Hind Limb Paresis Research Articles

Range of Neurological Signs in Cynomolgus Monkeys After Intrathecal Bolus Administration of Antisense Oligonucleotides.

Intrathecal (IT) dosing (ie, injection into the subarachnoidal space at the lumbar region) is a common route of administration in cynomolgus monkey preclinical safety studies conducted for antisense oligonucleotides (ASO) that target central nervous system diseases. Herein we report on neurological signs that have been observed in 28 IT studies conducted in 1,016 cynomolgus monkeys. Neurological signs were classified into 5 groups: (1) A nonadverse transient absence of lower spinal reflexes. This observation occurred at low incidence in nontreated animals and in those that were injected artificial cerebrospinal fluid. The incidence increased in animals that were injected an ASO. Reflexes were present again at 24 hours or 48 hours after dosing. The incidence appeared to increase with dose. (2) Test-article-related adverse muscle tremor or muscle spasticity occurring during the injection procedure or immediately thereafter. In one-third of animals this finding responded to treatment with diazepam, in two-third it required euthanasia. (3) Neurological findings occurring between 30 minutes and 4 hours after dosing were characterized by any combination of ataxia, paresis, nystagmus, urinary incontinence, or muscle tremor. Those conditions either spontaneously resolved or they slowly worsened, eventually resulting in a poor general condition. (4) Neurological findings due to spinal cord injury were characterized by rapidly progressing paralysis of hind limbs. Magnetic resonance imaging revealed a focal hyperintense lesion, indicative of spinal cord necrosis. (5) Test-article-related adverse hind limb paresis or paralysis that occurred between 2 and 18 days after dosing. Those findings were rare and resulted in a poor general condition requiring euthanasia.

MiSeq Sequencing of Salmonella enterica subsp. houtenae Isolates from a Dog Treated for Hind-Limb Paresis.

The genomes of three clinical isolates of Salmonella enterica subsp. houtenae were sequenced using an Illumina MiSeq instrument. These isolates came from the urine and cerebrospinal fluid of a dog treated for hind-limb paresis with immunosuppressive drugs. S. enterica subsp. houtenae has also been implicated in brain infections in humans.

Congenital intradural melanoma surrounding the spinal cord of a nine-day-old Saanen goat

A nine-day-old Saanen kid presented for progressive hind limb paresis since birth. Euthanasia was elected, and on postmortem examination a large, pigmented mass was present in the vertebral canal surrounding...

Severe nutritional deficiencies and osteopenia in a dog fed a homemade raw diet

A seven-month-old male entire Bulldog presented for a three-week history of progressive lethargy, exercise intolerance, hindlimb paresis, muscle atrophy and hyperaesthesia. The dog had initially been raised on the bitch’s...

Cecal Dilatation and Torsion Associated with Phytobezoar Obstruction in a Heifer

Background: Dilatation of the cecum associated with intestinal torsion is a fermentative digestive disease that has a low occurrence in veterinary medicine, particularly in large animal practice. This condition is most prevalent in dairy cattle. The etiology of this digestive system disorder is related to changes in nutritional management. As it is an uncommon condition that is frequently observed in the practice of veterinary medicine, the objective of this report was to describe a case of dilatation and torsion of the cecum associated with phytobezoar obstruction in a heifer that was examined at the Veterinary Hospital of the Federal Rural University of Pernambuco (HOVET-UFRPE), Recife, Brazil.Case: A 55-day-old heifer, with a history of abdominal distension associated with difficulty feeding and neurological signs of hind limb paresis, intentional head tremors, and prostration, was examined at the HOVET-UFRPE large animal clinic.A clinical examination demonstrated the presence of enophthalmos, abdominal distension, pale coloration of the ocular mucous membranes, and a moderate level of dehydration (3%). The dehydration was treated through the administration of 1.150 L of saline solution along with 6 mL of Bionew (Vetnil®), 15 mL of calcium solution, and 5 mL of 50% glucose. Subsequently, the animal underwent intestinal washing through the insertion of an oral probe, which resulted in the expulsion of putrid content. Afterward, the animal’s blood was collected and sent to the Clinical Pathology Laboratory of the Department of Veterinary Medicine at HOVET-UFRPE for a complete blood count and analysis of the total protein. The complete blood count showed intense anisocytosis, mild polycythemia, and leukocytosis associated with neutrophilia. The subject died 24 h after the initial consultation at HOVET-UFRPE. The corpse was subsequently sent for a necropsy examination at the Animal Pathology Department of the School of Veterinary Medicine of UFRPE. The necropsy examination of the abdomen showed dark coloration of the intestines and dilatation extending from the small intestine to the large intestine, which was associated with torsion at the level of the ileocecal junction. The rumen contained five structures that were compatible with phytobezoars. These were measured to be between five and 15 cm. The kidney was dark red in color, and the spleen was pale and retracted. The cause of death was a circulatory shock secondary to cecal dilatation and torsion caused by the phytobezoar obstruction.Discussion: Insufficient nutritional management is one of the most important factors associated with cecal dilatation and torsion, as it can influence the formation of phytobezoars. Intestinal obstruction caused by phytobezoars has a higher prevalence in dairy cows during the first two weeks of lactation, after a period of activity or in the final stages of pregnancy. Additionally, an increased intake of fast-fermenting foods rich in carbohydrates can also result in the occurrence of digestive disorders of the cecum. Therefore, a rapid and appropriate diagnosis is essential for a more favorable prognosis. Cecal dilatation and torsion associated with phytobezoar obstruction are considered a rarely occurring digestive disorder that can go unnoticed. Adequate nutritional management is an essential component in the prevention of this fermentative disorder.

Review on Major Protozoal Causes of Abortion in Cattle

Neospora caninum was organism described as parasite of domestic dog. The tissues cysts seen in neural tissues. The disease can be transmitted by vertical and horizontal. Trans-placental infected pubis: the typical presentation is a flaccid and hind limb paresis Neospora abortion tends to peaks at mid gestation. Serological positive calves will ultimately give birth to calves that are infective and seronegative. Seropositive cow produce less milk than seronegative cows. Neosparn caninum was shown to use cattle as intermediate host and dog as definitive hosts. The most recommendation for prevention is try to prevent fecal contamination of feed and water on the dairy. Trichomonas fetus found in the vagina, uterus, macerated fetus, prepuce, epididymis and vasdeferense. Bovine trichomoniasis is venereal disease manifest in the cow and heifers by infertility, abortion up to 5 ts month after breading pyometra, and fetal mummification. Therefore, some of the common causes of abortion on cattle are discussed in detail in this review. Keywords: abortion, cattle, trichomoniasis, diagnosis, neosporiasis DOI : 10.7176/JBAH/9-21-06 Publication date: November 30 th 2019

Improvement of motor conduction velocity in hereditary neuropathy of LAMA2-CMD dy2J/dy2J mouse model by glatiramer acetate

ObjectiveGlatiramer acetate (GA), an agent modulating the immune system, has been shown to cause significantly improved mobility and hind limb muscle strength in the dy2J/dy2J mouse model for LAMA2-congenital muscular dystrophy (LAMA2-CMD). In view of these findings and the prominent peripheral nervous system involvement in this laminin-α2 disorder we evaluated GA’s effect on dy2J/dy2J motor nerve conduction electrophysiologically. MethodsLeft sciatic-tibial motor nerve conduction studies were performed on wild type (WT) mice (n = 10), control dy2J/dy2J mice (n = 11), and GA treated dy2J/dy2J mice (n = 10) at 18 weeks of age. ResultsControl dy2J/dy2J mice average velocities (34.49 ± 2.15 m/s) were significantly slower than WT (62.57 ± 2.23 m/s; p < 0.0005), confirming the clinical observation of hindlimb paresis in dy2J/dy2J mice attributed to peripheral neuropathy. GA treated dy2J/dy2J mice showed significantly improved average sciatic-tibial motor nerve conduction velocity versus control dy2J/dy2J (50.35 ± 2.9 m/s; p < 0.0005). ConclusionIn this study we show for the first time improvement in motor nerve conduction velocity of LAMA2-CMD dy2J/dy2J mouse model’s hereditary peripheral neuropathy following GA treatment. SignificanceThis study suggests a possible therapeutic effect of glatiramer acetate on hereditary peripheral neuropathy in this laminin-α2 disorder.

Truncating SLC12A6 variants cause different clinical phenotypes in humans and dogs.

Clinical, pathological, and genetic findings of a primary hereditary ataxia found in a Malinois dog family are described and compared with its human counterpart. Based on the family history and the phenotype/genotype relationships already described in humans and dogs, a causal variant was expected to be found in KCNJ10. Rather surprisingly, whole-exome sequencing identified the SLC12A6 NC_006612.3(XM_014109414.2): c.178_181delinsCATCTCACTCAT (p.(Met60Hisfs*14)) truncating variant. This loss-of-function variant perfectly segregated within the affected Malinois family in an autosomal recessive way and was not found in 562 additional reference dogs from 18 different breeds, including Malinois. In humans, SLC12A6 variants cause "agenesis of the corpus callosum with peripheral neuropathy" (ACCPN, alias Andermann syndrome), owing to a dysfunction of this K+-Cl- cotransporter. However, depending on the variant (including truncating variants), different clinical features are observed within ACCPN. The variant in dogs encodes the shortest isoform described so far and its resultant phenotype is quite different from humans, as no signs of peripheral neuropathy, agenesis of the corpus callosum nor obvious mental retardation have been observed in dogs. On the other hand, progressive spinocerebellar ataxia, which is the most important feature of the canine phenotype, hindlimb paresis, and myokymia-like muscle contractions have not been described in humans with ACCPN so far. As this is the first report of a naturally occurring disease-causing SLC12A6 variant in a non-human species, the canine model will be highly valuable to better understand the complex molecular pathophysiology of SLC12A6-related neurological disorders and to evaluate novel treatment strategies.

Myelinating Glia-Specific Deletion of Fbxo7 in Mice Triggers Axonal Degeneration in the Central Nervous System Together with Peripheral Neuropathy.

Myelination of axons facilitates the rapid propagation of electrical signals and the long-term integrity of axons. The ubiquitin-proteasome system is essential for proper protein homeostasis, which is particularly crucial for interactions of postmitotic cells. In our study, we examined how the E3 ubiquitin ligase FBXO7-SCF (SKP1, Cul1, F-box protein) expressed in myelinating cells affects the axon-myelin unit. Deletion of Fbxo7 in oligodendrocytes and Schwann cells in mice using the Cnp1-Cre driver line led to motor impairment due to hindlimb paresis. It did not result in apoptosis of myelinating cells, nor did it affect the proper myelination of axons or lead to demyelination. It however triggered axonal degeneration in the CNS and resulted in the severe degeneration of axons in the PNS, inducing a full-blown neuropathy. Both the CNS and PNS displayed inflammation, while the PNS was also characterized by fibrosis, massive infiltration of macrophages, and edema. Tamoxifen-induced deletion of Fbxo7, after myelination using the Plp1-CreERT2 line, led to a small number of degenerated axons and hence a very mild peripheral neuropathy. Interestingly, loss of Fbxo7 also resulted in reduced proteasome activity in Schwann cells but not in cerebellar granule neurons, indicating a specific sensitivity of the former cell type. Together, our results demonstrate an essential role for FBXO7 in myelinating cells to support associated axons, which is fundamental to the proper developmental establishment and the long-term integrity of the axon-myelin unit.SIGNIFICANCE STATEMENT The myelination of axons facilitates the fast propagation of electrical signals and the trophic support of the myelin-axon unit. Here, we report that deletion of Fbxo7 in myelinating cells in mice triggered motor impairment but had no effect on myelin biogenesis. Loss of Fbxo7 in myelinating glia, however, led to axonal degeneration in the CNS and peripheral neuropathy of the axonal type. In addition, we found that Schwann cells were particularly sensitive to Fbxo7 deficiency reflected by reduced proteasome activity. Based on these findings, we conclude that Fbxo7 is essential for the support of the axon-myelin unit and long-term axonal health.

Radiculoneuropathy and myelopathy: An underappreciated cause of hindlimb paresis in aged pet rats?

Radiculoneuropathy and myelopathy: An underappreciated cause of hindlimb paresis in aged pet rats?

Intoxicación por monensina en ovinos en Uruguay

Monensin is an antibiotic widely used in domestic animals. The aim of this paper is to describe three monensin poisoning outbreaks in sheep, occurred in 2015 and 2016, in the eastern region of Uruguay. The main clinical symptoms were anorexia, rigidity, hindlimb paresis, and finally lying sack. At necropsy the main findings were generalized subcutaneous edema, hydrothorax, hydroperitoneum and hydropericardium. In one case the urine had a reddish color. The hindlimb muscle masses showed pallor in all cases, while paleness in the heart muscle was observed in one case. The main histological lesions were degeneration and necrosis of skeletal and cardiac muscle. It is concluded that monensin poisoning in sheep occurs by the use of rations or salts formulated for cattle and by errors in commercial ration processing plants.

Solitary spinal nephroblastoma progressing to multifocal disease in a dog

A two- year-old neutered Labrador dog was evaluated for acute onset hindlimb paresis and proprioceptive deficits. Spinal MRI revealed a lesion at the level of T9–T10, from which a presumptive...

Glyphosate Surfactant Herbicide Toxicosis in a Dog with Hindlimb Paresis and Urinary Incontinence

Glyphosate Surfactant Herbicide Toxicosis in a Dog with Hindlimb Paresis and Urinary Incontinence

Primary central nervous system neoplasms in African hedgehogs.

In this retrospective study, we describe the clinicopathologic and immunohistochemical findings in a series of primary central nervous system (CNS) neoplasms in African hedgehogs ( Atelerix albiventris). Twelve CNS neoplasms were found among 762 African hedgehog submissions (1.6%) to a private diagnostic laboratory in an 18-y period. The median age of affected hedgehogs was 3.5 y. No sex predilection was found. Hindlimb paresis, weakness, and ataxia were the most commonly reported clinical signs. Gangliogliomas ( n = 6) and astrocytomas ( n = 5) were the most commonly observed neoplasms; one oligodendroglioma was found. Gangliogliomas were found in the cerebellar white matter (2 of 6), brainstem (4 of 6), cervical spinal cord (1 of 6), and frontal lobe (1 of 6); one metastasized to the tongue. Gangliogliomas were immunoreactive for neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), S100, and CD34. All astrocytomas were gemistocytic, located in the cerebrum, and none of these neoplasms metastasized. Astrocytomas were positive for GFAP, S100, and CD34, but negative for NFP. The oligodendroglioma was located in the cerebrum, and was positive for S100, but negative for GFAP and NFP.

Don’t Hang Up Your Lead, Yet

Three botulinum neurotoxin type A (BoNT/A) products, incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA, all manufactured by different methods, are employed in clinical practice. Comparing the three BoNT/A products is difficult because their concentrations and volumes differ and the precise dose equivalence ratio is not known. We aimed to compare the neurotoxic potencies by a systematic analysis of injected volume and dose.The potency of BoNT in inducing hind limb paresis was assessed by analyzing the wheel-running performance of mice. To standardize the volume, the effect of an identical dose of incobotulinumtoxinA dissolved in different volumes of saline (15, 10, 5, and 2 μl) was studied in four groups of mice (n = 13–15). The potencies of the BoNT products were then compared by injecting identical volumes (10 μl) containing different doses into both hind leg muscles.Mice injected with incobotulinumtoxinA showed a volume-dependent reduction in wheel-running, with larger volumes inducing more intense paresis. A standardized volume containing the same number of mouse units of the BoNT/A products produced different degrees of paresis. The conversion ratio of incobotulinumtoxinA and onabotulinumtoxinA is estimated to be between 1:0.75 and 1:0.5. OnabotulinumtoxinA displayed a two-fold greater potency than abobotulinumtoxinA. Doses of onabotulinumtoxinA and abobotulinumtoxinA that produce an identical severity of pareses even result in the same duration of pareses.This wheel-running assay allows one to compare the neurotoxic potency of different volumes and doses of the BoNT products in vivo. Our results argue against common clinical practice because incobotulinumtoxinA and onabotulinumtoxinA are not readily interchangeable and a two-fold dose of abobotulinumtoxinA is needed to induce an effect identical to onabotulinumtoxinA. In addition, this emphasizes that the duration of BoNT-induced effect is the same as long as equipotent doses of BoNT are injected.

Elevated neuron-specific enolase in the cerebrospinal fluid in a Japanese black calf with hindlimb paresis

Elevated neuron-specific enolase in the cerebrospinal fluid in a Japanese black calf with hindlimb paresis

Comments on the dilemma in the May issue: Slipped disk and dyspnoea in a French bulldog

In the dilemma discussed in the May issue of In Practice, Laura McLellan described a scenario where ‘Bella’, a four-year-old female French bulldog, is presented to you as an emergency...

Clinical conundrum: Hindlimb paraparesis

James Guillem, of the Veterinary Referral Centre in Surrey, invites Companion readers to consider a Tibetan Terrier with hindlimb paresis that was seen while he was a rotating intern at the Willows Veterinary Centre and Referral Service.

Cauda equina syndrome in dogs - a review

A lesion of sacrococcygeal spinal nerve roots forming a structure that resembles a horse's tail results in the development of clinical entity identified as the cauda equina syndrome (CES). The disease can evolve slowly and symptomatology can be incomplete, but the fully developed CES is characterized by pain and altered sensation in the pelvic extremities, tail, perianogenital region, paresis or plegia of hind limbs, incontinence and impotence. Major causes of CES in dogs are degenerative changes of the lumbosacral vertebral column, haematoma, inflammation, neoplasm or trauma. The diagnosis is based on history, clinical presentation, neurological symptomatology, spinal röntgenography, computed tomography, and magnetic resonance imaging. In animals experiencing initial episodes of CES, conservative therapy can be attempted. But the only rational treatment of patients with severe neurological deficit is surgical decompression of the neural structures. The outcome depends on the underlying aetiology and the degree of sensory, motor and autonomic dysfunction. Canine and porcine experimental models mimicking the CES showed the involvement of intrinsic spinal cord structures. This points out the need for an early diagnosis followed by aggressive management before irreversible neuronal lesions develop. The search strategy involved the PubMed, Medline, Embase and ISI Web of Science from January 2000 to August 2017 using the terms 'cauda equina syndrome' and 'lumbosacral stenosis' in the English language literature; also references from selected papers were scanned and relevant articles included.

A clinical case of neosporosis in a 4-week-old holstein friesian calf which developed hindlimb paresis postnatally

A 4-week-old female Holstein Friesian calf presented with hindlimb paresis. Neurologic examination of spinal reflexes revealed depressed or absent reflexes of the hindlimbs. Menace responses on both sides disappeared on examination of cranial nerves. The calf was finally diagnosed with Neospora caninum infection by pathological findings including nonsuppurative inflammation associated with cysts in the cerebrum and spinal cord. High levels of antibody against recombinant surface antigen 1 of N. caninum (NcSAG1) were detected by ELISA from both serum and cerebrospinal fluid (CSF) samples. This result suggests that detection of antibodies against N. caninum by NcSAG1-ELISA in serum and CSF could be useful for the clinical diagnosis of neosporosis in calves with acquired neurological signs.