Pelvic Limb Weakness Research Articles

Canine RNF170 Single Base Deletion in a Naturally Occurring Model for Human Neuroaxonal Dystrophy.

Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been described to naturally occur in large animal models, such as dogs. A newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of a slowly progressive neurodegenerative syndrome, was diagnosed as NAD via histopathology. To describe the clinical and pathological phenotype together with the identification of the underlying genetic cause. Clinical and postmortem evaluations, together with a genome-wide association study and autozygosity mapping approach, followed by whole-genome sequencing. Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. The underlying genetic cause was identified as a 1-bp (base pair) deletion in RNF170 encoding ring finger protein 170, which perfectly segregates in an autosomal recessive pattern. This deletion is predicted to create a frameshift (XM_038559916.1:c.367delG) and early truncation of the RNF170 protein (XP_038415844.1:(p.Ala123Glnfs*11)). The age of this canine RNF170 variant was estimated at ~30 years, before the reproductive isolation of the MAS breed. RNF170 variants were previously identified in human patients with autosomal recessive spastic paraplegia-85 (SPG85); this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neurodegeneration in a domestic rabbit with severe malnourishment and low hepatic copper.

Copper is a trace element that plays an essential role in neurodevelopment and neurologic function. Acquired copper deficiency has a range of neurologic manifestations, with myelopathy being the most common association. We describe here the clinical, radiologic, histopathologic, and toxicologic findings of a rabbit with malnutrition, neurodegeneration, and suspected copper deficiency. A stray, adult female dwarf rabbit cross (Oryctolagus cuniculus) in poor body condition developed ataxia and pelvic limb weakness progressing to lateral recumbency and urine retention. The clinical findings suggested multifocal brainstem disease with right-sided central vestibular involvement; however, microscopic examination identified thoracic and lumbosacral spinal cord myelopathy. Differentials for the spinal cord changes included neurodegenerative disease, nutritional deficiency, neurotoxin, trauma to the lumbosacral region, and ischemia. Hepatic copper levels were suboptimal at 18 ppm dry weight (RI: 24-150 ppm dry weight). While speculative, copper-deficiency myelopathy is a treatable cause of non-compressive myelopathy that may occur in this species.

Mycobacterium kansasii Infection in a Farmed White-Tailed Deer (Odocoileus virginianus) in Florida, USA.

A 7-year-old farmed white-tailed deer doe was transported to a Levy County, Florida property and began to decline in health, exhibiting weight loss and pelvic limb weakness. The doe prematurely delivered live twin fawns, both of which later died. The doe was treated with corticosteroids, antibiotics, gastric cytoprotectants, and B vitamins but showed no improvement. The doe was euthanized, and a post mortem examination was performed under the University of Florida's Cervidae Health Research Initiative. We collected lung tissue after the animal was euthanized and performed histological evaluation, using H&E and Ziehl-Neelsen (ZN) staining, and molecular evaluation, using conventional PCR, followed by Sanger sequencing. The microscopic observations of the H&E-stained lung showed multifocal granuloma, while the ZN-stained tissue revealed low numbers of beaded, magenta-staining rod bacteria inside the granuloma formation. Molecular analysis identified the presence of Mycobacterium kansasii. This isolation of a non-tuberculous Mycobacterium in a white-tailed deer emphasizes the importance of specific pathogen identification in cases of tuberculosis-like disease in farmed and free-ranging cervids. We report the first case of M. kansasii infection in a farmed white-tailed deer (Odocoileus virginianus) in Florida. Although M. kansasii cases are sporadic in white-tailed deer, it is important to maintain farm biosecurity and prevent farmed cervids from contacting wildlife to prevent disease transmission.

Clinical and imaging features of a feline lumbar myelopathy resembling ossification of the posterior longitudinal ligament in humans

AbstractA 9‐year‐old, male, neutered Russian blue cat was presented for a 2‐week history of pelvic limb weakness and reluctance to jump and climb stairs. Neurological examination was consistent with an L4–L6 myelopathy. Ectopic calcification of soft tissues within the vertebral canal involving the dorsal longitudinal ligament over the L5–L6 vertebrae was diagnosed based on radiography, magnetic resonance imaging and computed tomography. The lesion was surgically excised, and histopathological examination demonstrated fibrous connective tissue with calcification. The patient was neurologically normal 2 months after surgery, and no relapses have occurred in a follow‐up period of 2 years. The findings in this case had not been previously reported in cats, and share some similarities with a clinical entity in humans named ossification of the posterior longitudinal ligament.

Antinociceptive effects of bupivacaine injected within the internal abdominis rectus sheath in standing healthy horses

ObjectiveTo evaluate a regional anesthetic technique for blocking the abdominal midline in horses. Study designAnatomical description and prospective, crossover, placebo-controlled, blinded study. AnimalsAdult horses; two cadavers, six healthy animals. MethodsIn stage 1, 0.5% methylene blue with 0.25% bupivacaine (0.5 mL kg–1) was injected using ultrasonography into the internal rectus abdominis sheath (RAS) of two cadavers with a one-point or two-point technique. The dye spread was described after the dissection of the abdomens. In stage 2, each horse was injected with 1 mL kg–1 of 0.9% NaCl (treatment PT) or 0.2% bupivacaine (treatment BT) using a two-point technique. The abdominal midline mechanical nociceptive threshold (MNT) was measured with a 1 mm blunted probe tip and results analyzed with mixed-effect anova. Signs of pelvic limb weakness were recorded. ResultsThe cadaver dissections showed staining of the ventral branches from the eleventh thoracic (T11) to the second lumbar (L2) nerve with the one-point technique and T9–L2 with the two-point technique. Baseline MNTs were, mean ± standard deviation, 12.6 ± 1.6 N and 12.4 ± 2.4 N in treatments PT and BT, respectively. MNT increased to 18.9 ± 5.8 N (p = 0.010) at 30 minutes, and MNT was between 9.4 ± 2.0 and 15.3 ± 3.4 N from 1 to 8 hours (p > 0.521) in treatment PT. MNTs in treatment BT were 21.1 ± 5.9 to 25.0 ± 0.1 N from 30 minutes to 8 hours (p < 0.001). MNTs after the RAS injections were higher in treatment BT than PT (p = 0.007). No pelvic limb weakness was observed. Conclusions and clinical relevanceAntinociception of at least 8 hours without pelvic limb weakness was observed in the abdominal midline in standing horses after the RAS block. Further investigations are necessary to evaluate suitability for ventral celiotomies.

Clinical resolution of systemic mycobacterial infection in a cat with a suspected spinal granuloma

AbstractAn 8‐year‐old, female, spayed, domestic longhair cat presented with progressive pelvic limb weakness, lethargy and weight loss. Physical examination identified bilateral pelvic limb proprioceptive ataxia, tachypnoea and a subcutaneous nodular lesion on the left flank. Investigations documented a diffuse broncho‐interstitial and nodular pulmonary pattern, pyogranulomatous inflammation in the spleen and an intradural‐extramedullary spinal lesion at the level of L3. Mycobacterium microti was confirmed based on demonstration of organisms on histopathology of the subcutaneous nodule using Ziehl–Neelsen stain together with positive polymerase chain reaction and interferon‐gamma release assay results. Therapy with rifampicin, azithromycin and pradofloxacin was administered for 7 months. Serial monitoring, including repeated magnetic resonance imaging, demonstrated resolution of the clinical signs, pulmonary, subcutaneous and spinal lesions.

Negative Antigenuria in a Dog with Suspected Central Nervous System Localized Blastomycosis.

A 7 yr old female spayed mixed-breed dog was presented for a 1 wk history of neck pain and pelvic limb weakness. Examination revealed nonambulatory paraparesis and thoracolumbar hyperesthesia. MRI revealed extensive intramedullary T2-weighted/short tau inversion recovery hyperintensity and diffuse severe T1-post contrast meningeal enhancement of the thoracolumbar spinal cord. An L5-L6 cerebrospinal fluid sample revealed a suppurative pleocytosis (81% neutrophils, total protein 4362.5 mg/dL and nucleated cell count 352,000/μL). While awaiting the results of infectious disease testing, the dog was treated for suspected meningoencephalitis of unknown etiology with corticosteroids, cyclosporine, and a cytarabine arabinoside infusion. The dog neurologically declined and was started on broad-spectrum antibiotics. The dog continued to decline despite antibiotics, and infectious disease titers subsequently revealed serum antibody positivity for blastomycosis. The dog was then referred to a multispecialty referral hospital and was treated with amphotericin B followed by fluconazole. Prednisone was continued at anti-inflammatory doses. Urine blastomycosis antigen testing was submitted for subsequent disease monitoring but was negative. Five months after presentation the dog was clinically doing well with no identifiable neurologic deficits. This case demonstrates that neurologic blastomycosis may have negative urine antigen concentrations in some dogs and that other diagnostic modalities should be pursued when central nervous system fungal disease is suspected.

An EHPB1L1 Nonsense Mutation Associated with Congenital Dyserythropoietic Anemia and Polymyopathy in Labrador Retriever Littermates.

In this report, we describe a novel genetic basis for congenital dyserythropoietic anemia and polymyopathy in Labrador Retriever littermates characterized by incidental detection of marked microcytosis, inappropriate metarubricytosis, pelvic limb weakness and muscle atrophy. A similar syndrome has been described in English Springer Spaniel littermates with an early onset of anemia, megaesophagus, generalized muscle atrophy and cardiomyopathy. Muscle histopathology in both breeds showed distinctive pathological changes consistent with congenital polymyopathy. Using whole genome sequencing and mapping to the CanFam4 (Canis lupus familiaris reference assembly 4), a nonsense variant in the EHBP1L1 gene was identified in a homozygous form in the Labrador Retriever littermates. The mutation produces a premature stop codon that deletes approximately 90% of the protein. This variant was not present in the English Springer Spaniels. Currently, EHPB1L1 is described as critical to actin cytoskeletal organization and apical-directed transport in polarized epithelial cells, and through connections with Rab8 and a BIN1-dynamin complex generates membrane vesicles in the endocytic recycling compartment. Furthermore, EHBP1L1 knockout mice die early and develop severe anemia. The connection of EHBP1L1 to BIN1 and DMN2 functions is particularly interesting due to BIN1 and DMN2 mutations being causative in forms of centronuclear myopathy. This report, along with an independent study conducted by another group, are the first reports of an association of EHBP1L1 mutations with congenital dyserythropoietic anemia and polymyopathy.

A true congenital pancreatic cyst in a dog

BackgroundTrue congenital pancreatic cysts are a rare pathological process reported within feline and human literature. To date there has been no documented case of a true congenital cyst affecting a canine patient. The objective of this case report is to document the clinical findings, diagnostic investigations, surgical treatment, histopathological diagnosis and long-term outcome of a dog with a true pancreatic cyst.Case presentationA 5-month-old crossbreed dog was presented with a six-week history of abdominal pain, apparent bilateral pelvic limb weakness, reluctance to walk and intermittent vomiting and diarrhoea. An abdominal ultrasound examination performed by the dog’s primary care veterinarian identified a large intra-abdominal structure of unclear origin. A computed tomographic examination identified a large ovoid structure measuring 156 mm in length, 95 mm in height and 89 mm in width and apparently originating from the left limb of the pancreas. An exploratory coeliotomy was performed and a partial pancreatectomy was performed to allow complete removal of the cystic structure. Histopathological analysis of sections of the wall of the large fluid-filled cyst identified a thick fibromuscular wall lined by a well regimented hyperplastic tall columnar epithelium with basally located round to ovoid nuclei featuring fine chromatin stippling and abundant apically located and surface mucin, concurrent with a true congenital pancreatic cyst. A long-term follow-up of twenty-nine months identified no clinical signs of recurrence.ConclusionA partial pancreatectomy and en bloc excision of a true pancreatic cyst provided an excellent long-term outcome in a dog.

West Nile Fever Virus Infection in Horses in São Paulo State, Brazil

Background: The West Nile virus (WNV) antibodies were reported in Brazil in the serum samples taken from horses and birds in the Midwest region and Paraíba state in 2008 and 2013, respectively. In 2014, the first human case was confirmed in a rural worker in the state of Piauí and, in 2018, the virus was isolated from the central nervous system of a horse with nervous symptoms in the state of Espírito Santo. The virus is a member of the Flaviviridae family of the genus Flavivirus (neurotropic), infecting several mammalian species, with humans and horses being the most susceptible. Approximately 35% of horses develop clinical signs, thus they are considered the best sentinels for this disease. The aim of this case report is to describe the first confirmed cases of West Nile Fever (WNF) in two horses in the state of São Paulo.Cases: Two horses with neurological symptoms were treated at the Veterinary Hospital of Cruzeiro do Sul University (São Paulo, SP), in 2019. Both horses came from neighboring regions that have a large Atlantic Forest preservation area and are also routes for migratory birds, known to be competent hosts for transmitting the West Nile Fever virus, such as the swallow, the falcon and the hawk. The first one had symptoms, such as weakness and sporadic seizures; however, after recovering, it was hospitalized a few days later due to kidney failure and laminitis. The second one showed incoordination, pelvic limb weakness, and was walking in circles, evolving to seizures. Both animals were euthanized, and their central nervous system samples and total blood samples were tested for rabies, herpes virus, and WNV; the first 2 tests showed negative results. Ribonucleic acids (RNA) were extracted from erythrocytes using the polymerase chain reaction (PCR) technique in-house. The WNV-specific reverse transcription-polymerase chain reaction amplification products were obtained using the nested PCR-multiplex PCR combination.Discussion: Since the 1940s, several WNF outbreaks have been reported around the world (Africa, Europe, Asia and Middle East). In the 2000s, the USA had the most amount of WNF cases reported; cases started being reported in Central and South America in the following years. The virus was identified for the first time in Brazil in 2014. Since then, our country is a route for migratory birds, with many states still having forests, several arboviruses are found such as WNF, which could become a public health problem. Both horses in the present study showed neurological signs and the horse that recovered had renal failure. Such signs are inconclusive, however, similar to those that occur in humans infected by the virus in its neurotropic form. The emergence of new diseases is an important aspect of public health. The literature is vast regarding the description of the pathogenesis, clinical signs, diagnosis, viral persistence and sequelae of WNF in humans, however, it is scarce regarding the viral persistence and sequelae of the disease in horses. Future studies are needed to understand the post-infection period in horses, as they are the most sensitive animals along with humans to this virus. Here, we report the first confirmed cases of WNF in the city of São Paulo to bring awareness about considering this disease while diagnosing horses with nervous system disorders.Keywords: encephalitis, horses, flavivirus, mosquito.Título: Infecção pelo vírus da Febre do Nilo Ocidental em equinos no Estado de São PauloDescritores: encefalite, equinos, flavivírus, mosquito.

Anaesthesia considerations for a patient with suspected myasthenia gravis

This extended case reports explores the pre-, peri- and post-anaesthetic considerations in a 2-year 7-month-old male entire crossbreed with suspected myasthenia gravis after presenting with gastrointestinal signs and pelvic limb weakness. Myasthenia gravis is an immune-mediated neuromuscular transmission disorder, which greatly increases the risk of mortality in patients undergoing anaesthesia. Following specific nursing care, in this case no complications occurred and the dog went home 3 days later.

JEPM July 2019 – Abstracts

Background: Lead intoxication is common in companion birds and frequently associated clinical signs include weakness, regurgitation, and central nervous system signs including seizures and tremors. Motor neuropathies and conduction disturbances are more commonly described in humans with lead intoxication, but are uncommon sequelae in psittacine birds. Case Description: Three pet psittacine birds were presented for acute-onset of distal pelvic limb abnormalities. Clinical Findings: An adult, female peach-faced lovebird (Agapornis roseicollis) was presented with acute, bilateral, distal pelvic limb paralysis and an adult, male peach-faced lovebird was presented with an acute inability to extend the digits of the feet bilaterally. An adult blue-streaked lorikeet (Eos reticulata) was presented for acute onset, bilateral pelvic limb weakness, and inability to rise from the bottom of the cage. All three birds had increased blood lead levels (30–110 μg/dL), but none exhibited overt central nervous, gastrointestinal, or other common clinical signs consistent with lead intoxication in birds. A potential source of lead could not be identified in two of the three cases. Conclusion and Case Relevance: Despite achieving persistent reduction of blood lead levels following parenteral chelation therapy using calcium disodium EDTA, all three birds had continued neurological deficits in both pelvic limbs. Birds were considered to maintain a good quality of life after husbandry changes were implemented to assist in ambulation. Lead intoxication should be considered a differential for acute-onset paralysis of the distal pelvic limbs in psittacine birds.

Insulin-secreting β-cell neoplasia in a 7-year-old female dog, case report and review

AbstractA 7-year-old female dog presented with intermittent episodes of urinary incontinence, tremors, intermittent episodes of pelvic limb weakness and collapse, and lethargy were noticed over a period of two months. Hypoglycaemia, secondary to an insulin-secreting β-cell tumour, was suspected on the basis of clinical signs, ultrasound and serum biochemistry. A laparotomy was then performed to remove the tumour mass. Post-surgical pancreatitis was a major complication. Histology revealed a malignant neuroendocrine neoplasia of the β-cells of the pancreas. This case review is reported to keep clinicians abreast of the canine insulinoma disorder and the complications surrounding its diagnosis and treatment.

Goniometry and Limb Girth in Miniature Dachshunds.

Purpose. To report the mean and median pelvic limb joint angles and girth measurements in miniature Dachshunds presenting with varying degrees of pelvic limb weakness secondary to thoracolumbar intervertebral disc extrusion. Methods. 15 miniature Dachshunds who presented to WSU-VTH for thoracolumbar disc extrusion. Dachshunds varied in neurologic status from ambulatory paraparetic to paraplegic at the time of measurements. Results. There were no significant differences in joint angles or girth among the three groups (ambulatory paraparetic, nonambulatory paraparetic, or paraplegic) (P > 0.05). When group was disregarded and values for extension, flexion, and girth combined, no differences existed. Conclusions. Goniometry and limb girth measurements can successfully be made in the miniature Dachshund; however, the shape of the Dachshund leg makes obtaining these values challenging. There were no differences in joint angle or girth measurements between dogs with varying neurologic dysfunction at the time of measurement.

Diagnosis and Treatment of Myasthenia Gravis in a Golden Retriever Dog

A four years old male Golden Retriever weighing 34 kg was brought to our clinics with the complaints of exhaustion and fatigue for the past month, inability to stand on its hind legs, loss of voice and anorexia. In clinical examination, difficulty in lifting the head, pelvic limb weakness and regurgitation were observed. Lateral thoracic radiograph showed enlarged thymus gland and megaesophagus. Myasthenia gravis was suspected and 2.5 mg of Edrophonium Chloride was administered IV. A positive response was seen within 30 minutes of drug application. The disease was diagnosed as Myasthenia gravis. Treatment improved the pelvic limb weakness however the dog died after 10 days.

Spatial and temporal distribution of incidence of acquired equine polyneuropathy in Norway and Sweden, 1995-2012.

BackgroundAcquired equine polyneuropathy (AEP) is an emerging disease in horses in Sweden, Norway and Finland since 1995. Affected horses show bilateral pelvic limb knuckling and weakness, sometimes progressing to recumbency and euthanasia. The aetiology is unknown but is thought to be non-infectious and non-genetic, though possibly toxic or toxico-infectious. The objectives of this study were to describe the spatial, temporal and spatio-temporal features of AEP in Norway and Sweden for the period of 1995 to 2012. Data from all documented case farms (n = 136) were used. Space-time interaction clustering of case farms was investigated with a retrospective space-time scan statistic with a space-time permutation model, the space-time K-function and the Jacquez k nearest neighbour (kNN) test.ResultsThere was a clear seasonality in disease occurrence, as 123 case farms presented their first case from January to May. However, there was large variation in the number of case farms between years. Case farms were more numerous in certain regions. Despite the larger horse population in Sweden, 120 of the case farms were in Norway. Space-time clustering was supported by the K-function and partly by the space-time scan, but not by the Jacquez k nearest neighbour (kNN) test.ConclusionsThe results suggest an aetiology for AEP where the exposure is not consistent in time, but varies during and between years, assuming that the incubation period does not vary greatly. The results further suggest that the exposure varies between regions as well. Two out of three different analytical methods supported spatio-temporal clustering of case farms, which rendered inconclusive results. The negative result in the kNN test might be explained by lack of power, which is due to the small number of outbreaks in relation to the size of the study area and length of the study period, and further by the low to moderate power of methods to detect space-time clustering when the background population is unknown. Further research is needed to study how management, meteorological variables and other factors with local or regional differences may explain outbreaks of AEP.

Tethered Cord Syndrome in the Pediatric-Adolescent Gynecologic Patient

Tethered Cord Syndrome in the Pediatric-Adolescent Gynecologic Patient

Congenital kyphosis secondary to lumbar vertebral hypoplasia causing paraparesis in a Friesian foal

A 5-day-old Friesian colt was presented with a history of severe bilateral pelvic limb weakness since birth. Clinical examination revealed a painful dorsal deviation of the spinous processes of the lumbar vertebrae, pelvic limb paraparesis and grade 4/5 ataxia. Radiographic examination revealed kyphosis due to hypoplasia and malformation of the 5 lumbar vertebrae present. At myelography performed immediately after euthanasia, dorsal deviation of the myelographic contrast column was demonstrated at the level of T18–L4 with suspected spinal cord compression noticeable at L1. There was no lateral deviation of the spinal cord or scoliosis of the vertebrae visible.

Clinical progression of X-linked muscular dystrophy in two German Shorthaired Pointers

2 full-sibling male German Shorthaired Pointer (GSHP) puppies (dogs 1 and 2) with X-linked muscular dystrophy and deletion of the dystrophin gene (gene symbol, DMD) each had poor growth, skeletal muscle atrophy, pelvic limb weakness, episodic collapse, and episodes of coughing. Initial examination revealed stunted growth, brachygnathism, trismus, and diffuse neuromuscular signs in each puppy; clinical signs were more severe in dog 2 than in dog 1. Immunohistochemical analysis revealed a lack of dystrophin protein in both dogs. During the next 3 years, each dog developed hyperinflation of the lungs, hypertrophy of the cervical musculature, and hypertrophy of the lateral head of the triceps brachii muscle. Monitoring and supportive care were provided at follow-up visits during an approximately 7-year period. No other specific treatment was provided. Neuromuscular signs in both dogs remained stable after 3 years of age, with dog 2 consistently more severely affected than dog 1. The dogs had multiple episodes of aspiration pneumonia; dogs 1 and 2 were euthanatized at 84 and 93 months of age, respectively. The clinical course of disease in these dogs was monitored for a longer period than has been monitored in previous reports of dystrophin-deficient dogs. The clinical progression of muscular dystrophy in the 2 GSHPs was compared with that for other breeds and species with dystrophin-deficient conditions, and the potential basis for the phenotypic variation observed between these littermates, along with potential therapeutic ramifications for dogs and humans, was evaluated.

Gait deficits in liver disease: Hepatic encephalopathy and hepatic myelopathy

Summary In this issue, the unusual clinical presentation of a horse diagnosed is described with severe liver cirrhosis and hepatic encephalopathy. The horse initially presented for thoracic and pelvic limb ataxia and weakness, and signs of forebrain disease were not apparent until later in the disease process. The typical pathology of central nervous system disease associated with liver disease is related to encephalopathy and forebrain disease; however, the spinal cord is occasionally also involved. Hepatic myelopathy is a rare syndrome usually associated with surgical or acquired portosystemic shunts, liver cirrhosis and/or portal hypertension in man. Where a gliopathy is the most prominent pathological feature seen in hepatic encephalopathy, in hepatic myelopathy the most remarkable feature is demyelination of the corticospinal tracts of the distal cervical and thoracic spinal cord with occasional axon loss. The clinical signs of hepatic myelopathy are spastic paresis/paralysis with normal sensory findings and preserved sphincter function. The prognosis for hepatic myelopathy is generally poor. In summary, in severe liver disease, motor deficits can occur secondary to the encephalopathy, but motor deficits can also occur as a result of spinal cord pathology such as seen in hepatic myelopathy. In examination of horses with myelopathies, liver disease as a cause of myelopathy should be included in our list of differentials.