Diagnosis and management of dogs with degenerative myelopathy: A survey of neurologists and rehabilitation professionals.

BACKGROUND: Antemortem diagnosis of degenerative myelopathy (DM) in dogs is presumptive and there are no accepted guidelines for the management of this condition. HYPOTHESIS/OBJECTIVES: Describe current practices of neurology clinicians and physical rehabilitation professionals in the diagnosis and management of DM. ANIMALS: None. METHODS: Online surveys examining diagnosis and management of DM were constructed and distributed via neurology and rehabilitation listservs. RESULTS: One hundred ninety neurology and 79 rehabilitation professionals from 20 countries participated. Most neurology (142/189) and rehabilitation (23/39) respondents required genetic testing for the superoxide dismutase 1 (SOD1) mutation and 82/189 neurologists also required spinal magnetic resonance imaging (MRI) for presumptive DM diagnosis. Most neurology respondents recommended exercise (187/190) and physical rehabilitation (184/190). Over 50% (102/190) of neurology respondents perform rechecks on dogs diagnosed with DM. Rehabilitation respondents reported preservation or improvement of strength (78/79) and coordination (77/79) as therapeutic goals. At-home exercises (75/79), underwater treadmill (64/79), gait training (55/79), and strength building exercises (65/79) were used to maintain strength (58/79), coordination (56/79), muscle mass (56/79), and improve overall wellbeing (54/79). Neurology respondents reported that owners elect euthanasia when dogs become nonambulatory paraparetic whereas rehabilitation respondents report euthanasia when paraplegia and incontinence develop. CONCLUSION AND CLINICAL IMPORTANCE: The majority of dogs diagnosed with DM have not undergone advanced imaging, the combination of history, neurological findings, and genetic testing is heavily relied upon. Whereas the diagnosis of DM is frequently made by veterinary neurologists, continued care is often performed by rehabilitation professionals or primary veterinarians.

Computed tomographic features of an axillary liposarcoma with hepatic metastasis.

A geriatric dog presented for lethargy, dyspnea, and urinary incontinence. Thoracic radiographs demonstrated a large, mixed fat, and soft tissue opaque axillary mass and a pulmonary mass. Computed tomography (CT) further characterized these masses and revealed innumerable fat-attenuating hepatic masses and cranial mediastinal lymphadenopathy. Histopathology of the axillary and hepatic masses confirmed grade two primary axillary liposarcoma with hepatic metastasis. Cytology of the pulmonary mass was consistent with a pulmonary carcinoma. This is the first published CT description of fat-attenuating metastatic hepatic liposarcoma in a dog.

Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases.

Mouse models of human disease remain the bread and butter of modern biology and therapeutic discovery. Nonetheless, more often than not mouse models do not reproduce the pathophysiology of the human conditions they are designed to mimic. Naturally occurring large animal models have predominantly been found in companion animals or livestock because of their emotional or economic value to modern society and, unlike mice, often recapitulate the human disease state. In particular, numerous models have been discovered in dogs and have a fundamental role in bridging proof of concept studies in mice to human clinical trials. The present article is a review that highlights current canine models of human diseases, including Alzheimer's disease, degenerative myelopathy, neuronal ceroid lipofuscinosis, globoid cell leukodystrophy, Duchenne muscular dystrophy, mucopolysaccharidosis, and fucosidosis. The goal of the review is to discuss canine and human neurodegenerative pathophysiologic similarities, introduce the animal models, and shed light on the ability of canine models to facilitate current and future treatment trials.

Prolonged survival after craniectomy with skull reconstruction and adjuvant definitive radiation therapy in three dogs with multilobular osteochondrosarcoma.

Multilobular osteochondrosarcoma is an uncommon canine tumor but presents a treatment challenge when arising on the skull. This retrospective case series study aimed to describe outcome of a multimodality treatment approach involving aggressive surgical resection and adjuvant definitive radiation therapy in a group of dogs with multilobular osteochondrosarcoma of the calvarium. Clinical, imaging, treatment, and outcome data were collected from retrospective review of medical records. Three dogs met inclusion criteria. The presenting clinical complaint was the presence of a mass effect of the skull in all three dogs and concurrent neurologic abnormalities in one dog. Advanced imaging revealed aggressive lytic and proliferative tumors arising from the calvarium in all three dogs. All dogs were treated surgically with a modified craniectomy, repaired with a titanium mesh-polymethyl methacrylate bone cement implant or a low prolife titanium mesh plate and followed by adjuvant definitive radiation therapy with 2.5 Gy per fraction for 22 daily fractions. There were no major immediate surgical complications and radiation was well tolerated overall. Neurologic improvement was seen in the patient that presented with neurologic disease. Survival times from surgery were 387, 422, and 730 days and from the time of radiation were 358, 397, and 677 days. Findings in this sample of three dogs supported the use of aggressive therapy with a combination of surgical craniectomy and cranioplasty utilizing a titanium mesh implant and high dose definitive radiation therapy for local control and prolonged survival times in dogs with multilobular osteochondrosarcoma of the skull.

Vaccination for invasive canine meningioma induces in situ production of antibodies capable of antibody-dependent cell-mediated cytotoxicity.

Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. IFN-γ-elaborating T cells were detected in the peripheral blood of 2 cases, but vaccine-induced tumor-reactive antibody responses developed in all dogs. Antibody responses were polyclonal, recognizing both intracellular and cell surface antigens, and HSP60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, showing common antigens across breed and species. Histologic analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in posttreatment compared with pretreatment samples. Tumor-reactive antibodies were capable of inducing antibody-dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data show the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development toward human trials.

Successful management of an intracranial phaeohyphomycotic fungal granuloma in a dog.

CASE DESCRIPTION: A 12-month-old castrated male Boxer was examined because of signs of acute, progressive intracranial disease. CLINICAL FINDINGS: Cytologic and histologic findings were consistent with an intracranial fungal granuloma in the right cerebral hemisphere. Fungal culture yielded a Cladophialophora sp. TREATMENT AND OUTCOME: The granuloma was surgically debulked to remove infected brain tissue and the avascular purulent core. Postoperatively, the patient was treated with fluconazole (2.3 mg/kg [1 mg/lb], PO, q 12 h) for 4 months, followed by voriconazole (3.4 mg/kg [1.5 mg/lb], PO, q 12 h) for a further 10 months. The outcome was considered excellent on the basis of resolution of neurologic signs and a lack of evidence of recurrence of the granuloma during magnetic resonance imaging and CSF analysis 8 months after surgery. Magnetic resonance imaging and CSF analysis 9 weeks after administration of antifungal medications was discontinued (16 months after surgery) confirmed resolution. CLINICAL RELEVANCE: Intracranial phaeohyphomycosis in small animals is rare and is most commonly associated with Cladophialophora infection. Phaeohyphomycosis frequently causes a focal granuloma, whereas other fungal infections typically cause diffuse meningoencephalitis. In all previous reports of phaeohyphomycosis of the CNS in dogs, treatment has been limited to medical management with conventional antifungal drugs and had failed to prevent death. The present report suggested that combined management of granulomas with surgery and newer triazole medications such as voriconazole may represent a novel strategy that improves the prognosis for this disease.

Magnetic resonance imaging apparent diffusion coefficients for histologically confirmed intracranial lesions in dogs.

Diffusion-weighted imaging is an advanced magnetic resonance imaging technique that is well established in the diagnosis of nonhemorrhagic infarction in people. However, recent investigations into intracranial neoplastic and inflammatory disease in people have identified variable and overlapping results. In this retrospective study of 37 dogs with histologically confirmed intracranial disease, we investigated whether histogram analysis of quantitative apparent diffusion coefficients (ADC) can differentiate specific disease processes. Disease categories included: meningiomas, glial cell tumors, choroid plexus tumors, pituitary tumors, inflammatory brain diseases, acute nonhemorrhagic infarcts, chronic nonhemorrhagic infarcts, and hemorrhagic infarcts. A wide range of ADC value distributions were identified within the disease groups, and there were overlapping ADC values between most groups. Low ADC values indicating restricted diffusion of water were identified in acute nonhemorrhagic infarcts as expected, but were also seen in meningiomas, glial cell tumors, and granulomatous meningoencephalitis. Based on this preliminary data it is unlikely that singular quantitative ADC values can be used to determine the histological type of canine intracranial disease.

Surgical management of a canine intracranial abscess due to a bite wound.

OBJECTIVE: To describe the successful surgical management of a brain abscess in a dog secondary to bite wound. CASE SUMMARY: A 10-year-old neutered female Welsh Corgi/Chihuahua, weighing 5.3 kg, was presented for evaluation of seizures, ataxia, and falling to the left 8 days after a presumptive fight with another dog. On examination at presentation, the dog was alert, responsive, and ambulatory with tetra-ataxia, falling to the left, left-sided postural deficits, and absent left menace response. Within 24 hours, the dog progressed to nonambulatory tetraparesis with minimal motor, absent postural reactions of all limbs, left nasal hypalgesia, reduced gag reflex, and depressed mentation. Computed tomographic images of the brain were suggestive of a bite wound fracture of the right parietal bone with secondary meningoencephalitis, right parietal lobe abscessation, and white matter edema adjacent to the bone fracture. A modified right rostrotentorial craniectomy was performed, the abscess was identified, contents of the abscess were removed, and the surgical site was flushed extensively before closing. Corynebacterium spp. was cultured from within the abscess. Within hours of surgery, the dog was quiet but alert, responsive, and sitting up in her cage. In addition to surgical intervention, intensive care, broad-spectrum IV antimicrobials, and supportive therapy led to significant neurologic improvement with only occasional seizures and mild postural reaction deficits of the left hindlimb remaining. NEW OR UNIQUE INFORMATION PROVIDED: Abscess formation within the CNS is uncommon in dogs and cats and is associated with a high mortality rate. In veterinary medicine the management of brain abscesses is controversial with limited information available regarding treatment. This is the first case report that demonstrates surgical intervention in combination with antimicrobial therapy can be used successfully in the treatment of a canine brain abscess.

Clinical use of an herbal-derived compound (Huperzine A) to treat putative complex partial seizures in a dog.

A Bernese mountain dog was diagnosed with complex partial seizures that were supported by electroencephalographic findings. Clinical signs of the problem included "star gazing," fly snapping, licking, vacuous chewing, and ongoing anxiety. Treatment with Huperzine A, a compound isolated from Chinese club moss with NMDA receptor blocking activity, anticholinesterase activity, and anticonvulsant properties, produced useful suppression of the abnormal behavior for more than months. A relapse occurred when the dog was treated with tramadol for joint pain and the improvement that had been made was not recaptured with Huperzine A. At this stage, phenobarbital therapy was instituted and the dog improved greatly. The role of Huperzine A in controlling seizures is discussed.

Multiple meningiomas in three dogs.

Three dogs with seizures were diagnosed with multiple intracranial meningiomas. Two of the three dogs were golden retrievers, and ages ranged from 9 to 11 years. Treatment consisted of surgery and radiation (n=2) or chemotherapy (n=1). In all three cases, the masses were two distinct tumors as determined by imaging, surgery, or necropsy. In two dogs, the meningiomas had the same histological pattern, while in one dog the histological subtypes were different.

Magnetic resonance imaging features of cervical spinal cord meningiomas.

The records of four dogs with cervical spinal cord meningiomas were retrospectively reviewed. Signalment, history, laboratory findings, neurological examination, and histopathological findings were evaluated. Magnetic resonance imaging (MRI) was performed using a 1.0-T superconducting magnet and T2-weighted (W) and noncontrast and postcontrast T1-W spin echo pulse sequences. Meningiomas were located at the level of the second, third, and fifth cervical vertebrae and the C2-3 intervertebral space. All meningiomas appeared as focal masses that were hyperintense to the spinal cord on T2-W images and iso- to hypointense on the T1-W images. They could be identified as intradural and extramedullary in origin based on a broad-based dural margin seen on at least one of the imaging planes and a gradual expansion of the subarachnoid space cranial and caudal to the mass, best noted on the transverse and dorsal plane images. On dorsal plane T2-W images in three dogs, expansion of the subarachnoid space adjacent to the mass appeared similar to the myelographic "golf tee" sign. All meningiomas exhibited moderate, well-defined contrast enhancement with dural tails seen in three of the four dogs. One dog had extension into the intervertebral foramen along the nerve and ipsilateral atrophy of the muscles of the neck. By differentiating the meningiomas from intramedullary tumors and by clearly depicting the extent of the masses, MRI provided valuable information about treatment options and prognosis.