Hindlimb Paraparesis Research Articles

Marek's Disease in an Indian Peafowl (Pavo cristatus) with Clinical Ocular Disease and Paraparesis

Marek's disease (MD) is caused by virulent strains of Gallid alphaherpesvirus type 2 (MD virus serotype 1; MDV 1) and frequently causes a lymphoproliferative disorder in poultry and other galliform birds worldwide. However, within the peafowl (Phasianinae) subfamily, there are only rare confirmed reports of MD. Here we report MD in an Indian peafowl (Pavo cristatus), which clinically presented with hindlimb paraparesis and intraocular swelling of the right eye. Soft, off-white to tan masses within the right eye, sciatic nerves and coelomic cavity were identified at post-mortem examination which effaced the cranial pole of the kidneys and diffusely effaced the testes. Lymphoid neoplasia was identified histologically at all of these sites and there was extensive hepatic lymphoid cell infiltration, which had not been grossly evident. The T-cell origin of the lymphoid cells was confirmed by immunohistochemistry for CD3 antigen. A virulent strain of MDV 1 was detected by real-time polymerase chain reaction in DNA samples extracted from the kidney and testes. As MD is rare in peafowl it should be considered as a differential diagnosis for intraocular and coelomic masses with associated clinical signs.

A case of a complete atrioventricular canal defect in a ferret

BackgroundAtrioventricular canal defect is a rare congenital disorder of the heart and describes the presence of an atrial septal defect, a variable presentation of ventricular septal alterations including ventricular septal defect malformations in the mitral and tricuspid valves. The defect has been described in human beings, dogs, cats, pigs, and horses.Case presentationThis paper describes the case of a complete atrioventricular canal defect in a four-year-old intact male pet ferret (Mustela putorius furo), which was presented due to posterior weakness, ataxia, and decreased appetite. A loud systolic murmur, dyspnea, and hind limb paraparesis were detected during the clinical examination. Thoracic radiographs showed generalized cardiomegaly and lung edema. ECG showed sinus rhythm with prolonged P waves and QRS complexes. Echocardiography showed a large atrial septal defect, atrioventricular dysplasia, and a ventricular septal defect. Palliative treatment with oxygen, furosemide, spironolactone, enalapril, diltiazem, and supportive care was chosen as the therapy of choice. The ferret recovered gradually during hospitalization. A follow-up examination at three and six months showed stabilization of cardiac function.ConclusionsTo the authors knowledge, this is the first time an atrioventricular canal defect has been described in a pet ferret.

Aortic and iliac thrombosis in a dog with adrenal-dependent hypercortisolism due to bilateral adrenocortical adenoma

ABSTRACT: Hypercortisolism is a common endocrinopathy in dogs; however, in a few cases, bilateral functional adrenocortical adenomas cause spontaneous disease, and thrombotic events are considered uncommon complications. The aim of this report was to describe a case of bilateral adrenocortical adenoma in a dog with hyperadrenocorticism associated with distal aortic and iliac thrombosis, with emphasis on clinical and pathological aspects. A 15-year-old spayed female Dachshund with a previous clinical history of hyperadrenocorticism presented with acute bilateral hindlimb paraparesis. A vertebral thoracolumbar radiography was performed and did not present any evidence of intervertebral disk disease or vertebral abnormalities; however, abdominal ultrasound and vascular Doppler evaluation revealed bilateral adrenal enlargement in addition to an aortic and external iliac artery thrombus. The animal was euthanized. At necropsy, both adrenal glands were enlarged by well-demarcated neoplastic nodules in the parenchyma, and a thrombus caudal to the abdominal aorta bifurcation within the external iliac arteries that extended to the left external iliac artery was noted. Histological evaluation revealed a well-differentiated neoplastic proliferation of cortical epithelial cells, consistent with bilateral adenoma, and muscular necrosis in the pelvic limbs was also observed. Bilateral functional adrenocortical adenoma; although, very rare, should be considered as a cause of hypercortisolism, and aortic thrombosis in dogs should be considered as a possible consequence.

Establishing a rabbit spinal tumor model for nonvascular interventional therapy through CT-guided percutaneous puncture inoculation.

An animal spinal tumor model is needed to better simulate the clinical situation and to allow percutaneous puncture, which may provide an experimental platform for the new nonvascular interventional therapies. We established a rabbit spinal tumor model through a CT-guided percutaneous puncture inoculation technique for nonvascular interventional therapy. VX2 tumor cells were inoculated into the lumbar vertebrae of 32 rabbits through a CT-guided percutaneous puncture technique; then, the development of hind limb paraparesis was observed in the rabbits twice a day. MR imaging and CT were performed on days 14, 21, and 28 postinoculation and at the development of hind limb paraparesis. On days 21 and 28 postinoculation, 2 rabbits, whose imaging suggested successful modeling without hind limb paraparesis, were chosen on each day. The lumbar vertebrae were sampled from 1 rabbit for histopathologic examination, and the other rabbit underwent PET-CT examination before percutaneous vertebroplasty. Finally the lesion vertebrae were sampled for histopathologic examination. The success rate of modeling was 90.6% (29/32) in our study. On day 21 postinoculation, successful modeling was achieved in 21 rabbits, with 19 having no hind limb paraparesis. On day 28 postinoculation, another 7 achieved successful modeling, and only 1 developed hind limb paraparesis. Percutaneous vertebroplasty treatment was successful for the 2 rabbit models. Establishment of a rabbit spinal tumor model through a CT-guided percutaneous puncture technique and inoculation of VX2 tumor is easy and has a high success rate. The established model can be used to study nonvascular interventional therapies for spinal tumor, including percutaneous vertebroplasty.

Janus-faced immunity to an enteric pathogen: how Campylobacter mediates colitis and autoimmunity (MUC2P.820)

Abstract Campylobacter jejuni is a leading cause of foodborne enteritis and has also been linked to the autoimmune neuropathy, Guillain Barré syndrome. IL-10−/− mice serve as C. jejuni colitis model, but a mouse model for GBS is lacking. Immune mechanisms responsible for C. jejuni mediated colitis, protection from colitis or initiation of autoimmune sequelae are also largely unknown. We demonstrate that IL-10−/− mice infected with colitogenic human isolates of C. jejuni had significantly upregulated Type1/17 but not Type2 cytokines in the colon coincident with infiltration of phagocytes, T cells and Innate Lymphoid Cells. Both ILCs and T cells participated in IFN-γ, IL-17 and IL-22 upregulation but in a time- and organ-specific manner. However, T cells were necessary for colitis. Furthermore, depleting IFN-γ, IL-17 or both significantly ameliorated colitis and drove the colonic responses towards Type2 cytokine and antibody induction. In contrast, C. jejuni GBS patient strains induced mild colitis associated with blunted Type 1/17 but enhanced Type2 responses. Moreover, IL-4 and CD4+ T cell dependent Type2 antibodies (but not the Type1/17 antibodies) elicited exclusively by the GBS strains cross-reacted with peripheral nerve antigens. This lead to macrophage mediated demyelination of sciatic nerves that manifested with gait ataxia and hind limb paraparesis in the IL-10-/- mice. Therefore, this is the first mouse model of an autoimmune disease induced directly by an enteric bacterium.

Status epilepticus attributed to inadvertent intrathecal injection of cefazolin during myelography

To describe a case of status epilepticus believed to be a consequence of inadvertent intrathecal administration of cefazolin in a dog undergoing a myelogram. A 4-year-old, 6.5 kg, male neutered Dachshund was referred for evaluation of an acute onset hind limb paraparesis. While performing a lumbar myelogram, cefazolin was inadvertently injected into the ventral subarachnoid space. Subsequent refractory seizure activity was attributed to the epileptogenic effects of intrathecally administered cefazolin. Supportive therapy led to eventual complete recovery. Although epileptogenic effects of intrathecally administered cefazolin are well documented in the human and experimental animal model literature, to the authors' knowledge this has not been characterized in the veterinary literature. This case highlights the need to be diligent and mindful when one administers medications, and describes the management of a dog adversely affected as a consequence of a medical error.

Discospondylitis Caused byStaphylococcus aureusin an African Black-footed Penguin (Spheniscus demersus)

A 22-year-old female African black-footed penguin (Spheniscus demersus), housed indoors with other African and rockhopper penguins, was presented acutely with lethargy, ataxia, and hind limb weakness after a molt. The penguin would assume a hunched position and, when resting, sat on its hocks or lay on its keel. Physical and neurologic examination revealed hind limb paraparesis, proprioceptive deficits, and tiptoe walking. Results of a complete blood cell count and biochemical analysis revealed mild heterophilic leukocytosis, anemia, mild hypoalbuminemia, hypokalemia, and hyperuricemia. Results of whole-body radiographs and coelioscopy were unremarkable. Two computed tomographies of the spine at a 3-month interval revealed a lesion at the mobile thoracic vertebra proximal to the synsacrum with associated spinal cord compression. The penguin was treated with itraconazole, doxycycline, and meloxicam, and it initially improved with return to near normal gait and behavior. However, 5 months after the onset of clinical signs, the penguin was euthanatized after a relapse with worsening of the neurologic signs. Postmortem and histopathologic examination revealed focal granulomatous discospondylitis at the penultimate mobile thoracic vertebra, with intralesional bacteria from which Staphylococcus aureus was cultured.

Meningomyelitis due to nematode infection in four cats

Spinal cord parasitic migrations in cats are uncommon. This report describes four cases of chronic hindlimb paraparesis in cats associated with nematode infection. Complete neurologic, hematologic, serum chemistry and radiographic examination was performed on all animals. Computed tomographic (CT)-myelographic examination at the lumbar area in one cat showed a slight swelling of the spinal cord. Necropsy examination of the spinal cord revealed generalized edema and marked submeningeal hemorrhage at the thoracic region in three cats. On histopathologic examination, numerous sections of adult nematodes and eggs were present in histological sections of the affected spinal cord segments in all cats. The morphologic features of the nematode, location and appearance of the lesions suggest that the parasite responsible for the paralysis in these cats is Gurltia paralysans.

Neuroblastoma with Neuronal Differentiation in the Spinal Cord in an Aberdeen Angus Heifer Calf

A 5-month-old, female, Aberdeen Angus heifer presented to the veterinary medical teaching hospital for evaluation of slowly progressive hindlimb ataxia. The calf was clinically normal until 4 months of age, following routine pregnancy and delivery. Neurologic examination revealed marked symmetric spastic hindlimb paraparesis. Thoracolumbar radiographs and cerebrospinal fluid (CSF) analysis were unremarkable. A presumptive diagnosis of T3-L3 myelopathy was made, and neurologic status remained static for 3 months with broad-spectrum antibiotic and nonsteroidal anti-inflammatory therapy. Additional diagnostic tests were refused, and a necropsy was performed following euthanasia. A moderately well delineated, reddish-tan, soft mass 18 mm in diameter replaced 80% of the fourth lumbar spinal cord segment. Histologic examination revealed two distinct features: undifferentiated, primitive, polygonal-to-round cells with typical morphologic characteristics of primitive neuroectoderm; and interspersed areas containing myelinated axons and cells with neuronal differentiation. Immunohistochemical examination confirmed the presence of primitive neuroepithelium and cells with neuronal differentiation.

Age-dependent paraparesis in WKA rats: evaluation of MHC k-haplotype and HTLV-1 infection.

Human T-cell leukemia virus type 1 (HTLV-1) infection is shown to be closely associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the occurrence of HAM/TSP was reported to be associated with MHC class II, the mechanism is still unclear. The WKA(RT1k) strain of rats was reported to develop HAM/TSP-like paraparesis after HTLV-1 infection, and was suggested to be an animal model of HAM/TSP. We asked whether MHC k-haplotype is specifically involved in the pathogenesis of paraparesis of WKA(RT1k) rats. We injected the HTLV-1 producing human T cells (MT-2 cells) intravenously into WKA(RT1k) rats and MHC congenic WKA.1L(RT1l) rats which have MHC l-haplotype of LEW rats on the WKA background. Positive antibody response to HTLV-1 antigens and presence of provirus in peripheral blood mononuclear cells confirmed that MT-2 cell-injected rats were infected with HTLV-1. Two of 13 MT-2 cell-injected WKA(RT1k) rats and five of 13 MT-2 cell-injected WKA.1L(RT1l) rats developed HAM/TSP-like hindlimb paraparesis between 16 and 26 months old. Interestingly, three of 14 MT-2 cell-uninjected WKA(RT1k) rats and four of 13 MT-2 cell-uninjected WKA.1L(RT1l) rats showed similar paraparesis between 15 and 26 months old. MHC k-haplotype is not specific to the development of paraparesis in WKA(RT1k) rats. The role of aging, genetic background, HTLV-1 infection and other factors on the development of HAM/TSP-like paraparesis in rats are discussed.

A rat model of human T lymphocyte virus type I (HTLV-I) infection: in situ detection of HTLV-I provirus DNA in microglia/macrophages in affected spinal cords of rats with HTLV-I-induced chronic progressive myeloneuropathy

To investigate the pathogenetic role of human T lymphocyte virus type I (HTLV-I) in central nervous system disease, a rat model for HTLV-I-associated myelopathy/tropical spastic paraparesis, designated as HAM rat disease, has been established. Wistar-King-Aptekman-Hokudai strain rats with induced HTLV-I infection develop a chronic progressive myeloneuropathy with paraparesis of hind limbs after an incubation period of 15 months. In the affected spinal cord in these rats, white matter degeneration, demyelination and vacuolar change with microglia/macrophage infiltration are present as are the provirus DNA and the virus mRNA. To identify infected cells in the affected lesions, we carried out in situ hybridization of amplified fragments of the provirus DNA by polymerase chain reaction on thin sections, plus immunohistochemistry on the same sections. The provirus DNA was localized in some microglia/macrophages in the spinal cord lesion. In addition, the HTLV-I provirus was clearly evident not only in ED-1-negative lymphoid cells but also in ED-1-positive macrophages from lymph nodes. These observations suggest that cells of microglia/macrophage lineage may be one of dominant viral reservoirs in the spinal cords and lymph nodes in HAM rat disease. These infected microglia/macrophages may relate to cause the myeloneuropathy through neurotoxic cytokine synthesis.

Central nervous system lesions in rats infected with Friend murine leukemia virus-related PVC441: ultrastructural and immunohistochemical studies

Newborn F344 rats were injected intraperitoneally with PVC441 virus, a neuropathogenic variant of Friend murine leukemia virus, and developed paraparesis of hind limbs 35-40 days after infection. Immunohistochemical study using monoclonal anti-PVC441 antibody revealed that in the central nervous system endothelial cells but not neuronal or glial cells were infected with PVC441 virus. The major pathological changes were myelin vacuolation and oligodendrocyte degeneration in the white matter at the white-gray border zone. Anterior and lateral funiculi and intercalated myelin of anterior horns were dominantly affected in the spinal cord from the sacral to cervical level. The midbrain was also vacuolated. An ultrastructural study demonstrated that many viral particles were present outside the endothelial cells but only sparsely inside endothelial cells and pericytes. Endothelial cell membranes and tight junctions were also disrupted. Immunohistochemical studies with antibodies against major histo-compatibility complex class Ia, intercellular adhesion molecule-I, glial fibrillary acidic protein, neurofilament protein, CD3 and OX42 revealed the presence of abundant microglia but not of lymphocytes or polymorphonuclear cells in the lesions. Axonal degeneration and astrogliosis were mild in degree. These pathological changes explain the observed spastic paraparesis in the rats, and represent a good model of spongiform diseases of the human central nervous system of retroviral origin, such as human T cell leukemia virus-associated myelopathy and AIDS.

A neuropathological study of paraparetic rats injected with HTLV-I-producing T cells

In order to clarify the pathogenesis of HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP), we injected HTLV-I-producing rabbit or human T cells intravenously into WKA and F344 rats. Infection was confirmed from increase in the anti-HTLV-I antibody titer and from the presence of HTLV-I proviral DNA. Only WKA rats developed hindlimb paraparesis 78 ∼ 124 weeks after the injection. Neuropathological examination of 5 rats showed degeneration of the anterolateral and posterior funiculi as well as the peripheral nerves, and this degeneration was characterized by prominent vacuolation and macrophage infiltration. The myelopathy and neuropathy were grossly similar to those in human HAM/TSP. Although pathological changes of the spinal cord were very mild in 2 paretic rats, and similar lesions were found in the spinal cords and peripheral nerves of 2 control WKA rats, the myelopathy, radiculoneuropathy, or both in the paretic rats showed greater severity than in the controls. The contribution of the aging process to the lesions of the spinal cord and peripheral nerve is discussed. It appears possible that HTLV-I may accelerate the aging process and give rise to paraparesis. The precise role of HTLV-I in the pathogenesis of rat paraparesis remains to be elucidated taking the role of the aging process of the spinal cord and peripheral nerve into account.

Lordosis of Thoracic Vertebral Column and Following Paraparesis of Hindlimbs Induced by Maternal Administration ofβ-β'-Iminodipropionitrile (IDPN) During Pregnancy in Rats

Lordosis of Thoracic Vertebral Column and Following Paraparesis of Hindlimbs Induced by Maternal Administration ofβ-β'-Iminodipropionitrile (IDPN) During Pregnancy in Rats