The CCL2-CCR4 axis promotes Regulatory T cell trafficking to canine glioma tissues.

PURPOSE: Spontaneously occurring glioma in pet dogs is increasingly recognized as a valuable translational model for human glioblastoma. Canine high-grade glioma and human glioblastomas share many molecular similarities, including the accumulation of immunosuppressive regulatory T cells (Tregs) that inhibit anti-tumor immune responses. Identifying in dog mechanisms responsible for Treg recruitment may afford to target the cellular population driving immunosuppression, the results providing a rationale for translational clinical studies in human patients. Our group has previously identified C-C motif chemokine 2 (CCL2) as a glioma-derived T-reg chemoattractant acting on chemokine receptor 4 (CCR4) in a murine orthotopic glioma model. Recently, we demonstrated a robust increase of CCL2 in the brain tissue of canine patients bearing high-grade glioma. METHODS: We performed a series of in vitro experiments using canine Tregs and patient-derived canine glioma cell lines (GSC 1110, GSC 0514, J3T-Bg, G06A) to interrogate the CCL2-CCR4 signaling axis in the canine. RESULTS: We established a flow cytometry gating strategy for identifying and isolating FOXP3+ Tregs in dogs. The canine CD4 + CD25high T-cell population was highly enriched in FOXP3 and CCR4 expression, indicating they are bona fide Tregs. Canine Treg migration was enhanced by CCL2 or by glioma cell line-derived supernatant. Blockade of the CCL2-CCR4 axis significantly reduced migration of canine Tregs. CCL2 mRNA was expressed in all glioma cell lines, and expression increased when exposed to Tregs but not CD4 + helper T-cells. CONCLUSION: Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.

The CCL2-CCR4 Axis Promotes Regulatory T Cell Trafficking to Canine Glioma Tissues.

Purpose: Spontaneously occurring glioma in pet dogs is increasingly recognized as a valuable translational model for human glioblastoma. Canine high grade glioma and human glioblastomas share many molecular similarities, including accumulation of immunosuppressive regulatory T cells (Tregs) that inhibit anti-tumor immune responses. Identifying in dog mechanisms responsible for Treg recruitment may afford targeting the cellular population driving immunosuppression, the results providing a rationale for translational clinical studies in human patients. Our group has previously identified C-C motif chemokine 2 (CCL2) as a glioma-derived T-reg chemoattractant acting on chemokine receptor 4 (CCR4) in a murine orthotopic model of glioma. Recently, we demonstrated a robust increase of CCL2 in the brain tissue of canine patients bearing high-grade glioma. Methods: We performed a series of in vitro experiments using canine Tregs and patient-derived canine glioma cell lines (GSC 1110, GSC 0514, J3T-Bg, G06A) to interrogate the CCL2-CCR4 signaling axis in the canine. Results: We established a flow cytometry gating strategy for identification and isolation of FOXP3+ Tregs in dogs. The canine CD4 + CD25high T-cell population was highly enriched in FOXP3 and CCR4 expression, indicating they are bona fide Tregs. Canine Treg migration was enhanced by CCL2 or by glioma cell line-derived supernatant. Blockade of the CCL2-CCR4 axis significantly reduced migration of canine Tregs. CCL2 mRNA was expressed in all glioma cell lines and expression increased when exposed to Tregs but not to CD4 + helper T-cells. Conclusion: Our study validates CCL2-CCR4 as a bi-directional Treg-glioma immunosuppressive and tumor-promoting axis in canine high-grade glioma.

Canine Nervous System Lymphoma Subtypes Display Characteristic Neuroanatomical Patterns.

Primary and secondary nervous system involvement occurs in 4% and 5%-12%, respectively, of all canine non-Hodgkin lymphomas. The recent new classification of canine malignant lymphomas, based on the human World Health Organization classification, has been endorsed with international acceptance. This histological and immunocytochemical classification provides a unique opportunity to study the histologic anatomic distribution patterns in the central and peripheral nervous system of these defined lymphoma subtypes. In this study, we studied a cohort of 37 dogs with lymphoma, which at necropsy had either primary (n = 1, 2.7%) or secondary (n = 36; 97.3%) neural involvement. These T- (n = 16; 43.2%) or B-cell (n = 21; 56.8%) lymphomas were further classified into 12 lymphoma subtypes, with predominant subtypes including peripheral T-cell lymphoma (PTCL) or diffuse large B-cell lymphoma (DLBCL), respectively. This systematic study identified 6 different anatomically based histologically defined patterns of lymphoma infiltration in the nervous system of dogs. Different and distinct combinations of anatomical patterns correlated with specific lymphoma subtypes. Lymphoma infiltration within the meningeal, perivascular, and periventricular compartments were characteristic of DLBCL, whereas peripheral nerve involvement was a frequent feature of PTCL. Similarly cell counts above 64 cells/µL in cerebrospinal samples correlated best with marked meningeal and periventricular lymphoma infiltration histologically. Prospective studies are needed in order to confirm the hypothesis that these combinations of histological neuroanatomic patterns reflect targeting of receptors specific for the lymphoma subtypes at these various sites.

Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts.

BACKGROUND: In children, frequent congenital malformations with concomitant agenesis of the corpus callosum are diagnosed by neuroimaging in association with other cerebral malformations, including interhemispheric cysts and ventriculomegaly. Similar studies providing full characterization of brain defects by in vivo magnetic resonance imaging (MRI), and correlations with the pertinent anatomic pathologic examinations are absent in veterinary medicine. HYPOTHESIS/OBJECTIVES: Congenital brain defects underlie the neurologic signs observed in Toyger cats selectively bred for a short ear phenotype. ANIMALS: Using proper pedigree analysis and genetic evaluations, 20 related Oriental-derived crossbred Toyger cats were evaluated. Seven clinically healthy (carrier) cats and 13 clinically affected cats that had neurologic signs, short ear phenotype and concomitant complex brain anomalies were studied. METHODS: Complete physical and neurologic examinations and MRI were performed in all clinically healthy and affected cats. Postmortem and histopathologic examinations were performed in 8 affected cats and 5 healthy cats. RESULTS: Neurologic and MRI investigations confirmed 13 clinically affected cats with structural brain abnormalities. Ventriculomegaly with frequent concomitant supratentorial interhemispheric, communicating ventricular type-1b cysts and multiple midline and callosal malformations were detected in all cats displaying neurologic signs. Genetic analysis confirmed autosomal recessive mode of inheritance with no chromosomal abnormalities. CONCLUSIONS AND CLINICAL IMPORTANCE: Neuroanatomic dissections and histopathology were helpful for evaluation of abnormalities in midline brain structures, and for the full characterization of cysts. However, MRI was more sensitive for detection of small cysts. In this feline model, MRI diagnosis had extremely good correlation with pathologic abnormalities noted in the subset of animals that were examined by both modalities.

Effect of screening abdominal ultrasound examination on the decision to pursue advanced diagnostic tests and treatment in dogs with neurologic disease.

BACKGROUND: Abdominal ultrasound examinations (AUS) are commonly performed before advanced neurodiagnostics to screen for diseases that might affect diagnostic plans and prognosis. OBJECTIVES: Describe the type and frequency of abnormalities found by AUS in dogs presenting with a neurological condition, identify risk factors associated with abnormalities, and evaluate treatment decisions based on findings. ANIMALS: Seven hundred and fifty-nine hospitalized dogs. METHODS: Retrospective study. Medical records of dogs presented from 2007 to 2009 for neurologic disease were searched for signalment, neuroanatomic localization, and AUS findings. Whether dogs had advanced neurodiagnostics and treatment was analyzed. RESULTS: Fifty-eight percent of dogs had abnormal findings on AUS. Probability of abnormalities increased with age (P < 0.001). Nondachshund breeds had higher probability of abnormal AUS than dachshunds (odds ratio [OR] = 1.87). Eleven percent of dogs did not have advanced neurodiagnostics and in 1.3%, this was because of abnormal AUS. Dogs with ultrasonographic abnormalities were less likely than dogs without to have advanced neurodiagnostics (OR = 0.3 [95% confidence interval [CI]: 0.17, 0.52]), however, the probability of performing advanced diagnostics was high regardless of normal (OR = 0.95 [95% CI: 0.92, 0.97]) or abnormal (OR = 0.85 [95% CI: 0.81, 0.88]) AUS. Treatment was more often pursued in small dogs and less often in dogs with brain disease. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings from screening AUS had a small negative effect on the likelihood of pursuing advanced neurodiagnostics. Although it should be included in the extracranial diagnostic workup in dogs with significant history or physical examination abnormalities, AUS is considered a low-yield diagnostic test in young dogs and dachshunds.

Electrophysiologic confirmation of heterogenous motor polyneuropathy in young cats.

BACKGROUND: Reports of motor polyneuropathies in young cats are scarce. Further, in-depth electrophysiologic evaluation to confirm a motor polyneuropathy in young cats of various breeds other than 2 Bengal cats is lacking. HYPOTHESIS/OBJECTIVES: To confirm a motor polyneuropathy in young cats of various breeds. ANIMALS: Five young cats with heterogenous chronic or relapsing episodes of weakness. METHODS: Retrospective case series. Cats were presented for evaluation of generalized neuromuscular disease and underwent electrophysiologic examination including electromyography, nerve conduction, and repetitive nerve stimulation. Minimum database and muscle and nerve biopsy analyses were carried out. Descriptive statistics were performed. RESULTS: Disease onset was at 3 months to 1 year of age and in 5 breeds. The most common clinical sign (5 of 5 cats) was weakness. Additional neurologic deficits consisted of palmigrade and plantigrade posture (4/4), low carriage of the head and tail (4/4), and variable segmental reflex deficits (5/5). Motor nerve conduction studies were abnormal for the ulnar (4/4), peroneal (5/5), and tibial (2/2) nerves (increased latencies, reduced amplitudes, slow velocities). A marked decrement was observed on repetitive nerve stimulation of the peroneal nerve in 3 cats for which autoimmune myasthenia gravis was ruled out. All sensory nerve conduction studies were normal. Histologic evaluation of muscle and nerve biopsies supported heterogenous alterations consistent with motor polyneuropathy with distal nerve fiber loss. CONCLUSIONS AND CLINICAL IMPORTANCE: Heterogenous motor polyneuropathies should be considered in young cats of any breed and sex that are presented with relapsing or progressive generalized neuromuscular disease.

Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California.

BACKGROUND: Cryptococcus spp. is a fungal pathogen with a predilection for the central nervous system (CNS). OBJECTIVES: To compare the clinical, advanced imaging, and neuropathologic findings in dogs and cats with CNS cryptococcosis, and to evaluate outcome of treatment in these animals. ANIMALS: Twenty-six cats and 21 dogs with CNS cryptococcosis. METHODS: Medical records were reviewed for clinical findings and results of CNS imaging. Archived cerebrospinal fluid and CNS tissue specimens were reviewed for pathology. Findings in cats were compared with those in dogs and the effects of variables on survival were determined by survival curve analysis. RESULTS: When present, pain was localized to the cervical region in dogs and was generalized or localized to the thoracolumbar spine or pelvic limbs in cats. Magnetic resonance imaging (MRI) findings were variable but correlated with CNS histopathological findings of meningitis, meningitis with gelatinous pseudocyst formation, and granulomatous mass lesions. Peripherally enhancing brain lesions were seen only in cats. Histopathologically, the inflammatory response was milder in cats compared with dogs. Remissions of ≥1 year occurred in 32% of treated animals. Altered mentation was associated with negative outcome. Glucocorticoid use after diagnosis was associated with improved survival in the first 10 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Lesions seen on MRI reflected neuropathological findings and were similar to those reported in human patients. The immune response to infection may differ between cats and dogs, or relate to the infecting cryptococcal species. Long-term (>6 month median survival time) survival may be possible in animals surviving ≥4 days after diagnosis.

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/microL 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/microL (median 84 cells/microL, reference range

Choroid plexus tumors in 56 dogs (1985-2007).

BACKGROUND: Choroid plexus tumors (CPTs) comprise approximately 10% of all primary brain tumors in dogs. The clinical utility of magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, or both in the presumptive diagnosis of CPTs has not been determined. OBJECTIVES: To report MRI and CSF findings in dogs with CPT and determine if there are distinguishing features that allow clinical discrimination between the tumor grades. ANIMALS: Fifty-six client-owned dogs with naturally occurring CPT. METHODS: Retrospective case series. The inclusion criterion was histologically confirmed CPT. Blinded review of cranial MRI and cisternal CSF analysis was performed. RESULTS: Thirty-six of 56 dogs had a choroid plexus carcinoma (CPC) and 20 had a choroid plexus papilloma (CPP). Golden Retrievers were overrepresented compared with the hospital population (frequency 3.7 times that expected, confidence interval 95%= 2.0-6.7, P< .0002). Median CSF protein concentration in CPCs (108 mg/dL, range 27-380 mg/dL) was significantly higher than in CPPs (34 mg/dL, range 32-80 mg/dL) (P= .002). Only dogs with CPCs had a CSF protein concentration >80 mg/dL. Cytological evidence of malignancy in CSF was seen in 7 of 15 CPCs. Only CPCs had evidence of intraventricular or subarachnoid metastases on MRI. CONCLUSIONS AND CLINICAL IMPORTANCE: MRI, CSF analysis or both can help to differentiate between CPPs and CPCs, and may provide valuable prognostic and pretreatment information.

Lumbar cerebrospinal fluid in dogs with type I intervertebral disc herniation.

BACKGROUND: Cerebrospinal fluid (CSF) in dogs with Hansen type I intervertebral disc herniation (IVDH) is classically described as normal or mildly inflammatory with a predominance of large mononuclear cells or neutrophils in severe acute herniations. However, we have observed a moderate to marked pleocytosis with a predominance of lymphocytes in some dogs with IVDH. HYPOTHESIS: Moderate to marked CSF pleocytosis occurs more commonly in dogs with type I IVDH than is reported in the literature. Lymphocytic predominance is more common than nonlymphocytic pleocytosis in dogs with chronic IVDH. ANIMALS: Four hundred twenty-three client-owned dogs with type I IVDH. METHODS: Retrospective study. Lumbar CSF of dogs with surgically confirmed type I IVDH was evaluated cytologically. Information obtained from medical records included signalment, prior clinical history, time from onset of signs to presentation, neurologic status, and intraoperative findings. Dogs with prior history and/or intraoperative evidence consistent with chronic IVDH before an acute herniation were termed acute-on-chronic (AOC). RESULTS: Pleocytosis (> 5 cells/uL) was present in 51% of dogs, including 23% with cervical IVDH and 61% with thoracolumbar IVDH. Moderate or marked inflammation (> or = 20 cells/uL) was identified in the CSF of 51% of dogs with thoracolumbar IVDH and pleocytosis. A predominance of lymphocytes was significantly more common in dogs examined > 7 days from onset of signs (P= .032) and in dogs with AOC IVDH (P= .0013). CONCLUSIONS AND CLINICAL IMPORTANCE: Moderate to marked CSF pleocytosis in dogs with type I IVDH is more common than previously reported. Lymphocytic pleocytosis is most common in dogs with chronic progression or AOC IVDH. Lymphocytic inflammation in the CSF of some dogs might suggest an immune-mediated response to chronically herniated disc material.

Canine intraspinal meningiomas: imaging features, histopathologic classification, and long-term outcome in 34 dogs.

BACKGROUND: Meningioma is the most common primary intraspinal nervous system tumor in dogs. Clinical findings, clinicopathologic data, and treatment of these tumors have been reported sporadically, but little information is available regarding cerebrospinal fluid (CSF) analysis, histologic tumor grade, or efficacy of radiation therapy as an adjunct to cytoreductive surgery. ANIMALS: Dogs with histologically confirmed intraspinal meningiomas (n = 34). METHODS: A retrospective study of dogs with intraspinal meningiomas between 1984 and 2006 was carried out. Signalment, historical information, physical examination, clinicopathologic data, radiation therapy protocols, surgery reports, and all available images were reviewed. All tumors were histologically classified and graded as defined by the international World Health Organization classification scheme for central nervous system tumors. RESULTS: Intraspinal mengiomas in dogs are most common in the cervical spinal cord but can be found throughout the neuraxis. Location is correlated with histologic grade, with grade I tumors more likely to be in the cervical region than grade II tumors. Myelography generally shows an intradural extramedullary compressive lesion. On magnetic resonance imaging, the masses are strongly and uniformly contrast enhancing and a dural tail often is present. CSF analysis usually shows increased protein concentration with mild to moderate mixed pleocytosis. Surgical resection is an effective means of improving neurologic status, and adjunctive radiation therapy may lead to an improved outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: Biopsy is necessary for definitive diagnosis, but imaging and CSF analysis can suggest a diagnosis of meningioma. Treatment of meningiomas with surgery and radiation therapy can result in a fair to excellent prognosis.

Necrotizing meningoencephalitis in five Chihuahua dogs.

An acute to chronic idiopathic necrotizing meningoencephalitis was diagnosed in 5 Chihuahua dogs aged between 1.5 and 10 years. Presenting neurologic signs included seizures, blindness, mentation changes, and postural deficits occurring from 5 days to 5.5 months prior to presentation. Cerebrospinal fluid analyses from 2 of 3 dogs sampled were consistent with an inflammatory disease. Magnetic resonance imaging of the brain of 2 dogs demonstrated multifocal loss or collapse of cortical gray/white matter demarcation hypointense on T1-weighted images, with T2-weighted hyperintensity and slight postcontrast enhancement. Multifocal asymmetrical areas of necrosis or collapse in both gray and white matter of the cerebral hemispheres was seen grossly in 4 brains. Microscopically in all dogs, there was a severe, asymmetrical, intensely cellular, nonsuppurative meningoencephalitis usually with cystic necrosis in subcortical white matter. There were no lesions in the mesencephalon or metencephalon except in 1 dog. Immunophenotyping defined populations of CD3, CD11d, CD18, CD20, CD45, CD45 RA, and CD79a immunoreactive inflammatory cells varying in density and location but common to acute and chronic lesions. In fresh frozen lesions, both CD1b,c and CD11c immunoreactive dendritic antigen-presenting cells were also identified. Immunoreactivity for canine distemper viral (CDV) antigen was negative in all dogs. The clinical signs, distribution pattern, and histologic type of lesions bear close similarities to necrotizing meningoencephalitis as described in series of both Pug and Maltese breed dogs and less commonly in other breeds.

Magnetic resonance imaging and histological classification of intracranial meningiomas in 112 dogs.

BACKGROUND: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated. HYPOTHESIS: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics. ANIMALS: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma. METHODS: Retrospective observational study. RESULTS: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied. CONCLUSIONS AND CLINICAL IMPORTANCE: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas.

Vascular endothelial growth factor mRNA expression and peritumoral edema in canine primary central nervous system tumors.

Vascular endothelial growth factor (VEGF) is an important regulator of tumor angiogenesis and vascular permeability, and has been implicated both in progression of central nervous system (CNS) tumors and development of vasogenic peritumoral edema. A retrospective study was done to characterize the levels of expression of the 3 major canine VEGF isoforms (VEGF(120), VEGF(164), VEGF(188)) in a variety of spontaneous canine CNS tumors using quantitative TaqMan reverse transcription real-time polymerase chain reaction. Presence and degree of peritumoral edema also were determined in sampled tumors using magnetic resonance imaging (MRI). Increased expression of VEGF relative to normal cerebral cortex tissue was seen predominantly in high grade astrocytic (grade IV) and oligodendroglial (grade III) tumors, with lower expression in low grade astrocytomas (grade II) and meningiomas (grade I). All 3 major VEGF isoforms were present; VEGF(164) was the predominant isoform, particularly in the tumors with the highest VEGF expression. Peritumoral edema was present in all tumor types; however, a significant association between the extent of peritumoral edema and the level of VEGF expression was not apparent.

Endoneurial microvascular pathology in feline diabetic neuropathy.

Endoneurial capillaries in nerve biopsies from 12 adult diabetic cats with varying degrees of neurological dysfunction were examined for evidence of microvascular pathology and compared to nerves obtained at necropsy from 7 adult non-diabetic cats without clinical evidence of neurological dysfunction. As reported previously [Mizisin, A.P., Nelson, R.W., Sturges, B.K., Vernau, K.M., LeCouteur, R.A., Williams, D.C., Burgers, M.L., Shelton, G.D., 2007. Comparable myelinated nerve pathology in feline and human diabetes mellitus. Acta Neuropathol. 113, 431-442.], the diabetic cats had elevated glycosylated hemoglobin and serum fructosamine levels, decreased motor nerve conduction velocity and compound muscle action potential (CMAP) amplitude, and markedly decreased myelinated nerve fiber densities. Compared to non-diabetic cats, there was a non-significant 26% increase in capillary density and a significant (P<0.009) 45% increase in capillary size in diabetic cats. Capillary luminal size was also significantly (P<0.001) increased, while an index of vasoconstriction was significantly decreased (P<0.001) in diabetic cats compared to non-diabetic controls. No differences in endothelial cell size, endothelial cell number or pericyte size were detected between non-diabetic and diabetic cats. In diabetic cats, basement membrane thickening, seen as a reduplication of the basal lamina, was significantly (P<0.0002) increased by 73% compared to non-diabetic controls. Regression analysis of either myelinated nerve fiber density or CMAP amplitude against basement membrane size demonstrated a negative correlation with significant slopes (P<0.03 and P<0.04, respectively). These data demonstrate that myelinated nerve fiber injury in feline diabetic neuropathy is associated with microvascular pathology and that some of these changes parallel those documented in experimental rodent and human diabetic neuropathy.

Comparable myelinated nerve pathology in feline and human diabetes mellitus.

The occurrence of diabetic neuropathy in cats provides an opportunity to study the development and treatment of neurological complications not present in diabetic rodent models, where few pathological alterations are evident. The present study further defines pathological alterations in nerve biopsies from 12 cats with spontaneously occurring diabetes mellitus. Peroneal nerve biopsies displayed concurrent injury to both Schwann cells and axons of myelinated fibers that was remarkably similar to that present in human diabetic neuropathy. In addition to demyelination, remyelination (constituting 20-84% of the total myelinated fiber population) was indicated by fibers with inappropriately thin myelin sheaths. Unlike our previous investigations, striking axonal injury was apparent, and consisted of dystrophic accumulations of membranous debris or neurofilaments, as well as degenerative fiber loss resulting in a 50% decrease in myelinated fiber density. In spite of extensive fiber loss, regenerative clusters were apparent, suggesting that axonal regeneration was not completely frustrated. These data highlight the potential utility of feline diabetic neuropathy as a model that faithfully replicates the nerve injury in human diabetes mellitus.

Granular cell tumor of the canine central nervous system: two cases.

Although pure granular cell tumors have been reported in various sites in the dog, only one tumor has been reported in the central nervous system. Two dogs presented with neurologic signs had brain lesions detected by magnetic resonance imaging in the area of the olfactory bulbs and frontal cortex. In both dogs, a clinical diagnosis of a granular cell tumor was made from tissues obtained from stereotactic biopsies guided by computed tomography. Surgical removal of the tumors was followed by histopathologic, ultrastructural, and immunocytochemical characterization. Although not conclusive, these studies indicated that the granular cells were not of leucocyte origin but may have been derived from the meninges. One dog died 12 months after surgery, and the other was alive 4 months later.

Extradural spinal synovial cysts in nine dogs.

Nine dogs presenting for investigation of cervical or thoracolumbar myelopathies were diagnosed with extradural spinal synovial cysts. Degenerative disease affecting the articular facets or intervertebral discs was present on plain spinal radiographs in all cases. Myelography was consistent with dorsolateral, extradural spinal cord compression. Two groups of dogs were identified: (1) young, giant breed dogs with multiple cysts involving one or more levels of the cervical spinal cord; and (2) older, large breed dogs with solitary cysts involving the thoracolumbar spinal cord. The synovial cysts constituted the major compressive lesions in four of the dogs. Analysis of lumbar cerebrospinal fluid demonstrated albuminocytological dissociation, consistent with chronic compressive myelopathy, in six dogs. All dogs underwent decompressive surgery and the diagnosis of synovial cysts was confirmed histologically. The mean follow-up period was 17 months (range four to 36 months). At the time of follow-up, all dogs were fully ambulatory with improved neurological function compared with that at initial presentation.

Suspected protozoal myeloencephalitis in a two-month-old colt.

A two-month-old Appaloosa colt developed neurological signs shortly after birth involving deficits affecting cranial nerves IV, VII, VIII, IX, X and XII, and possibly nerve VI. The most likely differential diagnoses were congenital anomalies, meningoencephalitides, trauma or nutritional causes. The foal was investigated by the analysis of cerebrospinal fluid (CSF), electromyelography (EMG), brain auditory evoked responses, magnetic resonance imaging (MRI), peripheral nerve biopsy, and Western blot analysis for the presence of intrathecal antibodies to Sarcocystis neurona, the causative agent of equine protozoal myeloencephalitis. Significantly abnormal EMG findings included spontaneous electrical activity of the tongue, suggesting denervation. The MRI was useful in ruling out masses, congenital anomalies and focal abscessation. The cytology of CSF revealed mild mononuclear reactivity. Western blot testing of CSF was positive, indicating the intrathecal presence of antibodies to S neurona. The foal was treated with pyrimethamine and trimethoprim-sulphadiazine for two months and returned to nearly normal neurologic status.