Correlation between fluorodeoxyglucose positron emission tomography and magnetic resonance imaging findings of non-suppurative meningoencephalitis in 5 dogs

This study characterized the [(18)F]2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) findings of encephalitis in dogs and assessed the role of FDG-PET in the diagnosis of meningoencephalitis. The medical records, magnetic resonance (MR), and FDG-PET images of 3 dogs with necrotizing meningoencephalitis (NME), 1 dog with granulomatous meningoencephalitis (GME), and 1 dog with meningoencephalitis of unknown etiology (MUE) were reviewed. On the FDG-PET, glucose hypometabolism was identified in the dog with NME, whereas hypermetabolism was noted in the dog with GME. The T2-weighted images (WI) and fluid attenuated inversion recovery (FLAIR) images were characterized by hyperintensity, whereas the signal intensity of the lesions on the T1-WI images was variable. The metabolic changes on the brain FDG-PET corresponded well to the hyper- and hypointense lesions seen on the MR imaging. This type of tomography (FDG-PET) aided in the differentiation of different types of inflammatory meningoencephalitis when the metabolic data was combined with clinical and MR findings.     

Amebic meningoencephalitis caused by Acanthamoeba castellani in a dog

A natural infection of Acanthamoeba castellani, a free-living ameba, was determined to be the cause of acute, hemorrhagic, necrotizing amebic meningoencephalitis in a dog. This case is unique because previous reports of infection by the Acanthamoeba spp in dogs have not indicated its presence in the brain. Naturally developing meningoencephalitis by Acanthamoeba spp in the dog may have a pathogenesis similar to that of human beings. The ameba in this case also was observed in the lungs and kidneys, which are believed to be the primary sites of lesions in human beings that develop amebic meningoencephalitis from Acanthamoeba spp.     

Necrotizing meningoencephalitis in five Chihuahua dogs

An acute to chronic idiopathic necrotizing meningoencephalitis was diagnosed in 5 Chihuahua dogs aged between 1.5 and 10 years. Presenting neurologic signs included seizures, blindness, mentation changes, and postural deficits occurring from 5 days to 5.5 months prior to presentation. Cerebrospinal fluid analyses from 2 of 3 dogs sampled were consistent with an inflammatory disease. Magnetic resonance imaging of the brain of 2 dogs demonstrated multifocal loss or collapse of cortical gray/white matter demarcation hypointense on T1-weighted images, with T2-weighted hyperintensity and slight postcontrast enhancement. Multifocal asymmetrical areas of necrosis or collapse in both gray and white matter of the cerebral hemispheres was seen grossly in 4 brains. Microscopically in all dogs, there was a severe, asymmetrical, intensely cellular, nonsuppurative meningoencephalitis usually with cystic necrosis in subcortical white matter. There were no lesions in the mesencephalon or metencephalon except in 1 dog. Immunophenotyping defined populations of CD3, CD11d, CD18, CD20, CD45, CD45 RA, and CD79a immunoreactive inflammatory cells varying in density and location but common to acute and chronic lesions. In fresh frozen lesions, both CD1b,c and CD11c immunoreactive dendritic antigen-presenting cells were also identified. Immunoreactivity for canine distemper viral (CDV) antigen was negative in all dogs. The clinical signs, distribution pattern, and histologic type of lesions bear close similarities to necrotizing meningoencephalitis as described in series of both Pug and Maltese breed dogs and less commonly in other breeds.     

Detection of Neospora caninum tachyzoites in cerebrospinal fluid of a dog following prednisone and cyclosporine therapy

Abstract: A 9‐year‐old female spayed Shetland Sheepdog was presented to the Kansas State University Veterinary Medical Teaching Hospital for evaluation following a 3‐week history of left rear limb lameness that had progressed to generalized ataxia. Multifocal or diffuse brain lesions were suspected based on physical examination findings. Cerebrospinal fluid (CSF) contained 52 nucleated cells/μL composed of mixed inflammatory cells. Treatment with prednisone and cyclosporine was initiated based on a presumptive diagnosis of granulomatous meningoencephalitis. Thirteen days later the dog was nonambulatory and mentally obtunded. Repeat CSF analysis revealed 298 nucleated cells/μL with 61% eosinophils. Rare protozoal tachyzoites consistent with Neospora caninum, Toxoplasma gondii, or Sarcocystis spp. were found extracellularly and within macrophages and an eosinophil. Despite cessation of prednisone and cyclosporine therapy and provision of supportive care, the dog died 6 days later. Examination of brain tissue sections revealed multifocally extensive, necrotizing, histiocytic, and lymphoplasmacytic meningoencephalitis with numerous protozoal zoites and cysts. Immunohistochemical analysis of brain tissue using a monoclonal antibody specific for N. caninum confirmed the diagnosis of neosporosis. Similar but less severe lesions were noted in the spinal cord, although organisms were not found. This case emphasizes the value of repeated CSF analysis when therapy is ineffective and the importance of excluding infectious causes of meningoencephalitis before commencement of immunosuppressive therapy.     

A canine case of necrotizing meningoencephalitis for long-term observation: clinical and MRI findings

A 3-year-old female pug presented with general seizure following a partial seizure. During the remaining 48 months till death, the dog showed various neurological signs such as disturbance of consciousness, myoclonus and various types of partial seizure after each occurrence of the seizure clusters, and the dog eventually exhibited inability to stand and dementia. Magnetic resonance imaging findings revealed atrophy of the brain over the course of the disease. On histopathological analysis, the dog was diagnosed with necrotizing meningoencephalitis. This case of a canine necrotizing meningoencephalitis observed over the long term is valuable.     

POSITRON EMISSION TOMOGRAPHY FEATURES OF CANINE NECROTIZING MENINGOENCEPHALITIS

A Yorkshire terrier and a Chihuahua were referred for acute onset, generalized tonic‐clonic seizures and were suspected to have meningoencephalitis based on magnetic resonance (MR) imaging findings. Brain lesions appeared hyperintense with T2‐weighted imaging and hypointense with T1‐weighted imaging, and were characteristic of necrotizing meningoencephalitis. Both dogs were diagnosed with necrotizing meningoencephalitis based on pathologic findings. Fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) was performed on both animals before euthanasia with the permission of the owner. In FDG‐PET images, these lesions seen in MR images were characterized by multifocal or diffuse hypometabolism. Our FDG‐PET results provided evidence of glucose hypometabolism in areas of necrosis and cavitation associated with necrotizing meningoencephalitis. FDG‐PET has the potential to provide valuable diagnostic information in dogs with suspected necrotizing encephalitis.     

Long-term immunosuppressive therapy with cyclosporine plus prednisolone for necrotizing meningoencephalitis in a Pekingese dog

A 4-year-old intact female Pekingese dog was presented with ataxia and seizure episodes. Based on magnetic resonance imaging and cerebrospinal fluid analysis results, meningoencephalitis of unknown etiology was suspected. The present case survived for 1,096 days under cyclosporine plus prednisolone therapy and was definitively diagnosed with necrotizing meningoencephalitis. This report describes the clinical findings, serial magnetic resonance imaging characteristics and pathologic features of a necrotizing meningoencephalitis and long-term survival after cyclosporine with prednisolone therapy.     

磁共振成像在犬脑膜脑炎中的诊断应用

通过介绍1例犬脑膜脑炎的磁共振成像(MRI)影像诊断,探讨MRI在临床上的应用。患犬2个月前出现后肢轻瘫症状,MRI扫描脊柱未见任何异常,当地兽医诊断为外周神经炎,按外周神经炎治疗2周出院。1个月后复发,遂转院。转院后第3天中午突发流涎、全身癫痫症状,使用多咪静注射液后抽搐症状未见好转。血常规、生化检查未见异常,神经学检查显示眼球垂直震颤。对患犬进行脑部MRI检查,MRI结果显示患犬大脑扣带回T1WI序列均质低强度信号,T2WI序列较均质高强度信号;T1WI序列显示右侧海马体尾部有1个椭圆形均质稍低信号,T2WI序列下呈较均质高信号。结合患犬病史、影像检查结果及临床症状,怀疑患犬扣带回为坏死性病变,海马体尾部椭圆形病变为肉芽肿性脑膜脑炎。治疗方法为抗炎及使用抗癫痫药物苯巴比妥治疗,用药1周后痊愈。     

Idiopathic granulomatous and necrotising inflammatory disorders of the canine central nervous system: a review and future perspectives

Granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and necrotizing leukoencephalitis are common inflammatory conditions of the canine central nervous system. Although each disease has unique histopathological features, these canine disorders collectively seem to be aberrant immune responses directed against the central nervous system. A review of the neurological signs and general neurodiagnostic approach to canine meningoencephalitis is followed by an overview of the specific clinical and neuropathological features of granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and necrotizing leukoencephalitis. The aetiopathogenesis of each disorder is explored including potential genetic, immunological, and environmental factors along with the current and prospective immunomodulatory therapies for meningoencephalitis.     

Magnetic resonance imaging findings in histologically confirmed Pug dog encephalitis

The purpose of the study was to describe magnetic resonance (MR) imaging features of histologically confirmed necrotizing encephalitis in four Pugs and to compare those findings with MR imaging characteristics of necrotizing encephalitis in other breeds. All dogs had the following common findings: lesions restricted to the forebrain, both cerebral hemispheres diffusely but asymmetrically affected, lesions affected gray and white matter resulting in loss of distinction between both, most severe lesions in occipital and parietal lobes, lesions were irregularly T2-hyperintense and T1-isointense to slightly T1-hypointense, and no cavitation. There were various degrees of contrast enhancement of brain and leptomeninges. Asymmetry of lateral ventricles and midline shift was seen in one dog each. Two dogs had brain herniation, which may have contributed to the progression of neurologic signs. Hyperintensity on T2-weighted and fluid attenuated inversion recovery images in the hippocampus and piriform lobe was consistent with excitotoxic edema, whereas similar imaging features in other forebrain areas corresponded to areas of inflammation or liquefaction on histopathology. In comparison with necrotizing encephalitis in other canine breeds, Pug dog encephalitis has some unique MR imaging features. Therefore, these characteristics cannot be applied to other breeds, nor should imaging features of necrotizing encephalitis of other canine breeds be used for interpretation of MR images in Pug dogs.     

Comprehensive immunohistochemical studies on canine necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME)

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.     

Greyhound meningoencephalitis: PCR-based detection methods highlight an absence of the most likely primary inducing agents

Greyhound meningoencephalitis is currently classified as a breed-associated idiopathic central nervous system inflammatory disorder. The non-suppurative inflammatory response can be distinguished from the other breed-associated disorders based on histopathology and lesion topography, however the nature of the response primarily suggests a viral infection. In the present study PCR and RT-PCR technologies were employed on frozen cerebral tissue from confirmed cases of meningoencephalitis to target specific viruses and protozoa likely to be implicated and to exclude the presence of bacterial 16SrRNA. Secondly, degenerate primers were used to detect viruses of the herpesvirus and flavivirus families. In addition cerebral tissues were probed for West Nile Virus. Viral nucleic acid sequences to Borna disease virus, to louping ill, tick borne encephalitis, West Nile and other flaviviruses were not detected. Canine distemper virus was detected in one animal with 97% homology to strain A75/15. Degenerate PCR for herpesviruses detected viral amplification products in one animal with 90% homology to canine herpesvirus DNA polymerase gene. Protozoal amplification products were only detected in a single dog with pathological confirmation of a combination of lesions of greyhound meningoencephalitis and a protozoal encephalomyelitis. Neospora was confirmed with sequence homology to Austrian strain 1. Bacterial 16SrRNA was not detected. The present study supports previous observations that many of the known microbial causes of canine meningoencephalitis are not involved. Findings could reflect that the causal agent was not specifically targeted for detection, or that the agent is at undetectable levels or has been eliminated from brain tissue. The potential roles of genetics and of molecular mimicry also cannot be discounted.     

Oligodendroglial gliomatosis cerebri in a poodle

Gliomatosis cerebri (GC) is a rare, diffusely infiltrating, glial cell tumour of neuroepithelial origin. This report describes a case of oligodendroglial GC in a 6-year-old male Poodle with central nervous system symptoms. Computed tomography revealed anomalous parenchyma density and ventricular asymmetry. Cerebrospinal fluid showed elevated protein (30 mg dL(-1)) and nucleated cell count (20 μL(-1)). Presumptive diagnosis of necrotizing meningoencephalitis was made. Because of rapid deterioration of the general condition of the animal, the dog was euthanized. Histologically there was an infiltration of round or ovoid neoplastic cells in the white matter of the left cerebral hemisphere and in leptomeninges. Immunohistochemistry showed that 80% of the neoplastic cells expressed Olig2 and some 50% expressed glial fibrilary acidic protein. On the basis of clinical, histological and immunohistochemical features, a diagnosis of oligodendoglial GC was done. This case represents the first report of a case of oligodendroglial GC in the canid.     

Brain Stem Auditory-Evoked Response Abnormalities in 14 Dogs With Confirmed Central Nervous System Lesions

Abnormal brain stem auditory-evoked responses (BAER) were recorded on 14 dogs with brain lesions confirmed by necropsy (n = 13) or magnetic resonance imaging and surgical biopsy (n = 1). Lesions included brain stem or cerebellar tumors (6 dogs), brain stem trauma (1 dog), forebrain tumors (3 dogs), hydrocephalus (2 dogs), granulomatous meningoencephalitis (1 dog), and meningoencephalitis (1 dog). Five affected dogs were comatose at the time of recording. BAER abnormalities could be classified as (1) absence of some or all of waves I to V, (2) increased latencies, with wave V being most frequently affected, or (3) a reduction in the amplitude ratio of waves V/1.     

COMPUTED TOMOGRAPHY OF NECROTIZING MENINGOENCEPHALITIS IN 3 YORKSHIRE TERRIERS

A necrotizing meningoencephalitis of Yorkshire terriers has recently been reported in 6 dogs in Switzerland, 1 dog in Japan and 1 dog in the United States. The purpose of this report is to describe the computed tomographic (CT) findings in 3 dogs with this disease, and to correlate the CT abnormalities with the clinical and pathologic findings in each case. Three Yorkshire Terriers between 2 and 10 years old were evaluated. Physical and neurologic examinations, complete blood count (CBC), serum biochemistry profile, cerebrospinal fluid analysis, and CT scan were performed on all 3 dogs. Brainstem auditory evoked responses (BAER) were evaluated for 2 dogs. Two dogs were euthanized at the owners' request and necropsies were performed. Neurologic examination findings were consistent with a multifocal/diffuse encephalitis involving the cerebrum and brainstem in all 3 dogs. Complete blood count and biochemistry profiles were normal. Elevated protein concentration and a mononuclear pleocytosis were demonstrated in 2 of 3 dogs on cerebrospinal fluid evaluation. Multifocal, extensive areas of decreased opacity throughout the cerebral hemispheres, asymmetric ventriculomegaly, and lack of contrast enhancement were appreciated on CT images of all three dogs. No mass effect was seen. These findings correlated well with pathologic findings at necropsy, which included multiple malacic cavitations within the brain, representing areas of locally extensive necrosis. CT abnormalities in combination with signalment, clinical findings and cerebrospinal fluid analysis should facilitate a presumptive diagnosis of Yorkshire Terrier necrotizing meningoencephalitis.     

Magnetic resonance imaging in two dogs with central nervous system disease

Accurate localization of the lesions in two dogs with progressive neurological disease was demonstrated with magnetic resonance imaging (MRI). The first dog had unilateral cerebellar signs with associated paradoxical vestibular symptoms. The CSF tap and clinical localization suggested a right-sided cerebellar tumour and this was confirmed with MRI scanning. The second dog had predominantly asymmetrical fore-brain signs with circling, personality changes, seizures and contralateral proprioceptive deficits. CSF analysis suggested an inflammatory or neoplastic condition. MRI showed a diffuse oedematous lesion of the left cerebral hemisphere which corresponded exactly with the lesions seen at necropsy. The advantages of MRI over CT scans are discussed.     

Magnetic resonance imaging and pathological findings in a case of canine idiopathic eosinophilic meningoencephalitis

A case of idiopathic eosinophilic meningoencephalitis in a six-month-old male Maremma shepherd dog is reported. The dog was referred with a four month history of progressive weakness and depression with loss of trained habits. Tendency to recumbency, disorientation, visual impairment, bilaterally decreased menace response and hindlimb conscious proprioception deficits were detected. Magnetic resonance imaging showed a diffuse hypointense signal involving the cerebral grey matter with enlargement of the cerebral sulci on T1-weighted and fast fluid-attenuated inversion recovery (FLAIR) sequences consistent with a diffuse necrosis or atrophy of the cortical grey matter. Histological examination revealed severe inflammatory infiltration mainly composed of eosinophils and macrophages in the subarachnoid space and in the superficial layer of the cerebral cortex where parenchymal rarefaction and necrosis of neurones were also evident. No parasites, cysts or fungi were detected, and an immunologically mediated disorder was suspected. Magnetic resonance imaging may represent a useful diagnostic tool to differentiate idiopathic eosinophilic meningoencephalitis from other inflammatory brain diseases of young dogs.     

A comparative pathological study on canine necrotizing meningoencephalitis and granulomatous meningoencephalomyelitis

Canine necrotizing meningoencephalitis (NME) and granulomatous meningoencephalomyelitis (GME) were compared pathologically. Gross observation exhibited lateral ventricular dilation and discoloration, malacia and/or cavitation of the cerebrum in NME. On the contrary, gross changes were milder in GME, except for occasional visible granulomatous mass formation. Histopathologically, the lesions of NME were distributed predominantly in the cerebral cortex and various degrees of inflammatory and necrotic changes were observed according to clinical stages. Besides, microscopic lesions of GME were mainly distributed in the white matter of the cerebrum, cerebellum and brainstem, which are characterized by perivascular cuffing, multiple granulomas and leptomeningeal infiltrates. Although macrophages and lymphocytes were predominant in the inflammatory lesions of both disorders, macrophages in GME transformed into epithelioid cells and exhibited more massive infiltration. Although lectin RCA-1-reactive cells were numerous in both disorders, lysozyme immunoreactive cells in NME were fewer than that in GME. Parenchymal infiltration of MAC387-positive cells was common in GME and limited in NME. The number of CD3-positive lymphocytes in the GME lesions tended to be greater than in NME, though the difference was not statistically significant. Morphological and immunohistochemical differences of the lesions, in particular, the characteristics of infiltrative macrophages may reflect these different pathogeneses of the two disorders.     

Bacterial meningoencephalitis and ventriculitis due to migrating plant foreign bodies in three dogs

Regional suppurative meningoencephalitis and ventriculitis of variable chronicity was diagnosed in three young dogs residing in Colorado. Grass awns were grossly identified in the right occipital cortex of one dog and in the right lateral ventricle of another. Intralesional plant material was microscopically evident in the dura mater overlying the right occipital cortex of the third dog. One grass awn was identified as a floret of Hordeum jabatum. In each case, aerobic culture of brain tissue identified multiple isolates of bacteria. The dogs presented with clinically variable, rapidly progressive neurologic dysfunction, including tetraplegia, depressed mentation, and episodic extensor rigidity, ataxia, circling, stupor, vocalization, and head-pressing. Encephalitis due to bacteria introduced from migrating plant foreign material is a potential sequela of intranasal, periocular, or pharyngeal foreign bodies.     

Necrotizing Meningoencephalitis in Atypical Dog Breeds: A Case Series and Literature Review

Background

Canine necrotizing meningoencephalitis (NME) is a fatal, noninfectious inflammatory disease of unknown etiology. NME has been reported only in a small number of dog breeds, which has led to the presumption that it is a breed‐restricted disorder.

Hypothesis/Objectives

Our objective was to describe histopathologically confirmed NME in dog breeds in which the condition has not been reported previously and to provide preliminary evidence that NME affects a wider spectrum of dog breeds than previously reported.

Animals

Four dogs with NME.

Methods

Archives from 3 institutions and from 1 author''s (BS) collection were reviewed to identify histopathologically confirmed cases of NME in breeds in which the disease has not been reported previously. Age, sex, breed, survival from onset of clinical signs, and histopathologic findings were evaluated.

Results

Necrotizing meningoencephalitis was identified in 4 small dog breeds (Papillon, Shih Tzu, Coton de Tulear, and Brussels Griffon). Median age at clinical evaluation was 2.5 years. Histopathologic abnormalities included 2 or more of the following: lymphoplasmacytic or histiocytic meningoencephalitis or encephalitis, moderate‐to‐severe cerebrocortical necrosis, variable involvement of other anatomic locations within the brain (cerebellum, brainstem), and absence of detectable infectious agents.

Conclusions and Clinical Importance

Until now, NME has only been described in 5 small dog breeds. We document an additional 4 small breeds previously not shown to develop NME. Our cases further illustrate that NME is not a breed‐restricted disorder and should be considered in the differential diagnosis for dogs with signalment and clinical signs consistent with inflammatory brain disease.