Cerebrospinal Fluid Eosinophilia in 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/μL 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/μL (median 84 cells/μL, reference range ≤3 cells/μL), with 22 to 95% (median 78%) eosinophils in the differential count. An infectious agent was identified on necropsy in 4 of 23 (17%) dogs ( Cryptococcus neoformans [n = 2], Neospora caninum [n = 1], and Baylisascaris procyonis [n = 1]). Each of these dogs had progressive neurologic deterioration. Sixteen dogs had idiopathic EME. Magnetic resonance imaging (MRI) findings were abnormal in 7 of 13 dogs with EME; 2 dogs had focal lesions and 5 dogs had multifocal lesions. Clinical signs in 12 of 16 (75%) dogs with idiopathic EME resolved with prednisone treatment. Three dogs with acute intervertebral disc herniations recovered after decompressive surgery alone.
Conclusions: Idiopathic EME is a common cause of eosinophilic pleocytosis in dogs. MRI findings are variable. Infectious causes of EME were less common and had a poor prognosis.     

Cerebrospinal Fluid Changes in Two Horses With Central Nervous System Nematodiasis (Micronema deletrix)

Two horses with cerebrospinal nematodiasis (Micronema deletrix) had signs similar to those of other neurologic diseases resulting from parasitic (fly larvae, protozoa, or other helminths) migration through the central nervous system (CNS). In one horse (horse 1), a 13-year-old Paso Fino stallion, the cerebrospinal fluid (CSF) was slightly xanthochromic (1+), with a pleocytosis (25 nucleated cells/microliter) and a normal protein level (69 mg/dl). A CSF differential cell count showed 15% neutrophils, 56% lymphocytes, 22% macrophages, 5% eosinophils, and 2% basophils. In the other horse (horse 2), a 19-year-old Tennessee Walking Horse stallion, the CSF was modestly xanthochromic (2+), with pleocytosis (81 nucleated cells/microliter) and a modestly elevated protein concentration (114 mg/dl). A CSF differential cell count showed 9% neutrophils, 41% lymphocytes, and 50% macrophages. The CSF changes were consistent with those described for equine protozoal myeloencephalitis and verminous encephalitis. The microscopic lesions in both brains contained multifocal areas of malacia and granulomatous inflammation. Meningeal vessels throughout the brain were greatly thickened and inflamed, and they contained parasites. The CSF changes were not specific and histopathologic examination was required for a definitive diagnosis.     

Clinical Features and Magnetic Resonance Imaging Findings in 7 Dogs with Central Nervous System Aspergillosis

Background

Systemic aspergillosis is a manifestation of Aspergillus sp. infection that can result in central nervous system (CNS) involvement with marked alterations in CNS function. Information regarding the clinical presentation and magnetic resonance imaging (MRI) findings in cases of aspergillosis with CNS involvement is lacking, resulting in a need for better understanding of this disease.

Hypothesis/Objectives

The primary objectives were to describe the clinical features and MRI findings in dogs with CNS aspergillosis. The secondary objectives were to describe clinicopathologic findings and case outcome.

Animals

Seven dogs with CNS aspergillosis.

Methods

Archived records from 6 institutions were reviewed to identify cases with MRI of CNS aspergillosis confirmed with serum galactomannan enzyme immunoassay (EIA) testing, culture, or supported by histopathology. Signalment, clinical, MRI, clinicopathologic, histopathologic, and microbiologic findings were recorded and evaluated.

Results

Aspergillosis of the CNS was identified in 7 dogs from 3 institutions. The median age was 3 years and six were German Shepherd dogs. Five dogs had signs of vestibular dysfunction as a component of multifocal neurological abnormalities. The MRI findings ranged from normal to abnormal, including hemorrhagic infarction and mass lesions.

Conclusions and Clinical Importance

Until now, all reported MRI findings in dogs with CNS aspergillosis have been abnormal. We document that CNS aspergillosis in dogs, particularly German Shepherd dogs, can be suspected based on neurologic signs, whether MRI findings are normal or abnormal. Confirmatory testing with galactomannan EIA, urine, cerebrospinal fluid (CSF) or tissue culture should be performed in cases where aspergillosis is a differential diagnosis.     

雏鸡感染柔嫩艾美耳球虫后脂质过氧化物的变化

为了探讨柔嫩艾美耳球虫 (E.tenella)对感染雏鸡的损伤机制 ,本试验给 10日龄海兰白公雏鸡口服柔嫩艾美耳球虫孢子化卵囊 8× 10 4个 /只 ,在感染后 2、4、6、7、9、12、16和 2 1d分别各取 5只雏鸡剖检 ,取盲肠并采血 ,观察盲肠病理组织学变化 ,测定盲肠组织及血清中的丙二醛 (MDA )、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH- Px)的水平。结果表明 ,雏鸡在感染 E.tenella后 2～ 4d,盲肠开始出现损伤 ,同时 SOD和 GSH- Px活性也开始下降 ;感染后 4～ 7d,盲肠粘膜上皮和肠腺上皮细胞大量变性、坏死崩解 ,发生严重损伤时 ,盲肠及血清中 MDA含量显著增加 ,并持续到 9d,同时 SOD和 GSH- Px活性也显著下降 ;感染 9d后 ,损伤的盲肠组织及 MDA、SOD和 GSH- Px水平逐渐恢复 ,至 2 1d基本达到正常     

蛋白质组学与神经系统疾病的研究进展

作者阐述了蛋白质组学和蛋白质组学研究方法的最新进展。通过蛋白质组学方法对中枢神经系统的研究有助于阐明CNS疾病发生、发展、转归的网络机制,寻找疾病特异性蛋白质,针对疾病靶点定向合成药物,构建分子药理模型。     

Cerebrospinal Fluid Myelin Basic Protein as a Prognostic Biomarker in Dogs with Thoracolumbar Intervertebral Disk Herniation

Background: Release of myelin basic protein (MBP) into the cerebrospinal fluid (CSF) is associated with active demyelination and correlates with outcome in various neurological diseases. Hypothesis/Objectives: To describe associations among CSF MBP concentration, initial neurological dysfunction, and long‐term ambulatory outcome in dogs with acute thoracolumbar intervertebral disk herniation (IVDH). Animals: Five hundred and seventy‐four dogs with acute thoracolumbar IVDH and 16 clinically normal dogs. Methods: Prospective case series clinical study. Signalment, initial neurological dysfunction as determined by a modified Frankel score (MFS), and ambulatory outcome at >3‐month follow‐up were recorded. Cisternal CSF MBP concentration was determined by an ELISA. Associations were estimated between CSF MBP concentration and various clinical parameters. Results: Dogs with thoracolumbar IVDH that did not ambulate at follow‐up had a higher CSF MBP concentration (median, 3.56 ng/mL; range, 0.59–51.2 ng/mL) compared with control dogs (median, 2.22 ng/mL; range, 0–3.82 ng/mL) (P= .032). A CSF MBP concentration of ≥3 ng/mL had a sensitivity of 78% and specificity of 76% to predict an unsuccessful outcome based on receiver‐operating characteristics curve analysis (area under the curve =0.688, P= .079). Affected dogs with a CSF MBP concentration ≥3 ng/mL had 0.09 times the odds of ambulation at follow‐up compared with affected dogs with CSF MBP concentration <3 ng/mL when adjusted for initial MFS (95% confidence interval 0.01–0.66, P= .018). Conclusions and Clinical Importance: These results would suggest that CSF MBP concentration may be useful as an independent prognostic indicator in dogs with thoracolumbar IVDH.     

Fungal infections of the central nervous system in the dog and cat

Fungal infections of the central nervous system (CNS) in dogs and cats are uncommon. The purpose of this paper is to review the clinical signs, diagnostic tests, and therapeutic options of fungal infections of the CNS in the dog and cat. Clinical signs are dependent on lesion location and are often multifocal. Extraneural involvement is common. Antemortem diagnosis can be difficult and is definitively made via cytology, biopsy, or culture of an affected organ or cerebrospinal fluid (CSF). Magnetic resonance imaging can support a diagnosis and may assist in therapeutic decisions. Fungal serology can support a diagnosis when direct visualization of the organism is not possible. Long-term azole maintenance therapy is suggested to enhance survival and prevent relapse. Serial cerebrospinal fluid evaluation and magnetic resonance imaging may identify early relapse.     

Significance of surface epithelial cells in canine cerebrospinal fluid and relationship to central nervous system disease

Background: The term “surface epithelium” is used to describe cells, including meningeal, choroid plexus, ependymal, and endothelial cells, that are found in human cerebrospinal fluid (CSF) and are difficult to distinguish cytologically. We hypothesized that the presence of surface epithelial cells in canine CSF was associated with specific diseases of the central nervous system (CNS). Objectives: In this retrospective study the frequency of surface epithelial cells in CSF from dogs with neurologic disease was investigated along with the potential association with age, specific type of CNS disease, and CSF total nucleated cell count (TNCC) and protein concentration. Methods: The frequency of surface epithelial cells in 359 canine CSF samples was analyzed for 5 disease groups: CNS neoplasia, CNS compression, CNS inflammation, idiopathic epilepsy, and miscellaneous diseases. Groups were also combined into those with and without expected meningeal involvement. Association of the presence of surface epithelial cells in CSF with age, disease type, and CSF TNCC and protein concentration was investigated. Results: Surface epithelial cells were found in 27 of 359 (7.5%) CSF samples: CNS neoplasia 2/30 (6.7%), CNS compression 7/64 (10.9%), CNS inflammation 1/39 (2.6%), idiopathic epilepsy 8/124 (6.5%), and miscellaneous diseases 9/102 (8.8%). Significant associations between surface epithelial cell presence in CSF and age, disease type, CSF TNCC, and CSF protein concentration were not found. Conclusions: The presence of surface epithelial cells was not related to a specific disease group or CSF changes in the studied population. Thus, the presence of surface epithelial cells should be interpreted carefully, as it could represent an incidental finding in CSF specimens.     

The Accident Case—IV. The Significance and Estimation of Damage to the Central Nervous System

Abstract— The effects of mechanical injury to the brain and spinal cord are considered, special reference being given to the correlation of clinical manifestations with localization of lesions. Emphasis is placed on the importance of vascular interference in the genesis of central nervous injury.     

荆芥等中药治疗犬真菌皮肤病的疗效观察

真菌引起的皮肤病是由犬小孢子菌感染为主,较为顽固,且久治不愈,用药后时好时坏。本试验用中药与西药进行对比治疗犬真菌性皮肤病,中药的治愈率为90%,中药毒副作用小,无药物残留,不产生耐药性。试验结果表明,中药治疗犬真菌性皮肤病优于西药组,P>0.01。     

Two‐Year Follow‐Up Magnetic Resonance Imaging and Spectroscopy Findings and Cerebrospinal Fluid Analysis of a Dog with Sandhoff's Disease

A 13‐month‐old female Toy Poodle was presented for progressive ataxia and intention tremors of head movement. The diagnosis of Sandhoff's disease (GM2 gangliosidosis) was confirmed by deficient β‐N‐acetylhexosaminidase A and B activity in circulating leukocytes and identification of the homozygous mutation (HEXB: c.283delG). White matter in the cerebrum and cerebellum was hyperintense on T2‐weighted and fluid‐attenuated inversion recovery magnetic resonance images. Over the next 2 years, the white matter lesions expanded, and bilateral lesions appeared in the cerebellum and thalamus, associated with clinical deterioration. Magnetic resonance spectroscopy showed progressive decrease in brain N‐acetylaspartate, and glycine‐myo‐inositol and lactate‐alanine were increased in the terminal clinical stage. The concentrations of myelin basic protein and neuron specific enolase in cerebrospinal fluid were persistently increased. Imaging and spectroscopic appearance correlated with histopathological findings of severe myelin loss in cerebral and cerebellar white matter and destruction of the majority of cerebral and cerebellar neurons.     

The profile of urinary lipid metabolites in healthy dogs

Polyunsaturated fatty acids, including arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), are converted to hundreds of lipid mediators by cyclooxygenases (COX), lipoxygenases (LOX), and cytochrome P450 (CYP), or through non-enzymatic processes, and they reflect inflammatory states of the body. We comprehensively analyzed lipid metabolites in dog urine using a liquid chromatograph-mass spectrometry (LC-MS/MS) to describe their metabolic characteristics. We detected 31 AA-derived metabolites, four EPA-derived metabolites, and a DHA-derived metabolite in all urine samples. Among AA-derived metabolites, 15, 5, 3, and 8 were generated by COX, LOX, CYP, and non-enzymatic oxidation respectively. This study will be the first step to use profiles of urinary lipid metabolites for better understanding and diagnosis of canine diseases.     

Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy

Background

Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs.

Hypothesis/Objectives

That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM‐affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)‐6 and monocyte chemoattractant protein‐1/chemokine ligand 2 (MCP‐1/CCL2).

Animals

Client‐owned GDs: 15 control, 15 CSM‐affected.

Methods

Prospective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti‐inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs.

Results

Affected GDs had significantly lower MCP‐1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85–161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68–260.11, P = .028). In affected GDs, MCP‐1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti‐inflammatory medications, disease duration, or disease severity. IL‐6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92–2.47, P < .001) in GDs with SC signal changes.

Conclusions and Clinical Importance

Lower MCP‐1/CCL2 in CSM‐affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL‐6 in CSM‐affected GDs with SC signal changes suggests more severe inflammation in this group.     

Clinical and Clinicopathologic Features in 11 Cats with Cuterebra Larvae Myiasis of the Central Nervous System

The medical records of 11 cats with histopathologic findings consistent with central nervous system (CNS) Cuterebra larvae myiasis were retrospectively examined to determine if clinical features could identify this disorder antemortem. Young to middleaged indoor-outdoor domestic shorthaired cats presenting with acute neurologic signs from July through September predominated. Many cats recently had clinical signs consistent with upper respiratory disease. Most cats presented for depression, lethargy, or seizures. Almost all cats had abnormal rectal temperatures, either hyperthermia or hypothermia. Peripheral leukocytosis and eosinophilia were not characteristic of cats with CNS cuterebriasis. Cerebrospinal fluid analysis did not consistently disclose evidence of inflammation. Common neurologic deficits included blindness, abnormal mentation, and signs of unilateral prosencephalic disease. No specific clinical or clinicopathologic test was diagnostic for CNS cuterebriasis.     

西安地区宠物犬真菌性皮肤病的分析研究

皮肤病是危害宠物健康的主要疾病之一。本文通过对西安地区宠物犬门诊收治50例皮肤病的分析,总结犬皮肤病的发病原因、常见病原、发病规律以及治疗效果,为今后宠物犬常见皮肤病的预防提供借鉴。     

Beta-2-microglobulin levels in the cerebrospinal fluid of normal dogs and dogs with neurological disease

BACKGROUND: Cerebrospinal fluid (CSF) analysis is the basis for establishing a diagnosis of central nervous system (CNS) inflammation. However, the information provided by routine CSF analysis is limited. Determination of CSF beta-2-microglobulin (beta2m) concentration has been used diagnostically in humans to identify inflammatory CNS disease; we hypothesized that it may have similar value in dogs. OBJECTIVES: The objective of this study was to measure (beta2m concentration in the CSF of clinically healthy dogs and compare the values to those observed in dogs with inflammatory CNS disease and intervertebral disc disease (IVDD). METHODS: CSF was collected from 10 clinically healthy laboratory dogs and 11 dogs each with inflammatory CNS disease and IVDD. Routine CSF analysis was performed, and (beta2m concentration was measured by ELISA. CSF (beta2m concentration and CSF:serum (beta2m ratio were compared between groups by ANOVA. Linear relationships between CSF total nucleated cell count (TNCC), RBC count, total protein concentration, and (beta2m concentration were assessed by regression analysis. RESULTS: The mean (+/- SD) CSF (beta2m concentration in clinically healthy dogs was 0.36 (+/- 0.05 microg/mL (cisternal) and 0.40 (+/- 0.07 microg/mL (lumbar). Median CSF (beta2m concentration in dogs with IVDD (0.46 microg/mL) and inflammatory CNS disease (0.85 microg/mL) differed from that of controls (0.36 microg/mL; P=.002). The concentration also differed between the 2 disease groups (P=.01). Five dogs with inflammatory CNS disease had CSF:serum (beta2m ratios >1. A correlation was identified between TNCC and (beta2m concentration (r=0.69, P=.0003). CONCLUSIONS: CSF (beta2m concentration is higher in dogs with IVDD and inflammatory CNS disease, with highest values seen with inflammatory disease. This may be attributed in part to the correlation between CSF (beta2m concentration and TNCC, but also may reflect intrathecal immune activation.     

Intracranial extension of retrobulbar blastomycosis (Blastomyces dermatitidis) in a dog

Blastomycosis (Blastomyces dermatitidis) is a fungal disease that is endemic in the southern United States. This case report illustrates the clinical, MRI and histopathologic findings in a dog with invasion of a retrobulbar blastomycotic lesion into the calvarium. A 5‐year‐old intact female Weimaraner was referred for a 2‐month history of change in behavior and recent onset of visual deficits. Magnetic resonance imaging (MRI) examination revealed a large (5.8 × 2.0 × 2.5 cm) mass extending from the left orbit through a circular defect in the left cranioventral aspect of the calvarium caudally to the level of the pituitary fossa and interthalamic adhesion. The mass was heterogeneously iso‐ to hypointense on T2‐W images, slightly hypointense on T1‐W images, did not attenuate on fluid attenuated inversion recovery (FLAIR) images, and did not show evidence of susceptibility artifact on T2*‐W gradient recalled echo (GRE) images. Vasogenic edema and associated mass effect were noted. The mass showed strong homogeneous contrast enhancement with well‐defined margins and had thickening of the adjacent meninges (dural tail sign). Based on MRI findings a malignant neoplastic process was considered most likely and the patient was placed on oral prednisone to decrease peri‐tumoral inflammation. The dog initially improved but was euthanized 3 weeks later for worsening clinical signs. Histopathologic assessment of the mass revealed marked pyogranulomatous optic neuritis with intralesional fungal yeasts consistent with blastomycosis (Blastomyces dermatitidis). To our knowledge this is the first report of invasion of a retrobulbar blastomycotic lesion into the calvarium in a dog.