Spinal Defects Research Articles

New treatments for spinal cord injuries

New treatments for spinal cord injuries

Should the Macular Lesions Around Spinal Dysraphism Be Excised? Analysis of Macular Lesions Accompanying Spinal Dysraphism.

Whether the macular lesions associated with spinal dysraphism should be preserved is controversial. This area is usually excised during reconstruction. This study aims to characterize the macular lesions associated with spinal dysraphism and to determine the outcomes of cases in which macular lesions are not excised. The patient cohort comprised 17 patients with spinal dysraphism who were treated at Mersin University Hospital from 2005 through 2007. Blood and tissue samples were obtained from these patients. Electron microscopy results of tissue samples obtained from macular lesions are not consistent with those of hemangiomas. Increased numbers of vessels and significant dilatation was noted upon examination by light microscopy. The number of mast cell numbers, blood estradiol levels, expression of tissue inhibitor matrix metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF), and dermal collagen fiber diameter were within normal range. Estrogen receptor-β was not expressed. The number of endothelial cells expressing von-Willebrand factor was higher in the macular lesions. The characteristics of macular lesions associated with spinal dysraphism are consistent with those of capillary malformations. We believe that the preservation of these macular lesions during soft tissue reconstruction of spinal dysraphism defects, either by mobilization on a flap or primary closure, does not compromise the viability of the macular region. By preserving these macular lesions, the creation of larger defects during excision is avoided.

A Retrospective Analyses of Newborns Operated Due to Midline Spinal Closure Defect: A Single Center Experience

A Retrospective Analyses of Newborns Operated Due to Midline Spinal Closure Defect: A Single Center Experience

Myelomeningocele Repair: Surgical Management Based on a 30-Year Experience.

Myelomeningocele (MMC) is a rare but severe spinal defect resulting from a failed neurulation process. Surgical repair is a delicate procedure that needs accurate neuroanatomical knowledge and adequate surgical planning. The authors report on the main problems of the surgical management of this type of dysraphism. The technique used for reconstruction, and the management strategies, are analyzed according to the authors' experience with more than 600 cases, in comparison with the relevant literature. Tip and tricks of more than 30 years of MMC surgical management are reported, with special mention of the timing of surgery, the management of early hydrocephalus, and the principles of the repair, from the dissection to the closure of five separate layers (arachnoid, dura, muscular fascia, subcutaneous layer, skin). Accuracy and attention to the reconstruction are crucial for achieving good results and avoiding perioperative complications.

Diagnostic value of CA 19-9 in pregnancies complicated by spinal neural tube defects: a preliminary study.

Various physiological and pathological conditions can induce significant variations in plasma concentrations of tumor markers, such as CA 19-9, which is present in the serum and amniotic fluid of pregnant women. Herein, we aimed to determine the clinical importance of maternal serum CA 19-9 levels in the diagnosis of neural tube defects (NTDs). A total of 100 women were included in this controlled cross-sectional study. Thirty-three patients whose pregnancies were complicated by isolated meningocele or meningomyelocele constituted the study group, whereas 33 normal, healthy pregnant women constituted the control group, and 34 age- and body mass index (BMI)-matched non-pregnant women were chosen for the validation group. The mean maternal serum CA 19-9 levels were 17.2 ± 17.0 IU/mL, 7.1 ± 5.9 IU/mL, and 4.7 ± 3.6 IU/mL in the study, control, and validation groups, respectively (p < 0.001). ROC analyses showed that elevated CA 19-9 values may predict NTDs (p < 0.001). The cut-off value for CA 19-9 was found to be 9.6 IU/mL at 70% (51%-84%, 95% CI) sensitivity and 84% (74%-92%, 95% CI) specificity. CA 19-9 may be a promising noninvasive marker for NTDs. Further studies are needed to reveal the clinical applicability and diagnostic potential of maternal serum CA 19-9 levels in the identification of NTDs.

Reduced inflammatory cell recruitment and tissue damage in spinal cord injury by acellular spinal cord scaffold seeded with mesenchymal stem cells.

Therapy using acellular spinal cord (ASC) scaffolds seeded with bone marrow stromal cells (BMSCs) has previously been shown to restore function of the damaged spinal cord and improve functional recovery in a rat model of acute hemisected spinal cord injury (SCI). The aim of the present study was to determine whether BMSCs and ASC scaffolds promote the functional recovery of the damaged spinal cord in a rat SCI model through regulation of apoptosis and immune responses. Whether this strategy regulates secondary inflammation, which is characterized by the infiltration of immune cells and inflammatory mediators to the lesion site, in SCI repair was investigated. Basso, Beattie, and Bresnahan scores revealed that treatment with BMSCs seeded into an ASC scaffold led to a significant improvement in motor function recovery compared with treatment with an ASC scaffold alone or untreated controls at 2 and 8 weeks after surgery (P<0.05). Two weeks after transplantation, the BMSCs seeded into an ASC scaffold significantly decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, as compared with the ASC scaffold only and control groups. These results suggested that the use of BMSCs decreased the apoptosis of neural cells and thereby limited tissue damage at the lesion site. Notably, the use of BMSCs with an ASC scaffold also decreased the recruitment of macrophages (microglia; P<0.05) and T lymphocytes (P<0.05) around the SCI site, as indicated by immunofluorescent markers. By contrast, there was no inhibition of the inflammatory response in the control and ASC scaffold only groups. BMSCs regulated inflammatory cell recruitment to promote functional recovery. However, there was no significant difference in IgM-positive expression among the three groups (P>0.05). The results of this study demonstrated that BMSCs seeded into ASC scaffolds for repair of spinal cord hemisection defects promoted functional recovery through the early regulation of inflammatory cell recruitment with inhibition of apoptosis and secondary inflammation.

Postnatal Gene Therapy Improves Spatial Learning Despite the Presence of Neuronal Ectopia in a Model of Neuronal Migration Disorder.

Patients with type II lissencephaly, a neuronal migration disorder with ectopic neurons, suffer from severe mental retardation, including learning deficits. There is no effective therapy to prevent or correct the formation of neuronal ectopia, which is presumed to cause cognitive deficits. We hypothesized that learning deficits were not solely caused by neuronal ectopia and that postnatal gene therapy could improve learning without correcting the neuronal ectopia formed during fetal development. To test this hypothesis, we evaluated spatial learning of cerebral cortex-specific protein O-mannosyltransferase 2 (POMT2, an enzyme required for O-mannosyl glycosylation) knockout mice and compared to the knockout mice that were injected with an adeno-associated viral vector (AAV) encoding POMT2 into the postnatal brains with Barnes maze. The data showed that the knockout mice exhibited reduced glycosylation in the cerebral cortex, reduced dendritic spine density on CA1 neurons, and increased latency to the target hole in the Barnes maze, indicating learning deficits. Postnatal gene therapy restored functional glycosylation, rescued dendritic spine defects, and improved performance on the Barnes maze by the knockout mice even though neuronal ectopia was not corrected. These results indicate that postnatal gene therapy improves spatial learning despite the presence of neuronal ectopia.

FEATURES OF SURGICAL TREATMENT OF SPINAL DYSRAPHISM OF THE SACRALCOCCYGEAL AREA OF INFANTS

Spinal dysraphism (SD) of children is a complicated and unsolved problem in pediatric neurosurgery. Pathology of sacral-coccygeal area is 30 % - 50 % of the total number of SD of children. The presence of a large number of nearest complications (wound abscess, meningitis, the gap of the wounds, liquorrhoea) and long-term postoperative period complications (impaired functions of the lower limbs and pelvic organs) are the basis to search for improved methods of treatment. 19 newborns with SD sacral-coccygeal area were operated. 16 children were aged 1 to 10 days and 3 from 11 to 28 days. Depending on the anatomical variants of SD sacral-coccygeal areas they were divided into: meningocele (26,32%); myelomeningoradiculocele (15,78%); myelomeningocele (31,58%). All surgery was performed with the use of microsurgical tools and microsurgical techniques under optical multiplication using electric coagulator for the tissue (EC-300M 1). A favourable condition for better results in the treatment of SD was selection of the optimal timing and techniques of surgery. The best results for surgery were the age of 7 to 10 days (12 children). The term of surgery from 11 until 28 days for 3 children was due to the presence of hernia infection and purulence, which required the implementation of preoperative preparation for 5-7 days. The approach was determined by: hernia localization, size and spine defect, the degree of subcutaneous tissue development, the condition of hernia layers, displacement and plasticity of the back tissues. The disadvantage of all methods of surgical treatment of SD there is a danger of iatrogenic damage to neural elements during surgery, depending on the quality of its performance. While performing surgical treatment of SD microsurgical radiculolysis with precision microsurgical excision of all cicatricial adhesions, cerebrospinal fluid cysts and other intraradicular formations, and thorough revision of the spinal canal should be undertaken. Dysfunction of the pelvic organs (urine and anal incontinence) and lower limbs are observed in 63,16% of children operated on for SD in the neonatal period that requires further development of methods of their surgical correction at a later age.

Prenatal myelomeningocele repair: Do bladders better?

Prenatal myelomeningocele (MMC) repair has been proven to significantly reduce the need for hydrocephalus shunting and improve lower-extremity motor outcomes. The aim of this study was to evaluate the effect of prenatal MMC repair on the urological outcome. All patients who underwent fetal MMC repair at our institution are followed prospectively. Assessments include medical history, renal and bladder ultrasound, voiding cystourethrogram and urodynamic study, need for clean intermittent catheterization (CIC) and anticholinergics, and the occurrence of urinary tract infections (UTI). Of the 30 patients who underwent prenatal MMC closure from December 2010 to December 2015, eight patients with a postnatal follow-up of at least 2 years were included in this study and compared with eight patients after postnatal MMC repair. The level of the bony spinal defect was similar in both groups. Urological evaluation at 2 years revealed normal bladder function in 50% after prenatal repair. Neurogenic bladder dysfunction requiring CIC and anticholinergic therapy was seen in 50% in the prenatal and in 100% in the postnatal group. Significant bladder wall thickening was found in 37.5% and 87.5%, respectively. Febrile UTIs occurred in 37.5% in the prenatal and 62.5% in the postnatal group during the observation period. Our data suggest a positive effect of prenatal MMC closure on lower urinary tract function. The long-term significance of these results remains unclear. Therefore, continued close monitoring of renal and bladder function are mandatory.

Developmental Acquisition of Wheelchair Mobility Skills in Children with Spinal Defects

Developmental Acquisition of Wheelchair Mobility Skills in Children with Spinal Defects

The Role of Steroid in Post Myelography Headache

Myelography is a diagnostic procedure to indicate spinal defects. After the inception of new means of spinal cord imaging, use of myelography has been limited. Since there are contraindications for other modalities in some patients, we have to use myelography. The most common complication of myelography is post myelography headache (PMH). Many methods have been proposed to alleviate the pain. In this clinical trial study we assess the role of steroid in PMH.

Differentiating Closed Versus Open Spinal Dysraphisms on Fetal MRI.

The purpose of this study is to identify differences in findings between open and closed spinal dysraphisms seen on fetal MR images. A single-institution retrospective analysis of fetal MR images for spinal dysraphism was performed. Postnatal images and clinical and operative reports were reviewed. Sixteen fetuses with postnatally confirmed closed spinal dysraphisms were included. Of these, 25% (4/16) had posterior fossa anomalies, 12.5% (2/16) had ventriculomegaly, and 37.5% (6/16) had OEIS (omphalocele, exstrophy, imperforate anus, and spinal defects) complex. Of 90 fetuses with postnatally confirmed open spinal dysraphism, 95.6% (86/90) had posterior fossa anomalies, 85.6% (77/90) had ventriculomegaly, and none had OEIS complex. Twenty fetuses with open spinal dysraphism were randomly selected to compare with fetuses with closed spinal dysraphisms. Continuity of the epidermal and subcutaneous tissues with the sac wall on fetal MR images was seen in 93.8% (15/16) of patients with closed spinal dysraphisms, as opposed to 5% (1/20) of patients with open spinal dysraphisms. The mean (± SD) sac wall thickness was less in open (0.7 ± 0.6 mm) than closed (2.9 ± 1.3 mm; p < 0.001) spinal dysraphism. None of the fetuses had T1-hyperintense fat within the defect. On fetal MR images, closed spinal dysraphisms tend to have a sac wall in continuity with the epidermal and subcutaneous tissues, a thicker sac wall, fewer posterior fossa anomalies, and high association with OEIS complex.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of the Neonatal and Infant Spine

AIUM Practice Parameter for the Performance of an Ultrasound Examination of the Neonatal and Infant Spine

Intrauterine Surgery for Spinal Defects: What is the Role of Ultrasound?

ABSTRACT Ultrasound imaging has led to the diagnosis of fetal anomalies that can affect many organ systems. Since the development of high-resolution real-time ultrasound, the possibility of surgical intervention before birth to correct or treat prenatally diagnosed abnormalities has been realized. Fetal surgery has become a new standard of care for the perinatal treatment of myelomeningocele for mothers and fetuses that meet the specific criteria. In this review, we will consider the role of ultrasound for open fetal surgery or minimally invasive fetal surgery approaches. How to cite this article Moreira de Sá RA, Peixoto-Filho F, Cima L. Intrauterine Surgery for Spinal Defects: What is the Role of Ultrasound? Donald School J Ultrasound Obstet Gynecol 2016;10(3):297-300.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of the Neonatal and Infant Spine.

AIUM Practice Parameter for the Performance of an Ultrasound Examination of the Neonatal and Infant Spine.

Spinal nerve defects in mouse embryos prenatally exposed to valproic acid.

To examine in detail spinal nerve defects induced by prenatal exposure to valproic acid in mice, pregnant ICR mice were subcutaneously injected with a single dose of 400mg/kg valproic acid on gestational day 6, 7, 8, or 9, and their embryos were observed on gestational day 10. The whole-mount immunostaining using an anti-neurofilament antibody allowed us to identify spinal nerve defects, such as a loss of bundle, anastomosis among bundles arising from adjacent segment, and a disrupted segmental pattern of the dorsal root ganglia, in valproic acid-exposed embryos. The prevalence of spinal nerve defects was the highest in the embryos exposed to valproic acid on gestational day 8 among the experimental groups. Then, effects of the administration dose of valproic acid on the prevalence of spinal nerve defects were examined on gestational day 10 and found to be dose-dependently increased. It was noteworthy that all embryos exposed to 600mg/kg of valproic acid on gestational day 8 suffered spinal nerve defects. Folic acid (3mg/kg/day) supplementation during gestational day 6-10 suppressed the prevalence of valproic acid-induced neural tube defects, which are common malformations in offspring prenatally exposed to valproic acid, but not that of spinal nerve defects. Thus, the spinal nerve defects due to prenatal valproic acid exposure might be induced by mechanisms different from those of neural tube defects. Because spinal nerve defects were predicted to be caused by the disrupted segmental arrangement of the somites and/or that of neural crest cells, which was the origin of the dorsal root ganglia and/or abnormal polarity of the somite, this mouse model with spinal nerve defects at high incidence would be useful to examine the effects of valproic acid on the somitogenesis and morphogenesis of somite-associated structures.

Multichannel silk protein/laminin grafts for spinal cord injury repair.

The physical, chemical, and bioactive cues provided by biomaterials are critical for spinal cord regeneration following injury. In this study, we investigated the bioactivity of a silk-based scaffold for nerve tissue remodeling that featured morphological guidance in the form of ridges as well as bioactive molecules. Multichannel/laminin (LN) silk scaffolds stimulated growth, development, and the extension of primary hippocampal neurons after 7 days of culture in vitro. And then, the multichannel/LN silk scaffolds were implanted into 2-mm-long hemisection defects in Sprague-Dawley rat spinal cords for 70 days to evaluate their bioactivities of spinal cord remolding. Our results demonstrated that animal behavior was significantly improved in the multichannel/LN group, as evaluated by Basso-Beattie-Bresnahan score, whereas the implantation of multichannels and random pores groups resulted in recurring limps. Moreover, histology and immunohistochemical staining revealed an increase in blood vessels and expression of growth associated protein-43 and neurofilament-200 as well as reduced expression of glial fibrillary acidic protein in the multichannel/LN group, which contributed to the rebuilding of spinal cord defects. Thus, multichannel/LN silk scaffolds mediated cell migration, stimulated blood capillary formation, and promoted axonal extension, suggesting the utility of these scaffolds for spinal cord reconstruction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3045-3057, 2016.

Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the fragile X mouse model.

Astrocytes are key participants in various aspects of brain development and function, many of which are executed via secreted proteins. Defects in astrocyte signaling are implicated in neurodevelopmental disorders characterized by abnormal neural circuitry such as Fragile X syndrome (FXS). In animal models of FXS, the loss in expression of the Fragile X mental retardation 1 protein (FMRP) from astrocytes is associated with delayed dendrite maturation and improper synapse formation; however, the effect of astrocyte-derived factors on the development of neurons is not known. Thrombospondin-1 (TSP-1) is an important astrocyte-secreted protein that is involved in the regulation of spine development and synaptogenesis. In this study, we found that cultured astrocytes isolated from an Fmr1 knockout (Fmr1 KO) mouse model of FXS displayed a significant decrease in TSP-1 protein expression compared to the wildtype (WT) astrocytes. Correspondingly, Fmr1 KO hippocampal neurons exhibited morphological deficits in dendritic spines and alterations in excitatory synapse formation following long-term culture. All spine and synaptic abnormalities were prevented in the presence of either astrocyte-conditioned media or a feeder layer derived from FMRP-expressing astrocytes, or following the application of exogenous TSP-1. Importantly, this work demonstrates the integral role of astrocyte-secreted signals in the establishment of neuronal communication and identifies soluble TSP-1 as a potential therapeutic target for Fragile X syndrome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0256-9) contains supplementary material, which is available to authorized users.

Congenital and Hereditary Diseases of the Spinal Cord

Congenital anomalies of the spinal cord can pose a diagnostic dilemma to the radiologist. Several classification systems of these anomalies exist. Antenatal ultrasound and fetal magnetic resonance imaging is playing an increasingly important role in the early diagnosis and management of patients. Understanding the underlying anatomy as well as embryology of these disorders can be valuable in correctly identifying the type of spinal cord dysraphic defect. Hereditary spinal cord diseases are rare but can be devastating. When the onset is in adulthood, delay in diagnosis is common. Although the spine findings are nonspecific, some imaging features combined with brain imaging findings can be distinctive. Sometimes, the radiologist may be the first to raise the possibility of these disorders.

Cellular Profiles and Molecular Mediators of Lesion Cascades in the Placode in Human Open Spinal Neural Tube Defects.

Myelomeningoceles (mmc) are clinically challenging CNS malformations. Although improvement in their management has been achieved with respect to antenatal diagnosis, prevention, and fetal surgery, the cellular mechanisms of damage in the neural placode are poorly understood. We aimed to identify cellular and molecular factors in lesion amplifying cascades in mmc placodes. Seventeen mmc specimens obtained during reconstructive surgery that harbored sufficient neuroepithelial tissue were investigated. Normal adult and stillborn spinal cord tissue served as controls. Placodes exhibited similar cellular profiles with consistent neuronal marker expression, elevated GFAP-/vimentin immunoreactivity in all, and CD3/CD11b/CD68-immunolabeling in some cases. Increased expression of pro-inflammatory (tumor necrosis factor, interleukin-1β [Il-1β]/IL-1 receptor type 1 [IL-R1]) and neuroprotective erythropoietin/erythropoietin receptor (Epo/EpoR) cytokines was detected by immunohistochemistry, double-fluorescence labeling, and real-time RT-PCR. In all cases, there was a multi-cellular induction of IL-1β and IL1-R1. EpoR and Epo immunoreactivity was elevated in some cases with neuronal expression patterns. Epo was further co-expressed with HIF-1/-2α, which paralleled Epo induction in the corresponding placodes. These observations confirm the induction of cellular and molecular alterations in human mmc placodes that resemble the secondary lesion cascades induced by spinal cord injury. The pro-inflammatory and neuroprotective cytokine expression in mmc placodes may represent new targets for the treatment of open neural tube defects.