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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., (© 2023. The Author(s).)

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/m 2 IV over 24 h), followed by a SC protocol (50 mg/m 2 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 (CA 1 2.28 µg/ml, range 0.97-2.67; CA 8 1.83 µg/ml, range 0.77-2.84) compared to the CRI (CA1 0.01 µg/ml, range 0-0.45; CA 8 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/m 2 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., (© 2021 John Wiley & Sons Ltd.)

Background: We report the first case of canine Salmonella meningoencephalomyelitis and second case of canine Salmonella bacteriuria, as well as the first reported case of Salmonella enterica subspecies houtenae in a dog., Case Presentation: Immunosuppressive treatment in a dog for a relapse of steroid-responsive meningitis and arteritis (SRMA) allowed for the opportunistic establishment of a bacteremia with Salmonella enterica subsp. houtenae, ultimately causing meningoencephalomyelitis and subclinical bacteriuria. The bacterial infections were treated with a four-month course of amoxicillin; clinical treatment success was determined by serial negative urine cultures and lack of clinical signs correlated to the meningoencephalomyelitis., Conclusions: Both the bacteriuria and meningoencephalomyelitis represented opportunistic infections in a dog immunosuppressed for SRMA. The clinical course of this infectious meningoencephalitis emphasizes the importance of differentiating relapse of initial disease from opportunistic infection occurring in a compromised central nervous system. The novel Salmonella species identified in this case acts as a reminder that infectious disease diagnostics should not be curbed by anecdotal prediction of routine pathogenic suspects.

A 4 mo old spayed female mixed-breed dog was presented for focal lower motor neuron signs of the right forelimb and marked hyperesthesia on axillary palpation. Her signs progressed rapidly over the following days to diffuse lower motor neuron signs in all limbs and a seizure. MRI demonstrated a focal, slightly right-sided, 2.5 cm region of noncontrast-enhancing T2 hyperintensity and T1 isointensity at C4-C5 spinal cord segments. Imaging of the brain was unremarkable. The dog was euthanized as a result of poor prognosis. Polymerase chain reaction on cerebrospinal fluid and immunohistochemistry of brain tissue were both positive for canine distemper virus. This report documents an atypical presentation of canine distemper encephalomyelitis causing lower motor neuron signs and hyperesthesia.

A one-year-old male Maltese terrier presented with mild ataxia and disorientation for 4 months. Over time, clinical signs progressed from paraparesis to non-ambulatory tetraparesis, voice change and dysphagia. Histological examination revealed concurrent leukoencephalomyelitis and polyneuritis. Infectious etiologies, including dengue, Japanese encephalitis, Zika, canine distemper, pseudorabies, rabies, toxoplasmosis, neosporosis, leishmaniasis, and encephalitozoonosis, were ruled out by PCR and/or immunohistochemical (IHC) staining. IHC tested on neurological tissues highlighted a heterogeneous population of infiltrating T and B lymphocytes admixed macrophages. Therefore, this case was diagnosed with current leukoencephalomyelitis and polyneuritis, resembling combined central and peripheral demyelination (CCPD), an autoimmune inflammatory demyelinating disease affecting both the CNS and PNS in humans.

Objective: To identify environmental and other variables associated with a diagnosis of granulomatous meningoencephalomyelitis (GME) in dogs., Design: Case-control study., Animals: 31 dogs that received a histologic diagnosis of GME (case dogs) from January 2003 to January 2014 and 91 age- and breed-matched dogs., Procedures: Data were obtained from each dog's medical records regarding home address, signalment, body weight, body condition score (BCS), vaccination history, and date of diagnosis (case dogs) or visit (control dogs). Home address data were used to determine the human population density in each dog's geographic region. Seasonal distributions of GME diagnoses in the case group were evaluated for differences. Case and control dogs were compared with respect to the remaining variables., Results: For case dogs, no significant difference was identified among seasons in the distribution of GME diagnoses; however, such diagnoses were more common in the spring than in other seasons. No significant differences were identified between case and control dogs in age, body weight, BCS, human population density, season of diagnosis or visit, or time of last vaccination. Although females appeared more likely than males to have a GME diagnosis, this association was not significant and did not change when BCS, time since last vaccination, or human population density was considered., Conclusions and Clinical Relevance: None of the evaluated factors, including investigated environmental triggers, were associated with a GME diagnosis in the dogs of this study. Additional research is warranted involving dogs from a broader geographic area.

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/m 2 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/m 2 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., (© 2018 John Wiley & Sons Ltd.)

The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client-owned dogs received a CRI of CA at a dose of 25 mg/m 2 /h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high-pressure liquid chromatography. The mean peak concentration (C MAX ) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1- and 8-h time points. The steady-state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma., (© 2016 John Wiley & Sons Ltd.)

Objectives: To summarise clinical presentation, diagnostic findings and long-term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone., Methods: Medical records were reviewed for dogs diagnosed with presumptive spinal-only meningoencephalomyelitis of unknown origin between 2006 and 2015., Results: 21 dogs were included; the majority presented with an acute (43%) or chronic (52%) onset of neurological signs. Ambulatory paresis was the most common neurological presentation (67%). Neurological examination most commonly revealed a T3-L3 myelopathy, and spinal hyperaesthesia was a common finding (71%). A spinal cord lesion was visible in 90% of cases on magnetic resonance imaging. Eighteen lesions (86%) showed parenchymal contrast enhancement and 17 lesions (81%) showed contrast enhancement of overlying meninges. All dogs were treated with immunosuppressive doses of glucocorticosteroids, sometimes combined with cytosine arabinoside. At time of data capture, 10/21 dogs (48%) had died or been euthanased because of the condition. Overall median survival time was 669 days., Clinical Significance: Meningoencephalomyelitis of unknown origin should be considered in the differential diagnosis of dogs presenting with a progressive myelopathy. Magnetic resonance imaging features can possibly help to distinguish presumptive meningoencephalomyelitis of unknown origin from other more common spinal diseases. Overall, long-term survival is guarded, approximately 50% of dogs will die or be euthanased despite appropriate therapy., (© 2017 British Small Animal Veterinary Association.)

The potential of microRNAs (miRNAs) as biomarkers for canine meningoencephalomyelitis of unknown origin (MUO) was investigated by using quantitative real-time (qRT)-PCR to determine the expression of microRNA-21 (miR-21) and microRNA-181c (miR-181c) in the cerebrospinal fluid (CSF) of dogs. Dogs with MUO (n = 10) had higher levels of expression of miR-21 and miR-181c in the CSF than dogs with non-inflammatory neurological diseases (n = 8). There was a positive correlation between CSF cellularity and expression of miRNAs in the CSF, particularly for miR-21 in the MUO group., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The objective of the study was to retrospectively evaluate the short-term safety of intrathecal administration of cytosine arabinoside alone or in combination with methotrexate in dogs and cats. One hundred and twelve dogs and eight cats admitted between September 2008 and December 2013, diagnosed with suspected inflammatory (meningoencephalomyelitis of unknown aetiology) or neoplastic disease affecting brain or spinal cord and treated with an intrathecal administration of cytosine arabinoside alone or in combination with methotrexate were included in the study. Recorded information regarding possible adverse events during administration while recovering from anaesthesia and during hospitalization period were evaluated. The results showed that one patient developed generalized tonic-clonic seizure activity after administration of cytosine arabinoside and methotrexate during recovery from anaesthesia, however responded to intravenous administration of diazepam. On the base of our results we can conclude that intrathecal administration of cytosine arabinoside alone or in combination with methotrexate is a safe procedure in dogs and cats., (© 2014 John Wiley & Sons Ltd.)

Central European tick-borne encephalomyelitis can be challenging to diagnose in dogs because the virus may not be detected in blood and cerebrospinal fluid (CSF) after the first viremic stage of the disease. The purpose of this retrospective case series study was to describe 3 Tesla magnetic resonance imaging (3T MRI) findings in a sample of dogs with a confirmed diagnosis of tick-borne encephalomyelitis. Dogs were included if they had neurological signs consistent with tick-borne encephalomyelitis, history of a stay in endemic areas for tick-borne encephalomyelitis virus, 3T MRI of the brain and/or spinal cord, cerebrospinal fluid changes compatible with viral infection and positive antibody titers in cerebrospinal fluid or pathologic confirmation of tick-borne encephalomyelitis. Twelve dogs met inclusion criteria. Ten out of 12 patients had 3T MRI lesions at the time of presentation. One patient had persistent lesions in follow-up MRI. The 3T MRI findings included bilateral and symmetrical gray matter distributed lesions involving the thalamus, hippocampus, brain stem, basal nuclei, and ventral horn on the spinal cord. All lesions were hyperintense in T2-weighted sequences compared to white matter, iso- to hypointense in T1-weighted, nonenhancing, and had minimal or no mass effect or perilesional edema. Six patients survived while the remaining six dogs were euthanized. Necropsy revealed neuronophagia and gliosis of the gray matter of the affected regions seen in 3T MRI, in addition to the cerebellum. Findings from the current study indicated that tick-borne encephalomyelitis should be included in the differential diagnosis list for dogs with the above described 3T MRI characteristics., (© 2015 American College of Veterinary Radiology.)

A two-year-old male, neutered, basset hound-beagle mix with progressive neurological impairment was examined postmortem. Grossly, the dog had multiple raised masses on the spinal cord between nerve roots. Microscopically, the dog had protozoal myeloencephalitis. Toxoplasma gondii and Sarcocystis neurona were detected in the CNS by immunohistochemistry and polymerase chain reaction (PCR). Sarcocysts in formalin-fixed muscle were negative for Sarcocystis by PCR. Banked serum was negative for T. gondii using the modified agglutination test, suggesting an acute case of T. gondii infection or immunosuppression; however, no predisposing immunosuppressive diseases, including canine distemper, were found. To the authors' knowledge, this is the first report of dual T. gondii and S. neurona infection in a dog., (Published by Elsevier B.V.)

Tick borne encephalitis virus (TBE) is an endemic infectious agent in northeastern Switzerland causing mainly meningoencephalomyelitis in dogs. We report a canine case of tick born meningoencephalomyelitis resulting in flaccid tetraplegia and, subsequently, fatal respiratory failure. Magnetic resonance imaging (MRI) demonstrated intra-axial bilateral, symmetric, and hyperintense lesions in T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) sequences affecting thalamus, basal nuclei, cerebral white matter and ventral horns of the caudal cervical spine. These radiological findings overlap those described during flavivirus encephalitis affecting human beings. These lesions in MRI and diffusion weighted images correlated with areas of vasogenic edema detected histopathologically. In endemic regions, clinicians should be aware that bilateral, symmetrical hyperintense thalamic lesions in T2WI can be suggestive of flavivirus infection in dogs with encephalitis.

In dogs, there are several idiopathic meningoencephalitides, such as necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME). Although they are often assumed to be immune mediated, the etiology of these diseases remains elusive. In this study, the histopathology of the lesions caused by these conditions and the inflammatory cell populations produced in response to them were examined among dogs affected with GME, NME, or NLE to understand their pathogeneses. The brain tissues of dogs with NME (n = 25), NLE (n = 5), or GME (n = 9) were used. The inflammatory cells were identified by immunohistochemistry using antibodies against CD3, IgG, CD20, CD79acy, and CD163. In NME and NLE, malacic changes were located in the cerebral cortex, as well as the cerebral white matter and thalamus, respectively. The distribution of the brain lesions in NME and NLE was breed specific. In GME, granulomatous lesions that were mostly composed of epithelioid macrophages were observed in the cerebral white matter, cerebellum, and brainstem. Although the proportions of IgG-, CD20-, and CD79acy-positive cells (B cells) were not significantly different among the GME, NME, and NLE lesions, that of CD3-positive cells (T cells) was increased in GME. In NME and NLE, CD163-positive cells (macrophages) had diffusely infiltrated the cerebral cortex and white matter, respectively. However, in GME, CD163-positive cells accumulated around the blood vessels in the cerebral and cerebellar white matter. The distributions of these lesions were quite different among GME, NME, and NLE, whereas there were no marked differences in the proportions of inflammatory cells.

Objective: To compare oral administration of lomustine and prednisolone with oral administration of prednisolone alone as treatment for granulomatous meningoencephalomyelitis (GME) or necrotizing encephalitis (NE) in dogs., Design: Retrospective cohort study., Animals: 25 dogs with GME and 18 dogs with NE (diagnosis confirmed in 8 and 5 dogs, respectively)., Procedures: Records of dogs with GME or NE were reviewed for results of initial neurologic assessments and clinicopathologic findings, treatment, follow-up clinicopathologic findings (for lomustine-treated dogs), and survival time. Dogs with GME or NE treated with lomustine and prednisolone were assigned to groups 1 (n = 14) and 3 (10), respectively; those treated with prednisolone alone were assigned to groups 2 (11) and 4 (8), respectively., Results: Prednisolone was administered orally every 12 hours to all dogs. In groups 1 and 3, mean lomustine dosage was 60.3 mg/m², PO, every 6 weeks. Median survival times in groups 1 through 4 were 457, 329, 323, and 91 days, respectively (no significant difference between groups 1 and 2 or between groups 3 and 4). Within the initial 12 months of treatment, median prednisolone dosage was reduced in all groups; dosage reduction in group 1 was significantly larger than that in group 2 at 6, 9, and 12 months. Combination treatment most frequently caused leukopenia, but had no significant effect on liver enzyme activities., Conclusions and Clinical Relevance: In dogs with GME and NE, oral administration of lomustine and prednisolone or prednisolone alone had similar efficacy. Inclusion of lomustine in the treatment regimen was generally tolerated well.

An aged Maltese dog (dog 1) showed gait ataxia for a month and suddenly died after convulsion. An aged Toy Poodle dog (dog 2) showed sudden blindness with unresponsive pupillary light reflexes and sudden death due to acute cardiac failure. Histological examination of the two dogs demonstrated severe granulomatous perivascular inflammation in the white matter throughout the central nervous system (CNS) including the brain and spinal cord. Based on the clinical and pathological findings, these dogs were diagnosed as granulomatous meningoencephalomyelitis (GME). In dog 2, the inflammatory changes predominated in the visual system such as the optic nerve, optic tract and optic radiation in the cerebrum (ocular form). Distribution pattern of the inflammatory lesions in the CNS was compared between the two dogs.

Background: Marked eosinophilic meningitis or meningoencephalomyelitis (EME) is rarely reported in dogs and the cause is usually undetermined. Long-term prognosis for dogs with cerebrospinal fluid (CSF) eosinophilia is variable., Animals: Twenty-three client-owned dogs., Methods: Retrospective case series. Dogs with eosinophilic CSF, defined as total nucleated cell count (TNCC) >3 cells/microL with >20% eosinophils, were identified by a computerized search of all dogs having cisternal and/or lumbar CSF analyzed as part of the diagnostic workup between 1992 and 2007., Results: TNCC in CSF ranged from 4 to 4,740 cells/microL (median 84 cells/microL, reference range

A 4-year-old female miniature dachshund presented with a history of progressive decrease in vision, neck pain, and ataxia for which an MRI was performed 21 days after the initial consultation. The optic nerves showed isointensities on T1- (T1W) and T2-weighted (T2W) images that were enhanced by the contrast medium. The optic chiasm was swollen. Other parts of the cerebral parenchyma, not only the visual pathway, showed symmetrical hyperintensities on T2W images. Cerebrospinal fluid showed increased anti-GFAP autoantibodies. The dog received corticosteroid therapy despite which she exhibited anorexia, vomiting, and lethargy. Hence, a follow-up MRI was repeated 30 days after the initial consultation in which T2W images showed enlargement of the hyperintense area. The dog died 45 days after the initial consultation. Postmortem pathological examination confirmed a diagnosis of granulomatous meningoencephalomyelitis (GME).

A 9-year-old male neutered Labrador Retriever presented with signs consistent with multifocal neurological disease. Cerebrospinal fluid analysis revealed a mononuclear pleocytosis and electromyography revealed abnormal electrical activity in distal appendicular and masticatory muscles. Treatment was declined and necropsy revealed disseminated granulomatous meningoencephalomyelitis with extensive involvement of the peripheral nervous system.

The characteristics of magnetic resonance imaging (mri) of the brains and spinal cords of 11 dogs with histologically confirmed granulomatous meningoencephalomyelitis (gme) were determined. The lesions were in the brain of eight of the dogs, in the brain and spinal cord of two, and in the spinal cord alone in one dog. A single lesion was present in four of the dogs and multiple lesions were found in six. In one dog with intracranial signs, no visible lesions could be detected on mri. No meningeal enhancement was detected in T1-weighted images post-contrast, or in fluid attenuation inversion recovery (flair) images, but there were histological lesions in the meninges in nine of the dogs. The T2-weighted images and flair sequences were characterised in all cases by hyperintensity, whereas the signal intensity of the lesions on T1-weighted images was variable. After the administration of paramagnetic contrast, some of the lesions showed no enhancement, but others showed marked patterns of enhancement. The lesions in 10 of the dogs were easily identifiable by mri and the images had several unifying characteristics, but they could not be considered disease-specific.

Eastern equine encephalitis virus (EEEV) is an Alphavirus that is endemic in the Southeastern United States. From 1993 to January 2005, the Veterinary Diagnostic and Investigational Laboratory in Tifton, Georgia, performed postmortem examinations on over 101 domestic canines exhibiting clinical neurological disturbances. In 12 of these dogs, brains were histologically suggestive of infection with EEEV. All dogs were less than 6 months of age, with no breed predilection. Clinical signs included pyrexia, depression, nystagmus, and lateral recumbency. Microscopically, brains from all 12 puppies contained infiltrates of lymphocytes, plasma cells, and histiocytes, with occasional neutrophils and random foci of astrocytosis and gliosis. There were mild to moderate perivascular infiltrates of neutrophils along with scattered lymphocytes, plasma cells, and macrophages in the meninges. Viruses isolated from brain homogenates of all 12 puppies were confirmed by indirect fluorescent antibody testing to be EEEV. Additionally, RNA extracted from the brains and viral cultures of 2 dogs were determined by a specific reverse-transcriptase polymerase chain reaction (RT-PCR) to contain EEEV. The single available serum sample exhibited a 1:8 serum neutralization titer to EEEV.

Several species of free-living amoebae can cause encephalomyelitis in animals and humans. Disseminated acanthamoebiasis was diagnosed in pyogranulomatous lesions in brain, thyroid, pancreas, heart, lymph nodes, and kidney of a one-year-old dog. Acanthamoeba sp. was identified in canine tissues by conventional histology, by immunofluorescence, by cultivation of the parasite from the brain of the dog that had been stored at -70 degrees C for two months, and by PCR. The sequence obtained from the PCR product from the amoeba from the dog was compared to other sequences in the Acanthamoeba sp. ribosomal DNA database and was determined to be genotype T1, associated with other isolates of Acanthamoeba obtained from granulomatous amebic encephalitis infections in humans.

To describe the signs that may be associated with intracranial inflammatory conditions, magnetic resonance (MR) images of 25 dogs that had inflammatory cerebrospinal fluid (CSF) were mixed with those of a control group of 40 dogs that had CSF negative for inflammatory disease and reviewed without knowledge of the clinical signs or diagnosis. CSF was considered inflammatory if the protein level was > 0.25 g/l and the white cell count was > 5 mm(-3). Abnormalities were found by MR imaging in 19 (76%) dogs with inflammatory CSF. Two dogs had focal lesions, 10 had multifocal lesions, and seven had diffuse lesions. Lesions affected all divisions of the brain. Mass effect was identified in seven (28%) dogs, including one that had a choroid plexus carcinoma. Lesions were hyperintense in T2-weighted images in 18 dogs and hypointense in T1-weighted images in six dogs. Multifocal or diffuse intraaxial lesions that were hyperintense in T2-weighted images were observed in 17 (68%) dogs with inflammatory CSF. Administration of gadolinium resulted in enhancement of intraaxial lesions in nine (36%) dogs and enhancement of meninges in seven (28%) dogs. Six (24%) dogs with inflammatory CSF had images interpreted as normal.

Histiocytic proliferative disorders in canine central nervous system (CNS) including granulomatous meningoencephalomyelitis (GME) and malignant histiocytosis were compared pathologically. Lesions of GME mainly existed in the white matter of the cerebrum, brainstem and cerebellum and consisted of characteristic perivascular cuffing, parenchymal granuloma and leptomeningeal infiltrates of mononuclear cells. In malignant histiocytosis, there were two histological patterns, diffuse proliferation of neoplastic histiocytes through the leptomeninges and neoplastic nodule formation in the parenchyma. Neoplastic histiocytes exhibited mild to severe cellular atypia and high ability of invasion into the brain parenchyma. Mitotic and phagocytic figures were also observed. Several histiocytic markers, including lysozyme, alpha1-antitrypsin and lectin RCA-1, revealed histiocytic origin of both inflammatory and neoplastic cells, however, those were not determinative for the discrimination between GME and malignant histiocytosis. CD3- and PCNA-positive cells existed in the lesions of both diseases. The number of CD3-positive cells in GME tended to be greater than in malignant histiocytosis, while the difference was not statistically significant.

The clinical records of 23 dogs (1990-1999) with histopathologically confirmed bacterial meningoencephalomyelitis were evaluated retrospectively. No breed, age, sex, or weight predisposition was found. All the dogs presented with clinical signs of a brain lesion, whereas 5 of 23 had neck pain. Pyrexia was detected in 11 of 23 dogs on admission. CBCs revealed neutrophilic leucocytosis in 7 of 21 dogs and thrombocytopenia in 3 of 21 dogs. The serum chemistry profiles were abnormal in 15 of 21 dogs. The results of cerebrospinal fluid (CSF) analysis were abnormal in 13 of 14 dogs and aerobic CSF culture was positive for bacteria in 1of 8 samples. At postmortem examination, the lesions were localized to the central nervous system. Escherichia coli, Streptococcus, and Klebsiella spp were the most frequently isolated bacteria from cultures collected at postmortem examination. Twelve papers reporting 51 total clinical cases of canine bacterial meningoencephalomyelitis were reviewed. The clinical signs and results of the CBC, serum chemistry, blood culture, and CSF analysis were collated and compared with those of this study. The results of the CSF analysis in this study were similar to those in the literature. CSF cultures documented in the literature were positive for Staphylococcus, Pasteurella. Actinomyces, Nocardia spp, and various anaerobic species including Peptostreptococcus, Eubacterium, and Bacteroides spp.

The data from 20 dogs with histopathologically confirmed granulomatous meningoencephalomyelitis were reviewed in an attempt to identify clinical signs and morphological and cellular parameters, particularly the infiltration of mast cells, which might be associated with the clinical course of the disease. Thirteen of the dogs had the acute form of the disease and seven had the chronic form. Young to middle-aged, small breed female dogs were over-represented. Central vestibular signs were observed in six of the dogs with the acute disease. Analyses of cerebrospinal fluid revealed moderate to severe pleocytosis and high protein concentrations in all cases. Histopathological investigations revealed disseminated perivascular cuffs, large confluent granulomata, tissue necrosis, infiltration with neutrophils and a large number of mitotic cells in the dogs with either of the clinical forms of the disease. Tryptase-positive mast cells were observed in all the cases, but there were significantly larger numbers in the dogs with the acute form.

Objective: To assess signalment, clinical signs, results of CSF analysis, treatment, and survival times in dogs with granulomatous meningoencephalomyelitis (GME) and to identify factors associated with survival., Design: Retrospective study., Sample Population: Medical records of 42 dogs with GME., Procedure: Information on signalment, neurolocalization, presence of focal or multifocal signs, results of CSF analysis, method of treatment, and time from onset of clinical signs to death was retrieved from medical records of each dog. Kaplan-Meier survival analysis was used to assess survival times. The Cox proportional hazards method was used to identify predictors of survival., Results: Females and toy and terrier breeds were predisposed to GME. Half of the dogs had focal neurologic signs, and half had multifocal involvement. Clinical signs referable to the forebrain were most common with focal involvement, whereas signs referable to the forebrain and brainstem were most commonly seen with multifocal involvement. Cerebrospinal fluid analysis commonly revealed a mononuclear pleocytosis. Survival times ranged from 1 to > 1,215 days. Significant differences in survival times were demonstrated for the following factors: focal versus multifocal clinical signs, neurolocalization of focal signs, and treatment with radiation. Radiation was the only independent predictor of survival., Clinical Implications: Dogs with signs suggesting focal involvement of GME tend to survive longer than those with multifocal involvement. Radiation is an effective treatment for dogs with GME, particularly those with clinical signs suggesting focal involvement.

Fetal neosporosis-associated myeloencephalitis was diagnosed in a 4-month-old Napolitan mastiff dog from Spain. Neospora caninum tachyzoites and tissue cysts were observed in lesions in the central nervous system and the diagnosis was confirmed by immunohistochemical staining with anti-N. caninum monoclonal and polyclonal antibodies.

A 12 week old female Labrador retriever dog with signs of progressive diffuse degeneration of the brain and spinal cord was found to have methylmalonic and malonic aciduria. Over a 5 month period, the dog developed neurologic signs compatible with disease of the central nervous system with predominant diffuse cerebral and right lateralizing brainstem deficits. Gross pathological examination of the brain showed that the lateral, third, and fourth ventricles of the brain were markedly enlarged and associated with white and grey matter atrophy. Syringomyelia and hydromyelia of the central canal into the dorsal funiculus of the spinal cord beginning at the level of the cervical intumescence and extending to the lumbar intumescence was also present. Significant biochemical abnormalities include methylmalonic and malonic aciduria, mild lactic and pyruvic aciduria. There was also accumulation of citric acid cycle intermediates including succinic, aconitic, and fumaric acids. Disordered fatty acid oxidation was suggested by increased excretion of adipic, ethylmalonic, suberic and sebacic acids. Neither ketoacidosis nor hyperammonemia were present, and serum cobalamin levels were normal. Overall, this dog demonstrates an inborn error of metabolism resulting in abnormal organic acid accumulation associated with a neurodegenerative disease.

A 6-year-old Doberman bitch was presented for an acute onset of circling, hemiparesis and depression. Clinical examination revealed conjunctivitis, abdominal pain, anaemia, decreased facial sensation, decreased jaw, tongue and pharyngeal tone, decreased conscious proprioception, decreased flexor withdrawal reflexes, and abnormal hemiwalking and hemistanding. Pancytopaenia was evident on haematological evaluation. Bone marrow cytology revealed a bacterial infection. Cerebrospinal fluid analysis was normal. Despite antibiotic treatment, the dog died. On autopsy, widespread multifocal inflammatory lesions were found to be present in the lungs, liver, spleen, meninges, lymph nodes, adrenal glands and kidneys. Listeria monocytogenes was isolated in pure culture from these organs and tissues. Histopathological examination showed numerous gram-positive intracellular rod-shaped bacteria seen in all the above-mentioned organs.

Neospora caninum is a recently identified protozoan parasite which was previously confused with Toxoplasma gondii. Neosporosis in puppies commonly causes signs referable to parasitic encephalomyelitis and myositis. The parasite was identified in tissues from 3 9-week-old Labrador littermates which showed signs of progressive hind limb hyperextension and paralysis. The diagnosis was confirmed, utilising a specific avidin-biotin immunohistochemical technique. Attempts to treat the pups with clindamycin were unsuccessful. One case was additionally treated with immunosuppressive doses of corticosteroids, but showed no improvement. Two pups were euthanased and necropsied. The predominant lesions were polymyositis and multifocal encephalomyelitis. Large clusters of tachyzoites were seen in the myofibres and thick-walled parasitic tissue cysts were found in the grey and white matter of the brain and spinal cord.

Nine puppies suffered from progressive paresis with muscle wasting, hyporeflexia and extensor rigidity. CK-activity in serum was elevated and electrodiagnostic findings were indicative of lower motor neuron disease. Although lesions were also found in the CNS, additional neurological signs were rare, but CSF examination revealed the presence of inflammatory lesions. On pathologic examination, all animals had a disseminated necrotizing myositis. In addition, a disseminated encephalomyelitis was found as well as, in 2 cases, a neuritis. In the lesions of 6 animals protozoal organisms were found which were immunocytochemically identified as Neospora caninum. Our results show that the protozoal myositis-encephalitis syndrome in puppies can be diagnosed in the clinic with high probability. A clinical differentiation between toxoplasmosis and Neospora caninum infection is presently difficult.

A 4-year-old castrated mixed-breed dog had atypical signs of chronic distemper encephalomyelitis. The predominant signs were related to visceral rather than somatic dysfunction. The visceral dysfunction was largely attributable to distemper-associated inflammatory lesions in the spinal cord and resulted in fecal incontinence, urinary incontinence, and priapism. Empirical treatment of the dog resulted in transitory improvement prior to euthanasia performed because of the progressive nature of the encephalomyelitis.

A 2-year-old Boston Terrier was referred because of depression and hindlimb and tail paresis. Clinical examination and serum biochemical analysis resulted in a diagnosis of encephalomyelitis and myositis. Results of testing for Dirofilaria immitis were positive. Gross and histologic examination revealed an aberrant adult heartworm infection resulting in thrombosis of the femoral artery and multiple muscular branches, with subsequent muscle necrosis and inflammation in one hindlimb. Additionally, an unusual larval-tissue interaction to microfilariae yielded a multifocal encephalomyelitis in the brain and spinal cord.

An acute progressive CNS disease characterized by fever, nystagmus, head tilt, facial paralysis, circling, and cervical pain was studied in 6 mature dogs. The term "granulomatous meningoencephalomyelitis" was proposed for the disease complex, which was characterized pathologically by disseminated granulomatous lesions having a predilection for brainstem structures.

Cerebrospinal fluid of 22 dogs with histologically confirmed granulomatous meningoencephalomyelitis was analyzed, retrospectively. Seventeen dogs had cisternal CSF analysis, 4 dogs had lumbar CSF analysis, and 1 dog had both. For cisternal CSF, the mean +/- SEM total WBC count was 800.8 +/- 300.9 cells/microliter. The WBC differential count was predominantly lymphoplasmacytic cells, but 13 of the 18 cisternal CSF had polymorphonuclear (PMN) cells, and the mean +/- SEM PMN cell percentage was 18.6 +/- 5.3%. The mean +/- SEM total protein content of cisternal CSF was 255.8 +/- 98 mg/dl. Of 5 cisternal CSF pressures measured, 4 were within the normal range. The mean +/- SEM total WBC count and total protein content of lumbar CSF were 533.4 +/- 256.5 cells/mu/microliter and 163.2 +/- 25 mg of protein/dl, respectively. As with cisternal CSF, the WBC differential count of lumbar CSF was predominantly lymphoplasmacytic cells. Of 5 lumbar CSF, 4 contained PMN cells, but the percentage was less than the PMN cell percentage of cisternal CSF. Although variable, the general pattern of CSF abnormality associated with granulomatous meningoencephalomyelitis was different from the CSF abnormalities commonly seen with viral, bacterial, or mycotic encephalitides.

A 10-week-old Boxer dog from Uppsala, Sweden, was killed because of hind limb paralysis. The hind limb muscles were grossly atrophied and encephalomyelitis and myositis were the predominant microscopic lesions. Neospora caninum-like tachyzoites were found in the brain and skeletal muscles, and tissue cysts were found in the brain. The organism was not Toxoplasma gondii, as T. gondii antibody was not found in the indirect fluorescent antibody test in serum samples from the puppy and the dam, and the organism in the dog's brain did not react with T. gondii antibody in the immunoperoxidase test.

In 27 adult dogs with a distinctive chronic granulomatous meningoencephalomyelitis there were locomotor problems, cervical meningitis and blindness. Lesions were widespread, but most severe in cerebral and cerebellar white substance and in the cervical spinal cord. Lesions were characterized by the development of epithelioid cell granulomas arising from mononuclear cuffs. There were secondary edema and necrosis in severe cases and eventual fibroplastic repair in chronic cases. The cause is unknown.

Granulomatous meningoencephalomyelitis (GME) was diagnosed in an 8-month-old Maltese with signs of CNS disease. Serum immunoglobulin (Ig) G concentration was decreased, and CSF analysis revealed high concentrations of mononuclear WBC and IgG. Initial improvement of the pup's signs in association with prednisolone treatment and postmortem examination of CNS tissues confirmed GME. Granulomatous meningoencephalomyelitis occurs rarely in young dogs and the abnormal Ig concentrations in this pup's serum and CSF suggest that immune responses may have a role in the cause and/or pathogenesis of GME.

Light-microscopy, including immuno-histochemical staining, and transmission and scanning electron microscopy were applied for the characterization of a Toxoplasma-like parasite associated with encephalomyelitis and myositis in dogs of the boxer breed. Most parasites were tachyzoites, occurring in clusters, up to 60 micron in diameter, in parasitophorous vacuoles of host cells. Cyst stages with a definite cyst wall were few, but could be demonstrated in all cases. Immunostaining with antiserum against Toxoplasma gondii was negative, while both tachyzoites and bradyzoites were stained with serum from affected dogs. Ultrastructurally, the parasite was characterized by a great number of rhoptries, few amylopectin granules, lack of micropores in the tachyzoites, and the occurrence of numerous dense bodies in the bradyzoites. Numerous intravacuolar tubules were present in the space of the parasitophorous vacuole. The cyst wall resembled that of T. gondii. Until a definite host is found, the parasite may be regarded as an "orphan", cyst-forming sporozoon that is ultrastructurally different from other known protozoan parasites. It has a light-microscopical similarity to T. gondii but is antigenically different.