Central nervous system (CNS) inflammation is a common cause of neurological dysfunction in dogs. Most dogs with CNS inflammation are diagnosed with presumptive autoimmune disease. A smaller number are diagnosed with an infectious etiology. Additionally, at necropsy, a subset of dogs with CNS inflammation do not fit previously described patterns of autoimmune disease and an infectious cause is not readily identifiable. Because viral infection is a common cause of meningoencephalitis in people, we hypothesize that a subset of dogs presented with CNS inflammation have an occult viral infection either as a direct cause of CNS inflammation or a trigger for autoimmunity. The goal of this research was to screen cerebrospinal fluid from a large number dogs with CNS inflammation for occult viral infection. One hundred seventy-two dogs with neurological dysfunction and cerebrospinal fluid (CSF) pleocytosis were identified. Of these, 42 had meningoencephalitis of unknown origin, six had steroid-responsive meningitis-arteritis, one had eosinophilic meningoencephalitis, five had documented infection, 21 had and undetermined diagnosis, and 97 had a diagnosis not consistent with primary inflammatory disease of the CNS (e.g., neoplasia). CSF samples were subsequently screened with broadly reactive PCR for eight viral groups: adenovirus, bunyavirus, coronavirus, enterovirus, flavivirus, herpesvirus, paramyxovirus, and parechovirus. No viral nucleic acids were detected from 168 cases screened for eight viral groups, which does not support occult viral infection as a cause of CNS inflammation in dogs. La Crosse virus (LACV) nucleic acids were detected from four cases in Georgia. Subclinical infection was supported in two of these cases but LACV could not be ruled-out as a cause of infection in the other two cases, suggesting further research is warranted to determine if LACV is an occult cause of CNS inflammation in dogs.

Patients harbouring mutations in genes encoding C-type natriuretic peptide (CNP; NPPC) or its receptor guanylyl cyclase B (GC-B, NPR2) suffer from severe growth phenotypes; loss-of-function mutations cause achondroplasia, whereas gain-of-function mutations cause skeletal overgrowth. Although most of the effects of CNP/GC-B on growth are mediated directly on bone, evidence suggests the natriuretic peptides may also affect anterior pituitary control of growth. Our previous studies described the expression of NPPC and NPR2 in a range of human pituitary tumours, normal human pituitary, and normal fetal human pituitary. However, the natriuretic peptide system in somatotropes has not been extensively explored. Here, we examine the expression and function of the CNP/GC-B system in rat GH3 somatolactotrope cell line and pituitary tumours from a cohort of feline hypersomatotropism (HST; acromegaly) patients. Using multiplex RT-qPCR, all three natriuretic peptides and their receptors were detected in GH3 cells. The expression of Nppc was significantly enhanced following treatment with either 100 nM TRH or 10 µM forskolin, yet only Npr1 expression was sensitive to forskolin stimulation; the effects of forskolin and TRH on Nppc expression were PKA- and MAPK-dependent, respectively. CNP stimulation of GH3 somatolactotropes significantly inhibited Esr1, Insr and Lepr expression, but dramatically enhanced cFos expression at the same time point. Oestrogen treatment significantly enhanced expression of Nppa, Nppc, Npr1, and Npr2 in GH3 somatolactotropes, but inhibited CNP-stimulated cGMP accumulation. Finally, transcripts for all three natriuretic peptides and receptors were expressed in feline pituitary tumours from patients with HST. NPPC expression was negatively correlated with pituitary tumour volume and SSTR5 expression, but positively correlated with D2R and GHR expression. Collectively, these data provide mechanisms that control expression and function of CNP in somatolactotrope cells, and identify putative transcriptional targets for CNP action in somatotropes.

Hypersomatotropism (HST) is an increasingly recognized endocrinopathy in cats and is mostly described associated with diabetes mellitus (DM). To evaluate the efficacy and safety of transsphenoidal hypophysectomy in treating HST and DM in cats. Sixty-eight client-owned cats with HST and DM treated by transsphenoidal hypophysectomy. Retrospective cohort study. Medical records were reviewed for glycemic control and serum insulin-like growth factor-1 (IGF-1) concentrations. Postoperative complications, death within 4 weeks, and proportion achieving diabetic remission were recorded. Survival times and DM-free intervals were calculated. Fifty-eight cats (85.3%) were alive 4 weeks postoperatively with 10 (15%) postoperative deaths. Complications included hypoglycemia (n = 9), electrolyte imbalance (n = 9), and transient congestive heart failure (n = 5). Fifty-five cats (95% of 58 surviving cats [81% of all cats undergoing surgery]) had improved control of diabetes. Diabetic remission occurred in 41 cats (71% of 58 surviving cats [60% of all cats]) with insulin administration discontinued after a median of 9 days (range, 2-120). Postoperative 4-week serum IGF-1 concentration nadir was significantly lower in cats achieving diabetic remission (median 20 ng/mL [15-708] than those that did not (324 ng/mL [15-1955]; P = .03). All cats received long-term levothyroxine and hydrocortisone PO, alongside desmopressin (conjunctival) in 38 of 53 cats (72%). Recurrence of DM occurred in 5 of 41 cats (12%) after a median of 248 days (range, 84-1232). Median survival time of all cats was 853 days (range, 1-1740). Transsphenoidal hypophysectomy is an effective treatment for cats with HST and DM, with a long-term outcome that compares favorably to existing options.

Abstract Background Hypersomatotropism (HST) is an increasingly recognized endocrinopathy in cats and is mostly described associated with diabetes mellitus (DM). Objectives To evaluate the efficacy and safety of transsphenoidal hypophysectomy in treating HST and DM in cats. Animals Sixty‐eight client‐owned cats with HST and DM treated by transsphenoidal hypophysectomy. Methods Retrospective cohort study. Medical records were reviewed for glycemic control and serum insulin‐like growth factor‐1 (IGF‐1) concentrations. Postoperative complications, death within 4 weeks, and proportion achieving diabetic remission were recorded. Survival times and DM‐free intervals were calculated. Results Fifty‐eight cats (85.3%) were alive 4 weeks postoperatively with 10 (15%) postoperative deaths. Complications included hypoglycemia (n = 9), electrolyte imbalance (n = 9), and transient congestive heart failure (n = 5). Fifty‐five cats (95% of 58 surviving cats [81% of all cats undergoing surgery]) had improved control of diabetes. Diabetic remission occurred in 41 cats (71% of 58 surviving cats [60% of all cats]) with insulin administration discontinued after a median of 9 days (range, 2‐120). Postoperative 4‐week serum IGF‐1 concentration nadir was significantly lower in cats achieving diabetic remission (median 20 ng/mL [15‐708] than those that did not (324 ng/mL [15‐1955]; P = .03). All cats received long‐term levothyroxine and hydrocortisone PO, alongside desmopressin (conjunctival) in 38 of 53 cats (72%). Recurrence of DM occurred in 5 of 41 cats (12%) after a median of 248 days (range, 84‐1232). Median survival time of all cats was 853 days (range, 1‐1740). Conclusions and Clinical Importance Transsphenoidal hypophysectomy is an effective treatment for cats with HST and DM, with a long‐term outcome that compares favorably to existing options.

Objectives The aim of this study was to describe the anaesthetic management and perianaesthetic complications encountered during hypophysectomy surgery in acromegalic cats. We explored relationships between animal demographic data, the anaesthetic protocol used and presence of perioperative complications. Methods Cats having undergone hypophysectomy surgery for the treatment of feline acromegaly at a single veterinary referral hospital were identified from hospital records. The anaesthesia records and clinical notes of these animals were retrospectively reviewed. Descriptive statistics were produced and binary logistic regression run to assess for any relationship between patient factors, anaesthetic management and complications during the perioperative period. Results Perianaesthetic complications identified included hypothermia, hypotension, bradycardia and airway obstruction. Mortality at 24 h post-anaesthesia was 8%. The use of alpha (α) 2 agonists was associated with a lower incidence of hypotension. Fentanyl infusion was associated with a higher incidence of airway obstruction compared with remifentanil. Subjectively assessed anaesthetic recovery quality had an association with the number of days spent in the intensive care ward postoperatively. Conclusions and relevance The anaesthetic management described seems effective for hypophysectomy surgery in cats. Intraoperative complications were common and, while not apparently associated with 24 h patient outcome, drugs and equipment to manage these complications should be available.

The prevalence of GH-secreting pituitary tumors in domestic cats (Felis catus) is 10-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D2 dopamine receptor (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly. The aim of this study was to describe pathological features of pituitaries from domestic cats with acromegaly, pituitary receptor expression, and investigate correlates with clinical data, including pituitary volume, time since diagnosis of diabetes, insulin requirement, and serum IGF1 concentration. Loss of reticulin structure was identified in 15 of 21 pituitaries, of which 10 of 15 exhibited acinar hyperplasia. SSTR1, SSTR2, SSTR5, and DRD2 mRNA were identified in the feline pituitary whereas SSTR3 and SSTR4 were not. Expression of SSTR1, SSTR2, and SSTR5 was greater in acromegalic cats compared with controls. A negative correlation was identified between DRD2 mRNA expression and pituitary volume. The loss of DRD2 expression should be investigated as a mechanism allowing the development of larger pituitary tumors.

Spinal trauma causing spinal cord injury is common in dogs and cats. Careful handling so as not to cause further injury is essential, as is aggressive management of spinal cord oxygenation and perfusion. Timely diagnosis and appropriate treatment are critical, and may lead to good functional outcomes for many patients.

BackgroundN‐terminal type III procollagen propeptide (PIIINP) is a biomarker of soft tissue proliferation. Hypersomatotropism (HS) is associated with soft tissue proliferation.HypothesisSerum PIIINP is increased in cats with HS and decreases with effective treatment, and may be an additional tool in the diagnosis and treatment of feline HS.AnimalsCats with uncomplicated diabetes mellitus (DM; n = 30) and with HS‐induced DM (HSDM; n = 30). Pre‐ and posttreatment samples were available from 5 cats undergoing radiotherapy (RT) and 16 cats undergoing hypophysectomy (HPX).MethodsRetrospective and prospective cross‐sectional study. Analytical performance of a serum PIIINP ELISA was assessed and validated for use in cats. PIIINP and insulin‐like growth factor 1 (IGF‐1) radioimmunoassays (RIA) were performed pre‐ and post‐treatment in cats with DM and HSDM. PIIINP and IGF‐1 were compared between cats treated by RT and HPX.ResultsSerum PIIINP concentrations were significantly higher (P < .001) in HSDM cats (median, 19.6 ng/mL; range, 1.7–27.9) compared to DM cats (median, 5.0 ng/mL; range, 2.1–10.4). A cut‐off of 10.5 ng/mL allowed differentiation between DM and HSDM cats with 87% sensitivity and 100% specificity (area under the curve [AUC], 0.91; 95% confidence interval [CI], 0.82‐1). After RT, PIIINP increased significantly (P = .043) with no significant change in IGF‐1 concentrations. After HPX, serum PIIINP (P = .034) and IGF‐1 concentrations (P < .001) decreased significantly.Conclusion and clinical importancePIIINP concentrations are increased in cats with untreated HSDM compared to those with DM, demonstrating the effect of excess GH on soft tissue. PIIINP concentrations decreased after HPX in most HSDM cats.

Four MRI variables have recently been suggested to be independently associated with a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion. Midline intervertebral disk herniation, and partial intervertebral disk degeneration were associated with intervertebral disk protrusion, while presence of a single intervertebral disk herniation and disk material dispersed beyond the boundaries of the intervertebral disk space were associated with intervertebral disk extrusion. The aim of this retrospective, cross-sectional study was to determine whether using these MRI variables improves differentiation between thoracolumbar intervertebral disk extrusions and protrusions. Eighty large breed dogs with surgically confirmed thoracolumbar intervertebral disk extrusions or protrusions were included. Randomized MRI studies were presented on two occasions to six blinded observers, which were divided into three experience categories. During the first assessment, observers made a presumptive diagnosis of thoracolumbar intervertebral disk extrusion or protrusion without guidelines. During the second assessment they were asked to make a presumptive diagnosis with the aid of guidelines. Agreement was evaluated by Kappa-statistics. Diagnostic accuracy significantly improved from 70.8 to 79.6% and interobserver agreement for making a diagnosis of intervertebral disk extrusion or intervertebral disk protrusion improved from fair (κ = 0.27) to moderate (κ = 0.41) after using the proposed guidelines. Diagnostic accuracy was significantly influenced by degree of observer experience. Intraobserver agreement for the assessed variables ranged from fair to excellent and interobserver agreement ranged from fair to moderate. The results of this study suggest that the proposed imaging guidelines can aid in differentiating thoracolumbar intervertebral disk extrusions from protrusions.

Convergence-retraction nystagmus is an irregular, jerky nystagmus in which both eyeballs rhythmically converge and retract into the orbit, particularly on attempting an upward gaze. In humans it is seen as part of Parinaud’s syndrome, also known as dorsal midbrain syndrome, in which a lesion of dorsally located midbrain structures (the ventral pretectum, the periaqueductal area, and the medial longitudinal fasciculus in the dorsal tegmentum) prevents upward or downward movement of the eyes. It has been hypothesized that convergence-retraction nystagmus is caused by damage (ischemia, neoplasia, compression, or demyelination) to supranuclear fibers that have an inhibitory effect on the convergence neurons or divergence neurons in the midbrain, resulting in a sustained discharge of medial rectus and other extraocular muscle neurons. The rostral interstitial nuclei of the medial longitudinal fasciculus (RINMLF) of the midbrain, located dorsal to the oculomotor nuclei, contain the final relays producing all vertical saccades, and hence it has been suggested that Parinaud’s syndrome may result from damage to their neuronal cell bodies, as well as their afferent and efferent pathways. Convergence-retraction nystagmus is a highly localizing clinical sign that to the best of our knowledge has not yet been described in the dog. Here, we report 3 large breed dogs that were presented with convergenceretraction nystagmus and in which magnetic resonance imaging (MRI) identified focal lesions within the dorsal midbrain. Case 1: An 11-year, 5-month-old male neutered Staffordshire Bull Terrier was presented with a 14-day history of acute onset, nonprogressive vestibular ataxia with lethargy and disorientation. General physical examination was normal. On neurological examination, the dog was found to be mildly obtunded with a mild right-sided head tilt and circling to the right. Convergence-retraction nystagmus was noted (Video S1), with decreased vestibulo-ocular reflex bilaterally. The remainder of the neurological examination was normal and the findings were considered consistent with a right brainstem neurolocalization. The CBC results were within reference intervals (RIs). Serum biochemistry results included a mildly increased alkaline phosphatase (ALKP) activity (313 U/ L; RI, 19–285 U/L), alanine transferase (ALT) activity (171 U/L; RI, 13–88 U/L), and calcium concentration (2.73 mmol/L; RI, 2.13–2.7 mmol/L). Serum thyroxine and thyroid-stimulating hormone (TSH) concentrations were within normal limits. Prothrombin time and activated partial thromboplastin time were within normal limits. Noninvasive blood pressure assessment identified a pressure of 170–175 mmHg. Urine-specific gravity was 1.043, and urine chemistry dipstrip analysis and sediment examination were normal. A Baermann test for Angiostrongylus was negative. The dog underwent general anesthesia. A combination of acepromazine maleate (0.01 mg/kg IV) and methadone (0.1–0.2 mg/kg IV) was used for premedication, followed by induction with propofol (4–6 mg/kg IV) and maintenance of anesthesia with isoflurane in oxygen. A MRI examination was performed and included T2weighted (T2W) (repetition time, [TR] [ms], echo time [TE], [ms] 3333/110) sagittal and transverse images, T2W fluid attenuated inversion recovery (FLAIR) (TR/TE, 3612/80, inversion time [TI] [ms] 2000) transverse images, and T2*W fast field echo (FFE) transverse images. Sagittal and transverse, T1-weighted (T1W) (TR/TE, 515/15) images were acquired before and after IV administration of gadolinium contrast (0.1 mmol/kg, gadobutrol). Slice From the Clinical Science and Services, Royal Veterinary College, University of London, Hatfield, Herts UK (Crawford, Beltran, Lam, Kenny). The work was conducted at the Royal Veterinary College. Corresponding author: A.H. Crawford, Clinical Science and Services, Royal Veterinary College, University of London, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK; e-mail: ahcrawford@rvc.ac.uk. Submitted February 3, 2016; Revised April 10, 2016; Accepted April 21, 2016. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. DOI: 10.1111/jvim.13966 Abbreviations:

BACKGROUND:Cerebellar cortical degeneration (CCD) is an increasingly recognised neurodegenerative disease process affecting many dog breeds. Typical presentation consists of a progressive cerebellar ataxia, with a variable age at onset and rate of progression between different breeds. Cerebellar histopathological findings typically consist of primary Purkinje neuronal degeneration and loss, with variable secondary depletion of the granular and molecular cell layers. Causative genes have been identified associated with CCD in several breeds, allowing screening for selective breeding to reduce the prevalence of these conditions. There have been no previous reports of CCD in Hungarian Vizslas.RESULTS:Two full-sibling Hungarian Vizsla puppies from a litter of nine presented with a history of progressive ataxia, starting around three months of age. Clinical signs included marked hypermetric and dysmetric ataxia, truncal sway, intention tremors and absent menace responses, with positional horizontal nystagmus in one dog. Routine diagnostic investigations were unremarkable, and magnetic resonance imaging performed in one dog revealed mild craniodorsal cerebellar sulci widening, supportive of cerebellar atrophy. Owners of both dogs elected for euthanasia shortly after the onset of signs. Histopathological examination revealed primary Purkinje neuron loss consistent with CCD. Whole genome sequencing was used to successfully identify a disease-associated splice donor site variant in the sorting nexin 14 gene (SNX14) as a strong causative candidate. An altered SNX14 splicing pattern for a CCD case was demonstrated by RNA analysis, and no SNX14 protein could be detected in CCD case cerebellum by western blotting. SNX14 is involved in maintaining normal neuronal excitability and synaptic transmission, and a mutation has recently been found to cause autosomal recessive cerebellar ataxia and intellectual disability syndrome in humans. Genetic screening of 133 unaffected Hungarian Vizslas revealed the presence of three heterozygotes, supporting the presence of carriers in the wider population.CONCLUSIONS:This is the first report of CCD in Hungarian Vizsla dogs and identifies a highly associated splice donor site mutation in SNX14, with an autosomal recessive mode of inheritance suspected.

Treatment recommendations differ for dogs with intervertebral disk extrusion vs. intervertebral disk protrusion. The aim of this retrospective, cross-sectional study was to determine whether clinical and magnetic resonance imaging (MRI) variables could be used to predict a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion in dogs. Dogs were included if they were large breed dogs, had an MRI study of the thoracolumbar or lumbar vertebral column, had undergone spinal surgery, and had the type of intervertebral disk herniation (intervertebral disk extrusion or protrusion) clearly stated in surgical reports. A veterinary neurologist unaware of surgical findings reviewed MRI studies and recorded number, location, degree of degeneration and morphology of intervertebral disks, presence of nuclear clefts, disk space narrowing, extent, localization and lateralization of herniated disk material, degree of spinal cord compression, intraparenchymal intensity changes, spondylosis deformans, spinal cord swelling, spinal cord atrophy, vertebral endplate changes, and presence of extradural hemorrhage. Ninety-five dogs were included in the sample. Multivariable statistical models indicated that longer duration of clinical signs (P = 0.01), midline instead of lateralized disk herniation (P = 0.007), and partial instead of complete disk degeneration (P = 0.01) were associated with a diagnosis of intervertebral disk protrusion. The presence of a single intervertebral herniation (P = 0.023) and dispersed intervertebral disk material not confined to the disk space (P = 0.06) made a diagnosis of intervertebral disk extrusion more likely. Findings from this study identified one clinical and four MRI variables that could potentially facilitate differentiating intervertebral disk extrusions from protrusions in dogs.

This is the peer reviewed version of the following article: De Decker, S., Gomes, S. A., Packer, R. M., Kenny, P. J., Beltran, E., Parzefall, B., Fenn, J., Nair, D., Nye, G. and Volk, H. A. (2016), EVALUATION OF MAGNETIC RESONANCE IMAGING GUIDELINES FOR DIFFERENTIATION BETWEEN THORACOLUMBAR INTERVERTEBRAL DISK EXTRUSIONS AND INTERVERTEBRAL DISK PROTRUSIONS IN DOGS. Veterinary Radiology & Ultrasound. doi: 10.1111/vru.12394 which has been published in final form at http://dx.doi.org/10.1111/vru.12394. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. The full details of the published version of the article are as follows:

Veterinary RecordVolume 179, Issue 6 p. 151-151 Letter Microchipping very small dogs Frances Taylor-Brown, Corresponding Author Frances Taylor-Brown ftaylor@rvc.ac.uk Queen Mother Hospital for Animals, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire, AL9 7TASearch for more papers by this authorPatrick J. Kenny, Patrick J. Kenny Queen Mother Hospital for Animals, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire, AL9 7TASearch for more papers by this authorMartin Whiting, Martin Whiting Queen Mother Hospital for Animals, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire, AL9 7TASearch for more papers by this author Frances Taylor-Brown, Corresponding Author Frances Taylor-Brown ftaylor@rvc.ac.uk Queen Mother Hospital for Animals, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire, AL9 7TASearch for more papers by this authorPatrick J. Kenny, Patrick J. Kenny Queen Mother Hospital for Animals, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire, AL9 7TASearch for more papers by this authorMartin Whiting, Martin Whiting Queen Mother Hospital for Animals, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire, AL9 7TASearch for more papers by this author First published: 06 August 2016 https://doi.org/10.1136/vr.i4120Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume179, Issue6August 2016Pages 151-151 RelatedInformation

Journal of Veterinary Internal MedicineVolume 30, Issue 4 p. 1216-1221 Case ReportOpen Access Hypersomatotropism in 3 Cats without Concurrent Diabetes Mellitus J.M. Fletcher, Corresponding Author J.M. Fletcher Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Corresponding author: J.M. Fletcher, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70810; e-mail: jmfletcher@lsu.eduSearch for more papers by this authorC.J. Scudder, C.J. Scudder Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorM. Kiupel, M. Kiupel Department of Pathobiology and Diagnostic Investigation, Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI, 48910Search for more papers by this authorH.N. Pipe-Martin, H.N. Pipe-Martin Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorP.J. Kenny, P.J. Kenny Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorP. Mantis, P. Mantis Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorJ. Fenn, J. Fenn Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorK. Smith, K. Smith Department of Pathology and Pathogen Biology, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorR.V. Blair, R.V. Blair Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorL.A. Granger, L.A. Granger Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorS.J.M. Niessen, S.J.M. Niessen Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this author J.M. Fletcher, Corresponding Author J.M. Fletcher Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Corresponding author: J.M. Fletcher, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70810; e-mail: jmfletcher@lsu.eduSearch for more papers by this authorC.J. Scudder, C.J. Scudder Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorM. Kiupel, M. Kiupel Department of Pathobiology and Diagnostic Investigation, Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, MI, 48910Search for more papers by this authorH.N. Pipe-Martin, H.N. Pipe-Martin Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorP.J. Kenny, P.J. Kenny Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorP. Mantis, P. Mantis Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorJ. Fenn, J. Fenn Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorK. Smith, K. Smith Department of Pathology and Pathogen Biology, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this authorR.V. Blair, R.V. Blair Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorL.A. Granger, L.A. Granger Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70810Search for more papers by this authorS.J.M. Niessen, S.J.M. Niessen Department of Clinical Science and Services, The Royal Veterinary College, University of London, North Mymms, AL9 7TA Herts, UKSearch for more papers by this author First published: 03 June 2016 https://doi.org/10.1111/jvim.14360Citations: 12AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abbreviations CSF cerebrospinal fluid CT computed tomography DM diabetes mellitus FSH follicle-stimulating hormone GH growth hormone HCM hypertrophic cardiomyopathy IGF-1 insulin-like growth factor 1 MRI magnetic resonance imaging MSH melanocyte-stimulating hormone TSH thyroid-stimulating hormone USG urine specific gravity Case 1 A 16-year-old, 6.8 kg, castrated male Domestic Short-haired cat was presented to Louisiana State University Veterinary Teaching Hospital with a 3-day history of progressive ataxia, tetraparesis, and altered mentation. The owner did not report having observed evidence of polyuria or polydipsia. The cat had been diagnosed with hypertrophic cardiomyopathy (HCM) 4 years earlier and was receiving atenolol, benazepril, and aspirin. Dull mentation, patchy truncal alopecia, and a grade III of VI systolic heart murmur were noted during the physical examination. The neurologic examination revealed ambulatory tetraparesis that was more severe in the pelvic limbs, plantigrade stance, proprioceptive deficits in all limbs, and positional vertical nystagmus. The CBC, biochemistry profile, and abdominal ultrasound were unremarkable. The blood glucose concentration measured with the chemistry analyzer was 130 mg/dL (7.2 mmol/L). Subsequent blood glucose measurements (n = 6) using a glucometer validated for use in cats1 ranged from 122 mg/dL (6.7 mmol/L) to 159 mg/dL (8.7 mmol/L) during the 5-day period the cat was hospitalized. These blood glucose concentrations combined with a normal serum fructosamine concentration (228 μmol/L, RI 192–288) ruled out overt diabetes mellitus (DM). Two-dimensional echocardiogram revealed severe asymmetric septal hypertrophy (8.7 mm in diastole). The left atrium was normal in size and all valves appeared normal. Continuous wave Doppler through the left ventricular outflow tract revealed dynamic outflow tract obstruction. Color Doppler demonstrated marked turbulence in the left ventricular outflow tract and a narrow eccentric jet of mitral regurgitation associated with systolic anterior motion of the mitral valve. Magnetic resonance imaging (MRI)2 images of the head were obtained in multiple planes prior to and following contrast3 administration at a dose of 0.1 mmol/kg. In the region of the pituitary gland, there was a T2 hyperintense, T1 hypointense nodule having marked uniform contrast enhancement (Fig 1). This nodule had moderate extension dorsal to the sella turcica and was increased in size compared to a normal pituitary gland: length (0.63 cm), width (0.83 cm), and height (0.85 cm). On T2* weighted (gradient recalled echo) images, some regions of reduced signal and small signal voids were present within the pituitary gland, mostly on the left side, consistent with magnetic susceptibility likely due to regions of hemorrhage within the nodule. Additionally, there was moderate dilation of the entire ventricular system with most severe ventricular enlargement occurring in the fourth ventricle, which caused dorsal elevation and compression of the cerebellum. Findings were most consistent with a pituitary macroadenoma, hydrocephalus, and hydrosyringomyelia. The degree of pituitary enlargement and severity of 4th ventricular dilation did not support obstruction due to the pituitary mass. A cystic accumulation of cerebrospinal fluid (CSF) within the 4th ventricle or obstructive hydrocephalus due to an additional lesion not visible on the MRI could not be ruled out. Figure 1Open in figure viewerPowerPoint Axial MRI images of the brain show a large nodule that is hyperintense on T2W images (A, white arrow), mildly hypointense on T1W images (C, white arrow), and strongly uniformly contrast enhancing (D, white arrow) in the region of the pituitary gland. A T2* gradient recalled echo sequence shows patchy regions of indistinct hypointensity (B, white arrow) with a small region of marked hypointensity or signal void (B, black arrow). A clinical diagnosis of hypersomatotropism was supported by the presence of a pituitary mass and a total serum Insulin-like growth factor 1 (IGF-1) concentration (radioimmunoassay) consistent with the presence of excess growth hormone (GH) secretion (855 ng/mL, RI <700). The cat was humanely euthanized approximately 8 days after the initial presentation due to a lack of response to medical management, which included corticosteroid treatment, mannitol, furosemide, and a proton-pump inhibitor. Histology revealed expansion of the pars distalis by a 0.5 cm diameter, unencapsulated densely cellular neoplasm. The neoplasm was composed of cords and packets of polygonal cells separated by blood filled sinusoids and supported on a fine fibrovascular stroma. Neoplastic cells had oval nuclei with finely stippled chromatin, and a variable amount of finely granular eosinophilic cytoplasm with indistinct cell borders (Fig 2). The cells exhibited mild to moderate anisocytosis and anisokaryosis with a low mitotic index (<1/10 high powered fields), consistent with a pituitary adenoma. Figure 2Open in figure viewerPowerPoint Neoplastic cells vary in their intensity of eosinophilic cytoplasmic staining with many cells resembling acidophils (A). Hematoxylin eosin staining, bar = 200 μm. Neoplastic cells have diffuse cytoplasmic labeling for growth hormone (B), adrenocorticotropic hormone (C), and follicle-stimulating hormone (D). Small numbers of cells within the neoplasm were positively labeled for melanocyte-stimulating hormone (E), while labeling for thyroid-stimulating hormone (F) was not observed. DAB, hematoxylin counterstain, bar = 100 μm. Immunohistochemistry of the neoplasm (Fig 2) revealed strong positive cytoplasmic labeling for GH, which supports a diagnosis of hypersomatotropism caused by a GH secreting pituitary adenoma. Additionally, there was strong positive labeling for ACTH and follicle-stimulating hormone (FSH) as well as a small number of cells within the neoplasm that were positively labeled for melanocyte-stimulating hormone (MSH). Cells with positive labeling for thyroid-stimulating hormone (TSH) were not identified in the neoplasm. The immunohistochemistry findings are consistent with a plurihormonal adenoma. Case 2 A 9-year-old, 7 kg, castrated male Domestic Short-haired cat was presented to Queen Mother Hospital for Animals at the Royal Veterinary College with a 2-month history of weight gain despite a normal appetite. The owner elected to have the cat evaluated for this reason and because a sibling had been previously diagnosed with hypersomatotropism-induced DM. The physical examination was unremarkable except for broad facial features. The CBC and biochemistry profile were unremarkable. The blood glucose measured at the time of admission using a handheld glucometer1 was 251 mg/dL (13.8 mmol/L). The serum fructosamine concentration measured initially and approximately 3 weeks later were both within reference range (233 and 259 μmol/L, respectively, RI 205–322 μmol/L). A repeat blood glucose concentration measured on a chemistry analyzer4 prior to surgery was 165 mg/dL (9.1 mmol/L). The urinalysis revealed a urine specific gravity (USG) of 1.038 and no detectable glucose. The recheck blood glucose concentration, normal fructosamine concentrations, absence of clinical signs compatible with DM, and lack of glucosuria support stress hyperglycemia as the likely cause of isolated hyperglycemia. Two-dimensional echocardiogram revealed mild left ventricular free wall hypertrophy (6.5 mm in diastole). A diagnosis of hypersomatotropism was supported by an increased IGF-1 concentration (1468 ng/mL, RI <700) and subsequent documentation of increased pituitary length (0.63 cm), width (0.65 cm), and height (0.4 cm) with contrast-enhanced5 (2 mL/kg by hand injection) computed tomography6 (CT) (Fig 3). Hypophysectomy was performed, and the pituitary was removed in several pieces. The small pieces were submitted for histology, which revealed nervous tissue most consistent with pars nervosa bordered by a densely cellular proliferation of acidophilic cells. The cells had indistinct borders, finely vacuolated eosinophilic cytoplasm, and large round to oval nuclei, with stippled chromatin and variably prominent nucleoli. The cells were arranged in sheets and displayed mild to moderate anisocytosis, anisokaryosis, and cellular pleomorphism. Immunohistochemistry of the pituitary mass revealed positive cytoplasmic labeling for GH as well as strong positive labeling for ACTH, FSH, and MSH consistent with a plurihormonal adenoma. A clinical diagnosis of hypersomatotropism caused by a GH secreting pituitary adenoma was established on the basis of an increased IGF-1 concentration, pituitary enlargement on CT scan, and the histopathology findings. An inability to control progressive epistaxis that developed post-hypophysectomy resulted in humane euthanasia. A postmortem examination was declined. Figure 3Open in figure viewerPowerPoint Postcontract CT image shows mild enlargement of the pituitary gland (white arrow). Case 3 A 16-year-old, 7 kg, castrated male Domestic Short-haired cat was presented to Queen Mother Hospital for Animals at the Royal Veterinary College with a 5-day history of generalized seizures. The owner had not observed and did not report polyuria or polydipsia. The physical examination revealed mild palmigrade and plantigrade stance and mild pelvic limb muscle atrophy. The neurological examination was unremarkable. The CBC and biochemistry profile were unremarkable with the exception of hyperglycemia 345 mg/dL (19 mmol/L). The urinalysis revealed glucosuria (3+) and a USG of 1.031. Absence of clinical signs suggestive of DM (i.e., weight loss, polyphagia, polyuria, and polydipsia) at the time of presentation and a normal serum fructosamine concentration (253 μmol/L, RI 205–322) make stress the most likely cause of hyperglycemia and resultant glucosuria. MRI7 images of the head before and after the administration of gadolinium8 at a dose of 28 mg/kg revealed pituitary enlargement: length (0.76 cm), width (0.65 cm), and height (0.59 cm). The region of the pituitary was mildly T2 hyperintense, T1 hyperintense, and strongly contrast enhancing (Fig 4). A round area within the left aspect of the pituitary gland was hypointense to surrounding region of the pituitary on the T1 and T2 weighted images. This same region had reduced contrast enhancement on postcontrast T1 weighted images when compared to the surrounding pituitary. Additionally, a focal extra-axial intracranial mass overlying the left temporal lobe, demonstrating marked contrast enhancement with a dural tail sign, compatible with a meningioma was seen. Pituitary enlargement combined with an increased IGF-1 concentration (1902 ng/mL, RI <700) supported a diagnosis of concurrent hypersomatotropism. Approximately 1 month after the initial evaluation, a craniotomy was performed to resect the left temporal lobe tumor. Histology of the tumor was consistent with a fibroblastic meningioma. Phenobarbital was administered postoperatively for approximately 4 weeks. Transition to a high protein and low carbohydrate diet9 was attempted but was not successful due to an unwillingness of the cat to consume the diet. The cat subsequently developed DM 3 months after the initial presentation and insulin treatment was prescribed. The owner declined treatment specifically targeting hypersomatotropism and the cat was humanely euthanized approximately 17 months later. A postmortem examination was declined. Figure 4Open in figure viewerPowerPoint Axial MRI images of the brain show enlargement of the pituitary gland that is mixed hyper and hypo intense on T2W images (A, white arrow), predominantly hyperintense on T1W images (B, white arrow), and strongly contrast enhancing (C, white arrow). A region within the left aspect of the pituitary gland was hypointense to surrounding pituitary on both the T1 and T2 W images. This same region had reduced contrast enhancement on postcontrast T1W images when compared to the surrounding pituitary. A focal, broad based, mildly T2 hypointense, T1 isointense, markedly uniformly contrast enhancing extraaxial mass with regional vasogenic edema is also noted in the left temporal lobe and internal capsule (A–C, black arrow). This case series presents three cats with GH-secreting pituitary adenomas that developed hypersomatotropism without concurrent DM. Hypersomatotropism is a state of excessive production and secretion of GH, which in the cat has been described to be the result of a pituitary acidophilic adenoma, carcinoma, or hyperplasia.1-4 Currently, most cats are diagnosed with hypersomatotropism once they are found to be insulin-resistant unless the clinician routinely screens all diabetic cats for hypersomatotropism shortly after DM is diagnosed. According to screening studies performed in the UK that measured IGF-1 concentrations in a large number of diabetic cats, as many as 26–32% were determined to have hypersomatotropism-induced DM.2, 4, 5 The reason that hypersomatotropism has not been previously reported in cats that are not diabetic is likely because there is a strong and long-standing clinical association between DM and the recognizable physical characteristics of acromegaly. The non-diabetic aspects of this clinical image are slow to appear, often subtle, and can go unrecognized.4 It was not possible to directly demonstrate increased GH concentrations in these cases because a validated method for measuring feline GH was not commercially available at the time these cases were evaluated; however, the diagnosis of hypersomatotropism in both people and cats is routinely made by demonstrating an increased IGF-1 concentration and presence of a pituitary mass or enlargement. In fact, recent practice guidelines for physicians recommend against relying on random GH concentrations to diagnose acromegaly in people.6 Human assays for feline IGF-1 have been validated, are readily available, and are useful for screening because IGF-1 reflects 24-hour GH secretion, parallels changes in GH, and is a sensitive marker for GH excess.4, 7-10 Unlike GH, IGF-1 secretion is not pulsatile which allows a single sample collected at any point during the day to have diagnostic utility. It is generally accepted that an IGF-1 concentration >1000 ng/mL is strongly suggestive of acromegaly in cats, with a positive predictive value of 95%.1, 2, 4 The first cat in this series had immunohistopathologic confirmation of a GH producing pituitary adenoma, but had an IGF-1 below this cutoff. This case supports recent speculation that the currently used arbitrary IGF-1 cutoff value of 1000 ng/mL is too high, underestimates the true prevalence of hypersomatotropism, and leads to underdiagnosis of mild or early forms of the disease.1, 7 This has led some authors to recently suggest considering 800–1000 ng/mL as a "gray zone" that warrants further investigation.7 Although the negative predictive value of an IGF-1 < 1000 ng/mL is low, a case of hypersomatotropism-induced DM with a lower IGF-1 was recently reported4 further supporting the existence of cats with hypersomatotropism that have IGF-1 concentrations below the currently accepted cut-off. It could be argued that the cats being reported were not diabetic because they had incidental or nonfunctional pituitary enlargement; however, the elevated serum IGF-1 concentrations and immunohistochemistry findings argue against such theory, as does the low incidence of incidental pituitary enlargements found in cats. A recent study reported on a cohort of 62 cats undergoing CT imaging for reasons other than pituitary visualization found only one cat (1.6%) with incidental pituitary enlargement.4 Finally, cat 3 ultimately became diabetic. There were also clinical features that could be compatible with the presence of hypersomatotropism: the weight gain seen in cat 2 and the ventricular myocardial hypertrophy and cardiac changes in cats 1 and 2. Additionally, on retrospective MRI assessment of the head features of cat 3, there was increased parietal bone thickness and increased distance between the lateral aspects of the zygomatic arches. These changes have been described in cats with hypersomatotropism.11 The immunohistochemistry findings of cat 1 and cat 2 were consistent with plurihormonal expression across three lineages of adenohypophysial differentiation (ie, corticotrophs, somatotrophs, gonadotrophs). Although plurihormonal expression in pituitary adenomas has been described in people and other domestic animals, there is only a single report of a somatotroph and corticotroph pituitary double adenoma in a cat with DM and hyperadrenocorticism.12, 13 It has been speculated that plurihormonal expression may be more common, but tumors are rarely analyzed immunohistochemically and instead classified by the hormone that dominates the clinical picture. It is important to note that although cat 1 and cat 2 had strong positive labeling for ACTH, neither cat had characteristic features associated with hyperadrenocorticism or ultrasonographic evidence of adrenomegaly. In addition, adrenomegaly was not identified during the postmortem examination of cat 1. To our knowledge, the only discussion of a nondiabetic acromegalic cat was an author's personal experience that was included in a textbook chapter.14 This has resulted in the dogma that all hypersomatotropic cats are insulin-resistant diabetics. It is this dogma and the idea of a "typical" acromegalic phenotype that has likely resulted in very few cats being screened for hypersomatotropism prior to the development of insulin-resistant DM and an acromegalic phenotype. As a result, the true prevalence in nondiabetic cats remains unknown. As in humans, feline hypersomatotropism likely has a gradual-onset and a period during which the GH and IGF-1 concentrations are increased, but DM and signs constituting the syndrome of acromegaly have yet to occur. If the cat does not have dysfunctional pancreatic beta cells, as is suggested to be the case in Type 2 DM, it is likely able to withstand a period of increasing insulin resistance without developing overt DM. This is further substantiated by the fact that most diabetic cats with hypersomatotropism will enter diabetic remission once the somatotrophinoma is removed.5, 15 It is also worth noting that approximately 2/3 of people diagnosed with hypersomatotropism do not become diabetic,16 further suggesting that by focusing only on the diabetic population, we could be missing hypersomatotropic cats prior to the development of overt DM as well as those that may never become diabetic. With recent evidence of a much higher prevalence of hypersomatotropism in diabetic cats than once realized1, 2, 4, 17-19 and an unknown prevalence in cats without DM, more work needs to be done to accurately determine the significance of this endocrinopathy in the general cat population. Hopefully, increased awareness and screening will lead to earlier detection and may allow the occurrence of the syndrome of acromegaly, DM, and conditions associated with progressive pituitary enlargement to be delayed or prevented. Finally, recent advances in our ability to treat hypersomatotropism (e.g., increasing availability of hypophysectomy, stereotactic radiation and Gamma Knife technology, and pasireotide) make early diagnosis and intervention more desirable. Acknowledgments Conflict of Interest Declaration: Authors disclose no conflict of interest. Off-label Antimicrobial Declaration: Authors declare no off-label use of antimicrobials. Footnotes 1 AlphaTrak and AlphaTrak2, Zoetis, Florham Park, NJ 2 Echelon 1.5T, Hitachi Medical Systems America, Twinsburg, OH 3 Magnevist, Bayer Healthcare, Wayne, NJ 4 Stat Profile pHOx Ultra, Nova Biomedical Corporation, Waltham, MA 5 Omnipaque 350, GE Healthcare Ireland, Cork, Ireland 6 Mx8000 IDT 16, Philips, Amsterdam, NL 7 Intera 1.5T, Philips Healthcare, Eindhoven,NL 8 Dotarem, Guerbet, Milton Keynes, UK 9 Hill's Prescription Diet m/d Feline, Hill's (registered trademark) Pet Nutrition, Inc., Topeka, KS, USA References 1Niessen SJM, Church DB, Forcada Y. Hypersomatotropism, acromegaly, and hyperadrenocorticism and feline diabetes mellitus. Vet Clin North Am Small Anim Pract 2013; 43: 319– 350. 2Niessen SJM, Petrie G, Gaudiano F, et al. Feline acromegaly: An underdiagnosed endocrinopathy? J Vet Intern Med 2007; 21: 899– 905. 3Niessen SJM, Khalid M, Petrie G, Church DB. Validation and application of a radioimmunoassay for ovine growth hormone in the diagnosis of acromegaly in cats. Vet Rec 2007; 160: 902– 907. 4Niessen SJM, Forcada Y, Mantis P, et al. Studying cat (Felis catus) diabetes: Beware of the acromegalic imposter. PLoS ONE 2015; 10: e0127794. 5Kenny PJ, Scudder C, Keyte SV, et al. Experiences of a newly established hypophysectomy clinic for treatment of feline hypersomatotropism. J Vet Intern Med 2015; 29: 423– 484 (Abstract). 6Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: An endocrine society clinical practice guideline. J Clin Endocr Metab 2014; 99: 3933– 3951. 7Feldman EC, Nelson RW, Reusch C, Scott-Moncrieff JC. Canine and Feline Endocrinology. St. Louis, MO: Elsevier Saunders; 2014. 8Le Roith D, Bondy C, Yakar S, et al. The somatomedin hypothesis: 2001. Endocr Rev 2001; 22: 53– 74. 9Freda PU. Current concepts in the biochemical assessment of the patient with acromegaly. Growth Horm IGF Res 2003; 13: 171– 184. 10Ribeiro-Oliveira A Jr, Barkan A. The changing face of acromegaly—advances in diagnosis and treatment. Nat Rev Endocrinol 2012; 8: 605– 611. 11Lamb CR, Ciasca TC, Mantis P, et al. Computed tomographic signs of acromegaly in 68 diabetic cats with hypersomatotropism. J Feline Med Surg 2014; 16: 99– 108. 12Kiupel M, Capen C, Miller M, Smedley R. Histological Classification of Tumors of the Endocrine System of Domestic Animals. Washington, DC: Armed Forces Institute of Pathology in cooperation with the CL Davis DVM Foundation and the World Health Organization Collaborating Center for Worldwide Reference on Comparative Oncology; 2008. 13Meij BP, van der Vlugt-Meijer RH, van den Ingh TSGAM, Rijnberk A. Somatotroph and corticotroph pituitary adenoma (double adenoma) in a cat with diabetes mellitus and hyperadrenocorticism. J Comp Pathol 2004; 130: 209– 215. 14Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. St. Louis, MO: Elsevier Saunders; 2004. 15Kenny P, Scudder C, Keyte S, et al. Treatment of feline hypersomatotropism- efficacy, morbidity and mortality of hypophysectomy. J Vet Intern Med 2015; 29: 1257– 1283 (Abstract). 16Wass JAH, Stewart PM. Oxford Textbook of Endocrinology and Diabetes, 2nd ed. Oxford: Oxford University Press; 2011. 17Elliott DA, Feldman EC, Koblik PD, et al. Prevalence of pituitary tumors among diabetic cats with insulin resistance. J Am Vet Med Assoc 2000; 216: 1765– 1768. 18Berg RIM, Nelson RW, Feldman EC, et al. Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly. J Vet Intern Med 2007; 21: 892– 898. 19Niessen SJM, Forcada K, Jensen B, et al. Routine screening of diabetic cats for acromegaly: Overdue or overkill? J Vet Intern Med 2011; 25: 1470– 509 (Abstract). Citing Literature Volume30, Issue4July/August 2016Pages 1216-1221 FiguresReferencesRelatedInformation

A1-year-old female neutered English Cocker Spaniel was presented with a 9 months history of progressive right pelvic limb lameness. Survey radiographs, computed tomography (CT), magnetic resonance imaging (MRI), and joint taps of the pelvis, stifles, hock joints and tarsi, performed before referral, were within normal limits. Medical management with meloxicam did not result in clinical improvement. Treatment with gabapentin, initiated 7 days before presentation, resulted in improvement. General physical examination did not reveal any abnormalities. Neurological examination revealed paraparesis, right pelvic limb lameness, a low tail carriage, proprioceptive deficits expressed by delayed hopping, but intact paw placement in both pelvic limbs, a reduced withdrawal reflex in the right pelvic limb and decreased tail tone. Pain was elicited on lumbosacral palpation, dorsal extension of the tail and extension of both hips. The remainder of the neurological examination was within normal limits. Her neurological lesion was localized to the L4-S3 spinal cord segments. A complete blood count and biochemistry panel were within normal limits. After premedication with methadone (0.2 mg/kg IM) and acepromazine (0.0 1mg/kg IM), anesthesia was induced with propofol (4–6 mg/kg, IV), and maintained with sevoflurane in oxygen. MRI1 of the lumbar and lumbosacral vertebral column was performed with the dog in dorsal recumbency with flexed limbs (ie, frog-leg position). The imaging protocol included sagittal and transverse plane T2-weighted (repetition time (ms) (TR), echo time (ms) (TE), 3000/120), sagittal and dorsal plane T2-weighted short-tau inversion recovery (TR/TE, 3612/80), and transverse plane T2-weighted BAL TGRAD (TR/TE, 7.9/3.9) sequences. Sagittal and transverse plane T1-weighted (T1W TSE) (TR/TE, 400/8) images were acquired before and after IV injection with gadolinium contrast.2 MRI demonstrated possible caudodorsal displacement of the conus medullaris. Mild lumbosacral intervertebral disk protrusion was also seen (Fig 1). After MRI, a CT examination of the lumbosacral vertebral column was performed using a 16-slice scanner.3 After completion of the transverse CT study, sagittal and dorsal reconstructions were made. CT imaging (Fig 2) confirmed the MRI findings and did not reveal any other vertebral or spinal abnormalities. Differential diagnoses included tethered cord syndrome and dynamic lumbosacral vertebral canal stenosis. Given her initial positive response, medical management was continued with gabapentin (10mg/kg, q8h, PO), carprofen (2mg/kg, q12h, PO) and restricted exercise for 4 weeks. A re-examination 4 weeks later demonstrated progression of her clinical signs characterized by more pronounced paraparesis and right pelvic limb lameness. General anesthesia was induced and maintained with the aforementioned protocol. A standard dorsal lumbosacral laminectomy, from L7 to S2 was performed. After opening the vertebral canal, a ligamentous structure was identified between the conus medullaris and the dorsal lamina of S2, which caused caudodorsal displacement and traction of the conus medullaris (Fig 3A,B). After sectioning and sampling the distal aspect of this ligamentous structure, the conus medullaris regained a more cranial position. The wound was closed routinely. Intraoperative analgesia was provided with ketamine (loading dose of 0.5 mg/kg IV followed by a CRI at 10 μg/kg/min IV) and methadone (0.1 mg/kg q4h, IV). Postoperative analgesia consisted of a combination of methadone (0.2 mg/kg, q4h, IV), carprofen (2 mg/kg, q12h, PO) and gabapentin (10 mg/kg, q8h, PO). The dog was discharged from hospitalization 4 days after surgery. The owner was advised to provide strict rest for 4 weeks in combination with gabapentin and carprofen for 2 more weeks. Histopathological evaluation revealed a combination of elastin and collagen fibers in parallel arrangement, confirming the ligamentous nature of the sampled tissue (Fig 3C). The surgical- and histopathological findings were considered diagnostic for tethered cord syndrome associated with a thickened and shortened filum terminale. A neurological examination 4 weeks after surgery revealed marked clinical improvement. At this time, the dog demonstrated mild lameness and proprioceptive deficits in the right pelvic limb. A neurological examination 10 weeks after surgery did not reveal any abnormalities. A telephone interview with the owner and referring veterinary surgeon 8 months after surgery revealed that the dog was free of clinical signs. Tethered cord syndrome (TCS) represents a spectrum of congenital anomalies characterized by an abnormal caudal position and traction of the conus medullaris.1, 2 It can be associated with a variety of spinal malformations, including fatty infiltration of the filum terminale and open and closed forms of spinal dysraphism.3 TCS can, however, also be associated with an abnormally thickened, inelastic, and shortened filum terminale without other spinal or vertebral malformations.3 In people, this is also referred to as true or primary TCS.1, 4 In the case presented here, no other spinal or vertebral malformations were present and caudal traction of the conus medullaris was most likely caused by an abnormally thickened, inelastic, and shortened filum terminale. Although reported in conjunction with an intradural lipoma, myelomeningocele, spina bifida, myeloschisis, and a split cord malformation5-9, this case report, to the best of the authors' knowledge, represents the first veterinary report of TCS associated with a thickened filum terminale. The conus medullaris is the tapered ending of the spinal cord and is continued by a filament, the filum terminale. The filum terminale extends caudally and attaches to a sacral or caudal vertebra.10 Thickening of the filum terminale and subsequent TCS results from abnormal embryological development of the filum terminale during the process of retrogressive differentiation.2 The process of neurulation is not responsible for formation of the entire spinal cord. Distal to the caudal neuropore, undifferentiated cells form the caudal cell mass. This structure will proliferate, canalize, fuse with the neural tube and will eventually develop into the conus medullaris, cauda equina, and filum terminale. The filum terminale forms through regression of the most caudal portion of the caudal cell mass during a process called retrogressive differentiation. A thickened filum terminale may result from incomplete involution of the caudal cell mass.2, 3, 11 The thickened and shortened filum terminale causes progressive and repeated traction on the conus medullaris and caudal spinal cord segments. This results in decreased blood flow and decreased oxidative metabolism of the spinal cord segments just cranial of the inelastic abnormality.1, 12 TCS therefore typically results in progressive dysfunction of the lumbosacral spinal cord segments.1, 2 The degree and reversibility of this dysfunction depends on both the magnitude and duration of the excessive traction.13 In the case reported here, reaching a diagnosis of TCS proved to be very challenging. Interpretation of advanced imaging was subjective and unfortunately inconclusive. A diagnosis of TCS was only confirmed during surgery. In people with TCS, MRI is considered the imaging modality of choice and abnormalities typically include a thickening of the filum terminale and an elongated conus medullaris in an abnormally caudodorsal position.1-3 This radiological definition is difficult to use in dogs, because there is considerable variability in termination of the conus medullaris14 and filum terminale.10 Furthermore, no specific data are available on normal MRI or CT characteristics of the canine filum terminale. A proportion of people with primary TCS present with the conus medullaris in a normal position. This is referred to as occult TCS.15, 16 Considering these arguments, it cannot be excluded the dog described here presented with occult TCS instead of TCS with an abnormal caudodorsal position of the conus medullaris. Performing MRI in different body positions has been evaluated to facilitate diagnosing occult TCS in people. Decreased spinal cord motion between the prone and supine position has been considered suggestive for TCS.15, 17 The dog presented here, recovered completely after surgical transection of the filum terminale. Because untreated TCS will lead to progressive deterioration of neurological function, surgical untethering is considered the treatment of choice in people.1, 16 The goal of surgery is to remove abnormal tension on the spinal cord without causing further trauma.1 In contrast to TCS associated with more complex vertebral malformations, such as spina bifida, transection of a thickened filum terminale is considered a technically straightforward procedure associated with a low postoperative morbidity and good prognosis for recovery. Rethetering with recurrence of clinical signs, caused by arachnoid adhesions, has been reported in a small proportion of surgically treated cases.16-20 In summary, this report described TCS associated with a thickened filum terminale in a dog. Reaching a diagnosis was challenging and surgery resulted in complete clinical recovery. TCS associated with a thickened filum terminale could be considered a rare differential diagnosis for lumbosacral neurological dysfunction in a young dog. Funding: No funding was received for this study. Conflict of Interest Declaration: Authors disclose no conflict of interest. Off-label Antimicrobial Declaration: Authors declare no off-label use of antimicrobials.

A 3-year-old, male neutered Miniature Dachshund was presented for investigation of an acute onset, slowly progressive ataxia of 2 months’ duration. Serum titers for Toxoplasma gondii and Neospora caninum evaluated before referral were negative. General physical examination was within normal limits. Neurological examination identified a “bouncy” generalized ataxia with exaggerated movements of all of the limbs, neck and head. No apparent paresis was present. The dog had proprioceptive deficits in all limbs manifested by a delay in hopping and paw placement. Clinical signs and neurological abnormalities were more severe in the pelvic limbs. The dog had bilaterally decreased menace responses and palpebral reflexes. The remainder of the neurologic examination was within normal limits. A diffuse or multifocal neuro-anatomic localization was considered most likely. Results of a CBC and serum biochemistry profile were within reference intervals. The dog was premedicated with butorphanol (0.2 mg/kg IV) and anesthesia was induced with propofol (3.5 mg/kg IV) and maintained with sevoflurane in oxygen. Magnetic resonance imaging1 (MRI) of the brain and cervical spinal cord included T2-weighted (repetition time, [TR] [ms], echo time [TE] [ms] 3333/110) sagittal and transverse images and transverse fluid attenuation inversion recovery (TR/TE, 6000/120) images. Sagittal and transverse plane T1-weighted images (TR/TE, 515/15) were acquired before and after IV injection of gadolinium contrast material.2 Slice thickness was 3.5 mm in all planes with an interslice gap of 0.9 mm in the sagittal and 1 mm in the transverse planes. No abnormalities were identified on MRI of the brain. In the cervical spinal cord, a linear, intra-parenchymal signal, hyperintense on T2-weighted images, delineated the dorsal funiculus (Fig 1). No contrast enhancement was observed. Differential diagnoses at this time included an inflammatory spinal cord disorder, a neurodegenerative disorder involving the cervical spinal cord, or a sensory neuronopathy. Analysis of cerebrospinal fluid, obtained by cisternal and lumbar punctures was within normal limits. Based on these findings, a sensory neuronopathy was considered the most likely diagnosis. Neurologic re-examination 1 month later identified worsening of the dog's ataxia, decreased patellar reflexes and decreased nociception in the digits of all limbs. Electrodiagnostic evaluation and spinal ganglion biopsy were offered, but declined by the owner. The dog was presented 15 months after its initial clinical presentation for assessment of perceived vision loss and further worsening of clinical signs. There was a known familial history of progressive retinal atrophy. Neurologic examination identified severe deterioration of clinical signs. Although paresis still was not apparent, the severity of the dog's ataxia impeded ambulation. Other findings included wide head and neck excursions, proprioceptive deficits in all limbs, absent bilateral menace responses, absent bilateral palpebral and corneal reflexes, bilaterally decreased responses after stimulation of the nasal mucosa, decreased pupillary light reflexes bilaterally (direct and indirect), absent patellar reflexes bilaterally and decreased nociception in the digits of all limbs. The remainder of the neurologic examination was within normal limits. A complete ophthalmic examination confirmed visual impairment and abnormalities of ocular reflexes as described above. Rudimentary corneal esthesiometry (ie, use of cotton-tipped applicator and the noncontact air-puff technique) indicated decreased corneal sensation. General anesthesia was induced and maintained by using the previously described protocol. A mixed rod-cone electroretinogram3 (ERG) disclosed no visible ERG in the right eye and a markedly diminished ERG in the left eye with barely discernible a and b waves. Findings of the ophthalmic and ERG examinations were in agreement with a presumptive diagnosis of progressive retinal atrophy. Electromyography4 of the left pelvic and thoracic limbs and epaxial musculature identified no abnormalities. Sciatic-tibial motor nerve conduction velocity was within normal limits (57 m/s; reference interval, 55–75 m/s). Tibial sensory nerve conduction velocity was decreased (31 m/s; reference interval, 63.4 ± 5.3 m/s).1 Magnetic resonance imaging of the cervical spinal cord confirmed the previous findings and additionally, identified a hyperintensity on T2-weighted images delineating bilaterally the caudal cerebellar peduncles and cerebellar white matter (Fig 2). Cerebral cortical atrophy also was evident (Fig 2). These findings were considered suggestive for progression of the previously diagnosed presumptive sensory neuronopathy. Based on the findings in a previous case report on sensory neuronopathy in a dog,2 medical treatment was started with cyclosporine (5 mg/kg PO q12h for 6 weeks). Serial neurologic examinations, by the same examiner (SDD), documented continued progression of the dog's clinical signs and development of difficulties prehending food. Because of concerns regarding the dog's quality of life, euthanasia was advised but declined by the owners. Thirty-three months after the initial clinical presentation, at age 5 years and 9 months, the dog died suddenly at home and was presented immediately for a post-mortem examination. The owners reported stabilization of the dog's condition until death after the last visit to our referral institution. Post-mortem examination disclosed poor body condition with decreased muscle mass. Additional abnormalities indicated left-sided congestive heart failure as the most likely cause of death. The spinal cord appeared grossly normal. Histopathologic examination of cervical and thoracic spinal cord sections disclosed a sparsely cellular appearance of the dorsal funiculus. Staining with luxol fast blue identified diffuse myelin loss throughout the dorsal funiculus of the cervical, thoracic and lumbar spinal cord segments (Fig 3A,B) with contracted myelin sheaths and axonal atrophy. Detailed examination of selected spinal ganglia (Fig 3C) identified a decreased number of neuronal cell bodies with a small population of round cells with large dark nuclei and scant cytoplasm. Immunohistochemistry for CD3 and CD79A of the spinal ganglia was largely negative, indicating that the population of round cells most likely represented perineural satellite cells with only rare T lymphocytes (CD3-positive cells). Examination of the brainstem disclosed focally extensive loss of myelin in the lateral cuneate nucleus, the nucleus gracilis, and the medial cuneate nucleus. No other abnormalities were detected in the brainstem. Examination of the cerebellum identified bilateral symmetrical marked demyelination of the cerebellar white matter (Fig 3D) and neuronal cell loss of cerebellar nuclei. Mild lymphoplasmacytic perivascular cuffing also was seen. Examination of the cerebrum confirmed cerebrocortical atrophy with mild enlargement of the lateral ventricles. No other abnormalities were identified in the forebrain or thalamus. Detailed examination of the sciatic nerves, eyes, and optic nerves did not disclose any abnormalities. Detailed examination of the retina unfortunately was not possible because of the presence of postmortem artifacts. Examination of the trigeminal ganglion was not performed. These abnormalities were considered suggestive for neuronal cell loss in the spinal ganglia with secondary axonal and myelin loss in the dorsal funiculus; myelin loss in the nucleus gracilis, medial and lateral cuneate nuclei, cerebellar white matter; and neuronal cell loss in the cerebellar nuclei. The dog's visual impairment most likely was not related to these findings and was attributed to a presumptive diagnosis of progressive retinal atrophy. We describe serial MRI findings in a dog with clinical, electrodiagnostic and pathologic evidence of a disorder selectively affecting some parts of the sensory nervous system. To the best of our knowledge, MRI findings in this type of disorder has not been reported previously. Disorders that selectively affect primary sensory pathways can anatomically be divided into sensory neuronopathies, in which the primary changes occur in the nerve cell bodies or spinal ganglia3 and sensory neuropathies, in which the more distal axon or myelin sheath primarily is affected. Although dogs with sensory neuronopathies and sensory neuropathies can have similar clinical signs, the clinical presentation of dogs with sensory neuronopathies is characterized by an obvious gait abnormality, consisting of a generalized “bouncy” ataxia,3-8 where dogs with pure sensory neuropathies often present predominantly with signs of auto-mutilation.9-15 The dog of this report suffered from a neuronopathy: histopathologic examination revealed abnormalities predominantly in the spinal ganglia. Although no histopathologic abnormalities were found in the sciatic nerves, electrodiagnostic evaluation indicated at least functional involvement of the sensory components of the peripheral nervous system. Sensory neuronopathies rarely occur in dogs, the most common cause being ganglioradiculitis.3-8 Ganglioradiculitis is a disease of unknown etiology affecting adult dogs of several breeds. Histopathologically, it is characterized by mononuclear inflammation of craniospinal sensory ganglia, autonomic ganglia and dorsal nerve roots with secondary Wallerian-like degeneration of the dorsal spinal funiculus.2-8 Clinical signs typically are acute in onset and slowly progressive, consisting of an unusual “bouncy” ataxia that most resembles cerebellar ataxia, generalized proprioceptive deficits, facial and peripheral hypalgesia, decreased patellar reflexes and difficulties prehending food.6 Masticatory muscle atrophy, megaesophagus, dysphagia, loss of vision and loss of hearing also have been reported in dogs with ganglioradiculitis.3-5, 7, 8 Although dogs can present with characteristic clinical signs, reaching a definitive diagnosis of a sensory neuronopathy requires post-mortem evaluation.3-5, 7, 8 Magnetic resonance imaging has been used in people with sensory neuronopathies for diagnosis and assessment of clinical severity.16 Similar to the dog presented here, MRI findings in people with sensory neuronopathies also are characterized by a linear intraparenchymal hyperintensity on T2-weighted images delineating the dorsal funiculus of the cervical spinal cord.16, 17 These selective MRI abnormalities of the dorsal spinal cord columns have been associated with a primary lesion located in the spinal ganglia and dorsal nerve roots.17 The distribution of MRI findings in the dog of this report corresponded well with our histopathologic findings and previously reported pathology reports of dogs with sensory neuronopathies.3-5, 7, 8 A consistent pathologic finding in dogs with sensory neuronopathies is a V-shaped discoloration in the dorsal funiculus of the cervical spinal cord. This finding can be explained by Wallerian-like degeneration throughout the ascending dorsal spinal cord columns secondary to a primary disease process in the spinal ganglia.6 After entering the spinal cord, the general proprioceptive axons concerned with conscious proprioception enter the dorsal funiculus without synapsing and course cranially in the fasciculus gracilis and fasciculus cuneatus, transmitting proprioceptive information respectively for the pelvic and thoracic limbs. The general proprioceptive pathways for cerebellar transmission, however, have a less uniform anatomy. Although most axons synapse near the spinal gray column before coursing cranially in 1 of the spinocerebellar tracts, axons forming the cuneocerebellar tract, similarly to the pathways for conscious proprioception, enter the dorsal funiculus without synapsing and course cranially in the fasciculus cuneatus.6 The linear hyperintense lesion on T2-weighted images restricted to the dorsal funiculus of the cervical spinal cord therefore is likely to represent Wallerian-like degeneration of the dorsal funiculus secondary to a primary disease process affecting the spinal ganglia and dorsal nerve roots. The second MRI study demonstrated hyperintensity on T2-weighted images delineating the caudal cerebellar peduncles. Although it cannot be excluded that the dog presented here suffered from a disorder independently affecting specific parts of the sensory nervous system, this imaging finding can be explained by considering the specific anatomy of the general proprioceptive pathways and the concept of trans-synaptic degeneration. The proprioceptive axons traveling cranially in the dorsal funiculus synapse in the caudal medulla. More specifically, the proprioceptive axons for conscious proprioception synapse in the nucleus gracilis and medial cuneate nucleus, whereas axons of the cuneocerebellar tract synapse in the lateral cuneate nucleus. Axons of neuronal cell bodies in the lateral cuneate nucleus finally enter the cerebellum via the caudal cerebellar peduncle.6 Neurons form interconnected networks, whereby axon terminals of a neuron synapse with other neurons. When a neuron degenerates, afferent and efferent synaptic contacts also degenerate. This process is commonly referred to as trans-synaptic degeneration.18 Considering this neuropathological concept the findings of hyperintensity in the caudal cerebellar peduncles may represent trans-synaptic degeneration caused by progression of the disease process. This hypothesis is supported by the observed histopathologic abnormalities in the nucleus gracilis, medial cuneate nucleus, lateral cuneate nucleus and cerebellar white matter. Histopathologic examination at the light microscopic level, however, identified no distinct abnormalities in the more rostral ascending proprioceptive pathways, such as the medial lemniscus, thalamus and cerebral white matter, explaining the cerebrocortical atrophy apparent on MRI and pathologic examination as a result of trans-synaptic degeneration. In agreement with previous reports, electromyography and motor nerve stimulation studies were within normal limits,4 whereas sensory nerve stimulation identified decreased sensory nerve conduction velocity.5 Although sensory neuronopathies in dogs are characterized by a primary disease process affecting the spinal ganglia and dorsal nerve roots, progression of the disease is expected to result in Wallerian-like degeneration of the more distal portions of the sensory peripheral nerves. Previous reports have identified mild degenerative abnormalities of mixed motor and sensory nerves, such as the sciatic nerves. These abnormalities included axonal loss, dilated myelin sheaths, and infiltration of mononuclear cells.2, 4, 5, 7 In the case presented here, examination of both sciatic nerves identified no abnormalities, making it more difficult to explain the abnormal sensory nerve conduction velocity. The electrodiagnostic evaluation and post-mortem examination, however, were separated by a period of 18 months. Although we cannot exclude that more sensitive diagnostic techniques, such as teased fiber preparations or electron microscopy,5 would have identified abnormalities in the peripheral nerve sections, it is also possible that morphological abnormalities present during the electrodiagnostic evaluation were no longer present at the time of histopathological examination. Although the clinical presentation of the dog of this report was similar to previously reported cases of ganglioradiculitis in dogs, the histopathological findings differed. Mononuclear inflammation of craniospinal ganglia and dorsal nerve roots, considered a histopathologic hallmark in dogs with ganglioradiculitis, was not present in the dog presented here.7 Two possibilities are considered to explain this difference: First, compared to most previously reported cases of ganglioradiculitis in dogs, the dog of this report had an exceptionally long duration of clinical signs before it was presented for post-mortem examination. Inflammation may only be present in the more acute stages of ganglioradiculitis, which subsequently subsides in the chronic stages of the disease, which may result in decreased numbers of neuronal cell bodies without an inflammatory infiltrate. We are aware of only 1 reported case of sensory neuronopathy in a dog with a comparably long duration of clinical signs before a post-mortem examination was performed.3 Interestingly, mononuclear infiltration of the spinal ganglia and dorsal nerve roots was almost nonexistent in this previous case. Secondly, neuronal cell loss without inflammation is a hallmark of neurodegenerative conditions. Therefore, the case described here could represent a novel neurodegenerative condition selectively affecting some parts of the sensory nervous system. In summary, this report described serial MRI findings in a dog with a sensory neuronopathy. Although the clinical signs were similar to ganglioradiculitis, the histopathologic findings differed. It is unclear if this discrepancy was caused by the chronicity of the dog's condition or if these findings are indicative of a novel, most likely neurodegenerative, disease. The authors thank Prof. Ken Smith, Department of Pathology and Pathogen Biology of the Royal Veterinary College, for his assistance in the pathologic and histopathologic examination. Conflict of Interest Declaration: None of the authors of this article has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper. Off-label Antimicrobial Declaration: Authors declare no off-label use of antimicrobials. Funding: No source of funding was received for this report.

Early post-operative neurological deterioration is a well-known complication following dorsal cervical laminectomies and hemilaminectomies in dogs. This study aimed to evaluate potential risk factors for early post-operative neurological deterioration following these surgical procedures. Medical records of 100 dogs that had undergone a cervical dorsal laminectomy or hemilaminectomy between 2002 and 2014 were assessed retrospectively. Assessed variables included signalment, bodyweight, duration of clinical signs, neurological status before surgery, diagnosis, surgical site, type and extent of surgery and duration of procedure. Outcome measures were neurological status immediately following surgery and duration of hospitalisation. Univariate statistical analysis was performed to identify variables to be included in a multivariate model. Diagnoses included osseous associated cervical spondylomyelopathy (OACSM; n = 41), acute intervertebral disk extrusion (IVDE; 31), meningioma (11), spinal arachnoid diverticulum (10) and vertebral arch anomalies (7). Overall 54% (95% CI 45.25-64.75) of dogs were neurologically worse 48 h post-operatively. Multivariate statistical analysis identified four factors significantly related to early post-operative neurological outcome. Diagnoses of OACSM or meningioma were considered the strongest variables to predict early post-operative neurological deterioration, followed by higher (more severely affected) neurological grade before surgery and longer surgery time. This information can aid in the management of expectations of clinical staff and owners with dogs undergoing these surgical procedures.

The common causes of hyperadrenocorticism (HAC) are pituitary ACTH-secreting corticotroph tumours, known as pituitary-dependent hyperadrenocorticism, and cortisol-secreting adrenal tumours. The only licensed medical treatment in the UK is trilostane. This treatment improves the clinical signs of HAC in the majority of cats and dogs. There are a number of alternative treatment options that are available for use in non-responders or as first-line treatment instead of trilostane. After a diagnosis of HAC is made, each option should be discussed with clients. This article discusses medical, surgical and radiotherapy options that should be considered to create an individualised treatment plan for each patient and owner.

Spinal disease in dogs is commonly encountered in veterinary practice. Numerous diseases may cause similar clinical signs and presenting histories. The study objective was to use statistical models to identify combinations of discrete parameters from the patient signalment, history and neurological examination that could suggest the most likely diagnoses with statistical significance. A retrospective study of 500 dogs referred to the Queen Mother Hospital for Animals before June 2012 for the investigation of spinal disease was performed. Details regarding signalment, history, physical and neurological examinations, neuroanatomical localisation and imaging data were obtained. Univariate analyses of variables (breed, age, weight, onset, deterioration, pain, asymmetry, neuroanatomical localisation) were performed, and variables were retained in a multivariate logistic regression model if P<0.05. Leading diagnoses were intervertebral disc extrusion (IVDE, n=149), intervertebral disc protrusion (n=149), ischaemic myelopathy (IM, n=48) and neoplasms (n=44). Multivariate logistic regression characterised IM and acute non-compressive nucleus pulposus extrusions as the only peracute onset, non-progressive, non-painful and asymmetrical T3-L3 myelopathies. IVDE was most commonly characterised as acute onset, often deteriorating, painful and largely symmetrical T3-L3 myelopathy. This study suggests that most spinal diseases cause distinctive combinations of presenting clinical parameters (signalment, onset, deterioration, pain, asymmetry, neuroanatomical localisation). Taking particular account of these parameters may aid decision making in a clinical setting.