[Overview of canine eosinophilic lung and bronchial diseases]. / Übersicht über die eosinophilen Lungen- und Bronchialerkrankungen des Hundes.

In dogs with chronic cough eosinophilic lung disease (ELD) may be present, especially in young dogs. A breed predisposition has been described in Alaskan Malamutes and Siberian Huskies. Chronic cough is the most common clinical sign. Other symptoms include nasal discharge, sneezing, poly- or dyspnea and exercise intolerance. The exact pathogenesis is unknown. Type 1 hypersensitivity reaction is suspected. Eosinophilic lung diseases may be classified into different groups (eosinophilic bronchitis, eosinophilic bronchopneumopathy and eosinophilic granuloma). Diagnostic work-up includes hematology, imaging, bronchoscopy and cytologic examination of bronchoalveolar lavage fluid. A wide spectrum is present in terms of the expression and severity of the changes. The current reported treatment is systemic or inhaled glucocorticoids, or a combination of both.Most patients respond well to therapy. Relapses after treatment discontinuation are common.

Neutrophil extracellular traps in CSF and serum of dogs with steroid-responsive meningitis-arteritis.

In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies.

Relationship between magnetic resonance imaging findings and histological grade in spinal peripheral nerve sheath tumors in dogs.

BACKGROUND: Peripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location. HYPOTHESIS/OBJECTIVES: Identify magnetic resonance imaging (MRI) features predictive of PNST histologic grade. ANIMALS: Forty-four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation. METHODS: A multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board-certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board-certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis. RESULTS: Forty-four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low-grade), 19 were PNSTs Grade 2 (medium-grade), and 9 were PNSTs Grade 3 (high-grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade. CONCLUSIONS AND CLINICAL IMPORTANCE: Grade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high-grade PNSTs including tumor size and peripheral contrast enhancement.

Biopsy Characteristics, Subtypes, and Prognostic Features in 107 Cases of Feline Presumed Immune-Mediated Polyneuropathy.

Inflammatory polyradiculoneuropathy (IMPN) is one of the causes of sudden onset of neuromuscular signs such as para-/tetraparesis in young cats. Even though most cases have a favorable outcome, persistent deficits, relapses, and progressive courses are occasionally seen. As clinical presentation does not always appear to predict outcome and risk of recurrence, this study was initiated to screen for prognostic biopsy findings in a large cohort of histologically confirmed IMPN cases with clinical follow-up. In total, nerve and muscle specimens of 107 cats with biopsy diagnosis of presumed autoreactive inflammatory polyneuropathy and 22 control cases were reviewed by two blinded raters for a set of 36 histological parameters. To identify patterns and subtypes of IMPN, hierarchical k-means clustering of 33 histologic variables was performed. Then, the impact of histological parameters on IMPN outcome was evaluated via an univariate analysis to identify variables for the final multivariate model. The data on immediate outcome and follow-up were collected from submitting neurologists using a purpose-designed questionnaire. Hierarchical k-means clustering sorted the tissues into 4 main categories: cluster 1 (44/129) represents a purely inflammatory IMPN picture, whereas cluster 2 (47/129) was accompanied by demyelinating features and cluster 3 (16/129) by Wallerian degeneration. Cluster 4 (22/129) reflects normal tissues from non-neuropathic control cats. Returned questionnaires provided detailed information on outcome in 63 animals. They were categorized into recovered and non-recovered. Thereby, fiber-invasive infiltrates by mononuclear cells and mild fiber loss in intramuscular nerve branches correlated with higher probabilities of recovery. Remyelination in semithin sections, on the other hand, is correlated with a less favorable outcome. Animals grouping in cluster 1 had a tendency to a higher probability of recovery compared to other clusters. In conclusion, diagnosis of feline IMPN from nerve and muscle biopsies allowed for the identification of histologic features that were positively or negatively correlated with outcome.

Clinical Course and Diagnostic Findings of Biopsy Controlled Presumed Immune-Mediated Polyneuropathy in 70 European Cats.

There is a paucity of information on the clinical course and outcome of young cats with polyneuropathy. The aim of the study was to describe the clinical features, diagnostic investigations, and outcome of a large cohort of cats with inflammatory polyneuropathy from several European countries. Seventy cats with inflammatory infiltrates in intramuscular nerves and/or peripheral nerve biopsies were retrospectively included. Information from medical records and follow up were acquired via questionnaires filled by veterinary neurologists who had submitted muscle and nerve biopsies (2011-2019). Median age at onset was 10 months (range: 4-120 months). The most common breed was British short hair (25.7%), followed by Domestic short hair (24.3%), Bengal cat (11.4%), Maine Coon (8.6%) and Persian cat (5.7%), and 14 other breeds. Male cats were predominantly affected (64.3%). Clinical signs were weakness (98.6%) and tetraparesis (75.7%) in association with decreased withdrawal reflexes (83.6%) and, less commonly, cranial nerve signs (17.1%), spinal pain/hyperesthesia (12.9%), and micturition/defecation problems (14.3%). Onset was sudden (30.1%) or insidious (69.1%), and an initial progressive phase was reported in 74.3%. Characteristic findings on electrodiagnostic examination were presence of generalized spontaneous electric muscle activity (89.6%), decreased motor nerve conduction velocity (52.3%), abnormal F-wave studies (72.4%), pattern of temporal dispersion (26.1%) and unremarkable sensory tests. The clinical course was mainly described as remittent (49.2%) or remittent-relapsing (34.9%), while stagnation, progressive course or waxing and waning were less frequently reported. Relapses were common and occurred in 35.7% of the cats' population. An overall favorable outcome was reported in 79.4% of patients. In conclusion, young age at the time of diagnosis and sudden onset of clinical signs were significantly associated with recovery (p < 0.05). Clinical and electrodiagnostic features and the remittent-relapsing clinical course resembles juvenile chronic inflammatory demyelinating polyneuropathy (CIDP), as seen in human (children/adolescents), in many aspects.

IMAGING DIAGNOSIS-CONCENTRIC PERIRADICULAR LIPOMA CAUSING LUMBAR NERVE ROOT COMPRESSION IN A DOG.

An 11-year-old, male neutered Jack Russell Terrier was presented with a nerve root signature of the right pelvic limb. Magnetic resonance imaging revealed a well demarcated, ovoid, extramedullary mass at the level of the L7 vertebral body. This showed, compared to normal spinal cord, hyperintense signal on T1- and T2-weighted images, which was suppressed on gradient echo short tau inversion recovery (GE-STIR) images. Additionally, the mass was characterized by a fat density on computed tomography images. Histopathology of the surgically excised mass was consistent with concentric periradicular lipoma, which has not been described in domestic animals yet.

Diagnostic utility of cerebrospinal fluid immunocytochemistry for diagnosis of feline infectious peritonitis manifesting in the central nervous system.

Objectives The aim of the study was to evaluate whether an ante-mortem diagnosis of central nervous system (CNS) feline infectious peritonitis (FIP) is possible via immunocytochemical staining (ICC) of feline coronavirus antigen (FCoV) within macrophages of cerebrospinal fluid (CSF). Methods Prospectively, CSF samples of 41 cats were investigated, including cats with histopathologically confirmed FIP and neurological signs (n = 10), cats with confirmed FIP without CNS involvement (n = 11), cats with neurological signs but another confirmed CNS disease (n = 17), and cats without neurological signs and a disease other than FIP (n = 3). ICC staining of CSF macrophages was performed in all cats. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of CSF ICC were calculated. Results Of 10 samples from cats with CNS FIP, eight had detectable CSF macrophages, seven of which were positive for FCoV. Ten of 11 samples from cats with confirmed FIP without neurological signs had macrophages in the CSF, with all 10 being ICC-positive. In cats with other CNS disorders, 11/17 had macrophages, two of which stained positively. In cats with diseases other than FIP and without neurological disorders, 2/3 revealed macrophages, with one cat showing positive ICC staining. Diagnosis of FIP via CSF ICC had a sensitivity of 85.0% and a specificity of 83.3%. PPV and NPV were 85.0% and 83.3%. Conclusions and relevance CSF ICC is a highly sensitive test for ante-mortem diagnosis of FIP manifesting in the CNS. However, CNS ICC specificity is too low to confirm FIP and the method should only be applied in conjunction with other features such as CSF cytology. CNS ICC could be helpful to discover pre-neurological stages of CNS FIP.

Outcome of ventriculoperitoneal shunt implantation for treatment of congenital internal hydrocephalus in dogs and cats: 36 cases (2001-2009).

OBJECTIVE: To examine outcome data for cats and dogs with congenital internal hydrocephalus following treatment via ventriculoperitoneal shunting to determine treatment-associated changes in neurologic signs, the nature and incidence of postoperative complications, and survival time. DESIGN: Retrospective multicenter case series. ANIMALS: 30 dogs and 6 cats with congenital internal hydrocephalus (confirmed via CT or MRI). PROCEDURES: Medical records for dogs and cats with internal hydrocephalus that underwent unilateral ventriculoperitoneal shunt implantation from 2001 through 2009 were evaluated. Data collected included the nature and incidence of postoperative complications, change in clinical signs following surgery, and survival time. To compare pre- and postoperative signs, 2-way frequency tables were analyzed with a 1-sided exact McNemar test. RESULTS: 8 of 36 (22%) animals developed postoperative complications, including shunt malfunction, shunt infection, and seizure events. Three dogs underwent shunt revision surgery. Thirteen (36%) animals died as a result of hydrocephalus-related complications or were euthanized. Following shunt implantation, clinical signs resolved in 7 dogs and 2 cats; overall, 26 (72%) animals had an improvement of clinical signs. After 18 months, 20 animals were alive, and the longest follow-up period was 9.5 years. Most deaths and complications occurred in the first 3 months after shunt placement. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that ventriculoperitoneal shunt implantation is a viable option for treatment of dogs or cats with congenital hydrocephalus. Because complications are most likely to develop in the first 3 months after surgery, repeated neurologic and imaging evaluations are warranted during this period.

Palliative intralesional interleukin-2 treatment in dogs with urinary bladder and urethral carcinomas.

AIM: The investigation of the influence of intralesional interleukin-2 (IL-2) on the clinical course and tumor progression in dogs suffering from urinary bladder and urethral carcinomas. MATERIALS AND METHODS: Medical records of 25 dogs diagnosed with advanced transitional cell carcinomas (TCC) were retrospectively reviewed. In 14 dogs, intralesional IL-2 treatment was performed by transabdominal ultrasound-guided injection. Seven dogs underwent cytoreductive surgery, followed by IL-2 injection into the tumor bed. All dogs received long-term non-steroidal anti-inflammatory drugs. RESULTS: Adverse effects associated with IL-2 treatment were not observed. At re-examination, 17 dogs showed marked clinical improvement and regression of tumor size. Four dogs were in complete remission. CONCLUSION: Intralesional IL-2 application is a safe and minimally-invasive palliative treatment option in dogs suffering from advanced transitional cell carcinoma when surgical cure is impossible. Prognosis depends on tumor localization and feasibility of concomitant cytoreductive surgery.

Effects of observer on the diagnostic accuracy of low-field MRI for detecting canine meniscal tears.

Low-field MRI (lfMRI) has become increasingly accepted as a method for diagnosing canine meniscal tears in clinical practice. However, observer effects on diagnostic accuracy have not been previously reported. In this study, 50 consecutive stifle joints with clinical and radiologic evidence of cranial cruciate ligament insufficiency were investigated by lfMRI and arthroscopy. Fifteen observers who had varying levels of experience and who were unaware of arthroscopic findings independently reviewed lfMRI studies and recorded whether lateral and medial meniscal tears were present. Diagnostic accuracy (sensitivity, specificity, positive (PPV) and negative predictive value (NPV)) was determined for each observer and median values were calculated for all observers, using arthroscopy as the reference standard. Interrater agreement was determined based on intraclass correlation coefficient (ICC) analysis. Observer level of experience was compared with diagnostic sensitivity and specificity using correlation analysis. Based on pooled data for all observers, median sensitivity, specificity, PPV, and NPV for lfMRI diagnosis of lateral meniscal tears were 0.00, 0.94, 0.05, and 0.94, respectively. Median sensitivity, specificity, PPV, and NPV for medial meniscal tears were 0.74, 0.89, 0.83, and 0.79, respectively. Interrater agreement for all menisci was fair (0.51). Menisci were less consistently scored as having no tears (ICC = 0.13) than those scored as having tears (ICC = 0.50). No significant correlations between observer experience and diagnostic sensitivity/specificity were identified. Findings indicated that the accuracy of lfMRI for diagnosing canine meniscal tears was poor to fair and observer-dependent. Future studies are needed to develop standardized and widely accepted lfMRI criteria for diagnosing meniscal tears.

A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy.

The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.

Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma.

OBJECTIVE: To compare response rates and remission and survival times in dogs with lymphoma treated with a continuous, multiagent, doxorubicin-based chemotherapeutic protocol or with a short-term single-agent protocol incorporating doxorubicin. DESIGN: Nonrandomized controlled clinical trial. ANIMALS: 114 dogs with lymphoma. PROCEDURES: Dogs were treated with a chemotherapeutic protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n=87) or doxorubicin alone (27). RESULTS: 63 of 86 (73%) dogs treated with the multiagent protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs treated with the single-agent protocol had a complete remission. Dogs with lymphoma classified as substage