Clinical, magnetic resonance imaging, surgical features and comparison of surgically treated intervertebral disc extrusion in French bulldogs.

Intervertebral disc (IVD) extrusion (IVDE) is the most reported neurological condition in French bulldogs (FBD). The aim of this study was to retrospectively evaluate neurological grade, magnetic resonance imaging (MRI), surgical findings and short-term recovery in surgically treated FBD diagnosed with IVDE referred to a single institution between January 2020 and March 2022 and to compare cervical and thoracolumbar IVDE. Data was gathered from medical records and analysed via Fischer's Exact-Test and Kruskal Wallis-tests. Statistical significance was assumed when p < 0.05. Thirty-nine FBD were diagnosed with IVDE. Cervical IVDE (C-IVDE) was diagnosed in 11/39 cases; the C3-C4 IVD space was the most commonly affected site (5/11). Thoracolumbar IVDE (TL-IVDE) was diagnosed in 28 cases; the L3-L4 IVD space was the most commonly affected site (7/28). At admission, C-IVDE was significantly associated with less severe neurological grade (grade 1-2) compared to TL-IVDE (grade 2-5) (p < 0.001). The extruded IVD material (EIVDM) was hypointense in T2w images in 11/11C-IVDE vs. 2/28TL-IVDE, and hypointense in T1w images in 10/11C-IVDE vs. 1/28TL-IVDE. The EIVDM was hyperintense in T2w images in 0/11C-IVDE vs. 26/28TL-IVDE and iso-to-hypointense in T1w images in 1/11C-IVDE vs. 27/28TL-IVDE (p < 0,001). The EIVDM extended over ≥2 IVD spaces in 0/11C-IVDE vs. 19/28TL-IVDE (p < 0,001). 10/11C-IVDE underwent single ventral slot, 1/11C-IVDE underwent unilateral cervical hemilaminectomy. All TL-IVDE underwent unilateral hemilaminectomy and 19/28TL-IVDE underwent unilateral hemilaminectomy over ≥2 IVD spaces (p < 0,001). Haemorrhagic EIVDM was noticed intraoperatively in 1/11C-IVDE vs. 28/28TL-IVDE (p < 0,001). Spinal cord compression was mild in 2/11C-IVDE and 3/28TL-IVDE; moderate in 9/11C-IVDE and 16/28TL-IVDE; severe in 0/11C-IVDE and 8/28TL-IVDE. There was no spinal cord compression in 1/28TL-IVDE with foraminal IVDE. There was no statistical difference between spinal cord compression and IVDE location (p = 0.112). The mean time to improvement was 1.1 day in C-IVDE (range 1-2 days). 90.1% of C-IVDE improved within the first 24 h. The mean time to improvement was 2.1 days in TL-IVDE (range from 1 day to 4 days). All dogs that did not improve (5/39) were grade 5 TL-IVDEs at presentation. In FBD, TL-IVDE tended to cause higher grade of neurological dysfunction, tended to result in compression of neural structures over multiple IVD spaces and required more extensive surgical treatment than C-IVDE.

Case Report: A Novel Lateral Approach to the C7, C8, and T1 Intervertebral Foramina for Resection of Malignant Peripheral Nerve Sheath Neoplasia, Followed by Adjunctive Radiotherapy, in Three Dogs.

This case report describes the diagnosis, management and outcome of three dogs with peripheral nerve sheath tumors (PNSTs) involving the brachial plexus, C7 (case 1), C8 (case 2), and C8 and T1 (case 3) spinal nerves and nerve roots with intrathoracic invasion. Surgical resection required thoracic limb amputation and removal of the first rib, facilitating a novel lateral approach to the spinal nerves and foramina in all cases. This was followed by hemilaminectomy and rhizotomy in cases 1 and 2. Adjunctive radiotherapy was then performed in all dogs. All three dogs regained a good quality of life in the short-term following surgery. Two were euthanased after 3 and 10 months, following detection of a pulmonary mass in one case and multiple thoracic and abdominal masses in the other. The third dog was alive and well at the time of writing (7 months post-surgery). This surgical approach facilitated good access and allowed gross neoplastic tissue to be resected. The ease of surgical access was dependent, to a degree, on the size of the patient. This surgical approach can be considered in cases of PNSTs involving the caudal cervical or cranial thoracic spinal nerves and nerve roots. Adjunctive radiotherapy should be considered as part of a multi-modal approach to these challenging tumors due to the difficulty of achieving clean margins, particularly proximally, even with optimal surgical access.

Paraneoplastic ganglioradiculoneuritis in a cat with a plasma cell tumour.

CASE SUMMARY: An 8-year-old neutered female domestic longhair cat was presented for investigation of a 48 h history of lethargy and pelvic limb ataxia. MRI of the spinal cord and vertebral column (C1 to sacrum) and brain was unremarkable. Lumbar cerebrospinal fluid analysis revealed pleocytosis and increased protein concentration. Thoracic radiographs and abdominal ultrasound were unremarkable. Anti-inflammatory doses of prednisolone were administered. Clinical deterioration occurred over the following 2 days, with the development of lower motor neuron deficits in both thoracic limbs. On repetition of the MRI, bilateral enlargement, T2-weighted hyperintensity, and marked contrast enhancement of the C7, C8 and T1 nerve roots, spinal nerves and brachial plexuses were observed. Infectious disease testing was negative. An immune-mediated inflammatory process was suspected and immunosuppressive doses of prednisolone were commenced. The clinical signs improved transiently, but marked deterioration occurred after 2 weeks. The patient was euthanased and a post-mortem examination was performed. A lymphocytic inflammatory infiltrate was detected in the C7, C8 and T1 nerve roots and dorsal root ganglia, and neoplastic plasma cells were identified in multiple organs. A diagnosis of non-cutaneous extramedullary plasmacytoma with multiorgan involvement and paraneoplastic ganglioradiculoneuritis was reached. RELEVANCE AND NOVEL INFORMATION: Paraneoplastic ganglioradiculoneuritis in association with a plasma cell neoplasia has not been previously reported in the cat and should be considered as a differential diagnosis for cats with clinical or imaging evidence of an inflammatory process affecting the nerve roots, spinal nerves or brachial plexuses.

Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats.

OBJECTIVES: The study objective was to investigate the prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. METHODS: The medical records of two veterinary referral clinics from 2007 to 2017 were searched for cats fulfilling the inclusion criteria of a diagnosis of epilepsy, treatment with phenobarbitone and available follow-up information on the occurrence of adverse effects. Follow-up information was obtained from the medical records of the primary veterinarian and referral institutions and a questionnaire completed by the cats' owners. RESULTS: Seventy-seven cats met the inclusion criteria. Fifty-eight were affected by idiopathic epilepsy and 19 by structural epilepsy. One or more of the following adverse effects were reported in 47% of the cats: sedation (89%); ataxia (53%); polyphagia (22%); polydipsia (6%); polyuria (6%); and anorexia (6%). Logistic regression analyses revealed significant associations between adverse effect occurrence and both phenobarbitone starting dosage and administration of a second antiepileptic drug (AED). For each 1 mg/kg q12h increment of phenobarbitone, the likelihood of adverse effects increased 3.1 times. When a second AED was used, the likelihood of adverse effects increased 3.2 times. No association was identified between epilepsy aetiology and adverse effect occurrence. An idiosyncratic adverse effect, characterised by severe neutropenia and granulocytic hypoplasia, was diagnosed in one cat. This resolved following phenobarbitone discontinuation. CONCLUSIONS AND RELEVANCE: The prevalence of phenobarbitone-associated adverse effects was 47%. Sedation and ataxia were most common. These are type A adverse effects and are predictable from phenobarbitone's known pharmacological properties. In the majority of cases, adverse effects occurred within the first month of treatment and were transient. Idiosyncratic (type B) adverse effects, which were not anticipated given the known properties of the drug, occurred in one cat. Increased phenobarbitone starting dosage and the addition of a second AED were significantly associated with the occurrence of adverse effects.

Congenital sensorineural deafness in English setters in the United Kingdom: prevalence and association with phenotype and sex.

BACKGROUND: The English setter (ES) is predisposed to congenital sensorineural deafness (CSD). CSD prevalence and association with phenotype in the UK ES population are previously unreported. METHODS: The database of the authors' institution was searched for ES puppies undergoing brainstem auditory evoked response (BAER) testing for CSD screening (2000-2018). Inclusion criteria were BAER performed at 5-10 weeks of age, testing of complete litters and available phenotypic data. The age, sex, presence of patches at birth, coat colour, iris colour, hearing status and BAER-determined parental hearing status of each puppy were recorded. Multivariable binary logistic regression was performed to determine the significance of these variables as predictors for the likelihood of puppies being unilaterally or bilaterally deaf. RESULTS: Inclusion criteria were met for 447 puppies. Hearing was bilaterally normal in 427 (95.5 per cent) puppies. The prevalence of unilateral and bilateral CSD was 3.6 per cent and 0.9 per cent, respectively. Females were 3.3 times more likely to be deaf than males, and puppies with both parents of unknown hearing status were 4.6 times more likely to be deaf than those with at least one normal parent. CONCLUSION: The prevalence of CSD was 4.5 per cent, with female puppies and those with two parents of unknown hearing status at greatest risk.

Life cycle of a star: Carl Sagan and the circulation of reputation.

It is a commonplace in the history of science that reputations of scientists play important roles in the stories of scientific knowledge. I argue that to fully understand these roles we should see reputations as produced by communicative acts, consider how reputations become known about, and study the factors influencing such processes. I reapply James Secord's 'knowledge-in-transit' approach; in addition to scientific knowledge, I also examine how 'biographical knowledge' of individuals is constructed through communications and shaped by communicative contexts. My case study is Carl Sagan, widely discussed - amongst scientists, media professionals and publics - for his skill as a charismatic popularizer, his perceived arrogance, his political activism, and his debated merit as a researcher. By examining how aspects of Sagan's reputation circulated alongside his scientific work - rather than existing as a static context for his scientific work - I show how different forms of knowledge (biographical and scientific) influence each other as they circulate.

Diverse landscapes beneath Pine Island Glacier influence ice flow.

The retreating Pine Island Glacier (PIG), West Antarctica, presently contributes ~5-10% of global sea-level rise. PIG's retreat rate has increased in recent decades with associated thinning migrating upstream into tributaries feeding the main glacier trunk. To project future change requires modelling that includes robust parameterisation of basal traction, the resistance to ice flow at the bed. However, most ice-sheet models estimate basal traction from satellite-derived surface velocity, without a priori knowledge of the key processes from which it is derived, namely friction at the ice-bed interface and form drag, and the resistance to ice flow that arises as ice deforms to negotiate bed topography. Here, we present high-resolution maps, acquired using ice-penetrating radar, of the bed topography across parts of PIG. Contrary to lower-resolution data currently used for ice-sheet models, these data show a contrasting topography across the ice-bed interface. We show that these diverse subglacial landscapes have an impact on ice flow, and present a challenge for modelling ice-sheet evolution and projecting global sea-level rise from ice-sheet loss.

A mitochondrial location for haemoglobins--dynamic distribution in ageing and Parkinson's disease.

Haemoglobins are iron-containing proteins that transport oxygen in the blood of most vertebrates. The mitochondrion is the cellular organelle which consumes oxygen in order to synthesise ATP. Mitochondrial dysfunction is implicated in neurodegeneration and ageing. We find that α and ß haemoglobin (Hba and Hbb) proteins are altered in their distribution in mitochondrial fractions from degenerating brain. We demonstrate that both Hba and Hbb are co-localised with the mitochondrion in mammalian brain. The precise localisation of the Hbs is within the inner membrane space and associated with inner mitochondrial membrane. Relative mitochondrial to cytoplasmic ratios of Hba and Hbb show changing distributions of these proteins during the process of neurodegeneration in the pcd(5j) mouse brain. A significant difference in mitochondrial Hba and Hbb content in the mitochondrial fraction is seen at 31 days after birth, this corresponds to a stage when dynamic neuronal loss is measured to be greatest in the Purkinje Cell Degeneration mouse. We also report changes in mitochondrial Hba and Hbb levels in ageing brain and muscle. Significant differences in mitochondrial Hba and Hbb can be seen when comparing aged brain to muscle, suggesting tissue specific functions of these proteins in the mitochondrion. In muscle there are significant differences between Hba levels in old and young mitochondria. To understand whether the changes detected in mitochondrial Hbs are of clinical significance, we examined Parkinson's disease brain, immunohistochemistry studies suggest that cell bodies in the substantia nigra accumulate mitochondrial Hb. However, western blotting of mitochondrial fractions from PD and control brains indicates significantly less Hb in PD brain mitochondria. One explanation could be a specific loss of cells containing mitochondria loaded with Hb proteins. Our study opens the door to an examination of the role of Hb function, within the context of the mitochondrion-in health and disease.