Challenges in the management of tumor-induced osteomalacia (TIO).

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare acquired paraneoplastic disease, which is challenging to diagnose and treat. TIO is characterized by hypophosphatemia resulting from excess levels of tumor-secreted fibroblast growth factor 23 (FGF23), one of the key physiological regulators of phosphate metabolism. Elevated FGF23 results in renal phosphate wasting and compromised vitamin D activation, ultimately resulting in osteomalacia. Patients typically present with progressive and non-specific symptoms, including bone pain, multiple pathological fractures, and progressive muscle weakness. Diagnosis is often delayed or missed due to the non-specific nature of complaints and lack of disease awareness. Additionally, the disease-causing tumour is often difficult to detect and localize because they are often small, lack localizing symptoms and signs, and dwell in widely variable anatomical locations. Measuring serum/urine phosphate should be an inherent diagnostic component when assessing otherwise unexplained osteomalacia, fractures and weakness. In cases of hypophosphatemia with inappropriate (sustained) phosphaturia and inappropriately normal or frankly low 1,25-dihydroxy vitamin D, differentiation of the potential causes of renal phosphate wasting should include measurement of FGF23, and TIO should be considered. While patients experience severe disability without treatment, complete excision of the tumour is typically curative and results in a dramatic reversal of symptoms. Two additional key current unmet needs in optimizing TIO management are: (1 and 2) the considerable delay in diagnosis and consequent delay between the onset of symptoms and surgical resection; and (2) alternative management. These may be addressed by raising awareness of TIO, and taking into consideration the accessibility and variability of different healthcare infrastructures. By recognizing the challenges associated with the diagnosis and treatment of TIO and by applying a stepwise approach with clear clinical practice guidelines, patient care and outcomes will be improved in the future.

Dynamics of bovine spleen cell populations during the acute response to Babesia bovis infection: an immunohistological study.

The spleen is a critical organ in defence against haemoparasitic diseases like babesiosis. Many in vitro and ex vivo studies have identified splenic cells working in concert to activate mechanisms required for successful resolution of infection. The techniques used in those studies, however, remove cells from the anatomical context in which cell interaction and trafficking take place. In this study, an immunohistological approach was used to monitor the splenic distribution of defined cells during the acute response of naïve calves to Babesia bovis infection. Splenomegaly was characterized by disproportionate hyperplasia of large versus small leucocytes and altered distribution of several cell types thought to be important in mounting an effective immune response. In particular, the results suggest that the initial crosstalk between NK cells and immature dendritic cells occurs within the marginal zone and that immature dendritic cells are first redirected to encounter pathogens as they enter the spleen and then mature as they process antigen and migrate to T-cell-rich areas. The results of this study are remarkably similar to those observed in a mouse model of malarial infection, suggesting these dynamic events may be central to the acute response of naïve animals to haemoparasitic infection.

Linear-accelerator-based modified radiosurgical treatment of pituitary tumors in cats: 11 cases (1997-2008).

OBJECTIVE: Determine the efficacy and safety of a linear-accelerator-based single fraction radiosurgical approach to the treatment of pituitary tumors in cats. DESIGN: Retrospective study. ANIMALS: Eleven client-owned cats referred for treatment of pituitary tumors causing neurological signs, or poorly controlled diabetes mellitus (DM) secondary either to acromegaly or pituitary-dependent hyperadrenocortism. PROCEDURES: Cats underwent magnetic resonance imaging (MRI) of the brain to manually plan radiation therapy. After MRI, modified radiosurgery was performed by delivering a single large dose (15 or 20 Gy) of radiation while arcing a linear-accelerator-generated radiation beam around the cat's head with the pituitary mass at the center of the beam. Eight cats were treated once, 2 cats were treated twice, and 1 cat received 3 treatments. Treated cats were evaluated for improvement in endocrine function or resolution of neurological disease by review of medical records or contact with referring veterinarians and owners. RESULTS: Improvement in clinical signs occurred in 7/11 (63.6%) of treated cats. Five of 9 cats with poorly regulated DM had improved insulin responses, and 2/2 cats with neurological signs had clinical improvement. There were no confirmed acute or late adverse radiation effects. The overall median survival was 25 months (range, 1-60), and 3 cats were still alive. CONCLUSIONS AND CLINICAL IMPORTANCE: Single fraction modified radiosurgery is a safe and effective approach to the treatment of pituitary tumors in cats.

Pneumonia after intracranial surgery in dogs.

OBJECTIVE: To determine factors associated with the occurrence of pneumonia after intracranial surgery in dogs. STUDY DESIGN: Retrospective cohort study. Animals-Forty-nine client-owned dogs. METHODS: The medical records of 49 dogs with space-occupying intracranial disease that underwent craniotomy were reviewed. Development of pneumonia after surgery was considered highly likely in 12 dogs (affected dogs) based on clinical signs, including acute dyspnea or coughing in association with typical radiographic findings or abnormal transtracheal wash results. Pneumonia was confirmed in 6 dogs based on necropsy findings. Affected dogs were compared with 37 dogs that did not develop pneumonia (unaffected dogs) subsequent to intracranial surgery. Based on the medical records of affected dogs, determinations were made regarding time between development of pneumonia and surgery, surgical procedure, intracranial lesion type, and intracranial lesion location. Risk factors examined for both affected and unaffected dogs included level of consciousness, body position during the postoperative recovery period, duration of anesthesia, occurrence of vomiting or regurgitation, presence of seizures, cranial nerve deficiencies, and the presence of megaesophagus before and after surgery. We also compared the feeding protocol after surgery for each group. RESULTS: Pneumonia typically occurred within the first week after surgery (median, 6.5 days); however, this was variable (range, 1-96 days). Of the factors that were present within 24 hours before the clinical signs of pneumonia, vomiting or regurgitation and megaesophagus were found to be significant risk factors. Dogs that vomited or regurgitated were 2.71 times more likely to develop pneumonia than dogs that did not. Vomiting or regurgitation occurred in 63% of the dogs that developed pneumonia in this cohort. Dogs with megaesophagus were 9.25 times more likely to develop pneumonia than dogs without megaesophagus. Seven dogs with pneumonia died. Five of these 7 dogs appeared to have died as a direct sequel to pneumonia. CONCLUSION: Dogs undergoing craniectomies for space-occupying intracranial disease may be at higher risk for development of pneumonia due to several factors, including vomiting, regurgitation, and megaesophagus.

Magnetic resonance imaging features of equine nigropallidal encephalomalacia.

Magnetic resonance imaging (MR) was used to make a diagnosis of equine nigropallidal encephalomalacia in a horse. Equine nigropallidal encephalomalacia is a neurodegenerative disease that has many characteristics with Parkinson-like diseases in humans. Historically, horses were euthanized based on clinical signs and exposure to the toxic weed, yellow star thistle (Centaurea solstitialis). Previously, the disease has only been confirmed on necropsy. MR imaging can provide accurate and sensitive visualization of typical lesions seen in the brain of horses affected with equine nigropallidal encephalomalacia. Lesions were seen on T1-weighted, T2-weighted and proton density images. There was no contrast enhancement following Gd-DTPA administration. Lesions seen on MR were confirmed at necropsy. Using MR to confirm a diagnosis of equine nigropallidal encephalomalacia will prevent unnecessary suffering of horses and expense to owners that would otherwise incur, while further diagnostics are performed.

Radiographic diagnosis: cartilaginous exostoses in a dog.

A 6 month-old dog was examined for progressive paraparesis. On physical examination bony malformations were palpated over the cranial lumbar vertebral bodies and on the left metatarsal bone. Neuroanatomic lesion localization for the paraparesis was a T3-L3 spinal cord lesion. Radiographs confirmed bony masses at L1-L2 and on the left 3rd metatarsal bone. Magnetic resonance imaging was performed from T3-L3. Severe spinal cord compression was identified at L1-L2. Surgical decompression and biopsy confirmed the mass to be cartilaginous exostoses. This paper is an example of cartilaginous exostoses imaged with MR.

Mensuration of the normal pituitary gland from magnetic resonance images in 96 dogs.

The pituitary gland was measured from transverse magnetic resonance T1-weighted images after Gadolinium administration in 96 dogs weighing from 13 to 45 kg. The measurements were done by hand with calipers. The mean (+/- standard deviation) pituitary gland height was 5.1 mm (+/-0.9 mm). The mean width was 6.4 mm (+/- 1.1 mm). The correlation coefficient between pituitary and brain measurements, between pituitary measurement and body weight, and brain measurements and body weight was 0.0 to 0.3. A hyperintense region was present on T1-weighted images in the center of the pituitary gland in 64% of the dogs. At necropsy the pituitary glands were grossly and histologically normal. No pituitary gland measurements were performed at necropsy.

Tolerance of the normal canine brain to epithermal neutron irradiation in the presence of p-boronophenylalanine.

Twelve normal dogs underwent brain irradiation in a mixed-radiation, mainly epithermal neutron field at the Brookhaven Medical Research Reactor following intravenous infusion of 950 mg of 10B-enriched BPA/kg as its fructose complex. The 5 x 10 cm irradiation aperture was centered over the left hemisphere. For a subgroup of dogs reported previously, we now present more detailed analyses including dose-volume relationships, longer follow-ups, MRIs, and histopathological observations. Peak doses (delivered to 1 cm3 of brain at the depth of maximum thermal neutron flux) ranged from 7.6 Gy (photon-equivalent dose: 11.8 Gy-Eq) to 11.6 Gy (17.5 Gy-Eq). The average dose to the brain ranged from 3.0 Gy (4.5 Gy-Eq) to 8.1 Gy (11.9 Gy-Eq) and to the left hemisphere, 6.6 Gy (10.1 Gy-Eq) to 10.0 Gy (15.0 Gy-Eq). Maximum tolerated 'threshold' doses were 6.7 Gy (9.8 Gy-Eq) to the whole brain and 8.2 Gy (12.3 Gy-Eq) to one hemisphere. The threshold peak brain dose was 9.5 Gy (14.3 Gy-Eq). At doses below threshold, some dogs developed subclinical MRI changes. Above threshold, all dogs developed dose-dependent MRI changes, neurological deficits, and focal brain necrosis.

Cerebellar cystic meningioma in a dog.

A 21-kg, seven-year-old, male, mixed-breed Labrador retriever was admitted for incoordination and a head tilt of approximately three months' duration. Ataxia was noted of the trunk and limbs, and there was a head tilt to the right side. Conscious proprioceptive deficits were present in the left thoracic and pelvic limbs (i.e., hemiparesis). These abnormalities were consistent with paradoxical vestibular syndrome and a lesion involving the caudal cerebellar peduncle. A mass lesion consisting primarily of fluid was present on magnetic resonance imaging and at craniectomy. Histopathological diagnosis was a cystic meningioma. Based upon previous reports and experience, the location of this tumor was unusual.

Comparison of the accuracy of positioning devices for radiation therapy of canine and feline head tumors.

The purpose of this retrospective study was to evaluate the repositioning accuracy of different positioning devices in order to determine their applicability for potential use in conformal radiation therapy for animals. Forty-four animals with spontaneous tumors of the head were included. The animals were divided into 3 groups determined according to the positioning device used. Group 1 animals were positioned using a thermoplastic mask. Group 2 animals were positioned using a head holder. Group 3 animals were positioned using the head holder and an inflatable pillow. The time of presentation determined which position device was used. Port films of the 44 patients were reviewed retrospectively, and the repositioning precision was recorded by measurements in three orthogonal planes. Groups 2 and 3 had significantly better repositioning accuracy (P < or = 0.05) compared to Group 1. The position variation was not significantly different (P < or = 0.05) between Groups 2 and 3 in the lateral and longitudinal direction. Group 3 had a median reposition variation of 0.5 to 1.0 mm, with a standard deviation of 1.0 to 1.5 mm.

Magnetic resonance imaging features of tumors of the spine and spinal cord in dogs.

Twenty-one dogs with confirmed tumors of the spinal cord or paraspinal tissues were imaged with magnetic resonance (MR) imaging. Anatomical location, location in relation to the dura and the medulla (spinal cord), and bone infiltration were assessed on the MR images and compared to findings at surgery or necropsy. Localization of tumors in the intradural-extramedullary compartment was not always possible. Bone infiltration was correctly assessed in all but one dog, and the anatomical locations involved were accurately determined in all dogs. Sagittal T2-weighted images were helpful to determine the anatomical location. Transverse T1-weighted images pre and post Gd-DTPA administration were helpful for additional localization and definition of tumor extension.

Use of magnetic resonance angiography for diagnosis of portosystemic shunts in dogs.

A prospective study was conducted to determine the sensitivity and specificity of diagnosis of portosystemic shunts (PSS) and the accuracy of anatomically locating single congenital PSS in dogs using magnetic resonance angiography (MRA). MRA was performed on 10 normal dogs and 23 dogs with PSS. Sensitivity and specificity of MRA to diagnose any shunt among all dogs were 80% and 100%, respectively. Among dogs identified with PSS, sensitivity and specificity of MRA for diagnosis of multiple extrahepatic shunts were 63% and 97%, respectively, and for diagnosis of single congenital shunts were 79% and 100%, respectively. Using MRA, radiologists correctly identified shunts as extrahepatic or intrahepatic in 83% of patients and correctly identified the origin and insertion of the shunts in 57% and 97% of patients, respectively. Use of MRA is specific for diagnosis of PSS and is a sensitive indicator of anatomic location of single congenital portosystemic shunts.

Clinical signs associated with brain tumors in dogs: 97 cases (1992-1997).

OBJECTIVE: To determine the prevalence of various clinical signs in dogs with brain tumors. DESIGN: Retrospective study. ANIMALS: 97 dogs with brain tumors. PROCEDURE: Medical records were reviewed for signalment, tumor type and location, and clinical signs. RESULTS: 33 breeds were represented; Golden Retrievers were most commonly affected. Most dogs were older (median age, 9 years); 95% of dogs were > or = 5 years old. Seventy-six percent of dogs had tumors in the supratentorial region. Seizures were the most common clinical sign at initial examination, with lower prevalence for circling, ataxia, and head tilt. Meningioma was the most common tumor. CONCLUSIONS AND CLINICAL RELEVANCE: Brain tumors develop most often in dogs > or = 5 years old and are uncommon in dogs < 5 years old. Seizures are a common clinical sign, and a brain tumor should be considered in dogs that have their first seizure after they are 4 years old.

Intracranial neoplasia.

A diagnosis of intracranial neoplasia in companion animals may be made by computed tomography (CT) or magnetic resonance imaging (MRI). MRI is the better method for detecting and characterizing intracranial tumors because of its superior depiction of soft tissues and relative lack of degrading artifacts, intracranial tumors may be characterized by distinct features; a systematic evaluation of these features on CT or MRI images may help to identify specific tumor types. In this article, guidelines for formulating differential diagnoses based on these imaging criteria will be discussed. Technical recommendations and protocols for CT and MR imaging will also be provided.

Seizures as a complication of brain tumors in dogs.

Seizures are a common reflection of a variety of intracranial physiologic abnormalities in dogs. In dogs with brain tumors, seizures often provide the clinical clue to the existence of an underlying structural brain disease. The majority of brain tumors that result in seizures affect the supratentorial nervous system, especially the olfactory and frontal lobes. Diagnosis requires advanced imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) to establish the presence of a structural abnormality. Therapy is directed both at tumor and seizure control to afford the best chance of successful management of dogs with brain tumors.

Clinical features of trigeminal nerve-sheath tumor in 10 dogs.

Nerve-sheath tumor was diagnosed in 10 dogs with clinical signs of unilateral trigeminal nerve dysfunction. Unilateral temporalis and masseter muscle atrophy were present in all cases. An enlarged foramen and distorted rostral petrous temporal bone were seen with computed tomography imaging in one case. Magnetic resonance imaging was used to identify the lesion accurately in seven cases. Surgery was performed for biopsy and lesion removal in three cases. Cases not treated had a progressive course eventually resulting in euthanasia or death. Of the cases treated surgically, one case is alive without disease progression 27 months after surgery. Survival times of the nontreated cases ranged from five to 21 months.

Retrospective review of 50 canine intracranial tumors evaluated by magnetic resonance imaging.

Magnetic resonance imaging (MRI) was performed on 50 dogs with intracranial neoplasia. The following tumor features were assessed: axial origin, location, shape, growth pattern, MRI signal intensity, evidence for edema, and paramagnetic contrast enhancement. Histologic diagnosis included 5 intracranially invading nasal tumors, 7 pituitary tumors, 22 meningiomas, 6 choroid plexus tumors, 7 astrocytomas, 1 ependymoma, and 2 oligodendrogliomas. Axial origin, site, shape, and growth pattern were important diagnostic characteristics for tumor type. Signal intensity and contrast enhancement pattern allowed further differentiation. Characteristic MRI features that facilitate diagnosis and prognosis were identified. Accurate diagnosis of tumor type based on these features was not always possible because of similarities in MRI appearance for some tumors. Tissue biopsy remains necessary for definitive diagnosis of intracranial tumors.

Acute, unilateral transverse sinus occlusion during craniectomy in seven dogs with space-occupying intracranial disease.

OBJECTIVE: The purpose of this study was to determine the effect of acute, unilateral transverse sinus occlusion on intracranial pressure (ICP) and postoperative mortality in dogs with structural intracranial disease. STUDY DESIGN: Affected dogs had a single transverse sinus occluded during craniectomy for intracranial mass biopsy or removal. ANIMALS: Seven dogs with space-occupying intracranial disease in the cerebellopontine angle area. METHODS: The ipsilateral transverse sinus was permanently occluded during the surgical approach to the intracranial lesion to increase surgical exposure by allowing a caudal lateral rostrotentorial craniectomy to be combined with a suboccipital craniectomy. In five dogs, intracranial pressure was monitored during surgery using a fiberoptic intracranial pressure monitoring device. RESULTS: Initial ICP varied among dogs, ranging from 7 to 21 mm Hg. Intracranial pressure, however, decreased in all dogs after craniectomy and durotomy (P < .05). No increase in intracranial pressure occurred after transverse sinus occlusion (P = .42). All dogs survived the surgical procedure. CONCLUSIONS: Acute, unilateral transverse sinus occlusion during craniectomy in dogs with space-occupying intracranial lesions did not result in significant increases in ICP or intraoperative mortality. CLINICAL RELEVANCE: Acute, unilateral transverse sinus occlusion during craniectomy can be used to increased surgical exposure to the caudal fossa of the brain without increased risk of increasing ICP.