Randomized Controlled Trial of Durotomy as an Adjunct to Routine Decompressive Surgery for Dogs With Severe Acute Spinal Cord Injury.

Although many interventions for acute spinal cord injury (SCI) appear promising in experimental models, translation directly from experimental animals to human patients is a large step that can be problematic. Acute SCI occurs frequently in companion dogs and may provide a model to ease translation. Recently, incision of the dura has been highlighted in both research animals and human patients as a means of reducing intraspinal pressure, with a view to improving perfusion of the injured tissue and enhancing functional recovery. Observational clinical data in humans and dogs support the notion that it may also improve functional outcome. Here, we report the results of a multi-center randomized controlled trial of durotomy as an adjunct to traditional decompressive surgery for treatment of severe thoracolumbar SCI caused by acute intervertebral disc herniation in dogs. Sample-size calculation was based on the proportion of dogs recovering ambulation improving from an expected 55% in the traditional surgery group to 70% in the durotomy group. Over a 3.5-year period, we enrolled 140 dogs, of which 128 had appropriate duration of follow-up. Overall, 65 (51%) dogs recovered ambulation. Recovery in the traditional decompression group was 35 of 62 (56%) dogs, and in the durotomy group 30 of 66 (45%) dogs, associated with an odds ratio of 0.643 (95% confidence interval: 0.320-1.292) and z-score of -1.24. This z-score indicates trial futility to reach the target 15% improvement over traditional surgery, and the trial was terminated at this stage. We conclude that durotomy is ineffective in improving functional outcome for severe acute thoracolumbar SCI in dogs. In the future, these data can be compared with similar data from clinical trials on duraplasty in human patients and will aid in determining the predictive validity of the "companion dog model" of acute SCI.

Diagnostic utility of serum bile acids in dogs presenting with epileptic seizures consistent with a tier 1 confidence level diagnosis of idiopathic epilepsy.

BACKGROUND: The International Veterinary Epilepsy Task Force consensus guidelines recommend performing fasting serum bile acid (SBA) and/or serum ammonia measurements as part of a tier 1 diagnosis of idiopathic epilepsy in dogs. The aim of this retrospective study was to determine the diagnostic utility of fasting SBA in this population. METHODS: Dogs that met the tier 1 confidence level diagnosis of idiopathic epilepsy, with the additional requirement of both fasting and 2-hour postprandial SBA measurements, were included. The incidence of significant hepatopathies and usefulness of dynamic SBA testing and minimum database results were analysed. RESULTS: A total of 233 dogs were included. All dogs diagnosed with clinically significant hepatopathy had elevations in postprandial SBA, with eight of 14 (57.14%) showing elevations in fasting SBA. The prevalence of clinically significant hepatopathies that could have been missed without using postprandial SBA measurement was 1.29%. LIMITATIONS: The further investigations performed were not uniform and there were limitations in the ability to control sampling techniques due to the retrospective nature of this study. Investigations into hepatopathy were not standardised across this study population. CONCLUSIONS: This study documents the importance of postprandial SBA measurements in the detection of hepatopathies and reveals that non-dynamic blood sampling has a negative predictive value of 91% for detecting elevated postprandial SBA, specific to dogs meeting the tier 1 confidence level diagnosis of idiopathic epilepsy.

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.

Clinical presentation, diagnostic findings and outcome of dogs undergoing surgical resection for intracranial meningioma: 101 dogs.

BACKGROUND: Meningioma is the most common primary brain neoplasm in dogs. Further information is required regarding the expected long-term prognosis of dogs following the surgical resection of an intracranial meningioma together with the influence of adjunctive therapies. Whilst there have been several studies reporting the long-term outcome of intracranial meningioma resection following surgery alone, surgery with the use of an ultrasonic aspirator, surgery combined with radiotherapy and surgery combined with the addition of hydroxyurea, it is currently unclear which type of adjunctive therapy is associated with the most favourable outcomes. The objective of this study is to describe the presentation and outcome of dogs undergoing surgery for the resection of an intracranial meningioma and the effect of clinical factors, adjunctive therapies and meningioma histopathological subtype on the long-term outcome. RESULTS: A hundred and one dogs that had intracranial surgery for meningioma resection were investigated from four referral centres. 94% of dogs survived to hospital discharge with a median survival time of 386 days. Approximately 50% of dogs survived for less than a year, 25% survived between 1 and 2 years, 15% survived between 2 and 3 years and 10% survived for greater than 3 years following discharge from hospital. One or more adjunctive therapies were used in 75 dogs and the analysis of the data did not reveal a clear benefit of a specific type of adjunctive therapy. Those dogs that had a transfrontal approach had a significantly reduced survival time (MST 184 days) compared to those dogs that had a rostrotentorial approach (MST 646 days; p < 0.05). There was no association between meningioma subtype and survival time. CONCLUSIONS: This study did not identify a clear benefit of a specific type of adjunctive therapy on the survival time. Dogs that had a transfrontal approach had a significantly reduced survival time. Intracranial surgery for meningioma resection offers an excellent prognosis for survival to discharge from hospital with a median long term survival time of 386 days.

Comparison of serum creatine kinase and aspartate aminotransferase activity in dogs with Neospora meningoencephalitis and noninfectious meningoencephalitis.

BACKGROUND: Creatine kinase (CK) and aspartate aminotransferase (AST) activity can be increased with myositis associated with Toxoplasma and Neospora infection in dogs. HYPOTHESIS/OBJECTIVES: Serum activity of CK and AST can be used as a rapid screen for predicting positive serology in meningoencephalitis caused by Toxoplasma gondii or Neospora caninum in dogs compared to dogs with noninfectious meningoencephalitis. ANIMALS: Eighty dogs with meningoencephalitis based on magnetic resonance imaging and cerebrospinal fluid analysis. METHODS: Retrospective case-control study. Serological cutoffs (≥1:800 immunofluorescence for Neospora and ≥1:400 IgG or ≥1:64 IgM or both for Toxoplasma) categorized dogs as infected (n = 21, all neosporosis) or noninfected (n = 59). Activities of CK and AST between infected and noninfected groups were compared using a Mann-Whitney U test and receiver operating characteristic curve analysis. RESULTS: No dogs were diagnosed with toxoplasmosis. Serum CK and AST activities were significantly increased (P < .001) in dogs with positive serology for Neospora (CK: median, 1334 U/L; range, 281-3633 U/L and AST: median, 124 U/L; range, 59-333 U/L) compared to noninfectious cases (CK: median, 215 U/L; range, 69-683 U/L and AST: median, 36 U/L; range, 19-139 U/L). A CK cutoff of 485 U/L had 95.24% sensitivity and 96.61% specificity with a negative predicative value of >99%. An AST cutoff of 57 U/L had 94.44% sensitivity and 85.71% specificity with an estimated negative predicative value of 99%. CONCLUSIONS AND CLINICAL IMPORTANCE: High serum CK and AST activity can increase suspicion for neosporosis while awaiting serological tests for dogs with meningoencephalitis.

C-reactive protein in dogs with suspected bacterial diskospondylitis: 16 cases (2010-2019).

OBJECTIVES: C-reactive protein (CRP) is an acute phase protein used in multiple canine inflammatory conditions including steroid responsive meningitis-arteritis, immune-mediated polyarthritis and bronchopneumonia. The aim of this study was to assess whether serum CRP is elevated in cases of diskospondylitis. METHODS: Medical records from 2010 to 2019 were searched to identify dogs diagnosed with diskospondylitis based on findings consistent on CT or MRI and with CRP tested. RESULTS: A total of 16 dogs met the inclusion criteria. All cases had back pain. Fourteen cases had elevated CRP, with a median value of 100.7 mg/l (reference range for CRP values: 0-10 mg/l), 12 were pyrexic and six had leucocytosis. The two dogs with normal CRP were normothermic and did not have leucocytosis. CRP was measured four to six weeks into antimicrobial treatment in eight of 14 dogs and was normal in all cases. One dog developed a suspected bacterial empyema diagnosed on MRI; this occurred two weeks after antibiotic treatment was discontinued based on a normal CRP level at follow-up. CONCLUSIONS: Serum CRP is elevated in cases of diskospondylitis and may be clinically more useful to screen dogs with back pain than pyrexia or leucocytosis alone. Further long-term clinical evaluation in a prospective study is needed to assess its use as a treatment monitoring tool and in decision making.

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.

Incidence and risk factors for neurological signs after attenuation of single congenital portosystemic shunts in 253 dogs.

OBJECTIVE: To determine the incidence, outcome, and risk factors for postattenuation neurological signs (PANS) and seizures after attenuation of single congenital portosystemic shunts (CPSS) in dogs. STUDY DESIGN: Retrospective cohort study. SAMPLE POPULATION: Dogs (N = 253) with single CPSS. METHODS: Medical records of dogs treated by surgical attenuation of a single CPSS between February 2000 and July 2015 were reviewed for signalment and preoperative and postoperative clinical outcomes, including the occurrence of PANS. Univariable and multivariable binary logistic regression was used to assess risk factors for PANS and for seizures. RESULTS: Twenty-eight (11.1%) dogs developed PANS, including 12 (4.7%) dogs with seizures. Five (17.9%) dogs with PANS did not survive to discharge. Risk factors for PANS included the presence of hepatic encephalopathy (HE) immediately preoperatively (P = .038, odds ratio [OR] 2.704, CI 1.057-6.922) and increasing age (P < .001, OR 1.476, CI 1.223-1.780). Risk factors for seizures included the presence of HE immediately preoperatively (P = .048, OR 3.538, CI 1.013-12.363) and increasing age (P = .009, OR 1.364, CI 1.082-1.720). No association was found between the location of portosystemic shunts (extrahepatic and intrahepatic) and post-operative PANS (P = .532) or seizures (P = .620). Similarly, preemptive administration of levetiracetam did not influence the risk of PANS (P = .991) or seizures (P = .752). CONCLUSION: Preoperative HE and older age in dogs with a CPSS increased the odds of developing PANS and seizures in our population. Preemptive administration of levetiracetam did not protect dogs against the development of PANS or seizures. CLINICAL SIGNIFICANCE: Surgical attenuation of a single CPSS should not be excessively delayed, and surgeons should stabilize the clinical signs of HE before surgery to prevent postoperative PANS and seizures.

Choices and Decisions in Decompressive Surgery for Thoracolumbar Intervertebral Disk Herniation.

Once decompressive surgery has been elected, the approach that maximizes the likelihood of gaining access to the herniated material for complete removal should be chosen. In most cases, a procedure that optimizes access to the ventrolateral aspect of the spinal cord will be advantageous but it is important to tailor the details of the surgical procedure to suit individual patients. Decompressive surgery for chronic (type II) herniations will frequently demand a ventral approach with partial corpectomy.

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.

Neuronal ceroid lipofuscinosis associated with an MFSD8 mutation in Chihuahuas.

The neuronal ceroid lipofuscinoses (NCLs) are hereditary neurodegenerative disorders characterized by progressive declines in neurological functions, seizures, and premature death. NCLs result from mutations in at least 13 different genes. Canine versions of the NCLs can serve as important models in developing effective therapeutic interventions for these diseases. NCLs have been described in a number of dog breeds, including Chihuahuas. Studies were undertaken to further characterize the pathology of Chihuahua NCL and to verify its molecular genetic basis. Four unrelated client owned Chihuahuas from Japan, Italy and England that exhibited progressive neurological signs consistent with a diagnosis of NCL underwent neurological examinations. Brain and in some cases also retinal and heart tissues were examined postmortem for the presence of lysosomal storage bodies characteristic of NCL. The affected dogs exhibited massive accumulation of autofluorescent lysosomal storage bodies in the brain, retina and heart accompanied by brain atrophy and retinal degeneration. The dogs were screened for known canine NCL mutations previously reported in a variety of dog breeds. All 4 dogs were homozygous for the MFSD8 single base pair deletion (MFSD8:c.843delT) previously associated with NCL in a Chinese Crested dog and in 2 affected littermate Chihuahuas from Scotland. The dogs were all homozygous for the normal alleles at the other genetic loci known to cause different forms of canine NCL. The MFSD8:c.843delT mutation was not present in 57 Chihuahuas that were either clinically normal or suffered from unrelated diseases or in 1761 unaffected dogs representing 186 other breeds. Based on these data it is almost certain that the MFSD8:c.843delT mutation is the cause of NCL in Chihuahuas. Because the disorder occurred in widely separated geographic locations or in unrelated dogs from the same country, it is likely that the mutant allele is widespread among Chihuahuas. Genetic testing for this mutation in other Chihuahuas is therefore likely to identify intact dogs with the mutant allele that could be used to establish a research colony that could be used to test potential therapeutic interventions for the corresponding human disease.

What progress has been made in the understanding and treatment of degenerative lumbosacral stenosis in dogs during the past 30 years?

An association between degenerative changes in the lumbosacral region of the vertebral column and clinical signs of pain and pelvic limb dysfunction has long been recognized in dogs and has become known as degenerative lumbosacral stenosis syndrome. Over the past two decades, methods of imaging this condition have advanced greatly, but definitive criteria for a reliable diagnosis using physical examination, imaging and electrodiagnostics remain elusive. Available treatment options have changed little over more than 30 years but, more importantly, there is a lack of comparative studies and little progress has been made in providing evidence-based recommendations for the treatment of affected dogs. This review provides an overview of the changes in diagnosis, understanding and treatment of lumbosacral disease in dogs over the past 30 years. Approaches to address the unanswered questions regarding treatment choice are also proposed.