Relationship between magnetic resonance imaging findings and histological grade in spinal peripheral nerve sheath tumors in dogs.

BACKGROUND: Peripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location. HYPOTHESIS/OBJECTIVES: Identify magnetic resonance imaging (MRI) features predictive of PNST histologic grade. ANIMALS: Forty-four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation. METHODS: A multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board-certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board-certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis. RESULTS: Forty-four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low-grade), 19 were PNSTs Grade 2 (medium-grade), and 9 were PNSTs Grade 3 (high-grade). Large volume (P = .03) and severe peripheral contrast enhancement (P = .04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade. CONCLUSIONS AND CLINICAL IMPORTANCE: Grade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high-grade PNSTs including tumor size and peripheral contrast enhancement.

Novel association of gluten sensitivity with immune-mediated neuromuscular syndrome in a dog.

Gluten-related disorders in humans comprise different entities, including coeliac disease. Patients typically have measurable titers of anti-gliadin IgG or IgA (AGAs) and anti-transglutaminase-2 IgA (TG2). In addition to intestinal symptoms, human patients often show various neurological complications. In dogs, the neurological manifestation is rarely reported. Here we describe the muscle and nerve biopsies of an 11-year-old, male Border Terrier presenting with lower motor neuron signs submitted for histological examination. Examination of the biopsies showed an oligofocal lymphohistiocytic and plasmocytic myositis and a diffuse neuropathy of mixed nodo-paranodal and demyelinating type. Suspecting a neuromuscular form of breed-related gluten hypersensitivity, measurements of AGAs and TG2 antibodies were performed. Both titers ranged above control values. Hence, a gluten-related neuromyopathy was diagnosed. A gluten-free diet was prescribed and a complete disappearance of clinical signs was observed. Gluten-related disorders should be considered as a differential diagnosis in dogs with intestinal and neuromuscular signs.

Biopsy Characteristics, Subtypes, and Prognostic Features in 107 Cases of Feline Presumed Immune-Mediated Polyneuropathy.

Inflammatory polyradiculoneuropathy (IMPN) is one of the causes of sudden onset of neuromuscular signs such as para-/tetraparesis in young cats. Even though most cases have a favorable outcome, persistent deficits, relapses, and progressive courses are occasionally seen. As clinical presentation does not always appear to predict outcome and risk of recurrence, this study was initiated to screen for prognostic biopsy findings in a large cohort of histologically confirmed IMPN cases with clinical follow-up. In total, nerve and muscle specimens of 107 cats with biopsy diagnosis of presumed autoreactive inflammatory polyneuropathy and 22 control cases were reviewed by two blinded raters for a set of 36 histological parameters. To identify patterns and subtypes of IMPN, hierarchical k-means clustering of 33 histologic variables was performed. Then, the impact of histological parameters on IMPN outcome was evaluated via an univariate analysis to identify variables for the final multivariate model. The data on immediate outcome and follow-up were collected from submitting neurologists using a purpose-designed questionnaire. Hierarchical k-means clustering sorted the tissues into 4 main categories: cluster 1 (44/129) represents a purely inflammatory IMPN picture, whereas cluster 2 (47/129) was accompanied by demyelinating features and cluster 3 (16/129) by Wallerian degeneration. Cluster 4 (22/129) reflects normal tissues from non-neuropathic control cats. Returned questionnaires provided detailed information on outcome in 63 animals. They were categorized into recovered and non-recovered. Thereby, fiber-invasive infiltrates by mononuclear cells and mild fiber loss in intramuscular nerve branches correlated with higher probabilities of recovery. Remyelination in semithin sections, on the other hand, is correlated with a less favorable outcome. Animals grouping in cluster 1 had a tendency to a higher probability of recovery compared to other clusters. In conclusion, diagnosis of feline IMPN from nerve and muscle biopsies allowed for the identification of histologic features that were positively or negatively correlated with outcome.

Clinical Course and Diagnostic Findings of Biopsy Controlled Presumed Immune-Mediated Polyneuropathy in 70 European Cats.

There is a paucity of information on the clinical course and outcome of young cats with polyneuropathy. The aim of the study was to describe the clinical features, diagnostic investigations, and outcome of a large cohort of cats with inflammatory polyneuropathy from several European countries. Seventy cats with inflammatory infiltrates in intramuscular nerves and/or peripheral nerve biopsies were retrospectively included. Information from medical records and follow up were acquired via questionnaires filled by veterinary neurologists who had submitted muscle and nerve biopsies (2011-2019). Median age at onset was 10 months (range: 4-120 months). The most common breed was British short hair (25.7%), followed by Domestic short hair (24.3%), Bengal cat (11.4%), Maine Coon (8.6%) and Persian cat (5.7%), and 14 other breeds. Male cats were predominantly affected (64.3%). Clinical signs were weakness (98.6%) and tetraparesis (75.7%) in association with decreased withdrawal reflexes (83.6%) and, less commonly, cranial nerve signs (17.1%), spinal pain/hyperesthesia (12.9%), and micturition/defecation problems (14.3%). Onset was sudden (30.1%) or insidious (69.1%), and an initial progressive phase was reported in 74.3%. Characteristic findings on electrodiagnostic examination were presence of generalized spontaneous electric muscle activity (89.6%), decreased motor nerve conduction velocity (52.3%), abnormal F-wave studies (72.4%), pattern of temporal dispersion (26.1%) and unremarkable sensory tests. The clinical course was mainly described as remittent (49.2%) or remittent-relapsing (34.9%), while stagnation, progressive course or waxing and waning were less frequently reported. Relapses were common and occurred in 35.7% of the cats' population. An overall favorable outcome was reported in 79.4% of patients. In conclusion, young age at the time of diagnosis and sudden onset of clinical signs were significantly associated with recovery (p < 0.05). Clinical and electrodiagnostic features and the remittent-relapsing clinical course resembles juvenile chronic inflammatory demyelinating polyneuropathy (CIDP), as seen in human (children/adolescents), in many aspects.

Primary orthostatic tremor and orthostatic tremor-plus in dogs: 60 cases (2003-2020).

BACKGROUND: Orthostatic tremor (OT) is a rare movement disorder characterized by high-frequency (>12 Hz) involuntary, rhythmic, sinusoidal movements affecting predominantly the limbs while standing. OBJECTIVE: To describe the signalment, presenting complaints, phenotype, diagnostic findings, treatment, and outcome of a large sample of dogs with OT. ANIMALS: Sixty dogs diagnosed with OT based on conscious electromyography. METHODS: Multicenter retrospective case series study. Dogs were included if they had a conscious electromyography consistent with muscle discharge frequency >12 Hz while standing. RESULTS: Fifty-three cases were diagnosed with primary OT (POT). Giant breed dogs represented most cases (83%; 44/53). Most dogs (79%; 42/53) were younger than 2 years of age at onset of signs, except for Retrievers which were all older than 3.5 years of age. The most common presenting complaints were pelvic limb tremors while standing (85%; 45/53) and difficulty when rising or sitting down (45%; 24/53). Improvement of clinical signs occurred in most dogs (85%; 45/53) treated medically with phenobarbital, primidone, gabapentin, pregabalin or clonazepam, but it was mostly partial rather than complete. Orthostatic tremor-plus was seen in 7 dogs that had concurrent neurological diseases. CONCLUSIONS AND CLINICAL IMPORTANCE: Primary OT is a progressive disease of young, purebred, giant/large-breed dogs, which appears to begin later in life in Retrievers. Primary OT apparently responds partially to medications. Orthostatic tremor-plus exists in dogs and can be concomitant or associated with other neurological diseases.

Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi-center randomized parallel group clinical study.

BACKGROUND: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. OBJECTIVES: To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. ANIMALS: Client-owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus. METHODS: Randomized parallel group clinical trial. Patients were randomly allocated to the IN-MDZ (n = 21) or IV-MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for ≥10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at α < .05. RESULTS: IN-MDZ and IV-MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P = .34). The median seizure cessation time was 33 and 64 seconds for IN-MDZ and IV-MDZ, respectively (P = .63). When the time to place an IV catheter was taken into account, IN-MDZ (100 seconds) was superior (P = .04) to IV-MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN-MDZ and IV-MDZ, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account.

Comparison of signalment and computed tomography findings in French Bulldogs, Pugs, and English Bulldogs with and without clinical signs associated with thoracic hemivertebra.

BACKGROUND: Although thoracic hemivertebra can cause neurological signs, they occur commonly in neurologically normal dogs. OBJECTIVES: To evaluate whether computed tomography (CT) findings and factors associated with signalment can be used to differentiate between dogs with and without neurological signs associated with hemivertebra. ANIMALS: One hundred sixty dogs with ≥1 hemivertebrae were retrospectively studied. This group consisted of 40 dogs with clinical signs caused by hemivertebra and 40 French Bulldogs, 40 Pugs, and 40 English Bulldogs that underwent CT for reasons unrelated to neurological disease. METHODS: All dogs underwent CT and affected dogs also underwent magnetic resonance imaging. All CT studies were randomly evaluated by an observer blinded to signalment and clinical status. The following variables were evaluated: presence, number, location, and subtype of hemivertebra; presence of vertebral subluxation; severity of vertebral canal stenosis; presence, location, and severity of kyphosis, and number of vertebrae involved in the kyphotic segment. Statistical modeling was performed to identify factors associated with clinical status. RESULTS: Pug breed (odds ration [OR], 10.8; P = .01), more severe kyphosis (OR, 1.1 per grade increase; P < .001), fewer instead of more observed hemivertebrae (OR, 0.8; P = 0.03), and ventrolateral hypoplasia hemivertebra subtype (OR, 4.0; P = .011) were associated with higher likelihood of neurological disease. A Cobb angle of 34.5 degrees corresponded with the highest combined sensitivity and specificity to differentiate between clinically affected and unaffected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The variables identified could aid in differentiating between clinically relevant and irrelevant hemivertebra in small breed brachycephalic dogs.

Ventral stabilization of thoracic kyphosis through bilateral intercostal thoracotomies using SOP (String of Pearls) plates contoured after a 3-dimensional print of the spine.

OBJECTIVE: To describe a novel vertebral body stabilization and report its outcome in dogs with thoracic kyphosis and secondary myelopathy. STUDY DESIGN: Case series. ANIMALS: Six pugs with thoracic kyphosis and secondary myelopathy. METHODS: Medical records (2012-2017) of dogs with chronic progressive pelvic limb ataxia and ambulatory proprioceptive paraparesis due to thoracic kyphosis were reviewed. Dogs were evaluated via MRI and computed tomography. A 3-dimensional print of the kyphotic vertebral segment was used to precontour the SOP (String of Pearls) plates. Bilateral double, dorsal intercostal thoracotomies were performed to place precontoured SOP on the vertebral bodies. Long-term (6-16 months) clinical outcome was determined on the basis of neurological scoring (NS) and owner questionnaire. RESULTS: The only intraoperative complication consisted of a lung laceration due to preexisting adhesions. Postoperative complications included seroma formation (n = 2) and incidental radiographic evidence of screw breakage (n = 2). NS at presentation ranged between 2 and 4 and improved to 1 at long-term follow-up in all dogs but 1 (NS = 2). All owners felt that their dog had excellent quality of life at follow-up. CONCLUSION: In spite of the challenging local anatomy, all dogs undergoing vertebral stabilization with SOP placement experienced a good clinical outcome. CLINICAL SIGNIFICANCE: Stabilization of vertebral bodies with precontoured SOP placed through bilateral thoracotomies may be considered as a treatment option for dogs with thoracic kyphosis and secondary myelopathy.

Ventral Slot Surgery to Manage Cervical Intervertebral Disc Disease in Three Cats.

OBJECTIVE: This case series describes the clinical presentation, management and outcome of three cats diagnosed with cervical intervertebral disc disease that underwent decompressive ventral slot surgery. METHODS: This is a retrospective case series evaluating client-owned cats undergoing a ventral slot surgical procedure to manage cervical intervertebral disc disease (n = 3). RESULTS: A routine ventral slot surgery was performed in each case without complication, resulting in postoperative neurological improvement in all three cases. CLINICAL SIGNIFICANCE: Ventral slot surgery can be used to achieve effective cervical spinal cord decompression with a good long-term outcome in the management of feline cervical intervertebral disc herniation. To avoid creating an excessively wide slot with the potential for postoperative complications including vertebral sinus haemorrhage, vertebral instability or ventral slot collapse, careful surgical planning was performed with preoperative measurement of the desired maximum slot dimensions.

Nodo-paranodopathy, internodopathy and cleftopathy: Target-based reclassification of Guillain-Barré-like immune-mediated polyradiculoneuropathies in dogs and cats.

Recent views on Guillain-Barré syndrome (GBS) question the accuracy of classification into axonal and demyelinating subtypes that represent convergent neurophysiological phenotypes rather than immunological targets. Instead it has been proposed to clarify the primarily affected fibre subunit in nerve biopsies. As nerve biopsies rarely are part of routine work-up in human patients we evaluated tissues taken from companion animals affected by GBS-like polyradiculoneuropathy to screen for distribution of immune cells, targeted fibre components and segregating non-inflammatory lesions. We identified that immune responses were directed either at Schmidt-Lanterman clefts, the paranode-node complex or both. Based on infiltrative and non-inflammatory changes, four subtypes and/or stages were distinguished, some of which indicate localisation of primary target antigens while others represent convergent late stage pictures, as a consequence to epitope spreading. The impact of histological subtyping onto clinical management and prognosis remains to be evaluated in future clinical trials. Natural development and clinical manifestation of large animal dysimmune neuropathy may reflect human Guillain-Barré syndrome more accurately than experimental models and therefore provide complementary clues for translational research.

Imaging diagnosis--degenerative intraspinal cyst associated with an intervertebral disc.

A 6-year-old neutered male Rottweiler had chronic episodic signs of thoracolumbar pain and inability to stand that did not improve after rest and nonsteroidal antiinflammatory medication. In magnetic resonance images, an extradural mass was identified between the spinal cord and the T13/L1 intervertebral disc; the mass was compressing the cord in a dorsoventral direction. The lesion had a low signal intensity rim that enhanced slightly after gadolinium administration, and contents with similar signal intensity to cerebrospinal fluid. The lesion was removed surgically by severing its attachments to the annulus fibrosus. The histologic diagnosis was degenerative intraspinal cyst. The origin of such cysts, and their relationship to synovial and ganglion cysts is discussed.

Results of magnetic resonance imaging in 14 cats with meningoencephalitis.

Medical records and magnetic resonance (MR) images of 14 cats with inflammatory diseases affecting the central nervous system (CNS) were reviewed retrospectively. Cases included eight cats with feline infectious peritonitis and two cats with toxoplasmosis. Abnormalities affecting the CNS were observed in MR images in 10 (71%) cats. Intracranial lesions appeared as slightly hypointense foci in T1-weighted images in two (14%) cats, as hyperintense foci in T2-weighted images in seven (50%) cats and as hyperintense foci after intravenous administration of a gadolinium-based contrast medium in 10 (71%) cats. In six cats with lesions in T1- and/or T2-weighted images, additional lesions were visible in T1-weighted images obtained after gadolinium-based contrast medium administration. In three cats, lesions were visible only after contrast medium administration. In our study, MR imaging (MRI) did not appear to detect all cases of CNS inflammation in the population of cats with inflammatory cerebrospinal fluid (CSF); however, MRI adds information about the sites and morphology of intracranial lesions that should help to distinguish between neoplasia and inflammatory conditions and, possibly, between different inflammatory conditions.

Notochordal cell produce and assemble extracellular matrix in a distinct manner, which may be responsible for the maintenance of healthy nucleus pulposus.

STUDY DESIGN: Analysis of proteoglycan synthesis, distribution and assembly of notochordal cells and small nucleus pulposus cells embedded in alginate beads and cultured in presence of [S]-Na2SO4. OBJECTIVE: To determine whether the degeneration of the nucleus pulposus of the intervertebral disc is associated with a change in the cell phenotype. SUMMARY OF BACKGROUND DATA: The loss of the notochordal cell from the nucleus pulposus is associated with ageing and disc degeneration. The reduction in their numbers after birth in humans and in the chondrodystrophoid dog has been suggested to result from cell death and replacement or differentiation by chondrocytes. The almost total disappearance of the notochordal cells in the nucleus pulposus correlates with early degenerative changes in the disc and a concomitant reduction in proteoglycan content, increased collagen, and loss of water content. The basic mechanism of this accelerated degeneration with ageing is poorly understood. METHODS: Nucleus pulposus and anulus fibrosus cells were isolated from the lumbar intervertebral discs of chondrodystrophoid and nonchondrodystrophoid dogs. The cells from the nucleus pulposus were further separated by size into notochordal cells and small nucleus pulposus cells. Cells were embedded in alginate beads and cultured in the presence of [S]-Na2SO4 to measure proteoglycan size, rate of synthesis, and distribution into the pericellular and intercellular compartments. RESULTS: Large notochordal cells in the nucleus pulposus of chondrodystrophoid dogs formed 13% of the cell population in young dogs and fell to 0.4% in adults, whereas they were the predominant cell type in the nonchondrodystrophoid dogs at all ages. These cells were capable of 1.5-fold greater rate of synthesis of proteoglycans than the small nucleus pulpous cells. Proteoglycans secreted by the large cells were evenly distributed between the pericellular and intercellular compartments,whereas the small cells distributed 3-fold more proteoglycan into the intercellular phase. By size exclusion chromatography, the proteoglycans synthesized by the small cells of the chondrodystrophoid dogs formed large-size aggregates (Kav = 0.1) within the pericellular region, which then moved to the intercellular region over 5 to 10 days. In contrast, proteoglycans secreted by the notochordal cells were capable of rapid migration to the intercellular phase before assembly into large-sized aggregates. The ability to form aggregates was independent of age of the animal. CONCLUSIONS: Our model shows that a change in intervertebral disc cell phenotype correlates with the grade of disc degeneration and that the notochordal cells synthesize proteoglycans, which exhibit delayed aggregation than those synthesized by the small nucleus pulposus cells. This implies that the cell type composition of the nucleus pulposus of the chondrodystrophoid and nonchondrodystrophoid dogs produces an extracellular matrix that is assembled in a distinct manner, which may affect tissue integrity.

Utility of magnetic resonance imaging for distinguishing neoplastic from non-neoplastic brain lesions in dogs and cats.

The aim of this study was to identify magnetic resonance (MR) signs that aid differentiation of neoplastic vs. non-neoplastic brain diseases in dogs and cats. MR images of 36 dogs and 13 cats with histologic diagnosis of intracranial disease were reviewed retrospectively. Diagnoses included 30 primary and three metastatic brain tumors, 11 infectious/inflammatory lesions, three vascular, one degenerative disease, and one developmental malformation. Upon univariate analysis of 21 MR signs, there were seven that had a significant association with neoplasia: single lesion (P = 0.004), shape (P = 0.015), mass effect (P = 0.002), dural contact (P = 0.04), dural tail (P = 0.005), lesions affecting adjacent bone (P = 0.008), and contrast enhancement (P = 0.025). Increasing age was also found to be associated with neoplasia (P = 0.0001). MR signs of non-neoplastic brain diseases in dogs and cats were more variable than those of brain neoplasia.

Magnetic resonance imaging findings in 25 dogs with inflammatory cerebrospinal fluid.

To describe the signs that may be associated with intracranial inflammatory conditions, magnetic resonance (MR) images of 25 dogs that had inflammatory cerebrospinal fluid (CSF) were mixed with those of a control group of 40 dogs that had CSF negative for inflammatory disease and reviewed without knowledge of the clinical signs or diagnosis. CSF was considered inflammatory if the protein level was > 0.25 g/l and the white cell count was > 5 mm(-3). Abnormalities were found by MR imaging in 19 (76%) dogs with inflammatory CSF. Two dogs had focal lesions, 10 had multifocal lesions, and seven had diffuse lesions. Lesions affected all divisions of the brain. Mass effect was identified in seven (28%) dogs, including one that had a choroid plexus carcinoma. Lesions were hyperintense in T2-weighted images in 18 dogs and hypointense in T1-weighted images in six dogs. Multifocal or diffuse intraaxial lesions that were hyperintense in T2-weighted images were observed in 17 (68%) dogs with inflammatory CSF. Administration of gadolinium resulted in enhancement of intraaxial lesions in nine (36%) dogs and enhancement of meninges in seven (28%) dogs. Six (24%) dogs with inflammatory CSF had images interpreted as normal.