUO. Neurological status improved in all 10 dogs during radiation therapy, with 4/10 returning to normal shortly after radiation therapy. Three dogs died within the first three months after radiation therapy. At follow-up MRI lesions completely resolved in two dogs, partially resolved in five dogs, and progressed in one dog. After follow-up MRI, dogs were further treated with prednisolone monotherapy (two dogs) and additional immunosuppressant drugs (five dogs). Overall, four dogs showed disease progression, with a mean time to progression of 691 days (95%CI: 396-987) and mean overall survival for all dogs was 723 days (95%CI: 436-1011) (both medians not reached). Histopathology confirmed MUO in three dogs but was suggestive for oligodendroglioma in one dog. Radiation induced side effects were not seen. Conclusion: Shortened whole-brain radiation therapy could be an additional treatment option for MUO in conjunction to prednisolone, specifically for cases that require rapid relief of symptoms and with relapsing history.

Association between neurofilament light chain concentration and lesion size in dogs with meningoencephalitis of unknown origin.

BACKGROUND: Neurofilament light chain (NfL) is an axonal cytoplasmic protein in neurons. Recently, NfL has shown potential as a diagnostic biomarker in dogs with meningoencephalitis of unknown origin (MUO). However, there have been no studies on the biomarkers of lesion progression and resolution in MUO. OBJECTIVES: To identify the potential of NfL as a biomarker for predicting changes in lesions. METHODS: Seven dogs with MUO who had undergone two magnetic resonance imaging (MRI) scans were included. The serum NfL levels were measured using a single-molecule array. The relationship between the rate of change in lesion size and the rate of change in serum NfL level was analysed using simple linear regression. To investigate the effect of changes in lesion size on NfL levels, the dogs were divided into two groups depending on the change in lesion size: decreased lesion size group (n = 5) and increased lesion size group (n = 2). Trends in lesion size change were identified in the second MRI compared with the first MRI. RESULTS: A significant positive relationship between the rate of lesion size change and the rate of NfL level change was identified (R2 = 0.9239, p = 0.0006). In the decreased lesion size group (n = 5), all NfL levels in each dog decreased, and in the increased lesion size group (n = 2), all NfL levels in each dog increased. CONCLUSIONS: This preliminary study showed a positive relationship between the rate of change in lesion size and rate of change in serum NfL levels. Therefore, the serum NfL level may be a promising biomarker of lesion progression and resolution in MUO.

A Preliminary Study of Pharmacokinetics and Pharmacodynamics of Oral Fingolimod in Dogs.

BACKGROUND/AIM: Fingolimod is a sphingosine-1-phosphate receptor modulator that prevents lymphocytes egress from lymphoid organs. It has been used as a disease-modifying drug for human multiple sclerosis and has shown better therapeutic effects than other conventional therapies. Therefore, this study was performed to obtain preclinical data of fingolimod in dogs. MATERIALS AND METHODS: Nine laboratory Beagle dogs were used and randomized into three groups for pharmacokinetics (PK) and pharmacodynamics (PD). The dogs were administered once with a low-dose (0.01 mg/kg, n=3), medium-dose (0.05 mg/kg, n=3), and high-dose (0.1 mg/kg, n=3) of fingolimod, orally. Samples were collected serially at predetermined time points, and whole blood fingolimod concentrations were measured using high-performance liquid chromatography-mass spectrometry. Differential counts of leukocytes over time were determined to identify immune cells' response to fingolimod. RESULTS: Regarding PK, the concentration of fingolimod in the blood increased in a dose-dependent manner, but it was not proportional. Regarding PD, the number of lymphocytes significantly decreased compared to baseline in all dose groups (low-dose, p=0.0002; medium-dose, p<0.0001; high-dose, p=0.0012). Eosinophils were significantly reduced in low- (p=0.0006) and medium- (p=0.0006) doses, and neutrophils were also significantly reduced in medium-(p=0.0345) and high- (p=0.0016) doses. CONCLUSION: This study provides the basis for future clinical applications of fingolimod in dogs with immune-mediated diseases, such as meningoencephalitis of unknown etiology.

QTL Mapping and Candidate Gene Identifying for N, P, and K Use Efficiency at the Maturity Stages in Wheat.

Nitrogen (N), phosphorus (P), and potassium (K) are the three most important mineral nutrients for crop growth and development. We previously constructed a genetic map of unigenes (UG-Map) based on their physical positions using a RIL population derived from the cross of "TN18 × LM6" (TL-RILs). In this study, a total of 18 traits related to mineral use efficiency (MUE) of N/P/K were investigated under three growing seasons using TL-RILs. A total of 54 stable QTLs were detected, distributed across 19 chromosomes except for 3A and 5B. There were 50 QTLs associated with only one trait, and the other four QTLs were associated with two traits. A total of 73 candidate genes for stable QTLs were identified. Of these, 50 candidate genes were annotated in Chinese Spring (CS) RefSeq v1.1. The average number of candidate genes per QTL was 1.35, with 45 QTLs containing only one candidate gene and nine QTLs containing two or more candidate genes. The candidate gene TraesCS6D02G132100 (TaPTR gene) for QGnc-6D-3306 belongs to the NPF (NRT1/PTR) gene family. We speculate that the TaPTR gene should regulate the GNC trait.

Evaluation of the blood neutrophil-to-lymphocyte ratio as a biomarker for meningoencephalitis of unknown etiology in dogs.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been identified as a biomarker in several inflammatory and autoimmune diseases. Multiple sclerosis (MS) has been found to be associated with changes in the NLR in humans. OBJECTIVES: To examine the diagnostic value of the NLR in meningoencephalitis of unknown etiology (MUE) in dogs. ANIMALS: Thirty-eight MUE dogs, 20 hydrocephalic dogs, 10 brain tumor (BT) dogs, 32 idiopathic epilepsy (IE) dogs, and 41 healthy dogs. METHODS: Retrospective study. Medical records were reviewed to identify dogs with a diagnosis of neurologic disease. The NLR was determined in all dogs. RESULTS: The median NLR was significantly higher in MUE dogs (6.08) than in healthy (1.78, P < .001), IE (2.50, P < .05), and hydrocephalic dogs (1.79, P < .05). The area under the receiver operating characteristic curve of the NLR for differentiation between MUE and healthy dogs was 0.96, and between the MUE dogs and dogs with other forebrain diseases was 0.86. An optimal cutoff of 4.16 for the NLR had a sensitivity of 71.1% and specificity of 83.9% to differentiate the MUE dogs from the dogs with other forebrain diseases. CONCLUSIONS AND CLINICAL IMPORTANCE: The NLR could be a biomarker for diagnosing MUE and distinguishing it from other intracranial diseases in dogs.

Treatment With Cytarabine at Initiation of Therapy With Cyclosporine and Glucocorticoids for Dogs With Meningoencephalomyelitis of Unknown Origin Is Not Associated With Improved Outcomes.

Meningoencephalomyelitis of unknown origin (MUO) is a common disorder of dogs that results in significant morbidity and mortality. The ideal treatment regimen is not known but a second immunosuppressive agent is often utilized in combination with glucocorticoids to increase efficacy and reduce side effects. Recently, a benefit to using a cytosine arabinoside (CA) constant rate infusion (CRI) at the time of diagnosis has been demonstrated. Here, a retrospective study was performed to determine if administration of CA at the time of diagnosis would alter prognosis in dogs receiving cyclosporine and prednisone for treatment of MUO. Medical records of 51 client-owned dogs diagnosed with MUO at one institution were reviewed (2009-2019). All dogs were treated with cyclosporine and a tapering course of prednisone. Twenty-one dogs received a single initial 200 mg/m2 treatment with CA either as a CRI or subcutaneously. Significantly more patients in the CA treatment group were obtunded on presentation but all other baseline parameters were similar between groups. No differences in success (defined as sustained improvement on neurological exam with owner perceived good quality of life), relapse, or death were identified at 1-, 3-, 6-, 9-, 12-, 18-, or 36-month time points. These results do not support treatment with CA (either as a CRI or subcutaneously) at the time of diagnosis in dogs treated with cyclosporine and prednisone.

Neurofilament light chain as a biomarker of meningoencephalitis of unknown etiology in dogs.

BACKGROUND: Neurofilament light chain (NfL) is a neuron-specific cytoskeletal protein expressed in axons. Damaged axons of the central nervous system release NfLs into the cerebrospinal fluid (CSF) and the blood. In humans with neurologic diseases, NfL is used as a biomarker. OBJECTIVES: To identify the potential of NfL as a supportive tool for the diagnosis, prognosis, and monitoring of meningoencephalitis of unknown etiology (MUE) in dogs. ANIMALS: Twenty-six client-owned healthy dogs, 10 normal Beagle dogs, and 38 client-owned MUE dogs. METHODS: Cohort study. The concentrations of NfL in serum and CSF were measured using single-molecule array technology. RESULTS: Median NfL concentration was significantly higher in MUE dogs (serum, 125 pg/mL; CSF, 14 700 pg/mL) than in healthy dogs (serum, 11.8 pg/mL, P < .0001; CSF, 1410 pg/mL, P = .0002). The areas under the receiver operating characteristic curves of serum and CSF NfL concentrations were 0.99 and 0.95, respectively. The cut-off values were 41.5 pg/mL (serum) and 4005 pg/mL (CSF) for differentiating between healthy and MUE dogs, with sensitivities of 89.19% and 90%, respectively, and specificities of 96.97% and 100%, respectively. The NfL concentration showed a significant decrease (pretreatment, 122 pg/mL; posttreatment, 36.6 pg/mL; P = .02) in the good treatment-response group and a significant increase (pretreatment, 292.5 pg/mL; posttreatment, 1880 pg/mL, P = .03) in the poor treatment-response group. CONCLUSIONS AND CLINICAL IMPORTANCE: Neurofilament light chain is a potential biomarker for diagnosing MUE and evaluating response to treatment.

Case Report: Meningoencephalomyelitis of Unknown Etiology Manifesting as a Bilateral Cranial Polyneuropathy in 3 Dogs.

A bilateral cranial polyneuropathy was the primary magnetic resonance imaging (MRI) finding in three medium to large breed dogs diagnosed with meningoencephalomyelitis of unknown etiology. All three dogs presented with a progressive history of vestibular ataxia with either central vestibular or multifocal central nervous system (CNS) neuroanatomical localization. Brain MRI revealed variable degree of bilateral enlargement and/or increased contrast enhancement of the optic, oculomotor, trigeminal, facial, and vestibulocochlear nerves, as well as enhancement of the orbital fissure (oculomotor, trochlear, ophthalmic branch of trigeminal, and abducens nerves). There was evidence of intracranial and cranial cervical meningeal contrast enhancement in all three dogs and of cervical spinal cord lesions in 2. In all cases, more cranial nerves were affected than indicated by neurological examination. Cerebrospinal fluid (CSF) analysis was consistent with a mononuclear pleocytosis in 2 cases and a mixed cell (predominantly lymphocytic) pleocytosis in 1 case. All dogs were treated with immune suppressing medications and showed clinical improvement, although some cranial nerve deficits were persistent at follow up 2 months later. These are the first known cases of MUE diagnosed ante-mortem in a canine population documenting bilaterally symmetrical lesions affecting multiple cranial nerves. While MUE is a common cause of non-infectious inflammatory disease in dogs, it likely encompasses more classifications than have previously been reported, and should remain a differential for dogs of all ages and sizes presenting with cranial nerve deficits.

Case Report: Mineralized Pulmonary Artery Thrombi in Two Dogs Treated for Meningoencephalitis of Unknown Origin.

Meningoencephalitis of unknown origin (MUO) is a relatively common and very serious canine neurologic condition, which is typically associated with a poor long term prognosis despite treatment. This case series chronicles two dogs diagnosed with MUO who were treated with long term corticosteroids and cytosine arabinoside and lived well-beyond the typical survival time for this condition. Both eventually succumbed to respiratory signs associated with mineralized thrombi in their pulmonary arteries. Adverse effects from the two drugs used for treatment are reviewed in order to propose a possible mechanism to explain how long term use of these medications could result in such a phenomenon.

Presence of cerebrospinal fluid antibodies associated with autoimmune encephalitis of humans in dogs with neurologic disease.

BACKGROUND: Presumed autoimmune diseases affecting the central nervous system (CNS) of dogs are common. In people, antibodies against neuronal cell surface antigens that are associated with a wide variety of neurological syndromes have been identified. The presence of cerebrospinal fluid (CSF) autoantibodies that target neuronal cell surface proteins has not been reported in dogs with neurologic disorders. OBJECTIVES: Autoantibodies to neuronal cell surface antigens can be found in the CSF of dogs with inflammatory CNS disease. Our aim was to determine whether 6 neuronal cell surface autoantibodies were present in the CSF of dogs diagnosed with inflammatory and noninflammatory CNS disease. ANIMALS: Client-owned dogs with CNS disease and complete diagnostic evaluation including magnetic resonance imaging and CSF analysis were included. One healthy dog was included as a negative control. METHODS: Cerebrospinal fluid was tested for 6 antigenic targets with a commercially available indirect immunofluorescence assay test kit. RESULTS: There were 32 dogs with neurological disease, 19 diagnosed with inflammatory disease (encephalitis and meningitis), 10 with noninflammatory disease (neoplasia, intervertebral disk disease, degenerative myelopathy, and epilepsy), 2 with no diagnosis, and 1 with neoplasia and meningoencephalitis. Anti-N-methyl-d-aspartate receptor 1 (NMDAR1) antibodies were detected in 3 dogs (3/32; 9.38%). All 3 dogs responded to treatment of meningoencephalomyelitis of unknown etiology (MUE). CONCLUSIONS AND CLINICAL IMPORTANCE: Further evaluation of the prevalence and clinical relevance of CSF and serum antibodies to neuronal cell surface antigens is warranted. Defining antigenic targets associated with encephalitis in dogs might allow diagnostic categorization of MUE antemortem.

Prognostic Factors for Recovery of Vision in Canine Optic Neuritis of Unknown Etiology: 26 Dogs (2003-2018).

Optic neuritis (ON) is a recognized condition, yet factors influencing recovery of vision are currently unknown. The purpose of this study was to identify prognostic factors for recovery of vision in canine ON of unknown etiology. Clinical databases of three referral hospitals were searched for dogs with presumptive ON based on clinicopathologic, MRI/CT, and fundoscopic findings. Twenty-six dogs diagnosed with presumptive ON of unknown etiology, isolated (I-ON) and MUE-associated (MUE-ON), were included in the study. Their medical records were reviewed retrospectively, and the association of complete recovery of vision with signalment, clinicopathologic findings, and treatment was investigated. Datasets were tested for normality using the D'Agostino and Shapiro-Wilk tests. Individual datasets were compared using the Chi-squared test, Fisher's exact test, and the Mann-Whitney U-test. For multiple comparisons with parametric datasets, the one-way analysis of variance (ANOVA) was performed, and for non-parametric datasets, the Kruskal-Wallis test was performed to test for independence. For all data, averages are expressed as median with interquartile range and significance set at p < 0.05. Twenty-six dogs met the inclusion criteria. Median follow-up was 230 days (range 21-1901 days, mean 496 days). Six dogs (23%) achieved complete recovery and 20 dogs (77%) incomplete or no recovery of vision. The presence of a reactive pupillary light reflex (p = 0.013), the absence of fundoscopic lesions (p = 0.0006), a younger age (p = 0.038), and a lower cerebrospinal fluid (CSF) total nucleated cell count (TNCC) (p = 0.022) were statistically associated with complete recovery of vision. Dogs with I-ON were significantly younger (p = 0.046) and had lower CSF TNCC (p = 0.030) compared to the MUE-ON group. This study identified prognostic factors that may influence complete recovery of vision in dogs with ON. A larger cohort of dogs is required to determine whether these findings are robust and whether additional parameters aid accurate prognosis for recovery of vision in canine ON.

Retrospective evaluation of combined mycophenolate mofetil and prednisone treatment for meningoencephalomyelitis of unknown etiology in dogs: 25 cases (2005-2011).

OBJECTIVE: To evaluate the use of a combined protocol of prednisone and mycophenolate mofetil (MMF) for the treatment of meningoencephalomyelitis of unknown etiology (MUE) and to describe response, adverse effects, and outcome. DESIGN: Retrospective study (2005-2011). SETTING: University teaching hospital. ANIMALS: Twenty-five client-owned dogs with clinical signs, neuroimaging, and cerebrospinal abnormalities consistent with MUE. Five dogs whose MMF treatment was discontinued after 7-14 days due to gastrointestinal clinical signs were evaluated only for adverse effects. INTERVENTIONS: Dogs were initially treated with prednisone 2 mg/kg PO every 12 hours and with MMF 20 mg/kg PO or IV every 12 hours. Prednisone was tapered after 4 days to 1 mg/kg every 12 hours for 14 days, then to every 24 hours for 30 days, and again reduced by half every 2-4 months thereafter. When prednisone was tapered completely or to 0.5 mg/kg every 24-48 hours without clinical relapse, MMF was tapered in a similar manner. MEASUREMENTS AND MAIN RESULTS: Partial or complete clinical response was achieved in 95% (19/20) of the dogs. Median survival time by the end of the study was 250 days (range 6 to >1,679) with 40% (8/20) of the dogs still alive (336-1,679 days after diagnosis). All Pug dogs (4/20) included in the study died with a median survival time of 14 days. Adverse effects attributed to MMF, which included hemorrhagic diarrhea within the first 2 weeks of treatment, were recorded in 20% (5/25) of the dogs. CONCLUSIONS: MMF can be used as an adjunctive treatment for dogs with MUE. This protocol enables reduction of prednisone treatment or, in some cases, its complete withdrawal. The possibility of intravenous administration is advantageous in cases with severe neurological abnormalities and mentation changes, often seen in MUE. Attention is warranted for gastrointestinal adverse effects, especially in the first 2 weeks of treatment.