Search

Two 1-day-old full-term female calves from different farms located in the Brazilian state of Rio Grande do Sul were unable to stand due to paresis of the pelvic limbs. Both calves had spina bifida on the spinal lumbar segment and were submitted to euthanasia due to poor prognosis. Postmortem examination revealed cerebellar herniation, caudal displacement of the brainstem, rostral deviation of the cranial nerves, caudal extension of occipital lobes, absence of dorsal lamina of lumbar vertebrae with exposed spinal cord, myelodysplasia, kyphosis, segmental spinal agenesis, renal fusion, muscular atrophy, and arthrogryposis. Histology highlighted myelodysplasia (syringomyelia and diplomyelia) and muscular atrophy. The reverse transcription-polymerase chain reactions for ruminant pestivirus were negative. Based on these lesions, the diagnosis of complex neural tube and skeletal malformations was made. A review of previous publications on calves diagnosed with these malformations, originally called Chiari or Arnold-Chiari malformations, revealed a wide range of nervous system and skeletal lesions. These variations amplified the uncertainty regarding whether all cases represent the same disorder and reinforced the importance of reconfiguring the terminology., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Neural tube defects (NTDs) are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure. Although folate supplementation has been shown to mitigate the incidence of NTDs, some cases, often attributable to genetic factors, remain unpreventable. The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation; at present, however, the underlying mechanism remains unclear. Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate. To determine the role of SHROOM3 in early developmental morphogenesis, we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase. Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei. These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins, namely fibrous actin (F-actin), myosin II, and phospho-myosin light chain (PMLC), to the apical side of the neuroepithelial cells. Notably, these defects were not rescued by folate supplementation. RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis. In summary, we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

We report a 9-year-old Thoroughbred gelding that had sudden onset lameness of the right forelimb with episodes of lateral decubitus and generalized pain after completion of a normal training session. The clinical signs subsequently became less pronounced with only mild right forelimb lameness. However, after further orthopaedic examination, it developed severe, acute ataxia and paraplegia, the Schiff-Sherrington phenomenon and risus sardonicus. At necropsy, a partial duplication of the cervical spinal cord was identified, consistent with split spinal cord malformation type II or diplomyelia. However, the clinical significance of this finding is not clear., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A rare dysraphic caudal spinal anomaly, or caudal agenesis, comprising a tethered spinal cord, was found in a tailless Holstein calf that presented ataxia and paresis with analgesia of the hind limbs. The gently and slimly tapered conus medullaris was poorly formed between S2 and S3 which indicated that it was lying more caudally. The caudal end of the filum terminale adhered to the inner periosteum of the vertebral arch at S4, which is compatible with tethering of the spinal cord. The dysraphic changes from the secondary neurulation error and the longitudinal deranged cord morphology that may have been caused by the caudad traction due to tethering were confirmed. This represents the first bovine case with definitive morphological confirmation.

Background: There is an association between Chiari malformations, syringomyelia (CMSM) and tethered cord syndrome (TCS) in people, suggesting Cavalier King Charles Spaniels (CKCS) with CMSM could also have TCS. Currently there are no data on the position of the caudal spinal cord structures in CKCS., Objective: To describe and compare location of spinal cord termination in CKCS with weight-matched controls and to examine the relationship between SM and spinal cord termination., Animals: Thirty-nine CKCS and 33 controls with thoracolumbar MRIs; 34 of 39 CKCS also had cervical MRIs., Methods: Blinded retrospective study. Spinal cord and dural sac termination were determined from T2-weighted sagittal and transverse images and half-Fourier acquisition single-shot turbo spin echo sequences. Intra-observer reliability was determined using kappa analysis. Presence of SM was compared with location of spinal cord and dural sac termination., Results: Intra-observer reliability was moderate for identifying spinal cord termination (Kappa = 0.6) and good for dural sac termination (Kappa = 0.8). The spinal cord terminated at lumbar vertebra 6 (L6) in 1, 7 (L7) in 22, and sacrum in 16 CKCS versus 9 at L6, 23 at L7, 1 at sacrum in controls. Spinal cord (P < .001) and dural sac (P = .002) termination were significantly more caudal in CKCS compared to controls. The presence of thoracolumbar SM was associated with more caudal dural sac termination in CKCS (P = .03)., Conclusions and Clinical Importance: The relationship between TL SM and possible spinal cord tethering because of a more caudal dural sac termination should be investigated., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

A 4-mo-old French bulldog was presented with acute onset pain and reluctance to move. A tubular structure arising in the dorsal thoracic midline and extending from a cutaneous orifice into deeper tissues was palpated on physical examination. Computed tomography with sinography revealed a dermoid sinus associated with spina bifida at the level of T3-T4. On surgical exploration, the dermoid sinus was found to communicate with the dura. Histology confirmed the diagnosis and classification as a type VI dermoid sinus. The pain response and hyperesthesia were suspected to be the result of tethered cord syndrome. Complete resolution of clinical signs was appreciated post-surgery, with the patient still free of clinical signs 3 mo later.

A 15-d-old female crossbreed calf was referred because of paraplegia since birth. Clinical examination revealed a skin defect covered by hair on the dorsal midline in the thoracic area of the spine. Thoracolumbar spinal cord neuroanatomic localization was determined based on neurologic examination. Computed tomography of the thoracolumbar spine revealed incomplete fusion of the vertebral arches from T6 to T10 and duplication of the vertebral arch of T7. At the level of T6-T7, duplication of the spinal cord with 2 segments completely separated by a septum of hyperattenuating, probably cartilaginous, tissue was noted. Histologically, the spinal segments had different degrees of duplication. Three central canals were detected in one region. Genetic investigation for the presence of methylenetetrahydrofolate reductase (MTHFR) polymorphism, which has been investigated in both human and veterinary medicine as a possible cause of neural tube defects and abortion, was carried out and was negative in both the calf and her dam.

Background: The teratogenic effects of immunomodulatory and certain antimicrobial therapies are described in small rodents and humans. While the described teratogenic effects in small rodents have been extrapolated to make conclusions about its use in the pregnant dam, teratogenic effects of prednisone and doxycycline have not yet been reported in the dog. Here we report and describe midline defects observed in a litter of golden retriever puppies exposed to mid-gestational immunosuppressive and antimicrobial therapy., Case Presentation: Twenty-one days into gestation, the dam of a litter of eight golden retriever puppies was administered prednisone, doxycycline, and tramadol as treatment for immune-mediated polyarthritis. The individuals in the litter were subsequently diagnosed with a variety of midline defects and congenital cardiac defects. This case series describes the variety of identified defects and presents a descriptive account of complex congenital abnormalities that are likely secondary to teratogenic effects of one or more drugs administered during gestation. The available puppies, dam, and grand dam underwent thorough physical examination, complete echocardiogram, and where indicated, advanced imaging with various surgical corrections when possible. Numerous midline congenital defects and congenital heart disease were identified in the puppies evaluated. Ultimately 5 of 8 puppies born to the dam were presented for thorough evaluation. The midline defects include: gastroschisis (1), peritoneopericardial diaphragmatic hernias (4, PPDH), umbilical hernia (4), unilateral cryptorchidism (1 of 4 males), cleft palate (1), renal agenesis (1), renal abnormalities (1), sternal and vertebral abnormalities (3), remnant liver lobe (1) and malformations consistent with ductal plate malformations with congenital hepatic fibrosis (1). The congenital cardiac defects include: ventricular septal defect (4, VSD) and subaortic stenosis (4, SAS). The presence of greater than one congenital defect was noted in all 5 of the dogs evaluated. Surgical correction was necessary for PPDH in 4 puppies. Medical intervention was recommended for congenital cardiac disease in 1 puppy., Conclusion: This case report is the first to describe midline defects in dogs that have been exposed to immunomodulatory therapy during gestation. A causative relationship between mid-gestational immunomodulatory exposure and midline defects cannot be proven, however, this case supports a clear association and provides case-based evidence to support its avoidance when possible.

Neuroectodermal developmental anomalies are reported rarely in cetaceans and central nervous system cysts are not described. We describe the gross, microscopical, histochemical and immunohistochemical features of a neuraxial myelencephalic cyst in a stranded neonatal Burmeister's porpoise (Phocoena spinipinnis). Grossly, a subdural, extra-axial, well-demarcated, yellow fluid-filled cystic structure (1.9 × 1.6 × 1 cm) expanded the left foramen of Luschka, the left caudolateral cerebellar recess and the left cranioventral myelencephalon. The cyst displaced the ipsilateral ventral paraflocculus and distended the underlying cranial nerves IX, X, XI and XII. Microscopically, the cystic structure was lined by a monolayer of low cuboidal to flattened epithelium supported by a thin fibrovascular matrix. Immunohistochemistry (IHC) revealed strong and diffuse expression of AE1/AE3 and focal positivity for vimentin. IHC for epithelial membrane antigen, glial fibrillary acid protein, synaptophysin and S100 was negative. Based on these findings, an extra-axial cyst of the choroid plexus of the fourth ventricle (CCPFV) was diagnosed. The pathological relevance of the CCPFV in this case is uncertain. The cause of death involved severe perinatal interspecific (shark) trauma. The present case provides the first evidence of a neuroepithelial cyst in cetacean species., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

CASE DESCRIPTION An 11-year-old English Cocker Spaniel was evaluated because of chronic progressive ataxia of the hind limbs. CLINICAL FINDINGS The dog had no history of previous illness, and findings of physical examination and laboratory tests were unremarkable. Neurologic examination revealed that the dog was ambulatory with severe ataxia of the hind limbs. Proprioception was decreased in the right and left hind limbs (right affected more than left), and spinal reflexes were bilaterally unremarkable. Moderate signs of pain were detected during palpation of the lumbar portion of the vertebral column. Findings suggested a lesion within the thoracolumbar or lumbar segments of the spinal cord. Magnetic resonance imaging revealed extradural spinal cord compression attributable to an extradural space-occupying lesion originating from or infiltrating the L4 lamina on the right side. TREATMENT AND OUTCOME Hemilaminectomy was performed to remove the extradural lesion. Histologic findings for tissue samples collected during the procedure were consistent with a neurenteric cyst. The late onset and progression of clinical signs of this rare congenital malformation were suspected to have been the result of enlargement of the neurenteric cyst through continuous production of mucus by goblet cells. The dog responded favorably to surgical decompression and was clinically normal 1 year after surgery. It was euthanized 2 years after surgery for an unrelated reason (end-stage heart disease), and no neurologic deficits were evident before that point. CLINICAL RELEVANCE Congenital neurenteric cysts should be considered as a differential diagnosis for neoplastic disease in dogs in which results of diagnostic imaging indicate the presence of an extradural mass affecting vertebral structures.

Two horses euthanized for neurologic deficits were diagnosed with hamartomatous myelodysplasia of the spinal cord. One was a 5-week-old Holsteiner colt exhibiting spasms of muscle rigidity in the extensor muscles of the limbs and epaxial muscles, and the other was a 3-year-old Thoroughbred colt exhibiting progressive ataxia and hypermetria in the pelvic limbs. Each had focal disorganization of the white and gray matter of the spinal cord forming a mass interspersed with neurons, glial cells, and disoriented axon bundles. In the Holsteiner colt, the mass was at the level of C5 and included islands of meningeal tissue contiguous with the leptomeninges. The mass occluded the central canal forming hydromyelia cranial to the occlusion. In the Thoroughbred colt, the mass was at the level of L1 on the dorsal periphery of the spinal cord and did not involve the central canal., (© The Author(s) 2016.)

Spina bifida with or without meningocele or meningomyelocele is encountered infrequently in small animal practice. The English bulldog and Manx cat are breeds predisposed. Although often silent clinically, in those animals with clinical signs, it is important to recognize the signs early and to understand the appropriate imaging modalities employed in establishing a diagnosis. In a select population of affected animals, proposed surgical intervention may be considered to prevent neurologic decline, prevent secondary complications, and potentially improve outcomes., (Published by Elsevier Inc.)

The present study records recurrent outbreaks of myelodysplasia of unknown origin occurring in a specific geographical location in the north of Spain, and involving up to 30% of the calves born in affected herds. The affected calves were of different breeds and displayed non-progressive signs of spinal cord dysfunction. The disease has occurred annually in February-March over a period of at least 15 years. Only calves born to cattle grazed on mountainside pastures and under high grazing pressure were affected. Seven calves were subjected to necropsy examination. Myelodysplasia was not associated with vertebral defects or arthrogryposis and involved the entire length of the spinal cord. Microscopically, there was abnormal distribution of the grey matter, aberrations of the central canal and failure of formation of the ventral median fissure. Infectious, nutritional and physical disorders were ruled out as possible aetiologies. A critical period of embryonic susceptibility to the causal agent was identified. This was during the time of secondary neurulation when cows in the early stages of gestation were grazed on mountainside pastures. Consequently, the presence of neuroteratogenic plants in these pastures is proposed as a likely cause. Two plants, Carex brevicollis and Erythronium dens-canis, which contain alkaloids, were identified on the mountainsides where affected cattle were grazed and not in other pastures, and are proposed as the possible aetiology of the disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A 9 yr old spayed female German shepherd dog was referred for MRI of the thoracic and lumbar spine because she had clinical signs of chronic neurogenic bladder dysfunction of an unknown cause. Transverse T2-weighted images identified a type II split cord malformation (i.e., diastematomyelia) in the thoracic spine. Split cord malformations are forms of spinal dysraphism where the abnormal development of spinal cord results in sagittal splitting of a portion of the cord into two hemicords. The location of the lesion in the thoracic spine was consistent with the dog's clinical signs of an upper motor neuron bladder. Split cord malformations that occur in humans have similar MRI characteristics and can result in similar clinical signs as those identified in the dog described in this report.

Nonhuman primates have been a common animal model to evaluate experimentally induced malformations. Reports on spontaneous malformations are important in determining the background incidence of congenital anomalies in specific species and in evaluating experimental results. Here we report on a stillborn cynomolgus monkey (Macaca fascicularis) with multiple congenital anomalies from the colony maintained at the Southwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, Texas. Physical findings included low birth weight, craniorachischisis, facial abnormalities, omphalocele, malrotation of the gut with areas of atresia and intussusception, a Meckel diverticulum, arthrogryposis, patent ductus arteriosus, and patent foramen ovale. The macaque had normal male external genitalia, but undescended testes. Gestational age was unknown but was estimated from measurements of the limbs and other developmental criteria. Although cytogenetic analysis was not possible due to the tissues being in an advanced state of decomposition, array Comparative Genomic Hybridization analysis using human bacterial artificial chromosome clones was successful in effectively eliminating aneuploidy or any copy number changes greater than approximately 3-5 Mb as a cause of the malformations. Further evaluation of the animal included extensive imaging of the skeletal and neural tissue defects. The animal's congenital anomalies are discussed in relation to the current hypotheses attempting to explain the frequent association of neural tube defects with other abnormalities., (Copyright © 2011 Wiley-Liss, Inc.)

A 7-month-old male neutered cat was referred for paraparesis and painful sensation at the level of T13 vertebra where a dermal cyst was observed. Spine radiographs and magnetic resonance imaging (MRI) showed a well-encapsulated cyst communicating with the meninges and spinal cord, suggestive of hydromyelia and myelodysplasia. Dorsal laminectomy was performed and the cyst was completely removed. The day after surgery, the cat was ambulatory paraparetic. Involuntary defecation was observed for only a few days. The surgical specimen was cystic and covered by skin. Microscopic examination revealed a hollow hemispheric mass of glial fibrillary acidic protein (GFAP)-positive neural tissue lined by ependyma and formed of glia and vascular structures consistent with myelomeningocele (MMC). Only anecdotal descriptions of MMC have been published in the veterinary literature, mainly in the lumbosacral spinal cord. To the authors' knowledge, this is the first report of a MMC with tethered spinal cord syndrome in a cat successfully treated surgically., (Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Myelodysplasia is a general term referring to abnormal development of the spinal cord. Unless associated with vertebral malformations, it can be difficult to distinguish clinically from other causes of spinal cord disease. These case reports describe the clinical and pathological findings in two calves with a distinctive non-progressive pelvic limb ataxia. The syndrome was observed in two calves on a large, extensively managed beef cattle property near Richmond, north Queensland. Both calves had similar clinical signs, including hindlimb ataxia with swaying of the pelvis and a well-coordinated bilateral hopping-like action. The differential diagnoses are discussed. A focal or diffuse myelodysplasia should be suspected in calves that have exhibited a non-progressive hindlimb ataxia from birth.

The features of a calf with a split cord malformation are described. Clinically, there was severe cervicothoracic kyphoscoliosis and an interscapular dermal sinus associated with cerebrospinal fluid drainage. Using magnetic resonance imaging, complete duplication of the spinal cord at the cervical intumescence was detected. There was associated syringohydromyelia, multiple cervicothoracic vertebral malformations resulting in kyphoscoliosis and rachischisis, herniation of the cerebellar vermis, meningoencephalocele, and calvarial defects.

In this preliminary study, differentially expressed genes were investigated in cranial tissues from chickens with hereditary exencephaly using cDNA microarrays containing 1,152 genes and expressed sequence tags (ESTs). Genes showing twofold or greater differences at P < 0.05 between affected and normal cranial cells were considered to be candidates for hereditary exencephaly in chicken. Eighteen ESTs (11 known genes/homologues) were upregulated and 108 ESTs (51 known genes/homologues) were downregulated. The EST AL584231 (ROS006C9), orthologous to human MTHFD1, a known candidate gene for human neural tube defects (NTDs), was expressed at the same level both in normal and affected chicken cranial tissues. ESTs AL584253 (ROS006F7, thioredoxin reductase 1) and AL585511 (ROS024H9, thioredoxin), both involved in NTD pathogenic pathways in mice, were downregulated and had mean ratios of 0.41 and 0.04 for expression in affected vs. normal cells respectively. Expression differences of these two ESTs were confirmed by quantitative real-time polymerase chain reaction. These data indicate that ESTs AL584253 and AL585511 are candidates for hereditary exencephaly in chickens.

The recessive mutant mouse jumonji (jmj), obtained by a gene trap strategy, shows neural tube defects in approximately half of homozygous embryos with a BALB/cA and 129/Ola mixed background, but no neural tube defects with BALB/cA, C57BL/6J, and DBA/2J backgrounds. Here, we show that neural tube and cardiac defects are observed in all embryos with a C3H/HeJ background. In addition, abnormal groove formation and prominent flexure are observed on the neural plate with full penetrance, suggesting that abnormal groove formation leads to neural tube defects. We found morphogenetic abnormalities in the bulbus cordis (future outflow tract and the right ventricle) of homozygous embryo hearts. Moreover, myocytes in the ventricular trabeculae show hyperplasia with cells filling the ventricles. Together with the observation that the jmj gene is expressed in the neural epithelium of the head neural plate and in myocytes in the bulbus cordis and trabeculae, the results show that the jmj gene plays essential roles in the normal development of the neural plate, morphogenesis of bulbus cordis, and proliferation of trabecular myocytes on a C3H/He background.

An unusual case of a Yorkshire terrier with a dermoid sinus associated with multiple spinal/costal malformations is described. The dog presented with ataxia and pain in the dorsal thoracic region. Diagnostic characterisation of the lesions was obtained with radiography, myelography and computed tomography. After surgical removal of the sinus, the dog showed marked clinical improvement over a two-year period.

Paraparesis (paraplegia) refers to partial (-paresis) or complete (-plegia) loss of voluntary motor function in the pelvic limbs. Similar involvement of all four limbs is termed tetraparesis (tetraplegia). Paraparesis generally results from spinal cord lesions caudad to the second thoracic spinal cord segment, whereas tetraparesis occurs because of lesions craniad to this segment (see discussion of spinal cord lesion localization in The Neurologic Examination and Lesion Localization, on page 328). The limbs may be affected equally; however, asymmetric lesions cause greater clinical involvement on the ipsilateral side. Strictly unilateral lesions at C1-T2 result in clinical involvement on only the affected side of the body (hemiparesis, hemiplegia). Monoparesis (monoplegia) occurs subsequent to unilateral T2-S1 lesions. Trauma and neoplasia are the most common spinal cord diseases affecting cats. Urinary and fecal incontinence often occur concomitant with paresis. General concepts relating to disorders of micturition are discussed at the conclusion of this chapter.

The incidence of neurovertebral defects in mutant mice of the curly-tail strain was investigated and found to be similar to that observed in the same mice twenty-five years ago. The results of breeding experiments support the hypothesis of Grüneberg that the defects in these mice are probably caused by a recessive gene, the expression of which is markedly affected by the genetic background. Selection against the curly-tail phenotype for six generations did not affect the incidence of abnormalities. A marked excess of females was found among exencephalic mice, as among humans with neural tube defects. Similarly, polyhydramnios, hydrocephaly, high levels of amniotic fluid alphafoetoprotein and distinctive, rapidly adhering cells in the amniotic fluid also occurred in these mice, as in humans. The curly-tail mice thus provide a useful model for the investigation of neural tube defects in man.