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.

In vitro and numerical support for combinatorial irreversible electroporation and electrochemotherapy glioma treatment.

Irreversible electroporation (IRE) achieves targeted volume non-thermal focal ablation using a series of brief electric pulses to kill cells by disrupting membrane integrity. Electrochemotherapy (ECT) uses lower numbers of sub-lethal electric pulses to disrupt membranes for improved drug uptake. Malignant glioma (MG) brain tumors are difficult to treat due to diffuse peripheral margins into healthy neural tissue. Here, in vitro experimental data and numerical simulations investigate the feasibility for IRE-relevant pulse protocols with adjuvant ECT drugs to enhance MG treatment. Cytotoxicity curves were produced on two glioma cell lines in vitro at multiple pulse strengths and drug doses with Bleomycin or Carboplatin. Pulses alone increased cytotoxicity with higher pulse numbers and strengths, reaching >90% by 800 V/cm with 90 pulses. Chemotherapeutic addition increased cytotoxicity by >50% for 1 ng/mL concentrations of either drug relative to 80 pulses alone with J3T cells at electric fields ≥400 V/cm. In addition to necrosis, transmission electron microscopy visualizes apoptotic morphological changes and Hoescht 33342 staining shows apoptotic cell fractions varying with electric field and drug dose relative to controls. Numerically simulated treatment volumes in a canine brain show IRE combined with ECT expands therapeutic volume by 2.1-3.2 times compared to IRE alone.

Intramedullary spinal cord neoplasia in 53 dogs (1990-2010): distribution, clinicopathologic characteristics, and clinical behavior.

BACKGROUND: Intramedullary neoplasms of the canine spinal cord are infrequently reported. OBJECTIVE: To describe distribution, clinicopathologic characteristics, radiographic findings, and clinical features of canine intramedullary spinal tumors. METHODS: Retrospective series of histologically confirmed canine intramedullary spinal tumors. Contingency tables were generated for categorical variables (breed, sex, treatment, pain, chief complaint, localization, histology, imaging, and site). Associations were assessed by Fisher's exact, Wilcoxon rank sum test, t-test, and one-way ANOVA. RESULTS: Intramedullary spinal cord tumors comprised 16% (53/331) of all tumors of the spinal cord. Primary tumors were diagnosed in 66% (35/53) of cases, with neuroepithelial-origin tumors comprising 51% (18/35) of all primary neoplasms. Intraparenchymal metastases of transitional cell carcinoma and hemangiosarcoma accounted for 66% (6/18 each) of all secondary tumors. Primary tumors were more likely to affect younger dogs. Dogs with intramedullary metastases were most commonly presented for primary myelopathic signs (8/18, 44%). The majority of all tumors (52.8%) occurred in the T3-L3 spinal cord segments. All dogs with cervical neurolocalization had primary tumors. Dogs with metastatic lesions had a shorter duration of clinical signs before presentation, but there was no difference in survival time between dogs with primary as compared with secondary tumors. CONCLUSIONS: Intramedullary spinal cord tumors are uncommon. Primary intramedullary spinal cord tumors are more common than secondary intramedullary spinal cord tumors and tend to occur in the cervical spinal cord of younger dogs. Intramedullary metastases occur in older dogs, are rarely asymptomatic, and neurologic dysfunction is a common clinical presentation. Dogs with primary tumors may have a protracted clinical course compared with those with intramedullary metastases.

Diagnostic utility of abdominal ultrasonography in dogs with chronic diarrhea.

BACKGROUND: Chronic diarrhea is common in dogs and has many causes. Ultrasonographic descriptions of many gastrointestinal diseases have been published, but the diagnostic utility of ultrasonography in dogs with chronic diarrhea has not been investigated. HYPOTHESIS: Diagnostic utility of abdominal ultrasound will be highest in dogs with GI neoplasia and lowest in those with inflammatory disorders. ANIMALS: 87 pet dogs with chronic diarrhea. METHODS: Prospective study in which medical records were reviewed and contribution of abdominal ultrasound toward making diagnosis was scored. RESULTS: In 57/87 (66%) of dogs, the same diagnosis would have been reached without ultrasonography. In 13/87 (15%) of dogs, the ultrasound examination was vital or beneficial to making the diagnosis. Univariable analysis identified that increased diagnostic utility was associated with weight loss (P = .0086), palpation of an abdominal or rectal mass (P = .0031), diseases that commonly have mass lesions visible on ultrasound examination (P < .0001), and a final diagnosis of GI neoplasia. Multivariable regression indicated that utility of abdominal ultrasonography would be 30 times more likely to be high in dogs in which an abdominal or rectal mass was palpated (odds ratio 30.5, 95% CI 5.5-169.6) (P < .0001) versus dogs without a palpable mass. In 15/87 (17%) of dogs, additional benefits of ultrasonography to case management, independent of the contribution to the diagnosis of diarrhea, were identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Overall, the diagnostic utility of abdominal ultrasonography was low in dogs with chronic diarrhea. Identification of factors associated with high diagnostic utility is an indication to perform abdominal ultrasonography in dogs with chronic diarrhea.

Clinicopathologic features of intracranial central neurocytomas in 2 dogs.

BACKGROUND: In humans, central neurocytomas are rare and typically benign intracranial tumors found within the lateral ventricles, although extraventricular variants have been reported. Intracranial central neurocytomas have not been previously recognized in domestic animals. OBJECTIVES: To describe the clinicopathologic features of canine intracranial central neurocytomas. ANIMALS: Two dogs with spontaneous intracranial and intraventricular neoplasms. RESULTS: Both dogs experienced seizures, rapid neurological deterioration, and death from tumor-associated complications within 5 days of the onset of clinical signs, and had neoplastic masses within the lateral ventricles. A brain MRI was performed in 1 dog, which revealed a T1-isointense, heterogeneously T2 and FLAIR hyperintense, and markedly and heterogeneously contrast-enhancing mass lesions within both lateral ventricles. Histologically, the neoplasms resembled oligodendrogliomas. The diagnosis of central neurocytoma was supported by documenting expression of multiple neuronal markers, including neuron-specific enolase, synaptophysin, neural-cell adhesion molecule, and neuronal nuclear antigen within the tumors, and ultrastructural evidence of neuronal differentiation of neoplastic cells. CONCLUSIONS AND CLINICAL IMPORTANCE: Central neurocytoma should be a differential diagnosis for dogs with intraventricular brain masses. Morphologic differentiation of central neurocytoma from other intraventricular neoplasms, such as ependymoma or oligdendroglioma, can be difficult, and definitive diagnosis often requires immunohistochemical or ultrastructural confirmation of the neural origin of the neoplasm.

Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient.

Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain.

Diagnostic utility of abdominal ultrasonography in dogs with chronic vomiting.

BACKGROUND: Chronic vomiting is a common problem in dogs that has many causes. Ultrasonographic descriptions of many gastrointestinal (GI) diseases have been published. However, diagnostic utility of ultrasonography in dogs with chronic vomiting has not been investigated. HYPOTHESIS: Diagnostic utility of abdominal ultrasound will be highest in dogs with GI neoplasia and lowest in those with inflammatory disorders. ANIMALS: Eighty-nine pet dogs with chronic vomiting. METHODS: Medical records were reviewed and the contribution of abdominal ultrasound to the clinical diagnosis was subjectively scored. RESULTS: In 68.5% of dogs, the reviewers thought that the same diagnosis would have been reached without performing ultrasonography. In 22.5% of dogs, the ultrasound examination was considered to be vital or beneficial to the diagnosis. Univariable analysis identified that increased diagnostic utility was associated with increasing age, a greater number of vomiting episodes per week, presence of weight loss, a greater percentage of lost body weight, and a final diagnosis of GI lymphoma or gastric adenocarcinoma. However, multivariate analysis only identified increasing age and a final diagnosis of gastric adenocarcinoma or GI lymphoma to be associated with increased diagnostic utility. In 12.4% of dogs, additional benefits of ultrasonography to case management, excluding the contribution to the vomiting problem, were identified. CONCLUSIONS AND CLINICAL IMPORTANCE: The diagnostic utility of abdominal ultrasonography was high in 27% of dogs. The presence of factors that are associated with high diagnostic utility is an indication to perform abdominal ultrasonography in dogs with chronic vomiting.

Resistance of the peripheral nervous system to the effects of chronic canine hypothyroidism.

BACKGROUND: Hypothyroidism has been implicated in the development of multiple peripheral mono- and polyneuropathies in dogs. The objectives of this study were to evaluate the clinical and electrophysiologic effects of experimentally induced hypothyroidism on the peripheral nervous system of dogs. HYPOTHESIS: Chronic hypothyroidism will induce peripheral nerve sensorimotor dysfunction. ANIMALS: Eighteen purpose-bred, female dogs. METHODS: Prospective, longitudinal study: Hypothyroidism was induced by radioactive iodine administration in 9 dogs, and the remaining 9 served as untreated controls. Neurological examinations were performed monthly. Electrophysiologic testing consisting of electromyography (EMG); motor nerve conduction studies of the sciatic-tibial, radial, ulnar, and recurrent laryngeal nerves; sciatic-tibial and ulnar F-wave studies; sensory nerve conduction studies of the tibial, ulnar, and radial nerves; and evaluation of blink reflex and facial responses were performed before and 6, 12, and 18 months after induction of hypothyroidism and compared with controls. RESULTS: Clinical evidence of peripheral nervous dysfunction did not occur in any dog. At 6 month and subsequent evaluations, all hypothyroid dogs had EMG and histologic evidence of hypothyroid myopathy. Hypothyroid dogs had significant (Por=.1) or sensory nerve conduction velocity (P>or=.24) or nerve roots (P>or=.16) throughout the study period, with values remaining within reference ranges in all dogs. CONCLUSION: Chronic hypothyroidism induced by thyroid irradiation does not result in clinical or electrophysiologic evidence of peripheral neuropathy, but does cause subclinical myopathy.

Cyclooxygenase-2 (COX-2) expression in canine intracranial meningiomas.

Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotherapeutic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis.

Safety and efficacy of oral low-volume sodium phosphate bowel preparation for colonoscopy in dogs.

BACKGROUND: Sodium phosphate (NaP) is a low-volume, hyperosmolar laxative that is an effective bowel-cleansing agent in humans. HYPOTHESIS: NaP will be as safe and efficacious as polyethylene glycol (PEG) bowel preparation for colonoscopy in dogs. ANIMALS: Eight purpose-bred healthy dogs. METHODS: In phase I, standard (NaP and enemas; NaP(1)) and control preparations (PEG and enemas) were compared in a crossover design to determine the safety and efficacy of NaP. Serial clinical and serum analytical evaluations were used to determine the safety of NaP. In phase II, the efficacy of the standard NaP preparation was compared with 3 other NaP variations, which excluded enema or included bisacodyl, with or without enemas in a crossover design. An observer blinded to the bowel preparation assigned a score of 1-4 (1=clean colon; 4=unacceptable colon cleansing preventing adequate endoscopic evaluation) to each of 5 regions of the colon. RESULTS: The mean total colon cleansing score (TCS), defined as the sum of scores from each region, of the control (9.4) was less than NaP(1) (13.6) (P < 0.05). There were no significant differences in regional or TCS for the remaining 4 NaP protocols. NaP(1) resulted in moderate, but clinically occult, hyperphosphatemia and hypocalcemia, which resolved within 24 hours. CONCLUSIONS AND CLINICAL IMPORTANCE: Despite the safety and ease of administration of the NaP preparations, the NaP bowel-cleansing preparations used in this study cannot be recommended for use because of the inadequate quality of bowel preparation compared with the protocol using PEG-containing fluids.

B-cell lymphoma in the peripheral nerves of a cat.

A B-cell, Burkitt-type lymphoma, diffusely affecting the peripheral nerves and intramuscular nerve branches was diagnosed in a 4-year-old domestic shorthair cat with a chronic progressive history of flaccid tetraparesis and generalized muscle atrophy. There was no evidence of cranial nerve, central nervous system, radicular, bone marrow, splenic, or lymph node involvement. The cat tested negative for feline retroviruses and a wide variety of herpes viruses, including Epstein-Barr virus. The clinical manifestation of this case was similar to the chronic polyneuropathic variant of human diffuse neurolymphomatosis; a condition most commonly caused by an axonopathy resulting from infiltration of peripheral nerves with non-Hodgkin's lymphoma.

Retroperitoneal hemangiosarcoma causing chronic hindlimb lameness in a dog.

The clinical, radiographic, ultrasonographic, computed tomographic, surgical and histopathological findings in a Boxer dog with retroperitoneal hemangiosarcoma are described in this study. A seven-year-old, male, castrated Boxer dog was referred for evaluation of chronic hindlimb lameness. The physical examination revealed muscle atrophy and sciatic nerve deficits. Radiography and ultrasonography revealed a caudodorsal abdominal mass. Computed tomography revealed that the mass involved the left margin of the L7 vertebra, lumbosacral canal, and lumbosacral plexus. At surgery, a large retroperitoneal haematoma was removed. Histopathology of amorphous tissue found near the haematoma was consistent with haemangiosarcoma. The owner declined any further treatment. Ten weeks after discharge, the dog was euthanatized due to collapse and haemo-abdomen.

Endostatin and vascular endothelial growth factor concentrations in healthy dogs, dogs with selected neoplasia, and dogs with nonneoplastic diseases.

To evaluate the relationship between endostatin and vascular endothelial growth factor (VEGF) in cancers of dogs, circulating concentrations of these 2 tumor-associated markers were measured prospectively in healthy dogs (n = 44), dogs with tumors (n = 54), and dogs with nonneoplastic diseases (n = 42 for endostatin; n = 16 for VEGF). A canine-directed enzyme-linked immunosorbent assay kit was used for determination of endostatin, and a human-directed kit was validated for detection of canine VEGF. Concentrations of endostatin for all dogs were 28-408 ng/mL. Increasing serum endostatin concentration was associated with increasing age (P = .0396). Concentrations of endostatin were not different among groups of dogs (P = .1989) when adjusted for age. Mean endostatin concentrations for all dogs were higher in dogs (P = .0124) with detectable VEGF concentrations. Endostatin concentrations, when corrected for age, were related to decreasing PCV (P = .032) but not white blood cell count (P = .225) or platelet count (P = .1990). Measurable VEGF (> or = 2.5 pg/mL) was detected in 3 (7.0%) of 43 healthy dogs. Dogs with tumors had detectable VEGF in 24 (44%) of 54 dogs, with concentrations ranging from 2.5-274 pg/mL; only 1 dog with a nonneoplastic disease process had detectable VEGF. VEGF concentrations for all dogs after correcting for age, endostatin, and disease categories were associated with increased white blood cell count (P = .0032) and platelet counts (P = .0064) and decreased PCV (P = .0017). Linkage between increased endostatin and VEGF concentrations suggests that similar factors may influence concentrations of these markers. Further evaluation of endostatin and VEGF associations in dogs with tumors may provide information on the extent and progression of the disease.

Surgical cytoreduction for the treatment of non-lymphoid vertebral and spinal cord neoplasms in cats: retrospective evaluation of 26 cases (1990-2005).

Medical records of 26 cats with non-lymphoid vertebral and spinal cord neoplasms treated surgically were reviewed to determine outcome and prognostic factors for survival. Of the factors examined, only tumour phenotype was significantly associated with survival. Osteosarcoma (3/26 cats) and meningioma (16/26 cats) were the most common malignant and benign tumours, respectively. The median survival time for cats with malignant neoplasms was 110.5 days, compared with 518 days for cats with benign tumours. Cytoreductive surgery resulted in clinical improvement in 25/26 cats, but local treatment failure occurred in 10/26 cats. Overall, 19/26 cats died of confirmed (12/19) or suspected (7/19) tumour-related causes, including all eight cats with malignant neoplasms. Results suggest that contemporary neurosurgical techniques commonly result in incomplete excision of feline non-lymphoid vertebral and spinal cord tumours but are efficacious at palliation of clinical signs of spinal cord dysfunction.

Hyperadrenocorticism and hyperprogesteronemia in a cat with an adrenocortical adenocarcinoma.

A seven-year-old, neutered male domestic shorthair cat was evaluated for poorly regulated diabetes mellitus and increased skin fragility. Imaging studies revealed a right adrenal gland tumor, but cortisol testing did not support a diagnosis of hyperadrenocorticism. Serum concentrations of progesterone and testosterone were increased compared with a group of normal cats, and the clinical signs were attributed to hyperprogesteronemia. At necropsy, a diagnosis of adrenocortical adenocarcinoma was confirmed, and immunohistochemical staining confirmed the presence of progesterone within the tumor. Clinical signs of hyperadrenocorticism in cats may occur due to increased serum concentrations of hormones other than cortisol.