Dynamic Lumbosacral Magnetic Resonance Imaging in a Dog with Tethered Cord Syndrome with a Tight Filum Terminale

A 1-year and 11-month- old English Cocker Spaniel was evaluated for clinical signs of progressive right pelvic limb lameness and urinary incontinence. Neurological examination was suggestive of a lesion localized to the L4–S3 spinal cord segments. No abnormalities were seen on magnetic resonance imaging (MRI) performed in the dog in dorsal recumbency and the hips in a neutral position and the conus medullaris ended halfway the vertebral body of L7. An MRI of the hips in extended and flexed positions demonstrated minimal displacement of the conus medullaris in the cranial and caudal directions, respectively. Similar to the images in neutral position, the conus medullaris ended halfway the vertebral body of L7 in both the extended and flexed positions. In comparison, an MRI of the hips in neutral, extended, and flexed positions performed in another English Cocker Spaniel revealed obvious cranial displacement of the conus medullaris with the hips in extension and caudal displacement with hips in flexion. A standard dorsal lumbosacral laminectomy was performed. Visual inspection of the vertebral canal revealed excessive caudal traction on the conus medullaris. After sectioning the distal aspect of the filum terminale, the conus medullaris regained a more cranial position. A neurological examination 4 weeks after surgery revealed clinical improvement. Neurological examinations at 2, 4, 7, and 12 months after surgery did not reveal any abnormalities, and the dog was considered to be clinically normal. Tethered cord syndrome with a tight filum terminale is a very rare congenital anomaly and is characterized by an abnormally short and inelastic filum terminale. Therefore, this disorder is associated with abnormal caudal traction on the spinal cord and decreased physiological craniocaudal movements of the neural structures within the vertebral canal. Although further studies are necessary to evaluate and quantify physiological craniocaudal movement of the spinal cord and conus medullaris in neurologically normal dogs, the results of this report suggest further exploration of dynamic MRI to demonstrate decreased craniocaudal displacement of the conus medullaris in dogs with tethered cord syndrome with a tight filum terminale

Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

BACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown. METHODS: We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients. RESULTS: Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression. CONCLUSIONS: This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD

Coronary artery fi stulas in children: Experience from a Southern African tertiary care centre complex

Coronary artery fi stulas (CAF) are unusual coronary artery connections with low pressure cardiac chambers or vessels. The majority are congenital, but can also be acquired. Complications include heart failure, myocardial infarction and arrhythmias. Symptomatic and large CAF require treatment and options include surgical ligation or percutaneous device embolisation of the fi stula which has emerged as a less invasive and equally effi cacious management modality. Careful interrogation of the CAF is required prior to occlusion in order not to compromise normal coronary artery vasculature that may arise from the fi stula which can lead to myocardial ischaemia and infarction. Several reported cases highlight thrombus formation within large CAF after surgical ligation with propagation of the thrombus into coronary vessels arising proximally, resulting in myocardial compromise. We present a series of 6 children with CAF, 2 were treated by percutaneous embolisation (one developed a myocardial infarction post procedure) and 3 were treated surgically

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

Diffusion MRI tractography with along-tract profiling reveals subtle neurodevelopmental differences between moderate and late preterm infants.

Moderately preterm (MP) infants (32-33 weeks' gestation) are at increased risk for developmental problems compared to late preterm (LP) infants (34-36 weeks' gestation). Fiber bundle tractography remains an unexplored avenue to understanding this risk-difference between MP and LP infants. This study aimed to examine along-tract profile differences between MP and LP infants at term-equivalent age (TEA). Ninety-five infants (31 MP and 64 LP), born between November 2020 and March 2023, underwent MRI around TEA (40-44 weeks postmenstrual age). MRI included T2-weighted imaging and diffusion MRI (dMRI) with b-values 800 and 2000 s/mm (single shell). dMRI scans were preprocessed to reduce common artifacts. For all infants, 15 fiber bundles were reconstructed using TractSeg and along-tract profiles, expressed as fractional anisotropy (FA) and mean diffusivity (MD), and were compared between MP and LP infants using tractometry. Reconstructions with TractSeg demonstrated shape, position, and orientation of fiber bundles consistent with known neuroanatomy. FA and MD profiles were not significantly different between MP and LP infants. However, alternating trends towards along-tract profile differences between MP and LP infants were observed for multiple bundles. Wide 95% confidence intervals indicated substantial variability in fiber bundle organization within groups. Although not significant, along-tract differences between MP and LP infants suggest subtle alterations in white matter maturation. These findings indicate along-tract variability as potential focus for future research aimed at uncovering the mechanisms underlying early maturational differences and their potential role in later neurodevelopmental challenges encountered in moderate-late preterm infants. [Abstract copyright: Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.

Population Genomic Analysis of a Bacterial Plant Pathogen: Novel Insight into the Origin of Pierce's Disease of Grapevine in the U.S.

Invasive diseases present an increasing problem worldwide; however, genomic techniques are now available to investigate the timing and geographical origin of such introductions. We employed genomic techniques to demonstrate that the bacterial pathogen causing Pierce's disease of grapevine (PD) is not native to the US as previously assumed, but descended from a single genotype introduced from Central America. PD has posed a serious threat to the US wine industry ever since its first outbreak in Anaheim, California in the 1880s and continues to inhibit grape cultivation in a large area of the country. It is caused by infection of xylem vessels by the bacterium Xylella fastidiosa subsp. fastidiosa, a genetically distinct subspecies at least 15,000 years old. We present five independent kinds of evidence that strongly support our invasion hypothesis: 1) a genome-wide lack of genetic variability in X. fastidiosa subsp. fastidiosa found in the US, consistent with a recent common ancestor; 2) evidence for historical allopatry of the North American subspecies X. fastidiosa subsp. multiplex and X. fastidiosa subsp. fastidiosa; 3) evidence that X. fastidiosa subsp. fastidiosa evolved in a more tropical climate than X. fastidiosa subsp. multiplex; 4) much greater genetic variability in the proposed source population in Central America, variation within which the US genotypes are phylogenetically nested; and 5) the circumstantial evidence of importation of known hosts (coffee plants) from Central America directly into southern California just prior to the first known outbreak of the disease. The lack of genetic variation in X. fastidiosa subsp. fastidiosa in the US suggests that preventing additional introductions is important since new genetic variation may undermine PD control measures, or may lead to infection of other crop plants through the creation of novel genotypes via inter-subspecific recombination. In general, geographically mixing of previously isolated subspecies should be avoided

Diffusion MRI tractography with along-tract profiling reveals subtle neurodevelopmental differences between moderate and late preterm infants

PURPOSE: Moderately preterm (MP) infants (32-33 weeks' gestation) are at increased risk for developmental problems compared to late preterm (LP) infants (34-36 weeks' gestation). Fiber bundle tractography remains an unexplored avenue to understanding this risk-difference between MP and LP infants. This study aimed to examine along-tract profile differences between MP and LP infants at term-equivalent age (TEA). METHODS: Ninety-five infants (31 MP and 64 LP), born between November 2020 and March 2023, underwent MRI around TEA (40-44 weeks postmenstrual age). MRI included T2-weighted imaging and diffusion MRI (dMRI) with b-values 800 and 2000 s/mm2 (single shell). dMRI scans were preprocessed to reduce common artifacts. For all infants, 15 fiber bundles were reconstructed using TractSeg and along-tract profiles, expressed as fractional anisotropy (FA) and mean diffusivity (MD), and were compared between MP and LP infants using tractometry. RESULTS: Reconstructions with TractSeg demonstrated shape, position, and orientation of fiber bundles consistent with known neuroanatomy. FA and MD profiles were not significantly different between MP and LP infants. However, alternating trends towards along-tract profile differences between MP and LP infants were observed for multiple bundles. Wide 95% confidence intervals indicated substantial variability in fiber bundle organization within groups. CONCLUSION: Although not significant, along-tract differences between MP and LP infants suggest subtle alterations in white matter maturation. These findings indicate along-tract variability as potential focus for future research aimed at uncovering the mechanisms underlying early maturational differences and their potential role in later neurodevelopmental challenges encountered in moderate-late preterm infants